Resumo: O objetivo deste estudo foi avaliar o efeito sub-letal do sulfato de cobre para a tilápia, na concentração de 0,5 e 2,0 mg.L-1 durante exposição e recuperação e determinar a toxicidade aguda para Ceriodaphnia dubia e para a alga Pseudokirchneriella subcapitata. Foram realizados dois ensaios (ensaios I e II) utilizando jovens de tilápia com peso médio de 38,29 g. Determinou-se neste estudo as concentrações de cobre nas brânquias, fígado e músculo dos animais, foram feitas também análises hematológicas, imunológicas, bioquímicas e histopatológicas durante exposição ao sulfato de cobre e posterior recuperação. Para o teste de toxicidade com C. dubia e P. subcapitata foram utilizadas as mesmas concentrações de sulfato de cobre do ensaio com peixes. Os cladóceros e as algas foram expostos a diluições dessas concentrações durante sete e três dias, respectivamente. Para a C. dubia observou-se a mortalidade e o efeito sobre a reprodução dos mesmos. Já para as algas foi observado o efeito inibitório sobre a taxa de crescimento. A exposição ao cobre no ensaio I e II resultou em acúmulo significativo de cobre nos tecidos analisados, com exceção do músculo. E no período de recuperação os valores de cobre permaneceram altos. O sulfato de cobre não provocou alterações hematológicas. Por outro lado, causou diminuição da capacidade fagocítica dos macrófagos de peixes expostos à concentração de 2,0mg.L-1 de CuSO4 no ensaio I. O cobre também causou diminuição da concentração de GSH. Com relação às análises histopatológicas houve alteração nas brânquias e hepatopâncreas em ambos os ensaios. Os resultados do teste ecotoxicológico com C. dubia P. subcapitata mostrou que o sulfato de cobre causou toxicidade aguda para estes organismos. O uso desse produto na aqüicultura pode comprometer o cultivo, uma vez que ocorreram danos a saúde dos peixes ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The copper sulphate is one of the most widely used chemicals for the control of parasites and for the control of phytoplankton in aquaculture. The purpose of this study was to evaluate sublethal effects of concentrations of copper sulphate on tilapia. In addition, ecotoxicity of this compound was determinate for microcrustaceans Ceriodaphnia dubia and the alga Pseudokirchneriella subcapitata. The biomarkers evaluated in this study were copper bioaccumulation in tissues, hematological, immunological, biochemical and histopathological parameters. The copper toxicity for microcrustacean C. dubia, was evaluated with acute tests through mortality. The exposure to copper in the experiments I and II resulted in significant accumulation of copper in the tissues, except for the muscle. In the recovery period, the copper values of remained high in all tissues. The haematological parameters were not affected by the copper sulphate. However, was observed in experiment I a significant change in the phagocytic capacity of macrophages in fish exposed to concentration 2.0 mg CuSO4.L-1. Copper sulphate also caused biochemical changes in both experiments. It was observed that this chemical causes a decrease in the concentration of GSH. The histopathological analysis showed hyperplasia and secondary lamellae fusion in the gills, and necrosis of the hepatopâncreas in both experiments. The tests results with C. dubia and P. subcapitata showed that copper sulphate caused acute toxicity to these organisms. This study showed that copper sulphate has caused chronic toxicity in fish and acute toxicity to algae and microcrustaceans. These results indicate that the pollutant can act at different trophic levels / Orientador: Maria José Tavares Ranzani Paiva / Coorientador: Julio Vicente Lombardi / Banca: José Roberto Ferreira / Banca: Fabiana Pilarski / Banca: Claudinei da Cruz / Banca: Monica Accaui Marcondes de Moura e Mello / Doutor

The complexity of biological matrices makes the detection and quantification of compounds of interest challenging. For successful targeted or untargeted identification of compounds within a biological environment, the use of complementary separation techniques is routinely required; in many situations, a single analytical technique is not sufficient. In the present dissertation, a multidimensional analytical technique was developed and evaluated, a combination of new sample preparation/extraction protocols, liquid chromatography, trapped ion mobility and mass spectrometry (e.g., LC-TIMS-MS and LC-TIMS-MS/MS). The performance of these techniques was evaluated for the detection of polybrominated diphenyl ethers metabolites, polychlorinated biphenyls metabolites in human plasma, opioid metabolites in human urine, and lipids in Dictyostelium discoideum cells. The new workflows and methods described in the body of this dissertation allows for rapid, selective, sensitive and high-resolution detection of biomarkers in biological matrices with increased confidence, sensitivity and shorter sample preparation and analysis time.

