Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia.

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry.

Stress oxydant chez l'enfant prématuré : causes, biomarqueurs et possibilités thérapeutiques [Oxidative stress after preterm birth: Origins, biomarkers, and possible therapeutic approaches].

The survival of preterm babies has increased over the last few decades. However, disorders associated with preterm birth, known as oxygen radical diseases of neonatology, such as retinopathy, bronchopulmonary dysplasia, periventricular leukomalacia, and necrotizing enterocolitis are severe complications related to oxidative stress, which can be defined by an imbalance between oxidative reactive species production and antioxidant defenses. Oxidative stress causes lipid, protein, and DNA damage. Preterm infants have decreased antioxidant defenses in response to oxidative challenges, because the physiologic increase of antioxidant capacity occurs at the end of gestation in preparation for the transition to extrauterine life. Therefore, preterm infants are more sensitive to neonatal oxidative stress, notably when supplemental oxygen is being delivered. Furthermore, despite recent advances in the management of neonatal respiratory distress syndrome, controversies persist concerning the oxygenation saturation targets that should be used in caring for preterm babies. Identification of adequate biomarkers of oxidative stress in preterm infants such as 8-iso-prostaglandin F2α, and adduction of malondialdehyde to hemoglobin is important to promote specific therapeutic approaches. At present, no therapeutic strategy has been validated as prevention or treatment against oxidative stress. Breastfeeding should be considered as the main measure to improve the antioxidant status of preterm infants. In the last few years, melatonin has emerged as a protective molecule against oxidative stress, with antioxidant and free-radical scavenger roles, in experimental and preliminary human studies, giving hope that it can be used in preterm infants in the near future.

Teaching mathematics and programming : new approaches with empirical evaluation

Programming and mathematics are core areas of computer science (CS) and consequently also important parts of CS education. Introductory instruction in these two topics is, however, not without problems. Studies show that CS students find programming difficult to learn and that teaching mathematical topics to CS novices is challenging. One reason for the latter is the disconnection between mathematics and programming found in many CS curricula, which results in students not seeing the relevance of the subject for their studies. In addition, reports indicate that students' mathematical capability and maturity levels are dropping. The challenges faced when teaching mathematics and programming at CS departments can also be traced back to gaps in students' prior education. In Finland the high school curriculum does not include CS as a subject; instead, focus is on learning to use the computer and its applications as tools. Similarly, many of the mathematics courses emphasize application of formulas, while logic, formalisms and proofs, which are important in CS, are avoided. Consequently, high school graduates are not well prepared for studies in CS. Motivated by these challenges, the goal of the present work is to describe new approaches to teaching mathematics and programming aimed at addressing these issues: Structured derivations is a logic-based approach to teaching mathematics, where formalisms and justifications are made explicit. The aim is to help students become better at communicating their reasoning using mathematical language and logical notation at the same time as they become more confident with formalisms. The Python programming language was originally designed with education in mind, and has a simple syntax compared to many other popular languages. The aim of using it in instruction is to address algorithms and their implementation in a way that allows focus to be put on learning algorithmic thinking and programming instead of on learning a complex syntax. Invariant based programming is a diagrammatic approach to developing programs that are correct by construction. The approach is based on elementary propositional and predicate logic, and makes explicit the underlying mathematical foundations of programming. The aim is also to show how mathematics in general, and logic in particular, can be used to create better programs.

What happens in the first 200 ms of word reading : ERP studies on visual word recognition with top-down and bottom-up approaches /

In this thesis, three main questions were addressed using event-related potentials (ERPs): (1) the timing of lexical semantic access, (2) the influence of "top-down" processes on visual word processing, and (3) the influence of "bottom-up" factors on visual word processing. The timing of lexical semantic access was investigated in two studies using different designs. In Study 1,14 participants completed two tasks: a standard lexical decision (LD) task which required a word/nonword decision to each target stimulus, and a semantically primed version (LS) of it using the same category of words (e.g., animal) within each block following which participants made a category judgment. In Study 2, another 12 participants performed a standard semantic priming task, where target stimulus words (e.g., nurse) could be either semantically related or unrelated to their primes (e.g., doctor, tree) but the order of presentation was randomized. We found evidence in both ERP studies that lexical semantic access might occur early within the first 200 ms (at about 170 ms for Study 1 and at about 160 ms for Study 2). Our results were consistent with more recent ERP and eye-tracking studies and are in contrast with the traditional research focus on the N400 component. "Top-down" processes, such as a person's expectation and strategic decisions, were possible in Study 1 because of the blocked design, but they were not for Study 2 with a randomized design. Comparing results from two studies, we found that visual word processing could be affected by a person's expectation and the effect occurred early at a sensory/perceptual stage: a semantic task effect in the PI component at about 100 ms in the ERP was found in Study 1 , but not in Study 2. Furthermore, we found that such "top-down" influence on visual word processing might be mediated through separate mechanisms depending on whether the stimulus was a word or a nonword. "Bottom-up" factors involve inherent characteristics of particular words, such as bigram frequency (the total frequency of two-letter combinations of a word), word frequency (the frequency of the written form of a word), and neighborhood density (the number of words that can be generated by changing one letter of an original word or nonword). A bigram frequency effect was found when comparing the results from Studies 1 and 2, but it was examined more closely in Study 3. Fourteen participants performed a similar standard lexical decision task but the words and nonwords were selected systematically to provide a greater range in the aforementioned factors. As a result, a total of 18 word conditions were created with 18 nonword conditions matched on neighborhood density and neighborhood frequency. Using multiple regression analyses, we foimd that the PI amplitude was significantly related to bigram frequency for both words and nonwords, consistent with results from Studies 1 and 2. In addition, word frequency and neighborhood frequency were also able to influence the PI amplitude separately for words and for nonwords and there appeared to be a spatial dissociation between the two effects: for words, the word frequency effect in PI was found at the left electrode site; for nonwords, the neighborhood frequency effect in PI was fovind at the right elecfrode site. The implications of otir findings are discussed.

Valuing and encouraging critical reflection in pre-service teacher education

This qualitative study was designed to investigate aspects related to valuing and encouraging critical reflection in pre-service teacher education. An examination of the place and function of practicum logbooks as used at Covenant Canadian Reformed Teachers' College, a small private college which offers pre-service teacher education formed the core of the research. An analysis of the practicum logbooks written by five student teachers during three different practicum placements was performed at two levels. First, a content analysis served to identify general and specific categories within the practice teaching contextas a learning experience. Secondly, in-depth intuitive and thematic analyses of the entries which related specifically to reflection as a learning experience gave rise to critical questions. Throughout the process, the five participants formed an active and involved group of co-researchers, adding their voices to the narrative of the learning experience. Variables such as personality type, learning style and self-directedness added a dimension which deepened and emiched the study. The result of the study suggests that practicum logbooks form a valuable base for valuing and encouraging critical reflection in pre-service teacher education. The results also suggest that not all students appear to be equally capable of critical reflection. Recognizing that teacher education exists as a continuum appears to support the findings that in their journey along this continuum, student teachers not only move from reflection-on-action to reflection-in-action, but also from content to process to premise reflection. An awareness of contributing factors such as personality type, degree of risk-taking, preferred learning style and self-directedness on the part of teacher-educators will serve to create a climate of trust in which student teachers can safely develop critical reflection, using practicum logbooks as one possible medium.

Power, Contextual Intelligence and Leadership: Research Approaches for Understanding Participatory Community Climate Change Adaptation

Analysis of power in natural resources management is important as multiple stakeholders interact within complex, social-ecological systems. As a sub-set of these interactions, community climate change adaptation is increasingly using participatory processes to address issues of local concern. While some attention has been paid to power relations in this respect, e.g. evaluating international climate regimes or assessing vulnerability as part of integrated impact assessments, little attention has been paid to how a structured assessment of power could facilitate real adaptation and increase the potential for successful participatory processes. This paper surveys how the concept of power is currently being applied in natural resources management and links these ideas to agency and leadership for climate change adaptation. By exploring behavioural research on destructive leadership, a model is developed for informing participatory climate change adaptation. The working paper then concludes with a discussion of developing research questions in two specific areas - examining barriers to adaptation and mapping the evolution of specific participatory processes for climate change adaptation.

Cerebral edema and acute liver failure : pathophysiological mechanisms and new therapeutic approaches

