Miracle-dz/UniFAR-FTUs huggingface dataset:
What is the risk‐benefit ratio of long‐term antipsychotic treatment in people with schizophrenia?

The long‐term benefit‐to‐risk ratio of sustained antipsychotic treatment for schizophrenia has recently been questioned. In this paper, we critically examine the literature on the long‐term efficacy and effectiveness of this treatment. We also review the evidence on the undesired effects, the impact on physical morbidity and mortality, as well as the neurobiological correlates of chronic exposure to antipsychotics. Finally, we summarize factors that affect the risk‐benefit ratio. There is consistent evidence supporting the efficacy of antipsychotics in the short term and mid term following stabilization of acute psychotic symptoms. There is insufficient evidence supporting the notion that this effect changes in the long term. Most, but not all, of the long‐term cohort studies find a decrease in efficacy during chronic treatment with antipsychotics. However, these results are inconclusive, given the extensive risk of bias, including increasing non‐adherence. On the other hand, long‐term studies based on national registries, which have lower risk of bias, find an advantage in terms of effectiveness during sustained antipsychotic treatment. Sustained antipsychotic treatment has been also consistently associated with lower mortality in people with schizophrenia compared to no antipsychotic treatment. Nevertheless, chronic antipsychotic use is associated with metabolic disturbance and tardive dyskinesia. The latter is the clearest undesired clinical consequence of brain functioning as a potential result of chronic antipsychotic exposure, likely from dopaminergic hypersensitivity, without otherwise clear evidence of other irreversible neurobiological changes. Adjunctive psychosocial interventions seem critical for achieving recovery. However, overall, the current literature does not support the safe reduction of antipsychotic dosages by 50% or more in stabilized individuals receiving adjunctive psychosocial interventions. In conclusion, the critical appraisal of the literature indicates that, although chronic antipsychotic use can be associated with undesirable neurologic and metabolic side effects, the evidence supporting its long‐term efficacy and effectiveness, including impact on life expectancy, outweighs the evidence against this practice, overall indicating a favorable benefit‐to‐risk ratio. However, the finding that a minority of individuals diagnosed initially with schizophrenia appear to be relapse free for long periods, despite absence of sustained antipsychotic treatment, calls for further research on patient‐level predictors of positive outcomes in people with an initial psychotic presentation.
LEARNING, ADAPTATION, AND CLIMATE UNCERTAINTY: EVIDENCE FROM INDIAN AGRICULTURE

The profitability of many agricultural decisions depends on farmers’ predictions about the weather. Climate change implies (possibly unknown) changes in the weather distribution. I study how farmers form predictions about a weather-dependent decision, the planting time, using rainfall signals. To capture the potential uncertainty caused by climate change, I develop an empirical framework that estimates, and finds support for, a general robust learning model in which farmers believe that the rainfall signals are drawn from a set of rainfall distributions. This indicates that farmers respond to greater (Knightian) uncertainty by modifying their predictions to be robust to such uncertainty. † MIT Sloan School of Management, NBER, BREAD and JPAL. kala@mit.edu, namratakala.com Date: December 2019. I am grateful to Michael Boozer for his invaluable guidance on this project. I would like to thank Dean Karlan, Robert Mendelsohn, Tavneet Suri, and Chris Udry for their guidance and support, and Achyuta Adhvaryu, Abhijit Banerjee, Prashant Bharadwaj, Gharad Bryan, Christopher Costello, Rahul Deb, Eric Edmonds, Jose-Antonio Espin-Sanchez, James Fenske, Xavier Gine, Daniel Keniston, Dominic Leggett, Robert McMillan, Anant Nyshadham, Rohini Pande, Debraj Ray, and seminar participants at Arizona State University, Boston College, Boston University, the Harris School at the University of Chicago, NBER Summer Institute Development meeting, Northeast Workshop on Energy Policy and Environmental Economics at Dartmouth, Pennsylvania State University, Rice University, Stanford Graduate School of Business, Stanford Environmental and Energy Policy Analysis Center Research Workshop, Yale University, University of Pennsylvania, University of Rochester, University of San Diego, and University of Toronto for helpful comments. All remaining errors are my own. 1 “The real challenge of dealing effectively with climate change is recognizing the value of wise and timely decisions in a setting where complete knowledge is impossible” Intergovernmental Panel for Climate Change (IPCC), 2014
Adsorption of carbon adatoms to graphene and its nanoribbons

