Factors associated with undergraduate marijuana use in

Summary To examine cigarette, alcohol and drug use among undergraduates in University College, Cork a precoded questionnaire was mailed to 1 in 7 (458) students, chosen systematically. The response rate was 97 per cent. Twenty-three per cent of males and 13 per cent of females have taken marijuana at least once. Student use of marijuana was significantly related to leisure money available, belief in a God, frequency of attendance at religious services, attitudes to marriage partner drinking and to misdemeanour considered most serious. It appears that peer group pressures as illustrated by friends' drug taking, siblings' drug taking, encouragement by friends to take drugs and faculty, had a greater influence on student marijuana use than family related factors. Current cigarette use, pattern of drinking behaviour, use of other drugs and attitude to future marijuana use also had significant associations with marihuana-related behaviour

The Origin of Solar Activity in the Tachocline

Solar active regions, produced by the emergence of tubes of strong magnetic field in the photosphere, are restricted to within 35 degrees of the solar equator. The nature of the dynamo processes that create and renew these fields, and are therefore responsible for solar magnetic phenomena, are not well understood. We analyze the magneto-rotational stability of the solar tachocline for general field geometry. This thin region of strong radial and latitudinal differential rotation, between the radiative and convective zones, is unstable at latitudes above 37 degrees, yet is stable closer to the equator. We propose that small-scale magneto-rotational turbulence prevents coherent magnetic dynamo action in the tachocline except in the vicinity of the equator, thus explaining the latitudinal restriction of active regions. Tying the magnetic dynamo to the tachocline elucidates the physical conditions and processes relevant to solar magnetism.Comment: 10 pages, 1 figure, accepted for publication in ApJ

Differentiating dark energy and modified gravity with galaxy redshift surveys

The observed cosmic acceleration today could be due to an unknown energy component (dark energy), or a modification to general relativity (modified gravity). If dark energy models and modified gravity models are required to predict the same cosmic expansion history H(z), they will predict different growth rate for cosmic large scale structure, f_g(z)=d\ln \delta/d\ln a (\delta=(\rho_m-\bar{\rho_m})/\bar{\rho_m}), a is the cosmic scale factor). If gravity is not modified, the measured H(z) leads to a unique prediction for f_g(z), f_g^H(z). Comparing f_g^H(z) with the measured f_g(z) provides a transparent and straightforward test of gravity. We show that a simple \chi^2 test provides a general figure-of-merit for our ability to distinguish between dark energy and modified gravity given the measured H(z) and f_g(z). We study a magnitude-limited NIR galaxy redshift survey covering >10,000 (deg)^2 and the redshift range of 0.5<z<2. The resultant data can be divided into 7 redshift bins, and yield the measurement of H(z) to the accuracy of 1-2% via baryon acoustic oscillation measurements, and f_g(z) to the accuracy of a few percent via the measurement of redshift space distortions and the bias factor which describes how light traces mass. We find that if the H(z) data are fit by both a DGP gravity model and an equivalent dark energy model that predict the same expansion history, a survey area of 11,931 (deg)^2 is required to rule out the DGP gravity model at the 99.99% confidence level. It is feasible for such a galaxy redshift survey to be carried out by the next generation space missions from NASA and ESA, and it will revolutionize our understanding of the universe by differentiating between dark energy and modified gravity.Comment: 6 pages, 2 color figures. Expanded version accepted by JCA

Interatrial block in patients with obstructive sleep apnea

Background: Obstructive sleep apnea (OSA) is a common disorder that affects 5% of the adult North American population. It is associated with atrial arrhythmias and stroke. The mechanisms of this association remain unclear. The aim to the study was to identify the factors associated with interatrial block (IAB) among patients with OSA. Methods: Patients referred for polysomnography were studied. Sleep apnea severity (apnea-hypopnea index [AHI]) was measured in each subject. 12-lead ECGs were scanned and amplified (× 10); P-wave duration and dispersion were measured using a semi-automatic caliper. IAB was defined as a P-wave duration &#8805; 120 ms. Results: Data from 180 consecutive patients was examined. Moderate-severe OSA (mean AHI = 56.2 &#177; 27.9) was present in 144 (OSA group). The remaining 36 had mild or no OSA (mean AHI = 5.6 &#177; 3.6) and were used as controls. Age distribution between the groups did not differ and there were more males in the OSA group (69.4% vs 47.2%, p = 0.01). Obesity (78.5% vs 39.4%, p < 0.001) and hypertension (51.4% vs 27.8%, p < 0.01) were more prevalent in the OSA group. IAB was more prevalent in patients with moderate-severe OSA (34.7% OSA vs 0% controls, p 30 were independent predictors of maximum P-wave duration (p = 0.001 and p < 0.001, respectively). P-wave dispersion was significantly higher in the severe OSA group (14.6 &#177; 7.5 for OSA, 8.9 &#177; 3.1 controls, p < 0.001). Conclusions: Older age and moderate-severe OSA are predictors of IAB. P-wave dispersion is increased in patients with moderate-severe OSA. This may partly explain the high prevalence of atrial arrhythmias in patients with OSA. (Cardiol J 2011; 18, 2: 171-175

Penetrance of HNPCC-related cancers in a retrolective cohort of 12 large Newfoundland families carrying a MSH2 founder mutation: an evaluation using modified segregation models

