3D matrix adhesion feedback controls nuclear force coupling to drive invasive cell migration.

Cell invasion is a multi-step process, initiated by the acquisition of a migratory phenotype and the ability to move through complex 3D extracellular environments. We determine the composition of cell-matrix adhesion complexes of invasive breast cancer cells in 3D matrices and identify an interaction complex required for invasive migration. ßPix and myosin18A (Myo18A) drive polarized recruitment of non-muscle myosin 2A (NM2A) to adhesion complexes at the tips of protrusions. Actomyosin force engagement then displaces the Git1-ßPix complex from paxillin, establishing a feedback loop for adhesion maturation. We observe active force transmission to the nucleus during invasive migration that is needed to pull the nucleus forward. The recruitment of NM2A to adhesions creates a non-muscle myosin isoform gradient, which extends from the protrusion to the nucleus. We postulate that this gradient facilitates coupling of cell-matrix interactions at the protrusive cell front with nuclear movement, enabling effective invasive migration and front-rear cell polarity.

A synthetic delivery vector for mucosal vaccination.

The success of mRNA-based vaccines during the Covid-19 pandemic has highlighted the value of this new platform for vaccine development against infectious disease. However, the CD8+ T cell response remains modest with mRNA vaccines, and these do not induce mucosal immunity, which would be needed to prevent viral spread in the healthy population. To address this drawback, we developed a dendritic cell targeting mucosal vaccination vector, the homopentameric STxB. Here, we describe the highly efficient chemical synthesis of the protein, and its in vitro folding. This straightforward preparation led to a synthetic delivery tool whose biophysical and intracellular trafficking characteristics were largely indistinguishable from recombinant STxB. The chemical approach allowed for the generation of new variants with bioorthogonal handles. Selected variants were chemically coupled to several types of antigens derived from the mucosal viruses SARS-CoV-2 and type 16 human papillomavirus. Upon intranasal administration in mice, mucosal immunity, including resident memory CD8+ T cells and IgA antibodies was induced against these antigens. Our study thereby identifies a novel synthetic antigen delivery tool for mucosal vaccination with an unmatched potential to respond to an urgent medical need.

Comparing Anxiety and Depression in Information Technology Workers with Others in Employment: A UK Biobank Cohort Study.

OBJECTIVES: Despite reported psychological hazards of information technology (IT) work, studies of diagnosed mental health conditions in IT workers are lacking. We investigated self-reported mental health outcomes and incident anxiety/depression in IT workers compared to others in employment in a large population-based cohort. METHODS: We evaluated self-reported mental health outcomes in the UK Biobank cohort and incident diagnosed anxiety/depression through health record linkage. We used logistic regression and Cox models to compare the risks of prevalent and incident anxiety/depression among IT workers with all other employed participants. Furthermore, we compared outcomes within IT worker subgroups, and between these subgroups and other similar occupations within their major Standard Occupational Classification (SOC) group. RESULTS: Of 112 399 participants analyzed, 4093 (3.6%) were IT workers. At baseline, IT workers had a reduced odds (OR = 0.66, 95%CI: 0.52-0.85) of anxiety/depression symptoms and were less likely (OR = 0.87, 95%CI: 0.83-0.91) to have ever attended their GP for anxiety/depression, compared to all other employed participants, after adjustment for confounders. The IT technician subgroup were more likely (OR = 1.22, 95%CI: 1.07-1.40) to have previously seen their GP or a psychiatrist (OR = 1.31, 95%CI: 1.06-1.62) for anxiety/depression than their SOC counterparts. IT workers had lower incident anxiety/depression (HR = 0.84, 95%CI 0.77-0.93) compared to all other employed participants, after adjustment for confounders. CONCLUSIONS: Our findings from this, the first longitudinal study of IT worker mental health, set the benchmark in our understanding of the mental health of this growing workforce and identification of high-risk groups. This will have important implications for targeting mental health workplace interventions.

A comparison of routine and case-managed pathways for recovery from musculoskeletal disorders in people in employment.

PURPOSE: To compare outcomes in employed people from an enhanced routine management pathway for musculoskeletal disorders within National Health Service Scotland with an existing active case-management system, Working Health Services Scotland. MATERIALS AND METHODS: The study comprised a service evaluation using anonymised routinely collected data from all currently employed callers presenting with musculoskeletal disorder to the two services. Baseline demographic and clinical data were collected. EuroQol EQ-5DTM scores at the start and end of treatment were compared for both groups, overall and by age, sex, socio-economic status, and anatomical site, and the impact of mental health status at baseline was evaluated. RESULTS: Active case-management resulted in greater improvement than enhanced routine care. Case-managed service users entered the programme earlier in the recovery pathway; there was evidence of spontaneous improvement during the longer waiting time of routine service clients but only if they had good baseline mental health. Those most disadvantaged through mental health co-morbidity showed the greatest benefit. CONCLUSIONS: People with musculoskeletal disorders who have poor baseline mental health status derive greatest benefit from active case-management. Case-management therefore contributes to reducing health inequalities and can help to minimise long-term sickness absence. Shorter waiting times contributed to better outcomes in the case-managed service. Implications for RehabilitationMusculoskeletal disorders are a major cause of inability to work.Case-management is effective in helping people with musculoskeletal disorders to return to work.People who have the poorest mental health are likely to gain the greatest benefit from case-management of their musculoskeletal disorders.

Using candidacy theory to explore unemployed over-50s perceptions of suitability of a welfare to work programme: A longitudinal qualitative study.

Welfare to work interventions seek to move out-of-work individuals from claiming unemployment benefits towards paid work. However, previous research has highlighted that for over-50s, particularly those with chronic health conditions, participation in such activities are less likely to result in a return to work. Using longitudinal semi-structured interviews, we followed 26 over-50s during their experience of a mandated welfare to work intervention (the Work Programme) in the United Kingdom. Focusing on their perception of suitability, we utilise and adapt Candidacy Theory to explore how previous experiences of work, health, and interaction with staff (both in the intervention, and with healthcare practitioners) influence these perceptions. Despite many participants acknowledging the benefit of work, many described a pessimism regarding their own ability to return to work in the future, and therefore their lack of suitability for this intervention. This was particularly felt by those with chronic health conditions, who reflected on difficulties with managing their conditions (e.g., attending appointments, adhering to treatment regimens). By adapting Candidacy Theory, we highlighted the ways that mandatory intervention was navigated by all the participants, and how some discussed attempts to remove themselves from this intervention. We also discuss the role played by decision makers such as employment-support staff and healthcare practitioners in supporting or contesting these feelings. Findings suggest that greater effort is required by policy makers to understand the lived experience of chronic illness in terms of ability to RTW, and the importance of inter-agency work in shaping perceptions of those involved.

What is meant by case management for the return-to-work of workers with musculoskeletal disorders? A scoping review.

BACKGROUND: Case management interventions have shown to be effective to prevent musculoskeletal pain and disability, but a single definition has not been achieved, nor an agreed profile for case managers. OBJECTIVE: To describe the elements that define case management and case managers tasks for return-to-work of workers with musculoskeletal disorders (MSDs). METHODS: A comprehensive computerized search of articles published in English until February 16, 2021 was carried out in several bibliographic databases. Grey literature was obtained through a search of 13 key websites. A peer-review screening of titles and abstracts was carried out. Full text in-depth analysis of the selected articles was performed for data extraction and synthesis of results. RESULTS: We identified 2,422 documents. After full-text screening 31 documents were included for analysis. These were mostly European and North American and had an experimental design. Fifteen documents were published between 2010 to 2021 and of these 7 studies were published from 2015. Fifteen elements were identified being the commonest "return-to-work programme" (44.4%) and "multidisciplinary assessment/interdisciplinary intervention" (44.4%). Of 18 tasks found, the most frequent was "establishing goals and planning return-to-work rehabilitation" (57.7%). Eighteen referral services were identified. CONCLUSIONS: Despite there were several elements frequently reported, some elements with scientific evidence of their importance to deal with MSDs (e.g. early return-to-work) were almost not mentioned. This study proposes key points for the description of case management and case managers tasks.

