Showing papers by "University of Exeter published in 2010"

Source partitioning using stable isotopes: coping with too much variation.

Abstract: Background Stable isotope analysis is increasingly being utilised across broad areas of ecology and biology. Key to much of this work is the use of mixing models to estimate the proportion of sources contributing to a mixture such as in diet estimation. Methodology By accurately reflecting natural variation and uncertainty to generate robust probability estimates of source proportions, the application of Bayesian methods to stable isotope mixing models promises to enable researchers to address an array of new questions, and approach current questions with greater insight and honesty. Conclusions We outline a framework that builds on recently published Bayesian isotopic mixing models and present a new open source R package, SIAR. The formulation in R will allow for continued and rapid development of this core model into an all-encompassing single analysis suite for stable isotope research.

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Abstract: Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Abstract: By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

The Impact of Conservation on the Status of the World’s Vertebrates

Abstract: Using data for 25,780 species categorized on the International Union for Conservation of Nature Red List, we present an assessment of the status of the world's vertebrates. One-fifth of species are classified as Threatened, and we show that this figure is increasing: On average, 52 species of mammals, birds, and amphibians move one category closer to extinction each year. However, this overall pattern conceals the impact of conservation successes, and we show that the rate of deterioration would have been at least one-fifth again as much in the absence of these. Nonetheless, current conservation efforts remain insufficient to offset the main drivers of biodiversity loss in these groups: agricultural expansion, logging, overexploitation, and invasive alien species.

Genome-wide meta-analyses identify multiple loci associated with smoking behavior

Abstract: Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.

The impact of global warming on the tropical Pacific Ocean and El Nino

Abstract: The El Nino-Southern Oscillation (ENSO) is a naturally occurring fluctuation that originates in the tropical Pacific region and affects ecosystems, agriculture, freshwater supplies, hurricanes and other severe weather events worldwide. Under the influence of global warming, the mean climate of the Pacific region will probably undergo significant changes. The tropical easterly trade winds are expected to weaken; surface ocean temperatures are expected to warm fastest near the equator and more slowly farther away; the equatorial thermocline that marks the transition between the wind-mixed upper ocean and deeper layers is expected to shoal; and the temperature gradients across the thermocline are expected to become steeper. Year-to-year ENSO variability is controlled by a delicate balance of amplifying and damping feedbacks, and one or more of the physical processes that are responsible for determining the characteristics of ENSO will probably be modified by climate change. Therefore, despite considerable progress in our understanding of the impact of climate change on many of the processes that contribute to El Nino variability, it is not yet possible to say whether ENSO activity will be enhanced or damped, or if the frequency of events will change.

Multiple marker parallel tag environmental DNA sequencing reveals a highly complex eukaryotic community in marine anoxic water

Abstract: Sequencing of ribosomal DNA clone libraries amplified from environmental DNA has revolutionized our understanding of microbial eukaryote diversity and ecology. The results of these analyses have shown that protist groups are far more genetically heterogeneous than their morphological diversity suggests. However, the clone library approach is labour-intensive, relatively expensive, and methodologically biased. Therefore, even the most intensive rDNA library analyses have recovered only small samples of much larger assemblages, indicating that global environments harbour a vast array of unexplored biodiversity. High-throughput parallel tag 454 sequencing offers an unprecedented scale of sampling for molecular detection of microbial diversity. Here, we report a 454 protocol for sampling and characterizing assemblages of eukaryote microbes. We use this approach to sequence two SSU rDNA diversity markers-the variable V4 and V9 regions-from 10 L of anoxic Norwegian fjord water. We identified 38 116 V4 and 15 156 V9 unique sequences. Both markers detect a wide range of taxonomic groups but in both cases the diversity detected was dominated by dinoflagellates and close relatives. Long-tailed rank abundance curves suggest that the 454 sequencing approach provides improved access to rare genotypes. Most tags detected represent genotypes not currently in GenBank, although many are similar to database sequences. We suggest that current understanding of the ecological complexity of protist communities, genetic diversity, and global species richness are severely limited by the sequence data hitherto available, and we discuss the biological significance of this high amplicon diversity.

Coherent nonlinear optical response of graphene.

Abstract: We investigate the nonlinear optical properties of graphene flakes using four-wave mixing. The corresponding third-order optical susceptibility is found to be remarkably large and only weakly dependent on the wavelength in the near-infrared frequency range. The magnitude of the response is in good agreement with our calculations based on the nonlinear quantum response theory.

Ultrasensitive detection and characterization of biomolecules using superchiral fields

Abstract: The spectroscopic analysis of large biomolecules is important in applications such as biomedical diagnostics and pathogen detection, and spectroscopic techniques can detect such molecules at the nanogram level or lower. However, spectroscopic techniques have not been able to probe the structure of large biomolecules with similar levels of sensitivity. Here, we show that superchiral electromagnetic fields, generated by the optical excitation of plasmonic planar chiral metamaterials, are highly sensitive probes of chiral supramolecular structure. The differences in the effective refractive indices of chiral samples exposed to left- and right-handed superchiral fields are found to be up to 10(6) times greater than those observed in optical polarimetry measurements, thus allowing picogram quantities of adsorbed molecules to be characterized. The largest differences are observed for biomolecules that have chiral planar sheets, such as proteins with high β-sheet content, which suggests that this approach could form the basis for assaying technologies capable of detecting amyloid diseases and certain types of viruses.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Abstract: Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Abstract: Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.

Caribbean corals in crisis: record thermal stress, bleaching, and mortality in 2005.

Abstract: Background: The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. Methodology/Principal Findings: Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the iming and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. Conclusions/Significance: Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.

Clouds, filaments, and protostars: The Herschel Hi-GAL Milky Way

Abstract: We present the first results from the science demonstration phase for the Hi-GAL survey, the Herschel key program that will map the inner Galactic plane of the Milky Way in 5 bands. We outline our data reduction strategy and present some science highlights on the two observed 2° × 2° tiles approximately centered at l = 30° and l = 59°. The two regions are extremely rich in intense and highly structured extended emission which shows a widespread organization in filaments. Source SEDs can be built for hundreds of objects in the two fields, and physical parameters can be extracted, for a good fraction of them where the distance could be estimated. The compact sources (which we will call cores' in the following) are found for the most part to be associated with the filaments, and the relationship to the local beam-averaged column density of the filament itself shows that a core seems to appear when a threshold around AV ~ 1 is exceeded for the regions in the l = 59° field; a AV value between 5 and 10 is found for the l = 30° field, likely due to the relatively higher distances of the sources. This outlines an exciting scenario where diffuse clouds first collapse into filaments, which later fragment to cores where the column density has reached a critical level. In spite of core L/M ratios being well in excess of a few for many sources, we find core surface densities between 0.03 and 0.5 g cm-2. Our results are in good agreement with recent MHD numerical simulations of filaments forming from large-scale converging flows.

Robust adaptation to climate change

Abstract: This is the peer reviewed version of the following article: WILBY, R.L. and DESSAI, S., 2010. Robust adaptation to climate change. Weather, 65 (7), pp.180-185, which has been published in final form at https://doi.org/10.1002/wea.543. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

Genome expansion and gene loss in powdery mildew fungi reveal tradeoffs in extreme parasitism

Abstract: Powdery mildews are phytopathogens whose growth and reproduction are entirely dependent on living plant cells. The molecular basis of this life-style, obligate biotrophy, remains unknown. We present the genome analysis of barley powdery mildew, Blumeria graminis f.sp. hordei (Blumeria), as well as a comparison with the analysis of two powdery mildews pathogenic on dicotyledonous plants. These genomes display massive retrotransposon proliferation, genome-size expansion, and gene losses. The missing genes encode enzymes of primary and secondary metabolism, carbohydrate-active enzymes, and transporters, probably reflecting their redundancy in an exclusively biotrophic life-style. Among the 248 candidate effectors of pathogenesis identified in the Blumeria genome, very few (less than 10) define a core set conserved in all three mildews, suggesting that most effectors represent species-specific adaptations.

The New Psychology of Leadership: Identity, Influence and Power

Abstract: According to John Adair, the most important word in the leader's vocabulary is "we" and the least important word is "I". But if this is true, it raises one important question: why do psychological analyses of leadership always focus on the leader as an individual - as the great "I"? One answer is that theorists and practitioners have never properly understood the psychology of "we-ness". This book fills this gap by presenting a new psychology of leadership that is the result of two decades of research inspired by social identity and self-categorization theories. The book argues that to succeed, leaders need to create, champion, and embed a group identity in order to cultivate an understanding of 'us' of which they themselves are representative. It also shows how, by doing this, they can make a material difference to the groups, organizations, and societies that they lead. Written in an accessible and engaging style, the book examines a range of central theoretical and practical issues, including the nature of group identity, the basis of authority and legitimacy, the dynamics of justice and fairness, the determinants of followership and charisma, and the practice and politics of leadership. The book will appeal to academics, practitioners and students in social and organizational psychology, sociology, political science and anyone interested in leadership, influence and power.

Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

Abstract: Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2- h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).

