Replacing a Cysteine Ligand by Selenocysteine in a [NiFe]-Hydrogenase Unlocks Hydrogen Production Activity and Addresses the Role of Concerted Proton-Coupled Electron Transfer in Electrocatalytic Reversibility.

Hydrogenases catalyze hydrogen/proton interconversion that is normally electrochemically reversible (having minimal overpotential requirement), a special property otherwise almost exclusive to platinum metals. The mechanism of [NiFe]-hydrogenases includes a long-range proton-coupled electron-transfer process involving a specific Ni-coordinated cysteine and the carboxylate of a nearby glutamate. A variant in which this cysteine has been exchanged for selenocysteine displays two distinct changes in electrocatalytic properties, as determined by protein film voltammetry. First, proton reduction, even in the presence of H2 (a strong product inhibitor), is greatly enhanced relative to H2 oxidation: this result parallels a characteristic of natural [NiFeSe]-hydrogenases which are superior H2 production catalysts. Second, an inflection (an S-shaped "twist" in the trace) appears around the formal potential, the small overpotentials introduced in each direction (oxidation and reduction) signaling a departure from electrocatalytic reversibility. Concerted proton-electron transfer offers a lower energy pathway compared to stepwise transfers. Given the much lower proton affinity of Se compared to that of S, the inflection provides compelling evidence that concerted proton-electron transfer is important in determining why [NiFe]-hydrogenases are reversible electrocatalysts.

Bacterial rhomboid proteases mediate quality control of orphan membrane proteins.

Although multiprotein membrane complexes play crucial roles in bacterial physiology and virulence, the mechanisms governing their quality control remain incompletely understood. In particular, it is not known how unincorporated, orphan components of protein complexes are recognised and eliminated from membranes. Rhomboids, the most widespread and largest superfamily of intramembrane proteases, are known to play key roles in eukaryotes. In contrast, the function of prokaryotic rhomboids has remained enigmatic. Here, we show that the Shigella sonnei rhomboid proteases GlpG and the newly identified Rhom7 are involved in membrane protein quality control by specifically targeting components of respiratory complexes, with the metastable transmembrane domains (TMDs) of rhomboid substrates protected when they are incorporated into a functional complex. Initial cleavage by GlpG or Rhom7 allows subsequent degradation of the orphan substrate. Given the occurrence of this strategy in an evolutionary ancient organism and the presence of rhomboids in all domains of life, it is likely that this form of quality control also mediates critical events in eukaryotes and protects cells from the damaging effects of orphan proteins.

Identification of Campylobacter jejuni and Campylobacter coli genes contributing to oxidative stress response using TraDIS analysis.

BACKGROUND: Campylobacter jejuni and Campylobacter coli are the major causative agents of bacterial gastroenteritis worldwide and are known obligate microaerophiles. Despite being sensitive to oxygen and its reduction products, both species are readily isolated from animal food products kept under atmospheric conditions where they face high oxygen tension levels. RESULTS: In this study, Transposon Directed Insertion-site Sequencing (TraDIS) was used to investigate the ability of one C. jejuni strain and two C. coli strains to overcome oxidative stress, using H2O2 to mimic oxidative stress. Genes were identified that were required for oxidative stress resistance for each individual strain but also allowed a comparison across the three strains. Mutations in the perR and ahpC genes were found to increase Campylobacter tolerance to H2O2. The roles of these proteins in oxidative stress were previously known in C. jejuni, but this data indicates that they most likely play a similar role in C. coli. Mutation of czcD decreased Campylobacter tolerance to H2O2. The role of CzcD, which functions as a zinc exporter, has not previously been linked to oxidative stress. The TraDIS data was confirmed using defined deletions of perR and czcD in C. coli 15-537360. CONCLUSIONS: This is the first study to investigate gene fitness in both C. jejuni and C. coli under oxidative stress conditions and highlights both similar roles for certain genes for both species and highlights other genes that have a role under oxidative stress.

Selective cysteine-to-selenocysteine changes in a [NiFe]-hydrogenase confirm a special position for catalysis and oxygen tolerance.

In [NiFe]-hydrogenases, the active-site Ni is coordinated by four cysteine-S ligands (Cys; C), two of which are bridging to the Fe(CO)(CN)2 fragment. Substitution of a single Cys residue by selenocysteine (Sec; U) occurs occasionally in nature. Using a recent method for site-specific Sec incorporation into proteins, each of the four Ni-coordinating cysteine residues in the oxygen-tolerant Escherichia coli [NiFe]-hydrogenase-1 (Hyd-1) has been replaced by U to identify its importance for enzyme function. Steady-state solution activity of each Sec-substituted enzyme (on a per-milligram basis) is lowered, although this may reflect the unquantified presence of recalcitrant inactive/immature/misfolded forms. Protein film electrochemistry, however, reveals detailed kinetic data that are independent of absolute activities. Like native Hyd-1, the variants have low apparent KMH2 values, do not produce H2 at pH 6, and display the same onset overpotential for H2 oxidation. Mechanistically important differences were identified for the C576U variant bearing the equivalent replacement found in native [NiFeSe]-hydrogenases, its extreme O2 tolerance (apparent KMH2 and Vmax [solution] values relative to native Hyd-1 of 0.13 and 0.04, respectively) implying the importance of a selenium atom in the position cis to the site where exogenous ligands (H-, H2, O2) bind. Observation of the same unusual electrocatalytic signature seen earlier for the proton transfer-defective E28Q variant highlights the direct role of the chalcogen atom (S/Se) at position 576 close to E28, with the caveat that Se is less effective than S in facilitating proton transfer away from the Ni during H2 oxidation by this enzyme.

Targeting belongingness among older people through engagement in senior centres: intervention development study in Denmark.

Adults often experience a loss of social relations and sense of belonging in later life, leading to the risk of social isolation. Municipal senior centres offer a potential site for intervention, as they provide social communities targeting older people. However, not all older people find it easy to access these social communities due to experiencing physical and/or psychosocial frailties and could therefore continue to experience a decline in social relations and sense of belonging, which potentiates poor physical and psychosocial health and well-being. To date, there are limited evidence-based interventions in Denmark. The present article describes the development of an intervention to increase belongingness and decrease social isolation among older people with frailties who attend Danish municipal senior centres. The development process was conducted with reference to the INDEX (IdentifyiNg and assessing different approaches to DEveloping compleX intervention) guidance. The development process resulted in a 6-month supportive intervention, consisting of four elements: skills development workshops for all staff members; a start conversation including frailty screening; allocation of a 'buddy' among existing service users; and monthly follow-up conversations with staff members. This theory-informed approach can progress to feasibility testing and outcome evaluation in order to generate an evidence base. Concurrently, the article reflects on current guidance for intervention development and how it may be used and optimized to strengthen developmental processes in the future.

Long-term impact of the Fostering Healthy Futures for Preteens program on suicide-related thoughts and behaviors for youth in out-of-home care: A randomized controlled trial.

Youth in out-of-home care are at high risk for suicide-related thoughts and behaviors (STB), yet there are no known efficacious interventions that reduce STB for this population. Fostering Healthy Futures for Preteens (FHF-P) is a 9-month community-based mentoring and skills training preventive intervention for children in out-of-home care. A randomized controlled trial enrolled 156 participants aged 9-11 years who were placed in out-of-home care over the prior year. Participants were 48.9% female, 54.1% Hispanic, 30.1% Black, and 27.1% American Indian. Follow-up interviews, conducted 7-12 years postintervention (85.2% retention rate), asked young adult participants, aged 18-22, to self-report lifetime STB as indexed by non-suicidal self-injury, suicidal thoughts, plans, and/or attempts. There was a nonsignificant reduction in the odds of STB for the intervention group at follow-up (OR = 0.74; CI, 0.32, 1.69). However, FHF-P significantly moderated the effect of baseline STB; control youth who reported baseline STB had 10 times the odds of young adult STB (OR = 10.44, CI, 2.28, 47.78), but there was no increase in the odds of adult-reported STB for intervention youth. Findings suggest that FHF-P buffers the impact of pre-existing STB on young adult STB for care-experienced youth. Further research is needed to identify mechanisms that may reduce STB in this population.

