bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence into action: implementing alcohol screening and brief interventions in the UK Armed Forces
Authors: Dermont Mark Andrew , Field P , Shepherd J , Rushton R 
Published: February 2020

IntroductionAlcohol-related harm continues to represent a major public health problem and previous evidence suggests that alcohol misuse within the UK Armed Forces is higher than in the general population. The aim was to introduce a population-level primary care intervention with an existing evidence base to identify and support Service Personnel whose drinking places them at greater risk of harm.ImplementationFollowing successful piloting, the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) brief screening tool was introduced as part of routine dental inspections by Defence Primary Healthcare (DPHC) dentists. Alcohol brief intervention (ABI) advice and signposting to support services was offered to personnel identified as being at increased risk and recorded in the patient’s electronic health record.Achievements to datePatients attending DPHC Dental Centres are now routinely offered AUDIT-C with 74% (109 459) personnel screened in the first 12 months rising to over 276 000 at 24 months, representing the single largest use of AUDIT-C and ABIs in a military population to date.DiscussionIntroduction of AUDIT-C has seen Defence successfully deliver a whole population alcohol initiative, overcoming implementation barriers to demonstrate the flexibility of a dental workforce to deliver a public health intervention at scale and contributing towards promoting positive attitudes towards alcohol use. The initiative represents a first step towards the goal of a standardised alcohol screening and treatment pathway across DPHC while recognising that the Defence Medical Services are only one aspect of the broader public health approach required to tackle alcohol-related harm in Service Personnel.
Blast injury of the hand related to warfare explosive devices: experience from the French Military Health Service
Authors: Pfister Georges , Murison J-C , Grosset A , Duhoux A , Lapeyre E , Bauer B , Mathieu L 
Published: February 2020

IntroductionThe objective was to report on the experience of the French Army Health Service in the management of blast injury of the hands related to warfare explosive devices.MethodsA retrospective study was conducted in the Percy Military Hospital (role 4 medical treatment facility) among French soldiers who presented with a combat-related blast injury of the hand between 2002 and 2018. The functional result was assessed by the disabilities of the arm, shoulder and hand (DASH) and the Orthotics and Prosthetics User Survey (OPUS, upper extremity functional status) scores. Proximal amputations (PAs) and distal amputations (DAs) were distinguished for the analysis.ResultsFifteen patients with a mean age of 31±8 years were included. They totalised 20 blasted hands. There were 16 traumatic amputations: 8 in each of the PA and DA groups. Twelve patients had additional injuries, four of which were polytraumatic. Skin closure time and flap use were higher in the DA group. Only one thumb reconstruction was performed. At a mean follow-up of 6.5±4 years, the number of amputees wearing a prosthesis was higher in the PA group. The mean DASH and OPUS scores were 35.5%±24.0% and 64.0%±19.0%, respectively, with no difference between the two groups.ConclusionThe severity of hand blasts related to warfare explosive devices requires the systematic application of damage control surgery. PAs are frequent and secondary reconstruction options are limited. The functional result is poor and similar between proximal and distal amputees.
Evaluating the use of cytosine arabinoside for treatment for recurrent canine steroid‐responsive meningitis‐arteritis
Authors: Günther Christian , Steffen Frank , Alder Daniela S , Beatrice Laura , Geigy Caroline , Beckmann Katrin 
Published: February 2020

BackgroundRelapses in steroid‐responsive meningitis‐arteritis (SRMA) are frequently observed but specific treatment protocols to address this problem are sparsely reported. Standard treatment includes prolonged administration of glucocorticoids as monotherapy or in combination with immunosuppressive drugs. The aim of this study was to assess the safety and efficacy of cytosine arabinoside (CA) in combination with glucocorticoids for treatment of SRMA relapses in 12 dogs on a retrospective basis.MethodsDogs with recurrent episodes of SRMA and treated with a combination of CA and prednisolone were included. Information about clinical course, treatment response and adverse events was collected from medical records. Ethical approval was not required for this study.ResultsTen dogs (10/12) responded well to the treatment with clinical signs being completely controlled. One dog is in clinical remission, but still under treatment. One dog (8%) showed further relapse. Mean treatment period was 51 weeks. Adverse events of variable severity (grade 1–4/5) were documented in all dogs during treatment according to the veterinary cooperative oncology group grading. Three dogs developed severe adverse events. Laboratory findings showed marked changes up to grade 4. Diarrhoea and anaemia were the most often observed adverse events (6), followed by dermatitis (4), alopecia (3) and pneumonia (3). Including blood chemistry changes (13), 50 adverse events were found in total.ConclusionTreatment with CA and glucocorticoids resulted in clinical remission in 10/12 dogs, but a high incidence of adverse events occurred requiring additional measures. All adverse events could be managed successfully in all cases.
PASSAT: particle accelerator helioScopes for Slim Axion-like-particle deTection
Authors: Bonivento Walter M. , Kim Doojin , Sinha Kuver 
Published: February 2020

