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Donation after circulatory death; cholangiopathy in the machine age
No full textPURPOSE OF REVIEW: Published work evaluating machine perfusion of DCD (donation after circulatory death) liver grafts in situ and ex situ is rapidly evolving, with several landmark studies published in the last 6 months. The central question in DCD liver transplant remains; which strategies most effectively reduce cholangiopathy? This condition, which results in repeated hospital admissions, interventions, re-transplantation and death, is a major deterrent to DCD utilization. This review considers current evidence in the mitigation of transplant cholangiopathy by machine perfusion in DCD liver grafts.RECENT FINDINGS: Studies which directly address DCD cholangiopathy as a primary outcome are few in number, despite their critical importance. In systematic reviews, Normothermic Regional Perfusion and Hypothermic Machine Perfusion consistently and significantly reduce transplant cholangiopathy rates. By contrast, the efficacy of Normothermic Machine Perfusion performed at donor or recipient centres is less well described and cautious interpretation is required. The most recent development, namely hypothermic followed by normothermic perfusion, has only now appeared in the literature but appears to offer advantages compared to either technology alone.SUMMARY: To reduce DCD cholangiopathy, current data best support the use of donor centre NRP or recipient centre HMP. However, utilization is also improved when warm perfusion is involved.</p
Leaf venation network evolution across clades and scales
No full textLeaf venation architecture varies greatly among living and fossil plants. However, we still have a limited understanding of when, why and in which clades new architectures arose and how they impacted leaf functioning. Using data from 1,000 extant and extinct (fossil) plants, we reconstructed approximately 400 million years of venation evolution across clades and vein sizes. Overall, venation networks evolved from having fewer veins and less smooth loops to having more veins and smoother loops, but these changes only occurred in small and medium vein sizes. The diversity of architectural designs increased biphasically, first peaking in the Paleozoic, then decreasing during the Cretaceous, then increasing again in the Cenozoic, when recent angiosperm lineages initiated a second and ongoing phase of diversification. Vein evolution was not associated with temperature and CO2 fluctuations but was associated with insect diversification. Our results highlight the complexity of the evolutionary trajectory and potential drivers of venation network architecture
Islands of solidarity? Migration and activism in Malta
No full textHow does geography shape possibilities for migration-related activism and advocacy? In this article, we investigate this question through a case study of the Maltese Islands. Though located on the edge of the European Union, Malta has long considered itself at the centre of a ‘migration crisis’ in the Mediterranean. Maltese politicians have denounced what they perceive as a lack of solidarity from ‘EUrope’ and argued that they carry a disproportionate ‘migration burden’. In response, they have adopted systematic practices of maritime abandonment and non-assistance of migrant boats in distress. While Maltese activist and advocacy groups and organisations voice criticism of Malta’s non-engagement at sea, their work largely focuses on the treatment of migrants within the island-nation. Investigating this limited engagement with the Mediterranean border and search and rescue activities, we explore how actors in Malta navigate the politically contentious issue of migration. Through this empirical focus, and by bringing social movements and island studies scholarship into conversation, we show how Malta’s specific island geography, its socio-political environment, as well as dominant maritime imaginaries condition forms of advocacy and activism. We argue that Malta’s islandness and its geographic location within the central Mediterranean borderzone are, perhaps counterintuitively, key factors in constraining Maltese engagement with maritime rescue.</p
Autistic traits and psychosocial predictors of depressive symptoms
No full textHigher rates of depression and of depressed mood are associated with autistic traits, and both are associated with social interaction factors, such as social self-efficacy, social motivation and loneliness. This study examined whether these social factors explain the association between autistic traits and depression. 658 participants (527 women) completed an online survey with measures of autistic traits (AQ), social self-efficacy (Social Self-Efficacy Scale), social motivation (Social Striving Assessment Scale), loneliness (UCLA Loneliness Scale) and depressive symptoms (Beck Depression Inventory-II). A mediation analysis found the relationship between autistic traits and depressive symptoms was fully mediated by the other three factors (β[indirect] =.005, z = 2.63, p <.01; β[direct] =.05, z = 1.58, p >.05), forming a pathway from autistic traits, to social self-efficacy, to social motivation, to loneliness and finally to depressive symptoms. These results suggest that targeting social self-efficacy may break this pathway and disrupt this relationship. Interventions targeting supporting positive social interaction should be considered
