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Aims While dopamine antagonists are an effective treatment for positive psychotic symptoms, they are rarely effective when it comes to treating the cognitive (memory, learning, planning, etc.) and negative (avolition and social withdrawal) symptoms of the disorder. Furthermore, for a sizeable proportion, standard dopamine antagonists are not effective for positive symptoms either. As such, refractory symptoms are a major burden for patients, carers, and clinical services. Methods To address this, The TUNE-UP (Treating Unmet Needs in Psychiatry) clinic in Oxford was established in September 2023 as an innovative solution aiming to: (A) Undertake an in-depth assessment of cognitive, negative, and positive symptoms; (B) Identify potentially modifiable causative factors contributing to refractory symptoms (e.g., cholinergic burden, sleep disturbances, physical comorbidities, affective symptoms); and (C) Implement management plans including community clozapine initiation where appropriate. We have analysed data from the clinic's initial five months of operation to establish a baseline understanding of our patient population and identify trends in symptoms. Results In the first five months of operations, 21 referrals were accepted comprising 80.9% males (mean age 43.3 years, SD 13.7). 3 were referred for cognitive symptoms, 1 for negative and cognitive symptoms, 11 for positive symptoms, 3 for medication optimisation, and 3 for clozapine re-titration. Of those fully assessed (N = 17), mean total symptom scores measured using the Positive and Negative Syndrome Scale (PANSS) were of mild/moderate severity (70.5, SD 18.4). Objective cognitive testing via the Screen for Cognitive Impairment in Psychiatry (SCIP) demonstrated a total mean score of 54.1 (SD 12.1), markedly below what would be expected in a matched control population (76.3). Cognitive scores were lower in those of older age (r = −0.62, p = 0.01). Subjective experience of cognitive impairment was measured using the Subjective Scale to Investigate Cognition in Schizophrenia, poor subjective cognition was associated with more severe negative symptoms (r = 0.57, p = 0.03), but not objective SCIP results (r = 0.12, p = 0.85). Conclusion Refractory positive symptoms remain a priority for clinicians, but cognitive and negative symptoms are highly prevalent reinforcing the need for a comprehensive approach. Routine structured assessment of all symptom domains is feasible in clinical practice. Future work should examine the longitudinal impact of various interventions on different symptom domains.

Aims Cognitive disorders, such as dementia, are a possible comorbidity and an important differential diagnosis to consider in older adults admitted to psychiatric wards with a functional disorder. Whilst cognitive assessment tools (e.g. ACE-III) and neuroimaging (e.g. MRI scans) are well established, there is significant variability in how and when they are used, which can result in inconsistences in their use. The aim was to identify the types of inconsistencies that may occur, and to provide a standardised framework in order for these tools to be used consistently on our functional rehabilitation ward. Methods This QIP retrospectively assessed data for all patients discharged over a 7-month period between October 2022 and May 2023, from an older adult functional rehabilitation ward. Clinical notes were reviewed to determine whether a cognitive assessment and neuroimaging had been considered, and if so, whether the assessment or investigation was appropriate and completed without delay. Correspondence to the GP or CMHT was reviewed to determine whether this had appropriate information about the relevant cognitive screening completed, and had included an appropriate follow-up plan. Data collected was checked for accuracy through screening by a second clinician, after which a consensus meeting was held to account for discrepancies. Results 25 patients were discharged during the 7-month period. 52% were identified as having an issue or delay in their cognitive screening and correspondence; 32% had a delay in completing a cognitive assessment; 32% did not have an appropriate follow-up plan communicated in their discharge summary regarding future monitoring of their cognition; and 8% had a delay in considering or requesting neuroimaging. Conclusion Team discussion identified that staff uncertainty relating to the use of cognitive tools and neuroimaging was a significant contributing factor to the issues identified in our results. We subsequently delivered training using a flowchart for doctors, nurses and allied healthcare professionals on the ward, which included information about the benefits and disadvantages of different screening tools and imaging modalities, in order to assist selection of the most appropriate tools on a case-by-case basis. The flowchart included the need for MDT discussion and senior psychiatrist involvement, but aimed to improve team confidence in understanding the rationale for these decisions. Based on the results of our post-intervention data, we will consider adapting the training and flowchart delivered to meet the needs of other older adult services in the trust.

Domain adaptation is important in agriculture because agricultural systems have their own individual characteristics. Applying the same treatment practices (e.g., fertilization) to different systems may not have the desired effect due to those characteristics. Domain adaptation is also an inherent aspect of digital twins. In this work, we examine the potential of transfer learning for domain adaptation in pasture digital twins. We use a synthetic dataset of grassland pasture simulations to pretrain and fine-tune machine learning metamodels for nitrogen response rate prediction. We investigate the outcome in locations with diverse climates, and examine the effect on the results of including more weather and agricultural management practices data during the pretraining phase. We find that transfer learning seems promising to make the models adapt to new conditions. Moreover, our experiments show that adding more weather data on the pretraining phase has a small effect on fine-tuned model performance compared to adding more management practices. This is an interesting finding that is worth further investigation in future studies.

