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Background and aimsENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).Approach and resultsPatients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events.ConclusionsPatients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.

Abstract Solid-state lithium-based batteries offer higher energy density than their Li-ion counterparts. Yet they are limited in terms of negative electrode discharge performance and require high stack pressure during operation. To circumvent these issues, we propose the use of lithium-rich magnesium alloys as suitable negative electrodes in combination with Li6PS5Cl solid-state electrolyte. We synthesise and characterise lithium-rich magnesium alloys, quantifying the changes in mechanical properties, transport, and surface chemistry that impact electrochemical performance. Increases in hardness, stiffness, adhesion, and resistance to creep are quantified by nanoindentation as a function of magnesium content. A decrease in diffusivity is quantified with 6Li pulsed field gradient nuclear magnetic resonance, and only a small increase in interfacial impedance due to the presence of magnesium is identified by electrochemical impedance spectroscopy which is correlated with x-ray photoelectron spectroscopy. The addition of magnesium aids contact retention on discharge, but this must be balanced against a decrease in lithium diffusivity. We demonstrate via electrochemical testing of symmetric cells at 2.5 MPa and 30∘C that 1% magnesium content in the alloy increases the stripping capacity compared to both pure lithium and higher magnesium content alloys by balancing these effects.

Abstract Background Research waste is defined as research outcomes with no or minimal societal benefits. It is a widespread problem in the healthcare field. Four primary sources of research waste have been defined: (1) irrelevant or low priority research questions, (2) poor design or methodology, (3) lack of publication, and (4) biased or inadequate reporting. This commentary, which was developed by a multidisciplinary group of researchers with spinal manipulative therapy (SMT) research expertise, discusses waste in SMT research and provides suggestions to improve future research. Main text This commentary examines common sources of waste in SMT research, focusing on design and methodological issues, by drawing on prior research and examples from clinical and mechanistic SMT studies. Clinical research is dominated by small studies and studies with a high risk of bias. This problem is compounded by systematic reviews that pool heterogenous data from varying populations, settings, and application of SMT. Research focusing on the mechanisms of SMT often fails to address the clinical relevance of mechanisms, relies on very short follow-up periods, and has inadequate control for contextual factors. Conclusions This call to action is directed to researchers in the field of SMT. It is critical that the SMT research community act to improve the way research is designed, conducted, and disseminated. We present specific key action points and resources, which should enhance the quality and usefulness of future SMT research.

This paper presents outcomes for a Housing First (HF) cohort in Aotearoa, New Zealand. Using integrated governmental administrative data, we analysed outcomes for a cohort of 357 people, comparing health, justice, income, and social welfare indicators the year prior to HF and five years after being housed. In the fifth year after being housed, improved outcomes across each of these sectors were noted, with particularly impressive improvements found in income levels (+38%) and mental health. These results demonstrate the efficacy of this HF programme in improving well-being. Despite such notable improvements, there is room for HF to have a greater impact in the context of wider system changes that support overall well-being, as well as the goal of making homelessness rare, brief, and non-recurring.

Introduction In liver cirrhosis, acute variceal bleeding (AVB) is associated with a 1-year mortality rate of up to 40%. Data on early or pre-emptive transjugular intrahepatic portosystemic stent–shunt (TIPSS) in AVB is inconclusive and may not reflect current management strategies. Randomised controlled trial of EArly transjugular intrahepatiC porTosystemic stent–shunt in AVB (REACT-AVB) aims to investigate the clinical and cost-effectiveness of early TIPSS in patients with cirrhosis and AVB after initial bleeding control.Methods and analysis REACT-AVB is a multicentre, randomised controlled, open-label, superiority, two-arm, parallel-group trial with an internal pilot. The two interventions allocated randomly 1:1 are early TIPSS within 4 days of diagnostic endoscopy or secondary prophylaxis with endoscopic therapy in combination with non-selective beta blockers. Patients aged ≥18 years with cirrhosis and Child-Pugh Score 7–13 presenting with AVB with endoscopic haemostasis are eligible for inclusion. The primary outcome is transplant-free survival at 1 year post randomisation. Secondary endpoints include transplant-free survival at 6 weeks, rebleeding, serious adverse events, other complications of cirrhosis, Child-Pugh and Model For End-Stage Liver Disease (MELD) scores at 6 and 12 months, health-related quality of life, use of healthcare resources, cost-effectiveness and use of cross-over therapies. The sample size is 294 patients over a 4-year recruitment period, across 30 hospitals in the UK.Ethics and dissemination Research ethics committee of National Health Service has approved REACT-AVB (reference number: 23/WM/0085). The results will be submitted for publication in a peer-reviewed journal. A lay summary will also be emailed or posted to participants before publication.Trial registration number ISRCTN85274829; protocol version 3.0, 1 July 2023.

Social cognition is shaped by cultural and social-psychological contexts. Depending on the social cues displayed, the cognitive processes that emerge during embodied social interactions can vary. This study explored the influence of gender diverse social cues on interpersonal coordination and decision-making during dyadic interaction in virtual reality. Participants embodied either a transgender or cisgender avatar and interacted with a transgender confederate (human-controlled virtual agent). Results suggest that transgender embodied women and men displayed more interpersonal affiliation, via their coordination dynamics with the confederate, after an explicit gender identity disclosure. Additionally, cognitive flexibility for ambiguous decisions was influenced by attributions of responsibility made toward the confederate. However, cisgender embodied men did not substantially change their decision-making behaviours or increase their coordination with the confederate. Viscerally taking on the perspective and appearance of a transgender person, achieved through virtual embodiment and interaction, may support positive interactions between cisgender and transgender communities.

Abstract We report on a new ground-level neutron monitor design for studying cosmic rays and fluxes of solar energetic particles at the Earth’s surface. The first-of-its-kind instrument, named the NM-2023 after the year it was standardised and following convention, will be installed at a United Kingdom Meteorological Office observatory (expected completion mid 2024) and will reintroduce such monitoring in the UK for the first time since ca. 1984. Monte Carlo radiation transport code is used for the development and application of parameterised models to investigate alternative neutron detectors, their location and bulk material geometry in a realistic cosmic ray neutron field. Benchmarked against a model of the current and most widespread design standardised in 1964 (the NM-64), two main parameterisation studies are conducted; a simplified standard model and a concept slab parameterisation. We show that the NM-64 standard is well optimised for the intended large-diameter boron trifluoride (BF $$_3$$ 3 ) proportional counters but not for multiple smaller diameter counters. The new design (based on a novel slab arrangement) produces comparable counting efficiencies to an NM-64 with six BF $$_3$$ 3 counters and has the added advantage of being more compact, lower cost and avoids the use of highly toxic BF $$_3$$ 3 .

We described insulin glargine (originator) and insulin glargine-yfgn (biosimilar) treatment patterns, assessed effectiveness and safety outcomes, and identified reasons for switching back to the originator product from the biosimilar. This retrospective study included 328,463 Veterans 18 years of age and older who received one or more outpatient prescriptions for insulin glargine and/or insulin glargine-yfgn between 1 June 2021 and 31 December 2022. Patients were assigned to subgroups based on the initial prescription during the study period, prevalent versus incident use for originator insulin glargine, and prior versus no prior use of the originator before the biosimilar (i.e., prevalent originator non-switcher (n = 189,734), originator switch to biosimilar (n = 81,010), incident originator non-switcher (n = 49,401), and incident biosimilar (n = 8318)). There were no differences in the outcome of mean HbA1c (7.9% for all subgroups). There were also no differences in the unadjusted rates of hospitalization and/or emergency room visits for hyper- and hypoglycemia between the prevalent originator non-switcher and originator switched to biosimilar subgroups (p = 0.09 and 0.38, respectively) or the incident originator non-switcher and incident biosimilar subgroups (p = 0.054 and 0.61, respectively). Finally, none of the HbA1c or hyperglycemia outcomes adjusted for baseline characteristics were statistically different. Adjusted analyses for rates of hospitalization and/or emergency room visits for hypoglycemia could not be performed due to the low number of events. Overall, patients who received insulin glargine-yfgn had similar effectiveness and safety outcomes as patients who received the originator.

Abstract Background Children are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine–artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM). Methods An integrated safety analysis of individual patient data from three randomized clinical trials included patients with microscopically-confirmed Plasmodium falciparum, body weight ≥ 5 kg to

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among children. Pharmacotherapy has been the primary treatment for ADHD, supplemented by behavioral interventions. Digital and exercise interventions are promising nonpharmacologic approaches for enhancing the physical and psychological health of children with ADHD. However, the combined impact of digital and exercise therapies remains unclear. ObjectiveThe aim of this study was to determine whether BrainFit, a novel digital intervention combining gamified cognitive and exercise training, is efficacious in reducing ADHD symptoms and executive function (EF) among school-aged children with ADHD. MethodsThis 4-week prospective randomized controlled trial included 90 children (6-12 years old) who visited the ADHD outpatient clinic and met the diagnostic criteria for ADHD. The participants were randomized (1:1) to the BrainFit intervention (n=44) or a waitlist control (n=46) between March and August 2022. The intervention consisted of 12 30-minute sessions delivered on an iPad over 4 weeks with 3 sessions per week (Monday, Wednesday, and Friday after school) under the supervision of trained staff. The primary outcomes were parent-rated symptoms of attention and hyperactivity assessed according to the Swanson, Nolan, and Pelham questionnaire (SNAP-IV) rating scale and EF skills assessed by the Behavior Rating Inventory of Executive Function (BRIEF) scale, evaluated pre and post intervention. Intention-to-treat analysis was performed on 80 children after attrition. A nonparametric resampling-based permutation test was used for hypothesis testing of intervention effects. ResultsAmong the 145 children who met the inclusion criteria, 90 consented and were randomized; ultimately, 80 (88.9%) children completed the study and were included in the analysis. The participants’ average age was 8.4 (SD 1.3) years, including 63 (78.8%) male participants. The most common ADHD subtype was hyperactive/impulsive (54/80, 68%) and 23 (29%) children had severe symptoms. At the endpoint of the study, the BrainFit intervention group had a significantly larger improvement in total ADHD symptoms (SNAP-IV total score) as compared to those in the control group (β=–12.203, 95% CI –17.882 to –6.523; P

Background & Aims: Guidelines for the management of primary biliary cholangitis (PBC) were published by the British Society of Gastroenterology in 2018. In this study, we assessed adherence to these guidelines in the UK National Health Service (NHS). Methods: All NHS acute trusts were invited to contribute data between 1 January 2021 and 31 March 2022, assessing clinical care delivered to patients with PBC in the UK. Results: We obtained data for 8,968 patients with PBC and identified substantial gaps in care across all guideline domains. Ursodeoxycholic acid (UDCA) was used as first-line treatment in 88% of patients (n = 7,864) but was under-dosed in one-third (n = 1,964). Twenty percent of patients who were UDCA-untreated (202/998) and 50% of patients with inadequate UDCA response (1,074/2,102) received second-line treatment. More than one-third of patients were not assessed for fatigue (43%; n = 3,885) or pruritus (38%; n = 3,415) in the previous 2 years. Fifty percent of all patients with evidence of hepatic decompensation were discussed with a liver transplant centre (222/443). Appropriate use of second-line treatment and referral for liver transplantation was significantly better in specialist PBC treatment centres compared with non-specialist centres (p

Abstract Background Presenting at professional and scientific conferences can be an important part of an individual’s career advancement, especially for researchers communicating scientific findings, and can signal expertise and leadership. Generally, women presenting at conferences are underrepresented in various science disciplines. We aimed to evaluate the gender of presenters at research-oriented chiropractic conferences from 2010 to 2019. Methods We investigated the gender of presenters at conferences hosted by chiropractic organisations from 2010 to 2019 that utilised an abstract submission process. Gender classification was performed by two independent reviewers. The gender distribution of presenters over the ten-year period was analysed with linear regression. The association of conference factors with the gender distribution of presenters was also assessed with linear regression, including the gender of organising committees and abstract peer reviewers, and the geographic region where the conference was hosted. Results From 39 conferences, we identified 4,340 unique presentations. Women gave 1,528 (35%) of the presentations. No presenters were classified as gender diverse. Overall, the proportion of women presenters was 30% in 2010 and 42% in 2019, with linear regression demonstrating a 1% increase in women presenting per year (95% CI = 0.4–1.6%). Invited/keynote speakers had the lowest proportion of women (21%) and the most stagnant trajectory over time. The gender of conference organisers and abstract peer reviewers were not significantly associated with the gender of presenters. Oceanic conferences had a lower proportion of women presenting compared to North America (27% vs. 36%). Conclusions Overall, women gave approximately one-third of presentations at the included conferences, which gradually increased from 2010 to 2019. However, the disparity widens for the most prestigious class of keynote/invited presenters. We make several recommendations to support the goal of gender equity, including monitoring and reporting on gender diversity at future conferences.

Abstract The Aso-4 explosive eruption on Kyushu, Japan, 89,500 years ago was one of the biggest eruptions in the last one hundred millennia, with a magnitude of approximately M8. Modern society requires the likelihood of natural events with potentially disastrous consequences to be evaluated, even if probabilities of occurrence are diminishingly small. For some situations, it is not satisfactory to assert an event scenario probability is “negligible” or can be “ignored”. Judicial hearings or litigation may require risk levels to be quantified, in which case, statements of scientific confidence could be decisive. Internationally, e.g., for nuclear site safety evaluations, event likelihoods on order of 10–7/year are often considered for quantitative assessment. At such hazard levels, this might include evaluating the proposition that a particular volcano can deliver a future super-eruption, a supposition that could be attached to Aso volcano. But, simplistically taking the average recurrence interval between past caldera-forming eruptions at a given volcano is an unreliable guide to the likelihood of a future repeat: each past event represented a unique set of tectonic and magmatic conditions within a continually evolving volcanic system. Such processes are not temporally stationary nor statistically uniform. To evaluate the probability of a new M8 event at Aso, within the next 100 years, we performed a comprehensive stochastic probability uncertainty analysis using a model implemented with advanced computational Bayes Net (BN) software. Our eruption process model is informed by multiple strands of evidence from volcanology, petrology, geochemistry and geophysics, together with estimates of epistemic (knowledge) uncertainty, adduced from reviews of published data, modelling and from expert judgement elicitation. Several lines of evidence characterise the likely structure, magmatic composition and eruptive state of the present-day Aso volcano, which has had numerous smaller eruptions since Aso-4. To calculate the probability of another M8 eruption of Aso, we implemented probabilistic ‘Importance Sampling’ in our model. With this approach, we find the chance of an Aso-4 scale eruption (characterised by mean volume 500 km3 DRE and approximate 90% credible interval [210 ‥ 1200] km3 DRE) is less than 1–in–1 billion in the next 100 years (i.e.,

Background: Several studies recently confirmed the emergence of resistance to antimalarial drugs in sub-Saharan Africa. Multiple first-line treatment (MFT) is one of the measures envisaged to respond to the emergence and spread of this resistance. The aim of this study was to identify the perceived advantages and disadvantages of several MFT deployment strategies and to better understand potential implementation drivers and barriers. Methods: A qualitative survey was conducted in seven sub-Saharan countries amongst key opinion leaders, national decision makers, and end users. A total of 200 individual interviews were conducted and findings were analyzed following a thematic inductive approach. Results: From a policy perspective, the new MFT intervention would require endorsement at the global, national, and regional levels to ensure its inclusion in guidelines. Funding of the MFT intervention could be a bottleneck due to costs associated with additional training of healthcare workers, adaptation of drug delivery mechanisms, and higher costs of drugs. Concerning the MFT deployment strategies, a slight preference for the segmentation strategy was expressed over the rotation and geographic approaches, due to the perception that a segmentation approach is already in place at country level. Conclusions: The findings highlighted the need for a collective approach to MFT deployment through the engagement of stakeholders at all levels of malaria management.

Abstract Background Spinal manipulative therapy (SMT) is a guideline-recommended treatment option for spinal pain. The recommendation is based on multiple systematic reviews. However, these reviews fail to consider that clinical effects may depend on SMT “application procedures” (i.e., how and where SMT is applied). Using network meta-analyses, we aim to investigate which SMT “application procedures” have the greatest magnitude of clinical effectiveness for reducing pain and disability, for any spinal complaint, at short-term and long-term follow-up. We will compare application procedural parameters by classifying the thrust application technique and the application site (patient positioning, assisted, vertebral target, region target, Technique name, forces, and vectors, application site selection approach and rationale) against: 1. Waiting list/no treatment; 2. Sham interventions not resembling SMT (e.g., detuned ultrasound); 3. Sham interventions resembling SMT; 4. Other therapies not recommended in clinical practice guidelines; and 5. Other therapies recommended in clinical practice guidelines. Secondly, we will examine how contextual elements, including procedural fidelity (whether the SMT was delivered as planned) and clinical applicability (whether the SMT is similar to clinical practice) of the SMT. Methods We will include randomized controlled trials (RCT) found through three search strategies, (i) exploratory, (ii) systematic, and (iii) other known sources. We define SMT as a high-velocity low-amplitude thrust or grade V mobilization. Eligibility is any RCT assessing SMT against any other type of SMT, any other active or sham intervention, or no treatment control on adult patients with pain in any spinal region. The RCTs must report on continuous pain intensity and/or disability outcomes. Two authors will independently review title and abstract screening, full-text screening, and data extraction. Spinal manipulative therapy techniques will be classified according to the technique application and choice of application sites. We will conduct a network-meta analysis using a frequentist approach and multiple subgroup and sensitivity analyses. Discussion This will be the most extensive review of thrust SMT to date, and will allow us to estimate the importance of different SMT application procedures used in clinical practice and taught across educational settings. Thus, the results are applicable to clinical practice, educational settings, and research studies. PROSPERO registration: CRD42022375836.

Objective Alcohol-related liver disease (ALD) is the most common cause of liver-related ill health and liver-related deaths in the UK, and deaths from ALD have doubled in the last decade. The management of ALD requires treatment of both liver disease and alcohol use; this necessitates effective and constructive multidisciplinary working. To support this, we have developed quality standard recommendations for the management of ALD, based on evidence and consensus expert opinion, with the aim of improving patient care.Design A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology ALD Special Interest Group developed the quality standards, with input from the British Liver Trust and patient representatives.Results The standards cover three broad themes: the recognition and diagnosis of people with ALD in primary care and the liver outpatient clinic; the management of acutely decompensated ALD including acute alcohol-related hepatitis and the posthospital care of people with advanced liver disease due to ALD. Draft quality standards were initially developed by smaller working groups and then an anonymous modified Delphi voting process was conducted by the entire group to assess the level of agreement with each statement. Statements were included when agreement was 85% or greater. Twenty-four quality standards were produced from this process which support best practice. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice and an audit tool provided.Conclusion It is hoped that services will review their practice against these recommendations and key performance indicators and institute service development where needed to improve the care of patients with ALD.

Abstract Background After a strong epidemiological link to diet was established in an outbreak of pancytopenia in cats in spring 2021 in the United Kingdom, 3 dry diets were recalled. Concentrations of the hemato‐ and myelotoxic mycotoxins T‐2, HT‐2 and diacetoxyscirpenol (DAS) greater than the European Commission guidance for dry cat foods were detected in the recalled diets. Objectives To describe clinical and clinicopathological findings in cats diagnosed with suspected diet induced pancytopenia. Animals Fifty cats presenting with pancytopenia after exposure to a recalled diet. Methods Multicenter retrospective case series study. Cats with known exposure to 1 of the recalled diets were included if presented with bi‐ or pancytopenia and underwent bone marrow examination. Results Case fatality rate was 78%. Bone marrow aspirates and biopsy examination results were available in 23 cats; 19 cats had a bone marrow aspirate, and 8 cats had a biopsy core, available for examination. Bone marrow hypo to aplasia—often affecting all cell lines—was the main feature in all 31 available core specimens. A disproportionately pronounced effect on myeloid and megakaryocytic cells was observed in 19 cats. Myelofibrosis or bone marrow necrosis was not a feature. Conclusion and Clinical Importance Mycotoxin induced pancytopenia should be considered as differential diagnosis in otherwise healthy cats presenting with bi‐ or pancytopenia and bone marrow hypo‐ to aplasia.

The objective of this study was to evaluate the association between fluoroquinolone (FQ) use and the occurrence of aortic aneurysm/dissection (AA/AD), acute myocardial infarction (AMI), ventricular arrhythmias (VenA), and all-cause mortality vs other commonly used antibiotics. We conducted a self-controlled case series analysis of patients who experienced the outcomes of AA/AD, AMI, and VenA, based on diagnosis codes from emergency department visits and hospitalizations within Veterans Health Administration, and death in FY2014-FY2018. These Veterans also received outpatient prescriptions for FQs. Conditional Poisson regression models were used to estimate the association between FQs and each of the outcomes vs antibiotics of interest (ie amoxicillin or amoxicillin/clavulanate, azithromycin, doxycycline, cefuroxime or cephalexin, or sulfamethoxazole-trimethoprim), adjusted for time-varying covariates. Using a 30-day risk period after each antibiotic prescription, adjusted incidence rate ratios (aIRRs) for FQs vs each comparator antibiotic were not statistically different for outcomes of VenA or AMI. For AA/AD, incidence was higher during FQ risk periods vs amoxicillin [aIRR 1.50 (95% CI 1.01, 2.25)] and azithromycin [aIRR 2.15 (95% CI 1.27, 3.64)] risk periods. A significantly increased risk of mortality was observed with FQs vs each antibiotic of interest. FQs were associated with an increased risk of AA/AD vs amoxicillin and azithromycin and an increased risk of all-cause mortality vs multiple antibiotics commonly used for outpatient infections. Although the differences in event rates are small, FQ use should be limited to serious infections without appropriate alternatives.

Scalable processing of thin and robust solid-electrolyte (SE) separators is key for the commercialization of high-energy all-solid-state batteries (ASSBs). Herein, we report the preparation of Li _6 PS _5 Cl-based thin SE separators incorporating suitable binders for potential use in ASSBs by two scalable wet processing techniques: tape-casting with nitrile-butadiene rubber (NBR) and calendering with carboxylated nitrile butadiene rubber (XNBR). By means of tensile testing and electrochemical impedance spectroscopy, the influence of processing on the mechanical as well as the electrochemical properties of the resulting thin SE separators is investigated. A trade-off between the mechanical and electrochemical properties is observed, which is due to the inextricably linked microstructures (particle size, binder content and distribution, and porosity) induced by the two different processes. Thin SE separators prepared using the tape-casting method with the more well-distributed binder network demonstrate superior tensile mechanical properties compared to the ones prepared by the calendering method. The results provide insights into the processing-structure-property relationships of the thin SE separators, which will contribute to advancing the application of practical thin solid electrolytes in ASSBs.

Japan and Great Britain are both island nations with long histories. Nationalists in both nations like to emphasise the things that separate members of 'our' nation from others across the sea, and this includes language. In the British case the arrogant assumption that 'everyone else can learn English' has led to a serious decline in the number of students who study foreign languages. In Japan, a certain amount of English is understood to be necessary for practical purposes, but nationalists warn against too much immersion in the language of an alien culture. These attitudes have helped to undermine the provision of advanced foreign language education that is necessary in a globalized world.

Metallic lithium is the desired anode material for high energy density solid state batteries and shows a factor of four range in elastic modulus and two orders of magnitude difference in creep properties dependent on sample preparation and testing method. In this paper we use in-situ nanoindentation to measure the anisotropic mechanical properties from the BCC crystal structure and the effect of strain-rate and temperature, which have an impact on battery cycle performance. This work clarifies the reasons for the range of property values reported in the literature with a global equation for yield strength with strain-rate. From this information conclusions can be drawn around variables to optimise in order to minimise the required pressure for a chosen stripping critical current in solid state batteries.

The thermal stability of carbon fibre-reinforced polymer (CFRP) and its constituents (neat epoxy resin and carbon fibre) are studied in terms of mass loss using a thermogravimetry technique at different heating rates and two atmospheric conditions (air and pure nitrogen). By interpreting the mass loss over a temperature range of 25–900 °C, it was possible to identify the specific mechanisms of polymer degradation. In an oxygen-free pure nitrogen atmosphere, the thermal degradation of epoxy resin used as the composite's matrix is strongly inhibited up to the temperature of 400 °C, after which it undergoes thermal decomposition, in contrast to the carbon fibre reinforcement that does not degrade in nitrogen. In an air atmosphere, however, the CFRP and its constituents degrade via a complex reaction pathway encompassing three endothermic reactions (pyrolysis of the epoxy resin, oxidation of the residue from the first pyrolysis reaction and carbon fibre oxidation) that overlap and one endothermic reaction in nitrogen (pyrolysis of the epoxy resin). A deconvolution technique based on fitting log-normal distributions to the first derivative of the mass loss data has also been undertaken to separate the thermal decomposition reactions for each CFRP to understand the effect of each reaction's contribution. It can be used to evaluate complex thermal degradation processes that can be characterised by finding the respective kinetic parameters of each reaction, e.g. by using combined kinetics analysis.

