CIF2OP Instruction Manual

No Abstract

Immune or genetic-mediated disruption of CASPR2 causes pain hypersensitivity due to enhanced primary afferent excitability

Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2 ) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens. Both primary afferent excitability and subsequent nociceptive transmission within the dorsal horn were increased in Cntnap2 mice. Either immune or genetic-mediated ablation of CASPR2 enhanced the excitability of DRG neurons in a cell-autonomous fashion through regulation of Kv1 channel expression at the soma membrane. This is the first example of passive transfer of an autoimmune peripheral neuropathic pain disorder and demonstrates that CASPR2 has a key role in regulating cell-intrinsic dorsal root ganglion (DRG) neuron excitability

Exercise-Based Rehabilitation for Heart Failure:Cochrane Systematic Review, MetaAnalysis, and Trial Sequential Analysis

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Objectives: This study performed a contemporary systematic review and meta-analysis of exercise-based cardiac rehabilitation (ExCR) for heart failure (HF). Background: There is an increasing call for trials of models of ExCR for patients with HF that provide alternatives to conventional center-based provision and recruitment of patients that reflect a broader HF population. Methods: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and PsycINFO databases were searched between January 2013 and January 2018. Randomized trials comparing patients undergoing ExCR to control patients not undergoing exercise were included. Study outcomes were pooled using meta-analysis. Metaregression examined potential effect modification according to ExCR program characteristics, and risk of bias, trial sequential analysis (TSA), and Grading of Recommendations Assessment Development and Evaluation (GRADE) were applied. Results: Across 44 trials (n = 5,783; median follow-up of 6 months), compared with control subjects, ExCR did not reduce the risk of all-cause mortality (relative risk [RR]: 0.89; 95% confidence interval [CI]: 0.66 to 1.21; TSA-adjusted CI: 0.26 to 3.10) but did reduce all-cause hospitalization (RR: 0.70; 95% CI: 0.60 to 0.83; TSA-adjusted CI: 0.54 to 0.92) and HF-specific hospitalization (RR: 0.59; 95% CI: 0.42 to 0.84; TSA-adjusted CI: 0.14 for 2.46), and patients reported improved Minnesota Living with Heart Failure questionnaire overall scores (mean difference: −7.1; 95% CI: −10.5 to −3.7; TSA-adjusted CI: −13.2 to −1.0). No evidence of differential effects across different models of delivery, including center- versus home-based programs, were found. Conclusions: This review supports the beneficial effects of ExCR on patient outcomes. These benefits appear to be consistent across ExCR program characteristics. GRADE and TSA assessments indicated that further high-quality randomized trials are needed

Search for the disappearance of muon antineutrinos in the NuMI neutrino beam

We report constraints on antineutrino oscillation parameters that were obtained by using the two MINOS detectors to measure the 7% muon antineutrino component of the NuMI neutrino beam. In the Far Detector, we select 130 events in the charged-current muon antineutrino sample, compared to a prediction of 136.4 ± 11.7(stat)^(+10.2)_(-8.9)(syst) events under the assumption │Δm^2│ = 2.32 X 10^(-3) eV^2, sin^2(2θ) = 1.0

Improved Search for Muon-Neutrino to Electron-Neutrino Oscillations in MINOS

We report the results of a search for ν_e appearance in a ν_μ beam in the MINOS long-baseline neutrino experiment. With an improved analysis and an increased exposure of 8.2×10^(20) protons on the NuMI target at Fermilab, we find 2sin^2(θ_(23))sin^2(2θ_(13))<0.12(0.20) at 90% confidence level for δ=0 and the normal (inverted) neutrino mass hierarchy, with a best-fit of 2sin^2(θ_(23))sin^2(2θ_(13))=0.041^(+0.047)_(-0.031)(0.079^(+0.071)_(-0.053). The θ_(13)= 0 hypothesis is disfavored by the MINOS data at the 89% confidence level

Measurement of the Neutrino Mass Splitting and Flavor Mixing by MINOS

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of 7.25×10^(20) protons on target. A fit to neutrino oscillations yields values of |Δm^2|=(2.32_(-0.08)^(+0.12))×10^(-3)  eV^2 for the atmospheric mass splitting and sin^2(2θ)>0.90 (90% C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively

First Direct Observation of Muon Antineutrino Disappearance

This Letter reports the first direct observation of muon antineutrino disappearance. The MINOS experiment has taken data with an accelerator beam optimized for ν̅ _μ production, accumulating an exposure of 1.71×10^(20) protons on target. In the Far Detector, 97 charged current ν̅ _μ events are observed. The no-oscillation hypothesis predicts 156 events and is excluded at 6.3σ. The best fit to oscillation yields |Δm̅ 2|= [3.36=_(-0.40)^(+0.46)(stat)±0.06(syst)]x10^(-3)eV^2,sin^2(2θ̅)=0.86 _(-0.12)^(+0.11)(stat)±0.01(syst). The MINOS ν̅ _μ and ν̅ _μ measurements are consistent at the 2.0% confidence level, assuming identical underlying oscillation parameters

Measurement of the underground atmospheric muon charge ratio using the MINOS Near Detector

The magnetized MINOS Near Detector, at a depth of 225 mwe, is used to measure the atmospheric muon charge ratio. The ratio of observed positive to negative atmospheric muon rates, using 301 days of data, is measured to be 1.266±0.001(stat)_(-0.014)^(+0.015)(syst). This measurement is consistent with previous results from other shallow underground detectors and is 0.108±0.019(stat+syst) lower than the measurement at the functionally identical MINOS Far Detector at a depth of 2070 mwe. This increase in charge ratio as a function of depth is consistent with an increase in the fraction of muons arising from kaon decay for increasing muon surface energie