Conception, synthèse et caractérisation d'assemblages supramoléculaires stabilisés par ponts hydrogènes nanotubes organiques et capsules moléculaires

Cet ouvrage porte sur la conception (modélisation moléculaire), la synthèse organique et la caractérisation (spectrométrie de masse, microscopie électronique à balayage, cristallographie) d'édifices supramoléculaires obtenus par un processus d'autoassemblage principalement induit par ponts hydrogènes. Plus spécifiquement, il traite de la fabrication de nouveaux types de nanotubes organiques via l'empilement de macrocycles divers. Le chapitre un couvre nos travaux qui ont trait aux cyclopeptides non naturels de type delta, epsilon, zêta et êta comportant l'une des fonctions suivantes: alcène, alcyne ou thiophène. Nous décrivons les résultats de nos recherches sur l'arrangement cristallin de plusieurs de ces lactames, en particulier sur les lactames de type delta et epsilon. La formation de complexes cobalt-alcyne y est aussi abordée. Enfin, à la suite d'un résultat inattendu en diffraction des rayons X d'un de nos monocristaux, nous discutons très brièvement de la formation d'un complexe de type"sandwich" entre un delta cyclopeptide et le trifluoroacétate de potassium. Le chapitre deux, quant à lui, se consacre á l'étude d'un déhydro[12]annulène fonctionnalisé par des groupements amides. Ce dernier projet est toutefois à un stade beaucoup moins avancé et il sera effleuré par conséquent de façon très sommaire. En plus des architectures tubulaires, nous nous sommes intéressés à la formation de nouvelles capsules moléculaires. Le troisième chapitre discute donc de leur création à partir de composés aromatiques hexasubstitués de symétrie C[indice inférieur 3] comportant des lactames de géométrie cis . L'utilisation de la spectrométrie de masse à ionisation par électronébuliseur nous a permis d'étudier le phénomène d'encapsulation d'un cation (Et[indice inférieur 4]N[indice supérieur +]). Le chapitre quatre, pour sa part, aborde les travaux préliminaires concernant l'utilisation de liaisons thioamides dans nos architectures supramoléculaires. Ces travaux sont réalisés dans le but de moduler la force des ponts H dans celles-ci. Finalement, nous présentons en annexe l'inhabituel arrangement cristallin du pentafluorophénolate de potassium

Insomnia and its relationship to health-care utilization, work absenteeism, productivity and accidents

Background and purpose To document and provide a micro analysis of the relationship between insomnia and health problems, health-care use, absenteeism, productivity and accidents. Participants and methods A population-based sample of 953 French-speaking adults from Québec, Canada. Participants were categorized as having insomnia syndrome (SYND) or insomnia symptoms (SYMPT) or as good sleepers (GS). They completed questionnaires on sleep, health, use of health-care services and products, accidents, work absences and reduced work productivity. Data were also obtained from the Québec-government-administered health insurance board on selected variables (e.g., consultations with health-care professionals, diagnoses). Results There were significantly more individuals in the SYND group relative to the GS group reporting at least one chronic health problem (83% vs. 53%; OR: 2.78) and who had consulted a health-care professional in the past year (81% vs. 60%; OR: 2.8). There were also higher proportions of individuals in the SYND group than in the GS group who had used prescription medications (57% vs. 30.7%; OR: 2.8), most notably to treat insomnia, mood and anxiety disorders, or who had used over-the-counter products (75.6% vs. 62.0%; OR: 1.8) and alcohol as a sleep aid (17.8% vs. 3.9%; OR: 4.6). In terms of daytime function, 25.0% of the SYND had been absent from work relative to 17.1% of GS (OR: 1.7), 40.6% reported having experienced reduced productivity compared to 12.3% of GS (OR: 4.8) and non-motor-vehicle accidents occurred at higher rates in the SYND group (12.5% vs. 6.4% for GS; OR: 2.4). No differences were found for hospitalisations or motor-vehicle accidents. Most of the associations remained significant even after controlling for psychiatric comorbidity. Rates for the SYMPT group were situated between SYND and GS on all major dependent variables. Furthermore, insomnia and fatigue were perceived as contributing significantly to accidents, absences and decreased work productivity, regardless of insomnia status. Conclusions This study indicates that insomnia is associated with significant morbidity in terms of health problems and health-care utilization, work absenteeism and reduced productivity, and risk of non-motor-vehicle accidents. Future studies should evaluate whether treating insomnia can reverse this morbidity

The natural history of insomnia : a population-based 3-year longitudinal study

Background Despite its high prevalence, little information is available about the natural history of insomnia. The extent to which episodes of insomnia will persist or remit over time is difficult to predict. We examined the natural history of insomnia and describe the most common trajectories over 3 years. Methods Three hundred eighty-eight adults (mean [SD] age, 44.8 [13.9] years; 61% women) were selected from a larger population-based sample on the basis of the presence of insomnia at baseline. They completed standardized sleep/insomnia questionnaires at 3 annual follow-up assessments. For each follow-up assessment, participants were classified into 1 of 3 groups (individuals with an insomnia syndrome, individuals with insomnia symptoms, and individuals with good sleep) on the basis of algorithms using standard diagnostic criteria for insomnia. Rates of persistent insomnia, remission, and relapse were computed for each group. Results Of the study sample, 74% reported insomnia for at least 1 year (2 consecutive assessments) and 46% reported insomnia persisting over the entire 3-year study. The course of insomnia was more likely to be persistent in those with more severe insomnia at baseline (ie, insomnia syndrome) and in women and older adults. Remission rate was 54%; however, 27% of those with remission of insomnia eventually experienced relapse. Individuals with subsyndromal insomnia at baseline were 3 times more likely to remit than worsen to syndrome status, although persistence was the most frequent course in that group as well. Conclusion These findings indicate that insomnia is often a persistent condition, in particular when it reaches the diagnostic threshold for an insomnia disorder

Lead Identification using 3D Models of Pancreatic Cancer: Development of 3D Tumor Models for High-throughput Screening.

Recent technological advances have enabled 3D tissue culture models for fast and affordable HTS. We are no longer bound to 2D models for anti-cancer agent discovery, and it is clear that 3D tumor models provide more predictive data for translation of preclinical studies. In a previous study, we validated a microplate 3D spheroid-based technology for its compatibility with HTS automation. Small-scale screens using approved drugs have demonstrated that drug responses tend to differ between 2D and 3D cancer cell proliferation models. Here, we applied this 3D technology to the first ever large-scale screening effort completing HTS on over 150K molecules against primary pancreatic cancer cells. It is the first demonstration that a screening campaign of this magnitude using clinically relevant, ex-vivo 3D pancreatic tumor models established directly from biopsy, can be readily achieved in a fashion like traditional drug screen using 2D cell models. We identified four unique series of compounds with sub micromolar and even low nanomolar potency against a panel of patient derived pancreatic organoids. We also applied the 3D technology to test lead efficacy in autologous cancer associated fibroblasts and found a favorable profile for better efficacy in the cancer over wild type primary cells, an important milestone towards better leads. Importantly, the initial leads have been further validated in across multiple institutes with concordant outcomes. The work presented here represents the genesis of new small molecule leads found using 3D models of primary pancreas tumor cells

Potentially inappropriate prescriptions for older patients in long-term care

BACKGROUND: Inappropriate medication use is a major healthcare issue for the elderly population. This study explored the prevalence of potentially inappropriate prescriptions (PIPs) in long-term care in metropolitan Quebec. METHODS: A cross sectional chart review of 2,633 long-term care older patients of the Quebec City area was performed. An explicit criteria list for PIPs was developed based on the literature and validated by a modified Delphi method. Medication orders were reviewed to describe prescribing patterns and to determine the prevalence of PIPs. A multivariate analysis was performed to identify predictors of PIPs. RESULTS: Almost all residents (94.0%) were receiving one or more prescribed medication; on average patients had 4.8 prescribed medications. A majority (54.7%) of treated patients had a potentially inappropriate prescription (PIP). Most common PIPs were drug interactions (33.9% of treated patients), followed by potentially inappropriate duration (23.6%), potentially inappropriate medication (14.7%) and potentially inappropriate dosage (9.6%). PIPs were most frequent for medications of the central nervous system (10.8% of prescribed medication). The likelihood of PIP increased significantly as the number of drugs prescribed increased (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.33 – 1.43) and with the length of stay (OR: 1.78, CI: 1.43 – 2.20). On the other hand, the risk of receiving a PIP decreased with age. CONCLUSION: Potentially inappropriate prescribing is a serious problem in the highly medicated long-term care population in metropolitan Quebec. Use of explicit criteria lists may help identify the most critical issues and prioritize interventions to improve quality of care and patient safety

The seeds of divergence: the economy of French North America, 1688 to 1760

Generally, Canada has been ignored in the literature on the colonial origins of divergence with most of the attention going to the United States. Late nineteenth century estimates of income per capita show that Canada was relatively poorer than the United States and that within Canada, the French and Catholic population of Quebec was considerably poorer. Was this gap long standing? Some evidence has been advanced for earlier periods, but it is quite limited and not well-suited for comparison with other societies. This thesis aims to contribute both to Canadian economic history and to comparative work on inequality across nations during the early modern period. With the use of novel prices and wages from Quebec—which was then the largest settlement in Canada and under French rule—a price index, a series of real wages and a measurement of Gross Domestic Product (GDP) are constructed. They are used to shed light both on the course of economic development until the French were defeated by the British in 1760 and on standards of living in that colony relative to the mother country, France, as well as the American colonies. The work is divided into three components. The first component relates to the construction of a price index. The absence of such an index has been a thorn in the side of Canadian historians as it has limited the ability of historians to obtain real values of wages, output and living standards. This index shows that prices did not follow any trend and remained at a stable level. However, there were episodes of wide swings—mostly due to wars and the monetary experiment of playing card money. The creation of this index lays the foundation of the next component. The second component constructs a standardized real wage series in the form of welfare ratios (a consumption basket divided by nominal wage rate multiplied by length of work year) to compare Canada with France, England and Colonial America. Two measures are derived. The first relies on a “bare bones” definition of consumption with a large share of land-intensive goods. This measure indicates that Canada was poorer than England and Colonial America and not appreciably richer than France. However, this measure overestimates the relative position of Canada to the Old World because of the strong presence of land-intensive goods. A second measure is created using a “respectable” definition of consumption in which the basket includes a larger share of manufactured goods and capital-intensive goods. This second basket better reflects differences in living standards since the abundance of land in Canada (and Colonial America) made it easy to achieve bare subsistence, but the scarcity of capital and skilled labor made the consumption of luxuries and manufactured goods (clothing, lighting, imported goods) highly expensive. With this measure, the advantage of New France over France evaporates and turns slightly negative. In comparison with Britain and Colonial America, the gap widens appreciably. This element is the most important for future research. By showing a reversal because of a shift to a different type of basket, it shows that Old World and New World comparisons are very sensitive to how we measure the cost of living. Furthermore, there are no sustained improvements in living standards over the period regardless of the measure used. Gaps in living standards observed later in the nineteenth century existed as far back as the seventeenth century. In a wider American perspective that includes the Spanish colonies, Canada fares better. The third component computes a new series for Gross Domestic Product (GDP). This is to avoid problems associated with using real wages in the form of welfare ratios which assume a constant labor supply. This assumption is hard to defend in the case of Colonial Canada as there were many signs of increasing industriousness during the eighteenth and nineteenth centuries. The GDP series suggest no long-run trend in living standards (from 1688 to circa 1765). The long peace era of 1713 to 1740 was marked by modest economic growth which offset a steady decline that had started in 1688, but by 1760 (as a result of constant warfare) living standards had sunk below their 1688 levels. These developments are accompanied by observations that suggest that other indicators of living standard declined. The flat-lining of incomes is accompanied by substantial increases in the amount of time worked, rising mortality and rising infant mortality. In addition, comparisons of incomes with the American colonies confirm the results obtained with wages— Canada was considerably poorer. At the end, a long conclusion is provides an exploratory discussion of why Canada would have diverged early on. In structural terms, it is argued that the French colony was plagued by the problem of a small population which prohibited the existence of scale effects. In combination with the fact that it was dispersed throughout the territory, the small population of New France limited the scope for specialization and economies of scale. However, this problem was in part created, and in part aggravated, by institutional factors like seigneurial tenure. The colonial origins of French America’s divergence from the rest of North America are thus partly institutional

Alien Registration- Baillargeon, Pierre H. (Biddeford, York County)

https://digitalmaine.com/alien_docs/2363/thumbnail.jp

Largeur de raie en résonnance paramagnétique électronique et fluctuations antiferromagnétiques chez les conducteurs organiques

Ce travail a pour but d'expliquer certains résultats expérimentaux de largeur de raie de résonnance paramagnétique électronique obtenus sur des conducteurs organiques, et plus spécifiquement, à son comportement singulier près de la température de transition antiferromagnétique. Pour ce faire, le calcul de la largeur de raie est fait à partir de l'expression générale obtenue par Mari et Kawasaki à partir du formalisme des fonctions de mémoire. Ainsi, le calcul reste valable dans le domaine qui nous intéresse, là où le temps de relaxation des fluctuations critiques diverge. Les sources d'élargissement considérées sont les interactions dipolaire et spin-orbite. Nous montrons comment les intégrer dans un même formalisme pour le cas des conducteurs organiques, et ce, pour le cas de spins fortement localisés comme pour le cas du magnétisme d'électrons itinérants ou à corrélations intermédiaires. Ces sources d'élargissement de la raie et les particularités du traitement des fonctions de corrélation chez les quasi-unidimensionnels, intégrées à l'expression de Mori et Kawasaki pour la largeur de raie, permettent d'extraire un comportement en température pour celle-ci qui tient compte des fluctuations magnétiques (ferromagnétiques comme antiferromagnétiques) du système. Un comportement théorique est ainsi déduit pour la région critique près de la transition, et un comportement pour le régime unidimensionnel est ensuite extrapolé et ce, pour tous les types de magnétisme (itinérant, corrélé ou localisé). La comparaison avec les résultats expérimentaux mènent aux deux conclusions suivantes: un accord excellent entre la théorie et l'expérience pour la région critique où les fluctuations sont tridimensionnelles et ont un caractère gaussien; pour le domaine où les fluctuations sont unidimensionnelles, l'approche utilisée dans ce travail est qualitativement intéressante mais reste incomplète pour expliquer les résultats expérimentaux