This paper investigates the adsorption of carbon adatoms on graphene and its nanoribbons using first-principles plane wave calculations within density functional theory. The stability at high carbon adatom coverage, migration, and cluster formation of carbon atoms are analyzed. Carbon adatoms give rise to important changes in electronic and magnetic properties even at low coverage. While bare graphene is nonmagnetic semimetal, it is metallized and acquires magnetic moment upon coverage of carbon adatoms. Calculated magnetic moments vary depending on the coverage of adatoms even for large adatom-adatom distances. Electronic and magnetic properties of hydrogen passivated armchair and zigzag nanoribbons show strong dependence on the adsorption site. We also predict a new type of carbon impurity defect in graphene, which has a small formation energy. Interactions between distant carbon adatoms imply a long ranged interaction.
Usage , Retention , and Abandonment of Agile Practices : A Reflection on Agile Maturity Models

Background: A number of Agile maturity models (AMMs) have been proposed to guide software organizations in their adoption of Agile practices. Typically the AMMs suggest that higher maturity levels are reached by gradually adding more practices. However, recent research shows that certain Agile practices, like test-driven development and continuous integration are decreasing in their adoption or being abandoned. Little is known on the rationales for abandoning Agile practices. Aim: We aim to identify which Agile practices are abandoned in industry, as well as the reasons for abandoning them. Method: We conducted a web survey and interviews with 11 industry practitioners with experience in Agile adoption to investigate why Agile practices are abandoned. Results: Of the 17 Agile practices that were included in the survey, all have been abandoned at some point. Nevertheless, respondents who retained all practices as well as those who abandoned one or more practices, perceived their overall adoption of Agile practices as successful. Conclusion: Some practices might need to be abandoned to sustain the overall benefits of Agile processes. This indicates that introducing Agile practices gradually in a certain sequence, as the AMMs suggest, may not always be suitable in different contexts.
Inhibition of dehydrogenase activity in bacterial isolates from palm wine by extracts of Vernonia amygdalina.

Inhibition of dehydrogenase activity of bacterial isolates from palm wine by leaf extracts of Vernonia amygdalina was investigated. The cultures were exposed to extract concentrations of 0-2500 μg/ml in a nutrient broth-glucose-TTC medium. The responses of the bacterial strains varied with extract concentration. In all the isolates, dehydrogenase activities were progressively inhibited with increasing concentration of extract. The IC50 ranges from 83.27 ± 4.9 to 736.82 ± 13.6 μg/ml. Total inhibitory concentrations for E. coli, Lactobacillus and Streptococcus species were 1984.93 ± 16.5, 2102.82 ± 22.8 and 2476.79 ± 27.7 μg/ml respectively. The total inhibitory concentrations of the remaining isolates ( Staphylococcus, Micrococcus and Bacillus species) were beyond the extract concentrations used. The findings may be of clinical relevance and further substantiates the traditional use of extracts of Vernonia amygdalina to control microbial load and foaming in palm wine. © 2010 International Formulae Group. All rights reserved. Keywords: Vernonia amygdalina , dehydrogenase activity, palm wine, Elaeis guineensis Raphia hookeri, Raphia vinetera.
Do changes in circulating biomarkers track with each other and with functional changes in older adults?

