Implementation of welfare maximizing networks

We consider network formation. A set of locations can be connected in various network configurations. Every network has a cost and every agent has an individual value of every network. A planner aims at implementing a welfare maximizing network and allocating the resulting cost, but information is asymmetric: agents are fully informed and the planner is ignorant. Full implementation in Nash and strong Nash equilibria is studied. We show the correspondence consisting of welfare maximizing networks and individually rational cost allocations is implementable. We construct a minimal Nash implementable, welfare maximizing, and individually rational solution in the set of upper hemi-continuous and Nash implementable solutions. It is not possible to have full implementation single valued solutions such as the Shapley value

Translation and cultural adaptation of the Chinese version of the International ‘Care Of the Dying Evaluation’ (CODE™) tool for assessing the quality of care for dying patients from the perspective of bereaved family members

Background Culturally appropriate assessments are needed to improve care during the last days of life. One way of assessment is to use a tool with bereaved family members after death. The aim of this study was to translate and cross-culturally adapt the International ‘Care Of the Dying Evaluation’ questionnaire (i-CODE) into Mandarin Chinese. Methods Translation and cultural adaptation process was performed according to the Brislin Classical Backtranslation Model and the principles of the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life group translation procedure. Fifteen bereaved family members, 5 palliative care experts and 4 translators were involved in the process, which followed 10 steps: a) Preparation; b) Forward translation; c) Reconciliation; d) Backward translation; e) Reconciliation; f) Backward translation review; g) Expert consultation; h) Cognitive interview; i) Cognitive interview review; h) Final proofreading. Results The translation and cultural adaptation followed established guidelines. items 1 (“washing”), 2 (“giving medicines”), 14 (“noisy rattle”), 18 (“giving fluids through a ‘drip’”) emerged divergence and reached a consensus among the research team, translators, and original author. In the cultural adaptation, demographic items were restructured to align with Chinese context. Gender-neutral terminology was employed by using “they/them”. Inconsistent subject, terminology “healthcare team” and Items 4 (“had adequate privacy”), 14 (“noisy rattle”), 27 (“in the right place”), and 28 (“at the actual time of his/her death”) was modified based on experts’ assessments and bereaved families’ comments. Linguistic, cultural, and conceptual equivalence was achieved in the process of translation and cultural adaptation. Conclusion A questionnaire allowing for international comparisons related to quality of care for dying individuals has been developed in Mandarin Chinese. Key cultural adaptations were required to ensure that the Chinese version of the i-CODE was suitable for use. It has proved content and face validity. Future work will focus on psychometric testing assessing the validity and reliability of questionnaire and its use in assessing and improving care

Integrated histopathology, spatial and single cell transcriptomics resolve cellular drivers of early and late alveolar damage in COVID-19

The most common cause of death due to COVID-19 remains respiratory failure. Yet, our understanding of the precise cellular and molecular changes underlying lung alveolar damage is limited. Here, we integrate single cell transcriptomic data of COVID-19 and donor lung tissue with spatial transcriptomic data stratifying histopathological stages of diffuse alveolar damage. We identify changes in cellular composition across progressive damage, including waves of molecularly distinct macrophages and depletion of epithelial and endothelial populations. Predicted markers of pathological states identify immunoregulatory signatures, including IFN-alpha and metallothionein signatures in early damage, and fibrosis-related collagens in late damage. Furthermore, we predict a fibrinolytic shutdown via endothelial upregulation of SERPINE1/PAI-1. Cell-cell interaction analysis revealed macrophage-derived SPP1/osteopontin signalling as a key regulator during early steps of alveolar damage. These results provide a comprehensive, spatially resolved atlas of alveolar damage progression in COVID-19, highlighting the cellular mechanisms underlying pro-inflammatory and pro-fibrotic pathways in severe disease

Aggregation–diffusion in heterogeneous environments

Aggregation–diffusion equations are foundational tools for modelling biological aggregations. Their principal use is to link the collective movement mechanisms of organisms to their emergent space use patterns in a concrete mathematical way. However, most existing studies do not account for the effect of the underlying environment on organism movement. In reality, the environment is often a key determinant of emergent space use patterns, albeit in combination with collective aspects of motion. This work studies aggregation–diffusion equations in a heterogeneous environment in one spatial dimension. Under certain assumptions, it is possible to find exact analytic expressions for the steady-state solutions when diffusion is quadratic. Minimising the associated energy functional across these solutions provides a rapid way of determining the likely emergent space use pattern, which can be verified via numerical simulations. This energy-minimisation procedure is applied to a simple test case, where the environment consists of a single clump of attractive resources. Here, self-attraction and resource-attraction combine to shape the emergent aggregation. Two counter-intuitive findings emerge from these analytic results: (a) a non-monotonic dependence of clump width on the aggregation width, (b) a positive correlation between self-attraction strength and aggregation width when the resource attraction is strong. These are verified through numerical simulations. Overall, the study shows rigorously how environment and collective behaviour combine to shape organism space use, sometimes in counter-intuitive ways

Goal-Conditioned Model Simplification for 1-D and 2-D Deformable Object Manipulation

Motion planning for deformable object manipulation has been a challenge for a long time in robotics due to its high computational cost. In this work, we propose to mitigate this cost by limiting the number of picking points on a deformable object within the action space and simplifying the dynamics model. We do this first by identifying a minimal geometric model that closely approximates the original model at the goal state; specifically, we implement this general approach for 1-D linear deformable objects (e.g., ropes) using a piece-wise line-fitted model, and for 2-D surface deformable objects (e.g., cloth) using a mesh-simplified model. Then a small number of key particles are extracted as the pickable points in the action space which are sufficient to represent and reach the given goal. Additionally, a simplified dynamics model is constructed based on the simplified geometric model, containing much fewer particles and thus being much faster to simulate than the original dynamics model, albeit with some loss of precision. We further refine this model iteratively by adding more details from the actually achieved final state of the original model until a satisfactory trajectory is generated. Extensive simulation experiments are conducted on a set of representative tasks for ropes and cloth, which show a significant decrease in time cost while achieving similar or better trajectory costs. Finally, we establish a closed-loop system of perception, planning, and control with a real robot for cloth folding, which validates the effectiveness of our proposed method

Review Article: Surrogate Endpoints to Assess Treatment Efficacy in Disorders of Gut–Brain Interaction of Lower Gastrointestinal Tract

Background Surrogate endpoints such as laboratory parameters that are not direct measurements of, but predict, clinical benefit are approved by regulatory agencies for initial proof of efficacy. No surrogate endpoints are approved for disorders of gut–brain interaction. Aim To assess the correlation of scintigraphic colonic transit (CT) with response rates according to patient-reported symptom-based endpoints (composite/global symptoms, abdominal pain or stool frequency/consistency) in irritable bowel syndrome (IBS) or chronic idiopathic constipation (CIC). Methods We reviewed available data from, randomised controlled trials (RCTs) reporting effects on CT at 24 h and 48 h with drug versus placebo and extracted the difference in the proportions responding to drug or placebo, using rates from individual RCTs or from meta-analyses when more than one RCT existed for a drug. We analysed associations between differences (drug vs. placebo) in CT and in response rates using Spearman correlation. Additional analyses of CT at 24 h with composite/global symptom or pain endpoints were performed with exclusion of alosetron (the only drug slowing CT). Results CT at 24 h correlated significantly with composite/global symptom endpoints (Rs = −0.755, p = 0.021). CT correlated with stool frequency or consistency (at 24 h, Rs = 0.506, p = 0.074; at 48 h, Rs = 0.631, p = 0.026). CT at 24 h did not correlate with abdominal pain (Rs = −0.054, p = 0.843). With the exclusion of alosetron data, CT at 24 h was non-significantly correlated with the composite/global symptom endpoint (Rs = −0.667, p = 0.073), but not with abdominal pain (Rs = 0.377, p = 0.419). Conclusion Scintigraphic CT measurement fulfils the expectation of a surrogate endpoint for symptom-based outcomes, particularly in IBS-D or IBS-C and CIC