Contamination of Air and Surfaces in Workplaces with SARS-CoV-2 Virus: A Systematic Review.

OBJECTIVES: This systematic review aimed to evaluate the evidence for air and surface contamination of workplace environments with SARS-CoV-2 RNA and the quality of the methods used to identify actions necessary to improve the quality of the data. METHODS: We searched Web of Science and Google Scholar until 24 December 2020 for relevant articles and extracted data on methodology and results. RESULTS: The vast majority of data come from healthcare settings, with typically around 6% of samples having detectable concentrations of SARS-CoV-2 RNA and almost none of the samples collected had viable virus. There were a wide variety of methods used to measure airborne virus, although surface sampling was generally undertaken using nylon flocked swabs. Overall, the quality of the measurements was poor. Only a small number of studies reported the airborne concentration of SARS-CoV-2 virus RNA, mostly just reporting the detectable concentration values without reference to the detection limit. Imputing the geometric mean air concentration assuming the limit of detection was the lowest reported value, suggests typical concentrations in healthcare settings may be around 0.01 SARS-CoV-2 virus RNA copies m-3. Data on surface virus loading per unit area were mostly unavailable. CONCLUSIONS: The reliability of the reported data is uncertain. The methods used for measuring SARS-CoV-2 and other respiratory viruses in work environments should be standardized to facilitate more consistent interpretation of contamination and to help reliably estimate worker exposure.

Clinical Case Complexity in Occupational Health: Contributing Factors and a Proposed Conceptual Framework Model.

OBJECTIVES: Clinical case complexity is an inherent factor in occupational health (OH), yet it is poorly defined and understood. Our aim was to identify the multiple sources of complexity in OH and propose a conceptual complexity framework model for clinical OH practice. METHODS: Through a scoping review, expert panel consensus, and content analysis of OH clinical case reports, we identified relevant complexity-contributing factors (CCFs) specifically tailored to the OH setting, which we defined and validated. RESULTS: The proposed model consists of three primary domains (PDs); health factors, workplace factors and biopsychosocial factors. Twenty-seven CCFs are described and defined within these PDs. CONCLUSIONS: This work lays the foundation for improved understanding, identification, and assessment of complexity in OH. This is imperative for ensuring high quality clinical practice standards, identifying training needs and appropriate triaging/resource allocation.

Finding Purpose in the Conservation of Biodiversity by the Commingling of Science and Ethics.

Averting the biodiversity crisis requires closing a gap between how humans tend to behave, individually and collectively, and how we ought to behave-"ought to" in the sense of behaviors required to avert the biodiversity crisis. Closing that gap requires synthesizing insight from ethics with insights from social and behavioral sciences. This article contributes to that synthesis, which presents in several provocative hypotheses: (i) Lessening the biodiversity crisis requires promoting pro-conservation behavior among humans. Doing so requires better scientific understanding of how one's sense of purpose in life affects conservation-relevant behaviors. Psychology and virtue-focused ethics indicate that behavior is importantly influenced by one's purpose. However, conservation psychology has neglected inquiries on (a) the influence of one's purpose (both the content and strength of one's purpose) on conservation-related behaviors and (b) how to foster pro-conservation purposes; (ii) lessening the biodiversity crisis requires governance-the regulation of behavior by governments, markets or other organization through various means, including laws, norms, and power-to explicitly take conservation as one of its fundamental purposes and to do so across scales of human behaviors, from local communities to nations and corporations; (iii) lessening the biodiversity crisis requires intervention via governance to nudge human behavior in line with the purpose of conservation without undue infringement on other basic values. Aligning human behavior with conservation is inhibited by the underlying purpose of conservation being underspecified. Adequate specification of conservation's purpose will require additional interdisciplinary research involving insights from ethics, social and behavioral sciences, and conservation biology.

