A Comprehensive Archival Search for Counterparts to Ultra-Compact High Velocity Clouds: Five Local Volume Dwarf Galaxies

We report five Local Volume dwarf galaxies (two of which are presented here for the first time) uncovered during a comprehensive archival search for optical counterparts to ultra-compact high velocity clouds (UCHVCs). The UCHVC population of HI clouds are thought to be candidate gas-rich, low mass halos at the edge of the Local Group and beyond, but no comprehensive search for stellar counterparts to these systems has been presented. Careful visual inspection of all publicly available optical and ultraviolet imaging at the position of the UCHVCs revealed six blue, diffuse counterparts with a morphology consistent with a faint dwarf galaxy beyond the Local Group. Optical spectroscopy of all six candidate dwarf counterparts show that five have an H$\alpha$-derived velocity consistent with the coincident HI cloud, confirming their association, the sixth diffuse counterpart is likely a background object. The size and luminosity of the UCHVC dwarfs is consistent with other known Local Volume dwarf irregular galaxies. The gas fraction ($M_{HI}/M_{star}$) of the five dwarfs are generally consistent with that of dwarf irregular galaxies in the Local Volume, although ALFALFA-Dw1 (associated with ALFALFA UCHVC HVC274.68+74.70$-$123) has a very high $M_{HI}/M_{star}$$\sim$40. Despite the heterogenous nature of our search, we demonstrate that the current dwarf companions to UCHVCs are at the edge of detectability due to their low surface brightness, and that deeper searches are likely to find more stellar systems. If more sensitive searches do not reveal further stellar counterparts to UCHVCs, then the dearth of such systems around the Local Group may be in conflict with $\Lambda$CDM simulations.Comment: 18 pages, 4 tables, 4 figures, ApJ Accepte

A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO)

Rationale Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. Objectives To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. Measurements and methods This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5–<30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6 weeks of treatment with three nonadjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. Main results 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20 000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39 800/QALY. Conclusions Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective

Cognitive behaviour therapy versus counselling intervention for anxiety in young people with high-functioning autism spectrum disorders: a pilot randomised controlled trial

The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12–18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability. Whilst each therapy produced improvements inparticipants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults

Ventriculo-arterial coupling detects occult RV dysfunction in chronic thromboembolic pulmonary vascular disease.

Chronic thromboembolic disease (CTED) is suboptimally defined by a mean pulmonary artery pressure (mPAP)  0.68 and Ees/Ea < 0.68 subgroups demonstrated constant RV stroke work but lower stroke volume (87.7 ± 22.1 vs. 60.1 ± 16.3 mL respectively, P = 0.006) and higher end-systolic pressure (36.7 ± 11.6 vs. 68.1 ± 16.7 mmHg respectively, P < 0.001). Lower Ees/Ea in CTED also correlated with reduced exercise ventilatory efficiency. Low Ees/Ea aligns with features of RV maladaptation in CTED both at rest and on exercise. Characterization of Ees/Ea in CTED may allow for better identification of occult RV dysfunction

Design, construction, and characterization of a compact DD neutron generator designed for 40Ar/39Ar geochronology

A next-generation, high-flux DD neutron generator has been designed, commissioned, and characterized, and is now operational in a new facility at the University of California Berkeley. The generator, originally designed for 40Ar/39Ar dating of geological materials, has since served numerous additional applications, including medical isotope production studies, with others planned for the near future. In this work, we present an overview of the High Flux Neutron Generator (HFNG) which includes a variety of simulations, analytical models, and experimental validation of results. Extensive analysis was performed in order to characterize the neutron yield, flux, and energy distribution at specific locations where samples may be loaded for irradiation. A notable design feature of the HFNG is the possibility for sample irradiation internal to the cathode, just 8 mm away from the neutron production site, thus maximizing the neutron flux (n/cm2/s). The generator's maximum neutron flux at this irradiation position is 2.58e7 n/cm2/s +/- 5% (approximately 3e8 n/s total yield) as measured via activation of small natural indium foils. However, future development is aimed at achieving an order of magnitude increase in flux. Additionally, the deuterium ion beam optics were optimized by simulations for various extraction configurations in order to achieve a uniform neutron flux distribution and an acceptable heat load. Finally, experiments were performed in order to benchmark the modeling and characterization of the HFNG.Comment: 31 pages, 20 figure

