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Non-HLA antibodies against heterogeneous targets on endothelial cells have been associated with allograft injuries. The endothelial cell crossmatch (ECXM) is used in the detection of non-HLA antibodies but remains non-discriminatory for specific antibody identification. The primary objective of this study was to delineate the specific non-HLA antibody signatures associated with ECXM positivity and to determine the correlation of ECXM status and non-HLA antibody signatures on allograft health. Serum specimens from 25 lung transplant recipients (LTRs) and 13 renal transplant recipients (RTRs) were collected as part of clinical evaluation, and testing for angiotensin II receptor type 1 (AT1R) and donor-specific MHC class I chain-related gene A (MICA) antibodies and ECXM was performed. Remnant sera were tested for non-HLA antibodies using the LABScreen™ Autoantibody (LSAUT) Group 1, 2, and 3 kits (One Lambda, Inc., Los Angeles, CA, USA). In both cohorts, the concordance of AT1R and MICA together or individually with ECXM+ status was poor (

Abstract Background OptiBreech Care is a care pathway for breech presentation at term, including where chosen, physiological breech birth attended by professionals with advanced training and/or proficiency. We aimed to assess the feasibility of implementing OptiBreech team care prior to proceeding with a planned pilot randomised controlled trial. Methods Our design was an observational implementation feasibility assessment across England and Wales, January 2021–June 2022. Our objectives were to determine whether Trusts could provide attendants with advanced training (implementation feasibility), who deliver protocol-consistent care (fidelity), within existing resources (costs), while maintaining low neonatal admission rates (safety) and adequate recruitment rates (trial feasibility). Participants included women > 37 weeks pregnant with a breech-presenting foetus, requesting support for a vaginal breech birth following standard counselling, and staff involved in the study. No randomisation occurred in this first stage of feasibility work. Results Thirteen National Health Service sites were recruited. A total of 82 women planned births in the study. Sites with a breech specialist midwife recruited at double the rate of sites without (0.90/month, 95% CI 0.64–1.16 vs 0.40, 95% CI 0.12–0.68). Referrals into the study came from midwives (46%), obstetricians (34%) and women themselves (20%). Vaginal births were attended by staff with OptiBreech training at 87.5% (35/40, 95% CI 0.732–0.958) and by staff who met additional proficiency criteria at 67.5% (27/40, 95% CI 0.509–0.814). Fidelity criteria were more consistently met by staff who also met proficiency criteria. There were four neonatal admissions (4.9%, 4/82), including one serious adverse outcome (1.2%, 1/82). Conclusions A prospective observational cohort of OptiBreech collaborative care, which could potentially support nested or cluster randomisation, appears feasible in sites willing to establish a dedicated clinic and strategically develop further proficient members of staff, with back-up plans for supporting rapidly progressing births. Randomisation procedures remain to be feasibility tested. It is funded by the NIHR (NIHR300582).

Background OptiBreech collaborative care is a multi-disciplinary care pathway for breech presentation at term. The OptiBreech Multiple Trial Cohort is designed to host multiple trials related to care for breech presentation. This design enables prospective data collection for a large cohort of women planning a vaginal breech birth (VBB), to assess rare safety outcomes, while answering questions requiring a smaller, randomised sample nested within this cohort. Methods OptiBreech database currently contains participants recruited from 10 January 2022, including 67 women randomised to either OptiBreech care or standard care, and 116 women who received OptiBreech care and were not randomised. Primary outcomes included vaginal birth rate, composite neonatal morbidity and mortality and composite maternal neonatal morbidity and mortality. Descriptive statistics for the entire cohort were analysed in SPSS Version 29. Sub-group analyses were identified through participant involvement and engagement work as important to support informed decision-making. Results Of 97 women who planned a VBB at any point, 44 (45.4%) achieved a vaginal birth, compared to 29/77 (37.7%) of women who did not plan a VBB. Admission rates to a neonatal unit were similar, 4/97 (4.1%) versus 3/77 (3.9%). In this cohort, there was no severe neonatal morbidity following planned VBB, compared to 3/77 (3.9%) among the cohort who did not plan a vaginal breech birth and 2/52 (3.7%) among women who planned a cephalic birth. Severe maternal morbidity following planned VBB was 7/89 (7.9%), compared to 9/76 (11.8%) for women who did not plan a VBB and 8/54 (14.8%) for women who planned a cephalic birth. Conclusions Planning a VBB with OptiBreech collaborative care has thus far been as safe as not planning a VBB. Detecting differences in rare outcomes will require thousands of births. Outcomes will continue to be monitored and reported here as the cohort grows.

Background Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date. Aims To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder. Method Euthymic individuals with bipolar disorder were recruited to a 6–8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198. Results Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6–8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication). Conclusions The recruitment and retention of euthymic individuals with bipolar disorder to a 6–8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.

This article argues that Robert Nozick's Anarchy, State, and Utopia has been widely misread as a crude defense of the inequalities of contemporary capitalist societies. Nozick's book was in fact a work of ideal theory that proposed an account of the emergence of the state as a new moral foundation for liberal thought and practice. Nozick believed a justification of the state derived from a hypothetical account of its emergence without violating anyone's rights was more plausible than the standard liberal claim that the legitimacy of the state followed from the hypothetical consent of the governed. An appreciation of the purpose and success of Nozick's account of the emergence of the state challenges established interpretations of his book as an inherently flawed, if at times ingenious, conservative political tract. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has led to disruptions in the provision of care at substance use disorder (SUD) treatment facilities. Stresses associated with the pandemic could also negatively impact treatment outcomes for clients. The aim of this study is to evaluate how SUD treatment facilities in Mississippi changed their operations following the start of the pandemic. The change in client success rates at the facilities is also assessed. Methods: An online survey was completed by 12 SUD treatment facilities in Mississippi between February and May 2021. Results: Generally, the facilities’ capacity to provide treatment to clientele was moderately affected by the pandemic. Facilities in the sample also adapted a variety of policies to limit the spread of COVID-19. Changes in the services provided by facilities was observed in the survey responses. For client success rates reported by the facilities, there was a decrease in the number of facilities stating that more than 80% of their clients completed treatment across the pre- and post-pandemic periods. However, the number of facilities with more than 80% of their clients successfully finishing treatment has increased in recent months. Conclusions: To continue serving their clientele during the pandemic, facilities enacted COVID-19-related policies and began offering new services such as telehealth. Although client success rates decreased at the beginning of the pandemic, they have returned to pre-pandemic levels in recent months. Our results indicate that SUD treatment facilities and clients have improved in terms of giving and receiving care as the pandemic has progressed.

Background Lockdown during the pandemic has had significant impacts on public mental health. Previous studies suggest an increase in self-harm and suicide in children and adolescents. There has been little research on the roles of stringent lockdown. Aims To investigate the mediating and predictive roles of lockdown policy stringency measures in self-harm and emergency psychiatric presentations. Method This was a retrospective cohort study. We analysed data of 2073 psychiatric emergency presentations of children and adolescents from 23 hospital catchment areas in ten countries, in March to April 2019 and 2020. Results Lockdown measure stringency mediated the reduction in psychiatric emergency presentations (incidence rate ratio of the natural indirect effect [IRRNIE] = 0.41, 95% CI [0.35, 0.48]) and self-harm presentations (IRRNIE = 0.49, 95% CI [0.39, 0.60]) in 2020 compared with 2019. Self-harm presentations among male and looked after children were likely to increase in parallel with lockdown stringency. Self-harm presentations precipitated by social isolation increased with stringency, whereas school pressure and rows with a friend became less likely precipitants. Children from more deprived neighbourhoods were less likely to present to emergency departments when lockdown became more stringent, Conclusions Lockdown may produce differential effects among children and adolescents who self-harm. Development in community or remote mental health services is crucial to offset potential barriers to access to emergency psychiatric care, especially for the most deprived youths. Governments should aim to reduce unnecessary fear of help-seeking and keep lockdown as short as possible. Underlying mediation mechanisms of stringent measures and potential psychosocial inequalities warrant further research.

