A genetic risk score combining 32 SNPs is associated with body mass index and improves obesity prediction in people with major depressive disorder.

BACKGROUND: Obesity is strongly associated with major depressive disorder (MDD) and various other diseases. Genome-wide association studies have identified multiple risk loci robustly associated with body mass index (BMI). In this study, we aimed to investigate whether a genetic risk score (GRS) combining multiple BMI risk loci might have utility in prediction of obesity in patients with MDD. METHODS: Linear and logistic regression models were conducted to predict BMI and obesity, respectively, in three independent large case-control studies of major depression (Radiant, GSK-Munich, PsyCoLaus). The analyses were first performed in the whole sample and then separately in depressed cases and controls. An unweighted GRS was calculated by summation of the number of risk alleles. A weighted GRS was calculated as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver operating characteristic (ROC) analysis was used to compare the discriminatory ability of predictors of obesity. RESULTS: In the discovery phase, a total of 2,521 participants (1,895 depressed patients and 626 controls) were included from the Radiant study. Both unweighted and weighted GRS were highly associated with BMI (P <0.001) but explained only a modest amount of variance. Adding 'traditional' risk factors to GRS significantly improved the predictive ability with the area under the curve (AUC) in the ROC analysis, increasing from 0.58 to 0.66 (95% CI, 0.62-0.68; χ(2) = 27.68; P <0.0001). Although there was no formal evidence of interaction between depression status and GRS, there was further improvement in AUC in the ROC analysis when depression status was added to the model (AUC = 0.71; 95% CI, 0.68-0.73; χ(2) = 28.64; P <0.0001). We further found that the GRS accounted for more variance of BMI in depressed patients than in healthy controls. Again, GRS discriminated obesity better in depressed patients compared to healthy controls. We later replicated these analyses in two independent samples (GSK-Munich and PsyCoLaus) and found similar results. CONCLUSIONS: A GRS proved to be a highly significant predictor of obesity in people with MDD but accounted for only modest amount of variance. Nevertheless, as more risk loci are identified, combining a GRS approach with information on non-genetic risk factors could become a useful strategy in identifying MDD patients at higher risk of developing obesity.

Targeted Therapy for Patients with BRAF-Mutant Lung Cancer: Results from the European EURAF Cohort.

INTRODUCTION: Approximately 2% of lung adenocarcinomas have BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations, including V600E and other types. Vemurafenib, dabrafenib, and sorafenib as BRAF inhibitors are currently tested in clinical trials, but access for patients is limited. The aim of this study was to document the clinical course of patients treated outside of clinical trials. METHODS: We conducted a retrospective multicenter cohort study in Europe of patients with advanced BRAF-mutant lung cancer treated with known BRAF inhibitors. Data were anonymized and centrally assessed for age, gender, smoking, histology, stage, local molecular diagnostic results, systemic therapies, and survival. Best response was assessed locally by RECIST1.1. RESULTS: We documented 35 patients treated in 17 centers with vemurafenib, dabrafenib, or sorafenib. Median age was 63 years (range 42-85); gender was balanced; 14 (40%) were never smokers; all (100%) had adenocarcinoma; 29 (83%) had V600E; 6 (17%) had other mutations; one of them had a concomitant KRAS mutation. Thirty (86%) patients had chemotherapy in the first line. Overall survival with first-line therapy was 25.3 months for V600E and 11.8 months for non-V600E. Thirty-one patients received one BRAF inhibitor, and four received a second inhibitor. Overall response rate with BRAF therapy was 53%, and disease control rate was 85%. Median progression-free survival with BRAF therapy was 5.0 months, and overall survival was 10.8 months. CONCLUSIONS: These results confirm the activity of targeted therapy in patients with BRAF-mutant lung adenocarcinoma. Further trials are warranted to study combination therapies and drug resistance mechanisms.

Les bifurcations du récit interactif: continuité ou rupture?

Ainsi que l'affirmaient les premiers narratologues, le récit est une forme qui transcende les médias et si l'on peut reconnaître ses « avatars » jusque dans les jeux de rôle et les jeux vidéo, alors la confrontation entre narratologie et ludologie peut s'avérer une étape incontournable dans la refondation des concepts de la théorie du récit. Ainsi que l'affirmait récemment Werner Wolf : « une approche intermédiale peut [...] contribuer à éviter les généralisations unilatérales que l'on a pu observer dans les recherches mono-médiales antérieures » en particulier dans les travaux « centrés sur les textes verbaux » (Wolf 2003 : 193, n.t.). En retour, on peut espérer que ce recadrage conceptuel offre un point de vue nouveau sur les phénomènes narratifs, dont l'impact pourrait aller jusqu'à transformer notre appréhension des romans de l'âge baroque jusqu'aux fictions télévisuelles qui dominent le paysage médiatique contemporain. Ce numéro des Cahiers de narratologie est issu d'une journée d'étude qui s'est tenue à l'Université de Lausanne (UNIL) le 14 février 2014. Cette journée était organisée par Raphaël Baroni, Marc Marti, Claire Clivaz et Frédéric Kaplan et elle a bénéficié du soutien de l'EFLE (UNIL), du LADHUL (UNIL), du LIRCES (Université de Nice Sophia Antipolis), du DHLAB (Ecole Polytechnique Fédérale de Lausanne) et du Réseau romand de narratologie.

Trabecular bone score in type 1 diabetes--a cross-sectional study.

UNLABELLED: Trabecular bone score (TBS) seems to provide additive value on BMD to identify individuals with prevalent fractures in T1D. TBS did not significantly differ between T1D patients and healthy controls, but TBS and HbA1c were independently associated with prevalent fractures in T1D. A TBS cutoff <1.42 reflected prevalent fractures with 91.7 % sensitivity and 43.2 % specificity. INTRODUCTION: Type 1 diabetes (T1D) increases the risk of osteoporotic fractures. TBS was recently proposed as an indirect measure of bone microarchitecture. This study aimed at investigating the TBS in T1D patients and healthy controls. Associations with prevalent fractures were tested. METHODS: One hundred nineteen T1D patients (59 males, 60 premenopausal females; mean age 43.4 ± 8.9 years) and 68 healthy controls matched for gender, age, and body mass index (BMI) were analyzed. The TBS was calculated in the lumbar region, based on two-dimensional (2D) projections of DXA assessments. RESULTS: TBS was 1.357 ± 0.129 in T1D patients and 1.389 ± 0.085 in controls (p = 0.075). T1D patients with prevalent fractures (n = 24) had a significantly lower TBS than T1D patients without fractures (1.309 ± 0.125 versus 1.370 ± 0.127, p = 0.04). The presence of fractures in T1D was associated with lower TBS (odds ratio = 0.024, 95 % confidence interval (CI) = 0.001-0.875; p = 0.042) but not with age or BMI. TBS and HbA1c were independently associated with fractures. The area-under-the curve (AUC) of TBS was similar to that of total hip BMD in discriminating T1D patients with or without prevalent fractures. In this set-up, a TBS cutoff <1.42 discriminated the presence of fractures with a sensitivity of 91.7 % and a specificity of 43.2 %. CONCLUSIONS: TBS values are lower in T1D patients with prevalent fractures, suggesting an alteration of bone strength in this subgroup of patients. Reliable TBS cutoffs for the prediction of fracture risk in T1D need to be determined in larger prospective studies.