AbstractWe propose a novel method to search for axion-like particles (ALPs) at particle accelerator experiments. ALPs produced at the target via the Primakoff effect subsequently enter a region with a magnetic field, where they are converted to photons that are then detected. Dubbed Particle Accelerator helioScopes for Slim Axion-like-particle deTection (PASSAT), our proposal uses the principle of the axion helioscope but replaces ALPs produced in the Sun with those produced in a target material. Since we rely on ALP-photon conversions, our proposal probes light (slim) ALPs that are otherwise inaccessible to laboratory-based experiments which rely on ALP decay, and complements astrophysical probes that are more model-dependent. As a first application, we reinterpret existing data from the NOMAD experiment in light of PASSAT, and constrain the parameter space for ALPs lighter than $$\sim 100~\mathrm{eV}$$∼100eV and ALP-photon coupling larger than $$\sim 10^{-4}~\mathrm{GeV}^{-1}$$∼10-4GeV-1. As benchmarks of feasible low-cost experiments improving over the NOMAD limits, we study the possibility of re-using the magnets of the CAST and the proposed BabyIAXO experiments and placing them at the proposed BDF facility at CERN, together with some new detectors. We find that these realizations of PASSAT allow for a direct probe of the parameter space for ALPs lighter than $$\sim 100~\mathrm{eV}$$∼100eV and ALP-photon coupling larger than $$\sim 4\times 10^{-6}~\mathrm{GeV}^{-1}$$∼4×10-6GeV-1, which are regions that have not been probed yet by experiments with laboratory-produced ALPs. In contrast to other proposals aiming at detecting single or two-photon only events in hadronic beam dump environments, that rely heavily on Monte Carlo simulations, the background in our proposal can be directly measured in-situ, its suppression optimized, and the irreducible background statistically subtracted. Sensitivity evaluations with other beams will be the subject of a future paper. The measurements suggested in this paper represent an additional physics case for the BDF at CERN beyond those already proposed.
The computational accelerator physics conference series: From its origins to the present day
Authors: Ryne Robert D. 
Published: February 2020

The first conference in what would become the International Computational Accelerator Physics (ICAP) series was held in 1988. At that time the most powerful computer in the world was a Cray YMP with 8 processors and a peak performance of 2 gigaflops. Today the fastest computer in the world has more than 2 million cores and a theoretical peak performance of nearly 200 petaflops. Compared to 1988, performance has increased by a factor of 100 million, accompanied by huge advances in memory, networking, big data management and analytics. By the time of the next ICAP in 2021 we will be at the dawn of the Exascale era. In this talk I will describe the advances in Computational Accelerator Physics that brought us to this point and describe trends in regard to large-scale accelerator simulation in the future.
High-Performance Multi-Layers Tubular Nanostructure Anode Materials for Lithium-Ion Batteries
Authors: Li Yanbo , Li Ke , Liu Jinjie , Zhang Xi , Dai Jintao , Ai Fanrong 
Published: February 2020

In order to reduce the negative volume effect of Silicon (Si) and Silica (SiO[Formula: see text] as anode materials, CNTs@SiO2/Si@C is prepared by sol–gel method and magnesiothermic reduction process. SEM and TEM results show that the surface of Carbon nanotubes (CNTs) is uniformly coated with active materials including SiO2 and Si. Active materials (SiO2/Si) closely contact with the conductive network constructed by CNTs, which greatly improves the conductivity of the composite anode material. Moreover, the large specific surface area of the tubular structure provides more Li[Formula: see text] diffusion channel. The cushion space of the hollow tube structure effectively alleviates the volume effect of SiO2/Si and enables the anode material excellent electrochemical performance in the cycling test. The initial discharge capacity of CNTs@SiO2/Si@C is 1064[Formula: see text]mAh/g at current density of 200 mA/g. The specific discharge capacity of CNTs@SiO2/Si@C is higher than 960 mAh/g after 100 cycles, and the coulomb efficiency maintains over 98% in the range from 30th to 100th cycle.
Mavacamten rescues increased myofilament calcium sensitivity and dysregulation of Ca2+ flux caused by thin filament hypertrophic cardiomyopathy mutations
Authors: Sparrow Alexander J. , Watkins Hugh , Daniels Matthew J. , Redwood Charles , Robinson Paul 
Published: February 2020

