Turbulent transport by diffusive stratified shear flows: from local to global models. Part II: Limitations of local models

This paper continues the systematic investigation of diffusive shear instabilities initiated in Part I of this series. In this work, we primarily focus on quantifying the impact of non-local mixing, which is not taken into account in Zahn's mixing model \citep{Zahn92}. We present the results of direct numerical simulations in a new model setup designed to contain coexisting laminar and turbulent shear layers. As in Part I, we use the Low P\'eclet Number approximation of \citet{Lign1999} to model the evolution of the perturbations. Our main findings are twofold. First, turbulence is not necessarily generated whenever Zahn's nonlinear criterion \citep{Zahn1974} $J{\rm Pr} < (J{\rm Pr})_c$ is satisfied, where $J=N^2/S^2$ is the local gradient Richardson number, ${\rm Pr} = \nu/ \kappa_T$ is the Prandtl number, and $(J{\rm Pr})_c \simeq 0.007$. We have demonstrated that the presence or absence of turbulent mixing in this limit hysteretically depends on the history of the shear layer. Second, Zahn's nonlinear instability criterion only approximately locates the edge of the turbulent layer, and mixing beyond the region where $J{\rm Pr} < (J{\rm Pr})_c$ can also take place in a manner analogous to convective overshoot. We found that the turbulent kinetic energy decays roughly exponentially beyond the edge of the shear-unstable region, on a lengthscale $\delta$ that is directly proportional to the scale of the turbulent eddies, which are themselves of the order of the Zahn scale (see Part I). Our results suggest that mixing by diffusive shear instabilities should be modeled with more care than is currently standard in stellar evolution codes.Comment: Submitted to Ap

Impact of Exercise in Community-Dwelling Older Adults

Background: Concern has been expressed that preventive measures in older people might increase frailty by increasing survival without improving health. We investigated the impact of exercise on the probabilities of health improvement, deterioration and death in community-dwelling older people. Methods and Principal Findings: In the Canadian Study of Health and Aging, health status was measured by a frailty index based on the number of health deficits. Exercise was classified as either high or low/no exercise, using a validated, selfadministered questionnaire. Health status and survival were re-assessed at 5 years. Of 6297 eligible participants, 5555 had complete data. Across all grades of frailty, death rates for both men and women aged over 75 who exercised were similar to their peers aged 65 to 75 who did not exercise. In addition, while all those who exercised had a greater chance of improving their health status, the greatest benefits were in those who were more frail (e.g. improvement or stability was observed in 34 % of high exercisers versus 26 % of low/no exercisers for those with 2 deficits compared with 40 % of high exercisers versus 22 % of low/no exercisers for those with 9 deficits at baseline). Conclusions: In community-dwelling older people, exercise attenuated the impact of age on mortality across all grades of frailty. Exercise conferred its greatest benefits to improvements in health status in those who were more frail at baseline

An Efficient Paradigm for Genetic Epidemiology Cohort Creation

Development of novel methodologies to efficiently create large genetic epidemiology cohorts is needed. Here we describe a rapid, precise and cost-efficient method for collection of DNA from cases previously experiencing an osteoporotic fracture by identifying cases using and administrative health-care databases. Over the course of 14 months we collected DNA from 1,130 women experiencing an osteoporotic fracture, at a cost of $54 per sample. This cohort is among the larger DNA osteoporotic fracture collections in the world. The novel method described addresses a major unmet health care research need and is widely applicable to any disease that can be identified accurately through administrative data

Pox proteomics: mass spectrometry analysis and identification of Vaccinia virion proteins

BACKGROUND: Although many vaccinia virus proteins have been identified and studied in detail, only a few studies have attempted a comprehensive survey of the protein composition of the vaccinia virion. These projects have identified the major proteins of the vaccinia virion, but little has been accomplished to identify the unknown or less abundant proteins. Obtaining a detailed knowledge of the viral proteome of vaccinia virus will be important for advancing our understanding of orthopoxvirus biology, and should facilitate the development of effective antiviral drugs and formulation of vaccines. RESULTS: In order to accomplish this task, purified vaccinia virions were fractionated into a soluble protein enriched fraction (membrane proteins and lateral bodies) and an insoluble protein enriched fraction (virion cores). Each of these fractions was subjected to further fractionation by either sodium dodecyl sulfate-polyacrylamide gel electophoresis, or by reverse phase high performance liquid chromatography. The soluble and insoluble fractions were also analyzed directly with no further separation. The samples were prepared for mass spectrometry analysis by digestion with trypsin. Tryptic digests were analyzed by using either a matrix assisted laser desorption ionization time of flight tandem mass spectrometer, a quadrupole ion trap mass spectrometer, or a quadrupole-time of flight mass spectrometer (the latter two instruments were equipped with electrospray ionization sources). Proteins were identified by searching uninterpreted tandem mass spectra against a vaccinia virus protein database created by our lab and a non-redundant protein database. CONCLUSION: Sixty three vaccinia proteins were identified in the virion particle. The total number of peptides found for each protein ranged from 1 to 62, and the sequence coverage of the proteins ranged from 8.2% to 94.9%. Interestingly, two vaccinia open reading frames were confirmed as being expressed as novel proteins: E6R and L3L