Objectives To assess the perception of global mentorship in neurosurgery among medical students across the world. Secondary aim included investigating the factors affecting the availability and benefits of providing global mentorship scheme in neurosurgery at a medical student level.Setting The Global Mentorship in Neurosurgery for Medical Students Study was a multinational cross-sectional audit that included medical students currently in the years 1–6 and intercalating programmes. They were invited to complete an online survey between 11 March and 1 May 2022.Participants The survey was disseminated to 243 medical university ambassadors worldwide from 60 countries who distributed the survey within their respective medical student cohorts across the duration of the study.Results Overall, 2962 of 3017 (98.2%) responses from medical students from 60 countries worldwide were included; 1439 of 2962 (49%) and 1523 of 2962 (51%) were from years 1–3 and 4–6 medical students including intercalating degree programmes, respectively. 1712, 1502 and 1359 of responses gathered indicated that possible reasons for the lack of neurosurgical mentorship are lack of time and resources from trainees in neurosurgery, time within medical school’s curriculum and awareness of societies in neurosurgery/neurology. 1276 and 1065 of medical students surveyed reported that it could also be due to lack of funding and overall inaccessibility within the area meaning there are few networking opportunities available.Conclusions This pilot study indicates that there is a scope for improvement regarding the availability and accessibility of neurosurgical mentorship programmes worldwide at a medical student level. The evaluation suggested that medical students would most benefit from the neurosurgical mentorship in the future by means of increased numbers of mentors within their universities, accessibility to neurosurgical departments and the ability to choose mentorship globally via a unified digital platform.

BackgroundThe objective of this study is to describe the use of targeted therapies for the treatment of advanced renal cell carcinoma (RCC) and overall survival (OS) among patients in clinical practice in the Veterans Health Administration (VHA).MethodsA retrospective cohort of 286 patients from 24 VHA Medical Centers diagnosed with advanced clear cell RCC between Fiscal Year (FY) 2010 and FY2014 was followed through September 30, 2016. Among patients who received targeted therapy, we described the medications taken, duration of therapy, and overall survival. We also assessed the effect of the first therapy received on overall survival using Cox Proportional Hazards models.ResultsThere were 66 patients who did not receive therapy for their advanced RCC. Of the 220 treated patients, the mean (sd) number of medications received was 1.9 (1.1). The medications most commonly used first were sunitinib (61.8%), pazopanib (17.3%), and temsirolimus (10.9%). The median duration of first-line therapy was 86 days (interquartile range [IQR] 42, 210). Median total duration of therapy was 159 days (IQR 58, 397). 62.3% of patients had ≥ 1 dose of therapy held or reduced, mainly due to an adverse drug event (ADE). Median survival from the start of treatment to death was 1.08 years (IQR 0.80, 1.31). Finally, receipt of temsirolimus vs sunitinib (HR 1.95 [95%CI 1.09,3.47]) as the first targeted therapy was independently associated with an increased hazard of death.ConclusionOur analysis of targeted therapies for advanced RCC in VHA suggests duration of treatment is shorter in a real-world setting than in clinical trials, and dose reductions and ADEs are more common.

We describe a method for calculating the probability that a distal geographic location is impacted by a pyroclastic density current (PDC) of a given size, considering the key related uncertainties. Specifically, we evaluate the minimum volume and mass of a PDC generated at the Aso caldera (Japan) that might affect each of five distal infrastructure (marker) sites, with model input parameter uncertainties derived from expert judgment. The 5 marker sites are all located 115–145 km from the caldera; as these lie in well-separated directions, we can test the effects of the different topographic shielding effects in each case. To inform our probabilistic analysis, we apply alternative kinetic energy assessment approaches, i.e., rock avalanche and density current dynamics. In the latter formulation, the minimum mass needed to reach the markers ranges between median values of ∼153×1012 and ∼465×1012 kg (M 7.2–7.7), depending on the site. Rock avalanche dynamics modeling indicates that a ∼3-times greater mass would be required to reach the marker sites with 50 % probability, while the hypothetical scenario of a relatively dilute distal ash cloud would require ∼3-times less mass. We compare our results with the largest recorded Aso eruption, showing that a catastrophic eruption, similar to Aso-4, ≈ M8, would present a significant conditional probability of PDCs reaching the marker sites, in the density current formulation and contingent on uncertainty in the erupted mass and on marker site direction.