243 research outputs found
T cell receptor signal strength in Treg and iNKT cell development as revealed by a novel fluorescent reporter mouse
Force dysmetria in spinocerebellar ataxia 6 correlates with functional capacity
Spinocerebellar ataxia type 6 (SCA6) is a genetic disease that causes pure cerebellar degeneration affecting walking, balance, and coordination. One of the main symptoms of SCA6 is dysmetria. The magnitude of dysmetria and its relation to functional capacity in SCA6 has not been studied. Our purpose was to quantify dysmetria and determine the relation between dysmetria and functional capacity in SCA6. Ten individuals diagnosed and genetically confirmed with SCA6 (63.7 ± 7.02yrs) and nine age-matched healthy controls (65.9 ± 8.5yrs) performed goal-directed isometric contractions with the ankle joint. Dysmetria was quantified as the force and time error during goal-directed contractions. SCA6 functional capacity was determined by ICARS and SARA clinical assessments. We found that SCA6 participants exhibited greater force dysmetria than healthy controls (P < 0.05), and reduced time dysmetria than healthy controls (P < 0.05). Only force dysmetria was significantly related to SCA6 functional capacity, as measured with ICARS kinetic score (R2 = 0.63), ICARS total score (R2 = 0.43), and SARA total score (R2 = 0.46). Our findings demonstrate that SCA6 exhibit force dysmetria and that force dysmetria is associated to SCA6 functional capacity. Quantifying force and time dysmetria in individuals with SCA6 could provide a more objective evaluation of the functional capacity and disease state in SCA6
Phase distribution, composition and disorder in Y2(Hf,Sn)2O7 ceramics : insights from solid-state NMR spectroscopy and first-principles calculations
The authors would like to thank the ERC (EU FP7 Consolidator Grant 614290 “‘EXONMR’”), and EPSRC for support for SS and ASG (EP/L005581/1). SEA would like to thank the Royal Society and Wolfson Foundation for a merit award. We acknowledge support from the Collaborative Computational Project on NMR Crystallography CCP-NC funded by EPSRC (EP/M022501/1).A NMR crystallographic approach, combining 89Y, 119Sn and 17O NMR spectroscopy with X-ray diffraction and first-principles calculations has been used investigate the number and type of phases present, and the local structure and disorder in Y2Hf2–xSnxO7 ceramics. Although a phase change is predicted with increasing Hf content, NMR spectra clearly show the presence of a significant two-phase region, with a Sn-rich pyrochlore and relatively Hf-rich defect fluorite phase co-existing for much of the compositional series. A single-phase pyrochlore is found only for the Sn end member, and a single defect fluorite phase only for x = 0 to 0.2. A solid-solution limit of ~10% is seen for the substitution of Hf into Y2Sn2O7, although no evidence is seen for any cation ordering or antisite disorder in this phase. In the defect fluorite phase there is preferential ordering of oxygen vacancies around Sn, which is only ever seen in a six-coordinate environment. The remaining vacancies are more likely to be associated with Hf than with Y, although this distinction is less apparent at higher Sn concentrations. To acquire 17O NMR spectra samples were post-synthetically exchanged with 17O2(g), although high temperatures (> 900 ºC) were required to ensure uniform enrichment of different chemical species. although these 17O NMR spectra confirm the formation of mixed-metal materials and the presence of two phases, more quantitative analysis is hindered by the overlap of signals from pyrochlore and defect fluorite phases. In all cases, DFT calculations play a vital role in the interpretation and assignment of the NMR spectra, and in understanding the local structure and disorder in these complex multi-phase materials.PostprintPostprintPeer reviewe
Neural Synchrony Examined with Magnetoencephalography (MEG) During Eye Gaze Processing in Autism Spectrum Disorders: Preliminary Findings
Gaze processing deficits are a seminal, early, and enduring behavioral deficit in autism spectrum disorder (ASD); however, a comprehensive characterization of the neural processes mediating abnormal gaze processing in ASD has yet to be conducted. This study investigated whole-brain patterns of neural synchrony during passive viewing of direct and averted eye gaze in ASD adolescents and young adults (M Age = 16.6) compared to neurotypicals (NT) (MAge = 17.5) while undergoing magnetoencephalography. Coherence between each pair of 54 brain regions within each of three frequency bands (low frequency (0 to 15 Hz), beta (15 to 30 Hz), and low gamma (30 to 45 Hz)) was calculated
Neural Synchrony Examined with Magnetoencephalography (MEG) During Eye Gaze Processing in Autism Spectrum Disorders: Preliminary Findings
Gaze processing deficits are a seminal, early, and enduring behavioral deficit in autism spectrum disorder (ASD); however, a comprehensive characterization of the neural processes mediating abnormal gaze processing in ASD has yet to be conducted. This study investigated whole-brain patterns of neural synchrony during passive viewing of direct and averted eye gaze in ASD adolescents and young adults (M Age = 16.6) compared to neurotypicals (NT) (MAge = 17.5) while undergoing magnetoencephalography. Coherence between each pair of 54 brain regions within each of three frequency bands (low frequency (0 to 15 Hz), beta (15 to 30 Hz), and low gamma (30 to 45 Hz)) was calculated
Single Event Effect Flight Data Analysis of Multiple NASA Spacecraft and Experiments
Abstract We present the spaceflight Single Event Effect (SEE) data for the emerging commercial technologies utilized in multiple NASA spacecraft and experiments. Analyses of device performance as well as design implications of the flight results are discussed
A phase II single-arm study of pembrolizumab with enzalutamide in men with metastatic castration-resistant prostate cancer progressing on enzalutamide alone.