Objectives: This study implemented a series of meetings in one rural community struggling with the opioid crisis. Set in the town of Ardmore, Oklahoma, these meetings presented local residents who dealt with the crisis as part of their jobs with four categories of programs aimed at preventing and treating opioid-related issues. The ultimate goal was for the participants to develop a consensus about where resources should be appropriated in the future, based off the needs of the area. Methods: Three community meetings were held over a six-week period, with an average of 40 attendees. Data was collected through surveys, study circles, and a participant voting exercise. Surveys were distributed at the beginning and end of the meetings to determine if participant views changed over the course of the study. Study circles broke participants into small groups and prompted them with questions regarding the crisis to encourage group discussion. The participant voting exercise allowed participants to note where they would like future resources to be directed. Findings: Listening to experts and holding group discussions led to changes in opinions for some participants. Most felt that the most pressing need was to provide accessible opioid treatment options in their community. Youth-based prevention efforts were also noted as being a program that the community should focus on. Conclusions: Local perceptions of the most appropriate strategies for combatting the rural opioid crisis can change with group discussions alongside others who are actively involved with this issue. Future research should actively involve affected communities in order to develop relevant and accepted action plans.

This perspective documents current thinking around climate actions in Canada by synthesizing scholarly proposals made by Sustainable Canada Dialogues (SCD), an informal network of scholars from all 10 provinces, and by reviewing responses from civil society representatives to the scholars’ proposals. Motivated by Canada’s recent history of repeatedly missing its emissions reduction targets and failing to produce a coherent plan to address climate change, SCD mobilized more than 60 scholars to identify possible pathways towards a low-carbon economy and sustainable society and invited civil society to comment on the proposed solutions. This perspective illustrates a range of Canadian ideas coming from many sectors of society and a wealth of existing inspiring initiatives. Solutions discussed include climate change governance, low-carbon transition, energy production, and consumption. This process of knowledge synthesis/creation is novel and important because it provides a working model for making connections across academic fields as well as between academia and civil society. The process produces a holistic set of insights and recommendations for climate change actions and a unique model of engagement. The different voices reported here enrich the scope of possible solutions, showing that Canada is brimming with ideas, possibilities, and the will to act.

The dysregulation of iron metabolism in Alzheimer's disease is not accounted for in the current framework of the amyloid cascade hypothesis. Accumulating evidence suggests that impaired iron homeostasis is an early event in Alzheimer's disease progression. Iron dyshomeostasis leads to a loss of function in several enzymes requiring iron as a cofactor, the formation of toxic oxidative species, and the elevated production of beta-amyloid proteins. Several common genetic polymorphisms that cause increased iron levels and dyshomeostasis have been associated with Alzheimer's disease but the pathoetiology is not well understood. A full picture is necessary to explain how heterogeneous circumstances lead to iron loading and amyloid deposition. There is evidence to support a causative interplay between the concerted loss of iron homeostasis and amyloid plaque formation. We hypothesize that iron misregulation and beta-amyloid plaque pathology are synergistic in the process of neurodegeneration and ultimately cause a downward cascade of events that spiral into the manifestation of Alzheimer's disease. In this review, we amalgamate recent findings of brain iron metabolism in healthy versus Alzheimer's disease brains and consider unique mechanisms of iron transport in different brain cells as well as how disturbances in iron regulation lead to disease etiology and propagate Alzheimer's pathology.

Over the past fifteen years in New Zealand, theology has come in from the tertiary educational cold in various ways. One of the results or reasons for this has been willingness on the part of the state to accredit and provide funding for theological education and research. This has taken place largely through a compliance system of accreditation and resource allocation. The result has been academic recognition and a precarious financial boon for theology and some theological institutions and their students. But little attention has been paid to the epistemological and pedagogical temptations of compliance. Drawing on the recent experience of the writer, this article seeks to identify a number of the subtle temptations posed by state sponsored theological education and research.

Interest in the potential of smart grid to transform the way societies generate, distribute, and use electricity has increased dramatically over the past decade. A smarter grid could contribute to both climate change mitigation and adaptation by increasing low-carbon electricity production and enhancing system reliability and resilience. However, climate goals are not necessarily essential for smart grid. Climate change is only one of many considerations motivating innovation in electricity systems, and depending on the path of grid modernization, a future smart grid might do little to reduce, or could even exacerbate, risks associated with climate change. This paper identifies tensions within a shared smart grid vision and illustrates how competing societal priorities are influencing electricity system innovation. Co-existing but divergent priorities among key actors’ are mapped across two critical dimensions: centralized versus decentralized energy systems and radical versus incremental change. Understanding these tensions provides insights on how climate change objectives can be integrated to shape smart grid development. Electricity system change is context-specific and path-dependent, so specific strategies linking smart grid and climate change need to be developed at local, regional, and national levels. And while incremental improvements may bring short term gains, a radical transformation is needed to realize climate objectives.

The effectiveness of a comprehensive intervention like Re-ED (Reeducation of Emotional Disturbed Children) requires a clear definition of the essential components of the model. This article describes an ongoing process to create a program assessment tool for Re-ED. Program fidelity requires being able to specify precisely what is meant by certain Re-ED principles. (GCP)

Disruption of iron homeostasis and increased glial response are known to occur in brains afflicted by Alzheimer’s disease (AD). While the APP/PS1 transgenic mouse model recapitulates the hallmark amyloid-beta plaque pathology of AD, it does so in a different neuronal mileu than humans. Understanding the iron characteristics and glial response of the APP/PS1 model is important when testing new treatment procedures and translating these results. Brain tissue from AD patients, APP/PS1 mice, and controls were stained for iron, H- and L-ferritin, microglia, astrocytes, Aβ40/42, and degenerating neurons. The histological data demonstrate differences in ferritin, iron distribution, gliosis, and Aβ plaque composition between APP/PS1 and AD tissue. Specifically, an association between focal iron deposition and Aβ plaques is found ubiquitously throughout the AD tissue and is not observed in the APP/PS1 mouse model. Ferritin, microglia, and astrocyte staining show differential response patterns to amyloid plaques in AD and the APP/PS1 tissue. Aβ 40 and 42 antibody and thioflavin staining demonstrate morphological differences in plaque composition. The histological data support the hypothesis that iron distribution, iron management, and glial response histologically differ between the APP/PS1 and AD brain. Acknowledging the caveat that there are distinct plaque, iron, and glial contrasts between the AD brain and the APP/PS1 mouse is crucial when utilizing this model.

Opioid misuse has been identified as a concern among the farming community. The aim of this study is to identify how opioid misuse is perceived in agricultural communities across the state of Mississippi. A series of focus groups were conducted with University Agricultural and Natural Resource Extension agents and agricultural producers in Mississippi between November 2020 and February 2021. Focus group transcripts were analyzed through thematic analysis. Both university Extension agents and agriculture producers believe that opioid misuse is more of a concern in the greater rural community, amongst younger individuals, as opposed to being a concern for producers themselves. Extension agents stated that the unique personalities of agricultural producers might prevent them from being upfront about any of their opioid misuse. Agricultural producers stated that alcohol misuse is more of a concern among their peers than opioid misuse and that opioid misuse is present in farm labor. Generally, the focus groups revealed that participants did not think that opioid misuse was an issue for agricultural producers in Mississippi. However, participants identified other groups in their communities as having issues with opioids. The private nature of agricultural producers could be a reason why opioid misuse is not perceived to be widespread in that group. Alcohol misuse was observed as an issue for agricultural producers in the producer focus groups. [ABSTRACT FROM AUTHOR]