Allocoprobacillus halotolerans gen. nov., sp. nov and Coprobacter tertius sp. nov., isolated from human gut microbiota.

Two novel bacterial isolates were cultured from faecal samples of patients attending the Breast Care clinic at the Norwich and Norfolk University Hospital. Strain LH1062T was isolated from a 58-year-old female diagnosed with invasive adenocarcinoma with ductal carcinoma in situ. Strain LH1063T was isolated from a healthy 51-year-old female. Isolate LH1062T was predicted to be a potential novel genus most closely related to Coprobacillus, whilst LH1063T was predicted to be a novel species belonging to Coprobacter. Both strains were characterized by polyphasic approaches including 16S rRNA gene analysis, core-genome analysis, average nucleotide identity (ANI) comparisons and phenotypic analysis. Initial screening of the 16S rRNA gene of LH1062T returned a nucleotide identity of 93.4 % to Longibaculum muris. For LH1063T, nucleotide identity was a 92.6 % to Coprobacter secundus. Further investigations showed that LH1062T had a genome size of 2.9 Mb and G+C content of 31.3 mol %. LH1063T had a genome size of 3.3Mb and G+C content of 39.2 mol %. Digital DNA-DNA hybridization (dDDH) and ANI values of LH1062T with its closest relative, Coprobacillus cateniformis JCM 10604T, were 20.9 and 79.54 %, respectively. For LH1063T, the dDDH and ANI values with its closest relative, Coprobacter secundus 177T, were 19.3 and 77.81 %, respectively. Phenotypic testing confirmed that LH1062T could not be matched to a known validly published isolate in any database; thereby indicating a novel genus for which the name Allocoprobacillus gen. nov. is now proposed with LH1062T (=DSM 114537T=NCTC 14686T) being the type strain of the proposed novel species Allocoprobacillus halotolerans sp. nov. Strain LH1063T (=DSM 114538T=NCTC 14698T) fits within the genus Coprobacter and, it being the third species within this genus, the name Coprobacter tertius sp. nov. is proposed.

Optimising a co-production framework for developing public health interventions: application and testing of school-based Research Action Groups.

Existing frameworks for developing public health interventions have limited guidance for researchers on how to work with stakeholders to co-produce context-specific interventions. To address this, a promising framework for the co-production of public health interventions was developed through a previous review of school-based co-production. The present study aimed to optimise this co-production framework through applying and testing it in real-world secondary school contexts. Within schools, Research Action Groups (RAGs) were established with multiple school stakeholders supported by an external facilitator to use school data to produce school-specific mental health and wellbeing interventions. A mixed method process evaluation of two contextually diverse case study secondary schools in the UK was used to optimise the co-production framework. The process evaluation sought the views of those involved (students, school staff, school Senior Management Team (SMT) members, and the external co-production facilitator/researcher) on the co-production functions they were involved in so they could be modified, if needed. Data collected for the process evaluation during co-production were a researcher diary (n = 45 entries), and observations of student photography (n = 21) and RAG meetings (n = 8). Post co-production, interviews, and surveys with RAG students (n = 18) and staff (n = 8), and two school-specific SMT focus groups (n = 10) were conducted. The study identified four recommendations to optimise and integrate co-production into real world practice. They include the need to: assess schools for their readiness to undertake co-production; more effectively communicate the necessity to have stakeholders from the whole system involved; work with SMTs throughout co-production functions; involve stakeholders outside the school to support producing solutions to change school mental health and wellbeing priorities. The framework is intended to be used by researchers to integrate stakeholders into a shared decision-making process to develop interventions that meet the needs and contexts of individual schools. It could be transferred to other settings to support the development of public health interventions for other health areas, and populations. Further evaluation to test its use in other settings is needed.

