Atypical work patterns and their associations with depressive symptoms, mental wellbeing, and sleep: findings from a UK population-based study

Objective: To examine whether, in the UK, relative to typical work patterns (open-ended, permanent, full-time, daytime, weekday employment, usually conducted at the employer’s premises), atypical work patterns (conceptualised as precarious, temporal and spatial work patterns) relate to worse or better mental health and sleep. Methods: Analysis of data from working men and women aged 16 and over, in Understanding Society, the UK Household Longitudinal Study. Regression models, adjusted for potential confounders and work conditions, estimated depressive symptoms (measured by GHQ-12), mental wellbeing (i.e., feeling good and functioning well measured by SWEMWBS), sleep duration (hours/night) and disturbance (difficulty falling and staying asleep and perceived poor quality sleep), across the three groups of atypical work patterns. Precarious was operationalised as temporary work and self-employment; spatial as remote working (including homeworking); and temporal as weekly work hours (e.g., part-time [<35 hours/week], long hours [41-54 hours/week], extra-long hours [≥55 hours/week]), nonstandard schedules (i.e., shifts and working outside 9am-5pm), and (some and most/all) weekends. Results: Cross-sectional analyses found part-time, extra-long hours, nonstandard schedules, and weekends were associated with elevated depressive symptoms, and self-employment with fewer symptoms. Mental wellbeing was poorer among nonstandard schedules and weekend workers, and better among self-employed and remote workers. Cumulative episodes of working nonstandard schedules and most/all weekends related to subsequent elevations of depressive symptoms, whilst cumulative episodes of self-employment related to fewer symptoms. Cross-sectional analysis found relative to sleeping 7-8 hours/night, remote, part-time and self-employed workers slept longer, individuals working ≥41 hours/week slept less, and those working weekends and nonstandard schedules slept both longer and shorter durations. Temporary work and all the atypical temporal work patterns were associated with sleep disturbance, whereas self-employment and remote working were inversely associated with sleep disturbance. Conclusion: Several atypical patterns, especially temporal ones, may contribute to poorer mental health and sleep; conversely self-employment and remote working may have a protective effect

Professional Pathways: Strategies to increase workforce diversity in the Australian library and information sector

In this article it is argued that the notion of a ‘diverse workforce’ extends beyond our understandings about the different cultural and linguistic backgrounds, the gender identity or the sexual orientation of individual staff members; it also considers the increasingly diverse skills required by library and information professionals. The work undertaken in the Australian Professional Pathways project is discussed.Peer Reviewe

Expression and function of calcium-activated potassium channels following in-stent restenosis in a porcine coronary artery model

AbstractIn-stent restenosis (ISR) occurs due to proliferation and migration of smooth muscle cells from media to intima resulting in re-narrowing of the vessel lumen. This study aims to investigate changes in the three main KCa channels in response to stent implantation in porcine coronary arteries as their expression and function in ISR is yet to be defined. Twenty-eight days after stent implantation, immunofluorescent labelling with anti-desmin and anti-vWF confirm the presence of both endothelial and smooth muscle cells within the neointimal layer. Using real-time PCR, significant increase in the SK3 and IKCa and BKCa channel mRNA was observed within this layer alone. Western blot analysis confirms the expression of KCa channels in neointima. Although expression of BKCa was increased in the neointima in comparison with medial region of the artery, microelectrode recordings showed that the function of this channel was unchanged. However, the presence of functional BKCa in both medial and intimal cells suggests that smooth muscle cells migration may contribute to neointimal hyperplasia.Functional analysis using 1-EBIO and Bradykinin produced hyperpolarization of neointimal but not medial myocytes, which indicated the expression of functional endothelial SK3 and IKCa in the former and not in the latter. The expression of IKCa and SK3 within the neointimal layer suggested that some degree of recovery of both endothelial as well as smooth muscle regeneration had occurred. Future development of selective modulators of IKCa and SK3 channels may decrease the progression of ISR and improve coronary vascular function after stent placement, and is an area for future investigation

A rapid multi-disciplinary biodiversity assessment of the Kamdebooberge (Sneeuberg, Eastern Cape, South Africa): implications for conservation

