Randomised trial of cord clamping and initial stabilisation at very preterm birth

Objectives: For very preterm births, to compare alternatives policies for umbilical cord clamping and immediate neonatal care. Design: Parallel group randomised (1:1) trial, using sealed opaque numbered envelopes. Setting: Eight UK tertiary maternity units. Participants: 261 women expected to have a livebirth before 32 weeks, and their 276 babies. Interventions: Cord clamping after at least two minutes and immediate neonatal care with cord intact, or clamping within 20 seconds and immediate neonatal care after clamping. Main outcome measures: Intraventricular haemorrhage (IVH), death before discharge. Results: 132 women (137 babies) were allocated clamping ≥2 minutes and neonatal care cord intact, and 129 (139) clamping ≤20 and neonatal care after clamping; 6 mother infant dyads were excluded (2, 4) as birth was after 35+6 weeks, 1 withdrew (death data only available) (0, 1). Median gestation was 28.9 weeks for those allocated clamping ≥2 minutes, and 29.2 for those allocated clamping ≤20 seconds. Median time to clamping was 120 and 11 seconds respectively. 7 of 135 infants (5.2%) allocated clamping ≥2 minutes died and 15 of 135 (11.1%) allocated clamping ≤20 seconds; risk difference (RD) -5.9% (95% confidence interval -12.4% to 0.6%). Of livebirths, 43 of 134 (32%) had IVH versus 47 of 132 (36%) respectively; RD -3.5% (-14.9% to 7.8%). There were no clear differences in other outcomes for infants or mothers. Conclusions: This is promising evidence that clamping after at least 2 minutes and immediate neonatal care with cord intact at very preterm birth may improve outcome; a large trial is urgently needed

Hard X-Ray Constraints on Small-Scale Coronal Heating Events

Much evidence suggests that the solar corona is heated impulsively, meaning that nanoflares may be ubiquitous in quiet and active regions (ARs). Hard X-ray (HXR) observations with unprecedented sensitivity $>$3~keV are now enabled by focusing instruments. We analyzed data from the \textit{Focusing Optics X-ray Solar Imager (FOXSI)} rocket and the \textit{Nuclear Spectroscopic Telescope Array (NuSTAR)} spacecraft to constrain properties of AR nanoflares simulated by the EBTEL field-line-averaged hydrodynamics code. We generated model X-ray spectra by computing differential emission measures for homogeneous nanoflare sequences with heating amplitudes $H_0$, durations $\tau$, delay times between events $t_N$, and filling factors $f$. The single quiescent AR observed by \textit{FOXSI-2} on 2014 December 11 is well fit by nanoflare sequences with heating amplitudes 0.02 erg cm$^{-3}$ s$^{-1}$ $<$ $H_0$ $<$ 13 erg cm$^{-3}$ s$^{-1}$ and a wide range of delay times and durations. We exclude delays between events shorter than $\sim$900 s at the 90\% confidence level for this region. Three of five regions observed by {\nustar} on 2014 November 1 are well fit by homogeneous nanoflare models, while two regions with higher fluxes are not. Generally, the {\nustar} count spectra are well fit by nanoflare sequences with smaller heating amplitudes, shorter delays, and shorter durations than the allowed \textit{FOXSI-2} models. These apparent discrepancies are likely due to differences in spectral coverage between the two instruments and intrinsic differences among the regions. Steady heating ($t_N$ = $\tau$) was ruled out with $>$99\% confidence for all regions observed by either instrument.Comment: 17 pages, 21 figures. Accepted for publication in The Astrophysical Journa

Standard care informed by the result of a placental growth factor blood test versus standard care alone in women with reduced fetal movement at or after 36+0 weeks’ gestation: a pilot randomised controlled trial

