Development and evaluation of a de-escalation training intervention in adult acute and forensic units: the EDITION systematic review and feasibility trial.

Background: Containment (e.g. physical restraint and seclusion) is used frequently in mental health inpatient settings. Containment is associated with serious psychological and physical harms. De-escalation (psychosocial techniques to manage distress without containment) is recommended to manage aggression and other unsafe behaviours, for example self-harm. All National Health Service staff are trained in de-escalation but there is little to no evidence supporting training's effectiveness. Objectives: Objectives were to: (1) qualitatively investigate de-escalation and identify barriers and facilitators to use across the range of adult acute and forensic mental health inpatient settings; (2) co-produce with relevant stakeholders an intervention to enhance de-escalation across these settings; (3) evaluate the intervention's preliminary effect on rates of conflict (e.g. violence, self-harm) and containment (e.g. seclusion and physical restraint) and understand barriers and facilitators to intervention effects. Design: Intervention development informed by Experience-based Co-design and uncontrolled pre and post feasibility evaluation. Systematic reviews and qualitative interviews investigated contextual variation in use and effects of de-escalation. Synthesis of this evidence informed co-design of an intervention to enhance de-escalation. An uncontrolled feasibility trial of the intervention followed. Clinical outcome data were collected over 24 weeks including an 8-week pre-intervention phase, an 8-week embedding and an 8-week post-intervention phase. Setting: Ten inpatient wards (including acute, psychiatric intensive care, low, medium and high secure forensic) in two United Kingdom mental health trusts. Participants: In-patients, clinical staff, managers, carers/relatives and training staff in the target settings. Interventions: Enhancing de-escalation techniques in adult acute and forensic units: Development and evaluation of an evidence-based training intervention (EDITION) interventions included de-escalation training, two novel models of reflective practice, post-incident debriefing and feedback on clinical practice, collaborative prescribing and ward rounds, practice changes around admission, shift handovers and the social and physical environment, and sensory modulation and support planning to reduce patient distress. Main outcome measures: Outcomes measured related to feasibility (recruitment and retention, completion of outcome measures), training outcomes and clinical and safety outcomes. Conflict and containment rates were measured via the Patient-Staff Conflict Checklist. Clinical outcomes were measured using the Attitudes to Containment Measures Questionnaire, Attitudes to Personality Disorder Questionnaire, Violence Prevention Climate Scale, Capabilities, Opportunities, and Motivation Scale, Coercion Experience Scale and Perceived Expressed Emotion in Staff Scale. Results: Completion rates of the proposed primary outcome were very good at 68% overall (excluding remote data collection), which increased to 76% (excluding remote data collection) in the post-intervention period. Secondary outcomes had high completion rates for both staff and patient respondents. Regression analyses indicated that reductions in conflict and containment were both predicted by study phase (pre, embedding, post intervention). There were no adverse events or serious adverse events related to the intervention. Conclusions: Intervention and data-collection procedures were feasible, and there was a signal of an effect on the proposed primary outcome. Limitations: Uncontrolled design and self-selecting sample. Future work: Definitive trial determining intervention effects. Trial registration: This trial is registered as ISRCTN12826685 (closed to recruitment). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/101/02) and is published in full in Health Technology Assessment; Vol. 28, No. 3. See the NIHR Funding and Awards website for further award information. Context: Conflict (a term used to describe a range of potentially unsafe events including violence, self-harm, rule-breaking, medication refusal, illicit drug and alcohol use and absconding) in mental health settings causes serious physical and psychological harm. Containment interventions which are intended to minimise harm from violence (and other conflict behaviours) such as restraint, seclusion and rapid tranquilisation can result in serious injuries to patients and, occasionally, death. Involvement in physical restraint is the most common cause of serious physical injury to National Health Service mental health staff in the United Kingdom. Violence to staff results in substantial costs to the health service in sickness and litigation payments. Containment interventions are also expensive (e.g. physical restraint costs mental health services £6.1 million and enhanced observations £88 million per annum). Despite these harms, recent findings indicate containment interventions such as seclusion and physical restraint continue to be used frequently in mental health settings. Clinical trials have demonstrated that interventions can reduce containment without increasing violence and other conflict behaviours (e.g. verbal aggression, self-harm). Substantial cost-savings result from reducing containment use. De-escalation, as an intervention to manage aggression and potential violence without restrictive practices, is a core intervention. 'De-escalation' is a collective term for a range of psychosocial techniques designed to reduce distress and anger without the need to use 'containment' interventions (measures to prevent harm through restricting a person's ability to act independently, such as physical restraint and seclusion). Evidence indicates that de-escalation involves ensuring conditions for safe intervention and effective communication are established, clarifying and attempting to resolve the patient's concern, conveyance of respect and empathy and regulating unhelpful emotions such as anxiety and anger. Despite featuring prominently in clinical guidelines and training policy domestically and internationally and being a component of mandatory National Health Service training, there is no evidence-based model on which to base training. A systematic review of de-escalation training effectiveness and acceptability conducted in 2015 concluded: (1) no model of training has demonstrated effectiveness in a sufficiently rigorous evaluation, (2) the theoretical underpinning of evaluated models was often unclear and (3) there has been inadequate investigation of the characteristics of training likely to enhance acceptability and uptake. Despite all National Health Service staff being trained in de-escalation there have been no high-quality trials evaluating the effectiveness and cost-effectiveness of training. Feasibility studies are needed to establish whether it is possible to conduct a definitive trial that can determine the clinical, safety and cost-effectiveness of this intervention.

Mental health hospitals are stressful places for patients and staff. Patients are often detained against their will, in places that are noisy, unfamiliar and frightening. Violence and self-injury happen quite frequently. Sometimes staff physically restrain patients or isolate patients in locked rooms (called seclusion). While these measures might sometimes be necessary to maintain safety, they are psychologically and physically harmful. To help reduce the use of these unsafe measures, staff are trained in communication skills designed to reduce anger and distress without using physical force. Professionals call these skills 'de-escalation'. Although training in de-escalation is mandatory, there is no good evidence to say whether it works or not, or what specific techniques staff should be trained in. The Enhancing de-escalation techniques in adult acute and forensic units: Development and evaluation of an evidence-based training intervention (EDITION) project aimed to develop and evaluate a de-escalation training programme informed by research evidence. We interviewed over one hundred people who either worked in or received treatment in a mental health hospital. These people were clear that the training should target key sources of interpersonal and environmental stress that prevent de-escalation from working. We also reviewed all the scientific studies on de-escalation and training, aiming to identify the elements of training that are most likely to increase use of de-escalation. Then, in partnership with current mental health service users and clinical staff, we developed the training programme. Training was delivered to more than 270 staff working in 10 different wards in mental health hospitals. We measured rates of violence, self-injury and use of physical restraint and seclusion 8 weeks before staff received training and 16 weeks after they received training (24 weeks of data collection in total). Analysis of these data showed that these unsafe events were occurring significantly less frequently after training than they were before training, which raised the possibility that the training was helping to reduce harm.

Staff support for workplace trauma: a freedom of information act request survey for NHS trusts providing mental health care in England.

INTRODUCTION: Workplace trauma in mental health settings is defined as exposure to verbal and physical aggression, witnessing self-harm or hearing about patients' histories of abuse. Support for workplace trauma is important for staff well-being, staff retention and ultimately patient care. Assessing the extent and adequacy of staff support for workplace trauma in mental health settings is important in identifying areas of need and good practice. AIM: To determine what staff support systems are in place for workplace trauma in mental health services across England. METHODS: Freedom of Information Act requests were sent to all 57 National Health Service Trusts providing mental health care in England to identify policies on the support to mental health staff after traumatic incidents that they have experienced in the course of their clinical duties. RESULTS: Fifty-five Trusts provided usable data. Only half provided evidence of a psychologically informed incident response that went beyond a fact-finding exercise and only a fifth of Trusts used an established model for the response process. A small proportion of policies acknowledged workplace traumas related to staff discrimination on the basis of protected characteristics. CONCLUSION: There is insufficient attention to supporting mental health staff with the effects of workplace trauma.

The influence of regional wind patterns on air quality during forest fires near Sydney, Australia.

Particulate pollution from forest fire smoke threatens the health of communities by increasing the occurrence of respiratory illnesses. Wind drives both fire behaviour and smoke dispersal. Understanding regional wind patterns would assist in effectively managing smoke risk. Sydney, Australia is prone to smoke pollution because it has a large population close to fire-prone eucalypt forests. Here we use the self-organising maps (SOM) technique to identify sixteen unique wind classes for the Sydney region from days with active fires, including identifying sea breeze occurrence. We explored differences in PM2.5 levels between classes and between hazard reduction burning (HRB) and wildfire days. For HRB days, classes with the highest PM2.5 mostly had a sea breeze, whereas better air quality days usually had winds aligned across the region (e.g. all westerly). The wind class with the most HRB days had low wind speeds and a sea breeze and was among the worst wind classes for air quality. For wildfire days, days with a sea breeze were also generally of poor air quality but many classes had at least some poor air quality days, most of which were during the 2019-2020 east coast wildfires in New South Wales. Some poor air quality days occurred in wind classes that sent strong plumes directly over air quality stations, spread smoke over a wide area or transported smoke from outside the region. The classes identified may be useful in scheduling HRBs, for example, identifying days with low pollution risk to conduct an HRB, or for assisting in understanding pollution risk and sending health warnings during HRBs and wildfires. Further development of the approach may allow the creation of multi-day classifications for fire managers to plan HRB ignitions over several days to ensure better smoke dispersal. Further research could incorporate other weather predictors or focus on other regions.

In Silico Quantification of Intersubject Variability on Aerosol Deposition in the Oral Airway.

The extrathoracic oral airway is not only a major mechanical barrier for pharmaceutical aerosols to reach the lung but also a major source of variability in lung deposition. Using computational fluid dynamics, deposition of 1−30 µm particles was predicted in 11 CT-based models of the oral airways of adults. Simulations were performed for mouth breathing during both inspiration and expiration at two steady-state flow rates representative of resting/nebulizer use (18 L/min) and of dry powder inhaler (DPI) use (45 L/min). Consistent with previous in vitro studies, there was a large intersubject variability in oral deposition. For an optimal size distribution of 1−5 µm for pharmaceutical aerosols, our data suggest that >75% of the inhaled aerosol is delivered to the intrathoracic lungs in most subjects when using a nebulizer but only in about half the subjects when using a DPI. There was no significant difference in oral deposition efficiency between inspiration and expiration, unlike subregional deposition, which shows significantly different patterns between the two breathing phases. These results highlight the need for incorporating a morphological variation of the upper airway in predictive models of aerosol deposition for accurate predictions of particle dosimetry in the intrathoracic region of the lung.

Simulation Modeling of Air and Droplet Temperatures in the Human Respiratory Tract for Inhaled Tobacco Products.

Respiratory tract dosimetry predictions for inhalation of tobacco product smoke and aerosols are sensitive to the values of the physicochemical properties of constituents that make up the puff. Physicochemical property values may change significantly with temperature, particularly in the oral cavity and upper airways of the lung, where the puff undergoes adjustments from high temperatures in the tobacco product to reach body temperature. The assumption of fixed property values may introduce uncertainties in the predicted doses in these and other airways of the lung. To obtain a bound for the uncertainties and improve dose predictions, we studied temperature evolution of the inhaled puff in the human respiratory tract during different puff inhalation events. Energy equations were developed for the transport of the puff in the respiratory tract and were solved to find air and droplet temperatures throughout the respiratory tract during two puffing scenarios: 1. direct inhalation of the puff into the lung with no pause in the oral cavity, and 2. puff withdrawal, mouth hold, and puff delivery to the lung via inhalation of dilution air. These puffing scenarios correspond to the majority of smoking scenarios. Model predictions showed that temperature effects were most significant during puff withdrawal. Otherwise, the puff reached thermal equilibrium with the body. Findings from this study will improve predictions of deposition and uptake of puff constituents, and therefore inform inhalation risk assessment from use of electronic nicotine delivery systems (ENDS) and combusted cigarettes.

'Commanded to be ill, accused of being well' a lived-experience-led, qualitative investigation of service user perspectives on the impact of emotionally unstable personality disorder diagnosis on self-concept.

