Differences in physical activity time-use composition associated with cardiometabolic risks

This study investigates the association between the overall physical activity composition of the day (sedentary behavior (SB), light intensity physical activity (LIPA) and moderate-to-vigorous physical activity (MVPA)) and cardiometabolic health, and examines whether improved health can be associated with replacing SB with LIPA. A cross-sectional analysis of the Health Survey for England 2008 on N = 1411 adults was undertaken using a compositional analysis approach to examine the relationship between cardiometabolic risk biomarkers and physical activity accounting for co-dependency between relative amounts of time spent in different behavior. Daily time spent in SB, LIPA and MVPA was determined from waist-mounted accelerometry data (Actigraph GT1M) and modelled against BMI, waist circumference, waist-to-hip ratio, blood pressure, total and HDL cholesterol, HbA1c, and VO2 maximum. The composition of time spent in SB, LIPA and MVPA was statistically significantly associated with BMI, waist circumference, waist-to-hips ratio, HDL cholesterol and VO2 maximum (p < 0.001), but not HbA1c, systolic and diastolic blood pressure, or total cholesterol. Increase of relative time spent in MVPA was beneficially associated with obesity markers, HDL cholesterol, and VO2 maximum, and SB with poorer outcomes. The association of changes in LIPA depended on whether it displaced MVPA or SB. Increasing the proportion of MVPA alone may have the strongest potential association with adiposity outcomes and HDL cholesterol but similar outcomes could also be associated with a lower quantity of MVPA provided a greater quantity of SB is replaced overall with LIPA (around 10.5 min of LIPA is equivalent to 1 min of MVPA). Keywords: MVPA, Sedentary behavior, Physical activity, Compositional data analysis, Cardiometabolic health, Adipoisit

Association between TV viewing and heart disease mortality: observational study using negative control outcome

AIMS: Sedentary behaviour (particularly television (TV) viewing) is thought to be a risk factor for cardiovascular disease. We employed a negative control outcome to explore whether the association between TV viewing and heart disease mortality is explained by confounding. METHODS: The sample was drawn from the UK Biobank study and comprised 479 658 participants (aged 56.5±8.0 years; 45.7% men) followed up over a mean of 10.4 years. TV viewing was measured from self-report. RESULTS: There were 1437 ischaemic heart disease (IHD) deaths, and 214 accidental deaths (employed as the negative control outcome). TV viewing was related to the following confounding variables: age, smoking, alcohol, diet, obesity, physical inactivity, cardiovascular disease and education. The confounding structures were similar for both outcomes. TV viewing (per hour/d) was associated with IHD (hazard ratio (HR)=1.30, 95% CI, 1.27 to 1.33) and accidental death (HR=1.15, 95% CI, 1.07 to 1.24) in unadjusted models. Associations were attenuated for both outcomes and were considerably converged after adjustment for confounders; IHD (HR=1.09, 95% CI, 1.06 to 1.12) and accidental death (HR=1.06, 95% CI, 0.98 to 1.15). CONCLUSION: The pattern of results for TV with an implausible outcome mirrored that of IHD, suggesting that observed associations between TV and heart disease are likely to be driven by confounding

Reconciling taxonomy and phylogenetic inference: formalism and algorithms for describing discord and inferring taxonomic roots

Although taxonomy is often used informally to evaluate the results of phylogenetic inference and find the root of phylogenetic trees, algorithmic methods to do so are lacking. In this paper we formalize these procedures and develop algorithms to solve the relevant problems. In particular, we introduce a new algorithm that solves a "subcoloring" problem for expressing the difference between the taxonomy and phylogeny at a given rank. This algorithm improves upon the current best algorithm in terms of asymptotic complexity for the parameter regime of interest; we also describe a branch-and-bound algorithm that saves orders of magnitude in computation on real data sets. We also develop a formalism and an algorithm for rooting phylogenetic trees according to a taxonomy. All of these algorithms are implemented in freely-available software.Comment: Version submitted to Algorithms for Molecular Biology. A number of fixes from previous versio

MPI-PHYLIP: Parallelizing Computationally Intensive Phylogenetic Analysis Routines for the Analysis of Large Protein Families

