"I Will Die by My Own Hand": Understanding the Development of Suicide Capability in the Narratives of Individuals Who Have Attempted Suicide.

Suicide capability is a multidimensional concept that facilitates the movement from suicidal ideation to suicide attempt. The three-step theory of suicide posits that three overarching contributors comprise suicide capability: acquired (fearlessness about death and high pain tolerance), dispositional (genetics), and practical (knowledge and access to lethal means) capability. Although extensive research has investigated relationships between individual contributors of capability and suicide attempts, little research has considered how an individual's capability for suicide develops as a combination of contributors. Given suicide is multifaceted and complex, our understanding of capability development is relatively limited. This potentially negatively impacts prevention and capacity reduction-focused intervention efficacy. Therefore, this study aimed to explore how suicide capability develops. Fourteen community-based suicide attempt survivors were recruited using convenience sampling. Individual narratives were collected using open-ended interviews, and data were analysed using narrative analysis. Results indicated that participant narratives contained two elements. The first included how capability development and suicide attempt facilitation were often underpinned by the relational interplay between acquired and practical contributors. For example, participants without a high pain tolerance seeking attempt methods that were perceived to be painless. The second element contained a novel finding relating to the agentic role of participants when deciding and attempting suicide. Agency was revealed within and across narratives emphasising the active role the individual plays in their movement from ideation-to-action. The role of individual agency in coming to a decision to take one's own life and then acting warrants further consideration within contemporary suicide theories.

A fully human anti-BMP6 antibody reduces the need for erythropoietin in rodent models of the anemia of chronic disease.

Recombinant erythropoietin (EPO) and iron substitution are a standard of care for treatment of anemias associated with chronic inflammation, including anemia of chronic kidney disease. A black box warning for EPO therapy and concerns about negative side effects related to high-dose iron supplementation as well as the significant proportion of patients becoming EPO resistant over time explains the medical need to define novel strategies to ameliorate anemia of chronic disease (ACD). As hepcidin is central to the iron-restrictive phenotype in ACD, therapeutic approaches targeting hepcidin were recently developed. We herein report the therapeutic effects of a fully human anti-BMP6 antibody (KY1070) either as monotherapy or in combination with Darbepoetin alfa on iron metabolism and anemia resolution in 2 different, well-established, and clinically relevant rodent models of ACD. In addition to counteracting hepcidin-driven iron limitation for erythropoiesis, we found that the combination of KY1070 and recombinant human EPO improved the erythroid response compared with either monotherapy in a qualitative and quantitative manner. Consequently, the combination of KY1070 and Darbepoetin alfa resulted in an EPO-sparing effect. Moreover, we found that suppression of hepcidin via KY1070 modulates ferroportin expression on erythroid precursor cells, thereby lowering potentially toxic-free intracellular iron levels and by accelerating erythroid output as reflected by increased maturation of erythrocyte progenitors. In summary, we conclude that treatment of ACD, as a highly complex disease, becomes more effective by a multifactorial therapeutic approach upon mobilization of endogenous iron deposits and stimulation of erythropoiesis.

Fluidity in capability: Longitudinal assessments of suicide capability using ecological momentary assessments.

INTRODUCTION: Suicide capability is posited to facilitate the movement from ideation-to-action. Emerging evidence suggests capability comprises both trait- and state-like facets. This study examined fluctuations in and associations of acquired, dispositional, practical, and perceived capabilities, and suicidal mental imagery, and suicidal ideation. METHOD: Seventy-five adults (48 females, Mage = 36.53 years) with lived experience of suicidal ideation and/or attempt responded to four prompts per day for 2 weeks that assessed suicide capability and suicidal ideation. Mean-squared successive differences and probability of acute change indices and multilevel models were used for analyses. RESULTS: All facets of suicide capability fluctuated. Acquired and dispositional capabilities were trait-like, with practical and perceived capabilities being state-like. Suicidal mental imagery was the only facet of suicide capability that distinguished participants with a suicide attempt in the past 12 months from participants with a suicide attempt more than 1 year ago and suicide ideators. Suicidal mental imagery was associated with concurrent suicidal ideation and predictive of next assessment suicidal ideation. CONCLUSION: Suicidal mental imagery may be uniquely associated with suicide capability. This study suggests there are trait- and state-like facets of capability that can combine to potentially ready an individual to engage in suicidal behaviors.

A human anti-matriptase-2 antibody limits iron overload, α-globin aggregates, and splenomegaly in ß-thalassemic mice.

ABSTRACT: Iron plays a major role in the deterioration of ß-thalassemia. Indeed, the high levels of transferrin saturation and iron delivered to erythroid progenitors are associated with production of α-globin precipitates that negatively affect erythropoiesis. Matriptase-2/TMPRSS6, a membrane-bound serine protease expressed in hepatocytes, negatively modulates hepcidin production and thus is a key target to prevent iron overload in ß-thalassemia. To address safety concerns raised by the suppression of Tmprss6 by antisense oligonucleotides or small interfering RNA, we tested a fully human anti-matriptase-2 antibody, RLYB331, which blocks the protease activity of matriptase-2. When administered weekly to Hbbth3/+ mice, RLYB331 induced hepcidin expression, reduced iron loading, prevented the formation of toxic α-chain/heme aggregates, reduced ros oxygen species formation, and improved reticulocytosis and splenomegaly. To increase the effectiveness of RLYB331 in ß-thalassemia treatment even further, we administered RLYB331 in combination with RAP-536L, a ligand-trapping protein that contains the extracellular domain of activin receptor type IIB and alleviates anemia by promoting differentiation of late-stage erythroid precursors. RAP-536L alone did not prevent iron overload but significantly reduced apoptosis in the erythroid populations of the bone marrow, normalized red blood cell counts, and improved hemoglobin and hematocrit levels. Interestingly, the association of RLYB331 with RAP-536L entirely reversed the ß-thalassemia phenotype in Hbbth3/+ mice and simultaneously corrected iron overload, ineffective erythropoiesis, splenomegaly, and hematological parameters, suggesting that a multifunctional molecule consisting of the fusion of RLYB331 with luspatercept (human version of RAP-536L) would allow administration of a single medication addressing simultaneously the different pathophysiological aspects of ß-thalassemia.

Online suicidal thoughts and/or behaviours talk: A scoping review protocol.

The anonymity that the internet and social media affords users means that suicidal thoughts and/or behaviours can be talked about with a sense of freedom and disinhibition that is often not possible in face-to-face contexts. Better understanding online suicidal thoughts and/or behaviour talk is critical as more people turn to online spaces for support. Without this the potentiality of such spaces as sites for suicide prevention and intervention is likely to remain unrealised. Currently there are no scoping or systematic review syntheses focusing on internet and/or on social media suicidal thoughts and/or behaviour talk. This lack of synthesis is problematic as it makes it more difficult for online suicide prevention and intervention practices, policies, and our understanding of suicide to advance in a coherent and evidence-based manner. A scoping review protocol following Arksey and O'Malley's six-step modified framework has been developed to address this synthesis gap. It aims to systematically map the empirical literature that has investigated online suicidal thoughts and/or behaviours talk. It is anticipated that review outcomes could inform the training of health practitioners and peer/professional online moderators in how to best talk with people experiencing suicidal thoughts and/or behaviours. Outcomes could also form an evidence-base for developing policies and practices that focus on online places as safe spaces to talk about suicidal thoughts and/or behaviours. Developers of safe language guidelines could also use the outcomes to audit how well current guidelines reflect empirical evidence. Outcomes could enable researchers to design future online suicidal thoughts and/behaviours talk studies that extend our understandings of suicide leading to potential refinements of contemporary suicide theories/models.

Suicide capability within the ideation-to-action framework: A systematic scoping review.

Suicide capability is theorised to facilitate the movement from suicidal ideation to suicide attempt. Three types of contributors are posited to comprise suicide capability: acquired, dispositional, and practical. Despite suicide capability being critical in the movement from ideation-to-attempt, there has been no systematic synthesis of empirical evidence relating to suicide capability that would enable further development and refinement of the concept. This study sought to address this synthesis gap. A scoping review was conducted on suicide capability studies published January 2005 to January 2022. Eleven electronic databases and grey literature sources were searched returning 5,212 potential studies. After exclusion criteria application, 90 studies were included for final analysis. Results synthesis followed a textual narrative approach allocating studies based on contributors of suicide capability. Most studies focused on investigating only one factor within contributors. Painful and provocative events appear to contribute to acquired capability more so than fearlessness about death. Whilst emerging evidence for dispositional and practical contributors is promising, the small number of studies prevents further conclusions from being drawn. An unexpected additional cognitive contributor was identified. The focus of a single factor from most studies and the limited number of studies on contributors other than acquired capability limits the theoretical development and practical application of suicide capability knowledge. Given that suicide is a complex and multifaceted behaviour, future research that incorporates a combination of contributors is more likely to advance our understandings of suicide capability.