Raccoon rabies control and elimination in the northeastern USA and southern Québec, Canada

Rabies virus (RABV) is a deadly zoonosis that circulates in wild carnivore populations in North America. Intensive management within the USA and Canada has been conducted to control the spread of the raccoon (Procyon lotor) variant of RABV and work towards elimination. We examined RABV occurrence across the northeastern USA and southeastern Québec, Canada during 2008–2018 using a multi-method, dynamic occupancy model. Using a 10 km× 10 km grid overlaid on the landscape, we examined the probability that a grid cell was occupied with RABV and relationships with management activities (oral rabies vaccination (ORV) and trap-vaccinate-release efforts), habitat, neighbour effects and temporal trends. We compared raccoon RABV detection probabilities between different surveillance samples (e.g. animals that are strange acting, road-kill, public health samples). The management of RABV through ORV was found to be the greatest driver in reducing the occurrence of rabies on the landscape. Additionally, RABV occupancy declined further with increasing duration of ORV baiting programmes. Grid cells north of ORV management were at or near elimination (ψnorth = 0.00, S.E. = 0.15), managed areas had low RABV occupancy (ψmanaged = 0.20, S.E. = 0.29) and enzootic areas had the highest level of RABV occupancy (ψsouth = 0.83, S.E. = 0.06). These results provide evidence that past management actions have been being successful at the goals of reducing and controlling the raccoon variant of RABV. At a finer scale we also found that vaccine bait type and bait density impacted RABV occupancy. Detection probabilities varied; samples from strange acting animals and public health had the highest detection rates. Our results support the movement of the ORV zone south within the USA due to high elimination probabilities along the US border with Québec. Additional enhanced rabies surveillance is still needed to ensure elimination is maintained

Factors Associated With Patient Engagement in Shared Decision-Making for Stroke Prevention Among Older Adults with Atrial Fibrillation

Objective: To examine the extent of, and factors associated with, patient engagement in shared decision-making (SDM) for stroke prevention among patients with atrial fibrillation (AF). Methods: We used data from the Systematic Assessment of Geriatric Elements-Atrial Fibrillation study which includes older ( \u3e /=65 years) patients with AF and a CHA2DS2-VASc \u3e /=2. Participants reported engagement in SDM by answering whether they actively participated in choosing to take an oral anticoagulant (OAC) for their condition. Multiple logistic regression was used to assess associations between sociodemographic, clinical, geriatric, and psychosocial factors and patient engagement in SDM. Results: A total of 807 participants (mean age 75 years; 48% female) on an OAC were studied. Of these, 61% engaged in SDM. Older participants ( \u3e /=80 years) and those cognitively impaired were less likely to engage in SDM, while those very knowledgeable of their AF associated stroke risk were more likely to do so than respective comparison groups. Conclusions: A considerable proportion of older adults with AF did not engage in SDM for stroke prevention with older patients and those cognitively impaired less likely to do so. Clinicians should identify patients who are less likely to engage in SDM, promote patient engagement, and foster better patient-provider communication which may enhance long-term patient outcomes

A Systematic Review and Meta-Analysis of Efficacy, Cost-Effectiveness, and Safety of Selected Complementary and Alternative Medicine for Neck and Low-Back Pain

Background. Back pain is a common problem and a major cause of disability and health care utilization. Purpose. To evaluate the efficacy, harms, and costs of the most common CAM treatments (acupuncture, massage, spinal manipulation, and mobilization) for neck/low-back pain. Data Sources. Records without language restriction from various databases up to February 2010. Data Extraction. The efficacy outcomes of interest were pain intensity and disability. Data Synthesis. Reports of 147 randomized trials and 5 nonrandomized studies were included. CAM treatments were more effective in reducing pain and disability compared to no treatment, physical therapy (exercise and/or electrotherapy) or usual care immediately or at short-term follow-up. Trials that applied sham-acupuncture tended towards statistically nonsignificant results. In several studies, acupuncture caused bleeding on the site of application, and manipulation and massage caused pain episodes of mild and transient nature. Conclusions. CAM treatments were significantly more efficacious than no treatment, placebo, physical therapy, or usual care in reducing pain immediately or at short-term after treatment. CAM therapies did not significantly reduce disability compared to sham. None of the CAM treatments was shown systematically as superior to one another. More efforts are needed to improve the conduct and reporting of studies of CAM treatments