The ABC of physical activity for health: A consensus statement from the British Association of Sport and Exercise Sciences

Abstract: Our understanding of the relationship between physical activity and health is constantly evolving. Therefore, the British Association of Sport and Exercise Sciences convened a panel of experts to review the literature and produce guidelines that health professionals might use. In the ABC of Physical Activity for Health, A is for All healthy adults, B is for Beginners, and C is for Conditioned individuals. All healthy adults aged 18-65 years should aim to take part in at least 150 min of moderate-intensity aerobic activity each week, or at least 75 min of vigorous-intensity aerobic activity per week, or equivalent combinations of moderate- and vigorous-intensity activities. Moderate-intensity activities are those in which heart rate and breathing are raised, but it is possible to speak comfortably. Vigorous-intensity activities are those in which heart rate is higher, breathing is heavier, and conversation is harder. Aerobic activities should be undertaken in bouts of at least 10 min and, ideally, should be performed on five or more days a week. All healthy adults should also perform muscle-strengthening activities on two or more days a week. Weight training, circuit classes, yoga, and other muscle-strengthening activities offer additional health benefits and may help older adults to maintain physical independence. Beginners should work steadily towards meeting the physical activity levels recommended for all healthy adults. Even small increases in activity will bring some health benefits in the early stages and it is important to set achievable goals that provide success, build confidence, and increase motivation. For example, a beginner might be asked to walk an extra 10 min every other day for several weeks to slowly reach the recommended levels of activity for all healthy adults. It is also critical that beginners find activities they enjoy and gain support in becoming more active from family and friends. Conditioned individuals who have met the physical activity levels recommended for all healthy adults for at least 6 months may obtain additional health benefits by engaging in 300 min or more of moderate-intensity aerobic activity per week, or 150 min or more of vigorous-intensity aerobic activity each week, or equivalent combinations of moderate- and vigorous-intensity aerobic activities. Adults who find it difficult to maintain a normal weight and adults with increased risk of cardiovascular disease or type 2 diabetes may in particular benefit from going beyond the levels of activity recommended for all healthy adults and gradually progressing towards meeting the recommendations for conditioned individuals. Physical activity is beneficial to health with or without weight loss, but adults who find it difficult to maintain a normal weight should probably be encouraged to reduce energy intake and minimize time spent in sedentary behaviours to prevent further weight gain. Children and young people aged 5-16 years should accumulate at least 60 min of moderate-to-vigorous-intensity aerobic activity per day, including vigorous-intensity aerobic activities that improve bone density and muscle strength.

Update on CO2 emissions

Abstract: Emissions of CO2 are the main contributor to anthropogenic climate change. Here we present updated information on their present and near-future estimates. We calculate that global CO2 emissions from fossil fuel burning decreased by 1.3% in 2009 owing to the global financial and economic crisis that started in 2008; this is half the decrease anticipated a year ago1. If economic growth proceeds as expected2, emissions are projected to increase by more than 3% in 2010, approaching the high emissions growth rates that were observed from 2000 to 20081, 3, 4. We estimate that recent CO2 emissions from deforestation and other land-use changes (LUCs) have declined compared with the 1990s, primarily because of reduced rates of deforestation in the tropics5 and a smaller contribution owing to forest regrowth elsewhere.

A review of methods for leakage management in pipe networks

Abstract: Leakage in water distribution systems is an important issue which is affecting water companies and their customers worldwide. It is therefore no surprise that it has attracted a lot of attention by both practitioners and researchers over the past years. Most of the leakage management related methods developed so far can be broadly classified as follows: (1) leakage assessment methods which are focusing on quantifying the amount of water lost; (2) leakage detection methods which are primarily concerned with the detection of leakage hotspots and (3) leakage control models which are focused on the effective control of current and future leakage levels. This paper provides a comprehensive review of the above methods with the objective to identify the current state-of-the-art in the field and to then make recommendations for future work. The review ends with the main conclusion that despite all the advancements made in the past, there is still a lot of scope and need for further work, especially in area of rea...

State of the Art for Genetic Algorithms and Beyond in Water Resources Planning and Management

Abstract: During the last two decades, the water resources planning and management profession has seen a dramatic increase in the development and application of various types of evolutionary algorithms (EAs). This observation is especially true for application of genetic algorithms, arguably the most popular of the several types of EAs. Generally speaking, EAs repeatedly prove to be flexible and powerful tools in solving an array of complex water resources problems. This paper provides a comprehensive review of state-of-the-art methods and their applications in the field of water resources planning and management. A primary goal in this ASCE Task Committee effort is to identify in an organized fashion some of the seminal contributions of EAs in the areas of water distribution systems, urban drainage and sewer systems, water supply and wastewater treatment, hydrologic and fluvial modeling, groundwater systems, and parameter identification. The paper also identifies major challenges and opportunities for the future, ...