Draft Genome Sequence of a Primate Isolate of Kazachstania pintolopesii.

Kazachstania pintolopesii is an opportunistic mammalian pathobiont from the K. telluris species complex. No draft genomes of this species are currently available. Here, we report the first draft genome sequence of a primate isolate of K. pintolopesii (NCYC 4417).

Police referrals for domestic abuse before and during the first COVID-19 lockdown: An analysis of routine data from one specialist service in South Wales.

BACKGROUND: COVID-19 lockdown measures may have led to more, and increasingly severe, domestic abuse. This study examines police referrals to a specialist domestic abuse service in Wales, UK before and during the first lockdown. METHODS: Routine data relating to 2292 police referrals for female adult victim-survivors from December 2019 until July 2020 were analysed and presented in the form of descriptive statistics to monitor changes in referral rates and the profile of those referrals. RESULTS: There was little increase in the overall volume of police referrals during lockdown, but the proportion assessed as high risk increased, and children became the primary source of third-party referrals, with a higher proportion of reports made by other third parties as restrictions eased. Police reports for cases of Child/Adolescent to Parent Violence (C/APV) occurred almost exclusively during lockdown. CONCLUSIONS: The increase in risk level despite less clear increase in volume may suggest unmet need, with victims less likely to seek help during lockdown other than for more severe instances. Increased reports by children suggest increased exposure of children to domestic abuse during school closure. Unmet need for women and children may have been made visible to services, and acquaintances, as measures began to ease.

Defining research priorities for youth public mental health: reflections on a coproduction approach to transdisciplinary working.

BACKGROUND: With most mental health problems established during childhood/adolescence, young people must be a key focus of public mental health approaches. Despite the range of factors known to influence mental health, evidence for effective interventions is lacking for this age group. This study aimed to define priorities for future public health intervention-focused research to support youth mental health by engaging with transdisciplinary stakeholder groups. METHODS: Our coproduction approach involved priority-setting workshops with young people, researchers, practitioners and policy-makers. Each workshop focused on three thematic areas: social connections and relationships; schools and other education settings; and key groups at greater risk of mental ill-health, specifically LGBTQ+ and care-experienced young people. Workshop outputs were synthesized to define research priorities. RESULTS: This paper presents the research priorities that were defined through the priority-setting workshops, and our reflections on the coproduction approach to guide future similar activities undertaken by others. Ten priorities for youth public mental health research were defined, covering the following areas: building supportive relationships; whole system approaches; social media; support at times of transition; improving links between different services; development and training for those who support young people; staff mental health; engaging with families; awareness of and access to services; and out-of-school and community settings. CONCLUSIONS: These research priorities can inform future intervention development to support youth public mental health. Our transdisciplinary approach means the identified research priorities are likely to be relevant to young people's experiences and needs, and to fit with the needs of those working in practice and policy to support young people.

Wellbeing in Secondary Education (WISE) Study to Improve the Mental Health and Wellbeing of Teachers: A Complex System Approach to Understanding Intervention Acceptability.

Teaching staff report poorer mental health and wellbeing than the general working population. Intervention to address this issue is imperative, as poor wellbeing is associated with burnout, presenteeism, and adverse student mental health outcomes. The Wellbeing in Secondary Education (WISE) intervention is a secondary school-based programme aimed at improving the mental health and wellbeing of teachers and students. There are three components: awareness-raising for staff; a peer support service delivered by staff trained in Mental Health First Aid (MHFA); and Schools and Colleges Mental Health First Aid (MHFA) training for teachers. A cluster randomised controlled trial with integrated process and economic evaluation was conducted with 25 secondary schools in the UK (2016-2018). The intervention was largely ineffective in improving teacher mental health and wellbeing. This paper reports process evaluation data on acceptability to help understand this outcome. It adopts a complex systems perspective, exploring how acceptability is a dynamic and contextually contingent concept. Data sources were as follows: interviews with funders (n = 3); interviews with MHFA trainers (n = 6); focus groups with peer supporters (n = 8); interviews with headteachers (n = 12); and focus groups with teachers trained in Schools and Colleges MHFA (n = 7). Results indicated that WISE intervention components were largely acceptable. Initially, the school system was responsive, as it had reached a 'tipping point' and was prepared to address teacher mental health. However, as the intervention interacted with the complexities of the school context, acceptability became more ambiguous. The intervention was seen to be largely inadequate in addressing the structural determinants of teacher mental health and wellbeing (e.g. complex student and staff needs, workload, and system culture). Future teacher mental health interventions need to focus on coupling skills training and support with whole school elements that tackle the systemic drivers of the problem.

An intervention to improve teacher well-being support and training to support students in UK high schools (the WISE study): A cluster randomised controlled trial.

BACKGROUND: Teachers are at heightened risk of poor mental health and well-being, which is likely to impact on the support they provide to students, and student outcomes. We conducted a cluster randomised controlled trial, to test whether an intervention to improve mental health support and training for high school teachers led to improved mental health and well-being for teachers and students, compared to usual practice. We also conducted a cost evaluation of the intervention. METHODS AND FINDINGS: The intervention comprised (i) Mental Health First Aid training for teachers to support students; (ii) a mental health awareness session; and (iii) a confidential staff peer support service. In total 25 mainstream, non-fee-paying secondary schools stratified by geographical area and free school meal entitlement were randomly allocated to intervention (n = 12) or control group (n = 13) after collection of baseline measures. We analysed data using mixed-effects repeated measures models in the intention-to-treat population, adjusted for stratification variables, sex, and years of experience. The primary outcome was teacher well-being (Warwick-Edinburgh Mental Well-being Scale). Secondary outcomes were teacher depression, absence, and presenteeism, and student well-being, mental health difficulties, attendance, and attainment. Follow-up was at months 12 (T1) and 24 (T2). We collected process data to test the logic model underpinning the intervention, to aid interpretation of the findings. A total of 1,722 teachers were included in the primary analysis. Teacher well-being did not differ between groups at T2 (intervention mean well-being score 47.5, control group mean well-being score 48.4, adjusted mean difference -0.90, 95% CI -2.07 to 0.27, p = 0.130). The only effect on secondary outcomes was higher teacher-reported absence among the intervention group at T2 (intervention group median number of days absent 0, control group median number of days absent 0, ratio of geometric means 1.04, 95% CI 1.00 to 1.09, p = 0.042). Process measures indicated little change in perceived mental health support, quality of relationships, and work-related stress. The average cost of the intervention was £9,103 per school. The study's main limitations were a lack of blinding of research participants and the self-report nature of the outcome measures. CONCLUSIONS: In this study, we observed no improvements to teacher or student mental health following the intervention, possibly due to a lack of impact on key drivers of poor mental health within the school environment. Future research should focus on structural and cultural changes to the school environment, which may be more effective at improving teacher and student mental health and well-being. TRIAL REGISTRATION: www.isrctn.com ISRCTN95909211.

Developing a whole-school mental health and wellbeing intervention through pragmatic formative process evaluation: a case-study of innovative local practice within The School Health Research network.

BACKGROUND: The evidence-base for whole school approaches aimed at improving student mental health and wellbeing remains limited. This may be due to a focus on developing and evaluating de-novo, research-led interventions, while neglecting the potential of local, contextually-relevant innovation that has demonstrated acceptability and feasibility. This study reports a novel approach to modelling and refining the programme theory of a whole-school restorative approach, alongside plans to scale up through a national educational infrastructure in order to support robust scientific evaluation. METHODS: A pragmatic formative process evaluation was conducted of a routinized whole-school restorative approach aimed at improving student mental health and wellbeing in Wales. RESULTS: The study reports the six phases of the pragmatic formative process evaluation. These are: 1) identification of innovative local practice; 2) scoping review of evidence-base to identify potential programme theory; outcomes; and contextual characteristics that influence implementation; 3) establishment of a Transdisciplinary Action Research (TDAR) group; 4) co-production and confirmation of an initial programme theory with stakeholders; 5) planning to optimise intervention delivery in local contexts; and 6) planning for feasibility and outcome evaluation. The phases of this model may be iterative and not necessarily sequential. CONCLUSIONS: Formative, pragmatic process evaluations can support researchers, policy-makers and practitioners in developing robust scientific evidence-bases for acceptable and feasible local innovations that do not already have a clear evidence base. The case of a whole-school restorative approach provides a case example of how such an evaluation may be undertaken.

Theorising health professionals' prevention and management practices with children and young people experiencing self-harm: a qualitative hospital-based case study.

Self-harm in young people remains a significant concern. Studies of emergency departments have centred on negative professional attitudes. There has been limited interrogation and theorisation of what drives such attitudes, and the contexts that sustain them. Adopting a complex systems lens, this study aimed to explore how systems shape professional and patient interactions. It draws upon interviews with healthcare and affiliated professionals (n = 14) in a UK case study hospital, with primary focus on the emergency department. Data were analysed using a thematic approach and the principles of grounded theory. Four themes emerged, with the first three centralising how professionals' practices operate within: (1) a framework of risk management; (2) expectations of progressing patients through the care pathway; and (3) a culture of specialist expertise, with resulting uncertainty about who is responsible for self-harm. The fourth theme considers barriers to system change. A small number of participants described efforts to enact positive modifications to practices, but these were frustrated by entrenched system structures. The potential detrimental impacts for patient care and professional wellbeing are considered. Future practice needs systemic action to support professionals in treating patients experiencing self-harm, while future research requires more ethnographic explorations of the complex system in situ.

Co-production as an Emerging Methodology for Developing School-Based Health Interventions with Students Aged 11-16: Systematic Review of Intervention Types, Theories and Processes and Thematic Synthesis of Stakeholders' Experiences.

Co-production affords an intervention's target population the opportunity to participate in intervention theory decision-making during the development process. This addresses the over-reliance on developing interventions through academic theories which can be devoid of contextual understanding and result in challenges to implementing school-based health programmes. There is an emergent empirical literature on co-producing school-based health interventions, but an understanding of appropriate theoretical types and processes and stakeholders' experiences is lacking. Through the conduct of a systematic review, this study seeks to understand the types and underlying theories and processes for co-production in school-based health interventions with students aged 11-16. A thematic synthesis explored stakeholders' experiences of the different types of co-production. A systematic search of five electronic bibliographic databases, citation tracking of included studies, and consultation with an expert international panel were employed. Of 27,433 unique papers, 30 papers representing 22 studies were retained to describe types, and 23 papers of 18 studies used to synthesise stakeholders' experiences. Three types were identified: external, individual-level, and system-level capacity-building. Whilst this review showed variability in co-production types, stakeholders involved and processes, shared functions were identified. Students', school staff, facilitators' and researchers' experiences in terms of acceptability, feasibility and undertaking decision-making are discussed. Recommendations for conceptualising and reporting co-production and process evaluations of co-produced school-based health interventions are highlighted.

Practitioner review: Co-design of digital mental health technologies with children and young people.

BACKGROUND: There is increasing interest in digital technologies to help improve children and young people's mental health, and the evidence for the effectiveness for these approaches is rising. However, there is concern regarding levels of user engagement, uptake and adherence. Key guidance regarding digital health interventions stress the importance of early user input in the development, evaluation and implementation of technologies to help ensure they are engaging, feasible, acceptable and potentially effective. Co-design is a process of active involvement of stakeholders, requiring a change from the traditional approaches to intervention development. However, there is a lack of literature to inform the co-design of digital technologies to help child and adolescent mental health. METHODS: We reviewed the literature and practice in the co-design of digital mental health technologies with children and young people. We searched Medline, PsycInfo and Web of Science databases, guidelines, reviews and reference lists, contacted key authors for relevant studies, and extracted key themes on aspects of co-design relevant to practice. We supplemented this with case studies and methods reported by researchers working in the field. RESULTS: We identified 25 original articles and 30 digital mental health technologies that were designed/developed with children and young people. The themes identified were as follows: principles of co-design (including potential stakeholders and stages of involvement), methods of involving and engaging the range of users, co-designing the prototype and the challenges of co-design. CONCLUSIONS: Co-design involves all relevant stakeholders throughout the life and research cycle of the programme. This review helps to inform practitioners and researchers interested in the development of digital health technologies for children and young people. Future work in this field will need to consider the changing face of technology, methods of engaging with the diversity in the user group, and the evaluation of the co-design process and its impact on the technology.

Inter-professional practice in the prevention and management of child and adolescent self-harm: foster carers' and residential carers' negotiation of expertise and professional identity.

Inter-professional collaboration remains a significant concern within healthcare and social care. However, there has been scant attention paid to practices at the interface of clinicians and carers, namely foster carers and residential carers. The present study considers child and adolescent self-harm management and prevention practices as a site of empirical interest due to reports that multi-agency teams are not effectively operating. Drawing upon a grounded theory approach, data were generated via semi-structured interviews and focus groups with residential carers (n = 15) and foster carers (n = 15) in Wales. Themes were developed through axial coding. The results present two central themes to explain the nature and perceived causes of inter-professional discord. First, there are clear contestations in expertise, with carers challenging clinicians' propositional knowledge in favour of their own experiential expertise. However, participants simultaneously endorse medical dominance, which contributes to their sense of disempowerment and marginalisation. Second, is the preclusion of carers' professional identity, primarily due to inadequate professionalisation procedures. Meanwhile, the privileging of their parenting role is perceived to support the perpetuation of courtesy stigma. Carers are then compelled to undertake the effortful labour of legitimisation. Together these thematic insights provide direction on mechanisms to improve inter-professional interactions, notably around training and accreditation.

The value of enzymes in solar fuels research - efficient electrocatalysts through evolution.

The reasons for using enzymes as tools for solar fuels research are discussed. Many oxidoreductases, including components of membrane-bound electron-transfer chains in living organisms, are extremely active when directly attached to an electrode, at which they display their inherent catalytic activity as electrical current. Electrocatalytic voltammograms, which show the rate of electron flow at steady-state, provide direct information on enzyme efficiency with regard to optimising use of available energy, a factor that would have driven early evolution. Oxidoreductases have evolved to minimise energy wastage ('overpotential requirement') across electron-transport chains where rate and power must be maximised for a given change in Gibbs energy, in order to perform work such as proton pumping. At the elementary level (uncoupled from work output), redox catalysis by many enzymes operates close to the thermodynamically reversible limit. Examples include efficient and selective electrocatalytic reduction of CO2 to CO or formate - reactions that are very challenging at the chemistry level, yet appear almost reversible when catalysed by enzymes. Experiments also reveal the fleeting existence of reversible four-electron O2 reduction and water oxidation by 'blue' Cu oxidases, another reaction of great importance in realising a future based on renewable energy. Being aware that such enzymes have evolved to approach perfection, chemists are interested to know the minimal active site structure they would need to synthesise in order to mimic their performance.

Patients' Experiences of Emergency Hospital Care Following Self-Harm: Systematic Review and Thematic Synthesis of Qualitative Research.

Rates of hospital presentation for self-harm have increased in recent years, and although clinical practice guidelines on clinical provision prioritize positive patient experiences, the quality of provision remains variable. This systematic review provides an updated and extended synthesis of qualitative research on the following: (a) patients' experiences of treatment following presentation to hospital; and (b) patients' perceptions of the impact of treatment on recurrent self-harm and/or suicidal ideation, and future help-seeking. Twenty-six studies were identified for inclusion in the final synthesis. Three meta-themes emerged: (a) individuals undertake extensive identity work when presenting with self-harm, navigating the process of becoming a patient, and negotiating the type of patient they want to be; (b) care ranges from gentle to hostile, with care at admission and discharge being particularly disorientating; and (c) negative experiences of clinical treatment may increase future self-harm. Emerging research gaps include the need for further theoretically informed qualitative research in this area.