Background: Phylogenetic study of protein sequences provides unique and valuable insights into the molecular and genetic basis of important medical and epidemiological problems as well as insights about the origins and development of physiological features in present day organisms. Consensus phylogenies based on the bootstrap and other resampling methods play a crucial part in analyzing the robustness of the trees produced for these analyses. Methodology: Our focus was to increase the number of bootstrap replications that can be performed on large protein datasets using the maximum parsimony, distance matrix, and maximum likelihood methods. We have modified the PHYLIP package using MPI to enable large-scale phylogenetic study of protein sequences, using a statistically robust number of bootstrapped datasets, to be performed in a moderate amount of time. This paper discusses the methodology used to parallelize the PHYLIP programs and reports the performance of the parallel PHYLIP programs that are relevant to the study of protein evolution on several protein datasets. Conclusions: Calculations that currently take a few days on a state of the art desktop workstation are reduced to calculations that can be performed over lunchtime on a modern parallel computer. Of the three protein methods tested, the maximum likelihood method scales the best, followed by the distance method, and then the maximum parsimony method. However, the maximum likelihood method requires significant memory resources, which limits its application to mor

A format for phylogenetic placements

We have developed a unified format for phylogenetic placements, that is, mappings of environmental sequence data (e.g. short reads) into a phylogenetic tree. We are motivated to do so by the growing number of tools for computing and post-processing phylogenetic placements, and the lack of an established standard for storing them. The format is lightweight, versatile, extensible, and is based on the JSON format which can be parsed by most modern programming languages. Our format is already implemented in several tools for computing and post-processing parsimony- and likelihood-based phylogenetic placements, and has worked well in practice. We believe that establishing a standard format for analyzing read placements at this early stage will lead to a more efficient development of powerful and portable post-analysis tools for the growing applications of phylogenetic placement.Comment: Documents version 3 of the forma

Bayesian Inference of Task-Based Functional Brain Connectivity Using Markov Chain Monte Carlo Methods

The study of functional networks in the brain is essential in order to gain a better insight into its diverse set of operations and to characterise the associated normal and abnormal behaviours. Present methods of analysing fMRI data to obtain functional connectivity are largely limited to approaches such as correlation, regression and independent component analysis, which give simple point estimates. By contrast, we propose a stochastic linear model in a Bayesian setting and employ Markov Chain Monte Carlo methods to approximate posterior distributions of full connectivity and covariance matrices. Through the use of a Bayesian probabilistic framework, distributional estimates of the linkage strengths are obtained as opposed to point estimates, and the uncertainty of the existence of such links is accounted for. We decompose the connectivity matrix as the Hadamard product of binary indicators and real-valued variables, and formulate an efficient joint-sampling scheme to infer them. The well-characterised somato-motor network is examined in a self-paced, right-handed finger opposition task based experiment, while nodes from the visual network are used for contrast during the same experiment. Unlike for the visual network, significant changes in connectivity are found in the motor network during the task. Our work provides a distributional metric for functional connectivity along with causality information, and contributes to the collection of network level descriptors of brain functions.Engineering and Physical Sciences Research Council Grant ID: EP/K020153/1; Yousef Jameel Scholarship Programm

Left inferior frontal cortex and syntax: function, structure and behaviour in patients with left hemisphere damage.

For the past 150 years, neurobiological models of language have debated the role of key brain regions in language function. One consistently debated set of issues concern the role of the left inferior frontal gyrus in syntactic processing. Here we combine measures of functional activity, grey matter integrity and performance in patients with left hemisphere damage and healthy participants to ask whether the left inferior frontal gyrus is essential for syntactic processing. In a functional neuroimaging study, participants listened to spoken sentences that either contained a syntactically ambiguous or matched unambiguous phrase. Behavioural data on three tests of syntactic processing were subsequently collected. In controls, syntactic processing co-activated left hemisphere Brodmann areas 45/47 and posterior middle temporal gyrus. Activity in a left parietal cluster was sensitive to working memory demands in both patients and controls. Exploiting the variability in lesion location and performance in the patients, voxel-based correlational analyses showed that tissue integrity and neural activity-primarily in left Brodmann area 45 and posterior middle temporal gyrus-were correlated with preserved syntactic performance, but unlike the controls, patients were insensitive to syntactic preferences, reflecting their syntactic deficit. These results argue for the essential contribution of the left inferior frontal gyrus in syntactic analysis and highlight the functional relationship between left Brodmann area 45 and the left posterior middle temporal gyrus, suggesting that when this relationship breaks down, through damage to either region or to the connections between them, syntactic processing is impaired. On this view, the left inferior frontal gyrus may not itself be specialized for syntactic processing, but plays an essential role in the neural network that carries out syntactic computations

Methylphenidate-mediated motor control network enhancement in patients with traumatic brain injury.

