MEAN-VARIANCE ANALYSIS OF ALTERNATIVE HEDGING STRATEGIES

Demand and Price Analysis,

Are sound abatement measures necessary in the cytology reading room? A study of auditory distraction

Objective Listening to music and other auditory material during microscopy work is common practice among cytologists. While many cytologists would claim several benefits of such activity, research in other fields suggests that it might adversely affect diagnostic performance. Using a cross-modal distraction paradigm, the aim of the present study was to investigate the effect of auditory stimulation on the visual interpretation of cell images. Methods Following initial training, 34 participants undertook cell interpretation tests under four auditory conditions (liked music, disliked music, speech and silence) in a counterbalanced repeated-measures study. Error rate, area under the ROC curve, criterion and response time were measured for each condition. Results There was no significant effect of auditory stimulation on the accuracy or speed with which cell images were interpreted, mirroring the results of a previous visual distraction study. Conclusions To the extent that the experiment reflects clinical practice, listening to music or other forms of auditory material whilst undertaking microscopy duties is an unlikely source of distraction in the cytopathology reading room. From a cognitive perspective the results are consistent with the notion that high focal-task engagement may have blocked any attentional capture the sound may otherwise have produced

Organisational Change Stressors and Nursing Job Satisfaction: The Mediating Effect of Coping Strategies

Aim: To examine the mediating effect of coping strategies on the consequences of nursing and non-nursing (administrative) stressors on the job satisfaction of nurses during change management. Background Organisational change can result in an increase in nursing and non-nursing-related stressors, which can have a negative impact on the job satisfaction of nurses employed in health-care organisations. Method: Matched data were collected in 2009 via an online survey at two time-points (six months apart).Results: Partial least squares path analysis revealed a significant causal relationship between Time 1 administrative and role stressors and an increase in nursing-specific stressors in Time 2. A significant relationship was also identified between job-specific nursing stressors and the adoption of effective coping strategies to deal with increased levels of change-induced stress and strain and the likelihood of reporting higher levels of job satisfaction in Time 2.Conclusions: The effectiveness of coping strategies is critical in helping nurses to deal with the negative consequences of organisational change. Implications for nursing management: This study shows that there is a causal relationship between change, non-nursing stressors and job satisfaction. Senior management should implement strategies aimed at reducing nursing and nonnursing stress during change in order to enhance the job satisfaction of nurses

SAPrIm, a semi-automated protocol for mid-throughput immunopeptidomics

Human leukocyte antigen (HLA) molecules play a crucial role in directing adaptive immune responses based on the nature of their peptide ligands, collectively coined the immunopeptidome. As such, the study of HLA molecules has been of major interest in the development of cancer immunotherapies such as vaccines and T-cell therapies. Hence, a comprehensive understanding and profiling of the immunopeptidome is required to foster the growth of these personalised solutions. We herein describe SAPrIm, an Immunopeptidomics tool for the Mid-Throughput era. This is a semi-automated workflow involving the KingFisher platform to isolate immunopeptidomes using anti-HLA antibodies coupled to a hyper-porous magnetic protein A microbead, a variable window data independent acquisition (DIA) method and the ability to run up to 12 samples in parallel. Using this workflow, we were able to concordantly identify and quantify ~400 - 13000 unique peptides from 5e5 - 5e7 cells, respectively. Overall, we propose that the application of this workflow will be crucial for the future of immunopeptidome profiling, especially for mid-size cohorts and comparative immunopeptidomics studies

Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited

By studying the loci that contribute to human longevity, we aim to identify mechanisms that contribute to healthy aging. To identify such loci, we performed a genome-wide association study (GWAS) comparing 403 unrelated nonagenarians from long-living families included in the Leiden Longevity Study (LLS) and 1670 younger population controls. The strongest candidate SNPs from this GWAS have been analyzed in a meta-analysis of nonagenarian cases from the Rotterdam Study, Leiden 85-plus study, and Danish 1905 cohort. Only one of the 62 prioritized SNPs from the GWAS analysis (P < 1 × 10−4) showed genome-wide significance with survival into old age in the meta-analysis of 4149 nonagenarian cases and 7582 younger controls [OR = 0.71 (95% CI 0.65–0.77), P = 3.39 × 10−17]. This SNP, rs2075650, is located in TOMM40 at chromosome 19q13.32 close to the apolipoprotein E (APOE) gene. Although there was only moderate linkage disequilibrium between rs2075650 and the ApoE ε4 defining SNP rs429358, we could not find an APOE-independent effect of rs2075650 on longevity, either in cross-sectional or in longitudinal analyses. As expected, rs429358 associated with metabolic phenotypes in the offspring of the nonagenarian cases from the LLS and their partners. In addition, we observed a novel association between this locus and serum levels of IGF-1 in women (P = 0.005). In conclusion, the major locus determining familial longevity up to high age as detected by GWAS was marked by rs2075650, which tags the deleterious effects of the ApoE ε4 allele. No other major longevity locus was found

Sex-differential genetic effect of phosphodiesterase 4D (PDE4D) on carotid atherosclerosis

<p>Abstract</p> <p>Background</p> <p>The phosphodiesterase 4D (PDE4D) gene was reported as a susceptibility gene to stroke. The genetic effect might be attributed to its role in modulating the atherogenic process in the carotid arteries. Using carotid intima-media thickness (IMT) and plaque index as phenotypes, the present study sought to determine the influence of this gene on subclinical atherosclerosis.</p> <p>Methods</p> <p>Carotid ultrasonography was performed on 1013 stroke-free subjects who participated in the health screening programs (age 52.6 ± 12.2; 47.6% men). Genotype distribution was compared among the high-risk (plaque index ≥ 4), low-risk (index = 1-3), and reference (index = 0) groups. We analyzed continuous IMT data and further dichotomized IMT data using mean plus one standard deviation as the cutoff level. Because the plaque prevalence and IMT values displayed a notable difference between men and women, we carried out sex-specific analyses in addition to analyzing the overall data. Rs702553 at the PDE4D gene was selected because it conferred a risk for young stroke in our previous report. Previous young stroke data (190 cases and 211 controls) with an additional 532 control subjects without ultrasonic data were shown as a cross-validation for the genetic effect.</p> <p>Results</p> <p>In the overall analyses, the rare homozygote of rs702553 led to an OR of 3.1 (p = 0.034) for a plaque index ≥ 4. When subjects were stratified by sex, the genetic effect was only evident in men but not in women. Comparing male subjects with plaque index ≥ 4 and those with plaque index = 0, the TT genotype was over-represented (27.6% vs. 13.4%, p = 0.008). For dichotomized IMT data in men, the TT genotype had an OR of 2.1 (p = 0.032) for a thicker IMT at the common carotid artery compared with the (AA + AT) genotypes. In women, neither IMT nor plaque index was associated with rs702553. Similarly, SNP rs702553 was only significant in young stroke men (OR = 1.8, p = 0.025) but not in women (p = 0.27).</p> <p>Conclusions</p> <p>The present study demonstrates a sex-differential effect of PDE4D on IMT, plaque index and stroke, which highlights its influence on various aspects of atherogenesis.</p

Genetic Signatures of Exceptional Longevity in Humans

Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity in 801 centenarians (median age at death 104 years) and 914 genetically matched healthy controls. Using these data, we built a genetic model that includes 281 single nucleotide polymorphisms (SNPs) and discriminated between cases and controls of the discovery set with 89% sensitivity and specificity, and with 58% specificity and 60% sensitivity in an independent cohort of 341 controls and 253 genetically matched nonagenarians and centenarians (median age 100 years). Consistent with the hypothesis that the genetic contribution is largest with the oldest ages, the sensitivity of the model increased in the independent cohort with older and older ages (71% to classify subjects with an age at death>102 and 85% to classify subjects with an age at death>105). For further validation, we applied the model to an additional, unmatched 60 centenarians (median age 107 years) resulting in 78% sensitivity, and 2863 unmatched controls with 61% specificity. The 281 SNPs include the SNP rs2075650 in TOMM40/APOE that reached irrefutable genome wide significance (posterior probability of association = 1) and replicated in the independent cohort. Removal of this SNP from the model reduced the accuracy by only 1%. Further in-silico analysis suggests that 90% of centenarians can be grouped into clusters characterized by different “genetic signatures” of varying predictive values for exceptional longevity. The correlation between 3 signatures and 3 different life spans was replicated in the combined replication sets. The different signatures may help dissect this complex phenotype into sub-phenotypes of exceptional longevity

Families’ roles in children’s literacy in the UK throughout the 20th century

This paper explores the changing roles of families in children’s developing literacy in the UK in the last century. It discusses how, during this time, understandings of reading and writing have evolved into the more nuanced notion of literacy. Further, in acknowledging changes in written communication practices, and shifting attitudes to reading and writ- ing, the paper sketches out how families have always played some part in the literacy of younger generations; though reading was frequently integral to the lives of many families throughout the past century, we consider in particular the more recent enhancement of children’s literacy through targeted family programmes. The paper considers policy implications for promoting young children’s literacy through work with families

A hierarchical and modular approach to the discovery of robust associations in genome-wide association studies from pooled DNA samples

[Background] One of the challenges of the analysis of pooling-based genome wide association studies is to identify authentic associations among potentially thousands of false positive associations. [Results] We present a hierarchical and modular approach to the analysis of genome wide genotype data that incorporates quality control, linkage disequilibrium, physical distance and gene ontology to identify authentic associations among those found by statistical association tests. The method is developed for the allelic association analysis of pooled DNA samples, but it can be easily generalized to the analysis of individually genotyped samples. We evaluate the approach using data sets from diverse genome wide association studies including fetal hemoglobin levels in sickle cell anemia and a sample of centenarians and show that the approach is highly reproducible and allows for discovery at different levels of synthesis. [Conclusion] Results from the integration of Bayesian tests and other machine learning techniques with linkage disequilibrium data suggest that we do not need to use too stringent thresholds to reduce the number of false positive associations. This method yields increased power even with relatively small samples. In fact, our evaluation shows that the method can reach almost 70% sensitivity with samples of only 100 subjects.Supported by NHLBI grants R21 HL080463 (PS); R01 HL68970 (MHS); K-24, AG025727 (TP); K23 AG026754 (D.T.)