Genomic architecture of sickle cell disease clinical variation in children from West Africa : a case-control study design

Contexte : L’anémie falciforme ou drépanocytose est un problème de santé important, particulièrement pour les patients d’origine africaine. La variation phénotypique de l’anémie falciforme est problématique pour le suivi et le traitement des patients. L’architecture génomique responsable de cette variabilité est peu connue. Principe : Mieux saisir la contribution génétique de la variation clinique de cette maladie facilitera l’identification des patients à risque de développer des phénotypes sévères, ainsi que l’adaptation des soins. Objectifs : L’objectif général de cette thèse est de combler les lacunes relatives aux connaissances sur l’épidémiologie génomique de l’anémie falciforme à l’aide d’une cohorte issue au Bénin. Les objectifs spécifiques sont les suivants : 1) caractériser les profils d’expressions génomiques associés à la sévérité de l’anémie falciforme ; 2) identifier des biomarqueurs de la sévérité de l’anémie falciforme ; 3) identifier la régulation génétique des variations transcriptionelles ; 4) identifier des interactions statistiques entre le génotype et le niveau de sévérité associé à l’expression ; 5) identifier des cibles de médicaments pour améliorer l’état des patients atteints d’anémie falciforme. Méthode : Une étude cas-témoins de 250 patients et 61 frères et soeurs non-atteints a été menée au Centre de Prise en charge Médical Intégré du Nourrisson et de la Femme Enceinte atteints de Drépanocytose, au Bénin entre février et décembre 2010. Résultats : Notre analyse a montré que des profils d’expressions sont associés avec la sévérité de l’anémie falciforme. Ces profils sont enrichis de génes des voies biologiques qui contribuent à la progression de la maladie : l’activation plaquettaire, les lymphocytes B, le stress, l’inflammation et la prolifération cellulaire. Des biomarqueurs transcriptionnels ont permis de distinguer les patients ayant des niveaux de sévérité clinique différents. La régulation génétique de la variation de l’expression des gènes a été démontrée et des interactions ont été identifiées. Sur la base de ces résultats génétiques, des cibles de médicaments sont proposées. Conclusion: Ce travail de thèse permet de mieux comprendre l’impact de la génomique sur la sévérité de l’anémie falciforme et ouvre des perspectives de développement de traitements ciblés pour améliorer les soins offerts aux patients.

Mainstreaming ESL : case studies in integrating ESL students into the mainstream curriculum.

Se recogen varios estudios de profesionales de las escuelas primarias y secundarias del Reino Unido, Estados Unidos,Canadá y Australia que describen sus experiencias docentes en la integración con éxito en las aulas regulares de niños con inglés como segundo idioma (ESL).

Comparing meta-analysis and ecological-longitudinal analysis in time-series studies: a case study of the effects of air pollution on mortality in three Spanish cities

The objective of this paper is to introduce a diVerent approach, called the ecological-longitudinal, to carrying out pooled analysis in time series ecological studies. Because it gives a larger number of data points and, hence, increases the statistical power of the analysis, this approach, unlike conventional ones, allows the complementation of aspects such as accommodation of random effect models, of lags, of interaction between pollutants and between pollutants and meteorological variables, that are hardly implemented in conventional approaches. Design—The approach is illustrated by providing quantitative estimates of the short-termeVects of air pollution on mortality in three Spanish cities, Barcelona,Valencia and Vigo, for the period 1992–1994. Because the dependent variable was a count, a Poisson generalised linear model was first specified. Several modelling issues are worth mentioning. Firstly, because the relations between mortality and explanatory variables were nonlinear, cubic splines were used for covariate control, leading to a generalised additive model, GAM. Secondly, the effects of the predictors on the response were allowed to occur with some lag. Thirdly, the residual autocorrelation, because of imperfect control, was controlled for by means of an autoregressive Poisson GAM. Finally, the longitudinal design demanded the consideration of the existence of individual heterogeneity, requiring the consideration of mixed models. Main results—The estimates of the relative risks obtained from the individual analyses varied across cities, particularly those associated with sulphur dioxide. The highest relative risks corresponded to black smoke in Valencia. These estimates were higher than those obtained from the ecological-longitudinal analysis. Relative risks estimated from this latter analysis were practically identical across cities, 1.00638 (95% confidence intervals 1.0002, 1.0011) for a black smoke increase of 10 μg/m3 and 1.00415 (95% CI 1.0001, 1.0007) for a increase of 10 μg/m3 of sulphur dioxide. Because the statistical power is higher than in the individual analysis more interactions were statistically significant,especially those among air pollutants and meteorological variables. Conclusions—Air pollutant levels were related to mortality in the three cities of the study, Barcelona, Valencia and Vigo. These results were consistent with similar studies in other cities, with other multicentric studies and coherent with both, previous individual, for each city, and multicentric studies for all three cities

Pediatric conversion to the HiResolution processing strategy: 6 case studies

This paper presents a study documenting the general trends in the programming techniques, aided behavioral thresholds, speech perception abilities, and overall behavior when converting children into processing strategy called HiResolution (HiRes), used with the Advanced Bionics Clarion II Cochlear Implant System.

The Ethics of Ethics Reviews in Global Health Research: Case Studies Applying a New Paradigm

With increasing calls for global health research there is growing concern regarding the ethical challenges encountered by researchers from high-income countries (HICs) working in low or middle-income countries (LMICs). There is a dearth of literature on how to address these challenges in practice. In this article, we conduct a critical analysis of three case studies of research conducted in LMICs.We apply emerging ethical guidelines and principles specific to global health research and offer practical strategies that researchers ought to consider. We present case studies in which Canadian health professional students conducted a health promotion project in a community in Honduras; a research capacity-building program in South Africa, in which Canadian students also worked alongside LMIC partners; and a community-university partnered research capacity-building program in which Ecuadorean graduate students, some working alongside Canadian students, conducted community-based health research projects in Ecuadorean communities.We examine each case, identifying ethical issues that emerged and how new ethical paradigms being promoted could be concretely applied.We conclude that research ethics boards should focus not only on protecting individual integrity and human dignity in health studies but also on beneficence and non-maleficence at the community level, explicitly considering social justice issues and local capacity-building imperatives.We conclude that researchers from HICs interested in global health research must work with LMIC partners to implement collaborative processes for assuring ethical research that respects local knowledge, cultural factors, the social determination of health, community participation and partnership, and making social accountability a paramount concern.

The Ethics of Ethics Reviews in Global Health Research: Case Studies Applying a New Paradigm

With increasing calls for global health research there is growing concern regarding the ethical challenges encountered by researchers from high-income countries (HICs) working in low or middle-income countries (LMICs). There is a dearth of literature on how to address these challenges in practice. In this article, we conduct a critical analysis of three case studies of research conducted in LMICs.We apply emerging ethical guidelines and principles specific to global health research and offer practical strategies that researchers ought to consider. We present case studies in which Canadian health professional students conducted a health promotion project in a community in Honduras; a research capacity-building program in South Africa, in which Canadian students also worked alongside LMIC partners; and a community-university partnered research capacity-building program in which Ecuadorean graduate students, some working alongside Canadian students, conducted community-based health research projects in Ecuadorean communities.We examine each case, identifying ethical issues that emerged and how new ethical paradigms being promoted could be concretely applied.We conclude that research ethics boards should focus not only on protecting individual integrity and human dignity in health studies but also on beneficence and non-maleficence at the community level, explicitly considering social justice issues and local capacity-building imperatives.We conclude that researchers from HICs interested in global health research must work with LMIC partners to implement collaborative processes for assuring ethical research that respects local knowledge, cultural factors, the social determination of health, community participation and partnership, and making social accountability a paramount concern.

Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample

Objective: Autism spectrum disorders are now recognized to occur in up to 1% of the population and to be a major public health concern because of their early onset, lifelong persistence, and high levels of associated impairment. Little is known about the associated psychiatric disorders that may contribute to impairment. We identify the rates and type of psychiatric comorbidity associated with ASDs and explore the associations with variables identified as risk factors for child psychiatric disorders. Method: A subgroup of 112 ten- to 14-year old children from a population-derived cohort was assessed for other child psychiatric disorders (3 months' prevalence) through parent interview using the Child and Adolescent Psychiatric Assessment. DSM-IV diagnoses for childhood anxiety disorders, depressive disorders, oppositional defiant and conduct disorders, attention-deficit/hyperactivity disorder, tic disorders, trichotillomania, enuresis, and encopresis were identified. Results: Seventy percent of participants had at least one comorbid disorder and 41% had two or more. The most common diagnoses were social anxiety disorder (29.2%, 95% confidence interval [CI)] 13.2-45.1), attention-deficit/hyperactivity disorder (28.2%, 95% CI 13.3-43.0), and oppositional defiant disorder (28.1%, 95% CI 13.9-42.2). Of those with attention/deficit/hyperactivity disorder, 84% received a second comorbid diagnosis. There were few associations between putative risk factors and psychiatric disorder. Conclusions: Psychiatric disorders are common and frequently multiple in children with autism spectrum disorders. They may provide targets for intervention and should be routinely evaluated in the clinical assessment of this group.

Time-based prospective memory in children with autism spectrum disorder

In this study, for the first time, prospective memory was investigated in 11 school-aged children with autism spectrum disorders and 11 matched neurotypical controls. A computerised time-based prospective memory task was embedded in a visuospatial working memory test and required participants to remember to respond to certain target times. Controls had significantly more correct prospective memory responses than the autism spectrum group. Moreover, controls checked the time more often and increased time-monitoring more steeply as the target times approached. These differences in time-checking may suggest that prospective memory in autism spectrum disorders is affected by reduced self-initiated processing as indicated by reduced task monitoring.

Case studies in interannual to decadal climate predictability

The predictability of ocean and climate variables is investigated, using a perfect model-based case study approach that recognises that predictability is dependent on the initial climate state. In line with previous studies, large scale ocean variables, show predictability for several years or more; by contrast, the predictability of climate variables is generally limited to, 2 years at most. That predictability shows high sensitivity to the initial state is demonstrated by predictable climate signals, arising in different regions, variables and seasons for different initial conditions. The predictability of climate variables, in the second year is of particular interest, because this is beyond the timescale that is usually considered to be the limit, of seasonal predictability. For different initial conditions, second year predictability is found in: temperatures in southeastern, North America (winter) and western Europe (winter and summer), and precipitation in India (summer monsoon) and in the tropical, South Atlantic. Second year predictability arises either from persistence of large-scale sea surface temperature (SST) and, related ocean heat content anomalies, particularly in regions such as the North Atlantic and Southern Ocean, or from mechanisms, that involve El Nino Southern Oscillation (ENSO) dynamics.

A double-blind, placebo-controlled, crossover-designed probiotic feeding study in children diagnosed with autistic spectrum disorders

There is growing interest in the role of gastrointestinal (GI) pathology and clinical expression of autism. Recent studies have demonstrated differences in the faecal clostridial populations harboured by autistic and non-autistic children. The potential of Lactobacillus plantarum WCSF1 (a probiotic) to modulate the gut microbiota of autistic subjects was investigated during a double-blind, placebo-controlled, crossover-designed feeding study. The faecal microbiota, gut function and behaviour scores of subjects were examined throughout the 12-week study. Lactobacillus plantarum WCFS1 feeding significantly increased Lab158 counts (lactobacilli and enterococci group) and significantly reduced Erec482 counts (Clostridium cluster XIVa) compared to placebo. Probiotic feeding also resulted in significant differences in the stool consistency compared to placebo and behaviour scores (total score and scores for some subscales) compared to baseline. The major finding of this work was the importance of study protocol in relation to the specific considerations of this subject population, with an extremely high dropout rate seen (predominantly during the baseline period). Furthermore, the relatively high inter-individual variability observed suggests that subsequent studies should use defined subgroups of autistic spectrum disorders, such as regressive or late-onset autism. In summary, the current study has highlighted the potential benefit of L. plantarum WCFS1 probiotic feeding in autistic individuals.