BACKGROUND It is unclear if changes in proposed circulating biomarkers of aging are strongly correlated to each other or functional change. We tested if biomarker changes track with each other and with functional measures over 9 years in older adults. METHODS Dehydroepiandrosterone sulfate (DHEAS), adiponectin, insulin-like growth factor 1 (IGF-1), IGF binding proteins 1 (IGFBP-1) and 3 (IGFBP-3), interleukin-6 (IL-6), cholesterol, and function (gait speed, grip strength, Modified Mini Mental Status Exam [3MSE] and Digit Symbol Substitution Test [DSST] scores) were measured in 1996-1997 and 2005-2006 in the Cardiovascular Health Study All Stars study (N = 901, mean [standard deviation, SD] age 85.3 [3.6] years in 2005-2006). Adjusted Pearson correlations illustrated if biomarkers tracked together. Multivariable linear regression demonstrated if biomarker changes tracked with functional changes. RESULTS Correlations among biomarker changes were mostly <0.2. In models with each biomarker entered separately, a 1-SD increase biomarker change was associated with change in function as follows: grip strength (DHEAS β = 0.61kg, p = .001; IL-6 β = -0.46kg, p = .012; cholesterol men β = 0.79kg, p = .016); gait speed (DHEAS β = 0.02 meters per second, p = .039; IL-6 β = -0.018 meters per second, p = .049); and DSST score (DHEAS women β = 1.46, p = .004; IL-6 β = -0.83, p = .027). When biomarkers were entered in the same model, significant associations remaining were as follows: grip strength (DHEAS β = 0.54kg, p = .005; IL-6 β = -0.43kg, p = .022); 3MSE score (IGF-1 β = 0.96, p = .04; IGFBP-3 β = -1.07, p = .024); and DSST score (DHEAS women β = 1.27, p = .012; IL-6 β = -0.80, p = .04). CONCLUSION Changes in biomarkers were poorly correlated, supporting a model of stochastic, independent change across systems. DHEAS and IL-6 tracked most closely with function, illustrating that changes in inflammation and sex steroids may play dominant roles in changes of these functional outcomes.
Learning Neural Random Fields with Inclusive Auxiliary Generators

Neural random fields (NRFs), which are defined by using neural networks to implement potential functions in undirected models (sometimes known as energy-based models), provide an interesting family of model spaces for machine learning, besides various directed models such as generative adversarial networks (GANs). In this paper we propose a new approach, the inclusive-NRF approach, to learning NRFs for continuous data (e.g. images), by developing inclusive-divergence minimized auxiliary generators and stochastic gradient sampling. As demonstrations of how the new approach can be flexibly and effectively used, specific inclusive-NRF models are developed and thoroughly evaluated for a number of tasks - unsupervised/supervised image generation, semi-supervised classification and anomaly detection. The proposed models consistently achieve strong experimental results in all these tasks compared to state-of-the-art methods. Remarkably, in addition to superior sample generation, one fundamental additional benefit of our inclusive-NRF approach is that, unlike GANs, it directly provides (unnormalized) density estimate for sample evaluation. With these contributions and results, this paper significantly advances the learning and applications of undirected models to a new level, both theoretically and empirically, which have never been obtained before.
Seasonal variability in stable isotopes of estuarine consumers under different freshwater flow regimes

Freshwater inflow from riverine sources is essential for estuarine productivity. How- ever, human alterations to freshwater flow have resulted in modifications to the seasonal complex- ities of estuarine communities. To quantify changes in energy transfer at the trophic guild and consumer levels that result from anthropogenic-altered flow, we evaluated seasonal trends over a 1 yr period in stable isotopes of carbon (δ 13 C), nitrogen (δ 15 N) and sulfur (δ 34 S) in nekton species sampled from 2 subtropical tidal rivers, one that is relatively natural and one that experiences reg- ulated flow discharges that result in autumnal high-flow events. Primary and secondary con- sumers in the flow-altered estuary exhibited a significant depletion in 13 C and enrichment in 15 N (~2‰ in both isotopes respectively) with the onset of the wet season, while the stable isotope val- ues of high trophic level species (i.e. ≥ tertiary consumers) remained relatively consistent, trends were not apparent in the natural estuary. These isotopic trends were evident in both benthic and pelagic consumers, suggesting a food web-wide influence of altered flow on nutrient dynamics. Although the relative trophic structure, based on δ 15 N, was consistent across seasons and among estuaries, the δ 34 S values were less seasonally variable in the flow-altered estuary and were indicative of more terrestrial/freshwater-influenced values compared to the natural estuary, suggesting a lengthened influence of high flow. Although limited in temporal scope, our results indicate a noteworthy difference in seasonal isotope dynamics of lower trophic level consumers in a flow-altered estuarine food web. The importance of this effect on ecosystem function warrants further attention.
Neighborhood Socioeconomic Disadvantage and Care After Myocardial Infarction in the National Cardiovascular Data Registry

Background: Patients living in disadvantaged neighborhoods are at high risk for adverse outcomes after acute myocardial infarction (MI). Whether residential socioeconomic status (SES) is associated with quality of in-hospital care among patients presenting with MI is unclear. Methods and Results: Multivariable logistic regression was used to examine the relationship between SES, quality of care, and in-hospital cardiovascular outcomes among patients with MI from diverse SES neighborhoods from July 2008 to December 2013, at 586 participating hospitals in the Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines quality improvement program. Patients were categorized according to which SES summary measure group they resided in through linkage with US census block data. Outcomes were in-hospital mortality and major adverse cardiovascular events. Quality of MI care was assessed with the defect-free care measure that delineates the proportion of eligible patients who received all acute and discharge guideline-recommended therapies. Among 390 692 patients, there was a substantially longer median arrival-to-angiography time in lower SES neighborhoods (lowest 8.0 hours, low 5.5 hours, medium 4.8 hours, high 4.5 hours, highest 3.4 hours; P<0.0001), and a higher proportion of ST-segment–elevation myocardial infarction patients treated with fibrinolysis (lowest 23.1%, low 20.2%, medium 18.0%, high 14.2%, highest 5.9%; P<0.0001). However, after adjustment for clinical risk factors, insurance status, and hospital characteristics, socioeconomic disadvantage was not associated with lower rates of guideline-recommended defect-free acute care. Patients presenting from more disadvantaged neighborhoods had a progressively higher independent risk of in-hospital mortality (Pglobal=0.03) and major bleeding (Pglobal<0.001), along with lower quality of discharge care. Conclusions: In this national registry of MI, patients living in the most disadvantaged neighborhoods received equitable in-hospital care compared with advantaged neighborhoods. However, they experienced substantial delays in receiving angiography. Furthermore, patients living in disadvantaged neighborhoods remain at higher risk of adverse in-hospital outcomes after MI, including mortality. These observations suggest there are further opportunities for improvement in acute and discharge MI care.
The structure of human Nocturnin reveals a conserved ribonuclease domain that represses target transcript translation and abundance in cells

Abstract The circadian protein Nocturnin (NOCT) belongs to the exonuclease, endonuclease and phosphatase superfamily and is most similar to the CCR4-class of deadenylases that degrade the poly-adenosine tails of mRNAs. NOCT-deficient mice are resistant to high-fat diet induced weight gain, and exhibit dysregulation of bone formation. However, the mechanisms by which NOCT regulates these processes remain to be determined. Here, we describe a pair of high-resolution crystal structures of the human NOCT catalytic domain. The active site of NOCT is highly conserved with other exoribonucleases, and when directed to a transcript in cells, NOCT can reduce translation and abundance of that mRNA in a manner dependent on key active site residues. In contrast to the related deadenylase CNOT6L, purified recombinant NOCT lacks in vitro ribonuclease activity, suggesting that unidentified factors are necessary for enzymatic activity. We also find the ability of NOCT to repress reporter mRNAs in cells depends upon the 3′ end of the mRNA, as reporters terminating with a 3′ MALAT1 structure cannot be repressed by NOCT. Together, these data demonstrate that NOCT is an exoribonuclease that can degrade mRNAs to inhibit protein expression, suggesting a molecular mechanism for its regulatory role in lipid metabolism and bone development.
Gist: Efficient Data Encoding for Deep Neural Network Training

Modern deep neural networks (DNNs) training typically relies on GPUs to train complex hundred-layer deep networks. A significant problem facing both researchers and industry practitioners is that, as the networks get deeper, the available GPU main memory becomes a primary bottleneck, limiting the size of networks it can train. In this paper, we investigate widely used DNNs and find that the major contributors to memory footprint are intermediate layer outputs (feature maps). We then introduce a framework for DNN-layer-specific optimizations (e.g., convolution, ReLU, pool) that significantly reduce this source of main memory pressure on GPUs. We find that a feature map typically has two uses that are spread far apart temporally. Our key approach is to store an encoded representation of feature maps for this temporal gap and decode this data for use in the backward pass; the full-fidelity feature maps are used in the forward pass and relinquished immediately. Based on this approach, we present Gist, our system that employs two classes of layer-specific encoding schemes – lossless and lossy – to exploit existing value redundancy in DNN training to significantly reduce the memory consumption of targeted feature maps. For example, one insight is by taking advantage of the computational nature of back propagation from pool to ReLU layer, we can store the intermediate feature map using just 1 bit instead of 32 bits per value. We deploy these mechanisms in a state-of-the-art DNN framework (CNTK) and observe that Gist reduces the memory footprint to upto 2x across 5 state-of-the-art image classification DNNs, with an average of 1.8x with only 4% performance overhead. We also show that further software (e.g., CuDNN) and hardware (e.g., dynamic allocation) optimizations can result in even larger footprint reduction (upto 4.1x).
A Survey of Domain Adaptation for Neural Machine Translation

Neural machine translation (NMT) is a deep learning based approach for machine translation, which yields the state-of-the-art translation performance in scenarios where large-scale parallel corpora are available. Although the high-quality and domain-specific translation is crucial in the real world, domain-specific corpora are usually scarce or nonexistent, and thus vanilla NMT performs poorly in such scenarios. Domain adaptation that leverages both out-of-domain parallel corpora as well as monolingual corpora for in-domain translation, is very important for domain-specific translation. In this paper, we give a comprehensive survey of the state-of-the-art domain adaptation techniques for NMT.
The impact of first-trimester intrauterine hematoma on adverse perinatal outcomes

Purpose The aim of this study was to evaluate whether the presence of an intrauterine hematoma (IUH) on an early pregnancy ultrasound scan showing a live fetus was related to adverse perinatal outcomes. Methods We performed a retrospective cohort study to evaluate pregnant women who underwent an ultrasound examination in early pregnancy, between 6 weeks 0 days and 10 weeks 6 days. We compared the perinatal outcomes between women with and without firsttrimester IUH using the Mann-Whitney and Fisher exact tests. Furthermore, we performed a stepwise regression analysis to identify possible predictors of miscarriage among maternal characteristics, ultrasound parameters, and IUH. Results During the study period, data from 783 pregnancies were included, and the incidence of IUH was 4.5% (35 of 783). We observed a higher proportion of miscarriage following the scan (28.6% vs. 10%, P=0.003) and a larger yolk sac diameter during the scan (4.8 mm vs. 3.8 mm, P<0.001) in the pregnant women with first-trimester IUH. There was no significant difference regard the prevalence of low birth weight (LBW; P=0.091), very LBW (P=0.370), or extremely LBW (P=0.600) between cases with IUH and without IUH, the cesarean section rate (68% vs. 81%, P=0.130), preterm delivery (16% vs. 16%, P>0.999), or the incidence of first-trimester vaginal bleeding (31% vs. 20%, P=0.130). Moreover, heart rate (HR) was the only variable that predicted miscarriage with statistical significance (P=0.017). Conclusion Women with first-trimester IUH had a higher risk of miscarriage after the ultrasound scan. HR was the only variable that predicted miscarriage with statistical significance.
Effects of nitrous acid exposure on baseline pulmonary resistance and Muc5ac in rats

Abstract We examined the baseline pulmonary resistance (RLung), baseline dynamic lung compliance (Cdyn), cytokine inductions, and histological alterations in rats exposed to nitrous acid (HONO) with secondary products of nitrogen dioxide (NO2) and nitric oxide (NO) to assess its biological effects. We exposed three groups of nine male F344 rats to different doses of HONO for six weeks (24 h/day). The cumulative values of HONO concentration were measured twice. The average concentrations of nitrogen oxide for each group were 5.8 parts per million (ppm) HONO with secondary products of 0.7 ppm NO2 and 2.3 ppm NO, 4.1 ppm HONO with 0.1 ppm NO2 and 0.6 ppm NO, and a clean air control. We measured baseline RLung and baseline Cdyn using tracheal cannulation. A tracheal tube was inserted into the trachea by tracheostomy, and lung function measurements (baseline RLung and baseline Cdyn) were conducted in mechanically ventilated rats. We measured mRNA levels of Cxcl-1, TNF-α, and Muc5ac in the right lung using quantitative RT-PCR, and observed histological alterations and the alveolar mean linear intercept (Lm) on the left lung. Our results demonstrated that HONO exposure significantly increased baseline RLung, Lm and Muc5ac expression, but did not affect baseline Cdyn or expression of Cxcl-1 and TNF-α. Further, we identified bronchial smooth muscle hypertrophy, pulmonary emphysema-like alterations in the alveolar duct centriacinar regions, and increased goblet cells in HONO-exposed rats. The present results suggest that HONO (with secondary products) adversely affects respiratory function, but that these pathologies may be unrelated to inflammation.