Evidence of widespread selection on standing variation in Europe at height-associated SNPs.

Strong signatures of positive selection at newly arising genetic variants are well documented in humans(1-8), but this form of selection may not be widespread in recent human evolution(9). Because many human traits are highly polygenic and partly determined by common, ancient genetic variation, an alternative model for rapid genetic adaptation has been proposed: weak selection acting on many pre-existing (standing) genetic variants, or polygenic adaptation(10-12). By studying height, a classic polygenic trait, we demonstrate the first human signature of widespread selection on standing variation. We show that frequencies of alleles associated with increased height, both at known loci and genome wide, are systematically elevated in Northern Europeans compared with Southern Europeans (P < 4.3 × 10(-4)). This pattern mirrors intra-European height differences and is not confounded by ancestry or other ascertainment biases. The systematic frequency differences are consistent with the presence of widespread weak selection (selection coefficients ∼10(-3)-10(-5) per allele) rather than genetic drift alone (P < 10(-15))

Cost-impact study of rotavirus vaccination programme in Scotland

Aim: In July 2013, the Scottish Government introduced a rotavirus vaccination programme into the childhood immunisation schedule. The aim of this research was to estimate the cost impact of this programme. Methods: Data for rotavirus-related resource use were identified including laboratory reports, hospitalisations, attendances at Accident and Emergency Departments, general practice consultations, calls to the National Health Service telephone helpline and prescriptions for common rehydration treatments. We used an interrupted time series analysis approach to assess the impact on resource utilisation in all categories. Appropriate costs were added to the models and predicted pre and post vaccination mean annual costs were estimated. The cost of the vaccination programme was estimated using costs from the literature. Results: The vaccination programme was associated with a reduction in utilisation in all measured healthcare resource categories. These reductions were all statistically significant (at the 95% level) with p-values less than 0.001. Reductions ranged from 18% in calls to NHS24 to 73% in positive laboratory reports. The vaccination programme was associated with a reduction in annual healthcare resource costs of 38% (£595,000 per 100,000 infants under five years old) in our measured categories (including £495,000 from a reduction in hospital stays). The annual overall cost-impact of the rotavirus vaccination programme (the cost of delivering the programme minus the reduction in resource costs) was estimated at approximately £435,000 per 100,000 infants under 5 years old. Conclusion: The rotavirus vaccination programme was associated with a reduction in all measured categories of rotavirus-related resource use by infants under 5 years old

Evidence of Widespread Selection on Standing Variation in Europe at Height-Associated SNPs

Strong signatures of positive selection at newly arising genetic variants are well-documented in humans, but this form of selection may not be widespread in recent human evolution. Because many human traits are highly polygenic and partly determined by common, ancient genetic variation, an alternative model for rapid genetic adaptation has been proposed: weak selection acting on many pre-existing (standing) genetic variants, or polygenic adaptation. By studying height, a classic polygenic trait, we demonstrate the first human signature of widespread selection on standing variation. We show that frequencies of alleles associated with increased height, both at known loci and genome-wide, are systematically elevated in Northern Europeans compared with Southern Europeans $(p<4.3×10^{−4})$. This pattern mirrors intra-European height differences and is not confounded by ancestry or other ascertainment biases. The systematic frequency differences are consistent with the presence of widespread weak selection (selection coefficients $~10^{−3}–10^{−5}$ per allele) rather than genetic drift alone $(p<10^{−15})$

Magnetar outbursts: an observational review

Transient outbursts from magnetars have shown to be a key property of their emission, and one of the main way to discover new sources of this class. From the discovery of the first transient event around 2003, we now count about a dozen of outbursts, which increased the number of these strongly magnetic neutron stars by a third in six years. Magnetar outbursts might involve their multi-band emission resulting in an increased activity from radio to hard X-ray, usually with a soft X-ray flux increasing by a factor of 10-1000 with respect to the quiescent level. A connected X-ray spectral evolution is also often observed, with a spectral softening during the outburst decay. The flux decay times vary a lot from source to source, ranging from a few weeks to several years, as also the decay law which can be exponential-like, a power-law or even multiple power-laws can be required to model the flux decrease. We review here on the latest observational results on the multi-band emission of magnetars, and summarize one by one all the transient events which could be studied to date from these sources.Comment: 34 pages, 6 figures. Chapter of the Springer Book ASSP 7395 "High-energy emission from pulsars and their systems", proceeding of the Sant Cugat Forum on Astrophysics (12-16 April 2010). Review updated to January 201

Determinants of adults' intention to vaccinate against pandemic swine flu

This article has been made available through the Brunel Open Access Publishing Fund.This article has been made available through the Brunel Open Access Publishing Fund.Background: Vaccination is one of the cornerstones of controlling an influenza pandemic. To optimise vaccination rates in the general population, ways of identifying determinants that influence decisions to have or not to have a vaccination need to be understood. Therefore, this study aimed to predict intention to have a swine influenza vaccination in an adult population in the UK. An extension of the Theory of Planned Behaviour provided the theoretical framework for the study. Methods: Three hundred and sixty two adults from the UK, who were not in vaccination priority groups, completed either an online (n = 306) or pen and paper (n = 56) questionnaire. Data were collected from 30th October 2009, just after swine flu vaccination became available in the UK, and concluded on 31st December 2009. The main outcome of interest was future swine flu vaccination intentions. Results: The extended Theory of Planned Behaviour predicted 60% of adults’ intention to have a swine flu vaccination with attitude, subjective norm, perceived control, anticipating feelings of regret (the impact of missing a vaccination opportunity), intention to have a seasonal vaccine this year, one perceived barrier: “I cannot be bothered to get a swine flu vaccination” and two perceived benefits: “vaccination decreases my chance of getting swine flu or its complications” and “if I get vaccinated for swine flu, I will decrease the frequency of having to consult my doctor,” being significant predictors of intention. Black British were less likely to intend to have a vaccination compared to Asian or White respondents. Conclusions: Theoretical frameworks which identify determinants that influence decisions to have a pandemic influenza vaccination are useful. The implications of this research are discussed with a view to maximising any future pandemic influenza vaccination uptake using theoretically-driven applications.This article is available through the Brunel Open Access Publishing Fund

Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series

The largest kindred with inherited prion disease P102L, historically Gerstmann-Sträussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-Sträussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers

The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic, Cardiovascular, and Anthropometric Traits

PMCID: PMC3410907This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Curved Tails in Polymerization-Based Bacterial Motility

The curved actin ``comet-tail'' of the bacterium Listeria monocytogenes is a visually striking signature of actin polymerization-based motility. Similar actin tails are associated with Shigella flexneri, spotted-fever Rickettsiae, the Vaccinia virus, and vesicles and microspheres in related in vitro systems. We show that the torque required to produce the curvature in the tail can arise from randomly placed actin filaments pushing the bacterium or particle. We find that the curvature magnitude determines the number of actively pushing filaments, independent of viscosity and of the molecular details of force generation. The variation of the curvature with time can be used to infer the dynamics of actin filaments at the bacterial surface.Comment: 8 pages, 2 figures, Latex2