Botanical work since 2008 on the Sleeping Giant section of the Kamdebooberge (Sneeuberg mountain complex, Eastern Cape, South Africa) has indicated that these mountains may be of significant conservation value. Accordingly, a precursory, rapid multi-disciplinary biodiversity assessment was undertaken in January 2011, focusing on plants, tetrapod vertebrates and leafhoppers. The botanical results confirm the Kamdebooberge as being of high botanical conservation value, hosting three strict endemics, healthy populations of five other Sneeuberg endemics, and fynbos communities comprising species not found elsewhere in the Sneeuberg. The Kamdebooberge are important for herpetofauna (excluding serpentoids) and mammals, hosting several range-restricted and regional endemics. The expedition uncovered three new leafhopper species, together with several species previously only known from the Cape Floristic Region. Further detailed faunal work may provide further interesting results from these mountains, which show a high conservation value unique to the southern Escarpment

The DExD/H box ATPase Dhh1 functions in translational repression, mRNA decay, and processing body dynamics

Dhh1 is a critical determinant in whether mRNAs are translated, stored, or decayed

Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/1 mouse model of huntington's disease

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6 mouse models of HD express a mutant version of exon 1 HTT and typically develop motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Unlike the more commonly used R6/2 mouse line, R6/1 mice have fewer CAG repeats and, subsequently, a less rapid pathological decline. Compared to the R6/2 line, fewer descriptions of the progressive pathologies exhibited by R6/1 mice exist. The association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood in many models of HD. In attempt to link these factors in the R6/1 mouse line, we have performed detailed assessments of behavior and of regional brain abnormalities determined through longitudinal, in vivo magnetic resonance imaging (MRI), as well as an end-stage, ex vivo MRI study and histological assessment. We found progressive decline in both motor and non-motor related behavioral tasks in R6/1 mice, first evident at 11 weeks of age. Regional brain volumes were generally unaffected at 9 weeks, but by 17 weeks there was significant grey matter atrophy. This age-related brain volume loss was validated using a more precise, semi-automated Tensor Based morphometry assessment. As well as these clear progressive phenotypes, mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the R6/1 brain and was accompanied by neuronal loss. Despite these seemingly concomitant, robust pathological phenotypes, there appeared to be little correlation between the three main outcome measures: behavioral performance, MRI-detected brain atrophy and histopathology. In conclusion, R6/1 mice exhibit many features of HD, but the underlying mechanisms driving these clear behavioral disturbances and the brain volume loss, still remain unclear. © 2013 Rattray et al

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors: Australian Breast Cancer Family Study

INTRODUCTION: Because CYP17 can influence the degree of exposure of breast tissues to oestrogen, the interaction between polymorphisms in this gene and hormonal risk factors is of particular interest. We attempted to replicate the findings of studies assessing such interactions with the -34T→C polymorphism. METHODS: Risk factor and CYP17 genotyping data were derived from a large Australian population-based case-control-family study of 1,284 breast cancer cases and 679 controls. Crude and adjusted odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analyses. RESULTS: We found no associations between the CYP17 genotype and breast cancer overall. Premenopausal controls with A(2)/A(2 )genotype had a later age at menarche (P < 0.01). The only associations near statistical significance were that postmenopausal women with A(1)/A(1 )(wild-type) genotype had an increased risk of breast cancer if they had ever used hormone replacement therapy (OR 2.40, 95% CI 1.0 to 5.7; P = 0.05) and if they had menopause after age 47 years (OR 2.59, 95% CI 1.0 to 7.0; P = 0.06). We found no associations in common with any other studies, and no evidence for interactions. CONCLUSION: We observed no evidence of effect modification of reproductive risk factors by CYP17 genotype, although the experiment did not have sufficient statistical power to detect small main effects and modest effects in subgroups. Associations found only in subgroup analyses based on relatively small numbers require cautious interpretation without confirmation by other studies. This emphasizes the need for replication in multiple and large population-based studies to provide convincing evidence for gene–environment interactions

Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease?

Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio