cssi/SciSciGPT-SciSciNet huggingface dataset:
A Live-Attenuated Pseudomonas aeruginosa Vaccine Elicits Outer Membrane Protein-Specific Active and Passive Protection against Corneal Infection

Pseudomonas aeruginosa can cause sight-threatening corneal infections in humans, particularly those who wear contact lenses. We have previously shown that a live-attenuated P. aeruginosa vaccine given intranasally protected mice against acute lethal pneumonia in a lipopolysaccharide (LPS) serogroup-specific manner. In the current study, we evaluated the protective and therapeutic efficacies, as well as the target antigens, of this vaccine in a murine corneal infection model. C3H/HeN mice were nasally immunized with the vaccine (an aroA deletion mutant of strain PAO1, designated PAO1DeltaaroA) or with Escherichia coli as a control and were challenged 3 weeks later by inoculating the scratch-injured cornea with P. aeruginosa. For passive prophylaxis and therapy, we utilized a serum raised in rabbits nasally immunized with PAO1DeltaaroA or E. coli. Outcome measures included corneal pathology scores and, in some experiments, reductions in total and internalized bacterial CFU. We found that both active and passive immunization reduced corneal pathology scores after challenge with a variety of P. aeruginosa strains, including several serogroup-heterologous strains. Even when given therapeutically starting as late as 24 h after infection, the rabbit antiserum to PAO1DeltaaroA was effective at reducing corneal pathology scores. Immunotherapy of established infections also reduced the numbers of total and internalized corneal P. aeruginosa bacteria. Experiments using absorbed sera showed that the protective antibodies are specific to outer membrane proteins. Thus, live-attenuated P. aeruginosa vaccines delivered nasally protect against corneal infections in mice and potentially can be used to prepare passive therapy reagents for the treatment of established P. aeruginosa corneal infections caused by diverse LPS serogroups.
Heterogeneous Spectrum of Coreceptor Usage among Variants within a Dualtropic Human Immunodeficiency Virus Type 1 Primary-Isolate Quasispecies

Human immunodeficiency virus type 1 (HIV-1) variants that use the coreceptor CCR5 for entry (R5; macrophage tropic) predominate in early infection, while variants that use CXCR4 emerge during disease progression. Some late-stage variants use CXCR4 alone (X4; T-cell tropic), while others use both CXCR4 and CCR5 (R5X4; dualtropic). It has been proposed that dualtropic R5X4 strains are intermediates in the evolution from R5 to X4, and we hypothesized that a dualtropic primary-isolate quasispecies might contain variants that represent the spectrum of coreceptor use in vivo. We generated a panel of 35 functional full-length env clones from the primary-isolate quasispecies of a dualtropic prototype strain, HIV-1 89.6PI. Thirty of the functional env clones (86%) were R5X4, four (11%) were R5, and one (3%) was predominantly X4. V3 to V5 sequences did not reveal clustering by coreceptor usage, and no specific sequence motif or V3 charge pattern corresponded to coreceptor utilization. Complete sequencing of seven functionally divergent Env proteins revealed >98.7% homology and conservation of structurally important domains. Chimeras between the R5X4 89.6 prototype and an R5 variant indicated that multiple regions contributed to the use of CXCR4, while chimeras with the X4 variant implicated a single residue in V4 in CCR5 use. These results confirm, at the molecular level, both that dualtropic variants are a predominant component of late-stage syncytium-inducing isolates and that variants restricted to each coreceptor coexist with dualtropic species in vivo. Coreceptor-restricted minority variants may reflect residual R5 species from earlier in disease as well as emerging X4 variants.
Propranolol Decreases Tachycardia and Improves Symptoms in the Postural Tachycardia Syndrome. Less Is More

Background— Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance with an excessive increase in heart rate on standing. β-Blockade is an appealing treatment approach, but conflicting preliminary reports are conflicting. We tested the hypothesis that propranolol will attenuate the tachycardia and improve symptom burden in patients with POTS. In protocol 1, a low dose (20 mg) was compared with placebo, and the dose response was assessed in protocol 2. Methods and Results— In protocol 1, patients with POTS (n=54) underwent acute drug trials of propranolol 20 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressure, heart rate, and symptoms were assessed while the patients were seated and after standing for up to 10 minutes before and hourly after the study drug. Supine (P<0.001) and standing (P<0.001) heart rates were significantly lower after propranolol compared with placebo. The symptom burden improvement from baseline to 2 hours was gr...
Specificity in reactive oxidant signaling: think globally, act locally

Although reactive oxidants have long been stigmatized as unwanted metabolic byproducts, the expression of oxidases specifically functioning to produce these same molecules in a regulated fashion is surprisingly pervasive throughout metazoan and plant evolution. Although the involvement of oxidants in many signaling pathways is well documented, the cellular strategies for conferring pathway specificity to such reactive molecules have remained more recondite. Recent studies now suggest that cells may spatially restrict oxidant production to allow microdomain-specific signaling.
An analysis of the structure and complexity of nonlinear binary sequence generators

A method of analysis is presented for the class of binary sequence generators employing linear feedback shift registers with nonlinear feed-forward operations. This class is of special interest because the generators are capable of producing very long "unpredictable" sequences. The period of the sequence is determined by the linear feedback connections, and the portion of the total period needed to predict the remainder is determined by the nonlinear feed-forward operations. The linear feedback shift registers are represented in terms of the roots of their characteristic equations in a finite field, and it is shown that nonlinear operations inject additional roots into the representation. The number of roots required to represent a generator is a measure of its complexity, and is equal to the length (number of stages) of the shortest linear feedback shift register that produces the same sequence. The analysis procedure can be applied to any arbitrary combination of binary shift register generators, and is also applicable to the synthesis of complex generators having desired properties. Although the discussion in this paper is limited to binary sequences, the analysis is easily extended to similar devices that generate sequences with members in any finite field.
High-Quality Stereo Video Matching via User Interaction and Space-Time Propagation

Even current state-of-the-art automatic stereo matching methods often struggle on natural images and videos, in great part due to fundamental matching ambiguities in low texture regions and a lack of higher level object knowledge. Stereo image matching can benefit greatly from user input to guide the matching process and help disambiguate matches. Applying interactive correction tools from scratch on each frame of a video would not only be throwing away valuable information provided by the user on other frames, but would also likely be too time consuming to be practical for video even if excellent disparity results could be obtained within a few minutes on each frame. In this work, we propose a stereo video matching system that allows user interaction to obtain high quality, dense disparity maps on key frames and then intelligently propagates the user input and key frame disparities to automatically produce high quality disparity maps on intermediate frames. The disparity maps on key frames are obtained using several novel, easy-to-use, and effective interactive tools. Our novel propagation algorithm estimates 3D transformations that map user corrected areas in key frames to intermediate frames. Experiments demonstrate the effectiveness and efficiency of our hybrid interactive/automatic approach.
The benefits of insulin pump therapy in children and adolescents with type 1 diabetes.

1 The Pediatric Endocrinology Nursing Society (PENS) is committed to the development and advancement of nurses in the art and science of pediatric endocrinology nursing and to improve the care of all children with endocrine disorders through the education of the pediatric healthcare The management of type 1 diabetes (T1D) requires lifelong administration of insulin. The primary treatment goal of T1D in children and adolescents is maintaining euglycemic levels through intensive insulin therapy and avoiding complications while maintaining as normal a life as possible (Malik & Taplin, 2014). Effective insulin therapy should meet the needs, preferences, and resources of the individual and the family for optimal management of T1D. In 1993, the Diabetes Control & Complications Trial (DCCT) concluded that tight diabetes control reduces long-term complications (Nathan, Cleary, Backlund, et al., 2005). To achieve target glycemic control, children and adolescents may use either multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII), also known as insulin pumps (Malik & Taplin, 2014). Significant improvement in the management of children with T1D has been associated with CSII. According to the consensus paper from the European Society for Pediatric Endocrinology, the Lawson Wilkins Pediatric Endocrine Society, and the International Society for Pediatric and Adolescent Diabetes, “CSII therapy may be appropriate for children and youth of all ages” (Phillip, Battelino, Rodriguez, Danne, & Kaufman, 2007). Insulin pumps, compared to MDI, deliver insulin in a more physiologic way, allowing for improved matching of insulin delivery to insulin requirements and greater lifestyle flexibility (McMahon et al., 2004 and Valenzuela et al., 2006). CSII therapy is designed to mimic physiological insulin exposure by delivering a daily basal rate while giving extra insulin for carbohydrate intake. The aim of CSII is to improve glycemic control while optimizing the flexibility of therapy (Campbell, 2008).
Development of Physiologically Based Pharmacokinetic/Pharmacodynamic Model for Indomethacin Disposition in Pregnancy

Findings of a recent clinical study showed indomethacin has lower plasma levels and higher steady-state apparent clearance in pregnant subjects when compared to those in non-pregnant subjects reported in separate studies. Thus, in the current work we developed a pregnancy physiological based pharmacokinetic/pharmacodynamic (PBPK/PD) model for indomethacin to explain the differences in indomethacin pharmacokinetics between pregnancy and non-pregnancy. A whole-body PBPK model with key pregnancy-related physiological changes was developed to characterize indomethacin PK in pregnant women and compare these parameters to those in non-pregnant subjects. Data related to maternal physiological and biological changes were obtained from literature and incorporated into the structural PBPK model that describes non-pregnant PK data. Changes in indomethacin area under the curve (AUC), maximum concentration (Cmax) and average steady-state concentration (Cave) in pregnant women were predicted. Model-simulated PK profiles were in agreement with observed data. The predicted mean ratio (non-pregnant:second trimester (T2)) of indomethacin Cave was 1.6 compared to the observed value of 1.59. In addition, the predicted steady-state apparent clearance (CL/Fss) ratio was almost similar to the observed value (0.46 vs. 0.42). Sensitivity analysis suggested changes in CYP2C9 activity, and to a lesser extent UGT2B7, as the primary factor contributing to differences in indomethacin disposition between pregnancy and non-pregnancy. The developed PBPK model which integrates prior physiological knowledge, in vitro and in vivo data, allowed the successful prediction of indomethacin disposition during T2. Our PBPK/PD model suggested a higher indomethacin dosing requirement during pregnancy.
The Twins Corpus of Museum Visitor Questions

