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Direct inoculation on Phoenix panels for identification and antimicrobial susceptibility from positive BACTEC cultures: first study from India. PURPOSE This was a prospective study planned in a super-specialty hospital in Delhi to reduce turnaround times of identification-susceptibility results of positive blood cultures. MATERIALS AND METHODS One hundred consecutive single morphology non-duplicate cultures were inoculated on Becton Dickinson Phoenix™ panels by growth recovered directly from liquid BACTEC™ media and after pure growth on solid media. RESULTS Complete concordance was observed in 72.4% of gram-negative and 45.8% of gram-positive isolates. For gram-negative isolates, categorical agreement (CA) was >83% and essential agreement (EA) was >96% among all antibiotics tested, very major errors (VME) were 0.13%, major errors (ME) 0.54%, and minor errors (MiE) were 3.01%. For gram-positive isolates, VME was 0.73%, 1.10% MiE and no ME. It was observed that average time from receipt of specimen to release of reports was 30:34 h and 32 h for gram-negative and gram-positive isolates if reports of "Direct" panels were to be released. CONCLUSIONS By direct panel inoculation, a decrease of at least 18-20 h in turnaround time was observed compared with the standard method. This helps early change to effective antibiotic therapy and also reduces the expenditure incurred for a patient's hospital stay by average Rs 20,000 ($443) per day.

Save-on-laptops is selling the Lenovo IdeaPad Z370 laptop for only £300 via eBay, a price that includes delivery and 300 Nectar points. The laptop runs on an Intel Core i3-2350M processor, one clocked at 2.3GHz with two cores, 3MB L3 cache and one which is based on the Sandy Bridge architecture (which means that it also sports an Intel HD 3000 Graphics solution). Other features include a 13.3in 1,366 x 768 pixel display, 4GB of RAM, 500GB hard disk drive, Windows 7 Home Premium (rather than Windows 8), Accutype keyboard, a DVD writer, a card reader, Bulldog Internet Security, Ethernet, three USB 2.0 ports (no USB 3.0 unfortunately), Wi-Fi, Bluetooth, VGA and HDMI ports, five hours battery life and a weight of only 2Kg. Lenovo also included nifty features called a OneKey Theater II which optimizes audio-visual settings with SRS Premium Surround sound or RapidBoot technology. How Lenovo managed to squeeze both a DVD writer in a product that weighs less than 2Kg is a mystery. Swap the mechanical hard disk drive for an SSD and you would have a very nimble and affordable Ultrabook.

This is simply a list of Christian bloggers who don’t happen to be white. This list so far is embarrassingly short. That’s evidence, I take it, that my own blog-reading habits have been even more culturally circumscribed than I had realized. So I’m asking for help here, because apparently I need it. What I’ve got here isn’t so much a list as the tip of an iceberg, and I hope you’ll be able to help me discover the many, many terrific voices I haven’t yet included here. Can I Brag on My Lord? Where Are You? Where Are You Going? You Feed Others, Who Feeds You?

Assessment of physiological signs associated with COVID-19 measured using wearable devices Respiration rate, heart rate, and heart rate variability (HRV) are some health metrics that are easily measured by consumer devices, which can potentially provide early signs of illness. Furthermore, mobile applications that accompany wearable devices can be used to collect relevant self-reported symptoms and demographic data. This makes consumer devices a valuable tool in the fight against the COVID-19 pandemic. Data on 2745 subjects diagnosed with COVID-19 (active infection, PCR test) were collected from May 21 to September 11, 2020, consisting of PCR positive tests conducted between February 16 and September 9. Considering male (female) participants, 11.9% (11.2%) of the participants were asymptomatic, 48.3% (47.8%) recovered at home by themselves, 29.7% (33.7%) recovered at home with the help of someone else, 9.3% (6.6%) required hospitalization without ventilation, and 0.5% (0.4%) required ventilation. There were a total of 21 symptoms reported, and the prevalence of symptoms varies by sex. Fever was present in 59.4% of male subjects and in 52% of female subjects. Based on self-reported symptoms alone, we obtained an AUC of 0.82±0.017 for the prediction of the need for hospitalization. Based on physiological signs, we obtained an AUC of 0.77±0.018 for the prediction of illness on a specific day. Respiration rate and heart rate are typically elevated by illness, while HRV is decreased. Measuring these metrics, taken in conjunction with molecular-based diagnostics, may lead to better early detection and monitoring of COVID-19. I. INTRODUCTION The year 2020 has seen the emergence of a global pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. The disease caused by this virus typically presents as a lower respiratory infection, though many atypical presentations have been reported. This has caused a major health challenge globally due to the apparent high transmissibility of this virus in a previously unexposed population. Of particular concern is that the primary mechanisms by which the disease is transmitted are still somewhat under debate (e.g., the importance of airborne transmission) 1, and the potential for infection by asymptomatic and pre-symptomatic patients (see for e.g., the discussion in Oran & Topol 2 ). The disease is highly contagious, with transmission possible 2.3 days prior to the onset of symptoms, and peaking 0.7 days prior to the onset of symptoms according to one model 3. As a result, a great deal of effort is underway to potentially diagnose COVID-19 early. The popularity and widespread availability of consumer wearable devices has made possible the use of health metrics such as respiration rate, heart rate, heart rate variability, sleep, steps, etc in order to predict the onset of COVID-19 or similar illnesses. A 1 C rise in body temperature can increase heart rate by 8.5 beats per minute on average 4. Measuring the resting heart rate, or heart rate during sleep can therefore be a useful diagnostic tool. Similarly, the respiration rate is elevated when patients present with a fever 5. Heart rate variability is the variability in the time between successive heart beats (the time between successive heart beats is called the "RR interval"), and is a valuable, non-invasive probe of the autonomic nervous system. Lowered values are indicative of increased mortality 9, and may provide early diagnosis of infection 10. A study of heart rate variability in critically ill COVID-19 patients showed that the approximate entropy and the sample entropy were decreased in COVID-19 patients compared to critically ill sepsis patients 11. Zhu et al. 12 studied heart rate, activity and sleep data collected from Huami wearable devices to potentially identify outbreaks of COVID-19, and concluded that at a population level an anomaly detection algorithm provided correlation with the measured infection rate. Menni et al. 13 analyzed symptoms reported through a smartphone app and developed a model to predict the likelihood of COVID-19 based on the symptoms. Marinsek et al. 14 studied data from Fitbit devices as a means for early detection and management of COVID-19. Miller et al. 15 used the respiration rate obtained from Whoop devices to detect COVID-19. Mishra et al. 16 analyzed heart rate, steps, and sleep data collected from Fitbit devices to identify the onset of COVID-19. In this paper, we consider the correlation between changes in physiological signs related to respiration rate, heart rate and heart rate variability, and the corresponding presence of diseases assessed both through confirmed laboratory testing and self-reported symptoms and the time-course of the disease. We show that it is possible to use changes in these physiological metrics to detect illness, and provide estimates of sensitivity and specificity. In addition, given the reporting of symptoms by study participants, we provide an estimate of predicted disease severity based solely on symptoms. A. Data Collection Fitbit is a global leader in wearable technology since 2007, and has a large established base of users (over 30 million as of 2020). A significant percentage of its devices are configured to measure heart rate, and the underlying interbeat intervals (RR) that characterize heart rate variability. The Fitbit app provides a convenient user-facing app that can be configured to present user-facing questions, and to reliably capture responses in a secure and scalable way. In this study, active Fitbit users in the USA and Canada were invited to participate in a survey of whether they have experienced COVID-19 or similar infections, whether they had been tested, and to report on symptoms they experienced. They could also optionally provide additional demographic data such as age, sex, body mass index, and relevant background medical information such as underlying conditions such as diabetes, coronary arterial disease, or hypertension. While the researcher hypothesis was that metrics that could be generated from heart rate were likely to be most predictive of infectious disease, we did not restrict the survey to only Fitbit users with heart rate enabled devices (in practice 95% of survey respondents had heart rate enabled devices). The survey and associated marketing and recruitment materials were approved by an Institutional Review Board (Advarra) and from May 21st 2020, the survey was available for completion by Fitbit users in the USA and Canada. The data presented here represent the analysis on survey results collected up to July 14, 2020. The survey contained the following questions in relation to COVID-19 and other likely confounding infectious diseases such as influenza, urinary tract infections etc. -a) have you been tested for COVID-19 (with separate sections provided for tests for active infection versus serological tests for previous infection), b) what were the symptoms experienced and the dates of onset and disappearance of the symptoms, c) were you tested for other infectious diseases such as influenza, strep throat etc. Table I shows the overall breakdown of the survey responses as well as providing summary demographic information on the survey respondents. The age distribution of survey respondents was very similar to Fitbit users' overall age distribution. Survey respondents skewed slightly more female than the corresponding figure for the overall general Fitbit population. Table II describes the self-reported major comorbidities of the participants who reported a positive diagnosis of COVID-19, either through a confirmed PCR test or a serological test (we assume that the vast major- ity of tests for active COVID-19 infection were done using PCR-based techniques). Note that participants could also decline to answer this question, so these numbers are only indicative of general trends in the disease population. In order to assess some metric of disease severity, we took the approach of asking about the person's treatment rather than through quantification of symptoms. The options provided to a survey participant were:. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 3. I self-treated with someone's help. 4. I required hospitalization without ventilation support. 6. Prefer not to say. We consider 1 as asymptomatic. 2 is assigned to category "mild". 3 is assigned to "moderate", 4 is "severe" and 5 is "critical". 11.0% of participants were asymptomatic, 47.2% had mild symptoms, 33.2% were moderate, 8.16% severe, and 0.448% critical. Those with mild symptoms recovered sooner than those with moderate or severe symptoms. The distribution in the duration of symptoms is shown in Fig. 1. B. Making predictions based on health metrics and symptoms Firstly, we wished to use the self-reported symptoms as a classifier of likely need for hospitalization. Using the symptoms along with the age, sex, and BMI as input features, we trained a logistic regression classifier to predict the need for hospitalization. We only considered symptomatic individuals for this analysis. Secondly, we considered the use of physiological signs to predict the presence of symptoms associated with COVID-19. Let us denote the n th day relative to the start of symptoms as D n. D 0 thus represents the day when symptoms started. We make the assumption that individuals are healthy, i.e. class "Negative" from day D a to day D b where D b < D 0. The days between D b and D 0 are treated as a buffer space when subjects may or may not be sick, and hence, ignored. Subjects are considered to be sick from day D c up to day D d where D c ≥ D 0. The choices of D a, D b, D c, and D d are made through cross validation. As a guide to choosing the days, we note the median incubation period is estimated at 5.1 days 17. Since we are using the date relative to the start of symptoms as the ground truth label, we consider only symptomatic individuals. The following physiological data was calculated for each user on a daily basis using the data recorded from their Fitbit device: The estimated mean respiration rate during deep (slow wave) sleep (we default to light sleep if deep. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The mean nocturnal heart rate during non-Rapid Eye Movement (NREM) sleep. The Root Mean Square of Successive Differences (RMSSD) of the nocturnal RR series. The Shannon entropy of the nocturnal RR series. Data are collected simultaneously from the PPG sensor and the accelerometer. RR data are only stored when no motion above a set threshold is detected, and when the coverage in a 5 minute window exceeds 70%. Data are only collected when the subjects are at rest. The RR data are then cleaned to remove noise due to missed heart beats, motion artifacts, electronic noise, etc. The Fitbit system estimates periods of light, deep (slow wave) and REM sleep 18 and this is used in deciding which sections of the overnight data to process. The respiration rate is obtained by fitting a Gaussian model to the spectrum of the interpolated RR intervals as a function of frequency -this relies on the phenomenon of respiratory sinus arrhythmia (RSA) to induce a measurable modulation of the RR interval series. In cases where there is no discernible RSA, we do not estimate the respiration rate. The RMSSD is a time domain measurement used to estimate vagally mediated changes 8. It is computed in 5 minute intervals, and the median value of these individual measurements over the whole night is calculated. The Shannon entropy is a non-linear time domain measurement computed using the histogram of RR intervals over the entire night. The RMSSD and entropy are computed between midnight and 7 am. The sleeping heart rate is estimated from non-REM sleep only. The respiration rate is computed from deep sleep when possible, and from light sleep in the case of insufficient deep sleep. Since health metrics such as respiration rate, heart rate, and heart rate variability can vary substantially between users, we use the Z−scored equivalents: where x could stand for respiration rate, heart rate, RMSSD, or entropy. x and x are the rolling mean and rolling standard deviation of the metric being measured. For each day D n, we construct a 5 4 matrix with the normalized Z−scores corresponding to the 4 health metrics, measured on days D n D n−4. Each day is represented by a matrix with that day's data along with the previous four days data. Each row of the matrix represents a day of data, while each column represents a metric. We linearly interpolate missing data, but only do so if there is a minimum of 3 days of data. We create an "image" from each matrix by resizing each 5 4 matrix to a 28 28 1 matrix, with the last dimension indicating that there is only one color channel. The pixel values are rescaled to the range. We included 673 symptomatic individuals with sufficient data for analysis. 70% The neural network architecture. The nocturnal respiration rate, heart rate, RMSSD, and entropy for day Dn along with the previous four days data are Z-scaled, arranged in the form of a 54 matrix and rescaled to 28 28 1. This image is fed to a 1-dim. convolutional layer with m filters. The first dense layer reduces these m features to a smaller number of N1 features which are concatenated with an array of external inputs such as age, gender, BMI, etc. The last dense layer leads to a softmax filter. of the subjects were randomly selected to comprise the training set. The remaining 30% of subjects were split equally into 2 hold-out sets: one for cross-validation, and one for testing. Fig. 2 shows the neural network architecture. Each image is input to a 1-dim. convolutional stage with m filters, and a filter size of k. After maxpooling, the convolutional stage produces a set of m features. Non-linearity in the form of a "Relu" layer is introduced. A dense layer is used to reduce the m convolutional features to a small feature set N 1. At this stage, an array of n external inputs is applied including features such as age, gender, and BMI that need to bypass the convolutional stage. We also input the sleep efficiency for day D n defined as the ratio of time asleep to the duration between wake time and bed time. In addition, we also include the Zscored respiration rate, heart rate, RMSSD, and entropy for day D n as a part of the array. The final dense layer leads to a softmax layer with two possible output classes. III. RESULTS Firstly we report on the prediction of hospitalization based on symptoms. We trained a logistic regression model to predict the need for hospitalization with four. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted August 16, 2020.. https://doi.org/10.1101/2020.08.14.20175265 doi: medRxiv preprint fold cross-validation, using the symptoms as input features, along with the age, sex, and BMI. Fig. 3 shows the ROC curve where "true positive" indicates a prediction of hospitalization for an individual who indeed required hospitalization. Averaged over four folds, the Area Under ROC (AUC) is 0.77 ± 0.05. The probability of the need for hospitalization p may be expressed as: where = −3.3457, s i is a symptom (1 if the symptom is present, and 0 otherwise), and w i is the weight corresponding to symptom s i. The weights for the various symptoms are shown in Table IV. We rescale the 2 continuous variables (age and BMI) as follows: where x s is the scaled version and x stands for age or BMI. x and x are the respective mean and standard deviation, which are (41.5 years, 12.5 years) for age and (30.8, 7.7) for BMI. For the sex, 1 indicates male and 0 indicates female. Let us now consider the problem of determining whether an individual is sick or healthy given the physiological metrics. Fig. 4 show the average Z-scores of symptomatic individuals for the respiration rate, heart rate, RMSSD, and entropy as a function of day, where day D 0 represents the start of symptoms. The error bars represent the standard error of the mean. The respiration rate shows the largest effect and also takes the longest time to return to its base value. The duration between day ≈ D +7 and ≈ D +21 may be thought of as a recovery phase during which the health metrics return to their normal values. It is interesting to note that the heart rate decreases on average, following day D +7, and returning to the base value by day D +20. The HRV metrics on the other hand, are slightly elevated on average in the recovery phase. We did not notice a decrease in respiration rate on average, during this phase. We trained a convolutional neural network to predict whether an individual is sick on any specific day given the Z−scores for respiration rate, heart rate, RMSSD, and entropy for that day and the preceding four days. Using the cross-validation set, we obtained the best performance considering negative classes from day D −21 to day D −8. The days from D −7 to D 0 are discarded. Data for the positive classes come from day D +1 to day D +7. The filter size k for 1-dimensional convolution was set to 5 pixels, while the number of filters m was set to 64. A drop-out of p = 0.4 was applied for regularization. The. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted August 16, 2020.. https://doi.org/10.1101/2020.08.14.20175265 doi: medRxiv preprint FIG. 4: Z-scores for respiration rate, heart rate, RMSSD, and entropy. Day 0 (D0) represents the start of symptoms. The respiration rate and heart rate are elevated during times of sickness, while the RMSSD and entropy are decreased. These metrics may change a few days prior to the start of symptoms. The duration from day D+7 to day D+21 may be thought of as a recovery period during which the heart rate is slightly below the normal value, while the HRV is slightly elevated. The respiration rate takes the longest time to return to its base value, and does not show a recovery phase unlike the heart rate or HRV. Shown are the mean and standard error of the mean. number of neurons in the first dense layer N 1 = 12, while the number of neurons in the second dense layer N 2 = 64. The data are randomly split into training and hold-out sets, but we do this four times using a different random seed each time, to reduce the risk of outliers influencing the results. The AUC for the four folds was found to be 0.81, 0.74, 0.78, and 0.74. The mean AUC over 4 folds is 0.77 ± 0.027. At 95% specificity, the sensitivity averaged over 4 folds is 44% ± 2.3%. Having set the network parameters, we retrained the classifier using all available data up to June 1, 2020. Data after June 1 was set aside a hold-out set for testing. On this dataset, the AUC was found to be 0.80, with a sensitivity of 47% at a specificity of 95%. Fig. 6 shows the fraction of symptomatic users who are classified as sick, for different days. Day 0 is the start of symptoms. Negative numbers indicate days prior to the start of symptoms, while positive numbers are days following the start of symptoms. Plot (a) shows the results for 95% specificity (solid, blue curve) and 90% specificity (dashed, green curve). Plot (b) shows the results for subjects at 95% specificity, who present with specific symptoms such as a fever, cough, or congestion. Plot (c) shows the effect of disease severity on the probability of illness detection, with a specificity of 95%. IV. DISCUSSION In this article, we analyzed data on 1,181 subjects diagnosed with COVID-19 using the active infection PCR swab test, in the time period May 21 -July 14, 2020. All subjects wore Fitbit devices and resided in the United States or Canada. The overall positivity rate was 7.26%. 11.0% of reported cases were asymptomatic. 8.16% of subjects required hospitalization without ventilation support, while 0.448% required ventilation. Fatigue was the most common symptom, present in 72% of cases. Symptoms such as rash and swelling in the fingers and toes presented rarely in less than 10% of cases.. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted August 16, 2020.. https://doi.org/10.1101/2020.08.14.20175265 doi: medRxiv preprint FIG. 6: Fraction of users in the test set who predict positive. The solid, blue curve in (a) shows the predictions for a 95% specificity scenario, while the dashed, green curve shows the same, for 90% specificity. Plot (b) shows the same predictions (95% specificity) but for subjects who present with specific symptoms. The presence of a fever (dashed, green) or a cough (dot-dashed, red) increases the probability of detection more than some other symptoms such as congestion (dotted, black). Plot (c) shows the same curves (95% specificity), but for different severity. As expected, severe (dotted, black) and moderate (dot-dashed, red) cases are easier to detect than mild (dashed, green) cases. The duration of symptoms depends on the severity: Mild cases show a median duration of 8 days, while moderate cases have a median duration of 15 days. The median duration for cases that required hospitalization was found to be 24 days with a large spread, with several cases with duration exceeding 2 months. We provided a simple formula to estimate the need for hospitalization given the symptoms, age, sex, and BMI. Shortness of breath is highly indicative of the need for hospitalization, while sore throat and stomach ache were the least likely. Rather surprisingly, gastrointestinal symptoms such as vomiting and loss of appetite were indicative of severe illness. Among demographic information, being older and having a high BMI show higher likelihoods for hospital-ization. We showed that respiration rate, heart rate, and heart rate variability are useful indicators of the onset of illness. We trained a convolutional neural network to predict illness on any specific day given health metrics for that day and the preceding four days. With 95% specificity, this classifier can detect 40% of cases on day D +1, where D 0 is the date when symptoms present. The classifier can detect 25% of cases on day D 0, and 21% of cases on day D −1. For the 90% specificity case, the corresponding numbers are 52% on day D +1, 32% on day D 0, and 29% on day D −1. The peak values for the 95% (90%) specificity scenarios are 52% (59%) on day D +4 (day D +5 ). Considering only subjects who present with a fever, we classify 63% of subjects as positive, on day D +6, with 95% specificity. The fraction who are classified positive increases with increased severity, but this effect is pronounced several days after the start of symptoms. Considering only subjects who show a moderate/severe/critical presentation, 65% of subjects are classified positive on day D +4, with 95% specificity. This study has multiple limitations which may confound some of its findings. The survey participants were all Fitbit users which may not represent the general US and Canadian population, and were all self-selecting in responding to the survey. Participants were asked to selfrecall the start-date and end-date of any symptoms they experienced which may be quite unreliable. Participants may also confuse active (PCR) tests with serological (antibody) tests. In order to simplify the survey, we did not ask for a breakdown of symptom presentation and severity through out the time-course of the disease. For the prediction of the need for hospitalization, our data consisted of 95 positive cases and 926 negative cases, so it is possible that our results are potentially affected by the small number of positive cases, as well as by the class imbalance. Nevertheless, we believe this survey provides an important scientific contribution by suggesting (a) hospitalization risk can be calculated from self-reported symptoms, and (b) relevant and predictive physiological signs related to COVID-19 may be detected by consumer wearable devices. Declaration of conflicts of interest: All authors are employees of Fitbit Inc.

The present invention relates to a method of forming patterned photoresist features that are useful for fabricating thin film circuits, such as magnetic, electronic, and semiconductor circuits. In the fabrication of electronic and magnetic circuit components, photolithographic processes are used to form miniaturized devices having features that are often sized less than 1 .mu.m. In conventional photolithographic methods, a layer of light-sensitive resist material is applied on a substrate, and a photomask is used to expose the resist to a desired pattern of radiation, such as ultraviolet light. The photomask can be superimposed on the resist (contact method), or a photomask can be projected onto the resist (projection method). Thereafter, the exposed photoresist is developed to form a pattern of raised photoresist features 10 on the substrate 12, as illustrated in FIG. 1. In modern circuit fabrication, proper control of the shape of the photoresist features 10 formed on the substrate is highly desirable. For example, when subsequent processing steps deposit material on, or etch material from, between the resist features 10, it is desirable for the resist features to have sidewalls 14 that are substantially vertical and perpendicular to the surface of the substrate. However, conventional photolithographic processes often produce resist features 10 having a spread-out foot 16 at the bottom of the features, as schematically illustrated in FIG. 1, that result from the chemical interaction of the resist layer with the substrate surface 18. Conventional methods have been developed to reduce the spreading out of the foot 16 of the resist feature 10. For example, Dean and Carpio, in OCG Interface 94 Proceedings, "Contamination of Positive Deep-UV Photoresist," Sematech, Austin, Tex. (1994), teach that a coating of silicon dioxide on the substrate can serve as a barrier which prevents undesirable chemical reaction between the resist and the substrate, allowing the resist features to have a substantially vertical sidewalls, and to minimize spreading-out at the bottom of the resist feature. However, such coatings are often difficult to remove on completion of the resist utilizing fabrication step, without adversely affecting the underlying or adjacent materials on the substrate surface. Also, the additional step adds to processing cost and reduces processing throughput. Moreover, in certain fabrication processes, it is desirable for the resist features to have cross-sectional profiles that are reentrant at the bottom of the features. By "reentrant profile," it is meant that the sidewalls of the resist features taper inwardly at the bottom of the feature, and more preferably form an elongated trench parallel to the substrate surface, the trench positioned along the junction of the resist feature and the substrate surface. Such a profile is particularly desirable when material is conformally deposited on and between the resist features to form electrical interconnect lines or to fill holes on the substrate. In these processes, a solvent is used to remove the residual resist, in a process commonly known as a lift-off process. The material conformally deposited over the resist features (which is often highly chemically resistant) prevents penetration of the solvent below the conductive layer to allow removal of the resist. However, the reentrant resist features cause a shadowing effect during deposition, that results in formation of an elongated void substantially absent deposition material, at the edge of the bottom surface of the resist feature in contact with the substrate. It is through this void that the solvent enters and dissolves the residual resist. Conventional methods used to obtain reentrant resist features using negative or image-reversal photoresist underexpose the bottom portion of the resist layer by limiting the exposure of the resist layer to radiation. However, these processes are sensitive to the chemical species on the surface of the substrate which affects the chemical reactions between the overlying resist and the substrate. Because different substrates have different surface chemistry and activity, such processes have often limited applications and reproducibility. Other methods have been used to control the profile of features formed using positive photoresist material. These methods typically chemically modify the surface of the resist layer to decrease the solubility of the surface of the resist to provide a larger width at the top surface as compared to the bottom of the feature. In one method, the resist layer is immersed into chlorobenezene solution; in another method, vapor silanation is used. However, many complex and difficult-to-control variables affect the surface chemistry of the features. Also, these methods often result in poor adhesion between the resist and the underlying substrate, and can also provide inconsistent resist development times. In yet another method, multiple coatings, typically 2 to 3 coatings, are used to produce the reentrant profiles. These methods depend on differences in the etch rate of the layers in a developing agent or plasma to produce the reentrant profiles. However, these processes use multiple and often complex process steps that can increase the cost of processing the substrate. Thus it is desirable to have a process for forming resist features having controlled and predefined cross-sectional profiles. It is further desirable to have a process for forming resist features having reentrant profiles at the bottom of the features. It is also desirable for the resist forming process to use materials that are chemically compatible with the substrate to reduce corrosion and/or contamination of the substrate during formation of the resist features. It is further desirable for the process to be compatible with conventional processes to allow easy integration into conventional manufacturing apparatus.

Esophageal striated muscle contractions in patients with Chagas disease and idiopathic achalasia Chagas disease causes degeneration and reduction of the number of intrinsic neurons of the esophageal myenteric plexus, with consequent absent or partial lower esophageal sphincter relaxation and loss of peristalsis in the esophageal body. The impairment of esophageal motility is seen mainly in the distal smooth muscle region. There is no study about esophageal striated muscle contractions in the disease. In 81 patients with heartburn (44 with esophagitis) taken as controls, 51 patients with Chagas disease (21 with esophageal dilatation) and 18 patients with idiopathic achalasia (11 with esophageal dilatation) we studied the amplitude, duration and area under the curve of esophageal proximal contractions. Using the manometric method and a continuous perfusion system we measured the esophageal striated muscle contractions 2 to 3 cm below the upper esophageal sphincter after swallows of a 5-ml bolus of water. There was no significant difference in striated muscle contractions between patients with heartburn and esophagitis and patients with heartburn without esophagitis. There was also no significant difference between patients with heartburn younger or older than 50 years or between men and women or in esophageal striated muscle contractions between patients with heartburn and Chagas disease. The esophageal proximal amplitude of contractions was lower in patients with idiopathic achalasia than in patients with heartburn. In patients with Chagas disease there was no significant difference between patients with esophageal dilatation and patients with normal esophageal diameter. Esophageal striated muscle contractions in patients with Chagas disease have the same amplitude and duration as seen in patients with heartburn. Patients with idiopathic achalasia have a lower amplitude of contraction than patients with heartburn. Correspondence Abstract Chagas' disease causes degeneration and reduction of the number of intrinsic neurons of the esophageal myenteric plexus, with consequent absent or partial lower esophageal sphincter relaxation and loss of peristalsis in the esophageal body. The impairment of esophageal motility is seen mainly in the distal smooth muscle region. There is no study about esophageal striated muscle contractions in the disease. In 81 patients with heartburn (44 with esophagitis) taken as controls, 51 patients with Chagas' disease (21 with esophageal dilatation) and 18 patients with idiopathic achalasia (11 with esophageal dilatation) we studied the amplitude, duration and area under the curve of esophageal proximal contractions. Using the manometric method and a continuous perfusion system we measured the esophageal striated muscle contractions 2 to 3 cm below the upper esophageal sphincter after swallows of a 5-ml bolus of water. There was no significant difference in striated muscle contractions between patients with heartburn and esophagitis and patients with heartburn without esophagitis. There was also no significant difference between patients with heartburn younger or older than 50 years or between men and women or in esophageal striated muscle contractions between patients with heartburn and Chagas' disease. The esophageal proximal amplitude of contractions was lower in patients with idiopathic achalasia than in patients with heartburn. In patients with Chagas' disease there was no significant difference between patients with esophageal dilatation and patients with normal esophageal diameter. Esophageal striated muscle contractions in patients with Chagas' disease have the same amplitude and duration as seen in patients with heartburn. Patients with idiopathic achalasia have a lower amplitude of contraction than patients with heartburn. Introduction Chagas' disease, caused by the flagellate protozoan Trypanosoma cruzi, affects the esophageal myenteric plexus causing degeneration and reduction of the number of in-trinsic neurons. The consequences for esophageal motility are absent or partial lower esophageal sphincter (LES) relaxation and loss of peristalsis in the esophageal body, a picture similar to that seen in idiopathic achalasia. Both diseases mainly involve the distal smooth muscle segment of the esophageal body, where there is a larger number of neurons in the myenteric plexus. However, there is also a reduction in the number of neurons in the myenteric plexus of the proximal third of the esophagus, where there is striated muscle. The contractions in the distal third of the esophagus are of low amplitude in Chagas' disease and in idiopathic achalasia. The duration is longer than normal in idiopathic achalasia, with results showing normal or longer duration in Chagas' disease. A recent study described a low contraction amplitude with dry swallows in the esophageal striated muscle of patients with idiopathic achalasia. In Chagas' disease there is no similar study. We know that the filling rate of the proximal esophagus in patients with the disease after swallowing a 10-ml bolus of water is slower than in normal subjects as a consequence of a longer oral phase in Chagas' disease, a fact that might influence esophageal proximal contractions. The objective of the present investigation was to study the esophageal striated muscle contractions in patients with Chagas' disease and compare them with those of patients with heartburn, taken as a control group, and patients with idiopathic achalasia. Material and Methods We retrospectively studied the esophageal striated muscle contractions of 81 patients who were submitted to esophageal manometric examination as part of the evaluation of heartburn, 51 patients with Chagas' disease, and 18 patients with idiopathic achalasia. The manometric examinations were performed from 1999 through 2001 as a contribution to the diagnosis of the diseases. All patients with heartburn (control group: 31 men and 50 women aged 17 to 87 years, median 41 years) were submitted to endo-scopic examination which showed a normal esophagus in 37 and esophagitis in 44 (grade I in 28, grade II in 7, and grade IV in 3 according to the classification of Savary-Miller), and Barrett esophagus in 6. Patients with dysphagia, chest pain, previous surgical treatment of gastroesophageal reflux disease, chronic cough, globus, esophageal stricture, laryngitis, pulmonary disease, and connective tissue diseases were excluded from the study. No patient had endocrine diseases or abnormalities in the manometric examination of the distal esophagus, with amplitude of contractions ranging from 35 to 180 mmHg, and more than 90% of swallows being followed by peristaltic contractions. In this group, which we used as control, we compared patients with esophagitis (N = 44) with patients without esophagitis (N = 37), patients aged 17 to 49 years (median: 37 years, N = 52) with patients aged 50 to 87 years (median: 61 years, N = 29), and men (N = 31) with women (N = 50). The patients with Chagas' disease (Chagas group) had a positive immunofluorescence test for T. cruzi. They were 19 men and 32 women aged 23 to 82 years, median 62 years. Radiologic esophageal examination showed that 30 patients had a normal diameter, 21 of them with slow transit, and 21 had an increase in esophageal diameter. No patient had been submitted to previous treatment. Dysphagia was a complaint in all patients with dilatation and in 25 without dilatation. All patients with idiopathic achalasia (achalasia group) had dysphagia. They were 10 men and 8 women aged 12 to 68 years, median 38 years. Eleven patients had esophageal dilatation in the radiologic examination, and 7 had only retention and slow transit. They had partial or absent LES relaxation and aperistalsis in the distal esophageal body. None had been submitted to previous treatment. All had a negative immunofluorescence test for T. cruzi. In the manometric examination we used a round eight-lumen polyvinyl catheter (Arndorfer Specialties Inc., Greendale, WI, USA) with an outer diameter of 4.5 mm and an internal diameter of 0.8 mm for each lumen. The four proximal lateral openings of the catheter were spaced 5 cm apart at 90 degree angles and the four distal openings were at the same level. For the manometric examination we used the four proximal channels and one distal channel, for a total of five channels spaced 5 cm apart. The channels were connected to five external pressure transducers (pvb Medizintechnik GmbH, Kirchseeon, Germany) with output to a PC Polygraph HR (Synectics Medical, Stockholm, Sweden). The manometric assembly was continuously perfused with water at a flow rate of 0.5 ml/min provided by a low compliance perfusion system (JS Biomedicals Inc., Ventura, CA, USA). The examination was performed during the morning after at least 12 h of fasting. The catheter was introduced through the nose until at least four side holes reached the stomach. After 10 min of stabilization the catheter was pulled at 1-cm intervals and at each station the patient swallowed a 5-ml bolus of water at room temperature. The esophagus was studied from the LES to the upper esophageal sphincter (UES). The esophageal segment 5 cm below the UES was defined as the striated muscle region of the esophageal body. We measured the maximum striated muscle contraction through the proximal side hole of the catheter consequent to one wet swallow when this side hole was at 2 or 3 cm below the UES. We analyzed the amplitude, duration and area under the curve (AUC) of the contractions with a computer program (Polygram for Windows 2.0 Medtronic Synectics, Stockholm, Sweden). We used one-way analysis of variance and the Tukey-Kramer multiple comparisons test for the statistical evaluation of the results, with the level of significance set at P<0.05. Data are reported as means ± SD and median. Results The Kolmogorov-Smirnov test applied to the results showed that the data followed Gaussian distribution in all groups. In the group of patients with heartburn we studied the effect of esophagitis, age and gender on amplitude, duration and AUC of the contractions. There were no differences between men and women, between patients older and younger than 50 years or between patients with or without esophagitis (P>0.05). The amplitude of contractions was 106.3 ± 45.0 mmHg in patients with esophagitis (N = 44) and 100.8 ± 36.7 mmHg in patients with normal endoscopy (N = 37). The amplitude of contractions was lower (P<0.01) in patients with idiopathic achalasia than in patients with heartburn ( Figure 1). There were no differences between the three groups studied (P>0.05) in the duration (Figure 2) or AUC (Figure 3) of contractions. The striated muscle contractions of patients with Chagas' disease did not differ (P>0.05) from those observed in the other groups (Table 1). Also, the patients with esophageal dilatation did not differ (P>0.05) Amplitude (mmHg) Discussion We did not find differences in the striated esophageal muscle contractions of patients with Chagas' disease compared with patients with heartburn or patients with idiopathic achalasia. The most important histological finding in Chagas' disease and idiopathic achalasia is the reduction in the number of neurons of the esophageal myenteric plexus. Ganglion cells rarely appear and are sparse in the myenteric plexus below the level of the cricoid cartilage. They continuously increase in number up to the middle portion and then maintain approximately the same number up to the cardia. The reduction of myenteric ganglion cells occurs along the entire length of the esophagus both in idiopathic achalasia and in Chagas' disease. The contractions of esophageal striated muscle are related to the extrinsic innervation. The extrinsic motor nerves to the striated muscle regions innervate muscle cells through motor end-plates. The neurotransmitter released at the end-plates is acetylcholine, which activates nicotinic cholinergic receptors in striated muscle. The neurons in the myenteric plexus of this region play a lesser role in the control of esophageal peristalsis than the myenteric plexus of the smooth muscle region. The cell bodies that send somatic nerves to the striated muscle region of the esophageal body are situated in the rostral nucleus ambiguus. Motor neurons cross the vagi to innervate this muscle. A very proximal bilateral vagotomy abolishes peristalsis in this segment of the esophageal body. Sensory afferent inputs modulate the central vagal output that controls the peristaltic contractions. Studies indicate that in Chagas' disease and idiopathic achalasia the predominant abnormalities exist within the myenteric plexus, but loss of neurons within the dorsal motor nucleus and degenerative changes of the vagal nerve fibers have been Chagas' disease Idiopathic achalasia Heartburn from patients without dilatation (Table 2). Although the results suggest that the patients with idiopathic achalasia might have lower AUC than the control group, the difference was not statistically significant (P = 0.07). * noted. The results of the study of proximal amplitude suggested that these alterations may be more important in idiopathic achalasia than in Chagas' disease. Patients with esophageal dilatation should have a low amplitude of contractions as a consequence of the increase in the diameter of the organ. However, this was not observed in the present study, perhaps because the diameter of the esophageal body was not increased in the upper esophagus a few centimeters from the UES. A previous study found a lower maximum striated muscle contraction amplitude in patients with achalasia than in controls in response to dry swallows. The results of the present study show that the amplitude of contractions in patients with achalasia is indeed decreased. We studied wet swallows, which may cause a higher amplitude than the dry swallows used in the previous study, as seen in esophageal smooth muscle contractions. Another study using wet swal-lows detected a lower contraction amplitude and longer contraction duration in patients with achalasia than in controls, measured 3 cm below the UES. As our results with wet swallows suggested the same conclusion when the contractions were studied with dry and wet swallows, we believe that the striated esophageal muscle contraction in achalasia is decreased. With these results we may assume that esophageal motor involvement by Chagas' disease differs somewhat from the involvement by idiopathic achalasia. Differences in the smooth muscle segment of the esophagus and in LES pressure, but not in UES pressure, have been reported. We studied proximal esophageal striated muscle contractions 2 or 3 cm below the UES. One study in humans showed that the area in which striated and smooth muscle portions were approximately equal was 4.7 ± 0.6 cm from the proximal portion of the cricopharyngeal muscle. This is the tran- sition zone and has the lowest esophageal amplitude of contraction, described as a "pressure trough". In another study this area was located at 21.7 ± 1.3% of the esophageal length. Below this transition the proportion of smooth muscle increases progressively until the middle esophagus, where the muscle is exclusively smooth. We performed the measurement at a site that has more than 50% of striated muscle. The manometric behavior of the striated muscle portion of the proximal esophagus shows characteristics similar to those of distal esophageal smooth muscle and different from the striated muscle of the pharynx. The slower contraction of the striated esophageal muscle than the striated muscle of the pharynx makes our perfusion system adequate to measure contraction. With the rapid contraction of the pharynx a solid state cath-eter is required. We did not detect differences caused by esophagitis, age or gender in the control group. Esophagitis was located in the distal esophagus where it can cause failed and low contraction amplitudes. The proximal esophageal contraction did not differ between patients with gastroesophageal reflux symptoms with or without esophagitis, with or without dysphagia or with moderate or severe esophagitis. We did not include patients with lesions or symptoms suggestive of involvement of the proximal esophagus in the control group. Esophageal striated muscle contractions seem to be normal in Chagas' disease and to have the same spectrum as seen in patients with heartburn. In idiopathic achalasia the proximal esophageal contraction is of low amplitude.

With less than two weeks left to return ballots, only 3.7 percent of Washington voters have done so, according to figures released Wednesday afternoon by the Secretary of State’s Office. The return rate is better in Spokane County, at 6 percent. This being an off-year election, Secretary of State Kim Wyman is expecting a turnout of about 46 percent. We urge Spokane County to beat the average. To be counted, ballots must be dropped off or mailed by Nov. 3. Along with two statewide initiatives, there are some important local races. The Spokesman-Review editorial board has wrapped up its endorsements. To read the full versions, go to http://www.spokesman.com/tags/2015-endorsement/. Spokane Mayor: The problem-solving David Condon has earned re-election with innovative solutions to water, sewer and infrastructure challenges. However, putting the Police Department on firmer footing is critical. Spokane Council President: Incumbent Ben Stuckart sometimes strays from the basics of city governance, but he is the clear choice over John Ahern and his divisive agenda. City Council, District 1: Incumbent Mike Fagan harbors some extreme views, but he works hard for constituents and understands the issues much better than his opponent. City Council, District 2: Businesswoman LaVerne Biel provides needed opposition to the council’s forays into regulating private-sector workplaces. City Council, District 3: Evan Verduin wants to narrow the council’s focus, making it more business-friendly. Spokane Valley Council, Position 3: Tom Towey’s embrace of sensible budgeting and regional cooperation make him the choice. Spokane Valley Council, Position 6: Ben Wick offers a working person’s perspective and an important focus on transportation. Spokane Public Schools Board, Position 3: Long-serving Rocky Treppiedi isn’t the most diplomatic board member, but he has a clear edge in experience and knowledge. Spokane Public Schools Board, Position 4: Close call, but Patricia Kienholz impresses with intellect and public service experience. City of Spokane, Proposition 1: A resounding no for a misguided plan that would give the city the highest minimum wage in the nation and constrain employer rights. If it were to pass, it would probably be tossed by the courts. Spokane County, Proposition 1: Expanding the County Commission to five members would provide a more reasonable workload and make them more accessible to citizens. Initiative 1366: Vote no on Tim Eyman’s messy, cynical bid to achieve a supermajority requirement for all tax increases. It would lead to the kind of gridlock haunting Congress. Initiative 1401: Vote yes to stymie the grotesque practice of slaughtering animals such as elephants and rhinos for profit.

Contracts between hospitals and health maintenance organizations This article describes the contractual relations that are emerging between health maintenance organizations (HMOs) and hospitals. Six HMOs in four large metropolitan areas provided information on 102 hospital contracts. The authors found that the HMOs are becoming more aggressive in placing hospitals in competition with each other for HMO patients. Staff and network HMOs are able to obtain a higher concentration of patients and substantially larger discounts for inpatient services than are individual practice association (IPA) plans in this study.

As I’ve stated many times on The Phantom Tollbooth, I’m utterly in awe over the differences between the genders and how these same differences shape our consequences in rather unique ways during life. The one thing in particular which always grabs my attention; the way Father Time seems to be much more forgiving on us dudez than he is on the womenz. Take it for what it’s worth, but I find it utterly astounding that a man in his late 30’s may not be out of ‘the race’ yet in terms of the dating/marriage market but a woman of the same lineage may be far closer to folding the deck that she would like to admit. In addition, just how far removed from reality most women tend to be nowadays in terms of this potentially severe situation unique to their gender. More importantly, how many of them rocket to a dismal future with little to no regard as to what it is they are actually doing to themselves in the process. I’ve always wondered as to what is going through a young woman’s mind, as she’s knee deep in her heady days of high market value, yet embarking on a future which odds are will set her up for a future fraught with loneliness and more cats than your local humane society. I have to thank Sunshine Mary for illuminating such thoughts for our consideration in one of her latest posts. I would suggest that you read the whole thing; her analysis of the situation is empathetic, sobering, and above all spot on. This quote from the ‘heroine’ of the article, who went by the handle of “A” had my head literally spinning as I read it. I’m a true feminist,” she added. “I’m a strong woman. I know what I want… Ten years from now, no one will remember — I will not remember — who I have slept with,” A. said. “But I will remember, like, my transcript, because it’s still there. I will remember what I did. I will remember my accomplishments and places my name is hung on campus. Really? Listen, as I’ve stated before, I’m not for pigeonholing women into certain roles, and why would I when women are doing this so effectively all on their own? Most women want to get married, but are so high on themselves at a young age they don’t see the forest for the trees. We don’t need statistics to tell us that when women are at the SMV peak (15 – 25) men are like buses. It doesn’t matter if they turn an approaching man down, there WILL be another along in a few minutes. The issue is that many women aren’t schooled in how men work in relation to their diminishing market value. No, women in the past would have taken them to task for being so foolish. Giving them the very painful but much needed truth in order to better preserve their uncertain futures. The issue is that the older generational women needed to show them the way has been perverted for selfish reasons and young women by and large are left to their own devices. What I find so interesting about the above quote, that this woman, and so many of her compatriots, are so completely ignorant of the consequences their actions will wreak on their respective futures. As we all know (or should by this point) negative consequences won’t come to pass for her at THIS point, they only happen to other people. She’s deep in the days where she has a regular FWB and men are probably hitting her up on a weekly basis. She has no inkling whatsoever that the parade of men coming into her life will ever stop so she has nothing to lose, thereby having no incentive to change her ways. However, that escalator of men DOES stop eventually so let’s take a look at what former blogger Troll King had to say to see where A’s future most likely will end up. I smell some projection that could be cut like a hot knife through butter. It is kinda interesting to look at baby boomer feminists these days. My mom is one. So are all of her friends. So, I have been around them and heard them gossip about things and I have seen their life paths dwindle as I grew up. Most are divorced and don’t have good relationships with their children. Many desperately want attention, whether it is from showing off their meager career success or from pestering their kids, assuming they have any or any that aren’t dead from suicide, for grandkids. What is really fascinating is how much they mellow out as they age. Their stories of putting on pant suits with thick pads in the shoulders to give themselves more masculine authority while fighting “the man” at work gives way to a sorta sad (if I gave a shit about those evil cunts I would think it was sad) realization that their lives were empty and hollow and fueled by something hazey irrationality that can really only be classified as some sort of mental illness that started to fade after they took off the padded pant-suit jackets (do you guys remember those from the 80s and 90s? My mom used to wear them all the time and so did all the women she knew and now they all dress much more conservatively…interesting eh?) and stopped trying to be men 24/7. Again, that entire section is nothing but projection that is not just about her but applies to the majority of baby boomer feminists.” (emphasis mine) Take another look at that folks. We have older more mature women who had sacrificed for career and when it was all over they found themselves chock full of accolades and virtually alone. What did those accomplishments give them at the end of the day? Where did the value of those accolades go now that their youth has given way to maturity? Yes this is only ONE anecdote in regards to women, however Troll King’s Mother and her friends aren’t alone. We have Liz Bollick, who has a career in entertainment yet was still vexed at ‘the system’ because she chose freedom and her career over marriage to her former fiancée. He moved on and married without her, but at least she still has her career. As one of my female and engaged co worker’s would say; “Oopie!” Then we have the illustrious Germaine Greer; ‘the saucy feminist that even men liked”; who eventually became a surly older woman when all she had left WAS her previous accolades. I’m willing to bet that Germaine is probably more successful that A will ever be; yet that didn’t keep her from being alone. Maybe Ms. Greer’s brusqueness has arisen from such loneliness. Perhaps, but could it possibly be that her surliness has cropped up from the knowledge that her own choices have lead her to her current (and irreversible) fate with the pained knowledge that she and she alone had the power to have altered things for the better? Finally (for this example) we have the illustrious Liz Jones and her current soul mate ‘Squeaky’. She actually had her own nuptials at one point in time and enjoyed wedded bliss for a scant 4 years. In the end, her own unwavering (bitchy?) attitude seemed to assist in the undermining of said marital arrangement and now she finds herself in a resolute relationship…with a four legged feline. This should offer no worries to A as Liz still has an memorable career in journalism in which she can find her absolution. Right, had anyone read the part about how she tried to get pregnant by stealing her partner’s sperm as she was entitled to it? C’mon…it’s fantastic and deathly intriguing!!! A is gung ho about her future achievements, that even if she doesn’t find love she will have her professional accomplishments to fall back on for satisfaction. In truth I really have no issue with this as far as women go, however, when we took a look at some women who had taken this very same approach to life, the results seemed very sobering. Gotta wonder as a woman how it would feel to come to the point of no return, with a sack full of career accomplishments, and none of those even turn an eligible man’s heads. To be seen as nothing but a cog in the wheel, a tool to be used by company’s and nothing more beyond that. Here’s a scenario for you; imagine a late 30’s , single career woman going out to dinner with her male co workers at an eatery. They talk shop as they sit down and look at the menu when an attractive 20 something waitress arrives to take their order. Imagine the consternation said career woman feels as this waif of a woman with nary the education, experience, or accolades our ‘heroine’ has achieved seems to garner the attention of all the men at the table while she is left reeling. What’s the deal gang; that her accomplishments do not translate whatsoever into the dating market, and she wallows in frustration as this woman who is younger, more approachable, and more ladylike grabs all the attention that she hasn’t seen in quite some time. The bottom line; while a career is ALMOST as good a thing to a woman as it is to a man, the issue is simply this. A man having a very good career almost always adds to his SMV/MMV, while it virtually always detracts from a woman’s. I bet money that this scenario or something very similar to it happens in Western Countries almost every day as women measure up their stock and realize that a younger, more ladylike woman trumps her amazing professional resume in the dating market. I find this whole thing ironic as A is unwittingly giving us a glimpse of what Liz Bollick’s, Germaine Greer’s, and Liz Jones’ thought process looked like way back when they still had significant time on the clock. It’s utterly mind boggling to see someone so dead set on doing something, which will ultimately undermine their own values go balls to the wall in doing so. Sadly, our warnings will fall on deaf ears until it’s too late. Omnipitron. Advertisements

Soluble Transferrin Receptor and SFI Index - A new biomarker to identify Iron Deficiency in Drug Nave Children with ADHD - A Case-Control Study Background: Children with Attention Deficit Hyperactivity Disorder (ADHD) have been associated with iron deficiency. Among several markers, serum ferritin and serum iron have been used frequently to identify iron deficiency; however, the results are inconclusive. Aims: To compare soluble transferrin receptor levels (sTfR), sTfR/log ferritin index (SFI), and conventional markers of iron deficiency among drug naive children with ADHD and healthy controls. Methods: We conducted this study in a tertiary care setting with a case-control study design. Thirty-five children with ADHD compared with age-matched 35 controls. Children were assessed on clinical aspects, hematology profile, iron biomarkers, inflammatory markers, sTfR, and SFI. Results: We found significantly reduced mean levels of serum iron and percentage transferrin saturation and an increase in the median levels of Erythrocyte sedimentation rate (ESR) in children with ADHD compared to healthy children. However, in a clinically meaningful categorical analysis, we found that socioeconomic strata, ESR, percentage transferrin saturation, and SFI were significantly different between the groups. Finally, we found that Children with SFI ≥1.5 were approximately four times more likely to be associated with ADHD as compared to the control group. However, the percentage transferrin saturation was not associated with ADHD, after controlling for socioeconomic strata and ESR Conclusions: SFI is a new marker, which is feasible and a better marker than serum ferritin in the identification of latent iron deficiency in children with ADHD. Serum iron and percentage transferrin saturation were also found to indicate an iron deficiency in children with ADHD. These findings must be explored in large community samples.

Cytokine regulation on the synthesis of nitric oxide in vivo by chronically infected human polymorphonuclear leucocytes To determine if nitric oxide (NO) is produced by chronically infected human polymorphonuclear leucocytes (PMNs) in vivo, inflamed exudates (periapical exudates: PE) collected from periapical periodontitis patients were examined. Cellfree supernatants and cells were separated by centrifugation. Significant levels of nitrite concentrations were observed in the supernatants. The production of inducible NO synthase (iNOS) in highly purified PMNs derived from PEs was then immunocytochemically determined using rabbit antihuman iNOS antiserum. In vitro, human peripheral blood PMNs (PBPMNs) isolated from patients were cultured with a combination of Esherichia colilipopolysaccharide (LPS), recombinant human interferon (rhIFN) and/or interleukin1 (rhIL1). The stimulated PBPMNs showed steadystate levels of nitrite. The stimulation of LPS, rhIFN and rhIL1 showed more NO induction than that of LPS with either IFN or IL1, suggesting the synergistic effects of cytokines. Cryostat sections of surgically removed periapical tissues were also immunohistochemically examined for iNOS, IFN and IL1. Twocolour immunohistochemistry revealed the interaction of iNOSproducing PMNs and IFN or IL1producing mononuclear cells. On the basis of these data, we concluded that with the stimulation of inflammatory cytokines derived from mononuclear cells, PMNs can spontaneously produce NO at the site of chronic infection. The present studies are consistent with a hypothesis suggesting that PMNs could be regulated and delicately balanced to produce NO by mononuclear cellderived cytokines in vivo. NOproducing cells may play a pivotal role in chronic inflammation.

Geno Morosi Geno Morosi (July 7, 1920 – September 20, 2016) was, prior to his death, among the last living sets of brothers to serve in the United States Navy and survive the attack on Pearl Harbor aboard the same ship. Geno and Albert Morosi were aboard the USS Maryland (BB-46), moored along Battleship Row, on the morning of December 7, 1941. Geno was watching other sailors play a card game when the Japanese attack began. Geno was initially assigned to a gun that did not have antiaircraft capabilities, so he was ordered to man a different gun on a higher deck. Geno was 21 at the time; Albert (born February 13, 1922) was 19. Geno Morosi received a Purple Heart for hearing loss sustained during the attack on Pearl Harbor. Born in Royalton, Illinois, to immigrants from the Province of Perugia, Umbria, Italy, Geno and Albert also had an older brother, August, who served in the European theater as a member of the United States Army. August died in 2008 in Springfield, Illinois. Geno Morosi served a total of six years, two months, and six days in the U.S. Navy. In addition to his Pearl Harbor service, he piloted landing craft for the USS Alpine (APA-92) at Guam, Leyte Gulf, Lingayen Gulf, and Okinawa. He was honorably discharged on November 15, 1946, as a Boatswain's mate (United States Navy), first class. In addition to the Purple Heart, he received the American Campaign Medal, American Defense Service Medal and One Star, Asiatic-Pacific Campaign Medal and Six Stars, Philippine Liberation Medal and Two Stars, World War II Victory Medal, and Navy Good Conduct Medal. Geno Morosi settled in Detroit, Michigan, after the war. He attended Lawrence Technological University on the G.I. Bill, and had a long career at Carboloy, a division of General Electric. He began at Carboloy with a low-level job as a metal mixer but retired as a unit manager in 1984.

Approaches to teaching in the multi-level language classroom ABSTRACT What approaches are used in the multi-level language class and what influences a teacher's choice of approach? Multi-level language classes, the combining of two or more senior year levels into a single class, is a relatively recent phenomenon and one that is becoming increasingly common in New Zealand secondary schools as a consequence of a decline in student numbers. Drawing on survey and interview data, this article discusses the pedagogical approaches that are used by New Zealand language teachers in responding to this challenge and change to their role. The findings show that three very different approaches are used by teachers: 1) completely separate programmes for each year level, 2) common topics across year levels with differentiated materials, and 3) a future-focussed programme drawing on self-directed technology assisted learning to free up teacher time to work individually with learners. A range of factors appear to influence choice of approach including teacher experience and knowledge of the curriculum, desire for the class to be a group, focus on communication, availability and inclination to use technology, and preparing students for end of year assessments. This study has practical implications for teacher professional development and initial teacher education programmes where mentoring and support for teachers in differentiated practices and resources is needed, particularly for early career teachers. While this study was conducted in a New Zealand secondary school context, it also has implications for broader language learning contexts where increased diversity of student cohorts is becoming increasingly common.

Cell specialization in the small intestinal epithelium of adult Xenopus laevis: functional aspects. The functional activity of the epithelial cells of the intestinal folds of Xenopus was analysed histochemically. There is a gradient of increasing absorptive, digestive and secretory activity from the trough regions to the crests of the longitudinal folds. The differences in functional activity correspond to differences in structural complexity, and confirm the existence of a more specialized population of cells at the fold crests and a less specialized population at the fold troughs, analogous to mammalian villous and crypt cells respectively.

The effect of various long-term tillage systems on soil properties and spring barley yield This study, performed on a soil that is classified as Albic Luvisols that developed on loamy sands overlying loamy material (1.4% organic matter and pH 6.5), concerns the impact of tillage systems on soil properties and the yield of spring barley. The experiment design included 3 tillage systems: conventional tillage, reduced tillage, and no-tillage. Continuous cultivation for 7 consecutive years by reduced tillage and no-tillage led to changes in the physical properties of the surface soil layer (0-5 cm). At the stem elongation growth stage of spring barley, conservation tillage systems resulted in a higher water content and bulk density in relation to conventional tillage. Conservation soil tillage resulted in decreased penetration resistance in the 0-10 cm layer, as compared with conventional tillage. Reduced tillage and no-tillage favored the surface accumulation of organic C and total N in the soil, as well as that of available K and Mg. Our results suggest that conservation tillage systems lead to progressive improvement in soil nutrient status, but have little or no effect on crop yield. Only the no-tillage system had a negative effect on yield of spring barley, by 6.8% in comparison with conventional tillage.

1. Field of the Invention This invention is related to an electrocoating process and particularly to an improved electrocoating process that utilizes a novel electrocoating composition containing a cationic film-forming polymer. 2. Description of the Prior Art Processes for electrocoating anionic carboxylic polymers are known as shown by Gilchrist U.S. Pat. No. 3,230,162, issued Jan. 18, 1966 and Gilchrist U.S. Pat. No. 3,362,899, issued Jan. 9, 1968. Also, processes for electrocoating cationic film-forming polymer are known as shown in Suematsu U.S. Pat. No. 3,755,093, issued Aug. 28, 1973; French Pat. No. 1,477,147, granted Mar. 6, 1967 and French Pat. No. 1,504,895, granted Oct. 30, 1967. But in these processes of electrocoating of anionic carboxylic polymers or cationic polymers, a problem arises in which an excess of neutralization agent accumulates as the polymers are deposited on articles being coated and the excess neutralization must be removed from the process. An ultrafiltration step has been used to remove excess neutralization agent but this step requires additional equipment and adds to the costs of these processes. In other methods used to avoid the above problem, the cathode or the anode of the electrocoating cell used in these processes is flushed with water or a filtrate from the processes to remove excess neutralization agent but these methods also add to the cost and increase the complexity of the processes. Another technique used to avoid the above problem is to add replenishment compositions to these processes which are deficient in neutralization agent but dispersion of these replenishment compositions can be difficult and can cause problems. In the novel process of this invention, the neutralization agent is deposited on the metal article being coated and does not need to be removed from the process and forms a corrosion retardant layer on the metal article being coated. Then a film-forming cationic polymer is electrocoated on the article and forms a coating on the article.

Stakeholder engagement in diabetes self-management: patient preference for peer support and other insights Background Self-management support (SMS) for patients with diabetes can improve adherence to treatment, mitigate disease-related distress, and improve health outcomes. Translating this evidence into real-world practice is needed, as it is not clear which SMS models are acceptable to patients, and feasible and sustainable for primary care practices. Objective To use the Boot Camp Translation (BCT) method to engage patient, practice, community resource and research stakeholders in translation of evidence about SMS and diabetes distress into mutually acceptable care models and to inform patient-centred outcomes research (PCOR). Participants Twenty-seven diabetes care stakeholders, including patients and providers from a local network of federally qualified health centres participated. Methods Stakeholders met in-person and by conference call over the course of 8 months. Subject matter experts provided education on the diabetes SMS evidence. Facilitators engaged the group in discussions about barriers to self-management and opportunities for improving delivery of SMS. Key Results BCT participants identified lack of social support, personal resources, trust, knowledge and confidence as barriers to diabetes self-management. Intervention opportunities emphasized peer support, use of multidisciplinary care teams and centralized systems for sharing information about community and practice resources. BCT informed new services and a PCOR study proposal. Conclusions Patients and family engaged in diabetes care research value peer support, group visits, and multidisciplinary care teams as key features of SMS models. SMS should be tailored to an individual patient's health literacy. BCT can be used to engage multiple stakeholders in translation of evidence into practice and to inform PCOR.

