The use of modelling in purchasing/supply management research

The purpose of this research to explore the use of modelling in the field of Purchasing and Supply Management (P/SM). We are particularly interested in identifying the specific areas of P/SM where there are opportunities for the use of modelling based methods. The paper starts with an overview of main types of modelling and also provides a categorisation of the main P/SM research themes. Our research shows that there are many opportunities for using descriptive, predictive and prescriptive modelling approaches in all areas of P/SM research from the ones with a focus on the actual function from a purely operational and execution perspective (e.g. purchasing processes and behaviour) to the ones with a focus on the organisational level from a more strategic perspective (e.g. strategy and policy). We conclude that future P/SM research needs to explore the value of modelling not just at the functional or operational level, but also at the organisation and strategic level respectively. We also acknowledge that while using empirical results to inform and improve models has advantages, there are also drawbacks, which relate to the value, the practical relevance and the generalisability of the modelling based approaches.

Supply Chain Resilience? Definition of concept and its formative elements.

The objective of this paper is to conceptualize Supply Chain Resilience (SCRes) and identify which supply chain capabilities can support the containment of disruptions and how these capabilities affect SCRes. Through a systematic and structured review of literature, this paper provides insights into the conceptualization and research methodological background of the SCM field. A total of one hundred and thirty four carefully selected refereed journal articles were systematically analyzed leading to the introduction of a novel definition for SCRes, which the authors view as the as “the ability to proactively plan and design the Supply Chain network for anticipating unexpected disruptive (negative) events, respond adaptively to disruptions while maintaining control over structure and function and transcending to a post-event robust state of operations, if possible, more favorable than the one prior to the event, thus gaining competitive advantage”. Finally, a critical examination of existing conceptual frameworks for understanding the relationships between the SCRes concept and its identified formative elements, is taking place.

Modelling and estimating models of physician labour supply and productivity

Ma thèse s’intéresse aux politiques de santé conçues pour encourager l’offre de services de santé. L’accessibilité aux services de santé est un problème majeur qui mine le système de santé de la plupart des pays industrialisés. Au Québec, le temps médian d’attente entre une recommandation du médecin généraliste et un rendez-vous avec un médecin spécialiste était de 7,3 semaines en 2012, contre 2,9 semaines en 1993, et ceci malgré l’augmentation du nombre de médecins sur cette même période. Pour les décideurs politiques observant l’augmentation du temps d’attente pour des soins de santé, il est important de comprendre la structure de l’offre de travail des médecins et comment celle-ci affecte l’offre des services de santé. Dans ce contexte, je considère deux principales politiques. En premier lieu, j’estime comment les médecins réagissent aux incitatifs monétaires et j’utilise les paramètres estimés pour examiner comment les politiques de compensation peuvent être utilisées pour déterminer l’offre de services de santé de court terme. En second lieu, j’examine comment la productivité des médecins est affectée par leur expérience, à travers le mécanisme du "learning-by-doing", et j’utilise les paramètres estimés pour trouver le nombre de médecins inexpérimentés que l’on doit recruter pour remplacer un médecin expérimenté qui va à la retraite afin de garder l’offre des services de santé constant. Ma thèse développe et applique des méthodes économique et statistique afin de mesurer la réaction des médecins face aux incitatifs monétaires et estimer leur profil de productivité (en mesurant la variation de la productivité des médecins tout le long de leur carrière) en utilisant à la fois des données de panel sur les médecins québécois, provenant d’enquêtes et de l’administration. Les données contiennent des informations sur l’offre de travail de chaque médecin, les différents types de services offerts ainsi que leurs prix. Ces données couvrent une période pendant laquelle le gouvernement du Québec a changé les prix relatifs des services de santé. J’ai utilisé une approche basée sur la modélisation pour développer et estimer un modèle structurel d’offre de travail en permettant au médecin d’être multitâche. Dans mon modèle les médecins choisissent le nombre d’heures travaillées ainsi que l’allocation de ces heures à travers les différents services offerts, de plus les prix des services leurs sont imposés par le gouvernement. Le modèle génère une équation de revenu qui dépend des heures travaillées et d’un indice de prix représentant le rendement marginal des heures travaillées lorsque celles-ci sont allouées de façon optimale à travers les différents services. L’indice de prix dépend des prix des services offerts et des paramètres de la technologie de production des services qui déterminent comment les médecins réagissent aux changements des prix relatifs. J’ai appliqué le modèle aux données de panel sur la rémunération des médecins au Québec fusionnées à celles sur l’utilisation du temps de ces mêmes médecins. J’utilise le modèle pour examiner deux dimensions de l’offre des services de santé. En premierlieu, j’analyse l’utilisation des incitatifs monétaires pour amener les médecins à modifier leur production des différents services. Bien que les études antérieures ont souvent cherché à comparer le comportement des médecins à travers les différents systèmes de compensation,il y a relativement peu d’informations sur comment les médecins réagissent aux changementsdes prix des services de santé. Des débats actuels dans les milieux de politiques de santé au Canada se sont intéressés à l’importance des effets de revenu dans la détermination de la réponse des médecins face à l’augmentation des prix des services de santé. Mon travail contribue à alimenter ce débat en identifiant et en estimant les effets de substitution et de revenu résultant des changements des prix relatifs des services de santé. En second lieu, j’analyse comment l’expérience affecte la productivité des médecins. Cela a une importante implication sur le recrutement des médecins afin de satisfaire la demande croissante due à une population vieillissante, en particulier lorsque les médecins les plus expérimentés (les plus productifs) vont à la retraite. Dans le premier essai, j’ai estimé la fonction de revenu conditionnellement aux heures travaillées, en utilisant la méthode des variables instrumentales afin de contrôler pour une éventuelle endogeneité des heures travaillées. Comme instruments j’ai utilisé les variables indicatrices des âges des médecins, le taux marginal de taxation, le rendement sur le marché boursier, le carré et le cube de ce rendement. Je montre que cela donne la borne inférieure de l’élasticité-prix direct, permettant ainsi de tester si les médecins réagissent aux incitatifs monétaires. Les résultats montrent que les bornes inférieures des élasticités-prix de l’offre de services sont significativement positives, suggérant que les médecins répondent aux incitatifs. Un changement des prix relatifs conduit les médecins à allouer plus d’heures de travail au service dont le prix a augmenté. Dans le deuxième essai, j’estime le modèle en entier, de façon inconditionnelle aux heures travaillées, en analysant les variations des heures travaillées par les médecins, le volume des services offerts et le revenu des médecins. Pour ce faire, j’ai utilisé l’estimateur de la méthode des moments simulés. Les résultats montrent que les élasticités-prix direct de substitution sont élevées et significativement positives, représentant une tendance des médecins à accroitre le volume du service dont le prix a connu la plus forte augmentation. Les élasticitésprix croisées de substitution sont également élevées mais négatives. Par ailleurs, il existe un effet de revenu associé à l’augmentation des tarifs. J’ai utilisé les paramètres estimés du modèle structurel pour simuler une hausse générale de prix des services de 32%. Les résultats montrent que les médecins devraient réduire le nombre total d’heures travaillées (élasticité moyenne de -0,02) ainsi que les heures cliniques travaillées (élasticité moyenne de -0.07). Ils devraient aussi réduire le volume de services offerts (élasticité moyenne de -0.05). Troisièmement, j’ai exploité le lien naturel existant entre le revenu d’un médecin payé à l’acte et sa productivité afin d’établir le profil de productivité des médecins. Pour ce faire, j’ai modifié la spécification du modèle pour prendre en compte la relation entre la productivité d’un médecin et son expérience. J’estime l’équation de revenu en utilisant des données de panel asymétrique et en corrigeant le caractère non-aléatoire des observations manquantes à l’aide d’un modèle de sélection. Les résultats suggèrent que le profil de productivité est une fonction croissante et concave de l’expérience. Par ailleurs, ce profil est robuste à l’utilisation de l’expérience effective (la quantité de service produit) comme variable de contrôle et aussi à la suppression d’hypothèse paramétrique. De plus, si l’expérience du médecin augmente d’une année, il augmente la production de services de 1003 dollar CAN. J’ai utilisé les paramètres estimés du modèle pour calculer le ratio de remplacement : le nombre de médecins inexpérimentés qu’il faut pour remplacer un médecin expérimenté. Ce ratio de remplacement est de 1,2.

Supply Chain Adaptation of Finnish Companies in Chinese Institutional Environment

Within the last few decades of operations and supply chain management, the field has seen the rise of so called best practices, methods that will help supply chains obtain their business goals and gain a competitive edge. These methods were thought to be universal. This however is not always the case, as the surrounding business environment could have a significant impact on what will be effective in gaining competitive edge. Contingency theory states that the success of a supply chain is determined by both internal capabilities, as well as external context aligning. This creates a strategic fit, which is a major determinant of success. In order for supply chains to reach this strategic fit, they must adapt. As China has seen rapid growth and over the last few decades become one of the major economies of the world, Western companies have tried to establish themselves there, only to find that the Chinese market is extremely difficult to operate in. The aim of this thesis was to investigate from contingency theory perspective, what are the institutional factors that affect supply chain management of Finnish companies operating in China, and how do Finnish companies adapt their supply chains to better fit the Chinese institutional environment. A theoretical model was created for this thesis, in which supply chains possess resources, which can be combined in a meaningful manner to create capabilities. Both resources and capabilities are affected by the surrounding institutional environment, which forces supply chains to adapt in order to find a better strategic fit. A total of six Finnish managers from three large and three small companies operating in China were interviewed. The results indicated that the Chinese business environment is significantly different, than that of Finland or Western countries in general. Three institutional factors were identified: Confucian though, fast-paced business environment, and managing labor force. These three institutional factors made the relationship and delivery capabilities particularly important, as well as human resources, reputation, physical resources and technological resources. In conclusion, it was discovered that the Chinese institutional environment is heavily affected by Confucian thought, as well as the rapid market growth. These are the two most important institutional factors that shape the Chinese market. If supply chains wish to be successful in China, adaptation regarding these two institutional factors should yield good results.

A NAIRU assessment: an applied case to Colombia’s labor markets

Given the discrepancy over the optimum levels of employment for Colombia, this research targets both, the national and urban, Non-Accelerating Inflation Rate of Unemployment (NAIRU) for the Colombian markets -- In doing so, there is a strong pertinence in estimating the constant NAIRU through raw and minimally altered data and providing the reader with a complete brief of the theory in which the model is founded -- The introduction of supply shocks is considered to attain improved estimations and a more reliable assessment of the NAIRU to those that have previously been attempted -- The backbone of the analysis is conducted through the relationship established by the Phillips curve from 2001 until 2015

Regional differences of outpatient physician supply as a theoretical economic and empirical generalized linear model

BACKGROUND: Regional differences in physician supply can be found in many health care systems, regardless of their organizational and financial structure. A theoretical model is developed for the physicians' decision on office allocation, covering demand-side factors and a consumption time function. METHODS: To test the propositions following the theoretical model, generalized linear models were estimated to explain differences in 412 German districts. Various factors found in the literature were included to control for physicians' regional preferences. RESULTS: Evidence in favor of the first three propositions of the theoretical model could be found. Specialists show a stronger association to higher populated districts than GPs. Although indicators for regional preferences are significantly correlated with physician density, their coefficients are not as high as population density. CONCLUSIONS: If regional disparities should be addressed by political actions, the focus should be to counteract those parameters representing physicians' preferences in over- and undersupplied regions.

Supply Chain Adaptation of Finnish Companies in Chinese Institutional Environment

Within the last few decades of operations and supply chain management, the field has seen the rise of so called best practices, methods that will help supply chains obtain their business goals and gain a competitive edge. These methods were thought to be universal. This however is not always the case, as the surrounding business environment could have a significant impact on what will be effective in gaining competitive edge. Contingency theory states that the success of a supply chain is determined by both internal capabilities, as well as external context aligning. This creates a strategic fit, which is a major determinant of success. In order for supply chains to reach this strategic fit, they must adapt. As China has seen rapid growth and over the last few decades become one of the major economies of the world, Western companies have tried to establish themselves there, only to find that the Chinese market is extremely difficult to operate in. The aim of this thesis was to investigate from contingency theory perspective, what are the institutional factors that affect supply chain management of Finnish companies operating in China, and how do Finnish companies adapt their supply chains to better fit the Chinese institutional environment. A theoretical model was created for this thesis, in which supply chains possess resources, which can be combined in a meaningful manner to create capabilities. Both resources and capabilities are affected by the surrounding institutional environment, which forces supply chains to adapt in order to find a better strategic fit. A total of six Finnish managers from three large and three small companies operating in China were interviewed. The results indicated that the Chinese business environment is significantly different, than that of Finland or Western countries in general. Three institutional factors were identified: Confucian though, fast-paced business environment, and managing labor force. These three institutional factors made the relationship and delivery capabilities particularly important, as well as human resources, reputation, physical resources and technological resources. In conclusion, it was discovered that the Chinese institutional environment is heavily affected by Confucian thought, as well as the rapid market growth. These are the two most important institutional factors that shape the Chinese market. If supply chains wish to be successful in China, adaptation regarding these two institutional factors should yield good results.

Trade Shocks and Local Labor Markets' Linkages: Theory and Evidence

In the past few years, there has been a concern among economists and policy makers that increased openness to international trade affects some regions in a country more than others. Recent research has found that local labor markets more exposed to import competition through their initial employment composition experience worse outcomes in several dimensions such as, employment, wages, and poverty. Although there is evidence that regions within a country exhibit variation in the intensity with which they trade with each other and with other countries, trade linkages have been ignored in empirical analyses of the regional effects of trade, which focus on differences in employment composition. In this dissertation, I investigate how local labor markets' trade linkages shape the response of wages to international trade shocks. In the second chapter, I lay out a standard multi-sector general equilibrium model of trade, where domestic regions trade with each other and with the rest of the world. Using this benchmark, I decompose a region's wage change resulting from a national import cost shock into a direct effect on prices, holding other endogenous variables constant, and a series of general equilibrium effects. I argue the direct effect provides a natural measure of exposure to import competition within the model since it summarizes the effect of the shock on a region's wage as a function of initial conditions given by its trade linkages. I call my proposed measure linkage exposure while I refer to the measures used in previous studies as employment exposure. My theoretical analysis also shows that the assumptions previous studies make on trade linkages are not consistent with the standard trade model. In the third chapter, I calibrate the model to the Brazilian economy in 1991--at the beginning of a period of trade liberalization--to perform a series of experiments. In each of them, I reduce the Brazilian import cost by 1 percent in a single sector and I calculate how much of the cross-regional variation in counterfactual wage changes is explained by exposure measures. Over this set of experiments, employment exposure explains, for the median sector, 2 percent of the variation in counterfactual wage changes while linkage exposure explains 44 percent. In addition, I propose an estimation strategy that incorporates trade linkages in the analysis of the effects of trade on observed wages. In the model, changes in wages are completely determined by changes in market access, an endogenous variable that summarizes the real demand faced by a region. I show that a linkage measure of exposure is a valid instrument for changes in market access within Brazil. By using observed wage changes in Brazil between 1991-2000, my estimates imply that a region at the 25th percentile of the change in domestic market access induced by trade liberalization, experiences a 0.6 log points larger wage decline (or smaller wage increase) than a region at the 75th percentile. The estimates from a regression of wages changes on exposure imply that a region at the 25th percentile of exposure experiences a 3 log points larger wage decline (or smaller wage increase) than a region at the 75th percentile. I conclude that estimates based on exposure overstate the negative impact of trade liberalization on wages in Brazil. In the fourth chapter, I extend the standard model to allow for two types of workers according to their education levels: skilled and unskilled. I show that there is substantial variation across Brazilian regions in the skill premium. I use the exogenous variation provided by tariff changes to estimate the impact of market access on the skill premium. I find that decreased domestic market access resulting from trade liberalization resulted in a higher skill premium. I propose a mechanism to explain this result: that the manufacturing sector is relatively more intensive in unskilled labor and I show empirical evidence that supports this hypothesis.

“Mais vale intervir, do que remediar" Cultura de segurança e resiliência: O futuro caminho das organizações

Dissertação de Mestrado apresentada ao Instituto Superior de Psicologia Aplicada para obtenção de grau de Mestre na especialidade de Psicologia Social e das Organizações.

Effects of gestational and postnatal exposure to chronic intermittent hypoxia on diaphragm muscle contractile function in the rat

Alterations to the supply of oxygen during early life presents a profound stressor to physiological systems with aberrant remodeling that is often long-lasting. Chronic intermittent hypoxia (CIH) is a feature of apnea of prematurity, chronic lung disease, and sleep apnea. CIH affects respiratory control but there is a dearth of information concerning the effects of CIH on respiratory muscles, including the diaphragm—the major pump muscle of breathing. We investigated the effects of exposure to gestational CIH (gCIH) and postnatal CIH (pCIH) on diaphragm muscle function in male and female rats. CIH consisted of exposure in environmental chambers to 90 s of hypoxia reaching 5% O2 at nadir, once every 5 min, 8 h a day. Exposure to gCIH started within 24 h of identification of a copulation plug and continued until day 20 of gestation; animals were studied on postnatal day 22 or 42. For pCIH, pups were born in normoxia and within 24 h of delivery were exposed with dams to CIH for 3 weeks; animals were studied on postnatal day 22 or 42. Sham groups were exposed to normoxia in parallel. Following gas exposures, diaphragm muscle contractile, and endurance properties were examined ex vivo. Neither gCIH nor pCIH exposure had effects on diaphragm muscle force-generating capacity or endurance in either sex. Similarly, early life exposure to CIH did not affect muscle tolerance of severe hypoxic stress determined ex vivo. The findings contrast with our recent observation of upper airway dilator muscle weakness following exposure to pCIH. Thus, the present study suggests a relative resilience to hypoxic stress in diaphragm muscle. Co-ordinated activity of thoracic pump and upper airway dilator muscles is required for optimal control of upper airway caliber. A mismatch in the force-generating capacity of the complementary muscle groups could have adverse consequences for the control of airway patency and respiratory homeostasis.

Urban Agriculture Oriented towards Self-Supply, Social and Commercial Purpose: A Typology

Urban agriculture, a dynamic multifunctional phenomenon, affects the spatial diversification of urban land use, its valorization and its governance. Literature acknowledges its contribution to the development of sustainable cities. The dimension and extent of this contribution depends significantly on the particular form and function of urban agriculture. However, the complexity of interests and dimensions is insufficiently covered by theory. This paper proposes a typology for urban agriculture, supporting both theory building and practical decision processes. We reviewed and mapped the diversity of the types of agriculture found along three beneficial dimensions (self-supply, socio-cultural, commercial) for product distribution scale and actors. We distinguish between ideal types, subtypes and mixed types. Our intention is to include a dynamic perspective in the typology of urban agricultural land use because transition processes between types are observable due to the existence of complex motivations and influences. In a pilot study of 52 urban agriculture initiatives in Germany, we tested the validity of the typology and discussed it with stakeholders, proving novelty and relevance for profiling discussions.

The role of inflammation in vascular function and pregnancy outcome in the pregnant stroke prone spontaneously hypertensive rat

