Genetic variants predicting aerobic capacity response to training are also associated with skeletal muscle oxidative capacity in moderate-to-severe COPD.

Muscle oxidative capacity is a major determinant of maximum oxygen uptake (V̇O2max). V̇O2max predicts survival in humans. Muscle oxidative capacity is low in chronic obstructive pulmonary disease (COPD), and can be assessed from the muscle oxygen consumption recovery rate constant ( k) using near-infrared spectroscopy. We hypothesized that 11 SNPs previously associated with the increase in V̇O2max following exercise training, would correlate with k in 152 non-Hispanic White and African American smokers with and without COPD. Associations were adjusted for age, weight, FEV1%predicted, steps/day and principal components of genetic ancestry. No SNPs were significantly associated with k. rs2792022 within BTAF1 (β=0.130, p=0.053) and rs 24575771 within SLC22A3 (β=0.106, p=0.058) approached nominal significance. Case-control stratification identified 3 SNPs nominally associated with k in moderate-to-severe COPD (rs6481619 within SVIL β=0.152, p=0.013; BTAF1 β=0.196, p=0.046 and rs7386139 within DEPTOR β=0.159, p=0.047). These data support further study of the genomic contributions to skeletal muscle dysfunction in COPD

Dynamic walking features and improved walking performance in multiple sclerosis patients treated with fampridine (4-aminopyridine)

Background: Impaired walking capacity is a frequent confinement in Multiple Sclerosis (MS). Patients are affected by limitations in coordination, walking speed and the distance they may cover. Also abnormal dynamic walking patterns have been reported, involving continuous deceleration over time. Fampridine (4-aminopyridine), a potassium channel blocker, may improve walking in MS. The objective of the current study was to comprehensively examine dynamic walking characteristics and improved walking capacity in MS patients treated with fampridine. Methods: A sample of N = 35 MS patients (EDSS median: 4) underwent an electronic walking examination prior to (Time 1), and during treatment with fampridine (Time 2). Patients walked back and forth a distance of 25 ft for a maximum period of 6 min (6-minute 25-foot-walk). Besides the total distance covered, average speed on the 25-foot distance and on turns was determined separately for each test minute, at Time 1 and Time 2. Results: Prior to fampridine administration, 27/35 patients (77 %) were able to complete the entire 6 min of walking, while following the administration, 34/35 patients (97 %) managed to walk for 6 min. In this context, walking distance considerably increased and treatment was associated with faster walking and turning across all six test minutes (range of effect sizes: partial eta squared = .34-.72). Importantly, previously reported deceleration across test minutes was consistently observable at Time 1 and Time 2. Discussion: Fampridine administration is associated with improved walking speed and endurance. Regardless of a treatment effect of fampridine, the previously identified, abnormal dynamic walking feature, i.e. the linear decline in walking speed, may represent a robust feature. Conclusions: The dynamic walking feature might hence be considered as a candidate for a new outcome measure in clinical studies involving interventions other than symptomatic treatment, such as immune-modulating medication. Trial registration: DRKS00009228 (German Clinical Trials Register). Date obtained: 25.08.2015

A record-linkage study of the development of hepatocellular carcinoma in persons with hepatitis C infection in Scotland

We investigated trends in first time hospital admissions and deaths attributable to hepatocellular carcinoma (HCC) in a large population based cohort of 22 073 individuals diagnosed with hepatitis C viral (HCV) infection through laboratory testing in Scotland in 1991 2006. We identified new cases of HCC through record linkage to the national inpatient hospital discharge database and deaths registry. A total of 172 persons diagnosed with HCV were admitted to hospital or died with first time mention of HCC. Hepatocellular carcinoma incidence increased between 1996 and 2006 (average annual change of 6.1, 95% confidence interval (CI):0.9 11.6%, P¼0.021). The adjusted relative risk of HCC was greater for males (hazard ratio¼2.7, 95% CI: 1.7 4.2), for those aged 60 years or older (hazard ratio ¼2.7, 95% CI: 1.9 4.1) compared with 50 59 years, and for those with a previous alcohol related hospital admission (hazard ratio¼2.5, 95% CI: 1.7 3.7). The risk of individuals diagnosed with HCV developing HCC was greatlyincreased compared with the general Scottish population (standardised incidence ratio¼127, 95% CI: 102 156). Owing to the advancing age of the Scottish HCV diagnosed population, the annual number of HCC cases is projected to increase, with a consequent increasing burden on the public healthcare system

Smc5/6: a link between DNA repair and unidirectional replication?

Of the three structural maintenance of chromosome (SMC) complexes, two directly regulate chromosome dynamics. The third, Smc5/6, functions mainly in homologous recombination and in completing DNA replication. The literature suggests that Smc5/6 coordinates DNA repair, in part through post-translational modification of uncharacterized target proteins that can dictate their subcellular localization, and that Smc5/6 also functions to establish DNA-damage-dependent cohesion. A nucleolar-specific Smc5/6 function has been proposed because Smc5/6 yeast mutants display penetrant phenotypes of ribosomal DNA (rDNA) instability. rDNA repeats are replicated unidirectionally. Here, we propose that unidirectional replication, combined with global Smc5/6 functions, can explain the apparent rDNA specificity

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

Consistency of aortic distensibility and pulse wave velocity estimates with respect to the Bramwell-Hill theoretical model: a cardiovascular magnetic resonance study

<p>Abstract</p> <p>Background</p> <p>Arterial stiffness is considered as an independent predictor of cardiovascular mortality, and is increasingly used in clinical practice. This study aimed at evaluating the consistency of the automated estimation of regional and local aortic stiffness indices from cardiovascular magnetic resonance (CMR) data.</p> <p>Results</p> <p>Forty-six healthy subjects underwent carotid-femoral pulse wave velocity measurements (<it>CF_PWV</it>) by applanation tonometry and CMR with steady-state free-precession and phase contrast acquisitions at the level of the aortic arch. These data were used for the automated evaluation of the aortic arch pulse wave velocity (<it>Arch_PWV</it>), and the ascending aorta distensibility (<it>AA_Distc, AA_Distb)</it>, which were estimated from ascending aorta strain (<it>AA_Strain</it>) combined with either carotid or brachial pulse pressure. The local ascending aorta pulse wave velocity <it>AA_PWVc </it>and <it>AA_PWVb </it>were estimated respectively from these carotid and brachial derived distensibility indices according to the Bramwell-Hill theoretical model, and were compared with the <it>Arch_PWV</it>. In addition, a reproducibility analysis of <it>AA_PWV </it>measurement and its comparison with the standard <it>CF_PWV </it>was performed. Characterization according to the Bramwell-Hill equation resulted in good correlations between <it>Arch_PWV </it>and both local distensibility indices <it>AA_Distc </it>(r = 0.71, p < 0.001) and <it>AA_Distb </it>(r = 0.60, p < 0.001); and between <it>Arch_PWV </it>and both theoretical local indices <it>AA_PWVc </it>(r = 0.78, p < 0.001) and <it>AA_PWVb </it>(r = 0.78, p < 0.001). Furthermore, the <it>Arch_PWV </it>was well related to <it>CF_PWV </it>(r = 0.69, p < 0.001) and its estimation was highly reproducible (inter-operator variability: 7.1%).</p> <p>Conclusions</p> <p>The present work confirmed the consistency and robustness of the regional index <it>Arch_PWV </it>and the local indices <it>AA_Distc and AA_Distb </it>according to the theoretical model, as well as to the well established measurement of <it>CF_PWV</it>, demonstrating the relevance of the regional and local CMR indices.</p

Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter

Reproducibility over a 1-month period of 1H-MR spectroscopic imaging NAA/Cr ratios in clinically stable multiple sclerosis patients

N-acetylaspartate/creatine (NAA/Cr) ratios, assessed with proton magnetic resonance spectroscopy, are increasingly used as a surrogate marker for axonal dysfunction and degeneration in multiple sclerosis (MS). The purpose of this study was to test short-time reproducibility of NAA/Cr ratios in patients with clinically stable MS. In 35 MS patients we analysed NAA/Cr ratios obtained with 1H-MR spectroscopic imaging at the centrum semiovale either with lateral ventricles partially included (group 1; n=15) or more cranially with no ventricles included (group 2; n=20). To test short-term reproducibility of the NAA/Cr measurements, patients were scanned twice 4 weeks apart. We determined mean NAA/Cr and Cho/Cr ratios of 12 grey matter and 24 white matter voxels. Mean NAA/Cr ratios of both the white and grey matter did not change after 4 weeks. Overall 4-week reproducibility of the NAA/Cr ratio, expressed as coefficient of variation, was 4.8% for grey matter and 3.5% for white matter. Reproducibility of cranial scanning of the ventricles was slightly better than with cerebrospinal fluid included. Our study shows good short-term reproducibility of NAA/Cr ratio measurements in the centrum semiovale, which supports the reliability of this technique for longitudinal studies

Stellar coronal astronomy - a review

Coronal astronomy is by now a fairly mature discipline, with a quarter century having gone by since the detection of the first stellar X-ray coronal source (Capella), and having benefitted from a series of major orbiting observing facilities. Several observational characteristics of coronal X-ray and EUV emission have been solidly established through extensive observations, and are by now common, almost text-book, knowledge. At the same time the implications of coronal astronomy for broader astrophysical questions (e.g. Galactic structure, stellar formation, stellar structure, etc.) have become appreciated. The interpretation of stellar coronal properties is however still often open to debate, and will need qualitatively new observational data to book further progress. In the present review we try to recapitulate our view on the status of the field at the beginning of a new era, in which the high sensitivity and the high spectral resolution provided by Chandra and XMM-Newton will address new questions which were not accessible before.Comment: Space Science Reviews, in press, 132 pages (full paper available at ftp://astro.esa.int/pub/ffavata/Papers/ssr-preprint.pdf