The curse of dimensionality associated with the Hilbert space of spin systems provides a significant obstruction to the study of condensed matter systems. Tensor networks have proven an important ...tool in attempting to overcome this difficulty in both the numerical and analytic regimes. These notes form the basis for a seven lecture course, introducing the basics of a range of common tensor networks and algorithms. In particular, we cover: introductory tensor network notation, applications to quantum information, basic properties of matrix product states, a classification of quantum phases using tensor networks, algorithms for finding matrix product states, basic properties of projected entangled pair states, and multiscale entanglement renormalisation ansatz states. The lectures are intended to be generally accessible, although the relevance of many of the examples may be lost on students without a background in many-body physics/quantum information. For each lecture, several problems are given, with worked solutions in an ancillary file.
Context. The elemental depletion of interstellar sulfur from the gas phase has been a recurring challenge for astrochemical models. Observations show that sulfur remains relatively non-depleted with ...respect to its cosmic value throughout the diffuse and translucent stages of an interstellar molecular cloud, but its atomic and molecular gas-phase constituents cannot account for this cosmic value toward lines of sight containing higher-density environments. Aims. We have attempted to address this issue by modeling the evolution of an interstellar cloud from its pristine state as a diffuse atomic cloud to a molecular environment of much higher density, using a gas-grain astrochemical code and an enhanced sulfur reaction network. Methods. A common gas-grain astrochemical reaction network has been systematically updated and greatly extended based on previous literature and previous sulfur models, with a focus on the grain chemistry and processes. A simple astrochemical model was used to benchmark the resulting network updates, and the results of the model were compared to typical astronomical observations sourced from the literature. Results. Our new gas-grain astrochemical model is able to reproduce the elemental depletion of sulfur, whereby sulfur can be depleted from the gas-phase by two orders of magnitude, and that this process may occur under dark cloud conditions if the cloud has a chemical age of at least 106 years. The resulting mix of sulfur-bearing species on the grain ranges across all the most common chemical elements (H/C/N/O), not dissimilar to the molecules observed in cometary environments. Notably, this mixture is not dominated simply by H2S, unlike all other current astrochemical models. Conclusions. Despite our relatively simple physical model, most of the known gas-phase S-bearing molecular abundances are accurately reproduced under dense conditions, however they are not expected to be the primary molecular sinks of sulfur. Our model predicts that most of the “missing” sulfur is in the form of organo-sulfur species that are trapped on grains.
The prevalence of obesity is increasing at an alarming rate in many parts of the world. About 2 billion people are overweight and one third of them obese. The plight of the most affected populations, ...like those in high-income countries in North America, Australasia and Europe, has been well publicized. However, the more recent increases in population obesity in low-and middle-income countries that are now increasingly being observed have been less recognized. Based on the existing prevalence and trend data and the epidemiological evidence linking obesity with a range of physical and psychosocial health conditions, it is reasonable to describe obesity as a public health crisis that severely impairs the health and quality of life of people and adds considerably to national health-care budgets. Intersectoral action to manage and prevent obesity is urgently required to reverse current trends.
The consumption of beverages that contain sugar is associated with overweight, possibly because liquid sugars do not lead to a sense of satiety, so the consumption of other foods is not reduced. ...However, data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain.
We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age. Participants were randomly assigned to receive 250 ml (8 oz) per day of a sugar-free, artificially sweetened beverage (sugar-free group) or a similar sugar-containing beverage that provided 104 kcal (sugar group). Beverages were distributed through schools. At 18 months, 26% of the children had stopped consuming the beverages; the data from children who did not complete the study were imputed.
The z score for the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group; the 95% confidence interval (CI) of the difference was -0.21 to -0.05. Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group (95% CI for the difference, -1.54 to -0.48). The skinfold-thickness measurements, waist-to-height ratio, and fat mass also increased significantly less in the sugar-free group. Adverse events were minor. When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study, the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group (P=0.06).
Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children. (Funded by the Netherlands Organization for Health Research and Development and others; DRINK ClinicalTrials.gov number, NCT00893529.).
Pharmacotherapy for NASH: Current and emerging Konerman, Monica A.; Jones, Jacob C.; Harrison, Stephen A.
Journal of hepatology,
February 2018, 2018-02-00, 20180201, Letnik:
68, Številka:
2
Journal Article
Recenzirano
Non-alcoholic fatty liver disease (NAFLD) has become one of the most prominent forms of chronic liver disease worldwide, reflecting the epidemic of global obesity. Those with the progressive variant ...of NAFLD, non-alcoholic steatohepatitis (NASH), are at significantly increased risk of multisystem morbidity and mortality. However, there are currently no approved pharmacologic therapies for NASH. Given the disease burden, there is an important unmet need for pharmacologic treatment options for this patient population. The underlying pathophysiologic mechanisms that contribute to the development and progression of NAFLD and NASH are complex and reflected by the myriad of therapies, with different targets, currently under investigation. In broad strokes, drug development has focused on modulation of metabolic pathways, inflammatory cascades, and/or mechanisms impacting fibrosis. Although much progress has been made in enhancing our understanding of NAFLD pathogenesis, development of pharmacologic treatments has been hindered by challenges in clinical trial enrollment and complexities in clinical trial design. The compounds in phase IIa have provided promising results in terms of potential benefits on various aspects of histopathology. Agents in later stages of development have shown fairly modest results in terms of reduction of hepatic steatosis, necroinflammation and fibrosis. If longer term safety and efficacy are established among heterogeneous cohorts, these medications may help mitigate potential morbidity and mortality for this burgeoning patient population.
Proportional data, in which response variables are expressed as percentages or fractions of a whole, are analysed in many subfields of ecology and evolution. The scale‐independence of proportions ...makes them appropriate to analyse many biological phenomena, but statistical analyses are not straightforward, since proportions can only take values from zero to one and their variance is usually not constant across the range of the predictor. Transformations to overcome these problems are often applied, but can lead to biased estimates and difficulties in interpretation.
In this paper, we provide an overview of the different types of proportional data and discuss the different analysis strategies available. In particular, we review and discuss the use of promising, but little used, techniques for analysing continuous (also called non‐count‐based or non‐binomial) proportions (e.g. percent cover, fraction time spent on an activity): beta and Dirichlet regression, and some of their most important extensions.
A major distinction can be made between proportions arising from counts and those arising from continuous measurements. For proportions consisting of two categories, count‐based data are best analysed using well‐developed techniques such as logistic regression, while continuous proportions can be analysed with beta regression models. In the case of >2 categories, multinomial logistic regression or Dirichlet regression can be applied. Both beta and Dirichlet regression techniques model proportions at their original scale, which makes statistical inference more straightforward and produce less biased estimates relative to transformation‐based solutions. Extensions to beta regression, such as models for variable dispersion, zero‐one augmented data and mixed effects designs have been developed and are reviewed and applied to case studies. Finally, we briefly discuss some issues regarding model fitting, inference, and reporting that are particularly relevant to beta and Dirichlet regression.
Beta regression and Dirichlet regression overcome some problems inherent in applying classic statistical approaches to proportional data. To facilitate the adoption of these techniques by practitioners in ecology and evolution, we present detailed, annotated demonstration scripts covering all variations of beta and Dirichlet regression discussed in the article, implemented in the freely available language for statistical computing, r.
Foreign Language 抽象
在生态学和进化学的许多子领域中分析比例数据时,其中的响应变量被表示为整体的百分比或分数。比例相对于数据尺度的独立性使得其适用于分析许多生物学现象。但是由于比例只能从0到1取值,并且它们的方差在预测值的范围内通常不恒定,使得统计分析结果不具有直观性。为了克服上述问题,研究者通常采用数学变换等方法,但也可能导致有有偏估计和解释上的困难。
在本文中,我们概述了不同类型的比例数据,并讨论了现行的不同类型的分析方法,特别是一些用来分析连续(也称为非计数或非二项式)比例(例如,百分比覆盖,动物特定行为时间比例):β回归和Dirichlet回归,以及它们最重要的一些扩展。目前,虽然这些方法的使用范围较窄,但是我们认为它们有着广泛的应用前景。
可以对计数产生的比例和连续测量产生的比例进行区分。对于由2个类别组成的比例,若数据是计数的,可以使用例如逻辑回归等完善的方法进行分析,若数据是连续的,可以使用β回归模型。对于类别大于2的比例,可以使用多项逻辑回归或Dirichlet回归。β回归和Dirichlet回归均在数据的原始尺度上对比例建模,这不仅使得统计推断更加简单,并且相对数学变换的方法能产生更少的有偏估计。我们对β回归的扩展方法做了概述,例如变量扩散模型、0‐1增强数据和混合效应设计,并将这些方法应用于案例研究。最后,我们简要地讨论了与β回归和Dirichlet回归特别相关的模型拟合和统计推断。
β回归和Dirichlet回归克服了将经典统计方法应用于比例数据时固有的一些问题。为了帮助生态学和进化学研究者采用这些技术,我们提供了详细的、带注释的演示脚本,涵盖了文章中讨论的所有β回归和Dirichlet回归变体,可以用免费的统计学计算机语言R来实现。
Excessive and recurring violent aggression is a serious concern for society and a symptom of many psychiatric diseases. Substance abuse, attack experience, and social and traumatic stress increase ...vulnerability to developing this type of aggression. Glutamate receptors are an intriguing target for long-term treatment. This review will assess the importance of glutamate receptors and glutamatergic pathways in aggression, focusing on the role of glutamate receptor-mediated synaptic plasticity in experience-dependent long-lasting aggression. By synthesizing what is known about glutamatergic systems in aggression, it is hoped more effective treatments can be developed.
•Substance abuse, attack experience, and stress are reliable predictors of aggression.•Substance abuse, attack experience, and stress induce synaptic plasticity in multiple aggression circuits.•Many of the plasticity mechanisms in aggression are glutamate-receptor dependent.•Examining glutamate receptor-dependent synaptic plasticity in aggression will be key in developing better treatments.
α5 subunit containing GABA type A receptors (GABA
Rs) have long been an enigmatic receptor subtype of interest due to their specific brain distribution, unusual surface localization and key role in ...synaptic plasticity, cognition and memory. These receptors are uniquely positioned to sculpt both the developing and mature hippocampal circuitry due to high overall expression and a distinct peak within the critical synapse formation period during the second postnatal week. Unlike the majority of other GABA
Rs, they exhibit both receptor clustering at extrasynaptic sites
interactions with the radixin scaffold as well as synaptic sites
gephyrin, thus contributing respectively to tonic currents and synaptic GABAergic neurotransmission. α5 GABA
R signaling can be altered in neurodevelopmental disorders including autism and mental retardation and by inflammation in CNS injury and disease. Due to the unique physiology and pharmacology of α5 GABA
Rs, drugs targeting these receptors are being developed and tested as treatments for neurodevelopmental disorders, depression, schizophrenia, and mild cognitive impairment. This review article focuses on advances in understanding how the α5 subunit contributes to GABA
R neurobiology. In particular, I discuss both recent insights and remaining knowledge gaps for the functional role of these receptors, pathologies associated with α5 GABA
R dysfunction, and the effects and potential therapeutic uses of α5 receptor subtype targeted drugs.
A new 5-stage cardiogenic shock (CS) classification scheme was recently proposed by the Society for Cardiovascular Angiography and Intervention (SCAI) for the purpose of risk stratification.
This ...study sought to apply the SCAI shock classification in a cardiac intensive care unit (CICU) population.
The study retrospectively analyzed Mayo Clinic CICU patients admitted between 2007 and 2015. SCAI CS stages A through E were classified retrospectively using CICU admission data based on the presence of hypotension or tachycardia, hypoperfusion, deterioration, and refractory shock. Hospital mortality in each SCAI shock stage was stratified by cardiac arrest (CA).
Among the 10,004 unique patients, 43.1% had acute coronary syndrome, 46.1% had heart failure, and 12.1% had CA. The proportion of patients in SCAI CS stages A through E was 46.0%, 30.0%, 15.7%, 7.3%, and 1.0% and unadjusted hospital mortality in these stages was 3.0%, 7.1%, 12.4%, 40.4%, and 67.0% (p < 0.001), respectively. After multivariable adjustment, each higher SCAI shock stage was associated with increased hospital mortality (adjusted odds ratio: 1.53 to 6.80; all p < 0.001) compared with SCAI shock stage A, as was CA (adjusted odds ratio: 3.99; 95% confidence interval: 3.27 to 4.86; p < 0.001). Results were consistent in the subset of patients with acute coronary syndrome or heart failure.
When assessed at the time of CICU admission, the SCAI CS classification, including presence or absence of CA, provided robust hospital mortality risk stratification. This classification system could be implemented as a clinical and research tool to identify, communicate, and predict the risk of death in patients with, and at risk for, CS.
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