Cognitive-affective neural plasticity following active-controlled mindfulness intervention.

Mindfulness meditation is a set of attention-based, regulatory, and self-inquiry training regimes. Although the impact of mindfulness training (MT) on self-regulation is well established, the neural mechanisms supporting such plasticity are poorly understood. MT is thought to act through interoceptive salience and attentional control mechanisms, but until now conflicting evidence from behavioral and neural measures renders difficult distinguishing their respective roles. To resolve this question we conducted a fully randomized 6 week longitudinal trial of MT, explicitly controlling for cognitive and treatment effects with an active-control group. We measured behavioral metacognition and whole-brain blood oxygenation level-dependent (BOLD) signals using functional MRI during an affective Stroop task before and after intervention in healthy human subjects. Although both groups improved significantly on a response-inhibition task, only the MT group showed reduced affective Stroop conflict. Moreover, the MT group displayed greater dorsolateral prefrontal cortex responses during executive processing, consistent with increased recruitment of top-down mechanisms to resolve conflict. In contrast, we did not observe overall group-by-time interactions on negative affect-related reaction times or BOLD responses. However, only participants with the greatest amount of MT practice showed improvements in response inhibition and increased recruitment of dorsal anterior cingulate cortex, medial prefrontal cortex, and right anterior insula during negative valence processing. Our findings highlight the importance of active control in MT research, indicate unique neural mechanisms for progressive stages of mindfulness training, and suggest that optimal application of MT may differ depending on context, contrary to a one-size-fits-all approach

FRAX™ and the assessment of fracture probability in men and women from the UK

SUMMARY: A fracture risk assessment tool (FRAX) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK. INTRODUCTION: The aim of this study was to apply an assessment tool for the prediction of fracture in men and women with the use of clinical risk factors (CRFs) for fracture with and without the use of femoral neck bone mineral density (BMD). The clinical risk factors, identified from previous meta-analyses, comprised body mass index (BMI, as a continuous variable), a prior history of fracture, a parental history of hip fracture, use of oral glucocorticoids, rheumatoid arthritis and other secondary causes of osteoporosis, current smoking, and alcohol intake 3 or more units daily. METHODS: Four models were constructed to compute fracture probabilities based on the epidemiology of fracture in the UK. The models comprised the ten-year probability of hip fracture, with and without femoral neck BMD, and the ten-year probability of a major osteoporotic fracture, with and without BMD. For each model fracture and death hazards were computed as continuous functions. RESULTS: Each clinical risk factor contributed to fracture probability. In the absence of BMD, hip fracture probability in women with a fixed BMI (25 kg/m(2)) ranged from 0.2% at the age of 50 years for women without CRF's to 22% at the age of 80 years with a parental history of hip fracture (approximately 100-fold range). In men, the probabilities were lower, as was the range (0.1 to 11% in the examples above). For a major osteoporotic fracture the probabilities ranged from 3.5% to 31% in women, and from 2.8% to 15% in men in the example above. The presence of one or more risk factors increased probabilities in an incremental manner. The differences in probabilities between men and women were comparable at any given T-score and age, except in the elderly where probabilities were higher in women than in men due to the higher mortality of the latter. CONCLUSION: The models provide a framework which enhances the assessment of fracture risk in both men and women by the integration of clinical risk factors alone and/or in combination with BMD

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

FEATHER PECKING AND CHRONIC FEAR IN GROUPS OF RED JUNGLEFOWL - THEIR RELATIONS TO DUSTBATHING, REARING ENVIRONMENT AND SOCIAL-STATUS

This paper examines the developmental causes of feather pecking, a common behaviour in caged chickens that leads to extensive feather damage. Small groups of junglefowl, Gallus gallus spadiceus, were raised from hatching either on a substrate containing sand and sod or on one consisting of wire mesh. Observations of social and other behaviour were made between 2 and 9 months of age. Feather pecking was most likely to occur when the birds were dustbathing or showed intention movements of dustbathing. Futhermore, the number of severe feather pecks received during dustbathing was correlated with the amount of feather damage on the recipient. The birds that did the most feather pecking were the ones found to be most fearful as assessed by a test of tonic immobility, and additionally the ones participating least during dustbathing in their group. Allopreening pecks could be distinguished from feather pecks: allopreening pecks were directed entirely at the anterior part of penmates and were gentle, while feather pecks were directed at the lower part of penmates and were often severe. Both were related to social status: lower ranking birds showed more allopreening while higher ranking birds showed more feather pecking. Sometimes, however, lower ranking individuals showed feather pecking in allopreening situations. The environment in which birds are reared may be significant for the development of feather pecking, and it is suggested that the primary cause of feather pecking is an abnormal development of the perceptual mechanism responsible for the detection of dust for dustbathing

The criterion validity of the web-based Major Depression Inventory when used on clinical suspicion of depression in primary care

Marie Germund Nielsen,1 Eva &Oslash;rnb&oslash;l,2 Per Bech,3 Mogens Vestergaard,1,4 Kaj Sparle Christensen1 1Research Unit for General Practice, Department of Public Health, Aarhus University, 2Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, Aarhus, 3Psychiatric Research Unit, Psychiatric Centre North Zealand, University Hospital of Copenhagen, Hiller&oslash;d, 4Section for&nbsp;General Medical Practice, Department of Public Health, Aarhus&nbsp;University, Aarhus, Denmark Background: The Major Depression Inventory (MDI) is widely used in Danish general practice as a screening tool to assess depression in symptomatic patients. Nevertheless, no validation studies of the MDI have been performed. The aim of this study was to validate the web-based version of the MDI against a fully structured telephone interview in a population selected on clinical suspicion of depression (ie, presence of two or three core symptoms of depression) in general practice.Materials and methods: General practitioners (GPs) invited consecutive persons suspected of depression to complete the web-based MDI in a primary care setting. The validation was based on the Munich-Composite International Diagnostic Interview (M-CIDI) by phone. GPs in the 22 practices in our study included 132 persons suspected of depression. Depression was rated as yes/no according to the MDI and M-CIDI. Sensitivity, specificity, and positive predictive value of the International Classification of Diseases, Tenth Revision (ICD-10) algorithms of the MDI were examined.Results: According to the M-CIDI interview, 87.9% of the included population was depressed and 64.4% was severely depressed. According to the MDI scale, 59.1% of the population was depressed and 31.8% was severely depressed. The sensitivity of the MDI for depression was 62.1% (95% confidence interval [95% CI]: 52.6&ndash;70.9) and the specificity was 62.5% (95% CI: 35.4&ndash;84.8). The sensitivity for severe depression was 42.2% (95% CI: 30.6&ndash;52.4) and the specificity was 85.1% (95% CI: 71.7&ndash;93.8). The receiver operating curve showed an area under the curve of 0.66 (95% CI: 0.52&ndash;0.81) for any depression and of 0.72 (95% CI: 0.63&ndash;0.81) for severe depression.Conclusion: The MDI is a conservative instrument for diagnosing ICD-10 depression in a clinical setting compared to the M-CIDI interview. Only a few false-positive diagnoses were identified when the MDI was used on clinical suspicion of depression. Keywords: Major Depression Inventory, depression, criterion validity, M-CIDI interview, diagnosin