Dissertations / Theses on the topic 'Clinal variation'

Two eucalypt clines were examined using morphological, ecophysiological and molecular analyses. The species complexes examined were an ironbark complex (Eucalyptus melanophloia x E. whitei) and a box complex (E. brownii x E. populnea). Both of these complexes demonstrate continuous morphological variation across their clines. The origin of these morphological clines has previously been interpreted as the product of secondary contact between allopatric species. In this study, an analysis of morphological variation across the clines did not identify an increase in trait variance in the intermediate populations, which suggests that previous theories concerning the origin of these clines may not be valid. Genetic structuring in nuclear and chloroplast DNA was examined across the clines to investigate whether the morphological clines were the product of secondary contact between two independent evolutionary lineages, or whether the clines represent a single evolutionary lineage that has undergone primary differentiation. The microsatellite analyses indicated that there was little genetic structuring across either cline, and that there were only low levels of population differentiation. The lack of hierarchical structuring in the distribution of nuclear genetic variation suggests that these clines are unlikely to be the product of recent gene flow between two formerly allopatric species/populations. A nested clade analysis of the JLA+ region of the cpDNA provides additional evidence to reject the null hypothesis that the morphospecies classifications represent distinct evolutionary lineages. Instead the analyses indicate that each cline represents a single cohesion species and a single evolutionary lineage. The phylogeographic distribution of cpDNA haplotypes is likely to have resulted from restricted seed mediated gene flow with isolation by distance. A more cogent explanation for the clines, based on the genetic data, is that they have arisen through the process of continuous morphological diversification that has been promoted by a directional selection gradient. Drought experiments were conducted in the glasshouse to investigate whether differences in physiological performance under water stress helps to explain the maintenance of the ironbark cline. Under increasing water stress, the morphotypes showed differences in their ability to maintain water status and photosynthetic rates, yet there was no obvious pattern to these differences across the cline. Physiological differences are therefore inadequate to explain the maintenance of the ironbark cline and highlight the compensatory role that morphological variation may play in alleviating water stress. The value of adopting the cohesion species concept and a hypothesis-testing framework to assess species status is demonstrated in this study. This framework provided a statistical approach to distinguish independent evolutionary lineages from interspecific populations and provides evidence to refute the current species status of the species complexes studied. Eucalypt classification is predominantly based on morphology, which results in taxonomic classification that may not reflect genealogical relationships. This is due to the disparity between morphological and phylogenetic relationships. I therefore suggest that current presumptions regarding the prevalence and importance of hybridisation within the genus may reflect taxonomic classification. An accurate assessment of the prevalence and importance of hybridisation requires species classification to be based on genealogical relationships.

Two eucalypt clines were examined using morphological, ecophysiological and molecular analyses. The species complexes examined were an ironbark complex (Eucalyptus melanophloia x E. whitei) and a box complex (E. brownii x E. populnea). Both of these complexes demonstrate continuous morphological variation across their clines. The origin of these morphological clines has previously been interpreted as the product of secondary contact between allopatric species. In this study, an analysis of morphological variation across the clines did not identify an increase in trait variance in the intermediate populations, which suggests that previous theories concerning the origin of these clines may not be valid. Genetic structuring in nuclear and chloroplast DNA was examined across the clines to investigate whether the morphological clines were the product of secondary contact between two independent evolutionary lineages, or whether the clines represent a single evolutionary lineage that has undergone primary differentiation. The microsatellite analyses indicated that there was little genetic structuring across either cline, and that there were only low levels of population differentiation. The lack of hierarchical structuring in the distribution of nuclear genetic variation suggests that these clines are unlikely to be the product of recent gene flow between two formerly allopatric species/populations. A nested clade analysis of the JLA+ region of the cpDNA provides additional evidence to reject the null hypothesis that the morphospecies classifications represent distinct evolutionary lineages. Instead the analyses indicate that each cline represents a single cohesion species and a single evolutionary lineage. The phylogeographic distribution of cpDNA haplotypes is likely to have resulted from restricted seed mediated gene flow with isolation by distance. A more cogent explanation for the clines, based on the genetic data, is that they have arisen through the process of continuous morphological diversification that has been promoted by a directional selection gradient. Drought experiments were conducted in the glasshouse to investigate whether differences in physiological performance under water stress helps to explain the maintenance of the ironbark cline. Under increasing water stress, the morphotypes showed differences in their ability to maintain water status and photosynthetic rates, yet there was no obvious pattern to these differences across the cline. Physiological differences are therefore inadequate to explain the maintenance of the ironbark cline and highlight the compensatory role that morphological variation may play in alleviating water stress. The value of adopting the cohesion species concept and a hypothesis-testing framework to assess species status is demonstrated in this study. This framework provided a statistical approach to distinguish independent evolutionary lineages from interspecific populations and provides evidence to refute the current species status of the species complexes studied. Eucalypt classification is predominantly based on morphology, which results in taxonomic classification that may not reflect genealogical relationships. This is due to the disparity between morphological and phylogenetic relationships. I therefore suggest that current presumptions regarding the prevalence and importance of hybridisation within the genus may reflect taxonomic classification. An accurate assessment of the prevalence and importance of hybridisation requires species classification to be based on genealogical relationships.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Australian School of Environmental Studies
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We reviewed the taxonomy of the Trogon rufus species-complex under the premises of the Biological Species Concept. Putative taxonomic units, breaks and transition zones, were visualised by heatmaps and isophenes (phenotypic contour lines) of the colour, barring, morphometric and song characters and tested by discriminant function analyses. Colourmetric data were obtained via spectrometry and barring patterns analysed via high quality digital photographs. We found four distinct biological species. Trogon chrysochloros Pelzeln 1856 from the Atlantic Forest with its denser and blacker undertail and wing covert barring, larger size and faster, generally higher song with more notes. Its upperparts vary from bluer to more coppery-green with increasing altitude. The bill is also relatively smaller and more serrated, linked to a diet that consists almost exclusively of large arthropods, making it the most insectivorous new world Trogon species yet known, which may account for its relative rarity compared to other Trogonids with which it is sympatric. Trogon tenellus Cabanis 1862, from Central America, and Trogon cupreicauda Chapman 1914 from the Chocó-Magdalena provide a classic case of typical biological species, coming into contact in the extreme NW Chocó Province, Colombia, but without intermediate forms. T. tenellus is identified by its blue to blue-green uppertail, blue or grey eye-rings, grey tarsi and song with 2-4 notes, longer note duration and greater change in peak and high frequencies between the intro note and loudsong. This contrasts with the shiny olive-green to coppery green uppertails, yellow eye-ring, usually olive tarsi, brown wash on the undertail of females and song with 6-8 notes of shorter duration and little change in frequency between the intro note and loudsong of T. cupreicauda. T. cupreicauda varies clinally from generally bluer- to more coppery-green plumage and from thicker to thinner black bars in a gradient from the Pacific coast on the border with Ecuador to the Magdalena Valley. The greater difference in colour and barring relative to T. tenellus in the region they come into contact provides possible evidence of character displacement as a result of the competitive exclusion between these two species, maintaining their parapatric distributions. The Amazonian population belongs to a single species, Trogon rufus Gmelin 1788, but with two highly distinct forms that we designate as Trogon rufus rufus in the Guiana Shield and Trogon rufus sulphureus in S & W Amazonia, for which Todd\'s amazonicus is synonymised. They are morphologically and, to a lesser extent, vocally distinct across the lower Rio Negro and matrix of highland and open habitats of the Rio Branco basin but show limited character exchange between the 52-58th parallels west on the southern bank of the Amazon, centred around the Rio Arapiuns on the left bank of mouth of the Tapajos. We postulate that this is the result of secondary contact as a consequence of shifts in the course of the main channel of the Amazon River at times of lower sea levels during the Plio-Pleistocene. T .r. sulphureus is identified by a typically coppery uppertail with subterminal tailband of greener hue, yellow eye-ring, low barring density and broad black bars of the undertail and wing-coverts barring with and lack of a pectoral band. They are also sometimes distinguishable in song by a higher frequency introduction note and/or more pronounced descending modulation across the loudsong. This varies clinally on a west-east gradient, from strong-coppery to shiny olive-green uppertails with more to less distinct subterminal tailbands, diminishing black bar widths with corresponding increasing density and decreasing intro note low frequency. T. r. rufus have green uppertails, blue eye-rings, presence or absence of a white pectoral band and denser undertail and wing panel barring with thinner black bars. These characters were shown to change as a function of geographic distance between specimens of sulphureus and rufus, connected via the \'Arapiuns contact zone\', suggesting isolation by distance. This is reminiscent of a ring species pattern and two specimens with a possible mixture of characters were indeed found from the upper Rio Negro and in Pantepui, where T. r. rufus and T. r. sulphureus would be expected to come into contact, effectively \'closing the ring\'. Whether Trogon rufus constitutes a valid ring species requires further testing, preferably including molecular characters, but this clearly illustrates that the distinction between clinal variation and ring-species is a matter of degree, not kind, with the formation of the ring-species necessarily passing through a clinal stage with no overlap between terminal taxa. We therefore propose the concept of a loop species, where the terminal forms do not overlap but are connected via a series of intergrading populations. It seems likely that such patterns are more widespread in Amazonia than presently known due to the propensity for clinal variation and parapatric speciation lended by its massive geographical extent and abundance of biogeographical semi-permeable barriers. With regards to the population from the Pernambuco Center of Endemism, the few records suggest that it is a valid taxonomic unit. It has the unique combination of a song very similar to T. r. sulphureus due to the high introduction note frequency and pronounced descent in frequencies across the loudsong, with a corresponding widening range but moderately large size, serrated bill and blue eye-ring but this certainly requires confirmation. This requires urgent attention, as the remnant population is very small and localised, recorded only from the Murici municipality, Alagoas.
Nós revisamos a taxonomia do complexo Trogon rufus sob o conceito Biológico de Espécies. Unidades taxonômicas possíveis, quebras e zonas de transição taxonômicas foram definidas usando mapas de calor e isofenas (linhas de contorno de fenótípo) baseados em caráteres de cor, barramento e morfometria. Esses possíveis táxons foram testados pelas análises de discriminantes. Dados de coloração foram obtidos por meio de espectrometria, e os padrões de barramento por meio de fotos de alta qualidade. Nós encontramos quatro espécies biológicas distintas Trogon chrysochloros Pelzeln 1856, da Mata Atlântica, diagnosticável pelo barramento mais escuro e denso na face inferior da cauda e coberteiras da asa, maior tamanho corpóreo, canto mais rápido, com mais notas e de frequência mais alta. Suas partes superiores (cabeça, dorso e cauda) variam de azul a verde acobreado com o aumento da altitude. O bico também é relativamente menor e mais serrilhado, o que está ligado a uma dieta que consiste quase exclusivamente de grandes artrópodes, fazendo desta espécie o Trogon mais insetívoro do mundo, o que deve ser a razão de sua relativa raridade quando comparado a outros Trogonidae com os quais vive em simpatia. Trogon tenellus Cabanis 1862, da América Central, e Trogon cupreicauda Chapman 1914, do Chocó-Magdalena, formam um caso clássico de espécies biológicas, entrando em contato no extremo noroeste da província de Chocó, na Colômbia, sem a presença de formas intermediárias. T. tenellus é identificável pela face superior da cauda azul ou azul esverdeado, anel perioftálmico azul ou cinza, tarso cinza, e voz com de 2 a 4 notas, maior duração das notas e maior mudança entre frequência de pico e frequência alta entre a nota introdutória e nota principal. Essas características contrastam com a cor verde-oliva brilhante da face superior da cauda, anel perioftámico amarelo, tarso geralmente oliva, presença de marrom claro na face inferior da cauda das fêmeas e canto com entre 6 e 8 notas, de menor duração, pouca mudança na frequência entre a primeira nota e o canto principal de T. cupreicauda. Este varia clinalmente de azul para uma plumagem mais verde acobreada e de barramento preto mais espesso para mais fino em uma gradiente da costa do Pacífico, do noroeste do Equador até o Vale do Magdalena. A maior distinção de estados de caráter relativa a T. tenellus na região onde os dois grupos se encontram provê uma possível evidência de deslocamento de caracteres como resultado de exclusão competitiva entre estas duas espécies, mantendo suas distribuições parapátricas. A população amazônica pertence a única espécie biológica Trogon rufus Gmelin 1788, mas com duas formas altamente distintas que designamos como Trogon rufus rufus do Escudo Guianense, e Trogon rufus sulphureus no sul e oeste da Amazônia, com a qual amazonicus de Todd é sinonimizada. Estas são morfologicamente, e em menor escala, vocalmente distintas nas duas margens do baixo Rio Negro e áreas abertas e/ou montanhosas da bacia do Rio Branco, mas apresentam troca de caracteres limitada nas longitudes entre 52 e 58 Oeste na margem sul do Rio Amazonas, centrado nos arredores do Rio Arapiuns, na margem esquerda da foz do Tapajós. Nós postulamos que isto é um resultado de contato secundário, como consequência de mudanças no curso principal do Rio Amazonas em tempos de níveis mais baixos do mar durante o Plio-Pleistoceno. T. r. sulphureus é identificado pela coloração tipicamente acobreada da face superior da cauda com uma banda sub-terminal de tonalidade esverdeada, anel perioftálmico amarelo, barras negras espessas e de baixa densidade na face inferior da cauda e nas coberteiras das asas e pela ausência de uma faixa peitoral. Em certos casos eles também podem ser distinguíveis pela voz com uma nota introdutória de maior frequência e/ou uma modulação descendente mais pronunciada no canto principal. Este grupo varia clinalmente em gradiente de oeste para leste, de uma coloração cobre forte até verde oliva na face superior da cauda com faixa sub-terminal mais ou menos distinta, anel perioftálmico azul, presença ou ausência de uma faixa peitoral branca e barramento na face inferior da cauda e coberteiras de menor espessura e, consequentemente, maior densidade. Nossos dados apontam que estes caracteres mudam linearmente entre sulphureus e rufus de acordo com a distância ao longo de uma gradiente clinal em forma de laço do Oeste Amazônico até o Escudo das Guianas, conectado pela zona de contato de Arapiuns, sugerindo isolamento por distância. Isto sugere um remanescente de um padrão de espécie em anel. Além disso, dois espécimes com possível mistura de caracteres foram de fato encontrados no alto Rio Negro e Pantepui, onde se espera que T. r. rufus e T. r. sulphureus entrem em contato, fechando o anel efetivamente. Ainda é necessário testar se Trogon rufus constitui uma espécie em anel válida, preferencialmente usando dados moleculares, mas este caso ilustra claramente que a distinção entre variação clinal e espécie em anel é uma questão de grau e não de tipo, com a formação de espécie em anel necessariamente passando por um estágio clinal sem sobreposição entre os grupos terminais. Nós assim sugerimos o conceito de espécie em laço, onde as formas terminais não se sobrepõem, mas são ligadas através de uma série de populações onde há fluxo gênico. Parece provável que estes padrões são mais amplamente distribuídos na Amazônia do que é sabido atualmente devido a uma propensão à variação clinal e especiação parapátrica causada por sua grande extensão geográfica e abundância de barreiras geográficas semipermeáveis. Em relação a população do Centro de Endemismo Pernambuco, os poucos registros sugerem que esta é uma unidade taxonômica válida. Este grupo apresenta uma combinação única de canto muito similar ao de T. r. sulphureus, devido à alta frequência da nota introdutória e pronunciada modulação descendente ao longo do canto principal, com uma maior amplitude da frequência, combinada a maior tamanho, bico serrilhado, e anel perioftálmico azul, mas isso requer confirmação. Este caso demanda atenção urgente, já que a população remanescente é muito pequena e de distribuição restrita ao município de Murici, em Alagoas.

