Explore the vast range of titles available.

ObjectiveThis study aims to estimate the cost-effectiveness of oral spironolactone plus routine topical treatment compared with routine topical treatment alone for persistent acne in adult women from a British NHS perspective over 24 weeks.DesignEconomic evaluation undertaken alongside a pragmatic, parallel, double-blind, randomised trial.SettingPrimary and secondary healthcare, community and social media advertising.ParticipantsWomen ≥18 years with persistent facial acne judged to warrant oral antibiotic treatment.InterventionsParticipants were randomised 1:1 to 50 mg/day spironolactone (increasing to 100 mg/day after 6 weeks) or matched placebo until week 24. Participants in both groups could continue topical treatment.Main outcome measuresCost-utility analysis assessed incremental cost per quality-adjusted life year (QALY) using the EQ-5D-5L. Cost-effectiveness analysis estimated incremental cost per unit change on the Acne-QoL symptom subscale. Adjusted analysis included randomisation stratification variables (centre, baseline severity (investigator’s global assessment, IGA <3 vs ≥3)) and baseline variables (Acne-QoL symptom subscale score, resource use costs, EQ-5D score and use of topical treatments).ResultsSpironolactone did not appear cost-effective in the complete case analysis (n=126 spironolactone, n=109 control), compared with no active systemic treatment (adjusted incremental cost per QALY £67 191; unadjusted £34 770). Incremental cost per QALY was £27 879 (adjusted), just below the upper National Institute for Health and Care Excellence’s threshold value of £30 000, where multiple imputation took account of missing data. Incremental cost per QALY for other sensitivity analyses varied around the base-case, highlighting the degree of uncertainty. The adjusted incremental cost per point change on the Acne-QoL symptom subscale for spironolactone compared with no active systemic treatment was £38.21 (complete case analysis).ConclusionsThe results demonstrate a high level of uncertainty, particularly with respect to estimates of incremental QALYs. Compared with no active systemic treatment, spironolactone was estimated to be marginally cost-effective where multiple imputation was performed but was not cost-effective in complete case analysis.Trial registration numberISRCTN registry (ISRCTN12892056).

In an international trial involving 450 patients with acute subdural hematoma, craniotomy (bone flap replaced) and decompressive craniectomy (bone flap left out) yielded similar disability-related outcomes at 12 months.

AbstractObjectiveTo assess the effectiveness of oral spironolactone for acne vulgaris in adult women.DesignPragmatic, multicentre, phase 3, double blind, randomised controlled trial.SettingPrimary and secondary healthcare, and advertising in the community and on social media in England and Wales.ParticipantsWomen (≥18 years) with facial acne for at least six months, judged to warrant oral antibiotics.InterventionsParticipants were randomly assigned (1:1) to either 50 mg/day spironolactone or matched placebo until week six, increasing to 100 mg/day spironolactone or placebo until week 24. Participants could continue using topical treatment.Main outcome measuresPrimary outcome was Acne-Specific Quality of Life (Acne-QoL) symptom subscale score at week 12 (range 0-30, where higher scores reflect improved QoL). Secondary outcomes were Acne-QoL at week 24, participant self-assessed improvement; investigator’s global assessment (IGA) for treatment success; and adverse reactions.ResultsFrom 5 June 2019 to 31 August 2021, 1267 women were assessed for eligibility, 410 were randomly assigned to the intervention (n=201) or control group (n=209) and 342 were included in the primary analysis (n=176 in the intervention group and n=166 in the control group). Baseline mean age was 29.2 years (standard deviation 7.2), 28 (7%) of 389 were from ethnicities other than white, with 46% mild, 40% moderate, and 13% severe acne. Mean Acne-QoL symptom scores at baseline were 13.2 (standard deviation 4.9) and at week 12 were 19.2 (6.1) for spironolactone and 12.9 (4.5) and 17.8 (5.6) for placebo (difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46), adjusted for baseline variables). Scores at week 24 were 21.2 (5.9) for spironolactone and 17.4 (5.8) for placebo (difference 3.45 (95% confidence interval 2.16 to 4.75), adjusted). More participants in the spironolactone group reported acne improvement than in the placebo group: no significant difference was reported at week 12 (72% v 68%, odds ratio 1.16 (95% confidence interval 0.70 to 1.91)) but significant difference was noted at week 24 (82% v 63%, 2.72 (1.50 to 4.93)). Treatment success (IGA classified) at week 12 was 31 (19%) of 168 given spironolactone and nine (6%) of 160 given placebo (5.18 (2.18 to 12.28)). Adverse reactions were slightly more common in the spironolactone group with more headaches reported (20% v 12%; p=0.02). No serious adverse reactions were reported.ConclusionsSpironolactone improved outcomes compared with placebo, with greater differences at week 24 than week 12. Spironolactone is a useful alternative to oral antibiotics for women with acne.Trial registrationISRCTN12892056

PurposeChildren in middle childhood are at an increased risk for injury in pedestrian environments. This study examined whether they are capable of showing evasive action (ie, adjusting crossing speed) to avoid injury when crossing streets.MethodsThe study used a fully immersive virtual reality (VR) system interfaced with a three-dimensional movement measurement system so that the actual crossing behaviour of 7–10-year-old children under different traffic conditions could be precisely measured. Relating outcomes to that which would have been obtained based on using the approach of estimating walking speed and assuming a constant speed provided insights into the realised benefits of the current movement monitoring VR system.ResultsControlling for age and sex, children showed evasive action, crossing more quickly as traffic conditions became more risky. Using an average and assuming a constant walking speed underestimated actual walking speed, failing to capture evasive action and leading to overestimation of children being hit compared with the actual incidence of hits.ConclusionsVR technology is a valuable tool for assessing child pedestrian behaviour. However, systems need to allow the child to cross the street so their level of pedestrian skill is appropriately measured. The current findings provide the first evidence that children are capable of implementing evasive action in reaction to risky traffic conditions.

Teaching has been noted to be one of the most demanding careers, yet, there is limited research exploring teachers’ experiences with respect to mental health or wellness. Research suggests that emotional exhaustion and mental health concerns may be on the rise among teachers; this not only has a negative impact on teachers’ well-being, but also on students’ learning, academic engagement and stress levels. While there is promising research that identifies emotional intelligence (EI) may be a protective factor in teacher wellness, there is a paucity of research exploring possible connections. The current study explores EI in relation to teacher mental health and burnout. Data was collected through an online survey via two teacher organizations in Canada. Findings revealed that as emotional intelligence increases, mental health concerns and feelings of burnout decrease. Caregiving responsibilities outside of work were not found to influence this relationship. Additionally, the well-being component of EI was identified as the most important predictor of mental health in teachers. These results highlight the importance of building EI skills for teachers as well as adjusting educational policies to support teachers’ well-being.

In the cell, DNA is arranged into highly-organised and topologically-constrained (supercoiled) structures. It remains unclear how this supercoiling affects the detailed double-helical structure of DNA, largely because of limitations in spatial resolution of the available biophysical tools. Here, we overcome these limitations, by a combination of atomic force microscopy (AFM) and atomistic molecular dynamics (MD) simulations, to resolve structures of negatively-supercoiled DNA minicircles at base-pair resolution. We observe that negative superhelical stress induces local variation in the canonical B-form DNA structure by introducing kinks and defects that affect global minicircle structure and flexibility. We probe how these local and global conformational changes affect DNA interactions through the binding of triplex-forming oligonucleotides to DNA minicircles. We show that the energetics of triplex formation is governed by a delicate balance between electrostatics and bonding interactions. Our results provide mechanistic insight into how DNA supercoiling can affect molecular recognition, that may have broader implications for DNA interactions with other molecular species. In cells, DNA is arranged into topologically-constrained (supercoiled) structures, but how this supercoiling affects the detailed double-helical structure of DNA remains unclear. Here authors use atomic force microscopy and atomistic molecular dynamics simulations, to resolve structures of negatively-supercoiled DNA minicircles at base-pair resolution.

Science is losing knowledge it cannot afford to lose. Negative results go unpublished, hard-won expertise walks out the door with departing researchers, and preservation efforts remain fragmented. The consequences are wasted resources, duplicated effort, and missed discoveries. In this perspective, we argue that the research community can act now by embracing alternative dissemination channels, improving documentation best practices, and building sustainable digital infrastructure. We envision moderated platforms for sharing null results and practical know-how, community-driven standards, and AI-powered tools that lower barriers to implementation. With coordinated effort, science can become more open, efficient, and resilient for future generations. Science routinely discards valuable knowledge, from unpublished negative results to the tacit expertise lost when researchers move on. Here, the authors propose a roadmap for preserving this hidden knowledge through community-driven platforms, open standards, and AI-assisted documentation.

Evidence from observational records and model simulations suggest that volcanic eruptions can strengthen mid- to high-latitude atmospheric circulation and enhance westerly wind strength, with recent proxy data-model assimilations supporting this. However, assessments of Holocene variability in storminess rarely consider whether major volcanic eruptions could be a possible driver of reconstructed periods of enhanced storminess. This research presents a new reconstruction of past storminess from a coastal peatbog situated in western Ireland spanning the last ∼ 7 ka. The record is based on the measurement of the sand content along the core, with XRF core scanning analysis also applied to test whether variations in quartz sand, shell sand and sea spray can be detected by variations in silica, calcium and bromine respectively. Ca measurements were similar to the long-term changes in sand content along the core, however, peaks in sand content were not detected, while Si reflected increases in sand content only within the last millennium when the inorganic content was highest. Br concentrations appear to have been influenced primarily by humification. We also compared sand-based storminess records from northwest Europe. Six multi-decadal to centennial periods with enhanced storminess are common to records from Ireland and Wales during the last 2.5 ka BP, centred at c. 2.25, 2, 1.4, 1.1, 0.5 and 0.2 ka BP, with less agreement between records before this time. The storm periods at 2.8, 2.2–2, 1.1 and 0.5 ka BP are more widespread events and agree with records from Sweden and Scotland. Each of the episodes of increased storminess coincide roughly with major volcanic eruptions during the late Holocene, as well as with periods of enhanced North Atlantic ice-rafting. We hypothesise, therefore, that both enhanced storminess and ice-rafting may have resulted from the climate and environmental impacts of these eruptions, aligning with the findings of recent observational and modelling studies on the climate response to eruptions. Challenges remain, however, in testing this hypothesis, given chronological uncertainties in peatland records and uncertain interpretations of the factors influencing sand deposition. Therefore, to provide an independent assessment of the influence of explosive eruptions on storminess for Ireland's northeast Atlantic position, we draw upon the rich tradition of annalistic record keeping on the island, including many reports of major storms and windy seasons, to develop a windiness index running from the sixth to seventeenth centuries CE. A set of superposed epoch analyses shows that the ice-core-based dates of explosive volcanic eruptions are statistically significantly associated with the dates of documented storms and windy seasons in Ireland, suggesting avenues for future research.

