UK clinical experience up to 52 weeks with linaclotide for irritable bowel syndrome with constipation

Background: Linaclotide, a guanylate cyclase C agonist, has been shown in clinical trials to improve symptoms of irritable bowel syndrome with constipation (IBS-C). Here we report data from a real-world study of linaclotide in the UK. Methods: This 1-year, multicentre, prospective, observational study in the UK enrolled patients aged 18 years and over initiating linaclotide for IBS-C. The primary assessment was change from baseline in IBS Symptom Severity Scale (IBS-SSS) score at 12 weeks, assessed in patients with paired baseline and 12-week data. Change from baseline in IBS-SSS score at 52 weeks was a secondary assessment. Adverse events were recorded. Results: In total, 202 patients were enrolled: 185 (91.6%) were female, median age was 44.9 years (range 18.1–77.2) and 84 (41.6%) reported baseline laxative use. Mean (standard deviation) baseline IBS-SSS score was 339 (92), with most patients (n = 129; 66.8%) classified as having severe disease (score ⩾300). In patients with paired data, there was a significant mean (95% confidence interval) decrease in IBS-SSS score from baseline to 12 weeks [−77.0 (−96.3, −57.7); p < 0.001; n = 124] and baseline to 52 weeks [−70.7 (−95.0, −46.5); p < 0.001; n = 76]. Overall, 174 adverse events were reported in 77 (38.1%) patients, most commonly diarrhoea (n = 54; 26.7%), abdominal pain (n = 21; 10.4%) and abdominal distension (n = 13; 6.4%). Conclusion: Linaclotide significantly improved IBS-SSS score at 12 and 52 weeks. These results provide insights into outcomes with linaclotide treatment over 1 year in patients with IBS-C in real-world clinical practice

Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results

The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

The International Pulsar Timing Array: First data release

International audienceThe highly stable spin of neutron stars can be exploited for a variety of (astro)physical investigations. In particular, arrays of pulsars with rotational periods of the order of milliseconds can be used to detect correlated signals such as those caused by gravitational waves. Three such 'pulsar timing arrays' (PTAs) have been set up around the world over the past decades and collectively form the 'International' PTA (IPTA). In this paper, we describe the first joint analysis of the data from the three regional PTAs, i.e. of the first IPTA data set. We describe the available PTA data, the approach presently followed for its combination and suggest improvements for future PTA research. Particular attention is paid to subtle details (such as underestimation of measurement uncertainty and long-period noise) that have often been ignored but which become important in this unprecedentedly large and inhomogeneous data set. We identify and describe in detail several factors that complicate IPTA research and provide recommendations for future pulsar timing efforts. The first IPTA data release presented here (and available on-line) is used to demonstrate the IPTA's potential of improving upon gravitational-wave limit

Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.New methods for child psychiatric diagnosis and treatment outcome evaluatio

Neuroimaging-based classification of PTSD using data-driven computational approaches: a multisite big data study from the ENIGMA-PGC PTSD consortium

Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for D-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.Stress-related psychiatric disorders across the life spa

The design, implementation, and performance of the LZ calibration systems

LUX-ZEPLIN (LZ) is a tonne-scale experiment searching for direct dark matter interactions and other rare events. It is located at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. The core of the LZ detector is a dual-phase xenon time projection chamber (TPC), designed with the primary goal of detecting Weakly Interacting Massive Particles (WIMPs) via their induced low energy nuclear recoils. Surrounding the TPC, two veto detectors immersed in an ultra-pure water tank enable reducing background events to enhance the discovery potential. Intricate calibration systems are purposely designed to precisely understand the responses of these three detector volumes to various types of particle interactions and to demonstrate LZ's ability to discriminate between signals and backgrounds. In this paper, we present a comprehensive discussion of the key features, requirements, and performance of the LZ calibration systems, which play a crucial role in enabling LZ's WIMP-search and its broad science program. The thorough description of these calibration systems, with an emphasis on their novel aspects, is valuable for future calibration efforts in direct dark matter and other rare-event search experiments