Abstract Both the length of the season that is favourable for insect growth and reproduction and the number of generations emerging per season (voltinism) increase with decreasing latitude. Thus, time constraints on reproduction and juvenile development decrease with decreasing latitude, except where voltinism changes and time constraints suddenly increase as the season must be shared with one more generation. I studied the evolution of insect life histories in relation to time constraints from two perspectives: polymorphism and clinal variation. Life history polymorphism in seasonal environments was studied with the butterfly Pieris napi that has discrete life history strategies, and polymorphic natural populations. Experimental studies showed that asymmetric intraspecific larval competition and divergent timing of reproduction between the strategies may promote the maintenance of polymorphism. A simulation model showed that the divergent timing of reproduction between the strategies is sufficient to maintain polymorphism even in the absence of intraspecific competition. Clinal variation was studied empirically with four geometrid moths (Cabera exanthemata, Cabera pusaria, Chiasmia clathrata and Lomaspilis marginata) and generally in theory. Due to latitudinal saw-tooth variation in time constraints, traditional theory predicts a saw-tooth cline in body size and development time. A common garden experiment with the four geometrid moths did not support the traditional theory even when a saw-tooth cline in body size was found, suggesting that the theory is based on unrealistic assumptions. A theoretical analysis showed that reproductive effort should be high in populations under intense time constraints and low in populations experiencing no time constraints, resulting in a saw-tooth cline. In the four geometrid moths, support for these predictions was found, although the observed clinal variation deviated from the predicted pattern. The results imply that clinal variation is expected in almost any continuous life history trait, whereas polymorphism of different strategies may emerge when life histories fall into discrete categories. When inferring the evolution of a single trait, complex interdependencies among several traits should be considered, as well as the possibility that the time constraints are not similar for each generation in multivoltine populations
Tiivistelmä Hyönteisten kasvu ja kehitys ovat pääsääntöisesti mahdollisia vain kesän aikana. Etelään päin mentäessä kesä pitenee, ja saman kesän aikana kehittyvien hyönteissukupolvien määrä kasvaa. Kesän pituus aiheuttaa lisääntymiseen ja toukkien kasvuun kohdistuvan aikarajoitteen, joka heikkenee etelään päin siirryttäessä. Aikarajoite kuitenkin tiukkenee siellä, missä yksi uusi sukupolvi ehtii juuri kehittymään saman kesän aikana, sillä kesä on nyt jaettava useamman sukupolven kesken. Väitöstyössä tarkastelin hyönteisten elinkierto-ominaisuuksien evoluutiota suhteessa aikarajoitteisiin sekä diskreetin että jatkuvan muuntelun näkökulmista. Diskreettiä muuntelua tutkin lanttuperhosella (Pieris napi), jolla esiintyy diskreettejä elinkiertostrategioita. Kokeellisesti osoitin, että toukkien välinen kilpailu on epäsymmetristä, mikä yhdessä eri elinkiertostrategioiden erilaisen lisääntymisen ajoittumisen kanssa voi ylläpitää diskreettiä muuntelua. Simulaatiomalli osoitti, että erilaiset elinkiertostrategiat voivat säilyä populaatiossa pelkästään niiden erilaisen lisääntymisen ajoittumisen ansiosta. Elinkierto-ominaisuuksien jatkuvaa muuntelua tutkin neljän mittariperhosen (Cabera exanthemata, Cabera pusaria, Chiasmia clathrata ja Lomaspilis marginata) avulla ja teoreettisesti yleisellä tasolla. Aikaisempi teoria ennustaa ruumiinkoon ja kehitysajan muuntelevan sahalaitakuvion mukaisesti siirryttäessä pohjoisesta etelään, koska aikarajoitteet muuntelevat samalla tavalla. Tämä teoria perustunee epärealistisiin oletuksiin, koska kokeelliset tulokset eivät tukeneet teoriaa silloinkaan, kun mittariperhosten ruumiinkoko muunteli ennustetulla tavalla. Teoreettinen tutkimus osoitti, että myös lisääntymispanostuksen tulisi muunnella sahalaitakuvion mukaisesti suhteessa kesän pituuteen siten, että se on korkeimmillaan siellä, missä aikarajoitteet ovat tiukat. Mittariperhosten tutkiminen antoi jossain määrin tukea tälle ennusteelle. Tulosten perusteella jatkuvaa maantieteellistä muuntelua ennustetaan elinkierto-ominaisuuksille, jotka muuntelevat jatkuvalla asteikolla. Erilaiset elinkiertostrategiat voivat sen sijaan säilyä populaatiossa, jos elinkierto-ominaisuuksien muuntelu on diskreettiä. Eri ominaisuuksien monimutkaiset vuorovaikutukset sekä eri sukupolvien mahdollisesti kokemat erilaiset aikarajoitteet olisi syytä tuntea, kun tarkastelun kohteena on yksittäisen ominaisuuden evoluutio

Common garden experiments in widely distributed tree species have demonstrated that phenotypic traits timing of bud set exhibit clinal variation across provenance climatic and geographic gradients, emphasizing the importance of these traits in local adaptation. With rapid advances in molecular techniques, spatial patterns of genomic variation underlying these traits can also be studied. Here I assess whether 17 putatively adaptive single nucleotide polymorphisms (SNPs) previously shown to be statistically associated with cold adaptation phenotypes vary clinally along a temperature gradient in natural, mature populations of Sitka spruce (Picea sitchensis). I also test the hypothesis that clinal strength is stronger in mature spruce populations than in seedling populations due to selection. Regressions were run for each of the 17 SNPs with logit-transformed major allele frequency as the dependent variable and provenance mean annual temperature (MAT) as the independent variable. Next, differences in strength of clines between mature and seedling populations were estimated for each SNP separately and for the 17 SNPs as a group. Finally, I ran two alternate analyses – a full analysis that included all seedling populations and a truncated analysis that limited the range of MAT observed in seedling populations to match that of mature populations. My results vary between the full and truncated analyses. In seedlings, the full analysis revealed clines in 11 SNPs (65%) compared to six SNPs (35%) in the truncated analysis. Mature populations had significant clines for five SNPs (29%). For the full analysis, the group test supported the one-sided hypothesis that mature populations have significantly steeper clines than seedlings across SNPs (P=0.027). Parallel clines in seedling and mature populations were observed for a subset of the SNPs, which strengthens their importance for local adaptation. However, low power limited my ability to make conclusive statements about differences in clinal strength between mature and seedling populations. While most SNPs were present in most populations, I also observed that the northern, disjunct population of Kodiak Island, AK was fixed for the highest proportion of SNPs (59%). This suggests that this recently founded population may lack adaptive diversity to respond to rapid climate change in the future.