BACKGROUND: Emotionally unstable personality disorder (EUPD) is a mental disorder impairing health and functioning and increasing suicide risk and it is a stigmatised condition among healthcare professionals. EUPD diagnosis may significantly affect self-concept, yet no previous investigation has explicitly examined this. AIMS: To explore service user perspectives on (a) the impact of EUPD diagnosis on self-concept and (b) mediators of positive and negative impacts. METHODS: Service user-led, qualitative semi-structured interviews with n = 10 participants with EUPD. RESULTS: Perceived impacts of diagnosis on self-concept were, broadly, negative. Factors mediating between positive and negative impacts included: exposure to online stigma and public understanding, the responses of relatives, friends, intimate partners and trusted communities, and the attitudes and behaviours of healthcare staff. There were indications that recent guideline and practice developments (guidelines recommending alternatives to inpatient admissions for people with EUPD and "recovery-focused" approaches to self-harm) may have worsened inpatient staff attitudes and led to more rejecting service user experiences. CONCLUSION: Mitigating negative impacts of EUPD diagnosis on self-concept may require addressing hateful, online content related to EUPD; revisiting use of the personality disorder label; improving medical communication around diagnosis and improving practice and policy in the management of EUPD in inpatient settings.

Prediction of air quality in Sydney, Australia as a function of forest fire load and weather using Bayesian statistics.

Smoke from Hazard Reduction Burns (HRBs) and wildfires contains pollutants that are harmful to human health. This includes particulate matter less than 2.5 µm in diameter (PM2.5), which affects human cardiovascular and respiratory systems and can lead to increased hospitalisations and premature deaths. Better models are needed to predict PM2.5 levels associated with HRBs so that agencies can properly assess smoke pollution risk and balance smoke risk with the wildfire mitigation benefits of HRBs. Given this need, our aim was to develop a probabilistic model of daily PM2.5 using Bayesian regression. We focused on the region around Sydney, Australia, which regularly has hazard reduction burning, wildfires and associated smoke. We developed two regional models (mean daily and maximum daily) from observed PM2.5, weather reanalysis and satellite fire hotspot data. The models predict that the worst PM2.5 in Sydney occurs when PM2.5 was high the previous day, there is low ventilation index (i.e. the product of wind speed and planetary boundary layer height), low temperature, west to northwest winds in the Blue Mountains, an afternoon sea breeze and large areas of HRBs are being conducted, particularly to the west and north of Sydney. A major benefit of our approach is that models are fast to run, require simple inputs and Bayesian predictions convey both predicted PM2.5 and associated prediction uncertainty. Future research could include the application of similar methods to other regions, collecting more data to improve model precision and developing Bayesian PM2.5 models for wildfires.

PROD-ALERT: Psychiatric restraint open data-analysis using logarithmic estimates on reporting trends.

Aims and Methods: Restraint reporting varies, which undermines regulation, obfuscates analyses, and incentivises minimisation. The English Mental Health Units Use of Force Act 2018, "Seni's Law" mandates reporting. This paper analysed open data from all psychiatric and learning disability institutions in England from September 2020 to August 2021. We correlated logarithms of "people restrained per month", against "bed days" per month and "people under legal mental health detention" per month, per institution. We designated institutions reporting some restraint for at least 11 of 12 months as reporting "completely" and used their trend to infer rates from non-"complete" institutions. Allowance was made for size. Our a priori manual can be shared on request. Results: Logarithms of people restrained per month and bed-days per month correlated among complete reporters: R2 0.90 (2.s.f). Persons detained per month also correlated with restraint: R2 0.78. "Partial" institutions reported intermittently. "Joiner" institutions reported firstly null, then substantive reporting. "Null" institutions (including the largest) reported no restraint. Precisely-reporting institutions with high inverse variance between months reported similar restraint-rates but less-precise reported lower rates. In institutions reporting no restraint, two independent "true rate" estimations, by bed-days or people detained, correlated across institutions: R2 0.95. Inference from size suggested non-complete reporters restrained 1,774 people in England per month 95% CI (1,449-2,174). Clinical implications: Restraint remains under-reported. Institutional size explains most restraint variation among complete reporting institutions, 90% of R2. Institutional restraint reports can be compared per-bed per-month. Rates of people detained are a useful independent "checking" comparator in England.

A Novel Framework for Modeling Person-to-Person Transmission of Respiratory Diseases.

From the beginning of the COVID-19 pandemic, researchers assessed the impact of the disease in terms of loss of life, medical load, economic damage, and other key metrics of resiliency and consequence mitigation; these studies sought to parametrize the critical components of a disease transmission model and the resulting analyses were informative but often lacked critical parameters or a discussion of parameter sensitivities. Using SARS-CoV-2 as a case study, we present a robust modeling framework that considers disease transmissibility from the source through transport and dispersion and infectivity. The framework is designed to work across a range of particle sizes and estimate the generation rate, environmental fate, deposited dose, and infection, allowing for end-to-end analysis that can be transitioned to individual and population health models. In this paper, we perform sensitivity analysis on the model framework to demonstrate how it can be used to advance and prioritize research efforts by highlighting critical parameters for further analyses.

The 2019-2020 Australian forest fires are a harbinger of decreased prescribed burning effectiveness under rising extreme conditions.

There is an imperative for fire agencies to quantify the potential for prescribed burning to mitigate risk to life, property and environmental values while facing changing climates. The 2019-2020 Black Summer fires in eastern Australia raised questions about the effectiveness of prescribed burning in mitigating risk under unprecedented fire conditions. We performed a simulation experiment to test the effects of different rates of prescribed burning treatment on risks posed by wildfire to life, property and infrastructure. In four forested case study landscapes, we found that the risks posed by wildfire were substantially higher under the fire weather conditions of the 2019-2020 season, compared to the full range of long-term historic weather conditions. For area burnt and house loss, the 2019-2020 conditions resulted in more than a doubling of residual risk across the four landscapes, regardless of treatment rate (mean increase of 230%, range 164-360%). Fire managers must prepare for a higher level of residual risk as climate change increases the likelihood of similar or even more dangerous fire seasons.

Exploring how to improve access to psychological therapies on acute mental health wards from the perspectives of patients, families and mental health staff: qualitative study.

BACKGROUND: Psychological therapy is core component of mental healthcare. However, many people with severe mental illnesses do not receive therapy, particularly in acute mental health settings. AIMS: This study identifies barriers to delivering and accessing psychological therapies in acute mental health settings, and is the first to recommend how services can increase access from the perspectives of different stakeholders (staff, patients and carers). METHOD: Sixty participants with experiences of acute mental health wards (26 staff, 22 patients and 12 carers) were interviewed about barriers to accessing therapy in in-patient settings and how therapies should be delivered to maximise access. RESULTS: Four themes were identified: (a) 'Models of care', including the function of in-patient wards, beliefs about the causes of mental health problems and the importance of strong leadership to support psychosocial interventions; (b) 'Integrated care', including the importance of psychologists being ward-based, as well as having strong links with community teams; (c) 'Acute levels of distress', including factors that aggravate or ameliorate the impact of this on engagement in therapy; and (d) 'Enhancing staff capability and motivation', which is influenced by contextual issues. CONCLUSIONS: It is possible to improve access to therapy through strong leadership (that is supportive of talking treatments), flexible delivery of therapy (that considers short admissions) and a whole-systems approach that promotes ward staff understanding of the psychosocial causes of mental illness and staff well-being. It is essential to ensure continuity between in-patient and community therapy services, and for wards to have physical space to carry out therapy.

A cluster randomised controlled trial of a ward-based intervention to improve access to psychologically-informed care and psychological therapy for mental health in-patients.

BACKGROUND: There is good evidence that psychological interventions improve patient well-being and independent living, but patients on acute mental health wards often do not have access to evidence-based psychological therapies which are strongly advised by NICE guidance for severe mental health problems. The overall aim of this programme of work is to increase patient access to psychological therapies on acute mental health inpatient wards. Stage one of the programme (which is complete) aimed to identify barriers and facilitators to delivering therapy in these settings through a large qualitative study. The key output of stage one was an intervention protocol that is designed to be delivered on acute wards to increase patient access to psychologically-informed care and therapy. Stage two of the programme aims to test the effects of the intervention on patient wellbeing and serious incidents on the ward (primary outcomes), patient social functioning and symptoms, staff burnout, ward atmosphere from staff and patient perspectives and cost effectiveness of the intervention (secondary outcomes). METHODS: The study is a single blind, pragmatic, cluster randomised controlled trial and will recruit thirty-four wards across England that will be randomised to receive the new intervention plus treatment as usual, or treatment as usual only. Primary and secondary outcomes will be assessed at baseline and 6-month and 9-month follow-ups, with serious incidents on the ward collected at an additional 3-month follow-up. DISCUSSION: The key output will be a potentially effective and cost-effective ward-based psychological intervention that increases patient access to psychological therapy in inpatient settings, is feasible to deliver in inpatient settings and is acceptable to patients. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03950388. Registered 15th May 2019. https://clinicaltrials.gov/ct2/show/NCT03950388.

De-escalation of conflict in forensic mental health inpatient settings: a Theoretical Domains Framework-informed qualitative investigation of staff and patient perspectives.

BACKGROUND: Violence and other harms that result from conflict in forensic inpatient mental health settings are an international problem. De-escalation approaches for reducing conflict are recommended, yet the evidence-base for their use is limited. For the first time, the present study uses implementation science and behaviour change approaches to identify the specific organisational and individual behaviour change targets for enhanced de-escalation in low and medium secure forensic inpatient settings. The primary objective of this study was to identify and describe individual professional, cultural and system-level barriers and enablers to the implementation of de-escalation in forensic mental health inpatient settings. The secondary objective was to identify the changes in capabilities, opportunities and motivations required to enhance de-escalation behaviours in these settings. METHODS: Qualitative design with data collection and analysis informed by the Theoretical Domains Framework (TDF). Two medium secure forensic mental health inpatient wards and one low secure mental health inpatient ward participated. 12 inpatients and 18 staff participated across five focus groups and one individual interview (at participant preference) guided by a semi-structured interview schedule informed by the TDF domains. Data were analysed via Framework Analysis, organised into the 14 TDF domains then coded inductively within each domain. RESULTS: The capabilities required to enhance de-escalation comprised relationship-building, emotional regulation and improved understanding of patients. Staff opportunities for de-escalation are limited by shared beliefs within nursing teams stigmatising therapeutic intimacy in nurse-patient relationships and emotional vulnerability in staff. These beliefs may be modified by ward manager role-modelling. Increased opportunity for de-escalation may be created by increasing service user involvement in antipsychotic prescribing and modifications to the physical environment (sensory rooms and limiting restrictions on patient access to ward spaces). Staff motivation to engage in de-escalation may be increased through reducing perceptions of patient dangerousness via post-incident debriefing and advanced de-escalation planning. CONCLUSIONS: Interventions to enhance de-escalation in forensic mental health settings should enhance ward staff's understanding of patients and modify beliefs about therapeutic boundaries which limit the quality of staff-patient relationships. The complex interactions within the capabilities-opportunities-motivation configuration our novel analysis generated, indicates that de-escalation behaviour is unlikely to be changed through knowledge and skills-based training alone. De-escalation training should be implemented with adjunct interventions targeting: collaborative antipsychotic prescribing; debriefing and de-escalation planning; modifications to the physical environment; and ward manager role-modelling of emotional vulnerability and therapeutic intimacy in nurse-patient relationships.

Barriers to fire spread in northern Australian tropical savannas, deriving fire edge metrics from long term high-frequency fire histories.

The savannas of northern Australia are amongst the most fire-prone landscapes in the world. However, over the last fifteen years, increasing effort has been put into reducing fire extent and severity using prescribed burning strategies early in the dry season. This study seeks to improve the application of strategic fire management by providing a more detailed understanding of the landscape features that impede fire spread in Australia's tropical savannas using long-term satellite-derived fire histories. Spatial analysis of fire edges in Kakadu National Park based on fine-scale (30 m) Landsat imagery found that most fires stopped along linear edges, which were primarily associated with known features (roads, rivers and cliffs). Further analysis found linear features with the highest stopping ability covered only 13% of the park but divided the whole park into smaller containment regions. The stopping power of each feature type was found to vary according to their width and to change during the fire season, results that could help plan strategic fuel reduction burns. Similar results were seen with the lower-resolution continental-scale MODIS satellite-derived edge data. The MODIS dataset provided a means for applying fire edge analysis to support planning in areas of northern Australia that lack fine scale fire history mapping.

A highly versatile fungal glucosyltransferase for specific production of quercetin-7-O-ß-D-glucoside and quercetin-3-O-ß-D-glucoside in different hosts.

Glycosylation is an effective way to improve the water solubility of natural products. In this work, a novel glycosyltransferase gene (BbGT) was discovered from Beauveria bassiana ATCC 7159 and heterologously expressed in Escherichia coli. The purified enzyme was functionally characterized through in vitro enzymatic reactions as a UDP-glucosyltransferase, converting quercetin to five monoglucosylated and one diglucosylated products. The optimal pH and temperature for BbGT are 35 ℃ and 8.0, respectively. The activity of BbGT was stimulated by Ca2+, Mg2+, and Mn2+, but inhibited by Zn2+. BbGT enzyme is flexible and can glycosylate a variety of substrates such as curcumin, resveratrol, and zearalenone. The enzyme was also expressed in other microbial hosts including Saccharomyces cerevisiae, Pseudomonas putida, and Pichia pastoris. Interestingly, the major glycosylation product of quercetin in E. coli, P. putida, and P. pastoris was quercetin-7-O-ß-D-glucoside, while the enzyme dominantly produced quercetin-3-O-ß-D-glucoside in S. cerevisiae. The BbGT-harboring E. coli and S. cerevisiae strains were used as whole-cell biocatalysts to specifically produce the two valuable quercetin glucosides, respectively. The titer of quercetin-7-O-ß-D-glucosides was 0.34 ± 0.02 mM from 0.83 mM quercetin in 24 h by BbGT-harboring E. coli. The yield of quercetin-3-O-ß-D-glucoside was 0.22 ± 0.02 mM from 0.41 mM quercetin in 12 h by BbGT-harboring S. cerevisiae. This work thus provides an efficient way to produce two valuable quercetin glucosides through the expression of a versatile glucosyltransferase in different hosts. KEY POINTS: • A highly versatile glucosyltransferase was identified from B. bassiana ATCC 7159. • BbGT converts quercetin to five mono- and one di-glucosylated derivatives in vitro. • Different quercetin glucosides were produced by BbGT in E. coli and S. cerevisiae.

Women's experiences of restrictive interventions within inpatient mental health services: A qualitative investigation.

Restrictive interventions (RI), such as physical restraint, seclusion, and rapid tranquilization, can have negative psychological effects on service users; however, there has been little investigation regarding their effects on women. The aim of this paper was to explore women's experiences of RI within UK inpatient mental health services. Twenty women accessing inpatient mental health services participated in semi-structured interviews. Using thematic analysis (TA), three primary themes were reported from women's experiences: (1) powerlessness, (2) dehumanization, and (3) relationships and communication. Clinical recommendations included ensuring gender-awareness and trauma-informed care training is mandatory for all mental health staff, for RI training to include awareness of gender differences, and for policies to be reviewed with regard to women being invasively searched and ensuring sanitary products are safely available for women within seclusion. Directions for future research include investigating the experiences of RI for women from minority ethnic groups and exploring important moderators and mediators in the relationship between RI and re-traumatization for women.

Naturally occurring cancer-associated mutations disrupt oligomerization and activity of protein arginine methyltransferase 1 (PRMT1).

