Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

Organizational citizenship behaviour as a protective factor against the occurrence of adverse nursing-sensitive outcomes: A multilevel investigation.

AIMS: This study aimed to investigate the association between organizational citizenship behaviour enacted by nurses and the occurrence of adverse nursing-sensitive patient outcomes. BACKGROUND: Managing psychosocial factors (i.e., aspects concerning the work environment) is key to ensure patient safety, to prevent exacerbation of case complexity and to cope with critical shortages in human and financial resources. METHODS: Self-report measures of nurses' organizational citizenship behaviour were combined with objective data on the incidence of adverse nursing-sensitive outcomes (i.e., pressure ulcers and restraint use) collected through patients' medical records. Participants were 11,345 patients and 1346 nurses across 52 teams working in 14 Italian hospitals. Data were analysed using multilevel binary logistic regression models. RESULTS: A negative relationship between nurses' organizational citizenship behaviour and restraint use was identified, with an odds ratio of 0.11. Thus, for a one-unit higher organizational citizenship behaviour score, the odds of using restraints shrink to about one eighth of the previous level. CONCLUSIONS: Intervention strategies to foster the implementation of organizational citizenship behaviour among nurses may inhibit the occurrence of critical outcomes affecting patients' health and well-being (i.e., using restraint devices). IMPLICATIONS FOR NURSING MANAGEMENT: In health care organizations, shaping a psychosocial environment encouraging organizational citizenship behaviour can mitigate the occurrence of adverse nursing-sensitive outcomes such as restraint use on patients.

Implementation of an organizational intervention to improve low-wage food service workers' safety, health and wellbeing: findings from the Workplace Organizational Health Study.

BACKGROUND: Many organizational interventions aim to improve working conditions to promote and protect worker safety, health, and well-being. The Workplace Organizational Health Study used process evaluation to examine factors influencing implementation of an organizational intervention. This paper examines the extent to which the intervention was implemented as planned, the dose of intervention implemented, and ways the organizational context hindered or facilitated the implementation of the intervention. METHODS: This proof-of-concept trial was conducted with a large, multinational company that provides food service through contractual arrangements with corporate clients. The 13-month intervention was launched in five intervention sites in October 2018. We report findings on intervention implementation based on process tracking and qualitative data. Qualitative data from 25 post-intervention interviews and 89 process tracking documents were coded and thematically analyzed. RESULTS: Over the 13-month intervention, research team representatives met with site managers monthly to provide consultation and technical assistance on safety and ergonomics, work intensity, and job enrichment. Approximately two-thirds of the planned in-person or phone contacts occurred. We tailored the intervention to each site as we learned more about context, work demands, and relationships. The research team additionally met regularly with senior leadership and district managers, who provided corporate resources and guidance. By assessing the context of the food service setting in which the intervention was situated, we explored factors hindering and facilitating the implementation of the intervention. The financial pressures, competing priorities and the fast-paced work environment placed constraints on site managers' availability and limited the full implementation of the intervention. CONCLUSIONS: Despite strong support from corporate senior leadership, we encountered barriers in the implementation of the planned intervention at the worksite and district levels. These included financial demands that drove work intensity; turnover of site and district managers disrupting continuity in the implementation of the intervention; and staffing constraints that further increased the work load and pace. Findings underscore the need for ongoing commitment and support from both the parent employer and the host client. TRIAL REGISTRATION: This study was retrospectively registered with the Clinical Trials. Gov Protocol and Results System on June 2, 2021 with assigned registration number NCT04913168 .

Preparation, Single-Molecule Manipulation, and Energy Transfer Investigation of a Polyfluorene-graft-DNA polymer.

Conjugated polymers have been intensively studied due to their unique optical and electronic properties combined with their physical flexibility and scalable bottom up synthesis. Although the bulk qualities of conjugated polymers have been extensively utilized in research and industry, the ability to handle and manipulate conjugated polymers at the nanoscale lacks significantly behind. Here, the toolbox for controlled manipulation of conjugated polymers was expanded through the synthesis of a polyfluorene-DNA graft-type polymer (poly(F-DNA)). The polymer possesses the characteristics associated with the conjugated polyfluorene backbone, but the protruding single-stranded DNA provides the material with an exceptional addressability. This study demonstrates controlled single-molecule patterning of poly(F-DNA), as well as energy transfer between two different polymer-DNA conjugates. Finally, highly efficient DNA-directed quenching of polyfluorene fluorescence was shown.

Using kaizen to improve employee well-being: Results from two organizational intervention studies.