Evolutionary process can be inferred at three different levels: the species level, the population level and the molecular level. In this thesis, I applied approaches at these three levels and aimed to get a comprehensive picture of conifer evolution, from speciation and demography to geographic variation and local adaptation, and then to the molecular evolution of proteins and small regulatory RNAs. Spruce species have been observed to possess a large number of trans-species shared polymorphisms. Using an “Isolation with migration” model, we found that the large effective population size of spruce retained these shared polymorphisms, inheriting them from the common ancestor. Post-divergence gene flow only existed between Picea abies and P. glauca, and between P. wilsonii and P. schrenkiana. The combination of Tajima’s D and Fay & Wu’s H at most of loci suggested an ancient and severe bottleneck for most species except P. breweriana. Furthermore, I investigated the effect of local selection in two parallel clines, which is one of the major forces that can cause divergence or even speciation. The timing of bud set and growth cessation was found correlated with latitude in populations of P. abies and P. obovata. Using allele frequency spectrum analyses we identified three genes under local selection in both species including two circadian-clock genes GI and PRR7, and one photoperiodic gene FTL2. This indicated that parallel evolution could occur through groups of genes within related pathways. Clinal variation at expression level provided stronger evidence of selection in FTL2, which has previously been associated with bud set in P. abies. Finally we focused on the molecular evolution of mRNA and small regulatory RNAs in P. abies. With the help of Next-Generation sequencing, we have achieved in spruce the first de novel assembly of the needle transcriptome and a preliminary characterization of sRNA populations. Along with features common in plants, spruce also exhibited novelties in many aspects including lower substitution rate and protein evolutionary rate, dominance of 21-nt sRNA, and a large proportion of TIR-NBS-LRR genes as sRNA sources and targets.

The cosmopolitan Pteridium aquilinum (L.) Kuhn is widespread throughout eastern North American, where it is represented primarily by Tryon's (1941) var. latiusculum (Desv.) Underw. and var. pseudocaudatum (Clute) Heller. The taxonomy of Pteridium is controversial. Fourteen isozyme loci and 12 morphological characters were used to assess the taxonomic relationship of these two varieties. Isozyme data indicated a high mean genetic identity (I = 0.976) between eleven bracken populations. Strong patterns of geographic variation for isozyme allele frequencies were also observed. The isozyme results did not separate the two taxa. Numerical analysis of the morphology distinguished the two taxa when the qualitative characters were used alone or in conjunction with some of the quantitative traits. All qualitative characters differed significantly between the two taxa. No perceptible geographic pattern of variation was observed. Morphological distinctiveness was maintained even in those localities where both taxa were present, with few or no intermediates being found. Isozyme evidence suggestive of gene flow between the two varieties was found at Greensboro, NC, where the two morphotypes were easily recognizable. The isozyme evidence strongly indicates conspecificity, while the morphological evidence supports their status at the varietal level.
Master of Science

The postglacial recolonization of northern Europe supposedly originated from Western Europe and the Russian Plain, however, recent molecular and macrofossil-based investigations suggest that the history may be more complex than previously thought. This study aims to investigate the genetic diversity and population structure of Scots pine from Scandinavia to Russia to re-evaluate its recolonization history, and to examine whether the pattern of spatial genetic diversity has any adaptive significance. Populations ranging from Norway to Russia were sampled and genotyped using genotyping-by-sequencing. The seedlings were freeze tested to provide an average degree of hardiness for every population. Eight hundred and thirty-two seedlings were analyzed, and 6,034 SNPs were recovered in these individuals after stringent filtering. Population structure was investigated using fastStructure and differentiation between populations was estimated with pairwise FST and analysis of molecular variance (AMOVA) to assess the genetic variability. Genetic diversity was measured as observed heterozygosity, H0, in populations, clusters and overall. Two genetic clusters were detected in the samples, one in Norway and Sweden and one in Russia. These clusters are weakly differentiated (FST = 0.01202) with only 0.66 % variation between them. Highest variation was found within populations (98.8 %) and the overall genetic diversity for all populations was high (Ho = 0.2573). The weak differentiation and high diversity are indicative of extensive gene flow between populations in this species. The composition of the clusters across the sampled area suggests a westward recolonization from the Russian Plain into Scandinavia, and a possible local origin of another polymorphism in Norway and Sweden. No clear relationship between cold hardiness and genetic variation was detected. The clinal variation in cold hardiness reflects local adaptation, and the difference between genetic and phenotypic variation is likely due to epigenetic regulation or polygenic inheritance. More extensive genome scan is needed to understand the genetic basis of local adaptation.

Within native and non-native plant species, the production of viable seeds can both promote range expansion and facilitate rapid climatic adaptations through the selection of adapted phenotypes. The success of sexual reproduction in many plant species has been linked to a critical level of accumulated growing degree-days (GDDs) throughout the season. However GDDs are often limited in northern climates. With climate change forecasted to cause temperature increases in many northern areas, GDDs are likely to increase and there exists the potential for some species currently limited by a lack of GDDs to undergo increases in sexual reproduction and ultimately range expansion. Field studies and in vitro germination trials were used to test the relationship between seasonal GDDs and development, height and sexual reproduction in an established invasive non-native species, Phragmites australis (Cav.) Trin. Ex Steud. (haplotype M) and its native conspecific, P. australis subsp. americanus. During the 2012 season, 29 populations were monitored within five isotherms along a1000-km long latitudinal gradient from New Jersey (USA) to Alma (Quebec). As seasonal GDDs decreased, non-native P. australis were on average shorter, required fewer GDDs to develop, and produced fewer viable seeds per floret. Within isotherms, native P. australis were shorter and developed earlier than non-native P. australis, and also generally produced more seeds per floret. Overall the response of native P. australis was not related to seasonal GDDs. Over the climate gradient of the study area it appears that a lack of GDDs is currently limiting the expansion of non-native P. australis through seed dispersal at the edge of its range. As local temperatures and ultimately GDDs increase with climate change, the adaptive response non-native P. australis has to climate will likely allow the species to rapidly expand its range to take advantage of newly available climatic niches.
La reproduction sexuée et la production subséquente de graines viables peuvent faciliter la dispersion d'espèces végétales indigènes ou non indigènes/envahissantes dans de nouvelles régions ainsi que possiblement une adaptation rapide à des conditions changeantes grâce à la sélection de phénotypes appropriés. Le succès de la reproduction sexuée pour de nombreuses espèces végétales a été lié à une accumulation critique de degrés-jours de croissance (DJCs) durant la saison. Cependant les DJCs sont souvent limités dans les climats nordiques. Avec les changements climatiques et les températures qui augmenteront particulièrement vers le nord, le DJCs sont susceptibles d'augmenter et des espèces actuellement limitées par un manque de DJCs pourraient voir une augmentation de leur reproduction sexuée et éventuellement une extension de leur aire de répartition. Un suivi sur le terrain et des essais de germination ont été utilisés pour tester la relation entre les DJCs saisonniers et le développement, la hauteur et la reproduction sexuée d'une espèce envahissante non indigène, Phragmites australis (Cav.) Trin. Ex Steud. (M haplotype) et sa congénère indigène, P. australis subsp. americanus. Durant la saison 2012, 29 populations ont été suivies dans cinq isothermes le long d'un gradient latitudinal de 1000 km du New Jersey (États-Unis) à Alma (Québec). Le P. australis non indigène était en moyenne plus court, requerrait moins de DJCs pour produire des inflorescences, et produisait moins de graines viables avec une diminution des DJCs saisonniers. Pour un même isotherme, le P. australis indigène était plus court et se développait plus tôt que le P. australis non indigène, et aussi généralement produisait plus de graines. Globalement, la réponse du P. australis indigène n'était pas liée au DJCs saisonniers. Le long du gradient climatique de la zone étudiée, il semble que le manque de DJCs limite actuellement l'expansion par dispersion de graines du P. australis non indigène, tout en ayant peu ou pas d'effet sur le P. australis indigène. Une production de graines accrue par les changements climatiques pourrait permettre au P. australis envahissant d'exploiter des niches climatiques nouvellement disponibles.

The Rufous-naped lark Mirafra africana complex consists of 22 subspecies spread across the African continent. Several of the subspecies have recently been suggested to potentially be treated as separate species. In this study a comparative analysis was done on the song from seven of the subspecies: M. a. africana, M. a. athi, M. a. grisescens, M. a. kabalii, M. a. nyikae, M. a. transvaalensis and M. a. tropicalis. The results showed that M. a. athi, M. a. kabalii and M. a. nyikae are all very divergent from each other as well as from the other four subspecies. In contrast, M. a. tropicalis, M. a. grisescens, M. a. africana and M. a. transvaalensis are not clearly separable from each other. Based on the results, I suggest that M. a. athi, M. a. kabalii and M. a. nyikae can be classified as separate species, with M. a. africana, M. a. tropicalis, M. a grisescens and M. a. transvaalensis forming a fourth species (M. africana sensu stricto). Finally, I conclude that this study shows that more studies need to be done on the subspecies of the Mirafra africana complex.

La reconstruction en tomosynthèse numérique du sein est considérée comme un problème inverse, pour lequel les méthodes itératives régularisées permettent de fournir une bonne qualité d'image. Bien que la tâche clinique joue un rôle crucial lors de l’examen des images par le radiologue, elle n'a pas été jusqu'à présent directement prise en compte dans le processus de reconstruction des images de tomosynthèse. Dans cette thèse, nous introduisons une nouvelle formulation variationnelle de la reconstruction des images en tomosynthèse numérique du sein qui intègre la tâche clinique du radiologue, notamment la détection des microcalcifications. Le but de cette approche est de permettre à la fois le rehaussement de la détectabilité des microcalcifications et une restauration de bonne qualité des tissus mammaires.Tout d'abord, nous proposons une nouvelle approche qui vise à rehausser la détectabilité des microcalcifications. Nous formulons une nouvelle fonction de détectabilité inspirée d’observateurs mathématiques. Nous l’intégrons, par la suite, dans une fonction objectif minimisée par un algorithme de reconstruction dédié. Nous montrons finalement l'intérêt de notre approche à l'égard des méthodes standards de reconstruction. Dans une deuxième partie, nous introduisons une nouvelle régularisation, Spatially Adaptive Total Variation (SATV), en complément de la fonction de détectabilité dans le problème de reconstruction en tomosynthèse. Nous proposons une formulation originale où l’opérateur de gradient est remplacé par un opérateur adaptatif appliqué à l'image qui incorpore efficacement la connaissance a priori relative à la localisation de petits objets. Ensuite, nous dérivons notre régularisation SATV et l'intégrons dans une nouvelle approche de reconstruction. Les résultats expérimentaux montrent que SATV est une piste prometteuse pour améliorer les méthodes de régularisation de l’état de l'art. Dans une troisième partie, nous étudions l'application de l’algorithme de Majoration-Minimisation à Mémoire de Gradient (3MG) à notre problème de reconstruction. Dans le but d’accroître sa vitesse de convergence, nous proposons deux améliorations numériques. Dès lors, les performances numériques sont évaluées en comparant la vitesse de convergence de la méthode proposée avec celles d'algorithmes d'optimisation convexe concurrents. La dernière partie de la thèse porte sur l'évaluation quantitative des contributions de l'approche de reconstruction proposée en tomosynthèse numérique du sein. Nous menons une étude de lecture d'images impliquant quatorze lecteurs dont neuf radiologues avec différents niveaux d'expertise et cinq experts en mammographie de GE Healthcare. Les résultats démontrent l'intérêt de notre approche de reconstruction par rapport à l'approche standard non-régularisée selon des critères visuels spécifiques
The reconstruction of a volumetric image from Digital Breast Tomosynthesis (DBT)measurements is an ill-posed inverse problem, for which existing iterative regularizedapproaches can provide a good solution. However, the clinical task is somehow omittedin the derivation of those techniques, although it plays a primary role in the radiologistdiagnosis. In this work, we address this issue by introducing a novel variational formulationfor DBT reconstruction. Our approach is tailored for a specific clinical task, namely the detection of microcalcifications. Our method aims at simultaneously enhancing the detectionperformance and enabling a high-quality restoration of the background breast tissues.First, we propose an original approach aiming at enhancing the detectability of microcalcifications in DBT reconstruction. Thus, we formulate a detectability function inspired from mathematical model observers. Then, we integrate it in a cost function which is minimized for 3D reconstruction of DBT volumes. Experimental results demonstrate the interest of our approach in terms of microcalcification detectability.In a second part, we introduce the Spatially Adaptive Total Variation (SATV) as a new regularization strategy applied to DBT reconstruction, in addition to the detectability function. Hence, an original formulation for the weighted gradient field is introduced, that efficiently incorporates prior knowledge on the location of small objects. Then, we derive our SATV regularization, and incorporate it in our proposed 3D reconstruction approach for DBT. We carry out several experiments, in which SATV regularizer shows a promising improvement with respect to state-of-the-art regularization methods.Third, we investigate the application of Majorize Minimize Memory Gradient (3MG) algorithm to our proposed reconstruction approach. Thus, we suggest two numerical improvements to boost the speed of the reconstruction scheme. Then, we assess the numerical performance of 3MG by comparing the convergence speed of the proposed method with state-of-the-art convex optimization algorithms.The last part of this thesis is focused on the quantitative assessment of the contribution of our proposed DBT reconstruction. Thus, we conduct a visual experiment trial involving fourteen readers including nine radiologists with different levels of expertise and five GE Healthcare experts in mammography. According to specific visual criteria, the results show the outperformance of our proposed reconstruction approach over the standard non-regularized least squares solution

In the clinical setting, the term 'unwarranted variation' refers to variations in patient outcomes that cannot be explained by the patient's illness or medical needs, or the dictates of evidence-based medicine. These variations persist even after adjusting for patient-related factors. Unwarranted variation depends on a mix of disparities, including inequalities in access to appropriate care in a wide variety of geographical and cultural settings, in the uptake and application of clinical knowledge, in the prioritisation and allocation of resources, and differences in organisational and professional culture. Nevertheless unwarranted variation has been inexorably linked with clinical practice. The Multidisciplinary team (MDT) is an important component of cancer care and is analysed as one of the two strands of clinical practice. Temporal trends in colorectal cancer care, resource utilisation and MDT workings are analysed using mix-method approaches. Colorectal cancer and Liver MDTs in Oxford and Gothenburg were observed and its members interviewed. The framework on unwarranted variation is reviewed with the view of assessing its utility in colorectal cancer care while the implication Cancer Drug Fund has on variation in clinical practice is also explored. Results indicate significant mortality amongst the elderly with colorectal cancer and a significant number of patients not receiving surgery within oneyear of diagnosis. However 90-day post surgical mortality has improved. No association between colorectal cancer spend and patient outcomes were found. Members of MDTs were observed to have diverse views on the roles and responsibilities of their MDT. Potential antecedents to unwarranted variation were identified through MDT workings. This study makes a distinction between professional uncertainty and clinical uncertainty to address the potential source of unwarranted variation. Recommendations on issues MDTs need to address such as defining its core purpose and developing reporting standards are made. A modification to the definition of unwarranted variation is also suggested. This study also proposes a conceptual risk scoring approach based on clinical pathways for addressing unwarranted variation. Several research areas have also been suggested.

Prognosis, literally translated from its Greek roots, means "fore-knowing." It is one of the three classic responsibilities of a physician, the others being diagnosis and therapy. Although the breadth and detail of scientific evidence to support medical practice has expanded significantly in recent decades, there is a case to be made that evidence about prognosis has lagged behind evidence for physicians' other work. Clinical questions in perinatal epidemiology demonstrate several important issues related to the conduct of prognostic research. Using examples from the study of prognosis for infants born with congenital diaphragmatic hernia, a condition for which estimates of survival vary widely, we illustrate the importance of selecting and specifying appropriate prognostic categories and contexts (e.g., time and place) to promote the appropriate interpretation of prognosis. In a study of extremely preterm birth--another condition with wide variation in available survival statistics--we show why decisions made by patients and physicians need to be accounted for in prognostic research. By revealing several potential pitfalls of prognostic research, each of the projects described in this thesis also illuminates important opportunities for the better conduct and interpretation of such work. Making predictions about the future and providing this information to patients may always be difficult work for physicians. But better scientific evidence and interpretation of that evidence can at least make predictions more accurate. The aim of this thesis is to advance our knowledge about how to achieve such improvements.

Members of the Mycobacterium tuberculosis complex, M. tuberculosis, M. bovis, M. microti, M. canettii and M. africanum, share over 99.9% identity at the DNA level. However, several recent studies have shown that there is considerably more genomic variation within the species when the organisation of the entire genome is considered, rather than primary sequences of individual genes. Therefore, to uncover the genomic variation within the species, one of the aims of this project was to compare the genome of several strains of M. tuberculosis, M. africanum, M. bovis (human and cattle isolates) and M. bovis BCG (Pasteur) using the M. tuberculosis H37Rv DNA microarray. The Beijing family of strains within the M. tuberculosis complex has been frequently associated with outbreaks of tuberculosis. Furthermore, several recent studies have shown that there are considerable selective advantages of the Beijing strains such as multidrug-resistance, higher adaptability to exposure to antituberculosis drugs and more infectivity in patients in countries such as China and Russia. The aim of this project was to understand the molecular basis for differences in virulence and infectivity amongst M. tuberculosis Beijing strains. The specific aims of the project were: (i) To investigate gene expression in response to stress conditions in the Beijing 94-1576 and Beijing 94-1707 strains. (ii) To investigate in vivo phenotypes of the Beijing 94-1576 and Beijing 94- 1707 strains. Comparative genomics was used to identify deletions of the RD1-RD14 regions as defined in M. bovis BCG. Regions of difference (RD) were used to reveal an evolutionary pathway for members of the M. tuberculosis complex and from this study, the presence of RD9 in one of the M. bovis isolated from cattle revealed a divergence from the published evolutionary pathway. It was anticipated that the selection of the M. tuberculosis strains from different sources might help uncover associations between genotype and host specificity in addition to exploring the scope of genotypic diversity. The M. tuberculosis isolates from India and different geographical areas such as Tanzania, Vietnam and Argentina did show a wide variation in the number, size and distribution of deletions. The Beijing strains showed a specific pattern of genomic variability with each having four large deletions compared to H37Rv. The genotypic characteristics of the Beijing family are (i) absence of the TbDl region, (ii) polymorphisms in the Rv3135 gene, the a/G463CTG (Leu) and gyrA95ACC (Thr) alleles and (iii) transposase insertion in the dnaA-dnaN and NTF-1 regions. In this study, the Beijing genotyping was performed and did confirm that the 94-1576 and 94-1707 strains were Beijing strains. The DNA microarray technique is only informative in detecting deletions that are present in the test strains compared with the reference strain H37Rv. To overcome this limitation, the subtractive hybridisation technique was applied and was able to identify a diverse polyketide synthase gene in the Beijing 94-1576 and Beijing 94-1707 strains. A study on gene expression in response to environmental stress conditions was performed to understand the influence of genome differences on gene regulation in H37Rv, Beijing 94-1576 and Beijing 94-1707. Using this, it proved possible to identify a number of significant differentially expressed genes involved (i) in oxidative and low pH stress for H37Rv, (ii) in oxidative and low pH stress for Beijing 94-1576, (iii) low pH and nitrosative stress for Beijing 94-1707. Finally, a number of experiments were done to investigate phenotypic differences between H37Rv, Beijing 94-1576 and Beijing 94-1707. This was done with a view to understand why the Beijing strains have become so successful in spreading across the world. In the initial stage of growth in the Balb/C mice, H37Rv, Beijing 94-1576 and Beijing 94-1707 grew progressively until day 28 before differences were seen between the strains. Infection in the human monocytic cell line THP-1 showed that the mycobacterial load of both Beijing 94-1576 and Beijing 94-1707 was higher than H37Rv. However, in C57BL/6 mice and murine bone marrow derived macrophages, the mycobacterial load of Beijing 94-1707 was significantly lower than H37Rv and Beijing 94-1576.

One of the tools a clinician has in disease diagnosis and treatment is genetic testing. To generate value in genetic testing, the link between genetic variants and disease must be discovered, documented, and shared within the community. Working with two existing genomic variation tools, Kafeen and Cordova, a new set of features referred to as Variant-Curation and Database Instantiation (Variant-CADI) was identified, designed, implemented and integrated into the existing Cordova system to unite data collection, management and distribution into one cohesive tool accessible through user interfaces. This eliminates the user needing specialized knowledge of the underlying implementation, data pipeline or data management to collect desired disease specific genetic variations. Using this tool, new disease-specific variation database instances have been initialized and created as demonstrations of the utility of these applications.

Introduction: There is an increasing number of Canadians living with end stage renal disease (ESRD). Kidney transplantation is currently the best treatment for ESRD but long-term outcomes remain suboptimal. Identifying factors associated with better outcomes may lead to interventions or practice change that could improve patient survival or quality of life. The objectives of this thesis were to: i) systematically review the literature to examine centre variation in kidney transplantation outcomes and identify centre and provider level factors that may contribute to variation in outcomes; ii) describe differences that may exist at the patient, centre and provider level at the time of kidney transplantation across the six transplant centres in Ontario, Canada; iii) examine variation in graft and patient survival rates across transplant centres in Ontario; and iv) examine whether patient, centre and provider level characteristics contribute to variation in graft and survival rates across transplant centres. Methods: The first objective of this thesis was met by conducting a systematic review of the literature according to a predefined protocol. The last three objectives of the thesis were met by conducting a population based retrospective cohort study using administrative data from Ontario. Differences at the patient, centre and provider level were described at the time of kidney transplantation. Outcomes of interest included total graft loss; graft loss with follow-up censored at death; death with graft function; and total mortality. All outcomes were assessed at one year post transplantation and at the end of study follow up. Cox proportional hazards regression was used to obtain hazard ratios (HR) for each centre relative to the average across all centres. The independent effect of centre volume and provider characteristics on outcomes was also examined. Results: The systematic review identified 24 eligible studies. Outcomes included graft survival (n=24) and patient survival (n=9). The main characteristics evaluated were centre volume (n=17) and provider volume (n=2). Centre variation in graft survival was described in 80% (12/15) of studies, while less than half of studies (8/17) found a significant association between volume and graft survival. The population based retrospective cohort included 5092 adults (≥18 years) who received a primary solitary kidney transplant across 6 transplant centres in Ontario between January 1st 2000 and December 31st 2013. Variation in patient, centre and provider level factors existed across centres at the time of transplantation. At the end of study follow-up, case-mix adjusted HRs for total graft loss ranged from 0.84 (95% CI 0.53-1.33) to 1.16 (95% CI 1.00-1.34) across centres (p-value for between centre variation 0.46). After adjusting for centre and provider factors, differences across centres persisted. Centre volume, provider experience and provider type were not independently associated with either short or long-term outcomes (all p>0.05) with the exception of graft loss with follow-up censored at death. Discussion: This thesis suggests that there is variation in clinical outcomes across transplant centres in Ontario which is not explained by patient factors, centre volume or provider characteristics at the time of transplantation. Additionally centre volume, provider type and experience were not independently associated with outcomes. Future prospective studies with a larger sample size of transplant centres that examine follow-up care after discharge from hospital (e.g. frequency of visits) are required to better understand this phenomenon.

Seasonal variations of mood, behavior and physiology have been of increasing interest. At least two different seasonal rhythms seem to exist: Descriptions of Seasonal Affective Disorder (SAD) with increased weight, increased sleep and fatigue during winter have attracted attention in academic psychiatry and in the general public the last two decades. In addition to such a difference in mood, weight and sleep between summer and winter, many studies describe a spring and fall increase in frequency of suicides and of admissions to hospital for mood disorders. In searching for a possible etiology for these seasonal changes, the main focus has been on variations in length of day.

The objective of this thesis was to study the existence and pattern of seasonal variation in some forms of behavior and of psychiatric illness among children and adults in Norway. Possible statistical connections between seasonal variations of behavior and changes in length of day and the influences of latitude, sex and age were also studied.

The monthly numbers of incidents in different groups were studied: All suicides in Norway 1969-96 (N=14.503), admissions to hospital for depression and mania in some hospitals 1992-96 (N=4.341), all violent episodes recorded by the police in Norway 1991-97 (N=82.537), all patient-staff incidents in a psychiatric department 1990-97 (N=502), all telephone calls to the Red Cross help-line for children and adolescents in Norway 1996-98 (N=691.787calls, 220.602 conversations) and in Trondheim, Norway 1991-97 (N=80.983 calls, 22.698 conversations) were included in the thesis. The monthly frequencies of these incidents were compared to an expected equal daily frequency of incidents through the year. Changes with increasing age and increasing latitude were examined. Correlations between the monthly frequencies of incidents and the length of day, with maximum impact at midsummer, and correlations between the monthly frequencies of incidents and the speed of change in length of day, with maximum impact at the equinoxes, were also studied.

In this thesis, an increased activity in April-June and in October-November is described for all the groups that were studied. In summer and winter there is less activity than in the rest of the year. Among children calling the help-line, a steady diminishing seasonal variation in number of calls with increasing age from 7 to 17 years of age and an increasing seasonal variation in number of calls with increasing latitude were found. Also the seasonal variation of violence increases with increasing latitude in Norway. Among men there is a correlation between the monthly number of suicides and the monthly number of admissions for mania and a correlation between the monthly number of suicides and the monthly number of admissions for depression. Among women there is a diminishing seasonal variation of admissions for depressions with increasing age. The monthly frequency of violence in Norway and the monthly frequency of calls to the Red Cross help-Line for children and adolescents correlated with a delay of 1-2 months with the monthly change in length of day with maximum impact at the equinoxes.

The results in the thesis correspond with earlier studies describing an increase in the frequency of suicides and an increase in admissions for depressions in spring and fall. A corresponding rhythm for other forms of human behavior is described in the present thesis, indicating that the seasonal rhythm of psychiatric illness reflects a seasonal rhythm of behavior in greater parts of the population. The seasonal variation in behavior seems to increase with increasing latitude, to be more dramatic in the northern than in the southern parts of Norway. In this thesis results supporting a hypothesis of human behavior being influenced by changes in length of day are given. Changes in length of day may induce changes in sleep and other disturbances in the daily rhythm that could change mood and other emotional qualities in vulnerable individuals. The demands on our capability to adapt to changes in length of day are largest at the equinoxes.

Årstidsvariasjon av sinnstemning og adferd.

Det er økende interesse for årstidsvariasjon av adferd og av forekomsten av psykiske lidelser. Det synes å foreligge minst to ulike årstidsrytmer i befolkningen; Størst oppmerksomhet har oppdagelsen av vinterdepresjon karakterisert ved tristhet, tretthet, økt vekt og forlenget søvn vakt. I tillegg til en slik forskjell i humør, vekt og søvn mellom sommer og vinter, er det en rekke beskrivelser av overhyppighet av selvmord og av innleggelser i sykehus for depresjoner vår og høst. Årsakene til disse to ulike årstidsrytmene er ikke kjent, men man har antatt at variasjon i dagslengde gjennom året spiller en rolle.

Hensikten med denne avhandlingen har vært å undersøke om det er årstidsvariasjon i forekomsten av ulike former for adferd og av psykiske lidelser hos barn og voksne i Norge. Videre er eventuelle statistiske sammenhenger mellom adferd og dagslengde gjennom året undersøkt. Til sist er forskjeller i årstidsrytme knyttet til breddegrad, alder og kjønn undersøkt.

Antallet hendelser pr måned i ulike grupper ble studert; Alle selvmord i Norge 1969-96 (N=14.503), innleggelser for depresjon og mani i en del sykehus 1992-96 (N=4.341), alle registrerte voldsepisoder i Norge 1991-97 (N= 82.537), personalskader i et psykiatrisk sykehus 1991-97 (N=502), alle telefoner til Røde Kors Kontakttelefon for barn og unge i Norge 1996–98 (N=691.787 oppringninger, 220.602 samtaler) og i Trondheim 1991-97 (N=80.983 oppringninger, 22.698 samtaler) ble inkludert i arbeidet. Hyppigheten av alle disse hendelsene i hver måned ble sammenlignet med en forventet lik fordeling av hendelsene året igjennom. Endringer med økende alder og med økende breddegrad ble undersøkt. Videre ble det gjort sammenligninger med dagslengde som er lengst ved sommersolverv og kortest ved vintersolverv, og sammenligninger med endringer av dagslengde som er hurtig ved vår og høstjamndøgn og sakte ved solvervene.

I alle disse materialene er det en økt aktivitet april – juni og oktober – november, videre er det stille perioder om vinteren og om sommeren. Blant barn som ringer kontakttelefonen er det gradvis avtagende årstidsvariasjon av henvendelser med økende alder fra 7 til 17 år og økende årstidsvariasjon i antallet henvendelser jo lenger nord man kommer i Norge. Også årstidsvariasjonen av vold i Norge endrer seg jo lengre nord man kommer i landet.

Blant menn er der en korrelasjon mellom det månedlige antallet av selvmord og av innleggelser for mani og mellom antallet selvmord og innleggelser for depresjon. Blant kvinner er det en avtagende årstidsvariasjon av innleggelser for depresjon med økende alder.

Den månedlige endring av dagslengde som er raskest ved jamndøgnene korrelerer med en viss forsinkelse med forekomsten av vold i Norge og med antallet oppringninger til Barn og Unges kontakttelefon.

Funnene i avhandlingen er i samsvar med tidligere beskrivelser av en markert økning av suicid og av innleggelser for depresjoner om våren og til dels om høsten. I avhandlingen er en tilsvarende rytme funnet for annen adferd. Dette tyder på at årstidsrytmen av psykiatrisk sykelighet avspeiler en årstidsrytme av adferd i store deler av befolkningen. Videre ser det ut til at forskjellene i adferd gjennom året blir mer markerte jo lengre nord man kommer i landet. I avhandlingen er det funn som støtter en hypotese om at endringer i dagslengde påvirker mennesket, det er mulig at dette skjer gjennom endret søvn og andre forstyrrelser i døgnrytmen. Vår døgnrytme er utsatt for størst krav til å tilpasse seg hurtige endringer i lysforhold rundt jamndøgnene.

