Is environmental radon gas associated with the incidence of neurodegenerative conditions? A retrospective study of multiple sclerosis in radon affected areas in England and Wales

To test whether an association exists between radon gas concentration in the home and increased multiple sclerosis (MS) incidence, a retrospective study was undertaken of MS incidence in known areas of raised domestic radon concentration in England and Wales, using The Health Improvement Network (THIN) clinical research database.The study population comprised 20,140,498 person-years of clinical monitoring (males: 10,056,628: 49.93%; females: 10,083,870: 50.07%), representing a mean annual population of 2.5 million individuals. To allow for the possible latency of MS initiation following exposure, data extraction was limited to patients with at least five years registration history with the same GP practice before first diagnosis. Patient records were allocated to one of nine radon concentration bands depending on the average radon level in their postcode sector.MS incidence was analysed by searching for patients with first MS diagnosis over the eight calendar years 2005-2012 inclusive. 1512 new MS cases were diagnosed, 1070 females, 442 males, equivalent to raw incidence rates of 7.51, 10.61 and 4.40 per 105person-years respectively, comparable to previously reported results. Of these new cases, 115 could be allocated to one of the radon bands representing high radon areas.Standardising to the UK 2010 population, excess relative risk (ERR) figures for MS were calculated for each radon band. Linear regression of ERR against mean band radon concentration shows a positive gradient of 0.22 per 100 Bq·m-3(R2= 0.25, p = 0.0961) when forced through the origin to represent a linear-no-threshold response. The null hypothesis falls inside the 95% confidence interval for the linear fit and therefore this fit is not statistically significant. We conclude that, despite THIN sampling around 5% of the population, insufficient data was available to confirm or refute the hypothesised association between MS incidence and radon concentration

Valuing Transgenic Cotton Technologies Using a Risk/Return Framework

Stochastic Efficiency with Respect to a Function (SERF) is used to rank transgenic cotton technology groups and place an upper and lower bound on their value. Yield and production data from replicated plot experiments are used to build cumulative distribution functions of returns for nontransgenic, Roundup Ready, Bollgard, and stacked gene cotton cultivars. Analysis of Arkansas data indicated that the stacked gene and Roundup Ready technologies would be preferred by a large number of risk neutral and risk averse producers as long as the costs of the technology and seed are below the lower bounds calculated in this manuscript.cotton, financial risk, market value, SERF, transgenic, Agribusiness, Crop Production/Industries, Risk and Uncertainty, Q12, Q16,

An assessment of the effectiveness of UK building regulations for new homes in Radon Affected Areas

Radon, a naturally occurring radioactive gas generated underground by radioactive decay of nuclides contained in certain types of rocks, can concentrate inside buildings, where it poses the second-largest risk factor for lung cancer, after smoking. The highest concentrations of domestic radon in the UK occur in the south-western counties of Devon and Cornwall, but certain areas in Northamptonshire and surrounding counties in the English Midlands also have high levels. It has been shown that it is possible both to reduce the radon concentrations in existing houses and to build new homes with appropriate protection. Since 1999, the UK's Building Regulations have specified that all new homes should be built with a combined radon-proof/damp-proof membrane plus, in Radon Affected Areas, a sump under the building. However, the building regulations do not require that the radon level is measured once the house is built and so there is little information on the effectiveness of these measures. Builders generally do not mention radon, and when asked, just confirm that their houses are built to current standards. To better understand the efficacy or otherwise of the currently mandated radon-protection measures, a cross-sectional investigation was carried out in 26 new housing developments in high-radon areas in Northamptonshire. In a targeted mail-shot, 1056 householders were invited to apply for a free radon test; 124 replied (11.7%). In total, 94 pairs of detectors were returned (70.1% of responders), of which two were spoiled, giving a total of 92 results. Following processing and seasonal correction, the arithmetic mean radon concentration in the target houses was 45% of the arithmetic mean radon concentration in existing houses in the postcode sectors where the houses were built and were approximately log-normally distributed. No results exceeded the UK Action Level of 200 Bq. m−3 but three were above the Target Level of 100 Bq. m−3. The results suggest that the radon-proof membranes in general ensure that radon concentrations in new homes constructed in accordance with the Building Regulations in Radon Affected Areas (RAAs) are satisfactorily low. However, there is a very small statistical probability that levels in a small number of homes will be close to or above the Action Level, particularly in areas of high radon potential. As a result, the Public Health England (PHE) recommendation for testing in the first year of occupation should be adopted as a legal requirement

Spiral-Induced Star Formation in the Outer Disks of Galaxies

The outer regions of galactic disks have received increased attention since ultraviolet observations with GALEX demonstrated that nearly 30% of galaxies have UV emission beyond their optical extents, indicating star formation activity. These galaxies have been termed extended UV (XUV) disks. Here, we address whether these observations contradict the gas surface density threshold for star formation inferred from Halpha radial profiles of galaxies. We run smoothed particle hydrodynamics simulations of isolated disk galaxies with fiducial star formation prescriptions and show that over-densities owing to the presence of spiral structure can induce star formation in extended gas disks. For direct comparison with observations, we use the 3-D radiative transfer code Sunrise to create simulated FUV and K_s band images. We find that galaxies classified as Type I XUV disks are a natural consequence of spiral patterns, but we are unable to reproduce Type II XUV disks. We also compare our results to studies of the Kennicutt-Schmidt relation in outer disks.Comment: Published in Ap

Low Frequency Variants in the Exons Only Encoding Isoform A of HNF1A Do Not Contribute to Susceptibility to Type 2 Diabetes

Background: There is considerable interest in the hypothesis that low frequency, intermediate penetrance variants contribute to the proportion of Type 2 Diabetes (T2D) susceptibility not attributable to the common variants uncovered through genome-wide association approaches. Genes previously implicated in monogenic and multifactorial forms of diabetes are obvious candidates in this respect. In this study, we focussed on exons 8-10 of the HNF1A gene since rare, penetrant mutations in these exons (which are only transcribed in selected HNF1A isoforms) are associated with a later age of diagnosis of Maturity onset diabetes of the young (MODY) than mutations in exons 1-7. The age of diagnosis in the subgroup of HNF1A-MODY individuals with exon 8-10 mutations overlaps with that of early multifactorial T2D, and we set out to test the hypothesis that these exons might also harbour low-frequency coding variants of intermediate penetrance that contribute to risk of multifactorial T2D. Methodology and principal findings: We performed targeted capillary resequencing of HNF1A exons 8-10 in 591 European T2D subjects enriched for genetic aetiology on the basis of an early age of diagnosis (≤ 45 years) and/or family history of T2D (≥ 1 affected sibling). PCR products were sequenced and compared to the published HNF1A sequence. We identified several variants (rs735396 [IVS9-24T>C], rs1169304 [IVS8+29T>C], c.1768+44C>T [IVS9+44C>T] and rd61953349 [c.1545G>A, p.T515T] but no novel non-synonymous coding variants were detected. Conclusions and significance: We conclude that low frequency, nonsynonymous coding variants in the terminal exons of HNF1A are unlikely to contribute to T2D-susceptibility in European samples. Nevertheless, the rationale for seeking low-frequency causal variants in genes known to contain rare, penetrant mutations remains strong and should motivate efforts to screen other genes in a similar fashion

The Formation of High Redshift Submillimeter Galaxies

We describe a model for the formation of \zsim 2 Submillimeter Galaxies (SMGs) which simultaneously accounts for both average and bright SMGs while providing a reasonable match to their mean observed spectral energy distributions (SEDs). By coupling hydrodynamic simulations of galaxy mergers with the high resolution 3D polychromatic radiative transfer code Sunrise, we find that a mass sequence of merger models which use observational constraints as physical input naturally yield objects which exhibit black hole, bulge, and H2 gas masses similar to those observed in SMGs. The dominant drivers behind the 850 micron flux are the masses of the merging galaxies and the stellar birthcloud covering fraction. The most luminous (S850 ~ 15 mJy) sources are recovered by ~10^13 Msun 1:1 major mergers with a birthcloud covering fraction close to unity, whereas more average SMGs ~5-7 mJy) may be formed in lower mass halos ~5x10^12 Msun. These models demonstrate the need for high spatial resolution hydrodynamic and radiative transfer simulations in matching both the most luminous sources as well as the full SEDs of SMGs. While these models suggest a natural formation mechanism for SMGs, they do not attempt to match cosmological statistics of galaxy populations; future efforts along this line will help ascertain the robustness of these models.Comment: MNRAS Accepted; Revised version includes expanded discussion of simulated radio properties of SMG

K+A Galaxies as the Aftermath of Gas-Rich Mergers: Simulating the Evolution of Galaxies as Seen by Spectroscopic Surveys

Models of poststarburst (or "K+A") galaxies are constructed by combining fully three-dimensional hydrodynamic simulations of galaxy mergers with radiative transfer calculations of dust attenuation. Spectral line catalogs are generated automatically from moderate-resolution optical spectra calculated as a function of merger progress in each of a large suite of simulations. The mass, gas fraction, orbital parameters, and mass ratio of the merging galaxies are varied systematically, showing that the lifetime and properties of the K+A phase are strong functions of merger scenario. K+A durations are generally less than ~0.1-0.3 Gyr, significantly shorter than the commonly assumed 1 Gyr, which is obtained only in rare cases, owing to a wide variation in star formation histories resulting from different orbital and progenitor configurations. Combined with empirical merger rates, the model lifetimes predict rapidly-rising K+A fractions as a function of redshift that are consistent with results of large spectroscopic surveys, resolving tension between the observed K+A abundance and that predicted when one assumes the K+A duration is the lifetime of A stars (~1 Gyr). The effects of dust attenuation, viewing angle, and aperture bias on our models are analyzed. In some cases, the K+A features are longer-lived and more pronounced when AGN feedback removes dust from the center, uncovering the young stars formed during the burst. In this picture, the K+A phase begins during or shortly after the bright starburst/AGN phase in violent mergers, and thus offers a unique opportunity to study the effects of quasar and star formation feedback on the gas reservoir and evolution of the remnant. Analytic fitting formulae are provided for the estimates of K+A incidence as a function of merger scenario.Comment: 26 pages, 13 figures; ApJ; minor changes to reflect accepted versio

Combining Information from Common Type 2 Diabetes Risk Polymorphisms Improves Disease Prediction

BACKGROUND: A limited number of studies have assessed the risk of common diseases when combining information from several predisposing polymorphisms. In most cases, individual polymorphisms only moderately increase risk (~20%), and they are thought to be unhelpful in assessing individuals' risk clinically. The value of analyzing multiple alleles simultaneously is not well studied. This is often because, for any given disease, very few common risk alleles have been confirmed. METHODS AND FINDINGS: Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been shown to predispose to type 2 diabetes mellitus across many large studies. Risk allele frequencies ranged from 0.30 to 0.88 in controls. To assess the combined effect of multiple susceptibility alleles, we genotyped these variants in a large case-control study (3,668 controls versus 2,409 cases). Individual allele odds ratios (ORs) ranged from 1.14 (95% confidence interval [CI], 1.05 to 1.23) to 1.48 (95% CI, 1.36 to 1.60). We found no evidence of gene-gene interaction, and the risks of multiple alleles were consistent with a multiplicative model. Each additional risk allele increased the odds of type 2 diabetes by 1.28 (95% CI, 1.21 to 1.35) times. Participants with all six risk alleles had an OR of 5.71 (95% CI, 1.15 to 28.3) compared to those with no risk alleles. The 8.1% of participants that were double-homozygous for the risk alleles at TCF7L2 and Pro12Ala had an OR of 3.16 (95% CI, 2.22 to 4.50), compared to 4.3% with no TCF7L2 risk alleles and either no or one Glu23Lys or Pro12Ala risk alleles. CONCLUSIONS: Combining information from several known common risk polymorphisms allows the identification of population subgroups with markedly differing risks of developing type 2 diabetes compared to those obtained using single polymorphisms. This approach may have a role in future preventative measures for common, polygenic diseases