Here we present a newly developed ice core gas-phase proxy that directly samples a component of the large-scale atmospheric circulation: synoptic-scale pressure variability. Surface pressure changes weakly disrupt gravitational isotopic settling in the firn layer, which is recorded in krypton-86 excess (86Krxs). The 86Krxs may therefore reflect the time-averaged synoptic pressure variability over several years (site “storminess”), but it likely cannot record individual synoptic events as ice core gas samples typically average over several years. We validate 86Krxs using late Holocene ice samples from 11 Antarctic ice cores and 1 Greenland ice core that collectively represent a wide range of surface pressure variability in the modern climate. We find a strong spatial correlation (r=-0.94, p<0.01) between site average 86Krxs and time-averaged synoptic variability from reanalysis data. The main uncertainties in the analysis are the corrections for gas loss and thermal fractionation and the relatively large scatter in the data. Limited scientific understanding of the firn physics and potential biases of 86Krxs require caution in interpreting this proxy at present. We show that Antarctic 86Krxs appears to be linked to the position of the Southern Hemisphere eddy-driven subpolar jet (SPJ), with a southern position enhancing pressure variability. We present a 86Krxs record covering the last 24 kyr from the West Antarctic Ice Sheet (WAIS) Divide ice core. Based on the empirical spatial correlation of synoptic activity and 86Krxs at various Antarctic sites, we interpret this record to show that West Antarctic synoptic activity is slightly below modern levels during the Last Glacial Maximum (LGM), increases during the Heinrich Stadial 1 and Younger Dryas North Atlantic cold periods, weakens abruptly at the Holocene onset, remains low during the early and mid-Holocene, and gradually increases to its modern value. The WAIS Divide 86Krxs record resembles records of monsoon intensity thought to reflect changes in the meridional position of the Intertropical Convergence Zone (ITCZ) on orbital and millennial timescales such that West Antarctic storminess is weaker when the ITCZ is displaced northward and stronger when it is displaced southward. We interpret variations in synoptic activity as reflecting movement of the South Pacific SPJ in parallel to the ITCZ migrations, which is the expected zonal mean response of the eddy-driven jet in models and proxy data. Past changes to Pacific climate and the El Niño–Southern Oscillation (ENSO) may amplify the signal of the SPJ migration. Our interpretation is broadly consistent with opal flux records from the Pacific Antarctic zone thought to reflect wind-driven upwelling. We emphasize that 86Krxs is a new proxy, and more work is called for to confirm, replicate, and better understand these results; until such time, our conclusions regarding past atmospheric dynamics remain speculative. Current scientific understanding of firn air transport and trapping is insufficient to explain all the observed variations in 86Krxs. A list of suggested future studies is provided.

We present a 2700-year annually resolved chronology and snow accumulation history for the Roosevelt Island Climate Evolution (RICE) ice core, Ross Ice Shelf, West Antarctica. The core adds information on past accumulation changes in an otherwise poorly constrained sector of Antarctica. The timescale was constructed by identifying annual cycles in high-resolution impurity records, and it constitutes the top part of the Roosevelt Island Ice Core Chronology 2017 (RICE17). Validation by volcanic and methane matching to the WD2014 chronology from the WAIS Divide ice core shows that the two timescales are in excellent agreement. In a companion paper, gas matching to WAIS Divide is used to extend the timescale for the deeper part of the core in which annual layers cannot be identified. Based on the annually resolved timescale, we produced a record of past snow accumulation at Roosevelt Island. The accumulation history shows that Roosevelt Island experienced slightly increasing accumulation rates between 700 BCE and 1300 CE, with an average accumulation of 0.25±0.02 m water equivalent (w.e.) per year. Since 1300 CE, trends in the accumulation rate have been consistently negative, with an acceleration in the rate of decline after the mid-17th century. The current accumulation rate at Roosevelt Island is 0.210±0.002 m w.e. yr−1 (average since 1965 CE, ±2σ), and it is rapidly declining with a trend corresponding to 0.8 mm yr−2. The decline observed since the mid-1960s is 8 times faster than the long-term decreasing trend taking place over the previous centuries, with decadal mean accumulation rates consistently being below average. Previous research has shown a strong link between Roosevelt Island accumulation rates and the location and intensity of the Amundsen Sea Low, which has a significant impact on regional sea-ice extent. The decrease in accumulation rates at Roosevelt Island may therefore be explained in terms of a recent strengthening of the ASL and the expansion of sea ice in the eastern Ross Sea. The start of the rapid decrease in RICE accumulation rates observed in 1965 CE may thus mark the onset of significant increases in regional sea-ice extent.