The associations between self-reported depression, self-reported chronic inflammatory conditions and cognitive abilities in UK Biobank

Background: Depression and chronic inflammatory medical conditions have been linked to impaired cognitive ability. However despite frequent comorbidity, their combined association with cognitive ability has rarely been examined. Methods: This study examined associations between self-reported depression and chronic inflammatory diseases and their interaction with cognitive performance in 456,748 participants of the UK Biobank, adjusting for sociodemographic and lifestyle factors. Numbers with available data ranged from 94,899 to 453,208 depending on the cognitive test. Results: Self-reported depression was associated with poorer performance compared to controls in several cognitive tests (fully adjusted models, reaction time: B = 6.08, 95% CI = 5.09, 7.07; pairs matching: incidence rate ratio = 1.02, 95% CI = 1.02, 1.03; Trail Making Test B: B = 1.37, 95% CI = 0.88, 1.87; Digit Symbol Substitution Test (DSST): B = −0.35, 95% CI = −0.44, −0.27). Self-reported chronic inflammatory conditions were associated with slower reaction time (B = 3.79, 95% CI = 2.81, 4.78) and lower DSST scores (B = −0.21, 95% CI = −0.30, −0.13). No interaction effects were observed. Discussion: In this large, population-based study we provide evidence of lower cognitive performance in both depression and a comprehensive category of chronic inflammatory conditions. Results are consistent with additive effects of both types of disorder on cognitive ability. Clinicians should be aware of such effects, particularly as cognitive impairment is linked to poorer disease outcomes and quality of life

Association between polygenic risk for Alzheimer’s disease, brain structure and cognitive abilities in UK Biobank

Previous studies testing associations between polygenic risk for late-onset Alzheimer’s disease (LOAD-PGR) and brain magnetic resonance imaging (MRI) measures have been limited by small samples and inconsistent consideration of potential confounders. This study investigates whether higher LOAD-PGR is associated with differences in structural brain imaging and cognitive values in a relatively large sample of non-demented, generally healthy adults (UK Biobank). Summary statistics were used to create PGR scores for n = 32,790 participants using LDpred. Outcomes included 12 structural MRI volumes and 6 concurrent cognitive measures. Models were adjusted for age, sex, body mass index, genotyping chip, 8 genetic principal components, lifetime smoking, apolipoprotein (APOE) e4 genotype and socioeconomic deprivation. We tested for statistical interactions between APOE e4 allele dose and LOAD-PGR vs. all outcomes. In fully adjusted models, LOAD-PGR was associated with worse fluid intelligence (standardised beta [β] = −0.080 per LOAD-PGR standard deviation, p = 0.002), matrix completion (β = −0.102, p = 0.003), smaller left hippocampal total (β = −0.118, p = 0.002) and body (β = −0.069, p = 0.002) volumes, but not other hippocampal subdivisions. There were no significant APOE x LOAD-PGR score interactions for any outcomes in fully adjusted models. This is the largest study to date investigating LOAD-PGR and non-demented structural brain MRI and cognition phenotypes. LOAD-PGR was associated with smaller hippocampal volumes and aspects of cognitive ability in healthy adults and could supplement APOE status in risk stratification of cognitive impairment/LOAD

Assessing for interaction between APOE ε4, sex and lifestyle on cognitive abilities

Objective: To test for interactions between APOE ε4 genotype and lifestyle factors on worse cognitive abilities in UK Biobank. Methods: Using UK Biobank cohort data, we tested for interactions between APOE ε4 allele presence, lifestyle factors of alcohol intake, smoking, total physical activity and obesity, and sex, on cognitive tests of reasoning, information processing speed, and executive function (n range = 70,988–324,725 depending on the test). We statistically adjusted for potential confounders of age, sex, deprivation, cardiometabolic conditions, and educational attainment. Results: There were significant associations between APOE ε4 and worse cognitive abilities, independent of potential confounders, and between lifestyle risk factors and worse cognitive abilities; however, there were no interactions at multiple correction-adjusted p < 0.05, against our hypotheses. Conclusions: Our results do not provide support for the idea that ε4 genotype increases vulnerability to the negative effects of lifestyle risk factors on cognitive ability, but rather support a primarily outright association between APOE ε4 genotype and worse cognitive ability