During pregnancy, the maternal cardiovascular system undergoes major adaptation. One of these changes is a 40-50 % increase in circulating blood volume which requires a systemic remodelling of the vasculature in order to regulate maternal blood pressure and maximise blood supply to the developing placenta and fetus. These changes are broadly conserved between humans and rats making them an appropriate pre-clinical model in which to study the underlying mechanisms of pregnancy-dependent cardiovascular remodelling. Whilst women are normally protected against cardiovascular disease; pregnancy marks a period of time where women are susceptible to cardiovascular complications. Cardiovascular disease is the leading cause of maternal mortality in the United Kingdom; in particular hypertensive conditions are among the most common complications of pregnancy. One of the main underlying pathologies of these pregnancy complications is thought to be a failure of the maternal cardiovascular system to adapt. The remodelling of the uterine arteries, which directly supply the maternal-fetal interface, is paramount to a healthy pregnancy. Failure of the uterine arteries to remodel sufficiently can result in a number of obstetric complications such as preeclampsia, fetal growth restriction and spontaneous pregnancy loss. At present, it is poorly understood whether this deficient vascular response is due to a predisposition from existing maternal cardiovascular risk factors, the physiological changes that occur during pregnancy or a combination of both. Previous work in our group employed the stroke prone spontaneously hypertensive rat (SHRSP) as a model to investigate pregnancy-dependent remodelling of the uterine arteries. The SHRSP develops hypertension from 6 weeks of age and can be contrasted with the control strain, the Wistar Kyoto (WKY) rat. The phenotype of the SHRSP is therefore reflective of the clinical situation of maternal chronic hypertension during pregnancy. We showed that the SHRSP exhibited a deficient uterine artery remodelling response with respect to both structure and function accompanied by a reduction in litter size relative to the WKY at gestational day (GD) 18. A previous intervention study using nifedipine in the SHRSP achieved successful blood pressure reduction from 6 weeks of age and throughout pregnancy; however uterine artery remodelling and litter size at GD18 was not improved. We concluded that the abnormal uterine artery remodelling present in the SHRSP was independent of chronic hypertension. From these findings, we hypothesised that the SHRSP could be a novel model of spontaneously deficient uterine artery remodelling in response to pregnancy which was underpinned by other as yet unidentified cardiovascular risk factors. In Chapter 1 of this thesis, I have characterised the maternal, placental and fetal phenotype in pregnant (GD18) SHRSP and WKY. The pregnant SHRSP exhibit features of left ventricular hypertrophy in response to pregnancy and altered expression of maternal plasma biomarkers which have been previously associated with hypertension in human pregnancy. I developed a protocol for accurate dissection of the rat uteroplacental unit using qPCR probes specific for each layer. This allowed me to make an accurate and specific statement about gene expression in the SHRSP GD18 placenta; where oxidative stress related gene markers were increased in the vascular compartments. The majority of SHRSP placenta presented at GD18 with a blackened ring which encircled the tissue. Further investigation of the placenta using western blot for caspase 3 cleavage determined that this was likely due to increased cell death in the SHRSP placenta. The SHRSP also presented with a loss of one particular placental cell type at GD18: the glycogen cells. These cells could have been the target of cell death in the SHRSP placenta or were utilised early in pregnancy as a source of energy due to the deficient uterine artery blood supply. Blastocyst implantation was not altered but resorption rate was increased between SHRSP and WKY; indicating that the reduction in litter size in the SHRSP was primarily due to late (>GD14) pregnancy loss. Fetal growth was not restricted in SHRSP which led to the conclusion that SHRSP sacrifice part of their litter to deliver a smaller number of healthier pups. Activation of the immune system is a common pathway that has been implicated in the development of both hypertension and adverse pregnancy outcome. In Chapter 2, I proposed that this may be a mechanism of interest in SHRSP pregnancy and measured the pro-inflammatory cytokine, TNFα, as a marker of inflammation in pregnant SHRSP and WKY and in the placentas from these animals. TNFα was up-regulated in maternal plasma and urine from the GD18 SHRSP. In addition, TNFα release was increased from the GD18 SHRSP placenta as was the expression of the pro-inflammatory TNFα receptor 1 (Tnfr1). In order to investigate whether this excess TNFα was detrimental to SHRSP pregnancy, a vehicle-controlled intervention study using etanercept (a monoclonal antibody which works as a TNFα antagonist) was carried out. Etanercept treatment at GD0, 6, 12 and 18 resulted in an improvement in pregnancy outcome in the SHRSP with an increased litter size and reduced resorption rate. Furthermore, there was an improved uterine artery function in GD18 SHRSP treated with etanercept which was associated with an improved uterine artery blood flow over the course of gestation. In Chapter 3, I sought to identify the source of this detrimental excess of TNFα by designing a panel for maternal leukocytes in the blood and placenta at GD18. A population of CD3- CD161+ cells, which are defined as rat natural killer (NK) cells, were increased in number in the SHRSP. Intracellular flow cytometry also identified this cell type as a source of excess TNFα in blood and placenta from pregnant SHRSP. I then went on to evaluate the effects of etanercept treatment on these CD3- CD161+ cells and showed that etanercept reduced the expression of CD161 and the cytotoxic molecule, granzyme B, in the NK cells. Thus, etanercept limits the cytotoxicity and potential damaging effect of these NK cells in the SHRSP placenta. Analysing the urinary peptidome has clinical potential to identify novel pathways involved with disease and/or to develop biomarker panels to aid and stratify diagnosis. In Chapter 4, I utilised the SHRSP as a pre-clinical model to identify novel urinary peptides associated with hypertensive pregnancy. Firstly, a characterisation study was carried out in the kidney of the WKY and SHRSP. Urine samples from WKY and SHRSP taken at pre-pregnancy, mid-pregnancy (GD12) and late pregnancy (GD18) were used in the peptidomic screen. In order to capture peptides which were markers of hypertensive pregnancy from the urinary peptidomic data, I focussed on those that were only changed in a strain dependent manner at GD12 and 18 and not pre-pregnancy. Peptide fragments from the uromodulin protein were identified from this analysis to be increased in pregnant SHRSP relative to pregnant WKY. This increase in uromodulin was validated at the SHRSP kidney level using qPCR. Uromodulin has previously been identified to be a candidate molecule involved in systemic arterial hypertension but not in hypertensive pregnancy thus is a promising target for further study. In summary, we have characterised the SHRSP as the first model of maternal chronic hypertension during pregnancy and identified that inflammation mediated by TNFα and NK cells plays a key role in the pathology. The evidence presented in this thesis establishes the SHRSP as a pre-clinical model for pregnancy research and can be continued into clinical studies in pregnant women with chronic hypertension which remains an area of unmet research need.

Relationship Between Orofacial Function, Dentofacial Morphology, And Bite Force In Young Subjects.

The aim was to evaluate the relationship between orofacial function, dentofacial morphology, and bite force in young subjects. Three hundred and sixteen subjects were divided according to dentition stage (early, intermediate, and late mixed and permanent dentition). Orofacial function was screened using the Nordic Orofacial Test-Screening (NOT-S). Orthodontic treatment need, bite force, lateral and frontal craniofacial dimensions and presence of sleep bruxism were also assessed. The results were submitted to descriptive statistics, normality and correlation tests, analysis of variance, and multiple linear regression to test the relationship between NOT-S scores and the studied independent variables. The variance of NOT-S scores between groups was not significant. The evaluation of the variables that significantly contributed to NOT-S scores variation showed that age and presence of bruxism related to higher NOT-S total scores, while the increase in overbite measurement and presence of closed lip posture related to lower scores. Bite force did not show a significant relationship with scores of orofacial dysfunction. No significant correlations between craniofacial dimensions and NOT-S scores were observed. Age and sleep bruxism were related to higher NOT-S scores, while the increase in overbite measurement and closed lip posture contributed to lower scores of orofacial dysfunction.

Impaired Compensatory Beta-cell Function And Growth In Response To High-fat Diet In Ldl Receptor Knockout Mice.

In this study, we investigated the effect of low density lipoprotein receptor (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the functional and growth response of pancreatic beta-cells in C57BL/6 mice fed a high-fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and morphometric islet parameters of wild-type (WT) and LDLr-/- mice were assessed. HF diet-fed WT animals became obese and hypercholesterolaemic as well as hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant, characterizing them as prediabetic. Also they showed a significant decrease in beta-cell secretory response to glucose. Overall, LDLr-/- mice displayed greater susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance to glucose and pronounced decrease in glucose-stimulated insulin secretion. HF diet induced similarly in WT and LDLr-/- mice, a significant decrease in Cx36 beta-cell content as revealed by immunoblotting. Prediabetic WT mice displayed marked increase in beta-cell mass mainly due to beta-cell hypertrophy/replication. Nevertheless, HF diet-fed LDLr-/- mice showed no significant changes in beta-cell mass, but lower islet-duct association (neogenesis) and higher beta-cell apoptosis index were seen as compared to controls. The higher metabolic susceptibility to HF diet of LDLr-/- mice may be explained by a deficiency in insulin secretory response to glucose associated with lack of compensatory beta-cell expansion.

Long-term Postoperative Atrophy Of Contralateral Hippocampus And Cognitive Function In Unilateral Refractory Mtle With Unilateral Hippocampal Sclerosis.

This study aimed to evaluate long-term atrophy in contralateral hippocampal volume after surgery for unilateral MTLE, as well as the cognitive outcome for patients submitted to either selective transsylvian amygdalohippocampectomy (SelAH) or anterior temporal lobe resection (ATL). We performed a longitudinal study of 47 patients with MRI signs of unilateral hippocampal sclerosis (23 patients with right-sided hippocampal sclerosis) who underwent surgical treatment for MTLE. They underwent preoperative/postoperative high-resolution MRI as well as neuropsychological assessment for memory and estimated IQ. To investigate possible changes in the contralateral hippocampus of patients, we included 28 controls who underwent two MRIs at long-term intervals. The volumetry using preoperative MRI showed significant hippocampal atrophy ipsilateral to the side of surgery when compared with controls (p<0.0001) but no differences in contralateral hippocampal volumes. The mean postoperative follow-up was 8.7 years (± 2.5 SD; median=8.0). Our patients were classified as Engel I (80%), Engel II (18.2%), and Engel III (1.8%). We observed a small but significant reduction in the contralateral hippocampus of patients but no volume changes in controls. Most of the patients presented small declines in both estimated IQ and memory, which were more pronounced in patients with left TLE and in those with persistent seizures. Different surgical approaches did not impose differences in seizure control or in cognitive outcome. We observed small declines in cognitive scores with most of these patients, which were worse in patients with left-sided resection and in those who continued to suffer from postoperative seizures. We also demonstrated that manual volumetry can reveal a reduction in volume in the contralateral hippocampus, although this change was mild and could not be detected by visual analysis. These new findings suggest that dynamic processes continue to act after the removal of the hippocampus, and further studies with larger groups may help in understanding the underlying mechanisms.