Connecting the dots: combined control of endocytic recycling and degradation.

Endocytosis is an essential process where proteins and lipids are internalised from the plasma membrane in membrane-bound carriers, such as clathrin-coated vesicles. Once internalised into the cell these vesicles fuse with the endocytic network where their contents are sorted towards degradation in the lysosome or recycling to their origin. Initially, it was thought that cargo recycling is a passive process, but in recent years the identification and characterisation of specialised recycling complexes has established a hitherto unthought-of level of complexity that actively opposes degradation. This review will summarise recent developments regarding the composition and regulation of the recycling machineries and their relationship with the degradative pathways of the endosome.

Occupation and risk of severe COVID-19: prospective cohort study of 120 075 UK Biobank participants.

OBJECTIVES: To investigate severe COVID-19 risk by occupational group. METHODS: Baseline UK Biobank data (2006-10) for England were linked to SARS-CoV-2 test results from Public Health England (16 March to 26 July 2020). Included participants were employed or self-employed at baseline, alive and aged <65 years in 2020. Poisson regression models were adjusted sequentially for baseline demographic, socioeconomic, work-related, health, and lifestyle-related risk factors to assess risk ratios (RRs) for testing positive in hospital or death due to COVID-19 by three occupational classification schemes (including Standard Occupation Classification (SOC) 2000). RESULTS: Of 120 075 participants, 271 had severe COVID-19. Relative to non-essential workers, healthcare workers (RR 7.43, 95% CI 5.52 to 10.00), social and education workers (RR 1.84, 95% CI 1.21 to 2.82) and other essential workers (RR 1.60, 95% CI 1.05 to 2.45) had a higher risk of severe COVID-19. Using more detailed groupings, medical support staff (RR 8.70, 95% CI 4.87 to 15.55), social care (RR 2.46, 95% CI 1.47 to 4.14) and transport workers (RR 2.20, 95% CI 1.21 to 4.00) had the highest risk within the broader groups. Compared with white non-essential workers, non-white non-essential workers had a higher risk (RR 3.27, 95% CI 1.90 to 5.62) and non-white essential workers had the highest risk (RR 8.34, 95% CI 5.17 to 13.47). Using SOC 2000 major groups, associate professional and technical occupations, personal service occupations and plant and machine operatives had a higher risk, compared with managers and senior officials. CONCLUSIONS: Essential workers have a higher risk of severe COVID-19. These findings underscore the need for national and organisational policies and practices that protect and support workers with an elevated risk of severe COVID-19.

Role of age and health in perceptions of returning to work: a qualitative study.

BACKGROUND: People aged over 50 years form a growing proportion of the working age population, but are at increased risk of unemployment compared to other age groups. It is often difficult to return to work after unemployment, particularly for those with health issues. In this paper, we explored the perceptions, attitudes, and experiences of returning to work after a period of unemployment (hereafter RTW) barriers among unemployed adults aged over 50 years. METHOD: In-depth semi-structured interviews were conducted with a diverse sample of 26 unemployed individuals aged 50-64 years who were engaged with the UK Government's Work Programme. Data were thematically analysed. RESULTS: Age alone was not discussed by participants as a barrier to work; rather their discussions of barriers to work focused on the ways in which age influenced other issues in their lives. For participants reporting chronic health conditions, or disabilities, there was a concern about being unfit to return to their previous employment area, and therefore having to "start again" in a new career, with associated concerns about their health status and managing their treatment burden. Some participants also reported experiencing either direct or indirect ageism (including related to their health status or need to access healthcare) when looking for work. Other issues facing older people included wider socio-political changes, such as the increased pension age, were felt to be unfair in many ways and contradicted existing expectations of social roles (such as acting as a carer for other family members). CONCLUSION: Over-50s experienced multiple and interacting issues, at both the individual and societal level, that created RTW barriers. There is a need for employability interventions that focus on supporting the over-50s who have fallen out of the labour market to take a holistic approach, working across healthcare, employability and the local labour market, providing treatment and skills training for both those out of work and for employers, in order to create an intervention that that helps achieve RTW and its associated health benefit.

