Abnormalities in homocysteine metabolism have been suggested as risk factors for stroke and myocardial infarction. In retrospective studies, elevated levels of total plasma homocysteine (tHcy) and/or methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism have indicated an increase in risk. However, the fewer prospective studies have not been as conclusive. To further explore this, tHcy was studied in four prospective settings. The first was a prospective nested case-referent cohort within the Västerbotten Intervention Program (VIP) and WHO MONICA project on 312 ischemic and 60 haemorrhagic first-ever strokes. The aim was to study tHcy and its main genetic determinant MTHFR. Risk for haemorrhagic stroke increased exponentially through tHcy quartiles, independent of hypertension and BMI, and increased for MTHFR 677 CT and TT. MTHFR 1298A>C appeared to be protective. In multivariate models, after adjustment for tHcy, BMI and hypertension, both tHcy and MTHFR remained as independent predictors for hemorrhagic stroke. Neither tHcy, nor the two MTHFR polymorphisms were significant predictors for ischemic strokes. The second was a prospective long-term follow-up study within the VIP and MONICA cohorts to determine whether a first-ever myocardial infarction (AMI) causes increased levels of tHcy. Fifty cases developing AMI after the first screening participated in a second screening (mean follow-up 8.5 years) with 56 matched referents. Increase in tHcy did not differ between cases and referents. tHcy was related to AMI at follow-up, but not at baseline and no longer significant after adjusting for creatinine and albumin. The third was a method study to determine if cystatin C, creatinine, albumin and other lipoprotein risk markers of cardiovascular disease could be analysed in Stabilyte™ plasma stored at -80°C. It was found to be suitable for all analyses tested and using this tube would simplify sampling for epidemiological studies. The fourth study was a prospective longitudinal long-term study of 735 subjects (340 men and 395 women, age 25-64 at first screening), participating in two MONICA screenings nine years apart, who donated blood in Stabilyte™ tubes to study change over time in tHcy and its determinants. We confirmed the age dependency in a cross sectional setting. In contrast, if followed longitudinally over time, no change in tHcy or in the prevalence of hyperhomocysteinemia was found. Cystatin C and creatinine increased, and albumin decreased. In multivariate models baseline levels of albumin, creatinine, cystatin C, and to some extent hs-CRP, were predictors of tHcy at follow-up but gender differences were seen. Age was not a major determinant of change in tHcy over nine years. In conclusion, tHcy and MTHFR are risk factors for first-ever haemorrhagic, but not ischemic stroke in a prospective setting. A first myocardial infarction does not cause an increase in tHcy. No long-term changes were seen in tHcy over a nine-year period in neither men, nor in women.

Both spinal pain and temporomandibular disorders (TMD) commonly occur in the general population. Previous studies demonstrate neurophysiologic and biomechanical couplings between the trigeminal and cervical regions. This investigation tested the null hypothesis of no relationship between spinal pain (neck, shoulder and/or low back) and TMD, by using questionnaires and clinical examinations of the jaw function. In an age- and sex-matched case-control study, the specific aim was to compare the prevalence of signs and symptoms of TMD among cases with long-term spinal pain and controls without spinal pain. The results showed that subjects with spinal pain had signs and symptoms of TMD significantly more often than did controls. The associations remained after excluding all participants with jaw pain. Furthermore, the comorbidity pattern was similar, regardless of location of spinal pain. In a cross-sectional study, the specific aim was to test whether there is a reciprocal cross-sectional dose-response-like relationship between spinal pain and TMD. Two different designs were used, one with frequency/severity of spinal pain as independent variable, and the other, with frequency/severity of TMD symptoms as independent variable. The analysis showed increasing odds for presence of TMD symptoms with increasing frequency/severity of spinal pain, and increasing odds for presence of spinal pain with increasing frequency/severity of TMD symptoms. In a case-control study within a 2-year prospective cohort, the specific aim was to test whether there is a reciprocal temporal relationship between signs and symptoms in trigeminally, and symptoms in spinally, innervated areas. Incidence of symptoms in these areas was analyzed in relation to presence of spinal pain, headaches, and signs and symptoms of TMD at baseline. The main findings were that presence of signs of TMD at baseline increased the onset of spinal pain and symptoms in the trigeminal area, and that spinal pain increased the onset of symptoms in the trigeminal area. An augmentation effect between the significant baseline variables was observed for the incidence of headaches and jaw pain. In conclusion, the investigation demonstrated a cross-sectional and temporal relationship between spinal pain and TMD; thus, the null hypothesis was rejected. The results indicate common pathophysiological mechanisms in the development of spinal pain and TMD. The comorbidity and reciprocal influence that were found call for an integrated and multidimensional approach in the management of individuals with long-term spinal pain and TMD.

Background Affective disorders are poorly defined and studied in sub-Saharan Africa despite their substantial public health impact. Objectives Overall objective: To describe the epidemiology of selected affective disorders in rural Ethiopia. Specific objectives 1. To describe the validity and utility of the concept of minor depressive disorder (mD). 2. To describe the manifestation, prevalence and the short-term clinical and functional course and outcome of bipolar disorder. Subjects and methods Population: Zay community residents (age ≥16), and residents of Butajira (ages 15-49), in Southern Ethiopia. Study design: Population-based cross-sectional and longitudinal studies Case identification: For the identification of cases with bipolar disorder, a two stage process was employed. An initial screen used key informants and interview with the Composite International Diagnostic Interview (CIDI) to identify cases with probable bipolar disorder. A second confirmatory diagnostic assessment stage employed the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). For the identification of cases with mD, data from the CIDI was used. Follow-up: 312 cases with bipolar disorder from Butajira were followed up for a mean of 2.5 years (ranging 1-4 years) through monthly clinical assessments and annual symptom and functional ratings. Results The CIDI was administered to 1714 adults among the Zay and to 68, 378 adults among the Butajira residents. The prevalence of mD among the Zay and Butajira was 20.5% and 2.2% respectively. Up to 80% of cases with mD had used services for their symptoms, while a third to a half of cases had thought about self harm. Up to a sixth of cases had attempted suicide. Age, marital status, education and somatic symptoms were independently associated with mD. The prevalence of bipolar disorder among the Zay was 1.8%. During a 2.5-year follow-up of 312 cases with bipolar disorder from Butajira, 65.9% relapsed (47.8% manic, 44.3% depressive and 7.7% mixed episodes) while 31.1% experienced persistent illness. Female gender predicted depressive relapse whereas male gender predicted manic relapse. Only being on psychotropic medication predicted remission (OR=3.42; 95% CI=1.82, 6.45). Disability was much worse among bipolar patients than in the general population and was predicted by symptom se3verity. Conclusions This is the largest study on mD and bipolar disorder in Africa. mD appears to have potential clinical utility in this setting given its association with service use and risk. The identified risk factors for mD also suggest potential aetiological continuity with major depression. The relatively high prevalence of bipolar disorder among the Zay may be related to genetic predisposition perhaps mediated through a founder effect, but other factors need exploring. In relation to the outcome of bipolar disorder, this study indicates that, contrary to previous assumptions, the course of bipolar disorder is characterised by both manic and depressive relapses in a relatively proportionate fashion. Bipolar disorder also leads to significant levels of disability. This is the only prospective outcome study of bipolar disorder in Africa where cases were monitored systematically at short assessment intervals. Therefore, findings are likely to be more robust than previous reports.

The objectives of the community-based Early Developmental Stages of Psychopathology (EDSP) Study are described along with a detailed account of the overall design, special design features, sample characteristics and instruments used. The EDSP employed a prospective-longitudinal design to study substance use and other mental disorders in a representative population sample of 3,021 subjects aged 14–24 years (birth cohorts 1970–1981) at ‘baseline’ – the outset of the study. Two follow-up investigations were conducted after the baseline investigation covering an overall period of 3–4 years. Special design features are the linkage with a family supplement (EDSP-FS) as well as neurobiological laboratory studies of high-risk subjects.

La thèse revisite les débats sur les conséquences socioéconomiques et le choix des modalités d'une fiscalité carbone. Un diagnostic est d'abord tiré de l'examen d'un échec français (la taxe carbone de N. Sarkozy, 2009-2010). Il distingue les problèmes d'acceptabilité politique, des limites de l'analyse économique pour définir les dispositifs. Il souligne l'importance de la discussion sur l'usage des recettes de la taxe, car ce point cristallise les difficultés politiques et conditionne la cohérence économique et juridique du projet au regard des objectifs recherchés (environnement, équité, compétitivité). Il montre que les outils d'analyse peuvent être améliorés pour accompagner cette discussion. Un outil de simulation numérique est ensuite proposé et construit. Il permet de comparer les performances de dispositifs sur divers indicateurs (émissions de CO2, activité, emploi, inégalités, pauvreté, endettement), de décrire plusieurs points de vue sur le fonctionnement de l'économie (actuelle et future), et de lier dans une démarche prospective le dossier climatique aux autres dossiers de réforme des prélèvements obligatoires (maîtrise des déficits, financement des retraites). L'outil est enfin utilisé pour revisiter les controverses, clarifier les arbitrages et identifier les meilleures pistes de compromis. Il apparaît qu'une fiscalité carbone peut offrir des co-bénéfices socioéconomiques (pour l'activité et l'emploi, la réduction des inégalités, la maîtrise des déficits). Mais cela n'est pas automatique, des choix politiques sensibles doivent être faits ; ces dernier portent, au-delà du seul dossier 'climat', sur la gestion d'une réforme générale des finances publiques.

Objectives: To determine risk factors of incident onset of use, abuse and dependence of cannabis in a community sample of adolescents and young adults. Methods: Risk factors were examined in a prospective longitudinal design across 4 years in a representative sample (N=2446) aged 14-24 at the outset of the study (EDSP). Patterns of DSM-IV defined cannabis use, abuse and dependence were assessed with the Composite International Diagnostic Interview (M-CIDI). Potential risk factors were assessed at baseline. Incident cannabis use, abuse and dependence at second follow-up (on average 42 months after baseline) were the main outcome measures in this study. Associations were analyzed with logistic and negative binomial regressions. Results: Using 11 of a total of 56 variables examined, the predictive value of the final multiple logistic regression for incident cannabis use was moderately good (area under the ROC curve=0.78). Cannabis use frequency was predicted in the final model by 18 variables, cannabis abuse by two variables in the younger subsample and nine factors in the older group, and dependence by eight variables (dependence: ROC curve area=0.97). Incident cannabis use was predicted mainly by availability of drugs, peers’ drug use, a more ‘positive’ attitude towards future drug use, and regular previous use of licit drugs, while cannabis dependence was predicted primarily by parental death before age 15, deprived socio-economic status, and baseline use of other illicit drugs. Conclusion: Different factors predict the onset or severity of cannabis use and the progression to abuse and dependence. In addition to well-documented risk factors such as peer group pressure, drug availability, and low self-esteem, findings suggest that family history (e.g. parental mental disorders, early parental death), and prior experiences with legal drugs play a significant role in the initiation of cannabis consumption and the transition to cannabis use disorders in adolescents and young adults. Findings suggest that early intervention and prevention might be improved by better targeted treatment.

Background Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. It usually strikes during young adulthood, and 2.5 million individuals are estimated to have the disease worldwide. The causes of MS are not known, but several factors have been shown to be associated with the risk of the disease, including certain genes, vitamin D, smoking and Epstein- Barr virus infection. Little is known about how/if these factors interact. Methods Study I: The risk of MS by month of birth was investigated using MS cases from the Swedish MS registry and using general population controls. Studies II–V: We identified MS cases who had donated blood prior to disease onset, and MS cases whose mothers had donated blood during pregnancy, by cross-linking a database of MS cases, and a database of mothers of MS cases, to two local biobank cohorts. One of them consisted of blood samples collected during early pregnancy, and one with samples collected during health controls. Levels of 25(OH)D (25-hydroxyvitamin D), RBP (retinol binding protein, a surrogate marker for vitamin A), CRP (C- reactive protein), cotinine (a nicotine metabolite) and anti Epstein-Barr virus nuclear antigen-1 (EBNA-1) antibodies were measured in cases and matched controls. The risk of MS by categories of these exposures was estimated in bi- and multivariable matched logistic regression models. Results Subjects born in spring had a higher risk of MS, but no influence of early gestational levels of the measured risk factors on the risk of MS in the offspring was observed. In prospective samples from MS cases and controls, 25(OH)D levels ≥75 nmol/l, intermediate RBP levels, and elevated CRP levels in young were associated with a decreased risk of MS. Elevated cotinine levels (suggestive of smoking) and high antibody reactivity against EBNA-1 were associated with an increased risk of MS. All factors but RBP were more clearly associated with MS in young subjects. Conclusion All factors analyzed in prospectively collected samples were associated with the risk of MS, and taken together, the data indicate that the key etiopathological events that lead to MS occur before the age of 20–30. Study II provides support for trials exploring the primary preventive potential of oral vitamin D supplementation.

The purpose of this study was to investigate the prospective teachers&rsquo / knowledge of mistakes held by elementary students in fractions and their proposed strategies to overcome those mistakes. The data were collected from 149 prospective elementary mathematics teachers enrolled in the elementary mathematics education programs from a public university in Central Anatolian Region. Fraction Knowledge Questionnaire was used to accomplish the purpose of the study. The data collection tool included nine open ended questions, and each question had two sub-tasks. In this study, the items in the &ldquo / Fraction Knowledge Questionnaire&rdquo / were analyzed in-depth in order to reach a detailed description of prospective teachers&rsquo / knowledge about students&rsquo / mistakes on fractions. The results of this study revealed that prospective elementary mathematics teachers mostly could identify the students&rsquo / mistakes. However, although prospective teachers could notice the students&rsquo / mistakes, they could give superficial reasons for these mistakes. Furthermore, verbal explanations, using area representation, using real life model, reviewing prior knowledge, teaching standard algorithm, asking guided questions, using simple examples, using counter examples, using drill and practice, making students aware of their mistakes, and increasing students&rsquo / motivation were the suggested strategies by prospective teachers in order to overcome students&rsquo / mistakes in fractions.

Les quantités de ressources en eau naturelles et renouvelables sont limitées : serait-il possible qu'elles ne suffisent plus, à l'avenir, pour approvisionner en eau l'ensemble des secteurs d'usage de l'eau dont les demandes continuent de croître ? quels pourraient être les impacts de cette limitation sur le développement des pays concernés ? Cette question de la raréfaction future de l'eau dans certains pays arides ou semi-arides fait l'objet d'un débat d'experts à l'échelle mondiale depuis plusieurs décennies. Elle est exemplaire des grandes questions environnementales actuelles. Cette question est également éminemment prospective. Cette thèse propose donc d'analyser ce débat mondial en le considérant comme un « dossier prospectif » exemplaire. Elle propose pour cela de construire un modèle descriptif du « dossier prospectif », à la croisée de plusieurs ressources théoriques, parmi lesquelles la prospective et la sociologie des sciences : comment sont construits les discours sur les évolutions futures à long terme qui sont mobilisés ? comment sont-ils mis en discussion ? dans quelles enceintes ? comment décrire les dynamiques de ce débat ? quelles sont les reformulations auxquelles il donne lieu ? La compréhension du fonctionnement de ce dossier prospectif permet-elle alors de faire des propositions pour améliorer la planification pour la gestion des ressources en eau, afin que soient mieux pris en compte les enjeux à long terme, comme ceux de la rareté future possible de l'eau ? A partir d'exemples d'interventions passées ayant cherché à structurer les dossiers prospectifs liés à la planification pour les ressources en eau, et à partir d'une recherche - intervention menée sur le processus de planification national tunisien pour l'eau, cette thèse propose des grilles d'analyse et des figures de référence pour concevoir, mettre en œuvre et évaluer une stratégie d'intervention prospective sur un tel processus de planification.

La filière viticole française subit une récession de longue période sur son marché domestique dont les raisons profondes sont autant d'ordre sociologique et culturelle qu'économique. Parallèlement, elle se doit de tenir son rang sur les marchés internationaux où l'on observe une croissance de la consommation et une compétition plus vive de la part d'acteurs du nouveau monde. Face ces évolutions, la compréhension du consommateur, des différents acteurs de la filière ainsi que des outils marketing qu'ils emploient doit être interrogée et revisitée. Le but de cette thèse sur travaux est de décrire des évolutions de la filière et de présenter une tendance à la dé-individuation économique de ce domaine. Le principe d'individuation, avant tout d'ordre psychologique et biologique, postule qu'un individu diffère de tout autre et le distingue. Dans un contexte managérial, l'individuation peut être perçue d'une part dans l'étude du consommateur au travers de ses attentes, de ses besoins et de son comportement lors d'expérience d'achat, d'autre part dans l'analyse du comportement des offreurs, ici essentiellement des industriels – négociants, dans leur comportement stratégique, leur structure financière et les outils de développement employés. Par ailleurs, les choix opérés dans la gouvernance de la filière par les pouvoirs publics et les Interprofessions peuvent, dans leurs objectifs influer sur cette individuation économique. A contrario, la dé-individuation exprime ici un comportement de l'ensemble des parties prenantes d'un domaine tendant à réduire le caractère unique et différencié de chacun pour aller vers des formes de standardisation. Afin de présenter la dé-individuation économique dans la filière viticole, notre recherche repose sur une série de publications antérieures faites dans trois domaines : tout d'abord l'analyse de l'acheteur et du consommateur de vin dans un contexte de postmodernité approché au travers de ses expériences de consommation et des représentations qu'il s'en fait. Puis auprès d'une population d'entreprises viticoles françaises en observant les disparités et les similarités de leur structure financière et de leur stratégie notamment pour expliquer leur performance à l'export. Enfin, en étudiant des outils marketing employés par la profession parmi lesquels la marque dont on connaît le pouvoir de standardisation des comportements. Nos contributions enrichissent le corps théorique sur le comportement du consommateur et des formes contemporaines de gouvernance des entreprises. Pour la profession viticole, nos recherches contribuent à une prospective du domaine pour élaborer des scénarios futurs, mais aussi pour les managers des entreprises concernées par des prises de décision plus opérationnelles. / The French wine industry has been facing a recession for a long period, on its domestic market. Main reasons are sociological, cultural and not only economical. Simultaneously this industry has to maintain its position on the international markets where a growth in consumption can be observed and also a more intense competition due to actors coming from the new world. In front of these evolutions, the understanding of the consumer and of the different actors on this industry but also of the used marketing tools has to be questioned and explored. The aim of our "thèse sur travaux", is to describe the evolution of the wine industry and to present a trend to economic de individuation in this sector. The individuation principle, a psychological concept at the origin, expresses the idea that each person is differentiated from others. In the managerial context, individuation can be perceived first thanks to the study of the consumer through his waiting's, needs and his behaviour during the purchasing experience, second with the analysis of the offers' behaviour, here particularly the wine merchants in their strategy, their financial structure and the promotional tools they use, and third with the choices made for the wine industry governance by public regulators and administrative boards of the different wine regions. In the contrary, the economic de individuation expresses behaviours of all the stakeholders of the domain, desiring to reduce their individual and differentiate character. In order to present the economic de individuation in the wine industry, our research will be based on a series of previous publications conducted in three domains: first, analysing the wine consumer in the context of postmodernism thanks to the observation of their experience and associated representations. Second, observing a sample of French wine merchants, the disparities and similarities of their financial structures and strategies particularly as explanation of their export performance. Third, studying the marketing tools used in this industry. The wine branding activity whose standardization power is well-known is above all developed. Our contributions provide theoretical background with consumer behaviour and contemporaneous forms of the firms' governance issues. For the wine industry, our investigations contribute to a prospective vision of the domain, in order to elaborate scenarios for the future, but also for managers of the concerned firms for their operational decisions.