Thin filament hypertrophic cardiomyopathy (HCM) mutations increase myofilament Ca2+ sensitivity and alter Ca2+ handling and buffering. The myosin inhibitor mavacamten reverses the increased contractility caused by HCM thick filament mutations, and we here test its effect on HCM thin filament mutations where the mode of action is not known. Mavacamten (250 nM) partially reversed the increased Ca2+ sensitivity caused by HCM mutations Cardiac troponin T (cTnT) R92Q, and cardiac troponin I (cTnI) R145G in in vitro ATPase assays. The effect of mavacamten was also analyzed in cardiomyocyte models of cTnT R92Q and cTnI R145G containing cytoplasmic and myofilament specific Ca2+ sensors. While mavacamten rescued the hypercontracted basal sarcomere length, the reduced fractional shortening did not improve with mavacamten. Both mutations caused an increase in peak systolic Ca2+ detected at the myofilament, and this was completely rescued by 250 nM mavacamten. Systolic Ca2+ detected by the cytoplasmic sensor was also reduced by mavacamten treatment, although only R145G increased cytoplasmic Ca2+. There was also a reversal of Ca2+ decay time prolongation caused by both mutations at the myofilament but not in the cytoplasm. We thus show that mavacamten reverses some of the Ca2+-sensitive molecular and cellular changes caused by the HCM mutations, particularly altered Ca2+ flux at the myofilament. The reduction of peak systolic Ca2+ as a consequence of mavacamten treatment represents a novel mechanism by which the compound is able to reduce contractility, working synergistically with its direct effect on the myosin motor. NEW & NOTEWORTHY Mavacamten, a myosin inhibitor, is currently in phase-3 clinical trials as a pharmacotherapy for hypertrophic cardiomyopathy (HCM). Its efficacy in HCM caused by mutations in thin filament proteins is not known. We show in reductionist and cellular models that mavacamten can rescue the effects of thin filament mutations on calcium sensitivity and calcium handling although it only partially rescues the contractile cellular phenotype and, in some cases, exacerbates the effect of the mutation.
RABL6A Is an Essential Driver of MPNSTs that Negatively Regulates the RB1 Pathway and Sensitizes Tumor Cells to CDK4/6 Inhibitors
Authors: Kohlmeyer Jordan L. , Kaemmer Courtney A. , Pulliam Casey , Maharjan Chandra K. , Samayoa Allison Moreno , Major Heather J. , Cornick Kendall E. , Knepper-Adrian Vickie , Khanna Rajesh , Sieren Jessica C. , Leidinger Mariah R. , Meyerholz David K. , Zamba K.D. , Weimer Jill M. , Dodd Rebecca D. , Darbro Benjamin W. , Tanas Munir R. , Quelle Dawn E. 
Published: February 2020

Abstract

Purpose:
Malignant peripheral nerve sheath tumors (MPNST) are deadly sarcomas that lack effective therapies. In most MPNSTs, the retinoblastoma (RB1) tumor suppressor is disabled by hyperactivation of cyclin-dependent kinases (CDK), commonly through loss of CDK-inhibitory proteins such as p27(Kip1). RABL6A is an inhibitor of RB1 whose role in MPNSTs is unknown. To gain insight into MPNST development and establish new treatment options, we investigated RABL6A-RB1 signaling and CDK inhibitor–based therapy in MPNSTs.

Experimental Design:
We examined patient-matched MPNSTs and precursor lesions by RNA sequencing (RNA-Seq) and IHC. Molecular and biological effects of silencing RABL6A and/or p27 in MPNST lines and normal human Schwann cells were determined. Tumor-suppressive effects of CDK inhibitors were measured in MPNST cells and orthotopic tumors.