An empirical study using permutation-based resampling in meta-regression

<p>Abstract</p> <p>Background</p> <p>In meta-regression, as the number of trials in the analyses decreases, the risk of false positives or false negatives increases. This is partly due to the assumption of normality that may not hold in small samples. Creation of a distribution from the observed trials using permutation methods to calculate <it>P </it>values may allow for less spurious findings. Permutation has not been empirically tested in meta-regression. The objective of this study was to perform an empirical investigation to explore the differences in results for meta-analyses on a small number of trials using standard large sample approaches verses permutation-based methods for meta-regression.</p> <p>Methods</p> <p>We isolated a sample of randomized controlled clinical trials (RCTs) for interventions that have a small number of trials (herbal medicine trials). Trials were then grouped by herbal species and condition and assessed for methodological quality using the Jadad scale, and data were extracted for each outcome. Finally, we performed meta-analyses on the primary outcome of each group of trials and meta-regression for methodological quality subgroups within each meta-analysis. We used large sample methods and permutation methods in our meta-regression modeling. We then compared final models and final <it>P </it>values between methods.</p> <p>Results</p> <p>We collected 110 trials across 5 intervention/outcome pairings and 5 to 10 trials per covariate. When applying large sample methods and permutation-based methods in our backwards stepwise regression the covariates in the final models were identical in all cases. The <it>P </it>values for the covariates in the final model were larger in 78% (7/9) of the cases for permutation and identical for 22% (2/9) of the cases.</p> <p>Conclusions</p> <p>We present empirical evidence that permutation-based resampling may not change final models when using backwards stepwise regression, but may increase <it>P </it>values in meta-regression of multiple covariates for relatively small amount of trials.</p

Vitamin D and subsequent all-age and premature mortality: a systematic review

&lt;br&gt;Background: All-cause mortality in the population &#60; 65 years is 30% higher in Glasgow than in equally deprived Liverpool and Manchester. We investigated a hypothesis that low vitamin D in this population may be associated with premature mortality via a systematic review and meta-analysis.&lt;/br&gt; &lt;br&gt;Methods: Medline, EMBASE, Web of Science, the Cochrane Library and grey literature sources were searched until February 2012 for relevant studies. Summary statistics were combined in an age-stratified meta-analysis.&lt;/br&gt; &lt;br&gt;Results: Nine studies were included in the meta-analysis, representing 24,297 participants, 5,324 of whom died during follow-up. The pooled hazard ratio for low compared to high vitamin D demonstrated a significant inverse association (HR 1.19, 95% CI 1.12-1.27) between vitamin D levels and all-cause mortality after adjustment for available confounders. In an age-stratified meta-analysis, the hazard ratio for older participants was 1.25 (95% CI 1.14-1.36) and for younger participants 1.12 (95% CI 1.01-1.24).&lt;/br&gt; &lt;br&gt;Conclusions: Low vitamin D status is inversely associated with all-cause mortality but the risk is higher amongst older individuals and the relationship is prone to residual confounding. Further studies investigating the association between vitamin D deficiency and all-cause mortality in younger adults with adjustment for all important confounders (or using randomised trials of supplementation) are required to clarify this relationship.&lt;/br&gt

Which circulating antioxidant vitamins are confounded by socioeconomic deprivation? The MIDSPAN family study

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Antioxidant vitamins are often described as having “independent” associations with risk of cancer, cardiovascular disease (CVD) and mortality. We aimed to compare to what extent a range of antioxidant vitamins and carotenoids are associated with adulthood and childhood markers of socioeconomic deprivation and to adverse lifestyle factors.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; Socioeconomic and lifestyle measures were available in 1040 men and 1298 women from the MIDSPAN Family Study (30–59 years at baseline) together with circulating levels of vitamins A, C, E, and carotenoids (α-carotene, β-carotene, lutein and lycopene). Markers of socioeconomic deprivation in adulthood were consistently as strongly associated with lower vitamin C and carotenoid levels as markers of adverse lifestyle; the inverse association with overcrowding was particularly consistent (vitamin C and carotenoids range from 19.1% [95% CI 30.3–6.0] to 38.8% [49.9–25.3] lower among those in overcrowded residencies). These associations were consistent after adjusting for month, classical CVD risk factors, body mass index, physical activity, vitamin supplements, dietary fat and fibre intake. Similar, but weaker, associations were seen for childhood markers of deprivation. The association of vitamin A or E were strikingly different; several adult adverse lifestyle factors associated with higher levels of vitamin A and E, including high alcohol intake for vitamin A (9.5% [5.7–13.5]) and waist hip ratio for vitamin E (9.5% [4.8–14.4]), with the latter associations partially explained by classical risk factors, particularly cholesterol levels.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Plasma vitamin C and carotenoids have strong inverse associations with adulthood markers of social deprivation, whereas vitamin A and E appear positively related to specific adverse lifestyle factors. These findings should help researchers better contextualize blood antioxidant vitamin levels by illustrating the potential limitations associated with making causal inferences without consideration of social deprivation.&lt;/p&gt