L’encéphalopathie hépatique (EH) se développe chez les patients atteints d’une maladie du foie et se caractérise par de nombreuses anomalies neuropsychiatriques. L’insuffisance hépatique aiguë (IHA) se caractérise par une perte progressive de l’état de conscience, par une augmentation rapide de l’œdème cérébral et une augmentation de la pression intracrânienne entraînant une herniation cérébrale et la mort. Plusieurs facteurs sont responsables du développement de l’EH mais depuis une centaine d’années, l’hyperammonémie qui peut atteindre des concentrations de l’ordre de plusieurs millimolaires chez les patients atteints d’IHA aux stades de coma est considérée comme un facteur crucial dans la pathogenèse de l’EH. La présente thèse comprend 4 articles suggérant l’implication de nouveaux mécanismes pathogéniques dans le développement de l’EH et de l’œdème cérébral associés à l’IHA et tente d’expliquer l’effet thérapeutique de l’hypothermie et de la minocycline dans la prévention de l’EH et de l’œdème cérébral: 1. L’IHA induite par dévascularisation hépatique chez le rat se caractérise par une augmentation de la production de cytokines pro-inflammatoires cérébrales (IL-6, IL-1, TNF-). Cette observation constitue la première évidence directe que des mécanismes neuro-inflammatoires jouent une rôle dans la pathogenèse de l’EH et de l’œdème cérébral associés à l’IHA (Chapitre 2.1, articles 1 et 2). 2. L’activation de la microglie telle que mesurée par l’expression de marqueurs spécifiques (OX42, OX-6) coïncide avec le développement de l’encéphalopathie (stade coma) et de l’œdème cérébral et s’accompagne d’une production accrue de cytokines pro-inflammatoires cérébrales (Chapitre 2.1, article 1 et 2). 3. Un stress oxydatif/nitrosatif causé par une augmentation de l’expression de l’oxyde nitrique synthétase et une augmentation de la synthèse d’oxyde nitrique cérébral participe à la pathogénèse des complications neurologiques de l’IHA (Chapitre 2.3, articles 3 et 4). 4. Des traitements anti-inflammatoires tels que l’hypothermie et la minocycline peuvent constituer de nouvelles approches thérapeutiques chez les patients atteints d’IHA (Chapitre 2.1, article 1; Chapitre 2.2, article 2). 5. Les effets bénéfiques de l’hypothermie et de la minocycline sur les complications neurologiques de l’IHA expérimentale s’expliquent, en partie, par une diminution du stress oxydatif/nitrosatif (Chapitre 2.3, article 3; Chapitre 2.4, article 4).

Production externalities : cooperative and non-cooperative approaches

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Edexcel A2 biology revision guide : for SNAB and concept-led approaches.

Guía para la revisión de los recursos Edexcel para la especificación General Certificate of Education (GCE ) Biología. Salters Nuffield Advanced Biology es el material de apoyo oficial. Curso completo diseñado para mostrar a los estudiantes cómo la comprensión de muchos problemas contemporáneos requiere de un conocimiento fundamental de las ideas biológicas. Favorece el aprendizaje autónomo de una amplia gama de conocimientos, incluidos el análisis de datos, evaluación crítica de información, comunicación y trabajo cooperativo. Se basa en datos de exámenes reales para ayudar a los estudiantes a evitar errores habituales y construir mejores respuestas. Los ejemplos de preguntas de examen incluyen las de opción múltiple. Tiene las soluciones a las preguntas del texto.

Edexcel AS biology revision guide : for SNAB and concept-led approaches.

Guía para la revisión de los recursos Edexcel para la especificación General Certificate of Education (GCE ) Biología. Salters Nuffield Advanced Biology es el material de apoyo oficial. Curso completo diseñado para mostrar a los estudiantes cómo la comprensión de muchos problemas contemporáneos requiere de un conocimiento fundamental de las ideas biológicas. Favorece el aprendizaje autónomo de una amplia gama de conocimientos, incluidos el análisis de datos, evaluación crítica de información, comunicación y trabajo cooperativo. Se basa en datos de exámenes reales para ayudar a los estudiantes a evitar errores habituales y construir mejores respuestas. Los ejemplos de preguntas de examen incluyen las de opción múltiple. Tiene las soluciones a las preguntas del texto.

Edexcel AS physics revision guide : for SHAP and concept-led approaches.

Guía para la revisión de los recursos Edexcel para la especificación General Certificate of Education (GCE ) Física. Salters-Horners Advanced Physics (SHAP) es el material de apoyo oficial. Es un curso completo que cubre la física a través de los contextos de la vida real, que combina los conceptos clave que sustenta la física, con la oportunidad de adquirir las habilidades que los físicos necesitan hoy. Favorece el aprendizaje autónomo y construye una amplia gama de conocimientos, incluidos el análisis de datos, evaluación crítica de información, comunicación y trabajo cooperativo. Se basa en datos de exámenes reales para ayudar a los estudiantes a evitar errores habituales y construir mejores respuestas. Los ejemplos de preguntas de examen incluyen las de opción múltiple. Tiene las soluciones a las preguntas del texto.

Edexcel A2 physics revision guide : for SHAP and concept-led approaches.

Guía para la revisión de los recursos Edexcel para la especificación General Certificate of Education (GCE ) Física. Salters-Horners Advanced Physics (SHAP) es el material de apoyo oficial. Es un curso completo que cubre la física a través de los contextos de la vida real, que combina los conceptos clave que sustenta la física, con la oportunidad de adquirir las habilidades que los físicos necesitan hoy. Favorece el aprendizaje autónomo con una amplia gama de conocimientos, incluidos el análisis de datos, evaluación crítica de información, comunicación y trabajo cooperativo. Se basa en datos de exámenes reales para ayudar a los estudiantes a evitar errores habituales y construir mejores respuestas. Los ejemplos de preguntas de examen incluyen las de opción múltiple. Tiene las soluciones a las preguntas del texto.

Classical and causal inference approaches to statistical mediation analysis

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