Underweight as a risk factor for respiratory death in the Whitehall cohort study: exploring reverse causality using a 45-year follow-up

Underweight adults have higher rates of respiratory death than the normal weight but it is unclear whether this association is causal or reflects illness-induced weight loss (reverse causality). Evidence from a 45-year follow-up of underweight participants for respiratory mortality in the Whitehall study (N=18 823; 2139 respiratory deaths) suggests that excess risk among the underweight is attributable to reverse causality. The age-adjusted and smoking-adjusted risk was 1.55-fold (95% CI 1.32 to 1.83) higher among underweight compared with normal weight participants, but attenuated in a stepwise manner to 1.14 (95% CI 0.76 to 1.71) after serial exclusions of deaths during the first 5-35 years of follow-up (Ptrend<0.001)

Twenty-Five-Year Alcohol Consumption Trajectories and Their Association With Arterial Aging: A Prospective Cohort Study.

BACKGROUND: Emerging evidence suggests that arterial stiffness, an important marker of cardiovascular health, is associated with alcohol consumption. However, the role of longer-term consumption patterns in the progression of arterial stiffness over time remains unclear. A longitudinal cohort design was used to evaluate the association between alcohol consumption over 25 years and subsequent changes in arterial stiffness. METHODS AND RESULTS: Data (N=3869; 73% male) were drawn from the Whitehall II cohort study of British civil servants, in which participants completed repeat pulse wave velocity assessments of arterial stiffness across a 4- to 5-year interval. Repeated alcohol intake measurements were used to categorize participants into alcohol consumer types, accounting for longitudinal variability in consumption. Sex-stratified linear mixed-effects modeling was used to investigate whether drinker types differed in their relationship to pulse wave velocity and its progression over time. Males with consistent long-term heavy intake >112 g of ethanol/week had significantly higher baseline pulse wave velocity (b=0.26 m/s; P=0.045) than those who drank consistently moderately (1-112 g of ethanol/week). Male former drinkers showed significantly greater increases in arterial stiffness longitudinally compared to consistently moderate drinkers (b=0.11 m/s; P=0.009). All associations were nonsignificant for females after adjustment for body mass index, heart rate, mean arterial pressure, diabetes mellitus, high-density lipoprotein, and triglycerides. CONCLUSIONS: This work demonstrates that consistently heavy alcohol consumption is associated with higher cardiovascular risk, especially among males, and also provides new insights into the potential impact of changes in drinking levels over time. It discusses the additional insights possible when capturing longitudinal consumption patterns in lieu of reliance on recent intake alone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02663791

Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

BackgroundScreening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions.MethodsOne hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information.ResultsPCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients.ConclusionWhile our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics

Is there a clinically significant seasonal component to hospital admissions for atrial fibrillation?

BACKGROUND: Atrial fibrillation is a common cardiac dysrhythmia, particularly in the elderly. Recent studies have indicated a statistically significant seasonal component to atrial fibrillation hospitalizations. METHODS: We conducted a retrospective population cohort study using time series analysis to evaluate seasonal patterns of atrial fibrillation hospitalizations for the province of Ontario for the years 1988 to 2001. Five different series methods were used to analyze the data, including spectral analysis, X11, R-Squared, autocorrelation function and monthly aggregation. RESULTS: This study found evidence of weak seasonality, most apparent at aggregate levels including both ages and sexes. There was dramatic increase in hospitalizations for atrial fibrillation over the years studied and an age dependent increase in rates per 100,000. Overall, the magnitude of seasonal difference between peak and trough months is in the order of 1.4 admissions per 100,000 population. The peaks for hospitalizations were predominantly in April, and the troughs in August. CONCLUSIONS: Our study confirms statistical evidence of seasonality for atrial fibrillation hospitalizations. This effect is small in absolute terms and likely not significant for policy or etiological research purposes