<p>Abstract</p> <p>Background</p> <p>Accurate risk (penetrance) estimates for associated phenotypes in carriers of a major disease gene are important for genetic counselling of at-risk individuals. Population-specific estimates of penetrance are often needed as well. Families ascertained from high-risk disease clinics provide substantial data to estimate penetrance of a disease gene, but these estimates must be adjusted for possible specific sources of bias.</p> <p>Methods</p> <p>A cohort of 12 independently ascertained HNPCC families harbouring a founder MSH2 mutation was identified from a cancer genetics clinic in St. John's, Newfoundland, Canada. Carrier status was known for 247 family members but phenotype information on up to 85 additional relatives with unknown carrier status was available; using modified segregation models these additional individuals could be included in the analyses. Three HNPCC-related phenotypes were evaluated as age at diagnosis of: any HNPCC cancer (first cancer), colorectal cancer (CRC), and endometrial cancer (EC) for females.</p> <p>Results</p> <p>Lifetime (age 70) risk estimates for male and female carriers were similar for developing any HNPCC cancer (Males = 98.2%, 95% Confidence Interval (CI) = (93.8%, 99.9%); Females = 92.8%, 95% CI = (82.4%, 99.1%)) but female carriers experienced substantially reduced lifetime risk for developing CRC compared to male carriers (Females = 38.9%, 95% CI = (24.2%, 62.1%); Males = 84.5%, 95% CI = (67.3%, 91.3%)). Female non-carriers had very low lifetime risk for these two outcomes while male non-carriers had lifetime risks intermediate to the female carriers and non-carriers. Female carriers had a lifetime risk of developing EC of 82.4%. Relative risks for developing any HNPCC cancer (carriers relative to non-carriers) were substantially greater for females compared to their male counterparts (Females = 54.8, 95%CI = (4.4, 379.8); Males = 9.7, 95% CI = (0.3, 23.8)). Relative risks for developing CRC at age 70 were substantially greater for females compared to their male counterparts (Females = 23.7, 95%CI = (5.6, 137.9); Males = 6.8%, 95% CI = (2.3, 66.2)). However, the risk of developing CRC decreased with age among both genders.</p> <p>Conclusion</p> <p>The proposed modified segregation-based models used to estimate age-specific risks for HNPCC phenotypes can reduce bias due to ascertainment and missing genotype information as well as provide estimates of absolute and relative risks.</p

On the compatibility of a flux transport dynamo with a fast tachocline scenario

The compatibility of the fast tachocline scenario with a flux transport dynamo model is explored. We employ a flux transport dynamo model coupled with simple feedback formulae relating the thickness of the tachocline to the amplitude of the magnetic field or to the Maxwell stress. The dynamo model is found to be robust against the nonlinearity introduced by this simplified fast tachocline mechanism. Solar-like butterfly diagrams are found to persist and, even without any parameter fitting, the overall thickness of the tachocline is well within the range admitted by helioseismic constraints. In the most realistic case of a time and latitude dependent tachocline thickness linked to the value of the Maxwell stress, both the thickness and its latitude dependence are in excellent agreement with seismic results. In the nonparametric models, cycle related temporal variations in tachocline thickness are somewhat larger than admitted by helioseismic constraints; we find, however, that introducing a further parameter into our feedback formula readily allows further fine tuning of the thickness variations.Comment: Accepted in Solar Physic

In silico assessment of potential druggable pockets on the surface of α1-Antitrypsin conformers

The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α1-antitrypsin (A1AT). Pathological mutations disturb the conformational landscape of A1AT, triggering polymerisation that leads to emphysema and hepatic cirrhosis. Computational screens for small molecule inhibitors of polymerisation have generally focused on one major druggable site visible in all crystal structures of native A1AT. In an alternative approach, we scan all surface clefts observed in crystal structures of A1AT and in 100 computationally produced conformers, mimicking the native solution ensemble. We assess the persistence, variability and druggability of these pockets. Finally, we employ molecular docking using publicly available libraries of small molecules to explore scaffold preferences for each site. Our approach identifies a number of novel target sites for drug design. In particular one transient site shows favourable characteristics for druggability due to high enclosure and hydrophobicity. Hits against this and other druggable sites achieve docking scores corresponding to a Kd in the µM–nM range, comparing favourably with a recently identified promising lead. Preliminary ThermoFluor studies support the docking predictions. In conclusion, our strategy shows considerable promise compared with the conventional single pocket/single conformer approach to in silico screening. Our best-scoring ligands warrant further experimental investigation

An Anti-Glitch in a Magnetar

Magnetars are neutron stars showing dramatic X-ray and soft $\gamma$-ray outbursting behaviour that is thought to be powered by intense internal magnetic fields. Like conventional young neutron stars in the form of radio pulsars, magnetars exhibit "glitches" during which angular momentum is believed to be transferred between the solid outer crust and the superfluid component of the inner crust. Hitherto, the several hundred observed glitches in radio pulsars and magnetars have involved a sudden spin-up of the star, due presumably to the interior superfluid rotating faster than the crust. Here we report on X-ray timing observations of the magnetar 1E 2259+586 which we show exhibited a clear "anti-glitch" -- a sudden spin down. We show that this event, like some previous magnetar spin-up glitches, was accompanied by multiple X-ray radiative changes and a significant spin-down rate change. This event, if of origin internal to the star, is unpredicted in models of neutron star spin-down and is suggestive of differential rotation in the neutron star, further supporting the need for a rethinking of glitch theory for all neutron stars

Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models

Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions