Inefficient Melt Transport Across a Weakened Lithosphere Led to Anomalous Rift Architecture in the Turkana Depression

The Turkana Depression, located between the Ethiopian and East African plateaus, displays an anomalous rift architecture. It is missing the narrow, magma‐rich morphology observed in the Main Ethiopian Rift that cuts through the Ethiopian Plateau. Instead, diffuse faulting and isolated volcanic centers are widespread over several hundred kilometers. Turkana has also experienced less magmatism over the last 30 Myr than adjacent plateaus, despite having a thin crust and residing above a mantle that is inferred to be hot and partially molten. We hypothesize that lithospheric weakening has been the key control on magma transport across the lithosphere in the Turkana Depression and subsequent rift development. Using poro‐viscoelastic–viscoplastic models of melt transport, we show that magma extraction across a thin, weakened lithosphere is slower than across a thick, elastic lithosphere. Our results suggest that pre‐rift lithospheric strength can explain the magma‐poor character of Turkana for most of its tectonic history

The utility of novel environmental impact metrics in UK ruminant mitigation

Much of the UK land sector’s environmental impact comes from the production of beef and dairy. Conventional metrics, which understate both the impact of methane reductions and the carbon opportunity cost of land, attribute most of this impact to enteric methane and land-use change from imported soy for feed. Recent developments in agricultural impact metrics necessitate investigation into whether continued reliance on conventional metrics could undermine national (and global) progress on climate and deforestation targets. This article estimates emissions and land use impacts associated with cattle in the UK and applies various combinations of metrics under four futures simulating a range of technological and policy levers. We find that the use of alternative metrics can highlight the potential impact of interventions that might have been overlooked when using conventional metrics, particularly encouraging more efficient production by including the carbon cost of foregone sequestration. We suggest that a range of metrics should be considered to ensure mitigation strategies which deliver on global outcomes, and show that estimates of absolute sectoral impact are acutely sensitive to methodological choices in how it is measured. We also find that the rank-ordering of different intervention strategies for the UK is largely insensitive to metric choice, though this may not be the case for all agricultural systems

The Prostate cancer–Exercise and Metformin randomised controlled feasibility Trial (Pre-EMpT) in men following active surveillance, radical prostatectomy and radiotherapy

Background: Moderate to vigorous physical activity and metformin are associated in epidemiological studies with reduced biochemical recurrence and mortality in men with prostate cancer. This study assessed the feasibility of a home-based physical activity and/or metformin intervention in men with non-metastatic prostate cancer following radical treatment (surgery or radiotherapy) or active surveillance. Methods: A 2 × 2 factorial design randomised men into one of four groups for 6 months: (1) physical activity (defined as brisk walking ≥ 30 min for ≥ 5 days per week, aiming for ≥ 10,000 steps a day); (2) metformin (one 500 mg slow-release tablet daily); (3) physical activity and metformin; and (4) control. Men were recruited from a single tertiary referral centre in the South West of England, UK, (September 2018–March 2020 which terminated slightly early due to the COVID-19 pandemic). Co-primary outcomes were rates of randomisation and adherence which was defined as men brisk walking ≥30 minutes on at least 5 days with 10,000 steps daily (measured over one week 6-months after randomisation) with ≥ 60% adherence to metformin between 3- and 6 months post-randomisation using returned pill count. Secondary outcomes included self-reported adverse events and physical activity, feasibility of wearing activity monitors and questionnaire completion. Results: In total, 295 men were eligible and 110 were randomised (37.3%, 95% confidence interval [CI] 31.8 to 43.1). Adherence to the physical activity and metformin interventions was 46.9% (95% CI 32.5 to 62.0) and 47.1% (95% CI 32.9 to 61.5) respectively. Adherence was > 60% for both the physical activity and metformin interventions on a complete case basis. Adverse events were infrequent (n = 7) across randomised groups. Completion of self-reported measures of physical activity, urinary incontinence, sexual function, quality of life and stages of change was over 80%. Step counts were not higher in men wearing activity monitors that alerted them about their step counts and sedentary behaviour. Retention over 6 months was 91.3% (95% CI 84.2 to 96.0). Follow up and intervention prompts were impacted by the pandemic. Conclusion: Home-based physical activity and metformin interventions show some promise for men with prostate cancer following radical treatment or active surveillance. Trial registration: ISRCTN, ISRCTN13543667. Registered 2 August 2018, https://www.isrctn.com/ISRCTN1354366

Protocol for a global menopause priority setting partnership

Introduction: All those born with functioning ovaries will eventually experience menopause, and many will be symptomatic. However, significant gaps in the evidence base for menopause care remain. This National Institute for Health and Care Research James Lind Alliance Menopause Priority Setting Partnership (MAPS) will engage with clinicians and those with lived experience globally to determine the leading priorities for future menopause research. Methods and analysis: MAPS will follow the established James Lind Alliance methodology which has already resulted in over 100 ‘top 10’ research priorities across health domains. It will be led by a steering group comprised of clinicians and lived experience members. Leveraging the networks of steering group members and partner organisations, the priority setting partnership will identify evidence uncertainties using an online survey. Evidence checking will be undertaken to determine which questions have already been answered. Prioritisation will be done in two stages, initially by online survey and then at a face-to-face workshop. Ethics and dissemination: Ethical approval was not required. The final top 10 priorities for menopause, as ranked by stakeholders at the final consensus workshop, will be disseminated in the relevant peer-reviewed journals. A final report will be available on the MAPS and James Lind Alliance websites. The leading priorities will inform the future global research agenda for menopause

Growth and peace: essays on economic growth, the causes of war, AI, and the possibility of a more peaceful future: Growth and peace

This thesis considers the Peaceful Future Hypothesis: the hypothesis that the future will be drastically more peaceful than the past. I clarify the hypothesis, then describe a two-step approach to judging its likelihood. The first step is to analyse historical trends in the rate of conflict and produce an initial forecast purely on this basis. The second step is to modify this initial forecast, by considering causal mechanisms that could explain past trends — or give us reasons to expect conflict to be more or less common than trend extrapolation would suggest. After conducting analysis on these lines, I suggest that a peaceful future is unlikely but not implausible. (For example, assigning it something like a 15% probability wouldn’t strike me as unreasonable.) One finding, which lends the hypothesis some plausibility, is that a noisy downward trend in the rate of interstate conflict seems to have started in the mid-20th-century. If this trend is real and lasts long enough, then the world would be very peaceful by the end of the present century. Economic growth may be one factor driving this trend: growth seems to have a strong-but-underrecognized pacifying effect, and many states began experiencing substantial growth around the right time. If growth is actually one driver of the trend, then that would be reassuring, since the world may become much wealthier over the next century. However, we can’t say anything with confidence. Historical trends and causal relationships are hard to reliably identify. Growth is far from the only factor that matters. Growth’s marginal effect will probably fall. AI might upend everything. And so on. Along the way, I make various secondary academic contributions. If nothing else, grappling with the hypothesis turns out to be a good way to grapple with fundamental questions in International Relations

Arm Based on LEg blood pressures (ABLE-BP): can systolic ankle blood pressure measurements predict systolic arm blood pressure? An individual participant data meta-analysis from the INTERPRESS-IPD Collaboration

ObjectivesTo determine associations between arm and ankle systolic blood pressures (SBPs), develop and validate a multivariable model predicting arm SBP from ankle SBP, and investigate associations between ankle SBP, cardiovascular disease and mortality.DesignAnkle-arm SBP differences were examined in two-stage individual participant data (IPD) meta-analyses using multivariable hierarchical linear regression models. Models were used to derive and validate a prediction model for arm SBP based on ankle SBP. Model performance was assessed using area under the receiver operating characteristic (AUROC) curve analyses. Prognostic associations of ankle SBP with outcomes were examined using Cox proportional hazards models.Data sourcesSearches identified cohorts for the Inter-arm Blood Pressure Difference IPD (INTERPRESS-IPD) Collaboration from Medline, Old Medline, Medline in process, Embase and CINAHL databases from inception until January 2017; unpublished data were also sought. Required primary outcomes were all-cause mortality, cardiovascular mortality, and/or fatal and non-fatal cardiovascular events.Eligibility criteriaProspective studies from community, primary care or general clinic settings, without language restriction, that recorded SBP in both arms were eligible. Adults aged ≥18 years with SBP measured in all four limbs, in a supine position, were included in the current analyses. People with peripheral artery disease were excluded.Data extraction and synthesisAnonymised datasets were individually cleaned and then combined into a single dataset for the INTERPRESS-IPD Collaboration.ResultsThe current dataset included 33 710 participants from 14 studies; mean age 58 years, 45% female, mean baseline arm blood pressure 138/80 (SD: 20/12) mm Hg. Mean ankle SBP was 12.0 mm Hg (95% CI 8.8 to 15.2) higher than arm SBP. The multivariable model predicting arm SBP from ankle SBP demonstrated excellent performance (AUROC curves, sensitivities and specificities were >0.82, 0.80 and 0.82, respectively, at all BP thresholds from 130 to 160 mm Hg). Model performance was superior to existing arithmetic formulae.Ankle SBP was neither associated with all-cause nor cardiovascular mortality (HR 1.000 (0.997 to 1.002; p=0.682) and 1.001 (0.996 to 1.005; p=0.840), respectively). However, lower-reading ankle SBP was associated with fatal or non-fatal cardiovascular events (HR 1.005 (1.002 to 1.007; p<0.001).ConclusionsOn average, ankle SBP is 12 mm Hg higher than arm SBP. Estimating individual arm SBP from ankle SBP measurements with a multivariable model is more accurate than existing fixed arithmetic formulae. This model, operationalised in an online calculator (https://ablebp.Researchexeter.ac.uk/), could facilitate hypertension management and cardiovascular care for people unable to have arm SBP measured.Prospero registration numberCRD42015031227

How to improve mental health in the older adults through AI-enhanced physical activity: an emerging research topic

With the global rise in aging populations, the demand for healthcare and long-term care services has grown, particularly for addressing mental health. While AI has shown promise for health management of older adults, its effects on physical activity, mental health, and their associations remain largely unexamined.This study aimed to investigate the role of AI in improving mental health among older adults through the promotion of physical activity and elucidating the underlying mechanisms.Bibliometric methods, including CiteSpace and VOSviewer, were employed to analyze 1831 publications, identifying trends, collaborations, hotspots, and potential applications in this domain.AI interventions significantly enhanced mental health in older adults by promoting physical activity. Prominent mechanisms included tailored psychological support, cognitive rehabilitation, and targeted cardiovascular and musculoskeletal interventions. These mechanisms drove better cognitive function, emotional regulation, and physical resilience. These interventions were supported in their effectiveness by biomarkers of BDNF, serotonin, and increased physical activity levels.The present study combines insights on AI, physical activity, and mental health to facilitate emerging research opportunities and practical applications. It highlights the importance of AI for individualized exercise interventions, smart health monitoring, and cognitive and emotional rehabilitation. These research insights provide important guidance for scholars and practitioners, helping them to more effectively leverage artificial intelligence technologies to address the growing mental health needs of aging societies. By systematically outlining the potential roles of AI in future interventions, this study contributes to advancing the use of AI-assisted physical activity to promote mental health in aging population life

Dynamic nanodomains dictate macroscopic properties in lead halide perovskites

Lead halide perovskites have emerged as promising materials for solar energy conversion and X-ray detection owing to their remarkable optoelectronic properties. However, the microscopic origins of their superior performance remain unclear. Here we show that low-symmetry dynamic nanodomains present in the high-symmetry average cubic phases, whose characteristics are dictated by the A-site cation, govern the macroscopic behaviour. We combine X-ray diffuse scattering, inelastic neutron spectroscopy, hyperspectral photoluminescence microscopy and machine-learning-assisted molecular dynamics simulations to directly correlate local nanoscale dynamics with macroscopic optoelectronic response. Our approach reveals that methylammonium-based perovskites form densely packed, anisotropic dynamic nanodomains with out-of-phase octahedral tilting, whereas formamidinium-based systems develop sparse, isotropic, spherical nanodomains with in-phase tilting, even when crystallography reveals cubic symmetry on average. We demonstrate that these sparsely distributed isotropic nanodomains present in formamidinium-based systems reduce electronic dynamic disorder, resulting in a beneficial optoelectronic response, thereby enhancing the performance of formamidinium-based lead halide perovskite devices. By elucidating the influence of the A-site cation on local dynamic nanodomains, and consequently, on the macroscopic properties, we propose leveraging this relationship to engineer the optoelectronic response of these materials, propelling further advancements in perovskite-based photovoltaics, optoelectronics and X-ray imaging

Impact of Long-Term Chemotherapy on Outcomes in Pancreatic Ductal Adenocarcinoma: A Real-World UK Multi-Centre Study

Background: We reviewed outcomes of short and long-term chemotherapy with or without breaks in pancreatic ductal adenocarcinoma (PDAC) patients. Methods: PDAC patients receiving ≥3 chemotherapy cycles between 2019 and 2024 at three institutions were included. Progression-free survival after first-line chemotherapy (PFS1), overall survival (OS) and best overall response (BOR) to chemotherapy were assessed using the Wilcoxon test, Kaplan-Meier test, and univariate and multivariate Cox regression models. Results: We screened 237 patients, and 135 patients met the study criteria. Among these patients, 25 had resectable disease, and 110 had unresectable/metastatic disease (13% borderline resectable (BRPC), 20% locally advanced (LAPC), 10% localised developing metastases, 57% de novo metastatic). Ten patients (7%) underwent genetic profiling; KRAS aberrations (N = 4), actionable PLAB2/BRCA2/FGFR2 mutations (N = 3), ATM/BRIP1 alteration (N = 1). Two patients were managed with PARP inhibitors after receiving multiple lines of chemotherapy. Median PFS1 and OS were concordant with the published literature, but select patient groups achieved prolonged survival outcomes. Among the 36 BRPC/LAPC patients, we observed >1-year PFS1 in 9 (25%) patients and >2-year OS in 3 (8%) patients. Among the 63 de novo metastatic patients, we observed >1-year PFS1 and >2-year OS in 6 (10%) patients. Among patients with localised disease, smoking history was a poor prognostic factor with respect to OS (p = 0.03). Improved PFS1 and OS was associated with ≥6 cycles of first-line chemotherapy, its duration of ≥3.66 months, and local treatment after first chemotherapy (p 1 line of chemotherapy (p = 0.003). Conclusion: Despite challenges, extended chemotherapy and multiple treatment lines may improve survival, with localised treatments benefiting select patients

Dynamic Contributions to Recent Observed Wintertime Precipitation Trends in Mediterranean‐Type Climate Regions

Many Mediterranean‐type climates (MCs) have experienced wintertime drying trends since 1979. Using a dynamical adjustment method, we separate the effects of circulation‐induced drying trends from other residual trends. Our analysis reveals that circulation trends are the leading cause of the observed drying in Central Chile and the US Southwest, and that models show the drying across Southern Hemisphere MCs is independent of trends in the Southern Annular Mode. All Mediterranean‐type climates have exhibited residual drying trends from both internal variability and externally forced thermodynamic processes. Large ensembles suggest internal variability contributes significantly to the observed drying. However, in many regions the observed drying lies outside the ensemble distribution, raising questions about model accuracy