A Vast Thin Plane of Co-rotating Dwarf Galaxies Orbiting the Andromeda Galaxy

Dwarf satellite galaxies are thought to be the remnants of the population of primordial structures that coalesced to form giant galaxies like the Milky Way. An early analysis noted that dwarf galaxies may not be isotropically distributed around our Galaxy, as several are correlated with streams of HI emission, and possibly form co-planar groups. These suspicions are supported by recent analyses, and it has been claimed that the apparently planar distribution of satellites is not predicted within standard cosmology, and cannot simply represent a memory of past coherent accretion. However, other studies dispute this conclusion. Here we report the existence (99.998% significance) of a planar sub-group of satellites in the Andromeda galaxy, comprising approximately 50% of the population. The structure is vast: at least 400 kpc in diameter, but also extremely thin, with a perpendicular scatter <14.1 kpc (99% confidence). Radial velocity measurements reveal that the satellites in this structure have the same sense of rotation about their host. This finding shows conclusively that substantial numbers of dwarf satellite galaxies share the same dynamical orbital properties and direction of angular momentum, a new insight for our understanding of the origin of these most dark matter dominated of galaxies. Intriguingly, the plane we identify is approximately aligned with the pole of the Milky Way's disk and is co-planar with the Milky Way to Andromeda position vector. The existence of such extensive coherent kinematic structures within the halos of massive galaxies is a fact that must be explained within the framework of galaxy formation and cosmology.Comment: Published in the 3rd Jan 2013 issue of Nature. 19 pages, 4 figures, 1 three-dimensional interactive figure. To view and manipulate the 3-D figure, an Adobe Reader browser plug-in is required; alternatively save to disk and view with Adobe Reade

True Neutrality as a New Type of Flavour

A classification of leptonic currents with respect to C-operation requires the separation of elementary particles into the two classes of vector C-even and axial-vector C-odd character. Their nature has been created so that to each type of lepton corresponds a kind of neutrino. Such pairs are united in families of a different C-parity. Unlike the neutrino of a vector type, any C-noninvariant Dirac neutrino must have his Majorana neutrino. They constitute the purely neutrino families. We discuss the nature of a corresponding mechanism responsible for the availability in all types of axial-vector particles of a kind of flavour which distinguishes each of them from others by a true charge characterized by a quantum number conserved at the interactions between the C-odd fermion and the field of emission of the corresponding types of gauge bosons. This regularity expresses the unidenticality of truly neutral neutrino and antineutrino, confirming that an internal symmetry of a C-noninvariant particle is described by an axial-vector space. Thereby, a true flavour together with the earlier known lepton flavour predicts the existence of leptonic strings and their birth in single and double beta decays as a unity of flavour and gauge symmetry laws. Such a unified principle explains the availability of a flavour symmetrical mode of neutrino oscillations.Comment: 19 pages, LaTex, Published version in IJT

Spatially Explicit Data: Stewardship and Ethical Challenges in Science

Scholarly communication is at an unprecedented turning point created in part by the increasing saliency of data stewardship and data sharing. Formal data management plans represent a new emphasis in research, enabling access to data at higher volumes and more quickly, and the potential for replication and augmentation of existing research. Data sharing has recently transformed the practice, scope, content, and applicability of research in several disciplines, in particular in relation to spatially specific data. This lends exciting potentiality, but the most effective ways in which to implement such changes, particularly for disciplines involving human subjects and other sensitive information, demand consideration. Data management plans, stewardship, and sharing, impart distinctive technical, sociological, and ethical challenges that remain to be adequately identified and remedied. Here, we consider these and propose potential solutions for their amelioration

Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus

BACKGROUND: Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. METHODS: We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium(R) HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. RESULTS: Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. CONCLUSION: This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy

Associations between psychological therapy outcomes for depression and incidence of dementia

BACKGROUND: Depression is an important, potentially modifiable dementia risk factor. However, it is not known whether effective treatment of depression through psychological therapies is associated with reduced dementia incidence. The aim of this study was to investigate associations between reduction in depressive symptoms following psychological therapy and the subsequent incidence of dementia. METHODS: National psychological therapy data were linked with hospital records of dementia diagnosis for 119808 people aged 65+. Participants received a course of psychological therapy treatment in Improving Access to Psychological Therapies (IAPT) services between 2012 and 2019. Cox proportional hazards models were run to test associations between improvement in depression following psychological therapy and incidence of dementia diagnosis up to eight years later. RESULTS: Improvements in depression following treatment were associated with reduced rates of dementia diagnosis up to 8 years later (HR = 0.88, 95% CI 0.83-0.94), after adjustment for key covariates. Strongest effects were observed for vascular dementia (HR = 0.86, 95% CI 0.77-0.97) compared with Alzheimer's disease (HR = 0.91, 95% CI 0.83-1.00). CONCLUSIONS: Reliable improvement in depression across psychological therapy was associated with reduced incidence of future dementia. Results are consistent with at least two possibilities. Firstly, psychological interventions to improve symptoms of depression may have the potential to contribute to dementia risk reduction efforts. Secondly, psychological therapies may be less effective in people with underlying dementia pathology or they may be more likely to drop out of therapy (reverse causality). Tackling the under-representation of older people in psychological therapies and optimizing therapy outcomes is an important goal for future research