Conservation geopolitics.

We reviewed recent work concerning the impact of geopolitics on wildlife conservation (and vice versa) and identified future priorities in conservation geopolitics research. Geopolitics is understood as both an analytical focus on geopolitical practices (especially concerning the behavior) of countries with respect to territory and national security and a set of theories developed to explain and predict those behaviors. We developed a typology of core geopolitical practices of relevance to conservation: territorial practices of colonization and the management of migrations and borders, and security practices relating to military, economic, and environmental security. We identified research that considers how these practices affect conservation situations and outcomes, noting the recent emergence of conceptual developments such as "environmental geopolitics" and "geopolitical ecology" that draw on multiple fields within the social sciences to theorize the links between geopolitics and environmental management. We defined a "geopolitical perspective" as a focus on geopolitical practices combined with an explicit engagement with geopolitical theory and identified conservation situations where this perspective could contribute to analytical clarity. We suggest the most pressing questions in conservation research to which the geopolitical perspective might contribute are how political and economic differences between countries affect biodiversity outcomes, how geopolitical practices to address those differences facilitate or frustrate conservation efforts, how national borders and human and wildlife movements can be better managed for the benefit of both, and how the most effective conservation strategies can be best selected to suit existing (and future) geopolitical realities.

Geopolítica de la Conservación Resumen Revisamos el trabajo reciente relativo al impacto que tiene la geopolítica sobre la conservación de la vida silvestre (y viceversa) e identificamos prioridades futuras para la investigación de la geopolítica de la conservación. Se define a la geopolítica como un enfoque analítico en las prácticas geopolíticas (especialmente en relación con el comportamiento) de los países con respecto al territorio y a la seguridad nacional y como un conjunto de teorías desarrolladas para explicar y predecir aquellos comportamientos. Desarrollamos una tipología de prácticas nucleares de geopolítica relevantes para la conservación: prácticas territoriales de colonización y el manejo de migraciones y de las fronteras, y prácticas de seguridad relacionadas con la seguridad militar, económica y ambiental. Identificamos las investigaciones que consideran cómo estas prácticas afectan a las situaciones de conservación y sus resultados, tomando en cuenta el surgimiento reciente de desarrollos conceptuales como los de "geopolítica ambiental" y "ecología geopolítica" que parten de múltiples campos de estudio situados dentro de las ciencias sociales para teorizar las conexiones entre la geopolítica y el manejo ambiental. Definimos una perspectiva geopolítica como el enfoque en las prácticas geopolíticas combinada con una participación explícita de la teoría geopolítica e identificamos situaciones de conservación en donde esta perspectiva podría contribuir a la claridad analítica. Sugerimos que las preguntas más urgentes para la investigación en la conservación para las cuales la perspectiva geopolítica podría contribuir son cómo las diferencias políticas y económicas entre los países afectan a los resultados de la biodiversidad, cómo las prácticas geopolíticas abordan esas diferencias facilita o frustra los esfuerzos de conservación, cómo las fronteras nacionales y los movimientos humanos y faunísticos pueden manejarse de mejor manera para el beneficio de ambos, y cómo las estrategias de conservación más efectivas pueden seleccionarse de mejor forma para acoplarse a las realidades geopolíticas existentes (y futuras).

Age, health and other factors associated with return to work for those engaging with a welfare-to-work initiative: a cohort study of administrative data from the UK's Work Programme.

OBJECTIVES: To investigate the role of individual factors (including age, health and personal circumstances) and external factors associated with clients having a job start while engaging with the Work Programme and variations by benefit type. SETTING: The UK Government's main return to work initiative (The Work Programme) in Scotland. DESIGN: Piecewise Poisson regression to calculate incident rate ratios using administrative data from 2013 to 2016 to identify factors associated with job start. PARTICIPANTS: 4322 Employment and Support Allowance (ESA) clients not in work due to poor health and 8996 Jobseeker's Allowance (JSA) clients, aged 18-64 years, referred to the Work Programme between April 2013 and July 2014. MAIN OUTCOME MEASURES: Starting a job and the time to first job start after entering the Work Programme. RESULTS: JSA clients (62%) were more likely to return to work (RTW) than ESA clients (20%). There is a strong negative relationship between age and the predicted probability of having a job start during the 2-year engagement with the programme for both JSA and ESA clients. JSA clients were most likely to RTW in the first 3 months, while for ESA clients the predicted probability of having a first job start was fairly constant over the 2 years. Health, including the number of health conditions, length of unemployment, client perception of job start and other individual factors were associated with job starts for both groups. CONCLUSIONS: Age plays an important role in influencing RTW; however, important potentially modifiable factors include the length of unemployment, the management of multimorbidity and the individual's perception of the likelihood of job start. Future welfare-to-work programmes may be improved by providing age-specific interventions which focus on health and biopsychosocial factors to enable more people to realise the potential health benefits of RTW.

Simulating impacts of rapid forest loss on population size, connectivity and genetic diversity of Sunda clouded leopards (Neofelis diardi) in Borneo.

Habitat loss is the greatest threat to biodiversity in Borneo, and to anticipate and combat its effects it is important to predict the pattern of loss and its consequences. Borneo is a region of extremely high biodiversity from which forest is being lost faster than in any other. The little-known Sunda clouded leopard (Neofelis diardi) is the top predator in Borneo and is likely to depend critically on habitat connectivity that is currently being rapidly lost to deforestation. We modeled the effects of landscape fragmentation on population size, genetic diversity and population connectivity for the Sunda clouded leopard across the entirety of Borneo. We modelled the impacts of land use change between the years 2000, 2010 and projected forwards to 2020. We found substantial reductions across all metrics between 2000 and 2010: the proportion of landscape connected by dispersal fell by approximately 12.5% and the largest patch size declined by around 15.1%, leading to a predicted 11.4% decline in clouded leopard numbers. We also predict that these trends will accelerate greatly towards 2020, with the percentage of the landscape being connected by dispersal falling by about 57.8%, the largest patch size falling by around 62.8% and the predicted clouded leopard population falling by 62.5% between 2010 and 2020. We predicted that these large declines in clouded leopard population size and connectivity will also substantially reduce the genetic diversity of the remaining clouded leopard population.

Current research priorities for UK occupational physicians and occupational health researchers: a modified Delphi study.

OBJECTIVES: Studies identifying national occupational health (OH) research priorities have been conducted in several countries to establish where OH research should be focused and where funding should be targeted. However, the UK findings are now over 20 years old, and OH practice is continuously evolving. The aim of this study was to identify current research priorities for UK occupational physicians (OPs) and occupational health researchers (OHRs). METHODS: Current research priorities in OH were identified using a modified Delphi technique. This was conducted in two rounds to achieve consensus. Research priorities were rated, and then ranked using questionnaires developed from expert panel discussions, key research topics identified from the medical literature and participant feedback. Overall and intergroup comparisons were completed for the ranking scores. RESULTS: Consensus among OPs and OHRs was high with almost all (9/10) primary domains rated as 'very important' or 'absolutely necessary' by more than 54% of respondents. The research priority areas ranked highest were jointly economic evaluation/cost effectiveness studies and disability management followed by occupational disease/injury/illness. Occupational health policy was ranked lowest after sickness absence management and health promotion. The secondary domain analysis identified priority emphasis on mental health and psychosocial hazards within the workplace and the need to further develop evidence-based guidance for clinical OH practice. CONCLUSIONS: We identified the current research priorities for UK OPs and OHRs. The findings will inform future national OH research strategy and support research that addresses important knowledge gaps within OH and other interdisciplinary specialties.