Participatory intervention approaches that are embedded in existing organizational structures may improve the efficiency and effectiveness of organizational interventions, but concrete tools are lacking. In the present article, we use a realist evaluation approach to explore the role of kaizen, a lean tool for participatory continuous improvement, in improving employee well-being in two cluster-randomized, controlled participatory intervention studies. Case 1 is from the Danish Postal Service, where kaizen boards were used to implement action plans. The results of multi-group structural equation modeling showed that kaizen served as a mechanism that increased the level of awareness of and capacity to manage psychosocial issues, which, in turn, predicted increased job satisfaction and mental health. Case 2 is from a regional hospital in Sweden that integrated occupational health processes with a pre-existing kaizen system. Multi-group structural equation modeling revealed that, in the intervention group, kaizen work predicted better integration of organizational and employee objectives after 12 months, which, in turn, predicted increased job satisfaction and decreased discomfort at 24 months. The findings suggest that participatory and structured problem-solving approaches that are familiar and visual to employees can facilitate organizational interventions.

Interacting environmental mosaics drive geographic variation in mussel performance and predation vulnerability.

Although theory suggests geographic variation in species' performance is determined by multiple niche parameters, little consideration has been given to the spatial structure of interacting stressors that may shape local and regional vulnerability to global change. Here, we use spatially explicit mosaics of carbonate chemistry, food availability and temperature spanning 1280 km of coastline to test whether persistent, overlapping environmental mosaics mediate the growth and predation vulnerability of a critical foundation species, the mussel Mytilus californianus. We find growth was highest and predation vulnerability was lowest in dynamic environments with frequent exposure to low pH seawater and consistent food. In contrast, growth was lowest and predation vulnerability highest when exposure to low pH seawater was decoupled from high food availability, or in exceptionally warm locations. These results illustrate how interactions among multiple drivers can cause unexpected, yet persistent geographic mosaics of species performance, interactions and vulnerability to environmental change.

A participatory physical and psychosocial intervention for balancing the demands and resources among industrial workers (PIPPI): study protocol of a cluster-randomized controlled trial.

BACKGROUND: Need for recovery and work ability are strongly associated with high employee turnover, well-being and sickness absence. However, scientific knowledge on effective interventions to improve work ability and decrease need for recovery is scarce. Thus, the present study aims to describe the background, design and protocol of a cluster randomized controlled trial evaluating the effectiveness of an intervention to reduce need for recovery and improve work ability among industrial workers. METHODS/DESIGN: A two-year cluster randomized controlled design will be utilized, in which controls will also receive the intervention in year two. More than 400 workers from three companies in Denmark will be aimed to be cluster randomized into intervention and control groups with at least 200 workers (at least 9 work teams) in each group. An organizational resources audit and subsequent action planning workshop will be carried out to map the existing resources and act upon initiatives not functioning as intended. Workshops will be conducted to train leaders and health and safety representatives in supporting and facilitating the intervention activities. Group and individual level participatory visual mapping sessions will be carried out allowing team members to discuss current physical and psychosocial work demands and resources, and develop action plans to minimize strain and if possible, optimize the resources. At all levels, the intervention will be integrated into the existing organization of work schedules. An extensive process and effect evaluation on need for recovery and work ability will be carried out via questionnaires, observations, interviews and organizational data assessed at several time points throughout the intervention period. DISCUSSION: This study primarily aims to develop, implement and evaluate an intervention based on the abovementioned features which may improve the work environment, available resources and health of industrial workers, and hence their need for recovery and work ability.

How do workers with common mental disorders experience a multidisciplinary return-to-work intervention? A qualitative study.

PURPOSE: Long-term sick leave due to common mental disorders (CMD) is an increasing problem in many countries. Recent reviews indicate that return to work (RTW) interventions have limited effect on reducing sickness absence among this group of sick-listed. The aims of this study were to investigate how sick-listed persons with CMD experienced participating in an RTW intervention and how workability assessments and RTW activities influenced their RTW-process, and to examine the working mechanisms of the intervention. The gained knowledge can help improve future RTW intervention design and implementation. METHODS: In-depth interviews were conducted with 17 participants on sick leave due to CMD who participated in an RTW intervention. Interviews were conducted at three time points with each participant. Principles of interpretative phenomenological analyses guided the analysis. RESULTS: The workability assessment consultations and RTW activities such as psychoeducative group sessions and individual sessions with psychologist could result in both motivation and frustration depending on the extent to which the RTW professionals practiced what we have termed an individual approach to the sick-listed person. CONCLUSIONS: The individual approach seems necessary for the realization of the positive potential in the RTW intervention. However, the fact that RTW professionals are both the facilitators and the controllers of the sick-listed persons' RTW process is an inherent paradox in the intervention, which can impede the necessary establishment of a high-quality relationship between the sick-listed persons and RTW professionals.