BENDIGO garbage trucks are being used to test the strength of signals transmitted by the free Internet of Things network, which could have future applications for agriculture, parking, meteorology and more. Sensors have been placed on the roof of the truck’s cabs as they travel around Bendigo throughout the week, giving researchers at La Trobe University an understanding of any weaknesses in the network. There are currently four gateways in Bendigo as part of the network, providing free long-range signals for sensors that have long battery life. Data from the garbage trucks will guide where more gateways are needed. La Trobe University IT associate professor Simon Egerton said the Internet of Things would allow devices to connect to the internet over long areas, aiding in data collection for weather, conservation and other uses. “It’s good for places that are remote and are outside Wi-Fi coverage to collect information from the environment,” he said. Related: Public to help council track major weather events through Internet of Things “One use at the moment is the real-time weather sensor network, allowing us to see weather parameters such as temperature, humidity and pressure. “It also aids in city planning. You can see which areas are hotter than the rest.” Still in its early stages in Bendigo, Dr Egerton was eager to hear of other potential uses for the network. He said sensors could be used to help drivers know which parks around town are vacant or occupied. “It could give you real-time information about parking availability, and you could use a mobile app to reserve a park,” Dr Egerton said. “An agricultural use could be with beehives. Apiarists need to travel long distances to inspect their beehives, but you could instead place sensors inside to remotely monitor them.” City of Greater Bendigo regional sustainable development manager Trevor Budge said garbage trucks were a “simple and cost effective” way to test the strength of the network. “To properly map the network would have taken much longer and been very costly if it had not been done using vehicles already travelling these routes,” he said. “The sensors on the trucks have simply been mapping how far and well the network extends, they are not measuring or collecting data on anything else. “The city has no immediate plans to collect more data using these sensors. “However there are other cities that use their garbage trucks to collect data, for example about road surfaces, and this is something we may consider in the future.” La Trobe University is hosting a meet-up in Room 1.30 at 6pm on Wednesday, October 24, for anyone interested in supporting the Internet of Things network. Sensors on top of Bendigo garbage trucks are mapping the strength of the free Internet of Things network, shown right. The signals come from four gateways throughout Bendigo, with red being a strong signal. BENDIGO garbage trucks are being used to test the strength of signals transmitted by the free Internet of Things network, which could have future applications for agriculture, parking, meteorology and more. Sensors have been placed on the roof of the truck’s cabs as they travel around Bendigo throughout the week, giving researchers at La Trobe University an understanding of any weaknesses in the network. There are currently four gateways in Bendigo as part of the network, providing free long-range signals for sensors that have long battery life. Data from the garbage trucks will guide where more gateways are needed. The garbage trucks receive the signal as they drive through the streets of Bendigo. La Trobe University IT associate professor Simon Egerton said the Internet of Things would allow devices to connect to the internet over long areas, aiding in data collection for weather, conservation and other uses. “It’s good for places that are remote and are outside Wi-Fi coverage to collect information from the environment,” he said. “One use at the moment is the real-time weather sensor network, allowing us to see weather parameters such as temperature, humidity and pressure. A sensor attached to the cab of a garbage truck. Still in its early stages in Bendigo, Dr Egerton was eager to hear of other potential uses for the network. He said sensors could be used to help drivers know which parks around town are vacant or occupied. “It could give you real-time information about parking availability, and you could use a mobile app to reserve a park,” Dr Egerton said. City of Greater Bendigo regional sustainable development manager Trevor Budge said garbage trucks were a “simple and cost effective” way to test the strength of the network. “To properly map the network would have taken much longer and been very costly if it had not been done using vehicles already travelling these routes,” he said. “The sensors on the trucks have simply been mapping how far and well the network extends, they are not measuring or collecting data on anything else. “The city has no immediate plans to collect more data using these sensors. La Trobe University is hosting a meet-up in Room 1.30 at 6pm on Wednesday, October 24, for anyone interested in supporting the Internet of Things network. Discuss "Bendigo garbage trucks mapping Internet of Things signal strength"

Interactive Learning-from-Observation through multimodal human demonstration Learning-from-Observation (LfO) is a robot teaching framework for programming operations through few-shots human demonstration. While most previous LfO systems run with visual demonstration, recent research on robot teaching has shown the effectiveness of verbal instruction in making recognition robust and teaching interactive. To the best of our knowledge, however, few solutions have been proposed for LfO that utilizes verbal instruction, namely multimodal LfO. This paper aims to propose a practical pipeline for multimodal LfO. For input, an user temporally stops hand movements to match the granularity of human instructions with the granularity of robot execution. The pipeline recognizes tasks based on step-by-step verbal instructions accompanied by demonstrations. In addition, the recognition is made robust through interactions with the user. We test the pipeline on a real robot and show that the user can successfully teach multiple operations from multimodal demonstrations. The results suggest the utility of the proposed pipeline for multimodal LfO. I. INTRODUCTION Household robots with manipulation capabilities are increasingly being considered as an alternative labor force in various scenes, including nursing homes, restaurants, and home environments. While typical robotic systems assume that the robot will perform specific operations in a fixed environment (e.g., on an assembly line), home systems need to provide the ability to program the robot to fit the user's needs and environment. Learning-from-Observation (LfO) is a framework that aims to teach robot manipulative operations by on-site human demonstrations without coding and thus is one of the promising solutions for home robot control. In LfO, a human demonstration is encoded into an intermediate representation of object manipulation, called as a task model (Fig. 1). The task model consists of a sequence of primitive robot actions, so-called tasks, and parameters to achieve the tasks, so-called skill parameters. Because the task model is an abstract representation of object operations, the encoded task model is theoretically applicable to multiple environments on arbitrary hardware. While several studies have demonstrated that LfO systems successfully work in both industrial and home environments, LfO has been developed based on visual demonstration. For instance, vision-based LfO systems have been developed for part assembly -, knot tying, grasping, and dancing -. On the other hand, studies have shown that human uses verbal instruction to make the teaching more interactive and efficient -. Inspired by the nature of 1 Applied Robotics Research, Microsoft, Redmond, WA 98052, USA naoki.wake@microsoft.com A robot encodes multimodal human demonstration (blue balloon) into an intermediate representation of object manipulation, referred to as task model. Task model composed of a sequence of primitive robot motions, so-called task and parameters to achieve tasks, so-called as skill parameter. This paper proposes a specific pipeline for encoding task models (red box). language, we have developed an LfO system that utilizes both visual and verbal information, namely, multimodal LfO,. However, the motivation for multimodal LfO has been limited to robust visual recognition and information enrichment, and applications that take advantage of interactivity have not yet been proposed. This paper aims to present a practical pipeline of the taskmodel encoder that employ interaction (Fig. 1). To facilitate teaching at the task granularity, we employed one of the simplest teaching styles; stop-and-go demonstration. In stopand-go demonstration, an user pauses the hand motions when tasks switch. At every pauses, the demonstrator gives a verbal instruction for the next task before resuming the hand movements. For a input of stop-and-go demonstration, the system encodes a task model through GUI-based interaction. We show that the proposed pipeline can encode task models that are operated by a real robot.The contributions of this paper are: proposing a pipeline for multimodal LfO proposing a pipeline that has interaction capability, and showing the effectiveness of the LfO system using a real robot with a dexterous robot hand. In what follows, Sec. II explains related studies and Sec. III explains assumptions for the proposed pipeline. Sec. IV explains the implementation. In Sec. V, we show several experiments where a variety of operations are taught to be executed by a real robot. A. Role of language in recognition Many studies have shown that natural language can serve as useful information to guide the visual system. For ex-ample, we have previously shown that the use of verbal input can guide the robot system to determine the timings and the location of grasping and releasing and thus make the LfO robust. In addition, language include semantic constraints in manipulations that are not explicitly taught through visual demonstration. Language can be applied not only to visual system guidance, but also to interactive education. Recent research has proposed interactive systems that utilize human language for remembering user's previous input, operation in a new environment, and clarifying uncertain instructions. However, to our knowledge, no multimodal LfO with user feedback has been proposed. In this study, we propose a system that implements a user-interaction feature to more effectively utilize verbal instructions for task recognition. B. Robot task planning from language Starting with the work of the SHRDLU, the problem of task planning based on language instructions has been studied for decades. Before the development of Natural language processing (NLP) technology, the dominant method of understanding sentences was by parsing verbs and syntax (e.g.,, ). In recent years, the use of NLP technology has become more common, and systems have been proposed to analyze abstract instructions and complex instructions, including conditional branching. For example, the authors in propose a framework that decompose abstract instruction into step-by-step procedures using large language models. While multimodal robot teaching is often employed in end-to-end methods based on large models, -, multimodal teaching has also been studied in symbolic robot teaching systems, Multimodal LfO systems are also classified as symbolic AI systems, and specific implementation methods have recently been proposed. However, the system used a simple knowledge base that maps tasks to verbs in a single sentence, which limits the length of task sequences that can be taught and the flexibility of input texts. Therefore, in this paper, we propose a system for teaching tasks of arbitrary length using less restrictive linguistic sentences by utilizing a step-by-step teaching method and a task recognition model based on NLP. The proposed system addresses this problem by requiring the user to give stepby-step language instructions that are broken down into task granularity. III. TEACHING STRATEGY FOR MULTIMODAL LFO The aim of the task-model encoder is "given a visual and speech demonstration, recognize the sequence of tasks and their temporal correspondence with the visual demonstration." This section defines the inputs and outputs of the encoder and describes the difference between human demonstration and task execution granularity. We propose a teaching method to bridge this difference in granularity. A. Unit of human demonstration In this paper, we define that an input to the multimodal LfO starts with grasping an object followed by several manipulative tasks, and ends with releasing the object. We call this unit a grasp-manipulation-release (GMR) operation. Note that we assume a single object is being manipulated in a GMR operation. GMR operation can sometimes involve both hands (such as carrying a hot pot with both hands). In this paper, we focus on an operation where each one of the hands operates dominantly, while the other hand is not involved or operates as a supportive action, such as holding (e.g., cutting vegetables with a knife in the right hand while holding the vegetables in the left hand). Although it seems that LfO for a single GMR operation limits the application of the system, we believe that many manipulative household tasks can be achieved as a result of multiple GMR operations. For example, cleaning the table after a meal can be broken down into the GMR of a plate for clearing dishes and the GMR of a sponge for wiping the table; LfO can be applied to a wide range of household tasks by being able to learn the units of GMR. B. Unit of robot execution On the other hand, the unit of robot execution, task, can be finer than GMR operations. In a typical LfO, a task is defined as a transition of a target object's state. An example is a contact state between polyhedral objects for part assembly or topology of a string for knot tying. We have previously defined a set of states for manipulative operations based on the types of motion constraints imposed on the object. As the result, a GMR operation is divided when the motion constraints to the object change. For example, a GMR operation of "picking up a cup and carrying it on the same table" is divided into the tasks of picking up the object (PTG11) bringing it (PTG12), and placing it (PTG13) (symbols in parentheses are from ). We also include grasp and release in the task set because these actions are accompanied by a transition in the contact state between the robot hand and the object. Table. I shows examples of GMR operations and their task components. C. Stop-and-go demonstration to resolve differences in granularity Many variations exist in how to give multimodal demonstrations. We designed a teaching methodology that allows users to effectively teach tasks at robot granularity. First, to allow users to teach multiple tasks in a GMR operation at once, we employed a method that implicitly informs the system of the task switching by momentarily stopping the hand (i.e., stop-and-go teaching). For an example of pick-place an object, the demonstrator should stop the hand motion when it approached the object, when the hand grasped the object when the hand lifted the object off the table when the hand carried the object above the table when the object was placed on the table, when the hand released the object, and when the hand moved to a home position Next, we employed a method in which visual demonstration and verbal instruction were taught separately. This is because simultaneous teaching is considered a form of dual tasking that requires a higher cognitive load for the user. Such teaching methods may not be suitable for unskilled users, especially the elderly. Furthermore, to efficiently teach the correspondence between verbal instructions and actions, we adopted a method in which the demonstrator gives a verbal instruction for the next task at the timing of each hand stop, rather than giving verbal instructions all at once before/after visual demonstrations (i.e., step-by-step instructions). IV. IMPLEMENTATIONS OF TASK-MODEL ENCODER This section explains the pipeline that we implemented to recognize tasks from the stop-and-go multimodal demonstration. Fig. 3 shows the overview of the pipeline. The pipeline is composed of two steps. In the first stage, the encoder detects segmenting timings based on the stopping motion and splits the video and speech based on the timings. It transcribes the speech using a third-party speech recognizer. The result of segmentation and speech recognition was previewed so that the user modify the result if necessary. After the confirmation, a task sequence is recognized from the verbal input using an NLP-based recognizer, and skill parameters are extracted for each task to compile a task model A. System input We used Azure Kinect sensor to record RGB-D images and a speech input during the demonstration. The sensor is placed in positions that could capture the entire demonstration. The image resolution is 1280x720, and the nominal sampling rate for the video and speech is 30 Hz and 48000 Hz, respectively. B. Video segmentation and speech recognition For a stop-and-go demonstration, the pipeline splits the video and audio at the times when a manipulating hand stopped. To detect the times, we characterized the intensity of hand motion based on the changes in luminance of images. For the calculation, RGB images are converted into YUV images and the Y channel is extracted as the luminance. The luminance images are spatially filtered using a moving average of 50x50 window, and the pixelwise absolute difference is taken between adjacent frames ( Fig. 4(a)). The mean of the difference is taken as the luminance change at each time. After the removal of outliers and low-pass filtering of 0.5 Hz, the local minimum of the time series is extracted as the stop timings ( Fig. 4(b)). After the confirmation of the split timings (in Sec. IV-C), the RGB-D video and the audio are split based on the detected timings. The split speech is transcribed using a third-party cloud speech recognition service and previewed to the user for additional confirmation. C. Previewing for the user modification Since the speech content and the correspondence between video and audio are critical to task recognition and the extraction of skill parameters, we implement the feature to ask for users' modifications on the computation result of video splitting and speech recognition. After the luminance-based video splitting, the user is prompted for each split video. The user can ignore videos unrelated to the teaching (e.g., movements before and after a GMR operation) and merge over-split videos through a button-based GUI (Fig. 5). Note that we assume that the user can give the demonstration again when the under-segmentation occurred instead of manually segmenting the video through the GUI. After confirming the video segmentation, the video and audio are re-partitioned and the split audios are transcribed using the speech recognition service of Sec. IV-B. The transcribed text is displayed to the user in order so that the user can modify using a GUI (Fig. 5). D. Task recognition After splitting the demonstration, the system recognizes each task based on the transcribed instruction. To this end, we trained a language-based recognition model. We first collected a dataset of textual instructions for videos of a single task. We annotated an existing video dataset of preparing a breakfast. We chose the cooking domain because cooking needs the use of a variety of foods and tools with manipulation. We labeled the video with task labels and prepared the video dataset of a single task using a third-party video annotation tool. The dataset contained 12 task classes with a total of 1340 videos. Table II shows the task classes and the number of data. For those videos, we collect the instruction that explains the motion using a could sourcing service, called Amazon Mechanical Turk. We collected 100 sentences for each task. Finally, a recognition model was trained to associate each instruction and corresponding tasks. This model was a random forest model trained on top of a fixed BERT model. Note that we used egocentric videos for the data collection because the demonstrator is assumed to give demonstrations while teaching, rather than while observing the demonstration from a third-person perspective. Table. III shows the examples of sentences collected by different cloud workers. We observed variation in the verbs and nouns that appear in the instructions. Fig. 6 shows shows the confusion matrix of the task recognition where 10% of the sentences were used for the testing. We conducted ten-fold cross-validation to validate the result. The averaged performance was 83%. This result suggests that the tasks can be robustly recognized from natural verbal instructions with variations. E. Skill parameter extraction Every task requires skill parameters for robots to decode.,. Once a task is determined, processes called daemon run to extract the parameters by analyzing the corresponding video. Here we explain the examples of skill parameters and computation for extracting the parameters. Video of washing a place with a sponge "Wash the plate under the faucet water." "Wipe the dish with the sponge in an anti-clockwise direction." "Clean the plate with the sponge in your hand." "Scrub the plate in the sink." "Wipe the plate with the sponge." Video of pouring a water from a kettle "Pour the water into the cup." "Pour water from the kettle into the mug." "Pour water into the mug." "Pour water from the pitcher into the cup." "Empty the water from the kettle into a cup." 1) The name of the target object: The name of the target object is used to help recognize other skill parameters. We assume that the name is specified in the verbal input, and extract it through a third-party language parser. In the current pipeline, we define a set of object names applicable to the LfO system and prepared an object detector for detecting the objects. 2) Hand laterality: Information on the laterality of hands used for the manipulation is important because the information should be consistent with other skill parameters such as grasp type, and approach direction to the target object. Hand laterality is extracted by analyzing the video of grasping the object, which starts with approaching the hand to the object and ends with grasping it. Assuming that the object location does not change during the grasping task, a daemon extracts the object's 2D location applying the object detector to the first RGB image of the video. Because the last frame corresponds to the timing of grasping the object, a hand detector detects the 2D locations of both hands in the last frame. The laterality of the manipulating hand is then determined as the hand closer to the object. 3) Grasp type: Grasp type is important for not only grasping an object but also for successfully operating a sequence of tasks. The pipeline detect a grasp type that is based on robot grasp theory using a image classifier model. The image of the manipulating hand at the last frame of the grasping video is fed into the model, and a grasp type is determined after correcting the model output with the likelihood of the grasp types tied to the object name,. 4) Hand positions and hand trajectory: How a demonstrator moved the manipulating hand is important because it contains the knowledge of successfully achieving a task without collision with an environment and how to manipulate an articulated object such as a shelf or a door. The 3d hand positions during the teaching are extracted by using the 2D hand detector and the depth images ( Fig. 7(a)). For a rotating hinge task, the hand trajectory is parameterized by applying a circular fitting to the hand positions during the corresponding video ( Fig. 7(b)). 5) Human pose: Human pose during the operation is shown to give a robot system implicit knowledge required to achieve tasks efficiently. Based on the design of task models that we previously proposed, we encode the human arm postured at the beginning and the end of each task video. Briefly, the 3D poses of the demonstrator are estimated using a third-party 3D pose estimator and each of the body parts (upper/lower arms of left and right arms) is encoded into spatially digitized 26-point directions on the unit sphere. 6) 3D Object positions: The 3D object position at the moment of grasping is calculated from the RGB-D image at the start of grasping. Our LfO system assumes that the object position may slightly differ from the one at the demonstration, and re-calculates the object position at the timing of robot execution through an on-site visual input (see Fig.1). Note that positional information including the human hand is represented relative to an AR marker set on the environment first and offset against the position of the target object before the manipulation. That is, the location of the object is the origin of the coordinate in task models. In robot on-site recognition, the estimated object position is set as the origin of the coordinate. V. EXPERIMENTS We tested the proposed task-model encoder based on the performance of multimodal LfO. To this end, we connected the encoder to a task-model decoder we have previously implemented. The decoder generated robot commands from the task model and on-site visual images using a set of policies trained by reinforcement learning,, while imitating the human poses during teaching. Since our LfO system is intended to be generalized to various home environments, the system was qualitatively examined from three aspects: if the system applies to a wide variety of GMR operations by combining tasks, if the system is flexible in modifying a GMR operation according to scenes To check the system applicability, we tested three GMR operations commonly observed in household situations: "pick-carry-place a box-shaped object from one,""open a fridge," and "open a drawer." To test the system flexibility, we considered a case of a pick-carry-place operation that accompanies multiple bring (PTG12) tasks to avoid obstacles. we tested the system with a humanoid robot, Nextage and a dexterous robot hand with four fingers. A. GMR of pick-bring-place an object Fig. 8 shows the overview teaching a "pick, carry, and place a box" operation. This GMR operation consists of grasp, pick (PTG11), bring from one location to another (PTG12), place (PTG13), and release tasks. The taught verbal input and the visual demonstration are shown at the top. The robot completed the operation. Importantly, To test the system flexibility, we tested the same "pickcarry-place a box-shaped object from one," operation when multiple bring (PTG12) tasks are inserted in-between the pick (PTG11) and place (PTG13) tasks. Such a case happens when several way points are required to avoid collision with the environment. Fig. 9 shows that the multiple bring tasks can be taught through the stop-and-go demonstration, suggesting the flexibility of modifying a GMR operation depending on teaching scenarios. B. GMR of throwing a cup and opening a door We tested if the system applies to a variety of GMR operations by teaching additional GMR operations of picking up a cup and throwing it in a dust box ( Fig. 10(a)) and the operation of opening a door ( Fig. 10(b)). The throwing operation consists of grasp, pick (PTG11), bring from one location to another (PTG12), and release tasks. The opening operation consists of grasp, open to a certain range (PTG5), and release tasks. Those operations were completed by the robot, suggesting that the proposed LfO system can operate variable operations by composing the task models. C. Failure cases of task-model recognition During the experiment, we observed several failure cases. One is the case where video splitting was not detected at the timing of task switching due to inefficient pausing during the stop-and-go motion. In addition, we observed several cases when skill-parameter extraction failed due to the incorrect recognition of hands, objects, grasp types, and human poses. Such misrecognition was typically caused by occlusion. For example, an occluded human hand caused the failure of extracting hand position and trajectory. In those cases, the user needed to discard the demonstration and repeat it. VI. DISCUSSION In this paper, we proposed a pipeline for task-model encoder for multimodal LfO system, assuming stop-andgo teaching with step-by-step instruction. This assumption allow the user to teach GMR operations at the granularity of task and to take correspondence between visual and verbal input. Furthermore, the encoder implemented a function to preview the processing result to allow the user to modify it on-the-fly (Fig. 3). Experiments tested the feasibility of the proposed pipeline for multiple types of GMR operations, and the encoded task models were successfully operated by a robot. In addition, we confirmed that these task models are operated by another robot that has different degrees of freedom (results are shown in ). These results suggest the utility of the system. Because the proposed pipeline relies on several recognition modules for extracting task-model encoder, the overall recognition performance depends on the performance of these modules. Although we addressed this issue by implementing the preview function in recognizing task sequences, the instability remains in skill-parameter extraction. Adding another GUI for visualizing and correcting the task models would facilitate the robustness of the pipeline as a future study.

Telomere Lengths in Cloned Transgenic Pigs1 Abstract Studies of cloned cattle and mice have resulted in controversies regarding the restoration of eroded telomere length of donor cells by the nuclear transfer process. Little is known about telomere lengths in pigs from either natural reproduction or nuclear transfer. In this study, we measured the telomere lengths in six major porcine organs from animals of different ages, and found that their lengths remained consistent throughout different tissues during fetal stages, and then shortened, in a tissue- specific manner, after birth. Telomeres of skin samples from six cloned transgenic pigs at 4 mo of age did not differ significantly from those of age-matched controls. Two cloned pigs that died shortly after birth had skin telomere lengths equivalent to those of late-stage fetuses.

Investigators believed Michael Coppola was ordering drugs through the internet and having it delivered to the post office box. Investigators believed Coppola was ordering drugs through the internet and having it delivered to the post office box, according to the Bergen County Prosecutor's Office. About five months later, Gurbir Grewal, then the county prosecutor and now the state attorney general, appointed Deputy Chief Timothy Condon as monitor . April 24, 2019, 6:56 a.m. April 24, 2019, 7:43 a.m.

. The clinical significance of varicoceles depends on their frequency and on the fact that they may produce infertility. The available operative forms of treatment are unsuccessful in about 10% of patinents. In these cases it is desirable to elucidate the very variable drainage pattern by means of transfemoral phlebography with the patient erect. The method was employed in 13 patients and demonstrated continuity of the testicular vein, or of one of its tributaries, in twelve. If the testicular vein appears to be absent, one must consider the possibility of a venous short circuit or drainage of the pampiniform plexus into the external iliac vein. In four patients out of the 13, scrotal phlebography in addition for complete definition was necessary.

May 10, 2018, 5:31 p.m. Indians have surpassed Americans when it comes to the total number of Facebook users. There are over 241 million active Facebook users in India, compared to 240 million users in the United States. This change in ranking came just days after Facebook announced it reached over two billion users. While the ranking between the United States and India is neck-and-neck, the number of active Facebook users is expected to grow as the Internet continues to penetrate rural India, and more Indians adopt smartphone use. This is why now it’s more important than ever to advertise towards India’s Facebook audience. Overwhelmingly, Indians use their smartphones to access the Internet (around 30% more than the global average), and 70% of that time is spent on social media apps like Facebook. When breaking it down to actual hours per day, Indians spend on average three hours online and two-and-a-half hours of this time is spent on social media. Let’s also take into consideration that in 2017, around the world 74% of all Internet traffic was video-based. It’s also true that video advertising has the highest click-through rate of any digital ad formats. So, looking at this, it seems that companies in India should be investing the majority of their ad space to video content on Facebook. It’s also important to consider how and why video content is the most appealing to an Indian audience. Considering this, along with the fact that Indians are on Facebook for the majority of time they’re online, undoubtedly Facebook video advertising is the way to reel in a potential consumer base for E-commerce. E-commerce in India is on the rise, seeing extraordinary growth from year-to-year. By 2026, online retail is expected to grow 1,200% by 2026. This is up from $15 billion in 2016. As of right now, just over 14% of the Indian population shop online. But, this shouldn’t be viewed as disheartening for potential investors. Instead, it should be appreciated for its massive potential. Globally, China is the largest country in terms of E-commerce, but, India is the fastest-growing. This is why so many companies are investing in the the future of E-commerce in India. And there is one sector in the rapidly expanding Indian E-commerce market that is seeing the most growth. While apparel and electronics are currently the largest segments in the Indian E-commerce market, beauty is the fastest growing. By, 2020, beauty is expected to have “very high penetration of over 10 percent,” reads a report by Google and the Boston Consulting Group. Companies are seeing the potential in the online beauty business, and are rapidly investing in this sector. For example, H&B Stores Ltd, just invested $1.3 billion into it’s new beauty E-commerce site, NewU. Since the company’s inception, they’ve been working with social media influencers to bring consumers engaging video content. They create long-format video ads of about 60-seconds, which have proven to be most shareable, to reel in a viewer and then show them the effectiveness of their wide-range of products. Traditional advertising is dying as more and more people spend more time in front of their smartphone screens instead of their televisions. But just television connected everyone to video, the Internet is connecting people to great video content around the world, and that content is shareable through social media. When the majority of that time spent on smartphones is on Facebook, it’s now more important than ever for companies to create content for these platforms. Video ads work best simply because we are living in a visually-rich age. By always putting their ads 100% mobile and social media first, Quantified Commerce has been able to reach a wide consumer base.

Isolated Flying Capacitor Multilevel Converters This paper presents the topology known as the isolated flying capacitor multilevel flyback converter (FCMFC). The topology uses isolated flying capacitors (FC) for high-gain, DC-DC power conversion while maintaining primary-secondary isolation and improving the efficiency and capability of a standard flyback transformer circuit. Three converters have been developed and tested, one flyback as a control, a 3 level FCMFC, and a 4 level FCMFC to prove the gain and efficiency benefits of this new topology. The FCMFC prototypes achieve higher gain and efficiencies relative to a flyback design utilizing the same off-the-shelf transformer. The stress of the input and output switches is reduced because of the fractioning of the output voltage across multiple output stages, allowing future iterations to utilize lower-rated components. The operating parameters are 5V to 40V boosting for a 10W load at 250kHz. Utilizing the same semiconductor components, the flyback converter control prototype achieves 78% efficiency while the proposed FCMFC converters reach 85% and 82% efficiency, even with the added isolated power, gate drive, and bootstrap circuitry. The FCMFCs have a multiplying effect on the gain of the traditional flyback which also increases near the 90% duty cycle flyback threshold. Additional testing was done at light load and at 100kHz, 250kHz, 452kHz, and 500kHz.

Rather than relaxing at home during the holidays after finishing up their exams, roughly 500 college-aged young people are expected to spend Christmas break working for Rep. Ron Paul. As part of the “Christmas Vacation with Ron Paul” program, the Texan’s presidential campaign is deploying troops of young activists to Iowa and New Hampshire where they will be knocking on doors and making phone calls in attempts to rally voters. And he’s asking his nationwide legion of supporters to help pick up the costs of the 76-year-old congressman’s college brigade. “I firmly believe the next generation needs us to fix our problems now, so there will be a great country left to give them,” Paul wrote in an email to his legion of youth supporters. With ‘Youth for Ron Paul‘ chapters stationed at college campuses across the country, Paul is building his army of young people to mobilize voters. Cornell University, the Ivy League school in upstate New York, boasts having over 1,370 members in their chapter. Paul’s campaign estimates the holiday activist surge will cost them $600,000, or roughly “a bargain” of $45 per student. “Although this program is very cost-effective, it still costs money. And that is something our campaign will need much, much more of in the coming weeks,” Paul said. In the most recent Real Clear Politics average of polls in the Iowa Republican presidential caucus, Paul is fourth with 13 percent, behind former Speaker Newt Gingrich (24 percent), former Massachusetts Gov. Mitt Romney and businessman Herman Cain (tied at 15.8 percent). Paul is looking to the youth to bridge that gap. “In this critical election, a well organized youth campaign could be the difference between winning and losing a key early primary or caucus state,” Youth for Ron Paul’s recruitment website reads.

Port Elizabeth - Port Elizabeth police in the Eastern Cape are searching for the mother of a newborn baby who was found dead in a dumping site at Missionvale on Tuesday evening. Police spokesperson, Colonel Priscilla Naidu, said police were alerted after two boys who were playing in the dump in Limpopo Street discovered the baby boy. It was alleged that the child was wrapped in a black bag with his umbilical cord still attached. Naidu said it was suspected that the child was born earlier on Tuesday. Anyone who can assist in tracing the mother of the infant is asked to contact SAPS Algoa Park on 041 401 1061.

United Airlines is offering to reimburse passengers who were on last Sunday's flight when a passenger was violently removed. Dr. David Dao, 69, was dragged off Flight 3411 by authorities in Chicago. United was left reeling by the now-infamous incident, widely seen after passengers shared videotapes. A United spokesperson says that "all customers" on the flight will get compensation for "the cost of their tickets." A United (UAL) email provided to CNN by a passenger on the flight says customers are eligible for vouchers toward future flights if they "release" the airline from lawsuits. The email offered a voucher worth $500. A United spokesperson later told CNN that it did not mean to send passengers emails with the "release" language in them and said no Flight 3411 passenger would have to agree to such terms. Dao's lawyer, Thomas Demetrio, said he plans to sue United and the authorities who manhandled his client. He said that Dao suffered a concussion, two missing teeth, a broken nose and injuries to his sinuses, and will have to undergo reconstructive surgery. Dao was forcibly removed, bloodied and screaming, at Chicago O'Hare International Airport, after refusing to give up his flight to Louisville, Kentucky, to make room for United crew members. The incident was captured by passengers on phone cameras, and caused a public backlash. United said it has apologized to Dao. But CEO Oscar Munoz initially released a tone-deaf statement to its employees about the need to "re-accommodate" passengers and said that Dao has been "disruptive and belligerent." He later said he didn't blame Dao for the "horrific event" and promised not to drag passengers off planes anymore. But it's unlikely that United or any other airline will drop the practice of overbooking its flights, because it's too important to how they operate. Also, most of the people who get bumped do so voluntarily for cash or travel vouchers.

Social Factors, Transaction Costs and Industrial Organization This article demonstrates how social factors affect industrial organization by a comparative case study of South Korea and Taiwan. By applying the social networks analysis to the transaction costs measurement, the author argues that the mutual reinforcement between social network and business network has nourished the development of the industrial organizational structure of the two economies. The characteristics of social networks, on the one hand, determine the costs of information and communication, and, on the other hand, control the costs and benefits of force and fraud. Thus the transaction costs vary in different societies. Since trust and reputation can provide valuable services for each transaction, the behaviour of firms is regulated not only by law and morals, but more effectively by the economic incentives derived from social networks.

Structure and stability of complexes between poly-5-bromouridylic acid and 2,9-dimethyladenine or 2-methyladenosine. The complexes formed between poly-5-bromouridylic acid (poly(BU)) and 2,9-dimethyladenine (m2m9A) or 2-methyladenosine (m2Ado) were investigated. The stoichiometry of the m2m9A-poly(BU) complex was found to be 1:1 as determined by equilibrium dialysis measurements. The CD spectra of the complexes showed the formation of helically ordered structure. This is also confirmed by the sharp melting profiles. A comparison of the CD spectra with that of poly(m2A). poly(BU) complex revealed a close relationship of the helical structures for these three types of complexes. It was observed that the m2m9A was able to form a thermally more stable complex with the poly(BU) than the m2Ado did.

The impact of the COVID-19 pandemic on the importance of urban green spaces to the public Green spaces provide people with countless intangible benefits, particularly important during crises. Restrictions imposed in many countries due to the COVID-19 pandemic forced people to maintain social distance, limit travels, and even refrain from visiting green spaces and stay at home at a certain point. The survey in one of the largest cities in Poland, Krakw, was intended to help understand the impact of the pandemic on the importance of urban green spaces to the public. The study focused on the first three stages of the pandemic in Poland, from March to November 2020. Nine weeks of the survey yielded over 1250 responses. Responses to spatial questions were analysed with GIS tools and geoprocessing algorithms. The number of visitors to green spaces during the pandemic fell to 78.9% of the population, which is down 13.1% compared to before the pandemic. At the same time, the percentage of people refraining from the visits fell with each phase of the crisis. According to the study, residents believed green spaces to be important for their mental and physical health. Over 75% of the participants considered visits to green spaces as having a very big or big impact on stress level reduction. The work provides empirical proof of the importance of green spaces to residents, particularly during a crisis. The results can affect urban spatial policies and management of green spaces and can potentially be applied in other cities. The COVID-19 pandemic: spread and social restrictions The new form of coronavirus (SARS-CoV-2) emerged in December 2019, in the Wuhan province of China, which causes coronavirus disease 2019. It was declared an international public health emergency on 11 March 2020 by the World Health Organisation. Since then, the virus has been spreading globally and caused an increasing number of deaths worldwide (Angiello, 2020;). In many parts of the world, concerns about the COVID-19 pandemic and city quarantine policy have led to a general decline in residents' physical and mental health due to insufficient social interaction (;Kavan, 2021;a;). The problems of the environmental and economic impact of COVID-19 on human activities and the environment call for a further investigation of this topic (Chernysh and Roubik, 2020). In an attempt to curb the COVID-19 pandemic, states have implemented various social restrictions. These measures varied among countries, but the most common ones included border and school closures, encouragement of teleworking, social distancing, and restrictions on mobility, including lockdowns (Karnon, 2020;Wilder-Smith and Freedman, 2020;). To prevent the spread of COVID-19, some types of public spaces, including urban green spaces, have been shut down (). Therefore, social, economic, and health consequences are inevitable (;). On 11 March 2020, the World Health Organisation (WHO) upgraded the status of the COVID-19 situation from epidemic to pandemic. The Polish Minister of Health reacted to this decision by imposing a state of epidemic emergency on 14 March 2020 due to SARS-CoV-2 infections (The Minister of Health, 2020). Then, on 31 March 2020, specific restrictions and regulations were enforced due to the state of epidemic (REGULATION, 2020b). One of the measures was a mobility restriction. It was an unprecedented lockdown that was not imposed even during the First or Second World Wars or in the communist era. The government decided to close down public administration, schools, universities, shops (apart from grocery stores and pharmacies), churches, and state borders. Even the ongoing presidential campaign was brought to a halt, with candidates virtually ceasing promotional activities. As of 1 April 2020, the public was barred from public beaches and green sites (REGULATION, 2020a). The ban involved parks, greens, promenades, embankments, botanic and zoological gardens, or special activity gardens for children and youth. These areas were believed to be social hubs with an increased chance of infection. Since 16 April, mouth and nose covering had been compulsory on the streets. On 20 April, some safety regulations changed. The lifting of the restrictions has been divided into four stages. The first limited restrictions (stage 1) were implemented on 20 April 2020 from which point forests, parks, and green squares could be used for recreation. The fourth stage of restriction loosening from 30 May 2020 annulled the obligation to cover the nose and mouth in open spaces. Additionally, open-space gyms, playgrounds, and small forest infrastructure could be used again (REGULATION, 2020c). Despite strict controls and the reintroduction of the mouth and nose covering in October, green sites were not closed again (REGULATION, 2020d). The authors divided the period of the pandemic in Poland into three phases depending on government actions: phase I (March to May 2020), phase II (June to August 2020), and phase III (September to November 2020). The role of urban green spaces in crises Due to increasing urbanisation, the distribution of human settlements is changing, leading to a rapid decline of vegetation cover in cities and towns (). Urbanisation tends to decrease the proportion of land that is dedicated to public green spaces. As the focal point of the urban natural ecosystem, urban green space is the primary source of the service functions of natural ecosystems for urban residents. Therefore, it has become a key measure of a city's development, quality of life, and sustainable development capabilities (Zhu and Xu, 2021). While the world is still struggling with the pandemic, there has been a lifestyle change in many countries and communities, which may have relatively longer socio-psychological and behavioural implications (). Mental and physical health problems have become one of the significant challenges faced by the global population (). A growing number of studies suggests beneficial health effects of contact with urban green spaces (;van den ;;;;;). Economically disadvantaged communities in neighbourhoods with poor access to green spaces are known to be burdened with health issues more, leading to intergenerational well-being problems (). Researchers have proven that urban green spaces may improve human health and well-being and are meeting spaces for various socioeconomic classes, reducing segregation and multiplying opportunities for the psychological restoration of residents (;;;). Living close to high-quality urban green spaces is associated with positive impacts on health, both physical and mental. Urban research related to previous pandemics is mainly focused on issues such as inequalities that make poor and marginalised groups more vulnerable to pandemics. With many indoor recreational spaces closed due to COVID-19 restrictions, the role of public green spaces in promoting population health is amplified () and redefined. Aim, research questions, and a new universal challenge According to the literature review, new research continues to emerge on the use of urban green spaces, also in the pandemic (;Sharifi and Khavarian-Garmsir, 2020;;Ciupa and Suligowski, 2021). Nevertheless, to the best of the authors' knowledge, the pandemic's impact on the physical and mental needs of residents are rarely tackled. What is more, few researchers conduct surveys among urban residents who are directly affected by the situation. The present paper is our response to the existing research gap to address the issue with a survey study. First, it analyses the social aspect of intangible benefits of visits to urban green spaces. Second, we identify and map urban green spaces that the residents visited the most during mobility restrictions. Therefore, the purpose of the paper is to determine whether visits to green spaces by residents of Krakw help meet their intangible needs (mental and physical) exposed during the COVID-19 pandemic. The objective was to determine the reasons residents of Krakw visited or did not visit green spaces during the pandemic and to identify the most popular places. To this end, the authors posed the following research questions: 1. Has the pandemic affected how people perceive urban green spaces? 2. Has the importance to and for the public of the use of urban green spaces changed for residents of Krakw? 3. Do residents of Krakw believe that visits to urban green spaces during the COVID-19 pandemic affect their mental and physical health? 4. Which urban green spaces were the most visited by residents of Krakw during the pandemic? Note the versatility of the study. The original survey questionnaire can be applied to cities worldwide because the COVID-19 pandemic is a global issue, and green areas are universally important. Hence, the present research can contribute to social and spatial comparative analyses in a broader international context. What is more, opinions of urban communities can help decision-makers and building developers better understand the relevance and universality of urban green spaces for satisfying human needs. They can further inspire rational planning of residential areas. Our results have been verified against the opinions of the largest building developers in Poland regarding changes in residential development planning brought by the pandemic. According to developers, they strive to provide residents with access to recreational areas and common green spaces. For the purpose of the paper, 'urban green spaces' are larger green areas that provide various social and recreational functions (such as parks, playgrounds or greenways) in accordance with national regulations. Methods The present research was conducted in three stages as specified below ( Fig. 1): identification of the research problem and selection of the study area; literature review and legal studies to define the purpose of the research; acquisition of spatial data on green spaces in Krakw; draft of a survey questionnaire; revision of the questionnaire by experts in social sciences, engineering and technology, and natural sciences, including a statistician; a pilot survey; a survey proper and analysis of results; spatial analyses of green spaces in Krakw using QGIS (and responses to survey questions); conclusions. Study area The study area was the city of Krakw, a city in southern Poland (Fig. 2). Krakw is one of Poland's largest cities (327 km 2 ) with a population of 781 thousand and about 150 thousand students. It used to be the capital of Poland and is now the capital of Maopolskie Voivodeship, which affects its growth. Krakw is an interesting place to investigate for several reasons. The first one is that, according to Telega et al., it combines the historical developments of three towns, Krakw's Old Town (established in 1257), Kazimierz (14th century), and Podgrze (18th) century). The other reasons is its situation on the Vistula, which significantly affects its land cover (;Kwartnik-Pruc and Trembecka, 2021). Of importance is its ring-and-wedge layout with a green belt encompassing the Old Town sited in place of demolished town walls and green wedges providing connectivity between its environment and suburban green areas (forests around the city). Urban green spaces are an important part of the Krakw's spatial system (Kwartnik-Pruc and Trembecka, 2021). Parks, green squares, embankments, and other green spaces are important elements of the landscape in Krakw and affect its identity (). The spaces managed by Krakw's Municipal Green Administration covers over 19 km 2, which is 6% of the total city area. Forests are the largest part of the urban green spaces. According to (Kwartnik-Pruc and Trembecka 2021), forests in Polish cities are normal. They complement the green fabric of the city. Street greenery, parks, and green squares also constitute a significant part of the urban green spaces. They are also popular venues for physical activity in the city. Survey design and implementation The authors designed and conducted an online survey to collect data from residents of Krakw who are the users of urban green spaces. It was impossible to carry out a traditional paper-and-pencil (PAP) survey due to the COVID-19 pandemic and restrictions such as official mobility and assembly bans. Moreover, online surveys have become a broadly employed method for quick and precise collection of responses from a relatively large population (Davidov and Depner, 2011). Online surveys are often used in interdisciplinary research on socioeconomic and, generally, cultural growth (;). The popularity of online tools is mostly due to their availability, cost-efficiency, multimedia capabilities, and versatility (). Data collection online can be faster, global, and cheaper (Krol and Hernik, 2020). It is why online surveys gradually replace traditional PAP surveys (Davidov and Depner, 2011). The survey questionnaire for the study was designed in November 2020 and revised by various experts in social sciences, engineering and technology, and natural sciences, including a statistician. The anonymous survey was available for two months, from 4 December 2020-4 February 2021 and took about five minutes to fill in. The questionnaire was divided into two parts with nine single or multiple answer questions. The first part included two questions about demographic data, the age interval and the district of Krakw where the respondent lived. The authors did not ask about sex for two reasons: gender dimension () and promotion of gender equality (responses were treated equally regardless of the sex). The other part of the questionnaire consisted of seven questions about reasons for visiting or not visiting urban green spaces during the COVID-19 pandemic, most often visited green spaces, and how visits to green spaces helped meet respondents' intangible needs (mental and physical) exposed during the COVID-19 pandemic. The survey did not collect any data to identify the respondents, such as telephone numbers, e-mail addresses, or IP numbers of their devices to improve anonymity. The survey was broadly promoted to ensure as large as possible a sample and encourage potential respondents. Information about the survey was disseminated among residents of Krakw on social media (such as Facebook, Instagram, or LinkedIn) and among councillors of district councils. Heads of each of the 18 districts of Krakw and heads of green space committees in each district were sent official letters to this end. They were asked to advocate the survey among residents and share it on district social media profiles and official district websites. The authors addressed a similar request to the Krakw's Municipal Green Administration as the body responsible for managing urban green spaces. Moreover, the authors used their private channels and encouraged residents of Krakw to complete the survey. Data composition and analysis The collected data were intended to provide the maximum amount of useful information with the minimum number of questions to take up to five minutes to complete the questionnaire. The questions involved such matters as: i. Whether the respondent visited urban green spaces before and during the COVID-19 pandemic (to identify preferences); ii. The main reasons for visiting or not visiting green spaces both before and during the pandemic (to understand what people believed to be important or unimportant in this domain); iii. To determine the degree to which visits to green spaces during the COVID-19 pandemic affected selected aspects of well-being (to identify potential preferences); iv. Green spaces most often visited in the COVID-19 pandemic (to determine the most popular green spaces); v. The district of residence (for spatial visualisation of results). The study involved an analysis of survey data. The data from the responses were verified for completeness and preprocessed for analysis (including by linking the district of residence to responses). The data were then analysed. The authors identified green spaces important to the respondents and determined which spaces were most often visited during COVID-19 restrictions. Moreover, the authors assessed the main reasons the respondents visited or did not visit the spaces and to what degree visits to green spaces during the COVID-19 pandemic affected selected aspects of well-being. Spatial analysis and GIS methods The analytical methods for spatial data on urban green spaces and methods for analysing spatial survey results used spatial data and GIS software, namely QGIS (ver. 3.14, GNU-GPL licence). Today, spatial relationships are most often identified using spatial information (Ferreira and Delazari, 2019). Also, GIS and big data technologies have played an important role in many aspects of the fight against COVID-19, as indicated by Zhou et al.. Data processing, analysis, and visualisation for the paper employed geoprocessing algorithms. They included the Cartesian product, spatial data matrix, aggregation, relational links, division of a dataset based on descriptive and geometric attributes, functions for calculating statistical parameters (such as GroupStats), and tools for generating choropleth maps and other methods for result visualisation. Spatial analyses were based solely on vector data models (ESRI Shapefile layers). The data on municipal green spaces provided by the Krakw's Municipal Green Administration and administrative and demographic data published by the Municipal Spatial Information System in Krakw were as in December 2020. Each type of data could be linked to a specific subdivision unit, district, with the topological geoprocessing operator intersect. Mathematical operations were carried out directly in an attribute table with the Field calculator and outside the attribute table with the GroupStats plugin. Data visualisation was based on a graduated data representation symbol and a signature symbol. Raster models on orthophotos improved the appearance of result visualisation. Respondents Respondents provided a total of 1251 responses over nine weeks the survey was conducted online (4 December 2020-4 February 2021). Almost 38% of the respondents were 18-24 years old, over 42% were 25-40, 15.9% were 41-59, 1.6% were 60-65%, and 1.9% were older than 66. The smaller share of respondents older than 60 can be accounted for by their preference for PAP surveys or in-depth interviews (Krol and Hernik, 2020). A pilot survey by (Krl and Hernik 2020) demonstrated that younger people prefer online questionnaires, which they handle with ease, while it is quite the opposite for people above 60. Regrettably, the COVID-19 pandemic made it impossible to conduct a traditional PAP survey. Nevertheless, 44 respondents, or 3.5%, were older than 60. The largest number of respondents lived in northern districts of Krakw, IV Prdnik Biay and V Krowodrza. They amounted to almost 26% of all the respondents. These districts have one of the lowest ratios of urban green space per capita (Fig. 3), mostly due to a small share of green spaces caused by a significant level of development. The smallest number of respondents were from districts X Swoszowice, XV Mistrzejowice, XVI Bieczyce, and XVII Wzgrza Krzesawickie. However, apart from district XV, they have the lowest populations. The share of green spaces per capita in these areas is similar to the level in the districts with the largest number of respondents. The perception of urban green spaces during the pandemic The respondents were asked whether they visited urban green spaces before and during the COVID-19 pandemic to identify their preferences. The vast majority, 92% indicated they visited green spaces before the pandemic. Only 8% indicated they did not visit green spaces before COVID-19. The most common reason was no time (54.5%), use of more attractive recreation (30.7%), or too large a distance to green spaces from the place of residence to reach them on foot (25.7%). During the COVID-19 pandemic, the number of visitors to green Fig. 3. The spatial distribution of the number of respondents and areas of green spaces in Krakw. spaces fell to 78.9%, down 13.1%. The pandemic clearly affected the number of visitors to green spaces, which can be accounted for by lockdowns, and the governmental regulation banning the use of green spaces in the first phase of the pandemic. The respondents were asked why they did not visit (Fig. 4) or what motivated them to visit (Fig. 5) urban green spaces in each phase of the pandemic. It was a multiple answer question. The main reason for residents of Krakw not to visit green spaces in the first phase of the COVID-19 pandemic was the compliance with governmental mobility restrictions (60%) and fear of infection (46.8%). The smallest number of respondents specified sickness (3%) and insufficient equipment in green spaces (5.7%) as their reasons in phase I. The reasons were similar for phase II and II of the pandemic (Fig. 4). The most common responses were compliance with mobility restrictions (36.6% on average), fear of infection (27.8%), and no spare time (37.9%). Interestingly, the share of people refraining from visits to green spaces due to mobility restrictions or fear of infection apparently fell for each consecutive phase of the pandemic. The percentage of people who indicated lack of free time grew (from 34% in phase I to 40% in phase III). The other reasons were indicated roughly the same number of times in each phase. Five main reasons for visiting green spaces in the first phase of the COVID-19 pandemic emerge from among those stated by the respondents (Fig. 5). The respondents most often indicated the urge to take a walk (69.8%), improvement of general well-being (68.9%), easy access (can be reached on foot) (65.7%), need to commune with nature (60.6%), and reduction of stress levels (59.1%). Note that these reasons were the most popular in phases II and III of the pandemic as well. The least indicated main reason to visit green spaces in all phases of the pandemic was the use of outdoor gyms. Interestingly, even pet walking was not one of the main reasons residents of Krakw visited green spaces. The impact of visits to urban green spaces on mental and physical health Another item in the survey was a Likert scale question about how visits to green spaces during the COVID-19 pandemic influenced selected factors. Its objective was to verify the importance of green spaces for mental and physical health of the city residents. The responses are shown in Fig. 6. Over 50% of the respondents indicated visits to green spaces during the pandemic as the most important factor for the improvement of their general well-being (54.2%), contact with nature (51%), and having a walk (50.6%). Only 2.4% of the respondents believed visits to green spaces to be of no consequence for the improvement of their general well-being, which is the lowest result for all the available factors. Over 75% of the participants considered visits to green spaces as having a very big (42.2%) or big (34.5%) impact on stress level reduction. Only 4.3% believed it had no effect on stress. Over 60% of the respondents indicated the need for physical activity, possibility to spend time with family and friends, and reduced gloom as the factors that had a big or very big influence on visits to green spaces during the COVID-19 pandemic. They also indicated factors that had no or very little impact on visits to green spaces during the pandemic. Over 55% of them believed the fear of infection was completely unimportant (35.8%) or had very little impact (20%) in this context. Exercise at an outdoor gym did not matter for 35.5% of the respondents and had a very small importance to 16.5% or them. The green spaces most often visited during the pandemic Finally, the authors checked which green spaces in Krakw were visited by residents of the city in the three phases of the COVID-19 pandemic. The respondents could select multiple locations from a list of 20 green spaces and add other places. This question had over 130 unique answers. The green spaces most frequently visited by residents of Krakw during the pandemic are shown in Fig. 7. The most popular green spaces are situated in the centre of the city. The most often visited green space was the Vistula Promenades (41.9%) followed by the Planty Gardens (35.5%). Note that these locations are adjacent to the most valuable urban sites, the Old Town and Kazimierz. Not far from them, there is the Krakw Bonia Meadow and Jordan Park, which were indicated by 30% of the respondents as places where they maintained contact with nature during the pandemic. The most popular locations outside the city core were the Polish Airmen Park (26.1%) and the Zalew Nowohucki Park (21.9%). These areas are the main points specified by the respondents as the most popular urban green spaces in eastern Krakw. The most popular site in western Krakw was the Wolski Forest with Pisudski Mound (23.2%). The most frequently visited green spaces are situated near developments (Fig. 7). One can conclude that the proximity of green spaces to the place of residence significantly affects the frequency and popularity of the location. On the other hand, the prevailing occurrence of parks located in the city centre among the responses indicates that the residents were prepared to cover larger distances to commune with nature in more appealing surroundings. This insight is supported by the fact that the most visited green spaces (the Vistula Promenades and the Planty Gardens) attracted users from virtually the entire area of Krakw. Fig. 4. The main reasons given by the respondents for the avoidance of green spaces in different phases of the COVID-19 pandemic. Discussion The COVID-19 pandemic emerged as an extraordinary global crisis, significantly altering how people live (Allam and Jones, 2020), changing how we can travel (), and barring people from public green spaces for a long period, both globally and in Poland. The number of visitors to green spaces in Krakw fell by 13.1% during the pandemic compared to before the pandemic due to mobility restrictions. The result diverts from other researchers' findings, such as in Oslo, Norway () or Burlington, Vermont, USA (). This fact could be accounted for with the decision of the Polish government in April 2020 to close down public green spaces. It is further confirmed by the reasons given by those respondents who claimed not to have visited green spaces in the three phases of the pandemic, mainly to comply with governmental mobility restrictions (60%) and fear of infection (46.8%). International research shows that contact and interaction with nature positively influence human health and well-being (Navarrete-Hernandez and Laffan, 2019;Kim and Miller, 2019). The lockdown caused by the COVID-19 pandemic stimulated interest in urban and home greenery. In Prez-Urrestarazu et al., 89.5% of the respondents strongly believed it was necessary to visit open green spaces to improve mental health, while keeping plants was correlated with positive emotions during the pandemic. Moreover, most of the respondents believed that indoor plants positively affected their emotional well-being during isolation (). These findings are consistent with our results where over 75% of the respondents believed visits to green spaces during the COVID-19 pandemic to have a very big or big influence on the reduction of their stress levels; for 54.2%, it had the greatest impact on the improvement of their general well-being. Similar conclusions were offered in an analysis of Twitter content (). It confirmed the mental benefits of contact with nature in urban areas. Schwartz et al. demonstrated that people who repeatedly visited urban green spaces experienced less negative emotions and had better emotional frames of mind expressed on Twitter. The disruption of the usual forms of activities and recreation due to limited or prevented access to green spaces harmed the well-being of their users. Hence, access to urban green spaces can help improve mental health during periods of exacerbated depression (). This conclusion is reflected in recommendations other researchers offered to their governments (). Note that according to the present study, the mental benefits seemed to be related not only to the sheer fact of visiting green spaces but also other factors, such as the ability to take a walk, close access to green spaces, the urge to commune with nature, or the possibility to meet friends and family. These results are in line with those by Wang et al., Prez-Urrestarazu et al., or Du et al. (2021, among others. The green spaces most popular with residents of Krakw during the pandemic are located mainly in the heavily urbanised centre of the city. The centre has a green belt of the Planty Gardens encircling the main square as a tremendously popular walking and relaxation place. The characteristic green belt surrounding highly urbanised areas is a reduction ring typical of compact cities (). The main purpose of green belts is to provide space for recreation to improve the quality of urban life. Green belts have been parts of cities all over the world for years (Pieck, 2019;). An interesting conclusion by Xie et al. (2020b) should be mentioned here that there is apparently no proof of the popular belief that strict implementation of green belts as urban development tools can prevent urban sprawl. River parks, including the Vistula Promenades situated on the Vistula as it flows through Krakw, were very popular as well. They are adjacent to the most valuable urban sites in the city, the Old Town and Kazimierz. Importantly, the Vistula Promenades offer a great view of the Wawel Royal Castle, the most important heritage site in Poland, right in the city's centre. The popularity of these sites among the respondents during the pandemic comes as no surprise. A simultaneous contact with nature and historical, cultural heritage promotes the sense of identity () and offers a high-level aesthetic experience after a long quarantine period (). Prez-Urrestarazu et al. believe that a higher frequency of visits and shorter distance to green spaces from home have positive psychological effects and build place attachment. One could propose that proximity to green spaces from home influences the frequency of visits and popularity of a place, but it was not a primary factor in Krakw. Amerio et al. pointed out various characteristics of the environment affecting mental health. Improved natural environment and attractive surroundings may alleviate the impact significantly (Kazak, 2018;Halecki and Stachura, 2021). According to the present research, residents of Krakw are willing to travel substantial distances to commune with nature in an attractive place. According to Mell and Whitten, COVID-19 changed how many people perceived and interacted with the natural environment. Green spaces started being recognised as areas beneficial for the mental and physical health of residents. They were dubbed the 'essential infrastructure' for well-being. In the present study, 59.1% of the respondents believed visits to green spaces to reduce their stress levels, with 70% claiming it improved their general well-being. According to Gola et al., the current COVID-19 pandemic has been causing significant upheavals in residents' daily lives and, consequently, their mood (stress, distraction, anxiety, etc). Life in the time of the COVID-19 pandemic shows that green spaces have non-tangible functions as well. The restoration of the (temporary) public life under the threat of COVID-19 entailed the emergence of what is often referred to as the 'new norm'. People lived by the slogan 'Stay at home. Save lives' (Goggin and Ellis, 2020). Pineda and Corburn pointed out that the global pandemic had to be viewed by global urban health advocates much like the urban epidemics of the nineteenth century, where reforms had helped improve population health. A vision for (re)building our cities to be more inclusive and healthier for all should be offered. The authors believe that urban and green planning has to change after the pandemic. The notion of city resilience has to be reinforced so that cities are more resistant to volatile, often harmful, factors (). Whereas urban green spaces should first of all support mental and physical public health. Conclusions The paper presents the results of a survey to demonstrate the value of urban green spaces for the local well-being during the global crisis caused by COVID-19. Urban green spaces play the key role during the pandemic by providing ecosystem services relevant to health, recreation, and temporarily limited public life. The present results confirm observations concerning green spaces during the crisis. Urban green spaces provide an important buffer to ameliorate the effects of crises in the mental (positive impact on well-being, reduced stress levels) and physical dimension (such as reduced temperature in cities). The conclusions are consistent with the literature review, numerous case studies, and the present analysis. Hence the answers to the first two research questions are affirmative. As is the answer to the third question. The results evidently indicate that the respondents believed that visits to urban green spaces during the COVID-19 pandemic had a significant impact on their mental and physical health and improvement of their well-being. Regarding the fourth research question, the most often visited green spaces were located near the Vistula, main square, and former Jewish district, Kazimierz or near the Wawel Royal Castle. The respondents were willing to travel long distances to spend time in attractive surroundings of green infrastructure. As the pandemic changed the public perception and importance of urban green spaces in Krakw, they need to be protected and even developed further. It helps improve human well-being and mental state. To sum up, the research on the influence of the COVID-19 pandemic on the importance of urban green spaces in Krakw yielded numerous insights that can be employed when new urban green policies are drafted, whether in Poland or internationally. Funding The paper was created as a result of a scientific action 'Monitoring and evaluation of land cover changes with remote sensing methods' financed by the National Science Centre, Poland, as part of Miniatura 3, application No. 2019/03/X/ST10/01728. Declaration of Interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Reversible photoswitching of dye-doped core-shell nanoparticles. We present a simple and versatile mechanism for the reversible photoswitching of dye-doped core-shell nanoparticles. Photochromic dithienylethenes are incorporated into the outer shell, close enough to the dyes entrapped in the core to efficiently quench them by energy transfer when photoconverted with UV light. The emission can be switched back on by irradiation with > 450 nm.

Constructions of sexuality and HIV risk among young people in Venda, South Africa: implications for HIV prevention The study explored constructions of sexuality among young people of Venda in Limpopo, South Africa, and cultural practices that can be used to develop context-specific HIV prevention programmes. HIV prevention can be promoted by including some cultural practices in prevention programmes and changing some aspects of culture that may contribute negatively to health. Six focus group discussions were held with school-going young people (Grades 10 to 12) in urban and rural areas to explore their constructions of sexuality and HIV risk. Four focus group discussions were held with community leaders in the same areas to explore their constructions of young peoples sexuality and cultural practices relevant to HIV prevention. Through discourse analysis, the following dominant discourses that influence young peoples sexual risk behaviour were identified: rite of passage, the male sexual drive discourse (sex is natural and unavoidable); discourse of hegemonic masculinity (sex to prove masculinity); sex as a commodity; non-adherence to cultural practices; and HIV is normalised (AIDS is like flu). Some alternative constructions and shifts in gender norms were noticed, especially among female participants. The constructions of young people were not culture-specific but similar to those identified in other South African cultures. Community leaders identified a few cultural practices that could be considered in HIV prevention, for example, reinstating the rite of passage to provide age-appropriate sex and HIV education (behavioural intervention), and promoting traditional male circumcision (biological intervention). Cultural practices that contribute negatively to health should be challenged such as current constructions of gender roles (masculinity and femininity) and the practice that parents do not talk to young people about sex (both structural interventions).

