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The cruel optimism of suicide prevention:Thinking beyond the mental health model
Get PDFSuicide has long been constructed as an individual, pathological problem of the mind, requiring a combination of clinical care and interpersonal support to prevent it. The endurance of this individualising and pathologising approach serves to reflect and maintain the marginalisation of sociology in suicide studies. This article contributes to redressing this balance, via analysis of creative, qualitative workshops which formed part of a broader study exploring the politics of suicide. Informed by 33 participants’ contributions from six creative-response workshop groups, in dialogue with Lauren Berlant’s concept of ‘cruel optimism’, we propose a creative sociological (re)turn in suicide studies. Our analysis explores how the politics of UK suicide prevention constitutes a form of ‘cruel optimism’, obfuscating structural and sociological approaches to preventing suicide, and giving primacy to individual mental health-led interventions. We argue this provides a vital opportunity and urgent call for sociology to contribute more robustly to suicide research
Dignity and human rights—Survey findings on undergraduate nursing students' conceptualisation and operationalisation of dignity
No full textAim: The aim of the study was to explore how students conceptualise and operationalise dignity with confidence in practice through a human rights lens. Design: A quantitative study using an online survey questionnaire. Methods: Data were collected using an online survey with 33 questions in three parts: students' conceptualisation of dignity, understanding of human rights and human rights law; students' operationalisation of dignity using a case study designed for this purpose [a fictional character named John]; lastly, students' preferred approaches to dignity education. Results: Survey findings revealed students' ambiguity or lack of agreement around dignity being associated with human rights and person-centred care. There was a sense of students feeling disempowered or lacking confidence in responding to dignity breaches in care, whilst some participants felt equipped to challenge this by most usually referring to clinical staff such as mentors and charge nurses due to the hierarchy in nursing systems within clinical contexts. Conclusion: Informed by the findings from this survey, the research team has developed DigniSpace (2024), the first online interactive space for Dignity Education co-produced with students focusing on the concept of dignity (through a consideration of human rights) that has been designed to help students learn more about the concept and to confidently promote and advocate dignity in practice. This is the first such resource to empower students to interrogate the concept of Dignity using the human rights lens and become change agents to promote and advocate dignity in care as a fundamental human right in any practice context. Implications for Nursing: Findings and outputs from this research have used the context of nursing education as a critical opportunity by placing students at the heart of developing DigniSpace (2024) to support the sustainable development of a culture of confidence to provide person-centred care embedded with dignity. Patient or Public Contributions: Findings from this first phase of the study were presented to our project advisory group that included experts with lived experience and their family care partners, who then participated in the co-design workshops in the second phase of the study to develop DigniSpace—a key output from this project.</p
Characterisation of the Avascular Mesenchyme during Digit Outgrowth
No full textThe avascular mesenchyme at the tip of the developing digit contributes to digit outgrowth and patterning, however, it has been poorly characterised. Using newly developed fate mapping approaches, tissue manipulation and single-cell mRNA sequencing data, we explore the transcriptional nature and developmental potential of this tissue. We find that the avascular mesenchyme is essential to normal segmental patterning of the digit and has a distinct transcriptional identity. In addition, we uncover an unexpected relationship between the unspecified tissue of the avascular mesenchyme and the committed phalanx forming region, which controls patterning, but not outgrowth of the digit. This multifaceted approach provides insights into the mechanics and genetic pathways that regulate digit outgrowth and patterning.</p
Age-related impairment of intestinal inflammation resolution through an eicosanoid-immune-microbiota axis
No full textAging manifests a decline of immune function, induces microbiome dysbiosis, drives organ inflammation, and impedes the resolution of inflammation. However, the mechanisms underlying age-related intestinal inflammation remain poorly described. Here we find that the resolution of T cell-initiated intestinal inflammation is impaired with aging. This impairment is mediated by disrupting the immune-microbiota interplay, controlled by intestinal eicosanoid metabolism. Pharmacologically inhibiting eicosanoid biosynthesis, blocking the prostaglandin E receptor subtype 4 (EP4), or genetically ablating EP4 diminishes age-related impairment of intestinal inflammation resolution. Mechanistically, mononuclear phagocyte-intrinsic eicosanoid-EP4 signaling impedes the resolution of intestinal inflammation, through fostering gut microbial dysbiosis and, more importantly, interrupting segmented filamentous bacteria adhesion to the intestinal epithelium. Colonization with EP4-ablated mouse microbiota or segmented filamentous bacteria improves the resolution of intestinal inflammation. These findings reveal that eicosanoid-dependent immune-microbiota interactions impair inflammation resolution in the aged intestine, highlighting potential intervention strategies for improving age-related gut health
Mutations in RNU4ATAC are associated with chilblain-like lesions and enhanced type I interferon signalling
No full textMutations in the non-coding RNA gene RNU4ATAC are associated with growth restriction and complications related to antibody deficiency. Here, we report that innate immune dysfunction is a previously unrecognised feature of this disorder. In particular, painful chilblain-like lesions are common in RNU4ATAC patients and are linked to dysregulated type I interferon signalling
Cross-tokenizer distillation via approximate likelihood matching
No full textDistillation has shown remarkable success in transferring knowledge from a Large Language Model (LLM) teacher to a student LLM. However, current distillation methods predominantly require the same tokenizer between the teacher and the student, restricting their applicability to only a small subset of teacher-student pairs. In this work, we develop a cross-tokenizer distillation method to solve this crucial deficiency. Our method is the first to enable cross-tokenizer distillation without a next-token prediction loss as the main objective, instead purely maximizing the student predictions' similarity to the teacher's predictions (known as pure distillation), while also being robust to large mismatches between the teacher and the student tokenizer function and vocabulary. Empirically, our method enables substantially improved performance as tested on two use cases. First, we show that viewing tokenizer transfer as self-distillation enables unprecedently effective transfer across tokenizers. We transfer (subword-level) Llama and Gemma models to byte-level tokenization more effectively than prior methods transfer to a similar subword tokenizer under a comparable training budget. Transferring different base models to the same tokenizer also enables ensembling them (e.g., via averaging their predicted probabilities) which boosts performance. Second, we use our cross-tokenizer distillation method to distil a large maths-specialized LLM into a smaller model, achieving competitive maths problem-solving performance. Overall, our results make substantial strides toward better adaptability and enhanced interaction between different LLMs
TrAGEDy—trajectory alignment of gene expression dynamics
No full textMotivationSingle-cell transcriptomics sequencing is used to compare different biological processes. However, often, those processes are asymmetric which are difficult to integrate. Current approaches often rely on integrating samples from each condition before either cluster-based comparisons or analysis of an inferred shared trajectory.ResultsWe present Trajectory Alignment of Gene Expression Dynamics (TrAGEDy), which allows the alignment of independent trajectories to avoid the need for error–prone integration steps. Across simulated datasets, TrAGEDy returns the correct underlying alignment of the datasets, outperforming current tools which fail to capture the complexity of asymmetric alignments. When applied to real datasets, TrAGEDy captures more biologically relevant genes and processes, which other differential expression methods fail to detect when looking at the developments of T cells and the bloodstream forms of Trypanosoma brucei when affected by genetic knockouts.Availability and implementationTrAGEDy is freely available at https://github.com/No2Ross/TrAGEDy, and implemented in R
Transmission dynamics of the 2022 mpox epidemic in New York City
Get PDFThe 2022 global mpox epidemic was caused by transmission of MPXV clade IIb, lineage B.1 through sexual contact networks, with New York City (NYC) experiencing the first and largest outbreak in the United States. By performing phylogeographic analysis of MPXV genomes sampled from 757 individuals in NYC between April 2022 and April 2023, and 3,287 MPXV genomes sampled around the world, we identify over 200 introductions of MPXV into NYC with at least 84 leading to onward transmission. These infections primarily occurred among men who have sex with men, transgender women and nonbinary individuals. Through a comparative analysis with HIV in NYC, we find that both MPXV and HIV genomic cluster sizes are best fit by scale-free distributions, and that people in MPXV clusters are more likely to have previously received an HIV diagnosis and be a member of a recently growing HIV transmission cluster. We model MPXV transmission through sexual contact networks and show that highly connected individuals would be disproportionately infected at the start of an epidemic, which would likely result in the exhaustion of the most densely connected parts of the network, and, therefore, explain the rapid expansion and decline of the NYC outbreak. By coupling the genomic epidemiology of MPXV and HIV with epidemic modeling, we demonstrate that the transmission dynamics of MPXV in NYC can be understood by general principles of sexually transmitted pathogens
Plastic partnerships:How corporations are hedging against the UN Global Plastics Treaty
Get PDFThe global plastic crisis has intensified over the past decade, pressuring corporations to address their environmental impact. In response to a UN resolution to negotiate a treaty to end plastic pollution, corporate actors have reoriented their sustainability strategies. This forum article examines how companies across the petrochemical–plastics industry have adopted a “hedging strategy” to undermine stricter regulations, promoting industry-led multistakeholder partnerships (“plastic partnerships”) aimed at minimizing disruptions to their business practices. This strategy seeks to hedge against transformative change by offering limited political and material concessions that co-opt circular economy rhetoric. We assess the effectiveness of these strategies in the context of protracted UN negotiations and the influence of transnational corporations in shaping emerging forms of global plastic governance
Association between Steroid Responsive Meningitis-Arteritis and Gastrointestinal Signs in Dogs: A Case-Control study
Get PDFObjective: To evaluate whether gastrointestinal signs are more frequently observed in dogs with steroid-responsive meningitis-arteritis (SRMA) compared to a control population. We hypothesized that dogs with SRMA would have higher odds of exhibiting gastrointestinal signs than controls. Methods: In a single-center, retrospective case-control study, dogs diagnosed with SRMA between December 2018 and December 2023 were identified through the institutional database medical records of the Hospital for Small Animals, Royal (Dick) School of Veterinary Studies, University of Edinburgh. Data collected included signalment, cerebrospinal fluid analysis results, serum C-reactive protein levels, presenting clinical signs, and the presence of gastrointestinal signs before and during the initial phase of corticosteroid treatment. The control group consisted of age-matched dogs hospitalized during the same time period and for a similar duration that had not been referred for gastrointestinal signs and had full medical records available. Results: 50 dogs were included in each group. Gastrointestinal signs were more frequently reported in the SRMA group, with significantly increased odds of vomiting (adjusted OR [ORa] = 7.37; 95% CI, 1.99 to 27.32) and diarrhea (ORa = 6.47; 95% CI, 2.00 to 20.91). No significant difference in regurgitation was observed (ORa = 0.49; 95% CI, 0.04 to 5.58). Among SRMA cases, gastrointestinal signs were more likely to be present prior to corticosteroid medication (ORa = 5.76; 95% CI, 2.07 to 15.97). Conclusions: Gastrointestinal signs (specifically vomiting and diarrhea) were more common in dogs with SRMA compared to controls. Clinical Relevance: Further research is needed to investigate concurrent gastrointestinal inflammatory disease in dogs with SRMA.</p
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