The Twins corpus is a collection of utterances spoken in interactions with two virtual characters who serve as guides at the Museum of Science in Boston. The corpus contains about 200,000 spoken utterances from museum visitors (primarily children) as well as from trained handlers who work at the museum. In addition to speech recordings, the corpus contains the outputs of speech recognition performed at the time of utterance as well as the system interpretation of the utterances. Parts of the corpus have been manually transcribed and annotated for question interpretation. The corpus has been used for improving performance of the museum characters and for a variety of research projects, such as phonetic-based Natural Language Understanding, creation of conversational characters from text resources, dialogue policy learning, and research on patterns of user interaction. It has the potential to be used for research on children’s speech and on language used when talking to a virtual human.
A method for rapid detection and genotype identification of hepatitis C virus 1–6 by one-step reverse transcription loop-mediated isothermal amplification

Summary Objective Hepatitis C virus (HCV) is probably the leading cause of liver cirrhosis and hepatocellular carcinoma globally. Diagnostic tools conventionally used for the detection and identification of HCV infection are technically demanding, time-consuming, and costly for resource-limited environments. This study reports the development of the first rapid loop-mediated reverse transcription isothermal amplification assay that rapidly detects and identifies HCV genotypes in blood components. Methods RNA extracted from donor plasma and serum specimens was applied to a one-step reverse transcription loop-mediated isothermal amplification reaction performed with HCV-specific oligonucleotides. Reactions were conducted at 63.5°C for 30–60min. The diagnostic characteristics of the assay were investigated and validated with clinical specimens. Results Electrophoretic analysis of amplification revealed detection and identification of HCV genotypes 1–6. Positive amplification revealed unique ladder-like banding patterns that identified each HCV genotype. The assay demonstrated a sensitivity of 91.5% and specificity of 100%. Rapid naked-eye detection of HCV infection was facilitated by observation of an intense fluorescent glow of amplified targets under UV illumination. Conclusion These diagnostic characteristics highlight the potential utility of this assay for the rapid detection and genotype identification of HCV infection in field and point-of-care settings in endemic regions and resource-limited environments.
Warming and Elevated CO2 Interact to Drive Rapid Shifts in Marine Community Production

Predicting the outcome of future climate change requires an understanding of how alterations in multiple environmental factors manifest in natural communities and affect ecosystem functioning. We conducted an in situ, fully factorial field manipulation of CO2 and temperature on a rocky shoreline in southeastern Alaska, USA. Warming strongly impacted functioning of tide pool systems within one month, with the rate of net community production (NCP) more than doubling in warmed pools under ambient CO2 levels relative to initial NCP values. However, in pools with added CO2, NCP was unaffected by warming. Productivity responses paralleled changes in the carbon-to-nitrogen ratio of a red alga, the most abundant primary producer species in the system, highlighting the direct link between physiology and ecosystem functioning. These observed changes in algal physiology and community productivity in response to our manipulations indicate the potential for natural systems to shift rapidly in response to changing climatic conditions and for multiple environmental factors to act antagonistically.
Meta Analysis of Etiology and its Clinical and Radiological Correlation in Cases of Craniomaxillofacial Trauma

Aim The present study was planned to investigate the etiology of injuries and to analyze correlation between clinical and radiological findings in cases of craniomaxillofacial trauma.
Trigonometry and Spherical Astronomy

In the first eleven chapters of Book I, Copernicus sets out a general description of the planetary system and of the movement of the earth. It is here that he presents his principal arguments for the heliocentric theory and attempts to answer astronomical and physical objections to the motion of the earth. These chapters are so well known, and have been commented upon at such length by so many historians and philosophers, who have devoted particular attention to just this part of Copernicus’s work, that anything we might have to say, after the hundreds if not thousands of pages that have already been written, would be bringing owls to Athens.1 Therefore, we shall pass immediately to the more practical, if less celebrated, expositions of trigonometry and spherical astronomy that occupy the greater part of Books I and II. It is of course true that Copernicus made no original contributions to either subject, but his presentation is on the whole admirable, and the rest of his work is either unintelligible, or of severely reduced intelligibility, without them.
E5 Monoclonal Immunoglobulin M Antibody for the Treatment of Gram-Negative Sepsis

