Cardiovascular disease in Switzerland - health care, mortality and geographical pattern

SUMMARY Switzerland is facing an aging population and a growing amount of patients with chronic diseases. It is crucial to display health care processes and pathways, to identify inequalities and obstacles, and to point out possibilities for improvements of the Swiss health care system (e.g. increase efficiency). The introductory part of the thesis presents a brief description of the Swiss health care system, health services research and regional variation as well as an introduction of CVD and its epidemiological key figures, aetiology and treatments. This is followed by the description of the utilized methods and data, and the objectives of this thesis. The subsequent sections present the four articles included in this thesis. The first article focuses on a small area analysis on regional variation of avoidable hospitalisations in Switzerland including density of primary care physicians and specialists, rurality and hospital supply factors as explanatory variables in the analysis. Lower rates of avoidable hospitalisations were found in areas with very high supply of primary care physicians, increased avoidable hospitalisation rates in areas with more specialists and in areas with higher proportion of rural residents. The second article aims to examine whether emergency patients with acute ST-segment elevation myocardial infarction were adequately treated, i.e. according to the treatment guidelines, in Switzerland. Results show that older and female patients were less likely to receive revascularization which suggests that the treatment guidelines may not be uniformly applied in Switzerland. Similar to the first article, also in the third article a small area analysis was performed but this time investigating regional variation in costs at the end of life. Strongest associations of cost was found with cause of death, age and language region of the decedents. The strong spatial variation of costs could only partly be explained by the included covariates. Article four aims to examine the relationship of distance to different hospital types and mortality from AMI or stroke. We found that AMI mortality in the Swiss population 30 and older and stroke mortality in those 65 and above increased with distance to central and university hospitals, while adjusting for sociodemographic and economic characteristics of the population. The presentation of the four articles is followed by a discussion, which summarizes the main findings and the strengths and limitations of the presented articles. The thesis concludes with a discussion about the challenges for policy, practice and future research.

Latitudinal variation in the planktic foraminifer Contusotruncana contusa in the terminal Cretaceous ocean

The morphological variability (coiling properties, size and shape) of the planktic foraminifer Contusortuncana contusa (Cushman) in the terminal Cretaceous ocean was examined at eight deep-sea sites and two continental sections from low (16°) to middle (42°) paleolatitudes in both hemispheres. The material used in this study includes samples from the South Atlantic (DSDP Sites 356, 527 and 525A), North Atlantic (Sites 384 and 548A), Indian and Pacific Oceans (DSDP Site 465A and ODP Sites 761C and 762C) and Tethyan Ocean (outcrop sections from El-Kef and Caravaca). On average 45 specimens from two samples per location were analysed, from an interval corresponding approximately to the last 60 kyr of the Cretaceous. No differences in coiling direction (dextral proportions were > 90% in all samples), percentage of kummerform specimens (usually > 50%) and number of chambers in the last whorl (4-5) were observed between the sites. Both test size (expressed as spiral outline area and test volume) and total number of chambers increase significantly towards lower latitudes. Similarly, test conicity, examined by shape coordinate and eigenshape methods, and angularity of the spiral outline show a rather continuous, slight increase towards lower latitudes. Kummerform specimens of C. contusa were slightly larger and more conical than normalforms and possessed substantially more chambers (both totally and in the last whorl). A principal components analysis of the sample means of five variables describing size and shape clearly distinguished high-latitude sites (525A, 527, 548A, 761C and 762C) from low-latitude sites (384, 465A, Caravaca and El-Kef). Specimens from Site 356 are transitional with respect to those two groups. The results indicate: (1) considerable morphological variation in C. contusa during the terminal Cretaceous comparable to that known in many Recent planktic foraminiferal species and (2) a geographical distribution of this variation corresponding to previously suggested biogeographic schemes based on quantitative analysis of planktic foraminiferal assemblages. Despite the differences in sample means, the overall morphology of C. contusa overlaps among the sites studied, supporting the classification of all C. contusa morphotypes as a single species. Similarly, no discrete morphologic groups could be distinguished within any of the samples.

Placing Heteronormativity : A micro-geographical approach to the school as a space of heteronormative (re)production

Within children's geographies there has been an absence concerning sexuality and in particular how this can lead to the discimination and marginalisation of individuals. Similarly, within geographies of sexualities the demographic of non-heterosexual children and youth has been under researched, with studies concerning the space of the school being very limited. This thesis sought to address these absences by carrying out qualitative interviews with non-heterosexual individuals about their school experiences. The interviews showed the importance and variation of both physical and time-spaces in the (re)production of heteronormativities, and that the agency of the indiviudal was asserted through the use of negotiation strategies that sought to navigate or resist heteronormativities.

CYP2D6: a global analysis of phenotypic and genotypic variation in search of radical cure of Plasmodium vivax malaria

Thesis (Master's)--University of Washington, 2016-06

Mutation scanning analysis of Marteilia sydneyi populations from different geographical locations in eastern Australia

Marteilia sydneyi (Paramyxea) is the causative agent of QX disease in oysters. In spite of the economic impact of this disease, its origin and the precise reason(s) for its apparent spread in Australian waters are not yet known. Given such knowledge gaps, investigating the population genetic structure(s) of M. sydneyi populations could provide insights into the epidemiology and ecology of the parasite and could assist in its prevention and control. In this study, single strand conformation polymorphism (SSCP)-based analysis of a region (195 bp) of the first internal transcribed spacer (ITS-1) of ribosomal DNA was employed to investigate genetic variation within and among five populations of M. sydneyi from oysters from five different locations in eastern Australia. The analysis showed the existence of a genetic variant of M. sydneyi common to the Great Sandy Strait, and the Richmond and Georges Rivers, as distinct from variants at the Pimpama and Clarence Rivers. Together with historical and other information relating to the QX disease outbreaks in eastern Australia, the molecular findings support the proposal that the parasite originated in the Great Sandy Strait and/or Richmond River and then extended southward along the coast. From a technical perspective, the study demonstrated the usefulness of SSCP as a tool to study the population genetics and epidemiology of M. sydneyi. (C) 2003 Elsevier Ltd. All rights reserved.

Is the distribution of Fiji leaf gall in Australian sugarcane explained by variation in the vector Perkinsiella saccharicida?

Fiji leaf gall (FLG) is an important virally induced disease in Australian sugarcane. It is confined to southern canegrowing areas, despite its vector, the delphacid planthopper Perkinsiella saccharicida, occurring in all canegrowing areas of Queensland and New South Wales. This disparity between distributions could be a result of successful containment of the disease through quarantine and/or geographical barriers, or because northern Queensland populations of Perkinsiella may be poorer vectors of the disease. These hypotheses were first tested by investigating variation in the ITS2 region of the rDNA fragment among eastern Australian and overseas populations of Perkinsiella. The ITS2 sequences of the Western Australian P. thompsoni and the Fijian P. vitiensis were distinguishable from those of P. saccharicida and there was no significant variation among the 26P. saccharicida populations. Reciprocal crosses of a northern Queensland and a southern Queensland population of P. saccharicida were fertile, so they may well be conspecific. Single vector transmission experiments showed that a population of P. saccharicida from northern Queensland had a higher vector competency than either of two southern Queensland populations. The frequency of virus acquisition in the vector populations was demonstrated to be important in the vector competency of the planthopper. The proportion of infected vectors that transmitted the virus to plants was not significantly different among the populations tested. This study shows that the absence of FLG from northern Queensland is not due to a lack of vector competency of the northern population of P. saccharicida.

The genetic structure of Australasian green turtles (Chelonia mydas): exploring the geographical scale of genetic exchange

Ecological and genetic studies of marine turtles generally support the hypothesis of natal homing, but leave open the question of the geographical scale of genetic exchange and the capacity of turtles to shift breeding sites. Here we combine analyses of mitochondrial DNA (mtDNA) variation and recapture data to assess the geographical scale of individual breeding populations and the distribution of such populations through Australasia. We conducted multiscale assessments of mtDNA variation among 714 samples from 27 green turtle rookeries and of adult female dispersal among nesting sites in eastern Australia. Many of these rookeries are on shelves that were flooded by rising sea levels less than 10 000 years (c. 450 generations) ago. Analyses of sequence variation among the mtDNA control region revealed 25 haplotypes, and their frequency distributions indicated 17 genetically distinct breeding stocks (Management Units) consisting either of individual rookeries or groups of rookeries in general that are separated by more than 500 km. The population structure inferred from mtDNA was consistent with the scale of movements observed in long-term mark-recapture studies of east Australian rookeries. Phylogenetic analysis of the haplotypes revealed five clades with significant partitioning of sequence diversity (Phi = 68.4) between Pacific Ocean and Southeast Asian/Indian Ocean rookeries. Isolation by distance was indicated for rookeries separated by up to 2000 km but explained only 12% of the genetic structure. The emerging general picture is one of dynamic population structure influenced by the capacity of females to relocate among proximal breeding sites, although this may be conditional on large population sizes as existed historically across this region.

Spring Phenology of Butterflies : The role of seasonal variation in life-cycle regulation

Animals and plants in temperate regions must adapt their life cycle to pronounced seasonal variation. The research effort that has gone into studying these cyclical life history events, or phenological traits, has increased greatly in recent decades. As phenological traits are often correlated to temperature, they are relevant to study in terms of understanding the effect of short term environmental variation as well as long term climate change. Because of this, changes in phenology are the most obvious and among the most commonly reported responses to climate change. Moreover, phenological traits are important for fitness as they determine the biotic and abiotic environment an individual encounters. Fine-tuning of phenology allows for synchronisation at a local scale to mates, food resources and appropriate weather conditions. On a between-population scale, variation in phenology may reflect regional variation in climate. Such differences can not only give insights to life cycle adaptation, but also to how populations may respond to environmental change through time. This applies both on an ecological scale through phenotypic plasticity as well as an evolutionary scale through genetic adaptation. In this thesis I have used statistical and experimental methods to investigate both the larger geographical patterns as well as mechanisms of fine-tuning of phenology of several butterfly species. The main focus, however, is on the orange tip butterfly, Anthocharis cardamines, in Sweden and the United Kingdom. I show a contrasting effect of spring temperature and winter condition on spring phenology for three out of the five studied butterfly species. For A. cardamines there are population differences in traits responding to these environmental factors between and within Sweden and the UK that suggest adaptation to local environmental conditions. All populations show a strong negative plastic relationship between spring temperature and spring phenology, while the opposite is true for winter cold duration. Spring phenology is shifted earlier with increasing cold duration. The environmental variables show correlations, for example, during a warm year a short winter delays phenology while a warm spring speeds phenology up. Correlations between the environmental variables also occur through space, as the locations that have long winters also have cold springs. The combined effects of these two environmental variables cause a complex geographical pattern of phenology across the UK and Sweden. When predicting phenology with future climate change or interpreting larger geographical patterns one must therefore have a good enough understanding of how the phenology is controlled and take the relevant environmental factors in to account. In terms of the effect of phenological change, it should be discussed with regards to change in life cycle timing among interacting species. For example, the phenology of the host plants is important for A. cardamines fitness, and it is also the main determining factor for oviposition. In summary, this thesis shows that the broad geographical pattern of phenology of the butterflies is formed by counteracting environmental variables, but that there also are significant population differences that enable fine-tuning of phenology according to the seasonal progression and variation at the local scale.

Variation in the chloroplast DNA of Swiss stone pine (Pinus cembra L.) reflects contrasting post-glacial history of populations from the Carpathians and the Alps

To characterize the genetic structure and diversity of Pinus cembra L. populations native to two disjunct geographical areas, the Alps and the Carpathians, and to evaluate the rate of genetic differentiation among populations.

Macro-geographical differences influenced by family-based expression on cultured pearl grade, shape and colour in the black-lip "pearl oyster" Pinctada margaritifera: a preliminary bi-local case study in French Polynesia

In French Polynesia, the aquaculture of P. margaritifera is carried out in numerous grow-out sites, located over three archipelagos (Gambier, Society and Tuamotu). To evaluate the impact of macro-geographical effects of these growing sites on pearl quality traits, five hatcheries produced families were used as homogeneous donor oysters in an experimental graft. The molluscs were then reared in two commercial locations: Tahaa island (Society) and Rangiroa atoll (Tuamotu). At harvest, eight pearl quality traits were recorded and compared: surface defects, lustre, grade, circles, shape categories, darkness level, body and secondary colour and visual colour categories. Overall inter-site comparison revealed that: 1) all traits were affected by grow-out location except for lustre and round shape, and 2) a higher mean rate of valuable pearls was produced in Rangiroa. Indeed, for pearl grade, Rangiroa showed twice as many A-B and less reject samples than Tahaa. This was related to the number of surface defects (grade component): in Rangiroa, twice as many pearls had no defects and less pearls had up to 10 defects. Concerning pearl shape, more circled and baroque pearls were found in Tahaa (+10%). For colour variation, 10% more pearls have an attractive green overtone in Rangiroa than in Tahaa, where more grey bodycolor were harvested. Lustre does not seem to be affected by these two culture site (except at a family scale). This is the first time P. margaritifera donor family have been shown to vary in the quality of pearls they produce depending on their grow-out location.

Seasonal variation of haemoglobin A1c in a Portuguese adult population

Haemoglobin A1c (Hb A1c) is routinely used for monitoring glycemic control in patients with diabetes. Hb A1c seasonal fluctuations can be directly related to different biological, geographical and cultural influences. Our purpose was to evaluate seasonal variation of Hb A1c in a hospital-based adult population over a period of 5 years.

Variation, correlation and heritability of interest characters for selection of African eggplant

The eggplant ( Solanum aethiopicum ) is the species of the Solanum genus, whose geographical distribution is broadest. It is grown throughout tropical Africa, and includes three groups of cultivars commonly called African or indigenous eggplant. Kumba group or “bitter eggplant” is an important Solanaceous vegetable crop in Burkina Faso. The objective of this study was to determine genetic variability, strength of association and level of heritability among agronomic interest traits. Phenotypic and genotypic variations and heritability of 14 traits were estimated in 61 accessions at Institut de Développement Rural (IDR), Gampela in Burkina Faso. High phenotypic and genotypic coefficients of variation were observed for fruit diameter, number of seeds per fruit, fruit weight, leaf blade length and width, and height at flowering. In addition, genetic and phenotypic variances were high for the number of seed, fruit weight, plant height at flowering and days to 50% flowering. High heritability estimates were recorded for all traits. Fruit weight showed a positive association with fruit diameter and thickness. The fifty percent flowering cycle registered positive correlations with plant height and fruit diameter. Fruit number showed a negative association with fruit weight and diameter, and 50% flowering cyle.

Genetic diversity across geographical scales in marine coastal ecosystems: Holothuria arguinensis a model species

Coastal lagoons are considered one of the most productive areas of our planet harboring a large variety of habitats. Their transitional character, between terrestrial and marine environments, creates a very particular ecosystem with important variations of its environmental conditions. The organisms that are able to survive on these ecosystems frequently experience strong selective pressures and constrictions to gene flowwith marine populations, which could contribute to genetic divergence among populations inhabiting coastal lagoon and marine environments. Therefore, the main aims of this study are to asses the genetic diversity and population structure of Holothuria arguinensis across geographical ranges, to test the hypothesis of coastal lagoons as hotspots of genetic diversity in the Ria Formosa lagoon, and to determine the role of exporting standing genetic variation from the lagoon to open sea and their implications to recent geographical expansion events. To reach these objectives, we investigate the genetic structure of H. arguinensis using two mitochondrial DNA markers (COI and 16S) at different spatial scales: i) small, inside Ria Formosa coastal lagoon, South Portugal; 2) large, including most of the geographical distribution of this species (South and Western Portuguese coast and Canary islands); these results will allow us to compare the genetic diversity of lagoonal and marine populations of H. arguinensis. On this framework, its recent geographical expansion events, recorded by Rodrigues (2012) and González-Wangüemert and Borrero-Pérez (2012), will be analyzed considering the potential contribution from lagoonal genetic pool. Non-significant genetic structure and high haplotypic diversity were found inside the Ria Formosa coastal lagoon. Both genes were unable to detect significant genetic differentiation among lagoonal and marine localities, suggesting a high rate of gene flow. The results supported our hypotheses that coastal lagoons are not only acting as hotspots of genetic diversity, but also contributing for the genetic variability of the species, working as a source of new haplotypes and enhancing adaptation to the high variable conditions. Different genetic patterns of colonization were found on H. arguinensis, but they must be studied more deeply.