BackgroundBiomarkers of placental function can potentially aid the diagnosis and prediction of pregnancy complications. This randomised controlled pilot trial assessed whether for women with reduced fetal movement (RFM), intervention directed by the measurement of a placental biomarker in addition to standard care was feasible and improved pregnancy outcome compared with standard care alone.MethodsWomen aged 16–50 years presenting at eight UK maternity units with RFM between 36+0 and 41+0 weeks’ gestation with a viable singleton pregnancy and no indication for immediate delivery were eligible. Participants were randomised 1:1 in an unblinded manner to standard care and a biomarker blood test result revealed and acted on (intervention arm) or standard care where the biomarker result was not available (control arm). The objectives were to determine the feasibility of a main trial by recruiting 175–225 participants over 9 months and to provide proof of concept that informing care by measurement of placental biomarkers may improve outcome. Feasibility was assessed via the number of potentially eligible women, number recruited, reasons for non-recruitment and compliance. Proof of concept outcomes included the rates of the induction of labour and caesarean birth, and a composite adverse pregnancy outcome.ResultsOverall, 2917 women presented with RFM ≥ 36 weeks, 352 were approached to participate and 216 (61%) were randomised (intervention n = 109, control n = 107). The main reason for not approaching women was resource/staff issues (n = 1510). Ninety-seven women declined the trial, mainly due to not liking blood tests (n = 24) or not wanting to be in a trial (n = 21). Compliance with the trial interventions was 100% in both arms. Labour was induced in 97 (45%) participants (intervention n = 49, control n = 48), while 17 (9%) had planned caesarean sections (intervention n = 9, control n = 8). Overall, 9 (8%) babies in the intervention arm had the composite adverse pregnancy outcome versus 4 (4%) in the control arm.ConclusionsA main trial using a placental biomarker in combination with delivery, as indicated by the biomarker, in women with RFM is feasible. The frequency of adverse outcomes in this population is low, hence, a large sample size would be required along with consideration of the most appropriate outcome measures

Brass Happenings

Presenting a student recital for brass students in USU\u27s Music Department.https://digitalcommons.usu.edu/music_programs/1107/thumbnail.jp

Optimising Digital Advance Care Planning Implementation in Palliative and End-of-life Care: A multi-phase mixed-methods national research programme and recommendations

Background: Digital advance care planning (DACP) is increasingly used globally for patients with life-limiting conditions to support real-time documentation and the sharing of preferences for care. There has been low engagement with DACP systems, with patients often having information about their care preferences documented late in their illness trajectory or not at all. To optimise implementation, the Optimal Care research programme sought to understand DACP system use from multiple perspectives to guide their development and evaluation.Methods: Between 2020 and 2023, our mixed-methods research programme sought an understanding of DACP implementation from multiple perspectives, including (i) national online survey of end-of-life care commissioning leads in England; (ii) online survey of community and hospital-based health and care professionals in two geographical regions; (iii) semi-structured interviews with a sample of survey respondents; (iv) focus groups and interviews with patients with life-limiting illness and their carers and (v) regional and national Theory of Change workshops. Findings were organised by five phases of a conceptual model of DACP generated during the programme and further categorised using the Non-adoption, Abandonment, Scale-up, Spread and Sustainability (NASSS) framework.Results: A total of 788 stakeholders participated. Twenty evidence-based recommendations were distilled from data collected across the research programme to guide the implementation of DACP in routine care. Considerations are provided across the five phases of DACP implementation (system design, recognition of clinical need for DACP, documentation processes, health and care professional engagement with DACP and DACP evaluation). Recommendations prioritise a focus on end-user needs and experiences, alongside highlighting the requisite need for DACP systems to support information exchange across settings involved in the care of people with life-limiting conditions.Conclusions: As currently designed and implemented, DACP systems may be falling short of their potential and are not working as intended for patients, carers and health and care professionals. The application of the recommendations should ensure consideration of the wider ecosystem in which DACP is being implemented, prioritising end-user experiences. Future research should prioritise developing approaches that target health and care professional DACP system engagement, alongside developing and evaluating patient and carer access to DACP systems

The Effects of Wildfire on Mortality and Resources for an Arboreal Marsupial: Resilience to Fire Events but Susceptibility to Fire Regime Change

BACKGROUND: Big environmental disturbances have big ecological effects, yet these are not always what we might expect. Understanding the proximate effects of major disturbances, such as severe wildfires, on individuals, populations and habitats will be essential for understanding how predicted future increases in the frequency of such disturbances will affect ecosystems. However, researchers rarely have access to data from immediately before and after such events. Here we report on the effects of a severe and extensive forest wildfire on mortality, reproductive output and availability of key shelter resources for an arboreal marsupial. We also investigated the behavioural response of individuals to changed shelter resource availability in the post-fire environment. METHODOLOGY/PRINCIPAL FINDINGS: We fitted proximity-logging radiotransmitters to mountain brushtail possums (Trichosurus cunninghami) before, during and after the 2009 wildfires in Victoria, Australia. Surprisingly, we detected no mortality associated with the fire, and despite a significant post-fire decrease in the proportion of females carrying pouch young in the burnt area, there was no short-term post-fire population decline. The major consequence of this fire for mountain brushtail possums was the loss of over 80% of hollow-bearing trees. The types of trees preferred as shelter sites (highly decayed dead standing trees) were those most likely to collapse after fire. Individuals adapted to resource decline by being more flexible in resource selection after the fire, but not by increased resource sharing. CONCLUSIONS/SIGNIFICANCE: Despite short-term demographic resilience and behavioural adaptation following this fire, the major loss of decayed hollow trees suggests the increased frequency of stand-replacing wildfires predicted under climate change will pose major challenges for shelter resource availability for hollow-dependent fauna. Hollow-bearing trees are typically biological legacies of previous forest generations in post-fire regrowth forests but will cease to be recruited to future regrowth forests if the interval between severe fires becomes too rapid for hollow formation