How to engage occupational physicians in recruitment of research participants: a mixed-methods study of challenges and opportunities.

PURPOSE: To investigate barriers and facilitators for research participant recruitment by occupational physicians (OPs). METHODS: A mixed-methods approach was used. Focus groups and interviews were conducted with OPs to explore perceived barriers and facilitators for recruitment. Based on data of a cluster-randomised controlled trial (cluster-RCT), univariate and multivariate analyses were conducted to investigate associations between OPs' personal and work characteristics and the number of recruited participants for the cluster-RCT per OP. RESULTS: Perceived barriers and facilitators for recruitment were categorised into: study characteristics (e.g. concise inclusion criteria); study population characteristics; OP's attention; OP's workload; context (e.g. working at different locations); and OP's characteristics (e.g. motivated to help). Important facilitators were encouragement by colleagues and reminders by information technology tools. Multivariate analyses showed that the number of OPs within the clinical unit who recruited participants was positively associated with the number of recruited participants per OP [rate ratio of 1.43, 95 % confidence interval 1.24-1.64]. CONCLUSIONS: When mobilising OPs for participant recruitment, researchers need to engage entire clinical units rather than approach OPs on an individual basis. OPs consider regular communication, especially face-to-face contact and information technology tools serving as reminders, as helpful.

Dependence of human cell survival and proliferation on the CASP3 prodomain.

Mechanisms that regulate cell survival and proliferation are important for both the development and homeostasis of normal tissue, and as well as for the emergence and expansion of malignant cell populations. Caspase-3 (CASP3) has long been recognized for its proteolytic role in orchestrating cell death-initiated pathways and related processes; however, whether CASP3 has other functions in mammalian cells that do not depend on its known catalytic activity have remained unknown. To investigate this possibility, we examined the biological and molecular consequences of reducing CASP3 levels in normal and transformed human cells using lentiviral-mediated short hairpin-based knockdown experiments in combination with approaches designed to test the potential rescue capability of different components of the CASP3 protein. The results showed that a ≥50% reduction in CASP3 levels rapidly and consistently arrested cell cycle progression and survival in all cell types tested. Mass spectrometry-based proteomic analyses and more specific flow cytometric measurements strongly implicated CASP3 as playing an essential role in regulating intracellular protein aggregate clearance. Intriguingly, the rescue experiments utilizing different forms of the CASP3 protein showed its prosurvival function and effective removal of protein aggregates did not require its well-known catalytic capability, and pinpointed the N-terminal prodomain of CASP3 as the exclusive component needed in a diversity of human cell types. These findings identify a new mechanism that regulates human cell survival and proliferation and thus expands the complexity of how these processes can be controlled. The graphical abstract illustrates the critical role of CASP3 for sustained proliferation and survival of human cells through the clearance of protein aggregates.

Protocol for a pilot cluster randomised controlled trial of a multicomponent sustainable return to work IGLOo intervention.

BACKGROUND: Long-term sickness costs businesses in the United Kingdom (UK) approximately £7 billion per annum. Most long-term sickness absences are attributed to common mental health conditions, which are also highly prevalent in people with acute or musculoskeletal health conditions. This study will pilot the IGLOo (Individual, Group, Leaders, Organisation, overarching context) intervention which aims to support workers in returning to and remaining in work following long-term sickness absence. The potential impact of the intervention is a timely return to work (main trial primary outcome) and prevention of a further episode of long-term sick leave. The intervention will be piloted in a randomised controlled trial (RCT) to examine the feasibility of the intervention (pilot trial primary outcome) and to inform a fully powered definitive trial to evaluate sustainable return to work (RTW) in people with primary or secondary mental ill-health who go on long-term sick leave. METHODS AND DESIGN: A two-arm feasibility randomised controlled trial (with a 30-month study period including 12-month follow-up) of the IGLOo intervention will be conducted in large organisations (≥ 600 workers) from the Yorkshire and Humberside regions, in the UK. Eight consenting organisations will be recruited and randomised to the intervention or control arms of the study (1:1 ratio), with a minimum recruitment target of 13 workers eligible to participate from each. Organisations assigned to the control group will continue with their usual practice. Feasibility data will include data collected on recruitment, retention and attrition of participants; completion of research outcome measures; and intervention compliance. Measurements of mental health, RTW, work outcomes, quality-of-life, workplace support and communication and other demographic data will be taken at baseline, 3, 6, 9 and 12 months in all participants. Qualitative interviews and survey data with all participants will explore the experiences of participants, acceptability of the intervention components and evaluation measures. Exploratory economic evaluation will be conducted to further inform a definitive trial. DISCUSSION: The findings from this pilot study will help to inform the development of a definitive cluster RCT designed to examine the efficacy of this intervention on health and work-related outcomes in UK workers on long-term sick leave. TRIAL REGISTRATION: ISRCTN11788559 (prospectively registered, date registered 6 October 2022).

The importance of training transfer of non-technical skills safety training of construction workers.

Safety training of migrant workers in construction has focused on technical skills with limited attention to non-technical skills, which support safety training transfer to the worksite, both immediately after training and in the long term. Using realist evaluation as our theoretical framework, this study explores the transfer of two key non-technical skills to construction sites: communication and decision-making. Trained workers completed questionnaires post-training and after six months. A moderated mediation model found an indirect link through training transfer between communication and decision-making skills immediately post-training and six months later. The results also revealed that high levels of safety self-efficacy moderated the relationship between communication, but not decision-making, safety skills post-training and the extent to which trained workers reported transferring these skills. The study has important practical implications, showing the significance of training transfer of non-technical skills, such as communication and decision-making, to the worksite.

Job demands, job resources and long-term sickness absence in the Danish eldercare services: a prospective analysis of register-based outcomes.

AIM: To investigate associations between psychosocial job demands, job resources and cases of registered long-term sickness absence among nursing staff in the eldercare services. BACKGROUND: Research has shown that psychosocial work environment exposures predict sickness absence in healthcare settings. However, only few studies have longitudinally investigated associations between specific job demands and job resources and risk of long-term sickness absence. METHODS: Questionnaire data were collected in 2004 and 2005 among all employees in the eldercare services in 35 Danish municipalities and were followed in a National register on payment of sickness absence compensation for a 1-year follow-up period (N = 7921). Three psychosocial job demands - emotional demands, quantitative demands and role conflicts - and three job resources - influence, quality of leadership and team climate - were investigated to predict risk of sickness absence for eight or more consecutive weeks in the follow-up period. Data were analysed using Cox proportional hazards model. RESULTS: A percentage of 6·5 of the respondents were absent for eight or more consecutive weeks during follow-up. The analyses showed that emotional demands, role conflicts, influence, quality of leadership and team climate were significantly associated with risk of long-term sickness absence. In an analysis with mutual adjustment for all job demands and job resources, influence constituted the strongest predictor of long-term sickness absence (negative association). CONCLUSIONS: Job demands and job resources are significantly associated with risk of long-term sickness absence. Interventions aimed at improving the psychosocial work environment may, therefore, contribute towards preventing long-term sickness absence in the eldercare services.

Mediating the effects of work-life conflict between transformational leadership and health-care workers' job satisfaction and psychological wellbeing.

AIM: To explore the mediating effects of work-life conflict between transformational leadership and job satisfaction and psychological wellbeing. BACKGROUND: The importance of work-life balance for job satisfaction and wellbeing among health-care employees is well-recognized. Evidence shows that transformational leadership style is linked to psychological wellbeing. It is possible that transformational leadership is also associated with employees' perceptions of work-life conflict, thereby influencing their job satisfaction and wellbeing. METHODS: A longitudinal design was used where staff working within Danish elderly care completed a questionnaire at baseline and 18-month follow-up (N=188). RESULTS: Regression analyses showed that transformational leadership style was directly associated with perceptions of work-life conflict, job satisfaction and psychological wellbeing. Work-life conflict mediated between transformational leadership and wellbeing, but not job satisfaction. CONCLUSION: The findings suggest transformational leadership style may improve perceptions of work-life balance and employee wellbeing. IMPLICATIONS FOR NURSING MANAGEMENT: Managers should adopt transformational leadership styles to reduce work-life conflict and enhance the wellbeing of their staff.

Influence at work is a key factor for mental health - but what do contemporary employees in knowledge and relational work mean by "influence at work"?