BMP9 Mutations Cause a Vascular-Anomaly Syndrome with Phenotypic Overlap with Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, is caused by mutations in genes involved in the transforming growth factor beta (TGF-β) signaling pathway (ENG, ACVRL1, and SMAD4). Yet, approximately 15% of individuals with clinical features of HHT do not have mutations in these genes, suggesting that there are undiscovered mutations in other genes for HHT and possibly vascular disorders with overlapping phenotypes. The genetic etiology for 191 unrelated individuals clinically suspected to have HHT was investigated with the use of exome and Sanger sequencing; these individuals had no mutations in ENG, ACVRL1, and SMAD4. Mutations in BMP9 (also known as GDF2) were identified in three unrelated probands. These three individuals had epistaxis and dermal lesions that were described as telangiectases but whose location and appearance resembled lesions described in some individuals with RASA1-related disorders (capillary malformation-arteriovenous malformation syndrome). Analyses of the variant proteins suggested that mutations negatively affect protein processing and/or function, and a bmp9-deficient zebrafish model demonstrated that BMP9 is involved in angiogenesis. These data confirm a genetic cause of a vascular-anomaly syndrome that has phenotypic overlap with HHT

Genetics and genomics of pulmonary arterial hypertension.

Since 2000 there have been major advances in our understanding of the genetic and genomics of pulmonary arterial hypertension (PAH), although there remains much to discover. Based on existing knowledge, around 25-30% of patients diagnosed with idiopathic PAH have an underlying Mendelian genetic cause for their condition and should be classified as heritable PAH (HPAH). Here, we summarise the known genetic and genomic drivers of PAH, the insights these provide into pathobiology, and the opportunities afforded for development of novel therapeutic approaches. In addition, factors determining the incomplete penetrance observed in HPAH are discussed. The currently available approaches to genetic testing and counselling, and the impact of a genetic diagnosis on clinical management of the patient with PAH, are presented. Advances in DNA sequencing technology are rapidly expanding our ability to undertake genomic studies at scale in large cohorts. In the future, such studies will provide a more complete picture of the genetic contribution to PAH and, potentially, a molecular classification of this disease

Approximating Optimal Behavioural Strategies Down to Rules-of-Thumb: Energy Reserve Changes in Pairs of Social Foragers

Functional explanations of behaviour often propose optimal strategies for organisms to follow. These ‘best’ strategies could be difficult to perform given biological constraints such as neural architecture and physiological constraints. Instead, simple heuristics or ‘rules-of-thumb’ that approximate these optimal strategies may instead be performed. From a modelling perspective, rules-of-thumb are also useful tools for considering how group behaviour is shaped by the behaviours of individuals. Using simple rules-of-thumb reduces the complexity of these models, but care needs to be taken to use rules that are biologically relevant. Here, we investigate the similarity between the outputs of a two-player dynamic foraging game (which generated optimal but complex solutions) and a computational simulation of the behaviours of the two members of a foraging pair, who instead followed a rule-of-thumb approximation of the game's output. The original game generated complex results, and we demonstrate here that the simulations following the much-simplified rules-of-thumb also generate complex results, suggesting that the rule-of-thumb was sufficient to make some of the model outcomes unpredictable. There was some agreement between both modelling techniques, but some differences arose – particularly when pair members were not identical in how they gained and lost energy. We argue that exploring how rules-of-thumb perform in comparison to their optimal counterparts is an important exercise for biologically validating the output of agent-based models of group behaviour

Why do hospital prescribers continue antibiotics when it is safe to stop? Results of a choice experiment survey

Background Deciding whether to discontinue antibiotics at early review is a cornerstone of hospital antimicrobial stewardship practice worldwide. In England, this approach is described in government guidance (‘Start Smart then Focus’). However, < 10% of hospital antibiotic prescriptions are discontinued at review, despite evidence that 20–30% could be discontinued safely. We aimed to quantify the relative importance of factors influencing prescriber decision-making at review. Methods We conducted an online choice experiment, a survey method to elicit preferences. Acute/general hospital prescribers in England were asked if they would continue or discontinue antibiotic treatment in 15 hypothetical scenarios. Scenarios were described according to six attributes, including patients’ presenting symptoms and whether discontinuation would conflict with local prescribing guidelines. Respondents’ choices were analysed using conditional logistic regression. Results One hundred respondents completed the survey. Respondents were more likely to continue antibiotics when discontinuation would ‘strongly conflict’ with local guidelines (average marginal effect (AME) on the probability of continuing + 0.194 (p < 0.001)), when presenting symptoms more clearly indicated antibiotics (AME of urinary tract infection symptoms + 0.173 (p < 0.001) versus unclear symptoms) and when patients had severe frailty/comorbidities (AME = + 0.101 (p < 0.001)). Respondents were less likely to continue antibiotics when under no external pressure to continue (AME = − 0.101 (p < 0.001)). Decisions were also influenced by the risks to patient health of continuing/discontinuing antibiotic treatment. Conclusions Guidelines that conflict with antibiotic discontinuation (e.g. pre-specify fixed durations) may discourage safe discontinuation at review. In contrast, guidelines conditional on patient factors/treatment response could help hospital prescribers discontinue antibiotics if diagnostic information suggesting they are no longer needed is available