Principe de précaution dans la gestion des OGM au Québec : analyse des difficultés d’application et proposition d’éléments de cadre de gestion

L’objectif de cet essai est d’analyser la difficulté d’appliquer le principe de précaution dans la gestion des organismes génétiquement modifiés au Québec et proposer des alternatives pour en faire une gestion encore plus durable. La prise de conscience collective sur la dégradation de l’environnement est susceptible de ramener au premier plan la controverse qui dure depuis plusieurs années sur l’utilisation de cette technologie en agriculture et plus précisément des impacts potentiels qu’elle pourrait entrainer sur la santé et l’environnement. Face à ce débat, la société pourrait être encline à s’interroger sur l’inaction des décideurs politiques en matière d’application du principe de précaution, un principe pourtant adopté par la communauté internationale qui vise explicitement à résoudre ce genre de situation. Cela dit, l’application de ce principe par le Québec est complexifiée par une multitude de composantes. Dans un premier temps, le contexte québécois/canadien défavorise sa mise en œuvre puisque l’exploitation d’organismes génétiquement modifiés occupe une place importante dans l’économie du pays. Dans un second temps, la répartition des compétences entre le fédéral et le provincial limite la marge de manœuvre de la province. En ce qui a trait au principe lui-même, il est empreint de nombreuses zones grises. Le manque de justesse de sa définition, les nombreuses modalités de sa mise en œuvre, tout comme l’incertitude de son statut juridique en sont quelques exemples. Ces éléments se répercutent également dans la légitimité qu’attribuent les différents États à ce principe, et les mécanismes prévus pour résoudre ses divergences d’interprétation semblent eux aussi faire défaut. Face à ces difficultés, il demeure tout de même possible pour le Québec d’entreprendre des actions qui lui permettraient de procéder à une gestion plus durable des organismes génétiquement modifiés sur son territoire. L’élaboration d’un cadre d’application clarifiant davantage les modalités et la mise en œuvre du principe, le développement d’une expertise sur le sujet et l’instauration de mesures de cohabitation entre les différentes cultures seraient bénéfiques. Enfin, une pression sur les instances fédérales pour assurer le respect des intérêts des Québécois, une révision du processus d’approbation des produits, un système d’étiquetage et une meilleure transparence augmenteraient la durabilité de ses actions

Retrospective Study Looking at Cinacalcet in the Management of Hyperparathyroidism after Kidney Transplantation

Objectives. The primary objective of this study is to evaluate the use of cinacalcet in the management of hyperparathyroidism in kidney transplant recipients. The secondary objective is to identify baseline factors that predict cinacalcet use after transplantation. Methods. In this single-center retrospective study, we conducted a chart review of all patients having been transplanted from 2003 to 2012 and having received cinacalcet up to kidney transplantation and/or thereafter. Results. Twenty-seven patients were included with a mean follow-up of 2.9±2.4 years. Twenty-one were already taking cinacalcet at the time of transplantation. Cinacalcet was stopped within the first month in 12 of these patients of which 7 had to restart therapy. The main reason for restarting cinacalcet was hypercalcemia. Length of treatment was 23±26 months. There were only 3 cases of mild hypocalcemia. There was no statistically significant association between baseline factors and cinacalcet status a year later. Conclusions. Discontinuing cinacalcet within the first month of kidney transplantation often leads to hypercalcemia. Cinacalcet appears to be an effective treatment of hypercalcemic hyperparathyroidism in kidney transplant recipients. Further studies are needed to evaluate safety and long-term benefits

Psychological treatments for people with epilepsy.

BackgroundGiven the significant impact epilepsy may have on the health-related quality of life (HRQOL) of individuals with epilepsy and their families, there is increasing clinical interest in evidence-based psychological treatments, aimed at enhancing psychological and seizure-related outcomes for this group. This is an updated version of the original Cochrane Review published in Issue 10, 2017.ObjectivesTo assess the impact of psychological treatments for people with epilepsy on HRQOL outcomes.Search methodsFor this update, we searched the following databases on 12 August 2019, without language restrictions: Cochrane Register of Studies (CRS Web), which includes randomized or quasi-randomized controlled trials from the Specialized Registers of Cochrane Review Groups including Epilepsy, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 09 August 2019), and PsycINFO (EBSCOhost, 1887 onwards), and from PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (ICTRP). We screened the references from included studies and relevant reviews, and contacted researchers in the field for unpublished studies.Selection criteriaWe considered randomized controlled trials (RCTs) and quasi-RCTs for this review. HRQOL was the main outcome. For the operational definition of 'psychological treatments', we included a broad range of skills-based psychological treatments and education-only interventions designed to improve HRQOL, seizure frequency and severity, as well as psychiatric and behavioral health comorbidities for adults and children with epilepsy. These psychological treatments were compared to treatment as usual (TAU), an active control group (such as social support group), or antidepressant pharmacotherapy.Data collection and analysisWe used standard methodological procedures expected by Cochrane.Main resultsWe included 36 completed RCTs, with a total of 3526 participants. Of these studies, 27 investigated skills-based psychological interventions. The remaining nine studies were education-only interventions. Six studies investigated interventions for children and adolescents, three studies investigated interventions for adolescents and adults, and the remaining studies investigated interventions for adults. Based on satisfactory clinical and methodological homogeneity, we pooled data from 11 studies (643 participants) that used the Quality of Life in Epilepsy-31 (QOLIE-31) or other QOLIE inventories (such as QOLIE-89 or QOLIE-31-P) convertible to QOLIE-31. We found significant mean changes for the QOLIE-31 total score and six subscales (emotional well-being, energy and fatigue, overall QoL, seizure worry, medication effects, and cognitive functioning). The mean changes in the QOLIE-31 total score (mean improvement of 5.23 points, 95% CI 3.02 to 7.44; P Authors' conclusionsImplications for practice: Skills-based psychological interventions improve HRQOL in adults and adolescents with epilepsy. Adjunctive use of skills-based psychological treatments for adults and adolescents with epilepsy may provide additional benefits in HRQOL when these are incorporated into patient-centered management. We judge the evidence to be of moderate certainty.Implications for researchInvestigators should strictly adhere to the CONSORT guidelines to improve the quality of reporting on their interventions. A thorough description of intervention protocols is necessary to ensure reproducibility. When examining the effectiveness of psychological treatments for people with epilepsy, the use of standardized HRQOL inventories, such as the Quality of Life in Epilepsy Inventories (QOLIE-31, QOLIE-31-P, and QOLIE-89) would increase comparability. Unfortunately, there is a critical gap in pediatric RCTs and RCTs including people with epilepsy and intellectual disabilities. Finally, in order to increase the overall quality of RCT study designs, adequate randomization with allocation concealment and blinded outcome assessment should be pursued. As attrition is often high in research that requires active participation, an intention-to-treat analysis should be carried out. Treatment fidelity and treatment competence should also be assessed. These important dimensions, which are related to 'Risk of bias' assessment, should always be reported

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Principe de précaution dans la gestion des OGM au Québec : analyse des difficultés d’application et proposition d’éléments de cadre de gestion

L’objectif de cet essai est d’analyser la difficulté d’appliquer le principe de précaution dans la gestion des organismes génétiquement modifiés au Québec et proposer des alternatives pour en faire une gestion encore plus durable. La prise de conscience collective sur la dégradation de l’environnement est susceptible de ramener au premier plan la controverse qui dure depuis plusieurs années sur l’utilisation de cette technologie en agriculture et plus précisément des impacts potentiels qu’elle pourrait entrainer sur la santé et l’environnement. Face à ce débat, la société pourrait être encline à s’interroger sur l’inaction des décideurs politiques en matière d’application du principe de précaution, un principe pourtant adopté par la communauté internationale qui vise explicitement à résoudre ce genre de situation. Cela dit, l’application de ce principe par le Québec est complexifiée par une multitude de composantes. Dans un premier temps, le contexte québécois/canadien défavorise sa mise en œuvre puisque l’exploitation d’organismes génétiquement modifiés occupe une place importante dans l’économie du pays. Dans un second temps, la répartition des compétences entre le fédéral et le provincial limite la marge de manœuvre de la province. En ce qui a trait au principe lui-même, il est empreint de nombreuses zones grises. Le manque de justesse de sa définition, les nombreuses modalités de sa mise en œuvre, tout comme l’incertitude de son statut juridique en sont quelques exemples. Ces éléments se répercutent également dans la légitimité qu’attribuent les différents États à ce principe, et les mécanismes prévus pour résoudre ses divergences d’interprétation semblent eux aussi faire défaut. Face à ces difficultés, il demeure tout de même possible pour le Québec d’entreprendre des actions qui lui permettraient de procéder à une gestion plus durable des organismes génétiquement modifiés sur son territoire. L’élaboration d’un cadre d’application clarifiant davantage les modalités et la mise en œuvre du principe, le développement d’une expertise sur le sujet et l’instauration de mesures de cohabitation entre les différentes cultures seraient bénéfiques. Enfin, une pression sur les instances fédérales pour assurer le respect des intérêts des Québécois, une révision du processus d’approbation des produits, un système d’étiquetage et une meilleure transparence augmenteraient la durabilité de ses actions

Contamination of mafic magmas by crustal material in the layered-igneous Complex of Duluth, Minnesota

Résumé de la présentation

ClusterCAD 2.0: an updated computational platform for chimeric type I polyketide synthase and nonribosomal peptide synthetase design

Megasynthase enzymes such as type I modular polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) play a central role in microbial chemical warfare because they can evolve rapidly by shuffling parts (catalytic domains) to produce novel chemicals. If we can understand the design rules to reshuffle these parts, PKSs and NRPSs will provide a systematic and modular way to synthesize millions of molecules including pharmaceuticals, biomaterials, and biofuels. However, PKS and NRPS engineering remains difficult due to a limited understanding of the determinants of PKS and NRPS fold and function. We developed ClusterCAD to streamline and simplify the process of designing and testing engineered PKS variants. Here, we present the highly improved ClusterCAD 2.0 release, available at https://clustercad.jbei.org. ClusterCAD 2.0 boasts support for PKS-NRPS hybrid and NRPS clusters in addition to PKS clusters; a vastly enlarged database of curated PKS, PKS-NRPS hybrid, and NRPS clusters; a diverse set of chemical 'starters' and loading modules; the new Domain Architecture Cluster Search Tool; and an offline Jupyter Notebook workspace, among other improvements. Together these features massively expand the chemical space that can be accessed by enzymes engineered with ClusterCAD

Association of Neutrophil-to-Lymphocyte Ratio With Inflammation and Erythropoietin Resistance in Chronic Dialysis Patients

Background: Neutrophil-to-lymphocyte ratio (NLR) was widely studied as a prognostic marker in various medical and surgical specialties, but its significance in nephrology is not yet established. Objective: We evaluated its accuracy as an inflammation biomarker in a dialysis population. Design setting: Single-center retrospective study. Patients: The records of all 550 patients who were treated with hemodialysis (HD) or peritoneal dialysis (PD) from September 2008 to March 2011 were included. Measurements: NLR was calculated from the monthly complete blood count. Methods: Association between NLR and markers of inflammation (C-reactive protein [CRP], serum albumin, and erythropoietin resistance index [ERI]) was measured using Spearman coefficient. Results: In total, 120 patients were eligible for the correlation analyses. We found a positive correlation between NLR and CRP (all patients: r = 0.45, P < .001; HD: r = 0.47, P < .001; PD: r = 0.48, P = .13). NLR and albumin were inversely correlated ( r = −0.51, P < .001). Finally, high NLR was associated with a nonsignificant increased ERI, but we have not demonstrated a direct correlation. Limitations: CRP and albumin are not measured routinely and were ordered for a specific clinical reason leading to an indication bias. Also, no relationship with clinical outcome was established. Conclusions: NLR seems to be a good inflammatory biomarker in dialysis in addition to being easily available. However, controlled studies should be conducted to properly assess and validate NLR levels that would be clinically significant and relevant, as well as its prognostic significance and utility in a clinical setting

ClusterCAD 2.0: an updated computational platform for chimeric type I polyketide synthase and nonribosomal peptide synthetase design

Megasynthase enzymes such as type I modular polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) play a central role in microbial chemical warfare because they can evolve rapidly by shuffling parts (catalytic domains) to produce novel chemicals. If we can understand the design rules to reshuffle these parts, PKSs and NRPSs will provide a systematic and modular way to synthesize millions of molecules including pharmaceuticals, biomaterials, and biofuels. However, PKS and NRPS engineering remains difficult due to a limited understanding of the determinants of PKS and NRPS fold and function. We developed ClusterCAD to streamline and simplify the process of designing and testing engineered PKS variants. Here, we present the highly improved ClusterCAD 2.0 release, available at https://clustercad.jbei.org. ClusterCAD 2.0 boasts support for PKS-NRPS hybrid and NRPS clusters in addition to PKS clusters; a vastly enlarged database of curated PKS, PKS-NRPS hybrid,&nbsp;and NRPS clusters; a diverse set of chemical 'starters' and loading modules; the new Domain Architecture Cluster Search Tool; and an offline Jupyter Notebook workspace, among other improvements. Together these features massively expand the chemical space that can be accessed by enzymes engineered with ClusterCAD