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This study tests a central theoretical assumption of stress process and job strain models, namely that increases in employees' control and support at work should promote well-being. To do so, we use a group-randomized field trial with longitudinal data from 867 information technology (IT) workers to investigate the well-being effects of STAR, an organizational intervention designed to promote greater employee control over work time and greater supervisor support for workers' personal lives. We also offer a unique analysis of an unexpected field effect— a company merger—among workers surveyed earlier versus later in the study period, before or after the merger announcement. We find few STAR effects for the latter group, but over 12 months, STAR reduced burnout, perceived stress, and psychological distress, and increased job satisfaction, for the early survey group. STAR effects are partially mediated by increases in schedule control and declines in family-to-work conflict and burnout (an outcome and mediator) by six months. Moderating effects show that STAR benefits women in reducing psychological distress and perceived stress, and increases non-supervisory employees' job satisfaction. This study demonstrates, with a rigorous design, that organizational-level initiatives can promote employee well-being.

We draw on panel data from a randomized field experiment to assess the effects of a flexibility/supervisor support initiative called STAR on turnover intentions and voluntary turnover among professional technical workers in a large firm. An unanticipated exogenous shock—the announcement of an impending merger—occurred in the middle of data collection. Both organizational changes reflect an emerging employment contract characterized by increasing employee temporal flexibility even as employers wield greater flexibility in reorganizing their workforces. We theorized STAR would reduce turnover intentions and actual turnover by making it more attractive to stay with the current employer. We found being in a STAR team (versus a usual practice team) lowered turnover intentions 12 months later and reduced the risk of voluntary turnover over almost three years. We also examined potential mechanisms accounting for the effects of these two organizational changes; STAR effects on reducing turnover intentions are partially mediated by reducing work-to-family conflict, family-to-work conflict, burnout, psychological distress, perceived stress, and increasing job satisfaction. The effect of learning about the merger on increasing turnover intentions is fully mediated by increased job insecurity. STAR also moderates the negative effects of learning about the merger on turnover intentions for different subgroups. Findings provide insights into the effectiveness of an organizational intervention, the dynamics of organizations, and how competing logics of two organizational changes affect employees’ labor market expectations and behavior.

Work identity is a multidimensional construct attached to job, occupation, workplace, or organization. This chapter highlights the precarious labor market that contemporary young workers confront worldwide and how the shifting economic terrain may be changing the ways younger workers understand their work and the formation of their work identities. Employment has become more transitory, insecure, and nonstandard, rendering young workers’ school-to-work transition increasingly prolonged and difficult; the authors propose that work identities may also become more individualized and destandardized. Stryker’s identity theory and Rosenberg’s theory of self-concept formation offer important insights regarding the mechanisms through which more insecure and less rewarding jobs for young workers may diminish work’s position in the hierarchy of role identities. Work identities may also become more flexible as workers adjust themselves to their changing employment circumstances. Given increasing inequalities in work conditions, growing disparities in the formation and character of work identities are expected.

AimTo determine the association between dementia and age-related macular degeneration (AMD) using meta-analysis.MethodsWe searched in the MEDLINE, EMBASE, Web of Knowledge, PsycInfo and Cochrane database of systematic reviews for studies published from March 1959 to March 2018. We included cross-sectional, case–control and cohort studies that evaluated the association of dementia/Alzheimer's disease (AD) with AMD (as outcome) and the association of AMD with dementia/AD (as outcome). Studies that compared cognitive functions between AMD and controls were also included. The summary outcomes, namely odds ratio (OR), relative risk, mean differences and corresponding 95% CIs, were estimated using random effects models. We performed sensitivity analysis based on study quality and individual study effect to control for potential biases.ResultsAmong 2159 citation records, we identified 21 studies consisting of 7 876 499 study subjects for meta-analysis. Patients with dementia (padjusted≤0.017, OR≥1.24, I2≤9%) or AD (p=0.001, ORunadjusted=2.22, I2=50%) were at risk for AMD, particularly for late AMD (padjusted<0.001, OR=1.37, I2=0). AMD was also significantly associated with increased risk of AD/cognitive impairment (padjusted=0.037, OR=2.42, I2=38%). Moreover, patients with AMD had poorer cognitive functions when compared with controls, including Mini-Mental State Examination (p<0.001, I2≤79%) and Trail Making Test A (p<0.001, I2=0). Sensitivity analysis and Egger’s test indicated our results were less likely biased.ConclusionsA significant association between dementia/AD and AMD calls for greater clinical awareness. The cost-effectiveness of routine screening for the other condition in patients with primary diagnosis of dementia/AD or AMD requires further study.

The prolyl isomerase Pin1 acts in various cellular processes. It has now been implicated in telomere maintenance by regulating the stability of the telomere binding protein TRF1. Telomeres are essential for maintaining cellular proliferative capacity and their loss has been implicated in ageing. A key regulator in telomere maintenance is the telomeric protein TRF1, which was also identified as Pin2 in a screen for Pin1. Pin1 is a unique prolyl isomerase that regulates protein conformation and function after phosphorylation. However, little is known about the role of Pin1 in telomere regulation or the modulation of TRF1 by upstream signals. Here we identify TRF1 as a major conserved substrate for Pin1 during telomere maintenance and ageing. Pin1 inhibition renders TRF1 resistant to protein degradation, enhances TRF1 binding to telomeres, and leads to gradual telomere loss in human cells and in mice. Pin1-deficient mice also show widespread premature ageing phenotypes within just one generation, similar to those in telomerase-deficient mice after 4–5 consecutive generations. Thus, Pin1 is an essential regulator of TRF1 stability, telomere maintenance and ageing.

Mucopolysaccharidosis I (MPS I) due to deficient α-l-iduronidase (IDUA) activity results in accumulation of glycosaminoglycans in many cells. Gene therapy could program liver to secrete enzyme with mannose 6-phosphate (M6P), and enzyme in blood could be taken up by other cells via the M6P receptor. Newborn MPS I mice were injected with 109 (high dose) or 108 (low dose) transducing units/kg of a retroviral vector (RV) expressing canine IDUA. Most animals achieved stable expression of IDUA in serum at 1240 ± 147 and 110 ± 31 units/ml, respectively. At 8 months, untreated MPS I mice had aortic insufficiency, increased bone mineral density (BMD), and reduced responses to sound and light. In contrast, MPS I mice that received high-dose RV had normal echocardiograms, BMD, auditory-evoked brain-stem responses, and electroretinograms. This is the first report of complete correction of these clinical manifestations in any model of mucopolysaccharidosis. Biochemical and pathologic evaluation confirmed that storage was reduced in these organs. Mice that received low-dose RV and achieved 30 units/ml of serum IDUA activity had no or only partial improvement. We conclude that high-dose neonatal gene therapy with an RV reduces some major clinical manifestations of MPS I in mice, but low dose is less effective.

Telomerase is activated in most human cancers and is critical for cancer cell growth. However, little is known about the significance of telomerase activation in chromosome instability and cancer initiation. The gene encoding the potent endogenous telomerase inhibitor PinX1 (PIN2/TRF1-interacting, telomerase inhibitor 1) is located at human chromosome 8p23, a region frequently exhibiting heterozygosity in many common human cancers, but the function or functions of PinX1 in development and tumorigenesis are unknown. Here we have shown that PinX1 is a haploinsufficient tumor suppressor essential for chromosome stability in mice. We found that PinX1 expression was reduced in most human breast cancer tissues and cell lines. Furthermore, PinX1 heterozygosity and PinX1 knockdown in mouse embryonic fibroblasts activated telomerase and led to concomitant telomerase-dependent chromosomal instability. Moreover, while PinX1-null mice were embryonic lethal, most PinX1+/- mice spontaneously developed malignant tumors with evidence of chromosome instability. Notably, most PinX1 mutant tumors were carcinomas and shared tissues of origin with human cancer types linked to 8p23. PinX1 knockout also shifted the tumor spectrum of p53 mutant mice from lymphoma toward epithelial carcinomas. Thus, PinX1 is a major haploinsufficient tumor suppressor essential for maintaining telomerase activity and chromosome stability. These findings uncover what we believe to be a novel role for PinX1 and telomerase in chromosome instability and cancer initiation and suggest that telomerase inhibition may be potentially used to treat cancers that overexpress telomerase.