BACKGROUND: Checkpoint inhibitors can induce profound anticancer responses, but programmed cell death protein-1 (PD-1) inhibition monotherapy has shown minimal activity in prostate cancer. A published report showed that men with prostate cancer who were resistant to the second-generation androgen receptor inhibitor enzalutamide had increased programmed death-ligand 1 (PD-L1) expression on circulating antigen-presenting cells. We hypothesized that the addition of PD-1 inhibition in these patients could induce a meaningful cancer response.
METHODS: We evaluated enzalutamide plus the PD-1 inhibitor pembrolizumab in a single-arm phase II study of 28 men with metastatic castration-resistant prostate cancer (mprogressing on enzalutamide alone. Pembrolizumab 200 mg intravenous was given every 3 weeks for four doses with enzalutamide. The primary endpoint was prostate-specific antigen (PSA) decline of ≥50%. Secondary endpoints were objective response, PSA progression-free survival (PFS), time to subsequent treatment, and time to death. Baseline tumor biopsies were obtained when feasible, and samples were sequenced and evaluated for the expression of PD-L1, microsatellite instability (MSI), mutational and neoepitope burdens.
RESULTS: Five (18%) of 28 patients had a PSA decline of ≥50%. Three (25%) of 12 patients with measurable disease at baseline achieved an objective response. Of the five responders, two continue with PSA and radiographic response after 39.3 and 37.8 months. For the entire cohort, median follow-up was 37 months, and median PSA PFS time was 3.8 months (95% CI: 2.8 to 9.9 months). Time to subsequent treatment was 7.21 months (95% CI: 5.1 to 11.1 months). Median overall survival for all patients was 21.9 months (95% CI: 14.7 to 28 .4 months), versus 41.7 months (95% CI: 22.16 to not reached (NR)) in the responders. Of the three responders with baseline biopsies, one had MSI high disease with mutations consistent with DNA-repair defects. None had detectable PD-L1 expression.
CONCLUSIONS: Pembrolizumab has activity in mCRPC when added to enzalutamide. Responses were deep and durable and did not require tumor PD-L1 expression or DNA-repair defects.
TRIAL REGISTRATION NUMBER: clinicaltrials.gov (NCT02312557)
A Smartphone-based Decision Support Tool Improves Test Performance Concerning Application of the Guidelines for Managing Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy
BACKGROUND: The American Society of Regional Anesthesia and Pain Medicine (ASRA) consensus statement on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy is the standard for evaluation and management of these patients. The authors hypothesized that an electronic decision support tool (eDST) would improve test performance compared with native physician behavior concerning the application of this guideline.
METHODS: Anesthesiology trainees and faculty at 8 institutions participated in a prospective, randomized trial in which they completed a 20-question test involving clinical scenarios related to the ASRA guidelines. The eDST group completed the test using an iOS app programmed to contain decision logic and content of the ASRA guidelines. The control group completed the test by using any resource in addition to the app. A generalized linear mixed-effects model was used to examine the effect of the intervention.
RESULTS: After obtaining institutional review board's approval and informed consent, 259 participants were enrolled and randomized (eDST = 122; control = 137). The mean score was 92.4 ± 6.6% in the eDST group and 68.0 ± 15.8% in the control group (P < 0.001). eDST use increased the odds of selecting correct answers (7.8; 95% CI, 5.7 to 10.7). Most control group participants (63%) used some cognitive aid during the test, and they scored higher than those who tested from memory alone (76 ± 15% vs. 57 ± 18%, P < 0.001). There was no difference in time to completion of the test (P = 0.15) and no effect of training level (P = 0.56).
CONCLUSIONS: eDST use improved application of the ASRA guidelines compared with the native clinician behavior in a testing environment
Prevalence and demographics of methicillin resistant Staphylococcus aureus in culturable skin and soft tissue infections in an urban emergency department
<p>Abstract</p> <p>Background</p> <p>The rising incidence of methicillin resistant <it>Staph. aureus </it>(MRSA) infections is a concern for emergency practitioners. While studies have examined MRSA in inpatients, few have focused on emergency department populations. We sought to describe predictors of MRSA skin infections in an emergency department population.</p> <p>Methods</p> <p>This was a prospective observational cohort study conducted over three months in 2005. A convenience sample of patients with culturable skin infections presenting to a busy, urban emergency department was enrolled. Demographic and risk factor information was collected by structured interview. The predictive value of each risk factor for MRSA, as identified by culture, was tested using univariable logistic regression, and a multivariable predictive model was developed.</p> <p>Results</p> <p>Patients were 43% black, 40% female and mean age was 39 years (SD 14 years). Of the 182 patients with cultures, prevalence of MRSA was 58% (95%CI 50% to 65%). Significant predictors of MRSA were youth, lower body mass index, sexual contact in the past month, presence of an abscess cavity, spontaneous infection, and incarceration. The multivariable model had a C-statistic of 0.73 (95%CI 0.67 to 0.79) with four significant variables: age, group living, abscess cavity, and sexual contact within one month.</p> <p>Conclusion</p> <p>In this population of emergency department patients, MRSA skin infection was related to youth, recent sexual contact, presence of abscess, low body mass index, spontaneity of infection, incarceration or contact with an inmate, and group home living.</p
Current Single Event Effect Test Results for Candidate Spacecraft Electronics
Abstract We present both proton and heavy ion single event effect (SEE) ground test results for candidate spacecraft electronics. A variety of digital and analog devices were tested, including EEPROMs, DRAMs, and DC-DC Converters
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