Thirty publications are submitted. They deal with findings of the genetic architecture of schizophrenia in an Afrikaner founder population and clinical related variables pertaining to this population. The initial research findings supported the appropriateness of the Afrikaner population for mapping complex traits using both linkage and linkage disequilibrium (LD) approaches. Basic sample descriptors and cardinal symptoms of schizophrenia in the US and South African populations were equivalent. It was concluded that the results from our genetic study of schizophrenia in the Afrikaner sample will be applicable to other populations. It was found that early non-psychotic childhood deviance (in the first ten years of life) distinguished a distinct subtype of schizophrenia patient, and that the form of early deviance manifested, was meaningful linked to later disease outcome; and that it may be a possible endophenotypic marker in schizophrenia but not in bipolar disorder. Schizophrenia genetic research used linkage analysis, association studies and exome sequencing studies as it became available in the last few years. We addressed the role of the individual genes from the 22q11 locus (prototype CNV described in schizophrenia). Systematic screening of the 26 genes residing in this locus identified PRODH2, ZDHHC8, NOGO Receptor 1 (RTN4R) gene as contributing to schizophrenia risk associated with this region. Linkage genome-wide scans, using both less dense (10cM) and more dense scans (2cM), identified a locus on chromosome 1 and 13. Recent fine mapping on chromosome 13q32-34 and brain expression analysis implicates MYO16 in schizophrenia (not included in the 30 publications). For the first time a probound with a uniparental disomy (UPD) of the entire chromosome 1, was identified, which further support the involvement of chromosome 1 in schizophrenia. We confirmed the previous reported rate of 2% frequency of 22q11 deletions in adult schizophrenia Afrikaner patients and provided a two-stage screening protocol to identify these patients in clinical practice. As more patients were recruited for this study certain comorbid conditions became obvious including marijuana use/abuse and obsessive compulsive disorder (OCD) and obsessive compulsive symptoms (OCS). Approximately half of the male patients and a quarter of the female patients used or abused marijuana. Male users of marijuana with prominent early non-psychotic deviant behaviour in the first 10 years of life had the lowest mean age of criteria onset (18.4 years) with a poor prognosis. The prevalence of OCD/OCS in this population was 13.2% and differs from other ethnic groups in South Africa, and was associated with significant psychopathology and poor prognosis. As the research progressed the emphasis has changed from familial cases with the disease to sporadic cases (non-familial). We offered the first clear view of the genetic landscape of schizophrenia. We found that rare de novo structural mutations at many different loci are significantly enriched and contribute to schizophrenia vulnerability in sporadic cases with the disease. We also demonstrated that genes contribute to familial schizophrenia, while new mutations are less prominent. The study of schizophrenia in the Afrikaner founder population has helped to clear the view of the genetic landscape of schizophrenia.
Thesis (DSc)--University of Pretoria, 2014.
tm2015
Psychiatry
DSc
Unrestricted

Thesis (Ph.D.)--Indiana University, Dept. of Psychological and Brain Sciences and Program in Neuroscience, 2007.
Source: Dissertation Abstracts International, Volume: 68-10, Section: B, page: 6979. Adviser: William P. Hetrick. Title from dissertation home page (viewed May 21, 2008).

Includes bibliographical references (leaves 63-77).
Depression is a significant problem for both developed and developing countries. Local and international literature indicates that there are culturally mediated differences in presentation that contribute to more women being diagnosed with depression than men and to the predominance of particualar features of the illness in different settings. The aim of this archival study was to explore the presentation of depression across race groups in female patients at Valkenberg Hospital in the Western Cape. The narratives of patients' presenting complaints were obtained from the history taking notes in 46 hospital files, comprised of three sets of 15 files belonging to Black, White and Coloured patients, and one file belonging to a patient of Asian origin. Thematic analysis was used to analyze the narratives. Findings revealed that patients across race groups viewed depression as occurring in and resulting from interpersonal problems. However, White and Coloured patients also related their main problem to emotional distress, which was the main trigger for seeking help. Black patients reported difficulties in coping with life stressors as their main complaint, and frequently cited experiences of gender based violence. Distress seems to be tolerated until it manifests in behavioural disturbances. It was found that Black patients sought help only when their behaviour became distruptive for those around them. It was also observed that depression with psychotic featues and a co-morbid HIV diagnosis were reported most frequently among Black patients. There were thus similarities and differences in the presentation of depression across race groups. Patients' understandings of depression are mediated by various socio-cultural factors.

Includes bibliographical references
The anatomical structure of circulus arteriosus cerebri was first described by Thomas Willis in 1664. Many variations in the circulus arteriosus cerebri have since been reported. The extent to which anatomical variations within the circle influence aneurysm formation in a South African sample has not yet been established. The results of such a study would be of value to clinicians treating patients with vascular diseases. The aim of the study was to determine if there is a correlation between arterial variations in the circulus arteriosus cerebri and cerebral aneurysm formation. The brains of 39 cadavers at the Faculty of Health Sciences were removed and the circulus arteriosus dissected. In addition, 113 patients who underwent a MRI or MRA of the circulus arteriosus cerebri at the Department of Radiology at the Groote Schuur Hospital, Cape Town were included. For both of these samples the anatomical variations and any aneurysms present were documented. The external diameters of the arteries forming the circulus arteriosus cerebri were also measured. No aneurysms were found in the cadaver sample, thus the correlation could not be tested. In the sample of images from the 113 patients, 111 images showed one or more anatomical variation of the circulus arteriosus cerebri. Of these, 59 had one or more cerebral aneurysm and 52 had no aneurysms. Statistical analysis showed no significant correlation between cerebral aneurysms and anatomical variations in the circulus arteriosus cerebri for a South Africans ample. This is contradictory to what is seen in the literature. Further investigation is required to establish the reason why the results from this South African sample differ from the results reported in the international literature.

Objectives: The accuracy of delivered dose depends directly upon initial beam calibration and subsequent maintenance of this beam output. The uncertainty associated with these measurements and its impact on clinical outcomes is not well documented. This work gives an evidence based approach to determining this variation and its clinical impact. Novelty: This work will quantify for the first time the variations present in the routine maintenance of beam output on a national scale. The novel application of these dosimetric uncertainties to radiobiological models is then employed to predict the variation in clinical outcome due to the quantified dosimetric variations for specific clinical cases, including both tumour control and associated treatment complications on both individual and patient populations. Results: The linear-quadratic and Lyman Kutcher Burman models have been implemented to allow flexibility in the modelling of individual patient doses on a fraction by fraction basis. The variation in delivered doses due to beam output variations is seen to be normally distributed with a standard deviation of 0.7%. These variations may lead to a typical patient experiencing a range in treatment outcome probabilities of over 10% for cancers with a steep dose response curve such as head and neck in both the case of an individual patient and for a patient population. Conclusions: The precise control of beam output is shown to be a major factor in the overall uncertainty for dose delivery in modern treatment techniques. With reductions in other uncertainties in radiotherapy treatments, now may be the time to consider reduction of tolerance levels to allow optimal patient treatment and outcomes.

Blunting of diurnal variability in some forms of secondary hypertension has been confirmed. Study of such patients provides an insight into potential mechanisms underlying the nocturnal dip. Catecholamine excess appears to have a profound effect, confirming the importance of the autonomic nervous system in its regulation. Attenuation of the dip in those with volume mediated hypertension and those with impaired renal function suggests that hypervolaemia resulting in posture related changes in BP may also impact upon this rhythm. Glucocorticoid excess has been shown to blunt diurnal variability, but a modest increase in glucocorticoid exposure in hypopituitary patients has no effect, suggesting that pathological but not physiological quantities of corticosteroid are required to modify the diurnal rhythm. Study of patients with accelerated phase hypertension has demonstrated loss of the diurnal rhythm which returns towards normal with successful treatment. However, such patients are commonly hospitalised and study of other groups requiring emergency hospital admission suggests that this process may in part explain this effect. Mean wake blood pressure has been shown to be the most important predictor of target organ damage, assessed by echocardiography and microalbuminuria, but some further independent predictive information is provided by knowledge of diurnal variability. The hypothesis that occult sleep apnoea or nocturnal hypoxia may account for loss of diurnal variability is tested. Patients with essential hypertension, sleep apnoea syndrome and chronic obstructive pulmonary disease were studied, with no direct link between nocturnal hypoxaemia and the night-time BP dip apparent. A potential active role for the heart in the control of the diurnal rhythm is examined in a study of patients with mild cardiac failure starting treatment with an ACE inhibitor. The nocturnal dip was preserved but blunted, and was reduced still further by treatment, due to a greater fall in day than night BP.

Anatomical research of the morphology of the corpus callosum (CC) has provided a baseline for normal development of the CC. Although a large extent of variation amongst individuals has been reported, there are certain asymmetries that are consistently found in the size and shape of the CC on a midsagittal view of the brain. As the CC is the major commissural tract in the brain, it is acceptable to assume that structural variation in the CC may give clues towards the diagnosis of specific diseases. Studies relating alterations in the size and shape of the CC to the diagnosis of disorders have been done in individuals with schizophrenia, bipolar disorder (and depression. Thus, knowledge of CC anatomy in association with sex and age related changes can be helpful in providing a baseline for the diagnosis and progression of a specific disease. Morphological changes with regard to sex and age have been the topic of an extensive amount of research. However, there still remains considerable controversy as some studies report significant differences and others report none. The aim of this study was to provide a detailed description of the anatomy and variations of the corpus callosum morphology in a South African population. A primary data set was compiled using a cadaveric population, and these results were compared to a secondary data set, using a healthy living population. Lastly, the results from both data sets were then compared with a third data set, comprising of a mental disorder population, and results gained from previous studies in order to determine possible diagnoses of certain mental disorders based on CC morphology. In this study, there was no sexual dimorphism observed in the thickness of the genu, splenium and trunk in all three samples. In the cadaver sample there was no difference in the length of the CC. In the mental disorder sample there was no sexual dimorphism in the length of the CC and cerebrum. However, in the cadaver sample there was a significant difference in the length of the cerebrum between the sexes. In the healthy MRI scan there was a statistically significant difference observed in the length of the CC and the length of the cerebrum. It was found that there was no statistically significant difference in the thickness of the genu, trunk, and length of the CC and length of the cerebrum with age in all three samples measured. There was a statistically significant difference observed in the thickness of the splenium in the healthy MRI scan sample in individuals over the age of 60 years of age. This difference was not observed in the cadaver or mental disorder sample. There were no statistically significant differences in the various CC parameters measured in the various mental disorders measured. With the exception of two parameters, no differences in measurements were observed between the cadaver and healthy MRI sample. The two exceptions were the thickness of the trunk and the length of the cerebrum. Therefore, with the exception of the above mentioned cases, measurements between cadavers and living samples can be used interchangeably. Thus, the concerns about shrinkage in cadaver studies are negligible. However, when comparing the cadaver and healthy MRI scan sample with the mental disorder CT scan sample there was a statistically significant difference observed in every CC parameter measured. Thus, there is a rather noticeable difference in the anatomical structure of the CC in individuals suffering from mental disorders. Data on normal CC morphology is under represented in the South African population. Observations of variations from normal CC morphology can be used as an indicator for the possibility of a mental disorder.
Dissertation (MSc)--University of Pretoria, 2017.
Anatomy
MSc
Unrestricted

Population genetic analyses can provide information about both neutral and selective evolutionary processes shaping genetic variation. In this thesis, extensive population genetic methods were used to make inferences about genetic drift and selection in spruce species. In paper I we studied four species from the Qinghai-Tibetan Plateau (QTP): Picea likiangensis, P. purpurea, P. wilsonii and P. schrenkiana. Big differences in estimates of genetic diversity and Ne were observed in the more restricted species, P. schrenkiana, and the other more widely distributed species. Furthermore, P. purpurea appears to be a hybrid between P. likiangensis and P. wilsonii. In paper II we used Approximate Bayesian Computation (ABC) to find that the data support a drastic reduction of Ne in Taiwan spruce around 300-500 kya, in line with evidence from the pollen records. The split from P. wilsonii was dated to between 4-8 mya, around the time that Taiwan was formed. These analyses relied on a small sample size, and so in Paper III we investigated the impact of small datasets on the power to distinguish between models in ABC. We found that when genetic diversity is low there is little power to distinguish between simple coalescent models and this can determine the number of samples and loci required. In paper IV we studied the relative importance of genetic drift and selection in four spruce species with differing Ne: P. abies, P. glauca, P. jezoensis and P. breweriana. P. breweriana, which has a low Ne, exhibits a low fraction of adaptive substitutions, while P. abies has high Ne and a high fraction of adaptive substitutions. The other two spruce, however, do not support this suggesting other factors a more important. In paper V we find that several SNPs correlate with both a key adaptive trait (budset) and latitude. The expression of one in particular (PoFTL2) correlates with budset and was previously indentified in P. abies. These studies have helped characterise the importance of different population genetic processes in shaping genetic variation in spruce species and has laid some solid groundwork for future studies of spruce.

Cell biological exposure studies in magnetic resonance imaging (MRI) environment, where a complex mixture of strong magnetic fields are present, have attracted considerable interest in recent years. The outcome of such studies might depend strongly on the conditions, for example exposure parameters and spatial variations of exposure. The aim of this thesis has been to give a detailed description of how the radio frequency (RF) magnetic field varies with position and sequence choice within an MRI bore from a patient perspective and to highlight the need of better consistency in future research. Method: A straightforward theoretical description on the contribution to the RF magnetic field from a birdcage coil is given. A one dimensional coaxial loop antenna has been used as a probe to measure spatial variations of the RF magnetic field in a 1.5T MRI scanner. An exposure matrix containing RF magnetic field strength (H1-field) amplitudes in three dimensions was constructed and used to study several clinical protocols and sequences. A qualified correspondence measurement was also made on a 3T MRI scanner. Results: Around isocenter, for a common field-of-view (FOV), changes in exposure conditions were small; however, rapid changes of exposure conditions occurred upon approaching the end rings. The dominating H1-field component switched from lying in the xy-plane to pointing the z-direction and was roughly 3 times larger than in isocenter. Practical difficulties indicate even larger differences at positions not measurable with the equipment at hand. The strongest H1-field component was 32.6 A/m at position (x,y,z)=(-24,8,24) cm from the isocenter. Conclusions: Machine parameters such as repetition time, echo time and flip angle have little to do with actual exposure. Specic absorption rate (SAR) values correlated well with the square of measured root-mean-square (RMS) values of the magnetic field (B1,RMS) but not with peak values of the magnetic field (B1,peak), indicating that peak values are not unlikely to be part of compromising factors in previous contradictory exposure research on genotoxicity. Furthermore exposure conditions depend strongly on position and unfavorable situations may occur in the periphery of the birdcage coil. Potentially elevated risks for conducting surfaces, for example arms or external fixations, in the proximity of the end rings, are proposed. Aside from spatial variation consideration on which type of geometry exposed cell-biological samples are placed in should be held since eddy currents, hot-spots and proper SAR depend on geometry. Conditions may vary considerably between in-vitro, ex-vivo and in-vivo studies since geometries of test tubes, petri dishes and humans differ.

Introduction The presented research sought to understand variation in the clinical quality of general practice. Methods Clinical quality indicators relating to Cardiovascular Disease and Diabetes were analysed in general practices in Sandwell and the Black Country. General practices showing unusually high or low performance across indicators were identified. Semi-structured interviews were then conducted with practice staff to explore reasons for variation. Results Differences emerged between practices' leadership, culture, care systems and approaches to quality measurement and improvement. General practices were categorised into four types within a newly developed typology of general practice organisations: "biomedical", "holistic", "corporate" and "externally reactive", where there was some evidence that practice type influenced variation. Discussion Variation in general practice clinical quality appeared linked to differences staff held in their views of what constitutes quality in general practice, as explained through the practice typology, with an implied trade-off between achievement of different quality priorities. The research is limited by the study population, specified disease focus and quality measures adopted to examine variation. However, the results highlight the importance of moving to a shared definition of quality in general practice which may influence the measurement and understanding of variation in this setting and the developed practice typology.

The natural selection imposed by host immunity and antimalarial drugs has driven extensive adaptive evolution in Plasmodium falciparum, leading to an ever-changing landscape of genetic variation. We have carried out whole-genome sequencing of 93 P. falciparum clinical isolates from Malawi and used population genetic methods to investigate the genetic diversity and regions under selection. In addition, by computing XP-EHH, PCA and FST we have compared the Malawi isolates to five dispersed others (Kenya, Mali, Burkina Faso, Cambodia and Thailand), and identified genes potentially under positive directional selection. Geographic stratification of genetic diversity in the populations followed continental lines and small population differences were observed within Africa. Positive directional selection signals were identified at or near pfdhps, pfcrt, pfmdr1 and pfgch1 (known drug targets) and in several merozoite invasion ligands (e.g., msp3.8, trap and ama1). We discuss the role of drug selection in promoting fixation of alleles between populations with differing adaptation to local drug pressure. Analysis of copy number variation in Malawi provides a detailed catalogue of new and previously identified gene deletions and duplications with critical roles in cytoadherence, gametocytogenesis, invasion and drug response. This work provides the first genome-wide scan of selection and CNV in Malawi to guide future studies in investigating parasite evolution, changing malaria epidemiology, and monitoring and evaluating impact of malaria interventions as they are deployed.

Thesis (MScMedSc)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: Background: The assignment of radiation weighting factors to high energy neutron sources is important as there is reason to believe that neutron relative biological effectiveness (RBE) may be related to the inherent radiosensitivity of different individuals. A study was undertaken to quantify the inherent radiosensitivities of lymphocytes obtained from different donors to 60Co y-rays and p(66)/Be neutrons. For this a novel semi-automated image analysis process has been employed. In addition the responses of lymphocytes with different inherent radiosensitivities have also been tested using Auger electrons emitted by 123I. Methods: The RBE of neutrons was determined from dose-response curves for lymphocytes from different donors. Isolated T-lymphocytes irradiated in vitro were cultured to induce micronuclei in binucleated cells and micronuclei (MN) formations numerated using a semi-automated Metafer microscope system. The accuracy in obtaining dose response curves with this method has been tested by evaluating dispersion parameters of MN formations in the response to the different treatment modalities. Differences in the inherent radiosensitivities of cells from different donors were ascertained using 95 % confidence ellipses. [123I]Iododeoxyuridine was prepared in a formulation that allows incorporation of 123I into the DNA of lymphocytes. Micronucleus formations to this treatment were evaluated in lymphocytes with established differences in inherent radiosensitivities. Results: The image analysis system proved to be consistent in detecting micronuclei frequencies in binucleated lymphocytes. As a result, differences in the inherent radiosensitivities of different individuals were distinctive and could be stated at the 95% confidence level. The inter-individual radiosensitivity variations were considerably smaller for blood cells exposed to high energy neutrons compared to 60Co y-rays. Relative biological effectiveness (RBEM) values between 2 and 13 were determined that are highly correlated with the inherent radioresistance of lymphocytes obtained from different individuals. As such radiation weighting factors for high energy neutrons cannot be based on cytogenetic damage determined in lymphocytes from a single donor. Dispersion parameters for micronuclei formations proved to vary according to ionization density. The variation in RBE with neutron dose changed according to theoretical considerations and automated image analysis detection of MN is thus a suitable method to quantify radiation weighting factors. A clear reduction in the variation in radiosensitivity is noted for lymphocytes exposed to Auger electrons compared to 60Co y-rays. The effectiveness of Auger electrons from [123I]IUdR to induce biological damage is demonstrated as the number of disintegrations needed to yield micronuclei formations was found to be more than two orders of magnitude less than that of other compounds. An increase in the RBE of Auger electrons with radioresistance can be inferred from these findings and constitutes a basis for therapeutic gain in treating cells compared to using radioisotopes emitting low-LET radiation.
AFRIKAANSE OPSOMMING: Agtergrond: Die bepaling van straling gewigsfaktore vir hoë energie neutron bronne is belangrik, aangesien daar rede is om te glo dat die relatiewe biologiese effektiwiteit (RBE) kan verband hou met die inherente stralings sensitiwiteit van verskillende individue. Hierdie studie is onderneem om die inherente radiosensitiwiteit van limfosiete verkry vanaf verskillende skenkers te kwantifiseer na blootstelling aan 60Co y -strale en p(66)/Be neutrone. Vir hierdie doel is daar van 'n semi-outomatiese beeldontleding metode gebruik gemaak. Daarbenewens is die reaksie van limfosiete met vooraf bepaalde inherente radiosensitiwiteite ook getoets aan die hand van Auger elektrone wat uitgestraal word deur 123I. Metodiek: Die RBE van neutrone was bepaal uit dosis mikrokerne frekwensie verwantskappe verkry vir limfosiete. Geïsoleerde T-limfosiete was in vitro bestraal en gekweek om mikrokerne te vorm in dubbelkernige selle. Die mikrokerne was gekwantifiseer deur die gebruik van 'n semi-outomatiese Metafer mikroskoop stelsel. Die akkuraatheid in die verkryging van dosis-effek krommes met hierdie metode is getoets deur die ontleding van verspreidings parameters van MN vorming in reaksie op behandeling met die verskillende stralings modaliteite. Verskille in die inherente stralingsensitiwiteite van die selle van verskillende skenkers was vasgestel deur die konstruksie van 95 % betroubaarheidsinterval ellipse. [123I]Iododeoxyuridine was ook berei om 123I in die DNA van limfosiete in te bou. Die mikrokerne vorming op die behandeling is beoordeel in limfosiete met gevestigde verskille in inherent radiosensitiwiteite. Resultate: Die beeld analise stelsel bewys om konsekwent te wees in die opsporing van mikrokerne wat vorm in dubbelkernige limfosiete. Verskille in die inherente radiosensitiwiteite van verskillende skenkers kon vasgestel word op die 95 % betroubaarheidsvlak. Die skommeling in inter-individuele stralings sensitiwiteite was kleiner vir bloed selle blootgestel aan hoë-energie neutrone in vergelyking met 60Co y-strale. Relatiewe biologiese effektiwiteit (RBEM) waardes tussen 2 en 13 is bepaal wat sterk verband hou met die inherente radioweerstandbiedendheid van limfosiete verkry vanaf verskillende persone. As sodanig kan straling gewigsfaktore vir hoë energie neutrone nie gebaseer word op sitogenetiese skade in limfosiete van 'n enkele skenker nie. Verspreidings parameters vir mikrokern vorming het gewissel as ‘n funksie van ionisasiedigtheid van die straling. Die verandering in RBE met neutron dosis verloop volgens teoretiese oorwegings en die semi-outomatiese beeldontledings metode om mikrokerne op te spoor is dus geskik om stralings gewigsfaktore te kwantifiseer. 'n Duidelike afname in die verandering in die stralingsensitiwiteite is waargeneem vir limfosiete blootgestel aan Auger elektrone in vergelyking met 60Co y-strale. Die hoë doeltreffendheid van Auger elektrone afkomstig van [123I]IUdR om biologiese skade te veroorsaak, word weerspieël deur die feit dat die getal disintegrasies wat nodig is om mikrokerne te vorm meer as twee ordes grootte minder is as dié van ander verbindings. 'n Toename in die RBE van Auger elektrone in selle wat radioweerstandbiedend is kan afgelei word uit hierdie bevindinge. Dit vorm 'n basis vir terapeutiese wins in die behandeling van selle in vergelyking met die gebruik van radio-isotope wat lae ionisasie digthede tot stand bring.

Includes abstract.
Includes bibliographical references.
Infectious diseases are endemic in Africa, especially tuberculosis (TB), malaria and human immunodefiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Genomics research has the potential to improve the health of Africans through identification of genetic markers associated with either disease susceptibility or therapeutic drug response. This project was set to investigate the genetic correlates for drugs associated with mitochondrial toxicity that are used as part of HIV therapy, especially nucleoside reverse transcriptase inhibitors (NRTIs). Toxicity from NRTIs manifests through metabolic diseases such as peripheral neuropathy, lipodystrophy, lactic acidosis and hyperlactatemia but show interpatient variability. Studying African populations is likely to open the door for the population to benefit from novel diagnostic tools and drugs developed on the basis of pharmacogenomics knowledge. In an effort to contribute to this knowledge, the role of variation in mitochondrial DNA (mtDNA) and polymerase gamma (POL-γ) on how patients respond to stavudine-containing antiretroviral therapy (ART) among adult Malawian HIV/AIDS patients was investigated.

The retromolar foramen represents a little known anatomical variation in the posterior mandible of uncertain clinical importance. It has been the subject of limited study. Findings and conclusions of these studies have been placed under little scrutiny. Suggested clinical consequences associated with the presence of the retromolar foramen include local anaesthetic failure, local haemorrhage during surgery, perineural spread of infectious and invasive pathology, and loss of sensation in the normal distribution of the buccal nerve due to surgical intervention. Reports of the possibility of these complications seem to suggest that the retromolar foramen, canal and its associated neurovascular bundle are structures of great clinical importance. Case reports seem to have, however, only included reports of loss of gingival and buccal sensation as a consequence of third molar surgery in the presence of this anomaly. This study therefore aimed to report the prevalence of the retromolar foramen and canal in the South African population, describe its course and structure, and produce a clinical framework in which to approach the presence of the retromolar foramen. Comparisons between the present and existing studies were made and conclusions concerning the clinical importance of this structure were drawn. Inspection of a sample containing 946 mandibles was performed. Of these, 885 were regarded as suitable for inclusion. These mandibles were inspected for the presence of a retromolar foramen in which a 1 mm diameter needle could pass through without resistance. The distance from the last tooth in the arch to the retromolar foramen was also measured. Fifty of these mandibles were then randomly selected and scanned using microfocus computed tomography. Seventy mandibles were found to have at least one retromolar foramen (7.9% of the total sample). No statistically significant differences were found when the presence of the retromolar foramen was correlated with race, sex or age. The finding that sex and age played no significant role in the presence of the retromolar foramen is in agreement with available literature. Detected prevalence seemed to be heavily influenced by the method used to determine the presence of the retromolar foramen. The average distance between the second mandibular molar and the retromolar foramen was 16.83 ± 5.57 mm and the average distance between the third mandibular molar and the retromolar foramen was 10.47 ± 3.77 mm. These findings were found to be in agreement with most other reports. Fifty retromolar canals were selected at random and scanned using microfocus computed tomography. Analysis revealed four basic patterns. These were type A, a vertical canal between the inferior alveolar canal and the retromolar area of the mandible, type B, a curved canal taking a recurrent course between the inferior alveolar canal and the retromolar area, type C, a canal with an approximately horizontal path between the inferior alveolar canal and the retromolar area, and the temporal crest canal (TCC, not designated as type D to create a distinction between it and types A, B and C), a canal terminating on either side of the temporal crest. Type B was the most common presentation (68% of retromolar canals in the study), a finding contrary to that of other studies. The presence of the retromolar neurovascular bundle is of uncertain clinical importance and requires further anatomical and pharmacological study to determine its effect on local anaesthetic failure. A model in which the retromolar canal branches from the inferior alveolar canal does not seem to support a conclusion in which local anaesthetic failure may be directly attributable the presence of this anatomical variation alone. Classification of the retromolar canal is of limited clinical use and may require a revised scheme if clinical application is sought. Complications associated with the presence of the retromolar foramen are poorly documented and seem to be of little consequence.
Dissertation (MSc)--University of Pretoria, 2014.
tm2015
Anatomy
MSc
Unrestricted

The studies presented in this thesis employ neurophysiological outcome measures and the application of artificially induced cortical stimulation plasticity paradigms to study the effects of human genetic variation on human cortical neuroplasticity. The introductory chapter includes a review of illustrative models of neuroplasticity. I also cover the principles, physiology and pharmacology of TMS and rTMS. With this background, I set out the scope and principles of such an approach applied to the study of human genetic variation, and define the field of Stimulation Genomics. I set out the case for such an approach, highlighting previous studies that have employed neurophysiological outcome measures and the application of artificially induced cortical stimulation plasticity paradigms to study the effects of disease-causing human genetic mutations. In the subsequent introductory chapters I have focused on the rationale of selecting the Brain Derived Neurotrophic Factor polymorphism Rs6265 (BDNF Val66 Met) as the candidate polymorphism for our studies, covering the molecular biology and physiological roles of this highly conserved protein, and with a particular focus on its diverse roles in neuroplasticity. The 1st experiment presented here used established rTMS and TDCS paradigms to probe the effects of the BDNF Val66Met SNP on cortical plasticity and metaplasticity. The results generated from this study, and particularly the results suggesting an effect on metaplasticity, formed the basis for the studies in patients. We investigated the influence of this SNP on the rate of onset of Levodopa-Induced Dyskinesia (LID) in patients with Parkinson's disease and on the penetrance of DYT1 Dystonia. The final experiment presented here was designed to confirm the effects of the BDNF Val66Met polymorphism on the iTBS paradigm, and quantify its effects alongside other variables thought to influence the response to rTMS paradigms. This study also provides some crucial insights into the iTBS paradigm itself.

Anti-Müllerian hormone (AMH) is a homodimeric glycoprotein that is best known for its role in regression of the Müllerian duct in the male fetus. Accumulating evidence indicates that AMH also has an important role during different physiological processes after birth. In contrast to other species, relatively little is known about AMH in the horse. In chapter one, developmental and seasonal changes in serum AMH concentrations in male horses were determined, and the use of AMH for determination of retained cryptorchid testes was established. In chapter two, the interrelationship between plasma AMH concentrations, antral follicle counts (AFC), and age in mares was evaluated. Molecular and hormonal changes in the equine follicle with regard to variations in antral follicle count and follicular development were examined in chapter three. In chapter four, the effect of AFC on age-related changes in follicular parameters in light-type horse mares was examined. Peripheral AMH concentrations were significantly higher in prepubertal colts than in postpubertal stallions and varied with season in mature stallions with higher concentrations during the physiological breeding season. Furthermore, serum AMH concentrations were significantly higher in cryptorchid stallions compared to intact stallions or geldings. Circulating AMH concentrations varied widely amongst mares of the same age while the repeatability of AMH was high within and between estrous cycles. More importantly, AMH concentrations were positively associated with AFC, and this relationship increased with mare age. In addition, variations in AMH concentrations or AFC were associated with molecular differences in granulosa cells of growing follicles, and the expression of AMH and genes co-expressed with AMH in the equine follicle as well as intrafollicular AMH concentrations decreased during follicular development. Finally, the inter-ovulatory interval and length of the follicular phase is increased in aged mares with low AFC. In conclusion, AMH is a useful biomarker for cryptorchidism in stallions and ovarian reserve in mares. Furthermore, follicular function was interrelated to AFC or AMH based upon molecular differences in growing follicles, while age-related changes in follicular parameters are linked to differences in AFC.

Ce travail montre que les trois radiometres de meteosat sont des instruments pertinents pour des etudes climatiques sur l'afrique et que leur utilisation conjointe avec des resultats de modele permet d'analyser les mecanismes de grande echelle. La distribution de l'eau atmospherique est etudiee pour les trois mois de juillet 1983, 1984 et 1985. Les canaux infra-rouge mettent en evidence de fortes variations interannuelles des statistiques de radiances. Elles sont interpretees ici en terme de circulation moyenne. Enfin on etudie la possibilite d'utiliser le radiometre visible pour surveiller les variations d'albedo de la surface. L'ensemble de ces resultats amenent des arguments importants pour la comprehension des mecanismes de secheresse