Modelling a response as a function of high frequency count data: the association between physical activity and fat mass

We present a new statistical modelling approach where the response is a function of high frequency count data. Our application is about investigating the relationship between the health outcome fat mass and physical activity (PA) measured by accelerometer. The accelerometer quantifies the intensity of physical activity as counts per epoch over a given period of time. We use data from the Avon longitudinal study of parents and children (ALSPAC) where accelerometer data is available as a time series of accelerometer counts per minute over seven days for a subset of children. In order to compare accelerometer profiles between individuals and to reduce the high dimension a functional summary of the profiles is used. We use the histogram as a functional summary due to its simplicity, suitability and ease of interpretation. Our model is an extension of generalised regression of scalars on functions or signal regression. It allows also multi-dimensional functional predictors and additive non-linear predictors for metric covariates. The additive multidimensional functional predictors allow investigating specific questions about whether the effect of PA varies over its intensity, by gender, by time of day or by day of the week. The key feature of the model is that it utilises the full profile of measured PA without requiring cut-points defining intensity levels for light, moderate and vigorous activity. We show that the (not necessarily causal) effect of PA is not linear and not constant over the activity intensity. Also, there is little evidence to suggest that the effect of PA intensity varies by gender or whether it happens on weekdays or on weekends

Global Pharmacovigilance for Antiretroviral Drugs: Overcoming Contrasting Priorities

Jur Strobos and colleagues describe the deliberations of a recent multi-stakeholder meeting discussing the creation of a sustainable global pharmacovigilance system for antiretroviral drugs that would be applicable in resource limited settings

Spatial Guilds in the Serengeti Food Web Revealed by a Bayesian Group Model

Food webs, networks of feeding relationships among organisms, provide fundamental insights into mechanisms that determine ecosystem stability and persistence. Despite long-standing interest in the compartmental structure of food webs, past network analyses of food webs have been constrained by a standard definition of compartments, or modules, that requires many links within compartments and few links between them. Empirical analyses have been further limited by low-resolution data for primary producers. In this paper, we present a Bayesian computational method for identifying group structure in food webs using a flexible definition of a group that can describe both functional roles and standard compartments. The Serengeti ecosystem provides an opportunity to examine structure in a newly compiled food web that includes species-level resolution among plants, allowing us to address whether groups in the food web correspond to tightly-connected compartments or functional groups, and whether network structure reflects spatial or trophic organization, or a combination of the two. We have compiled the major mammalian and plant components of the Serengeti food web from published literature, and we infer its group structure using our method. We find that network structure corresponds to spatially distinct plant groups coupled at higher trophic levels by groups of herbivores, which are in turn coupled by carnivore groups. Thus the group structure of the Serengeti web represents a mixture of trophic guild structure and spatial patterns, in contrast to the standard compartments typically identified in ecological networks. From data consisting only of nodes and links, the group structure that emerges supports recent ideas on spatial coupling and energy channels in ecosystems that have been proposed as important for persistence.Comment: 28 pages, 6 figures (+ 3 supporting), 2 tables (+ 4 supporting

Emerging Infectious Disease leads to Rapid Population Decline of Common British Birds

Emerging infectious diseases are increasingly cited as threats to wildlife, livestock and humans alike. They can threaten geographically isolated or critically endangered wildlife populations; however, relatively few studies have clearly demonstrated the extent to which emerging diseases can impact populations of common wildlife species. Here, we report the impact of an emerging protozoal disease on British populations of greenfinch Carduelis chloris and chaffinch Fringilla coelebs, two of the most common birds in Britain. Morphological and molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became epidemic within greenfinch, and to a lesser extent chaffinch, populations in 2006. By 2007, breeding populations of greenfinches and chaffinches in the geographic region of highest disease incidence had decreased by 35% and 21% respectively, representing mortality in excess of half a million birds. In contrast, declines were less pronounced or absent in these species in regions where the disease was found in intermediate or low incidence. Also, populations of dunnock Prunella modularis, which similarly feeds in gardens, but in which T. gallinae was rarely recorded, did not decline. This is the first trichomonosis epidemic reported in the scientific literature to negatively impact populations of free-ranging non-columbiform species, and such levels of mortality and decline due to an emerging infectious disease are unprecedented in British wild bird populations. This disease emergence event demonstrates the potential for a protozoan parasite to jump avian host taxonomic groups with dramatic effect over a short time period