PURPOSE: Common mental health problems are a substantial burden in many western countries. Studies have pointed out that work related factors can both increase and decrease the risk of developing mental health problems. Influence at work is a key factor relating the psychosocial work environment to employees mental health. However, little is known regarding how contemporary employees experience and understand influence at work. The purpose of this study is to explore this in depth. METHODS: We conducted semi-structured interviews with 59 employees in knowledge and relational work and analysed the data using principles from Interpretative Phenomenological Analysis (IPA). FINDINGS: TWe identified three themes each consisting of two interrelated parts, where the second part describes the consequences of the identified type of influence for employees: 1) work tasks and performance, 2) relations and belonging, 3) identity and becoming. CONCLUSIONS: The interviewed employees had a multifaceted understanding of influence at work and that influence at work mattered to them in different but important ways. Our hope is that managers, employees and consultants will be inspired by the three themes when designing work tasks, organizations and interventions in order to increase the level of influence and thereby help enhance the mental well-being of employees.

Gender differences in patient-reported outcomes in patients with acute myocardial infarction.

AIMS: Women report worse health-related patient-reported outcomes (PROs) compared with men following acute myocardial infarction (AMI). However, this association is not well established when accounting for demographic and clinical patient characteristics at discharge. This knowledge is essential for clinicians when planning individualised care for patients following AMI. The aim of this study is to examine whether gender is associated with health-related PROs at discharge from a Danish heart centre, combining PROs with data from the national health and administrative registries. METHODS AND RESULTS: A cross-sectional study of 2131 patients with AMI discharged from a Danish heart centre responding to the following health-related PRO questionnaires: the Health-survey Short-Form-12 (SF-12), generating a physical component summary (PCS) and a mental component summary (MCS) score; the HeartQoL, providing a global, emotional, and physical score; the EuroQol five-dimensional questionnaire (EQ-5D-5L) and the EQ visual analogue scale (EQ VAS); the Hospital Anxiety and Depression Scale (HADS), generating an anxiety and depression score (HADS-A and HADS-D); the Edmonton Symptom Assessment Scale (ESAS); the Brief Illness Perception Questionnaire (B-IPQ). Patient-reported outcomes were linked to registry-based information adjusting for potential demographic and clinical confounding factors. In adjusted regression models, women reported worse health-related PROs compared with men in SF-12 PCS and SF-12 MCS, HeartQoL global, the HeartQoL emotional and HeartQoL physical score, EQ-5D-5L and EQ VAS, the HADS-A, ESAS, and in six out of eight B-IPQ items. CONCLUSIONS: Women reported worse health-related PROs compared with men. Health-related PROs have the potential to be further investigated to facilitate a more individualised healthcare follow-up after AMI.

Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma.

Oncogenic KRAS mutations are absent in approximately 10% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) and may represent a subgroup of mPDAC with therapeutic options beyond standard-of-care cytotoxic chemotherapy. While distinct gene fusions have been implicated in KRAS wildtype mPDAC, information regarding other types of mutations remain limited, and gene expression patterns associated with KRAS wildtype mPDAC have not been reported. Here, we leverage sequencing data from the PanGen trial to perform comprehensive characterization of the molecular landscape of KRAS wildtype mPDAC and reveal increased frequency of chr1q amplification encompassing transcription factors PROX1 and NR5A2. By leveraging data from colorectal adenocarcinoma and cholangiocarcinoma samples, we highlight similarities between cholangiocarcinoma and KRAS wildtype mPDAC involving both mutation and expression-based signatures and validate these findings using an independent dataset. These data further establish KRAS wildtype mPDAC as a unique molecular entity, with therapeutic opportunities extending beyond gene fusion events.

Positive Participatory Organizational Interventions: A Multilevel Approach for Creating Healthy Workplaces.

In the following perspective paper, we argue for the importance of conducting research on positive participatory organizational interventions. We propose that these types of interventions are important because they not only focus on eliminating or reducing adverse job demands but focus also on developing job resources. To achieve the best effects, actions should be taken to address demands and resources at the individual, group, leader and organizational levels. We furthermore suggest that the participatory intervention process itself may also build resources at these four levels.

The Role of Adequate Resources, Community and Supportive Leadership in Creating Engaged Academics.

The vast majority of research in academia focuses on the adverse working conditions and poor wellbeing. The present paper presents a positive view on the factors that may promote work engagement in academia. Based on conservation of resources theory, we suggest that academic resources may be related to a social community at work, which in turn creates work engagement among academics. Having positive leadership in the form of fair leadership may be an important contextual factor ensuring that resources are shared fairly and openly. In a study of 1499 academics in Norwegian universities, we found that sufficient administrative resources to support teaching duties were positively related with work engagement, and that a sense of community mediated the relationship between academic resources for teaching and work engagement. These results propose that building academics' social resources by providing them with the necessary resources to perform their jobs will buffer the impact of a leadership that is perceived to be unfair and help them to perform their work in a positive way. Our results carry important implications for how positive psychology may be used to support engaged workers in academia.