Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase II Dose Escalation Study of Caspofungin for Invasive Aspergillosis

ABSTRACT Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade ≥4 in 2 of 8 patients or ≥3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics were linear across the investigated dosages and followed a two-compartment model, with weight as the covariate on clearance and sex as the covariate on central volume of distribution. Simulated peak plasma concentrations at steady state ranged from 14.2 to 40.6 mg/liter (28%), trough concentrations from 4.1 to 11.8 mg/liter (58%), and area under the concentration-time curve from 175 to 500 mg/liter/h (32%) (geometric mean, geometric coefficient of variation). Treatment was well tolerated without dose-limiting toxicity. The rate of complete or partial responses was 54.3%, and the overall mortality at 12-week follow-up was 28.3%. In first-line treatment of invasive aspergillosis, daily doses of up to 200 mg caspofungin were well tolerated and the maximum tolerated dose was not reached. Pharmacokinetics was linear. Response rates were similar to those previously reported for voriconazole and liposomal amphotericin.
Preliminary Results Towards Reinforcement Learning with Mixed-Signal Memristive Neuromorphic Circuits

As the end of Moore's law seems to be imminent, emerging technologies that enable high performance neuromorphic hardware systems are attracting increasing attention. A very promising approach is to utilize memristors, programmable nonvolatile memory devices, as synaptic weights in neuromorphic circuits. One of the challenges for memristive hardware with integrated learning capabilities is prohibitively larger number of write cycles that might be required during learning process. In this work we propose a memristive neuromorphic hardware implementation for reinforcement learning based on temporal difference actor-critic algorithm. As a case study, we consider a task of balancing an inverted pendulum, a classical problem in both reinforcement learning and control theory. We introduce training techniques that significantly reduce the number of weight updates and are suitable for efficient in-situ learning hardware implementations. We believe that this study shows the promise of using memristor-based hardware neural networks for handling complex tasks through in-situ reinforcement learning.
Uncertainty in soil carbon accounting due to unrecognized soil erosion

The movement of soil organic carbon (SOC) during erosion and deposition events represents a major perturbation to the terrestrial carbon cycle. Despite the recognized impact soil redistribution can have on the carbon cycle, few major carbon accounting models currently allow for soil mass flux. Here, we modified a commonly used SOC model to include a soil redistribution term and then applied it to scenarios which explore the implications of unrecognized erosion and deposition for SOC accounting. We show that models that assume a static landscape may be calibrated incorrectly as erosion of SOC is hidden within the decay constants. This implicit inclusion of erosion then limits the predictive capacity of these models when applied to sites with different soil redistribution histories. Decay constants were found to be 15–50% slower when an erosion rate of 15 t soil ha−1 yr−1 was explicitly included in the SOC model calibration. Static models cannot account for SOC change resulting from agricultural management practices focused on reducing erosion rates. Without accounting for soil redistribution, a soil sampling scheme which uses a fixed depth to support model development can create large errors in actual and relative changes in SOC stocks. When modest levels of erosion were ignored, the combined uncertainty in carbon sequestration rates was 0.3–1.0 t CO2 ha−1 yr−1. This range is similar to expected sequestration rates for many management options aimed at increasing SOC levels. It is evident from these analyses that explicit recognition of soil redistribution is critical to the success of a carbon monitoring or trading scheme which seeks to credit agricultural activities.
Disparities and Despair: Changes in Regional Income Distributions in New Zealand 1981-96

Among developed economies, New Zealand is one of the countries that experienced a large increase in personal income inequality since the mid 1980s. This paper focuses on income inequality at the regional level. Smith (2000) and Karagedikli et al. (2000) found that the variation in mean income across regions also grew sharply, but that there was convergence among regions in measures of intra-regional income inequality. This paper further investigates changes in inter and intra-regional income dispersion. Excluding the metropolitan regions Auckland and Wellington, real mean incomes converged across the regions (and declined for males). Regional Gini coefficients were higher in 1996 than in 1981 for males, but lower for females. However, women experienced a higher increase in inequality during the second half of the economic reform decade (1986-1996), while men experienced a higher increase during the first half. Regional labour market characteristics play an important role in explaining the regional income distributions. We also focus on the interaction between income inequality and economic growth at the regional level.
Shear-Modulus Estimation by Application of Spatially-Modulated Impulsive Acoustic Radiation Force

We present a method for determining the shear modulus of an elastic material wherein a spatially-modulated acoustic radiation force is used to generate a disturbance of known spatial frequency (wavelength). The propagation of this initial displacement as a shear wave is measured using ultrasound tracking methods and the temporal frequency of the shear wave is estimated. Given the known wavelength and material density and the measured estimate of temporal frequency, the shear modulus at the point of excitation may be calculated easily. Using this method, the shear moduli of two gelatin phantoms was estimated to be 1.4 and 5.8 kPa, in good agreement with 1.5 and 5.6 kPa values determined though quasistatic material testing.
Expression of 5'-nucleotidase and alkaline phosphatase in human aqueous drainage channels.

PURPOSE Lymphatic vessels and blood vessels can be distinguished histochemically by their expression of 5'-nucleotidase and alkaline phosphatase. The aim of this study was to compare the expression of these enzymes in human aqueous drainage channels with that seen in lymphatics and blood vessels. METHODS Histological sections from the angular regions of human eyes were prepared both by enzyme histochemical and immunohistochemical methods to analyse 5'-nucleotidase and alkaline phosphatase expression. In some of these eyes, Indian ink-stained gelatin was injected into Schlemm's canal and the suprachoroidal space to facilitate the identification of aqueous drainage routes. RESULTS There was no expression of 5'-nucleotidase in the endothelium of aqueous drainage channels. Ocular blood vessels were characterized by strong expression of alkaline phosphatase, whereas the cellular lining of Schlemm's canal, the collector channels, the aqueous veins and a scleral channel from the suprachoroidal space showed significantly weaker expression or no expression at all. CONCLUSION The study failed to show a histochemical similarity between lymphatics and human aqueous drainage channels, as no expression of 5'-nucleotidase could be found in any part of the aqueous outflow pathway. The endothelium of aqueous drainage channels also differed from normal blood vessels by a much weaker expression of alkaline phosphatase. This makes a histochemical distinction between aqueous veins and scleral veins possible.
Comparison of German labour costs with other European countries: only a marginal increase Analysis of current Eurostat statistics for 2008

Labour costs in Germany rose more sharply in 2008 than in previous years, but the increase was once again less pronounced than in virtually all other European countries. This brought about a further strenghtening of Germany’s international competitiveness and contributed towards the country’s current account surplus. Global trade imbalances contributed significantly towards causing the current crisis and have only declined as it has run its course. However this marginal overall increase in German labour costs conceals varying levels of costs in the different economic sectors. At EUR 32.501 per hour in the manufacturing sector, Germany occupies a mid-way position in the top 50 per cent of countries in the eurozone, while private services sector labour costs correspond to the eurozone average of EUR 26 per hour. German industry is improving its competitive position considerably, thanks to favourable intermediate inputs of the services sector due to comparatively low labour costs of this sector’s. In the current crisis, which is characterised by a huge decline in foreign demand, the disadvantages of an export oriented economic model and the limits of an economic policy focussed solely on improved international competitiveness are now becoming clear. If the intention is to correct this in the future and to try to achieve a balanced growth of exports and domestic demand, then higher wage growth is also required.
Phase-based SSVEPs for real-time control of a motorised bed

Brain-computer interface (BCI) systems have emerged as an augmentative technology that can provide a promising solution for individuals with motor dysfunctions and for the elderly who are experiencing muscle weakness. Steady-state visually evoked potentials (SSVEPs) are widely adopted in BCI systems due to their high speed and accuracy when compared to other BCI paradigms. In this paper, we apply combined magnitude and phase features for class discrimination in a real-time SSVEP-based BCI platform. In the proposed real-time system users gain control of a motorised bed system with seven motion commands and an idle state. Experimental results amongst eight participants demonstrate that the proposed real-time BCI system can successfully discriminate between different SSVEP signals achieving high information transfer rates (ITR) of 82.73 bits/min. The attractive features of the proposed system include noninvasive recording, simple electrode configuration, excellent BCI response and minimal training requirements.
Adalimumab: efficacy and safety in psoriasis and rheumatoid arthritis

ABSTRACT: The next generation of targeted biologic therapies for psoriasis will either be directed against new protein targets or improve on the efficacy, safety, or convenience of medications available for an already validated area in the immune response. Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor‐α, a central cytokine in the immune response in psoriasis that has already been shown to be an effective target for therapy. This medication is approved by the US Food and Drug Administration (USFDA) for the treatment of rheumatoid arthritis. Early phrase II studies with adalimumab have shown excellent efficacy for psoriasis with either weekly or every other week subcutaneous injection. Moreover, the safety and tolerability of adalimumab in large clinical studies of rheumatoid arthritis have shown good results. Thus, adalimumab shows significant promise for the therapy of psoriasis in the future.
Calculation of the risk of ovarian cancer from serial CA-125 values for preclinical detection in postmenopausal women.

PURPOSE Previous studies of CA-125 levels from screening trials for ovarian cancer have indicated that serial CA-125 levels may identify cases better than a fixed CA-125 cutoff. We conducted a study to assess the screening performance of the risk of ovarian cancer calculation based on serial CA-125 levels from prospectively collected serum samples compared with a fixed CA-125 cutoff. PATIENTS AND METHODS The calculation was applied to data from a prospective trial of screening for ovarian cancer involving 22,000 postmenopausal women older than 45 years. The analysis was performed using 33,621 CA-125 results from 9,233 women for whom two or more serial samples were available. All serum samples from the patients with ovarian cancer were obtained before clinical detection. Sensitivity and specificity levels for preclinical detection of index cancers were calculated for various cutoffs for the risk and a single CA-125 measurement, and receiver operator curves were constructed. RESULTS The risk calculation significantly improved the area under the curve from 84% to 93% compared with a fixed cutoff for CA-125 (P =.01). For a target specificity of 98%, the risk achieved a sensitivity of 86% for preclinical detection of ovarian cancer, whereas CA-125 achieved a sensitivity of 62%. The estimates of performance are unbiased, because the risk calculation was derived independent of the data from this trial. CONCLUSION These results provide the first evidence that preclinical detection of ovarian cancer using serial CA-125 levels interpreted with the risk calculation significantly improves screening performance compared with a fixed cutoff for CA-125. The results justify the incorporation of the risk calculation in a prospective, randomized, controlled trial.
Management of oral leukoplakia by laser surgery: relation between recurrence and malignant transformation and clinicopathological features.

OBJECTIVE The aim of the present study was to assess the clinical usefulness of laser surgery for oral leukoplakia. BACKGROUND Recurrence and/or malignanT transformation of oral leukoplakia have occasionally been observed following laser surgery. It is reported that the rate of recurrence was 7.7-38.1%, while malignant transformation was 2.6-9%. MATERIALS AND METHODS A total of 154 oral leukoplakias from 116 patients were treated in our department. Comparisons with the rate of recurrence, malignant transformation and clinical futures, epithelial dysplasia, location, and treatment procedure were examined. To evaluate recurrence and malignant transformation, the cases were restricted to those with a minimum follow-up of 6 months. RESULTS A total of 97 lesions fulfilled this criterion. The rate of recurrence had no association with the location or the epithelial dysplasia, although it differed with the treatment procedure. The rate of recurrence in laser surgery was approximately 29%. Malignant transformation was observed in four of 97 lesions. They were observed in 13.6% of tongue cases and 1.8% of gingival cases. Three of four lesions were treated with excision surgery, and the remaining one treated with laser vaporization. Only 1.2% malignant transformation in laser surgery was revealed. CONCLUSION Laser excision is suitable for leukoplakia cases on non-keratinized epithelia (i.e., the tongue and buccal mucosa), while laser vaporization is suitable for the gingival cases. Management of oral leukoplakia prevents not only recurrence and malignant transformation, but also postoperative dysfunction. We believe that laser surgery is an excellent procedure.
Delayed Termination Following Pacing Induced Shifts from Monomorphic to Polymorphic Ventricular Tachycardia: Implications for Antitachycardia Pacing

Interactions between paced wavefronts and monomorphic ventricular tachycardia (VT) dictate antitachycardia pacing outcomes. Monomorphic VTs were initiated in isolated rabbit hearts (n=6) that were endocardially cryoablated to limit viable tissue to the visible epicardium and the ablated apex served as an anatomic anchor. Preparations were optically mapped during single and dual site pacing at 50% to 90% of VT cycle length with 8 pulses per trial. Of these trials, responses to the 48 single site pulses and to the 172 dual site pulses that captured tissue were analyzed. Overall, we found most pulses reset the VT, and a small number of pulses that abruptly terminated the VT. Of particular interest, we found 12 pulses that shifted the anatomically anchored VT to functionally reentrant wavefronts, and thereby induced polymorphic VT. Delayed termination was observed following 6 of these instances, and the underlying non-sustained polymorphic VT's presented temporal characteristics similar to those presented by delayed termination after antitachycardia pacing in ICD patients
Emerging role of nanog in tumorigenesis and cancer stem cells

Nanog is a transcription factor that is well‐established as a key regulator of embryonic stem cell (ESC) maintenance. Recent evidence demonstrates that Nanog is dysregulated and intimately involved in promoting tumorigenesis in part through regulation of the cancer stem cell (CSC) population. Elevated Nanog is associated with poorer outcome in numerous epithelial malignancies. Nanog is enriched in CSCs and ablation of Nanog is sufficient to reduce the CSC pool. Nanog has also been implicated to promote chemoresistance and epithelial‐mesenchymal transition (EMT). Insight into the Nanog signaling cascade, upstream regulators and downstream effectors, is beginning to emerge but remains to be fully elucidated. This review highlights the current literature on the emerging role of Nanog in tumorigenesis and CSCs.
Postprandial Oxidative Stress

Abstract Consumption of a meal containing oxidized and oxidizable lipids gives rise to an increased plasma concentration of lipid hydroperoxides, detectable by a sensitive chemiluminescence procedure. This is associated with increased susceptibility of LDL to oxidation, apparently due a structural perturbation at the particle surface brought about by lipid oxidation products. The postprandial modification of LDL is at least partially accounted for by an increase of LDL, a subfraction containing lipid oxidation products where apoproteinB-100 (apoB-100) is denatured. Consuming the meal with a suitable source of antioxidants, such as those found in red wine, minimizes this postprandial oxidative stress. The inhibition of peroxidation of lipids present in the meal during digestion is a possible mechanism for the observed protection of LDL. The in vivo oxidatively modified LDL has numerous features that correspond to the atherogenic minimally modified LDL produced in vitro. These modified particles could account for a relevant link between nutrition and early biological processes that foster the development of atherosclerosis.
Universal predictability of mobility patterns in cities

Despite the long history of modelling human mobility, we continue to lack a highly accurate approach with low data requirements for predicting mobility patterns in cities. Here, we present a population-weighted opportunities model without any adjustable parameters to capture the underlying driving force accounting for human mobility patterns at the city scale. We use various mobility data collected from a number of cities with different characteristics to demonstrate the predictive power of our model. We find that insofar as the spatial distribution of population is available, our model offers universal prediction of mobility patterns in good agreement with real observations, including distance distribution, destination travel constraints and flux. By contrast, the models that succeed in modelling mobility patterns in countries are not applicable in cities, which suggests that there is a diversity of human mobility at different spatial scales. Our model has potential applications in many fields relevant to mobility behaviour in cities, without relying on previous mobility measurements.
UAV-Enabled Cooperative Jamming for Improving Secrecy of Ground Wiretap Channel

This letter proposes a novel unmanned aerial vehicle (UAV)-enabled mobile jamming scheme to improve the secrecy rate of ground wiretap channel. Specifically, a UAV is employed to transmit jamming signals to combat against eavesdropping. Such a mobile jamming scheme is particularly appealing since the UAV-enabled jammer can fly close to the eavesdropper and opportunistically jam it by leveraging the UAV’s mobility. We aim to maximize the average secrecy rate by jointly optimizing the UAV’s trajectory and jamming power over a given flight period. To make the problem more tractable, we drive a closed-form lower bound for the achievable secrecy rate, based on which the UAV’s trajectory and transmit power are optimized alternately by an efficient iterative algorithm applying the block coordinate descent and successive convex optimization techniques. Simulation results demonstrate that the proposed joint design can significantly enhance the secrecy rate of the considered wiretap system as compared to benchmark schemes.
[Psychological sequelae of accidents. Symptoms are seldom recognized].

OBJECTIVE To present the problems possibly associated with psychological sequelae of accidents and make proposals for appropriate therapy. MAJOR POINTS Accidents experienced by the victim as threatening, whether associated with immediate physical or mental impairment or not, often trigger multiple psychological reactions, and may lead to psychological disorders of either a temporary or a permanent nature. Accident-related psychological symptoms or problems are almost regularly overlooked during the acute medical treatment phase. Not until psychological symptoms become evident are psycho-diagnostic and therapeutic measures undertaken. If such psychological problems, which may often manifest in physical symptoms or behavioral changes, are not recognized early on and vigorously treated, recovery of the patient may be appreciably impaired. CONCLUSIONS The care-providing physician should expect psychological accident sequelae and give consideration to them in his overall treatment plan.
Persistence of Escherichia coli O157[ratio ]H7 in dairy cattle and the dairy farm environment

The persistence of Escherichia coli O157[ratio ]H7 in cattle and the farm environment was investigated on eight Ontario dairy farms positive for E. coli O157[ratio ]H7 in a longitudinal study commenced one year previously. Faecal samples from cows, calves, humans, cats, rodents, wild birds, a composite fly sample and numerous composite and individual environmental samples were cultured and tested for verotoxin-producing E. coli (VTEC). VTEC isolates were serotyped and E. coli O157[ratio ]H7 isolates were phage typed. E. coli O157[ratio ]H7 phage type 34 was isolated from one calf on each of two farms. The same phage type had been isolated on one of these farms 12 months earlier. Most E. coli O157[ratio ]H7-positive animals and farms became culture-negative within 2 and 3 months, respectively. E. coli O157[ratio ]H7 was not isolated from any environmental samples, although evidence of VTEC was found in composite samples from calf feeders (19·1%), calf barn surfaces (18%), cow feeders (14·9%), flies (12·5%), cow barn surfaces (11·3%), and individual milk filters (12·5%). VTEC belonging to 21 non-O157 serotypes were isolated from 24 cows (8·2%), 21 calves (18·3%), 2 cow feeder samples (3·0%), and 1 calf feeder sample (4·8%). Shedding of E. coli O157[ratio ]H7 by infected dairy cattle appears to be transient and persistence of E. coli O157[ratio ]H7 was not demonstrated from the farm environment sites tested.