Logarithmic rate dependence in deforming granular materials

Rate-independence for stresses within a granular material is a basic tenet of many models for slow dense granular flows. By contrast, logarithmic rate dependence of stresses is found in solid-on-solid friction, in geological settings, and elsewhere. In this work, we show that logarithmic rate-dependence occurs in granular materials for plastic (irreversible) deformations that occur during shearing but not for elastic (reversible) deformations, such as those that occur under moderate repetitive compression. Increasing the shearing rate, \Omega, leads to an increase in the stress and the stress fluctuations that at least qualitatively resemble what occurs due to an increase in the density. Increases in \Omega also lead to qualitative changes in the distributions of stress build-up and relaxation events. If shearing is stopped at t=0, stress relaxations occur with \sigma(t)/ \sigma(t=0) \simeq A \log(t/t_0). This collective relaxation of the stress network over logarithmically long times provides a mechanism for rate-dependent strengthening.Comment: 4 pages, 5 figures. RevTeX

ASCORE: an up-to-date cardiovascular risk score for hypertensive patients reflecting contemporary clinical practice developed using the (ASCOT-BPLA) trial data.

A number of risk scores already exist to predict cardiovascular (CV) events. However, scores developed with data collected some time ago might not accurately predict the CV risk of contemporary hypertensive patients that benefit from more modern treatments and management. Using data from the randomised clinical trial Anglo-Scandinavian Cardiac Outcomes Trial-BPLA, with 15 955 hypertensive patients without previous CV disease receiving contemporary preventive CV management, we developed a new risk score predicting the 5-year risk of a first CV event (CV death, myocardial infarction or stroke). Cox proportional hazard models were used to develop a risk equation from baseline predictors. The final risk model (ASCORE) included age, sex, smoking, diabetes, previous blood pressure (BP) treatment, systolic BP, total cholesterol, high-density lipoprotein-cholesterol, fasting glucose and creatinine baseline variables. A simplified model (ASCORE-S) excluding laboratory variables was also derived. Both models showed very good internal validity. User-friendly integer score tables are reported for both models. Applying the latest Framingham risk score to our data significantly overpredicted the observed 5-year risk of the composite CV outcome. We conclude that risk scores derived using older databases (such as Framingham) may overestimate the CV risk of patients receiving current BP treatments; therefore, 'updated' risk scores are needed for current patients

Validation of the Thai version of the family reported outcome measure (FROM-16)© to assess the impact of disease on the partner or family members of patients with cancer

© The Author(s). 2019Background: Cancer not only impairs a patient's physical and psychosocial functional behaviour, but also contributes to negative impact on family members' health related quality of life. Currently, there is an absence of a relevant tool in Thai with which to measure such impact. The aim of this study was to translate and validate the Family Reported Outcome Measure (FROM-16) in Thai cancer patients' family members. Methods: Thai version of FROM-16 was generated by interactive forward-backward translation process following standard guidelines. This was tested for psychometric properties including reliability and validity, namely content validity, concurrent validity, known group validity, internal consistency, exploratory and confirmatory factor analysis. Construct validity was examined by comparing the Thai FROM-16 version with the WHOQOL-BREF-THAI. Results: The internal consistency reliability was strong (Cronbach's alpha = 0.86). A Negative moderate correlation between the Thai FROM-16 and WHOQOL-BREF-THAI was observed (r = - 0.4545, p < 0.00), and known group validity was proved by a statistically significant higher score in family members with high burden of care and insufficient income. The factor analysis supported both 3-factor and 2-factor loading model with slight difference when compared with the original version. Conclusions: The Thai FROM-16 showed good reliability and validity in Thai family members of patients with cancer. A slight difference in factor analysis results compared to the original version could be due to cross-culture application.Peer reviewedFinal Published versio

Risk factors for race-day fatality in flat racing Thoroughbreds in Great Britain (2000 to 2013)

A key focus of the racing industry is to reduce the number of race-day events where horses die suddenly or are euthanased due to catastrophic injury. The objective of this study was therefore to determine risk factors for race-day fatalities in Thoroughbred racehorses, using a cohort of all horses participating in flat racing in Great Britain between 2000 and 2013. Horse-, race- and course-level data were collected and combined with all race-day fatalities, recorded by racecourse veterinarians in a central database. Associations between exposure variables and fatality were assessed using logistic regression analyses for (1) all starts in the dataset and (2) starts made on turf surfaces only. There were 806,764 starts in total, of which 548,571 were on turf surfaces. A total of 610 fatalities were recorded; 377 (61.8%) on turf. In both regression models, increased firmness of the going, increasing racing distance, increasing average horse performance, first year of racing and wearing eye cover for the first time all increased the odds of fatality. Generally, the odds of fatality also increased with increasing horse age whereas increasing number of previous starts reduced fatality odds. In the ‘all starts’ model, horses racing in an auction race were at 1.46 (95% confidence interval (CI) 1.06–2.01) times the odds of fatality compared with horses not racing in this race type. In the turf starts model, horses racing in Group 1 races were at 3.19 (95% CI 1.71–5.93) times the odds of fatality compared with horses not racing in this race type. Identification of novel risk factors including wearing eye cover and race type will help to inform strategies to further reduce the rate of fatality in flat racing horses, enhancing horse and jockey welfare and safety

