Malfunctions of potassium channels are increasingly implicated as causes of neurological disorders. However, the functional roles of the large-conductance voltage- and Ca2+-activated K+channel (BK ...channel), a unique calcium, and voltage-activated potassium channel type have remained elusive. Here we report that mice lacking BK channels ( BK-/-) show cerebellar dysfunction in the form of abnormal conditioned eye-blink reflex, abnormal locomotion and pronounced deficiency in motor coordination, which are likely consequences of cerebellar learning deficiency. At the cellular level, the BK-/-mice showed a dramatic reduction in spontaneous activity of the BK-/-cerebellar Purkinje neurons, which generate the sole output of the cerebellar cortex and, in addition, enhanced short-term depression at the only output synapses of the cerebellar cortex, in the deep cerebellar nuclei. The impairing cellular effects caused by the lack of postsynaptic BK channels were found to be due to depolarization-induced inactivation of the action potential mechanism. These results identify previously unknown roles of potassium channels in mammalian cerebellar function and motor control. In addition, they provide a previously undescribed animal model of cerebellar ataxia.
Synchrotron radiation (SR) reflction is an important issue for future linear colliders. High fluxes of SR might impact the performance of the detector, through irradiation of the forward luminosity ...and beam quality calorimeters or of the innermost layers of the vertex detector. The photon reflections depend on the beam pipe apertures' size, their shape, and materials used with various surface roughness. In this work, we present a study of SR including reflection for the 380GeV and 3 TeV beam parameters and optics of the Compact Linear Collider's Final Focus System. The simulations of the SR reections using the Synrad+ software are presented and the impact on the detector is discussed.
Abstract Introduction Multiple System Atrophy (MSA) is a neurodegenerative disease which presents heterogeneously with symptoms and signs of parkinsonism, ataxia and autonomic dysfunction. Although ...MSA typically occurs sporadically, rare pathology-proven MSA families following either autosomal recessive or autosomal dominant patterns have been described, indicating a heritable contribution to the pathogenesis. Methods We used Genome-Wide Complex Trait Analysis (GCTA) to estimate the heritable component of MSA due to common coding variability in imputed genotype data of 907 MSA cases and 3866 population-matched controls. GCTA only assesses the effect of putative causal variants in linkage disequilibrium (LD) with all common SNPs on the genotyping platform. Results We estimate the heritability among common variants of MSA in pooled cases at 2.09–6.65%, with a wider range of values in geographic and diagnostic subgroups. Meta-analysis of our geographic cohorts reveals high between-group heterogeneity. Contributions of single chromosomes are generally negligible. We suggest that all calculated MSA heritability among common variants could be explained by the presence of misdiagnosed cases in the clinical subgroup based on a Bayesian estimate using literature-derived rates of misdiagnosis. Discussion MSA is a challenging disease to study due to high rates of misdiagnosis and low prevalence. Given our low estimates of heritability, common genetic variation appears to play a less prominent role in risk for MSA than in other complex neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and Amyotrophic Lateral Sclerosis. The success of future gene discovery efforts rests on large pathologically-confirmed case series and an interrogation of both common and rare genetic variants.
Purpose: In a country of free selection of providers, general practitioners (GPs) remain the most visited health-care professionals by the vast majority of persons with spinal cord injury (SCI) in ...Switzerland; yet, little is known about these contacts. The study aims to explore reasons for encounters (RFEs) in general practice, and their relationships to first-contact of care (GP or specialist) and GP's competence in managing SCI-specific problems. Patients and Methods: Cross-sectional study from baseline data of non-randomized controlled trial. Persons with SCI in the chronic phase and living in Swiss rural communities were invited. Participants were asked about RFEs (reasons and health problems) of their last visit to a GP. RFEs were coded according to the International Classification of Primary Care (ICPC-2), and analyzed according to first-contact and participants' ratings of GPs' competence in managing SCI-specific problems. Results: Out of 395, 226 (57%) persons participated, of which 89% have reported 2.1 (SD + or -1.4) RFEs and 2.4 (+ or -1.7) health problems per GP visit, on average. Participants visited GPs for medications (49%), urgent medical problems (33%) and follow-up (30%). Most RFEs were related to general/unspecified problems (65%). Persons whose first contact was a specialist were more likely to visit GPs for medications (Specialist = 60% vs GP = 42%). There were no associations between RFEs and the perceived GP's competence at P < 0.05. Conclusion: Irrespective of first contact of care, persons with SCI visit GPs for medication, urgent issues, and follow-up care, and more often for general problems than for secondary health conditions. Strengthening collaboration between GPs in rural communities and specialized centers is recommended; promoting such a connection potentially aids GPs in meeting their information needs for managing secondary health conditions and improving the quality of SCI care for this population. Keywords: general practitioners, spinal cord injury, specialists, health problems, competence
Infant femoral arterial access is an essential part of interventional procedures, hemodynamic monitoring, and support of critically ill patients. Due to small luminal diameter, superficial location, ...mobility, and increased risk of vasospasm, dissection, and thrombosis, femoral artery access in the infant is a technically demanding procedure. The purpose of this manuscript is to describe an approach to successful common femoral arterial access and arteriography in infants including common pearls and pitfalls.
CPU cycles for small experiments and projects can be scarce, thus making use of all available resources, whether dedicated or opportunistic, is mandatory. While enabling uniform access to the LCG ...computing elements (ARC, CREAM), the DIRAC grid interware was not able to use OSG computing elements (GlobusCE, HTCondor-CE) without dedicated support at the grid site through so called 'SiteDirectors', which directly submit to the local batch system. This in turn requires additional dedicated effort for small experiments on the grid site. Adding interfaces to the OSG CEs through the respective grid middleware is therefore allowing accessing them within the DIRAC software without additional site-specific infrastructure. This enables greater use of opportunistic resources for experiments and projects without dedicated clusters or an established computing infrastructure with the DIRAC software. To allow sending jobs to HTCondor-CE and legacy Globus computing elements inside DIRAC the required wrapper classes were developed. Not only is the usage of these types of computing elements now completely transparent for all DIRAC instances, which makes DIRAC a flexible solution for OSG based virtual organisations, but it also allows LCG Grid Sites to move to the HTCondor-CE software, without shutting DIRAC based VOs out of their site. In these proceedings we detail how we interfaced the DIRAC system to the HTCondor-CE and Globus computing elements and explain the encountered obstacles and solutions developed, and how the linear collider community uses resources in the OSG.
This was a cross-sectional questionnaire survey.
The objective of this study was to identify the care-seeking behavior of persons with spinal cord injury (SCI) with respect to the various health care ...providers and ascertain circumstances that lead to situations where required care was not received.
This study was conducted in the entire country of Switzerland.
Statistical analysis of frequency of annual visits to health care providers by 17 specialties, and description of situations where health care was required but not received, in persons with chronic SCI living in the community.
Main medical contact person was the general practitioner (GP; visited by 88% during last 12 months). The physiotherapist (visited by 72%) was the health care provider with the most visits (average of 30 visits in 12 months). GPs, physiotherapists, urologists and spinal medicine specialists were often contacted in combination, by many participants, often for check-up visits. A situation where care was required but not received was reported by 53 (11%) of participants, with a substantially higher rate in migrants (29%). Main problems why care was not received were bladder and bowel problems and main reasons of care not received were regional or temporal unavailability.
Individuals with SCI are frequent users of medical services. There is no group of medical specialists that covers all needs of persons with SCI, what emphasizes health care provision from a comprehensive perspective including a wide array of services. Instances with care required but not received appeared to be rare and more likely in participants with migration background.
Abnormally elevated blood pressure is the most prevalent risk factor for cardiovascular disease. The large-conductance, voltage- and Ca2+-dependent K+ (BK) channel has been proposed as an important ...effector in the control of vascular tone by linking membrane depolarization and local increases in cytosolic Ca2+ to hyperpolarizing K+ outward currents. However, the BK channel may also affect blood pressure by regulating salt and fluid homeostasis, particularly by adjusting the renin-angiotensin-aldosterone system.
Here we report that deletion of the pore-forming BK channel alpha subunit leads to a significant blood pressure elevation resulting from hyperaldosteronism accompanied by decreased serum K+ levels as well as increased vascular tone in small arteries. In smooth muscle from small arteries, deletion of the BK channel leads to a depolarized membrane potential, a complete lack of membrane hyperpolarizing spontaneous K+ outward currents, and an attenuated cGMP vasorelaxation associated with a reduced suppression of Ca2+ transients by cGMP. The high level of BK channel expression observed in wild-type adrenal glomerulosa cells, together with unaltered serum renin activities and corticotropin levels in mutant mice, suggests that the hyperaldosteronism results from abnormal adrenal cortical function in BK(-/-) mice.
These results identify previously unknown roles of BK channels in blood pressure regulation and raise the possibility that BK channel dysfunction may underlie specific forms of hyperaldosteronism.
Detector Simulations with DD4hep Petrič, M; Frank, M; Gaede, F ...
Journal of physics. Conference series,
10/2017, Letnik:
898, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Detector description is a key component of detector design studies, test beam analyses, and most of particle physics experiments that require the simulation of more and more different detector ...geometries and event types. This paper describes DD4hep, which is an easy-to-use yet flexible and powerful detector description framework that can be used for detector simulation and also extended to specific needs for a particular working environment. Linear collider detector concepts ILD, SiD and CLICdp as well as detector development collaborations CALICE and FCal have chosen to adopt the DD4hep geometry framework and its DDG4 pathway to Geant4 as its core simulation and reconstruction tools. The DDG4 plugins suite includes a wide variety of input formats, provides access to the Geant4 particle gun or general particles source and allows for handling of Monte Carlo truth information, eg. by linking hits and the primary particle that caused them, which is indispensable for performance and efficiency studies. An extendable array of segmentations and sensitive detectors allows the simulation of a wide variety of detector technologies. This paper shows how DD4hep allows to perform complex Geant4 detector simulations without compiling a single line of additional code by providing a palette of sub-detector components that can be combined and configured via compact XML files. Simulation is controlled either completely via the command line or via simple Python steering files interpreted by a Python executable. It also discusses how additional plugins and extensions can be created to increase the functionality.
Prospective observational cohort study.
To describe time to occur and time until closure of hospital-acquired pressure ulcers (HAPUs) in patients with spinal cord injury (SCI).
Specialised SCI acute ...care and rehabilitation clinic in Switzerland.
Daily registration of the presence and severity of HAPUs in a consecutive sample of SCI patients during their entire in-patient stay.
Out of 185 observed SCI patients, 55 patients (29.7%) developed at least one HAPU. Within the first 30 days after admission, 50% of all HAPUs occurred. Less severe HAPUs occurred earlier than severe HAPUs. The occurrence of HAPUs was significantly associated with reason of admission (P<0.01), and was highest in first rehabilitation (51.4%) and orthopaedic surgery patients (41.4%). The incidences of first HAPU in these groups were 1.04 and 2.31 per patient-year, respectively. Patients in first rehabilitation or readmitted because of pressure ulcer (PU) showed an initial lower risk for HAPUs in the Kaplan-Meier curve compared with patients readmitted for other reasons. Cox regression analysis revealed an association between longer time since SCI and time until occurrence (P=0.01). Closure of the HAPUs during hospitalisation was observed in 37 patients (67.3%) after 38.9 days on average. No significant associations were found between patient characteristics and time until closure.
The dynamics of HAPUs varied according to admission reason and time since lesion. However, ongoing awareness to prevent HAPUs is needed in all patients with SCI.
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