2,185 research outputs found
RPGR mutation associated with retinitis pigmentosa, impaired hearing, and sinorespiratory infections
Note on a Micropolar Gas-Kinetic Theory
The micropolar fluid mechanics and its transport coefficients are derived
from the linearized Boltzmann equation of rotating particles. In the dilute
limit, as expected, transport coefficients relating to microrotation are not
important, but the results are useful for the description of collisional
granular flow on an inclined slope.
  (This paper will be published in Traffic and Granular Flow 2001 edited by
Y.Sugiyama and D. E. Wolf (Springer))Comment: 15 pages, 0 figure. To be published in Traffic and Granular Flow 2001
  edited by Y.Sugiyama and D. E. Wolf (Springer
Drug interactions in primary health care in the George subdistrict, South Africa: a cross-sectional study
Objectives: To investigate the prevalence of potential drug-drug interactions in primary healthcare clinics in the George subdistrict, to determine which drugs were involved, and to identify associated risk factors. Design: A cross-sectional retrospective folder review was performed. Setting and subjects: Four hundred randomly selected patient files from four primary care clinics in the George subdistrict. Outcome measures: The prevalence of potential drug-drug interactions in primary care, drugs involved in potential drugdrug interactions and associated risk factors. Results: The prevalence of scripts containing at least one moderate potential interaction was 42%; severe potential interaction, 5.25%; and contraindicated combinations, 0.5%. The most common drugs involved were enalapril, aspirin, ibuprofen, furosemide and fluoxetine. The most common implicated drugs in potentially severe interactions were warfarin, aspirin, fluoxetine, tramadol and allopurinol. Two contraindicated combinations were found, namely verapamil plus simvastatin, and hyoscine butyl bromide plus oral potassium chloride. Advancing age and polypharmacy were associated with an increased risk of potential drug-drug interactions. Input from the regional hospital specialist departments greatly increased the risk of a patient being given a prescription that contained a potential drug-drug interaction. Eighty one per cent of severe interactions were from this group. Conclusion: The potential for drug-drug interactions occurring was common in primary healthcare clinics in the George subdistrict. Drug interactions are predictable and preventable. The risk factors identified in this study may assist in the design of interventions that reduce the risk.Keywords: potential drug-drug interactions, adverse drug events, polypharmacy, primary health care, pharmacokinetic interactions, pharmacodynamic interaction
Exclusive neuronal expression of SUCLA2 in the human brain
SUCLA2 encodes the ATP-forming subunit (A-SUCL-) of succinyl-CoA ligase, an enzyme of the citric acid cycle. Mutations in SUCLA2 lead to a mitochondrial disorder manifesting as encephalomyopathy with dystonia, deafness and lesions in the basal ganglia. Despite the distinct brain pathology associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here we show that immunoreactivity of A-SUCL- in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling with a fluorescent Nissl dye. A-SUCL- immunoreactivity co-localized >99% with that of the d subunit of the mitochondrial F0-F1 ATP synthase. Specificity of the anti-A-SUCL- antiserum was verified by the absence of labeling in fibroblasts from a patient with a complete deletion of SUCLA2. A-SUCL- immunoreactivity was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming subunit (G-SUCL-) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL- immunoreactivity that was however, not upregulated in samples obtained from diabetic versus non-diabetic patients, as has been described for murine brain. Our work establishes that SUCLA2 is expressed exclusively in neurons in the human cerebral cortex
Two Earth-sized planets orbiting Kepler-20
Since the discovery of the first extrasolar giant planets around Sun-like
stars, evolving observational capabilities have brought us closer to the
detection of true Earth analogues. The size of an exoplanet can be determined
when it periodically passes in front of (transits) its parent star, causing a
decrease in starlight proportional to its radius. The smallest exoplanet
hitherto discovered has a radius 1.42 times that of the Earth's radius (R
Earth), and hence has 2.9 times its volume. Here we report the discovery of two
planets, one Earth-sized (1.03R Earth) and the other smaller than the Earth
(0.87R Earth), orbiting the star Kepler-20, which is already known to host
three other, larger, transiting planets. The gravitational pull of the new
planets on the parent star is too small to measure with current
instrumentation. We apply a statistical method to show that the likelihood of
the planetary interpretation of the transit signals is more than three orders
of magnitude larger than that of the alternative hypothesis that the signals
result from an eclipsing binary star. Theoretical considerations imply that
these planets are rocky, with a composition of iron and silicate. The outer
planet could have developed a thick water vapour atmosphere.Comment: Letter to Nature; Received 8 November; accepted 13 December 2011;
  Published online 20 December 201
Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans
The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans
Genome sequencing reveals a splice donor site mutation in the SNX14 gene associated with a novel cerebellar cortical degeneration in the Hungarian Vizsla dog breed
Age differences in physiological responses to self-paced and incremental testing
Purpose: A self-paced maximal exercise protocol has demonstrated higher  values when compared against traditional tests. The aim was to compare physiological responses to this self-paced  protocol (SPV) in comparison to a traditional ramp  (RAMP) protocol in young (18–30 years) and old (50–75 years) participants.  Methods: Forty-four participants (22 young; 22 old) completed both protocols in a randomised, counter-balanced, crossover design. The SPV included 5 × 2 min stages, participants were able to self-regulate their power output (PO) by using incremental ‘clamps’ in ratings of perceived exertion. The RAMP consisted of either 15 or 20 W min.  Results: Expired gases, cardiac output (Q), stroke volume (SV), muscular deoxyhaemoglobin (deoxyHb) and electromyography (EMG) at the vastus lateralis were recorded throughout. Results demonstrated significantly higher  in the SPV (49.68 ± 10.26 ml kg min) vs. the RAMP (47.70 ± 9.98 ml kg min) in the young, but not in the old group (>0.05). Q and SV were significantly higher in the SPV vs. the RAMP in the young (0.05). No differences seen in deoxyHb and EMG for either age groups (>0.05). Peak PO was significantly higher in the SPV vs. the RAMP in both age groups (<0.05).  Conclusion: Findings demonstrate that the SPV produces higher , peak Q and SV values in the young group. However, older participants achieved similar  values in both protocols, mostly likely due to age-related differences in cardiovascular responses to incremental exercise, despite them achieving a higher physiological workload in the SPV
Barriers and opportunities for evidence-based health service planning: the example of developing a Decision Analytic Model to plan services for sexually transmitted infections in the UK
Decision Analytic Models (DAMs) are established means of evidence-synthesis to differentiate between health interventions. They have mainly been used to inform clinical decisions and health technology assessment at the national level, yet could also inform local health service planning. For this, a DAM must take into account the needs of the local population, but also the needs of those planning its services. Drawing on our experiences from stakeholder consultations, where we presented the potential utility of a DAM for planning local health services for sexually transmitted infections (STIs) in the UK, and the evidence it could use to inform decisions regarding different combinations of service provision, in terms of their costs, cost-effectiveness, and public health outcomes, we discuss the barriers perceived by stakeholders to the use of DAMs to inform service planning for local populations, including (1) a tension between individual and population perspectives; (2) reductionism; and (3) a lack of transparency regarding models, their assumptions, and the motivations of those generating models
The Formation and Evolution of the First Massive Black Holes
The first massive astrophysical black holes likely formed at high redshifts
(z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations.
These black holes grow by mergers and gas accretion, evolve into the population
of bright quasars observed at lower redshifts, and eventually leave the
supermassive black hole remnants that are ubiquitous at the centers of galaxies
in the nearby universe. The astrophysical processes responsible for the
formation of the earliest seed black holes are poorly understood. The purpose
of this review is threefold: (1) to describe theoretical expectations for the
formation and growth of the earliest black holes within the general paradigm of
hierarchical cold dark matter cosmologies, (2) to summarize several relevant
recent observations that have implications for the formation of the earliest
black holes, and (3) to look into the future and assess the power of
forthcoming observations to probe the physics of the first active galactic
nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant
  Universe", Ed. A. J. Barger, Kluwer Academic Publisher
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