A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis

BACKGROUND: Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. METHODS: We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. RESULTS: We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. CONCLUSIONS: Our results suggest that the innate immune system is central to SSc disease processes but that subtle distinctions exist between tissues. Our approach provides a framework for examining molecular signatures of disease in fibrosis and autoimmune diseases and for leveraging publicly available data to understand common and tissue-specific disease processes in complex human diseases

Steam reforming on transition-metal carbides from density-functional theory

A screening study of the steam reforming reaction (CH_4 + H_2O -> CO + 3H_2) on early transition-metal carbides (TMC's) is performed by means of density-functional theory calculations. The set of considered surfaces includes the alpha-Mo_2C(100) surfaces, the low-index (111) and (100) surfaces of TiC, VC, and delta-MoC, and the oxygenated alpha-Mo_2C(100) and TMC(111) surfaces. It is found that carbides provide a wide spectrum of reactivities towards the steam reforming reaction, from too reactive via suitable to too inert. The reactivity is discussed in terms of the electronic structure of the clean surfaces. Two surfaces, the delta-MoC(100) and the oxygen passivated alpha-Mo_2C(100) surfaces, are identified as promising steam reforming catalysts. These findings suggest that carbides provide a playground for reactivity tuning, comparable to the one for pure metals.Comment: 6 pages, 4 figure

Whole-genome sequencing to understand the genetic architecture of common gene expression and biomarker phenotypes.

Initial results from sequencing studies suggest that there are relatively few low-frequency (&lt;5%) variants associated with large effects on common phenotypes. We performed low-pass whole-genome sequencing in 680 individuals from the InCHIANTI study to test two primary hypotheses: (i) that sequencing would detect single low-frequency-large effect variants that explained similar amounts of phenotypic variance as single common variants, and (ii) that some common variant associations could be explained by low-frequency variants. We tested two sets of disease-related common phenotypes for which we had statistical power to detect large numbers of common variant-common phenotype associations-11 132 cis-gene expression traits in 450 individuals and 93 circulating biomarkers in all 680 individuals. From a total of 11 657 229 high-quality variants of which 6 129 221 and 5 528 008 were common and low frequency (&lt;5%), respectively, low frequency-large effect associations comprised 7% of detectable cis-gene expression traits [89 of 1314 cis-eQTLs at P &lt; 1 × 10(-06) (false discovery rate ∼5%)] and one of eight biomarker associations at P &lt; 8 × 10(-10). Very few (30 of 1232; 2%) common variant associations were fully explained by low-frequency variants. Our data show that whole-genome sequencing can identify low-frequency variants undetected by genotyping based approaches when sample sizes are sufficiently large to detect substantial numbers of common variant associations, and that common variant associations are rarely explained by single low-frequency variants of large effect

An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial

Background: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin ± aspirin) for prescription when appropriate; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification. Methods: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed. Discussion: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN1261600023342

Theory of Star Formation

We review current understanding of star formation, outlining an overall theoretical framework and the observations that motivate it. A conception of star formation has emerged in which turbulence plays a dual role, both creating overdensities to initiate gravitational contraction or collapse, and countering the effects of gravity in these overdense regions. The key dynamical processes involved in star formation -- turbulence, magnetic fields, and self-gravity -- are highly nonlinear and multidimensional. Physical arguments are used to identify and explain the features and scalings involved in star formation, and results from numerical simulations are used to quantify these effects. We divide star formation into large-scale and small-scale regimes and review each in turn. Large scales range from galaxies to giant molecular clouds (GMCs) and their substructures. Important problems include how GMCs form and evolve, what determines the star formation rate (SFR), and what determines the initial mass function (IMF). Small scales range from dense cores to the protostellar systems they beget. We discuss formation of both low- and high-mass stars, including ongoing accretion. The development of winds and outflows is increasingly well understood, as are the mechanisms governing angular momentum transport in disks. Although outstanding questions remain, the framework is now in place to build a comprehensive theory of star formation that will be tested by the next generation of telescopes.Comment: 120 pages, to appear in ARAA. No changes from v1 text; permission statement adde