Racial Disparities in Stroke Recovery Persistence in the Post-Acute Stroke Recovery Phase: Evidence from the Health and Retirement Study. Background and Purpose Blacks have a higher burden of post-stroke disability. Factors associated with racial differences in long-term post-stroke disability are not well-understood. Our aim was to assess the long-term racial differences in risk factors associated with stroke recovery. Methods We examined Health and Retirement Study (HRS) longitudinal interview data collected from adults living with stroke who were aged >50 years during 2000-2014. Analysis of 1,002 first-time, non-Hispanic, Black or White stroke survivors with data on activities of daily living (ADL), fine motor skills (FMS) and gross motor skills (GMS) was conducted. Ordinal regression analysis was used to assess the impact of sex, race, household residents, household income, comorbidities, and the time since having a stroke on functional outcomes. Results Black stroke survivors were younger compared with Whites (69 ± 10.4 vs 75 ± 11.9). The majority (~65%) of Black stroke survivors were female compared with about 54% White female stroke survivors (P=.007). Black stroke survivors had more household residents (P<.001) and comorbidities (P<.001). Aging, being female, being Black and a longer time since stroke were associated with a higher odds of having increased difficulty in ADL, FMS and/or GMS. Comorbidities were associated with increased difficulty with GMS. Black race increased the impact of comorbidities on ADL and FMS in comparison with Whites. Conclusion Our data suggest that the effects of aging, sex and unique factors associated with race should be taken into consideration for future studies of post-stroke recovery and therapy.

This invention relates in general to planting containers and in particular to a planting container for planting seeds or seedlings by a machine or by aerial drop. Present methods of planting seeds or seedlings involve clearing the land of stubble and growth and plowing the soil into furrows to receive the seeds or seedlings which are planted mechanically by modified agricultural equipment or manually by grub hoes, spades or dibbles. Planting by these conventional methods may be made difficult by the nature of the terrain which may render the planting site inaccessible or difficult to traverse or cultivate. Several types of containers and methods of planting have been devised for seeding remote or inaccessible areas, for example as in reforesting operations. Exemplary teachings of this kind are disclosed in U.S. Pat. No. 2,592,052 issued to J. C. McKenna, Jr., Apr. 8, 1952 and U.S. Pat. No. 3,651,772 issued to R. V. Garabedian, Mar. 28, 1972 wherein a seed or the roots of a seedling are frozen into a cube or a conically shaped block respectively. The cube or block may be planted manually, mechanically or by air drop. However, the freezing operation disclosed in these references may damage or even kill the seed or the seedling. U.S. Pat. No. 3,273,284 issued to G. N. Anagnostou, Sept. 20, 1966 and U.S. Pat. No. 3,755,926 issued to J. Walters et al, Sept. 4, 1973 disclose planting containers for the seeding of remote or inaccessible terrain by air drop. While both the references disclose containers possessing sufficient structural strength to protect the seed and seedling and to achieve sufficient penetration of the soil, the relatively heavy mass of the container disclosed by Anagnostou and the use of a nonbiodegradable material for the container, such as plastic as taught by Walters et al, may inhibit the growth of the emplanted root structure. Additionally, the amount of water supplied by the Anagnostou container is relatively limited due to the size limitations of the water pocket formed therein. Furthermore, the container disclosed by Walters et al has no provision for a self contained water supply at all, but rather must depend upon an external source of moisture for watering the seedling. The foregoing illustrates limitations of the known prior art. In view thereof, it would be advantageous to provide an alternative to the prior art.

A hard limit on how long inmates can be in solitary confinement could be dangerous, the federal government argues in asking the Supreme Court of Canada to set aside the 15-day cap Ontario’s top court recently imposed on administrative segregation. The government also wants last month’s ruling by the Ontario Court of Appeal — slated to take effect Friday — to be put on hold pending the proposed challenge. In this week’s notice of application for leave to appeal, the government maintains the lower court did not appear to take into account the potential danger of imposing a hard cap on administrative segregation. Late last month, Ontario’s Appeal Court struck down parts of the Corrections and Conditional Release Act, which allows authorities to keep inmates in solitary confinement when they are deemed to pose a risk to themselves or others and there is no reasonable alternative. The court found segregation longer than 15 consecutive days violates the charter because it amounts to cruel and unusual punishment. It gave Ottawa until April 12 to change the practice. While the government argues that’s not enough time, it remains unclear whether it will comply by Friday given that its stay request to the Supreme Court won’t be heard by then. Ottawa did not immediately respond to a request to discuss the situation. Critics of isolation say studies indicate that depriving inmates of meaningful human contact for much of their day can cause long-term, even permanent, psychological damage. The Canadian Civil Liberties Association, which mounted the constitutional challenge to the legislation, said the government is trying to continue the practice with its request to appeal. In its request to the Supreme Court, Ottawa says the time limit is inappropriate, in part because it interferes with other regulations aimed at keeping prisons and those in them safe. The Appeal Court judgment could also lead to inconsistency among provinces, the government says. The notice points to an ongoing segregation challenge in British Columbia, raising the possibility of “another inconsistent or contrary” judgment. “This will lead to further confusion as to the state of the law,” the government says. The leave application calls on the Supreme Court to decide whether it’s enough to strike down a law based on the possibility that it goes too far, and whether courts have to consider the reason and purpose of the law. It’s also important to decide whether the Ontario Court of Appeal was wrong to put its ruling on hold for only 15 days “without considering the risk to safety and security of federal correctional institutions,” the government says. In December 2017, Superior Court Justice Frank Marrocco ruled that the solitary confinement legislation was unconstitutional because the system lacked proper safeguards. Marrocco put his ruling on hold for one year — later extended to April 30 — to give Parliament a chance to fix the problem. Ottawa, which did not appeal Marrocco’s ruling, also wants that decision put on hold until the end of November to allow for legislative changes.

Therapeutic Exercise Platform for Type-2 Diabetic Mellitus Exercise enables continuous glycemic control for diabetic patients, and it is effective in preventing diabetic complications and maintaining emotional stability. However, it is difficult for diabetic patients to know the appropriate intensity and duration of exercise. Excessive exercise causes sudden hypoglycemia, and patients avoid therapeutic exercise or perform it conservatively owing to the repeated hypoglycemia symptoms. In this paper, we propose a new therapeutic exercise platform that supports type 2 diabetes patients to exercise regularly according to the exercise prescription received from the hospital. The proposed platform includes the following three significant contributions. First, we develop a hardware platform that automatically tracks and records all aerobic exercise performed by a patient indoors or outdoors using a wearable band and aerobic exercise equipment. Second, we devise a patient-specific exercise stress test to know whether the patient is exercising according to his or her usual exercise regimen. Finally, we develop a mobile application that informs patients in real-time whether they are exercising appropriately for their exercise regimen each time they exercise. For platform evaluation and future improvement, we received satisfaction ratings and functional improvements through a questionnaire survey on 10 type 2 diabetes patients and 10 persons without a diabetes diagnosis who had used the proposed platform for more than 3 months. Most users were satisfied with automatic exercise recording, and exercise time increased. Diabetics reported that their fasting blood glucose was dropped, and they were more motivated to exercise. These results prove that exercise must be combined with medication for blood glucose management in chronic diabetic patients. The proposed platform can be helpful for patients to continue their daily exercise according to their exercise prescription. Introduction Type 1 diabetes is caused by a lack of insulin, which controls blood glucose levels in the body due to inherited genetic traits, lifestyle, and aging. Type 2 diabetes is caused by a combination of resistance to insulin action and an inadequate compensatory insulin secretory response. The number of type 2 diabetic patients is increasing rapidly because of the increasing elderly population and lifestyle changes. Complications are more dangerous than diabetes itself, such as kidney disease, retinopathy, and neurological disorders. Diabetic patients commonly experience emotional stress when blood glucose management is neglected, such as anxiety, depression, and regret. Mental stress and physical pain make the patient's quality of life worse when diabetes develops into a chronic disease. It is essential to develop a convenient and accurate blood glucose management program that helps diabetic patients to manage their blood glucose levels by themselves. The purpose of diabetes treatment is to keep blood glucose levels within the normal range, that is, diabetes self-management. The key is balancing between lifestyle habits that affect blood glucose. The patient should exercise regularly, control diet to maintain adequate calories, and take diabetes medications. Blood glucose monitoring can help the patient understand the link between blood glucose, food, exercise, and medication. Furthermore, the patients should try to improve their poor lifestyle continuously. Most diabetic patients take their diabetes medications on time. The patients who manage blood glucose well should record blood glucose readings before and after meals and the amount of food consumed. It will help balance food intake and blood glucose levels. In addition, exercise is another lifestyle that significantly affects blood glucose levels. However, it is hard to record precisely the exercise performed by the patient and to calculate the patient's appropriate amount of exercise. Although there have been many studies on the relationship between exercise and blood glucose levels for decades, the number of mobile applications that patients can use for blood glucose management are few or limited. A therapeutic exercise significantly affects the patient's emotional stability, reducing the risk of cardiovascular disease which is related to complications. However, it is difficult for diabetic patients to know the appropriate intensity and duration of exercise due to fear of hypoglycemia caused by excessive exercise and different physical conditions for each individual. Therefore, most diabetic patients are less aware of the importance of therapeutic exercise. Most previous studies about therapeutic exercise have attempted to analyze the effect of exercise on blood glucose levels. They attempted to determine the appropriate intensity, duration, frequency of exercise for blood glucose management in diabetics. Several studies considered exercise therapy for diabetic patients, focusing mainly on aerobic exercise using a treadmill, ergometer, or stepper; or exercising without a device, such as walking or running. A study using an ergometer showed a comparison of the reduction in blood glucose levels after exercise in healthy people and diabetics. According to this study, both diabetic patients and persons without a diabetes diagnosis have lower blood glucose levels after exercise than pre-exercise blood glucose levels. However, after 60 minutes of exercise in persons without a diabetes diagnosis, blood glucose levels were not significantly different from before exercise. In contrast, after 60 minutes of exercise in diabetic patients, blood glucose levels were up to 80% before exercise. This fact indicates that exercise helps people with diabetes manage their blood glucose levels. A study on blood glucose response concerning exercise intensity for type 1 diabetes patients showed that high-intensity exercise made patients more sensitive to exercise intensity immediately after exercise. It also presented that moderate-intensity and intermittent high-intensity exercise program reduces blood glucose levels more effectively than continuous moderate-intensity exercise. Resistance exercise using a band or similar device has also been effective, particularly for type 2 diabetic patients who have difficulty with aerobic exercise. Although most patients agreed that they should perform regular exercise individually at home, research on developing a continuous healthcare system supporting this is insufficient. This paper proposes a therapeutic exercise platform to help diabetic patients exercise with appropriate exercise intensity when walking or running outdoors or using aerobic exercise equipment indoors. Patients diagnosed with diabetes receive an appropriate exercise prescription in the hospital. As time passes after receiving an exercise plan, the patient's condition changes. It is difficult for the patient to know the appropriate exercise intensity. The proposed platform provides an exercise program to achieve prescribed exercise goals. It automatically obtains heart rate and exercise information during exercise session and supports a real-time monitoring mode to ensure that the patient is exercising correctly. In addition, a patient's health and fitness will change over time. The proposed platform also provides an exercise stress test mode to adjust the exercise intensity according to the current patient's condition. Figure 1 shows the exercise sequence of the proposed platform. The patient visits a hospital and receives an exercise prescription after an exercise stress test. It includes the type of exercise, specific workloads, duration, and frequency of exercise sessions for their blood glucose management. Electronics 2021, 10, 1820 3 of 22 The proposed platform sets the patient's exercise program according to the exercise prescription. Then, it provides the program during the exercise session. The patient exercises during the exercise session according to the exercise program. The proposed platform automatically obtains heart rate and exercise information and provides them in real-time to check their exercise. At the end of the exercise session, the proposed platform evaluates whether the patient exercised according to the exercise prescription. If the difference is significant, the platform fine-tunes the exercise program to maintain the original exercise prescription with additional exercise stress testing. The patient visits a hospital and receives an exercise prescription after an exer stress test. It includes the type of exercise, specific workloads, duration, and frequenc exercise sessions for their blood glucose management. The proposed platform sets the patient's exercise program according to the e cise prescription. Then, it provides the program during the exercise session. The patient exercises during the exercise session according to the exercise p gram. The proposed platform automatically obtains heart rate and exercise informa and provides them in real-time to check their exercise. At the end of the exercise session, the proposed platform evaluates whether patient exercised according to the exercise prescription. If the difference is significant, platform fine-tunes the exercise program to maintain the original exercise prescrip with additional exercise stress testing. As a result, the proposed platform helps the patient exercise while maintaining initial goal by adjusting the exercise program, even if the patient's condition or exer sensitivity changes from when receiving an exercise prescription. This paper presents hardware configuration, the exercise stress test for adjustment of the exercise progr and the user application of the proposed platform. To develop this platform, we built a hardware system that monitors patient mo ment indoors and outdoors. The proposed platform analyzes the patient's exercise adjusts the exercise intensity according to the result to provide the patient with an exer session. A total of 10 diabetic patients and 10 persons without a diabetes diagnosis u the proposed platform for 3 months, and we analyzed the effectiveness of the propo platform through their survey. Therapeutic Exercise and Blood Glucose Management Most self-managed programs for diabetes support balancing between physical e cise, insulin dosage or medication, blood glucose monitoring, and diet. Each patient different physical strength, and the effect of exercise on blood glucose levels is also dif ent. Therefore, most patients consider exercise as a supplemental glycemic con method. It is essential to study the effect of exercise on blood glucose levels to use exer as an effective glycemic control method. In particular, it is crucial to develop a therape exercise program that can recommend an exercise suitable for glycemic control to patie according to their preferred exercise pattern and individual exercise ability. For decades, many kinds of research have been conducted to use therapeutic exer for blood glucose management. The aim of therapeutic exercise for diabetic As a result, the proposed platform helps the patient exercise while maintaining the initial goal by adjusting the exercise program, even if the patient's condition or exercise sensitivity changes from when receiving an exercise prescription. This paper presents the hardware configuration, the exercise stress test for adjustment of the exercise program, and the user application of the proposed platform. To develop this platform, we built a hardware system that monitors patient movement indoors and outdoors. The proposed platform analyzes the patient's exercise and adjusts the exercise intensity according to the result to provide the patient with an exercise session. A total of 10 diabetic patients and 10 persons without a diabetes diagnosis used the proposed platform for 3 months, and we analyzed the effectiveness of the proposed platform through their survey. Therapeutic Exercise and Blood Glucose Management Most self-managed programs for diabetes support balancing between physical exercise, insulin dosage or medication, blood glucose monitoring, and diet. Each patient has different physical strength, and the effect of exercise on blood glucose levels is also different. Therefore, most patients consider exercise as a supplemental glycemic control method. It is essential to study the effect of exercise on blood glucose levels to use exercise as an effective glycemic control method. In particular, it is crucial to develop a therapeutic exercise program that can recommend an exercise suitable for glycemic control to patients according to their preferred exercise pattern and individual exercise ability. For decades, many kinds of research have been conducted to use therapeutic exercise for blood glucose management. The aim of therapeutic exercise for diabetic patients is to increase insulin sensitivity. It is to mitigate or ideally to prevent diabetes complications. Insulin secretion decreases as the prevalence period of diabetes increases and fasting plasma glucose increases. Pan et al. presented that long-term regular exercise can improve lipid metabolism by reducing blood glucose levels and increasing insulin sensitivity to muscles, thereby improving various risk factors such as arteriosclerosis. Oshida Additionally, they concluded that aerobic exercise, including resistance one, can improve insulin resistance and quality of life. Table 1 summarizes recent findings regarding how long-term regular aerobic and resistance exercises help manage patients' blood glucose levels. Diabetic patients should perform exercise stress tests and receive exercise prescriptions before starting exercise. Resistance exercise is a fundamental factor in exercise prescription constituted by exercise modality. In this paper, only aerobic exercise is focused as the main exercise factor. The three essential factors in exercise prescription are the intensity, duration, and frequency of exercise. These are all quantitative conditions, and highlighting one condition can increase the effectiveness of exercise. In particular, the most important thing is the exercise intensity. Many studies have been conducted to determine the appropriate exercise intensity. In general, exercise intensity should be based on the anaerobic threshold measured by cardiopulmonary exercise testing (CPX). The test is both expensive and time-consuming, and most exercise facilities do not have a respiratory gas analyzer. Instead of CPX, it is possible to set the desired training intensity, expressed as a % of maximum heart rate, HR max, with the Karvonen formula. First, target heart rate (THR) is obtained from Karvonen's formula. The maximum heart rate is roughly estimated using Equation. The heart rate reserve (HRR) is obtained from subtracting resting heart rate, HR rest, from HR max as Equation. Target heart rate is calculated from predicted heart rate reserve, exercise intensity, and resting heart rate using Equation. HR max = 220 -age where Exercise intensity is the constant number of exercise intensity and is the coefficient determined by a value ranging from 0.3 to 0.8 based on the desired exercise intensity. HR max describes the highest heart rate achieved by a subject exercising to exhaustion and is verified by a plateau of heart rate. In the literature, HR max refers to the peak heart rate at the termination of a graded maximal exercise test. HR max predicted by age alone may be practically convenient for the various groups. However, the magnitude and possible modifying effect are not fully established. Nes et al. presented that HR max was linearly and inversely related to age explained by the formula; 211 − (0.64 age). Gellish et al. suggested 206.9 -(0.67 age), which has become the de-facto standard approach to determine maximum heart rate. The simplest method is the Bogs scale method, which scores the feeling of difficulty during exercise: 13 = a little hard, 15 = hard, etc. However, the myocardial burden, i.e., the burden on the heart depending on aerobic exercise type, cannot be the same for all patients, even if the exercise prescription sets the correct exercise intensity based on heart rate or maximum oxygen intake or user awareness. Exercise intensity for diabetic patients is evaluated by the amount of oxygen intake or heart rate during an exercise stress test. The American Diabetes Association recommends that appropriate exercise intensity for diabetic patients is 50-70% of HR max, whereas the Japanese Medical Association recommends 40-60% of HR max as optimal exercise intensity for type 2 diabetics. Appropriate exercise intensity in Korean diabetic patients was determined after deriving patient HR max or maximum oxygen intake through an exercise stress test. Regression analysis using data from 581 diabetic patients determined by Equation. MET (metabolic equivalents) and RPE (ratings of perceived exertion) must be considered for each exercise device to include individual deviations. Exercise duration and frequency must also be considered, and exercise type and duration should be tailored to individual patient circumstances. The exercise test is mainly performed on aerobic exercise equipment, such as ergometers and treadmills. Treadmills provide exercise load with walking slope and speed, while ergometers provide exercise load with pedal resistance and speed. Vital signs, such as blood pressure and heart rate, are measured during the exercise stress test. Blood glucose levels are also monitored before and after exercise to analyze the relationship between exercise load and blood glucose levels. Several studies have shown that blood glucose levels decrease during high or mediumintensity exercise [13,. The intermittent high-intensity exercise produced more significant blood glucose level reduction than continuous moderate-intensity exercise. Blood glucose reduction due to exercise was proportional to exercise intensity and time. Thus, moderate and intermittent high-intensity exercise for 45 minutes or more is beneficial for blood glucose than high-intensity exercise for a short period. In general, when diabetes is diagnosed, the appropriate amount of exercise considering the patient's physical strength is determined through CPX. However, if the patient repeats the same intensity for a long time, the patient's exercise ability should be improved. In practice, a method other than CPX is needed to predict AT (anaerobic threshold) and determine exercise intensity. The best way is to develop an exercise platform that allows patients to determine the exercise intensity using their aerobic exercise equipment easily. While the patient is exercising like always, the exercise information and the heart rate are obtained automatically. After the exercise intensity is determined using the obtained information, the result is notified to the patient. Because the patient can test easily, exercise tests can be performed whenever they feel that their exercise ability has changed. Consequently, it can help the patient quickly know the appropriate exercise intensity. Proposed Therapeutic Exercise Platform This study proposes a system that supports diabetic patients to manage their blood glucose levels using the proposed therapeutic exercise platform, as shown in Figure 2. The proposed system has three main functions. proposed system has three main functions. 1. Automatically obtain exercise information whenever patients exercise outdoors or indoors. 2. Analyze the change of exercise ability due to the long-term exercise regime, i.e., a simple exercise stress test that allows the user to test their athletic ability. 3. Provide exercise coaching that informs the user whether they are exercising appropriately during a session. The proposed exercise platform is composed mainly of hardware parts and smartphone applications. The hardware part serves to acquire exercise information and heart rate during exercise automatically. The smartphone application provides a simple exercise test and real-time exercise monitoring results using the hardware part's information. Each of them is described in detail below. Hardware Configuration of the Proposed Therapeutic Exercise Platform The proposed platform supports therapeutic exercise for blood glucose management based on aerobic options, i.e., jogging and walking outdoors and using a stationary bike or treadmill indoors. During the exercise session, the proposed platform automatically acquires exercise information such as exercise type, speed, and exercise time. It transfers the data to the proposed smartphone application in real-time. The hardware configuration of the proposed platform includes five elements, as shown in Figure 2a. First, it uses a radio frequency identification (RFID) module to identify the user, which is embedded into the exercise equipment. Second, it uses a wearable band or ear-clip heart rate sensor to check heart rate during the exercise session. Third, the wearable band is responsible for monitoring outdoor exercise, including the heart rate of patients. Fourth, an exercise data acquisition (DAQ) device is added to the exercise devices to monitor the indoor aerobic exercise. Finally, glucometers are used to record the blood glucose readings. Figure 3 shows the data flow of the proposed therapeutic exercise platform. The collected data is calculated as necessary information, and then it is stored in the internal memory of each device. When the smartphone and each device are synchronized, this information is transmitted to the smartphone application. 1. Automatically obtain exercise information whenever patients exercise outdoors or indoors. 2. Analyze the change of exercise ability due to the long-term exercise regime, i.e., a simple exercise stress test that allows the user to test their athletic ability. 3. Provide exercise coaching that informs the user whether they are exercising appropriately during a session. The proposed exercise platform is composed mainly of hardware parts and smartphone applications. The hardware part serves to acquire exercise information and heart rate during exercise automatically. The smartphone application provides a simple exercise test and real-time exercise monitoring results using the hardware part's information. Each of them is described in detail below. Hardware Configuration of the Proposed Therapeutic Exercise Platform The proposed platform supports therapeutic exercise for blood glucose management based on aerobic options, i.e., jogging and walking outdoors and using a stationary bike or treadmill indoors. During the exercise session, the proposed platform automatically acquires exercise information such as exercise type, speed, and exercise time. It transfers the data to the proposed smartphone application in real-time. The hardware configuration of the proposed platform includes five elements, as shown in Figure 2a. First, it uses a radio frequency identification (RFID) module to identify the user, which is embedded into the exercise equipment. Second, it uses a wearable band or ear-clip heart rate sensor to check heart rate during the exercise session. Third, the wearable band is responsible for monitoring outdoor exercise, including the heart rate of patients. Fourth, an exercise data acquisition (DAQ) device is added to the exercise devices to monitor the indoor aerobic exercise. Finally, glucometers are used to record the blood glucose readings. Figure 3 shows the data flow of the proposed therapeutic exercise platform. The collected data is calculated as necessary information, and then it is The hardware part of the proposed platform acquires exercise information and heart rate information whenever a patient exercises. The hardware part obtains information by dividing outdoor exercise and indoor exercise. During exercise, the patients monitor various exercise factors using the proposed hardware configuration. The device configuration differs depending on the outdoor exercise and indoor exercise using a stationary bike and treadmill. When the patients perform jogging or walking outdoors, a wearable band acquires exercise and heart rate information by itself. When exercising indoors, the patient first identifies the user of the exercise equipment using their RFID tag containing their information. Then, they start to exercise using exercise equipment, including DAQ, to obtain the exercise information automatically. They also wear a wearable band or ear-clip heart rate sensor to measure their heart rate. First, we describe the hardware configuration and operation for outdoor exercise. The proposed platform can monitor outdoor exercise using commercial wearable bands such as Xiaomi's MiBand. They incorporate low-power processors, inertial sensors, and optical biosensors connected to a smartphone through a Bluetooth network. These can measure the number of steps and heart rate and store the obtained data in their memory, with append data synchronization time stored separately. The sum of the magnitudes of the acceleration vectors, EA is calculated as Equation. where x, y, and z are signal values along each axis. An interrupt signal is generated when EA > threshold (held in the sensor memory), and the processor then classifies behavior type by interrupt occurrence frequency. The wearable band starts at the start stage and precedes system initialization as shown in Figure 4. By executing Global variable unit (), System setup (), and Bluetooth setup (), system-wide variables are initialized, processor I/O pins are set, and Bluetooth profiles are set, respectively. Then, the smartphone application initiates information synchronization with the wearable band over a Bluetooth network when it is connected. Next, it compares the data stored by the wearable band and the smartphone application. If the data are matched, it ends immediately. Otherwise, it starts to perform the data synchronization process after device authentication of the wearable band. In the wearable band, every information is determined through the occurrence time interval when a sensor interrupt signal is generated from the three-axis MEMS (microelectro-mechanical system) accelerometer. If it does not occur, the system switches the processor to deep sleep mode to reduce power consumption. The wearable band begins to calculate the number of steps by performing the Data processing () process if the interrupt occurs. Patient physical activity information is automatically transmitted to the smartphone, including walking count, heart rate, and sleeping time. Thus, exercise start The hardware part of the proposed platform acquires exercise information and heart rate information whenever a patient exercises. The hardware part obtains information by dividing outdoor exercise and indoor exercise. During exercise, the patients monitor various exercise factors using the proposed hardware configuration. The device configuration differs depending on the outdoor exercise and indoor exercise using a stationary bike and treadmill. When the patients perform jogging or walking outdoors, a wearable band acquires exercise and heart rate information by itself. When exercising indoors, the patient first identifies the user of the exercise equipment using their RFID tag containing their information. Then, they start to exercise using exercise equipment, including DAQ, to obtain the exercise information automatically. They also wear a wearable band or ear-clip heart rate sensor to measure their heart rate. First, we describe the hardware configuration and operation for outdoor exercise. The proposed platform can monitor outdoor exercise using commercial wearable bands such as Xiaomi's MiBand. They incorporate low-power processors, inertial sensors, and optical biosensors connected to a smartphone through a Bluetooth network. These can measure the number of steps and heart rate and store the obtained data in their memory, with append data synchronization time stored separately. The sum of the magnitudes of the acceleration vectors, E A is calculated as Equation. where x, y, and z are signal values along each axis. An interrupt signal is generated when E A > threshold (held in the sensor memory), and the processor then classifies behavior type by interrupt occurrence frequency. The wearable band starts at the start stage and precedes system initialization as shown in Figure 4. By executing Global variable unit (), System setup (), and Bluetooth setup (), system-wide variables are initialized, processor I/O pins are set, and Bluetooth profiles are set, respectively. Then, the smartphone application initiates information synchronization with the wearable band over a Bluetooth network when it is connected. Next, it compares the data stored by the wearable band and the smartphone application. If the data are matched, it ends immediately. Otherwise, it starts to perform the data synchronization process after device authentication of the wearable band. In the wearable band, every information is determined through the occurrence time interval when a sensor interrupt signal is generated from the three-axis MEMS (microelectro-mechanical system) accelerometer. If it does not occur, the system switches the processor to deep sleep mode to reduce power consumption. The wearable band begins to calculate the number of steps by performing the Data processing () process if the interrupt occurs. Patient physical activity information is automatically transmitted to the smartphone, including walking count, heart rate, and sleeping time. Thus, exercise start time, duration, speed per minute, and end time are derived from the number of steps whenever the patient performs aerobic exercise such as running or walking outdoors. The only exception is a command to measure heart rate. It acts as an external interrupt, Ext.interrupt, and it is transmitted to the wearable band periodically. After this interrupt is received, the wearable band is activated. The acquired heart rate is stored together with time in its internal memory. PEER REVIEW 8 of 23 time, duration, speed per minute, and end time are derived from the number of steps whenever the patient performs aerobic exercise such as running or walking outdoors. The only exception is a command to measure heart rate. It acts as an external interrupt, Ext.interrupt, and it is transmitted to the wearable band periodically. After this interrupt is received, the wearable band is activated. The acquired heart rate is stored together with time in its internal memory. Second, we use exercise equipment such as stationary bikes and treadmills for indoor exercise. We devised an exercise DAQ board for indoor aerobic exercise equipment to obtain exercise information. The proposed DAQ was linked with a smartphone and wearable band through a Bluetooth network to acquire detailed exercise information, such as exercise start time, duration, end time, exercise load (each minute), and heart rate, in realtime whenever the patient exercised. The mainboard of DAQ is an Intel Curie board, which has a built-in NRF51822 BLE chipset from Nordic. We adopt the magnetic sensor as the SainSmart hall sensor module and the heart rate sensor as the Grove ear-clip heart rate sensor. The exercise information acquisition device fabricated in this paper was attached to a treadmill and an ergometer. Table 2 shows the exercise information acquired to help the diabetic patient manage exercise therapy. Exercise start and end times were obtained from the real-time clock module, with average speed, moving distance, exercise load (average heart rate), and calories consumed calculated from the DAQ information. Table 2 shows exercise information that was transmitted in real-time when the smartphone was connected. The data was summarized and automatically stored in the memory unit. Second, we use exercise equipment such as stationary bikes and treadmills for indoor exercise. We devised an exercise DAQ board for indoor aerobic exercise equipment to obtain exercise information. The proposed DAQ was linked with a smartphone and wearable band through a Bluetooth network to acquire detailed exercise information, such as exercise start time, duration, end time, exercise load (each minute), and heart rate, in real-time whenever the patient exercised. The mainboard of DAQ is an Intel Curie board, which has a built-in NRF51822 BLE chipset from Nordic. We adopt the magnetic sensor as the SainSmart hall sensor module and the heart rate sensor as the Grove ear-clip heart rate sensor. The exercise information acquisition device fabricated in this paper was attached to a treadmill and an ergometer. Table 2 shows the exercise information acquired to help the diabetic patient manage exercise therapy. Exercise start and end times were obtained from the real-time clock module, with average speed, moving distance, exercise load (average heart rate), and calories consumed calculated from the DAQ information. Table 2 shows exercise information that was transmitted in real-time when the smartphone was connected. The data was summarized and automatically stored in the memory unit. Exercise amount was obtained from the rotational speed measured by attaching a permanent magnet to the rotating body, as shown in Figure 5 using a hall effect. The processor calculates movement distance, D total, and Instantaneous movement speed, V t as and where C dist is a fixed movement distance constant, N rot is the number of rotation signals, and ∆t is the time difference between the current time, t, and previous time, t − 1, when the processor recognized the magnetic field monitoring signal from the sensor. where Cdist is a fixed movement distance constant, Nrot is th and t is the time difference between the current time, t, an the processor recognized the magnetic field monitoring sign Figure 6 shows the motion information acquisition operation. All system variables are initialized when booting starts from the system boot loader. System setup includes peripheral I/O setup, Bluetooth profile setup, memory index processing, and display initialization. Bluetooth connection is checked after initialization completes. The system only measures and stores exercise information if it is not connected, whereas real-time information transmission and synchronization are also performed if it is connected. The proposed indoor aerobic exercise monitoring method is as follows. 1. The user wears an exercise band or Bluetooth low energy (BLE) based heart rate monitor and starts exercising. 2. The band identifies the user to the exercise equipment through the RFID tag. 3. The proposed exercise monitoring system recognizes exercise commencement when the rotating body starts to rotate and initializes user status and start date, and time. 4. The proposed DAQ device collects exercise information during exercising: instantaneous exercise speed every second, heart rate every minute. 5. Each exercise equipment stores user identification, date, start time, end time, duration, type, distance, speed per minute, and total distance. It also stores user biometric information, including exercise intensity and heart rate change per minute. The obtained information is transmitted to the smartphone in real-time. Figure 6 shows the motion information acquisition operation. All system variables are initialized when booting starts from the system boot loader. System setup includes peripheral I/O setup, Bluetooth profile setup, memory index processing, and display initialization. Bluetooth connection is checked after initialization completes. The system only measures and stores exercise information if it is not connected, whereas real-time information transmission and synchronization are also performed if it is connected. Figure 6. The data synchronization process between aerobic equipment and smartphone application in the proposed therapeutic exercise platform. Simple Exercise Stress Test to Reflect Changes in the Patient's Athletic Ability An exercise stress test is often used to diagnose coronary heart disease. In sports medicine, exercise stress testing is presently used to assess physical fitness, determine functional capacity, diagnose cardiac disease, define the prognosis of known cardiac disease, prescribe an exercise plan, and guide cardiac rehabilitation. Guidelines on whether or not to perform systematic exercise stress tests for diabetic individuals vary according to the region and professional associations. Riebe et al. stated that preparticipation health screening would be based on the individual's current physical activity level, the desired exercise intensity, the presence of symptoms, and his medical history. The American Diabetes Association pointed out pre-exercise medical clearance is unnecessary if the patients want to begin low-or moderate-intensity physical activity not exceeding the demands of brisk walking or everyday living. In this section, the proposed platform introduces a simple exercise test that calculates the appropriate amount of exercise for patients during their usual exercise. The proposed exercise test is based on either the Karvonen formula or modified Borg RPE. Patients periodically perform the proposed exercise test to determine their moderate exercise intensity and help them exercise at the right intensity. In general, the exercise test is performed according to protocols. The most common protocol used during the exercise test is the Bruce protocol. The test is performed in a designated lab, supervised by trained healthcare personnel. The patient closed their eyes for 5 minutes, and then their heart rate and blood pressure were measured at rest. The exercise test was terminated if the patient had experienced any subjective symptoms (difficulty breathing, local fatigue, leg pain) or maximum blood pressure increased by 250/115 mmHg (millimeters of Mercury) or more. The test used a treadmill, electrocardiogram (ECG), metabolic cart, blood pressure monitor, perceived exertion, and pulse meter. The modified Bruce protocol is preferred for exercise stress testing, as shown in Table 3. Its outcomes are well-validated, and exercise capacity measured in MET has a good prognostic value. Kim et al. presented the study to provide valuable data for CR-10 as the RPE. Using these results, we reconstructed as shown in Table 3 as an exercise load test scale for the proposed platform. The test started at low intensity and gradually increased intensity for each step, as shown in Table 3. Borg developed a RPE. It is a widely used and reliable indicator to monitor and guide exercise intensity by allowing patients to rate their level of exertion during exercise subjectively. Two RPE scales are commonly used; the original Borg scale (6 to 20 scale) and the revised category-rate scale, CR-10 (0 to 10 scale). A high correlation exists between a person's perceived exertion rating times ten and the actual heart rate during physical activity, so a person's exertion rating may provide a relatively good estimate of the actual heart rate during activity. In the proposed therapeutic exercise platform, we used the CR-10 Borg scale, not the original Borg scale, increasing exercise awareness between 1~3 MET each step. The other most significant advantage of the CR-10 is its easy handling by allowing daily changes in the exercise. Most patients undergo exercise stress tests in hospitals at the initial diagnosis of diabetes, and they receive appropriate exercise prescriptions. As patients repeat the same intensity exercise for a long time, they feel the exercise intensity gradually lower. Besides, the patient's physical strength varies depending on several factors. To maintain the prescribed intensity of exercise, patients should repeatedly check their exercise stress during their usual exercise. The proposed therapeutic exercise platform supports a simple exercise stress test to check the effect of exercise intensity on heart rate and RPE. It adjusts the exercise intensity according to the results and informs the patient about the adjusted exercise intensity to continue exercising according to the exercise prescription. Figure 7 shows an example of an exercise prescription at the early stages of diabetic diagnosis. After the exercise test, the patient receives the prescribed target heart rate and weekly target exercise intensity based on heart rate, as shown in Figure 7a. Figure 7b shows a look-up table. During the exercise test, the patient's heart rate and the RPE are linked with the exercise intensity at each test step, and they are recorded in a look-up table. This table shows the relationship between the heart rate and exercise speed obtained each time the patient exercised. It is used to tune the exercise speed in the exercise session before the patient exercises. The proposed exercise test is based on the modified Bruce protocol, and it is conducted for about 20 minutes at the exercise intensity shown in Table 3 using a treadmill or a stationary bike. The patient maintains a low exercise intensity for 9 mins. For the remaining 15 mins, the intensity is increased gradually to reach the target heart rate. During the test, the patient's heart rate, exercise intensity, and RPE are obtained in real-time. A wearable band or ear-clip heart rate sensor is to obtain the heart rate. Exercise intensity and RPE are obtained from the proposed DAQ and chatbot, respectively. cise stress test to check the effect of exercise intensity on heart rate and RPE. It adjusts the exercise intensity according to the results and informs the patient about the adjusted exercise intensity to continue exercising according to the exercise prescription. Figure 7 shows an example of an exercise prescription at the early stages of diabetic diagnosis. After the exercise test, the patient receives the prescribed target heart rate and weekly target exercise intensity based on heart rate, as shown in Figure 7a. Figure 7b shows a look-up table. During the exercise test, the patient's heart rate and the RPE are linked with the exercise intensity at each test step, and they are recorded in a look-up table. This table shows the relationship between the heart rate and exercise speed obtained each time the patient exercised. It is used to tune the exercise speed in the exercise session before the patient exercises. The patient performs the proposed test by selecting one of the following three methods depending on the available exercise equipment and vital sensors. The first method is based on the modified Bruce protocol, and it is used when the patient has a treadmill suitable for the protocol. The second method is used when the user exercises using a treadmill or indoor bike with a heart rate sensor. The third method is used when the user exercises outdoors or wants to test with RPE with a wearable band. In all cases, patients should measure their resting heart rate, HR rest before the exercise test. The first method performs an exercise test according to the modified Bruce protocol shown in Table 3. At each stage, the patient's heart rate is measured, and the CR-10 RPE felt by the patient is also recorded. According to the heart rate measured in each stage, the speed and grade are determined as the recommended exercise intensity. The second method is to perform an exercise test by simply measuring the heart rate in real-time. As shown in Table 3, the patient starts the exercise from the low intensity according to the exercise protocol using a treadmill or a stationary cycle. They perform the exercise for 9 mins when it reaches 58% of the heart rate reserve. Then, the patient increases the exercise intensity until the target heart rate is reached, as shown in Table 3. During the proposed exercise test, the measured heart rate is displayed to the patient. After the examination, the exercise speed of the treadmill or cycle for each stage is recommended as the patient's exercise intensity. The last method is to perform a simple exercise test with a modified Borg RPE that the patient feels himself. The patient maintains low-intensity exercise on a treadmill or bike for 9 mins before reaching level 1.48 of the modified Borg RPE. As shown in Table 3, the patient increases the exercise speed until the target RPE level is reached and maintains the exercise speed for 3 minutes. The recommended exercise intensity is determined by the average exercise speed of each stage of each RPE recorded. The proposed test allows the patients to run simply exercise tests whenever necessary. The test result is used to adjust the intensity of exercise to match the patient's exercise ability. Busch et al. presented the classification of physical activity intensity using the 2009 ACSM (American College of Sports Medicine) classifications. Low intensity is classified as 50-63% HRR max. Moderate and vigorous intensities are 64-76% HRR max and 77-93% HRR max, respectively. We considered the appropriate exercise intensity to be sufficient to reach 50-76% HRR max. Additionally, moderate and intermittent medium or high-intensity exercise for 45 min or more is beneficial for blood glucose management. Consequently, patients can adjust their exercise intensity and time after setting the coaching algorithm according to their abilities. We developed a smartphone application to provide an exercise monitoring and coaching program based on their exercise stress test results. Proposed Real-Time Exercise Monitoring Application For diabetics, exercise therapy is vital for blood glucose management. However, diabetic patients are less aware of the importance of exercise therapy due to the fear of hypoglycemia caused by excessive exercise and the different physical abilities. This section describes the proposed exercise monitoring and coaching method to inform the patient of the appropriate exercise intensity and exercise time using the proposed therapeutic exercise platform. In this section, exercise intensity refers to the exercise speed according to the patient's heart rate during exercise. The proposed exercise monitoring and coaching application help diabetics continue to exercise according to a prescribed exercise protocol. First, the patients launch the coaching application, and they enter the type of exercise and the scheduled exercise time. The coaching application recommends an exercise plan that combines intermediate and intermittent high-intensity exercises according to the exercise test results in advance. For example, each exercise coaching instance consists of a set of 45 min. The patient exercises according to a predetermined exercise coaching algorithm. This application measures the patient's heart rate every minute during exercise and guides them to maintain the recommended exercise speed. The proposed application alerts the patient in real-time if the patient's exercise speed is too low or too high (e.g., if the patient's heart rate is below 50% of HRmax or above 75% of HRmax). It also sends a warning if the patient does not exercise at the recommended exercise speed. After completing an exercise, the collected exercise information is summarized, and statistics are generated. The data acquisition of the proposed platform supports not only automatic input from sensors, but also voice or manual input by the user as shown in Figure 8. The proposed application allows the user to voice input of RPE values using a chatbot during exercise. In addition, the user can manually modify the record when not exercising. The information collected during the patient's exercise fine-tunes the exercise program to the patient's exercise goal. The real-time monitoring of the proposed application has four display modes. The first mode is an exercise plan mode. If there is an exercise prescription, a recommended exercise plan is displayed. Otherwise, it displays the exercise mode selected by the user. The remaining three modes show the comparison result of the recommended exercise and the exercise being performed for exercise speed, heart rate, and RPE, as shown in Figure 8. tient of the appropriate exercise intensity and exercise time using the proposed therapeutic exercise platform. In this section, exercise intensity refers to the exercise speed according to the patient's heart rate during exercise. The proposed exercise monitoring and coaching application help diabetics continue to exercise according to a prescribed exercise protocol. First, the patients launch the coaching application, and they enter the type of exercise and the scheduled exercise time. The coaching application recommends an exercise plan that combines intermediate and intermittent high-intensity exercises according to the exercise test results in advance. For example, each exercise coaching instance consists of a set of 45 min. The patient exercises according to a predetermined exercise coaching algorithm. This application measures the patient's heart rate every minute during exercise and guides them to maintain the recommended exercise speed. The proposed application alerts the patient in realtime if the patient's exercise speed is too low or too high (e.g., if the patient's heart rate is below 50% of HRmax or above 75% of HRmax). It also sends a warning if the patient does not exercise at the recommended exercise speed. After completing an exercise, the collected exercise information is summarized, and statistics are generated. The data acquisition of the proposed platform supports not only automatic input from sensors, but also voice or manual input by the user as shown in Figure 8. The proposed application allows the user to voice input of RPE values using a chatbot during exercise. In addition, the user can manually modify the record when not exercising. The information collected during the patient's exercise fine-tunes the exercise program to the patient's exercise goal. The real-time monitoring of the proposed application has four display modes. The first mode is an exercise plan mode. If there is an exercise prescription, a recommended exercise plan is displayed. Otherwise, it displays the exercise mode selected by the user. The remaining three modes show the comparison result of the recommended exercise and the exercise being performed for exercise speed, heart rate, and RPE, as shown in Figure 8. Evaluation Results We devised the following three hardware configurations to acquire exercise data and vital signs during exercise. First, the proposed platform used Xiaomi's Mi band, a commercial wearable band, to acquire the number of steps and heart rate by time. Second, an Evaluation Results We devised the following three hardware configurations to acquire exercise data and vital signs during exercise. First, the proposed platform used Xiaomi's Mi band, a commercial wearable band, to acquire the number of steps and heart rate by time. Second, an exercise DAQ device was added to the treadmill and stationary bike to obtain the exercise information. Third, an ear-clip heart rate sensor was added to obtain the heart rate during exercise. These were linked with a smartphone application through BLE communication with a glucometer. The exercise DAQ was mounted on the aerobic exercise device, and it included a magnetic sensor, SD card, and BLE module in a 32-bit processor. We chose an Intel Curie board as microcontroller unit because it was also easy to use and compatible with Genuino and Arduino 101. It connected with an external RFID unit and a heart rate sensor to obtain user identification and heart rate information. The first experiment was to evaluate the accuracy of the exercise speed information acquired through DAQ. As shown in Tables 4 and 5, the rotation axis of two stationary bikes (A, B) and two treadmills (A, B) was rotated 1,000 times at different speeds and then obtained from DAQ. Both experiments had less than 2% error and accuracy close to 100% at low speeds. The results indicate that the exercise speed obtained from the designed DAQ had an accuracy of at least 98%. The second experiment was to measure the accuracy of the heart rate acquired from the heart rate sensor. During exercise using a stationary bike and a treadmill, the heart rate obtained from DAQ and the result of Polar's T34 heart rate monitor were compared. The result is shown in Figure 9. The measurement error was up to 2%, and the average error was within 1%, indicating that an error rate is irrespective of the movement speed. Therefore, the proposed DAQ could measure real-time heart rate with at least 98% accuracy regardless of changes in exercise intensity. After we evaluated the proposed therapeutic exercise platform, including the hardware part and the smartphone application, we tested the accuracy in an actual exercise environment. The comparison results of the proposed DAQ and a commercial heart rate monitor, Polar T34, are shown in Figure 10. The exercise was performed in the order of warm-up, intermittent high intensity, and medium intensity. Figure 10 shows the patient's heart rate change according to the change in exercise intensity. In the warm-up phase, the heart rate gradually increased, and in the high-intensity exercise section, the heart rate increased to 80% of the maximum heart rate. After that, it indicates that the heart rate stably lowered in the middle-intensity exercise section. The average difference is within 2%. This result proves that the proposed therapeutic exercise platform was suitable for monitoring exercise in real-time. Electronics 2021, 10, x FOR PEER REVIEW 15 of 23 Figure 9. The experiment result of heart rate sensing between proposed DAQ and other counterparts. After we evaluated the proposed therapeutic exercise platform, including the hardware part and the smartphone application, we tested the accuracy in an actual exercise environment. The comparison results of the proposed DAQ and a commercial heart rate monitor, Polar T34, are shown in Figure 10. The exercise was performed in the order of warm-up, intermittent high intensity, and medium intensity. Figure 10 shows the patient's heart rate change according to the change in exercise intensity. In the warm-up phase, the heart rate gradually increased, and in the high-intensity exercise section, the heart rate increased to 80% of the maximum heart rate. After that, it indicates that the heart rate stably lowered in the middle-intensity exercise section. The average difference is within 2%. This result proves that the proposed therapeutic exercise platform was suitable for monitoring exercise in real-time. After we evaluated the proposed therapeutic exercise platform, including the hardware part and the smartphone application, we tested the accuracy in an actual exercise environment. The comparison results of the proposed DAQ and a commercial heart rate monitor, Polar T34, are shown in Figure 10. The exercise was performed in the order of warm-up, intermittent high intensity, and medium intensity. Figure 10 shows the patient's heart rate change according to the change in exercise intensity. In the warm-up phase, the heart rate gradually increased, and in the high-intensity exercise section, the heart rate increased to 80% of the maximum heart rate. After that, it indicates that the heart rate stably lowered in the middle-intensity exercise section. The average difference is within 2%. This result proves that the proposed therapeutic exercise platform was suitable for monitoring exercise in real-time. The proposed therapeutic exercise application was implemented using two languages, Java 1.8 and Kotlin. The smartphone operating system was set to Android. The minimum version of the supported Android operating system was set to API (application programming interface) 19 (version name: Kitkat) that supports low-power Bluetooth. The proposed application was implemented as shown in Figure 11. It consisted of the initial screen, entered user information, device registration, and management. Furthermore, the patients input their exercise prescription or exercise setting determined by patients. Then, the application could help the patients to exercise their prescription or exercise plan. Figure 12 shows the results of exercise monitoring. First, the patient could perform a simple exercise test. The proposed simple exercise load test could be performed by selecting one of the modified Bruce protocol, HRR, and RPE modes. The test results were used to determine the appropriate exercise intensity for the patient, as shown in Figure 12a. During exercise, the patient can monitor in real-time whether he exercises according to the exercise plan. In this case, the patient could select monitoring mode three modes of exercise speed, heart rate, or RPE. Figure 12b is a real-time monitoring screen showing whether the patient was exercising according to the exercise plan based on the heart rate. After the exercise is over, the exercise result was summarized and displayed to the patient, as shown in Figure 12c. The proposed therapeutic exercise application was implemented using two languages, Java 1.8 and Kotlin. The smartphone operating system was set to Android. The minimum version of the supported Android operating system was set to API (application programming interface) 19 (version name: Kitkat) that supports low-power Bluetooth. The proposed application was implemented as shown in Figure 11. It consisted of the initial screen, entered user information, device registration, and management. Furthermore, the patients input their exercise prescription or exercise setting determined by patients. Then, the application could help the patients to exercise their prescription or exercise plan. Figure 11. Proposed mobile application user interface (UI); (a) log-in, (b) application setting, (c) device scan, (d) input of exercise prescription or user's plan and recommended exercise plan. Figure 12 shows the results of exercise monitoring. First, the patient could perform a simple exercise test. The proposed simple exercise load test could be performed by selecting one of the modified Bruce protocol, HRR, and RPE modes. The test results were used to determine the appropriate exercise intensity for the patient, as shown in Figure 12a. During exercise, the patient can monitor in real-time whether he exercises according to the exercise plan. In this case, the patient could select monitoring mode three modes of exercise speed, heart rate, or RPE. Figure 12b is a real-time monitoring screen showing whether the patient was exercising according to the exercise plan based on the heart rate. After the exercise is over, the exercise result was summarized and displayed to the patient, as shown in Figure 12c. Table 6 shows the comparison results between the proposed therapeutic exercise platform and other counterparts. Automatic refers to the ability of an application to connect with a device and automatically record relevant data to the application. Manual represents that the user directly enters the relevant records into the application. Additionally, exercise plan adjust refers to a function of automatically adjusting an exercise program Table 6 shows the comparison results between the proposed therapeutic exercise platform and other counterparts. Automatic refers to the ability of an application to connect with a device and automatically record relevant data to the application. Manual represents that the user directly enters the relevant records into the application. Additionally, exercise plan adjust refers to a function of automatically adjusting an exercise program according to a user's exercise experience. The significate feature is that the proposed platform was linked with aerobic exercise equipment, a wearable band, and a heart-rate sensor. The platform gathered precise exercise information and heart rate during exercise. It used the information to adjust the exercise program of the exercise session to keep the excise intensity indicated from the exercise prescription. An exercise stress test in the proposed therapeutic exercise platform could estimate the relationship between the patient's heart rate and exercise speed. If the patients keep doing aerobic exercise for a long time, it is good to improve their physical fitness and exercise ability. Therefore, the intensity and loads should continually increase over time. Whenever a patient felt that his or her exercise ability improved, an exercise stress test was performed to obtain a relationship between maximum heart rate reserve and exercise speed. The proposed platform adjusted the exercise intensity in the exercise session by reflecting the exercise stress test results. The exercise speed of the exercise session was adjusted to match the maximum heart rate reserve of the exercise plan. Patients could exercise by adjusting the exercise intensity according to their physical changes. A closed beta service has been performed since 2017. We released our application to Google play store for a closed test. Among the users who used the application who answered that they had a high understanding of diabetes, diabetic patients and those who did not have a diagnosis of diabetes were selected and the experimental group was recruited. Finally, we selected the patient population from patients with a prevalence of 3 years or more and a fasting blood glucose level greater than 160 mg/dL. The questionnaire is shown in Figure 13. For platform evaluation and future improvement, we received satisfaction ratings and functional improvements through a questionnaire survey as shown in Figure 14 on 10 type 2 diabetes patients and ten persons without a diabetes diagnosis as shown in Table 7. Overall, the patients and others expressed high satisfaction with ease of use. The patient's additional opinions are as follows. First, it is necessary to update diabetes education about therapeutic exercise. Second, exercises after a meal increased compared to before use. Third, if the function to share experiences with other users is added, motivation will be better. Fourth, it is necessary to provide the personal exercise coaching or consulting function for an exercise. Finally, the number of symptoms of hypoglycemia decreased after exercise. Moreover, it became possible to control the exercise time and intensity according to the amount of meal. Conclusions In this paper, we present a therapeutic exercise platform. The proposed platform can support diabetic patients in managing their blood glucose levels by balancing physical exercise, insulin dosage or medication, blood glucose monitoring, and diet. In particular, well-planned and structured exercise is vital to control blood glucose levels in diabetes and reduce the risk of developing diabetes complications. The proposed system has three main functions. First, it automatically obtains exercise information precisely whenever patients exercise outdoors or indoors. Second, it can analyze the change of exercise ability due to the long-term exercise regime, i.e., a simple Conclusions In this paper, we present a therapeutic exercise platform. The proposed platform can support diabetic patients in managing their blood glucose levels by balancing physical exercise, insulin dosage or medication, blood glucose monitoring, and diet. In particular, well-planned and structured exercise is vital to control blood glucose levels in diabetes and reduce the risk of developing diabetes complications. The proposed system has three main functions. First, it automatically obtains exercise information precisely whenever patients exercise outdoors or indoors. Second, it can analyze the change of exercise ability due to the long-term exercise regime, i.e., a simple Conclusions In this paper, we present a therapeutic exercise platform. The proposed platform can support diabetic patients in managing their blood glucose levels by balancing physical exercise, insulin dosage or medication, blood glucose monitoring, and diet. In particular, well-planned and structured exercise is vital to control blood glucose levels in diabetes and reduce the risk of developing diabetes complications. The proposed system has three main functions. First, it automatically obtains exercise information precisely whenever patients exercise outdoors or indoors. Second, it can analyze the change of exercise ability due to the long-term exercise regime, i.e., a simple exercise test that frequently allows the user to test their athletic ability. Third, it provides an exercise monitoring and coaching program that informs the user whether they are exercising appropriately during a session. Therefore, most patients consider exercise as a supplemental glycemic control method with medication or diet. The proposed therapeutic exercise platform is crucial to develop a therapeutic exercise program that can recommend an exercise suitable for glycemic control to patients according to their preferred exercise pattern and individual exercise ability. The proposed therapeutic exercise platform consists of a hardware part responsible for obtaining exercise and heart-rate data and smartphone applications that provide a simple exercise test and real-time exercise monitoring results. The proposed exercise test is to calculate the appropriate amount of exercise for the patient. The proposed test can be performed not only by the typical modified Bruce protocol but also by the method based on heart rate reserve and rated perceived exertion for convenience. The evaluation result shows that the exercise speed and heart rate in the proposed hardware part have less than 2% error. This fact proves that the proposed DAQ can be applicable for various exercise environments regardless of exercise intensity changes. Ten diabetic patients and ten person without a diabetes diagnosis used the proposed platform for more than three months, and we analyzed the effectiveness of the proposed platform through their survey. Overall, the patients expressed high satisfaction with ease of use. Besides, most of the patients reported that both the number of blood glucose measurements and the exercise increased. This study conducted a usability evaluation of the proposed exercise platform with limited users only. Future studies should aim to address the limitations that exist in our work. We plan to verify the functionality of the blood glucose management platform, including exercise therapy, by accumulating pre-and post-exercise blood glucose levels for a long period of time for diabetic patients. Consequently, the proposed therapeutic exercise platform can be useful for the patients to make a well-planned and structured exercise for their glycemic control. Conflicts of Interest: The authors declare no conflict of interest.

The Fountain is the Fountain at Texas De Brazil in Addison on Belt Line. An Arctic cold front pushed into the Metroplex early Thursday morning, bringing bitterly cold weather into North Texas that is expected to last through the weekend. Temperatures are not expected to rise above freezing until Saturday afternoon, and the wind chill is expected to dip below zero. The temperature dropped to 13 degrees at Dallas/Fort Worth International Airport on Saturday morning, one degree shy of the record low of 12 set in 1977, said NBCDFW meteorologist Samantha Davies. Get a complete forecast here. "It's very cold this week, and this weekend, I'm probably going to stay in, because it's just windy and cold, and I'm looking forward to Sunday when it's above freezing," Brent Glover said. But power companies are also encouraging people to turn down the heat a notch to conserve energy. The bitter cold has generated two winter peak demand records in as many days on the state's biggest electrical grid. "Try to keep your thermostat at 68 degrees," said Oncor Electric Delivery spokeswoman Jeamy Molina. "I know that's kind of iffy, but it's going to help you out in the long run to hopefully help your usage come down and help you become more energy efficient in your homes." In Dallas, code compliance crews continue to look for businesses or residents who may be violating city rules by running a sprinkler during inclement weather. The runoff can cause roads to ice over and pose a danger to drivers. Dallas& Water Utilities also has repair crews on standby in the event of a water main break. On Monday, temperatures are expected to rise back into the 50s with a low of 28. On Tuesday, sunny weather is expected with a low of 43. Lita Beck contributed to this report.

A builder that's done a series of large rental communities in close-in Dallas neighborhoods is heading to Frisco with a new development. Wood Partners is working on plans for the next phase of the 16-year-old Frisco Square development at the southeast corner of the Dallas North Tollway and Main Street. The 145-acre mixed-use project includes Frisco's civic center, shops, apartments, retail space and medical facilities. Wood Partners plans to build a 298-unit apartment complex on one of the largest vacant tracts left in Frisco Square at Main and Frisco streets, according to plans filed with the city by the developer. The four-story rental community would fill the 4-acre side on the south side of Main Street. Along with the apartments, a 455-space parking garage will be included in the development. Wood Partners' Ryan Miller said this will be the firm's first Frisco project since 2009. He said the new development is "still early in the design process." Frisco Square was one of the first major mixed-use developments planned for Frisco and has continued to grow with the addition of new apartments. When the development was unveiled in 2000, it was estimated to be a $600 million project. Frisco's municipal building is Frisco Square's centerpiece. And just across the street is the 21,000-seat Toyota Stadium. Georgia-based Wood Partners has built about a dozen rental communities in Dallas, with projects downtown, Uptown, in the Design District and in Oak Cliff.

Detection-estimation of more uncorrelated sources than sensors in noninteger sparse linear antenna arrays We introduce a new approach for the detection-estimation problem for sparse linear antenna arrays comprising M identical sensors whose positions may be noninteger values (expressed in half-wavelength units). This approach considers the (noninteger) M/sub /spl alpha//-element co-array as the most appropriate virtual array to be used in connection with the augmented covariance matrix. Since the covariance matrix derived from such virtual arrays is usually very underspecified, we discuss a maximum-likelihood (ML) completion philosophy to fill in the missing elements of the partially specified Hermitian covariance matrix. Next, a transformation of the resulting unstructured ML matrix results in a sequence of properly structured positive-definite Hermitian matrices, each with their (M/sub /spl alpha//-/spl mu/) smallest eigenvalues being equal, appropriate for the candidate number of sources /spl mu/. For each candidate model (/spl mu/=1 to M/sub /spl alpha//-1), we then find the set of directions-of-arrival (DOAs) and powers that yield the minimum fitting error for the specified covariance lags in the neighbourhood of the MUSIC-initialised DOAs. Finally, these models describe a hypothesis with respect to the actual number of sources, and allow us to select the "best" hypothesis using traditional information criteria (AIC, MDL, MAP, etc.) that are based on the likelihood ratio.

1. Field of the Invention The present invention relates to an extruder cutter assembly for extruding filled food pieces. More particularly, the present invention relates to an extruder cutter assembly, which includes an extrusion member having a filling tube therein and a cutter member for cutting extrudate exiting the extrusion member to form a filled food piece having the shape of a natural food piece. 2. Description of Background Art Extruders for producing extruded food pieces are known. Such extruders can conventionally include a pressure vessel for containing, under pressure, a mash of the food to be extruded. Furthermore, pressure exerting means for maintaining pressure in the pressure vessel, a manifold in fluid communication with the pressure vessel, and an extruder cutter assembly, generally located underneath the pressure vessel, in fluid communication with the manifold can be included. The extruded food is cut to size by the extruder cutter assembly. Food products that can be extruded in such extruders include, e.g., meats, poultry, seafood, cereal grains, vegetables, fruits, and solid dairy products. As specific examples, the mash may be prepared from beef, chicken, shrimp, wheat, corn, rice, potatoes, apples, and cheese. The food is ground to a particle size consistent with forming a fluid mash, e.g., particle sizes that will pass through a U. S. Screen Series No. 5 screen, more usually a No. 10 screen, and often a No. 20 screen up to about a No. 100 screen. Water or other dispersing liquids, e.g., 3% to 70%, may be added to the ground food in order to produce a liquid mash. Binders, flavors, preservatives, colors, stabilizers, antioxidants, and the like may be added to the mash, in conventional amounts. Most often, a gelling material is added to the mash, e.g., a settable gum or pectate, for example, guar gum and sodium alginate, in conventional amounts of about 0.1% to 25%. The gum or pectate is set by a gelling agent, e.g., a 0.5% to 10% solution of calcium chloride and sodium alginate. The present inventor has invented an extruder cutter assembly for extruding a food piece in the shape of a natural food piece. In U.S. Pat. No. 5,773,043, an extruder cutter assembly includes an extrusion member and a tubular cutter member for cutting extrudate exiting the extrusion member. However, the '043 Patent does not include a filling tube for extruding a filling along with a mash of food to be cut with the cutter member. U.S. Pat. No. 5,773,043 is hereby incorporated by reference. The present inventor has also invented an extruder cutter assembly for extruding foodstuff containing a filling. In U.S. application Ser. No. 09/576,766 filed on May 24, 2000, an extruder cutter assembly includes an extension formed on the extrusion member and a filling tube to allow for the extrudate to exit the extruder cutter assembly from the side. This extruder is directed to the formation of a foodstuff in stick form, not in the shape of a natural food piece as in the present invention. Accordingly, it is necessary to include the extension on both cutter member and the extrusion member, which is not included in the cutter assembly of the present invention. U.S. application Ser. No. 09/576,766 is hereby incorporated by reference.

Identification and Characterization of a Novel-type Ferric Siderophore Reductase from a Gram-positive Extremophile* Iron limitation is one major constraint of microbial life, and a plethora of microbes use siderophores for high affinity iron acquisition. Because specific enzymes for reductive iron release in Gram-positives are not known, we searched Firmicute genomes and found a novel association pattern of putative ferric siderophore reductases and uptake genes. The reductase from the schizokinen-producing alkaliphile Bacillus halodurans was found to cluster with a ferric citrate-hydroxamate uptake system and to catalyze iron release efficiently from Fe-dicitrate, Fe-schizokinen, Fe-aerobactin, and ferrichrome. The gene was hence named fchR for ferric citrate and hydroxamate reductase. The tightly bound cofactor of FchR was identified by UV-visible, EPR, CD spectroscopy, and mass spectrometry. Iron release kinetics were determined with several substrates by using ferredoxin as electron donor. Catalytic efficiencies were strongly enhanced in the presence of an iron-sulfur scaffold protein scavenging the released ferrous iron. Competitive inhibition of FchR was observed with Ga(III)-charged siderophores with Ki values in the micromolar range. The principal catalytic mechanism was found to couple increasing Km and KD values of substrate binding with increasing kcat values, resulting in high catalytic efficiencies over a wide redox range. Physiologically, a chromosomal fchR deletion led to strongly impaired growth during iron limitation even in the presence of ferric siderophores. Inductively coupled plasma-MS analysis of fchR revealed intracellular iron accumulation, indicating that the ferric substrates were not efficiently metabolized. We further show that FchR can be efficiently inhibited by redox-inert siderophore mimics in vivo, suggesting that substrate-specific ferric siderophore reductases may present future targets for microbial pathogen control.

HOPKINTON — Elmwood third-grader Mia Tinnirello never imagined running a few laps around the front of her school alongside elite Kenyan runner Edna Kiplagat, who won last year’s Boston Marathon women’s title. The two didn’t seem to mind being in the back of the pack. Mia, along with two classmates in teacher Tom Keane’s third-grade classroom, designed a poster as part of a project on Kiplagat. “We learned that she is really good at running and never gives up,” said Mia, 9. On Monday, Kiplagat will join Geoffrey Kirui, who won the men’s title last year, in this year's Boston Marathon. For Elmwood students, the race kicks off with a pre-Marathon rally at the school with the field of elite Kenyan runners. The rally, part of John Hancock’s “Scholars and Stars” program, gave the students a chance to meet the athletes and learn about Kenya’s culture and lifestyles. Over the 26-year tradition, the visiting runners have won a combined 35 Boston Marathon titles. With students hoping to snag a high-five or fist bump, each of the 10 runners was announced into the gymnasium like rock stars with pop songs blasting, colorful lights and fog machines. Among them was Caroline Rotich, who took the women's title in 2015. “May your feet carry you to Boston safely and may you hold the encouragement of our students in your hearts as you run,” Principal Anne Carver said. The second- and third-grade students raised about $4,000 for the Kenyan Kids Foundation, founded by 2012 champ Wesley Korir and his wife, Tarrah, to help build classrooms, provide books and offer high school scholarships in Kenya. Hopkinton High School senior Calli Korbey, 17, a member of the track team, called Kenya Day a highlight of her time at the school. Kiplagat was pleased to be back in Hopkinton to visit the students again after last year's win. Before the rally in Keane’s classroom, runner Philemon Rono took a selfie with 8-year-old Konstantinos Selibas. This will be Rono's first Boston Marathon. The class learned songs and phrases in Swahili to greet the runners, Konstantinos said. Along with many other classmates, Konstantinos had his Kenya Day T-shirt signed by Kirui. “I am never throwing this away,” he said.

Clear Cell Sarcoma of the Kidney with Invasion of the Inferior Vena cava Objective: We present a case of clear cell sarcoma of the kidney (CCSK) in 53-year-old white man who was treated with surgery. This case represents the oldest patient with CCSK published in the English literature. Methods: Right radical nephrectomy with lymphadenectomy and thrombectomy was performed. Results: Histological findings indicated a CCSK. Tumor cells showed positive vimentin staining. Conclusion: CCSK is considered a rare and highly malignant renal tumor. The malignant nature may relate not only to the biological features of these tumor cells, but also to the high resistance against radiation and chemotherapy. The treatment of CCSK has been a subject of controversy.

A health insurance company has said that Germans are going to the doctor twice as much as they actually need to. But doctors disagree. “We don't have too few doctors, but actually too much contact with doctors,” KKH CEO Ingo Kailuweit told Bild on Tuesday. The OECD's Health Statistics report for this year showed that Germans went to the doctor on average more than 18 times in 2008, while another OECD report showed that Germans visited the doctor about ten times each in 2013. This made Germans one of the top ten countries for doctors' consultations in the world that year. And Kailuweit also said that it's not necessarily the patients' fault: general practitioners “keep their patients too long”, for fear of transferring them elsewhere. Therefore patients might consult multiple doctors if they feel they haven't received the treatment they wanted. But Andreas Gassen, head of the German Association of Statutory Health Insurance Physicians, denounced the health insurance company leader's statements. "Where are the facts behind the KKH's claims?" Gassen wrote in a statement. "Health insurance companies themselves drive up the number of doctors' visits, for example, by aggressively promoting to their clients that they can get a second opinion. "Qualified doctors worry every day about the patients at their practices, under difficult circumstances. Every tenth service is on average not compensated. So there is absolutely no interest in unnecessarily increasing the number of patient visits." The chair of the board of the German Foundation for Patient Protection, Eugen Brysch, said that the KKH leader's statements were “hot air”.

Throughout Monday night’s presidential debate on foreign policy, President Obama used past positions that Mitt Romney has taken over the course of the campaign to depict him as the wrong candidate to run U.S. foreign policy. Obama used the tactic both to defend his own initiatives — particularly his Libya policy — and to characterize Romney as an untrained foreign policy hand who has been wobbly and inconsistent. “I know you haven’t been in a position to execute foreign policy,” Obama said, in summarizing his theme of attack, “but every time you have offered an opinion, you have been wrong.” Russia Obama took the chance to needle Romney on his adversarial position on Russia. “I’m glad that you recognize al Qaeda is a threat. Because a few months ago when you were asked the biggest threat facing America, you said Russia,” Obama said. “The Cold War has been over for 20 years. But governor, when it comes to our foreign policy, you seem to want to import the foreign policies of the 1980s, just like the social policies of the 1950s and the economic policies of the 1920s.” Later Obama said directly to Romney, “You indicated that we shouldn’t be passing nuclear treaties with Russia, despite the fact that 71 senators, Democrats and Republicans, voted for it.”Libya Regarding Romney’s campaign positions on the revolution in Libya, Obama said, “[T]o the governor’s credit, you supported us going into [L]ibya and the coalition that we organized,” Obama said. “But when it came time to making sure that Moammar Gaddhafi did not stay in power, that he was captured, governor, your suggestion was that this was mission creep.” Syria Responding to Romney’s call for arming Syrian opposition and his critique of the Obama administration’s more cautious policy, Obama noted that “to get more entangled militarily in Syria is a serious step. And we have to do so making absolutely certain that we know who we are helping, that we’re not putting arms in the hands of folks who eventually could turn them against us or allies in the region. I’m confident that Assad’s days are numbered. But what we can’t do is simply suggest that as governor at times as suggested that giving heavy weapons, for example, to the Syrian opposition is a simple proposition that would lead us to be safer over the long-term.” Osama bin Laden Obama reprised a familiar line based on Romney’s position in the 2008 campaign that locating and killing Osama bin Laden would not be a top priority. “[Y]ou said we shouldn’t move heaven and earth to get one man,” Obama said. “If we would have asked Pakistan for permission, we wouldn’t have got him.” Iraq “You say that you’re not interested in duplicating what happened in Iraq, but just a few weeks ago, you said you think we should have more troops in Iraq right now,” Obama said pointedly. “You said we should have gone into Iraq despite the fact there were no weapons of mass destruction. You said that we should still have troops in Iraq, to this day.” Afghanistan You said that first we should not have a timeline in Afghanistan, then you said we should. Now you say maybe or it depends. Which means not only were you wrong, but you were confused and sending mixed messages to our troops and allies.”

Tell me how long it takes for light to travel and I will tell you how fast you go The Italian Governments Ministry of Public Education has introduced the special theory of relativity for students in their last year of high school. For this reason, we often organize in-depth lessons on modern physics, in general, and on relativity theory in particular. Often, even simple new comers of physics participate. For example, we would like to show, in a subsequence lesson in the classroom, a relation proposed by the first author of this paper, a distinguished jurist and lover of general science. This relation allows us to deduce the Lorentz factor without knowing the relative velocity between the reference frames.

The Full House reboot you thought only existed in your best and most nostalgic dreams could become a reality. Warner Bros. Television is said to be in very early and preliminary talks to bring back the Tanners in a new show that would include some of the original cast, according to a report from TV Guide. News of the possible reboot are not surprising, however. The show, which originally aired from 1987-95, lives on not just on repeats but in a cloud of fond nostalgia. Every mini cast reunion — be it on late night or in Super Bowl commercials — gets former fans talking. Moreover, Disney Channel had great success in bringing back character from 90s sitcom Boy Meets World via spin-off Girl Meets World, which centered on Cory (Ben Savage) and Topanga's (Danielle Fishel) pre-teen daughter. According to the report, John Stamos, who played Uncle Jesse, is said to be championing the idea, and original executive producers Bob Boyett and Jeff Franklin are said to be involved as well. On the cast side, D.J., Stephanie and Kimmy — er, Candace Cameron Bure, Jodie Sweetin and Andrea Barber — are also interested, as are Bob Saget and Dave Coulier. Don't hold your breath for any mention of Mary Kate and Ashley Olsen being involved. Keep in mind, "talks" happen all the time in Hollywood, with a fraction of projects actually moving forward. So this reboot is far from reality at this point, but as Jesse and the Rippers sang, it's ok to dream.

Mini-grid based electrification in Bangladesh: Technical configuration and business analysis This paper presents a local level study of a village off-grid system in Bangladesh. It applies an integrated methodology that identifies the demand in the off-grid village context using alternative scenarios. The techno-economic analysis of the optimal off-grid system architecture is then presented using HOMER software. Three energy resources are considered, namely solar energy, wind and diesel fuel. The optimal configuration suggested for the scenarios consists of diesel generators for the basic level of demand and PV-diesel hybrid for higher demand and reliable supply scenarios. The cost of electricity per kWh remains high for the basic level of supply and decreases as the system size increases. However, the capital and asset replacement costs increased considerably for bigger systems. The business case is then analysed for each scenario and it was found that it is practically impossible to reach grid price parity even with full capital cost subsidy, indicating significant amount of operating cost subsidy requirement that makes the larger systems financially unsustainable. Moreover, the small mini-grid system for the basic level of supply emerges as a cheaper option than providing the consumers with solar home systems. But the monthly electricity bill will become unaffordable for most consumers when demand restrictions are removed. Accordingly, the paper suggests a mini-grid based electricity supply to provide the basic level of provision alongside productive energy use during off-peak hours as the starting point. If the business develops and the demand improves, the system can be expanded subsequently using appropriate technology combinations. Introduction Being at the forefront of Solar Home System (SHS) dissemination in the world, Bangladesh holds a special place in any discussion on off-grid electrification. In this densely populated, low-income country of 152 million people (in 2012), the overall rate of electrification is reported at 56% in 2011, thereby forcing about 40% of the population to rely on kerosene for lighting purposes. However, there exists a significant variation between the rural and urban areas. 80% of the population resides in rural areas but only about 49% of the rural population is electrified whereas about 89% of the urban population is said to be electrified. Although SHS has been successfully introduced in the country, particularly by Grameen Shakti, it has reached only 4% of the rural households and 0.5% of the urban households so far. The Government aims to provide electricity to all by 2021 and although the strategy appears to consider both off-grid and grid extension options, the task looks increasingly challenging. Although a lot of academic and other studies have analysed the case of Bangladesh, the literature focuses on two dimensions: the success of Bangladesh in introducing rural electrification through the rural electrification co-operatives (Palli Bidyut Samitis or PBS) (see Ref. for example) and the success of Grameen Shakti in introducing SHS (see Refs. and for example). However, neither PBS nor SHS has succeeded in ensuring universal electrification of the country and in the case of SHS the use of electricity for productive purposes has remained insignificant. Moreover, a fieldbased appraisal of SHS in Bangladesh reported various shortcomings including use of poor quality components, poor installation and an inadequate quality control mechanism. A few other studies (e.g. Refs. and ), among others) have considered the case of hybrid off-grid systems for rural electricity supply but their analysis remains limited to just techno-economic analysis using a simulation tool, namely HOMER. Most of these studies are hypothetical in nature, rely on representative households consuming identical levels of energy for a given period of time, use generic technology/financial information and thus provide an overall understanding of the hybrid option. Although these provide useful information, such techno-economic analysis does not really indicate whether the service can be provided as a viable business, whether costs can be recovered through affordable tariffs and whether the investment can be mobilized and if so, under what conditions. The purpose of this paper is to argue for a transition to mini-grid based off-grid power supply in Bangladesh through a comprehensive analysis of the business case. The main aim is to understand the needs of the rural communities and identify the appropriate solutions based on local resource availability so that an affordable solution can be proposed that is financially viable and socially desirable. This work thus goes beyond the standard application of a simulation tool and adds value by bridging the above knowledge gap. The paper is organized as follows: Section 2 presents the methodology used in this work; Section 3 presents the case study background information, Section 4 presents the techno-economic analysis of alternative scenarios using HOMER, and Section 5 presents the business case analysis. Finally some concluding remarks are provided in the concluding section. Methodology Unlike most studies that focus on techno-economic feasibility of a given solution or alternative solutions (e.g. see Refs. ), this study presents a multi-dimensional analysis covering the technoeconomic, business and governance dimensions. Although technoeconomic analysis still remains relevant, the work does not stop there. The outcome is further processed to consider the appropriate business delivery option and the conditions required to achieve such a delivery model. Moreover, given the diversity of local conditions that exist in reality, instead of using a stereotypical representative village or locality with fixed characteristics, this paper relies on scenarios of cases that capture different socio-economic conditions, stakeholder preferences, potential opportunities and alternative options. Thus this analysis aims to add value by expanding the knowledge frontier through a holistic analysis of off-grid systems. The analysis starts with a detailed needs assessment which involves local information gathering to understand the socioeconomic characteristics of the local population, their existing and potential livelihood, commercial and productive activities (agriculture and small-scale industries) as well as community-related needs. Instead of developing a single point energy demand estimate, alternative scenarios are developed considering different levels of energy service development (e.g. basic lighting needs, lighting and some livelihood/productive needs, service for a limited period of time, and reliable round-the-clock service, among others). It is also possible to consider multi-village systems for economies of scale. The techno-economic analysis of appropriate electricity supply system for each scenario is then carried out using HOMER software package developed by NREL. Each case study considers alternative resource options taking local resource availability into consideration as well as alternative scenarios for electricity needs developed in the previous step. This also leads to a further level of iteration that provides a rich set of system configurations and their life-cycle costs corresponding to alternative development paths. Information has also been used to reflect the local cost of energy system components wherever possible. Whereas other studies end here, this study takes a step further to analyse the results obtained from the techno-economic analysis to consider the practical electricity supply business issues such as viability, funding, tariff and cost recovery, as well as issues related to business environment such as regulatory governance. The flowchart of the framework is presented in Fig. 1. This work thus enhances the framework suggested in Ref. and complements it. In the following section, the above framework is implemented using a case study. Village background This paper considers a non-electrified village in Netrokona district of Dhaka division. Netrokona has the lowest level of electrification in the Dhaka division and is comparable to other poorly electrified districts of the country. Although Netrolona Palli Bidyut Samiti (PBS or village co-operative) exists and has electrified the urban areas, the villages remain non-electrified. The district is in the north of the country and its remoteness has resulted in poor level of electrification in many semi-urban and rural areas. The chosen village, Mahishpur, comes under Atpara sub-district and is situated at 90 50 0 E and 24 48 0 N. Atpara is a remote subdistrict, many parts of which are not well connected by road. The village under consideration holds 108 households with a total population of 546 people as per 2011 Census (of which 295 are male and 251 female). The average household size is 5.1 persons but the household size follows a bell-shaped curve with a minimum of 2 persons and a maximum of 8 persons. The village is not electrified and does not have piped water supply. All households live in houses owned by them but more than 97% of the houses are "kutcha". 47% of the population is less than 14 years old while about 5% is above 60 years of age. Of the working-age population, women largely take care of household activities and men work in agriculture for living. The village is connected through rural roads from Atpara and Baniajan, which are bigger villages nearby but part of it gets disconnected during the rainy season. Being non-electrified, the local population relies on kerosene and candles for lighting purposes and fuel-wood, agricultural residues (e.g. jute sticks) and cow-dung cakes for cooking energy. The energy resources for cooking are collected or procured locally. Needs assessment and scenarios As an agricultural village, the local population is highly dependent on agricultural activities for living. The soil is fertile and generally multiple crops are produced. The main crops are paddy, wheat, jute, mustard seed and potato. The village also supplies various fruits, namely mango, jackfruit, banana, and papaya. The area receives more than 2400 ml of rainfall during the year but the monsoon brings most of the rain, thereby causing floods in the area on a regular basis. The area, being part of the freshwater wetland ecosystem, boasts of a number of large water bodies (ponds, lakes, etc.) and fishing is also an important activity. However, due to lack of electricity no processing of food or fish takes place locally and most of the produce is sold in raw form in the nearby markets. However, natural drying of food crops, fruit and cash crops like jute takes place in the village. To analyse the possibility of electrification through off-grid systems, the scenario approach is used to develop alternative electrification options and pathways. Given the non-electrified nature of the village, the demand is unknown but through alternative scenarios, a range of demand possibilities is considered as follows: a) Basic: Basic Service (residential demand) e In this scenario, it is assumed that the poor households only use electricity for lighting purposes, while the middle income and rich households use it for fans, TV and battery charging. There is no demand for productive use and the service is available for a limited period of time in the evening hours. b) Basic: Basic evening load along with day-time productive demand e This scenario extends the earlier scenario by adding demand for productive uses of electricity during any off-peak time. Such activities can include local artisanal activities and agro-based activities such as grinding, fooddrying, rice milling, and similar small-scale activities or even agricultural water pumping at night. c) Reliable: Reliable supply scenario e This scenario relaxes the time limited supply constraint by providing reliable supply to all consumers. In this scenario, demand from households at any time of the day and commercial/productive demand as they arise are considered. d) Unconstrained: Full-fledged supply e This is similar to RS but here a higher demand is considered and 24/7 supply is envisaged. Although more scenarios can be created, the above cases will provide a good understanding of local demand-supply conditions and the effect of them on the techno-economic performance of the system. In the absence of income distribution information for the specific village, this work relies on the national income distribution profile for rural areas to capture the distribution of households by income categories. Income categories are classified into three groups as follows: households with less than 6000 taka/month income is classed as poor, household with income above 6000 taka/ month but less than 15,000 taka/month are considered as medium income and any household with income above 15,000 taka/month are considered as rich. According to the above regrouping, 46% of the households are poor, 15% are rich while 39% of the households come under the middle income population. This results in 50 households in the poor category, 42 in the middle income category and 16 in the rich category. Based on the Household Income and Expenditure Survey 2010, it is estimated that the poor are likely to spend 468 taka/month on lighting and fuel, while the middle income and rich households are likely to spend 572 taka and 768 taka per month respectively. As the village is non-electrified, the consumption pattern is not available. However, past studies on Bangladesh provide a very standard pattern of consumption in off-grid areas: for example Roy considers that rural households use 3 efficient lamps of 15 W each, 2 or 3 ceiling fans of 80 W each, a television of 80e120 W also uses the same load assumptions. Lights are operated for 6e7 h a day, fans are operated 8e10 h per day during summer and a television is operated for 5e6 h a day. Ref. on the other hand considers 3 lights of 15 W each, 2 fans of 40 W each and a TV of 40 W. The assumptions behind the needs assessment are indicated in Table 1. A number of alternative possibilities is considered. For example, initially the load may be limited to domestic use and the supply may be limited during evening hours only. This is captured in the Basic scenario. The possibility of developing limited commercial load in the evening and some productive load during the off-peak day hours is considered in Basic scenario. As the table suggests, the demand pattern varies by the economic condition of the households and by season (summer and winter). The overall distribution of demand is obtained by summing the demand in each category of consumer in a given period. Load profile for different scenarios Given our scenarios discussed above, the load profiles are quite different in each case thereby allowing us to analyse a range of load situations. a) Basic e basic load profile As the demand is restricted only during evening hours, following the demand logic indicated in Table 2, the daily demand profile for the basic load is shown in Fig. 2 while the seasonal profile is shown in Fig. 3. The winter load is almost half of that in summer due to absence of fan load of middle and high income households. A 5% day-to-day random variation in load is assumed. The peak load of the system is 15.7 kW for 108 households and the average energy need is 53 kWh/day. Clearly, the average to peak load is low in this case, thereby resulting in a low system load factor of 0.14. b) Basic scenario (off-peak productive load and some commercial load added to Basic case) In this case, it is considered that 10 kW of productive load is serviced during the day time (between 7 AM and 5 PM) during summer months while the load reduces to 5 kW during the winter months. The average load improves, resulting in a better system load factor of 0.34. The average daily energy need comes to 135 kWh. The peak load is 16.3 kW. The summer and winter daily load profiles are presented in Fig. 4 while the seasonal profile is indicated in Fig. 5. c) The Reliable supply scenario focuses on reliable supply in rural areas both for residential needs as well as productive needs. This allows any load to operate at any time of the day. The load profile changes considerably here as some residential load at night (mainly for fans in summer) and up to 10 kW water pumping load for irrigation in summer has been considered. In winter, the demand for irrigation water reduces but a 5 kW load is considered at night. During the day time, up to 10 kW productive load in summer and up to 5 kW in winter have been considered. Here the system load factor further improves to 0.472 due to a better load distribution. The daily load profile and seasonal load profile are presented in Figs. 6 and 7 respectively. The peak load here is 28.5 kW and the daily energy demand is 323 kWh. Note that the winter base load is 5 kW whereas the summer base load is 10 kW in this case, which makes the system requirement quite different from the previous cases. d) Unconstrained supply scenario The scenario allows full demand potential development for the rich consumers and removes all supply restrictions. Consequently, the peak demand increases to 44 kW here and the overall load factor improves to 0.55. The average daily energy requirement increases to 589 kWh. The daily load profiles and seasonal profile are presented in Figs. 8 and 9 respectively. Table 2 compares load profiles of different scenarios. Energy resources For the case study, three energy resources, namely solar PV, wind and diesel fuel have been considered. The site does not have any micro-hydro potential but biomass is readily available and is widely used for cooking purposes. However, as there is limited use of biomass for power generation in Bangladesh, this option has not been considered in this study, although it may be considered in a future study. The solar energy availability in the case study village is obtained from HOMER. Based on the latitude e longitude information for the village location, HOMER estimated the annual average solar insolation of 4.58 kWh/m 2 /d. However, the insolation level increases between March and May and reduces during the monsoon season (JulyeSeptember). The monthly pattern of radiation and the trend of cleanliness index are shown in Fig. 10. The data for wind resources is not readily available for Bangladeshi villages. However, provides monthly average wind speed for a nearby location in the Dhaka Division. In the absence of any specific data for the village, this information has been used (see Fig. 11). It can be seen that wind blows all year round but the speed tends to be higher during the summer-monsoon months. The diurnal pattern strength of 0.0323 is used for the location and the wind speed peaks at 15 h. For diesel generators, it has been assumed that the fuel is available from the national supply system and being incremental in nature, the village level demand will not affect the market conditions adversely. The prevailing local rates for diesel have been used, which may not reflect the true economic cost of the fuel. Component details Based on the above resource and demand considerations, the following components were considered: Solar PV, a generic 1 kW wind turbine, a generic 3 kW wind turbine, a diesel generator, batteries and converters. The specific details of each are provided below. Solar PV The unit cost of solar PV systems has declined considerably in recent time. For this study, a 1 kW PV system is assumed to require $2800 and the replacement cost is $2000 per kW. A low operating and maintenance cost of $10/year/kW is considered. The cost is based on. It is assumed that no tracking device is used. The life of solar panels is assumed to be 20 years. The simulation is carried out for various quantityecapacity combinations to facilitate optimal sizing of the system. Wind turbines Two generic small wind turbines, namely of 1 kW capacity and 3 kW capacity suitable for rural application are included. According to, the civil construction and erection cost of wind turbines can be significant compared to the equipment cost, particularly in the small size range. Although the capital cost of 1 kW wind turbine can be close to $2500/kW, the overall cost of installation can be as high as $5000 to 6000. Accordingly, a capital cost of $4000/kW is used while the replacement cost is taken as $2500. The O&M cost is taken as $50/year for this turbine. It is assumed to have a life of 15 years and the hub height is 25 m. For the 3 kW wind turbine, the capital cost is taken as $10,000 whereas the replacement cost is taken as $8000, with $250/year considered towards O&M costs. Although and others have used lower costs for Bangladesh, our cost assumptions are closer to the reality. Diesel generator Diesel generators are widely used for electricity generation in rural areas and are widely available. There is minimal civil work involved in this case and the generator cost captures the overall investment requirement. The capital cost of 1 kW of generator is considered to be $600 and the replacement cost is considered as $500. The operational and maintenance cost of the generator is taken as $0.5/hr for every 10 kW of generator size. It is assumed that the generator can be operated for 15,000 h in its lifetime and the minimum load it can take is 10% of its rated capacity. Diesel price is taken as $0.6/litre which is based on the local market price in Bangladesh. Battery For this analysis, Trojan L16P has been considered. This is a 6 V battery with a nominal capacity of 360 Ah and a normal life of 10 years. 4 batteries in a string are used so that a 24 V bus bar can be used. The cost of batteries varies widely depending on the make and source of supply. For this study, a cost of $150 for each battery is used while the replacement cost is taken as $100. Inverter The cost of converter is taken as $200/kW and the replacement cost is taken as $150/kW. It has a normal life of 15 years and is assumed to have an efficiency of 85%. Other system costs: As HOMER does not include the cost of distribution network separately, a capital cost of $3000 towards the cost distribution network for 108 households is used and $200 per year towards fixed O&M costs. The project life is taken as 15 years e this is done to match the project life with the debt repayment period. HOMER calculates any salvage value of the assets based on its remaining life and the replacement cost of the asset. Therefore, although components have different life periods, the project cost is fairly attributed for the project life. A real discount rate of 5.3% has been used in the analysis, based on the cost of capital in dollar terms. Clearly, the economic parameters affect the overall results significantly. As mentioned earlier, some recent studies on Bangladesh have used quite different economic parameters (see Table 3 for some examples). Clearly, a lower capital and operating cost of any equipment makes it more desirable for the optimal solution and the cost of generation reduces. However, unrealistic costs reduce the relevance of the analysis and distort the optimal solution. Results of the techno-economic analysis For the techno-economic analysis, HOMER software package was used. The results for each scenario are presented below. Basic supply scenario Considering the demand, component cost characteristics and resource availability, a diesel generator of 20 kW emerges as the optimal architecture for this scenario. The capital cost comes to $15,000 and the annualized operating cost comes to $7514/year (see Table 4 for cost summary). The levelised cost of electricity comes to $0.465/kWh. The diesel generator operates 1825 h/year and consumes 8209 L of diesel/year. As the life of the generator is limited to 15,000 h, a replacement is required after 8.2 years and an investment of $10,000 is required at this time. The generator produces 19,345 kWh in a year and there is no excess electricity production that goes waste in this case. The power generation profile is indicated in Fig. 12. Scenario Basic The optimized system architecture for this scenario consists of a 10 kW PV system and a 10 kW diesel generator alongside 72 Trojan L16P batteries, and a 10 kW inverter e rectifier. The capital cost for this system comes to $49,800 and the net present cost (NPC) comes to $184,509, with a levelised cost of $0.368/kWh of electricity generated. 27% of electricity output comes from the PV system, whereas 73% comes from the diesel generator. Practically no excess electricity is produced in the process that goes unused. The monthly generation profile is indicated in Fig. 13 below. The mean output of PV system is 40.3 kWh/day and the annual electricity generation amounts to 14,719 kWh. The PV system operates for 4378 h in a year and the levelised electricity cost from PV is $0.178/kWh. The monsoon months generally record reduced solar output (see Fig. 14). The capital cost of PV arrays comes to $28,000 and the PV system achieves a capacity utilisation of 16.8%. The diesel generator runs for 4133 h per year, leading to a capacity utilisation of 44.5%. It produces 38,970 kWh/year and consumes 14,926 L of diesel. The diesel generator costs $6000 but adds another $16,253 for fuel costs over the project life time. Due to higher utilisation of the generator, its overall life reduces to 3.6 years and accordingly, four replacements are required during the project life. Each time, $5000 will be required to replace the generator. The power generation profile of the diesel generator is shown in Fig. 15. The battery system has a nominal capacity of 156 kWh and provides an autonomy of 19 h. The annual throughput of the batteries is 10,261 kWh. The expected life of the batteries is 7.5years and they have to be replaced once during the project lifetime requiring an investment of $7200. The capital cost for the battery system comes to $10,800 and the net present value of batteryrelated costs comes to $19,301. The second best configuration consists of a 10 kW PV, 1 kW Generic wind turbine and a 10 kW diesel generator supported by a battery bank of 64 batteries and a 10 kW converter. The initial capital cost comes to $52,600 while the NPC comes to $188,049 and the levelised cost of electricity comes to $0.375/kWh. The renewable energy share improves to 30% in this case but the reduction in diesel use is more than offset by the increased investment required for the wind turbine, thereby increasing the capital requirement and the levelised cost of supply. A diesel-only system comes as the least capital intensive option but in terms of cost of supply, it ranks towards the bottom of the range. A 20 kW diesel generator that runs for 5475 h and consumes 21,736 L of diesel can meet the demand effectively. But the cost of electricity increases to $0.471/kWh, making this one of the least preferred option in terms of net present cost. However, the system requirement simplifies here as the generator can be operated as required. The excess electricity generation is practically nonexistent in this case and the capacity utilisation improves to 28%. Although this scenario requires a bigger system compared to the Basic Supply Scenario, a better load distribution improves the capacity utilization of the system and hence reduces the unit cost of electricity generation. However, the capital cost is about 3.3 times higher than the basic system suggested in Basic Supply scenario. This requires further attention, which is considered in the business case analysis. Reliable supply scenario The optimal system corresponding to this scenario requires 30 kW PV and a 20 kW diesel generator alongside 160 batteries, and a 15 kW inverter-rectifier. The capital cost comes to $126,000 while the NPC comes to $435,552. The levelised electricity generation cost comes to $0.363/kWh. As shown in Fig. 16, PV arrays provide 34% of the electricity output while the remaining 66% comes from the diesel generator. The system also produces about 1% excess electricity that remains unused. The solar PV produces 121 kWh/day and operates for 4378 h per year producing 44,157 kWh of electricity per year (see Fig. 17). The levelised cost of solar electricity comes to $0.178/kWh and achieves a capacity factor of 16.8%. The capital cost of PV system comes to $84,000. The diesel generator operates for 4939 h and produces 86,701 kWh/year. It consumes 33,550 L of diesel and achieves a capacity utilization rate of 49.5%. The capital cost required for the diesel generator is $ 12,000 but the fuel cost comes to $204,767 over the life of the project. Accordingly, the diesel system accounts for the highest share of the net present cost in this scenario. The power output is shown in Fig. 18. The expected life of the generator is about 3 years and consequently, 4 replacements are required during the project life, requiring $10,000 each time in investment. The battery system has a nominal capacity of 346 kWh in this case and provides an autonomy of 18 h. The charging status of the batteries is shown in Fig. 19. The capital cost of batteries comes to $24,000 but the expected life of batteries is 5.9 years, thus requiring two replacements during the project life. The second-best solution comes with a 30 kW PV system alongside a 1 kW wind turbine and a 20 kW diesel generator supported by a set of 160 batteries and a 15 kW converter. The capital cost comes to $130,000 but the net present cost comes to $436,792. The diesel generator requires 441 L of diesel less than the optimal case but this does not offset the capital cost of a wind turbine, making the option less attractive in terms of cost of electricity supply. However, it achieves 35% renewable energy share compared to 34% in the optimal case. A 30 kW diesel generator could also meet the needs effectively and would require about $21,000 in capital investment but the operating cost makes this the least preferred solution in terms of cost of supply. The levelised cost of electricity comes to $0.463/ kWh. The diesel requirement also increases to 52,045 L in this case. In terms of levelised cost, this becomes the least preferred option, despite being the least capital intensive option. However, a 20 kW diesel generator along with 56 batteries and 1 10 kW converter turns out to be a better option than a diesel generator alone, as it can serve the load at a cost of $0.379/kWh. The capital cost increases to $25,400 but the fuel requirement reduces by more than 3600 L, thereby reducing the cost of supply substantially. Unconstrained supply scenario The optimal system architecture for this scenario requires 50 kW PV, and a 30 kW diesel plant supported by 200 Trojan L16P batteries and a 25 kW inverter-rectifier. The capital cost for this system is $196,000 while the NPC comes to $752,290. The levelised cost of electricity for the system is $0.344/kWh. The electricity generation mix for this scenario is as follows: 31% of output comes from PV, and 69% from the diesel plant. Thus, renewable energy penetration in the optimal system is 31%. Like other scenarios, excess electricity amounting to about 1% of the demand is produced which is not used. The electricity production mix is shown in Fig. 20. The PV arrays produce 202 kWh/day and over the year produce 73,595 kWh. The monthly distribution of solar output is shown in Fig. 21. The capital cost for the PV system comes to $140,000. The diesel generator operates 5889 h per year and produces 160,621 kWh (see Fig. 22). It consumes 61,835 L of diesel and has an expected life of 2.55 years. Thus, although the initial capital required for the diesel generator is $18,000, the present worth of the replacement cost comes to $51,424. The present value of the fuel-related cost, $377,407, is however the most important cost element for this scenario. The second best solution consists of a 50 kW PV system, 1 kW wind turbine and a 30 kW diesel generator alongside 200 Trojan L16P batteries and a 25 kW converter. The capital cost of this system comes to $200,000 but the NPC comes to $753,517, making the levelised cost higher than the optimal solution ($0.345/kWh). A 50 kW diesel generator can meet the demand with the least capital investment (of $33,000) but as before it emerges as a less preferred solution due to high operating cost. The diesel requirement increases to 92,845 L and the generator operates 8760 h per year. The above scenarios provide alternative pathways of development of the off-grid electrification system. They also can be viewed as pathways to improve the system as the benefits of electrification lead to higher demand. A comparison of the optimal solutions for four scenarios shows (see Table 5) the following: -It appears that a diesel-based system is a preferable solution when the demand is limited and the supply is restricted. As the demand improves and the supply is provided round the clock, hybrid systems appear to be more appropriate. -The initial investment cost is considerable for the hybrid systems. This happens due to intermittent nature of the renewable resources that require back-up capacities. Accordingly, all hybrid systems require a significant spare capacity, thereby reducing the overall system capacity factor. The reserve capacity in all these cases is high. -Depending on the size of excess capacity maintained in each scenario, the cost per kW of peak load serviced varies. But the initial investment cost of diesel-based systems tends to be comparatively low but the capacity replacement charges can be high for both diesel-based systems and hybrid systems. This is an important consideration for business viability analysis. While initial capital grants can help develop a system, unless there is adequate revenue generation to meet future costs, the longterm sustainability of a solution cannot be guaranteed. This aspect is hardly considered in the techno-economic analyses. -The cost of service remains quite high for all cases and considering the size of the poor population in the area, the cost can be unaffordable to many users. The electricity tariff approved by the Electricity Regulatory Commission for residential consumers is just $0.04/kWh for consumption up to 100 kWh. It is evident that in all scenarios the levelised cost of supply from off-grid sources is much higher. Therefore, the issue of business case for the investment needs to be considered separately, which is considered next. Business and governance analysis of alternative scenarios The techno-economic analysis considered above is useful in analysing the optimal technology combinations for a given energy demand. However, it does not perform any financial analysis of business investment. For example, the capital requirement is different for different optimal solutions and some sub-optimal solutions in a technical sense may even make more business sense, particularly when private investment is being looked into. Moreover, as the cost of supply turned out to be high, options for reducing the supply cost becomes important to make supply affordable to consumers. However, any such cost reduction mechanism has financial implications for the government, or the supply business or both. Therefore, a balance has to be achieved between affordable supply to consumers and business viability from the investors' perspective. In this section a number of business-related questions is considered to see how the off-grid options considered in the previous scenarios can be delivered. Financial cost-benefit analysis The analysis presented here follows the principles of financial cost-benefit analysis. It is considered that a viable investment project (from the investors' perspective) must generate positive net present benefits (i.e. the net present value of costs should be less than the net present value of benefits). In the case of our off-grid electricity supply project, the costs include initial investment, fuel-related costs, operating and maintenance related costs, and the cost of replacing assets. The benefits on the other hand come from sale of electricity and for the financial analysis, this only considers the revenue generated from sale of electricity. For each type of stakeholder (namely investor, consumer and the government), different aspects are considered. For example, an investor while looking for adequate return on the investment has to ensure that the debt is repaid on time and the asset is replaced on schedule so that the business can be run effectively. This requires ensuring adequate funding for debt repayment and asset replacement. Similarly, consumers of different groups pay different tariffs for grid connected supply. A similar approach is used here as well. As the consumers are likely to compare the charges for off-grid service to the tariff charged for grid-based supply, this is considered in our analysis to see if grid price parity can be achieved. The effect of grid parity tariff on other stakeholders is also considered. Further, the rental charges paid for solar home systems is considered as an alternative and analyse the effects of such tariffs on the business. Finally, the burden on the government finances is also analysed. Basic supply scenario Here, an initial investment of $15,000 is required, followed by an investment of $10,000 in the 9th year. In addition, $4925 per year is spent on fuel and $1825/year is spent on operating and maintenance costs. Accordingly, these recurring costs contribute significantly to the overall cost of electricity supply. In this scenario only residential demand exists and each household, whether rich or poor, consumes less than 40 kWh per month. All consumers use electricity when it is available and hence contribute to the peak load in proportion to their demand. The regulated tariff for residential consumers using up to 100 kWh per month is set at taka 3.05 ($0.04). Is it possible to achieve grid tariff parity for the off-grid supply in this scenario? Out of the two major cost components, if the capital required for the assets is supported through a grant, the consumers would need to bear the operating costs only. Assuming that 100% of the asset replacement costs are borne through a grant, the cost of electricity comes to $0.387/kWh. This implies that even if $15,000 is provided to the project operator as a capital grant, the cost of electricity reduces slightly and the average electricity cost remains almost 10 times higher than the grid-based electricity. If the initial capital as well as the capital required for asset replacement is provided through a grant fund, thereby reducing the entire capital-related cost, the electricity charge per unit for the operating cost recovery comes to $0.359. Thus, just capital subsidy cannot ensure grid tariff-parity for this off-grid solution e some operating cost subsidy will also be required. In fact, if grid parity pricing is charged, the net present value of revenue comes to $7871 over the project life which will not recover even the operator's cost and the distribution system fixed cost. Thus, it appears that aiming for a grid parity price for the off-grid system is a non-starter from any perspective. No business case can be made for such an option. However, a more appropriate reference point could involve a comparison with the solar home systems (SHS). Given that solar home systems are popular in Bangladesh, it is legitimate to ask whether it makes economic sense to go for a diesel-based mini-grid instead of promoting SHS in such off-grid areas. Grameen Shakti, the leading SHS provider in Bangladesh, provides the equipment costs for various system capacities. A 10 W system costs $130, a 20 W system costs $170, a 50 W system costs $380, a 80 W system costs $560 and a 135 W system costs $970. 1 In our scenario, a low income consumer is considered to use a 20 W load, while the medium and rich consumers use 190 W and 240 W respectively. As the systems are not directly comparable, it is assumed that the low income groups would go for a 10 W SHS, while the medium and high income groups would go for 50 W and 80 W systems respectively. Based on the household distribution used in our analysis, there are 50 poor households, 42 medium income households and 16 rich families. The total system cost for SHS for all these families comes to $31,420. Even considering a 4% discount offered for 100% down-payment, the capital requirement comes to $30,163 (i.e. two times the capital requirement for the mini-grid in Basic supply case). Clearly, from the capital cost perspective, the diesel mini-grid makes economic sense. As the batteries have to be replaced at least twice over the 15 year period and the electricity output will be much less than the diesel-based system, the cost of electricity delivered from the SHS would come to $0.715/kWh. 2 Thus, from the life-cycle cost perspective, the SHS investment does not make economic sense compared to the diesel-based minigrid considered in the Basic supply Scenario. If consumers are buying SHS in Bangladesh, it is likely that consumers elsewhere will be willing to pay similar charges for electricity from a mini-grid. Grameen Shakti offers a number of financing options to SHS owners. The least demanding option requires them to pay 15% initially and the rest 85% in 36 equal monthly instalments with a flat rate service charge of 8%. For our three chosen system sizes of 20 Wp, 50 Wp and 80 Wp, the initial payment comes to $20, $59, and $80 respectively while the monthly payment comes to a flat charge of $3.3, $10 and $14.3 respectively. Can these amounts be sufficient for the off-grid service suggested in BS Scenario? In this scenario, our households consume more in summer than in winter due to fan loads for the medium and high income groups but for the low income group, the consumption pattern does not vary seasonally. Accordingly, the summer consumption is considered to find out their monthly expenditure at full levelised cost and with capital grant support. This is presented in Table 6. As can be seen, the poor consumer groups would be paying about 50% of the cost they would be paying for a SHS while the middle income and high income groups would pay slightly more than that for a SHS in summer months. However, it needs to be kept in mind that the SHS would not provide the same level of electricity service as they get from the diesel-based mini-grid. But if they consume less, as is shown in the case of winter months, their payment will be reduced and can be lower than that of the SHS. Similarly, with 100% capital grant subsidy, the cost reduces but not very dramatically. It can thus be concluded that for a limited level of supply over a fixed number of evening hours, a diesel-generator based mini-grid option can be a suitable option that requires about one-half of the capital cost of SHS based supply and provides a higher installed capacity. Poorer consumers with just fixed lighting loads can be charged a fixed monthly rate whereas other consumers can be charged based on their consumption level. The cost recovery is considered based on the costs payable for a SHS, this option can be suitable for implementation by socially-responsible private entities and by community-based organisations. Moreover, the technology in this case is widely available and can be operated using locally available skills. The option is however less environment friendly as it depends on a fossil fuel. It also faces the risk of fuel price fluctuations, but as a less capital intensive option, this offers a good starting point for building demand in off-grid areas. However, even for such a small-scale initiative, the investor has to secure more than a million taka, which may need financial and organizational support. Basic scenario In this scenario, a day-time productive load of 10 kW has been considered in addition to the evening residential-commercial loads. Thus, the productive load is serviced outside the evening peak. The system configuration changes in this case and a hybrid system emerges as the optimal choice. The capital cost required for this option is $49,800. In addition, the batteries require one replacement in the 8th year ($7200) and the diesel generator requires four replacements in the 4th, 8th, 11th and 15th years. The total capital requirement for asset replacement is $27,000 but its net present value comes to $17,671. Following the economic pricing principle, if the off-peak consumption is charged to cover the operating cost only, the tariff for productive use comes to $0.242 (or about 18 taka per kWh). Although this is about 3 times the prevailing rate for this category of consumers of grid electricity, it is cheaper than the alternative supply from a diesel generator (which comes to $0.33/kWh for operating cost coverage and $0.423 for full cost coverage). For other peak load consumers, the economic principle requires the tariff to recover full costs including capital costs. The levelised cost for full cost recovery comes to $0.368, which is lower than that for Basic scenario. Consequently, residential consumers pay less on average compared to the previous scenario and they can expect to reduce their spending even compared to owning a SHS. However, as shown in Table 7, the revenue so generated is not sufficient to meet the revenue requirement of the electricity supplier. Thus, the strict economic cost recovery principle cannot be applied in this case. One option could be to allocate the balancing cost to the productive users. This can be done in a number of ways but the most common options would be either to charge a fixed per kW/month charge in addition to the energy rate or to increase the energy rate without adding any fixed charge. The fixed charge has some merit as a part of the revenue will flow even if the user does not consume energy for any reason. Given the size of the productive load considered here, a monthly fixed charge per kW can be a logical choice. It becomes clear that the addition of a productive load brings the average cost of supply down and improves the financial position of the supplier. This happens despite an increase in the capital requirement, although only small companies may become interested in this size of business. As the cost recovery is likely to be possible even without any government intervention, this can become a viable business opportunity in Bangladesh. However, it may be difficult to realise the full potential of productive load instantaneously. This highlights the importance of mapping local level opportunities and enlisting support of local stakeholders early in the development process. In addition, support for such ventures through some risk sharing arrangements can improve the attractiveness of the business. Although this is a hybrid system, the diesel generator still plays an important role. Thus, this option can be viewed as an extension of the previous scenario where the operation starts with a diesel generator for a restricted period of supply and then expands to include off-peak productive load. However, the supplier is likely to continue with its diesel generator in such a case, which, as mentioned earlier, is not the least-cost option given the high fuel cost and asset replacement cost. However, such a gradual approach may make practical sense given the limited stress on initial capital requirement. Reliable supply scenario In this scenario, the supply reliability is considered, when 24 h of service is made available, allowing consumers to use electricity at night. This changes the demand situation considerably and the system configuration changes accordingly. All consumers now contribute to the peak demand, which increases the peak capacity requirement. Accordingly, all consumers should bear the responsibility for the peak load. In such a case, a time-differentiated tariff could be appropriate but given the small volume of consumption involved, the metering cost is likely to outweigh the benefits. Accordingly, a simple pricing system with flat rates for residential and commercial consumers and a fixed charge coupled with an energy charge for the productive uses could be appropriate. The supply system for this scenario requires more PV arrays compared to Basic scenario. The capital cost increases to $122,000 while the diesel generator requires four replacements (at a nondiscounted cost of $40,000) and the batteries require two replacements (at a non-discounted cost of $32,000). The levelised cost of electricity comes to $0.363/kWh, whereas the energyrelated charge comes to $0.227/kWh. However, as before, sufficient revenue will not be recovered if productive users are charged only at the energy-related charge while others are charged at the full levelised cost. Moreover, in this case, there is no justification for the preferential treatment of the productive use, particularly when part of it coincides with the peak hours. Therefore, the tariff has to be carefully designed to avoid undesirable effects. An example is provided in Table 8 where an energy-related charge of $0.31 is used for productive uses supplemented by a fixed charge of $30/kW/ month. Alternative tariff schemes can be developed to suit the specific requirements but a full-scale analysis of this aspect is beyond the scope of this paper. Table 8 shows that the low income consumers will still pay less than that required for owning a SHS for a comparable service. However, a comparison with the SHS cost becomes somewhat less relevant for the middle and high income groups as they receive round-the-clock power from the mini-grid compared to a limited supply from the SHS. Although they are likely to spend more on electricity cost for a reliable supply, the cost per unit of electricity is less. The average monthly bill between $20 and $27 for these categories is however much higher than these groups pay on fuel and electricity as per the Household Income Expenditure Survey. Moreover, the monthly bill for productive loads will be significant due to high consumption level and this can be a disincentive for promoting productive loads. A 100% capital grant would reduce the cost to $0.261/kWh but this could still make productive activities reluctant to consume significant quantities of electricity. As the system size increases, the capital requirement increases as well. More importantly, the cost of asset replacement becomes important. Depending on the capital structure and repayment requirement, it is possible that the supplier faces some funding mismatch. This would require access to flexible funding arrangements and short term funding for working capital. However, unless the business is not organized around a bankable contractual arrangement, securing finance from traditional sources can be a challenge. As indicated before, this option can also be considered as an extension of the earlier scenarios, particularly Basic Supply scenario. The advantage here is that the PV system along with the battery and converters can be appended to the diesel generator system suggested for Basic supply scenario. This gradual expansion of the system can work for rural areas where the demand is likely to develop once the benefits of electricity are realized by the population. Similarly, this also allows time for developing the productive load that can act as an anchor for the system. Unconstrained supply scenario This scenario removes supply restriction and allows for full demand development. Accordingly, the high income consumers can use electric appliances like refrigerators, while commercial consumers can use electricity at any time. Consequently, the consumption of middle income and high income households as well as commercial activities increases compared to reliable supply scenario. This scenario results in the least levelised cost of electricity of four scenarios. As in Reliable supply scenario, all consumer categories contribute to peak demand and accordingly are required to bear the consequences by paying appropriate charges. Although the economically efficient tariff would have to distinguish between peak and off-peak periods, the time-of-use metering cost may be difficult to justify for such small consumers. Accordingly, energyrelated tariff supplemented by fixed charges may be relevant. However, as the consumption of poor households does not change compared to reliable supply, they may be charged at a flat rate only. As shown in Table 9, if electricity is charged at the levelised cost of energy, the required revenue can be collected but the monthly bill for average high income households, commercial users and productive consumers becomes quite big, even by developed country standards, thereby suggesting limited attractiveness of such high level consumption for these categories of consumers. The operating cost component in the charge comes to $0.224/kWh, which is closely related to diesel fuel use in the system. The monthly bill will not change significantly even if the charge recovers only the operating costs. This perhaps shows the limitation of a diesel-based hybrid system. Moreover, the capital cost of this system increases to $196,000 (or about 15 million taka), which may be attractive to medium sized firms. As before, the capital requirement for asset replacement also increases to $115,000 (non-discounted). Thus, financing the capital requirement becomes another constraint for this option. Based on the above, analysis, it becomes clear that small-scale supply as indicated in the first three scenarios (Basic, Basic and reliable) can be developed into businesses for rural electricity delivery but as the system becomes bigger with higher demand, the monthly bill can be very high for high energy using consumers. The relatively high cost of supply may not be attractive for consumers and is unlikely to be sustainable. The capital constraint is another issue that can become difficult to overcome. Moreover, capital subsidy alone will not reduce the costs significantly as the operating costs remain high and providing capital and operating subsidy for village level supplies will not be sustainable in the longrun. Remote area power supply system in Bangladesh Bangladesh has set a target of providing universal electrification by 2020. The state-owned agencies like Bangladesh Power Development Board (BPDB), Rural Electricity Board (REB) and Palli Bidyut Samity (PBS) are involved in providing electricity in rural areas. In addition, Grameen Shakti, a non-profit organization, is also actively involved in promoting renewable energy solutions, mainly the SHS. However, recognizing the challenge faced by the country in reaching its target, the Government introduced a new initiative, called the Remote Area Power Supply System (RAPSS) in 2007. This allows the private sector to get involved in rural power supply and the guidelines 3 for the RAPSS indicate that: a) The Power Division of the Government will identify the potential RAPSS areas. These areas would cover the geographical area of two or more sub-districts. b) The system can cover both off-grid and on-grid areas. c) The operator will be selected through a competitive bidding process. d) The operator will operate under a licence from the Bangladesh Electricity Regulatory Commission for a period up to 20 years. e) A fund called RAPSS Fund will be created to support the rural electrification process and will receive funds from the government, donor agencies and other sources. The fund can be used for providing capital grant support, to provide loans of 5e10 years duration, to subsidise connection charges and to offset duty, tax and VAT. f) The retail supply tariff will be set initially through the bidding process but if the tariff is significantly higher than the tariff charged by the nearest PBS, then the government may decide to provide subsidy to close the gap, depending on the funding available from the RAPSS Fund. 4 g) The capital cost subsidy can be given up to a maximum limit of 60% and if the retail tariff still remains high, soft loan can be provided from the fund. The RAPSS Guidelines provide a framework for private sector involvement in rural electricity supply but from our analysis it becomes clear that even if 100% capital cost subsidy is provided, the cost of supply will remain higher than the retail tariff approved by the regulatory commission for different categories of consumers. Table 10 shows the amount of capital subsidy required under different scenarios and the operating subsidy required to reach the grid price parity in rural areas under the optimal configurations considered in this study. Clearly, it shows that trying to reach the grid price parity will impose significant financial burden on the government, particularly for reliable supply, and unconstrained supply scenarios. They are unlikely to be sustainable solutions. This happens even after providing significant capital support. The first two options could still be considered as the capital subsidy requirement is not too demanding and the price parity can be restricted to poor consumers while others may be charged the levelised cost. This will reduce the operating cost subsidy. The case of sub-district level operation can provide the required scale economy and may ensure larger systems for local grids where higher technical efficiency of operation can also be expected. This can be an area for further research where an analysis using the terms and conditions offered by RAPSS guidelines can also be considered. Conclusions This paper has considered the village-level electrification in Bangladesh and analysed the viability and business case of a hybrid mini-grid system for a remote non-electrified village in Dhaka division. The analysis developed alternative demand scenarios, considered local resources for electricity generation, conducted techno-economic analyses of all scenarios using HOMER and performed business analysis. The demand scenarios captured alternative development pathways e starting from basic level supply for 5 h per day to unrestricted, reliable supply consisting of residential, commercial and productive loads. The techno-economic analysis suggested optimal configurations that consisted of diesel generators for the basic level of supply and hybrid PV-diesel solutions for more elaborate services. The renewable energy share in all configurations varies between 0% (in the basic cases) to 60% (in S5) and the cost of electricity per kWh decreases as the system size increases. However, the hybrid systems require significant excess capacity due to intermittent nature of solar energy and consequently, the initial investment requirement increases. Moreover, during the project life some assets (such as batteries and diesel generators) need to be replaced depending on their life and extent of use. This requires significant investment at regular intervals to keep the system going. The analysis of business case of the investments revealed that the levelised cost of electricity from the off-grid options is much higher than the regulated tariff for various categories of consumers who receive grid electricity. However, the cost of off-grid supply is likely to be cheaper than the cost of owning a SHS. Low income consumers will pay almost one half of the cost of owning a SHS for a comparable level of energy use while the high income users may be paying somewhat more for the restricted level of supply, although the monthly bill will not be too burdensome for low level of supplies. However, the problem arises when demand restrictions are removed allowing consumers to use high volumes of energy. Their monthly bills will be burdensome, making higher consumption unattractive. This happens despite a reduction in cost of electricity per kWh due to high capacity-related costs and operating costs of the system. It is also found that capital cost subsidy will not be sufficient to ensure grid price parity and significant amount of operating cost subsidy will be required. As the operating cost subsidy will impose a recurring burden on government's finances, it is unlikely to be sustainable. This makes the energy access challenge significant. Our analysis suggests that the basic electricity supply provision through a mini grid is the most preferable business solution e it requires less capital, less subsidy volume and moderate monthly bills for Table 9 Example of electricity bill and revenue generation at the levelised cost of electricity for unconstrained supply scenario. consumers. Such a business can be organized by local entrepreneurs, private investors or local community organisations. Bangladesh has been promoting Remote Area Power Supply System since 2007 where private investors can enter into rural electricity supply through a competitive bidding process for a maximum period of 20 years. This allows sub-district level geographical areas under the jurisdiction of the licensee. However, the objective of achieving grid-like pricing may be difficult to attain with capital subsidy and soft loans, unless the system has a low operating cost. This is an area for further investigation.

Comparative nephrotoxicity of a novel platinum compound, cisplatin, and carboplatin in male Wistar rats. The nephrotoxicity of three platinum-containing antitumor agents was compared at doses that approximate the LD10 (cisplatin) or the LD50 (CI-973, carboplatin) doses. Male Wistar rats were administered single iv doses of 45 mg/kg CI-973, 6.5 mg/kg cisplatin, or 65 mg/kg carboplatin and observed for 4 days. Cisplatin treatment increased blood urea nitrogen (4x), creatinine (3x), glucose, and fractional electrolyte excretions, and decreased creatinine clearance by Day 4. These parameters were not significantly altered in CI-973- and carboplatin-treated animals. Cisplatin increased urinary excretion of LDH (six-fold), GGT (twofold), and NAG (twofold); CI-973 and carboplatin increased GGT excretion (approximately twofold). Cisplatin induced the following functional changes as a consequence of direct nephrotoxicity: decreases in GFR (84%), ERPF (97%), ERBF (96%), and ERTS (95%), and increases in FF (fivefold). Functional changes, attributed to prerenal effects of CI-973, included a decrease in ERPF (35%) and an increase in FF (48%). No changes were seen following carboplatin treatment. All cisplatin-treated rats had proximal tubular necrosis in the outer stripe of the outer medulla, extending multifocally into inner cortical medullary rays. No renal lesions were detected by light or electron microscopy in the control or CI-973- or carboplatin-treated rats. Cisplatin produced marked nephrotoxicity as determined by biochemical, functional, and histopathologic endpoints. CI-973 and carboplatin were significantly less nephrotoxic than cisplatin.

Perioperative application of salvianolate on oxidative stress and plasma IMD/ADM2 in patients with acute myocardial infarction undergoing PCI The present study was conducted to investigate the effects of salvianolate on perioperative oxidative stress and plasma Intermedin/adrenomedullin 2 (IMD/ADM2) in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). The clinical data of 108 patients with AMI treated by PCI were retrospectively analyzed. According to the use of salvianolate in perioperative period, the patients were divided into the study group (n=62) and the control group (n=46). The control group was given routine treatment while the study group was given routine treatment combined with intravenous infusion of salvianolate (200 mg administered once at 24 h before operation, once/day after operation, 1 week later, the curative effect was observed). The changes in levels of hemodynamic indexes , oxidative stress indexes , cardiac function indexes , related biochemical indexes and plasma IMD/ADM2 in the two groups at 24 h pre-operation and the 8th day postoperation were analyzed. On the 8th day post-operation, hemodynamic indexes such as FIB (3.3±1.0 and 3.9±0.9) g/l, PAG (20.6±6.5 and 41.6±7.7)%, plasma viscosity (1.1±0.5 and 1.7±0.6) mPas/120 s−1 and PCV (40.0±3.8 and 45.5±3.7)%, the related biochemical indexes such as hs-CRP (55.1±4.8 and 79.3±5.3) mg/l and NT-proBNP (435.6±305.2 and 788.6±310.8) ng/l in the two groups were significantly decreased compared to those pre-operation; the differences were statistically significant (P<0.05). The oxidative stress indexes such as SOD (43.6±1.9 and 24.2±2.0) U/ml and GSH-Px (822.6±13.52 and 742.6±62.6) enzyme activity unit, the cardiac function indexes such as LVEF (45.1±3.5 and 41.9±3.3)% and CO (4.6±0.5 and 4.1±0.5) l/min and plasma IMD/ADM2 (163.5±20.2 and 144.2±22.5) pg/ml in the two groups were significantly increased compared to those pre-operation; the differences were statistically significant (P<0.05). In conclusion, applying intravenous infusion of salvianolate in patients with AMI during perioperative period of PCI can effectively improve the oxidative stress reaction and have positive effects on regulating plasma IMD/ADM2 level, which promoted cardiac function recovery and enhances myocardial perfusion volume. Introduction According to previous literature, the incidence of acute myocardial infarction (AMI) in China tends to increase gradually year by year, with an estimated >500,000 new AMI cases each year. Its high incidence and mortality rates have caught extensive attention of clinicians and society. The way to improve the clinical curative effect on AMI and reduce the risk of death through scientific and effective curative methods has become a hot topic of investigation. With salvianolic acid as its main active component, salvianolate is the purified extract of saliva and can activate blood and disperse stagnation. When applied in the clinical treatment of AMI, salvianolate has positive effects on promoting the recovery of myocardial perfusion volume, relieving myocardial blood microcirculation and improving lipid peroxidation. An increasing number of scholars have found that Intermedin/adrenomedullin 2 (IMD/ADM2) can exert its effect together with the common receptor of calcitonin gene-related peptide (CGRP) superfamily and play a positive role in regulating the homeostasis of cardiovascular and respiratory system. The higher the plasma IMD/ADM2 level is, the greater its effect on cardiovascular protection. At present, there are quite a few clinical reports on the effect of salvianolate on the hemodynamic state and myocardial damage of patients with AMI, but few studies have conducted extensive investigations on its effect on the plasma IMD/ADM2 of the subjects. As a result, this study retrospectively analyzed the clinical data of 108 patients with AMI treated by percutaneous coronary intervention (PCI), compared the oxidative stress indexes, inflammatory indexes, cardiac function indexes, hemodynamic indexes and plasma IMD/ADM2 level in the two groups and investigated the effects of perioperative application of salvianolate on promoting cardiac function recovery and improving its prognostic quality. The present study was conducted in order to seek more effective approaches to provide a basis for improving the postoperative recovery of patients with AMI treated by PCI. Materials and methods Data source. The clinical data of 108 patients with AMI treated by PCI from October 2012 to April 2014 in our hospital were retrospectively analyzed. Inclusion criteria were as follows: i) Patients who met relevant AMI diagnostic criteria according to American College of Cardiology/American Heart Association ; ii) patients who met relevant treatment indications for PCI; iii) patients who were classified as Killip Ⅱ-Ⅲ; iv) patients with time window <6 h. Exclusion criteria were as follows: i) Patients complicated with infectious disease, severe autoimmune disease, hemorrhagic disease, coagulation disorder, severe organ dysfunction syndrome or malignant tumor; ii) patients complicated with mental diseases or consciousness disturbance; iii) patients with allergic constitutions or relevant treatment contraindications; iv) patients who were >80 years old; v) pregnant or lactating women; vi) patients who were classified as Killip Ⅰ or Ⅳ; vii) patients who were dead or transferred or whose therapeutic schedules were changed during perioperative period or who were out of touch during follow-up period. According to the use of salvianolate in perioperative period, 108 patients were divided into the study group (n=62) and the control group (n=46). The study group included 39 males and 23 females, aged from 45-79 years, with an average of (66.4±8.2) years. Time window was 2.2±1.0 h. A total of 42, 21 and 38 cases, respectively, were complicated with hypertension, diabetes and hyperlipidemia; 25 cases were complicated with family heredity history. The control group included 29 males and 17 females, aged from 44-80 years, with an average of 66.7±8.0 years. Time window was 2.3±1.1 h. A total of 32, 18 and 27 cases, respectively, were complicated with hypertension, diabetes and hyperlipidemia; 20 cases with family heredity history. Basic data of the two above groups were of no statistical significance (P>0.05) and comparable. Curative methods. Patients in the two groups were all treated by PCI according to the Guidelines of American College of Cardiology/American Heart Association. Patients were administered oral medication of 300 mg clopidogrel + 300 mg aspirin before operation and atorvastatin calcium tablets, aspirin and clopidogrel after operation, and administered nitrates, receptor blocker and angiotensin converting enzyme inhibitor as ordered by doctors according to the severity of the illness. The study group was given the above-mentioned treatment combined with intravenous infusion of salvianolate. Salvianolate (200 mg, license no. NMPN: Z20050248; Shanghai Green Valley Pharmaceutical Co., Ltd., Shanghai, China), was administered intravenously once at 24 h before operation, once/day after operation, administered on the day of operation, 1 week later, the curative effect was observed. Indexes of detection methods. From each patient 5 ml morning fasting antecubital venous blood was drawn at 24 h before operation and the 8th day after operation, and the high-sensitivity C-reactive protein (hs-CRP) level was detected by ELISA according to the operation instruction of hs-CRP kit (Shanghai Xinyu Biotechnology Co., Ltd., Shanghai, China), the NT-proBNP level was detected by colloidal gold method according to the operation instruction of NT-proBNP kit (Hangzhou Puwang Biotechnology Co., Ltd., Hangzhou, China), the superoxide dismutase (SOD) level was detected by xanthine oxidase method according to the operation instruction of SOD kit (Shanghai Solarbio Biotechnology Co., Ltd., Shanghai, China), the GSH-Px level was detected by colorimetric method according to the operation instruction of GSH-Px kit (Shanghai Huzheng Biotechnology Co., Ltd., Shanghai, China), the plasma IMD/ADM2 level was detected by radioimmunoassay according to the operation instruction of IMD/ADM2 kit (Phoenix Pharmaceutical Inc., St. Joseph, MO, USA). Cardiac function indexes such as left ventricular ejection fraction (LVEF) and cardiac output (CO) were detected by diasonograph (ACUSON X300; Siemens AG, Munich, Germany). The plasma viscosity was detected by blood viscometer (LG R 80 series; Beijing Zhongqinshidi Scientific Apparatus Co., Ltd., Beijing, China). Fibrinogen (FIB) was detected by automated coagulation analyzer (ACL7000; Beckman Coulter, Inc., Brea, CA, USA). Platelet aggregation rate (PAG) level was detected by kinetic turbidimetry method. Packed-cell volume (PCV) level was detected by Wen's method. Observation indexes. Clinical data from the two groups were retrospectively analyzed. The changes in levels of hemodynamic indexes (FIB, PAG, plasma viscosity, PCV), oxidative stress indexes , cardiac function indexes (LVEF and CO), related biochemical indexes (hs-CRP, N-terminal pro brain natriuretic peptide) and plasma IMD/ADM2 at 24 h before operation and the 8th day after operation were compared. Statistical processing. SPSS 19.0 (SPSS, Inc., Chicago, IL, USA) statistical software was used for recording and analysis. The data are expressed as mean ± standard deviation, and evaluated by t-test. P<0.05 was considered to indicate a statistically significant difference. Results Comparison of hemodynamic indexes between the two groups before and after treatment. On the 8th day postoperation, hemodynamic indexes such as FIB, PAG, plasma viscosity and PCV in the two groups were significantly decreased compared with those before operation; the differences were statistically significant (P<0.05) ( Table I). Comparison of oxidative stress indexes between the two groups before and after treatment. On the 8th day postoperation, oxidative stress indexes such as SOD and GSH-Px in the two groups were significantly increased compared with those pre-operation; the differences were statistically significant (P<0.05) ( Table II). Comparison of cardiac function indexes between the two groups before and after treatment. On the 8th day postoperation, cardiac function indexes such as LVEF and CO in the two groups were significantly increased compared to those pre-operation; the differences were statistically significant (P<0.05) ( Table III). Comparison of related biochemical indexes between the two groups before and after treatment. On the 8th day postoperation, the level of hs-CRP and NT-proBNP in the two groups were significantly decreased compared to those pre-operation; the differences were statistically significant (P<0.05) ( Table IV). Comparison of plasma IMD/ADM2 level between the two groups before and after treatment. On the 8th day postoperation, plasma IMD/ADM2 level in the two groups were significantly increased compared to those pre-operation; the differences were statistically significant (P<0.05) ( Table V). Discussion AMI is a common clinical cardiovascular disease with high mortality rates and great influence on the health, safety, prognosis and quality of life of patients. At present, there are numerous clinical reports on the pathogenesis of AMI. Overwork, emotional excitement, overeating, cold and hot stimulation, long-term alcohol abuse or smoking can increase the risk of AMI, which needs clinical attention. Currently, PCI is one of the most important clinical operations that can rebuild blood supply of patients with AMI. PCI has positive effects on shrinking myocardial infarction areas, promoting the recovery of myocardial blood supply, relieving ischemia and anoxia. Relevant studies have shown that the epicardial-vascular blood perfusion volume of most patients with AMI gradually recovered after treatment of PCI, which may increase the risk of thrombus detachment or distant embolism of microcirculation, damage the microcirculation after treatment, affect cardiovascular reflow, increase the probability of re-infarction and harm to the prognosis recovery of patients. Methods to promote the recovery of hemodynamic indexes after treatment of PCI and regulate the oxidative stress response of the human body through effective curative methods has become an important investigation field. As main active component of the Chinese medicinal material salvia, salvianolate is a kind of salt compound whose main constituents are salvia magnesium acetate and magnesium lithospermate B. It is known to exert multiple effects on activating blood, dispersing stagnation, anti-oxidation, anti-platelet aggregation, scavenging free radical and improving blood microcirculation. It has also been widely used in clinical treatment of multiple cardiovascular and cerebrovascular diseases. The present study retrospectively analyzed the clinical data of 62 patients treated by intravenous infusion of salvianolate during perioperative period of PCI and found that on the 8th day postoperation, cardiac function indexes such as LVEF and CO in the two groups were significantly increased compared with those before operation. These results showed that intravenous infusion of salvianolate peri-operatively is more beneficial for the cardiac function recovery of patients and has positive effects on improving myocardial perfusion volume and promoting the recovery of CO. Fan et al also acknowledged the conclusions mentioned above in their reports, and they believed that >80% of salvianolate is salvia magnesium acetate, which can play an important role in expanding cardiovascular blood flow, inhibiting the synthesis of endothelin, and help improve myocardial ischemia and anoxia to promote a positive outcome. Apart from cardiac function, the effects of salvianolate on the oxidative stress response, inflammatory response and the changes in levels of hemodynamic indexes in perioperative period of patients with AMI were also analyzed in the study. We found that the plasma viscosity, FIB level, PCV and PAG in the patients in the study group, who used salvianolate during perioperative period, were all lower compared to those in the control group. These results are consistent with the conclusion of Yang et al. This confirms that the peri-operative application of salvianolate can effectively reduce plasma viscosity, facilitate fibrinolysis, accelerate thrombolysis and inhibit re-thrombosis post-operationally by activating plasminogen to promote the recovery of patients with AMI. In addition, the function of anti-oxidation and scavenging free radical can also help regulate the oxidative stress response of the human body and increasing the SOD level post-operation so as to exert SOD's function of regulating blood lipid metabolism and anti-aging, doubly improve the hemodynamic state during the perioperative period to reduce the risk of re-infarction postoperation. As a common clinical inflammatory marker of AMI and an important risk factor for cardiovascular diseases, hp-CRP is a type of highly-sensitive, non-specific acute phase reaction protein which can correctly reflect the inflammatory status. After PCI, the hp-CRP level in the study group was significantly lower than that in the control group, showing that salvianolate can regulate the systemic inflammation to some degree which may be related with the spontaneous reduction of systemic inflammation after the improvement of cardiac function and the recovery of hemodynamic state. IMD/ADM2, whose structural function is similar to adrenomedullin, is a new member of CGRP superfamily and can ideally protect the cardiovascular system in cardiovascular disease. Previous study has demonstrated that IMD/ADM2 is closely related with the incidence, development and outcome of coronary heart disease ; although its structure is similar to AMD, the mechanism of action and the physiopathological significance of the two have obvious differences, which should be taken seriously. The present study also places emphasis on the influence of salvianolate on the plasma IMD/ADM2 level of patients with AMI during PCI peri-operative period, and found that the plasma IMD/ADM2 level of the patients with AMI was significantly decreased compared to the Table V. Comparison of plasma IMD/ADM2 level between the two groups before and after treatment (mean ± standard deviation, pg/ml). Before The 8th normal value, showing that the protective effect of human body on the cardiovascular system was weakened. Furthermore, the study found that the plasma IMD/ADM2 level post-treatment of PCI and intravenous infusion of salvianolate was significantly increased compared to that before treatment and than that in the control group. This confirms that the application of salvianolate during PCI perioperative period can regulate the IMD/ADM2 level of human body to some degree. After the medicine, the oxidative stress indexes, the status of blood lipid metabolism and hemodynamic status were all significantly improved compared to those before treatment. This was beneficial for relieving cardiovascular damage and promoting the recovery of the function of cardiovascular system. Apart from above-mentioned conclusions, Liu et al included some other clinical application methods of salvianolate into the research, and found that it can not only exert positive effects on cardiovascular and cerebrovascular diseases, but also achieve antitumor effect in vitro by functioning in cell cycle and inducing tumor cell apoptosis. This mechanism can be further investigated as another clinical feasible direction of therapy of salvianolate. Limited by the number of samples, the present study did not analyze the effect of salvianolate on inhibiting tumors in cancer patients by listing patients with AMI as key research subjects. As a result, the accuracy of the conclusions mentioned above is hard to evaluate, but it can be further analyzed as a follow-up research topic after enrolling more patients. The present study found that applying intravenous infusion of salvianolate in patients with AMI during perioperative period of PCI can not only promote the recovery of disease of patients with AMI, improve the hemodynamic status and accelerate the recovery of myocardial microcirculation, but also regulate the oxidative stress reactions of human body, reduce inflammatory responses and improve the plasma IMD/ADM2 level. However, due to the limited quantity of samples and the time of follow-up visits, certain parts of the present study are significantly different from other reports, which can be further analyzed as follow-up after enlarging the quantity of samples. In conclusion, applying intravenous infusion of salvianolate in patients with AMI during perioperative period of PCI can effectively improve the oxidative stress reactions, have positive effects on regulating plasma IMD/ADM2 level, promote cardiac function recovery, enhance myocardial perfusion volume, and help the recovery of the patients.

THE GROWTH AND DECLINE OF THE ANCIENT MAYA CITY OF LA MILPA, BELIZE: NEW DATA AND NEW PERSPECTIVES FROM THE SOUTHERN PLAZAS Abstract Construction histories of ancient Maya monumental centers have long been used to interpret the growth and decline of Lowland Maya polities. Changes in the built environment at monumental centers reflect labor appropriation by ruling elites and may indirectly serve to gauge changes in political clout over time. Consequently, the precision and accuracy with which archaeologists measure these changes take on increased importance when assessing the ancient Maya political landscape. Recent excavations in the monumental core of La Milpa, Belize, have generated new data that call for a re-assessment of the center's historical trajectory. Our data indicate that La Milpa had a larger Late Preclassic foundation, likely grew much more incrementally through the Classic period, and persisted centuries longer than previously understood. The apparent persistence of occupation into the tenth century a.d. challenges the traditionally accepted dates for La Milpa's abandonment, and, the ceramic sequence upon which it is often based.

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Prophase I arrest and progression to metaphase I in mouse oocytes: comparison of resumption of meiosis and recovery from G2-arrest in somatic cells. Mammalian oocytes are arrested at prophase I until puberty when luteinizing hormone (LH) induces resumption of meiosis of follicle-enclosed oocytes. Resumption of meiosis is tightly coupled with regulating cyclin-dependent kinase 1 (CDK1) activity. Prophase I arrest depends on inhibitory phosphorylation of CDK1 and anaphase-promoting complex-(APC-CDH1)-mediated regulation of cyclin B levels. Prophase I arrest is maintained by endogenously produced cyclic adenosine monophosphate (cAMP), which activates protein kinase A (PKA) that in turn phosphorylates (and activates) the nuclear kinase WEE2. In addition, PKA-mediated phosphorylation of the phosphatase CDC25B results in its cytoplasmic retention. The combined effect maintains low levels of CDK1 activity that are not sufficient to initiate resumption of meiosis. LH triggers synthesis of epidermal growth factor-like factors in mural granulosa cells and leads to reduced cGMP transfer from cumulus cells to oocytes via gap junctions that couple the two cell types. cGMP inhibits oocyte phosphodiesterase 3A (PDE3A) and a decline in oocyte cGMP results in increased PDE3A activity. The ensuing decrease in oocyte cAMP triggers maturation by alleviating the aforementioned phosphorylations of WEE2 and CDC25B. As a direct consequence CDC25B translocates into the nucleus. The resulting activation of CDK1 also promotes extrusion of WEE2 from the nucleus thereby providing a positive amplification mechanism for CDK1 activation. Other kinases, e.g. protein kinase B, Aurora kinase A and polo-like kinase 1, also participate in resumption of meiosis. Mechanisms governing meiotic prophase I arrest and resumption of meiosis share common features with DNA damage-induced mitotic G2-checkpoint arrest and checkpoint recovery, respectively. These common features include CDC14B-dependent activation of APC-CDH1 in prophase I arrested oocytes or G2-arrested somatic cells, and CDC25B-dependent cell cycle resumption in both oocytes and somatic cells.

Propagation studies in the region of the oxygen absorption band in an urban environment Experimental results obtained from a propagation study carried out on a 55GHz mobile radio link in Central London are presented. Results indicate that frequencies in this region are a viable proposition for a potential mobile radio system from the propagation point of view. The bandwidth in the multipath environment appears to be adequate and polarisation diversity is also a possibility.

Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease. Treatment of chronic obstructive pulmonary disease (COPD) exacerbations improves outcomes; however, responses to treatment are variable, and patients with COPD often delay presentation or fail to seek therapy. The impact on exacerbation outcomes, hospitalization, and health status of delaying or failing to seek treatment is poorly understood. We studied between 1996 and 2002 a cohort of 128 patients with COPD, mean (SD) FEV of 1.07 (0.43) L. Patients recorded respiratory symptoms daily and reported exacerbations to the outpatient-based study team or to their primary care physician; 1,099 exacerbations were recorded by the patients, of which 658 were reported to a physician. The time between exacerbation onset and treatment was a median (interquartile range) of 3.69 (2.0-5.57) days, and the exacerbation recovery time was 10.7 (7.0-14.0) days. Earlier treatment was associated with a faster recovery (regression coefficient 0.42 days/day delay) (confidence interval, 0.19-0.65; p < 0.001). Patients who reported a higher proportion of exacerbations for treatment had better health-related quality of life than those patients with more untreated exacerbations (rho = -0.22, p = 0.018). Failure to report exacerbations was associated with an increased risk of emergency hospitalization (rho = 0.21, p = 0.04). Patient recognition of exacerbation symptoms and prompt treatment improves exacerbation recovery, reduces risks of hospitalization, and is associated with a better health-related quality of life.

--LHP Tyler Matzek got the start on Wednesday in the series finale against the Nationals. He was not involved in the decision as he was lifted with one out in the seventh with the score 3-3. "He was about at his ceiling" after throwing 95 pitches, manager Walt Weiss said of Matzek. --LHP Franklin Morales will start on Thursday in Los Angeles against the Dodgers. He is 17-22 in his career with an ERA of 4.68. --1B Justin Morneau had three hits Monday against the Nationals and had two more Wednesday to finish with six hits in the series. But most of hits in the series went to waste -- once again Wednesday he did not score or drive in a run. --SS Troy Tulowitzki did not start Tuesday as he was given a night off, according to manager Walt Weiss. He was back in the starting lineup Wednesday and helped make two double days in the first two innings. Second baseman DJ LeMahieu flipped him the ball with his glove and Tulowitzki turned and threw the ball to first for a highlight-reel double play. "One of the best double plays I have seen this year," said Weiss, a former major league shortstop. QUOTE TO NOTE: "It was a breaking ball. Desi got the barrel on it. Those are the ones we have to put away." -- Rockies manager Walt Weiss on the homer by Nationals SS Ian Desmond in a 4-3 loss on Wednesday. --LHP Brett Anderson (broken left index finger) went on the 15-day disabled list retroactive to April 13, and he was transferred to the 60-day DL on April 25. He had pins surgically inserted in the finger April 17. He had the pins removed from the finger May 27. He pitched for Triple-A Colorado Springs on July 2. --3B Nolan Arenado (left middle finger mallet fracture) went on the 15-day disabled list May 24. He was examined by a hand specialist in Cleveland on May 30, and it was decided he would not need surgery. He began a rehab assignment June 28 with Triple-A Colorado Springs and should come off the DL on July 3.

Standardized experiments in mutant mice reveal behavioural similarity on 129S5 and C57BL/6J backgrounds Behavioural analysis of mice carrying engineered mutations is widely used to identify roles of specific genes in components of the mammalian behavioural repertoire. The reproducibility and robustness of phenotypic measures has become a concern that undermines the use of mouse genetic models for translational studies. Contributing factors include low individual study power, nonstandardized behavioural testing, failure to address confounds and differences in genetic background of mutant mice. We have examined the importance of these factors using a statistically robust approach applied to behavioural data obtained from three mouse mutations on 129S5 and C57BL/6J backgrounds generated in a standardized battery of five behavioural assays. The largest confounding effect was sampling variation, which partially masked the genetic background effect. Our observations suggest that strong interaction of mutation with genetic background in mice in innate and learned behaviours is not necessarily to be expected. We found composite measures of innate and learned behaviour were similarly impacted by mutations across backgrounds. We determined that, for frequently used group sizes, a single retest of a significant result conforming to the commonly used P<0.05 threshold results in a reproducibility of 60% between identical experiments. Reproducibility was reduced in the presence of strain differences. We also identified a Pvalue threshold that maximized reproducibility of mutant phenotypes across strains. This study illustrates the value of standardized approaches for quantitative assessment of behavioural phenotypes and highlights approaches that may improve the translational value of mouse behavioural studies.

Arjen Robben made a promise yesterday to not dive next season. The Dutchman has been criticised for going to ground too easily, particularly against Liverpool in February when José Reina raised his hand, while Didier Drogba's recent tumbling has further damaged Chelsea's reputation for fair play. "Those things happened," said Robben. "Diving has been a very big issue this season, I think. Everyone has his opinion about it. I have mine. You have yours. I don't want to look back. I want to look forward. Next season I won't be in the headlines for diving again. That's a promise. Next year you won't write about me diving again." Robben said the regularity with which he fell last season was because of his mental state, created by bad experiences in 2004-05. "If you look back to the season before this, I had three injuries," he said. "I think people forget that sometimes. At that time I had comments like: 'You have to jump sometimes' and 'you have to avoid getting kicked' because I broke my foot three times. Sometimes you just jump out of the way. Sometimes maybe the style of jumping or falling is not the nicest but I haven't been kicked this season and that's a good thing. I'm not a diver. I know that. Next season I'll just carry on the way I play and I won't change my game at any time." The flak Robben endured for his style of avoiding injury this season - with Chelsea's manager Jose Mourinho believed to have been unhappy about it - means Robben could be forgiven for seeking refuge by leaving Stamford Bridge. With the arrival of Michael Ballack imminent, a move would seem logical but Robben feels he still has a lot to offer. "People forget I'm still only 22. I have a lot of confidence. I'm not afraid about losing my place. Maybe with some extra world-class players coming in it's going to be even harder but I am very confident."

Relationship Bank s Management Efficiency and Client Firm s Performance : A Case of Pakistan Author s Details : Firm-bank relationship is a matter of interest as a strong bonding may lead to a better performance of the client firm. The foggy mirror of the fate of such relationships needs more clarification on the said matter. This research investigated the effect of management efficiency of relationship bank on its client firms performance. The data set consists of the observations for the period from 2006-2016. All the non-financial listed firms on Pakistan Stock Exchange are taken for analysis. We have taken all the common proxies for the firm performance like ROA, ROS, ROE and Tobins Q and regressed them over bank-specific and firm-specific variables. For management efficiency, two types of measurements are considered, i.e., ME and LME. Our results have reported management efficiency of the relationship bank as a vital factor in explaining the fate of firm-bank relationship and its performance. It is found to be significant and positive for client firms performance. Further analysis has exposed that if the increased number of firmbank relationship causes an increase in financial cost as well, then the benefit of maintaining a relationship with a bank (efficient in management) is set off.

Fri., Oct. 28, 2016, 8:24 p.m. It took two extra days and several bags of drying compound, but University finally got its slowpitch softball championship. Kylee Hughes went 3 for 3 with a home run, Kirsten Anstrom had three hits and scored twice and University (22-0) defeated visiting Mead 10-1 in the Greater Spokane League title game on Friday. It’s the second year in a row the teams have faced off for the title. U-Hi has won nine GSL titles and has played in every district championship game in the 11 years that slowpitch has been an official sport in the GSL. The title game, originally planned for Wednesday, had to be rescheduled twice because of rain. “Mother nature finally cooperated,” U-Hi coach Jon Schuh said. All but one Titans starter had a hit and eight of their 10 batters scored, with no errors on defense. U-Hi trailed 1-0 headed to the bottom of the third. With two outs, Anstrom started the rally with a triple and scored on a double by Courtney Awbery. Awbery came home on a single by Natasha Nelson to give U-Hi the lead for good. The Titans busted it open in the fourth. Hughes led off with a homer to right. Consecutive singles by Hannah Click and Emily Stannard put runners on the corners. Kourtney Richardson plated a run with a single, Sierra Apocada drove in a run with a sacrifice fly to center and the last run came in on Anstrom’s single to make it 6-1. Anstrom, a senior, said coming into the title game undefeated made it that much more challenging. “It’s definitely more nerve-wracking,” she said. “It’s not like we were coming in with nothing to lose. It’s like ‘Oh, we gotta win it. We have to play good.’ Everybody wants to take us down. Nelson doubled to lead off the fifth and scored on Brooklyn Hecker’s single to put the Titans up 7-1. U-Hi padded its lead and picked up three more runs in the sixth on four straight singles by Apodaca, Anstrom, Awbery and Nelson. The 10th run came home on a sacrifice fly to center by Hecker, but Nelson was thrown out trying to move up to third to end the inning. By then, the Titans had built a comfortable lead. Click retired Mead in order in the top of the seventh, and the Titans were left to celebrate their title. Click went the distance and limited Mead to one run on 10 hits – all singles. Mead (17-6) was led by Ashley Hammond and Destiny Scott with three hits apiece. Published: Oct. 28, 2016, 8:24 p.m.

GRASP for WDM network design problem with traffic grooming Two important problems arise in WDM network planning: network design to minimize the construction cost and traffic grooming to maximize the usage of high capacity channels. They are usually settled simultaneously and are denoted as the network design problem with traffic grooming (NDG). This paper proposes an approach based on Greedy Randomized Adaptive Search Procedure (GRASP) to solve the NDG problem. A mathematical formulation of the NDG problem is presented and a set of benchmarks generated according to real application scenarios are given for future research in this area, which are missing in the previous literature. Computational results show the effectiveness of the proposed GRASP algorithm by comparison with the public software CPLEX and the lower bound. This paper also shows an analysis on explaining the essential ingredients of the algorithm.

Determining golden process routes in semiconductor manufacturing process for yield management Managing the yield of wafer is one of the most important tasks to the semiconductor manufacturers. A lot of efforts for enhancing the yield of wafer have been conducted in both industries and academia. Thanks to the advance of IoT and data analytics techniques, huge amount of process operational data, such as indices of process parameters, equipment condition data, or historical data of manufacturing process, is collected and analyzed in real-time. Though the amount and availability of process operational data have been increased, existing yield management approaches on semiconductor manufacturing process have only considered a single process or few processes among the overall processes. This study proposes a way to find process routes which maximize the yield of wafer (i.e., golden process routes) in view of multiple process steps. This work is expected to complement the existing efforts for managing the yield of wafer by adding results of process-oriented analysis.

Exploring agent-based simulations in political science using Aggregate Temporal Graphs Agent-based simulation has become a key technique for modeling and simulating dynamic, complicated behaviors in social and behavioral sciences. As these simulations become more complex, they generate an increasingly large amount of data. Lacking the appropriate tools and support, it has become difficult for social scientists to interpret and analyze the results of these simulations. In this paper, we introduce the Aggregate Temporal Graph (ATG), a graph formulation that can be used to capture complex relationships between discrete simulation states in time. Using this formulation, we can assist social scientists in identifying critical simulation states by examining graph substructures. In particular, we define the concept of a Gateway and its inverse, a Terminal, which capture the relationships between pivotal states in the simulation and their inevitable outcomes. We propose two real-time computable algorithms to identify these relationships and provide a proof of correctness, complexity analysis, and empirical run-time analysis. We demonstrate the use of these algorithms on a large-scale social science simulation of political power and violence in present-day Thailand, and discuss broader applications of the ATG and associated algorithms in other domains such as analytic provenance.

As fans get ready for a new chapter of the Ghostbusters universe, attendees of the first-ever Ghostbusters Fan Fest, presented by Wizard World, will hear from Jason Reitman, the director and co-writer (with Gil Kenan) of Sony Pictures' upcoming 2020 Ghostbusters film, on the famed Sony Pictures Studio Lot this June 7th and 8th in Culver City, California. With Ghostbusters (1984) stars Dan Aykroyd (Dr. Raymond Stantz), Ernie Hudson (Winston Zeddemore) and director and producer Ivan Reitman already slated to attend the event with several other stars from across the franchise and a bevy of themed activities, it's the ultimate, once-in-a-lifetime celebration of everything Ghostbusters. "I am thrilled that my role of Brownstone Boy #2 will finally be given proper recognition. Might also chat about the upcoming Ghostbusters film," said Reitman. Reitman is a four-time Academy Award® nominated filmmaker. He made his feature film debut with the 2006 Sundance hit Thank You For Smoking. Reitman notably earned Academy Award® nominations for directing Juno and Up In The Air, the latter of which earned him a Golden Globe® Award, WGA Award and BAFTA Award for Best Screenplay. Other films include Young Adult, Tully, and The Front Runner. Reitman also produced four seasons of the Hulu comedy series Casual through his Right of Way Films. He also executive produced the Academy Award®-winning film Whiplash, Karyn Kusama's Jennifer's Body and Jean-Marc Vallee's Demolition. Jeffrey Godsick, EVP, Brand Management and Global Partnerships, Sony Pictures Motion Picture Group said: "We're excited to be collaborating with Jason Reitman on this new chapter in the franchise. This will be a unique opportunity for fans to get a sneak peek of Jason's vision for the film. The Ghostbusters Fan Fest is shaping up as a can't-miss celebration of Ghostbusters and we couldn't be more pleased that Jason will be such a big part of it." John D. Maatta, CEO of Wizard Entertainment said: "We will continue to bring additional value to fans to ensure the greatest Ghostbusters experience imaginable on June 7 and 8 on the Sony Pictures Studio Lot. Adding Jason to Ghostbusters Fan Fest is the next big step and one that fans will be excited to hear about." Following the event on June 7-8, Wizard World will continue its Ghostbusters touring experience at its conventions throughout the country featuring a pop-up shop featuring exclusive Ghostbusters merchandise. Tickets for the premier event are on sale now. Packages range in price from a just added $149.99 general admission ticket to $1499 for the ultimate VIP experience, with autographs and photo ops included in some packages. Fans can learn more about the Ghostbusters Fan Fest presented by Wizard World.

Coding theorems for the nonsynchronized channel Capacity and error bounds are derived for a memoryless binary symmetric channel with the receiver having no a priori information as to the starting time of the code words. The channel capacity is the same as the capacity of the synchronized channel. For all rates below capacity, the minimum probability of error for the nonsynchronized channel decreases exponentially with the code-block length. For rates near channel capacity, the exponent in the upper bound on the probability of error for the nonsynchronized channel is the same as the corresponding exponent for the synchronized channel. For low rates, the largest exponent obtained for the nonsynchronized channel with conventional block coding is inferior to the exponent obtained for the synchronized channel. Stronger results are obtained for a new form of coding that allows for a Markov dependency between successive code words. Bounds on the minimum probability of error are obtained for unconstrained binary codes and for several classes of parity-check codes and are used to obtain asymptotic distance properties for various classes of binary codes. At certain rates there exist codes whose minimum distance, in the comma-free sense, is not only greater than one, but is proportional to the block length.

Approximation Algorithms for Three-Machine Open Shop Scheduling This paper shows that a greedy algorithm for three machine open shop scheduling with the objective to minimize the makespan provides schedules with the worst-case performance ratio 5/3. A linear time heuristic is presented which improves the schedules and reduces the ratio to 3/2. INFORMS Journal on Computing, ISSN 1091-9856, was published as ORSA Journal on Computing from 1989 to 1995 under ISSN 0899-1499.

A new projective exact penalty function for a general constrained optimization A new projective exact penalty function method is proposed for the equivalent reduction of constrained optimization problems to unconstrained ones. In the method, the original objective function is extended to infeasible points by summing its value at the projection of an infeasible point on the feasible set with the distance to the set. The equivalence means that local and global minimums of the problems coincide. Nonconvex sets with multivalued projections are admitted, and the objective function may be lower semicontinuous. The particular case of convex problems is included. So the method does not assume the existence of the objective function outside the allowable area and does not require the selection of the penalty coefficient.

He may already be established at under-23 level but Norwich City right-back Max Aarons is ‘buzzing’ for FA Youth Cup action at Carrow Road tomorrow night. The 18-year-old has made 18 appearances for City’s U23s this season but has also played in every round of the U18s’ run to the quarter-finals of the Youth Cup, which has teed up Tuesday’s clash with Birmingham (7pm). “It’s really good to play above your age group, it helps you progress a lot more than playing with your own age group,” Aarons said. “So I’m really happy with how the season has gone – and the run we’ve gone on in the Youth Cup as well. Aarons, originally from Milton Keynes, is another to have followed former academy manager Gregg Broughton across from Luton Town, with first teamer Jamal Lewis and U18s team-mate Alan Fleming having followed the same path. The youngster also has an ideal sounding board for advice, in cousin Rolando Aarons, who has progressed through the Newcastle academy, represented England at U20 level and is currently on loan in Italy with Verona. “He spoke to me before the Newcastle game, because he plays for them and just said ‘don’t score!’ and things like that,” Aarons said, of the fifth round 4-3 defeat of the Magpies in extra-time. The young Canaries have had to come from behind in all of their ties so far, beating Barnsley 4-1 in round three and Derby 4-2 in round four, but intend to start quickly against the Blues as they play a fourth successive tie at Carrow Road. Chelsea or Fulham await the winners in the semi-final, with the first leg at home for City or Birmingham.

Prevalence and Risk Factors of Smoking and Vaping among Nursing Students in a Private University in Manila, Philippines Nursing students trained to be health advocates have engaged in cigarette and electronic cigarette (EC) use. Our study aimed to determine the prevalence of cigarette and EC use among nursing students and examine how EC vaping and cigarette smoking are associated with various risk factors. This cross-sectional survey of smoking and vaping was administered to 249 nursing students in a private university in Manila, Philippines. An online-based self- assessment questionnaire (SAQ) that includes socio-demographic information, cigarette and EC usage, Perceived Stress Scale (PSS), and other risk factors was administered using on-campus and online recruitment strategies. Generalized linear models were fitted to estimate the effect of stress and other risk factors on smoking and vaping. Approximately one out of eight were exclusive vapers, one out of 25 were exclusive smokers, and one out of five were both smokers and vapers. The prevalence of smoking/vaping was 47% higher among students with high-stress levels than students with low to moderate stress levels. In addition, students who were sophomores (aPR: 1.69, 95% CI: 1.122.53, p-value = 0.012), juniors (aPR: 3.22, 95% CI: 1.915.42, p-value < 0.001), and seniors (aPR: 1.53, 95% CI: 0.763.08, p-value = 0.230) had a higher prevalence of smoking/vaping compared to freshmen students. Having a positive attitude towards vaping health impacts and a smoker/vaper peer was also associated with a higher prevalence of smoking/vaping. Therefore, effective health communication strategies and policies in universities and the community are recommended to reinforce existing smoking and vaping control efforts.

Assessing the Health and Environmental Benefits of a New Zealand Diet Optimised for Health and Climate Protection Population diets have impacts on both human and planetary health. This research aims to optimise a New Zealand (NZ) version of the EAT-Lancet diet and to model the impact of this diet on population health if it was adopted in NZ. The optimisation methods used mathematical equations in Excel to ensure: population diets met the nutritional recommendations; diet-related greenhouse gas (GHG) emissions did not exceed the NZ GHG boundary; and diet costs did not exceed baseline costs of the average diet. The EAT-Lancet diet was also directly mapped onto the NZ adult nutrition survey food groups, as another estimate of a NZ EAT-Lancet diet. Both diets were modelled using a DIET multi-state life-table model to estimate lifetime impacts on quality adjusted life years (QALYs), ethnic health inequities and health system costs. The optimised diet differed greatly from baseline intake with large amounts of fruits and vegetables, some fish but no beef, lamb, pork or poultry. Modelling nationwide adoption of the NZ EAT-Lancet diets generated large health savings (approximately 1.4 million QALYs), and health system cost savings (around NZD 20 billion). A healthy, climate-friendly, cost-neutral diet is possible for NZ and, if adopted, could provide large health gain, cost savings and reductions in ethnic health inequities.

Doped Ferrite Nanoparticles Exhibiting Self-Regulating Temperature as Magnetic Fluid Hyperthermia Antitumoral Agents, with Diagnostic Capability in Magnetic Resonance Imaging and Magnetic Particle Imaging Simple Summary Hyperthermia, a limited increase in tumor tissue temperature up to a maximum of 45 °C, has long been used in cancer treatment, either as a stand-alone therapy or in conjunction with chemo-/radiotherapy. Among the different physical procedures used, a particularly promising technique is magnetic fluid hyperthermia (MFH): this consists of the local administration of magnetic nanoparticles, followed by the application of alternating magnetic fields. One concern with this technique is the possibility of damage to healthy peritumoral tissue. The present study investigates innovative nanoparticles with self-regulating temperature, which should reduce this risk and thus mark a significant step forward in MFH. In an experimental model of aggressive breast cancer, we demonstrated a substantial reduction of tumor growth rate by using an experimental MFH protocol, transferable to clinical practice. These innovative nanomaterials present the added advantage of allowing non-invasive monitoring of temperature, by magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Abstract This paper reports a comprehensive investigation of a magnetic nanoparticle (MNP), named M55, which belongs to a class of innovative doped ferrite nanomaterials, characterized by a self-limiting temperature. M55 is obtained from M48, an MNP previously described by our group, by implementing an additional purification step in the synthesis. M55, after citrate and glucose coating, is named G-M55. The present study aimed to demonstrate the properties of G-M55 as a diagnostic contrast agent for MRI and magnetic particle imaging (MPI), and as an antitumoral agent in magnetic fluid hyperthermia (MFH). Similar specific absorption rate values were obtained by standard MFH and by an MPI apparatus. This result is of interest in relation to the application of localized MFH by MPI apparatus. We demonstrated the biocompatibility of G-M55 in a triple-negative human breast cancer line (MDA-MB-231), and its efficacy as an MFH agent in the same cell line. We also demonstrated the efficacy of MFH treatment with G-M55 in an experimental model of breast cancer. Overall, our results pave the way for the clinical application of G-M55 as an MFH agent in breast cancer therapy, allowing not only efficient treatment by both standard MFH apparatus and MPI but also temperature monitoring. Introduction Breast cancer is one of the leading causes of cancer morbidity and mortality. A recent review reported that it is the second most diagnosed malignancy, accounting for more than 11.6% of female cancers, and the fifth most common cause of cancer deaths, making up 6.6% of all cancer mortality worldwide. The same review reports that breast cancer induces a substantial public health burden, leading to a loss of 14.8 million Disability Adjusted Life Years (DALYs). Despite progress in early diagnosis of the disease and the variety of therapeutic approaches available, it is still the most frequently reported cause of female cancer deaths. Nowadays, primary mammary tumors can be treated by surgery, followed by chemotherapy or radiotherapy-an invasive and debilitating approach, contributing to the abovementioned public health burden. Chemotherapy and radiotherapy can damage healthy tissues, while surgery entails risks of infection and bleeding and is not always curative for metastatic tumors. Innovative, minimally invasive treatment methods, devoid of negative impacts, are desirable to reduce mortality and morbidity in breast cancer patients. One candidate is hyperthermia, which can be generated from sources such as ultrasound, RF waves and laser beams. Recent advances in nanotechnology have paved the way for magnetic fluid hyperthermia (MFH), combining magnetic nanoparticles (MNPs) with alternating magnetic fields (AMFs). MFH has shown great promise in cancer research, with the potential to overcome many of the limitations presented by other hyperthermia techniques. The challenges of MFH are the need to deliver a large quantity of MNPs to the tumor tissue, and the risk of overheating healthy peritumoral tissue. In currently applied preclinical and clinical protocols, nanoparticles are injected directly into the tumor tissue. For tumors in anatomical regions not readily accessible by injection, an invasive procedure entailing surgery and anesthesia may be required. This is not the case for breast tumors: given that image-guided biopsy is routinely performed in breast cancer, the intratumoral injection of MNPs for MFH treatment could be easily carried out as an outpatient procedure, thus avoiding invasive surgery. For the treatment of tumors located deep in the body, systemic administration of MNPs could be envisaged, although considerably limited by their non-specific uptake to the liver and spleen, typically exceeding specific uptake to the tumor. In this respect, the application of magnetic particle imaging (MPI) to excite MNPs in specific regions of the body has been reported. The field-free region of MPI instrumentation, which can be localized over the tumor with millimetric precision, allows space-selective irradiation of the tumor region. This makes MFH by MPI apparatus compatible with systemic MNP administration, without risk of damage to the liver and spleen, provided sufficient MNPs are delivered to tumor tissue. The risk of overheating healthy peritumoral tissue has been previously addressed by us and by other groups using self-regulating temperature MNPs. Gerosa et al. report an extensive investigation of a self-regulating temperature nanomaterial, synthesized by MBN Nanomaterialia S.p.A. (Treviso, Italy). Such nanomaterials undergo a stable temperature increase when exposed to an AMF, up to a maximum value (TSR, self-regulating temperature) lower than the Curie temperature (T C ). T C values can be modulated by adjusting the composition of the nanomaterial. Above the T C, magnetization is negligible and the heating effect of the AMF ceases. Interestingly, above Tc, a sharp decrease in transverse MRI relaxivity occurs, meaning that the MNP is suitable for use as a temperature-sensitive contrast agent. In principle, these properties are particularly useful when the nanomaterial is integrated into biological matrices, making it possible to limit the maximum temperature and, at the same time, monitor temperature changes by means of imaging. M55, the MNP studied in the present paper, is obtained from previously described M48 material, by implementing an additional purification step in the synthesis process so as to remove potential paramagnetic by-products from the liquid suspension. In investigating this class of materials, we have already considered their properties as theranostic agents for MPI, in view of the foreseen application of MPI in MFH. The capability of M55 as a bimodal contrast agent was demonstrated in vitro, and in a cellular imaging experiment. In addition, we demonstrated the marked therapeutic efficacy of M55 in an experimental protocol, in which four MFH treatments are applied after a single intratumoral injection of MNPs. Synthesis of the Iron-Based NPs The NPs were prepared by MBN Nanomaterialia S.p.A. (Treviso, Italy) following a proprietary mechanochemical process. Briefly, MgO, Fe 2 O 3, and TiO 2 powders with a 4:2:1 molar ratio, respectively, were thoroughly mixed, and the reaction was carried out using ball milling equipment for 6 h. A heat treatment at 1200 C for 4 h in the air was then carried out. The obtained powders were finely ball-milled for 1 h, then homogeneously dispersed in isopropanol and ultrasonicated to promote de-aggregation. Centrifugation was used to extract nanosized particles (<200 nm). This process further improves the one previously used : detailed processing parameters are provided courtesy of MBN Nanomaterialia S.p.A. Structural Characterization The phase and crystal characterization were analyzed by X-ray powder diffraction (XRPD) technique. The X-ray diffraction pattern was measured using an X-ray powder diffractometer (Thermo ARLX'TRA, Waltham, MA, USA) in Bragg-Brentano geometry (Cu source, Si (Li)-cooled solid-state detector) with a scan rate of 0.09 /min. The sample was homogenized in an agate mortar adding some drops of ethanol. The sample was then deposited on a low background stage. The ICSD database was used for phase analysis. Morphological Analysis and Dimensional Characterization The morphology of the NPs was analyzed with transmission electron microscopy (TEM, FEI TECNAI G2). The sample was deposited on a copper grid and then desiccated for one day before the measurements. The hydrodynamic size and zeta potential of the coated nanoparticles were determined with a Malvern Zetasizer Nano instrument. The sample was prepared in an appropriate plastic cuvette, repeating the size and zeta potential measurements for the following 7 days to assess the stability of the coating. Coating of the Iron-Based NPs The NPs were coated with citrate ions, using sodium citrate dihydrate (99%-Alfa Aesar, Haverhill, MA, USA) and glucose (D-(+)-glucose SigmaUltra 99.5%) with a procedure described in. The citrate-and glucose-coated NPs will be referred to below as G-M55. Analysis of the NPs Coating The NPs coating was analyzed by FT-IR spectroscopy with a JASCO FT/IR-660 plus spectrometer. The sample was prepared by dispersing 3 mg of powders of G-M55 in 300 mg KBr and preparing a pellet of 1 cm diameter. Cytotoxicity was assessed through the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-dipheny ltetrazolium bromide) assay after 2, 24, and 48 h of incubation. Then, 100 L of MTT solution (5 mg/mL) was added to each well and incubated for an additional 4 h. Then, the MTT solution was removed and 100 L of DMSO was added to each well to dissolve the formazan crystal. Absorbance was read using an HTX microplate reader (BioTek Instruments, Winooski, VT, USA) at a wavelength of 570 nm. Four measurements of optical density (OD) were recorded for each sample, and cell viability (%) was calculated with the following equation: CV% = (ODsample/ODcontrol) 100. Magnetic Characterization The efficiency of G-M55 as a multimodal contrast agent was assessed in MPI by using a RELAX module (Magnetic Insight Inc., Alameda, CA, USA), and in MRI by using a 7T Bruker Biospec system. In MPI, two components of the measurement were assessed: the signal efficiency was measured through the amount of MPI signal per mass of iron (high signal efficiency results in improved SNR and lower detection limits) and full width at halfmaximum (FWHM), which is related to the imaging resolution (lower FWHM results in less signal spread and improved imaging resolution). The resolution, defined as the distance for 2 objects separated at 50%, was estimated according to the following relationship: Resolution (mm) = FWHM (mT)/Gradient (T/m). A sample containing G-M55 with a concentration of 5.5 g of Fe in 10.0 L volume was vortexed for 5 min and sonicated in a room temperature water bath sonicator for 5 min before testing. Relaxometry measurements were performed, using the RELAX module on naked and coated nanoparticles at the same concentration, and compared to VivoTrax (Ferucarbotran, Magnetic Insight Inc., Alameda, CA, USA). The 1D signal acquisition mode was used for relaxometry measurements. A 2D projection image was used to test the nanoparticles with the following imaging parameters: standard mode, coronal acquisition, 2-channel, FOV = 6 6 cm 2. In order to measure transverse relaxivity (spin-spin relaxation process) in MRI, the transverse relaxation time T 2 of water containing different amounts of G-M55 was measured by acquiring a MSME (multi-slice multi-echo) pulse sequence, with the following parameters: TR = 2000 ms, TE from 6.5 to 170 ms, FOV = 55 55 mm, matrix size = 128 128, slice thickness = 1 mm, number of echoes = 25. The signals coming from each phantom at different TEs were averaged to obtain the relaxation curve decay, which was fitted with a single exponential decay function to obtain the T 2 value. Transverse relaxivity r 2 was then obtained by measuring the modified relaxation time of water through the presence of G-M55 at different NP concentrations, and extrapolated via linear fit using the following equation: 1 where T 2,0 is the relaxation time of pure water, c the concentration of G-M55 (expressed as mM of Fe), and T 2 the modified relaxation time of water. Multimodal Imaging of Cells Labeled with NPs To test the efficiency of G-M55 as an MPI contrast agent in a biologically significant context, it was used in a cellular imaging experiment. MDA-MB-231 cells were seeded and cultured in DMEM with 10% FBS, 1% penicillin/streptomycin 1:1 mix, and 1% L-glutamine 200 mM, in a T-75 flask (5 10 6 cells) and accommodated for 24 h. MDA-MB-231 cells were incubated with 0.1 mgFe/mL (corresponding to 0.256 mg/mL of MNP) of G-M55 for 24 h, to observe iron uptake. Cells were then washed 3 times with 5.0 mL of phosphate buffered saline solution (PBS) and detached with 1.5 mL of 0.25% trypsin, harvested, and centrifuged (1200 rpm for 3 min). After collecting and throwing out the supernatant, the pellet was resuspended in 1.0 mL of PBS. The sample was divided into three portions of 4 10 6 cells in 0.1 mL PBS each, for MPI. Serial dilutions were performed, to obtain samples containing decreasing amounts of cells (from 4 10 6 to 30 10 3 cells). Images of the pellets were acquired with a Momentum MPI scanner (Magnetic Insight Inc., Alameda, CA, USA), using a 2D projection mode scan with the default mode setting (5.7 T/m gradient). The imaging parameters adopted were: field of view (FOV) = 4 12 cm 2 ; single average; acquisition time = 10.0 s for each projection; reconstruction time = 4.0 min. For quantitative MPI analysis, the cell pellet was outlined in a single slice with a freehand region of interest (ROI). The MPI signal was calculated using the sum function of the VivoQuant software; this function calculates the sum of pixel signal intensity within a given ROI, normalized to the number of pixels. A calibration curve of the tracer was set up by 2D scanning of NPs at different concentrations, expressed as iron content. A duplicate of each dilution was scanned. After computing the calibration curves, the MPI signal collected from the cell pellets was converted into iron content, using the following equation based on the calibration curves and the doses employed: Sum Tissue Sur f ace Tissue Sum Tracer Sur f ace Tracer Cell pellets were also prepared in the bottom of Eppendorf tubes, for MRI. A gradient echo acquisition sequence was used, with the following parameters: TR = 460 ms, TE = 5 ms, flip angle = 30, FOV = 43 43 mm 2, matrix size = 384 384, NEX = 6. Magnetic Fluid Hyperthermia and Magnetic Particle Imaging HYPER Module Magnetic nanoparticles, in the presence of an external AMF, convert magnetic energy into heat. This ability is quantified from the value of the specific absorption rate (SAR). The SAR value of nanoparticles in solution is calculated by using the following equation: where C is the specific heat capacity of the solvent (4.186 J/g C), ∆T is temperature variation ( C), ∆t is the time interval (s), and mFe is the iron mass fraction in the compound. Temperature variation was calculated over the first 60 s of heating. SAR was measured using a Nanotherics MagneTherm system (Warrington, UK), with samples diluted in water. The heat dissipation value depends on the frequency and amplitude of the AMF. The AMF apparatus yields a maximum magnetic field intensity of 23.0 kA/m (approximately 29.0 mT). A multichannel thermometer equipped with optical fiber probes (FOTEMP4, Optocon AG, Dresden, Germany) was used to assess temperature variation within the sample, every 10.0 s. The multichannel thermometer was placed inside the sample throughout the entire acquisition time. MNP concentration was 6 mg/mL. The specific time window was chosen considering previous results obtained with G-M48, as well as translatability to clinical practice. The characteristic parameters of AMF were chosen in order to satisfy the Hergt criterion for clinical translatability : in particular, magnetic field intensity was set at H = 8.75 kA/m, with a frequency of 473.1 kHz. The samples were kept in a homemade closed box with a thermostatic air stream at 37 C. SAR was also measured with the HYPER module of the Magnetic Particle Imager Momentum scanner (Magnetic Insight Inc., Alameda, CA, USA). The change in temperature over time was recorded for both coated and naked nanoparticles, for 300 s (the necessary time window to evaluate SAR), starting at thermostated room temperature with a magnetic field excitation of 12.75 kA/m at a 1600 kA/m 2 gradient. The samples used had a volume of 100 L, with the same Fe concentration as for the measurement with the Nanotherics system. MFH was also performed in cell culture as previously described. Briefly, cells were incubated with 150 g/mL of G-M55, and after 24 h of incubation, cells were placed in a homemade closed box with a thermostatic air stream for 15 min and then an external AMF (MFH treatment) was applied to the cells for an additional 20 min. The efficiency of the MFH treatment was assessed through the MTT assay as described in Section 2.6. Cells subjected to MFH and cells incubated with 150 g/mL of G-M55, but not exposed to MFH, were used as controls. Twenty-four hours later than the MFH treatment, the cytotoxicity assays were performed. The viability of MDA-MB-231 cells was evaluated after one and two hyperthermia treatments (24 h apart) and normalized to that of the respective controls. In Vivo Studies The biodistribution of G-M55 was investigated in four normal nude homozygote female mice, 6-8 weeks old (supplied by Envigo, Bresso, Italy). MRI was performed with a Bruker Biospin 7T scanner (Bruker Biospin, Ettlingen, Germany). Animals were placed in a heated animal bed and inserted in a 7.2 cm internal diameter bird-cage coil under anesthesia (1.5% isofluorane in a mixture of O 2 and air). G-M55 was injected at a dosage of 4.0 mg Fe/kg (corresponding to 10.3 mg MNPs/kg dissolved in a volume of 150 L) through the tail vein. Images were acquired before, and 10 min, 30 min, 60 min, 24 h, and 72 h post-injection. The sequences adopted were the following: T 2 RARE sequence with TR = 1200 ms, TE eff = 36 ms, FOV = 35 35 mm 2, MTX = 128 128, slice thickness = 1.0 mm. The efficacy of G-M55 as a MFH agent was investigated in a group of 18 Balb/c nu/nu female mice (Harlan Laboratories, Udine, Italy). Mice were maintained under standard environmental conditions (temperature, humidity, and 12 h/12 h light/dark cycle, with water and food ad libitum) and veterinary control, in the University of Verona animal facility. Two million cells were injected subcutaneously into the right flank of each mouse. The size of the tumor was measured every 3 days by MRI, starting from 15 days postinoculation. After 21 days (when tumor volume reached about 200 mm 3 ), the mice were divided into three different intratumoral treatment groups. The first group (CTRL) received saline, the second (G-M55) received G-M55 (1.2 mg Fe/mL, total volume 100 L), the third group (G-M55 + MFH) received G-M55 (1.2 mg Fe/mL) and MFH treatments. Animals belonging to the third group were exposed to four MFH cycles: immediately, and after 24, 48, and 96 h. Each MFH treatment comprised the application of an AMF for 1200 s, at an intensity of 8.75 kA/m and a frequency of 473.1 kHz. Tumor size in all mice was measured by MRI before receiving G-M55 (day 0), and 4-, 6-, and 9-days post-injection. Transversal T 2 weighted images were acquired using a RARE 3D sequence with TR = 1200 ms, TE eff = 47.5 ms, NEX = 1, field of view = 25 25 25 cm 3, MTX = 256 128 32, slice thickness = 0.8 mm, FA = 90, RARE factor = 16. The tumor volume was obtained by manually drawing ROIs slice by slice using the Paravision software. The percentage increase in tumor volume was calculated at each time point as 100 (V t − V 0 )/V 0, where V t is the tumor volume at time t and V 0 is the initial volume. Individual animal body weight and clinical signs (spontaneous movement, head posture, and social behavior) were monitored. The experimental plan received authorization from the Italian Ministry of Health (protocol number 56DC9.38) and was approved by the local ethical committee. Animal experiments were conducted in full compliance with Italian law (D.L. 4 March 2014 no. 26) and European Union regulations (2010/63/EU). Histology Once the in vivo experiments were completed, mice were sacrificed, and relevant tissue (tumor, liver, kidneys, spleen, lungs, stomach, intestine, and heart) was removed for histology. Excised samples were washed with PBS 0.1 M and fixed in Carnoy solution for 2.5 h. Tissues were embedded in paraffin, cut into 8 m sections with a microtome, and dried at 37 C for 24 h. Prussian blue staining was performed to evaluate the presence of iron in the tissues: sections were incubated with PB solution (5% hydrochloric acid and 5% potassium ferrocyanide) for 20 min and counterstained with nuclear fast red (Bioptica, Milan, Italy) for 2 min. To evaluate tissue damage and morphology, sections were stained with hematoxylin and eosin. Sections were examined under a light microscope (Olympus BXS1, Hamburg, Germany), equipped with a charge-coupled device camera. Immunofluorescence Immunofluorescence was used to observe the overexpression of HSP70 within the cell culture (MDA-MB-231). After two and four MFH treatments, cells were fixed with 4% PFA solution at room temperature, and then with 70% ethanol at −20 C overnight. After fixation, cells were permeabilized with 0.1% Triton X-100 in PBS for 10 min at room temperature. Subsequently, cells were incubated in blocking solution for 30 min and immunostained with primary Rabbit Anti HSP70 (Abcam 1:50, Cambridge, UK) antibody, overnight at 4 C. Secondary rabbit antibody (Alexa Fluor ® 488) ab150077 was used at 1:100 dilution. Cells were then washed with PBS, counterstained with Trypan Blue (GIBCO 1:10) for 15 s, washed with PBS, stained for 5 min with 1 g/mL of Hoechst 33342 (Sigma, Burlington, MA, USA) in PBS, and mounted in PBS:glycerol (1:1) for inspection with a LEICA TCS-SP5 inverted confocal microscope. A diode laser was used for Hoechst 33342, with = 405 nm; a visible laser for HSP70, with = 496 nm; and a He/Ne laser for Trypan Blue, with = 543 nm. Statistical Analysis Statistical analysis was conducted with MatLab (Mathworks, Natick, MA, USA), then confirmed and plotted using Prism software (9, GraphPad Inc., La Jolla, CA, USA). All data reported in the paper are expressed as mean ± standard error of the mean (mean ± SEM). A two-way ANOVA test was applied to evaluate statistically significant differences with multiple comparisons, using the Tukey-Kramer test. The statistical significance level was placed at p < 0.05. Structural Characterization and Stability of G-M55 The obtained XRPD experimental pattern is shown in Figure 1a, together with others reported for some iron oxide crystal structures from the ICSD database. A comparison with the literature patterns reveals that the sample under investigation is compatible with a mixture of different iron oxides, such as hematite (-Fe 2 O 3 ), magnesium ferrite (MgFe 2 O 4 ), and magnesium titanate (MgTiO 3 ). A precise analysis of the different phase contents is not straightforward, due to the nanosized nature of the sample and the strong overlaps of the XRPD reflections of the three above-mentioned crystal phases. Nonetheless, an analysis of the XRPD reflection intensities using a powder diffraction software (SIeve for PDF-4), indicates that a mass ratio of 60:30:10 among the MgFe 2 O 4, Mg 2 TiO 4 and -Fe 2 O 3 phases, respectively, is reasonably present. FTIR spectra of the G-M55 NPs, shown in Figure 1b, underline the presence of both citrate ions and glucose molecules, as capping agents, on the surface of the NPs. Figure 1b shows broad bands around 3300 cm −1 and 2900 cm −1, due to -OH and -CH stretching, respectively, ascribed to glucose and citrate groups. The presence of citrate groups is confirmed by evident features in the 1600-1800 cm −1 region (see Figure S1) corresponding to asymmetric stretching of the carboxylate group. The positions of these bands for the NPs show an offset with respect to the free citrate moiety, related to the presence of relevant interactions between the carboxylate groups and the metal ions on the surface. These findings clearly demonstrate the capping of the ligands on the NPs surface. Bands due to other vibrations of the glucose molecular skeleton in the 900-1200 cm −1 region (see Figure S1) are observed, consistent with those in the infrared absorbance spectrum of the free glucose molecule (red line in Figure 1b). Metal-oxygen vibrations, such as Fe-O, Mg-O, and Ti-O ones, are assigned to the strong band around 560 cm −1. Magnetic Properties of G-M55 To define the ability of G-M55 to serve as a multimodal contrast agent for both MPI and MRI, two different magnetic characterizations were performed. First, the MPI performance of G-M55 was assessed, in comparison to its naked version (M55) and to a commercially available MPI tracer, VivoTrax (Magnetic Insight Inc., Alameda, CA, USA). Second, the signal efficiency (i.e., the signal per ng of iron), the full-width half-maximum (FWHM), and the approximate resolution were measured through the Magnetic Particle Imager Momentum scanner RELAX module (Magnetic Insight Inc., Alameda, CA, USA). Figure 2a shows the relaxometry measurement of naked (M55) and coated (G-M55) nanoparticles. This measurement allows quantification of signal efficiency and space resolution given by the tracer (see Table 1). Dynamic light scattering (DLS) was used to investigate the colloidal stability of water dispersion of G-M55 through zeta potential and hydrodynamic size measurements (Figure 1c,d). The average zeta potential of −32.1 ± 8.2 mV showed good colloidal stability in aqueous environments. The average hydrodynamic diameter was 113.1 ± 30 nm. Colloidal stability and hydrodynamic size were investigated as a function of time for an entire week. The zeta potential and the size of the nanoparticles remained substantially unvaried, confirming excellent colloidal stability in water, as well as the chemical stability of the coating. In order to further investigate the colloidal properties of the G-M55 NPs in a physiological medium, we considered a dispersion in Dulbecco's Modified Eagle Medium (DMEM), which is a widely used basal medium for supporting the growth of many different mammalian cells, modified with the addition of 10% of Fetal Bovine Serum and 1% Penicillin-Streptomycin (P/S). A comparison of the hydrodynamic diameter for the G-M55 NPs in water and in a culture medium is shown in Figure S2. Interestingly, the NPs' average hydrodynamic size notably increases from about 100 nm to 300 nm, indicating a relevant bonding of large molecules as serum proteins, present in the growth medium, to the NPs. The corresponding zeta potential for the NPs dispersion in the growth medium is lower than that measured in pure water (change from −30 mV to −10 mV), confirming the bonding of the large (serum protein) molecules. The increase of the hydrodynamic size is compatible with the formation of a protein corona surrounding the G-M55 NPs, suggesting a possible stabilization in the physiological medium. TEM images, shown in Figure 1e, are in line with the DLS measurements (Figure 1d), denoting a particle size, as single nanoparticles or as aggregates, from 60 nm to 250 nm. Magnetic Properties of G-M55 To define the ability of G-M55 to serve as a multimodal contrast agent for both MPI and MRI, two different magnetic characterizations were performed. First, the MPI performance of G-M55 was assessed, in comparison to its naked version (M55) and to a commercially available MPI tracer, VivoTrax (Magnetic Insight Inc., Alameda, CA, USA). Second, the signal efficiency (i.e., the signal per ng of iron), the full-width half-maximum (FWHM), and the approximate resolution were measured through the Magnetic Particle Imager Momentum scanner RELAX module (Magnetic Insight Inc., Alameda, CA, USA). Figure 2a shows the relaxometry measurement of naked (M55) and coated (G-M55) nanoparticles. This measurement allows quantification of signal efficiency and space resolution given by the tracer (see Table 1). As can be observed from Table 1, even if signal efficiency is approximately 89% (for M55) and 92% (for G-M55) lower than for VivoTrax, resolution, calculated on the basis of the FWHM, is comparable to that of VivoTrax. These observations led us to define M55 and G-M55 as good tracers for MPI. Further developments in the synthesis procedure will be needed to sharpen and intensify the signal efficiency of M55 and its coated version, G-M55. Figure 2b shows the transverse relaxation rates (1/T2) of water dispersion containing G-M55 at varying iron concentrations, ranging from 1.6 mM to 0.32 mM. Values of 1/T2 vs. Fe concentration were fitted, using a straight line whose slope determines the transverse relaxivity of the nanoparticles under investigation (Figure 2b). The transverse relaxivity (r2) value, 53.20 mM −1 s −1, is comparable to that of a commercial iron oxide MRI contrast agent, such as Endorem ®, Sinerem ®, Resovist ®, Ferumuxytol, confirming the As can be observed from Table 1, even if signal efficiency is approximately 89% (for M55) and 92% (for G-M55) lower than for VivoTrax, resolution, calculated on the basis of the FWHM, is comparable to that of VivoTrax. These observations led us to define M55 and G-M55 as good tracers for MPI. Further developments in the synthesis procedure will be needed to sharpen and intensify the signal efficiency of M55 and its coated version, G-M55. Figure 2b shows the transverse relaxation rates (1/T 2 ) of water dispersion containing G-M55 at varying iron concentrations, ranging from 1.6 mM to 0.32 mM. Values of 1/T 2 vs. Fe concentration were fitted, using a straight line whose slope determines the transverse relaxivity of the nanoparticles under investigation (Figure 2b). The transverse relaxivity (r 2 ) value, 53.20 mM −1 s −1, is comparable to that of a commercial iron oxide MRI contrast agent, such as Endorem ®, Sinerem ®, Resovist ®, Ferumuxytol, confirming the potential of G-M55 as a contrast agent for MRI. Figure 2c shows T 2 -weighted MR images of G-M55 phantoms. The signal intensity of phantoms decreases with increasing iron concentrations, a characteristic property of a T 2 contrast agent. To evaluate the efficiency of G-M55 as an MPI contrast agent in a biologically significant context, it was used in a cellular imaging experiment testing its capability to label and detect MDA-MB-231 cells by multimodal imaging. The incubation protocol, MPI image collection, and analysis are described above (see Section 2.9). Results are reported in Figure 3. A calibration curve of the tracer was set up by 2D scanning of different MNP concentrations, expressed as iron content (as shown in Figure 3a). This calibration curve was then used to estimate the iron content of cells. Figure 3b shows quantitative values for the MPI signal, obtained in different numbers of cells. The series of images in Figure 3c shows the ability of G-M55 to label cells and make them observable by MPI, up to approximately 30,000 cells. After labeling, cells were also detectable by MRI: images of cell pellets, collected in the bottom of Eppendorf-type tubes are shown in Figure 3d, where the hypointense spots (indicated by arrows) are attributable to the presence of G-M55 inside the cells. Signal voids in MR images are clearly detectable up to 1.25 10 5 cells. Similar tubes containing unlabeled cells were used as controls. Figure 3a). This calibration curve was then used to estimate the iron content of cells. Figure 3b shows quantitative values for the MPI signal, obtained in different numbers of cells. The series of images in Figure 3c shows the ability of G-M55 to label cells and make them observable by MPI, up to approximately 30,000 cells. After labeling, cells were also detectable by MRI: images of cell pellets, collected in the bottom of Eppendorf-type tubes are shown in Figure 3d, where the hypointense spots (indicated by arrows) are attributable to the presence of G-M55 inside the cells. Signal voids in MR images are clearly detectable up to 1.25 10 5 cells. Similar tubes containing unlabeled cells were used as controls. Cytotoxicity, Internalization Mechanism, and In Vitro MFH Before using nanoparticles as hyperthermia mediators, it is fundamental to evaluate biocompatibility with an in vitro cytotoxicity assay. The toxicity of G-M55 was therefore assessed after 2, 24, and 48 h of incubation with MDA-MB-231 cells, at different concentrations. MTT assay demonstrates that G-M55 is safe up to a concentration of 150 g/mL for long incubation times (48 h), as shown in Figure 4a. No statistically significant differ- Cytotoxicity, Internalization Mechanism, and In Vitro MFH Before using nanoparticles as hyperthermia mediators, it is fundamental to evaluate biocompatibility with an in vitro cytotoxicity assay. The toxicity of G-M55 was therefore assessed after 2, 24, and 48 h of incubation with MDA-MB-231 cells, at different concentrations. MTT assay demonstrates that G-M55 is safe up to a concentration of 150 g/mL for long incubation times (48 h), as shown in Figure 4a. No statistically significant difference was found for the concentrations tested. Considering these results, the highest non-toxic concentration of 150 g/mL was chosen for MFH in vitro experiments. TEM images obtained in MDA-MB-231 cells demonstrated that G-M55 is internalized mainly via endocytosis and compartmentalized into endosomes (see Figure 4b), consistent with previously reported findings for G-M48. With a view to a biomedical application as a heat exchange mediator, the SAR of G-M55 was evaluated in two different ways. First, it was assessed by Nanotherics Magnetherm, as described in Gerosa et al.. Second, it was tested by means of the MPI HY-PER module. In both measurements, thermograms were collected starting from a specific bulk temperature, about 37.0 °C. This starting condition was chosen to simulate an in vivo experimental setting. Once the good heating ability of the naked nanoparticle (M55) was observed, the measurements were carried out on the coated version, G-M55. The same iron concentration was used to estimate SAR in an aqueous solution, with the two methods. Figure 4c,d shows the thermograms collected in aqueous suspensions of G-M55, using Nanotherics Magnetherm and the MPI HYPER module, respectively. As shown in With a view to a biomedical application as a heat exchange mediator, the SAR of G-M55 was evaluated in two different ways. First, it was assessed by Nanotherics Magnetherm, as described in Gerosa et al.. Second, it was tested by means of the MPI HYPER module. In both measurements, thermograms were collected starting from a specific bulk temperature, about 37.0 C. This starting condition was chosen to simulate an in vivo experimental setting. Once the good heating ability of the naked nanoparticle (M55) was observed, the measurements were carried out on the coated version, G-M55. The same iron concentration was used to estimate SAR in an aqueous solution, with the two methods. Figure 4c,d shows the thermograms collected in aqueous suspensions of G-M55, using Nanotherics Magnetherm and the MPI HYPER module, respectively. As shown in Figure 4c, a temperature increase of about 4 C was detected at the concentration used. SAR estimated with Nanotherics Magnetherm was 18 ± 1.0 Wg −1, when expressed in terms of Fe mass. In this case, the parameter C = H*f amounted to 4.1 10 9 Am −1 s −1. It is noteworthy that a similar initial slope was determined when thermograms were acquired with the MPI RELAX module, using C = H f = 4.4 10 9 Am −1 s −1. In the last case, SAR was equal to 20 ± 1.4 Wg −1. Considering that similar SAR values were obtained with the two different methods, we have chosen to develop our magnetic hyperthermia strategy using the Nanotherics Magnetherm, because its significantly lower safety criterion, as evaluated by the C parameter (see the discussion, below), enables a more reliable and scalable solution for clinical use. In addition, the Nanotherics Magnetherm experimental set-up is readily usable for both in vitro and in vivo treatments. G-M55 was tested as a hyperthermia mediator on a triple-negative mammary carcinoma cell line, MDA-MB-231, at a concentration of 150 g/mL. MDA-MB-231 cells were incubated with G-M55 for 24 h and exposed to two cycles of AMF, 24 h apart. Cell viability data after MFH are shown in Figure 4e. Cell viability was significantly affected by AMF application, compared to control conditions (untreated cells and cells treated only with G-M55, but not exposed to MFH). MDA-MB-231 cells treated with G-M55 and exposed to AMF showed a percentage of 84.45 ± 1.67% and 63.15 ± 3.44% viability, after the first and the second MFH treatment, respectively. The percentage of viability for cells treated with G-M55 but not exposed to AMF was about 100% at both time points, thus confirming the safety of nanoparticles at the concentration of 150 g/mL. The viability of cells subjected to MFH cycles, but not incubated with MNPs, was not different from that of native cells. To gain insight into the mechanism of cell death, after two and four MFH treatments, cells were processed for an immunofluorescence protocol to evaluate the expression of HSP70, selected as an indicator of cellular stress, including temperature increase. As shown in Figure 4f, the expression of HSP70 is more evident in the samples treated with hyperthermia (G-M55 + MFH) than in controls (G-M55 and CTRL), especially after two MFH treatments. This finding is consistent with an increase in temperature in the samples during MFH treatments, as expected. Surprisingly, the expression of HSP70 in the sample treated with G-M55 and exposed to four MFH treatments is lower than that observed in the sample exposed to two treatments, possibly indicating an effect of thermotolerance induced by multiple AMF exposures. In Vivo Biomedical Application of G-M55 as a MFH Mediator The biodistribution and clearance of G-M55 were investigated in vivo. Figure 5a shows T2w-MR images of a representative mouse body, acquired basally and 10 min, 60 min, and 72 h after injection of G-M55. Signal intensity (SI) in the liver decreased by 29.9 ± 3.7% (Figure 5b) 10 min after injection, and by 11.7 ± 2.8% 72 h after injection, indicating early hepatic accumulation of the nanoparticles followed by clearance. On the other hand, the percentage SI decrease in the kidney went from 12.5 ± 2.3% 10 min after injection, to about 40%, 24 and 72 h after injection, suggesting renal clearance of G-M55. Figure 5c shows histological slices of the liver, excised 72 h after G-M55 injection and stained with Prussian blue. The slight presence of iron in the liver supports the in vivo findings, confirming early NP clearance. To evaluate the safety of G-M55, morphological tissue evaluation of major organs (including liver, lungs, kidneys, and heart) was performed 72 h post-administration (Figure 5d). H&E staining provides evidence of G-M55 biocompatibility in vivo. No alteration in the tissue morphology of relevant organs was detected, as compared to organs of control mice, confirming the absence of systemic toxicity. Specifically, the parenchymal architecture of the liver showed hepatocytes without evidence of steatosis, and was comparable to the control group. Likewise, morphological evaluation of the lungs, kidneys, and heart showed no signs of fibrosis, inflammatory infiltration, or necrosis. Moreover, no significant alteration was detected in individual animal body weight and in clinical signs. The efficacy of intratumoral G-M55 injection in MFH was tested in an experimental breast cancer model. Figure 6a shows MR images of representative mice belonging to the G-M55 and G-M55 + MFH groups, basally and at different time points during the treatment protocol. The presence of G-M55 in the tumor tissue is detectable by MRI as signal voids, consistent with its ability to behave as a negative contrast agent. It is noteworthy that MRI clearly shows the presence of G-M55 within the tumor up to 9 days after injection. In Figure 6b, the tumor volume progression in the three groups is shown on day 0 (prior to G-M55 injection), day 4 (after 4 MFH treatments), day 6, and day 9. The same data are shown in Figure 6c, as percentage tumor growth; here, the timing of MFH treatments is indicated by arrows on the horizontal axis. Starting from day 4, the tumor volume in G-M55 + MFH mice remains significantly lower than in control animals (saline solution and G-M55). In Figure 6d, histological slices of tumor tissue, stained either with Prussian blue (for iron detection) or H&E (for tissue morphology evaluation), are shown for the G-M55 and G-M55 +MFH groups. The blue spots (Figure 6d, arrows) indicate the presence of iron inside the tumor 9 days after G-M55 injection, supporting the in vivo MRI findings (Figure 6a). Absence of evident parenchymal alteration and good preservation of cellular morphology were observed in G-M55 tumor tissue, while G-M55 + MFH tumor tissue The efficacy of intratumoral G-M55 injection in MFH was tested in an experimental breast cancer model. Figure 6a shows MR images of representative mice belonging to the G-M55 and G-M55 + MFH groups, basally and at different time points during the treatment protocol. The presence of G-M55 in the tumor tissue is detectable by MRI as signal voids, consistent with its ability to behave as a negative contrast agent. It is noteworthy that MRI clearly shows the presence of G-M55 within the tumor up to 9 days after injection. In Figure 6b, the tumor volume progression in the three groups is shown on day 0 (prior to G-M55 injection), day 4 (after 4 MFH treatments), day 6, and day 9. The same data are shown in Figure 6c, as percentage tumor growth; here, the timing of MFH treatments is indicated by arrows on the horizontal axis. Starting from day 4, the tumor volume in G-M55 + MFH mice remains significantly lower than in control animals (saline solution and G-M55). In Figure 6d, histological slices of tumor tissue, stained either with Prussian blue (for iron detection) or H&E (for tissue morphology evaluation), are shown for the G-M55 and G-M55 +MFH groups. The blue spots (Figure 6d, arrows) indicate the presence of iron inside the tumor 9 days after G-M55 injection, supporting the in vivo MRI findings (Figure 6a). Absence of evident parenchymal alteration and good preservation of cellular morphology were observed in G-M55 tumor tissue, while G-M55 + MFH tumor tissue shows extensive areas of necrosis (Figure 6d N), attributable to MFH treatment. Differently from other papers from our group, in the present experimental set-up, the presence of a closed box with a thermostatic air stream prevented the possibility to acquire IR images. shows extensive areas of necrosis (Figure 6d N), attributable to MFH treatment. Differently from other papers from our group, in the present experimental set-up, the presence of a closed box with a thermostatic air stream prevented the possibility to acquire IR images. Discussion Thermal therapy, i.e., a local increase of tumor tissue temperature, is widely applied in cancer treatment. Both hyperthermia, i.e., heating to 39-45 °C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 °C destroy tumor cells directly, are frequently applied in clinical practice. Among the different approaches that can be used to induce local temperature increase in tumor tissue, MFH is regarded as a minimally invasive method without systemic toxicity. MFH is based on a limited temperature increase (42-46 °C) of tumor tissue that can lead to apoptosis, avoiding extensive necrosis. It is well known, that cancer cells are more sensitive to temperature increase than non-tumoral cells, and that temperatures around 46 °C can usually induce tumor cell apoptosis. The use of self-regulating temperature materials, which heat only to the TC, i.e., the temperature at which a magnetic phase transition from ferromagnetic to paramagnetic occurs, is seen as an undoubted advantage of this technique: it affords an intrinsic safety mechanism, guarding against the risk of damage to surrounding tissues. The innovative nanomaterial-developed and patented by MBN, and functionalized by the University of Verona-has a TC that can be modulated by synthesis, providing a temperaturelimiting effect during AMF heating. M55, the magnetic core of the NP investigated in the Discussion Thermal therapy, i.e., a local increase of tumor tissue temperature, is widely applied in cancer treatment. Both hyperthermia, i.e., heating to 39-45 C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 C destroy tumor cells directly, are frequently applied in clinical practice. Among the different approaches that can be used to induce local temperature increase in tumor tissue, MFH is regarded as a minimally invasive method without systemic toxicity. MFH is based on a limited temperature increase (42-46 C) of tumor tissue that can lead to apoptosis, avoiding extensive necrosis. It is well known, that cancer cells are more sensitive to temperature increase than non-tumoral cells, and that temperatures around 46 C can usually induce tumor cell apoptosis. The use of self-regulating temperature materials, which heat only to the T C, i.e., the temperature at which a magnetic phase transition from ferromagnetic to paramagnetic occurs, is seen as an undoubted advantage of this technique: it affords an intrinsic safety mechanism, guarding against the risk of damage to surrounding tissues. The innovative nanomaterial-developed and patented by MBN, and functionalized by the University of Verona-has a T C that can be modulated by synthesis, providing a temperature-limiting effect during AMF heating. M55, the magnetic core of the NP investigated in the present study, has a T C value of about 95 C (see Gerosa et al. ). Since MFH ideally produces a limited increase in tissue temperature (42-46 C), this T C value may seem too high. However, recent experimental results have demonstrated that the very marked temperature increase, up to ∆t = 45 C within a distance of 0.5 nm from the MNPs' surface, falls off exponentially as this distance increases. Therefore, a T C value of about 95 C could ensure that NPs reach a sufficiently high temperature to be effective MFH agents while remaining intrinsically safe for healthy tissues. Indeed, no damage to tumor-neighboring organs was observed in the present study. We have demonstrated that G-M55 has diagnostic capabilities in bimodal imaging. G-M55 displays r 2 relaxivity comparable to commercial MRI contrast agents such as Endorem ®. As far as MPI is concerned, the signal efficiency of G-M55 is about 10% of that of a commercial MPI agent (such as VivoTrax), with comparable spatial resolution. G-M55 thus has good properties as a bimodalcontrast agent. In addition, in a biologically significant context, namely in a cellular imaging experiment, G-M55 allowed the labeling and detection of cells in vitro. Cells labeled by using G-M55 were detectable by both MPI and MRI. MPI allowed the detection of a lower number of cells than MRI, this result being consistent with the greater sensitivity of the former. Although preliminary, this experiment indicates that G-M55 has potential for application in the field of cellular imaging. Another interesting characteristic of G-M55 is that it can be detected by both MRI and MPI. Moreover, with a view to future clinical applications, the finding that SAR values with standard MFH and MPI measurements are similar is of particular interest for the prospective use of G-M55 as a magnetic fluid hyperthermia agent, in both classical and advanced applications. In addition, the experimental conditions adopted are transferable to clinical protocols. The timing of the in vivo experiment was decided with potential clinical application in mind-i.e., a single injection of G-M55, followed by multiple applications of AMF in rapid succession. This protocol was very effective in reducing tumor growth rate. Moreover, MRI showed the substantial presence of MNPs within the tumor up to 9 days after injection, enabling delayed AMF without further injections of MNPs. In this paper, we have examined the application of a synthetic MNP, namely G-M55, in MFH in preclinical studies with reference to both diagnostic and therapeutic capabilities. G-M55 revealed good performances as a bimodal diagnostic contrast agent and as a therapeutic agent in MFH, with either standard or MPI-based systems. Our results demonstrate the efficacy of MFH in the treatment of breast cancer [8,. Conclusions M55 belongs to a class of innovative nanomaterials, made up of doped ferrites with the potential for application in tumor therapy, as agents for MFH, and in diagnosis, as contrast agents for MRI and MPI. We have demonstrated the marked efficacy of G-M55 in tumor growth inhibition, by administering a single intratumoral injection followed by repeated AMF treatments in rapid succession. It is noteworthy that SAR values as measured with standard MFH apparatus and MPI methods are similar, opening the way for the application of G-M55 in localized hyperthermia by MPI apparatus. We have demonstrated that G-M55 has diagnostic capabilities in bimodal imaging since it displays r2 relaxivity comparable to commercial MRI contrast agents such as Endorem ®, as well as good sensitivity/resolution in MPI. In addition, in the biologically significant context of a cellular imaging experiment, G-M55 allowed the labeling and detection of cells in vitro. Overall, our results pave the way for efficient and minimally invasive cancer therapy and diagnosis, by application of a single nanomaterial with self-regulating temperature properties. Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/cancers14205150/s1, Figure S1: Detail of the FT-IR spectrum of G-M55 nanoparticles, sodium citrate and glucose molecules; Figure S2: Hydrodynamic diameter of G-M55 NPs in water (black line) and in DMEM with 10% FBS (red line), using a NPs concentration of 6 mg/mL. Funding: Financial support obtained from the Foundation for Nanotheranostics Research in Cancer Therapy, RNC (Treviso, Italy) is gratefully acknowledged. Institutional Review Board Statement: The animal study protocol was approved by the University of Verona Ethics Committee and the Italian Ministry of Health (protocol code 56DC9.38). Informed Consent Statement: Not applicable. Data Availability Statement: The data presented in this study are available on request from the corresponding author.

