Estranged relations: coercion and care in narratives of supported decision-making in mental healthcare

Supported decision-making has become popular among policymakers and mental health advocates as a means of reducing coercion in mental healthcare. Nevertheless, users of psychiatric services often seem equivocal about the value of supported decision-making initiatives. In this paper we explore why such initiatives might be rejected or ignored by the would-be beneficiaries, and we reflect on broader implications for care and coercion. We take a critical medical humanities approach, particularly through the lens of entanglement. We analyse the narratives of 29 people diagnosed with mental illness, and 29 self-identified carers speaking of their experiences of an Australian mental healthcare system and of their views of supported decision-making. As a scaffolding for our critique we consider two supported decision-making instruments in the 2014 Victorian Mental Health Act: the advance statement and the nominated person. These instruments presuppose that patients and carers endorse a particular set of relationships between the agentic self and illness, as well as between patient, carer and the healthcare system. Our participant narratives instead conveyed ‘entangled’ relations, which we explore in three sections. In the first we show how ideas about fault and illness often coexisted, which corresponded with shifting views on the need for more versus less agency for patients. In the second section, we illustrate how family carers struggled to embody the supported decision-making ideal of the independent yet altruistic nominated person, and in the final section we suggest that both care and coercion were narrated as existing across informal/formal care divisions. We conclude by reflecting on how these dynamic relations complicate supported decision-making projects, and prompt a rethink of how care and coercion unfold in contemporary mental healthcare

Susceptibility of boar spermatozoa to heat stress using in vivo and in vitro experimental models

Induction of heat stress as an experimental procedure in animals is commonly used to examine heat-related impacts on sperm quality. This study aimed to develop potential heat stress models that could be used at any time of the year, to advance the study of seasonal infertility in the pig under controlled conditions. Heat stress was induced by either housing boars (n = 6) at 30 °C inside a hot room for 42 days (55–65% humidity; LD 12:12 h; in vivo), or by heating boar semen (n = 7) for 30 min at various temperatures (35.5, 38.8, 40, 42, 46, 50, 54 and 60 °C; in vitro). Sperm motility was then characterized by computer-assisted sperm analysis (CASA; IVOS version 10: Hamilton Thorne, USA), and DNA integrity was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) and flow cytometry. Our in vivo hot room model induced biologically meaningful levels of DNA damage in boar spermatozoa (10.1 ± 1.9 hot room vs. 6.7 ± 1.7% control; P > 0.05), although not statistically significant from controls. Moreover, sperm concentration and motility parameters did not differ between treatments (P > 0.05). Compared to the 38.8 °C control, our in vitro heat shock model significantly increased sperm DNA damage after incubation at 54 and 60 °C (3.0 ± 1.0, 2.9 ± 1.0, 1.2 ± 0.3, 2.5 ± 0.7, 9.0 ± 3.7, 16.2 ± 7.1, 14.2 ± 5.8 and 41.8 ± 18.6% respectively; P ≤ 0.05). However, these temperatures rendered sperm completely immotile or dead, with most motility parameters declining rapidly to zero above 40 or 42 °C. In conclusion, our results suggest that temperature combined with individual factors may contribute to a boar’s overall susceptibility to heat stress. Refinement of these models particularly of the in vitro heat shock model could be further pursued to overcome environmental variability, reduce whole animal experiments and provide a putative diagnostic fertility screening tool to evaluate heat tolerance in the boar.A JCU Development Grant; College of Public Health, Medical and Veterinary Sciences PhD Research Funds and the Australia Awards Scholarship.http://link.springer.com/journal/11250hj2022Production Animal Studie

Tropical summer induces DNA fragmentation in boar spermatozoa: implications for evaluating seasonal infertility

Summer infertility continues to undermine pig productivity, costing the pig industry millions in annual losses. The boar’s inefficient capacity to sweat, non-pendulous scrotum and the extensive use of European breeds in tropical conditions, can make the boar particularly vulnerable to the effects of heat stress; however, the link between summer heat stress and boar sperm DNA damage has not yet been demonstrated. Semen from five Large White boars was collected and evaluated during the early dry, late dry and peak wet seasons to determine the effect of seasonal heat stress on the quality and DNA integrity of boar spermatozoa. DNA damage in spermatozoa during the peak wet was 16-fold greater than during the early dry and nearly 9-fold greater than during the late dry season. Sperm concentration was 1.6-fold lower in the peak wet than early dry whereas no difference was found across several motility parameters as determined by computer-assisted sperm analysis. These results demonstrate that tropical summer (peak wet season) induces DNA damage and reduces concentration without depressing motility in boar spermatozoa, suggesting that traditional methods of evaluating sperm motility may not detect inherently compromised spermatozoa. Boar management strategies (such as antioxidant supplementation) need to be developed to specifically mitigate this problem

International variation in ethics committee requirements: comparisons across five Westernised nations

