Evaluating the accuracy of a functional SNP annotation system

Many common and chronic diseases are influenced at some level by genetic variation. Research done in population genetics, specifically in the area of single nucleotide polymorphisms (SNPs) is critical to understanding human genetic variation. A key element in assessing role of a given SNP is determining if the variation is likely to result in change in function. The SNP Integration Tool (SNPit) is a comprehensive tool that integrates diverse, existing predictors of SNP functionality, providing the user with information for improved association study analysis. To evaluate the SNPit system, we developed an alternative gold standard to measure accuracy using sensitivity and specificity. The results of our evaluation demonstrated that our alternative gold standard produced encouraging results

Сучасний стан і проблеми управління залізничним транспортом України

Проаналізовано стан і тенденції розвитку залізничного транспорту. Розглянуті основні завдання державного регулювання галузі.Проанализировано состояние и тенденции развития железнодорожного транспорта. Рассмотренны основные задания государственного регулирования отрасли.The condition and trends of railway transport has been anilized. The main tasks of state regulation of railway transport has been considereted

A Transcriptional Enhancer from the Coding Region of ADAMTS5

The revelation that the human genome encodes only approximately 25,000 genes and thus cannot account for phenotypic complexity has been one of the biggest surprises in the post-genomic era. However, accumulating evidence suggests that transcriptional regulation may be in large part responsible for this observed mammalian complexity. Consequently, there has been a strong drive to locate cis-regulatory regions in mammalian genomes in order to understand the unifying principles governing these regions, including their genomic distribution. Although a number of systematic approaches have been developed, these all discount coding sequence.Using the computational tool PRI (Pattern-defined Regulatory Islands), which does not mask coding sequence, we identified a regulatory region associated with the gene ADAMTS5 that encompasses the entirety of the essential coding exon 2. We demonstrate through a combination of chromatin immunoprecipitation and reporter gene studies that this region can not only bind the myogenic transcription factors MYOD and myogenin and the E-protein HEB but can also function as a very strong myogenic transcriptional enhancer.Thus, we report the identification and detailed characterization of an exonic enhancer. Ultimately, this leads to the interesting question of why evolution would be so parsimonious in the functional assignment of sequence

Tuberculous meningitis in Denmark: a review of 50 cases

<p>Abstract</p> <p>Background</p> <p>Tuberculous meningitis is the most severe manifestation of extrapulmonary tuberculosis with a high mortality rate and a high rate of sequelae among survivors. The aim of this study is to assess the current epidemiology, clinical features, diagnostic procedures, treatment and outcome in patients with tuberculous meningitis in Denmark, a country with a low tuberculosis incidence.</p> <p>Methods</p> <p>A nationwide retrospective study was conducted, comprising all patients notified with tuberculous meningitis (TBM) in Denmark from 2000-2008. Medical records were reviewed using a standardised protocol.</p> <p>Results</p> <p>Fifty patients, including 12 paediatric patients, were identified. 78% of the patients were immigrants from countries of high tuberculosis endemicity. 64% of all patients had a pre-existing immunosuppressive condition; 10% were HIV positive, 48% were HIV seronegative and 42% had an unknown HIV status. Median symptom duration before admission was 14 days in the Danish patient population and 20 days in the immigrant group. Biochemical analysis of cerebrospinal fluid (CSF) samples revealed pleocytosis in 90% with lymphocyte predominance in 66%. Protein levels were elevated in 86%. The most common findings on neuro-radiological imaging were basal meningeal enhancement, tuberculomas and hydrocephalus. Lumbar puncture was performed on 42 patients; 31 of these specimens (74%) had a positive CSF culture for mycobacteria and 9.5% were smear positive for acid-fast bacilli. The overall mortality rate was 19% and 48% of the remaining patients had neurological sequelae of varying degree.</p> <p>Conclusion</p> <p>TBM is a rare but severe manifestation of extrapulmonary TB in Denmark. The clinician must be prepared to treat empirically if the suspicion of TBM has arisen to improve treatment outcome.</p

Search for nu(mu)-->nu(e) Oscillations in the NOMAD Experiment

We present the results of a search for nu(mu)-->nu(e) oscillations in the NOMAD experiment at CERN. The experiment looked for the appearance of nu(e) in a predominantly nu(mu) wide-band neutrino beam at the CERN SPS. No evidence for oscillations was found. The 90% confidence limits obtained are delta m^2 < 0.4 eV^2 for maximal mixing and sin^2(2theta) < 1.4x10^{-3} for large delta m^2. This result excludes the LSND allowed region of oscillation parameters with delta m^2 > 10 eV^2.Comment: 19 pages, 8 figures. Submitted to Phys. Lett.

Search for the exotic Θ+\Theta^+ resonance in the NOMAD experiment

A search for exotic Theta baryon via Theta -> proton +Ks decay mode in the NOMAD muon neutrino DIS data is reported. The special background generation procedure was developed. The proton identification criteria are tuned to maximize the sensitivity to the Theta signal as a function of xF which allows to study the Theta production mechanism. We do not observe any evidence for the Theta state in the NOMAD data. We provide an upper limit on Theta production rate at 90% CL as 2.13 per 1000 of neutrino interactions.Comment: Accepted to European Physics Journal

A Precise Measurement of the Muon Neutrino-Nucleon Inclusive Charged Current Cross-Section off an Isoscalar Target in the Energy Range 2.5 < E_\nu < 40 GeV by NOMAD

We present a measurement of the muon neutrino-nucleon inclusive charged current cross-section, off an isoscalar target, in the neutrino energy range $2.5 \leq E_\nu \leq 40$ GeV. The significance of this measurement is its precision, $\pm 4$% in $2.5 \leq E_\nu \leq 10$ GeV, and $\pm 2.6$% in $10 \leq E_\nu \leq 40$ GeV regions, where significant uncertainties in previous experiments still exist, and its importance to the current and proposed long baseline neutrino oscillation experiments.Comment: 14 pages, 3 figures, submitted to Phys.Lett.

A Study of Strange Particles Produced in Neutrino Neutral Current Interactions in the NOMAD Experiment

Results of a detailed study of strange particle production in neutrino neutral current interactions are presented using the data from the NOMAD experiment. Integral yields of neutral strange particles (K0s, Lambda, Lambda-bar) have been measured. Decays of resonances and heavy hyperons with an identified K0s or Lambda in the final state have been analyzed. Clear signals corresponding to K* and Sigma(1385) have been observed. First results on the measurements of the Lambda polarization in neutral current interactions have been obtained.Comment: Accepted for publication in Nuclear Physics B as a rapid communicatio

A Measurement of Coherent Neutral Pion Production in Neutrino Neutral Current Interactions in NOMAD

We present a study of exclusive neutral pion production in neutrino-nucleus Neutral Current interactions using data from the NOMAD experiment at the CERN SPS. The data correspond to $1.44 \times 10^6$ muon-neutrino Charged Current interactions in the energy range $2.5 \leq E_{\nu} \leq 300$ GeV. Neutrino events with only one visible $\pi^0$ in the final state are expected to result from two Neutral Current processes: coherent $\pi^0$ production, {\boldmath $\nu + {\cal A} \to \nu + {\cal A} + \pi^0$} and single $\pi^0$ production in neutrino-nucleon scattering. The signature of coherent $\pi^0$ production is an emergent $\pi^0$ almost collinear with the incident neutrino while $\pi^0$'s produced in neutrino-nucleon deep inelastic scattering have larger transverse momenta. In this analysis all relevant backgrounds to the coherent $\pi^0$ production signal are measured using data themselves. Having determined the backgrounds, and using the Rein-Sehgal model for the coherent $\pi^0$ production to compute the detection efficiency, we obtain {\boldmath $4630 \pm 522 (stat) \pm 426 (syst)$} corrected coherent-$\pi^0$ events with $E_{\pi^0} \geq 0.5$ GeV. We measure {\boldmath $\sigma (\nu {\cal A} \to \nu {\cal A} \pi^0) = [ 72.6 \pm 8.1(stat) \pm 6.9(syst) ] \times 10^{-40} cm^2/nucleus$}. This is the most precise measurement of the coherent $\pi^0$ production to date.Comment: 23 pages, 9 figures, accepted for publication in Phys. Lett.

Treatment Outcome in Patients Receiving Assertive Community Treatment

In an observational study of severely mentally ill patients treated in assertive community treatment (ACT) teams, we investigated how treatment outcome was associated with demographic factors, clinical factors, and motivation for treatment. To determine psychosocial outcome, patients were routinely assessed using the Health of the Nation Outcome Scales (HoNOS). Trends over time were analyzed using a mixed model with repeated measures. The HoNOS total score was modeled as a function of treatment duration and patient-dependent covariates. Data comprised 637 assessments of 139 patients; mean duration of follow-up was 27.4 months (SD = 5.4). Substance abuse, higher age, problems with motivation, and lower educational level were associated with higher HoNOS total scores (i.e., worse outcome). To improve treatment outcome, we recommend better implementation of ACT, and also the implementation of additional programs targeting subgroups which seem to benefit less from ACT