Despite legislation on diversity in the workplace, people with disabilities still do not experience the same access to work opportunities as do their counterparts without disabilities. Many employers have been shown to harbor sincere yet ill-founded views about the work-related abilities of people with disabilities; these negative views are often a result of interrelated concerns that permeate the entire employment cycle. In this paper, we provide evidence-based responses to 11 specific concerns that employers have about people with disabilities, from pre-employment and entry experiences to the final dissolution of the employment relationship. At each stage of the employment cycle, we summarize and evaluate the relevant empirical evidence and provide recommendations for organizations committed to creating more effective, equitable, and inclusive workplaces for all individuals. We also suggest avenues for future research.

The stresses encountered during islet isolation and culture may have deleterious effects on beta-cell physiology. However, the biological response of human islet cells to isolation remains poorly characterized. A better understanding of the network of signaling pathways induced by islet isolation and culturing may lead to strategies aimed at improving islet graft survival and function. Laser capture microdissection (LCM) was used to extract beta-cell RNA from 1) intact pancreatic islets, 2) freshly isolated islets, 3) islets cultured for 3 days, and changes in gene expression were examined by microarray analysis. We identified a strong inflammatory response induced by islet isolation that continues during in-vitro culture manifested by upregulation of several cytokines and cytokine-receptors. The most highly upregulated gene, interleukin-8 (IL-8), was induced by 3.6-fold following islet isolation and 56-fold after 3 days in culture. Immunofluorescence studies showed that the majority of IL-8 was produced by beta-cells themselves. We also observed that several pancreas-specific transcription factors were down-regulated in cultured islets. Concordantly, several pancreatic progenitor cell-specific transcription factors like SOX4, SOX9, and ID2 were upregulated in cultured islets, suggesting progressive transformation of mature beta-cell phenotype toward an immature endocrine cell phenotype. Our findings suggest islet isolation and culture induces an inflammatory response and loss of the mature endocrine cell phenotype. A better understanding of the signals required to maintain a mature beta-cell phenotype may help improve the efficacy of islet transplantation.

Purpose Employers increasingly are asked to accommodate workers living with physical and mental health conditions that cause episodic disability, where periods of wellness are punctuated by intermittent and often unpredictable activity limitations (e.g., depression, anxiety, arthritis, colitis). Episodic disabilities may be challenging for workplaces which must comply with legislation protecting the privacy of health information while believing they would benefit from personal health details to meet a worker’s accommodation needs. This research aimed to understand organizational perspectives on disability communication-support processes. Methods Twenty-seven participants from diverse employment sectors and who had responsibilities for supporting workers living with episodic disabilities (e.g., supervisors, disability managers, union representatives, occupational health representatives, labour lawyers) were interviewed. Five participants also had lived experience of a physical or mental health episodic disability. Participants were recruited through organizational associations, community networks and advertising. Semi-structured interviews and qualitative content analysis framed data collection and analyses, and mapped communication-support processes. Results Seven themes underpinned communication-support process: (1) similarities and differences among physical and mental health episodic disabilities; (2) cultures of workplace support, including contrasting medical and biopsychosocial perspectives; (3) misgivings about others and their role in communication-support processes; (4) that subjective perceptions matter; (5) the inherent complexity of the response process; (6) challenges arising when a worker denies a disability; and (7) casting disability as a performance problem. Conclusions This study identifies a conceptual framework and areas where workplace disability support processes could be enhanced to improve inclusion and the sustainability of employment among workers living with episodic disabilities.

An understanding of the complex interactions and patterns of relationships in HCT can assist health policy makers and practitioners in determining key areas of intervention, the impact of these interventions on the system and the potential intended and unintended consequences of change. This paper provides initial examination of applying systems thinking to inform future research and practice on HCT.

Study design: Meta-analysis of cross-sectional, quasi-experimental and experimental studies. Objective: To determine if there is an association between physical activity (PA) and subjective wellbeing (SWB) among people living with spinal cord injury (SCI). Methods: Literature searches were conducted using multiple databases (Embase, CINAHL, Medline, PsychINFO and SPORTDiscus) to identify studies involving people with SCI that included a measure of PA and at least one measure of SWB (for example, symptoms of depression, life satisfaction, mood). Relevant data were extracted from the studies and subjected to meta-analysis. Results: A total of 21 studies were retrieved yielding 78 effect sizes and a total sample size of 2354. Overall, there were statistically significant, small-to medium-sized effects for the relationships between PA and SWB (broadly defined), PA and depressive symptoms, and PA and life satisfaction. Studies using experimental and quasi-experimental designs yielded larger effects for SWB (broadly defined) and life satisfaction, than studies using nonexperimental study designs. Conclusions: There is a small-to medium-sized positive relationship between PA and SWB among people with SCI that holds across a wide range of measures and operational definitions of these constructs.