Prophylactic antibiotics in interventional paediatric cardiac catheterisation: old habits die hard? Abstract Antibiotic prophylaxis in congenital cardiac disease has long been a topic of debate. Although there is little dispute around antibiotic cover for surgical procedures and catheter interventions where foreign material is being inserted, there are little data specific to non-device-placement procedures such as atrial septostomy or balloon valvotomy. We sought to assess the effect of routine prophylaxis on post-interventional infections via a retrospective pseudo-randomised analysis, and an online survey on paediatric interventional cardiologists in the United Kingdom and United States.

Global Trade Limitations to HIV Medication Access in Developing Countries International trade and patent laws pose monetary and logistical challenges to all countries affected by the HIV/AIDS epidemic in their abilities to access the most current and effective treatments. The development of international patent law applicable to medications has undergone significant changes since the 1990s under The Agreement on Trade Related Aspects of Intellectual Property Rights (TRIPS) established by the World Trade Organization (WTO). Case studies of China, India and Brazils implementation of pharmaceutical patent protection reveal the limitations of TRIPS and its subsequently recognized flexibilities. Although the goal of these flexibilities is to allow for greater access to medications, they fall short in reaching the universally accepted goal of a right to health.

Preoperative Brush and Impression Cytology in Ocular Surface Squamous Neoplasms OBJECTIVE Preoperative cytologic diagnoses of ocular surface squamous neoplasms were evaluated and compared with histologic diagnoses. STUDY DESIGN Impression cytology (Millipore filter paper) and brush cytology were applied to 32 patients who had conjunctival neoplasms. Papanicolaou-stained cytologic preparations and hematoxylin and eosin-stained histologic sections were examined by light microscopy. RESULTS The brush technique was used on 27 patients; impression cytology was applied in 5 cases. Cytologic and histologic diagnoses were concordant in 26 cases. Squamous cell carcinoma or carcinoma in situ was diagnosed in 18 and dysplasia in 4 cases. Squamous metaplasia and normal-appearing conjunctival epithelial cells were diagnosed cytologically in four cases; of those histologic diagnoses, one was pterygium and three, conjunctival nevus. Four cases revealed discrepancies between the cytologic and histologic preparations. There was one false positive result, and one case was subconjunctival invasion of basal cell carcinoma of the eyelid. CONCLUSION Impression and brush cytology are fast, cost-effective, reliable and noninvasive diagnostic tools for ocular surface squamous neoplasms. However, the brush technique has several advantages over impression cytology.

Response to Comment on Water harvesting from air with metal-organic frameworks powered by natural sunlight In their comment, Bui et al. argue that the approach we described in our report is vastly inferior in efficiency to alternative off-the-shelf technologies. Their conclusion is invalid, as they compare efficiencies in completely different operating conditions. Here, using heat transfer and thermodynamics principles, we show how Bui et al.s conclusions about the efficiencies of off-the-shelf technologies are fundamentally flawed and inaccurate for the operating conditions described in our study.

Portland, OR: Last Friday, the Centers for Medicare and Medicaid Services announced that seniors in Oregon will face another major cut to their Medicare Advantage benefits. Jeff Merkley promised our seniors that wouldn’t happen. This is the latest in a long litany of promises Jeff Merkley has made about the ACA that simply are not true. Q: I’ve heard that there are going to be cuts to Medicare Advantage. I receive health coverage through Medicare Advantage and I’m afraid of losing my benefits. Are the proposed cuts going to hurt my coverage? A: Before I get into details, I want to be clear that if you’re already enrolled in a Medicare Advantage plan, nothing will change. Despite warnings to the contrary, Jeff Merkley promised our seniors that their benefits would not be affected by the hundreds of billions of dollars he voted to take away from Medicare in order to fund Obamacare. Yet, for the300,465 seniors in Oregon who depend on Medicare Advantage (43% of all Medicare enrolees in Oregon, the 2nd highest percentage in the nation) that promise has not been kept. Worse, in 2010 Jeff Merkley had the opportunity to protect our seniors from having their Medicare Advantage benefits cut. Instead, he voted to kill a measure that would have prevented those cuts from taking place. Recently, after enormous political pressure he signed onto a letter requesting to right the wrong that he created in the first place. Oregonians deserve better. They deserve a U.S. Senator who gets things right the first time. As a pediatric neurosurgeon, Dr. Monica Wehby doesn’t have the luxury of a do-over. We could use a little more of that attitude in Washington, D.C. “The problem with passing a massive takeover of the health care system is that the unintended consequences stack up faster than they can be fixed. The reduction of Medicare Advantage benefits for our seniors is just the latest example of why the ACA is bad law and must be replaced. That’s why last Fall, I put forward a patient centered, market based replacement plan for Obamacare that doesn’t rely on making our seniors pay for the Democrats’ flawed health care agenda. Last week was another great week on the campaign. I am honored and humbled to have Senator Tom Coburn endorse my candidacy. – U.S. Senator Tom Coburn, M.D. Just last week a columnist at the Oregonian labeled me the “Frontrunner” in the race. Click here to read the article. Please consider making a donation today to help me keep up the momentum. If you would like to join me along the campaign trail, please consider coming to one (or more) of my fundraising events below. Please feel free to forward these invitations along to others you think might like to join us. To RSVP for any of these events, please follow the instructions on the invite or call Tiffany at 503.224.5489. Even if you are unable to attend, please support the events above by making a donation.

Safety evaluation method of bridge plate rubber bearing based on SVM In order to comprehensively evaluate the working state and safety performance of the bridge plate rubber bearing (PRB), the basic principle and method of SVM in machine learning theory (Support Vector Machine) was introduced in this paper. Firstly, the performance indices (such as the average compression stress, tangent value of the shear angle and the rotation angle of the PRB) were analyzed and calculated through its finite element model considering the different working conditions (axial compression, shear deformation and the rotation deformation of the PRB). Subsequently, considering the relevant indices affecting the safety performance of the PRB, the Pearson Correlation Coefficients (PCC) were calculated by SVM method for assessing the internal correlation of the performance indices of the PRB for different cases, respectively. The threshold values of the influential factors for different cases considering the PCC and the weight coefficient were obtained for grading the working state of the PRB as five levels. Moreover, in order to verify the validity and suitability of the evaluation of the working state of the plate rubber bearing by the SVM method, three apparent indices for grading the performance level of the PRB such as the crack, the undistributed spalling deformation and the dislocation of the PRB were analyzed and compared with the qualitative descriptions and the quantitative values. Finally, the corresponding threshold values for grading the performance levels of the PRB working states were proposed. It was shown that the SVM based evaluation method for the PRB is feasible and convenient, especially for the bridges with real-time monitoring devices to get the response data of the PRB.

You may (or may not) have seen these before – I thought they’re interesting enough to share with you all. Maybe you’ll spot one or two you knew about, and maybe a few more you didn’t 🙂 VOMERONASAL ORGAN (VNO), or Jacobson’s organ: a tiny hole on each side of the nasal bridge that is considered to be connected to nonfunctional chemical receptors. Could be all that is left from our once great ability to detect pheromones. EXTRINSIC EAR MUSCLES: These three muscles most likely made it possible for our ancestors to move their ears independently of their heads, as rabbits and dogs do. We still have them, which is why most people can learn to wiggle their ears. WISDOM TEETH: Early humans had to chew a lot of plants to get enough calories to survive, making another row of molars helpful, but unless you chew a lot of branches, these will eventually come out in a painful procedure. Only about 5 percent of the population has a healthy set of these third molars. NECK RIB: A set of cervical ribs—possibly leftovers from the age of reptiles, still appear in less than 1 percent of the population. They often cause nerve and artery problems. THIRD EYELID: A common ancestor of birds and mammals may have had a membrane for protecting the eye and sweeping out debris. Humans retain only a tiny fold in the inner corner of the eye, exactly there where you always catch a spec of dust or debris. DARWIN’S POINT: A small folded point of skin toward the top of each ear is occasionally found in modern humans. It may be a remnant of a larger shape that helped focus distant sounds. SUBCLAVIUS MUSCLE: This small muscle stretching under the shoulder from the first rib to the collarbone would be useful if humans still walked on all fours. Some people have one, some have none, and a few have two. PALMARIS MUSCLE: This long, narrow muscle runs from the elbow to the wrist and is missing in 11 percent of modern humans. It may once have been important for hanging and climbing. Surgeons harvest it for reconstructive surgery. MALE NIPPLES: Lactiferous ducts form well before testosterone causes sex differentiation in a fetus. Men have mammary tissue that can be stimulated to produce milk. This just makes me angry; I’ve been spending a fortune on milk all these years! I’ll have to test this tomorrow with my Special K. ERECTOR PILI: Bundles of smooth muscle fibers allow animals to puff up their fur for insulation or to intimidate others. Humans retain this ability (goose bumps are the indicator) but have obviously lost most of the fur. APPENDIX: This narrow, muscular tube attached to the large intestine served as a special area to digest cellulose when the human diet consisted more of plant matter than animal protein. It also produces some white blood cells. Annually, more than 300,000 Americans have an appendectomy. BODY HAIR: Brows help keep sweat from the eyes, and male facial hair may play a role in sexual selection, but apparently most of the hair left on the human body serves no function. THIRTEENTH RIB: Our closest cousins, chimpanzees and gorillas, have an extra set of ribs. Most of us have 12, but 8 percent of adults have the extras. PLANTARIS MUSCLE: Often mistaken for a nerve by freshman medical students, the muscle was useful to other primates for grasping with their feet. It has disappeared altogether in 9 percent of the population. MALE UTERUS: A remnant of an undeveloped female reproductive organ hangs off the male prostate gland. FIFTH TOE: Lesser apes use all their toes for grasping or clinging to branches. Humans need mainly the big toe for balance while walking upright, the other four are for holding when you slam them on a coffee table at night! FEMALE VAS DEFERENS: What might become sperm ducts in males become the epoophoron in females, a cluster of useless dead-end tubules near the ovaries. PYRAMIDALIS MUSCLE: More than 20 percent of us lack this tiny, triangular pouch-like muscle that attaches to the pubic bone. It may be a relic from pouched marsupials. COCCYX: These fused vertebrae are all that’s left of the tail that most mammals still use for balance and communication. Our hominid ancestors lost the need for a tail before they began walking upright. All they’re good for now is give us painful falls on the butt. PARANASAL SINUSES: The nasal sinuses of our early ancestors may have been lined with odor receptors that gave a heightened sense of smell, which aided survival. No one knows why we retain these perhaps troublesome mucus-lined cavities, except to make the head lighter and to warm and moisten the air we breathe.

A group representing Digambara Jains has approached the Madhya Pradesh government seeking exemption for their monks to defecate in the open, which they say is the ascetics’ way of life. The Digambara and Shwetambara are the two main sects of of the Jain order, which account for 0.4 % of India’s population. The nomadic monks of the Digambara sect don’t wear clothes and defecate in the open— a century-old practice which the group fears will run afoul of the Central government diktat to panchayats to frame a law to penalise open defecators. The memorandum seeking exemption was submitted to state minister of panchayat and rural development Gopal Bhargava by the Digamber Jain Social Group Federation. They are worried Madhya Pradesh might go the way of Rajasthan in penalizing open defecators. “We have asked the government to allow our monks and seers to attend the nature’s call in the open as they never use toilets for doing so,” said Ravindra Jain, the acting president of the federation. “They follow a centuries-old strict lifestyle in which they only go in secluded or forested areas to attend nature’s call and that too once in a day,” said Jain. The Bharatiya Janata Party-led union government has undertaken an ambitious toilet construction programme—part of the Swachh Bharat (Clean India) Mission to make the country open-defecation free by 2019. To achieve the target, the government is nudging states to adopt a stricter law to curb the menace. “Madhya Pradesh is one of the states where Jain monks travel, and if this rule is implemented then it will surely create problems for them who are very strict about following their lifestyle,” he said. The minister has denied receiving any such memorandum from the Jain community. “The minister has not received any such memorandum in the last one week from any representative body of the Jain community,” said Bhargava’s personal assistant. Last year in September, one of Jain religions controversial orthodox rituals -- Santhara -- had run into trouble. A court had banned Jain religion’s centuries-old religious ritual that allows a person to opt death by stop taking food. The apex court later stayed the lower court’s ban. First Published: Apr 30, 2016 22:55 IST

Rudolf Hilf Life Hilf, born in 1923, served as a soldier in the Luftwaffe between 1942 and 1945. After the end of the war, his family was expelled from their homeland and settled down in Bavaria. He studied history at the University of Munich, and, in 1951, advanced onto political science. After that and until 1959, he worked as a foreign policy speaker of the first speaker of the Sudetendeutsche Landsmannschaft in Germany, along with Rudolf Lodgman von Auen. From 1960 to 1966, he was the private secretary of Prince Max Egon von Hohenlohe-Langenburg, a representative of the Bohemian Hochadels. From 1967 to 1973, he was managing director of the national association of the Federation of Expellees. After that, he was a speaker at the Bavarian State Center for Political Education until his retirement in 1988. From 1995 until his death, he has been a member of the Sudeten German Council and the executive committee of the Bavarian State Group of the Sudetendeutsche Landsmannschaft. In 1977, together with Josef Stingl, the former President of the Federal Labor Office, Felix Ermacora, Theodor Veiter, Otto Kimminich and others, he founded the International Institute of Nationality Law and Regionalism (Intereg). He was also the initiator of the German-Czech cross-border region "Euregio Egrensis", founded shortly after 1990. He was also an author of many books, studies, and articles.

Calculating thermal radiation fields from 3D flame reconstruction Designing fire safety into a building requires a designer to think through issues that include fire ignition, growth and spread. Radiative heat transfer from flames is the dominant method of spread. It is, therefore, necessary to determine the thermal radiation field surrounding a fire. This can be estimated from the size and shape of the flame. In this paper we present a method to determine flame size and shape using image-processing techniques. The images of the fire are recorded using multiple cameras. Once the surface of the flame has been defined it is possible to calculate the heat flux at a given target. By repeating this process for multiple targets we can build up a thermal radiation field. This can then be used to find out which adjacent objects are threatened and which are safe.

Gardner's syndrome presenting with proptosis The triad of familial polyposis of the colon, osteomatosis and multiple soft tissue tumours was first identified by E. G. Gardner and later reported in a series of articles (Gardner 1951, Gardner and Plank 1952, Gardner and Richards 1953). Today this syndrome bears his name. Its incidence has been estimated to be one per 14,025 live births (Hsu et al,, 1983). Though several cases have been reported, the present case appears to be the only one to present with proptosis. Our experience with one such case is reported for its clinical interest.

Alicia Zubasnabar de De la Cuadra Biography Alicia Zubasnabar de De la Cuadra was born in the small town of Sauce, Corrientes Province, in 1915. While living there she married Roberto Luis De la Cuadra and had five children with him. In 1945 they moved to settle in La Plata city, capital of Buenos Aires Province. During the military dictatorship named by its leaders as the National Reorganisation Process (1976-1983) her husband, a worker at the Propulsora Siderúrgica (Iron and Steel Propellent) in Ensenada, her son Roberto José and her daughter Elena, who was pregnant, and her sons-in-law Héctor Baratti and Gustavo Ernesto Fraire were abducted, along with her grandson who was later recovered. It would later be discovered that her granddaughter was born in captivity on June 16, 1977, named Ana Libertad by her mother. Except for her grandson, none of them were ever seen again. Monseñor Emilio Graselli, private secretary to the army chaplain Mons. Adolfo S. Tortolo, who had a register listing many abducted individuals and particularly with information on the fates of children born in captivity, told her that her son had died and that her daughter was being held under arrest. A year later, Alicia received news of the birth of her granddaughter and of the deplorable conditions under which her daughter and son-in-law were suffering: On that day (11 July 1977) a young man came to my house and said that he had been in the Quinta police station, La Plata, in the same room as Elena's husband. He didn't tell me anything about my son. But he told me that Elena had had a baby girl, who she named Ana, who weighed 3k 750g and whose footprints were recorded. He told me that Elena shared her cell with five other girls - in an absolute and total lack of hygiene - and who gave birth without medical assistance and while lying on the floor while her cellmates shouted in horror, asking for help. He told me that Elena's husband, along with 35 other men, were at that moment in the next cell, in handcuffs and blindfolded, being periodically tortured. In the end, very hurt, he confessed to me that four days after being born Ana was separated from her mother and that Hector had sent a sort of last message: "Look for our daughter". The judges systematically refused to start any sort of investigative activities. Shortly afterwards, thanks to the negotiations of that Italian Jesuit order, Monseñor Mario Pichi intervened, meeting with Colonel Rospide Rospide to ask him if he could give the child to its grandmother. The Colonel replied: What you are asking me for is impossible, monseñor. The girl - and this is an irreversible fact - has already been given to a very important family. Grandmothers of the Plaza de Mayo The coup d'état of March 24, 1976, established a regime of state terrorism based on the forced disappearance of the opposition and the imposition of an atmosphere of terror designed to avoid complaints. At that time, the family members of the disappeared were completely defenceless and powerless, as neither any of the world's democracies, nor the Catholic Church, nor international humanitarian organisations were ready to condemn the atrocities committed by the military regime and on the contrary even cooperated with this illegal repression in some cases. Nor was it possible to call on the judiciary system for help. Under these conditions a group of mothers, fathers and other family members of the disappeared started a nonviolent resistance movement which made history. The idea was put forward by Azucena Villaflor, later kidnapped and murdered by the dictatorship: We have to go straight to the Plaza de Mayo and stay there until they answer us. On April 30, 1977, they began marching every Thursday around the Pirámide de Mayo in the square of the same name, located opposite the House of Government. To call attention to themselves, the women decided to cover their heads with white cloth. The group quickly became known as the Mothers of the Plaza de Mayo, and by their simple presence they began to exert national and international pressure on the question of the fates of those who disappeared in Argentina. Amongst these mothers and grandmothers was Alicia Zubasnabar de De la Cuadra, "Licha", who had started to participate in the marches in September 1977 along with her husband and Hebe de Bonafini. At that time, another mother and grandmother, María Isabel Chorobik de Mariani or "Chicha", had started looking for other mothers of the disappeared who were, like her, looking for their grandchildren. Mariani had been pushed towards joining up with other grandmothers by Lidia Pegenaute, a lawyer working as an advisor to minors in the courts of La Plata, where she had tried without success to find a solution to her case. In the second half of 1977 Mariani went to see De la Cuadra at her house in La Plata: On the day I met Alicia she was wearing a pink dressing-gown and tidying her house. We started talking and lost track of time. On that day I started to find out what was really happening and to understand that the search had to happen in a different way, that there was not just a single missing child but at least two of them. And if there were two, how many more could there be? For the first time I felt the horrific feeling that we couldn't find the children because they didn't want to give them to us. That same day, Chicha and Licha made the decision to form a group of grandmothers and unite those whom they knew from the Thursday marches in the Plaza de Mayo. Licha (Alicia de De la Cuadra) looked for the other grandmothers that she already knew from the Plaza de Mayo, we met up and we decided to work together. There were 12 of us at that time. It astonished me to see them so calm; I was a wreck, constantly crying, I saw them all looking so calm and I said "I have to be like them". First of all we were known as the "Argentinian Grandmothers with Disappeared Grandchildren". But as we grew, people came to know us and to call us the "Grandmothers of the Plaza de Mayo". (Chicha Mariani) The twelve founding mothers and grandmothers were María Isabel Chorobik de Mariani, Beatriz H. C. Aicardi de Neuhaus, Eva Márquez de Castillo Barrios, Alicia Zubasnabar de De la Cuadra, Vilma Delinda Sesarego de Gutiérrez, Mirta Acuña de Baravalle, Haydee Vallino de Lemos, Leontina Puebla de Pérez, Delia Giovanola de Califano, Raquel Radio de Marizcurrena, Clara Jurado y María Eugenia Casinelli de García Irureta Goyena. Licha Zubasnabar was the group's first president. They were initially known as the "Argentinian Grandmothers with Disappeared Grandchildren", but in 1980 they became legally organised under their publicly recognised name, "Grandmothers of the Plaza de Mayo". The subgroup of "The Mothers" understood that the situation of the children kidnapped by security forces was different from that of their parents, and that specific strategies and methods were needed for their recovery. "Search for our grandchildren without forgetting our children" was the motto which united them. During the military dictatorship and despite the risks, the Grandmothers of the Plaza de Mayo began investigations in order to find their grandchildren, without abandoning the search for their children, at the same time as starting a national and international public awareness campaign focusing on their missing grandchildren and the dictatorship's systematic kidnapping of children. Once democracy was restored on December 10, 1983, the grandmothers promoted the use of the most recent genetic advances to establish a system for identifying their stolen grandchildren, a system unprecedented in the world, and pressured the state into indicting those responsible for the kidnapping of children, considering them to be part of a plan of repression. In 1984, the Grandmothers became a civil non-profit association, with Alicia stepping down as president and the role passing on to María Isabel de Mariani (Chicha). At that time, her husband had just died. From then on, Alicia continued as the group's spokeswoman. By 2008, the Grandmothers of the Plaza de Mayo had recovered 88 grandchildren. It is estimated that, in total, about five hundred children born between 1975 and 1980 were kidnapped. And despite that, one keeps hoping. We keep hoping. And I think that we'll continue to hope for our entire lives. I have often felt desperate and powerless before this wall of silence and total denial of what happened. But I never, never feel beaten, and I always have this conviction to continue to fight until I find all the grandchildren and my own granddaughter, until they are returned to their true homes, until I can hold her in my arms as her parents wanted. And if I can't have my vanished children, I will keep on fighting for what happened to be uncovered, so that Argentina and the whole world know, with no room for doubt, who the murderers were. (Alicia de De la Cuadra)

Localization in a random phase-conjugating medium We theoretically study reflection and transmission of light in a one-dimensional disordered phase-conjugating medium. Using an invariant imbedding approach a Fokker-Planck equation for the distribution of the probe light reflectance and expressions for the average probabilities of reflection and transmission are derived. A new crossover length scale for localization of light is found, which depends on the competition between phase conjugation and disorder. For weak disorder, our analytical results are in good agreement with numerical simulations. We theoretically study reflection and transmission of light in a one-dimensional disordered phase-conjugating medium. Using an invariant imbedding approach a Fokker-Planck equation for the distribution of the probe light reflectance and expressions for the average probabilities of reflection and transmission are derived. A new crossover length scale for localization of light is found, which depends on the competition between phase conjugation and disorder. For weak disorder, our analytical results are in good agreement with numerical simulations. Over the last two decades scattering of light from random optical media has received a lot of attention. In passive random media many interesting multiplescattering effects were discovered, such as enhanced backscattering of light, intensity correlations in reflected and transmitted waves and Anderson localization. Also absorbing or amplifying random optical media have been investigated. In the latter, the combination of coherent amplification and confinement by Anderson localization leads to amplified spontaneous emission and laser action without using mirrors, which have been observed in laser dyes and semiconductor powders resp. These being linear random media, it is interesting to ask what happens in a nonlinear active random medium, such as a disordered phase-conjugating medium (PCM). A PCM consists of a nonlinear optical medium with a large third-order susceptibility, see Fig. 1. The medium is pumped by two intense counterpropagating laser beams of frequency 0. When a probe beam of frequency 0 + is incident on the material, a fourth beam will be generated due to the nonlinear polarization of the medium. This conjugate wave has frequency 0 − and travels with the reversed phase in the opposite direction as the probe beam. The medium thus acts as a "phase-conjugating mirror". Depending on the characteristics of the PCM, the reflected beam is either stronger or weaker than the incoming one, while the transmitted probe beam is always amplified. It has been shown that phase conjugation also occurs in disordered -media. This raises several interesting questions with respect to reflection and transmission of light at such a disordered medium: how are the amplifying properties of a transparent PCM affected in the presence of disorder? What are the fundamental similarities and differences between a nonlinear random phase-conjugating medium and a linear amplifying or absorbing random medium? Is there a regime in which Anderson localization occurs, and what are the requirements to observe this? These questions and their answers form the subject of this paper. Our starting point is the wave equation describing a one-dimensional (1D) disordered PCM   ∂ 2 Here, with E p (x) and E * c (x) the slowly-varying amplitudes of the probe and conjugate electric fields respectively. The offdiagonal parameter ≡ 0 e i = 6 2 0 0c 2 E 1 E 2 is the pumping-induced coupling strength between the probe and conjugate waves in the PCM, with E 1, E 2 the electric field amplitudes of the two pump beams. The disorder is modeled by a randomly fluctuating part (x) in the relative dielectric constant. In order to calculate the reflection and transmission coefficients r p, r c, t p and t c, we use an invariant imbedding approach. Following Ref. we obtain the evolution equations for the probe and conjugate waves in the medium with k 0 ≡ 0 /c and ≡ 2 + 2 0 /c. Using the boundary conditions from Fig. 1 at x = 0 and x = L then yields In the absence of phase conjugation, for 0 = 0, equations (5a) and (5c) reduce to the well-known imbedding equations for a linear random medium, and r c = t c = 0. In the absence of disorder, equations (5b) and (5c) reduce to the evolution equations for r c and t p in a transparent PCM, and r p = t c = 0. Equations satisfy the energy conservation law R p + T p − R c − T c = 1, with R p ≡ |r p | 2 the probe reflectance etc. They form the basis of all our results here. We first derive a Fokker-Planck (FP) equation for the probability distribution of R p. We set r p ≡ R p e ip, substitute this into (5a), subsequently into the Liouville equation is the density of points (R p, p ) in phase space, and average over the disorder. Assuming a gaussian distribution for (L), with (L) = 0 and (L)(L ) = g(L − L ), where pointed brackets denote an average over disorder, yields Here W ≡ Q, l ≡ L/ 0, M (L) ≡ 0 B(L) and −1 0 ≡ 1 2 gk 0 2 p, the inverse localization length in the absence of phase conjugation. In deriving we have neglected angular variations of W, the random-phase approximation (RPA), which applies to the situation of weak disorder when 0 ≫ 1/. Equation is of the same form as the equation for the probability distribution of the reflectance at a linear active random medium, with the important difference that in the latter case M(L) is an L-independent constant, proportional to the imaginary part of the dielectric constant. Using this analogy, our phase-conjugating medium alternates between a linear amplifying (for M (L) < 0) and linear absorbing (for M (L) > 0) random medium. For M (L) = 0 the well-known FP equation for a passive random medium is retrieved. Multiplying both sides of by R n p and integrating by parts leads to a recursion relation for the moments of the probe reflectance, For n = 1 and setting R 2 p ≈ R p, integration of yields for the average probe reflectance with C ≡ (4 2 + 2 )(2 2 + 2 0 ) and ≡ 1/ 0. In the absence of phase conjugation, this reduces to R p = 1 − e −L/0 and in the absence of disorder R p = 0, as for a transparent PCM. Using equations (5a) and (5b), one can directly obtain an evolution equation for the average Z n,m ≡ R n p R m c, which is given by and equivalent to for m = 0. Solving for the conjugate reflectance yields Similarly, one obtains for the probe transmittance from (5a) and (5c) The conjugate transmittance is then given by R c = 0, through the conservation law R p + T p − R c − T c = 1. In order to test these analytical predictions we have carried out numerical simulations. Using a transfer matrix method, equations are discretized on a 1D lattice with lattice constant d, into which disorder is introduced by letting (x) randomly fluctuate from site to site. Figures - show the probe and conjugate reflectance and transmittance as a function of the length L of the medium for various values of the detuning and disorder. In all cases we took d = 10 −4 m and 0 = 10 15 s −1 and typical PCM parameters. Fig. 2 shows how the periodic behavior of R c and T p which is characteristic of a transparent PCM becomes "modulated" by an exponentially decaying envelope in the presence of weak disorder. Simultaneously, and with the same periodicity, some probe light is now reflected and some conjugate light transmitted, due to normal reflections in the disordered medium. When the amount of disorder is increased, the oscillatory behavior of the reflectances and transmittances is less and becomes suppressed for large L, see Fig. 3. The reflected probe and conjugate intensities then both saturate, with lim L→∞ R c = lim L→∞ R p − 1, and T p and T c decay to zero (localization). For a transparent PCM the conservation law T p − R c = 1 applies, i.e. for each pump photon scattered into the forward (probe) beam in the medium, a photon from the other pump is scattered into the backward (phase-conjugate) beam. In the localization regime of Fig. 3, on the other hand, the conservation law R p − R c = 1 applies (cf. Eq. ). Hence T p has exchanged roles with R p due to disorder: all pump photons which are absorbed into probe and conjugate beams are now reflected and despite amplification, transmitted intensities are suppressed. This suppression has also been found in linear amplifying random media. The saturation of R c suggests that the phaseconjugate reflected beam arises in the region into which the probe beam penetrates and that amplification takes mostly place within a localization length of the point of incidence. The behavior of the transmitted intensities with increasing length of the medium is determined by two competing effects: on the one hand, enhancement occurs due to increased probability of multiple reflections. On the other hand, less light is transmitted due to increased probability of retroreflection of the incoming probe light. For small L, the latter effect dominates T p in Fig. 3. As L increases, the increasing amplification of probe light due to multiple scattering takes over, which leads to exponential increase and a maximum in T p. For again larger L, most of the probe light is reflected, and T p decreases exponentially to zero, as in a normal disordered medium. The crossover length scale L c between exponential increase and decrease is given by the solution of 2 + 2 0 cos 2 (L) = 2 2 0 0 cos(L) sin(L), which for ≪ 0 becomes In the opposite limit of ≫ 0 phase-conjugate reflection is weak (maximum value of R c = 0.16) and we retrieve exponential localization, see Fig. 4. Randomness now dominates over phase conjugation and has almost washed out the oscillatory behavior of R p and T p. Comparing the numerical results with the analytic ones from, and we find good agreement (deviations < 5 %) for weak disorder as in Fig. 2, and for stronger disorder and weak phase conjugation as in Fig. 4. In the intermediate regime, for 0 > 1/ ≈ c/ 0 results differ considerably, see inset in Fig. 3. There the RPA and the assumption R 2 p ≈ R p are not valid and a different approach is needed. In conclusion, we have studied reflection and transmission of light at a 1D disordered phase-conjugating medium in the limit of small disorder, for 0 ≫ 1. The predicted behavior of reflectances and transmittances arising from the interplay between amplification and Anderson localization displays similar features as that in a linear disordered amplifying medium. The main difference is the coupling of two waves in the PCM, which leads to additional interference effects. In future work we intend to: investigate the strong disorder regime. There the reflection of the pump beams cannot be neglected, and a full nonlinear analysis is required. Study the distribution of reflection and transmission eigenvalues and the statistical fluctuations in reflectance and transmittance for a multimode 2D or 3D disordered phase-conjugating medium. This is relevant to experiments, which mostly employ 3D PCM's, and interesting in the context of random lasers: in a linear disordered amplifying medium the average reflectance becomes infinitely large with increasing amplification, upon approaching threshold. It would be interesting to investigate whether something similar occurs in a disordered PCM, this being a "naturally" amplifying medium and feasible candidate for nonlinear random lasing. The author gratefully acknowledges stimulating discussions with D. Lenstra. This work was supported by the Netherlands Organisation for Scientific Research (NWO).