PRIMARY OBJECTIVE: To investigate functional improvement late (>6 months) after traumatic brain injury (TBI). To this end, we conducted a double-blind, placebo-controlled experimental medicine study to test the hypothesis that a widely used cognitive enhancer would benefit patients with TBI. RESEARCH DESIGN: We focused on motor control function using a sequential finger opposition fMRI paradigm in both patients and age-matched controls. METHODS AND PROCEDURES: Patients' fMRI and DTI scans were obtained after randomised administration of methylphenidate or placebo. Controls were scanned without intervention. To assess differences in motor speed, we compared reaction times from the baseline condition of a sustained attention task. MAIN OUTCOMES AND RESULTS: Patients' reaction times correlated with wide-spread motor-related white matter abnormalities. Administration of methylphenidate resulted in faster reaction times in patients, which were not significantly different from those achieved by controls. This was also reflected in the fMRI findings in that patients on methylphenidate activated the left inferior frontal gyrus significantly more than when on placebo. Furthermore, stronger functional connections between pre-/post-central cortices and cerebellum were noted for patients on methylphenidate. CONCLUSIONS: Our findings suggest that residual functionality in patients with TBI may be enhanced by a single dose of methylphenidate.The study was funded by the Evelyn Trust- grant number 06/20. C.D. was funded by the Clinical Academic Research Awards organized by the East of England Multi Professional Deanery. B.J.S. consults for Cambridge Cognition, Otsuka, Servier and Lundbeck. She holds a grant from Janssen/J&J and has share options in Cambridge Cognition. D.K.M. is supported by the Neuroscience Theme of the NIHR Cambridge Biomedical Research Centre and NIHR Senior Investigator awards, and by Framework Program 7 funding from the European Commission (TBIcare). He has received lecture and consultancy fees and support for research from Glaxo SmithKline, Solvay and Linde. E.A.S. is funded by the Stephen Erskine Fellowship, Queens' College, Cambridge, UK

Sitting Time, Physical Activity, and Risk of Mortality in Adults

BACKGROUND It is unclear what level of moderate to vigorous intensity physical activity (MVPA) offsets the health risks of sitting. OBJECTIVES The purpose of this study was to examine the joint and stratified associations of sitting and MVPA with all-cause and cardiovascular disease (CVD) mortality, and to estimate the theoretical effect of replacing sitting time with physical activity, standing, and sleep. METHODS A longitudinal analysis of the 45 and Up Study calculated the multivariable-adjusted hazard ratios (HRs) of sitting for each sitting-MVPA combination group and within MVPA strata. Isotemporal substitution modeling estimated the per-hour HR effects of replacing sitting. RESULTS A total of 8,689 deaths (1,644 due to CVD) occurred among 149,077 participants over an 8.9-year (median) follow-up. There was a statistically significant interaction between sitting and MVPA only for all-cause mortality. Sitting time was associated with both mortality outcomes in a nearly dose-response manner in the least active groups reporting <150 MVPA min/week. For example, among those reporting no MVPA, the all-cause mortality HR comparing the most sedentary (>8 h/day) to the least sedentary (<4 h/day) groups was 1.52 (95% confidence interval: 1.13 to 2.03). There was inconsistent and weak evidence for elevated CVD and all-cause mortality risks with more sitting among those meeting the lower (150 to 299 MVPA min/week) or upper ($300 MVPA min/week) limits of the MVPA recommendation. Replacing sitting with walking and MVPA showed stronger associations among high sitters (>6 sitting h/day) where, for example, the per-hour CVD mortality HR for sitting replaced with vigorous activity was 0.36 (95% confidence interval: 0.17 to 0.74). CONCLUSIONS Sitting is associated with all-cause and CVD mortality risk among the least physically active adults; moderate-to-vigorous physical activity doses equivalent to meeting the current recommendations attenuate or effectively eliminate such association