The adipocyte hormone leptin acts centrally and peripherally to regulate body weight and glucose homeostasis. The pancreatic beta-cell has been shown to be a key peripheral target of leptin, with leptin suppressing insulin synthesis and secretion from beta-cells both in vitro and in vivo. Mice with disrupted leptin signaling in beta-cells (lepr(flox/flox) RIPcre tg+ mice) display hyperinsulinemia, insulin resistance, glucose intolerance, obesity, and reduced fasting blood glucose. We hypothesized that hyperinsulinemia precedes the development of insulin resistance and increased adiposity in these mice with a defective adipoinsular axis. To determine the primary defect after impaired beta-cell leptin signaling, we treated lepr(flox/flox) RIPcre tg+ mice with the insulin sensitizer metformin or the insulin-lowering agent diazoxide with the rationale that pharmacological improvement of the primary defect would alleviate the secondary symptoms. We show that improving insulin sensitivity with metformin does not normalize hyperinsulinemia, whereas lowering insulin levels with diazoxide improves insulin sensitivity. Taken together, these results suggest that hyperinsulinemia precedes insulin resistance in beta-cell leptin receptor-deficient mice, with insulin resistance developing as a secondary consequence of excessive insulin secretion. Therefore, pancreatic beta-cell leptin receptor-deficient mice may represent a model of obesity-associated insulin resistance that is initiated by hyperinsulinemia.

Monoclonal antibody (mAb) candidates from high-throughput screening or binding affinity optimization often contain mutations leading to liabilities for further development of the antibody, such as aggregation-prone regions and lack of solubility. In this work, we optimized a candidate integrin α11-binding mAb for developability using molecular modeling, rational design, and hydrophobic interaction chromatography (HIC). A homology model of the parental mAb Fv region was built, and this revealed hydrophobic patches on the surface of the complementarity-determining region loops. A series of 97 variants of the residues primarily responsible for the hydrophobic patches were expressed and their HIC retention times (RT) were measured. As intended, many of the computationally designed variants reduced the HIC RT compared to the parental mAb, and mutating residues that contributed most to hydrophobic patches had the greatest effect on HIC RT. A retrospective analysis was then performed where 3-dimentional protein property descriptors were evaluated for their ability to predict HIC RT using the current series of mAbs. The same descriptors were used to train a simple multi-parameter protein quantitative structure-property relationship model on this data, producing an improved correlation. We also extended this analysis to recently published HIC data for 137 clinical mAb candidates as well as 31 adnectin variants, and found that the surface area of hydrophobic patches averaged over a molecular dynamics sample consistently correlated to the experimental data across a diverse set of biotherapeutics.

Objective. To examine work absenteeism, job disruptions, and perceived productivity loss and factors associated with each outcome in young adults living with systemic lupus erythematosus (SLE) and juvenile arthritis (JA). Methods. One hundred forty-three young adults, ages 18-30 years with SLE (54.5%) and JA (45.5%), completed an online survey of work experiences. Demographic, health (e.g., fatigue, disease activity), psychosocial (e.g., independence, social support), and work context (e.g., career satisfaction, job control, self-disclosure) information was collected. Participants were asked about absenteeism, job disruptions, and perceived productivity loss in the last 6 months. Log Poisson regression analyses examined factors associated with work outcomes. Results. A majority of participants (59%) were employed and reported a well-managed health condition. Employed respondents were satisfied with their career progress and indicated moderate job control. More than 40% of participants reported absenteeism, job disruptions, and productivity loss. Greater job control and self-disclosure, and less social support, were related to a higher likelihood of absenteeism. More disease activity was related to a greater likelihood of reporting job disruptions. Lower fatigue and higher job control were associated with a reduced likelihood of a productivity loss. Conclusion. Young adult respondents with rheumatic disease experienced challenges with employment, including absenteeism, job disruptions, and productivity loss. While related to greater absenteeism, job control could play a role in a young person's ability to manage their health condition and sustain productive employment. Greater attention should also be paid to understanding health factors and social support in early work experiences.