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Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.
To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.
The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.
In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.
This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
This article assesses how social innovations in the field of local domiciliary long-term care are shaped and implemented. It proposes a mapping of innovations in terms of two structuring discourses that inform welfare state reforms: a libertarian and a neo-liberal discourse. It then provides an analysis of the concrete trajectories of three local innovations for elderly people in Hamburg (Germany), Edinburgh (Scotland) and Geneva (Switzerland). Theoretically, social innovation is considered as a discursive process of public problem redefinition and institutionalisation. New coalitions of new actors are formed along this double process, and these transform the original discourse of innovation. The comparative analysis of the three processes of institutionalisation of local innovation shows that, in the context of local policy making, social innovations inspired by a libertarian critique of the welfare state undergo differentiated processes of normalisation.
The gene product of the ABCB1 gene, the P-glycoprotein, functions as a custodian molecule in the blood–brain barrier and regulates the access of most antidepressants into the brain. Previous studies showed that ABCB1 polymorphisms predicted the response to antidepressants that are substrates of the P-gp, while the response to nonsubstrates was not influenced by ABCB1 polymorphisms. The aim of the present study was to evaluate the clinical application of ABCB1 genotyping in antidepressant pharmacotherapy.
Data came from 58 depressed inpatients participating in the Munich Antidepressant Response Signature (MARS) project, whose ABCB1 gene test results were implemented into the clinical decision making process. Hamilton Depression Rating Scale (HAM-D) scores, remission rates, and duration of hospital stay were documented with dose and kind of antidepressant treatment.
Patients who received ABCB1 genotyping had higher remission rates [χ2(1) = 6.596, p = 0.005, 1-sided] and lower Hamilton sores [t(111) = 2.091, p = 0.0195, 1-sided] at the time of discharge from hospital as compared to patients without ABCB1 testing. Among major allele homozygotes for ABCB1 single nucleotide polymorphisms (SNPs) rs2032583 and rs2235015 (TT/GG genotype), an increase in dose was associated with a shorter duration of hospital stay [rho(28) = –0.441, p = 0.009, 1-sided], whereas other treatment strategies (eg, switching to a nonsubstrate) showed no significant associations with better treatment outcome.
The implementation of ABCB1 genotyping as a diagnostic tool influenced clinical decisions and led to an improvement of treatment outcome. Patients carrying the TT/GG genotype seemed to benefit from an increase in P-gp substrate dose.
Results suggest that antidepressant treatment of depression can be optimized by the clinical application of ABCB1 genotyping.
The first reconnaissance survey of the Wadi ash-Shati, the northernmost line of the oases of the Fazzan, was carried out in 2007 and 2008. This survey aimed to locate archaeological sites of the Garamantian and historic periods in a region that, despite being on record as the most populated of the Fazzan in the historic period, was never previously systematically surveyed. Following the field survey, further examination of high-resolution satellite imagery was carried out. This allowed for the discovery of more sites and the detailed tracing of a number of cemeteries that were only partially surveyed during fieldwork. The report presents the first cross-chronological map of the Wadi ash-Shati and some interpretations of the history of occupation of the area. The future investigation of specific sites, a structured dating programme and further, more detailed, study of historic sources will provide a fuller understanding of this region.