Elephants’ habitat use and behaviour when outside of Gonarezhou National Park

Elephant conservation in Africa occurs within and beyond gazetted protected areas. We collared and tracked 19 male and seven female savanna elephants (Loxodonta africana) in Gonarezhou National Park (GNP), Zimbabwe, between 2016 and 2022. We investigated the extent of elephant activity outside the park and the role that season and diel played in this. We further documented habitat use, including the use of human-dominated landscapes. Our results showed that male elephants were more likely to move outside the GNP than females, dispersing at greater distances than females. Male elephants moved as far as 60 km from Gonarezhou, while females typically did not disperse farther than 15 km. Most movement outside protected area boundaries were during the cool-dry season (April–July). Male and female elephants returned to the GNP during the hot-wet season (December to March). When outside the GNP, male elephants preferred forested land cover types, while females remained in shrublands. Collared elephants avoided areas adjacent to GNP where human population densities were high. Surface water may also play a role in elephant movement outside of Gonarezhou, but we did not have reliable data to validate this. Our results indicate some use of areas neighbouring GNP by elephants, particularly in Mozambique, but not widespread dispersal. Conservation implications: To achieve a stable elephant population growth rate in GNP, conservation planning in the region should consider immediate interventions for addressing barriers to the movement of elephants to Zinave and Banhine National Parks in Mozambique to avoid the risk of escalating fragmentation of the landscape. In addition, the communal area linking Gonarezhou to Kruger National Park should be prioritised for conservation efforts and pilot projects to test the functionality of the Sengwe corridor

Efficacy of gut–brain neuromodulators in irritable bowel syndrome: an updated systematic review and meta-analysis

Background Gut–brain neuromodulators might be efficacious for irritable bowel syndrome (IBS), but there has been no synthesis of evidence from randomised controlled trials (RCTs) of some drug classes, and whether they have pain-modifying properties in IBS is unclear. We updated a previous systematic review and meta-analysis of RCTs examining these questions. Methods We searched MEDLINE (from Jan 1, 1946, to Jan 1, 2025), Embase and Embase Classic (from Jan 1, 1947, to Jan 1, 2025), and the Cochrane Central Register of Controlled Trials (from database inception to Jan 1, 2025). Trials recruiting adults with IBS and that compared gut–brain neuromodulators versus placebo over at least 4 weeks of treatment were eligible. Dichotomous symptom data were pooled using a random effects model to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% CI. Findings The search strategy identified 3625 citations. 28 RCTs were eligible containing 2475 patients. Ten RCTs were identified since our previous meta-analysis, containing 1348 patients. The RR of global IBS symptoms not improving with gut–brain neuromodulators versus placebo in 22 RCTs (2222 patients) was 0·77 (95% CI 0·69–0·87). The best evidence in terms of persistence of global IBS symptoms was for tricyclic antidepressants (TCAs) in 11 trials (1144 patients; RR 0·70, 0·62–0·80). The RR of abdominal pain not improving with gut–brain neuromodulators versus placebo in 19 RCTs (1792 patients) was 0·72 (95% CI 0·62–0·83). The best evidence was for TCAs in seven trials (708 patients; RR 0·69, 0·54–0·87), but there was also a benefit of selective serotonin reuptake inhibitors in seven RCTs (324 patients; RR 0·74, 0·56–0·99), and serotonin and norepinephrine reuptake inhibitors in two trials (94 patients; RR 0·22, 0·08–0·59). Adverse events were not significantly more common with gut–brain neuromodulators, although rates of withdrawal due to adverse events were significantly higher. The certainty in the evidence for tricyclic antidepressants for global IBS symptoms was moderate, but it was low to very low for all other endpoints and drug classes studied. Interpretation Some gut–brain neuromodulators are efficacious in reducing global symptoms and abdominal pain in IBS. The findings support guidelines that recommend use of tricyclic antidepressants for ongoing global symptoms or abdominal pain but also highlight a potential for SSRIs to be modestly effective for abdominal pain. More data for SNRIs, azapirones, and tetracyclic antidepressants in IBS are required. Funding None