BACKGROUND: Ethics committees typically apply the common principles of autonomy, nonmaleficence, beneficence and justice to research proposals but with variable weighting and interpretation. This paper reports a comparison of ethical requirements in an international cross-cultural study and discusses their implications. DISCUSSION: The study was run concurrently in New Zealand, UK, Israel, Canada and USA and involved testing hypotheses about believability of testimonies regarding alleged child sexual abuse. Ethics committee requirements to conduct this study ranged from nil in Israel to considerable amendments designed to minimise participant harm in New Zealand. Assessment of minimal risk is a complex and unreliable estimation further compounded by insufficient information on probabilities of particular individuals suffering harm. Estimating potential benefits/ risks ratio and protecting participants' autonomy similarly are not straightforward exercises. SUMMARY: Safeguarding moral/humane principles should be balanced with promotion of ethical research which does not impede research posing minimal risk to participants. In ensuring that ethical standards are met and research has scientific merit, ethics committees have obligations to participants (to meet their rights and protect them from harm); to society (to ensure good quality research is conducted); and to researchers (to treat their proposals with just consideration and respect). To facilitate meeting all these obligations, the preferable focus should be promotion of ethical research, rather than the prevention of unethical research, which inevitably results in the impediment of researchers from doing their work. How the ethical principles should be applied and balanced requires further consideration

Syntactic comprehension deficits across the FTD-ALS continuum

To establish the frequency, severity, relationship to bulbar symptoms, and neural correlates of syntactic comprehension deficits across the frontotemporal dementia–amyotrophic lateral sclerosis (FTD-ALS) disease spectrum. In total, 85 participants were included in the study; 20 amyotrophic lateral sclerosis (ALS), 15 FTD-ALS, 27 progressive nonfluent aphasia (PNFA), and 23 controls. Syntactic comprehension was evaluated in ALS, FTD-ALS, PNFA, and controls using the Test for Reception of Grammar. Voxel-based morphometry examined neuroanatomical correlates of performance. Syntactic comprehension deficits were detected in 25% of ALS (p = 0.011), 92.9% of FTD-ALS (p < 0.001), and 81.5% of PNFA (p < 0.001) patients. FTD-ALS was disproportionately impaired compared to PNFA. Impaired Test for Reception of Grammar performance was frequent in ALS with early bulbar involvement but did not correlate with bulbar impairment overall. Left peri-insular atrophy correlated with syntactic comprehension deficits. Syntactic comprehension deficits are frequent in FTD-ALS, more severe than in PNFA, and related to left peri-insular atrophy. A significant minority of ALS patients are impaired, but the relationship between bulbar symptoms and syntactic impairment is not understood

Human BRCA1-BARD1 ubiquitin ligase activity counters chromatin barriers to DNA resection

The opposing activities of 53BP1 and BRCA1 influence pathway choice of DNA double-strand break repair. How BRCA1 counters the inhibitory effect of 53BP1 on DNA resection and homologous recombination is unknown. Here we identify the site of BRCA1-BARD1 required for priming ubiquitin transfer from E2~ubiquitin. We demonstrate that BRCA1-BARD1’s ubiquitin ligase activity is required for repositioning 53BP1 on damaged chromatin. We confirm H2A ubiquitylation by BRCA1-BARD1 and show that an H2A-ubiquitin fusion protein promotes DNA resection and repair in BARD1 deficient cells. We show BRCA1-BARD1 function in homologous recombination requires the chromatin remodeler SMARCAD1. SMARCAD1 binding to H2A-ubiquitin, optimal localization to sites of damage and activity in DNA repair requires its ubiquitin-binding CUE domains. SMARCAD1 is required for 53BP1 repositioning and the need for SMARCAD1 in Olaparib or camptothecin resistance is alleviated by 53BP1 loss. Thus BRCA1- BARD1 ligase activity and subsequent SMARCAD1-dependent chromatin remodeling are critical regulators of DNA repair

2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

Correction to: 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales. Archives of Virology (2021) 166:3567–3579. https://doi.org/10.1007/s00705-021-05266-wIn March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.This work was supported in part through Laulima Government Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC under Contract No. HHSN272201800013C. This work was also supported in part with federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH), under Contract No. 75N91019D00024, Task Order No. 75N91019F00130 to I.C., who was supported by the Clinical Monitoring Research Program Directorate, Frederick National Lab for Cancer Research. This work was also funded in part by Contract No. HSHQDC-15-C-00064 awarded by DHS S&T for the management and operation of The National Biodefense Analysis and Countermeasures Center, a federally funded research and development center operated by the Battelle National Biodefense Institute (V.W.); and NIH contract HHSN272201000040I/HHSN27200004/D04 and grant R24AI120942 (N.V., R.B.T.). S.S. acknowledges partial support from the Special Research Initiative of Mississippi Agricultural and Forestry Experiment Station (MAFES), Mississippi State University, and the National Institute of Food and Agriculture, US Department of Agriculture, Hatch Project 1021494. Part of this work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001030), the UK Medical Research Council (FC001030), and the Wellcome Trust (FC001030).S

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV