Étude des cellules dendritiques chez les patients qui ont subi une greffe de cellules souches allogéniques

La vigueur de la réponse immunitaire générée par les cellules dendritiques (DC) a positionné ces cellules comme médiatrices centrales dans l’activation des lymphocytes T. La vulnérabilité des cellules cancéreuses de leucémie myéloïde chronique (LMC) à l’intervention immunitaire résulte apparemment de la capacité des cellules leucémiques de se différencier en DC. Ces DC ont alors la capacité de présenter des peptides provenant des cellules souches leucémiques aux lymphocytes T. Dans ce travail, nous démontrons que la plupart des patients atteints d’une LMC présentent un déficit important en DC au niveau du sang et de la moelle osseuse avant la greffe de cellules souches allogéniques. Les faibles niveaux de DC circulantes résultent en grande partie d’une perte de la diversité au niveau des cellules progénitrices CD34+ leucémiques au niveau de la moelle osseuse. Ces cellules progénitrices CD34+ présentent d’ailleurs une capacité réduite à se différencier en DC in vitro. Nous avons trouvé qu’un décompte faible de DC avant une greffe allogénique était associé à une diminution significative de la survie et une augmentation considérable du risque de développer une des complications mortelles. Puisque la reconstitution des DC suite à la greffe est absente, notre étude appuie aussi la thèse que ce sont les cellules DC pré greffe qui sont primordiales dans l'effet du greffon contre leucémie (GVL). Dans ce contexte, notre étude suggère que le compte des DC avant la greffe allogénique pourrait servir de marqueur pronostique pour identifier les patients LMC à risque de développer certaines complications suite à une greffe allogénique.The intensity of the immune response that is generated by the dendritic cells (DCs) has established these cells as central mediators in the activation of T lymphocytes. The vulnerability of leukemic cells present in chronic myeloid leukemia is mostly attributable to the ability of the leukemic stems cell to differentiate themselves into potent DCs. The latter are then able to present peptides which come from endogenous origin and from leukemic stem cells to the T lymphocytes. In this thesis, we demonstrate that, before allogeneic stem cell transplant, the majority of patients afflicted by CML have a considerable lack of DCs in their peripheral blood as well as in their bone marrow. The low levels of circulating DCs result to a great extent from a loss of diversity in the CD34+ leukemic progenitor cells located in the bone marrow. Moreover, these CD34+ leukemic progenitor cells display a reduced capacity to differentiate themselves into DCs in vitro. Our findings show that having a low level of DCs prior to an allogeneic transplant is associated with a significant decline in survival rates as well as with increased risks of developing life threatening complications. Since the DCs’ reconstitution following an allogeneic bone marrow transplant is missing, our study supports the thesis that pre graft DCs are essential in the Graft versus leukemia effect (GVL).Therefore, our research suggests that tallying DC before proceeding with an allogeneic transplant could act as a prognostic marker to identify LMC patients who present risks of complications after an allogeneic transplant

Véhicules zéro émission et lutte contre les changements climatiques: survol des tendances et politiques à l’échelle mondiale

Le secteur des transports est le deuxième principal émetteur mondial de gaz à effet de serre.Depuis les cinq dernières années, l’électrification des transports et la question des voitures électriques sont devenues des enjeux très en vogue dans le cadre des négociations climatiques internationales, autant auprès desgouvernements centraux que noncentraux. D’ailleurs, la province de Québec est de ceux exerçant un grand leadership en matière d’électromobilitéà l’échelle mondiale.Cette note de recherche fait un état des lieux des principaux engagements internationaux et des nombreuses initiatives et tendances mondiales dans le secteur de l’électrification des transports. Elle explore égalementdes cas de gouvernements centraux et non centraux, tels la Norvège, l’État de la Californie et l’Écosse,ayant développé des politiques innovantes en matière d’électromobilité. Finalement,elle identifieles bonnes pratiques applicables au Québec.Parallèlement, cette note de recherchetémoigne dela marge de manœuvre ainsi que de l’éventail de possibilités dont disposent les gouvernements non centraux pour participer à l’édification du complexe de régimes internationauxtraitant des changements climatiques

Sex effect in the temporal perception of faces expressing anger and shame

The aim of the present study was to investigate sex-related variations in the perception of the duration of emotional stimuli (human faces). Twenty male and 20 female participants estimated the duration of angry, ashamed and neutral faces marking 0.4 to 1.6 s intervals. Female faces were used in one session, and male faces in the other. Compared to the angry faces condition, intervals were underestimated when ashamed faces were shown. However, the intervals in neither conditions were significantly overestimated or underestimated compared to the neutral condition. Even more critical is the fact that there was an underestimation by male participants of the duration of male faces compared to female faces; and female participants overestimated the duration in the anger condition, compared with the shame condition, only when male faces were presented. Moreover, the emotional effects on the participants’ performance were correlated to inter-individual differences in empathic abilities. The findings are discussed in terms of sex differences, of social context, and of how attention is solicited and arousal generated by emotions. Keywords: Psychological time, emotions, sex differenc