GENETIC VARIATION, LOCAL ADAPTATION AND POPULATION STRUCTURE IN NORTH AMERICAN RED OAK SPECIES, QUERCUS RUBRA L. AND Q. ELLIPSOIDALIS E. J. HILL

Forest trees, like oaks, rely on high levels of genetic variation to adapt to varying environmental conditions. Thus, genetic variation and its distribution are important for the long-term survival and adaptability of oak populations. Climate change is projected to lead to increased drought and fire events as well as a northward migration of tree species, including oaks. Additionally, decline in oak regeneration has become increasingly concerning since it may lead to decreased gene flow and increased inbreeding levels. This will in turn lead to lowered levels of genetic diversity, negatively affecting the growth and survival of populations. At the same time, populations at the species’ distribution edge, like those in this study, could possess important stores of genetic diversity and adaptive potential, while also being vulnerable to climatic or anthropogenic changes. A survey of the level and distribution of genetic variation and identification of potentially adaptive genes is needed since adaptive genetic variation is essential for their long-term survival. Oaks possess a remarkable characteristic in that they maintain their species identity and specific environmental adaptations despite their propensity to hybridize. Thus, in the face of interspecific gene flow, some areas of the genome remain differentiated due to selection. This characteristic allows the study of local environmental adaptation through genetic variation analyses. Furthermore, using genic markers with known putative functions makes it possible to link those differentiated markers to potential adaptive traits (e.g., flowering time, drought stress tolerance). Demographic processes like gene flow and genetic drift also play an important role in how genes (including adaptive genes) are maintained or spread. These processes are influenced by disturbances, both natural and anthropogenic. An examination of how genetic variation is geographically distributed can display how these genetic processes and geographical disturbances influence genetic variation patterns. For example, the spatial clustering of closely related trees could promote inbreeding with associated negative effects (inbreeding depression), if gene flow is limited. In turn this can have negative consequences for a species’ ability to adapt to changing environmental conditions. In contrast, interspecific hybridization may also allow the transfer of genes between species that increase their adaptive potential in a changing environment. I have studied the ecologically divergent, interfertile red oaks, Quercus rubra and Q. ellipsoidalis, to identify genes with potential roles in adaptation to abiotic stress through traits such as drought tolerance and flowering time, and to assess the level and distribution of genetic variation. I found evidence for moderate gene flow between the two species and low interspecific genetic differences at most genetic markers (Lind and Gailing 2013). However, the screening of genic markers with potential roles in phenology and drought tolerance led to the identification of a CONSTANS-like (COL) gene, a candidate gene for flowering time and growth. This marker, located in the coding region of the gene, was highly differentiated between the two species in multiple geographical areas, despite interspecific gene flow, and may play a role in reproductive isolation and adaptive divergence between the two species (Lind-Riehl et al. 2014). Since climate change could result in a northward migration of trees species like oaks, this gene could be important in maintaining species identity despite increased contact zones between species (e.g., increased gene flow). Finally I examined differences in spatial genetic structure (SGS) and genetic variation between species and populations subjected to different management strategies and natural disturbances. Diverse management activities combined with various natural disturbances as well as species specific life history traits influenced SGS patterns and inbreeding levels (Lind-Riehl and Gailing submitted).

Geographical gradients in Argentinean terrestrial mammal species richness and their environmental correlates.

We analysed the main geographical trends of terrestrial mammal species richness (SR) in Argentina, assessing how broad-scale environmental variation (defined by climatic and topographic variables) and the spatial form of the country (defined by spatial filters based on spatial eigenvector mapping (SEVM)) influence the kinds and the numbers of mammal species along these geographical trends. We also evaluated if there are pure geographical trends not accounted for by the environmental or spatial factors. The environmental variables and spatial filters that simultaneously correlated with the geographical variables and SR were considered potential causes of the geographic trends. We performed partial correlations between SR and the geographical variables, maintaining the selected explanatory variables statistically constant, to determine if SR was fully explained by them or if a significant residual geographic pattern remained. All groups and subgroups presented a latitudinal gradient not attributable to the spatial form of the country. Most of these trends were not explained by climate.We used a variation partitioning procedure to quantify the pure geographic trend (PGT) that remained unaccounted for. The PGT was larger for latitudinal than for longitudinal gradients. This suggests that historical or purely geographical causes may also be relevant drivers of these geographical gradients in mammal diversity.