This article seeks to unpack the potential and limits of markets as instruments of economic planning in sustainability capitalism. Recent policies for sustainability transitions in the United States (USA) and the European Union (EU) (eg, Infrastructure Law, EU Green Deal) have signaled aspirations for a more prominent role of the state in coordinating the economy, while still relying primarily on market mechanisms for such coordination. Yet, could the market itself be conceptualised and structured as a political instrumentality for the achievement of social objectives? An important part of the puzzle of sustainability transitions is the transportation sector, and specifically the transition to Electric Vehicles, or New Energy Vehicles (NEVs). I explore the comparative legal constructions of markets for NEVs in China – the current global leader in NEVs – the USA, and the EU. Drawing from this case study, I first argue that law makes planning possible within markets, as the functional power of market processes can be strategically deployed for the achievement of politically set objectives. Acknowledging the deliberate and artificial character of markets raises the question of what we want markets for, broadening the scope of the political possibilities enclosed in them. I, then, proceed to challenge the enduring argument of the epistemic deficit of central planners, which morphs into prescriptions of decentralisation. I show that arguments against legal centralism and planning cannot stand on just epistemological grounds and are inevitably political. Finally, I attempt to outline the limits of planning within markets – and thus, to a certain extent, the limits of the constitutive function of law – for broader projects of social transformation.

Background The recent World Health Organization (WHO) blueprint for dementia research and Lancet Commission on ending stigma and discrimination in mental health has identified a gap around dementia-related measures of stigma and discrimination that can be used in different cultural, language and regional contexts. Aims We aimed to characterise experiences of discrimination, and report initial psychometric properties of a new tool to capture these experiences, among a global sample of people living with dementia. Method We analysed data from 704 people living with dementia who took part in a global survey from 33 different countries and territories. Psychometric properties were examined, including internal consistency and construct validity. Results A total of 83% of participants reported discrimination in one or more areas of life, and this was similar across WHO Regions. The exploratory factor analysis factor loadings and scree plot supported a unidimensional structure for the Discrimination and Stigma Scale Ultra Short for People Living with Dementia (DISCUS-Dementia). The instrument demonstrated excellent internal consistency, with most of the construct validity hypotheses being confirmed and qualitative responses demonstrating face validity. Conclusions Our analyses suggest that the DISCUS-Dementia performs well with a global sample of people living with dementia. This scale can be integrated into large-scale studies to understand factors associated with stigma and discrimination. It can also provide an opportunity for a structured discussion around stigma and discrimination experiences important to people living with dementia, as well as planning psychosocial services and initiatives to reduce stigma and discrimination.

The rise of digital capitalism was marked by significant changes in the processes of value generation and capture in the economy. However, its impact on competition has only been recently explored. Taking a Law and Political Economy perspective we analyse four central developments challenging the traditional competition law framework and raising important questions regarding the broader institutional environment for the protection of competition: the transition towards financialisation and the logic of futurity, in particular in the digital economy, which gives rise to new competitive strategies of undertakings, structured around the ‘shareholder value’ principle; the extraction of economic value through new types of labour, which fall outside traditional employment relationships and hence affect the scope of competition law in the digital economy; the emergence of digital value chains that rely on multi-sided platforms and the formation of digital ecosystems, which challenge the usual focus of competition law on markets; the generation and extraction of value in the digital economy through new types of commodities and natural and artificial scarcities, that shape new social relations of production in accordance with the logic of futurity and lead to the emergence of competitive bottlenecks. Based on this analysis, we emphasize the need for a comprehensive theory-building for competition law and regulation that engages with these new processes of value generation and capture. We highlight how the underlying theories of ‘value’ and the institutional set-up have led to inequality and reduced competition. Existing institutions could not respond to these changes, which led to the initiation of significant institutional reforms. The prevailing conception of competition law had to evolve in congruence with different regulatory alternatives (a ‘toolkit’ approach). The article concludes by analysing how the emerging competition and regulatory compass for the digital economy in the European Union (EU) contributes to this dialectic between value generation/capture and institutional choice.

Inspired by the contributions of Poul Kjaer and Kerry Rittich to this Special Issue, this article extends the reflection on the role and potential of law for social transformation. More specifically, I attempt to build on a revised framing of the constitutive role of law to draw the contours of a transformative instrumentalism, where law functions as an instrument for the articulation of political and social objectives. My account shifts the attention from transformative law’s form to its content, based on the premise that engagement with ‘political’ economy necessarily entails an engagement with the substantive standards that shape social relations of production and define the nature and extent of exploitation. Yet, I argue that the endorsement of law’s constitutive function and the turn to law’s content need not lead to the kind of instrumentalism that exhausts itself in particular policy reforms or prescriptions to assume control over processes of legal coding. Relying on a tentatively redrawn conception of the constitutive role of law that draws from both legal institutionalism and Marxist perspectives, I suggest that instrumentalism may instead be transformative by prioritising material ends, leaving open the question of the concrete legal and institutional forms that will materialise them. The directions of such transformative instrumentalism involve an element of ‘mobilisational democracy’ against the insulation of the economy from democratic control; reforms generative of collective subjects and centres of democratic power (‘non-reformist reforms’); and a focus on the planning and coordinating function of law among diverse – but united in their objective – legal rationales and institutional forms.

Background In addition to the devastating impact on the individual and their families, suicides on the roads can cause distress and harm to other people who might be involved in a collision or witness an attempt. Despite an increased focus on the characteristics and circumstances of road-related suicides, little is known about why people choose to end their lives in this way. Aims The aim of the current study was to investigate the factors prompting and deterring the decision to attempt suicide on the roads. Method We conducted a secondary analysis of survey data, as well as seven in-depth qualitative interviews. Participants had lived experience of suicidal ideation or behaviour at a bridge or road location. We also carried out an online ethnography to explore interactions in different online communities relating to this method of suicide. Results Participants perceived a road-related suicide to be quick, lethal, easy and accessible and to have the potential to appear accidental. The proportion of participants who described their thoughts and attempts as impulsive appeared to be higher than had been observed with other method choices. The potential impact on other people was a strongly dissuasive factor. Conclusions Measures designed to prevent access to potentially lethal sites may be particularly important, given that many participants described their thoughts and behaviour as impulsive. In addition, fostering a culture of care and consideration for other road users may help to dissuade people from taking action on the roads.

The growing need for agricultural products and the challenges posed by environmental and economic factors have created a demand for enhanced agricultural systems management. Machine learning has increasingly been leveraged to tackle agricultural optimization problems, and in particular, reinforcement learning (RL), a subfield of machine learning, seems a promising tool for data-driven discovery of future farm management policies. In this work, we present the development of CropGym, a Gymnasium environment, where a reinforcement learning agent can learn crop management policies using a variety of process-based crop growth models. As a use case, we report on the discovery of strategies for nitrogen application in winter wheat. An RL agent is trained to decide weekly on applying a discrete amount of nitrogen fertilizer, with the aim of achieving a balance between maximizing yield and minimizing environmental impact. Results show that close to optimal strategies are learned, competitive with standard practices set by domain experts. In addition, we evaluate, as an out-of-distribution test, whether the obtained policies are resilient against a change in climate conditions. We find that, when rainfall is sufficient, the RL agent remains close to the optimal policy. With CropGym, we aim to facilitate collaboration between the RL and agronomy communities to address the challenges of future agricultural decision-making.

Abstract Aims Multiple studies have connected parenting styles to children's internalising and externalising mental health symptoms (MHS). However, it is not clear how different parenting styles are jointly influencing the development of children's MHS over the course of childhood. Hence, the differential effects of parenting style on population heterogeneity in the joint developmental trajectories of children's internalising and externalising MHS were examined. Method A community sample of 7507 young children (ages 3, 5 and 9) from the Growing Up in Ireland cohort study was derived for further analyses. Parallel-process linear growth curve and latent growth mixture modelling were deployed. Results The results indicated that the linear growth model was a good approximation of children's MHS development (CFI = 0.99, RMSEA = 0.03). The growth mixture modelling revealed three classes of joint internalising and externalising MHS trajectories (VLMR = 92.51, p < 0.01; LMR = 682.19, p < 0.01; E = 0.86). The majority of the children (83.49%) belonged to a low-risk class best described by a decreasing trajectory of externalising symptoms and a flat low trajectory of internalising MHS. In total, 10.07% of the children belonged to a high-risk class described by high internalising and externalising MHS trajectories, whereas 6.43% of the children were probable members of a mild-risk class with slightly improving yet still elevated trajectories of MHS. Adjusting for socio-demographics, child and parental health, multinomial logistic regressions indicated that hostile parenting was a risk factor for membership in the high-risk (OR = 1.47, 95% CI 1.18–1.85) and mild-risk (OR = 1.57, 95% CI 1.21–2.04) classes. Consistent (OR = 0.75, 95% CI 0.62–0.90) parenting style was a protective factor only against membership in the mild-risk class. Conclusions In short, the findings suggest that a non-negligible proportion of the child population is susceptible to being at high risk for developing MHS. Moreover, a smaller proportion of children was improving but still displayed high symptoms of MHS (mild-risk). Furthermore, hostile parenting style is a substantial risk factor for increments in child MHS, whereas consistent parenting can serve as a protective factor in cases of mild-risk. Evidence-based parent training/management programmes may be needed to reduce the risk of developing MHS.

Abstract Objective: To assess the effect of new legislation on the dispensing of antimicrobials without prescription from pharmacies in Greece. Design: In-person survey. Setting: The study included 110 pharmacies in the greater Athens Metropolitan area. Methods: Volunteer collaborators visited 110 pharmacies in the greater Athens Metropolitan area in December 2021 and January 2022. They asked for either ciprofloxacin or amoxicillin-clavulanate acid (6:5 ratio) without providing a prescription, without simulating symptoms, and without offering justification or insisting. Fluoroquinolones have additional dispensing restrictions in Greece. Results were compared to a 2008 study. In 2020, legislation allowed the dispensing of antibiotics from pharmacies only with an electronic prescription, overriding the 1973 forbidding the dispensing of all medications without prescriptions. Results: All pharmacists refused to dispense ciprofloxacin without a prescription. Only 1 pharmacy dispensed amoxicillin-clavulanate without a prescription. Compared to the 2008 study, dispensing of amoxicillin-clavulanate without a prescription dropped from 100% in 2008 to 1% in 2021 and dispensing ciprofloxacin without a prescription dropped from 53% in 2008 to 0% in 2021. Conclusions: A new and enforced law that requires electronic prescribing led to a dramatic reduction of antibiotic dispensing without prescription compared to 12 years ago. Similar initiatives could help solve the problem of antibiotic consumption and resistance in Greece and elsewhere.

Background Cognitive therapy and behavioural activation are both widely applied and effective psychotherapies for depression, but it is unclear which works best for whom. Individual participant data (IPD) meta-analysis allows for examining moderators at the participant level and can provide more precise effect estimates than conventional meta-analysis, which is based on study-level data. Aims This article describes the protocol for a systematic review and IPD meta-analysis that aims to compare the efficacy of cognitive therapy and behavioural activation for adults with depression, and to explore moderators of treatment effect. (PROSPERO: CRD42022341602) Method Systematic literature searches will be conducted in PubMed, PsycINFO, EMBASE and the Cochrane Library, to identify randomised clinical trials comparing cognitive therapy and behavioural activation for adult acute-phase depression. Investigators of these trials will be invited to share their participant-level data. One-stage IPD meta-analyses will be conducted with mixed-effects models to assess treatment effects and to examine various available demographic, clinical and psychological participant characteristics as potential moderators. The primary outcome measure will be depressive symptom level at treatment completion. Secondary outcomes will include post-treatment anxiety, interpersonal functioning and quality of life, as well as follow-up outcomes. Conclusions To the best of our knowledge, this will be the first IPD meta-analysis concerning cognitive therapy versus behavioural activation for adult depression. This study has the potential to enhance our knowledge of depression treatment by using state-of-the-art statistical techniques to compare the efficacy of two widely used psychotherapies, and by shedding more light on which of these treatments might work best for whom.

Background Psychiatric morbidity in prisons and police custody is well established, but little is known about individuals attending criminal court. There is international concern that vulnerable defendants are not identified, undermining their right to a fair trial. Aims To explore the prevalence of a wide range of mental disorders in criminal defendants and estimate the proportion likely to be unfit to plead. Method We employed two-stage screening methodology to estimate the prevalence of mental illness, neurodevelopmental disorders and unfitness to plead, in 3322 criminal defendants in South London. Sampling was stratified according to whether defendants attended court from the community or custody. Face-to-face interviews, using diagnostic instruments and assessments of fitness to plead, were administered (n = 503). Post-stratification probability weighting provided estimates of the overall prevalence of mental disorders and unfitness to plead. Results Mental disorder was more common in those attending court from custody, with 48.5% having at least one psychiatric diagnosis compared with 20.3% from the community. Suicidality was frequently reported (weighted prevalence 71.2%; 95% CI 64.2–77.3). Only 16.7% of participants from custody and 4.6% from the community were referred to the liaison and diversion team; 2.1% (1.1–4.0) of defendants were estimated to be unfit to plead, with a further 3.2% (1.9–5.3) deemed ‘borderline unfit’. Conclusions The prevalence of mental illness and neurodevelopmental disorders in defendants is high. Many are at risk of being unfit to plead and require additional support at court, yet are not identified by existing services. Our evidence challenges policy makers and healthcare providers to ensure that vulnerable defendants are adequately supported at court.

Background For every suicide on the British railway network, at least six potential attempts are interrupted by front-line staff or rail commuters. However, the factors that maximise or hinder the likelihood and effectiveness of such interventions are poorly understood. Aims The aim of the current study was to shed light on the experience of intervening to prevent a suicide at a railway location, including how and why people intervene, and their feelings and reflections in the aftermath. Method In-depth interviews were carried out with rail commuters (n = 11) and front-line railway staff (n = 10) who had intervened to stop a suicide by train. Data were analysed thematically. Results Participants had intervened to prevent suicide in several ways, both from afar (e.g. by calling a member of staff) and more directly (verbally or non-verbally), in some cases with no prior training or experience in suicide prevention, and often as a ‘quick, gut reaction’ given the limited time to intervene. In more ‘reasoned’ interventions, poor confidence and concerns around safety were the greatest barriers to action. Although often privy to their final outcome, most participants reflected positively on their intervention/s, stressing the importance of training and teamwork, as well as small talk and non-judgemental listening. Conclusions Suicides in railway environments can present bystanders with little time to intervene. Potential interveners should therefore be resourced as best as possible through clear infrastructure help/emergency points, visibility of station staff and training for gatekeepers.

Abstract Objective: We surveyed antimicrobials used in Greek pediatric hematology–oncology (PHO) and bone marrow transplant (BMT) units before and after an intervention involving education regarding the 2017 clinical practice guidelines (CPG) for the management of febrile neutropenia in children with cancer and hematopoietic stem-cell transplant recipients. Design: Antibiotic prescribing practices were prospectively recorded between June 2016 and November 2017. Intervention: In December 2017, baseline data feedback was provided, and CPG education was provided. Prescribing practices were followed for one more year. For antibiotic stewardship, days of therapy, and length of therapy were calculated. Setting: Five of the 6 PHO units in Greece and the single pediatric BMT unit participated. Participants: Admitted children in each unit who received the first 15 new antibiotic courses each month. Results: Administration of ≥4 antibiotics simultaneously and administration of antibiotics with overlapping activity for ≥2 days were significantly more common in PHO units in general hospitals compared to children’s hospitals. Use of at least 1 antifungal was recorded in ∼47% of the patients before and after the intervention. De-escalation and/or discontinuation of antibiotics on day 6 of initial treatment increased significantly from 43% to 53.5% (P = .032). Although the number of patients requiring intensive care support for sepsis did not change, a significant drop was noted in all-cause mortality (P = .008). Conclusions: We recorded the antibiotic prescribing practices in Greek PHO and BMT units, we achieved improved prescribing with a simple intervention, and we identified areas in need of improvement.

