Smoke-free legislation and hospitalizations for childhood asthma

<b>BACKGROUND:</b> Previous studies have shown that after the adoption of comprehensive smoke-free legislation, there is a reduction in respiratory symptoms among workers in bars. However, it is not known whether respiratory disease is also reduced among people who do not have occupational exposure to environmental tobacco smoke. The aim of our study was to determine whether the ban on smoking in public places in Scotland, which was initiated in March 2006, influenced the rate of hospital admissions for childhood asthma.<br></br> <b>METHODS:</b> Routine hospital administrative data were used to identify all hospital admissions for asthma in Scotland from January 2000 through October 2009 among children younger than 15 years of age. A negative binomial regression model was fitted, with adjustment for age group, sex, quintile of socioeconomic status, urban or rural residence, month, and year. Tests for interactions were also performed. <br></br> <b>RESULTS:</b> Before the legislation was implemented, admissions for asthma were increasing at a mean rate of 5.2% per year (95% confidence interval [CI], 3.9 to 6.6). After implementation of the legislation, there was a mean reduction in the rate of admissions of 18.2% per year relative to the rate on March 26, 2006 (95% CI, 14.7 to 21.8; P<0.001). The reduction was apparent among both preschool and school-age children. There were no significant interactions between hospital admissions for asthma and age group, sex, urban or rural residence, region, or quintile of socioeconomic status. <b>CONCLUSIONS:</b> In Scotland, passage of smoke-free legislation in 2006 was associated with a subsequent reduction in the rate of respiratory disease in populations other than those with occupational exposure to environmental tobacco smoke. (Funded by NHS Health Scotland.

A few things we do not know about stars and model atmospheres

We list a few things that we do not understand about stars and that most people ignore. These are all hard problems. We can learn more cosmology by working on them to reduce the systematic errors they introduce than by trying to derive cosmological results that are highly uncertain.Comment: 12 pages. Presented at the conference, The Link between Stars and Cosmology, 26-30 March, 2001, Puerto Vallarta, Mexico. To be published by Kluwer, eds. M. Chavez, A. Bressan, A. Buzzoni, and D. Mayy

Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.

Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy. Incoming peptides are recognized according to the global stability of the final pMHC-I product and anneal in a native-like conformation to be edited by TAPBPR. Our results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. These results suggest a similar mechanism for the function of tapasin in the peptide-loading complex

Genotyping faecal samples of Bengal tiger Panthera tigris tigris for population estimation: A pilot study

BACKGROUND: Bengal tiger Panthera tigris tigris the National Animal of India, is an endangered species. Estimating populations for such species is the main objective for designing conservation measures and for evaluating those that are already in place. Due to the tiger's cryptic and secretive behaviour, it is not possible to enumerate and monitor its populations through direct observations; instead indirect methods have always been used for studying tigers in the wild. DNA methods based on non-invasive sampling have not been attempted so far for tiger population studies in India. We describe here a pilot study using DNA extracted from faecal samples of tigers for the purpose of population estimation. RESULTS: In this study, PCR primers were developed based on tiger-specific variations in the mitochondrial cytochrome b for reliably identifying tiger faecal samples from those of sympatric carnivores. Microsatellite markers were developed for the identification of individual tigers with a sibling Probability of Identity of 0.005 that can distinguish even closely related individuals with 99.9% certainty. The effectiveness of using field-collected tiger faecal samples for DNA analysis was evaluated by sampling, identification and subsequently genotyping samples from two protected areas in southern India. CONCLUSION: Our results demonstrate the feasibility of using tiger faecal matter as a potential source of DNA for population estimation of tigers in protected areas in India in addition to the methods currently in use

Mechanisms of ring chromosome formation, ring instability and clinical consequences

<p>Abstract</p> <p>Background</p> <p>The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients.</p> <p>Methods</p> <p>Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification) and FISH (Fluorescent <it>in situ </it>Hybridization).</p> <p>Results</p> <p>The ring chromosomes of patients I to XIV were determined to be, respectively: r(3)(p26.1q29), r(4)(p16.3q35.2), r(10)(p15.3q26.2), r(10)(p15.3q26.13), r(13)(p13q31.1), r(13)(p13q34), r(14)(p13q32.33), r(15)(p13q26.2), r(18)(p11.32q22.2), r(18)(p11.32q21.33), r(18)(p11.21q23), r(22)(p13q13.33), r(22)(p13q13.2), and r(22)(p13q13.2). These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion (patients IV, VIII, IX, XI, XIII and XIV); a break in one chromosome arm followed by fusion with the subtelomeric region of the other (patients I and II); a break in one chromosome arm followed by fusion with the opposite telomeric region (patients III and X); fusion of two subtelomeric regions (patient VII); and telomere-telomere fusion (patient XII). Thus, the r(14) and one r(22) can be considered complete rings, since there was no loss of relevant genetic material. Two patients (V and VI) with r(13) showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes (II, XIII and XIV).</p> <p>Conclusions</p> <p>We concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r(14) and r(22).</p

Distinguishing the Impacts of Inadequate Prey and Vessel Traffic on an Endangered Killer Whale (Orcinus orca) Population

Managing endangered species often involves evaluating the relative impacts of multiple anthropogenic and ecological pressures. This challenge is particularly formidable for cetaceans, which spend the majority of their time underwater. Noninvasive physiological approaches can be especially informative in this regard. We used a combination of fecal thyroid (T3) and glucocorticoid (GC) hormone measures to assess two threats influencing the endangered southern resident killer whales (SRKW; Orcinus orca) that frequent the inland waters of British Columbia, Canada and Washington, U.S.A. Glucocorticoids increase in response to nutritional and psychological stress, whereas thyroid hormone declines in response to nutritional stress but is unaffected by psychological stress. The inadequate prey hypothesis argues that the killer whales have become prey limited due to reductions of their dominant prey, Chinook salmon (Oncorhynchus tshawytscha). The vessel impact hypothesis argues that high numbers of vessels in close proximity to the whales cause disturbance via psychological stress and/or impaired foraging ability. The GC and T3 measures supported the inadequate prey hypothesis. In particular, GC concentrations were negatively correlated with short-term changes in prey availability. Whereas, T3 concentrations varied by date and year in a manner that corresponded with more long-term prey availability. Physiological correlations with prey overshadowed any impacts of vessels since GCs were lowest during the peak in vessel abundance, which also coincided with the peak in salmon availability. Our results suggest that identification and recovery of strategic salmon populations in the SRKW diet are important to effectively promote SRKW recovery

Testing for Hardy–Weinberg equilibrium at biallelic genetic markers on the X chromosome

Testing genetic markers for Hardy–Weinberg equilibrium (HWE) is an important tool for detecting genotyping errors in large-scale genotyping studies. For markers at the X chromosome, typically the ¿2 or exact test is applied to the females only, and the hemizygous males are considered to be uninformative. In this paper we show that the males are relevant, because a difference in allele frequency between males and females may indicate HWE not to hold. The testing of markers on the X chromosome has received little attention, and in this paper we lay down the foundation for testing biallelic X-chromosomal markers for HWE. We develop four frequentist statistical test procedures for X-linked markers that take both males and females into account: the ¿2 test, likelihood ratio test, exact test and permutation test. Exact tests that include males are shown to have a better Type I error rate. Empirical data from the GENEVA project on venous thromboembolism is used to illustrate the proposed tests. Results obtained with the new tests differ substantially from tests that are based on female genotype counts only. The new tests detect differences in allele frequencies and seem able to uncover additional genotyping error that would have gone unnoticed in HWE tests based on females onlyPeer ReviewedPostprint (published version

A bayesian test for Hardy-Weinberg equilibrium of bi-allelic X-chromosomal markers

The X chromosome is a relatively large chromosome, harboring a lot of genetic information. Much of the statistical analysis of X-chromosomal information is complicated by the fact that males only have one copy. Recently, frequentist statistical tests for Hardy–Weinberg equilibrium have been proposed specifically for dealing with markers on the X chromosome. Bayesian test procedures for Hardy–Weinberg equilibrium for the autosomes have been described, but Bayesian work on the X chromosome in this context is lacking. This paper gives the first Bayesian approach for testing Hardy–Weinberg equilibrium with biallelic markers at the X chromosome. Marginal and joint posterior distributions for the inbreeding coefficient in females and the male to female allele frequency ratio are computed, and used for statistical inference. The paper gives a detailed account of the proposed Bayesian test, and illustrates it with data from the 1000 Genomes project. In that implementation, a novel approach to tackle multiple testing from a Bayesian perspective through posterior predictive checks is used.Peer ReviewedPostprint (author's final draft