Trends in Multicultural Education Research : A Five-Year Content Analysis of Turkish and ERIC Databases This study aims to determine trends in research on multicultural education in Turkish and Eric databases, to compare and to discuss them. Within the scope of the study, research on multicultural education in the International Education Resources Information Center (ERIC) and ULAKBM TR Index (Turkey National Academic Network and Information Center) databases were included. In the study, 308 articles reached in ERIC database and 60 articles in ULAKBM database were analyzed using content analysis. As a result of the analysis, it was determined that there has been an increase in multicultural education publications in ULAKBM TR Index since 2015 and a decrease in the ERIC database. In Turkey, it is seen that there is a tendency to determine attitudes, perceptions and opinions towards multicultural education with larger sample groups; nevertheless, there is a tendency to multicultural education practices and experiences with smaller groups in the ERIC database. INTRODUCTION Multiculturality points to the existence of cultural groups that differ in the social structure. The concept can be used both to explain cultural diversity and to emphasize the fact that cultural diversity is richness (Trk, 2016). Multiculturality, defined as seeking equal rights and recognition for ethnic, racial, religious or sexually defined groups, is one of today's most widespread and controversial intellectual and political movements (Joppke, 1996, p.449). Multiculturality recognizes that different cultures can exist in a society and that all individuals are equal. The content of the concept can vary according to countries with different cultural understandings. Multiculturality is used for the right of immigrants to express their ethnic identities without the fear of prejudice or discrimination in Canada, the sharing of powers among national communities in Europe and to meet the demands of the marginalized social groups in the United States (Snmez-Seluk, 2011). There are number of racial, ethnic, linguistic, religious, belief-related and cultural diversity in countries around the world. However, the emergence of multicultural societies in Europe and North American continents has accelerated, especially with economic migrations beginning in the 1960s. This has led to the emergence of debates about the demands for recognition of cultural differences, citizenship rights and education. The discussion of multiculturality in the contemporary world started with the struggle of indigenous peoples in North America and intense immigration to Western Europe and the Americas after the Second World War. Both the possibilities offered by globalization and the closeness of nation-state policies to cultural diversity have made the concept controversial (zensel, 2013). Multiculturality had emerged in the immigrant countries at first, the United States, Australia and Canada, furthermore, was adopted for the first time as a policy in Australia and Canada. The European states were also faced with multicultural debates, usually as a result of workers' migrations. Cultural diversity in Europe is mainly nourished from three sources. The first source, called "national minorities," is indigenous minorities whose history dates back to old times. The second source is the minorities of immigrant origin. These migrations took place rapidly towards the inner parts of Europe, especially after the Second World War. The other source is the free movements within the EU. The movement particularly due to the mobility of workers' migrations has caused ethnic and religious diversities of European societies and initiated discussions. In England, for example, the languages and cultures of immigrants were regarded as inadequate and their linguistic and cultural differences were underestimated. Therefore, with the debate that began in the late 1960s, improving the legal status of migrants living in the Commonwealth of Nations became a priority issue and the struggle for multicultural education began in the 1970s. Multiculturality was first used in Switzerland in 1957 as a concept but became more widespread after it was used in Canada in the late 1960s. The concept has spread rapidly to other English-speaking countries as well. (Kallen, 1982 cited by Sengstock, 2009, p.239). Therefore, multiculturality in the modern sense is a concept emerged in North America. In the United States and Canada, people who speak a different language and live in the lands they thought belong to; have asked for the recognition of their cultural identity (zensel, 2012). Although the United States has been diverse since its establishment, the ethnic fabric has become even more diverse after the Immigration Reform Act in 1965. The proposals for multicultural curriculum reform, which developed in the USA after 1960 and spread from the centers such as Blacks, Women and Latin Studies in the 1990s, were trying to intertwine the aims of education and the political aims of democratizing society (zkazan, 2000). In the 1960s and 1970s, blacks, Latinos and other minority groups were fighting for their rights, which were virtually invisible in the White Anglo-Saxon Protestant (WASP) curriculum that continued to shape American schools largely. Canada's multiculturality approach, which supports a social structure in which its citizens can experience their cultural differences, differs from the United States. Cultural policies of the United States are defined as the melting pot, while Canada's are defined as the salad bowl. Here, it is emphasized that the individuals in the US society are transformed into a different cultural structure in a melting pot, and in Canada, each society can maintain its own culture, just like the varieties of salad (zensel, 2012). However, multiculturality also takes the flak of some criticism. Some scholiasts pointed out that multiculturality includes a 'divide and rule' strategy on ethnic minorities. There are also criticisms of multiculturality that the protection of "culture" is over-emphasized and therefore less attention has been paid to socio-economic inequalities. However, despite these criticisms, multiculturality has been successfully disseminated in the public sphere in most places in the world. Multicultural Education The education system creates one of the most important reflections of multiculturality in the public area. Multicultural education has become the term often discussed by educators to define education for cultural pluralism involving cultural diversity (Akaln, 2010;Aydn, 2013;Grant & Sleeter, 2010). According to Banks (2010, p.3) multicultural education includes the idea that all students (regardless of gender, social class and ethnic, racial or cultural characteristics) should have equal learning opportunities at school. Babay & Kanc described multicultural education as the process of building the learning and teaching process in a structure to promote cultural pluralism. The important thing in this process is to show respect to different cultures and to create an environment that will ensure a common understanding. According to Gorski, multicultural education is an approach that criticizes current deficiencies in education, failures and discriminatory practices and seeks to transform education in this context. It is based on social justice, equality of education and dedication to facilitate the educational experience that all students can access locally, nationally and globally. Multicultural education helps students develop positive attitudes towards individuals from different cultural groups, reducing discriminatory attitudes and increasing the level of tolerance between groups. Thus, it provides students with opportunities and experiences to recognize their own culture as well as other cultures. In the education system based on a single cultural structure that denies the existing diversity in social structure, individuals may develop negative and marginalizing attitudes towards different cultural groups. Single culture education prevents the development of the ability to criticize, and it not only increases the tendency of rejecting, judging, finding worthless but also aggression, insensitivity, and racism for students who only look at the world from the narrow point of view of their own culture (Parekh, 2002, p.288). Because individuals who try to understand the world only from their own cultural perspectives are deprived of an important part of the human experience and limited from the cultural aspect. In this context, multicultural education offers important opportunities for the development of skills to recognize, accept, to be sensitive, respect, communicate effectively and live together with different cultural groups. If a high-quality life away from inter-group conflicts is desired, it is necessary to teach students how to develop relationships with individuals from different ethnic backgrounds, races, cultures, languages, and gender, including closer knowledge, value, performance, interest, and sharing of power, resources, and responsibilities. The result of not being able to raise individuals who respect cultural diversity can drag individuals or society to moral monism and this understanding can also constitute the basis of social conflicts (Babay, 2014). People or ethnic groups, who have anxiety for not to reproduce their culture and not to transfer it to their children, will politicize their identity and formulate their demands through this identity (ayr, 2016). Such a situation can have the potential to create a basis for inter-group conflicts by increasing isolation, threat perception, anxiety and concerns among different cultures. In this respect, it can be said that multicultural education is a policy that is sensitive to different cultures, which is opposed to educating a single type of individuals and to relying on a single culture and which respects the cultural diversity of individuals and provides an opportunity to develop on an equal scale (Polat & Kl, 2013). In societies embodying different cultural structures, both social cohesion and the interaction of the groups constituting this unity on the axis of recognition and acceptance are at the focal point of multicultural education. Multicultural education is not an approach to specific cultural groups. For example, considering multicultural education as an issue only associated with ethnic problems constitutes the most important prejudice or lack of knowledge (Cokun, 2012). Such lack of knowledge or prejudices leads to the development of fears or concerns about different cultural groups or educational demands of these groups. It is argued that the country can be divided by multicultural education practices, and therefore the unitary state structure can be disrupted (Crk, 2008;Gnay & Aydn, 2015). However, understanding of multicultural education, which is organized to unite a country divided rather than dividing, supports the idea "we are all one". The elimination of such fears and anxieties, prejudices or lack of knowledge can be possible through multicultural education that will provide an environment for interaction and awareness. Multicultural education aims to reduce prejudices, identity conflicts and power struggles in societies with cultural differences in education, ethnicity, race, language, religion, gender etc. and to implement educational policies that address the expectations of society and support pluralism (Acar-ifti & Aydn, 2014). One of the main aims of education for a multicultural society is to increase the awareness of young people about cultural differences and to help them see cultural differences as a natural part of life (zgen & Kker, 2019). Therefore, the necessity of education in order to gain the perception that differences enrich society and to ensure harmony and integration by increasing inter-cultural interactions is indisputable. Multiculturality and Multicultural Education in Turkey Anatolia is a place which has been nurtured with the richness of life practices of different cultures throughout the human history. Turkey, the heir to this cultural heritage, has a rich social structure that includes various cultural differences, ethnic, belief-related and religious. Turkey is a multiethnic and multicultural country that hosts fifty Muslim and/or non-Muslim ethnic groups, including Turks, Kurds, Circassians, Lazs Armenians, Georgians, Jews, Greeks, Arabs, Assyrians, Alawis and Sunnis. Besides, the existence of intertwined sub-definitions in Turkey can be mentioned. In this context, sub-definitions can be made such as those with the same ethnic origin but different languages, those with the different ethnic origins but same beliefs, those with different religious and ethnic origin with the same language and sectarian differences (Polat & Kl, 2013). However, despite the multicultural social structure that exists in Turkey, the founding philosophy of the Republic is based on the creation of a homogenous society in which different cultural structures are expressed with a single identity in line with the nation-state understanding (Arslan, 2016;Kaya, 2005;Kaya & Aydn, 2014). In this context, the construction of a homogenous society on the basis of "Turkishness" rather than a multicultural foundation constituted the basis of educational policies (apar, 2004; ztan, 2011; stel, 2014). The new nation was aimed to be a nation of single-language, single-religion with a single ethnic structure on the basis of national culture and in line with this goal, education is considered as the most important factor in providing national unity and togetherness, and curriculums are prepared in this direction (ayr, 2003). In this respect, the main purpose of national education, which was the way to transform the Turkish people into a nation, was to melt or assimilate the "foreign cultures", thus building the uniform Turkish nation. This circumstance presented itself in the textbooks of the period. For example, in the geography textbook of 1929, where the human characteristics of the country's population were expressed, nomadic peoples were counted one by one, the tribal structures of Yoruks, Turkmens, and Kurds and the names of their settlements and even the names and sub-branches of the Kurdish tribes were included, in short, all human characteristics of Anatolia have been elaborated (zgen, 2011). However, then, a "taboo model" was observed dominated by a concept of unmanned geography, far from multicultural and multi-perspective approach, which ignores all the differences in the country (Kahyaolu, 2003). The education in the early years of the Republic based on the understanding of ethno-cultural citizenship showed a transition towards the understanding of political citizenship in the 1950s, since the second half of the 1980s, with the reflection of military coup in education, Islam has been regarded as an important component of citizenship and in addition to the "language and race", religious elements have been added to the material elements that made up the nation (stel, 2014). In 1999, with the European Union's promise of candidacy to Turkey, mutual harmonization agreements were signed for the understanding of international social and cultural phenomena in depth (Gnay & Aydn, 2015). Within the framework of the European Union harmonization laws, Turkey had to consider the language, culture and religious characteristics of various groups in Anatolia in the field of education (Crk, 2008). Multicultural ascensions have started since 2004 and various languages and dialects (Kurdish, Zaza, Laz, Adyghe, Abaza, Georgian) were introduced in the 2012-2013 academic year as elective courses in the secondary and high school curriculum, with the aim of learning different languages and dialects in the name of "living languages and dialects" (Aktrk, 2018;Erdomu & Orkin, 2018). However, the current historical narrative and collective identity in the textbooks is still only created through Turkishness and Turkish language (ayr, 2016). Therefore, education in Turkey still has a single culture-based quality. However, the current multicultural structure stemming from the historical structure of Turkey is increasingly diversified with increasing migration and refugee populations in recent years. According to the data of the General Directorate of Migration Administration, the increase in the number of irregular migrant arrivals and apprehensions to Turkey from Syria, Afghanistan, Pakistan and Iraq since 2016 leads to the diversification of cultural groups. This situation has led to different repercussions in the education system as in many areas. Therefore, policies on new concepts, projects, programs, school organization types, teacher training models, development of education and teaching materials need to be developed in the field of education (Cokun, 2006). One of the most important ways of integrating different cultures into society and ensuring social cohesion is education. Studies in the field of education stem from social needs and their findings play a decisive role in educational policies. In order to make education systems effective, international research and research in developing countries constitute two important sources of information (Karip & Kksal, 1996). Therefore, these two sources of information are important in establishing an effective multicultural education policy. The first of these is international research which is done as both theoretical and practical in the field of multicultural education. These studies present valuable findings in terms of national studies and practices. The second important source is the national studies that present the current situation and needs. Academic research in multicultural education has a guiding function on presenting the current situation, development, and needs and in the development of educational content, practices and training policies. In this context, it can be said that multicultural education studies in national and international fields will provide versatile and alternative perspectives in line with their theoretical and practical contributions and will create opportunities for international cooperation. Thus, it was targeted in this research to identify trends in research on multicultural education, to put forward their point of view, to determine, compare and discuss loaded meaning to multicultural education in Turkish and Eric database scale. Research on multiculturalism has gained a prominent place in the literature. Although these studies are carried out with many different research patterns, the scarcity of content analysis studies is remarkable. When the international literature is examined, it was reached studies as follows; gender orientations in multicultural education textbooks (Jennings & Macgillivray, 2011), 20-year content analysis of multicultural guidance competence (Worthington, Soth-McNett & Moreno, 2007), representation of differences in picture books, examination of teacher training course contents in terms of multiculturalism, 10 years of journal content analysis for multicultural guidance (Arredondo, Rosen, Rice, Perez & Tovar-Gamero, 2005), ethnicity investigation in high school history textbooks (Woyshner & Schocker, 2015), 17-year content analysis for multiculturalism, diversity and social advocacy, including guidance training and supervision (Smith, Ng, Brinson & Mityagin, 2008), and content analysis for multicultural counseling course content (;Pieterse, Evans, Risner-Butner, Collins & Mason, 2009) and representation of disabled people in textbooks (Johnson & Nieto, 2007). It is seen that the content analysis researches toward multicultural education in Turkish literature are even more limited. In this context, only a content analysis study was conducted by Gnay and Aydn which examined the multicultural studies in Turkish literature between the years 2005-2014. In spite of all these researches, we could not encounter the study that examines multicultural education researches comparatively. This study aims to determine the trends by comparing multicultural education research in ERIC (Education Resources Information Center) and Turkish ULAKBM TR (National Academic Network and Information Center) databases. For this purpose, look for answer the following research questions: RQ1: What is the distribution of the studies in the field of multicultural education between the years 2014-2018? RQ2: What is the distribution of the studies in the field of multicultural education between the years 2014-2018 according to research methods? RQ3: What is the distribution of the studies in the field of multicultural education between the years 2014-2018 according to data collection tools and data analysis methods? RQ4: What is the distribution of the studies in the field of multicultural education between the years 2014-2018 according to sampling method, sampling size and sampling level? RQ5: What is the distribution of the studies in the field of multicultural education between the years 2014-2018 according to research topics? Research Design This study that aims to examine multicultural educational research in ERIC and ULAKBIM databases is a descriptive comparative research. Within the scope of the research, it was aimed to make various conclusions by focusing on articles related to multicultural education through content analysis method. Although content analysis is a method first used in mass media and public speech, it is also used in educational research to contribute to the summarizing and reporting of written materials (Cohen, Manion & Morrison, 2007, p.475). According to Krippendorff (2004, p.18), content analysis is a research technique that can be renewed from a variety of texts and used to make valid conclusions in accordance with the field of usage. On the basis of content analysis, there are large sets of data which are analyzed according to various characteristics. For this reason, content analysis is described as the process of discovering the meaning and consistency of products by making qualitative products a focal point (Patton, 2014, p.453). Sampling In the determination of the articles to be included in the research, firstly ERIC and ULAKBIM databases were accessed and the search was conducted with the keyword "multicultural education" (Figure 1). Since it is aimed to reach current publications, a time limit has been applied for 5 years between 2014 and 2018. After that, the full text and refereed articles within the scope of multicultural education Figure 1. Article determination process (ME) databases are stored in a computer environment by the researchers. The final check was carried out by removing irrelevant publications. Publications in journals scanned in both ERIC and ULAKBIM databases were evaluated only under ULAKBIM. In this context, 308 articles in ERIC database and 60 articles in ULAKBIM database were subjected to content analysis. Data Collection Tool The research data were collected through the article analysis form, originally developed by Szbilir, Kutu and Yaar and revised by the researchers in accordance with the research scope. Within the scope of the research, it is aimed to reach the findings related to the distribution of multicultural education studies, method preferences, target audience and scope within a five-year period, article analysis form consists of eight categories (research year, research method, data collection tool, data analysis method, sampling method, sampling size and level, and research topic) for the analysis of articles. Data Analysis Firstly, 308 articles from ERIC database and 60 articles from ULAKBIM database were ranked and were analyzed through eight categories (research year, research method, data collection tool, data analysis method, sampling method, sampling size and sampling level and research topic) determined by the article analysis form. Then, an analysis form was created for each article and content analysis was applied to the listed forms. Content analysis consists of five basic phases: meeting with data, generating codes, defining themes, creating thematic networks, integrating and interpreting. In the data analysis process, the data set was first examined by adhering to the phases, coding was performed in accordance with the data collection tool, theme names were made explicit, data set was integrated, visualized and interpreted with tables and charts. In order to ensure the validity and reliability of the research, expert opinion was taken for the articles. Thus, two experts working in the field of multicultural education were reviewed the articles for suitability. In addition, the article evaluation form revised by the researchers was presented to same experts, then the analysis process was initiated. In the analysis process, the data sets were encoded by the researchers individually, the themes were determined by applying constant comparative process and the coding was collected under themes by consensus. Thus, a more objective and coherent process was aimed to carry out. Table 1 is examined, it is seen that publications for Multicultural Education (ME) in the journals indexed by ULAKBIM in Turkey have increased since 2016. In this context, when the journals indexed by ERIC, an international index, are examined, it is also noted that multicultural education publications show a large increase (50%) compared with 2015 to the previous year, and that there is a tendency to decrease in the number of publications after 2015. When When the findings in Table 2 are examined, it is observed that the quantitative methods have a usage rate of 46.66% in ME related publications in the journals in ULAKBIM index. In ERIC index, on the other hand, it was found that qualitative research was preferred by 42.86%. This indicates that there is a tendency towards quantitative research in Turkey and qualitative research in the international arena. In addition, it was found that in the studies in ULAKBIM database, qualitative research was preferred 38.33%, literature research 8.33% and mixed method research 6.7% were preferred. ERIC database, on the other hand, includes quantitative research approach with a rate of 28.57%, mixed method research 4.55%, and literature research 24.02%. It is observed that literature studies are preferred more frequently in the international arena than in Turkey. The results of detailed analysis of the methods used are presented in Table 3. As can be seen in Table 3, survey research design of the quantitative methods (33.33%) and the phenomenology research design (15%) were frequently used in the studies related to ME in the ULAKBM database. In the mixed research method, it was determined that the convergent parallel (quantitative-qualitative) research design (3.66%) was used the most. When looked at ERIC database findings, it was found that the descriptive research design was more preferred (10.72%) in quantitative research, case study design (19.15%) was more preferred in qualitative research, exploratory design (3.24%) was more preferred in the mixed approach. As shown in Figure 2, there is an increase in the use of quantitative research methods in the ULAKBIM database since 2014. The use of qualitative research methods was seen to be more in 2016, but it was observed that there was a tendency to decline from this date. Again, mixed research methods were not used in 2016 and 2017. It is observed that In line with the findings in Table 4, it was determined that the scale aimed at generating attitudes, perceptions and opinions in the ULAKBIM database was used more as a data collection tool (37.68%). The other data collection tools that were frequently preferred after the scales were interview (26.08%) and document (18.84%). It was seen that questionnaires (8.69%), and observation (8.69%) were the least preferred methods. When data collection tool trends were examined in articles in ERIC database, it was found that documents (28.26%), followed by interviews (23.43%), alternative tools (16.67%), questionnaires (11.25%), observation (8.94%) and achievement test (0.24%) were preferred the most. In Figures 3 and 4, there are findings of quantitative and qualitative data analysis of the articles published on ME in journals indexed by ULAKBIM and ERIC. When the findings are examined, it is observed that quantitative predictive analysis methods (f=63) are mostly preferred in ULAKBIM database. When the findings regarding qualitative data analysis were evaluated in Figure 4, it was determined that the content analysis was used more (f=17). In the articles in ERIC database, it is observed that descriptive analysis methods (f=98) in quantitative dimension and content analysis methods (f=167) in qualitative dimension are preferred the most. The findings related to the data analysis methods used in the articles are detailed in Table 5. The results of the sample group selection of articles published on ME in the journals indexed by ERIC and ULAKBIM were presented in Figure 5. In the articles in ULAKBIM database, it is observed that non-random sampling selection (f=28) is frequently preferred. In line with the results obtained, it is determined that the authors did not give a statement on the sample selection in 23.91% of the articles. Again, it is determined that there was no explanation for the sample selection method in 73.05% of the articles in ERIC database. In the articles that explain the sampling selection, on the other hand, it was determined that non-random sampling (f=51) methods were most frequently used ( Figure 5). As can be seen in Table 6, in the articles related to ME in ULAKBIM database, purposeful and convenience, and in the articles in ERIC database, purposeful sampling methods are observed to be preferred frequently. Notably, many studies in the ERIC database do not have sampling methods. When Table 7 is examined, it is observed that the articles in ULAKBIM index are frequently carried out with the sample group in the range of 301-1000 (32.6%). After this range, the range of 101-300 (26%) was preferred the most. In qualitative studies, the range of 11-30 (15.2%) was preferred frequently. The preference rate of sample groups with more than 1000 people is the lowest (2.2%). When looked at the articles in ERIC index, it is seen that the sample size in the range of 1-10 (31.51%) was preferred more frequently because of the preference of qualitative research method. Then it was found that 11-30 (21.46%) and 31-100 sample range (20.55%) were preferred. This finding can be interpreted as more in-depth research conducted with smaller sample groups in ERIC database. In Table 8, the results of the sample level distribution of articles published on ME in the journals indexed by ULAKBIM and ERIC were presented. When the findings in ULAKBIM database are examined, it is observed that students who continue their undergraduate studies (42.8%) and teachers (30.3%) are frequently preferred in the studies. These two groups are followed by the sample group of high school students (12.5%). In the articles in ULAKBIM database, 75% of the undergraduate sample group (f= 18) consists of students of education faculties. It was determined that the students at pre-school were not selected as sample groups in the studies related to multicultural education. Another important finding is that there are no researches on multiculturality and multicultural education on parents who have a direct impact on the life of the individual. In the ERIC database, a sample group (37.01%) was selected prominently at the undergraduate level. Besides, 39.47% of the studies at undergraduate level are consist of education faculty students (f=45). The undergraduate group is followed by teachers (15.58%) and academics (8.12%). As a remarkable finding, "pre-school students, parents and adults" sample levels are not found in the articles in ULAKBIM database, but included in the articles in ERIC database. When the Table 9 is examined, it is observed in the articles in ULAKBIM database that the researchers conducted studies mainly on attitudes (21.7%), views (16.7%) and perception (15%). These studies are followed by studies on self-efficacy (13.3%) and ME tools (curriculum and textbooks) (10%). A more limited number of studies for ME practices (3.3%) and ME implementation in Turkey (3.3%) have been conducted. Studies in ERIC database show that studies focusing on ME practices (23.7%) and experiences (15.27%) are predominant. These studies are followed by studies general situation assessment related to ME (9.74%), determination of perception (7.79%) and attitudes (7.14%) and analysis of ME tools (7.14%). There are fewer studies conducted on self-efficacy (5.84%), awareness (4.55%) and personal qualifications (2.6%) and determination of views (2.27%). DISCUSSION, CONCLUSION AND SUGGESTIONS This study set out to better understand the dispositions of multicultural education research in international (ERIC Index) and national (ULAKBM TR Index) scale comparatively. This is the first research compare ULAKBM TR and ERIC indexes in terms of multicultural education research. Therefore, the results of the research provide important implications for the multicultural education literature studies. According to the results of the research, although there has been an increase in the number of publications related to multicultural education in Turkey since 2015, a downward trend in the international arena took place after 2015. In the study carried out by Gnay and Aydn, it is stated that researches on multicultural education in Turkey has increased since 2005. The main dynamics underlying this situation is also the reason for the change in the national literature. It is thought that in line with an initiative process which started by Turkey towards owned different cultural groups, the developments occurred in the education system affected multicultural educational researches. In addition, Turkey is becoming the first stop for the refugees as a result of the Syrian Civil War (duygu, 2015;Baban, Ilcan & Rygiel, 2016), the increase in asylum demands of Iranian, Iraqi, Palestinian, Uzbek, Somalis, and Sudanese people (duygu & Aksel, 2012) and the increase in the number of irregular migrants have led to changes in Turkey's social structure and to the emergence of needs for the recognition and integration of different cultures in education. In order to ensure that individuals who are raised in a multi-lingual and multicultural society do not experience socio-cultural disconnection with the society they live in and that integration can be carried out in a healthy way, the correct infrastructure needs to be prepared (Aknc, Nergiz & Gedik, 2015). This circumstance creates a need for studies in the field of multicultural education more than ever. The increases in the number of academic works for multicultural education in Turkey can be utilized in line with these needs and developments. Education policies, which have been established on a solid basis today as a result of the understanding of the need and importance of multicultural policies and practices in the early period from Turkey, can be shown as the reason of the downward trend in the number of publications in ERIC indexed journals. Unlike this situation, in Europe and the United States today, nationalist policies are rising due to immigrants and the nationalist rhetoric of country leaders draws attention. For example, the election campaign and policies directed towards discrimination and xenophobia carried out by Trump praising white and middle-class Americans (Harris, Davidson, Fletcher & Harris, 2017), the declaration of failure of multiculturality by Chancellor Merkel for the first time (Yardm, 2017), and the clash of cultures with the UK's desire to isolate itself from Europe and the influx of refugees who reach Europe have caused changes in view of multiculturality and multicultural policies. This can also be shown as a result of the tendency to decrease in the publications related to multicultural education in the international arena. It has been determined that the method preferences of articles for multicultural education are different in ERIC and ULAKBIM databases. In the research in ULAKBIM database, it was determined that the survey pattern, the scale aimed to determine attitude, perception and view as a data collection tool, and the predictive statistical methods used in the data analysis process were frequently used within the scope of quantitative research approach. Furthermore, while the use of quantitative methods has an increase trend by years, qualitative and literature studies show a decline. In national multicultural education research reached by Gnay and Aydn, it is observed that quantitative research and attitude scales as a data collection tool were predominantly preferred until 2014. In ERIC database, on the other hand, qualitative research, and in this context, case study pattern weighted study tendency is observed. In accordance with this research direction, document and interview methods were employed during the data collection process. In the analysis process, content analysis is dominant within the context of qualitative analysis. In contrast to our study, it was reached in the study conducted by Soth-Mcnett and Moreno that quantitative research was used to most within the scope of multicultural counseling competence, while literature studies were used to most in content analysis conducted by Arredondo et al.. In addition, it has been determined within the scope of this study that literature studies are more in ERIC database. The rate of mixed-method research in both databases is very limited. The sampling preferences of the studies in ERIC and ULAKBIM databases show different tendencies. While studies are conducted with large sample groups since the quantitative screening pattern was preferred in Turkey, small sample groups were preferred in ERIC indexed articles in accordance with the nature of qualitative research. Similarly, Gnay and Aydin concluded that previous studies in Turkey were carried out with large sample groups. Although quantitative studies are conducted with larger groups in a shorter period of time, it is not possible for them to give the opportunity to reveal the perception, value, or experience of individuals in depth. Qualitative research, on the other hand, include numerous methods and variations, an interpretive framework and makes it easier to understand the situation in depth by allowing detailed information to be obtained. Therefore, qualitative studies are needed in order to reflect the diversity present in Turkey on the educational environment and to evaluate the political arrangements in this regard in terms of experiences, needs and problems with depth and multiple perspectives. When sampling methods in researches are examined, while non-random sampling methods are frequently preferred in articles within the scope of ULAKBIM, the majority of ERIC indexed articles (73%) did not state their sampling methods. This compromises of the generalizability and validity of the research in ERIC database. However, in the context of multiculturality and in the field of guidance and counseling, it has been found by Worthington, Soth-McNett and Moreno to be the most frequently used sampling method. When sampling levels were examined, it was determined that the studies in two indexes focused on the undergraduate level. While 75% (f= 18) of the undergraduate sample group in the ULAKBIM database consists students of education faculties, this rate in ERIC database is 39.47% (f=45). In the studies indexed by ERIC, unlike the studies in ULAKBIM database, it is remarkable that all the stakeholders involved in education are involved in the sample level. For example, it was also studied in the sample groups of pre-school students, parents and adults which were not involved in the researches in ULAKBIM database. However, it is observed in both databases that policy makers and senior managers in the education field are not involved as sample level. When the topic preferences in researches are examined, researches in the ULAKBIM index focuses on descriptive issues such as attitudes, views and perceptions related to multicultural education. In the researches indexed in ERIC database, on the other hand, it was determined that there was a tendency towards applied topic areas such as multicultural education practices and experiences. This is proof that multiculturality and multicultural educational research show a much more recent development in Turkey than in the international area. On the contrary, it has been observed that the research in the international field is at a stage in which the practices and the experience related to this process are examined in line with the prevalence of multicultural education practices (Baltes, Hernandez & Collins, 2015;Golub, 2014;Guth, McAuliffe & Michalak, 2014;Perveen, 2014). Studies conducted on multiculturality in Turkey generally show that teacher candidates, teachers, administrators and academics are positive in multiculturality and multicultural education (Akkaya, Krmz & i, 2018;Alanay & Aydn, 2016;Avc & Faiz, 2018;Baarr, Sar & etin, 2014;Damgac & Aydn, 2013;Kahraman & Sezer, 2017;Polat, 2012), although there are many deficiencies in curricula and textbooks (Akar & Keyvanolu, 2016;Akhan & Yaln, 2016;ayr, 2016;Keskin & Yaman, 2014;Seban & Uyank, 2016). Therefore, education policies in Turkey are still not equipped to bring multiculturality into educational environments (Kker & zgen, 2018). At this stage, the insufficiency of visionary academic studies also constitutes an important deficiency. All these results, despite the cultural diversity in Turkey, indicate that the nation-state reflex is still active and the insufficiency of political reflections and practices despite the presence of positive attitudes and views of multicultural understanding. Due to its cultural diversity and large number of refugee populations (United Nations High Commissioner for Refugees , 2015), and the increase in the number of international students, Turkey must develop multicultural education policies and implement them on a solid basis. In this context, various configurations are needed for the development of educational policies to meet the needs of Turkey, the multicultural school environment, school management, curriculum and teaching process, teacher competencies and counseling. It is certain that the studies related to the topic will be decisive, explanatory and guiding sources in this process. Although the study has gone some way towards enhancing our understanding of dispositions on multicultural education research in 5-year period, it has certain limitations. This study covers a 5-year process between 2014 and 2018 and ULAKBIM TR and ERIC indexes. In order to move multicultural education studies to a more advanced level, multicultural education researches in journals covered by different indexes (Social Sciences Citation Index, British Education Index, and Australian Education Index etc.) can also be analyzed. Thus, the current situation of multicultural education research can be considered in a more holistic way. Furthermore, unlike this study, finding out with which discipline the research is conducted will be useful to find out which disciplines have multicultural education accumulation or inadequacy and to determine the needs in this regard. Besides, in addition, a broader analysis can be made by differentiating the years covered by this research. Finally, the direction of multicultural education research can be revealed statistically with meta-analysis studies.

Research on optimization method of primary frequency modulation capability based on different ratios of hydropower With the continuous development of Chinas cross-regional interconnected power grid, large- capacity and long-distance transmission have become an important feature of Chinas power grid. As the transmission capacity of single-return transmission lines continues to increase, the risk of frequency fluctuations increases, making grid operation scheduling more concerned with the performance of the units primary frequency modulation. This paper tests the frequency stability of a power system under different scenarios, in which the proportion of water and thermal power in the system is different. The results represent that a system with a large proportion of hydropower has poorer frequency stability. This paper offers a method of primary frequency modulation, which proposed to improve the frequency stability of the system by increasing the time delay of the hydropower units governor. The results of simulation prove that this method is an available solution to solve the problem of poor system frequency stability when a system has a high ratio of hydropower.

Nongenomic effects of progesterone on spermatozoa: mechanisms of signal transduction and clinical implications. Progesterone (P) is one of the physiological stimuli of human sperm acrosome reaction. It is present in high levels at the site of fertilization (cumulus oophorus) and has been describe to affect several sperm functions including motility, capacitation and acrosome reaction. The effects of the steroid, which is present in high levels in the cumulus matrix that surrounds the oocyte, are mediated by an increase of intracellular calcium concentrations, efflux of chloride, stimulation of activity of phospholipases and phosphorylation of proteins. These effects are due to activation of a rapid/nongenomic pathway. Two different types of receptors for P, distinct from the genomic ones, have been recently identified on the surface of human spermatozoa. The affinities of P for these receptors are respectively in the nano- and in the micromolar range. Sperm responsiveness to progesterone is impaired in subfertile patients and is strictly correlated to the ability of fertilize the oocyte. In addition, the determination of sperm responsiveness is predictive of fertilizing ability with a positive predictive value of 90% and can be clinically useful for the preliminary assessment of the male partner to select the appropriate assisted reproductive technique.

A 64-year-old Grande Prairie "tax protestor" has been fined $40,208 and will go to jail for 15 months for tax evasion, says Canada Revenue Agency. Edwin McCallum Siggelkow’s fine represents 150% of the tax evaded, stresses the CRA. Siggelkow was found guilty by a jury Sept. 18. He evaded federal income taxes of $13,826 for the 2005 to 2007 tax years. In addition, Siggelkow failed to collect and remit goods and services tax (GST) of $12,978 for the 2005 to 2007 tax years. He was also found guilty of counselling others to commit fraud contrary to the Criminal Code. Evidence provided to the court showed that Siggelkow — an "educator" with the Paradigm Education Group operated by Russell Porisky — adopted Paradigm’s beliefs to allege that, as a "natural person," he was not subject to the Income Tax Act. Court heard that Siggelkow knowingly evaded taxes and was also aiding, abetting and counselling others to commit tax evasion. Porisky was convicted in the Supreme Court of British Columbia on Jan. 18, 2013, of tax evasion and counselling others to commit tax evasion. Canada Revenue Agency warns all Canadians to beware of individuals that claim Canadians do not have to pay tax on the income they earn. These individuals, also known as tax protesters, not only fail to report their own earnings, but they also conspire, counsel, and promote these tax schemes. Canadian courts have repeatedly and consistently rejected all arguments made in these tax protester schemes. For those involved in tax protester schemes, the CRA will reassess income tax and interest, and charge penalties. In some cases, these individuals will be prosecuted for tax evasion. If convicted, they could face significant fines and possibly jail time. When individuals are convicted of income tax and GST evasion, they must still repay the full amount of taxes owing, plus interest and any civil penalties that may be assessed by the CRA. In addition, the court may fine them up to 200% of the taxes evaded and impose a jail term of up to five years.

Problems related to voiding pattern in patients with hypospadias repair: i s the problem related to only operation? study, the ABSTRACT Background: Problems related to the urine flow are rather common in hypospadias patients. As these problems are detected during follow-up of urine flow in the post-operative period, it is difficult to determine whether it is a problem emerging secondary to the surgery or it is a congenital condition. Objective: The objective of this study was to evaluate the lower urinary tract functions in hypospadias patients with pre-operative and post-operative uroflowmetric examinations and to determine whether it is a complication of the surgery or a congenital condition. Materials and Methods: A total of 63 patients who underwent hypospadias surgery and were monitored postoperatively between January 2012 and January 2013 were enrolled in the study. Data about the pre- and post-operative uroflowmetry parameters were collected and compared. Results: Of total 83 patients, only 63 (76.8%) patients, whose parents provided the written consent, were studied. The mean age was 6.9±2.4 years (314 years). The mean bladder volume estimated according to the age of the patients was 266.5±71.7 ml. The mean bladder volume before and after the surgery was 179±56 ml and 189±53 ml, respectively, and the bladder volumes were 67% and 71% of the estimated bladder volume, respectively. There was no significant difference between the bladder volumes measured before and after the surgery (p=0.159). Furthermore, no significant change in the measurements regarding the maximum flow rate, time to maximum flow rate, total time of the urine flow, mean flow rate, voided volume, voiding time, and post-void residual volume was observed. Conclusion: The uroflowmetry is an easy-to-use, non-invasive, and objective method, which can be used for the early diagnosis of the urethral stricture following the hypospadias surgery and the evaluation of the obstructions in the lower urinary tract. T he incidence of the hypospadias is one in every 300 live male births and is one of the congenital urogenital anomalies, which most commonly require a surgical intervention. The main goal of the hypospadias surgery is to establish a normal appearance and form a functional urethra. Problems related to the urine flow are rather common in hypospadias patients. As these problems are detected during the monitoring of the urination in the post-operative period, it is difficult to determine whether the problem is related to the surgical intervention or is a congenital condition. The uroflowmetry is an easy-to-use and inexpensive method for the evaluation of the urine flow. In this study, the objective was to evaluate the lower urinary tract functions in hypospadias patients with pre-operative and post-operative uroflowmetric examinations and to determine whether it is a complication of the surgery or a congenital condition. MATERIALS AND METHODS A total number of 83 patients who were followed up due to the hypospadias in our clinic between 2012 and 2013, were included in our study with the approval of ethics committee (29/05/2012/41). Only the patients, who were older than 3 years, had no urinary incontinence and were able to feel a full bladder (urge), were enrolled in the study. Patients and their families were informed about the study, the planned intervention was explained in detail and the informed consents were obtained from the patients, who accepted to participate in the study. The participating patients underwent uroflowmetric examination for the urine flow before the surgery during the examination in the outpatient clinic and 2 months after the surgery. The urethral dilatation was performed in patients, who were diagnosed with urethral stricture and the uroflowmetry was repeated after the intervention. In all patients, the medical history was recorded and physical examination was carried out. The place of the hypospadic meatus, concomitant urogenital anomalies, and the presence of the chordee were examined. The presence of a urinary tract infection was evaluated in patients with complaints related to the urine voiding. Patients, who had no toilet training, urinary incontinence, urine volume more than 100 ml, fistula after the surgery, and urinary tract infection, were excluded from the study, as the urine flow parameters measured with the uroflowmetry would have been affected. The patients drunk sufficient amount of liquid and waited until they had an urge. After the bladder was full, the uroflowmetry measurements were carried out followed by measurement of the residual urine volumes with the ultrasonographic examination. The residual urine volume was calculated with the multiplication of the horizontal (D1), vertical (D2), and oblique (D3) lengths of the bladder with the coefficient 0.7. Residual urine volume up to 5 ml was defined as a normal volume, whereas a residual urine volume between 5 and 20 ml was defined as a volume over the normal limit. If the residual urine volume was over 20 ml, the measurement was repeated after which a residual urine volume over 20 ml was evaluated as incomplete voiding or abnormal voiding. The estimated bladder volume was calculated according to the ages of the patients and the results were analyzed with the Siroky nomogram, which was preinstalled in the uroflowmetry device. The results of the pre-and post-operative uroflowmetry measurements were evaluated according to the maximum flow rate, time to maximum flow rate, total time of the urine flow, mean flow rate, voided volume, voiding time, and post-void residual volume. Statistical analysis was done with the SPSS v15.0 software package, and the analysis of results was performed with the descriptive statistical methods (frequency, percentage, mean, and standard deviation) along with the examination of the normal distribution (Kolmogorov-Smirnov test). Data without a normal distribution were analyzed with the Mann-Whitney U-test, and the results were expressed as minimum and maximum values. Data with normal distribution were tested with Student's t-test and standard deviation values were calculated. Wilcoxon signed-rank test was used for the intergroup comparison of the parameters. The results were evaluated at a confidence interval of 95% and significance level of p<0.05. RESULTS Of total 83 patients, only 63 (76.8%) patients whose parent's provided the written consent were studied. The mean age was 6.9±2.4 years (3-14 years). According to the Barcat classification, 54 patients (85.6%) were evaluated as the distal group and 9 (14.4%) as middle and proximal group. The mean bladder volume estimated according to the age of the patients was 266.5±71.7 ml. The mean bladder volume before and after the surgery was 179±56 ml and 189±53 ml, respectively, and the bladder volumes were 67% and 71% of the estimated bladder volume, respectively. The bladder volume was smaller than expected in the hypospadias patients (p<0.001). There was no statistically significant difference between the bladder volumes measured before and after the surgery (p=0.159). Furthermore, no significant change in the measurements regarding the maximum flow rate, time to maximum flow rate, total time of the urine flow, mean flow rate, voided volume, voiding time, and post-void residual volume was observed (Table 1). Regarding the group with the distal location of the meatus, the maximum flow rate was 9.9±4.1 ml/s and 11.0±4.9 ml/s before and after the surgery, respectively. The increase in the maximum flow rate after the surgery was statistically significant in the same group (p=0.008). The evaluation of the voiding curves calculated with the uroflowmetry showed that the curve had a bell shape in 35 patients (55.6%) before the surgery and in 44 patients (69.8%) after the surgery ( Table 2). The comparison of the voiding curve pattern, pre-and post-operatively, revealed that the percentage of the patients with a plateau-shaped voiding curve declined after the surgery. However, the difference was not statistically significant (p=0.093). The evaluation of the uroflowmetry results with Siroky nomogram showed that 27 patients (42.9%) had an obstruction lower than two standard deviations (<−2 standard deviation); the rate of the patients with the suspicion of obstruction was 42.9% before the surgery and 25.4% after the surgery (Table 2). However, the difference was not statistically significant (p>0.05). There was no statistically significant difference between the pre-operative and post-operative results in the patients with the proximally located meatus in respect of the maximum flow rate, time to maximum flow rate, total time of the urine flow, mean flow rate, voided volume, voiding time, and post-void residual volume (p>0.05), and the same observations were noted, among the 18 patients (28.6%), who had chordee. The evaluation of the patients with a bell-shaped and bellshaped voiding curve pattern before the surgery, both showed that there was no statistically significant difference between the uroflowmetry measurements before and after the surgery regarding the maximum flow time, time to the maximum flow rate, flow time, mean flow rate, voided volume, and residual urine volume (Table 3). In patients with a plateau-shaped curve, the maximum flow rate was 8.4±4.1 ml/s and 10.3±5.1 ml/s before and after the surgery, respectively. The increase was statistically significant (p=0.017), and the statistically significant (p=0.017) mean flow rate was 6.9±3.8 ml/s and 7.5±2.5 ml/s, before and after the surgery, respectively. 13 patients (20.6%) complained of "dar ieme" and strangury in the post-operative period. In the post-operative period, 16 patients (25.4%) were <2 standard deviations according to the Siroky nomogram and were considered in the stricture group. In these patients, the maximum flow rate, mean flow rate, and voiding time were significantly lower compared to the patients, who did not need dilatation (p<0.01). These patients underwent urethra dilatation under general anesthesia. Following the dilatation, the flow rate, mean flow rate, and voiding time improved significantly (p=0.003, p=0.004, and p=0.007). There was no statistically significant difference in the maximum flow (p=0.317) and mean flow rate (p=0.206) after the dilatation compared to the patients, who did not need dilatation. DISCUSSION The patients with hypospadias may have an abnormal voiding pattern depending on the dysfunctions of the lower urinary tract, Vol 5 | Issue 8 | August 2018 Indian J Child Health 542 the anomalies of the vesicoureteral junction, prostatic utricle, and abnormally located external urethral meatus. Regarding the post-operative period, in addition to these disorders, the absence of a normal spongy supports to the urethra, the development of stricture in the urethra, particularly in the external urethral meatus may have an adverse effect on the voiding pattern. Urethral stricture is the second common complication in the hypospadias surgery after urethral fistula. Barbagli et al. reported in their 19-year series consisting of 1176 patients that 25.5% of the patients developed urethral stricture after the hypospadias surgery. The strictures tend to emerge on the suture line of the proximal anastomosis following the closure of the urethral meatus and glans. This condition manifests itself with the weakening of the urine flow force, strangury, or urinary tract infection within 2 months after the hypospadias repair. Furthermore, the patient may apply with complaints of split stream, urethral fistula, and urinary retention. The uroflowmetry is an easy-to-use, non-invasive, and objective test, which can be used for the early diagnosis of the urethral stricture following the hypospadias surgery and the evaluation of the obstructions of the lower urinary tract natural micturation. Uroflowmetry is a method based on the measurement of the change of the urinary flow rate during the natural micturition and its visualization with a two-dimensional graphic. The urine flow is visualized with a graphic of flow rate and time axes (ml/s)/s in the uroflowmetry. The urine flow is a result of the detrusor pressure, the pressure created by the abdominal muscles and applied on the bladder, urethra and sphincter resistance, and other factors impairing or facilitating the urine flow. As far as the reliability of uroflowmetry measurements is concerned, reaching half of the estimated bladder volume at the time of the full bladder according to the age of the patient provides important information about the maximum flow rate, mean flow rate, and the voiding pattern. There are studies demonstrating the significance of the voided urine volumes at least over 100 ml for expressing the maximum flow rate regardless of the age of the patient. The maximum flow rate declines in urethral stricture and the bell-shaped flow pattern, which is expected in normal conditions, is not observed. The urinary flow rate enables the mutual evaluation of the urethra and bladder functions. If the bladder functions are normal after the hypospadias surgery, a decrease in the urinary flow rate and the emptying curve pattern are important parameters for the urethral stricture. In several studies, with large subject sizes, it was reported that a maximum flow rate under 10 ml/s and below two standard deviations or 5 percentile according to the nomograms may be consistent with the urethral stricture. The main concern, whether the abnormal flow rate is a component of the malformation and whether the post-operative flow rate is related to the success of the surgery, still persists. Some studies compared the bladder volume, which corresponds to the volume at the time of full bladder in hypospadias patients, with the bladder volume measured in healthy children and found that the bladder volume of hypospadias patients was relatively smaller, and this finding was consistent with our findings. The pre-and post-operative mean bladder volumes were 67% and 71% of the estimated bladder volume according to the age, respectively. We believed this finding depended on two factors: The intervention was carried out under the conditions of the outpatient clinic, and the children in this age group have difficulty to feel and express the full bladder. Gutierrez Segura had conducted a study on 1361 healthy children and analyzed their urination patterns. He demonstrated that the maximum flow rate and mean flow rate increased parallel to the increases in the age and body surface. In the healthy children, who had minimum 100 ml urine volume and a body surface of 1.1 2 m, the maximum flow rate was 17.5±4.5 ml/s, mean flow rate was 10.8±2.7 ml/s, voiding time (flow time) 14.1±4.2 s, and time to the maximum flow rate was 5.8±1.7 s. Holmdahl et al. performed a uroflowmetry test on 126 hypospadias patients 2 months after the surgery and measured a maximum flow rate of 10.6 ml/s in patients with distal hypospadias. The maximum flow rate was <10 ml/s in 23 of the patients (49%). The mean flow rate was 6.6 ml/s in 15 patients, who had proximal hypospadias and the maximum flow rate was under 10 ml/s in 87% of the patients. In our study, the maximum flow rate was 10.8±4.8 ml/s in the uroflowmetry analysis, and this result was consistent with the literature. The comparison of this result with the pre-operative maximum flow rate (10.1±4.1 ml/s) showed no statistically significant difference. This finding indicated that the low maximum flow rate in the hypospadias patients might depend on the deformity itself and might not be related to the surgical intervention. Malyon et al. determined that the mean value of the maximum flow rate was 20 ml/s in healthy children and 11 ml/s in patients with hypospadias and demonstrated that the voiding curves of the hypospadias patients were under the curves of the normal population. In the same study, it was shown that the maximum flow rate was lower, flow pattern and its curve and the plateau and urination time were longer in the patients with hypospadias compared to the normal population. In another study, it was demonstrated that in 1/3 of the hypospadias patients, the maximum flow rate was already decreased and the urination curve was plateau-shaped before the surgery. In our study, 44.4% (n=28) of the patients had a plateau-shaped urination curve before the surgery and this percentage dropped to 30.2% (n=19) in the uroflowmetry analysis after the surgery. The urination curve had improved in the remaining nine patients. The results of our study showed that in the hypospadias patients, the maximum flow rate was already lower than normal. Almost half of the patients had an abnormal urination curve which pointed at the necessity of a uroflowmetry analysis before the surgery. Holmdahl et al. performed urethral calibration and dilatation to 26 of 126 patients (20.6%), as they considered urethral stricture in these patients according to the results of the uroflowmetry. In this study, low maximum flow rate and plateau-shaped voiding curve were considered as urethral stricture. These patients underwent urethral calibration and dilatation under general anesthesia. No stricture was determined in 8% of these patients during the examination under general anesthesia. In our study, 25.4% of the post-operative patients (n=16) underwent dilatation -according to the Siroky nomogram in the uroflowmetry, and this rate was consistent with the literature. We determined urethral stricture with the uroflowmetry in three patients, although they had no clinical complaints. Following the dilatation, the maximum flow rate and mean flow rate increased up to the level of the patients, who did not need such an intervention. In our study, the maximum flow rate was 9.9±4.1 ml/s and 11.0±4.9 ml/s in the pre-operative and post-operative periods, respectively, and the difference was statistically significant. The maximum flow rate dropped from 11.7±3.9 ml/s to 9.7±4.2 ml/s after the surgery; however, the difference was not statistically significant. Some studies in the literature reported that the urethral stricture was more common in the patients with proximal hypospadias and the length of the tubularized urethra affects the flow rate, and these findings explained the decline in the post-operative maximum flow rate in our patient group. CONCLUSION We conclude that the pre-and post-operative uroflowmetry evaluation is critically important in children with hypospadias. It should be kept in mind that the urine flow parameters and the urination curves are lower in the patients with hypospadias compared to the healthy children. The pre-operative uroflowmetry analysis is important for the evaluation of a suspected urethral stricture. Even though urethral dilatation provides satisfactory result for the treatment of the urethral stricture at the early stage, in patients with a delayed diagnosis urethroplasty may be required.

For the first time ever, scientists have captured an image of a black hole, and a Missouri University of Science and Technology graduate played an important role. Dr. Frederick K. Baganoff, a research scientist at the Massachusetts Institute of Technology’s Kavli Institute for Astrophysics and Space Research, is among the collaborators on the international Event Horizon Telescope project to produce the first direct images of a black hole. Baganoff earned a bachelor of science degree in physics from Missouri S&T in 1985. Baganoff, an expert in observational high energy astrophysics, and over 200 scientists worldwide announced this breakthrough on Wednesday, April 10, in a series of papers published in a special issue of Astrophysical Journal Letters. The researchers released four images of a supermassive black hole at the center of Messier 87, or M87. M87 is a galaxy within the Virgo galaxy cluster, 55 million light years from earth. The images were taken by the Event Horizon Telescope (EHT), a global array of eight radio telescopes, each in a remote, high-altitude environment, including the mountaintops of Hawaii, Spain, Chili and the Antarctic ice sheet. "First M87 Event Horizon Telescope Results. I. The Shadow of the Supermassive Black Hole," a summary of the project, and "First M87 Event Horizon Telescope Results. V. Physical Origin of the Asymmetric Ring,” an analysis of the data. “We learned about 20 years ago that a relationship exists between the mass of a supermassive black hole and the mass of stars and gas in the bulge of its host galaxy, and that the two systems evolve together in each galaxy,” says Baganoff. “We also know that when a supermassive black hole is in an active phase, furiously accreting matter, powerful particle jets are launched along the poles of its spin axis. The jets heat molecular gas in their host galaxy and eventually inhibit or turn off star formation until the supermassive black hole becomes starved for fuel and re-enters a quiescent phase. “Supermassive black holes act as regulators of star formation, which they depend on for future growth, intimately tying the structure and evolution of each galaxy to its supermassive black hole,” he says. When Baganoff entered the EHT project, he was also lead researcher for the team that discovered the flaring of Sagittarius A*, the supermassive black hole at the center of the Milky Way Galaxy. Baganoff was also part of a team lead by Dr. Sheperd Doeleman who submitted the scientific case for building the EHT to the National Research Council (NRC). Their proposal became a priority of the NRC’s 2010 Astronomy and Astrophysics Decadal Survey, which drives the funding priorities for new telescopes, observatories and computational facilities for U.S. astronomy and astrophysics advancements for the subsequent 10 years. S&T recently expanded its astrophysics program by joining the Laser Interferometer Gravitational-wave Observatory (LIGO) Scientific Collaboration of researchers dedicated to detecting cosmic gravitational waves. This research explores the fundamental physics of gravity using the emerging field of gravitational wave science as a tool for astronomical discovery. Leading S&T’s new astrophysics initiative are newly hired physics faculty Dr. Marco Cavaglia and Dr. Shun Saito. The program will train scientists who will extend the legacy established by alumni such as Baganoff; NASA astronauts Thomas Akers, Dr. Janet Kavandi and Dr. Sandra Magnus; NASA scientists Ron Epps and Paul Blackmon; and university faculty Dr. John Asher Johnson of Harvard University.

Joseph Tilley Brown Early life Brown was born at St. John's, Surrey, England, to marine captain Joseph Brown and Amelia, née Tilley. The family migrated to Victoria, Australia when young Joseph was seven. He was educated at Geelong Church of England Grammar School before becoming a clerk, eventually joining the Bank of New South Wales. At Rochester, where he was the bank's first manager, he married Mary Ann Seward on 6 January 1874. Local politics Brown resigned from the bank due to a subordinate's irregularities and became a stock and commission agent. In 1878 he was charged with "boss-cockie dummying"; he subsequently admitted that he helped those in his family and circle of friends to exploit the 1869 Land Act. He continued to be active in the area as president of the Rochester Farmers' Union (1879) and the Agricultural Society of Echuca (1881–82), as well as an Echuca Shire councillor from 1876; he was president of the council 1888–89. State and federal politics Brown entered the Victorian Legislative Assembly in 1886 as a moderate protectionist in the seat of Mandurang. Defeated in 1889, and unsuccessful in his attempts to return in 1892 (in Gunbower), 1893 and 1894, he was elected to the Assembly again in 1897 for the seat of Shepparton and Euroa as a supporter of Sir George Turner. He was unsuccessful in his attempt to transfer to Goulburn Valley in 1904. In 1906, Brown entered the federal House of Representatives as a member of the Anti-Socialist Party, and was noted for his opposition to the ministry of Alfred Deakin. He held the seat until 1910 when he was defeated; an attempt to regain the seat in 1913 earned him only 67 votes. In his retirement, Brown managed a rural property at Moyhu until he died at Brighton on 28 September 1925, survived by a daughter.

BIOMASS ESTIMATION USING VERTICAL FOREST STRUCTURE FROM SAR TOMOGRAGHY: A CASE STUDY IN CANADIAN BOREAL FOREST. A major goal of current research is to address temporal climatic variations that are related to CO2 emissions. A significant portion of these emissions are due to forest destruction and the resulting conversion of biomass to CO2. As 30% of the earth's landmass is forest-covered, it is important to understand the biomass content with better estimates than are currently available. This research has addressed the determination of forest biomass in a Northern Alberta forest site, using novel techniques known as POLInSAR (Polarimetry Interferometry SAR) to study the 3D vegetated structure of forests through using an L-Band single-pass airborne system. Results of this study indicate strong relation between vertical structure and above ground biomass. In this paper we show the preliminary results of the work including the resulting tomographic expression of the test forest area.

