Diagnostic and cost utility of whole exome sequencing in peripheral neuropathy.

OBJECTIVE: To explore the diagnostic utility and cost effectiveness of whole exome sequencing (WES) in a cohort of individuals with peripheral neuropathy. METHODS: Singleton WES was performed in individuals recruited though one pediatric and one adult tertiary center between February 2014 and December 2015. Initial analysis was restricted to a virtual panel of 55 genes associated with peripheral neuropathies. Patients with uninformative results underwent expanded analysis of the WES data. Data on the cost of prior investigations and assessments performed for diagnostic purposes in each patient was collected. RESULTS: Fifty patients with a peripheral neuropathy were recruited (median age 18 years; range 2-68 years). The median time from initial presentation to study enrollment was 6 years 9 months (range 2 months-62 years), and the average cost of prior investigations and assessments for diagnostic purposes AU$4013 per patient. Eleven individuals received a diagnosis from the virtual panel. Eight individuals received a diagnosis following expanded analysis of the WES data, increasing the overall diagnostic yield to 38%. Two additional individuals were diagnosed with pathogenic copy number variants through SNP microarray. CONCLUSIONS: This study provides evidence that WES has a high diagnostic utility and is cost effective in patients with a peripheral neuropathy. Expanded analysis of WES data significantly improves the diagnostic yield in patients in whom a diagnosis is not found on the initial targeted analysis. This is primarily due to diagnosis of conditions caused by newly discovered genes and the resolution of complex and atypical phenotypes

Surface Chemistry of Perfluoropolyethers and Hydrogenated Analogs: Are Studies of Model Compounds Useful?

We have studied adsorption, desorption, and decomposition of ethers on Ru(001), an atomically-smooth metal surface. We have compared diethers with monoethers, and fluorinated ethers with hydrogenated ethers. The number of ether linkages does not strongly influence adsorption bond strength, nor the extent of decomposition. Fluorination does weaken the adsorption bond strength and prevents decomposition. These studies suggest that the surface properties of monomeric ethers can be used to predict properties of oligomeric, and perhaps even polymeric, ethers

Using BOX-PCR to exclude a clonal outbreak of melioidosis

Background Although melioidosis in endemic regions is usually caused by a diverse range of Burkholderia pseudomallei strains, clonal outbreaks from contaminated potable water have been described. Furthermore B. pseudomallei is classified as a CDC Group B bioterrorism agent. Ribotyping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) have been used to identify genetically related B. pseudomallei isolates, but they are time consuming and technically challenging for many laboratories. Methods We have adapted repetitive sequence typing using a BOX A1R primer for typing B. pseudomallei and compared BOX-PCR fingerprinting results on a wide range of well-characterized B. pseudomallei isolates with MLST and PFGE performed on the same isolates. Results BOX-PCR typing compared favourably with MLST and PFGE performed on the same isolates, both discriminating between the majority of multilocus sequence types and showing relatedness between epidemiologically linked isolates from various outbreak clusters. Conclusion Our results suggest that BOX-PCR can be used to exclude a clonal outbreak of melioidosis within 10 hours of receiving the bacterial strains

Methamphetamine Use among Newly Diagnosed HIV-Positive Young Men in North Carolina, United States, from 2000 to 2005

Methamphetamine (MA) is a new arrival to the Southeastern United States (US). Incidence of HIV is also increasing regionally, but data are limited regarding any association between this trend and MA use. We examined behavioral data from North Carolina (NC) residents newly diagnosed with HIV, collected by the Department of Health between 2000-2005.Among 1,460 newly diagnosed HIV-positive young men, an increasing trend was seen from 2000-2005 in MA use (p = 0.01, total n = 20). In bivariate analyses, users of MA had significantly greater odds of reporting other substance use, including alcohol, powder or crack cocaine, marijuana, and methylenedioxymethamphetamine (MDMA, "ecstasy"). They were also more likely to have reported sexual activity while traveling outside NC; sex with anonymous partners; and previous HIV testing. In a predictive model, MA use had a negative association with nonwhite race, and strong positive associations with powder cocaine, "ecstasy," or intravenous drug use and being a university student.Similar to trends seen in more urban parts of the US, MA use among newly diagnosed, HIV-positive young men is increasing in NC. These data are among the first to demonstrate this relationship in a region with a burgeoning epidemic of MA use. Opportunities exist for MA-related HIV risk-reduction interventions whenever young men intersect the healthcare system

THG113.31, a specific PGF2alpha receptor antagonist, induces human myometrial relaxation and BKCa channel activation

BACKGROUND: PGF2alpha exerts a significant contractile effect on myometrium and is central to human labour. THG113.31, a specific non-competitive PGF2alpha receptor (FP) antagonist, exerts an inhibitory effect on myometrial contractility. The BKCa channel is ubiquitously encountered in human uterine tissue and plays a significant role in modulating myometrial cell membrane potential and excitability. The objective of this study was to investigate potential BKCa channel involvement in the response of human myometrium to THG113.31. METHODS: Single and whole-cell electrophysiological BKCa channel recordings from freshly dispersed myocytes, were investigated in the presence and absence of THG113.31. Functional studies investigated the effects of THG113.31 on isolated spontaneous myometrial contractions, in the presence and absence of the BKCa channel blocker, iberiotoxin. RESULTS: Single channel recordings identified the BKCa channel as a target of THG113.31. THG113.31 significantly increased the open state probability of these channels [control 0.023+/-0.006; 10 microM THG113.31 0.087+/-0.012 (P = 0.009); and 50 microM THG113.31 0.1356+/-0.018 (P = 0.001)]. In addition, THG113.31 increased whole-cell BKCa currents over a range of membrane potentials, and this effect was reversed by 100 nanoM IbTX. Isometric tension studies demonstrated that THG113.31 exerted a significant concentration-dependent relaxant effect on human myometrial tissue and pre-incubation of strips with IbTX abolished this effect on spontaneously occurring contractions. CONCLUSION: These data suggests that activation of the BKCa channel may contribute, at least partially, to the uterorelaxant effect of THG113.31

Anti-malarial prescriptions in three health care facilities after the emergence of chloroquine resistance in Niakhar, Senegal (1992–2004)

<p>Abstract</p> <p>Background</p> <p>In the rural zone of Niakhar in Senegal, the first therapeutic failures for chloroquine (CQ) were observed in 1992. In 2003, the national policy regarding first-line treatment of uncomplicated malaria was modified, replacing CQ by a transitory bi-therapy amodiaquine/sulphadoxine-pyrimethamine (AQ/SP), before the implementation of artemisinin-based combination therapy (ACT) in 2006.</p> <p>The aims of the study were to assess the evolution of anti-malarial prescriptions in three health care facilities between 1992 and 2004, in parallel with increasing CQ resistance in the region.</p> <p>Methods</p> <p>The study was conducted in the area of Niakhar, a demographic surveillance site located in a sahelo-sudanese region of Senegal, with mesoendemic and seasonal malaria transmission. Health records of two public health centres and a private catholic dispensary were collected retrospectively to cover the period 1992–2004.</p> <p>Results</p> <p>Records included 110,093 consultations and 292,965 prescribed treatments. Twenty-five percent of treatments were anti-malarials, prescribed to 49% of patients. They were delivered all year long, but especially during the rainy season, and 20% of patients with no clinical malaria diagnosis received anti-malarials. Chloroquine and quinine represented respectively 55.7% and 34.6% of prescribed anti-malarials. Overall, chloroquine prescriptions rose from 1992 to 2000, in parallel with clinical malaria; then the CQ prescription rate decreased from 2000 and was concomitant with the rise of SP and the persistence of quinine use. AQ and SP were mainly used as bi-therapy after 2003, at the time of national treatment policy change.</p> <p>Conclusion</p> <p>The results show the overall level of anti-malarial prescription in the study area for a considerable number of patients over a large period of time. Even though resistance to CQ rapidly increased from 1992 to 2001, no change in CQ prescription was observed until the early 2000s, possibly due to the absence of an obvious decrease in CQ effectiveness, a lack of therapeutic options or a blind follow-up of national guidelines.</p

A three-year cohort study of the relationships between coping, job stress and burnout after a counselling intervention for help-seeking physicians

<p>Abstract</p> <p>Background</p> <p>Knowledge about important factors in reduction of burnout is needed, but there is a dearth of burnout intervention program studies and their effects among physicians. The present three-year follow-up study aimed to investigate the roles of coping strategies, job stress and personality traits in burnout reduction after a counselling intervention for distressed physicians.</p> <p>Methods</p> <p>227 physicians who attended a counselling intervention for burnout at the Resource Centre Villa Sana, Norway in 2003-2005, were followed with self-report assessments at baseline, one-year, and three-year follow-up. Main outcome measures were emotional exhaustion (one dimension of burnout), job stress, coping strategies and neuroticism. Changes in these measures were analyzed with repeated measures ANOVA. Temporal relationships between changes were examined using structural modelling with cross-lagged and synchronous panel models.</p> <p>Results</p> <p>184 physicians (81%, 83 men, 101 women) completed the three-year follow-up assessment. Significantly reduced levels of emotional exhaustion, job stress, and emotion-focused coping strategies from baseline to one year after the intervention, were maintained at three-year follow-up.</p> <p>Panel modelling indicated that changes in emotion-focused coping (z = 4.05, p < 0.001) and job stress (z = 3.16, p < 0.01) preceded changes in emotional exhaustion from baseline to three-year follow-up. A similar pattern was found from baseline to one-year follow-up.</p> <p>Conclusion</p> <p>A sequential relationship indicated that reduction in emotion-focused coping and in job stress preceded reduction in emotional exhaustion. As a consequence, coping strategies and job stress could be important foci in intervention programs that aim to reduce or prevent burnout in help-seeking physicians.</p

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO