Despite numerous Government efforts to tackle the problem of child under-nutrition in Malawi, the levels of child under-nutrition remain high with stunting estimated at 47% and underweight at 12.7% . This thesis investigates whether the levels and patterns of stunting and underweight in Malawi have changed between the years 2000 and 2010 and if so how. It studies how feeding patterns and child immunisation affects child’s nutritional status in Malawi and analyses the different pathways through which household and community level socio-economic factors affect a child’s nutritional status in Malawi. The Malawi Demographic and Health Survey (MDHS) data sets of 2000, 2004 and 2010 are used in the study of levels and patterns of child under-nutrition in Malawi whilst the 2004 MDHS is used to investigate how feeding patterns and child immunisation affect a child’s nutritionals status in Malawi. The 2004 Malawi Integrated Household Survey data is merged with the 2004 Community level to analyse the pathways through which household and community level socio-economic factors affect child nutritional status in Malawi. Results of this study show that children from communities that have a daily market are less likely to be stunted compared to children from communities without a daily market. Children from communities that trace their descendants through their father have a lower likelihood of stunting compared to children from communities that trace their descendants through the mother due to being of relatively higher economic status. The levels of stunting and underweight have gone down significantly from 54.1% and 21.4% respectively in the year 2000 to 47.1% and 12.7% respectively in 2010. However, the percentage of children that are stunted but not affected with other under-nutrition problems has hardly changed, estimated at 37.2% in 2000 and 36.2% in 2010. Although generally female children are less likely to be stunted and less likely to be underweight, female children are more likely to be underweight as they get older. Contrary to what one would expect, children are more likely to be stunted during harvest time compared to the hunger season. Most of the children are fed food from the local grain, whilst in fact children aged between 7 to 36 months who consume food from animal sources are less likely to be undernourished. Children whose mothers are in possession of a child health card1 are less likely to be underweight. The Malawi Government should therefore intensify its efforts of encouraging mothers to attend under-five clinics, feed children that are undergoing weaning food from animal sources and should invest more in programmes that boost socio-economic status such as education and entrepreneurship skills.

A methodology is developed to estimate comparable international migration flows between a set of countries. International migration flow data may be missing, reported by the sending country, reported by the receiving country or reported by both the sending and receiving countries. For the last situation, reported counts rarely match due to differences in defnitions and data collection systems. In this thesis, reported counts are harmonized using correction factors estimated from a constrained optimization procedure. Factors are applied to scale data known to be of a reliable standard, creating an incomplete migration flow table of harmonized values. Cells for which no reliable reported flows exist are then estimated from a negative binomial regression model fitted using the Expectation- Maximization (EM) type algorithm. Covariate information for this model is drawn from international migration theory. Finally, measures of precision for all missing cell estimates are derived using the Supplemented EM algorithm. Recent data on international migration between countries in Europe are used to illustrate the methodology. The results represent a complete table of comparable ows that can be used by regional policy makers and social scientist alike to better understand population behaviour and change.

Hospital-associated infections (HAIs) are infections patients contract as a result of being hospitalized. HAI rates decreased for almost all pathogens in the past few years, with the exception of Clostridium difficile infections (CDIs), which have been steadily climbing, placing hospital-acquired CDI at the top of the HAI list. The Center for Disease Control and Prevention reported in 2010 almost a half a million people were infected with CDIs yearly in the United States, and CDIs claimed the lives of approximately 29,000 people, representing a 4-fold increase from 1993. To address the problem in the local hospital, a quality improvement initiative called Bleach-It-Away was initiated. The initiative involved nurses wiping down the high touch areas in the patient's medical intensive care (MICU) rooms once every shift. The purpose of this quantitative research project was to evaluate the effectiveness of the Bleach-It-Away practice. The project question asked if the Bleach-It-Away practice was effective in reducing CDI rates. Deidentified CDI rates were provided by the clinical practice site covering a period of 12 months prior to implementation and 12 months after implementation of the practice. An independent t-test was used to determine whether there were significant improvements in CDI rates in the MICU. No significant improvement was seen in the postimplementation total CDI rates (p=.07) compared to the preimplementation rates. While the process did not demonstrate a significant improvement, positive social change is possible as hospitals recognize the many factors contributing to CDIs and the need for collaboration from various disciplines to control the problem.

Mishkan ha-‘Edut, la Résidence du Témoignage, est le dernier ouvrage important écrit par le kabbaliste castillan R. Moshe de Leon (1240-1305). On peut considérer cet ouvrage comme une œuvre de couronnement et de maturation de la pensée de l’auteur. Connu à travers plusieurs ouvrages écrits en hébreu, R. Moshe de Leon est, d’après les jugements des historiens, l’un des auteurs principaux du prestigieux Sefer ha-Zohar, rédigé en araméen, et que la tradition rabbinique et populaire attribue à R. Shim’one bar Yohaï, rabbin galiléen ayant vécu entre le premier et le deuxième siècle de l’ère chrétienne. Le Mishkan ha-‘Edut traite de plusieurs questions fondamentales : la raison de l’existence du monde et son fondement dans la divinité ; la place de l’homme dans ce monde, la signification théologique profonde et la raison de son parcours terrestre; la nature de la transgression du commandement divin et la possibilité de repentir pour l’homme en tant qu’être psycho-physique doté d’une âme d’origine divine ; l’eschatologie de l’âme : le sort de chacune de ses composantes après la mort, sa purification dans la géhenne et la nature de son séjour dans le jardin de l’Eden. R. Moshe de Leon reprend, de manière plus structurée, plusieurs sujets abordés dans ses précédents écrits, en particulier, une théorie de l’âme et de ses « revêtements » (malbushim) après la mort. L’auteur insiste sur le caractère ésotérique des sujets développés en se considérant détenteur d’un savoir reçu. A plusieurs reprises, l’auteur insiste sur son hésitation à dévoiler « les secrets de la sagesse redoutable et intérieure ». Il ne cessera de préciser qu’il s’adresse à une élite, à ceux qui sont à la recherche de cette intériorité indispensable pour entendre le message de la transmission fondée sur l’enseignement ésotérique. Nous retrouvons dans cet ouvrage quelques-unes des idées les plus fascinantes de la Kabbale : que l’existence de Dieu n’est une que dans l’union des différents monde, le divin, le céleste et le terrestre ; que la relation entre Dieu et le monde est assimilable à la respiration. Ceci renvoie à la tâche de l’homme pendant son court parcours terrestre, qui n’est pas le caprice d’un créateur cruel mais correspond au projet d’unification des mondes. Naturellement, R. Moshe de Leon s’inspire du texte biblique pour confirmer ses idées, et bien d’autres. Le Mishkan ha-‘Edut est émaillé de citations bibliques, ses arguments sont construits comme un commentaire de la Bible, dont on exclut comme superficiel et fourvoyant le sens obvie. Les affirmations des rabbins du Talmud sont également très présentes, ainsi que celles des « anciens » (qadmonim), qui sont en réalité les kabbalistes de son époque ou des générations précédentes. / Mishkan ha-‘Edut, is the last important work written by Castilian cabalist R.Moshe de Leon (1240-1305). One can consider this work as an oeuvre of maturation of the author’s thought. Known by several works written in Hebrew, R.Moshe de Leon is, according to historians, one of the main authors of the prestigious Sefer ha-Zohar, written in Aramean, that the popular and rabbinic tradition attributes to R. Shim’one bar Yohaï, Galilean rabbi living in the first and second century of the Christian era. The Mishkan ha-‘Edut addresses several fundamental questions: the reason of the existence of the world and its foundation in divinity; the place of man in this world, the profound theological signification and the reason of its path on earth; the nature of transgression of divine commandment and the possibility of repentance for men as psychological beings carrying a divine derived soul; eschatology of the soul, the fate of each of its components after death, its purification in the géhenne and the nature of its stay in the garden of Eden. R.Moshe de Leon goes over, in a more structured way, several topics addressed in his previous writings. In particular, a theory of the soul and its “protections” (malbushim) after death. He insists on the esoteric aspect of the developed topics considering himself as owning a given knowledge. On several occasions, he also insists on his hesitation to disclose “the secrets of formidable and interior wisdom”. He stresses he addresses an elite, those who are seeking this necessary interiority to listen to the message of transmission based on esoteric teaching. One can find in this work some of the Kabbalah’s most fascinating ideas: that god existence is only one in the context of the merging of different worlds, the divine, the celestial and terrestrial; that the relationship between god and the world mimics breathing. This reflects to the task of man during his path on earth, not being directed by a cruel creator but that corresponds to the project of unification of these worlds. Naturally, R. Moshe de Leon takes inspiration in the bible text to confirm his ideas and many others. Mishkan ha-‘Edut is dotted with biblical citations, its arguments are built as a biblical commentary, from which is excluded, as if superficial, the spontaneous interpretation. Talmudic rabbi’s affirmations are equally present, as well as the “old”( qadmonim), who are in reality the kabbalists of his time or previous generations.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Influenza virus is a pleiomorphic human pathogen which causes self-limiting respiratory illness lasting one-two weeks in most individuals. However, in immunologically compromised individuals, influenza infection may lead to severe morbidity and fatality. Annual epidemics cause 250,000-500,000 deaths worldwide and remain a major public health threat. The virus has evolved mechanisms of antigenic ‘drift’ and ‘shift’ to evade the host immune response. Hence, current influenza vaccines need to be updated every few years. Moreover, the currently available inactivated/live attenuated vaccines entail virus culture in embryonated chicken eggs hindering rapid scale-up. The aforementioned limitations of the current vaccines has had debilitating effect when strain mismatch between vaccine formulation and influenza viruses circulating within the population has occurred in the past, despite intensive monitoring. Public health is further compromised when an unpredictable mixing event among influenza virus genomes leads to antigenic shift, facilitating a potential pandemic outbreak. These concerns have expedited efforts towards developing a ‘universal’ flu vaccine. Influenza hemagglutinin (HA) is the primary target of the humoral response during infection/vaccination. The precursor polypeptide, HA0, is assembled into a trimer along the secretory pathway and transported to the cell surface. Cleavage of HA0 generates the mature, disulfide linked HA1 and HA2 subunits. Mature HA has a globular head domain which mediates receptor binding and is primarily composed of the HA1 subunit while the stem domain predominantly comprises of the HA2 subunit. The HA stem is trapped in a metastable state and undergoes an extensive low-pH induced conformational rearrangement in the host-cell endosomes to adopt the virus-host membrane fusion competent state. The ‘antigenic sites’ on the immunodominant globular head of HA are subjected to heightened immune pressure resulting in escape variants, thereby limiting the breadth of head-directed neutralizing antibodies (nAbs). As opposed to the highly-variable head domain, the HA stem is conserved and targeted by several broadly neutralizing antibodies (bnAbs) with neutralizing activity against diverse influenza A virus subtypes. Although several bnAbs bind to the conserved HA stem, focusing the immune response to this conserved, subdominant stem domain in presence of the variable head domain of HA has been challenging. Alternatively, mimicking the epitope of these stem-directed bnAbs in the native, pre-fusion conformation in a ‘headless’ stem immunogen capable of eliciting a broadly protective immune response has been difficult because of the metastable conformation of HA. Addressing the aforementioned challenges, we describe the design and characterization of novel influenza immunogens by HA protein minimization. Chapter 1 gives an overview of the influenza virus life cycle, and outlines the structural organization and function of viral proteins. The conventional vaccines that are currently used and their limitations are described in this chapter. Recent improvements in influenza vaccine production focusing on recombinant HA as an alternate solution are discussed. Painstaking efforts of several groups in the recent past has led to the isolation of bnAbs that recognize novel ‘antigenic signatures’ within the globular head and the HA stem domains. Attempts to focus the immune response to these ‘cross-protective’ epitopes are described. The design and characterization of trimeric HA stem-fragment immunogens from influenza A Group-1 viruses which mimic the native, pre-fusion conformation of HA are described in Chapter 2. We engineered ‘headless’ HA stem immunogens based on influenza A/Puerto Rico/8/34 (H1N1) subtype. H1HA10-Foldon, a trimeric derivative of our parent construct (H1HA10), bound conformation sensitive stem-directed bnAbs such as CR6261, F10 and FI6v3 with high affinity (equilibrium dissociation constant [KD] of 10-50nM). The designed immunogens elicited broadly cross-reactive antiviral antibodies which neutralized highly drifted influenza virus strains belonging to both Group-1 (H1, H5 subtypes) and 2 (H3 subtype) in vitro. Significantly, stem immunogens designed from unmatched, highly drifted influenza strains conferred protection against a lethal (2LD90) heterologous A/Puerto Rico/8/34 virus challenge in mice. Our immunogens conferred robust subtype-specific and modest heterosubtypic protection in vivo. In contrast to previous HA stem domain immunogens, the designed immunogens described here were purified from the soluble fraction in E.coli. These HA stem-fragment immunogens do not aggregate even at high concentrations and are cysteine-free which eliminates the complications arising from incorrect disulfide-linked, misfolded conformations. The aforementioned properties of the HA stem-fragment immunogens make it amenable for scalability at short notice which is vital during pandemic outbreaks. The detailed mechanism(s) by which our ‘headless’ stem immunogens provide protection need further investigation. The long central α-helices (LAH) located in the HA stem assemble together into a parallel, trimeric coiled-coil. Immunization with the wt-LAH (76-130 of HA2) derived synthetic peptide designed from an H3 subtype (H3N2 A/Hong Kong/1/68) and conjugated to keyhole limpet hemocyanin (KLH) was shown previously to elicit antibodies reactive in ELISA with multiple hemagglutinin subtypes and to confer protection against challenge with H3N2, H1N1 and H5N1 virus strains. The LAH peptide sequence was chosen based on maximal binding to the monoclonal antibody (MAb), 12D1, which has broad neutralizing activity against influenza viruses of the H3 subtype. These results motivated us to rationally design stabilized derivatives of wt-LAH and test their protective capacity in a mouse challenge model of influenza. This work is described in Chapter 3. Additionally, to understand the contribution towards protection conferred by the two distinct surface exposed patches on LAH, we designed constructs spanning different stretches of LAH. The biophysical characterization of the LAH-derived constructs indicates that most of them were well-folded. All these constructs were moderately immunogenic in mice but at best, conferred limited protection from lethal viral challenge. In contrast to previously reported results, our data suggests that the LAH in the absence of other regions of HA may require not only strong, but also specific adjuvantation to induce a robust and functional immune response in vivo. Chapter 4 describes an immunogen design (H1pHA9) based on the globular head domain of pandemic H1N1 HA which can be produced using a prokaryotic expression system. The HA-fragment, H1pHA9, stably refolds to mimic the conformation sensitive neutralizing epitopes in the globular head domain of HA. We have also successfully engineered the HA head domain to delineate the epitope of antibodies neutralizing the pandemic H1N1 virus using a yeast cell-surface display platform. In this direction, we report the isolation of a novel, neutralizing murine MAb, MA2077, against the pandemic H1N1 virus. The epitope of this MAb has been mapped onto the ‘Sa’ antigenic site. The ability of the head domain fragment, H1pHA9, which binds MA2077 with high affinity to elicit such neutralizing antibodies in vivo needs to be further explored. Structural analysis has shown that elements of the HA stem diverge between the two phylogenetic groups. Therefore, to mitigate the threat of circulating influenza A viruses from these distinct structural classes (H1 and H3 belonging to Groups 1 and 2 respectively), in lieu of a ‘universal’ vaccine, a combination of immunogens derived from both the groups is a practical alternative. In Chapter 5 we describe the design of stem-fragment immunogens from an influenza A Group-2 virus strain. We report the characterization of engineered ‘headless’ HA stem immunogens based on influenza A/Hong Kong/1/68 (H3N2) subtype. The designed immunogens were expressed in E.coli and purified from the soluble fraction with abundant yields (~15mg/lt). The HA stem-fragment immunogens could be concentrated to high concentrations without aggregation. While, H3HA10-IZ and H3HA10-Foldon, the trimeric derivatives of our parent construct (H3HA10) which were folded, conferred modest protection against a lethal homologous virus challenge in mice, there is considerable scope to improve our immunogen design. Analyzing the results from our previous work (Chapter 2), we speculate that structural elements at the N-terminus of A-helix are critical for helix initiation. We therefore extended the design to include residues from the start of the A-helix. We designed the extended stem immunogens from both H3 and H7 subtypes. The proteins were purified from the soluble fraction of the E.coli cell culture lysate. Preliminary studies suggest that extension of the A-helix has aided proper folding. These proteins need to be further characterized and evaluated in an animal model.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal. / Pour respecter les droits d'auteur, la version électronique de cette thèse ou ce mémoire a été dépouillée, le cas échéant, de ses documents visuels et audio-visuels. La version intégrale de la thèse ou du mémoire a été déposée au Service de la gestion des documents et des archives de l'Université de Montréal.

Cette thèse vise à examiner la représentation des mémoires fictionnelles dans le cadre global de la littérature chinoise contemporaine, en montrant l’influence du déplacement et du translinguisme sur les œuvres des auteurs qui écrivent soit de la Chine continentale soit d’outre-mer, et qui s’expriment à travers des langues différentes. Les quatre romans Zha gen (Prendre racine) par Han Dong, Balzac et la petite tailleuse chinoise par Dai Sijie, The Crazed (La démence du sage) par Ha Jin et Rou zhi tu (Beijing Coma) par Ma Jian seront comparés en tant qu’images des mémoires individuelles de la Révolution Culturelle et du mouvement pour la démocratie qui a eu lieu à Tian’anmen en 1989. Dans la première partie, nous discuterons les nouvelles approches théoriques qui configurent la littérature chinoise contemporaine comme une entité polyglossique et déterritorialisée. Dans la deuxième partie, nous nous concentrerons sur deux exemples d’autofiction, à savoir Zha gen et Balzac et la petite tailleuse chinoise, en comparant leur représentation du temps figuré comme une évolution identitaire de l’individu. Dans la troisième partie, nous analyserons les deux romans The Crazed et Rou zhi tu, en mettant en évidence le caractère spatial de la mémoire, transposé en forme de témoignage fictionnel. Finalement, dans la quatrième partie, nous explorerons les interactions entre la littérature chinoise et la littérature mondiale, en plaçant les cas analysés dans une perspective translinguistique. À travers la comparaison entre les versions chinoise, anglaise et française des romans, nous montrerons comment les mémoires déterritorialisées sont modulées par la traduction et l’autotraduction. / This thesis aims to investigate the representation of fictional memories in the context of global Chinese literature, showing how displacement and translingualism affect the works by authors from the Mainland and from overseas, who express their creativity in different languages. The four novels Zha gen (Striking Root) by Han Dong, Balzac et la petite tailleuse chinoise (Balzac and the Little Chinese Seamstress) by Dai Sijie, The Crazed by Ha Jin, and Rou zhi tu (Beijing Coma) by Ma Jian are compared as reflections of individual memories of the Cultural Revolution and of the 1989 Tiananmen Square protests. The first part of the thesis addresses the new theoretical approaches configuring contemporary Chinese literature as a polyglossic and deterritorialised entity. The second part focuses on the analysis of two examples of autofictions, Zha gen and Balzac et la Petite Tailleuse chinoise, comparing their representation of time as reflected in the evolution of the individual. The third part explores the two novels The Crazed and Rou zhi tu, focusing on the spatial character of memory transposed in the form of a fictional témoignage. Finally, the fourth part investigates the interactions between Chinese literature and world literature, placing the cases analysed in a translingual perspective. The comparison between the Chinese, the English and the French versions of the novels shows how deterritorialised memories are modulated through translation and self-translation. / La tesi esamina la rappresentazione narrativa della memoria nel quadro globale della letteratura cinese contemporanea, mostrando l’influenza di dislocamento e translinguismo sulle opere di autori cinesi che scrivono tanto dalla RPC quanto dall’estero, in cinese o in altre lingue. I quattro romanzi Zha gen (Mettere radici) di Han Dong, Balzac et la petite tailleuse chinoise (Balzac e la piccola sarta cinese) di Dai Sijie, The Crazed (Pazzia) di Ha Jin e Rou zhi tu (Beijing Coma) di Ma Jian saranno comparati come immagini di memorie individuali della Rivoluzione Culturale e delle proteste studentesche di Piazza Tian’anmen. La prima parte si incentrerà sulla discussione di nuovi approcci teorici che inquadrano la letteratura cinese come un’entità poliglossica deterritorializzata. La seconda sarà dedicata all’analisi comparata di Zha gen e Balzac et la petite tailleuse chinoise e metterà in evidenza la rappresentazione del tempo in termini di evoluzione identitaria dell’individuo. Nella terza parte, il paragone tra The Crazed e Rou zhi tu sottolineerà il carattere spaziale della memoria come testimonianza narrativa. La quarta parte, infine, esplorerà le interazioni tra la letteratura cinese e la letteratura mondiale da una prospettiva translinguistica. La comparazione tra le versioni in cinese, inglese e francese dei romanzi mostrerà come tali memorie deterritorializzate sono modulate dalla traduzione e dall’autotraduzione.

Als Schlüsselenzym im Renin-Angiotensin System übernimmt das Angiotensin Converting Enzyme (ACE) eine wichtige Rolle bei der Blutdruckregulierung. ACE spaltet das biologisch inaktive Angiotensin I zum vasokonstriktorisch wirksamen Angiotensin II, was zu einem Anstieg des Blutdruckes führt. Tier- und Humanstudien zeigten, dass die Aufnahme bekannter, aus dem Proteinabbau stammender ACE-Inhibitoren eine Absenkung des Blutdruckes bewirkte. In der Lebensmittelindustrie finden Hydrolysate von Milchproteinen, im speziellen von Molkenproteinen, Einsatz in hypoallergenen (HA) Säuglingsnahrungen. Obwohl das Phänomen einer ACE-Inhibierung durch HA-Nahrungen in vitro in der Literatur bereits Erwähnung fand, existieren bislang keine Angaben zu einer potentiellen Wirkung in vivo. In der vorliegenden Arbeit konnte für kommerzielle hypoallergene (HA) Säuglingsnahrung eine sehr starke ACE-Hemmung in vitro zeigen (IC50-Werte zwischen 20 und 104 mg Protein/liter), welche die für fermentierte Sauermilchprodukte dokumentierte Wirkung bei weitem überstieg.] Mittels RP-HPLC und ESI-TOF-MS konnte neben zahlreichen bekannten Peptiden mit ACE-hemmendem Effekt erstmals das aus der Primärsequenz von -Lactalbumin freigesetzte Dipeptid Ile-Trp in den HA-Nahrungen identifiziert und quantifiziert werden. Ile-Trp ist der bislang potenteste in Lebensmitteln nachgewiesene ACE-Inhibitor (IC50 = 0,7µM). HA-Nahrungen zeigten auch ex vivo im Zellsystem (HUVECs) einen stark ACE-hemmenden Effekt. Aus diesem Grunde wurde ein möglicher Einfluss der HA-Nahrungen auf den Blutdruck spontan hypertensiver Ratten untersucht. Hierfür wurden die Tiere im Rahmen einer Fütterungsstudie über 14 Wochen mit standardisiertem Futter, welchem HA-Nahrung (Gruppe 1), konventionelle Säuglingsnahrung (Gruppe 2) bzw. der bekannte ACE-Inhibitor Captopril (Gruppe 3) zugesetzt war, gefüttert. Eine vierte Gruppe mit Standardfutter diente als Kontrolle. Der Blutdruck wurde am wachen Tier nichtinvasiv mittels tail-cuff-Methode gemessen. Der systolische Blutdruck sank bei Verabreichung der HA-Nahrung nach 7 Wochen signifikant um 21 ± 8 mmHg ab im Vergleich zur Kontrollgruppe bzw. den mit konventioneller Säuglingsnahrung gefütterten Tieren. Captopril führte zur einer Blutdrucksenkung um 30 ± 7 mmHg.

published_or_final_version / Architecture / Master / Master of Architecture