Phase Separation, Magnetism and Superconductivity in Rutheno-Cuprates The properties of the superconducting ferromagnets RuSr2(Gd/Eu)Cu2O8 and RuSr2(Ln/Ce)2Cu2O10 are reviewed. The problem of coexistence and competition between magnetic and superconducting states is discussed. A model of phase separation into ferromagnetic and anti-ferromagnetic structures is proposed. INTRODUCTION The discovery of superconductivity coexisting with weak ferromagnetism in a class of ruthenium-based high-T C compounds has initiated intensive experimental and theoretical investigations in recent years. Bauernfeind et al. reported the first synthesis of RuSr 2 LnCu 2 O 8 (Ru-1212) and RuSr 2 (Ln 1+x Ce 1-x )Cu 2 O 10 (Ru-1222), with Ln=Sm, Eu, and Gd, and the appearance of superconductivity below 45 K in the latter compound for 0.3 ≤ x ≤ 0.5. A drop of resistivity, a possible indication of a superconducting transition, was also observed in Ru-1212, but no shielding signal could be detected by the ac susceptibility measurements. The superconductivity in Ru-1222 was independently confirmed by Ono who attributed a strong magnetic signal below 100 K in RuSr 2 Sm 1.2 Ce 0.8 Cu 2 O 10 to secondary magnetic phases. The coexistence of weak ferromagnetism and superconductivity was first proposed by Felner et al. in RuSr 2 R 1.4 Ce 0.6 Cu 2 O 10. It is of particular interest that in these compounds the magnetic transition temperature, T m, is far higher than the superconducting T c which makes this a unique class of materials as compared to some intermetallic compounds (e.g. RRh 4 B 4, RMo 6 S 8, RNi 2 B 2 C) known as magnetic superconductors with T m < T c. Whereas the signature of superconductivity in Ru-1222 appears to be clear the situation in Ru-1212 is more complicated. The published data for this material spread from samples without any diamagnetic signal in the susceptibility, through samples showing zero-resistance and zero-field cooled (ZFC) diamagnetic signal but not field cooled (FC) Meissner signal in the magnetic susceptibility, and eventually samples with a large FC diamagnetic signal. Although most of the Ru-1212 materials synthesized in different laboratories are chemically and structurally comparable it was shown that the superconducting properties are extremely sensitive to tiny details of sample synthesis and annealing procedures. This may explain some of the contradictory results reported in the literature. Despite extensive research the magnetic as well as the superconducting orders are far from being understood. In particular, the coexistence of both order parameters and how they accommodate each other is still a matter of controversial discussions. In conventional s-wave superconductors the Cooper pairs are easily broken by local magnetic moments and superconductivity is completely suppressed by the presence of as little as 1 % magnetic impurities. This pair breaking mechanism may be less effective if the crystallographic site of the magnetic ion is well isolated from the conduction path, weakening the interaction between the local magnetic moment and the Cooper pairs. This "spatial" separation of magnetic moments and conduction electrons obviously explains the observed coexistence of antiferromagnetism (AFM) (T N <T C ) and superconductivity in ternary intermetallic compounds and borocarbide systems. The competition between the pair breaking magnetic forces and the superconductivity may even lead to exotic effects like the resistive reentrant behavior observed at zero field in HoNi 2 B 2 C. In the rutheno-cuprates the Ru ions are also well separated from the CuO 2 planes where Cooper pairs are formed. However, the major difference to the aforementioned intermetallic compounds is that a more-or-less homogeneous ferromagnetic (FM) order parameter was suggested by dc magnetic susceptibility measurements over a broad temperature range (and far above T c ). This FM long-range order, if homogeneous on a microscopic scale, generates an internal magnetic field at the CuO 2 planes that may break the Cooper pairs and destroy superconductivity if the internal field is larger than the critical field. In order to coexist with superconductivity, however, the FM order parameter should be non-uniform in a domain-like or spiral structure. In fact, a spiral FM structure was found in ErRh 4 B 4 and a domain-like FM structure was observed in HoMo 6 S 8 and HoMo 6 Se 8, both coexisting with superconductivity. In these examples the magnetic ordering always develops in the superconducting phase, i.e. T m <T C. For the superconducting ferromagnet RuSr 2 GdCu 2 O 8 Pickett at al. discussed various physical conditions under which superconductivity and ferromagnetism could coexist. They came to the conclusion that the major limiting mechanism for singlet superconductivity is the electronically mediated exchange field that splits the majority and minority Fermi surfaces and that the superconducting order parameter could develop a spatial variation with non-zero total momentum as described by Fulde-Ferrell-Larkin-Ovchinnikov type theories. Another interesting aspect in the coexistence of FM and superconductivity in type II superconductors is the possible formation of a "spontaneous vortex phase" (SVP) due to the interaction between the wave function of the Cooper pairs and the magnetic field. If the internal magnetic field generated by the spontaneous FM order is smaller than the upper critical field (H c2 ) but larger than the lower critical field (H c1 ) of the superconducting state a vortex lattice state can be formed forcing the internal magnetic field to penetrate the superconductor as quantized flux lines. The formation of a SVP in RuSr 2 R 1.5 Ce 0.5 Cu 2 O 10 (Ru-1222) was proposed by Sonin and Felner and various possible scenarios have been discussed in detail by Chu et al.. Depending on the temperature dependence of the internal field, 4M (M = magnetization), and the lower critical field, H c1, the SVP may exist below T C to zero temperature or transform into a Meissner state at a temperature T MS <T C if H c1 increases above 4M. For Ru-1212 and Ru-1222 the FM transition sets in at far higher temperature than superconductivity (T m >T C ). At T C, according to the SVP model, the FM order parameter should survive and the long-range correlation between the magnetic moments of different RuO planes is established via the flux lattice penetrating the superconducting CuO 2 layers. To better understand the complex interaction between magnetic and superconducting orders it is of particular interest to gather information about both the magnetic order (above and below T C ) and the superconducting one. Most recent work to explore the magnetic structure was focused on the Ru-1212 compounds, RuSr 2 (Gd/Eu)Cu 2 O 8. The internal magnetic field, 4M, was probed by zero-field muon-spin rotation experiments above as well as below T C. It was found that the FM order sets in at about 133 K in accordance with dc susceptibility measurements and that the FM order parameter was not altered significantly in passing into the superconducting phase. The zero-temperature internal field at the muon site was extrapolated to be about 700 G. However, neutron powder-diffraction experiments have revealed that the magnetic order is predominantly antiferromagnetic with antiparallel Ru moments in all three crystallographic directions (G-type AFM). The estimated magnetic moment, ≈ 1.18 B, of the Ru ion along the c-axis is compatible with the low spin state of Ru 4+, although NMR experiments on RuSr 2 YCu 2 O 8 suggest that the Ru ion may be in a mixed valence state with 40 % Ru 4+ (S=1) and 60 % Ru 5+ (S=3/2). The net FM component of the order parameter was estimated to be not larger than 0.1 B per Ru ion by NPD that is appreciably lower than the local magnetic moment of the Ru detected by NMR. Based on the magnetic scattering experiments a canted arrangement of the AFM Ru moments with a small net FM moment perpendicular to the c-axis has been proposed. Whereas superconductivity in the CuO 2 planes may well coexist with the AFM ordered Ru moments the accommodation of a large FM component is still a puzzling issue. For the sister compound, Ru-1222, the exploration of the magnetic structure is far less advanced. Susceptibility measurements show several anomalies (at about 180 K and 90 K in RuSr 2 (Gd/Ce) 2 Cu 2 O 10 ) indicating a more complex magnetic ordering in this compound. Superconductivity appears below 45 K with a stronger diamagnetic signal in field cooling experiments than observed in the Ru-1212 system. One of the most disputed questions about superconducting ferromagnets is whether the superconducting state is microscopically homogeneous. This discussion was sparked by the fact that the majority of the Ru-1212 and some of the Ru-1222 samples synthesized by different groups did not show a distinct diamagnetic signal in the field cooled susceptibility, i.e. the Meissner effect typical for a bulk superconductor [3,7,8,24,. Evidence for a large Meissner signal in RuSr 2 GdCu 2 O 8 was later reported, but only under very low applied magnetic field and below a temperature T MS much smaller than the onset of superconductivity. The data, therefore, was discussed in terms of a transition from SVP to the Meissner state. Additional evidence for bulk superconductivity was derived from specific heat measurements. Tallon et al. reported a specific heat anomaly at T C of RuSr 2 GdCu 2 O 10 with an unusual magnetic field dependence -the peak of the electronic specific heat at T C shifted to higher temperature with increasing field. This atypical behavior for a superconducting phase transition was not confirmed by the data of Chen et al.. The thermodynamic transition into the superconducting state, the nature of superconductivity, the details of the magnetic order above and below T C, and the mechanisms of coexistence of superconducting and FM order in the superconducting ferromagnets remain a matter of discussion. In this work we provide experimental evidence for the occurrence of phase separation in the magnetic phase of the Ru-1212 and Ru-1222 compounds. The predominantly AFM domains are separated by nanoscale FM domains. This explains both, the AFM order observed in neutron scattering experiments and the weak FM signal detected in the dc susceptibility measurements. The magnetic domains are of typical nanometer size and are formed within the grains of the material. The superconductivity then develops in the AFM domains that are coupled across the non-superconducting FM regions by the Josephson effect. The onset of the intra-grain superconductivity is explained as the phase-lock transition of an array of Josephson junctions. The synthesis of Ru-1212 and Ru-1222 compounds proceeds via the solid-state reaction of the proper constituents. Since it was shown that the magnetic and, in particular, the superconducting properties strongly depend on the details of the synthesis and annealing procedures we review the basic steps in this paragraph. As an example, we describe the synthesis procedure of RuSr 2 GdCu 2 O 8. Fig. 1 explains the details of the typical synthesis process as described e.g. in. The starting materials RuO 2, Gd 2 O 3, SrCO 3, and CuO were first preheated at 600 -800 °C for about 12 h. The powder with cation ratio Ru:Sr:Gd:Cu = 1:2:1:2 was then mixed and calcined at 960 °C for 16 h followed by grinding, compacting and two or more sintering steps (each step 10-24 hours) at successively increasing temperature. The final steps include the long-term sintering (7 -14 days) in oxygen atmosphere. The optimal temperature for this final procedure was estimated to about 1065 °C. After the calcination step the characteristic x-ray reflections for the 1212 phase are already visible in the powder diffraction spectra. Figure 2 shows two examples of x-ray spectra taken after the starting materials were calcined at 960 °C (spectrum A in Fig. 2) and at 1000 °C (spectrum C in Fig. 2). The dots indicate the reflections of the 1212 structure and the crosses show reflections of a secondary phase (identified as SrRuO 3 ). With additional sintering steps the SrRuO 3 phase disappears and the spectra B and D in Fig. 2 show the high phase purity of the final product, RuSr 2 GdCu 2 O 8. Fig. 2: X-ray spectra of two samples of RuSr or RuSr 2 (Gd/Ce) 2 Cu 2 O 10-, is very similar to the procedure described above. Preparing the Ru-1222 structure requires slightly higher temperatures with good results obtained if the final annealing was done at about 1090 °C although the conditions reported from different groups vary slightly. The lattice structure of both Ru-1212 and Ru-1222 is schematically shown in Fig. 3. Both compounds crystallize in tetragonal symmetry with space groups P4/mmm (Ru-1212) and I4/mmm (Ru-1222), respectively. The structure of Ru-1212 ( Fig. 3 A) may be derived from the well-known lattice of YBa 2 Cu 3 O 7- (YBCO) by the following replacement: Y ⇒ Gd, BaO layer ⇒ SrO layer, and CuO chains ⇒ RuO 2 planes. In contrast to YBCO the RuO 2 layers are fully occupied by oxygen resulting in a change of symmetry from orthorhombic (YBCO) to tetragonal (Ru-1212). The Ru ion is octahedrally coordinated and the RuO 6 octahedra deviate from their ideal positions by a small rotation (about 13 °) around the c-axis and a slight tilting that reduces the Cu-O-Ru angle to 173 °. The c-axis lattice parameter (c=11.5731 ) is about three times larger than the a-axis parameter (a=3.8348 ). The almost perfect match of a=c/3 gives rise to the formation of mcirodomains, and the c-axis of adjacent domains may be aligned in different principal directions. SrO SrO The Ru-1222 structure (Fig. 3 B) is derived from the Ru-1212 structure in replacing the Gd ion by a three-layer fluorite-type (Gd/Ce) 2 O 2 -block that causes a shift of the subsequent perovskite block along direction and doubles the unit cell along the c-axis. The tetragonal lattice constants are of the order of a=3.85 and c=28.7. The structure and lattice parameters have been confirmed and refined very recently and a tilt and rotation of the RuO 6 octahedra similar to that discussed for Ru-1212 was reported. MAGNETISM IN Ru-1212 AND Ru-1222 There is still no common agreement on the magnetic structure of these rutheno-cuprates, although almost all possible probes, i.e. neutron powder diffraction (NPD), nuclear magnetic resonance NMR (in particular, zero-field NMR, ZFNMR), macroscopic magnetizations, ferromagnetic resonance (FMR), muon-spin rotation (SR), and Mssbauer spectroscopy (MS), have been used. It is particularly striking that the observations of different probes often were interpreted as mutually exclusive structures when the results of the same technique merge remarkably well. This should be an indication that our interpretation may need to be modified, but most of the experimental data are valid. The issue is particularly important because it may decide how SC coexists with FM, as will be discussed in the next section. NPD typically is the most powerful tool in determining long-range average spin-structures of homogeneous magnets. The aligned magnetic moments interact with the magnetic dipole of neutrons, which leads to extra magnetic scattering on the top of the usual nuclear scatterings. For example, an AFM spin-order in a particular crystalline orientation may double the unit cell in that direction. Super-lattice like lines, therefore, appear with corresponding Miller indices. An FM ordering, on the other hand, alters the scattering amplitudes of neutrons by adding a magnetic contribution, which can be identified by the change of the line-intensities across T m. The orientation of the ordered moments can be further extracted from intensity ratios of these magnetic lines based on the dipole interactions between neutrons and electrons. The data interpretation, therefore, is relatively straightforward and reliable for the average structure of localized moments. However, it has limitations. In particular, randomly dispersed short-range ordering can be missed due to the line-broadening caused by the uncertainty principle ∆ = h/kd, there h, k, and d are the Planck constant, the neutron momentum, and the spatial extension of the spin-order, respectively. In contrast, NMR is a local probe and sensitive to the nearest neighbor interactions, although its interpretation is more model-dependent. NMR essentially measures the rf transverse susceptibility of the chosen nucleus and allows an estimation of the hyperfine field there, typically caused by the induced wave-function deformation of the inner-shell electrons. Although the data might appear similar in both AFM and FM spin-orderings, it has been demonstrated that the two can be identified through both the signal-enhancement and the lineshift by the external field. On one hand, the external rf field acting on a nucleus will be enhanced by the coherent motion of the FM (or canted AFM) moment. Simultaneously, the signal is suppressed by the exchange field in case of an AFM magnet or by the magnetic anisotropy field in case of a bulk FM magnet. As the result the signal of FM magnets are much stronger. For example, the 375 MHz ZFNMR line of the FM clusters is fivefold stronger than the 290 MHz line of the AFM matrix in La 0.35 Ca 0.65 MnO 3, although the volume fraction of the FM clusters is only 8%. On the other hand, the NMR line of an AFM magnet (with or without a small canting angle) will only be broadened without a significant shift by external fields, especially in ceramics with random grain orientations. This is in contrast with FM magnets, where a field-induced line-shift is noticeable with typical hyperfine fields around 10-100 T. It is therefore possible to distinguish between AFM-and FM-dominated spin-orders based on the field effects. In addition, the orientation of the ordered moment can be extracted from the interference between the NMR and the quadrupole-splitting caused by the crystalline electric fields, which can be calculated. It is almost impossible to extract the detailed magnetic structure from macroscopic magnetization measurements alone. However, it should serve as the decisive constraint, which all interpretations need to meet. This, for example, can be well demonstrated in the case of La 0.35 Ca 0.65 MnO 3, where the magnetization shows two-step like drops around 275 K and 160 K, respectively. The two transitions were initially interpreted as charge-order and AFM transitions, respectively. The rather large low-T magnetization, M/H ≈ 0.01 emu/mole at 100 K, further suggests that either a spin canting or the coexistence of FM species may occur below the AFM transition. A NPD investigation, however, observed no evidences for longrange FM correlations. Detailed ZFNMR data finally revealed that 8% of the compound should be in a FM state. The small size of the FM species was used to justify the difference between the NPD and the ZFNMR data. Similar contrasts are even more drastic in the rutheno-cuprates. Even in the relatively simple case of Ru-1212, where the spin alignment from both NPD and NMR seems to fit the mean-field theory rather well below a well-defined T m ≈ 135 K, controversies still persist. Although a homogeneous spin-canted model was proposed to accommodate the G-type AFM structure suggested by the (1/2, 1/2, l/2) lines of NPD and the significant spontaneous moment (≈ 0.28 B /Ru for Ru-1212-Gd at 5 K) derived from the macroscopic magnetization, both the spin orientation and the magnitude of FM components are controversial. By comparing the (00l) line intensities below and above T m, three independent NPD investigations concluded that the possible FM component is < 0.3 and < 0.1 B /Ru for Ru-1212-Gd and 0.34±0.1 B /Ru for Ru-1212-Y at H = 0. Lynn et al. further suggested that the Ru contribution to the FM component at 80 K will be kept below 0.2 B /Ru with H up to 7 T by subtracting the expected paramagnetic Gd contribution. These rather strict limits are even in disagreement with the macroscopic magnetizations. In fact, the spontaneous magnetization, M r, of a ceramic Ru-1212-Gd sample was reported to be 800 emu/mole and corresponded to a FM component of 0.28 B /Ru at 5 K and H = 0 after a geometric correction for the random distribution of the magnetic easy-axis, i.e. the orientation of the grains. This is noticeably larger than the upper limit of 0.1 B /Ru at H = 0 by NPD on the sample from the same group. Although the FM-component at higher fields is masked by the paramagnetic contribution of Gd, it is not unreasonable to estimate the value by extrapolating the linear high-field magnetization to H = 0 since the paramagnetic part should be linear and the canted FMcomponent of Ru may be more-or-less H-independent (as suggested by the NPD data above 1 T). This extrapolated moment of the Ru-1212-Gd sample, ≈ 4000 emu/mole (0.6 B /Ru) at 50 K, however, is again several times higher than the upper limit set by the NPD data. It is interesting to note that the rather similar high-field magnetizations of Ru-1212-Gd and Ru-1212-Eu, i.e. ≈ 4000-5000 emu/mole at 50 K and 5 T, suggest that the overall Gd contribution to the aligned moment should be relatively minor up to 5 T. This is again in disagreement with the NPD interpretation reported. Some other magnetization data even directly challenge the G-type AFM ordering (with or without canting) suggested by NPD. Butera et al. summarized: "it seems to be incompatible with magnetization measurements in several aspects: i) We have found a positive Curie-Weiss constant smaller than the ordering temperature indicating that the predominant interaction among Ru ions is FM. The G-type structure, in fact, requires AF interactions. ii) The lowtemperature magnetization, which is close to the saturation value, is not consistent with a small canting of the AF alignment. iii) EPR results show that there is a net magnetic field of ≈ 600 Oe at the Gd site coming from the ordered array of Ru, whereas a cancellation of the Gd-Ru interaction is predicted in a G-type-ordered AF." Some of the FM aligned Ru-spins, which should add up to the macroscopic magnetization observed, seem to be missing in the NPD. The ZFNMR data appear to support this speculation. Both a signal-enhancement by a factor of about 100 and a shift to lower frequency with the external field were reported in a Ru-1212-Y sample. Similar enhancements have also been observed in Ru-1212-Gd. The authors, therefore, urged to conduct new detailed NPD experiments. The situation about the orientation of the ordered Ru-spins is similarly confusing. The NPD data suggest that the Ru moments are ordered along the c axis based on the intensity ratio between {1/2, 1/2, 1/2} and {1/2, 1/2, 3/2} lines, i.e. with the observed ratio of 2.5 compared to a calculated value of 2.2 in this direction. Both ZFNMR experiments, however, show that the moments should be aligned within the RuO 2 plane. The same conclusion has been reached by the FMR investigation of Ru-1212-Gd. The rather large magnetic anisotropy field of H z ≈ 11 T from FMR is in contrast with the much smaller threshold of 0.4 T for the spin-flop observed in NPD. The same question of whether NPD and NMR/magnetizations/FMR probe the same magnetic correlations, therefore, can be raised again. The magnetic structure of Ru-1222 is even more complicated. There is apparently more than one magnetic transition above T c. Whereas the main low-H transition, defined by the large step-like increase of the field-cooled magnetization (M FC ) with the sample cooling at H < 0.1 T, typically occurs below 100 K, an AFM-like transition at a much higher temperature of T 1 ≈ 160-250 K is clearly detected in the high field differential susceptibility ( Fig. 4). The interpretation that the bulk part of Ru-1222 is in an ordered AFM state seems to be supported by the MS data. The MS of trace 57 Fe in a RuSr 2 Gd 1.4 Ce 0.6 CuO 10 sample close to T 1 ≈ 180 K was interpreted as the result of a hyperfine field of 467 kOe at the Ru site, i.e. the Ru moments are ordered up to ≈ 2T m. Moreover, two additional minor M FC steps appear in almost all reported magnetization data around 120 and 160 K, respectively. Either several sequential AFM/FM transitions or nanoscale phase-separation should occur. In particular, the wide separation between low-H FM-like transition at T m and the AFM-like transition at T 1 makes a simple canted AFM model less likely. It should be noticed that several data sets have been used to argue that the magnetic order in the rutheno-cuprates is homogeneous on a microscopic scale. One is the widely quoted ZF SR data of Bernhard et al.. However, the resolution of this experiment is rather limited. The random orientation of the grains (therefore, the random angle between the spontaneous magnetization and the muon spin) makes the internal field deducable only as an average. The authors, therefore, estimated that the resolution for the possible magnetization inhomogeneity <∆B>/B is no better than 20% with B ≈ 700 Oe. The diamagnetic field of a homogeneous FM magnet with a spontaneous magnetization of 800 emu/mole would be well within this range of uncertainty. In addition, the estimated resolution for minor magnetic species is only 20%. The possible phase separation can hardly be excluded by the SR data, in our opinion. Another suggested evidence for magnetic homogeneity is the temperature dependence of the spin-lattice relaxation rate 1/T 1 of the 101 Ru ZFNMR line. The relaxation seems to be similar to that of 63 Cu at 10 T, which should be dominated by the formation of the superconducting gap. The authors, therefore, concluded that the aligned Ru-spins and the supercarriers in the CuO 2 planes do coexist on a microscopic scale. The coexistence, however, is not necessarily the same as a homogeneous magnetic state. The Josephson-junction like superconductivity observed in these rutheno-cuprates suggests that the FM domains should have a dimension comparable to the proximity length of Cooper pairs if they serve as the tunneling junctions. This geometric proximity may make the 1/T 1 of 63 Cu and 101 Ru look similar, but still belong to different magnetic species. To accommodate these apparent discrepancies in the reported data, we investigated the magnetizations of both Ru1212 and Ru1222. Our data suggest that a mesoscopic phaseseparation between FM and AFM species occurs in both Ru-1212 and Ru-1222. Separable and Tunable AFM and FM Transitions The zero-field-cool magnetization (M ZFC ) and field-cool one (M FC ) at 5 Oe of a Ru-1222-Eu sample (A) are shown in Fig 4. The T m appears around 65 K with a transition width around 20 K. Two additional transitions can be noticed at 120 and 150 K, respectively. To explore the magnetic signature of the AFM transition, the contributions from the Eu and CuO 2 are subtracted from the differential susceptibility at 5 T and the dc magnetization at 1 T according to the procedure proposed by Butera et al. (Fig. 4). Both are in agreement above 200 K, and a Currie-Weiss (CW) fit has been made in this temperature range with the deduced Currie temperature and the Ru-moment of 80 K and 2.6 B/Ru, respectively. The calculated differential 1/ Ru follows the extrapolated Currie-Weiss (CW) fit (the solid line) rather well above 150 K. It, however, deviates to the higher value, i.e. a smaller magnetization, at lower-T and finally bends around T 1 ≈ 120 K, a temperature still far above T m (Fig. 4). However, the dc magnetization at 1 T is higher than the CW fit below 200 K. This non-linear H-dependence, in our opinion, is an indication of the existence of nanodomains with FM correlations, a phenomenon widely discussed in CMR compounds. It should be noticed that the suppression of the susceptibility caused by the aligned FM species is relatively small and cannot count for the AFM-like minimum. For example, the dc magnetization at 5 T and 100 K is only ≈ 0.3 B/Ru, far smaller than the estimated Ru paramagnetic contribution of 2.6 B/Ru. In contrast, the value of T⋅, i.e. a parameter proportional to the number of the paramagnetic spins, is only a quarter of that expected from the CW fit at 100 K. AFM spin-spin correlations may be the only reasonable interpretation to count for such large suppression, which is supported by the large hyperfine field observed in MS spectra. The AFM and FM transitions, therefore, seem to occur at very different temperatures in Ru-1222, which challenge the simple canted AFM models proposed. It is interesting to note that a noticeable extrapolated zero-field magnetization appears even above T 1, e.g. up to T 1 ' = 140 K in the Ru-1212-Eu sample with T 1 = 120 K (Fig 5). This non-zero magnetization and the associated non-linear isothermal M(H), as will be discussed below, can be easily understood as embedded superparamagnetic species. The two additional transitions in the low-field M FC of Fig. 4 may have the similar origin. Their deposition from the otherwise AFM-correlated matrix reminisces the phase-separation widely observed in CMR, e.g. in La 0.35 Ca 0.65 MnO 3. Felner et al. has previously identified the AFM transition of Ru-1222 with the non-zero extrapolated zero-field magnetization, our differential susceptibility data seem to provide a reasonable explanation, although the two temperatures are slightly different. The T m ( ) and T 1 (g) of (Ru 1-x Cu x )Sr 2 EuCu 2 O 8 as functions of x. The T m (∆) and T 1 of the Ru1212Eu sample reported in Ref. are also included. It should be pointed out that a similar situation is observed in Ru-1212, however, the temperature difference between T m and T 1 is far smaller than in Ru-1222. The rough agreement between the T m ≈ 138 K and the T 1 ≈ 145 K reported in a Ru-1212-Eu sample may only be a coincident. Several (Ru 1-x Cu x )Sr 2 Eu 1.4 Cu 2 O 8 samples were measured by us to explore the issue. The T m decreases with the x rather quickly (about 20 K with 0.1 Rureplacement) (Fig. 5). The T 1, however, is insensitive to this doping with no more than 5 K decrease up to x = 0.1. The wide separation between the two transitions, therefore, exists even in Ru-1212 if the ferromagnetic interaction has been slightly suppressed (as evidenced by the lower T m ). It is also interesting to note that this correlation between T m and T 1 under the Cu-Ru replacement of Ru-1212 is rather similar to that in Ru-1222-Eu with a Ce-Eu replacement, specially considering that T 1 ' and T 1 are used for Ru-1222 and Ru-1212, respectively (Fig. 6). Ru-1212 and Ru-1222 seem to share the same basic magnetic structure, although the competing magnetic interactions seem to tend more to FM in Ru-1212. Only with such multistage transitions and possible phase-separation, in our opinion, the extremely broad C p anomaly on the higher-T side in Ru-1212-Gd can be naturally accommodated with the narrow mean-field-like transition below T m observed in NPD and NMR. T m vs. T 1 of: the Cu-doped Ru-1212-Eu (h, using the differential susceptibility to determine T 1 ) and Ce-doped Ru-1222 of Ref. (∇, using the non-zero extrapolated zero-field-magnetization to determine T 1 ) Superparamagnetism in Ru-1212/Ru-1222 far Above T m To further explore the magnetic states of these rutheno-cuprates, the isothermal M(H) was measured for Ru-1222-Eu (Sample A, Fig. 7) and a Ru-1212-Eu sample (Sample B, Fig. 8a, 8b). The reversible non-linear M(H) is evident up to T 1 or higher. Although H-dependent M(H)'s are a common phenomenon in magnets near T m due to spin fluctuation, its appearance up to temperatures as high as 2*T m is highly unusual. Spin fluctuations, H-induced rotation of the canting angle, and phase separations have been invoked to interpret the data. Regardless of the microscopic mechanism (except for rotation of the canting angle of an AFM magnet), however, the spin-alignment under fields can always be treated as a competition between the thermal energy and magnetic energy. if the magnetic correlations can be truncated at some distance l and the FM spins are treated as isolated clusters (i.e. the interaction is much stronger than k B T within l but much weaker at longer distance), m 0, and k B are the saturation moment, the average moment of individual clusters and the Boltzmann constant, respectively. It has been demonstrated that the deviations caused by the truncation, e.g. the interactions smoothly scaled with l in a second order transition, only underestimate the. Typical spin-fluctuations and phase-separation, therefore, can be identified by the value of, which should involve no more than the nearest neighbors in the case of fluctuations far above T m. In the case of Ru-1212/Ru-1222, an additional linear term should be added to account for the paramagnetic contribution of Gd. It is interesting that the fits (solid lines) are so good for both Ru-1212 and Ru-1222 over a broad temperature range (Figs. 8a, 8b). It is more remarkable that the estimated size of the correlated moments is about 300-2000 B far above T m, corresponding to magnetically correlated regions of 20-50 size assuming a moment of 1 B /Ru. This is decisively different from the case of Ni, a classical sample of critical fluctuation. The cluster size is comparable to the lattice parameters above 1.1 T m there (Fig. 9). The layered structure and the presumed 2D FM in Ru-1212/Ru-1222 have been often used to argue in favor of the critical fluctuation model. We disagree. Spin-fluctuations are essentially a competition between k B T and the magnetic energy, which is proportional to the spins coherently bound. The number of the bound spins, however, will be (/a) 3 in 3D but a much smaller value of (/a) 2 in 2D, there a and are the lattice parameter and the correlation length, respectively. This is the root for the stronger fluctuation in 2D below T m. Far above T m, however, the smaller coherent volume in a 2D magnet can only make the M(H) more linear. In a second-order transition, in fact, it is widely accepted that the scaling equation can be written in a dimensionless form, Experimentally, the values of 1+/ range from 3 (some 3D magnets) to > 10 (quasi-2D magnets), i.e. 1+/ is even larger in 2D magnets. Non-linear M(H) may not be expected as a sole effect of lower dimensionality. An example is the quasi-2D ferromagnet La 1.2 Sr 1.8 Mn 2 O 7. It has been demonstrated that the non-linear M(H) far above T m in this compound is a result of mesoscopic phase-separations instead of dimensionality. To verify the existence of superparamagnetic clusters, the magnetic relaxations were explored far above T m. The field was increased to 5 Oe after the sample being zero-fieldcooled to the given temperature. The slow dynamics also appears as a function of the cooling rate of the samples. A Ru-1212-Gd sample (Sample D), for example, was cooled at given fields from room temperature to 60 K with a rate ranging from 0.5 to ≈ 50 K/min (by dropping the sample directly into the pre-cooled chamber). The sample magnetizations were then measured 30 minutes after the temperature being stabilized at 60 K. A decrease of the M FC with the increase of the cooling rate was observed (Fig. 11). The decrease can be up to 6 %, i.e. a significant amount of the spins can be aligned only after 10-100 sec close to T m. The smaller dependence at higher fields again suggests that the cluster size is the origin of the slow dynamics. Combining the slow dynamics with the non-linear isothermal M(H), we estimated that 1-10 % of the sample is in the form of superparamagntic clusters above 70 K. This is a strong support for the phase-separation models. Evidences for a Spatial Correlation Between FM and AFM species To explore the spatial correlation between these different magnetic species, we measured the hysteresis caused by the demagnetizating fields of the 120 K/150 K FM species in Ru-1222. It was observed that two additional step-like jumps and a main one appear in the M FC at 150 K, 120 K, and at T m = 85 K, respectively, in a Ru-1222-Gd sample, Sample E. This is rather similar to that of Fig. 4. The 85 K FM species should nucleate, therefore, under the combination of the external field H and the demagnetizing fields of the 120 K/150 K species. The combined field, in turn, can be estimated by the difference, ∆M FC, between the M FC 's at 95 K and 60 K, since our early data demonstrate that M FC /H between 40 K and T m is H-independent below 5 Oe. To enhance the effect of the demagnetizing fields the following experimental procedure was used: A (field-cooling under a fixed field of 10 Oe from 200 K to 105 K) -B (switching field from 10 Oe to a lower field of -1 Oe < H S < 1 Oe) -C (field-cooling under H S from 105 K to 60 K) -D (raising the temperature under the same H S to 200 K) -E (field-cooling under H S from 200 K to 60 K). In the sequence of cooling and heating steps described above a significant hysteresis was observed (Fig. 12). In fact, the ∆M FC can even be negative under a positive H S. The ∆M FC in step E, i.e. under a simple field cooling, is the linear function of H S through the origin, as expected (Inset, Fig. 13). The ∆M FC in the procedure C, however, intercepts with the H-axis at finite value (H d ≈ 0.6 Oe in this case) although still being a linear function of H S (Inset, Fig. 13). It is only natural, therefore, to interpret the H d as the demagnetizing field of the 120 K/150 K species . It is remarkable that all of the measured ∆M FC, i.e. in both procedures C and E, fit onto the same straight line of ∆M FC ∝ H-f⋅4M FC (95 K) with f being an effective demagnetizating factor. T (K) The demagnetization field will be independent of the Ru-1222 particle size of diluted powders when the particle size is larger than the average distance between the adjacent FM species. It, however, should disappear when the particle size is smaller. Several powders with particle size down to 0.8 m were made from Sample E, and the deduced demagnetizing fields of the 120 K/150 K species field-cooled under 10 Oe field are found to be sizeindependent. This demonstrates that all these FM species are distributed uniformly at least down to the length scale of 0.8 m, although the crystalline grain size observed under SEM is much larger (2-20 m for the sample). We, therefore, attribute the FM species to mesoscopic phase-separations. Another important result from the measurement is the universal value of f ≈ 0.36 ± 0.1 for all Ru-1222 samples we measured. After a geometric correction for the random orientation of the easy axis of the 120 K/150 K species, the microscopic demagnetizing factor f o, i.e. the ratio between the demagnetizing field "felt" by a 85 K species and the moment of the adjacent 120 K/150 K species, should be 0.12 ± 0.03, as supported by our partially aligned powder sample. The small demagnetizing factor, which should be determined by the spatial correlation between the adjacent 120 K/150 K species and the 85 K species, suggests that the three types of species prefer to be aligned along their easy axis. This can occur only if the FM species occupy only a small part of the crystalline grains, a scenario of phase separation again. Based on the magnetization measurements, therefore, we conclude that the magnetic structure of these rutheno-cuprates has to be inhomogeneous on a microscopic scale. The Underdoped Nature of the Superconducting State The existence of superconductivity was first documented by Bauernfeind et al. in the Ru-1222 system based on resistivity and ac susceptibility measurements. The bulk superconductivity in Ru-1212, however, was questioned because of the lack of a clear Meissner signal in field-cooled magnetization experiments in the majority of 1212 compounds investigated by different groups (c.f. the extensive discussion in Section 1). The nature of Cooper pair formation and superconductivity is most likely to be similar to that widely discussed for many high-temperature superconducting cuprate materials, e.g. YBa 2 Cu 3 O 7-. In particular, the structural similarity of YBCO and Ru-1212, as discussed in Section 2, is indicative for a similar mechanism of superconductivity in both compounds. More than a decade of research on high-T c perovskites revealed a characteristic phase diagram and universal relations between normal-state transport properties, the onset of superconductivity (T c ), and the doping state (the average hole density p in the CuO 2 -planes) that are common to all high-T c systems. Comparing all these characteristic quantities we will see that the Ru-1212 and Ru-1222 cuprates are typical underdoped high-T c systems. The first indication of the underdoped nature of the superconducting state comes from transport measurements in the normal state. The resistivity,, of a RuSr 2 GdCu 2 O 8 sample is shown in Fig. 14. The magnetic transition at about 130 K is reflected in a sharp change of slope of the derivative, d/dT (upper left inset). Moreover, the resistivity below room temperature also shows the typical curvature that was observed in other underdoped high-T c materials and was interpreted as the opening of the pseudo-gap. The strongest evidence for the low carrier density is the high value of the room-temperature Seebeck coefficient (lower inset in Fig. 14). For the RuSr 2 GdCu 2 O 8 system the value of S(290 K) varies between 70 and 80 V/K and it was shown that it is almost independent of the conditions of synthesis, annealing etc.. Adapting the empirical relation between S(290 K) and the hole density p that was shown to be valid for most high-T c cuprates, S(290 K)=992 exp{-38.1 p}, the hole density in the CuO 2 plane can be estimated as p ≈ 0.07. This value of the carrier density for the stoichiometric Ru-1212 appeared to be very rigid and could not be increased by optimizing the conditions of synthesis or by annealing in (high pressure) oxygen. This indicates that in Ru-1212 the oxygen content is very close to 8 and cannot be varied at will to change the hole density (as e.g. in YBCO). This conclusion is also in agreement with the results of a thermogravimetric analysis. The systematic change of carrier density in Ru-1212 may be achieved by cation doping, e.g. by replacing Ru with Cu. Thermoelectric power measurements on RuSr 2 (Gd,Ce) 2 Cu 2 O 10+ yield typical values at 290 K of about 20 V/K corresponding to a hole density of p = 0.1. This value is distinctly larger than the carrier density in Ru-1212 but is still well below the optimal doping value of 0.16. Unlike the Ru-1212 system, the oxygen content () in Ru-1222 can be modified by high pressure oxygen annealing resulting in an increase of the carrier density. This was clearly demonstrated by measuring the Seebeck coefficient and by measuring the oxygen content directly in gas effusion experiments. As shown in Fig. 15, S(290 K) decreases systematically with annealing of the as synthesized sample in oxygen pressures of 20 bar and 300 bar. However, the change of S(290 K) from 20 V/K (as) to 11.5 V/K (300 bar O 2 ) is small corresponding to an increase of the hole density, p, by not more than 0.015. Inter-and Intra-Grain Superconductivity in Superconducting Ferromagnets The synthesis process described in Section 2 leads to the formation of powder or ceramic pellets of the rutheno-cuprates. Superconductive single crystals of Ru-1212 have been reported but the high density of defects/weaklinks suggested by the small ZFC diamagnetic signal severely limit their advantage. Most granular high-temperature superconductors, however, exhibit a weak inter-grain coupling in the superconducting state resulting in a lower zero resistance temperature and large differences in the FC and ZFC diamagnetic signals. In particular, two well resolved steps in passing through the transition are frequently observed in susceptibility as well as the resistivity data. The onset of superconductivity is usually observed at T c where the grains become superconducting. Different grains are coupled via the Josephson effect resulting in a phase coherence of the superconducting order parameter across the grain boundaries at a lower temperature T p, the phase-lock temperature. These features of a granular superconductor are clearly seen in the Ru-1212/Ru-1222 compounds. Fig. 16 displays a typical example for RuSr 2 GdCu 2 O 8. The ZFC dc susceptibility exhibits a strong diamagnetic drop at about T p =30 K. The inset of Fig. 16 enlarging the data in the vicinity of the transition shows, however, that the diamagnetic decrease of dc actually sets in at a higher T c =44 K. The same two-step like drop is also detected in the real part of the ac-susceptibility. ' ac measures the shielding signal of a bulk superconducting sample and should be compared to the ZFC dc. Fig. 17 shows the ac susceptibility of another RuSr 2 GdCu 2 O 8 sample with the magnified transition region in the inset. Although the characteristic temperatures are slightly different for this sample (T p ≈36 K, T c ≈43 K), the similarity to the ZFC dc data of Fig. 14 is obvious. It should be noted that the intra-grain diamagnetic signal is extremely small for reasons that will be discussed in the next paragraphs. This typical behavior was observed for many different Ru-1212 as well as Ru-1222 samples. The inter-and intra-grain superconducting transitions are expected to affect the resistivity at the transition since the electrical transport is sensitive to weak links across the grain boundaries. In fact, a broad resistive superconducting transition, sometimes well divided into two steps, has been observed in most transport investigations. One example is shown in Fig. 18. The derivative, d/dT, clearly reveals the superposition of two peaks corresponding to the two resistive transitions observed at T c (intra-grain) and T p (intergrain). The magnetic field dependence of the resistivity is used to further verify the interpretation because the weak inter-grain links are supposed to be quickly suppressed by small fields. The resistivity data of Fig. 18 for low magnetic fields of 200 and 500 Oe show the expected dramatic decrease of the inter-grain T p. The zero resistance state is strongly suppressed by the external field. All these observations can well be understood within the simple picture of intra-and inter-grain superconducting transitions in ceramic superconductors. To collect additional evidence for our interpretation of T p and T c we have conducted measurements of the ac susceptibility of sorted powders of Ru-1212/Ru-1222 samples with well-defined particle size. As discussed above, ac for a bulk granular sample shows two distinct steps (Fig. 17). For powders with particle size well above the grain size the two steps should still exist, but the inter-grain shielding signal will decrease with the particle size. If the particle size of the powder is comparable to or smaller than the grain size of the starting material the inter-grain diamagnetic signal will be completely suppressed but the intra-grain signal is expected to survive. Fig. 19 shows an example of the ac susceptibility for sorted powders of RuSr 2 GdCu 2 O 8. The bulk sample, also shown for comparison, reveals the strongest inter-grain diamagnetic shielding signal. The grain size of this sample was estimated from scanning electron microscopy between 2 and 5 m. The inter-grain shielding signal is largely reduced for the 40 m powder and completely suppressed for powders with average particle size of 2.3 and 0.8 m, i.e. smaller than the original grain size. The intra-grain transition, however, is detected also for the powdered samples with an unaltered T c. It should be noted that the diamagnetic signals in ac (Fig. 19) appear on top of a paramagnetic background. This paramagnetic signal can be attributed to the magnetic moments of the Gd/Ru ions. It was shown that the Gd moments order antiferromagnetically at a far lower temperature of about 2.8 K. A similar analysis of the diamagnetic shielding signal of bulk and powdered samples on RuSr 2 (Gd 0.7 Ce 0.3 ) 2 Cu 2 O 10+ led to analogous conclusions for the Ru-1222 system. Apparently, the properties of the superconducting ferromagnets are affected to a large extent by the weakly coupled grains. This explains why in transport measurements the zero resistance temperatures reported by many groups scatter over a broad temperature range. A more detailed analysis how various conditions of sample synthesis and annealing procedures affect the grain-grain coupling as well as the intra-grain superconductivity was given in Ref.. However, the foregoing discussion proofs that inter-and intra-grain transitions can well be separated in both, magnetic and transport measurements. This is a basic preposition to investigate the "intrinsic" properties of the superconducting state. In the following section, therefore, we focus our attention on the intra-grain superconducting properties of the ruthenocuprates. Effects of Magnetic Phase Separation on the Intra-Grain Superconducting Properties With the discussion of the magnetic structure and the conclusion of the appearance of phase separation into FM and AFM domains on a sub-grain nanoscopic scale (Section 3) it is expected that the intra-grain superconductivity exhibits exotic features that are not characteristic for a bulk superconductor. SC may well exist within the AFM domains. The coupling of the order parameter through the FM domains can consequentially be established via the Josephson effect resulting in a phase-lock transition and "bulk" intra-grain superconductivity over the whole grain. This scenario is quit similar to that discussed for the granular ceramic samples in the previous paragraphs. However, the characteristic length scale is different (sub-grain size) and the "intra-grain granularity" is of magnetic origin, i.e. separation between AFM (superconducting) and FM (non-superconducting) domains. To verify the physical model we focus onto the influence of a small external magnetic field on the intra-grain superconducting properties of Ru-1212 and Ru-1222. The magnetic penetration depth,, is an important characteristic quantity and can be deduced from ac susceptibility measurements of powdered samples. For a magnetically aligned powder of superconducting particles with diameter d the real part of the ac susceptibility is expressed as ' = -3/(8){1 -6(/d)coth(d/2) + 12(/d) 2 The formula basically presents a scaling relation expressing ' as a function of the reduced variable d/. It can be used to estimate the penetration depth from systematic measurements of ' of sorted powders. In randomly oriented powders a geometric correction factor of 1/3 has to be considered to take account of the SC anisotropy. Furthermore, the particle size of sorted powders usually spreads around an average value that was estimated in our experiments by averaging over the measured size distribution, d= 1/2, with d i the diameter of an individual particle, where the largest particles found still being smaller than 2d. The above formula was verified using a standard YBa 2 Cu 3 O 6.4 ceramic sample ground into powders with different average particle sizes between 0.75 and 2.1 m. The fit of ' to the formula yields =0.42 m and T c =42 K. The estimated penetration depth is in good agreement with literature data on YBCO and the T c is close to the value of 40 K measured for the bulk sample. The same procedure was applied to RuSr 2 GdCu 2 O 8. Since these materials show a magnetic background (Fig. 19) measures have been taken to estimate that background signal and to correct the ' accordingly. Fig. 20 shows the raw data of the ac susceptibility measurement. The magnetic background was estimated based on the 0.3 m data (It was shown that the magnetic background was independent of the particle size if the different powders were prepared from one and the same starting material). The intra-grain penetration depth was estimated as (0 K) = 3 m. This value is unusually large compared with other bulk high-T c materials, e.g. the YBCO sample used as a reference. However, the large is in accordance with the very small intra-grain diamagnetic signal (corresponding to about 0.2 % volume fraction) observed in all bulk samples. A natural explanation can be given by employing the phase separation model discussed above. T c only represents the phase-lock temperature of a Josephson junction array (JJA) coupled through links between the AFM domains, if Ru1212 is not homogeneous on a nanoscopic scale because of the coexistence of AFM and FM domains. The intra-grain penetration depth may then be considered as an indirect measure of the (average) Josephson coupling strength. This physical picture can also explain the variations in T c depending on subtle details of the materials synthesis. Since in Ru-1212 the doping level is rather fixed (c.f. discussion in Section 4.1) the variance in T c of different samples has to be related to the details of the magnetic nanostructure and the resulting JJA below T c. In fact, extending the analysis described above to different RuSr 2 GdCu 2 O 8 samples with T c varying between 30 K and 40 K it was found that the penetration depth increased from 2-3 m (T c = 40 K) to > 6 m (T c = 30 K). This suggests a correlation between T c and. This correlation can be understood within the picture of intragrain JJA's. For smaller (average) Josephson coupling T c is expected to be lower and will be larger. To further support our physical picture of an intra-grain JJA we measure the magnetic field dependence of T c using ac susceptibility as well as resistivity () experiments. The experiments are conducted using a ceramic sample of RuSr 2 EuCu 2 O 8. The substitution of Gd by Eu reduces the paramagnetic background of Gd, and is beneficial for resolving the small intra-grain diamagnetic signal. The magnetic and superconducting transition temperatures of this compound are a few degree lower than the corresponding critical temperatures for RuSr 2 GdCu 2 O 8 but the physical properties of the FM and SC states are very similar. As shown before, T c is well resolved in ' and. In susceptibility measurements T c is defined as the intersection point between the linear extensions of the high temperature signal and the intra-grain diamagnetic drop (shown in Fig. 21). A dc bias magnetic field up to 1 Tesla is applied. The intra-grain drop of the resistivity can be separated by a deconvolution of the two peaks observed in the derivative d/dT. In the example of Fig. 22 the deconvolution is demonstrated by fitting d/dT at 500 Oe to two Gaussian shaped peaks (dotted lines). The intra-grain T c is defined by the 95 % drop of the intra-grain resistance (double arrow in Fig. 22 b). T (K) The magnetic field dependence of T c as obtained from both measurements (Fig. 23) shows a very steep decrease at low field (about 100 K/Tesla). This strong decrease of T c (H) is not expected for a bulk, homogeneous superconductor. Ginzburg-Landau theory, for example, predicts a slower decrease for small fields and an opposite curvature over the whole temperature range (see inset of Fig. 23). The data of Fig. 23, however, show the typical field dependence of the critical temperature of a Josephson junction array of coupled superconducting domains. This is in further support of the phase separation model. Within this physical picture the thermodynamic superconducting transition in the AFM domains is expected at a temperature higher than T c. Despite extensive efforts to search for an anomaly related to this thermodynamic transition in magnetic susceptibility experiments a convincing signature of it is still missing. However, transport measurements show that the drop of resistivity and of the Seebeck coefficient sets in at a slightly higher temperature than the estimated intra-grain T c. This is best documented in the derivative d/dT shown in Fig. 14. Below the magnetic transition d/dT is a perfectly linear function of T over a wide temperature range (60 to 130 K). The deviation from linearity at the low-T side might be related to the onset of superconductivity in the AFM domains (inset in Fig. 14). Further work needs to be conducted to explore this matter in more detail. T c,max is the maximum T c in the system at the optimal hole concentration of p=0. 16. Since we have seen that in Ru-1212 the oxygen content and the hole density can barely be controlled by oxygen annealing we focus our attention onto the Ru-1222 structure in which doping and oxygen content can be controlled by annealing the samples in high-pressure oxygen atmosphere. Three samples from the same batch of RuSr 2 (Gd 0.7 Ce 0.3 ) 2 Cu 2 O 10+ have been prepared for susceptibility and transport measurements. The first sample (A) was taken as synthesized, the second (B) and third (C) samples were annealed for 2 hours at 600 °C at oxygen pressures of 20 bar and 300 bar, respectively. The oxygen annealing results in an increase of the intra-grain T c from 26 to 40 K (as determined from dc susceptibility as well as transport measurements). The carrier densities of these samples are calculated from the room temperature Seebeck coefficient (shown in Fig. 15) as: p A = 0.102, p B = 0.109, and p C = 0.118. This is a very moderate increase of hole density by only 0.016 from sample A to C. To verify these values we have also estimated the change of the oxygen content with the O 2 annealing. Heating samples A and C to 800 °C in a gas-effusion cell the released oxygen was measured by both a pressure gauge and a mass spectrometer. The estimated difference in the oxygen content between A and C of ∆ ≈ 0.015 is in excellent agreement with the difference in hole density deduced from the Seebeck coefficients. The observed increase of T c by 14 K can barely be explained as a sole carrier density effect. Using the numbers p A and p C with a value of T c ≈ 40 K for sample C the expected difference of T c between samples A and C would not be larger than 6 K (we used the universal formula relating T c and p). Therefore, the change of carrier density induced by oxygen annealing cannot be the dominant factor determining the change of T c. The enhancement of T c from samples A to C is accompanied by a systematic increase of the diamagnetic signal in FC as well as ZFC dc susceptibility data. For example, the drop of the magnetic moment, ∆M ZFC, measured at 5 Oe increases from 0.15 (sample A) to 0.2 (sample B) and to 0.3 emu/cm 3 (sample C). This implies a change of the magnetic penetration depth, i.e. the increase of T c and ∆M ZFC is related to the increase of 1/ 2 (the superfluid density of a bulk superconductor). To verify the conclusion we measure the intra-grain penetration depth according to the same procedure applied to RuSr 2 GdCu 2 O 8 (see above). The ac susceptibility of sorted powders of RuSr 2 (Gd 0.7 Ce 0.3 ) 2 Cu 2 O 10+ was measured and was calculated from the particle size dependence using a regression procedure that includes geometrical corrections and a magnetic background contribution to ' (see for details). With no arbitrarily adjustable parameter the regression allows to determine (T) within an estimated error of less than 30 %. Fig. 24 shows the results obtained for samples A and C. The zero temperature 1/ 2 of the as synthesized sample A (≈ 3.5 m -2 ) is about twice the value of that of sample C (≈ 7 m -2 ) indicating that the oxygen annealing effect on 1/ 2 is more pronounced than that on the carrier density p, i.e. intra-grain Josephson junctions play the dominating role. This view is further supported by the fast decrease of T c if a small dc magnetic field is applied. The initial slope of T c (H) is of the same order (about 100 K/Tesla) as discussed above for Ru-1212 (Fig. 23). We have treated a large number of Ru-1222 samples under different annealing conditions including pure argon and mixed argon + oxygen atmospheres and applied the same analysis to extract the 1/ 2 and T c. The range of 1/ 2 extends from 0.3 to about 7 m -2 with a T c stretching from 15 K to 40 K. The large increase of 1/ 2 by a factor of more than 20 is significantly higher than expected from the change of both, p and T c, and it deserves further attention. In principle, 1/ 2 may be affected by the normal state effective mass m * of the carriers, scattering resulting in pair-breaking of the Cooper pairs, and the intra-grain granularity discussed above (in the latter case 1/ 2 is determined by the Josephson coupling between the SC domains that can be sensitive to the annealing conditions). The effective mass effect can be excluded since the room temperature resistivity of samples A and C shows only a minor difference. For an underdoped bulk high-T c superconductor Uemura et al. proposed that the critical temperature T c is proportional to the superfluid density. This relation (Uemura-line) appears to be universal and was also shown to hold for Zn substituted high-T c superconductors where T c decreased due to pairbreaking effects. In Fig. 25 we plot 1/ 2 versus T c. Obviously, the data for our Ru-1222 samples do not fit to the Uemura-line but lay all far left/above the proposed universal line. The data are comparable with our results for Ru-1212 where samples with penetration depths as large as 3 m still have a T c > 20 K. This provides strong evidence that the differences in 1/ 2 are not generated by pair-breaking mechanisms. Although T c still increases linearly with 1/ 2 the distinct offset from the Uemura-line provides compelling evidence that the intragrain superconducting state cannot be considered as "homogeneous". This is in favor of our suggestion that the SC state within a grain is more likely described by a JJA of coupled SC sub-grain domains. The T c of a JJA is proportional to the coupling energy of a junction. The of the junction may depend on the junction length but the T c does not. Therefore, a comparably large phase-lock T c can coexist even with a long (or a small value of 1/ 2 ). Competition Between Superconducting and Ferromagnetic States One of the big puzzles in the superconducting ferromagnets is the coexistence of both antagonistic states over a wide temperature range. Therefore, the question arises if FM and SC compete with one another or if there is no mutual interference. Based on muon spin rotation experiments it was suggested that the magnetic moments are not affected by the onset of superconductivity in Ru-1212 below T c ≈ 45 K. However, experiments on chemical substitution (doping) of Ru-1212 show that T c and T m are changed in an opposite way. Decreasing the hole density by partially replacing Gd with Ce or Sr with La results in a decrease of T c (with an ultimate suppression of superconductivity) and an increase of the FM transition temperature. This observation is in line with the fact that the magnetic transition temperature for non-superconducting Ru-1212 is a few degree higher than that of superconducting samples. These results may be an indication of competition between FM and SC states. However, the chemical substitution affects several parameters simultaneously. Besides the change of carrier density it may also introduce disorder, reduce the magnetic coupling in the RuO 2 layers, and cause changes of the microstructure. The use of thermodynamic variables to tune the FM and SC states appears to be interesting because it usually does not change the chemistry of the compounds. We, therefore, decided to use hydrostatic pressure to investigate its effect on the intra-grain superconductivity and on the ferromagnetic state of RuSr 2 GdCu 2 O 8. As shown above, both transition temperatures (T c and T m ) can well be determined from resistivity as well as ac susceptibility measurements (see Figs. 14,17,18,22). The two transitions were investigated at pressures up to 2 GPa by measuring simultaneously the real part of the ac susceptibility and the resistivity. A dual coil system was mounted to a ceramic pellet of RuSr 2 GdCu 2 O 8 and four platinum wires were attached to the sample for resistance measurements. Both, '(T) and (T), were measured in parallel employing the resistance and mutual inductance bridge LR 700 (Linear Research). Hydrostatic pressure was generated in a beryllium-copper pistoncylinder clamp. The sample was mounted in a Teflon container filled with a 1:1 mixture of Fluorinert FC70 and FC77 as a pressure-transmitting medium. The pressure was measured in situ at about 7 K by monitoring the shift of the superconducting transition temperature of a small piece of high purity (99.9999 %) lead. The temperature was measured by a thermocouple inside the Teflon pressure cell as well as a germanium resistor built into the BeCu clamp close to the sample position. It is particularly important in this experiment that we can separate the inter-and intragrain SC transitions in order to discuss the "intrinsic" pressure effect. There is an additional contribution to the pressure coefficient of the inter-grain critical temperature (T p ) due to the fact that pressure naturally compresses the polycrystalline sample and, therefore, improves the grain-grain connectivity resulting in an increase of the inter-grain Josephson coupling. This effect is not "intrinsic" and should not interfere with the intra-grain shift of T c. Since we have shown that T p and T c are well distinguished in our experiments the application of pressure can be used to reveal any correlations between the intra-grain superconductivity and magnetism. The pressure dependence of T c and T p is shown in Fig. 26. The pressure coefficients of T c of 1.02 K/GPa and 1.06 K/GPa as obtained from ' and, respectively, are in excellent agreement. The small offset between the two data sets is due to the different criteria to estimate T c from ' and. The larger pressure shift of the inter-grain phase-lock temperature, dT p /dP = 1.8 K/GPa reflects the abovementioned pressure-induced improvement of the graingrain contacts. The pressure shift of the magnetic T m (Fig. 27), dT m /dP = 6.7 K/GPa, is distinctly larger than that of T c. Comparing the relative enhancements, dlnT c /dP = 0.025 GPa -1 and dlnT m /dP = 0.054 GPa -1, it becomes obvious that the magnetic T m increases about twice as fast with P as the superconducting T c. For a further exploration of the pressure effect in Ru1212 we compare the pressure coefficient of T c with that of other high-T c compounds in a similar doping state. Ru-1212 is a typical underdoped material with a hole concentration of about 0.07 (see discussion in Section 4.1). The pressure coefficients of other underdoped cuprates were recently estimated for a number of different compounds, e.g. La 2-x (Sr,Ba) x CuO 4, La 2 CuO 4+, YBa 2 Cu 3 O 7-, or YBa 2 Cu 3-x M x O 7-, and typical values ranging from 3 to 4 K/GPa or even higher were reported. This number can be considered as a universal value for underdoped cuprates. The equivalent value for Ru-1212 of only 1 K/GPa is at least 3 to 4 times lower than the pressure coefficient expected in the particular doping state. This unusually small dT c /dP of RuSr 2 GdCu 2 O 8 leads us to the conclusion that it is primarily an effect of the enhancement of the FM order by pressure. It is then an immediate consequence of an apparent competition of the FM and SC phases. Due to this competition the stronger enhancement of the magnetic phase results in a reduced (as compared to other high-T c compounds) pressure effect on T c. This effect can be understood within our physical picture of intra-grain FM and AFM phase separation. The P-induced increase of T m indicates an enhanced ferromagnetic exchange interaction in the non-superconducting FM domains. This will result in a reduced Josephson coupling between the superconducting (AFM) domains and a relative reduction of the intragrain T c. The intrinsic pressure effect on the intra-grain superconductivity is, therefore, reduced to the small value of 1 K/GPa observed in our experiments. Our high-pressure experiments provide additional indirect support for the explanation of the intra-grain superconductivity as the phase-lock transition of a JJA that originates from the magnetic phase separation into AFM and FM domains. SUMMARY The magnetic and superconducting properties of a class of newly discovered compounds, superconducting ferromagnets, have been extensively investigated. Magnetic susceptibility measurements (dc and ac) as well as electrical transport experiments (resistivity and thermoelectric power) were employed to understand the unusual magnetic and superconducting properties and, in particular, the coexistence and competition between these antagonistic states of matter. We conclude that in both ruthenium based high-T c structures, Ru-1212 and Ru-1222, the magnetic order is very complex and shows the typical signatures of phase separation into antiferromagnetic and ferromagnetic domains on a sub-grain scale. Accordingly, the intra-grain superconductivity in these compounds is understood as a phase-lock transition between superconducting and anti-ferromagnetic domains with a weak Josephson like coupling across the ferromagnetic (but non-superconducting) domains. The exotic and yet not well understood properties of the superconducting state can be explained by the model. For example, the extremely small diamagnetic signal, the small and sometimes missing Meissner signal, the large intra-grain penetration depth, the unusual magnetic field dependence of the intra-grain T c, and the pressure effects on the magnetic and superconducting states can be explained within the physical picture described above and lend strong support to the model of magnetic phase separations appearing in superconducting ferromagnets.

The ability to breathe new life into an aging satellite using robot mechanics could potentially boost satellite industry efficiency and reduce mission costs, and at least one aerospace firm is forging ahead with plans to do just that. Now, all the company needs is customers. "We're ready to sell, we're ready to build, we're ready to deliver," said Edward Horowitz, ViviSat's chairman of the board. ViviSat is a joint venture of rocket manufacturer Alliant Techsystems (ATK) and aerospace firm U.S. Space. ViviSat's Mission Extension Vehicle (MEV) is being designed to dock to satellites in orbit, and then use its own thrusters to provide propulsion and attitude control. Among other functions, the spacecraft will be able to adjust an older satellite's orbit, rescue fully fueled satellites that may have launched into the wrong location, or move a satellite into a different orbit for a completely new purpose. "Our target market is both commercial spacecraft as well as government spacecraft," Horowitz, told SPACE.com at the 28th National Space Symposium in mid-April. "If you just look at the commercial market, there are 350 to 360 satellites in geostationary orbit. Every year, 25 or so reach the end of their fuel life. Of that 25, we figure 10 are good target customers for this." The MEV is being built by ATK, the company that manufactured the reusable solid rocket motors for NASA's now-retired space shuttles. Prototypes of the MEV's rendezvous and docking mechanisms are currently being tested at a special facility in Beltsville, Md. that simulates the microgravity environment of space. Horowitz declined to comment on the cost of the MEV program, but said that work on the spacecraft systems are continuing to evolve. "We've really made a lot of progress," said Tom Wilson, vice president and general manager of ATK's space systems division. "The technology that we need exists off the shelf today, and most of it has been tested in orbit. For us, this reduces a huge amount of risk." The way that the MEV vehicle operates is also considered much less invasive than other similarly proposed projects, Horowitz said. Since the MEV does not add fuel or remove any materials on the satellite itself, it is less intrusive. It also allows satellite operations to continue uninterrupted even with the MEV attached. "Satellites were designed to not be tampered with, and this is a passive approach, which is appealing to operators," Horowitz said. "This enhances profitability because it allows operators to keep operating, so they keep their margins. It's no fuss, no muss and no mechanics." "The economic environment has created a crisis," Horowitz said. "Change usually comes about in periods of crisis, and we have such a period now. This is a way of cost effectively maintaining perfectly good on-orbit assets. In this tight economic environment, logic says it would help. There's an opportunity for people to start looking at new things and new ways of doing things." This so-called Space Infrastructure Servicing vehicle will be able to refill a satellite's fuel tanks and perform minor repairs, as needed. The ambitious project has the potential to greatly improve how a commercial satellite company operates, but so far, MDA has struggled to lock in committed customers. Satellite operator Intelsat initially agreed to pay $280 million over time for MDA's SIS vehicle to refuel certain satellites in its fleet. The first of these refueling missions was targeted to occur in 2015, but in January, both companies announced they have scrapped the agreement. But ViviSat is confident it can attract enough customers to make a viable business case, which includes up to five docks and undocks per MEV, Wilson said. With much of the technology already in place, the development of the spacecraft could also be a faster and less risky process. In fact, if a satellite operator purchases the service today, the first MEV spacecraft could be launched as early as 2015, Wilson said. But the trick is to find that first customer. "I call it the penguin theory," Horowitz said, "You have all these people, all these potential customers, all these penguins standing on the ice, all creeping up to the edge. It's not until the first penguin goes in that the rest follow. So, we have the penguin theory, which is that someone's waiting for others to be first."

Diaspora (Christian Scott album) Background The title Diaspora refers to the entirety of Adjuah's listening public, even though the term has specific meanings in the African-American experience, celebrating the rhythmic feels and traditions that arose from the historic movement of African peoples to the Americas and around the globe. Adjuah explains "We're trying to highlight the sameness between seemingly disparate cultures of sound as a means of showing a broader reverence and love for the people who create the sound and the experiences that lead them to those places." Reception Jeff Terich of Treble wrote "Diaspora, meanwhile, shifts away from some of the first installment’s darker, more hallucinatory tones. The title track alone marks a pretty dramatic transition, its laid-back trip-hop beats ushering in a more accessible, immediate sound that features a little less in the way of stylistic experimentation. Which isn’t to say there isn’t any; in fact, Diaspora is largely cut from the same cloth, albeit with results that skew a bit more toward the pop-friendly. “Desire and the Burning Girl,” for instance, is one of the album’s most surreal, with a heavy dose of effects clouding Scott’s horn playing as a rhythmic pulse grooves in the background. Yet there’s more of a lightness about these tracks overall; “Lawless,” for instance, is by production standards a pretty hectic and dramatic track, though it’s ultimately a highly melodic piece, even loungey in a way that’s not so obvious." Jason P. Woodbury of Flood Magazine noted "If Ruler Rebel was a NOLA-fied New Hope, thematically centered on, in part, “the return of the Demagogue,” Diaspora is the mysterious, downtempo Empire Strikes Back. Much of the record maintains this hazy, noirish hue: the fuzzy, Dilla-esque “No Love” and the John Key Jr.–penned “Uncrown Her” evoke the neo-soul of the late ’90s and early ’00s. But Scott never settles entirely into an easy groove. The complex drumming of “Lawless” keeps it from working as aural wallpaper, its constant twitching always too arresting to function as background music. Same for “Bae” and “New Jack Bounce.” Though both are labeled as interludes, they feel as engaging as the longer suites, offering rhythmic asides that punctuate the airy gauze of Scott’s trumpet, which shifts from clear, bell-like tones into phased, psychedelic washes of sound."

Archaic Genes in Modern People? PHYSICAL ANTHROPOLOGY/PALEOANTHROPOLOGY MEETINGSMILWAUKEE, WISCONSIN-- About 1200 researchers gathered near the shores of Lake Michigan here from 5 to 9 April. Two independent groups presented data from the X chromosome hinting that modern humans interbred with other human species sometime in the past: The teams found possible traces of archaic hominids in our genes.

The Association of Tobacco mosaic virus with Green Spot of Cured Wrapper Tobacco Leaves. Near-isogenic lines of cigar wrapper tobacco resistant or susceptible to Tobacco mosaic virus (TMV) were used to evaluate the association of TMV infection with green spot symptoms in cured leaves. TMV infection, as determined by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), was detected on susceptible but not resistant plants in field experiments. Green spot severity on cured leaves was greater for susceptible than resistant plants, even when symptoms of TMV were not evident in the field. Some green spots were present on resistant leaves despite the fact that the virus was not detected by ELISA. Resistant and susceptible plants had similar responses to virus infection and similar ELISA detection of TMV when plants were held at continuous temperatures over 28°C in growth chambers. Plant resistance was not compromised in the field in cloth-covered shade tents even when 33.5 of the 96 h immediately following inoculation were above 28°C. Green spot of cured leaves was strongly associated with TMV infection in susceptible plants, even when plants were infected after leaf expansion and mosaic symptoms were not present. Green spot also occurred to a lesser extent and for a limited time in inoculated resistant plants. The development of green spot symptoms on cured leaves may be the result of either systemic infection of TMV-susceptible plants or associated with the systemic resistance response to TMV inoculation of resistant plants.

0. Pre-lim. Why are you reading this? (because your not lazy and want to run Gimp and Resynthesize pics on your own; I hope) This is short tutorial on how to remove crazy-complicated artifacts, trash pieces, etc from photos and all for free! This technique was demoed as for inclusion in CS5 as a content-aware plugin that removed trees from the background, a piece of trash on the golf course, and removed a tree out of the sky. Another picture shows a complete removal of a road going through a desert. What content aware plug-ins do is completely re-synthesize the area that is selected for removal by using algorithms that hunt for near-by similar pixels. This, also maybe used to fill in the gaps in panoramas of mountains, landscapes, where the edges of the photos don't line up. So now you know what this whole tutorial is about, and after you get through this, removing objects or re-creating areas of photos will be simple. No more getting mad at the STAMPY TOOL! Now, I should state that even though I'm lucky enough to be able to use an 8-core Mac Pro, this installation doesn't really seem to use more then one-core. I hope this is fixed in the future, but this seems to pertain to most computers right now...so it's not as quick as say CS5 will be running in a fully-utilized Mac OS X environment. Let’s get this thing started. 0.5. Make sure you have X11 environment installed from Apple. Be sure after downloading X11, to run updates like mad. (Apple Menu > Software Updates) [DOWNLOAD] > X11 1. Install Gimp. As of this writing I have version 2.6.8 [DOWNLOAD] > The Gimp > Which OS do you have? Mac OS X 10.6, 10.5, 10.4 direct downloads] 2. The Gimp should show up in Hard Drive > Applications open it to see if you have everything installed right, if it doesn’t work, run Software Update again until there isn’t anything X11-related to update. 3. Open the picture you want to edit into Gimp either by dragging it onto the Gimp icon in the dock or by going to File > Open. I’ve chosen this picture I took of an apocalyptic like situation, completely unedited. reddit.com/r/atheism: even in times of end-of-times discontent, fun times can be had. 4. Next choose the lasso selection tool and select the object you want to get rid of. Here I’ve chosen to get rid of a stick that divides my whole composition in half: “Grr” one might say in the pre-Gimp past, but keep in mind, this is the post gimp-a-limptic future. 5. Now Choose Filters > Map > Resynthesize from the menus that appear in the same window as your picture. Rendering and X11 with multiple Cores. 6. Just push OK on the window that comes up, but if you want to compare settings, or whatever else, here is my setup. Notice the Rendering Bar right below your image: Notice how many cores are used in my octo-core Mac: The Intel Core Duos (with 2 cores) would probably have only 1 core in use at one time as well. Hopefully this will be fixed either by future Gimp versions or by Apple’s X11 environment. When working on the full size image which is about 5k x 3k pixels, the mac 8-core struggled a little more, taking about a minute to render on a single core. Granted, for making things quick, you can resize to a quarter the size. That brings time down to about 10 seconds and better for playing around with this plug-in. 7. Now that you’ve done all the dirty work, you should have a very clean picture. Lasso, Resynth, Repeat as needed. See !! No more stick! “WHOchA GOOD boy!” Thanks for reading. Advertisements

Fluorescence and Raman microscopy analysis of dental tissues The variety of optical spectroscopic techniques is used for chemical analysis of normal and carious tissues. Polarization light microscopy, fluorescence spectroscopy/microscopy, Raman and IR spectroscopy/microscopy all provide valuable information on the tooth structure and chemical composition; however, near-IR laser-induced fluorescence measurements proved to be the most efficient indicator of bacterially infected tooth.

Mycobacterial infections in Norway. Tuberculosis was a major health problem in Norway in the first part of the century, but since the thirties there has been a dramatic and steady decline in incidence. However, for various reasons, including tuberculosis in foreign-born residents, there has been no definite decrease in notified cases during the last decade. The emergence of drug resistant strains of M. tuberculosis has up to now not been a problem of any significance. Leprosy reached its peak incidence in the 19th century. Nowadays the few imported cases seen, on average less than one a year, may represent a diagnostic challenge. Therapeutically, we have adopted a modification of the multidrug regime introduced and recommended by WHO a decade ago. Available figures indicate that diseases due to other mycobacteria, so-called atypical mycobacteria, may be an increasing problem. A small part of the observed increase is due to infections with Mycobacterium avium-intracellulare complex in AIDS patients.