Educating the educators: Implementing cultural safety in the nursing and midwifery curriculum.

BACKGROUND: The Australian Nursing and Midwifery Accreditation Council mandates the teaching of cultural safety in Bachelor of Nursing and Midwifery programs in Australia. However nursing and midwifery academics may lack the awareness and knowledge required to share and develop cultural safety practices with their students. Specific cultural safety professional development for academics may be needed. OBJECTIVES: This research explores how nursing and midwifery academics at an Australian university understand cultural safety and whether they are equipped to embed it in the curriculum. It also examines whether professional development workshops can support academics to prepare for cultural safety. METHODS: An intervention involving three cultural safety professional development workshops was offered to nursing academics at an Australian university. The authors used qualitative surveys to consider whether the workshops deepened participants' understanding of cultural safety and developed the self-reflection required to embed cultural safety in teaching. RESULTS: The workshops contributed to participants' improved understandings of culture, colonisation, white privilege and the need for self-reflection, but not all participants developed a working knowledge of cultural safety practice. CONCLUSION: Professional development workshops can assist nursing and midwifery academics to develop their knowledge of cultural safety, but detailed, contextual understanding is likely to need more than three sessions. Academics' motivations to include cultural safety in their teaching may be linked to their desire for patient-driven and equitable services and a desire to meet accreditation requirements.

Suicide capacity within the ideation-to-action framework: a scoping review protocol.

INTRODUCTION: A core facilitator of the transition from suicidal thoughts to suicide attempt is the individual's capacity for suicide. Suicide capacity is a theoretically universal concept adaptable for specific groups that is hypothesised to comprise three contributing factors: acquired capability, for example, previous self-harm; dispositional, such as genetic influences and practical, knowledge of and access to lethal means. Given that suicide capacity as a concept is continuing to develop, a review and synthesis of the current literature is timely to ensure future research and development of suicide prevention strategies are based on evidential knowledge. The aim of this review is to map the available evidence to provide an overview of factors that contribute to an adult's capacity for suicide. METHODS AND ANALYSIS: This review will encompass five stages. Studies will be identified through broad search strings applied to 11 academic databases: Academic Search Ultimate, APA PsycArticles, APA PsycINFO, CINAHL, Psychology & Behavioural Sciences, & Sociology Source Ultimate via EBSCOHost Megafile Ultimate; PubMed; Science Direct; Wiley Online; Taylor & Francis and ProQuest dissertations and theses. Grey literature databases and key suicide organisations will also be searched for relevant literature. Two reviewers will independently screen titles and abstracts then review full texts to identify articles meeting inclusion criteria. Articles will be assessed for eligibility based on suicide attempt history, primary research study design, language and publication date. Data from eligible full texts will be extracted using a predesigned template for analysis. The synthesisation method will be textual narrative synthesis with an incorporated quality appraisal checklist tool. ETHICS AND DISSEMINATION: Ethics approval is not required for this scoping review as no human participants are involved. Study findings will be shared with key suicide organisations, through peer-reviewed publications, and conference presentations.

Complete humanization of the mouse immunoglobulin loci enables efficient therapeutic antibody discovery.

If immunized with an antigen of interest, transgenic mice with large portions of unrearranged human immunoglobulin loci can produce fully human antigen-specific antibodies; several such antibodies are in clinical use. However, technical limitations inherent to conventional transgenic technology and sequence divergence between the human and mouse immunoglobulin constant regions limit the utility of these mice. Here, using repetitive cycles of genome engineering in embryonic stem cells, we have inserted the entire human immunoglobulin variable-gene repertoire (2.7 Mb) into the mouse genome, leaving the mouse constant regions intact. These transgenic mice are viable and fertile, with an immune system resembling that of wild-type mice. Antigen immunization results in production of high-affinity antibodies with long human-like complementarity-determining region 3 (CDR3H), broad epitope coverage and strong signatures of somatic hypermutation. These mice provide a robust system for the discovery of therapeutic human monoclonal antibodies; as a surrogate readout of the human antibody response, they may also aid vaccine design efforts.