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Area-level socioeconomic deprivation and suicide by restrictable method of death: Trends in Japan, 1995–2022
No full textBackground:
To establish an effective and equitable suicide prevention strategy, it is critical that we understand the distribution, according to area-level socioeconomic deprivation, of deaths by methods of suicide that are restrictable. We aimed to reveal this distribution and associated trends in Japan.
Methods:
This serial cross-sectional study used vital statistics in Japan from 1995 to 2022. Area-level socioeconomic deprivation at municipality level was estimated by the Area Deprivation Index in Japan. Suicide by four restrictable methods—pesticide ingestion, jumping from a high place, intentional collision, and medication overdose—were identified based on vital statistics according to area-level socioeconomic deprivation.
Results:
From 1995 to 2022, 738,810 suicides were observed, with 108,628 suicides by the four restrictable methods. Suicide rates by pesticide ingestion, jumping from a height, and medication overdose were higher in deprived areas than in non-deprived areas, while the suicide rate by intentional collision was higher in non-deprived areas than in deprived areas. Both suicide by pesticide ingestion and its inequality between deprived and non-deprived areas have continuously decreased since 2000. Suicide by jumping from a height and medication overdose have decreased since 2010, with widened inequality observed between deprived and non-deprived areas.
Conclusion:
Area-level socioeconomic deprivation was associated with a higher suicide rate by pesticide ingestion, jumping from a height, and medication overdose while suicide rate by intentional collision was higher in non-deprived areas than in deprived areas. Integrating method restrictions tailored to residential characteristics into suicide prevention strategies may help promote health equity across areas
Graph neural network surrogates for contacting deformable bodies with necessary and sufficient contact detection
No full textSurrogate models for the rapid inference of nonlinear boundary value problems in mechanics are helpful in a broad range of engineering applications. However, effective surrogate modeling of applications involving the contact of deformable bodies, especially in the context of varying geometries, is still an open issue. In particular, existing methods are confined to rigid body contact or, at best, contact between rigid and soft objects with well-defined contact planes. Furthermore, they employ contact or collision detection filters that serve as a rapid test but use only the necessary and not sufficient conditions for detection. In this work, we present a graph neural network architecture that utilizes continuous collision detection and, for the first time, incorporates sufficient conditions designed for contact between soft deformable bodies. We test its performance on two benchmarks, including a problem in soft tissue mechanics of predicting the closed state of a bioprosthetic aortic valve. We find a regularizing effect on adding additional contact terms to the loss function, leading to better generalization of the network. These benefits hold for simple contact at similar planes and element normal angles, and complex contact at differing planes and element normal angles. We also demonstrate that the framework can handle varying reference geometries. However, such benefits come with high computational costs during training, resulting in a trade-off that may not always be favorable. We quantify the training cost and the resulting inference speedups on various hardware architectures. Importantly, our graph neural network implementation results in up to a hundred- to thousand-fold speedup on GPU, and twenty- to two hundred-fold speedup on CPU for our benchmark problems at inference
Future Faith: Public and Practical Theologies for the Contemporary World, Graeme Smith and Andrew Todd (eds) Routledge, London and New York, 2025, pp x, 253. ISBN 9781032466507. Hbk. £135.00
No full textNo abstract available
Lost in transplantation? the challenge of deploying “comply or explain” in Scottish higher education governance
No full textThis article questions the appropriateness of a recent transplant of the comply or explain (CorE) approach from corporate governance to higher education governance. This mechanism, a crucial part of the UK Corporate Governance Code (UKCGC), relies on disclosure to shareholders who, if unhappy with management's explanations, can act to discipline management. This article compares and contrasts governance issues in both the corporate sector and the higher education sector. This article argues that the inclusion of CorE into a governance code for Scottish Higher Education Governance (SHEG) is an unwelcome transplant from UK corporate law that fails to provide equivalent discipline of management but provides a veneer of doing so, causing more harm than if it were not deployed
Tirzepatide and change in uric acid and its association with weight reduction: post hoc analyses of the SURMOUNT-1 randomised placebo-controlled trial
Get PDFObjectives:
This study aimed to test whether tirzepatide, a dual GLP-1RA/GIP agonist, approved for weight management, would be associated with lowered serum uric acid (SUA) levels via its weight reduction properties.
Methods:
A post hoc analysis of the SURMOUNT-1 trial, a randomised placebo-controlled trial involving 2539 adults with obesity or overweight (body mass index [BMI] ≥ 30 kg/m2 or ≥27 kg/m2 and at least 1 weight-related complication), randomised to tirzepatide (5, 10, or 15 mg) or placebo for 72 weeks. Tirzepatide treatment over 72 weeks decreased weight by up to 20.9%. SUA was measured at baseline and multiple time points during the 72-week study across the 3 active trial arms, and changes were compared to the placebo arm. The association between weight changes and SUA changes was evaluated by mediation analysis.
Results:
Treatment with all dose groups of tirzepatide was associated with significant reductions in SUA, compared to placebo. At week 72, the mean change in SUA was -0.69 mg/dL (SE: 0.04), -0.92 mg/dL (0.04), and -0.95 mg/dL (0.04) with 5, 10, and 15 mg of tirzepatide (all P < .001), respectively, and -0.18 mg/dL (0.04) with placebo. SUA levels reduced significantly over time compared to placebo, regardless of baseline uric acid quartiles (P = .610) and baseline BMI values (P = .362). Mediation analysis suggested that weight reduction explained 72.7% of SUA reduction.
Conclusions:
In this post hoc analysis, in participants with obesity or overweight, tirzepatide was associated with meaningfully reduced SUA levels, regardless of participants’ baseline BMI or SUA levels, and appeared to be so primarily via weight reduction. These findings warrant further investigation into the possible role that tirzepatide/intentional weight loss may play in the treatment of patients with gout living with obesity
'Off-the-shelf' dual CAR-iNKT cell immunotherapy eradicates medullary and leptomeningeal KMT2A-rearranged leukemia
No full textCurrent therapies, including autologous CAR-T immunotherapy, fail to cure half of infants with KMT2A-rearranged acute lymphoblastic leukemia (KMT2Ar-ALL), a disease characterized by frequent central nervous system involvement, poor treatment response, early relapse and lineage switching. More effective treatment strategies, including the availability of ‘off-the-shelf’ immunotherapies is particularly relevant in infants. PROM1/CD133 is a direct target of KMT2A-fusion oncoproteins and is expressed on leukemic cells. Allogeneic iNKT cells, ‘innately’ more powerful effectors than T cells can be deployed ‘off-the-shelf’ without risk of acute graft-versus-host disease. Here, we equip iNKT with CD19- and/or CD133-targeting CARs and investigate their anti-leukaemia activity against KMT2Ar-ALL in relevant in vitro and in vivo models. Compared to monospecific counterparts and dual, bispecific CAR-T, bispecific CD19-CD133 CAR-iNKT have a more potent antileukemia activity, effectively targeting both CAR antigen-high and -low leukemia. Bi-specific CAR-iNKT eradicate medullary and, notably, leptomeningeal leukemia and induce sustained remissions without discernible hematologic toxicity. Mechanistically, the more potent anti-leukemia effect of CAR-iNKT over CAR-T cells is mediated by a pronounced CAR- and CAR antigen-dependent upregulation of the innate activating receptor NKG2D on CAR-iNKT and its engagement by its corresponding ligands on KMT2Ar-ALL cells. This ensures effective leukemia targeting even with downregulation of CD133 or CD19. Thus, by engaging with two different types of leukemia-associated antigens i.e., CAR antigens and NKG2D ligands, CAR-iNKT provide a powerful platform for the treatment of KMT2Ar-ALL. This approach can be readily adapted for other high-risk malignancies, including those with otherwise difficult to target leptomeningeal involvement
Advancing convection-permitting regional climate modelling for monsoon extremes in data-scarce, topographically complex regions of South Asia
No full textExtreme precipitation events are among the most damaging hydroclimatic hazards, particularly in monsoon-dominated, topographically complex, and data-scarce regions of South Asia. Despite advances in global and regional climate modeling, accurate simulations of such extreme events remain challenging due to the nonlinear interactions between deep convection, orography, and large-scale circulation. This study evaluates the performance of the Regional Climate Model RegCM5, developed by the Abdus Salam International Centre for Theoretical Physics (ICTP), and reproduces two severe monsoon-driven precipitation events: July 2010 and August 2022. High-resolution simulations were conducted using convection-permitting (3 km) non-hydrostatic cores (MOLOCH and MM5) and are compared with coarser hydrostatic (12 km, MM4) simulations employing parameterized convection. Model outputs were validated against ERA5 and ERA5-Land reanalysis, satellite-based GPM precipitation, the Gloh2 ensemble product, and in-situ observations. Results indicate that the 3 km MOLOCH configuration significantly improves the simulation of precipitation intensity, spatial distribution, and temporal variability relative to hydrostatic runs. Notably, RegCM5-MOLOCH effectively captures the 500 hPa geopotential height patterns associated with the extreme event of the 2010 Russian blocking ridge, underscoring its utility in resolving key synoptic drivers.
RegCM5-MOLOCH reproduces the large-scale moisture transport while capturing terrain-induced convergence along the Sulaiman mountain ranges of Balochistan. Diagnostics of Moisture Flux Convergence (MFC) and Integrated Vapor Transport (IVT) further reveal strong southwesterly moisture inflow from the Arabian Sea converging over Sindh and Balochistan during August 2022, consistent with the flood-affected areas. Furthermore, Spearman rank correlation analysis reveals robust linkages between simulated precipitation and sea surface temperature-related changes in La Niña and the Indian Ocean Dipole (IOD). This highlights the combined influence of large-scale ocean-atmosphere modes on monsoon extremes. Whilst, overall, convection-permitting simulations reduce biases, some persistent wet biases remain, likely due to the unresolved uncertainties in cloud microphysics, land–atmosphere coupling, and moisture transport. These findings enhance the application of high-resolution regional modeling for enhanced flood risk assessment, improved early warning systems, and more effective climate adaptation strategies in monsoon-affected regions
Hybrid-Regularized Magnitude Pruning for Robust Federated Learning under Covariate Shift
No full textFederated Learning offers a solution for decentralised model training, addressing the difficulties associated
with distributed data and privacy in machine learning. However,
the fact of data heterogeneity in federated learning frequently
hinders the global model’s generalisation, leading to low performance and adaptability to unseen data. This problem is
particularly critical for specialised applications such as medical imaging, where both the data and the number of clients
are limited. In this paper, we empirically demonstrate that
inconsistencies in client-side training distributions substantially
degrade the performance of federated learning models across
multiple benchmark datasets. We propose a novel FL framework
using a combination of pruning and regularisation of clients’
training to improve the sparsity, redundancy, and robustness
of neural connections, and thereby the resilience to model
aggregation. To address a relatively unexplored dimension of data
heterogeneity, we further introduce a novel benchmark dataset,
CelebA-Gender, specifically designed to control for within-class
distributional shifts across clients based on attribute variations,
thereby complementing the predominant focus on inter-class
imbalance in prior federated learning research. Comprehensive
experiments on many datasets like CIFAR-10, MNIST, and the
newly introduced CelebA-Gender dataset demonstrate that our
method consistently outperforms standard FL baselines, yielding
more robust and generalizable models in heterogeneous settings
Life without Clocks: experimental autoethnography for strange-ing time and queering futures, in and through Higher Education
No full textThis paper argues that to imagine futures otherwise we must surface, explore, and disrupt the naturalized ideas of time that shape our everyday academic practice. I present autoethnography as an experimental method and medium for strange-ing time and queering futures, in and through Higher Education (HE). Drawing on four autoethnographic stories—including a two-week experiment of living without clocks—I illustrate how dominant temporalities are materially, relationally, and affectively sustained, and how practicing time differently can catalyze a wider queering of futures. In dialogue with Barad’s concepts of intra-action and performativity, I argue that queering time and futures is not simply an intellectual exercise but must be a practice-based intervention in the socio-material conditions through which they are enacted. Reflecting on the situated tensions, frictions, and other relational entanglements that arise when stepping outside normative rhythms, I propose that dissonance becomes a compass to more plural possibilities. By thinking and writing from this dissonance and queering established methodologies by defamiliarizing the cadence and form of academic work itself, this paper offers a lived account of how unsettling time can expand our shared horizons of possible futures, and helps situate queer futurity directly in the complexities of HE life
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