Protein arginine methylation is a posttranslational modification catalyzed by the protein arginine methyltransferase (PRMT) enzyme family. Dysregulated protein arginine methylation is linked to cancer and a variety of other human diseases. PRMT1 is the predominant PRMT isoform in mammalian cells and acts in pathways regulating transcription, DNA repair, apoptosis, and cell proliferation. PRMT1 dimer formation, which is required for methyltransferase activity, is mediated by interactions between a structure called the dimerization arm on one monomer and a surface of the Rossman Fold of the other monomer. Given the link between PRMT1 dysregulation and disease and the link between PRMT1 dimerization and activity, we searched the Catalogue of Somatic Mutations in Cancer (COSMIC) database to identify potential inactivating mutations occurring in the PRMT1 dimerization arm. We identified three mutations that correspond to W215L, Y220N, and M224V substitutions in human PRMT1V2 (isoform 1) (W197L, Y202N, M206V in rat PRMT1V1). Using a combination of site-directed mutagenesis, analytical ultracentrifugation, native PAGE, and activity assays, we found that these conservative substitutions surprisingly disrupt oligomer formation and substantially impair both S-adenosyl-L-methionine (AdoMet) binding and methyltransferase activity. Molecular dynamics simulations suggest that these substitutions introduce novel interactions within the dimerization arm that lock it in a conformation not conducive to dimer formation. These findings provide a clear, if putative, rationale for the contribution of these mutations to impaired arginine methylation in cells and corresponding health consequences.

Smoke health costs and the calculus for wildfires fuel management: a modelling study.

BACKGROUND: Smoke from uncontrolled wildfires and deliberately set prescribed burns has the potential to produce substantial population exposure to fine particulate matter (PM2·5). We aimed to estimate historical health costs attributable to smoke-related PM2·5 from all landscape fires combined, and the relative contributions from wildfires and prescribed burns, in New South Wales, Australia. METHODS: We quantified PM2·5 from all landscape fire smoke (LFS) and estimated the attributable health burden and daily health costs between July 1, 2000, and June 30, 2020, for all of New South Wales and by smaller geographical regions. We combined these results with a spatial database of landscape fires to estimate the relative total and per hectare health costs attributable to PM2·5 from wildfire smoke (WFS) and prescribed burning smoke (PBS). FINDINGS: We estimated health costs of AU$ 2013 million (95% CI 718-3354; calculated with the 2018 value of the AU$). $1653 million (82·1%) of costs were attributable to WFS and $361 million (17·9%) to PBS. The per hectare health cost was of $105 for all LFS days ($104 for WFS and $477 for PBS). In sensitivity analyses, the per hectare costs associated with PBS was consistently higher than for WFS under a range of different scenarios. INTERPRETATION: WFS and PBS produce substantial health costs. Total health costs are higher for WFS, but per hectare costs are higher for PBS. This should be considered when assessing the trade-offs between prescribed burns and wildfires. FUNDING: None.

Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19.

While evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The median infectious dose, assessed by seroconversion, was 52 TCID50 (95% CI: 23-363 TCID50), and was significantly lower than the median dose for fever (256 TCID50, 95% CI: 102-603 TCID50), resulting in a group of animals that developed an immune response post-exposure but did not develop fever or other clinical signs of infection. In a subset of these animals, virus was detected in nasopharyngeal and/or oropharyngeal swabs, suggesting that infected animals without signs of disease are able to shed virus and may be infectious, which is consistent with reports of asymptomatic spread in human cases of COVID-19. These results suggest that differences in exposure dose may be a factor influencing disease presentation in humans, and reinforce the importance of public health measures that limit exposure dose, such as social distancing, masking, and increased ventilation. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, and, ultimately, mitigation strategies. Additionally, these data will be useful to inform dose selection in future studies examining the efficacy of therapeutics and vaccines against inhalational COVID-19, and as a baseline in healthy, young adult animals for assessment of the importance of other factors, such as age, comorbidities, and viral variant, on the infectious dose and disease presentation.

A study on the feasibility of delivering a psychologically informed ward-based intervention on an acute mental health ward.

Acute mental health inpatient wards have been criticized for being nontherapeutic. The study aimed to test the feasibility of delivering a psychologically informed intervention in these settings. This single-arm study evaluated the feasibility of clinical psychologists delivering a ward-based psychological service model over a 6-month period on two acute mental health wards. Data were gathered to assess trial design parameters and the feasibility of gathering patient/staff outcome data. Psychologists were able to deliver key elements of the intervention. Baseline staff and patient participant recruitment targets were met. However, there was significant patient attrition at follow-up, with incorrect contact details on discharge being the primary reason. Implementation of a ward-based psychological intervention appears feasible when implemented flexibly. It is feasible to recruit staff and patient participants and to collect staff outcome measures over a 6-month period. However, greater efforts need to be taken to trace patient movement following discharge.