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Study design: Cross-sectional survey. Objectives: To investigate annual rates and geographic variation of health care utilization in persons with spinal cord injury (SCI), and to identify factors associated with health care utilization. Setting: Community setting, entire country of Switzerland. Methods: Annual rates of planned and emergency visits to the general practitioner (GP), planned and emergency outpatient clinic visits and in-patient hospitalizations were compared between individuals with chronic SCI, over 16 years of age residing in Switzerland between late 2011 and early 2013 and a population sample (2012) of the Swiss general population. Risk factors for increased health service utilization were identified by means of regression models adjusted for spatial variation. Results: Of 492 participants (86.2% response rate), 94.1% visited a health care provider in the preceding year, with most persons visiting GPs (88.4%) followed by outpatient clinics (53.1%) and in-patient hospitals (35.9%). The increase in utilization as compared with the general population was 1.3-, 4.0- and 2.9-fold for GP, outpatient clinic and in-patient hospital visit, respectively. GP utilization was highest in persons with low income (incidence rate ratio (IRR) 1.85) and old age (IRR 2.62). In the first 2 years post injury, health service visits were 1.7 (GP visits) to 5.8 times (emergency outpatient clinic visits) more likely compared with those later post injury. Conclusions: People with SCI more frequently use health services as compared with the general population, across all types of medical service institutions. GP services were used most often in areas where availability of specialized outpatient clinic services was low.

Large-conductance calcium- and voltage-activated potassium channels (BKCa) are dually activated by membrane depolarization and elevation of cytosolic calcium ions (Ca²⁺). Under normal cellular conditions, BKCa channel activation requires Ca²⁺ concentrations that typically occur in close proximity to Ca²⁺ sources. We show that BKCa channels affinity-purified from rat brain are assembled into macromolecular complexes with the voltage-gated calcium channels Cav1.2 (L-type), Cav2.1 (P/Q-type), and Cav2.2 (N-type). Heterologously expressed BKCa-Cav complexes reconstitute a functional \"Ca²⁺ nanodomain\" where Ca²⁺ influx through the Cav channel activates BKCa in the physiological voltage range with submillisecond kinetics. Complex formation with distinct Cav channels enables BKCa-mediated membrane hyperpolarization that controls neuronal firing pattern and release of hormones and transmitters in the central nervous system.

The WD repeat-containing protein 4 (WDR4) has repeatedly been associated with primary microcephaly, a condition of impaired brain and skull growth. Often, faulty centrosomes cause microcephaly, yet aberrant cilia may also be involved. Here, we show using a combination of approaches in human fibroblasts, zebrafish embryos and patient-derived cells that WDR4 facilitates cilium formation. Molecularly, we associated WDR4 loss-of-function with increased protein synthesis and concomitant upregulation of proteasomal activity, while ubiquitin precursor pools are reduced. Inhibition of proteasomal activity as well as supplementation with free ubiquitin restored normal ciliogenesis. Proteasome inhibition ameliorated microcephaly phenotypes. Thus, we propose that WDR4 loss-of-function impairs head growth and neurogenesis via aberrant cilia formation, initially caused by disturbed protein and ubiquitin homeostasis.

Study design: This was a prospective cohort study. Objectives: The objective was to describe the incidence, prevalence, characteristics of pressure ulcers (PUs) and the association with specific patient characteristics in a consecutive sample of in-patients with a spinal cord injury (SCI). Setting: An acute care and rehabilitation clinic specialized in SCIs in Switzerland. Methods: The presence and characteristics of PUs for all adult patients with a SCI admitted to the clinic from 1 September 2009 to 28 February 2010 were recorded on a daily basis during their complete hospitalization. Risk factors were analyzed in univariate and multivariate logistic regression models. Results: A total of 185 patients were included in the study and observed for the entirety of their hospitalization. The prevalence of at least one PU was 49.2% in all patients, compared with 25.4% in the group of patients admitted without PUs. The incidence was 2.2 per person and year. In 91 patients, a total of 219 PUs were observed. PUs were most frequently located on the foot (36.1%), and the coccyx/sacrum (15.1%). The risk for occurrence of a PU increased with age (odds ratio (OR)=1.04) and post SCI (OR=1.03). In the multivariate analyses, the risk for PUs was lower for patients with the American Spinal Injury Association (ASIA) Impairment Scale (AIS) of C or D (OR C =0.25, OR D =0.28) compared with patients with an AIS of A. Conclusion: Using a daily documentation system, PUs were detected as a frequent complication of SCIs. Completeness of injury, age and time since injury were significant risk factors for PUs. The foot was a region at high risk for PUs.

Study design:Prospective controlled before-and-after study.Objectives:To investigate the effects of antimuscarinic treatment of neurogenic lower urinary tract dysfunction on the cognition of individuals with spinal cord injury (SCI) during the early post-acute phase.Setting:Single SCI rehabilitation center.Methods:Patients with acute traumatic SCI admitted for primary rehabilitation from 2011 to 2015 were screened for study enrollment. Study participants underwent baseline neuropsychological assessments prior to their first urodynamic evaluation (6-8 weeks after SCI). Individuals suffering from neurogenic detrusor overactivity received antimuscarinic treatment, and those not requiring antimuscarinic treatment constituted the control group. The neuropsychological follow-up assessment was carried out 3 months after the baseline assessment. The effects of group and time on the neuropsychological parameters were investigated.Results:The data of 29 individuals were evaluated (control group 19, antimuscarinic group 10). The group had a significant (P≤0.033) effect on immediate recall, attention ability and perseveration. In the control group, individuals performed significantly (P≤0.05) better in immediate recall both at baseline (percentile rank 40, 95% CI 21-86 versus 17, 95% CI 4-74) and follow-up (percentile rank 40, 95% CI 27-74 versus 16, 95% CI 2-74). The time had a significant (P≤0.04) effect on attention ability, processing speed, word fluency and visuospatial performance. The individuals in both groups performed better at the follow-up compared to the baseline assessment.Conclusion:Even though, we did not observe cognitive deterioration in the investigated, cognitively intact SCI individuals during the first 3 treatment months, the concerns regarding deleterious effects of antimuscarinics on cognition remain.

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.

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.

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.

Study design: Prospective observational cohort study. Objectives: To describe time to occur and time until closure of hospital-acquired pressure ulcers (HAPUs) in patients with spinal cord injury (SCI). Setting: Specialised SCI acute care and rehabilitation clinic in Switzerland. Methods: Daily registration of the presence and severity of HAPUs in a consecutive sample of SCI patients during their entire in-patient stay. Results: 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. Conclusion: 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.

Study design: This was a cross-sectional questionnaire survey. Objectives: 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. Setting: This study was conducted in the entire country of Switzerland. Methods: 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. Results: 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. Conclusions: 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.