Despite the advent of aminoglycoside and beta-lactam antibiotics and early antimicrobial intervention, overall morbidity and mortality associated with gram-negative sepsis and bacteremia remain high. Complications of sepsis have been related to the release of endotoxin from the cell walls of gram-negative bacilli. Although antibiotics can effectively kill gram-negative bacteria, they have no effect on lipopolysaccharide lipopolysaccharide (LPS) and may, in fact, enhance its release when cell lysis occurs. Lipid A, the lipid portion of LPS, is composed of glucosamines, polar phosphate groups, and fatty acids. It represents the endotoxic component of gram-negative bacteria and is responsible for host responses to LPS, including fever, hypotension, and shock. E5 is a murine monoclonal immunoglobulin M antibody directed against the lipid A portion of the cell-wall endotoxin that is common to clinically important gram-negative bacilli. A clinical evaluation program of E5 included patients who were moderately to severely ill with clinical evidence of an infection usually caused by gram-negative bacteria. In pharmacokinetic and safety studies, laboratory tests revealed no evidence of antibody-mediated toxicity and serum antibody concentrations in the desired therapeutic range (greater than 5 microgramS/mL) were found as late as 72 hours after initial infusion of E5. In a Phase II study, mortality rates at seven days in patients with documented gram-negative infection were 22 percent in the placebo group compared with 7 percent in the E5-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Threshold Rules as Tools of Deference?: Circuit Judge Gatekeeping in Administrative Agency Cases

Given the importance of the courts in monitoring agency decisions, the extent of deference they offer to agencies is very important. Thus, existing research on administrative agencies and the courts has naturally focused on the extent to which courts defer to agency decisions on the merits of legal claims. Previous scholars, however, have not systematically assessed whether deference is also achieved via the use of threshold rules. In this article, we investigate the extent to which threshold rules are raised in administrative agency litigation and explore the nature of their use. Although our analysis reveals that procedural questions of access are considered in a nontrivial number of administrative agency cases heard by the U.S. Courts of Appeals, the results do not suggest that circuit judges consistently use such rules to curb the consideration of all claims raised in a given case. In addition, circuit judges are not more likely to deny access in challenges against executive as opposed to independent ...
Bionomics of Psylliodes chalcomera , a Candidate for Biological Control of Musk Thistle

Psylliodes chalcomera (Illiger) is oligophagous on Carduus spp., is widely distributed throughout Europe and is not a pest of cultivated crop plants. In the field at Rome, Italy, eggs were laid from January to June on the base of the plants or in the soil adjacent to the plants. The larvae fed in both flower and leaf buds, matured in mid-May, and pupated in the soil near the plant. Adults emerged early June, fed heavily, and commenced aestivation in the 2nd half of June, so they were well-synchronized with the senescence of the host plants. Aestivation terminated in early November and oviposition commenced in late January. Females kept at outside temperature produced an avg. 296 eggs each, and some lived 20 mo, through 2 aestivations and 2 ovipositional periods.
Defining “Credible Faults” - A Risk-Based Approach

Fault protection and mission assurance criteria for space applications often include a requirement of the form, “no single credible fault shall prevent mission loss.” Faults deemed “not credible” are exempted by the requirement providing relief when complexity, structure, cost, mass, or other constraints are not compatible with adding redundancy and fault protection mechanisms. There are at least two major problems with this requirement statement. First, the requirement implies that simply adding redundancy for credible faults is sufficient for satisfaction while ignoring the reality that infinite spares are not effective if the fault protection design is weak. Second, lacking an objective definition for “credible,” the requirement is susceptible to different subjective interpretations, disagreements, and potentially mission-ending design gaps. Unfortunately, faults deemed “not-credible” or poorly designed fault protection have been the cause of failure in a number of space missions. In this paper, we propose a metric that enables objective evaluation of credibility by addressing both fault protection effectiveness and the risk of a “non-credible” fault eventually causing mission failure.
Port security training and education in Europe—a framework and a roadmap to harmonization

ABSTRACTTraining of human resources in port facilities is of particular importance, especially if one considers that cargo crime could be facilitated by negligence or support of personnel. Recommendations regarding training and education are available in the SOLAS Chapter XI-2 and ISPS code. However, experts claim that too much freedom of interpretation is given to these frameworks in the process to define security training and education. As a consequence, harmonization of security may be hindered, leaving weak points and compromising commitment, security culture and awareness. In this paper, we aim to understand the present status of port security training and education courses that today are offered in Sweden. In particular, we look at the market for these services and the current level of harmonization. Results show that level of commitment, size of ports, cultural and working conditions may affect the outcome of security courses. From a harmonization viewpoint, we found that more work need to be done ...
Study on GA3 application technology for super hybrid rice seed production of Luliangyou996 combinations

In order to probe into a high yield and efficiency techniques for Luliangyou996 combination,the effect of GA3 on improving the out-crossing characteristics of its female parent,Lu18S and the seed yield were studied.The results indicated that using GA3 at proper spraying periods with appropriate dosages was an effective measure for improving the heading characteristics,panicle layer carriage of Lu18S and the seed production yield.It was optimal to spraying GA3 at the dosage of 210 g/hm2 and at the initial heading panicle rate of about 25% under the conditions of high level of population and growth uniformity of Lu18S.
Is alcohol required for effective pancreatic cyst ablation? The prospective randomized CHARM trial pilot study.

Background and study aims: In this study, we aim to determine the safety and feasibility of an alcohol-free approach to pancreatic cyst ablation using a chemotherapeutic ablation cocktail. Patients and methods: In this prospective, randomized, double-blinded pilot study, 10 patients with known mucinous type pancreatic cysts underwent endoscopic ultrasound (EUS)-guided fine needle aspiration and then lavage with either 80 % ethanol or normal saline. Both groups were then treated with a cocktail of paclitaxel and gemcitabine. Primary outcomes were reduction in cyst volume and rates of complications. Results: At 6 months, patients randomized to the alcohol arm had an 89 % average volume reduction, with a 91 % reduction noted in the alcohol-free arm. Complete ablation was achieved in 67 % of patients in the alcohol-free arm at both 6 and 12 months, whereas the alcohol group recorded complete ablation rates of 50 % and 75 % at 6 and 12 months, respectively. One patient in the alcohol arm developed acute pancreatitis (20 %) with no adverse events in the alcohol-free arm. Conclusions: This study revealed similar ablation rates between the alcohol ablation group and the alcohol-free arm and demonstrates the safety and feasibility of an alcohol-free ablation protocol. This pilot study suggests that alcohol may not be required for effective cyst ablation.
You, your public health department and the next flu pandemic.

Family physicians and public health officials each should recognize, respect and enhance each other's roles at all times, especially in a public health emergency such as an influenza pandemic. If we communicate and collaborate, our communities will benefit.
Management of Stage A Prostate Cancer

Transrectal ultrasonography has defined a new category of stage A disease, namely nonpalpable lesions diagnosed by needle biopsy. How this type relates to classic stage A disease is unclear. Stage A1 carcinoma becomes clinically significant only in a distinct minority of patients, and even in this group, progression does not necessarily mean significant morbidity or death from prostate cancer. An aggressive approach is not justified. In contrast, stage A2 cancer is usually virulent, and aggressive therapy with curative intent is justified in patients of appropriate age and health. Both radical prostatectomy and external irradiation appear to provide long-term survival rates superior to those obtained with observation alone, but nearly 20% of these patients will die of cancer despite therapy. Unfortunately, forecasting the outcome in an individual case is still not possible, and efforts to identify prognostic features must continue. In the meantime, emotional arguments in favor of the treatment of all discovered cancers must be suppressed by an informed and objective understanding of the natural history of nonpalpable prostate cancer and the potential impact of treatment.
Effect of pulse sequence parameter selection on signal strength in positive-contrast MRI markers for MRI-based prostate postimplant assessment.

Purpose: For postimplant dosimetric assessment, computed tomography (CT) is commonly used to identify prostate brachytherapy seeds, at the expense of accurate anatomical contouring. Magnetic resonance imaging (MRI) is superior to CT for anatomical delineation, but identification of the negative-contrast seeds is challenging. Positive-contrast MRI markers were proposed to replace spacers to assist seed localization on MRI images. Visualization of these markers under varying scan parameters was investigated. Methods: To simulate a clinical scenario, a prostate phantom was implanted with 66 markers and 86 seeds, and imaged on a 3.0T MRI scanner using a 3D fast radiofrequency-spoiled gradient recalled echo acquisition with various combinations of scan parameters. Scan parameters, including flip angle, number of excitations, bandwidth, field-of-view, slice thickness, and encoding steps were systematically varied to study their effects on signal, noise, scan time, image resolution, and artifacts. Results: The effects of pulse sequence parameter selection on the marker signal strength and image noise were characterized. The authors also examined the tradeoff between signal-to-noise ratio, scan time, and image artifacts, such as the wraparound artifact, susceptibility artifact, chemical shift artifact, and partial volume averaging artifact. Given reasonable scan time and managable artifacts, the authors recommended scan parameter combinations that can provide robust visualization of the MRI markers. Conclusions: The recommended MRI pulse sequence protocol allows for consistent visualization of the markers to assist seed localization, potentially enabling MRI-only prostate postimplant dosimetry.
A comparison of consequences for correct responses during discrete-trial instruction

Abstract We used an adapted-alternating treatments design to compare the effects of four types of consequences for correct responses on skill acquisition during discrete-trial instruction for four children diagnosed with autism spectrum disorder. Contingent on correct responses, the therapist provided either praise, tangible items, tokens, or no differential consequence. Three of four participants acquired target skills in the fewest number of sessions when correct responses resulted in immediate access to tangible items or tokens exchangeable for tangible items at the end of the session. One participant did not acquire target skills in any condition. We assessed participants’ preferences for different consequences using a concurrent-chains assessment. Three of the four participants demonstrated a preference for conditions associated with immediate or delayed tangible items, and one participant demonstrated a preference for descriptive praise. Findings in the current study generally suggest that immediate or delayed tangible items should be used as consequences for correct responses during discrete-trial instruction.
Analyzing degradation data with a random effects spline regression model

ABSTRACTThis article proposes using a random effects spline regression model to analyze degradation data. Spline regression avoids having to specify a parametric function for the true degradation of an item. A distribution for the spline regression coefficients captures the variation of the true degradation curves from item to item. We illustrate the proposed methodology with a real example using a Bayesian approach. The Bayesian approach allows prediction of degradation of a population over time and estimation of reliability is easy to perform.
Single- versus multiple-item assessment of quality of life in patients with advanced cancer

e20528 Background: The main objective of palliative cancer care is to improve quality of life (QOL). As multiple dimensions impact on the construct of QOL, multi-dimensional instruments are usually used in its measurement. These are time consuming and burdensome for repeated use. Recent authors have suggested that brief single-item global assessments can provide a reliable measure of QOL. We assessed the performance of the Edmonton Symptom Assessment System ‘feeling of well-being’ item (ESAS WB) using the Functional Assessment of Cancer Therapy - General (FACT-G) instrument as a gold standard. Methods: After obtaining IRB approval, we reviewed the data from 213 advanced cancer patients who had participated in six studies from March 2006 to June 2008 and determined the level of association between baseline ESAS WB and FACT-G total score and subscale domains (Physical (Pwb), Social/Family (Swb), Emotional (Ewb), and Functional (Fwb) Well-Being) and also the 9 ESAS symptom intensity scores using Spearman cor...
Delayed Otolith Development Does Not Impair Vestibular Circuit Formation in Zebrafish.

What is the role of normally patterned sensory signaling in development of vestibular circuits? For technical reasons, including the difficulty in depriving animals of vestibular inputs, this has been a challenging question to address. Here we take advantage of a vestibular-deficient zebrafish mutant, rock solo AN66 , in order to examine whether normal sensory input is required for formation of vestibular-driven postural circuitry. We show that the rock solo AN66 mutant is a splice site mutation in the secreted glycoprotein otogelin (otog), which we confirm through both whole genome sequencing and complementation with an otog early termination mutant. Using confocal microscopy, we find that elements of postural circuits are anatomically normal in rock solo AN66 mutants, including hair cells, vestibular ganglion neurons, and vestibulospinal neurons. Surprisingly, the balance and postural deficits that are readily apparent in younger larvae disappear around 2 weeks of age. We demonstrate that this behavioral recovery follows the delayed development of the anterior (utricular) otolith, which appears around 14 days post-fertilization (dpf), compared to 1 dpf in WT. These findings indicate that utricular signaling is not required for normal structural development of the inner ear and vestibular nucleus neurons. Furthermore, despite the otolith’s developmental delay until well after postural behaviors normally appear, downstream circuits can drive righting reflexes within ∼1–2 days of its arrival, indicating that vestibular circuit wiring is not impaired by a delay in patterned activity. The functional recovery of postural behaviors may shed light on why humans with mutations in otog exhibit only subclinical vestibular deficits.
In vivo super-resolution imaging of vasa vasorum in rabbit atherosclerotic plaque model using deconvolution-based localization technique

Angiogenic vasa vasorum (VV) is an important marker for atherosclerotic plaque progression and vulnerability. However, current in vivo imaging of tiny VV near a major vessel is limited. The super-resolution ultrasound imaging (SRI) can be a promising candidate. Microbubbles (MBs) localization technique for common SRI excludes signals from densely distributed MBs, requiring a large number of frames, which makes it impractical for assessing dynamic information. Here, we developed a SRI technique using deconvolution that allows localizing all MBs in a frame and therefore significantly reduces acquisition time, which enables dynamic SRI and evaluated it in vivo rabbit VV detection.
Wavelet Pooling for Convolutional Neural Networks

Convolutional Neural Networks continuously advance the progress of 2D and 3D image and object classification. The steadfast usage of this algorithm requires constant evaluation and upgrading of foundational concepts to maintain progress. Network regularization techniques typically focus on convolutional layer operations, while leaving pooling layer operations without suitable options. We introduce Wavelet Pooling as another alternative to traditional neighborhood pooling. This method decomposes features into a second level decomposition, and discards the first-level subbands to reduce feature dimensions. This method addresses the overfitting problem encountered by max pooling, while reducing features in a more structurally compact manner than pooling via neighborhood regions. Experimental results on four benchmark classification datasets demonstrate our proposed method outperforms or performs comparatively with methods like max, mean, mixed, and stochastic pooling.
Adenovirus Vector Vaccination Impacts NK Cell Rheostat Function following Lymphocytic Choriomeningitis Virus Infection