Results:
RABL6A was dramatically upregulated in human MPNSTs compared with precursor lesions, which correlated inversely with p27 levels. Silencing RABL6A caused MPNST cell death and G1 arrest that coincided with p27 upregulation, CDK downregulation, and RB1 activation. The growth-suppressive effects of RABL6A loss, and its regulation of RB1, were largely rescued by p27 depletion. Importantly, reactivation of RB1 using a CDK4/6 inhibitor (palbociclib) killed MPNST cells in vitro in an RABL6A-dependent manner and suppressed MPNST growth in vivo. Low-dose combination of drugs targeting multiple RB1 kinases (CDK4/6, CDK2) had enhanced antitumorigenic activity associated with potential MPNST cell redifferentiation.

Conclusions:
RABL6A is a new driver of MPNST pathogenesis that acts in part through p27-RB1 inactivation. Our results suggest RB1 targeted therapy with multiple pathway drugs may effectively treat MPNSTs.
MET Alterations Are a Recurring and Actionable Resistance Mechanism in ALK-Positive Lung Cancer
Authors: Dagogo-Jack Ibiayi , Yoda Satoshi , Lennerz Jochen K. , Langenbucher Adam , Lin Jessica J. , Rooney Marguerite M. , Prutisto-Chang Kylie , Oh Audris , Adams Nathaniel A. , Yeap Beow Y. , Chin Emily , Do Andrew , Marble Hetal D. , Stevens Sara E. , Digumarthy Subba R. , Saxena Ashish , Nagy Rebecca J. , Benes Cyril H. , Azzoli Christopher G. , Lawrence Michael S. , Gainor Justin F. , Shaw Alice T. , Hata Aaron N. 
Published: February 2020

Abstract

Purpose:
Most ALK-positive lung cancers will develop ALK-independent resistance after treatment with next-generation ALK inhibitors. MET amplification has been described in patients progressing on ALK inhibitors, but frequency of this event has not been comprehensively assessed.

Experimental Design:
We performed FISH and/or next-generation sequencing on 207 posttreatment tissue (n = 101) or plasma (n = 106) specimens from patients with ALK-positive lung cancer to detect MET genetic alterations. We evaluated ALK inhibitor sensitivity in cell lines with MET alterations and assessed antitumor activity of ALK/MET blockade in ALK-positive cell lines and 2 patients with MET-driven resistance.

Results:
MET amplification was detected in 15% of tumor biopsies from patients relapsing on next-generation ALK inhibitors, including 12% and 22% of biopsies from patients progressing on second-generation inhibitors or lorlatinib, respectively. Patients treated with a second-generation ALK inhibitor in the first-line setting were more likely to develop MET amplification than those who had received next-generation ALK inhibitors after crizotinib (P = 0.019). Two tumor specimens harbored an identical ST7-MET rearrangement, one of which had concurrent MET amplification. Expressing ST7-MET in the sensitive H3122 ALK-positive cell line induced resistance to ALK inhibitors that was reversed with dual ALK/MET inhibition. MET inhibition resensitized a patient-derived cell line harboring both ST7-MET and MET amplification to ALK inhibitors. Two patients with ALK-positive lung cancer and acquired MET alterations achieved rapid responses to ALK/MET combination therapy.

Conclusions:
Treatment with next-generation ALK inhibitors, particularly in the first-line setting, may lead to MET-driven resistance. Patients with acquired MET alterations may derive clinical benefit from therapies that target both ALK and MET.
Scientific Concepts as Forward-Looking: How Taxonomic Structure Facilitates Conceptual Development
Authors: Bloch-Mullins Corinne L. 
Published: February 2020

Abstract
This paper examines the interplay between conceptual structure and the evolution of scientific concepts, arguing that concepts are fundamentally ‘forward-looking’ constructs. Drawing on empirical studies of similarity and categorization, I explicate the way in which the conceptual taxonomy highlights the ‘relevant respects’ for similarity judgments involved in categorization. I then propose that this taxonomy provides some of the cognitive underpinnings of the ongoing development of scientific concepts. I use the concept synapse to illustrate my proposal, showing how conceptual taxonomy both facilitates and constrains the accommodation of newly discovered phenomena. I end by briefly considering the implications of the proposed approach for a normative evaluation of scientific concepts.
Weather Radar Network Benefit Model for Flash Flood Casualty Reduction
Authors: Cho John Y. N. , Kurdzo James M. 
Published: February 2020

ABSTRACTA monetized flash flood casualty reduction benefit model is constructed for application to meteorological radar networks. Geospatial regression analyses show that better radar coverage of the causative rainfall improves flash flood warning performance. Enhanced flash flood warning performance is shown to decrease casualty rates. Consequently, these two effects in combination allow a model to be formed that links radar coverage to flash flood casualty rates. When this model is applied to the present-day contiguous U.S. weather radar network, results yield a flash flood–based benefit of $316 million (M) yr−1. The remaining benefit pools are more modest ($13 M yr−1 for coverage improvement and $69 M yr−1 maximum for all areas of radar quantitative precipitation estimation improvements), indicative of the existing weather radar network’s effectiveness in supporting the flash flood warning decision process.
Verification of placental growth factor and soluble-fms-like tyrosine kinase 1 assay performance in late pregnancy and their diagnostic test accuracy in women with reduced fetal movement
Authors: Armstrong-Buisseret Lindsay K , Haslam Shonagh , James Tim , Bradshaw Lucy , Heazell Alexander EP 
Published: February 2020

Background Placental growth factor (PlGF) and soluble-fms-like tyrosine kinase 1 (sFlt-1) are biomarkers of placental function used to aid the diagnosis and prediction of pregnancy complications. This work verified the analytical performance of both biomarkers and provides preliminary diagnostic accuracy data to identify adverse pregnancy outcome in women with reduced fetal movement. Methods Verification of sFlt-1 and PlGF assays included a comparative accuracy assessment of 24 serum samples analysed at six different sites and laboratory-specific precision estimates. The sFlt-1/PlGF ratio was assessed in serum samples obtained prospectively from 295 women with reduced fetal movement ≥36 weeks’ gestation; diagnostic accuracy was evaluated using 2 × 2 tables and area under the receiver operator characteristic (AUROC) curve. Results Regression analysis showed that performance between sites was good with Passing-Bablok slopes ranging from 0.96 to 1.05 (sFlt-1) and 0.93 to 1.08 (PlGF). All sites had a mean bias <15%, although there was poorer agreement at the lowest PlGF concentrations. All within- and between-batch coefficients of variation were <10%. In 289 women with an appropriately grown fetus, an sFlt-1/PlGF ratio ≥38 had a sensitivity of 0.20 (95% confidence interval [CI] 0.07, 0.41), specificity of 0.88 (95% CI 0.83, 0.92) and AUROC curve of 0.58 (95% CI 0.47, 0.68) to identify adverse pregnancy outcome. Conclusions Analytical performance of the sFlt-1 and PlGF assays was comparable across different sites. The sensitivity of sFlt-1/PlGF to identify adverse pregnancy outcome in women with reduced fetal movement was considered acceptable, in the absence of other tests, to progress to a pilot randomized controlled trial.
Understanding usual care in randomised controlled trials of complex interventions: A multi-method approach
Authors: Yorganci Emel , Evans Catherine J , Johnson Halle , Barclay Stephen , Murtagh Fliss EM , Yi Deokhee , Gao Wei , Pickles Andrew , Koffman Jonathan 
Published: February 2020

Background: Evaluations of complex interventions compared to usual care provided in palliative care are increasing. Not describing usual care may affect the interpretation of an intervention’s effectiveness, yet how it can be described remains unclear. Aim: To demonstrate the feasibility of using multi-methods to describe usual care provided in randomised controlled trials (RCTs) of complex interventions, shown within a feasibility cluster RCT. Design: Multi-method approach comprising usual care questionnaires, baseline case note review and focus groups with ward staff completed at study end. Thematic analysis of qualitative data, descriptive statistics of quantitative data, followed by methodological triangulation to appraise approach in relation to study aim. Setting/participants: Four general medical wards chosen from UK hospitals. Purposive sampling of healthcare professionals for usual care questionnaires, and focus groups. Review of 20 patients’ notes from each ward who died during admission or within 100 days of discharge. Results: Twenty-three usual care questionnaires at baseline, two focus groups comprising 20 healthcare professionals and 80 case note reviews. Triangulation of findings resulted in understanding the usual care provided to the targeted population in terms of context, structures, processes and outcomes for patients, families and healthcare professionals. Usual care was described, highlighting (1) similarities and embedded practices, (2) heterogeneity and (3) subtle changes in care during the trial within and across sites. Conclusions: We provide a feasible approach to defining usual care that can be practically adopted in different settings. Understanding usual care enhances the reliability of tested complex interventions, and informs research and policy priorities.