An Evaluation of the Performance of Tag SNPs Derived from HapMap in a Caucasian Population

The Haplotype Map (HapMap) project recently generated genotype data for more than 1 million single-nucleotide polymorphisms (SNPs) in four population samples. The main application of the data is in the selection of tag single-nucleotide polymorphisms (tSNPs) to use in association studies. The usefulness of this selection process needs to be verified in populations outside those used for the HapMap project. In addition, it is not known how well the data represent the general population, as only 90–120 chromosomes were used for each population and since the genotyped SNPs were selected so as to have high frequencies. In this study, we analyzed more than 1,000 individuals from Estonia. The population of this northern European country has been influenced by many different waves of migrations from Europe and Russia. We genotyped 1,536 randomly selected SNPs from two 500-kbp ENCODE regions on Chromosome 2. We observed that the tSNPs selected from the CEPH (Centre d'Etude du Polymorphisme Humain) from Utah (CEU) HapMap samples (derived from US residents with northern and western European ancestry) captured most of the variation in the Estonia sample. (Between 90% and 95% of the SNPs with a minor allele frequency of more than 5% have an r (2) of at least 0.8 with one of the CEU tSNPs.) Using the reverse approach, tags selected from the Estonia sample could almost equally well describe the CEU sample. Finally, we observed that the sample size, the allelic frequency, and the SNP density in the dataset used to select the tags each have important effects on the tagging performance. Overall, our study supports the use of HapMap data in other Caucasian populations, but the SNP density and the bias towards high-frequency SNPs have to be taken into account when designing association studies

Incidence, predictive factors and haemodynamic consequences of acute stent recoil following transcatheter aortic valve implantation with a balloon-expandable valve

Aims: The elastic behaviour (acute recoil) of a valve prosthesis stent following transcatheter aortic valve implantation (TAVI) is unknown. This study sought to determine the occurrence, severity, predictive factors and haemodynamic consequences of acute recoil following TAVI. Methods and results : A prospective angiographic analysis of the stent frame dimensions in 111 consecutive patients who underwent TAVI with a balloon-expandable valve (36 Edwards SAPIEN; 75 SAPIEN XT) was performed. Acute recoil was defined as the difference between minimal lumen diameter (MLD) at full balloon expansion and immediately after balloon deflation. MLD during balloon inflation was significantly larger than MLD after balloon deflation (23.40±2.31 mm vs. 22.29±2.21 mm, p<0.001), which represented an absolute and percent decrease in stent dimension of 1.10±0.40 mm and 4.70±1.76%, respectively. In the multivariate analysis, the predictors of larger recoil were a higher prosthesis/annulus ratio (r²=0.0624, p=0.015) and the SAPIEN XT prosthesis (r²=0.1276, p=0.001). No significant changes in haemodynamic performance were observed at discharge and follow-up in patients with larger recoil. Conclusions : TAVI with a balloon-expandable valve was systematically associated with a certain degree of valve stent recoil after balloon deflation. A higher degree of valve oversizing and the SAPIEN XT prosthesis predicted a larger degree of stent recoil

Can we quickly and thoroughly assess pain with the PACSLAC-II? : a convergent validity study in long-term care residents suffering from dementia.

Abstract : A previous study found that the modified version of the Pain Assessment Checklist for Seniors with Limited Ability to Communicate (PACSLAC-II) is a valid tool to assess pain in elderly individuals suffering from dementia and who are unable to communicate verbally. The primary objective of this study was to confirm the convergent validity of the PACSLAC-II using direct evaluation of long-term care residents in real-life situations, using two other well-validated pain assessment scales (i.e., PACSLAC and Pain Assessment in Advanced Dementia [PAINAD]). A secondary objective was to document and compare the time required to complete and score each assessment scale. During two potentially painful procedures (i.e., transfer/mobilization), 46 long-term care residents (mean age = 83 ± 10 years) suffering from dementia were observed by three independent evaluators, each using one of the assessment scales (randomly assigned). Correlational analyses and analysis of variance were used to evaluate the association between each scale and to compare scoring time. The PACSLAC (r = 0.61) and the PAINAD (r = 0.65) were both moderately associated with the PACSLAC-II (all p values < .001). The PAINAD's average scoring time (63 ± 19 seconds) was lower than the PACSLAC-II's (96 ± 2 seconds), which was lower than the PACSLAC's (135 ± 53 seconds) (all p values < .001). These results suggest that the PACSLAC-II is a valid tool for assessing pain in individuals with dementia. The time required to complete and score the PACSLAC-II was reasonable, supporting its usefulness in clinical settings

DataSHIELD: taking the analysis to the data, not the data to the analysis

Research in modern biomedicine and social science requires sample sizes so large that they can often only be achieved through a pooled co-analysis of data from several studies. But the pooling of information from individuals in a central database that may be queried by researchers raises important ethico-legal questions and can be controversial. In the UK this has been highlighted by recent debate and controversy relating to the UK's proposed 'care.data' initiative, and these issues reflect important societal and professional concerns about privacy, confidentiality and intellectual property. DataSHIELD provides a novel technological solution that can circumvent some of the most basic challenges in facilitating the access of researchers and other healthcare professionals to individual-level data. Commands are sent from a central analysis computer (AC) to several data computers (DCs) storing the data to be co-analysed. The data sets are analysed simultaneously but in parallel. The separate parallelized analyses are linked by non-disclosive summary statistics and commands transmitted back and forth between the DCs and the AC. This paper describes the technical implementation of DataSHIELD using a modified R statistical environment linked to an Opal database deployed behind the computer firewall of each DC. Analysis is controlled through a standard R environment at the AC. Based on this Opal/R implementation, DataSHIELD is currently used by the Healthy Obese Project and the Environmental Core Project (BioSHaRE-EU) for the federated analysis of 10 data sets across eight European countries, and this illustrates the opportunities and challenges presented by the DataSHIELD approach. DataSHIELD facilitates important research in settings where: (i) a co-analysis of individual-level data from several studies is scientifically necessary but governance restrictions prohibit the release or sharing of some of the required data, and/or render data access unacceptably slow; (ii) a research group (e.g. in a developing nation) is particularly vulnerable to loss of intellectual property-the researchers want to fully share the information held in their data with national and international collaborators, but do not wish to hand over the physical data themselves; and (iii) a data set is to be included in an individual-level co-analysis but the physical size of the data precludes direct transfer to a new site for analysis

The fecal immunochemical test (fit): Selected aspects regarding its effectiveness for colorectal cancer screening in Quebec City

Background and aims: FIT's value has been ascertained across Canada and worldwide, but still needs to be assessed within the province of Quebec. There also remains a gap between formal indications for FIT, and its actual use in clinical practice. This research aims to evaluate some aspects of FIT's effectiveness in our setting, and its application by prescribers. Methods: We retrospectively identified and reviewed all the colonoscopies conducted for a positive FIT in 2014 at 2 hospitals located in Quebec City. Results: Five hundred and fifty-nine (559) colonoscopies were reviewed. We obtained PPVs of 6.8% and 46.9% for the detection of CRC and AA, respectively. The PPV for the detection of SCL was higher in men compared to women (OR 1.56, 95%CI 1.11–2.20) and among justified FITs compared to unwarranted ones (OR 1.88, 95%CI 1.34–2.63). The PPV for CRC detection was 25.0% in the presence of unexplained iron deficiency anemia and 6.5% when anemia was absent (p = 0.0058). In 49.9% of cases, the prescription of a FIT was inappropriate. Conclusion: The FIT holds a better PPV for detecting SCL among men and when it is indicated. Anemia is associated with a higher CRC detection rate. Half of the FITs were not initially indicated. Keywords: Colorectal neoplasms, Mass screening, Gastroenterology, Occult blood, Colonoscop

Economic and environmental assessment on the energetic valorization of organic material for a municipality in Quebec, Canada

Waste-to-energy provides a solution to two problems: waste management and energy generation. An integrated anaerobic waste valorization process is an interesting option, but because of investments cost and low energy value in the province of Quebec, it is hard for a municipality to commit to that solution. This paper investigated the economic possibilities to manage organic material, organic fraction of municipal solid waste, and municipal wastewater sludge by anaerobic digestion for a 150,000 inhabitant municipality, with consideration to energy generation and greenhouse gas emission reduction. Using the biogas to co-generation solution brings a payback time on investment (PBT) of 3.7 years with electricity price at 0.10 $Cdn/kW h. The addition of manure from surrounding farms increases the biogas production by 37%, but increases the PBT to 6.8 years unless the leftover digestate can be used for agronomic valorization; then it becomes economically advantageous. The natural gas purchasing cost is too low to promote the enrichment of biogas into renewable natural gas. However, this scenario has the lowest energetic payback time (3.3 years) and reduces the most greenhouse gas emissions (4261 tCO2eq/a).Waste management Energy Biogas Co-generation Greenhouse gas Organic waste