Characterisation and disposability assessment of multi-waste stream in-container vitrified products for higher activity radioactive waste

Materials from GeoMelt® In-Container Vitrification (ICV)™ of simulant UK nuclear wastes were characterised to understand the partitioning of elements, including inactive surrogates for radionuclide species of interest, within the heterogeneous products. Aqueous durability analysis was performed to assess the potential disposability of the resulting wasteforms. The vitrification trial aimed to immobilise a variety of simulant legacy waste streams representative of decommissioning operations in the UK, including plutonium contaminated material, Magnox sludges and ion-exchange materials, which were vitrified upon the addition of glass forming additives. Two trials with different wastes were characterised, with the resultant vitreous wasteforms comprising olivine and pyroxene crystalline minerals within glassy matrices. Plutonium surrogate elements were immobilised within the glassy fraction rather than partitioning into crystalline phases. All vitrified products exhibited comparable or improved durability to existing UK high level waste vitrified nuclear wasteforms over a 28 day period

Retreatment for hepatitis C virus direct-acting antiviral therapy virological failure in primary and tertiary settings: The REACH-C cohort

Virological failure occurs in a small proportion of people treated for hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapies. This study assessed retreatment for virological failure in a large real-world cohort. REACH-C is an Australian observational study (n = 10,843) evaluating treatment outcomes of sequential DAA initiations across 33 health services between March 2016 to June 2019. Virological failure retreatment data were collected until October 2020. Of 408 people with virological failure (81% male; median age 53; 38% cirrhosis; 56% genotype 3), 213 (54%) were retreated once; 15 were retreated twice. A range of genotype specific and pangenotypic DAAs were used to retreat virological failure in primary (n = 56) and tertiary (n = 157) settings. Following sofosbuvir/velpatasvir/voxilaprevir availability in 2019, the proportion retreated in primary care increased from 21% to 40% and median time to retreatment initiation declined from 294 to 152 days. Per protocol (PP) sustained virological response (SVR12) was similar for people retreated in primary and tertiary settings (80% vs 81%; p = 1.000). In regression analysis, sofosbuvir/velpatasvir/voxilaprevir (vs. other regimens) significantly decreased likelihood of second virological failure (PP SVR12 88% vs. 77%; adjusted odds ratio [AOR] 0.29; 95%CI 0.11–0.81); cirrhosis increased likelihood (PP SVR12 69% vs. 91%; AOR 4.26; 95%CI 1.64–11.09). Indigenous Australians had lower likelihood of retreatment initiation (AOR 0.36; 95%CI 0.15–0.81). Treatment setting and prescriber type were not associated with retreatment initiation or outcome. Virological failure can be effectively retreated in primary care. Expanded access to simplified retreatment regimens through decentralized models may increase retreatment uptake and reduce HCV-related mortality

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Humanity's Last Exam

Benchmarks are important tools for tracking the rapid advancements in large language model (LLM) capabilities. However, benchmarks are not keeping pace in difficulty: LLMs now achieve over 90\% accuracy on popular benchmarks like MMLU, limiting informed measurement of state-of-the-art LLM capabilities. In response, we introduce Humanity's Last Exam (HLE), a multi-modal benchmark at the frontier of human knowledge, designed to be the final closed-ended academic benchmark of its kind with broad subject coverage. HLE consists of 3,000 questions across dozens of subjects, including mathematics, humanities, and the natural sciences. HLE is developed globally by subject-matter experts and consists of multiple-choice and short-answer questions suitable for automated grading. Each question has a known solution that is unambiguous and easily verifiable, but cannot be quickly answered via internet retrieval. State-of-the-art LLMs demonstrate low accuracy and calibration on HLE, highlighting a significant gap between current LLM capabilities and the expert human frontier on closed-ended academic questions. To inform research and policymaking upon a clear understanding of model capabilities, we publicly release HLE at https://lastexam.ai