Long-term costs associated with healthcare use of people with cancer in Scotland
No full textBACKGROUND: Evidence for the long-term costs of cancer is limited, particularly in the Scottish population. Our aim was to better understand the long-term healthcare use and associated costs of cancer in Scotland, and their relationship with cancer survival.METHODS: This was a retrospective study using routine healthcare data to measure inpatient, outpatient, community prescription use and their costs from a national health service perspective. Per-episode incidence costs were assigned using reference costs and charted over eight years during the period 2009 to 2018 by year and phase of care. Risk factors for survival and costs were analysed using Cox regression and generalised linear model regression.RESULTS: In total, 55,807 adults with cancer were followed over eight years after their diagnosis. Trajectories indicated a complex relationship with survival. Mean cumulative per-patient costs for all cancers were £29,460 at 2017/18 price levels (95% CI £29,199 to £29,720). Considerable variation was observed between cancer types with the highest costs in non-Hodgkin lymphoma at £47,672 (95%CI £45,500 to £49,843) and the lowest in malignant melanoma of skin at £19,217, (95%CI £18,251 to £20,184). Variables negatively associated with costs tended to be positively associated with hazard of death. Only screening was significantly associated with both lower costs (adjusted cost ratio 0.85, p < 0.001) and lower hazard of death (adjusted hazard ratio 0.30, p < 0.001).CONCLUSIONS: Substantial costs were observed in all cancer types studied, with the highest costs measured in the year following diagnosis. Screening was associated with both lower costs and better survival, supporting the focus on early detection.</p
Memcontrol:Mitigating memorization in medical diffusion models via automated parameter selection
No full textDiffusion models excel in generating images that closely resemble their training data but are also susceptible to data memorization, raising privacy, ethical, and legal concerns, particularly in sensitive domains such as medical imaging. We hypothesize that this memorization stems from the overparameterization of deep models and propose that regularizing model capacity during fine-tuning can mitigate this issue. Firstly, we empirically show that regulating the model capacity via Parameter-efficient fine-tuning (PEFT) mitigates memorization to some extent, however, it further requires the identification of the exact parameter subsets to be fine-tuned for high-quality generation. To identify these subsets, we introduce a bi-level optimization framework, MemControl, that automates parameter selection using memorization and generation quality metrics as rewards during fine-tuning. The parameter subsets discovered through MemControl achieve a superior tradeoff between generation quality and memorization. For the task of medical image generation, our approach outperforms existing state-of-the-art memorization mitigation strategies by fine-tuning as few as 0.019% of model parameters. Moreover, we demonstrate that the discovered parameter subsets are transferable to non-medical domains. Our framework is scalable to large datasets, agnostic to reward functions, and can be integrated with existing approaches for further memorization mitigation. To the best of our knowledge, this is the first study to empirically evaluate memorization in medical images and propose a targeted yet universal mitigation strategy. The code is available at https://github.com/Raman1121/Diffusion_Memorization_HPO
Unique Nash equilibrium of a nonlinear model of opinion dynamics on networks with friction-inspired stubbornness
No full textThe modeling of opinion dynamics has seen much study in varying academic disciplines. Understanding the complex ways information can be disseminated is a complicated problem for mathematicians as well as social scientists. We present a nonlinear model of opinion dynamics that utilizes an environmental averaging protocol similar to the DeGroot and Freidkin-Johnsen models. Indeed, the way opinions evolve is complex and nonlinear effects ought to be considered when modeling. For this model, the nonlinearity destroys the translation invariance of the equations, as well as the convexity of the associated payout functions. The standard theory for well-posedness and convergence no longer applies and we must utilize the Brouwer topological degree and nonconvex analysis in order to achieve these results. Numerical simulations of the model reveal that the nonlinearity behaves similarly to the well-known Friedkin-Johnsen for so-called ‘reasonable’ opinions, but better models the way agents that hold ‘extreme’ opinions are more stubborn than their reasonable counterparts.</p
The same but different:Teacher and student experiences of partnership
No full textNorwegian Higher Education institutions are increasingly adopting partnership and co-creation approaches, in common with other universities internationally. The Centres for Teaching Excellence (SFU) initiative supports Norwegian Higher Education in embedding these approaches in different disciplines. We explore common experiences shared by students and teachers involved in partnership work in the iEarth network (an SFU). Through reflexive thematic analysis of surveys and interviews we identify five shared themes: the value of relationship building; voice, agency, and power; the importance of positive past experiences for engaging in partnerships multiple understandings of partnership; and uncertainty. The ‘uncertainty’ theme, whilst appearing briefly in some previous studies, is particularly interesting in this study, as our data suggests students’ and teachers’ experience uncertainty in partnership differently. Teachers reported reduced uncertainty due to partnership, owing to enhanced relationships with students. Students found partnership increases uncertainty as it challenges their ideas about learning in higher education. We also found participants shared a practical, ‘down to earth’ approach to partnerships’ benefits and challenges, and suggest this is related to the context in which partnership was introduced. Additionally, this study suggests that staff and students who have no positive past experiences in partnership, may be a group who find partnership challenging and may need further support. With increasing emphasis on partnership in higher education, it is important to understand and explore shared partnership experiences to align participants’ goals and expectations and potentially unlock new benefits
Early-onset type 2 diabetes:the next major diabetes transition
No full textThe incidence of early-onset type 2 diabetes appears to be increasing, with a growing number of cases now occurring in children, adolescents, and young adults. This transition is primarily driven by the rising prevalence of obesity in younger populations, especially in high-income countries. However, the relationship between obesity and early-onset type 2 diabetes varies across ethnic groups, with some populations exhibiting a higher risk at lower BMI thresholds, likely due to differences in insulin resistance and beta-cell function. Socioeconomic factors further shape disease patterns, with early-onset type 2 diabetes disproportionately affecting lower-income populations in high-income settings, whereas in low- and middle-income countries, economic development and urbanisation have contributed to increasing incidence among more affluent groups. The consequences of this transition to early-onset type 2 diabetes are severe, with accelerated disease progression, heightened risks of microvascular and macrovascular complications, and significant societal and healthcare burdens. Given the continuing rise in childhood and adolescent obesity, the incidence of early-onset type 2 diabetes is expected to increase further, placing mounting pressure on healthcare systems worldwide. In this first of three review articles, we examine global trends in the incidence and prevalence of early-onset type 2 diabetes, identifying key drivers of this transition to diagnosis at younger ages and review the evidence for risk factors both at population and individual level
Genetics of monozygotic twins reveals the impact of environmental sensitivity on psychiatric and neurodevelopmental phenotypes
No full textIndividual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes, but these variants have proven challenging to detect. Genome-wide association studies of monozygotic twin differences are conducted through family-based variance analyses, which are more robust to the systemic biases that impact population-based methods. We combined data from 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct one of the largest genome-wide association study meta-analyses of monozygotic phenotypic differences, in children, adolescents and adults separately, for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism and wellbeing. The proportions of phenotypic variance explained by single-nucleotide polymorphisms in these phenotypes were estimated (h2 = 0–18%), but were imprecise. We identified 13 genome-wide significant associations (single-nucleotide polymorphisms, genes and gene sets), including genes related to stress reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. This is the largest genetic study of monozygotic twins to date by an order of magnitude, evidencing an alternative method to study the genetic architecture of environmental sensitivity. The statistical power was limited for some analyses, calling for better-powered future studies
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