Maturity-onset diabetes of the young (MODY): how many cases are we missing?

Abstract: Aims/hypothesis Maturity-onset diabetes of the young is frequently misdiagnosed as type 1 or type 2 diabetes. A correct diagnosis of MODY is important for determining treatment, but can only be confirmed by molecular genetic testing. We aimed to compare the regional distribution of confirmed MODY cases in the UK and to estimate the minimum prevalence. Methods UK referrals for genetic testing in 2,072 probands and 1,280 relatives between 1996 and 2009 were examined by region, country and test result. Referral rate and prevalence were calculated using UK Census 2001 figures. Results MODY was confirmed in 1,177 (35%) patients, with HNF1A (52%) and GCK mutations (32%) being most frequent in probands confirmed with MODY. There was considerable regional variation in proband referral rates (from 50 per million for South West England and Scotland) and patients diagnosed with MODY (5.3 per million in Northern Ireland, 48.9 per million in South West England). Referral rates and confirmed cases were highly correlated (r=0.96, p 80% of MODY is not diagnosed by molecular testing. The marked regional variation in the prevalence of confirmed MODY directly results from differences in referral rates. This could reflect variation in awareness of MODY or unequal access to genetic testing. Increased referral for diagnostic testing is required if the majority of MODY patients are to have the genetic diagnosis necessary for optimal treatment.

Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans

Abstract: The purpose of this study was to elucidate the mechanistic bases for the reported reduction in the O2 cost of exercise following short-term dietary nitrate (NO3−) supplementation. In a randomized, ...

Pharmaceuticals in the aquatic environment: a critical review of the evidence for health effects in fish.

Abstract: The authors review the current data on the presence and reported biological effects in fish of some of the most commonly detected pharmaceuticals in the aquatic environment; namely nonsteroidal anti-inflammatory drugs (NSAIDs), fibrates, β-blockers, selective serotonin reuptake inhibitors (SSRIs), azoles, and antibioticsReported biological effects in fish in the laboratory have often been shown to be in accordance with known effects of pharmaceuticals in mammalsWater concentrations at which such effects have been reported, however, are generally, between μg L −1 and mg L −1 , typically at least 1 order of magnitude higher than concentrations normally found in surface waters (ng L −1 )� There are exceptions to this, however, as for the case of synthetic oestrogens, which can induce biological effects in the low ng L −1 rangeAlthough generally effect levels for pharmaceuticals are higher than those found in the environment, the risks to wild fish populations have not been thoroughly characterised, and there has been a lack of consideration given to the likely chronic nature of the exposures, or the potential for mixture effectsAs global consumption of pharmaceuticals rises, an inevitable consequence is an increased level of contamination of surface and ground waters with these biologically active drugs, and thus in turn a greater potential for adverse effects in aquatic wildlife �

Global research priorities for sea turtles: informing management and conservation in the 21st century

Abstract: Over the past 3 decades, the status of sea turtles and the need for their protection to aid population recovery have increasingly captured the interest of government agencies, non-governmental organisations (NGOs) and the general public worldwide. This interest has been matched by increased research attention, focusing on a wide variety of topics relating to sea turtle biology and ecology, together with the interrelations of sea turtles with the physical and natural environments. Although sea turtles have been better studied than most other marine fauna, management actions and their evaluation are often hindered by the lack of data on turtle biology, human–turtle interactions, turtle population status and threats. In an effort to inform effective sea turtle conservation a list of priority research questions was assembled based on the opinions of 35 sea turtle researchers from 13 nations working in fields related to turtle biology and/or conservation. The combined experience of the contributing researchers spanned the globe as well as many relevant disciplines involved in conservation research. An initial list of more than 200 questions gathered from respondents was condensed into 20 metaquestions and classified under 5 categories: reproductive biology, biogeography, population ecology, threats and conservation strategies.

Association of Urinary Bisphenol A Concentration with Heart Disease: Evidence from NHANES 2003/06

Abstract: Background Bisphenol A (BPA) is a high production volume chemical widely used in food and drinks packaging. Associations have previously been reported between urinary BPA concentrations and heart disease, diabetes and liver enzymes in adult participants of the National Health and Nutrition Examination Survey (NHANES) 2003/04. We aimed to estimate associations between urinary BPA concentrations and health measures in NHANES 2005/06 and in data pooled across collection years.