Large Scale Association Analysis Identifies Three Susceptibility Loci for Coronary Artery Disease

Genome wide association studies (GWAS) and their replications that have associated DNA variants with myocardial infarction (MI) and/or coronary artery disease (CAD) are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3), and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR = 0.68, p = 0.0035), while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR = 1.33, p = 0.0086). Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology

« Collision tumor » chez les patients atteints d’une maladie lymphoproliférative en association avec un cancer du sein, un cancer colorectal, un cancer pulmonaire ou un mélanome.

Introduction A « collision tumor » (CT) is a rare phenomenon defined by the proximity of two different tumor cells during a histopathological analysis. As our study is focused on the CT in the lymph nodes, we considered only cancers that usually have an excision of a lymph node during the staging or the treatment of the tumor. There are few studies about the CT and almost exclusively case reports found in the literature. Therefore, its frequency and the prognostic of the patients with CT is not well known. The treatment of patients with CT have not been extensively studied either, but in the literature, there appears to be a tendency to treat initially the cancer with the worse prognostic and have a regular follow-up of the two malignancies. The aim of our study is to evaluate the incidence, the treatment and the prognostic of this phenomenon in the CHUV over 10 years. Method This is a retrospective study which was conducted on patients who had been diagnosed with a breast cancer, a colorectal cancer, a lung cancer or a melanoma in the CHUV between 2005 and 2015 and have been diagnosed with a lymphoproliferative disease before, or at the same time. Our inclusion and exclusion criteria matched for 28 patients: a diagnostic of a lymphoproliferative disease before or at the same time of the second cancer, an excision of a lymph node, the evidence of the report of the anatomopathological analyze in the medical file. Due to the limited number of patients with CT, we chose to conduct a qualitative analysis. Results Four patients over the 28 included presented a CT in a lymph node. They were 61, 65, 80 and 84 years-old when they developed the CT. Two of them had an immunodeficiency. The median time between the lymphoproliferative disease and the second cancer was 192 months (2- 240). Three patients had an association of melanoma and chronic lymphocytic leukemia (CLL). The last one had an association of lung cancer and CLL that has been discovered because of a reevaluation of the histological section. All of the patients have been presented at a multidisciplinary meeting to discuss the appropriate treatment. Two of the 4 patients had an adjuvant treatment. The median time of the follow-up was 18 months (12-24) during which the 4 patients had a progression or a relapse of one of their malignancies. For this reason, the treatment has been changed for 3 patients. None of the patients died during the follow-up. Conclusion Our study, whilst based on a limited number of cases, shows that the risk of developing a CT might increase when a CLL is associated with a melanoma and when a patient has an immunodeficiency. The rare phenomenon such as CT can be underestimated because of the lack of notion of the lymphoproliferative disease in many histopathological reports, leading to missing a diagnostic of other pathological cells by the expert. As reported in the literature, the treatment was initially directed at the tumor with the worse prognostic for all the patients with CT. It had to be changed for 3 patients because of the progression or relapse of the other cancer which shows the importance of a good follow-up. In our study, the prognostic of patients with CT (all having had a progression or a relapse of one of their tumor during the two years of follow-up) is worse than the patient without a CT

NUMERICAL SIMULATION OF A PREMIXED TURBULENT V-SHAPED FLAME

In this paper we simulate a turbulent premixed V-shape flame stabilized on a hot wire. The device used is composed of a vertical combustion chamber where the methane-air mixture is convected upwards with a mean velocity of 4ms-1. The flow was simulated running Fluent 6.3, which numerically solved the stationary Favre-averaged mass balance; Navier-Stokes equations; combustion progress variable, and k-ε equations on a two-dimensional numerical mesh. We model gaseous mixture, ignoring Soret and Dufour effects and radiation heat transfer. The progress variable balance equation was closed using Eddy Break Up model. The results of our simulations allow us to analyze the influence of equivalence ratio and the turbulent intensity on the properties of the flame (velocity, fluctuation, progress variable and Thickness of flame).This work gives us an idea on the part which turbulence can play to decrease the risks of extinction and instabilities caused by the lean premixed combustion

Psychiatric outpatient clinic for emerging psychological disorders (PREPP Program): validation of the frech version of CAARMS

Introduction: Our purpose was to validate the discriminative of the CAARMS in an Psychiatric outpatient clinic for emerging psychological disorders (PREPP Program). Methods: The original version of the Comprehensive Assessment for At Risk Mental State was translated and back translated and submitted to the original authors. Then, we first compare three groups of subjects (patients referred as prodomal, n = 27, with first episode, n = 22 and a normal controls group n = 15). In a second step, 18−25 years old patients referring with emerging psychological disorders were consecutively explored and enrolled in a prospective study. Results: We compared 'inclusion groups' to groups issued from the CAARMS. CAARMS readily distinguished the three contrasted group of subjected. 100% of controls and 75 of first episode patients were correctly classified and total scores were significantly different across the groups. In a second step, we explore 80 patients reffered as for a emerging psychological disorders (PREPP Program) were explored and compared regarding to CAARMS criteria for sociodemographic, cognitive and clinical characterisitics and substance abuse. There was no significant difference between the groups at inclusion for sociodemographic variables, including cannabis exposure; though regular use of cannabis was higher in patients reaching the "psychosis" threshold (P: 66%) compared to at risk (AR: 53%) and not at high risk subject (NAR: 33%). Psychopathological severy also differ in the three groups. Outcome is currenty under analysis. Discussion: This paper reports for the first time on the validation of a French version of CAARMS and confirm its discriminative value