Natural killer (NK) cells respond rapidly as a first line of defense against infectious pathogens. In addition, NK cells may provide a "rheostat" function and have been shown to reduce the magnitude of antigen-specific T cell responses following infection to avoid immunopathology. However, it remains unknown whether NK cells similarly modulate vaccine-elicited T cell responses following virus challenge. We used the lymphocytic choriomeningitis virus (LCMV) clone 13 infection model to address whether NK cells regulate T cell responses in adenovirus vector-vaccinated mice following challenge. As expected, NK cell depletion in unvaccinated mice resulted in increased virus-specific CD4+ and CD8+ T cell responses and immunopathology following LCMV challenge. In contrast, NK cell depletion had minimal to no impact on antigen-specific T cell responses in mice that were vaccinated with an adenovirus serotype 5 (Ad5)-GP vector prior to LCMV challenge. Moreover, NK cell depletion in vaccinated mice prior to challenge did not result in immunopathology and did not compromise protective efficacy. These data suggest that adenovirus vaccine-elicited T cells may be less sensitive to NK cell rheostat regulation than T cells primed by LCMV infection.IMPORTANCE Recent data have shown that NK cell depletion leads to enhanced virus-elicited T cell responses that can result in severe immunopathology following LCMV infection in mice. In this study, we observed that NK cells exerted minimal to no impact on vaccine-elicited T cells following LCMV challenge, suggesting that adenovirus vaccine-elicited T cells may be less subject to NK cell regulation. These data contribute to our understanding of NK cell regulatory functions and T cell-based vaccines.
Benchmarking building energy efficiency using quantile regression

Abstract We propose a new building energy use benchmarking system to rank buildings via quantile regression. This methodology addresses several leading issues with current benchmarking practices by constructing a data-driven probabilistic model of performance, reducing outlier-effects, determining the varying effect of inputs across the distribution, and creating a theoretical maximum performance-level for each building. Influence plots constructed to examine a variable's effect on the conditional distribution can identify main drivers of energy consumption at each quantile, visually displaying any nonlinear effects on energy consumption. The methodology produces a score for each building based on efficiency, compares buildings with their constructed distribution of scores, and extracts the strongest indicators of energy use. To illustrate the model's effectiveness, we analyzed electricity consumption from a dataset containing ∼1000 buildings and found that cooling degree days and the presence of gyms, spas, and elevators were large drivers of energy use. Additionally, the number of employees per unit area had a larger effect on total energy consumption for poor performing buildings as compared to top performers. This more robust and standardized benchmarking model may improve resource allocation for energy-efficient programs, encourage competition between buildings, put pressure on poor performers, and provide insight into building energy drivers.
Use of alcohol biomarkers to identify alcohol misuse in organ donors

Abstract Phosphatidylethanol is a direct alcohol biomarker for identifying alcohol misuse. It carries several advantages over other alcohol biomarkers, including a detection half-life of several weeks and little confounding by patient characteristics or organ dysfunction. The aim of this study is to derive an optimal phosphatidylethanol cut point to identify organ donors with alcohol misuse, and to assess the impact of alcohol misuse on organ allocation. Discrimination of phosphatidylethanol was evaluated using the area under the ROC curve from a mixed effects logistic regression model. Phosphatidylethanol had an area under the ROC curve of 0.89 (95% CI 0.80–0.98). A phosphatidylethanol cut point of ≥84 ng/mL provided optimal discrimination for the identification of alcohol misuse with a sensitivity of 75% (95% CI 52.9%–89.4%) and a specificity of 97% (95% CI 91%–99%), a positive predictive value of 82% (95% CI 59%–94%), and a negative predictive value of 95% (95% CI 89%–98%). In deceased organ donors who had been critically ill, phosphatidylethanol had good test characteristics to discriminate alcohol misuse. Other alcohol biomarkers performed poorly in deceased organ donors. Liver allocation was decreased in donors with alcohol misuse by proxy history, but not in those with phosphatidylethanol >84 ng/mL, revealing possible information bias in liver allocation.
AN ENVIRONMENTAL CHARACTERIZATION OF CHESAPEAKE BAY AND A FRAMEWORK FOR ACTION

Abstract: The scientific findings and management implications of the Environmental Protection Agency's Chesapeake Bay Program are reviewed. They suggest that the Bay has dramatically changed in the last century and this change has accelerated in the last thirty years. Many of the valued living resources of the Bay, such as the submerged aquatic vegetation, shad, striped bass, and oysters are declining. Paralleling this decline, there has been an increase in nutrients and toxic compounds in the Bay. It appears that the Bay acts as a “filter”, essentially trapping and recycling pollutants. Thus, to restore the Bay's ecological integrity we must reduce pollutant discharge to the Bay.
The Anxiety of the Unknown—Choice, Risk, Responsibility

Within the last several years we have seen a plethora of research findings and demographic data describing current social changes, especially as they affect women. The changes that have received greatest attention include the lengthening life-span, the widespread movement of women into the labor force, the rising divorce rate, and steadily growing inflation. These massive changes in our social environment have undoubtedly affected women’s views of themselves and their life satisfaction. Yet explicit work on exploring the implications of these widely discussed social shifts on the psychological experiences of women and on the issues they bring into therapy has not kept pace. Several recent reviews (Maracek and Johnson, 1980; McMahon, 1980) focus on the process of therapy—the form, not the content. Other overviews deal with the psychiatric aspects of particular and frequent presenting problems, such as abortion, sexual dysfunctions, eating disorders (see, for example, Notman and Nadelson, 1978). These efforts, however, rarely address the impact that the sweeping changes in the social and political definitions of women’s roles have had on the issues with which adult women are grappling, especially in their middle years.
The Nature of Emotions: Clinical Implications

Regardless of how much or how little education we have on various subjects, there is one topic on which each of us is the world’s leading expert, and that subject is ourselves. And just as we know a great deal about the public and private sides of ourselves, we know a great deal about that part of ourselves called emotions. We all believe that we know our own emotions and can recognize emotions in other people. Yet, despite this belief, experts in this field seem to have a great deal of difficulty coming to any agreement about what emotions really are. But one thing that everyone does agree on is that emotions are the source of our greatest pleasures and our greatest pains. And when we have problems in life we often refer to them as emotional problems.
The Damaging Effects of Light on the Eye and Implications for Understanding Changes in Vision across the Life Span

Damage to the lens and retina by photochemical processes upon absorption of light, especially ultraviolet radiation (UVR), has been well documented through laboratory experiments involving short, intense exposures. Throughout life, chronic exposure to less intense light produces the same photochemical effects on molecules contained within cells of the lens and retina, and this absorption may lead to cumulative deterioration in function. Such cumulative damage may explain why lenticular senescence and loss of receptor sensitivity are continuous throughout life. Support for this interpretation was found in patients who had lower short-wave cone sensitivity when chronically exposed to higher, ambient UVR following surgical removal of a cataractous lens and implantation of a prosthetic lens that did not absorb most of the incident UVR.
Managing Data in R

In this Chapter, we will discuss strategies to import data and export results. Also, we are going to learn the basic tricks we need to know about processing different types of data. Specifically, we will illustrate common R data structures and strategies for loading (ingesting) and saving (regurgitating) data. In addition, we will (1) present some basic statistics, e.g., for measuring central tendency (mean, median, mode) or dispersion (variance, quartiles, range); (2) explore simple plots; (3) demonstrate the uniform and normal distributions; (4) contrast numerical and categorical types of variables; (5) present strategies for handling incomplete (missing) data; and (6) show the need for cohort-rebalancing when comparing imbalanced groups of subjects, cases or units.
Vagus Nerve Stimulation and the Cardiovascular System

The vagus nerve plays an important role in maintaining physiological homeostasis, which includes reflex pathways that regulate cardiac function. The link between vagus nerve activity and the high-frequency component of heart rate variability (HRV) has been well established, correlating with vagal tone. Recently, vagus nerve stimulation (VNS) has been investigated as a therapeutic for a multitude of diseases, such as treatment-resistant epilepsy, rheumatoid arthritis, Crohn's disease, and asthma. Because of the vagus nerve's innervation of the heart, VNS has been identified as a potential therapy for cardiovascular disorders, such as cardiac arrest, acute myocardial infarction, and stroke. Here, we review the current state of preclinical and clinical studies, as well as the potential application of VNS in relation to the cardiovascular system.
Cannabis in homes with children: use and storage practices in a legalised state.

Our objective was to examine the prevalence of cannabis in homes with children and temporal trends in storage practices among caregivers. Caregivers of children ages 1–14 in Colorado, identified through a representative population-based telephone survey, participated in a repeated telephone survey from 2014 to 2017. Representing 79 805 households in Colorado with children, 8.6% (95% CI 7.3 to 10.0) of caregivers reported cannabis in the home. From 2014 to 2017, the prevalence of reporting cannabis in the home increased significantly from 6.9% to 11.2% (p=0.02). Among caregivers who reported cannabis in the home, 91.4% reported storage locations inaccessible to children, such as ‘out of reach’. Fewer, 67.0%, caregivers reported storage in a locked container, such as a cabinet, drawer or safe. In a state with recreational cannabis, an increasing number of children live in homes where cannabis is present. Public health practitioners should promote messages to caregivers about safe cannabis storage practices.
Purple bacteria photo-bioelectrochemistry: enthralling challenges and opportunities

Purple non-sulfur bacteria are anoxygenic photosynthetic microorganisms characterized by an extremely versatile metabolism, allowing them to grow in a broad variety of conditions as well as in the presence of different contaminants. This characteristic motivates the interest in their employment in photo-bioelectrochemical systems applicable in environments with dynamic physico-chemical properties. While the photochemistry of purple bacteria has been intensively studied, their photo-bioelectrochemistry and extracellular electron transfer process with an electrode surface remain largely unexplored. Herein, the process of harvesting electrons from intact purple bacteria is reviewed, and the perspective of enthralling future research possibilities is presented, placing emphasis on the major challenges in the photo-bioelectrochemistry of purple bacteria.