Examining the roles of body composition, energy expenditure and substrate metabolism in the control of daily energy intake in adolescents with obesity

Background The implication of body composition and energy metabolism in the control of human energy intake (EI) has been well described in adults, remaining however unexplored in adolescents with obesity. The aim of this study was to question the role of body composition, energy expenditure (EE) and substrate metabolism in the control of EI of adolescents with obesity. Methods Ad libitum 24-h EI, body composition (Dual X-ray absorptiometry), Resting Metabolic Rate (RMR, indirect calorimeter) where measured and Total EE obtained during a 36-h stay in metabolic chambers in 26 adolescents (14.1 ± 1.5 years; 14 girls) with severe obesity. Results The mean body weight and Body Mass index were 92.2 ± 17.2 kg and 33.98 ± 4.14 kg.m‾² respectively. 24-h EI was positively correlated with body weight (rho = 0.597, p = 0.014), Fat Free Mass (FFM) kg (rho = 0.576, p = 0.019), 24-h Total EE (TEE (rho =0.675, p < 0.001)), RMR (rho =0.632, p = 0.005), 24-h Carbohydrate (CHO) oxidation rates (rho = 0.716, p < 0.001), and urinary nitrogen excretion (rho =0.28, p < 0.001). According to the path analysis FFM (kg) but not Fat Mass (FM) (kg) was positively correlated with RMR, with direct effects of 0.87 (p < 0.001) and 0.027 (p = 0.74) respectively. The effect of FFM on 24-h EI was mediated by RMR (96% of the effect), while the effect of FM on 24-h EI was also mediated by RMR (67% of the effect). Conclusions The present study provides the first evidence regarding the role of RMR as a main tonic signal of appetite control mediating the effect of body composition and mainly FFM (over FM) on daily EI in adolescents with obesity. It also suggests for the first-time relationships between 24-h CHO and protein oxidation and daily EI in this population

Stuck in the middle: men experience countervailing reactions to discussions about misogyny and violence against women.

Across three pre-registered studies (total N = 1344), we sought to understand how men react to discussions about violence against women. Initially, we expected that highly identified men would react defensively. That is, exposure to anti-violence advocacy would lead highly identified men to engage in outgroup derogation (i.e., minimise the prevalence of violence against women, exaggerate women’s gender-based privilege), ingroup favouritism (i.e., subtype perpetrators of violence, support men’s rights activism); and reduce their willingness to engage in collection action to end violence against women. We further expected that these reactions would be explained by social identity threat over concerns that men were being unfairly derided and negatively stereotyped. However, the findings revealed a more complex pattern of responding. On the one hand, exposure to these discussions (versus a control message) elicited social identity threat which, in turn, predicted higher outgroup derogation and ingroup favouring responses (Studies 1-3) and lower action intentions (Studies 2 and 3). But exposure also elicited collective guilt (Studies 2 and 3) and perceived injustice regarding women’s disadvantage (Study 3), which predicted lower outgroup derogation and ingroup favouritism, and higher action intentions. These opposing reactions fully offset each other and were not moderated by ingroup identification. These findings uncover a paradox in the fight for gender parity by showing that, in the face of messages that highlight inequality, men exhibit countervailing motivations to both protect their group’s interests and better women’s treatment. We discuss the implications of these findings for involving men in gender equality effort