Comparing plasma and faecal measures of steroid hormones in Adelie penguins Pygoscelis adeliae

Physiological measurements of both stress and sex hormones are often used to estimate the consequences of natural or human-induced change in ecological studies of various animals. Different methods of hormone measurement exist, potentially explaining variation in results across studies; methods should be cross-validated to ensure that they correlate. We directly compared faecal and plasma hormone measurements for the first time in a wild free-living species, the Adelie penguin (Pygoscelis adeliae). Blood and faecal samples were simultaneously collected from individual penguins for comparison and assayed for testosterone and corticosterone (or their metabolites). Sex differences and variability within each measure, and correlation of values across measures were compared. For both hormones, plasma samples showed greater variation than faecal samples. Males had higher mean corticosterone concentrations than females, but the difference was only statistically significant in faecal samples. Plasma testosterone, but not faecal testosterone, was significantly higher in males than females. Correlation between sample types was poor overall, and weaker in females than in males, perhaps because measures from plasma represent hormones that are both free and bound to globulins, whereas measures from faeces represent only the free portion. Faecal samples also represent a cumulative measure of hormones over time, as opposed to a plasma ‘snapshot’ concentration. Our data indicate that faecal sampling appears more suitable for assessing baseline hormone concentrations, whilst plasma sampling may best define immediate responses to environmental events. Consequently, future studies should ensure that they select the most appropriate matrix and method of hormone measurement to answer their research questions

The use of a tailored surgical technique for minimally invasive esophagectomy

ObjectiveUncertainty exists among surgeons as to whether minimally invasive esophagectomy (MIE) is a comparable operation to open esophagectomy (OE). The surgical technique and oncologic dissection should not be degraded when using a minimally invasive approach.MethodsWe reviewed a single hospital’s experience with both OE and MIE. From 2000 to 2010, 257 patients underwent esophagectomy by 1 of 3 surgical techniques: transhiatal, Ivor Lewis, or 3-hole.ResultsOf the 257 patients (median age, 67 years; range, 58–74), 92 underwent MIE. Both groups were comparable in terms of gender, age, comorbidities, surgical technique, and induction chemotherapy and radiotherapy. The overall median follow-up was 29.5 months (range, 9.9–61.5). The MIE group had a significantly shorter operative time (MIE vs OE, 330 vs 365 minutes, P = .04), length of stay (MIE vs OE, 9 vs 12 days, P < .01), intensive care unit admission rate (MIE vs OE, 55% vs 81%, P < .01), intensive care unit length of stay (MIE vs OE, 1 vs 2 days, P < .01), and estimated blood loss (MIE vs OE, 100 vs 400 mL, P < .01). More lymph nodes were harvested in the MIE group than in the OE group (17 vs 11 nodes, P < .01). There were insignificant differences in 30-day mortality (MIE vs OE, 2.2% vs 3.0%; P = .93) and overall survival (P = .19), as well as in the rates of all complications, except pneumonia (MIE vs OE, 2% vs 13%; P = .01).ConclusionsA thoracic surgeon can safely tailor the MIE to a patient’s anatomy and oncologic demands while maintaining equivalent survival

Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity

Apolipoprotein (APOE) e4 genotype is an accepted risk factor for accelerated cognitive aging and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank (N = 8395 after exclusions). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95% confidence intervals = 0.036 to 0.139, P = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4’s potential link with cerebrovascular contributions to cognitive aging

Young Australians navigating the ‘Careers Information Ecology’

The policy orientations of advanced neoliberal democracies situate young people as rational actors who are responsible for their own career outcomes. While career scholars have been critical of how this routinely ignores the unequal effects of structural constraints on personal agency, they have long suggested that young people should have access to the best available ‘roadmaps’ and advice to navigate the uncertainties baked into the contemporary economic landscape. Complementing the significant attention that is given to the (potentially emancipatory) experience of formal careers guidance, we present findings from a multi-method study. We explore young Australians’ (aged 15–24) navigation of careers information through a nationally representative survey (n = 1103), focus groups with 90 participants and an analysis of 15,227 social media comments. We suggest that the variety of formal and informal sources pursued and accessed by young people forms a relational ‘ecology’. This relationality is twofold. First, information is often sequential, and engagements with one source can inform the experience or pursuit of another. Second, navigation of the ecology is marked by a high level of intersubjectivity through interpersonal support networks including peers, family and formal service provision. These insights trouble a widespread, but perhaps simplistic, reading of young people having largely internalised a neoliberal sensibility of ‘entrepreneurial selfhood’ in their active pursuit of a range of career advice. Throughout our analysis, we attend to the ways that engagement in the career information ecology is shaped by social inequalities, further underscoring challenges facing careers guidance and social justice goals

Alzheimer’s disease susceptibility gene apolipoprotein e (APOE) and blood biomarkers in UK Biobank (N=395,769)

Background: Alzheimer’s disease (AD) is a neurodegenerative condition where the underlying etiology is still unclear. Investigating the potential influence of apolipoprotein E (APOE), a major genetic risk factor, on common blood biomarkers could provide a greater understanding of the mechanisms of AD and dementia risk. Objective: Our objective was to conduct the largest (to date) single-protocol investigation of blood biomarkers in the context of APOE genotype, in UK Biobank. Methods:After quality control and exclusions, data on 395,769 participants of White European ancestry were available for analysis. Linear regressions were used to test potential associations between APOE genotypes and biomarkers. Results: Several biomarkers significantly associated with APOE ɛ4 ‘risk’ and ɛ2 ‘protective’ genotypes (versus neutral ɛ3/ɛ3). Most associations supported previous data: for example, ɛ4 genotype was associated with elevated low-density lipoprotein cholesterol (LDL) (standardized beta [b] = 0.150 standard deviations [SDs] per allele, p &lt; 0.001) and ɛ2 with lower LDL (b = –0.456 SDs, p &lt; 0.001). There were however instances of associations found in unexpected directions: e.g., ɛ4 and increased insulin-like growth factor (IGF-1) (b = 0.017, p &lt; 0.001) where lower levels have been previously suggested as an AD risk factor. Conclusion: These findings highlight biomarker differences in non-demented people at genetic risk for dementia. The evidence herein supports previous hypotheses of involvement from cardiometabolic and neuroinflammatory pathways

A One Health Framework for the Evaluation of Rabies Control Programmes: A Case Study from Colombo City, Sri Lanka

<div><p>Background</p><p>One Health addresses complex challenges to promote the health of all species and the environment by integrating relevant sciences at systems level. Its application to zoonotic diseases is recommended, but few coherent frameworks exist that combine approaches from multiple disciplines. Rabies requires an interdisciplinary approach for effective and efficient management.</p><p>Methodology/Principal Findings</p><p>A framework is proposed to assess the value of rabies interventions holistically. The economic assessment compares additional monetary and non-monetary costs and benefits of an intervention taking into account epidemiological, animal welfare, societal impact and cost data. It is complemented by an ethical assessment. The framework is applied to Colombo City, Sri Lanka, where modified dog rabies intervention measures were implemented in 2007. The two options included for analysis were the control measures in place until 2006 (“baseline scenario”) and the new comprehensive intervention measures (“intervention”) for a four-year duration. Differences in control cost; monetary human health costs after exposure; Disability-Adjusted Life Years (DALYs) lost due to human rabies deaths and the psychological burden following a bite; negative impact on animal welfare; epidemiological indicators; social acceptance of dogs; and ethical considerations were estimated using a mixed method approach including primary and secondary data. Over the four years analysed, the intervention cost US $1.03 million more than the baseline scenario in 2011 prices (adjusted for inflation) and caused a reduction in dog rabies cases; 738 DALYs averted; an increase in acceptability among non-dog owners; a perception of positive changes in society including a decrease in the number of roaming dogs; and a net reduction in the impact on animal welfare from intermediate-high to low-intermediate.</p><p>Conclusions</p><p>The findings illustrate the multiple outcomes relevant to stakeholders and allow greater understanding of the value of the implemented rabies control measures, thereby providing a solid foundation for informed decision-making and sustainable control.</p></div