An AdS/EFT correspondence at large charge

Considering theories in sectors of large global charge $Q$ results in a semiclassical effective field theory (EFT) description for some strongly-coupled conformal field theories (CFTs) with continuous global symmetries. Hence, when studying dualities at large charge, we can have control over the strongly coupled side of the duality and gain perturbative access to both dual pairs. In this work we discuss the AdS/CFT correspondence in the regime $Q \gg C_T \gg 1$ where both the EFT and gravity descriptions are valid and stable ($C_T$ being the central charge). We present the observation that the ground state energy as a function of the Abelian charge $Q$ for a simple EFT in some three-dimensional CFT coincides with the expression for the mass of an anti-de Sitter-Reissner-Nordstr\"om black hole as a function of its charge. This observation allows us to introduce a dictionary relating CFT, EFT and holographic descriptions. We also find agreement for the higher-derivative corrections on both sides, suggesting a large-$C_T$ expansion on the EFT side.Comment: 23 pages. Matches published version in Nucl.Phys.

Soluble Intracellular Adhesion Molecule-1 in Patients with Unipolar or Bipolar Affective Disorders

Background: Immunological and vascular markers may play a role in the pathophysiology of mood disorders and mood changes. Aim: To test whether the cell adhesion molecule soluble intracellular adhesion molecule-1 (sICAM-1) may serve as a biomarker for patients with unipolar or bipolar affective disorders when compared to a healthy control group, and whether sICAM-1 blood levels change during different mood states. Methods: sICAM-1 serum concentrations were compared between 20 healthy controls and 48 patients with affective disorders (unipolar, bipolar II and bipolar I disorder) during different mood states (euthymic mood state, depression or mania). Results: When compared to healthy controls, patients with affective disorders had significantly higher sICAM-1 levels during the euthymic state (p = 0.015). Differences became more pronounced during depression (p = 0.013). When unipolar and bipolar patients were analyzed separately, unipolar patients significantly differed from controls during the euthymic and depressive mood state, while bipolar II patients showed a trend towards higher sICAM-1 levels during depression. Patients with bipolar I disorders had significantly higher sICAM-1 levels during manic states when compared to controls (p = 0.007). Conclusions: sICAM-1 elevation in unipolar and bipolar patients, independent of mood changes, might support the hypothesis of chronic immune activation and endothelial dysfunction in patients with affective disorders. (C) 2016 S. Karger AG, Base

Cloud System Evolution in the Trades (CSET): Following the Evolution of Boundary Layer Cloud Systems with the NSFNCAR GV

The Cloud System Evolution in the Trades (CSET) study was designed to describe and explain the evolution of the boundary layer aerosol, cloud, and thermodynamic structures along trajectories within the North Pacific trade winds. The study centered on seven round trips of the National Science FoundationNational Center for Atmospheric Research (NSFNCAR) Gulfstream V (GV) between Sacramento, California, and Kona, Hawaii, between 7 July and 9 August 2015. The CSET observing strategy was to sample aerosol, cloud, and boundary layer properties upwind from the transition zone over the North Pacific and to resample these areas two days later. Global Forecast System forecast trajectories were used to plan the outbound flight to Hawaii with updated forecast trajectories setting the return flight plan two days later. Two key elements of the CSET observing system were the newly developed High-Performance Instrumented Airborne Platform for Environmental Research (HIAPER) Cloud Radar (HCR) and the high-spectral-resolution lidar (HSRL). Together they provided unprecedented characterizations of aerosol, cloud, and precipitation structures that were combined with in situ measurements of aerosol, cloud, precipitation, and turbulence properties. The cloud systems sampled included solid stratocumulus infused with smoke from Canadian wildfires, mesoscale cloudprecipitation complexes, and patches of shallow cumuli in very clean environments. Ultraclean layers observed frequently near the top of the boundary layer were often associated with shallow, optically thin, layered veil clouds. The extensive aerosol, cloud, drizzle, and boundary layer sampling made over open areas of the northeast Pacific along 2-day trajectories during CSET will be an invaluable resource for modeling studies of boundary layer cloud system evolution and its governing physical processes

Opposite Modulation of RAC1 by Mutations in TRIO Is Associated with Distinct, Domain-Specific Neurodevelopmental Disorders

The Rho-guanine nucleotide exchange factor (RhoGEF) TRIO acts as a key regulator of neuronal migration, axonal outgrowth, axon guidance, and synaptogenesis by activating the GTPase RAC1 and modulating actin cytoskeleton remodeling. Pathogenic variants in TRIO are associated with neurodevelopmental diseases, including intellectual disability (ID) and autism spectrum disorders (ASD). Here, we report the largest international cohort of 24 individuals with confirmed pathogenic missense or nonsense variants in TRIO. The nonsense mutations are spread along the TRIO sequence, and affected individuals show variable neurodevelopmental phenotypes. In contrast, missense variants cluster into two mutational hotspots in the TRIO sequence, one in the seventh spectrin repeat and one in the RAC1-activating GEFD1. Although all individuals in this cohort present with developmental delay and a neuro-behavioral phenotype, individuals with a pathogenic variant in the seventh spectrin repeat have a more severe ID associated with macrocephaly than do most individuals with GEFD1 variants, who display milder ID and microcephaly. Functional studies show that the spectrin and GEFD1 variants cause a TRIO-mediated hyper- or hypo-activation of RAC1, respectively, and we observe a striking correlation between RAC1 activation levels and the head size of the affected individuals. In addition, truncations in TRIO GEFD1 in the vertebrate model X. tropicalis induce defects that are concordant with the human phenotype. This work demonstrates distinct clinical and molecular disorders clustering in the GEFD1 and seventh spectrin repeat domains and highlights the importance of tight control of TRIO-RAC1 signaling in neuronal development.<br/

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat