Exploration of Chronic Kidney Disease Prevalence Estimates Using New Measures of Kidney Function in the Health Survey for England

BackgroundChronic kidney disease (CKD) diagnosis relies on glomerular filtration rate (eGFR) estimation, traditionally using the creatinine-based Modification of Diet in Renal Disease (MDRD) equation. The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) equation performs better in estimating eGFR and predicting mortality and CKD progression risk. Cystatin C is an alternative glomerular filtration marker less influenced by muscle mass. CKD risk stratification is improved by combining creatinine eGFR with cystatin C and urinary albumin to creatinine ratio (uACR). We aimed to identify the impact of introducing CKDEPI and cystatin C on the estimated prevalence and risk stratification of CKD in England and to describe prevalence and associations of cystatin C.LimitationsCross sectional study, single eGFR measure, no measured (‘true’) GFR.ConclusionsIntroducing the CKDEPI equation and targeted cystatin C measurement reduces estimated CKD prevalence and improves risk stratification.     

Desperate Prawns: Drivers of Behavioural Innovation Vary across Social Contexts in Rock Pool Crustaceans

Innovative behaviour may allow animals to cope with changes in their environment. Innovative propensities are known to vary widely both between and within species, and a growing body of research has begun to examine the factors that drive individuals to innovate. Evidence suggests that individuals are commonly driven to innovate by necessity; for instance by hunger or because they are physically unable to outcompete others for access to resources. However, it is not known whether the factors that drive individuals to innovate are stable across contexts. We examined contextual variation in the drivers of innovation in rock pool prawns (Palaemon spp), invertebrates that face widely fluctuating environments and may, through the actions of tides and waves, find themselves isolated or in groups. Using two novel foraging tasks, we examined the effects of body size and hunger in prawns tested in solitary and group contexts. When tested alone, small prawns were significantly more likely to succeed in a spatial task, and faster to reach the food in a manipulation task, while hunger state had no effect. In contrast, size had no effect when prawns were tested in groups, but food-deprived individuals were disproportionately likely to innovate in both tasks. We suggest that contextual variation in the drivers of innovation is likely to be common in animals living in variable environments, and may best be understood by considering variation in the perception of relative risks and rewards under different conditions.     

SBOL Visual: A Graphical Language for Genetic Designs

Synthetic Biology Open Language (SBOL) Visual is a graphical standard for genetic engineering. It consists of symbols representing DNA subsequences, including regulatory elements and DNA assembly features. These symbols can be used to draw illustrations for communication and instruction, and as image assets for computer-aided design. SBOL Visual is a community standard, freely available for personal, academic, and commercial use (Creative Commons CC0 license). We provide prototypical symbol images that have been used in scientific publications and software tools. We encourage users to use and modify them freely, and to join the SBOL Visual community: http://www.sbolstandard.org/visual.     

Common Variation at 1q24.1 (ALDH9A1) Is a Potential Risk Factor for Renal Cancer

So far six susceptibility loci for renal cell carcinoma (RCC) have been discovered by genome-wide association studies (GWAS). To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background) with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs) and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA). A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (P _combined =2.30x10^-8). Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1). We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC) GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; P _combined =2.73x10^-5). While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation.     

Emergency Department Presentations following Tropical Cyclone Yasi

Introduction

Emergency departments see an increase in cases during cyclones. The aim of this study is to describe patient presentations to the Emergency Department (ED) of a tertiary level hospital (Townsville) following a tropical cyclone (Yasi). Specific areas of focus include changes in: patient demographics (age and gender), triage categories, and classification of diseases.

Methods

Data were extracted from the Townsville Hospitals ED information system (EDIS) for three periods in 2009, 2010 and 2011 to coincide with formation of Cyclone Yasi (31 January 2011) to six days after Yasi crossed the coast line (8 February 2012). The analysis explored the changes in ICD10-AM 4-character classification and presented at the Chapter level.

Results

There was a marked increase in the number of patients attending the ED during Yasi, particularly those aged over 65 years with a maximum daily attendance of 372 patients on 4 Feb 2011. The most marked increases were in: Triage categories - 4 and 5; and ICD categories - diseases of the skin and subcutaneous tissue (L00-L99), and factors influencing health care status (Z00-Z99). The most common diagnostic presentation across all years was injury (S00-T98).

Discussion

There was an increase in presentations to the ED of TTH, which peaked in the first 24 – 48 hours following the cyclone and returned to normal over a five-day period. The changes in presentations were mostly an amplification of normal attendance patterns with some altered areas of activity. Injury patterns are similar to overseas experience.     

Algae in Fish Feed: Performances and Fatty Acid Metabolism in Juvenile Atlantic Salmon

Algae are at the base of the aquatic food chain, producing the food resources that fish are adapted to consume. Previous studies have proven that the inclusion of small amounts (<10% of the diet) of algae in fish feed (aquafeed) resulted in positive effects in growth performance and feed utilisation efficiency. Marine algae have also been shown to possess functional activities, helping in the mediation of lipid metabolism, and therefore are increasingly studied in human and animal nutrition. The aim of this study was to assess the potentials of two commercially available algae derived products (dry algae meal), Verdemin (derived from Ulva ohnoi) and Rosamin (derived from diatom Entomoneis spp.) for their possible inclusion into diet of Atlantic Salmon (Salmo salar). Fish performances, feed efficiency, lipid metabolism and final product quality were assessed to investigated the potential of the two algae products (in isolation at two inclusion levels, 2.5% and 5%, or in combination), in experimental diets specifically formulated with low fish meal and fish oil content. The results indicate that inclusion of algae product Verdemin and Rosamin at level of 2.5 and 5.0% did not cause any major positive, nor negative, effect in Atlantic Salmon growth and feed efficiency. An increase in the omega-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) content in whole body of fish fed 5% Rosamin was observed.     

Modelling Future Coronary Heart Disease Mortality to 2030 in the British Isles

Objective

Despite rapid declines over the last two decades, coronary heart disease (CHD) mortality rates in the British Isles are still amongst the highest in Europe. This study uses a modelling approach to compare the potential impact of future risk factor scenarios relating to smoking and physical activity levels, dietary salt and saturated fat intakes on future CHD mortality in three countries: Northern Ireland (NI), Republic of Ireland (RoI) and Scotland.

Methods

CHD mortality models previously developed and validated in each country were extended to predict potential reductions in CHD mortality from 2010 (baseline year) to 2030. Risk factor trends data from recent surveys at baseline were used to model alternative future risk factor scenarios: Absolute decreases in (i) smoking prevalence and (ii) physical inactivity rates of up to 15% by 2030; relative decreases in (iii) dietary salt intake of up to 30% by 2030 and (iv) dietary saturated fat of up to 6% by 2030. Probabilistic sensitivity analyses were then conducted.

Results

Projected populations in 2030 were 1.3, 3.4 and 3.9 million in NI, RoI and Scotland respectively (adults aged 25–84). In 2030: assuming recent declining mortality trends continue: 15% absolute reductions in smoking could decrease CHD deaths by 5.8–7.2%. 15% absolute reductions in physical inactivity levels could decrease CHD deaths by 3.1–3.6%. Relative reductions in salt intake of 30% could decrease CHD deaths by 5.2–5.6% and a 6% reduction in saturated fat intake might decrease CHD deaths by some 7.8–9.0%. These projections remained stable under a wide range of sensitivity analyses.

Conclusions

Feasible reductions in four cardiovascular risk factors (already achieved elsewhere) could substantially reduce future coronary deaths. More aggressive polices are therefore needed in the British Isles to control tobacco, promote healthy food and increase physical activity.     

SEXUAL CONFLICT AND INTERACTING PHENOTYPES: A QUANTITATIVE GENETIC ANALYSIS OF FECUNDITY AND COPULA DURATION IN DROSOPHILA MELANOGASTER

Many reproductive traits that have evolved under sexual conflict may be influenced by both sexes. Investigation of the genetic architecture of such traits can yield important insight into their evolution, but this entails that the heritable component of variation is estimated for males and females—as an interacting phenotype. We address the lack of research in this area through an investigation of egg production and copula duration in the fruit fly, Drosophila melanogaster. Despite egg production rate being determined by both sexes, which may cause sexual conflict, an assessment of this trait as an interacting phenotype is lacking. It is currently unclear whether copula duration is determined by males and/or females. We found significant female, but not male, genetic variance for egg production rate that may indicate reduced potential for ongoing sexually antagonistic coevolution. In contrast, copula duration was determined by significant genetic variance in both sexes. We also identified genetic variation in egg retention among virgin females. Although previously identified in wild populations, it is unclear why this should be present in a laboratory stock. This study provides a novel insight into the shared genetic architecture of reproductive traits that are the subject of sexual conflict.     

Evidence that MEK1 positively promotes interhomologue double-strand break repair

During meiosis there is an imperative to create sufficient crossovers for homologue segregation. This can be achieved during repair of programmed DNA double-strand breaks (DSBs), which are biased towards using a homologue rather than sister chromatid as a repair template. Various proteins contribute to this bias, one of which is a meiosis specific kinase Mek1. It has been proposed that Mek1 establishes the bias by creating a barrier to sister chromatid repair, as distinct from enforcing strand invasion with the homologue. We looked for evidence that Mek1 positively stimulates strand invasion of the homologue. This was done by analysing repair of DSBs induced by the VMA1-derived endonuclease (VDE) and flanked by directly repeated sequences that can be used for intrachromatid single-strand annealing (SSA). SSA competes with interhomologue strand invasion significantly more successfully when Mek1 function is lost. We suggest the increase in intrachromosomal SSA reflects an opportunistic default repair pathway due to loss of a MEK1 stimulated bias for strand invasion of the homologous chromosome. Making use of an inhibitor sensitive mek1-as1 allele, we found that Mek1 function influences the repair pathway throughout the first4–5 h of meiosis. Perhaps reflecting a particular need to create bias for successful interhomologue events before chromosome pairing is complete.     

Stimulation of mitochondrial reactive oxygen species production by unesterified,unsaturated fatty acids in defective human spermatozoa

Male infertility is a relatively common condition affecting 1 in 20 men of reproductive age. The etiology of this condition is thought to involve the excessive generation of reactive oxygen species by human spermatozoa; however, the cause of this aberrant activity is unknown. In this study we demonstrate that defective human sperm populations are characterized by high cellular contents of both esterified and unesterified fatty acids and a decrease in the proportion of the total fatty acid pool made up by docosahexaenoic acid. The free unsaturated fatty acid content of these cells was positively correlated with the induction of mitochondrial superoxide generation (P < 0.001). This relationship was causal and mediated by the range of unesterified, unsaturated fatty acids that are present in human spermatozoa. Thus direct exposure of these cells to free unsaturated fatty acids stimulated mitochondrial superoxide generation and precipitated a loss of motility and an increase in oxidative DNA damage, two key attributes of male infertility. We conclude that defective human spermatozoa are characterized by an abnormally high content of fatty acids that, in their unesterified, unsaturated form, promote ROS generation by sperm mitochondria, creating a state of oxidative stress and a concomitant loss of functional competence.