Although psychopathy is widely conceptualised as a mental disorder, some researchers question the maladaptive nature of psychopathy, and argue that it might be advantageous from an evolutionary point of view. According to this view, psychopathy can be seen as an evolutionary adaptative strategy that relies on deception and manipulation to gain short-term reproductive benefits. Psychopathy is also identified as a fast life strategy in response to early life stress and an adaptation to harsh environments. This paper investigates the evidence that psychopathic traits are adaptive, while also addressing the limitations of current evolutionary models of psychopathy based on frequency-dependent selection and life history theory. We review recent studies on the fitness correlates of psychopathy and find that psychopathic traits present potential adaptive trade-offs between fertility and mortality, and offspring quantity and quality. On a proximate level, individual differences in stress reactivity and environmental risk factors in early development predispose to psychopathy through gene–environment interactions. We propose that environmental, developmental, social and cultural factors can mediate the relationship between psychopathic traits and fitness and therefore should be considered to make accurate predictions on the adaptive potential of psychopathy. We end by outlining gaps in the literature and making recommendations for future evolutionary research on psychopathy.

This paper studies the critical and near-critical regimes of the planar random-cluster model on $\mathbb Z^2$ with cluster-weight $q\in [1,4]$ using novel coupling techniques. More precisely, we derive the scaling relations between the critical exponents $\beta $ , $\gamma $ , $\delta $ , $\eta $ , $\nu $ , $\zeta $ as well as $\alpha $ (when $\alpha \ge 0$ ). As a key input, we show the stability of crossing probabilities in the near-critical regime using new interpretations of the notion of the influence of an edge in terms of the rate of mixing. As a byproduct, we derive a generalisation of Kesten’s classical scaling relation for Bernoulli percolation involving the ‘mixing rate’ critical exponent $\iota $ replacing the four-arm event exponent $\xi _4$ .

Some consider potatoes to be unhealthy vegetables that may contribute to adverse cardiometabolic health outcomes. We evaluated the association between potato consumption (including fried and non-fried types) and three key cardiometabolic outcomes among middle-aged and older adults in the Framingham Offspring Study. We included 2523 subjects ≥30 years of age with available dietary data from 3-d food records. Cox-proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for hypertension, type 2 diabetes or impaired fasting glucose (T2DM/IFG), and elevated triglycerides, adjusting for anthropometric, demographic and lifestyle factors. In the present study, 36 % of potatoes consumed were baked, 28 % fried, 14 % mashed, 9 % boiled and the rest cooked in other ways. Overall, higher total potato intake (≥4 v.

Most approaches to estimate ecological value use monetary valuation. Here, we propose a different framework accounting ecological value in biophysical terms. More specifically, we are implementing the ecosystem natural capital accounting framework as an operational adaptation and extension of the UN System of Economic and Environmental Accounting/Ecosystem Accounting. The proof-of-concept study was carried out at the Rhône river watershed scale (France). Four core accounts evaluate land use, water and river condition, bio-carbon content of various stocks of biomass and its uses, and the state of ecosystem infrastructure. Integration of the various indicators allows measuring ecosystems overall capability and their degradation. The 12-year results are based on spatial–temporal geographic information and local statistics. Increasing levels of intensity of use are registered over time, that is, the extraction of resources surpasses renewal. We find that agriculture and land artificialisation are the main drivers of natural capital degradation.

We examine the relative effect of warming events (storms) and snow cover on thermodynamic growth of Arctic sea ice in winter. We use a 1-D snow and ice thermodynamic model to perform sensitivity experiments. Observations from the winter period of the Norwegian young sea ICE (N-ICE2015) campaign north of Svalbard are used to initiate and force the model. The N-ICE2015 winter was characterized by frequent storm events that brought pulses of heat and moisture, and a thick snow cover atop the sea ice (0.3–0.5 m). By the end of the winter, sea-ice bottom growth was negligible. We show that the thermodynamic effect of storms to the winter sea-ice growth is controlled by the amount of snow on sea ice. For 1.3 m initial ice thickness, the decrease in ice growth caused by the warming events ranged from −1.4% (for 0.5 m of snow) to −7.5% (for snow-free conditions). The decrease in sea-ice growth caused by the thick snow (0.5 m) was more important, ranging from −17% (with storms) to −23% (without storms). The results showcase the critical role of snow on winter Arctic sea-ice growth.

Background Compliance with government-recommended preventive measures represents a key factor in mitigating the negative consequences of coronavirus disease 2019 (COVID-19). Aims The study investigated the relation between health anxiety, perceived risk and perceived control as predictors of coronavirus disease 2019 (COVID-19)-related anxiety and preventive behaviours (both adaptive and dysfunctional/excessive) during the early pandemic response in Romania. Method Data were collected in April–May 2020, and the sample comprised 236 participants, 192 women, mean age 31.44 (s.d. = 10.30, age range 16–67). Results Our results showed that health anxiety and perceived control, but not perceived risk predicted adaptive preventive behaviours, whereas dysfunctional behaviours were predicted by health anxiety alone. COVID-19-related anxiety was predicted by health anxiety and perceived risk, with perceived control emerging as a non-significant predictor. Also, we found that the effect of health anxiety on COVID-19-related anxiety was mediated by perceived risk, and that perceived control acted as a moderator in the relation between health anxiety and dysfunctional (but not adaptive) preventive behaviours. Conclusions Our results suggest health anxiety is a significant predictor of COVID-19-related anxiety and preventive behaviours. Also, adaptive, but not dysfunctional, preventive behaviours were additionally predicted by perceived control, pointing to the important role of control and self-efficacy in explaining adherence to recommendations.

Background Harassment and discrimination in the National Health Service (NHS) has steadily increased over the past 5 years with London being the worst performing region. There is a lack of data and research on the impact this is having on staff health and job satisfaction. Such data are necessary to inform the development of effective workplace interventions to mitigate the effects these experiences have on staff. Aims Examine the impact of harassment and discrimination on NHS staff working in London trusts, utilising data from the 2019 TIDES cross-sectional survey. Method In total, 931 London-based healthcare practitioners participated in the TIDES survey. Regression analysis was used to examine associations between the sociodemographic characteristics of participants, exposure to discrimination and harassment, and how such exposures are associated with physical and mental health, job satisfaction and sickness absence. Results Women, Black ethnic minority staff, migrants, nurses and healthcare assistants were most at risk of discrimination and/or harassment. Experiencing either of the main exposures was associated with probable anxiety or depression. Experiencing harassment was also associated with moderate-to-severe somatic symptoms. Finally, both witnessing and experiencing the main exposures were associated with low job satisfaction and long periods of sickness absence. Conclusions NHS staff, particularly those working in London trusts, are exposed to unprecedented levels of discrimination and harassment from their colleagues. Within the context of an already stretched and under-resourced NHS, in order to combat poor job satisfaction and high turnover rates, the value of all healthcare practitioners must be visibly and continuously reinforced by all management and senior leaders.

Climate change is one of the most significant and pressing issues faced by humanity; it frequently results in major natural disasters, such as catastrophic floods, which require the establishment of effective management policies by local and national authorities. These policies involve complex multistep decision-making processes that require combined assessment of various sources of data by different stakeholders. Even though an abundance of data is being collected to monitor climate change and estimate its consequences on the society, the environment, and the economy, policy-making is still largely based on intuition rather than evidence due to lack of a structured approach for modeling the decision-making process and considering the appropriate use of data in every step of the process. The goal of this work is to introduce a novel decision support system that can guide policy makers through a structured data-driven decision-making process aiming to create policies for flood risk management. The proposed system is a multifacet platform that guides policy makers through five phases—inform, advise, monitor, evaluate, and revise—of the policy cycle. For each phase, different dashboards provide relevant information regarding the environmental, social, and economic conditions. To demonstrate the potential of the proposed system, we use it to assess a flood protection policy in the city of Vicenza, Italy. The results reveal the benefits and challenges of the proposed decision support tool for public administrations involved in flood risk management.

Proton electrochemical gradient-driven multidrug efflux activity of representatives of the major facilitator superfamily (MFS) of secondary active transporters contributes to antimicrobial resistance of pathogenic bacteria. Integral to the mechanism of these transporters is a proposed competition between substrate and protons for the binding site of the protein. The current work investigated the competition between protons and antimicrobial substrate for binding to the Escherichia coli MFS multidrug/H+ antiporter MdtM by measuring the quench of intrinsic protein fluorescence upon titration of substrate tetraphenylphosphonium into a solution of purified MdtM over a range of pH values between pH 8.8 and 5.9. The results, which revealed that protons inhibit binding of substrate to MdtM in a competitive manner, are consistent with those reported in a study on the related MFS multidrug/H+ antiporter MdfA and provide further evidence that competition for binding between substrate and protons is a general feature of secondary multidrug efflux.

Abstract Background Neurodevelopmental disorders (NDDs) are conditions affecting a child's cognitive, behavioural, and emotional development. Appropriate and validated outcome measures for use in children with NDDs in sub-Saharan Africa are scarce. The aim of this study was to validate the Communication Profile Adapted (CP-A), a measure developed in East Africa to assess caregivers' perception of communication among children with NDDs. Methods We adapted the CP-A for use in Ethiopia, focusing on the communicative mode (CP-A-mode) and function (CP-A-function) scales. The CP-A was administered to a representative sample of caregivers of children with NDDs and clinical controls. We performed an exploratory factor analysis and determined the internal consistency, test-retest reliability, within-scale, known-group, and convergent validity of the identified factors. Results Our analysis included N = 300 participants (N = 139 cases, N = 139 clinical controls, N = 22 who did not meet criteria for either cases or controls). Within the CP-A-mode, we identified two factors (i.e. verbal and physical communication); the CP-A-function scale was unidimensional. Combining both scales into one summary variable (the CP-A-total) resulted in a scale with excellent internal consistency and test-retest reliability (Cronbach's alpha = 0.97; Kappa = 0.60–0.95, p < 0.001; ICC = 0.97, p < 0.001). Testing known-group validity, the CP-A-total scores were significantly higher for controls than cases (Δ mean = 33.93, p < 0.001). Convergent validity assessment indicated that scores were negatively and moderately correlated with clinical severity (ρ = −0.25, p = 0.04). Conclusion The CP-A is a valid tool for the assessment of communication among children with NDDs in Ethiopia. It holds promise as a brief, quantitative, and culturally appropriate outcome measure for use in sub-Saharan Africa.

Abstract Background and study objectives This study aimed to assess among Ukrainian adults: (1) knowledge of mental disorders; (2) attitudes towards people with mental health disorders, and to the delivery of mental health treatment within the community; and (3) behaviours towards people with mental disorders. Methodology A cross-sectional survey of Ukrainian adults aged 18–60 was conducted. Stigma-related mental health knowledge was measured using the mental health knowledge schedule. Attitude towards people with mental health disorders was assessed using the Community Attitudes towards Mental Illness scale. The Reported and Intended Behaviour scale was used to assess past and future intended behaviour towards people with mental health disorders. Results Associations between gender, age, and educational level and the knowledge and attitudes measures were identified. There was evidence of a positive association between being male and positive intended behaviours towards people with mental health disorders [mean difference (MD) = 0.509, 95% confidence interval (CI) 0.021–0.998]. Older age was negatively associated with positive intended behaviours towards people with mental health disorders (MD = −0.017, 95% CI 0.0733 to −0.001). Higher education was positively associated with stigma-related mental health knowledge (MD = 0.438, 95% CI 0.090–0.786), and negatively associated with authoritarian (MD = 0.755, 95% CI 0.295–1.215) attitudes towards people with mental health problems. Conclusion Overall, the findings indicate a degree of awareness of, and compassion towards, people with mental illness among Ukrainian adults, although this differed according to gender, region, and education level. Results indicate a need for the adoption and scaling-up of anti-stigma interventions that have been demonstrated to be effective.

Policy-making in local public administrations is still largely based on intuition rather than being backed up by data and evidence. The goal of this work is to introduce the methodology and software tools for contributing toward transforming the existing intuition-based paradigm of policy-making into an evidence-driven approach enabled by heterogeneous sources of data already available in the city. More specifically, methods for data collection, efficient data storage, and data analysis are implemented to measure the economic activity, assess the environmental impact and evaluate the social consequences of certain policy decisions. Subsequently, the extracted pieces of evidence are used to inform, advise, monitor, evaluate, and revise the decisions made by policy planners. Our contribution in this work is on outlining and deploying an easily extendable system architecture to harmonize and analyze heterogeneous data sources in ways that are found to be useful for policy-makers. For evaluating this architecture, we examine the case of a controlled parking system in the city of Thessaloniki and try to optimize its operation by balancing effectively between economic growth, environmental protection, and citizen satisfaction.

The concept of a “digital twin” as a model for data-driven management and control of physical systems has emerged over the past decade in the domains of manufacturing, production, and operations. In the context of buildings and civil infrastructure, the notion of a digital twin remains ill-defined, with little or no consensus among researchers and practitioners of the ways in which digital twin processes and data-centric technologies can support design and construction. This paper builds on existing concepts of Building Information Modeling (BIM), lean project production systems, automated data acquisition from construction sites and supply chains, and artificial intelligence to formulate a mode of construction that applies digital twin information systems to achieve closed loop control systems. It contributes a set of four core information and control concepts for digital twin construction (DTC), which define the dimensions of the conceptual space for the information used in DTC workflows. Working from the core concepts, we propose a DTC information system workflow—including information stores, information processing functions, and monitoring technologies—according to three concentric control workflow cycles. DTC should be viewed as a comprehensive mode of construction that prioritizes closing the control loops rather than an extension of BIM tools integrated with sensing and monitoring technologies.

AbstractBackground.Premorbid adjustment (PA) abnormalities in psychotic disorders are associated with an earlier age at onset (AAO) and unfavorable clinical outcomes, including treatment resistance. Prior family studies suggest that familial liability, likely reflecting increased genetic risk, and socioeconomic status (SES) contribute to premorbid maladjustment. However, their joint effect possibly indicating gene–environment interaction has not been evaluated.Methods.We examined whether family history of psychosis (FHP) and parental SES may predict PA and AAO in unrelated cases with first-episode psychosis (n = 108) and schizophrenia (n = 104). Premorbid academic and social functioning domains during childhood and early adolescence were retrospectively assessed. Regression analyses were performed to investigate main effects of FHP and parental SES, as well as their interaction. The relationships between PA, AAO, and response to antipsychotic medication were also explored.Results.Positive FHP associated with academic PA difficulties and importantly interacted with parental SES to moderate social PA during childhood (interaction p = 0.024). Positive FHP and parental SES did not predict differences in AAO. Nevertheless, an earlier AAO was observed among cases with worse social PA in childhood (β = −0.20; p = 0.005) and early adolescence (β = −0.19; p = 0.007). Further, confirming evidence emerged for an association between deficient childhood social PA and poor treatment response (p = 0.04).Conclusions.Familial risk for psychosis may interact with parental socioeconomic position influencing social PA in childhood. In addition, this study supports the link between social PA deviations, early psychosis onset, and treatment resistance, which highlights premorbid social functioning as a promising clinical indicator.

This manuscript reports structure–function studies of Catechol 2,3-dioxygenase (C23O64), which is the second enzyme in the metabolic degradation pathway of 3-nitrotoluene by Diaphorobacter sp. strain DS2. The recombinant protein is a ring cleavage enzyme for 3-methylcatechol and 4-methylcatechol products formed after dioxygenation of the aromatic ring. Here we report the substrate-free, substrate-bound, and substrate-analog bound crystal structures of C23O64. The protein crystallizes in the P6(2)22 space-group. The structures were determined by molecular replacement and refined to resolutions of 2.4, 2.4, 2.2 Å, respectively. A comparison of the structures with related extradiol dioxygenases showed 22 conserved residues. A comparison of the active site pocket with catechol 2,3-dioxygenase (LapB) from Pseudomonas sp KL28 and homoprotocatechuate 2,3-dioxygenase (HPCD) from Brevibacterium fuscum shows significant similarities to suggest that the mechanism of enzyme action is similar to HPCD.

OBJECTIVES/SPECIFIC AIMS: The overall objective of this study is to develop a novel, clinically-relevant, image-guided mouse model for radiation-induced cardiotoxicity, which can be used to gain insight into clinically-targetable, pathophysiologic mechanisms of cardiac injury in thoracic radiotherapy patients. METHODS/STUDY POPULATION: Photon or sham radiation will be administered at differential doses to a defined portion of the heart and/or lungs of C57BL/6 female mice using micro-CT visualization of the heart with Xstrahl’s MuriSlice Software applied to the Small Animal Radiation Research Platform (SARRP). Cardiac and lung segments from a subset of mice will be harvested at specific time points for confirmation of radiation targeting, local apoptosis assessment, and evaluation of fibrosis and vascular tissue morphology. Quantitative echocardiography, myocardial 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT), and myocardial perfusion imaging (MPI) with Technicium-99 (Tc-99) sestamibi will be implemented to identify sensitive imaging measures of cardiac injury and asses myocardial mechanics, inflammation, and perfusion deficits, respectively. Concurrently, a multiparametric analysis will be conducted to identify novel, circulating biomarkers of cardiotoxicity. RESULTS/ANTICIPATED RESULTS: We hypothesize that a clinically-relevant mouse model can be generated by the in situ, focal irradiation of a portion of heart and/or lung tissue segments, and can be used to elucidate molecular mechanisms of radiation-induced cardiac damage. We anticipate time-dependent and dose-dependent, focal histopathologic changes in the mouse heart, with cardiac fibrosis development, vascular damage, and cellular apoptosis in irradiated mice. Additionally, we anticipate that our mouse model of focal heart irradiation will reveal radiologic and biochemical changes that can be used to characterize and predict radiation-induced cardiac injury. Specifically, we expect our quantitative echocardiography, FDG-PET, and MPI parameters to identify and characterize cardiac damage that topographically matches histopathological analysis, and expect levels of select biochemical markers to differentially vary with time. DISCUSSION/SIGNIFICANCE OF IMPACT: Our mouse model of radiation-induced cardiotoxicity has the potential to shift current preclinical research paradigms to more closely mimic the radiation plans most commonly administered in clinical practice. The primary technologic innovation to be developed here is the use of the SARRP to deliver image-guided, in situ, focal radiation to a defined portion of the mouse heart. From a conceptual perspective, we propose a novel approach for phenotyping radiation-induced cardiac damage in patients undergoing chest radiation therapy, integrating sensitive radiomic and biochemical markers into a predictive model of cardiotoxicity.

Aims and method The new 2021 UK Foundation Programme Curriculum mandates foundation doctors to acquire mental health competencies. This study aimed to evaluate the effectiveness of psychiatry placements in facilitating competency attainment, foundation doctors’ perceived importance of acquiring these and their preferred teaching methods. Utilising Kirkpatrick's evaluation framework, the study employed a pre–post intervention design assessing the impact of psychiatry placements on 135 foundation doctors across three cohorts from August 2021 to March 2022. Results Initially, foundation doctors assigned high importance to mental health competencies. Post-placements, this perceived importance improved slightly, whereas that of clinical skills scenarios slightly decreased. Significant confidence increases were observed in recognising and assessing specific psychiatric disorders. Foundation doctors favoured small seminar groups and on-the-job ad hoc teaching. Qualitative insights underscored the need for context-specific teaching. Clinical implications Psychiatry placements enhance foundation doctors’ confidence and perceived importance of mental health competencies as specified by the curriculum. Addressing clinical scenario gaps through context-specific teaching and transferable skills development is essential. Customised teaching approaches, especially small seminars and ad hoc teaching, hold promise for effective mental health training.

Aims and method There is currently a lack of monitoring and standardisation of diabetes care in the National Health Service (NHS) psychiatric in-patient setting. We surveyed healthcare professionals in psychiatric in-patient units across England to understand current diabetes care. A 13-item questionnaire was piloted via think-aloud interviews. The survey was completed by healthcare professionals across 19 wards in 11 NHS mental health trusts. Results were analysed via descriptive statistics and thematic analysis. Results Of 150 respondents, 98% agreed that addressing physical health needs was an important part of the mental health team's role; 68% agreed that they had adequate skills and knowledge to manage diabetes safely. Thematic analysis identified themes relating to individual, organisational and patient-level factors. Clinical implications Psychiatric admission could be used opportunistically to improve the healthcare disparities for people with comorbid diabetes and severe mental illness. This national survey highlights areas that need to be addressed to optimise diabetes care in this setting.