A Phylogenetic Analysis of the Globins in Fungi

BACKGROUND: ALL GLOBINS BELONG TO ONE OF THREE FAMILIES: the F (flavohemoglobin) and S (sensor) families that exhibit the canonical 3/3 α-helical fold, and the T (truncated 3/3 fold) globins characterized by a shortened 2/2 α-helical fold. All eukaryote 3/3 hemoglobins are related to the bacterial single domain F globins. It is known that Fungi contain flavohemoglobins and single domain S globins. Our aims are to provide a census of fungal globins and to examine their relationships to bacterial globins. RESULTS: Examination of 165 genomes revealed that globins are present in >90% of Ascomycota and ∼60% of Basidiomycota genomes. The S globins occur in Blastocladiomycota and Chytridiomycota in addition to the phyla that have FHbs. Unexpectedly, group 1 T globins were found in one Blastocladiomycota and one Chytridiomycota genome. Phylogenetic analyses were carried out on the fungal globins, alone and aligned with representative bacterial globins. The Saccharomycetes and Sordariomycetes with two FHbs form two widely divergent clusters separated by the remaining fungal sequences. One of the Saccharomycete groups represents a new subfamily of FHbs, comprising a previously unknown N-terminal and a FHb missing the C-terminal moiety of its reductase domain. The two Saccharomycete groups also form two clusters in the presence of bacterial FHbs; the surrounding bacterial sequences are dominated by Proteobacteria and Bacilli (Firmicutes). The remaining fungal FHbs cluster with Proteobacteria and Actinobacteria. The Sgbs cluster separately from their bacterial counterparts, except for the intercalation of two Planctomycetes and a Proteobacterium between the Fungi incertae sedis and the Blastocladiomycota and Chytridiomycota. CONCLUSION: Our results are compatible with a model of globin evolution put forward earlier, which proposed that eukaryote F, S and T globins originated via horizontal gene transfer of their bacterial counterparts to the eukaryote ancestor, resulting from the endosymbiotic events responsible for the origin of mitochondria and chloroplasts

Predicting Impacts of Climate Change on Fasciola hepatica Risk

Fasciola hepatica (liver fluke) is a physically and economically devastating parasitic trematode whose rise in recent years has been attributed to climate change. Climate has an impact on the free-living stages of the parasite and its intermediate host Lymnaea truncatula, with the interactions between rainfall and temperature having the greatest influence on transmission efficacy. There have been a number of short term climate driven forecasts developed to predict the following season's infection risk, with the Ollerenshaw index being the most widely used. Through the synthesis of a modified Ollerenshaw index with the UKCP09 fine scale climate projection data we have developed long term seasonal risk forecasts up to 2070 at a 25 km square resolution. Additionally UKCIP gridded datasets at 5 km square resolution from 1970-2006 were used to highlight the climate-driven increase to date. The maps show unprecedented levels of future fasciolosis risk in parts of the UK, with risk of serious epidemics in Wales by 2050. The seasonal risk maps demonstrate the possible change in the timing of disease outbreaks due to increased risk from overwintering larvae. Despite an overall long term increase in all regions of the UK, spatio-temporal variation in risk levels is expected. Infection risk will reduce in some areas and fluctuate greatly in others with a predicted decrease in summer infection for parts of the UK due to restricted water availability. This forecast is the first approximation of the potential impacts of climate change on fasciolosis risk in the UK. It can be used as a basis for indicating where active disease surveillance should be targeted and where the development of improved mitigation or adaptation measures is likely to bring the greatest benefits

Ultradian Cortisol Pulsatility Encodes a Distinct, Biologically Important Signal

Cortisol is released in ultradian pulses. The biological relevance of the resulting fluctuating cortisol concentration has not been explored.Determination of the biological consequences of ultradian cortisol pulsatility.A novel flow through cell culture system was developed to deliver ultradian pulsed or continuous cortisol to cells. The effects of cortisol dynamics on cell proliferation and survival, and on gene expression were determined. In addition, effects on glucocorticoid receptor (GR) expression levels and phosphorylation, as a potential mediator, were measured.Pulsatile cortisol caused a significant reduction in cell survival compared to continuous exposure of the same cumulative dose, due to increased apoptosis. Comprehensive analysis of the transcriptome response by microarray identified genes with a differential response to pulsatile versus continuous glucocorticoid delivery. These were confirmed with qRT-PCR. Several transcription factor binding sites were enriched in these differentially regulated target genes, including CCAAT-displacement protein (CDP). A CDP regulated reporter gene (MMTV-luc) was, as predicted, also differentially regulated by pulsatile compared to continuous cortisol delivery. Importantly there was no effect of cortisol delivery kinetics on either GR expression, or activation (GR phosphoSer(211)).Cortisol oscillations exert important effects on target cell gene expression, and phenotype. This is not due to differences in cumulative cortisol exposure, or either expression, or activation of the GR. This suggests a novel means to regulate GR function

Impact of Environmental Parameters on Marathon Running Performance

PURPOSE: The objectives of this study were to describe the distribution of all runners' performances in the largest marathons worldwide and to determine which environmental parameters have the maximal impact. METHODS: We analysed the results of six European (Paris, London, Berlin) and American (Boston, Chicago, New York) marathon races from 2001 to 2010 through 1,791,972 participants' performances (all finishers per year and race). Four environmental factors were gathered for each of the 60 races: temperature (°C), humidity (%), dew point (°C), and the atmospheric pressure at sea level (hPA); as well as the concentrations of four atmospheric pollutants: NO(2)-SO(2)-O(3) and PM(10) (μg x m(-3)). RESULTS: All performances per year and race are normally distributed with distribution parameters (mean and standard deviation) that differ according to environmental factors. Air temperature and performance are significantly correlated through a quadratic model. The optimal temperatures for maximal mean speed of all runners vary depending on the performance level. When temperature increases above these optima, running speed decreases and withdrawal rates increase. Ozone also impacts performance but its effect might be linked to temperature. The other environmental parameters do not have any significant impact. CONCLUSIONS: The large amount of data analyzed and the model developed in this study highlight the major influence of air temperature above all other climatic parameter on human running capacity and adaptation to race conditions

Guidance for Evidence-Informed Policies about Health Systems: Assessing How Much Confidence to Place in the Research Evidence

In the third paper in a three-part series on health systems guidance, Simon Lewin and colleagues explore the challenge of assessing how much confidence to place in evidence on health systems interventions