acase@tulane.edu

The prevalence of obesity is continually rising in developed countries like the United States. Based on the association between periodontitis and obesity and the relationship between periodontitis and peri-implantitis, it is important to understand the implications of obesity on peri-implant health. A potential relationship between obesity and peri-implant health has practical, biological and financial implications. The primary objective of this study was to determine the association between obesity as measured by the body fat indices (body mass index (BMI), waist circumference (WC), and body fat percent (fat %)) and the levels of inflammatory biomarkers in saliva. In addition, this study explored the correlations between the levels of these biomarkers in saliva versus their corresponding levels in peri-implant sulcular fluid (PISF) and gingival crevicular fluid (GCF) samples collected from the same subjects. Periodontal maintenance patients (N=73) were enrolled in this cross-sectional study. Anthropometric measurements (BMI, WC, and body fat %), intraoral assessment (full mouth plaque index, periodontal, and peri-implant comprehensive examinations) and unstimulated whole saliva samples were collected from the subjects. GCF and PISF were also collected. Levels of interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12(p40), IL-17α, tumor necrosis factor (TNF)-α, osteoprotegerin (OPG), letpin and C-reactive protein (CRP) in saliva, GCF and PISF were analyzed using multiplex immunoassays. Statistical analyses were performed to explore the correlations of interest. Data from 63 subjects were included in the analysis. No statistically significant correlations were noted between any of the body fat indices and any of the biomarkers measured in saliva (p>0.05 in all instances). A significant positive correlation was noted between salivary and GCF levels of IL-1α (r=0.29, p=0.0232), IL-8 (r=0.29, p=0.0207) and between saliva and PISF levels of leptin (r=0.32, p=0.0284). The employed linear model also revealed the significant impact of tooth brushing frequency on the salivary levels of IL-1α, IL-1β and TNF-α (p<0.05). Based on this cross-sectional study of 63 patients, I conclude that there was no statistically significant correlation noted between salivary inflammatory biomarkers and any of the obesity measures. However, the levels of key inflammatory markers in saliva strongly correlated with their corresponding levels in GCF/PISF. In addition, frequency of tooth brushing was also related to levels of certain biomarkers in GCF/PISF.

O transplante autólogo de células-tronco hematopoéticas (TACTH) é efetivo para o tratamento da esclerose sistêmica (ES), com controle do acometimento pulmonar, e melhora da fibrose cutânea, da qualidade de vida e aumento da sobrevida global, quando comparado a pacientes não transplantados. Neste tratamento, utiliza-se ciclofosfamida em altas doses, uma droga imunossupressora associada a cardiotoxicidade, potencialmente fatal. A avaliação de potenciais fatores de risco e monitorização clínica durante o procedimento podem contribuir para identificar precocemente a lesão cardíaca aguda e, assim, melhorar o desfecho clínico do paciente. O objetivo deste estudo foi identificar a ocorrência de disfunções cardíacas e avaliar os fatores de risco clínicos e laboratoriais para o desenvolvimento de toxicidade cardíaca aguda induzida pela ciclofosfamida, em pacientes com ES submetidos ao TACTH. Trata-se de um estudo longitudinal e prospectivo, conduzido no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, em pacientes com ES com idade superior a 18 anos, no período de novembro de 2016 a maio de 2018, aprovado por Comitê de Ética em Pesquisa. Os pacientes foram avaliados quanto aos dados clínicos e laboratoriais, incluindo dosagem de peptídeo natriurético, no período pré, durante e 6 meses após o transplante. Foram incluídas 16 mulheres com ES, das quais uma optou por descontinuar a participação no estudo, tendo seus dados excluídos. Nenhum dos participantes apresentava história de uso de substâncias psicoativas ou diagnóstico de diabetes mellitus. Uma paciente era tabagista passiva e uma era tabagista ativa há 24 anos, abstinente desde há três meses antes do início do transplante. Duas pacientes eram hipertensas, controladas com medicamentos anti-hipertensivos. Durante o transplante, 7 (46,7%) pacientes apresentaram alterações cardíacas associadas à ciclofosfamida. As pacientes apresentaram taquicardia, ganho ponderal, aumento de pressão venosa central e dispneia iniciados em menos de 24 horas e até 4 dias após o término da infusão da dose total de ciclofosfamida (200mg/kg) do transplante. Em três, de cinco pacientes submetidas a ecocardiografia, foram detectadas alterações sugestivas de disfunção cardíaca, corroborando os achados clínicos. Uma paciente evoluiu com choque refratário e posterior óbito por falência múltipla de órgãos. Uma paciente necessitou de pericardiocentese de alívio e, nos demais, o manejo com medicações reverteu as alterações clínicas. A dosagem dos níveis séricos de peptídeo natriurético mostrouse mais elevada (p<0,0005) nos pacientes que apresentaram sinais de toxicidade cardíaca. Concluímos que as avaliações clínicas sistematizadas por equipe de enfermagem permitiram a detecção de disfunções cardíacas pós-infusão de altas doses de ciclofosfamida, quadros retrospectivamente comprovados por elevação dos níveis sérico de peptídeo natriurético. O número reduzido de participantes não permitiu fazer análises estatísticas preditoras de cardiotoxicidade e foi uma limitação do estudo. Futuramente, objetivamos aumentar o número de pacientes do estudo e identificar marcadores preditivos de toxicidade cardíaca antes e durante o transplante / Autologous hematopoietic stem cell transplantation (AHSCT) is effective for the treatment of systemic sclerosis (SSc), with stabilization of pulmonary involvement and improvement of cutaneous fibrosis, quality of life and overall survival, when compared to non-transplanted patients. Transplant includes high dose cyclophosphamide, an immunosuppressive drug associated with potentially fatal cardiotoxicity. The evaluation of potential risk factors and clinical monitoring during the procedure may contribute to early identification of acute cardiac injury and thus improve the patient\'s clinical outcome. The aim of this study was to detect cardiac dysfunctions and to evaluate clinical and laboratory risk factors for the development of acute cardiac toxicity induced by cyclophosphamide in SSc patients submitted to AHSCT. This is a longitudinal and prospective study, conducted in the University Hospital of the Ribeirão Preto Medical School (Brazil), in patients with SSc, older than 18 years of age, from November 2016 to May 2018. The protocol has been approved by the Institutional Research Ethics Committee and all patients signed informed consent. Patients were evaluated for clinical and laboratory data, including natriuretic peptide dosage before, during and at the 6 months post-transplant time point Sixteen women with SSc were included, one of whom chose to discontinue participation in the study, having their data excluded. None of the participants had a history of psychoactive substance abuse or a diagnosis of diabetes mellitus. One patient was a passive smoker and another, an active smoker for 24 years, not smoking in the three months before transplantation. Two patients had their blood pressure controlled with antihypertensive drugs. During transplantation, 7 (46.7%) patients had cardiac changes associated with cyclophosphamide. The patients presented tachycardia, weight gain, increased central venous pressure and dyspnoea initiated in less than 24 hours and up to 4 days after the end of the infusion of the total cyclophosphamide dose (200mg / kg) of the transplant. In three of five patients investigated by echocardiography, alterations suggestive of cardiac dysfunction were detected, corroborating the clinical findings of cardiac dysfunction. One patient evolved with refractory shock and subsequent death due to multiple organ failure. One patient required pericardiocentesis due to cardiac tamponade and, in the others, management with medications reversed the clinical alterations. Serum natriuretic peptide levels were higher (p<0,0005) in the patients with than in the patients without any signs of cardiac toxicity. Clinical evaluations by the nursing staff allowed the detection of cardiac dysfunctions after infusion of high dose cyclophosphamide, retrospectively confirmed by elevation of serum levels of natriuretic peptide. The reduced number of participants did not allow for statistical analyzes to predict cardiotoxicity and was a limitation of the study. In the future, we aim to increase the number of patients in the study and to identify predictive markers of cardiotoxicity before and during transplant procedure

En élevage bovin, la détection précoce des femelles non gravides grâce au diagnostic de gestation permet une réinsémination rapide des animaux. Idéalement, ce diagnostic devrait être réalisé avant la fin du cycle sexuel, pendant la période péri-implantatoire, ce qui n’est pas possible actuellement. Pendant cette étape de la gestation précoce, le conceptus produit un facteur de reconnaissance maternelle de la gestation, l’interféron tau (IFNt), qui occupe un rôle important dans le dialogue entre le conceptus et l’organisme maternel. Plusieurs études ont montré que l’expression de gènes régulés par l’IFNt était augmentée dans l’endomètre et dans les leucocytes sanguins des ruminants, pendant la période péri-implantatoire.Les récentes avancées technologiques permettant l’analyse fonctionnelle du génome ont ouvert de nouvelles perspectives pour l’utilisation de ces marqueurs biologiques à des fins diagnostiques. L'objectif de ce travail a donc été l'identification de marqueurs diagnostiques fiables et précoces de la gestation, dans les cellules immunitaires circulantes des ruminants, ainsi que la caractérisation de la réponse locale (endomètre) et systémique (leucocytes sanguins) de l'organisme maternel à la gestation.Pour identifier de nouveaux candidats, nous avons réalisé un transcriptome des leucocytes d’animaux gravides et non gravides, que nous avons combiné à une analyse transcriptomique de l’endomètre caronculaire et des nœuds lymphatiques drainant spécifiquement l'utérus. Pour des raisons pratiques, ces prélèvements ont été réalisés chez l’ovin. A partir de ces résultats, nous avons sélectionné, parmi les gènes différentiellement exprimés (DEG), des candidats pour mettre au point un test de diagnostic précoce de gestation chez la brebis dans un premier temps, puis chez la vache dans un second temps. L’expression de ces gènes a été évaluée par RT-qPCR et des tests de diagnostic de gestation basés sur les niveaux d‘expression de ces gènes ont été conduits sur 2 lots expérimentaux de brebis et de vaches puis, sur un lot de brebis provenant d’élevages commerciaux. Cinq candidats ont été identifiés et évalués : CXCL10, STAT1, MX1, MX2, ISG15. Les tests, performants dans les lots expérimentaux, n’ont pas permis de discriminer efficacement la gestation dans le lot d’animaux d’élevage commerciaux. Chez ces animaux, une grande variabilité de l’expression des gènes candidats a été observée et suggère un défaut de spécificité de ces gènes dans le cadre du diagnostic de gestation en élevage.Pour comprendre ce défaut de spécificité, une analyse conjointe des transcriptomes des leucocytes sanguins, des nœuds lymphatiques et de l’endomètre caronculaire a montré un différentiel d’expression pour respectivement 118, 17 et 2823 gènes dans les 3 tissus explorés. Peu de DEG ont été trouvés dans les nœuds lymphatiques. Mais, si 78 % des DEG dans les leucocytes sanguins l’étaient aussi dans l’endomètre, les DEG communs à l’endomètre et aux leucocytes ne représentent que 3 % des DEG de l’endomètre. Les analyses de data mining ont mis en évidence dans les leucocytes et dans l’endomètre une réponse forte associée à la gestation, une réponse de type interféron liée à l’IFNt. Cependant, cette signature transcriptomique commune aux deux tissus n’est pas spécifique de la gestation et peut être associée à la présence d’agents infectieux.Ce travail a ainsi permis de mettre en évidence une certaine concordance entre la réaction locale et la réponse périphérique de l’organisme maternel à la gestation. Mais il a également montré que la signature transcriptomique de type interféron observée n’est pas spécifique de la gestation. Ce défaut de spécificité est à l’origine du manque de fiabilité du test de diagnostic de gestation basés sur les niveaux d’expression des gènes régulés par l’interféron que nous avons tenté de mettre au point. D’autres études sont nécessaires pour identifier des marqueurs alternatifs de la gestation, indépendants de l’IFNt / In cattle farming, reproductive performance is closely linked to farm profitability. The early identification of non-pregnant females, using pregnancy diagnosis tests, would allow rapid re-insemination of the animals, thus shortening the interbreeding interval. Ideally, pregnancy detection would be performed prior to the return to oestrous, namely at the time of implantation, which is not possible using current state-of-the-art pregnancy diagnosis techniques. At this early stage of pregnancy, the conceptus produces a ruminant-specific antiluteolytic signal, the interferon tau, which is responsible for the maternal pregnancy recognition. This interferon is critical in the communication between conceptus and maternal organism. The expression of numerous genes has been reported to be regulated by the interferons, in the endometrium and in blood leucocytes of ruminants, at the time of implantation.Recent technical advances for functional analysis of the genome have provided new opportunities for the use of these biological markers in pregnancy diagnosis. The main purpose of this work was to identify non-invasive, reliable and early pregnancy diagnostic markers in immune circulating cells, along with the characterisation of the local and systemic responses of the maternal organism to pregnancy.In order to identify new candidate genes, we performed a transcriptome analysis of pregnant and non-pregnant peripheral blood mononuclear cells, which we combined to a transcriptome analysis of the caroncular endometrium and the lymph nodes that specifically drain the uterus. For practical and cost-effectiveness reasons, these samples were collected in sheep. Based on the results of the transcriptome analysis, we selected, among the differentially expressed genes (DEG), a set of candidate genes in order to develop an early pregnancy diagnosis test initially in ewes and in cows in a second step. Expression of these genes was assessed using real time qPCR. Based on the expression levels of these candidate genes, pregnancy diagnosis tests were performed on different sets of animals: an experimental set of ewes, an experimental set of cows and finally, on a set of ewes from commercial herds. Five candidate genes were identified and evaluated: CXCL10, STAT1, MX1, MX2 and ISG15. Diagnosis tests displayed reliable results in the experimental sets of animals but failed to discriminate pregnancy in the set of farm animals. In this group, we observed high variations in interferon stimulated genes (ISG) expression levels highlighting the low specificity of ISG based pregnancy diagnosis tests performed in farm on heterogeneous batch of animals.To understand this lack of specificity, a simultaneous transcriptome analysis of blood leucocytes, lymph nodes and caroncular endometrium revealed respectively 118, 17 and 2823 DEG. Very few DEG were noticed in the lymph nodes. But if 78% of the DEG in blood leucocytes were found in the endometrium as well, only 3% of the DEG in the endometrium were shared with blood cells. Data mining analysis of the lists of DEG showed a strong pregnancy associated response in both blood leucocytes and the endometrium, an interferon response type, related to the implication of the interferon tau. However, this transcriptomic signature, identified in both biological tissues, is not pregnancy specific as it is frequently associated with pathogen agents.Finally, this work has enabled to highlight the slight correlation between the local (endometrium) and the peripheral (blood leucocytes) response during early pregnancy. But this work has also pointed out that the transcriptomic signature related to pregnancy, an interferon response type, is not pregnancy-specific. This lack of specificity is due to the unreliability of ISG based pregnancy diagnosis tests. Further investigations are needed to identify alternative pregnancy markers, independent of the interferon tau

Le système turbiditique profond associé au fleuve Ogooué s’étend sur plus de 500 km au large des côtes Gabonaises. Le bassin versant du fleuve est soumis à un climat équatorial propice à la mise en place d’une couverture végétale très dense et les apports fluviatiles en nutriments conduisent à une forte productivité primaire océanique dans le Golfe de Guinée. Ce système est ainsi un objet d’étude privilégié pour analyser les différents modes d’accumulation de matière organique au niveau d’une marge continentale dominée par un fleuve. Une analyse morpho-bathymétrique de la zone, associée à l’interprétation de données de sismique très haute résolution a permis d’appréhender l’architecture et le mode de fonctionnement de ce système. Cette étude a permis de mettre en évidence une zone à forte densité de chenaux turbiditiques méandriformes alimentés par une rampe de plusieurs canyons entaillant le plateau continental mais non connectés au delta actuel du fleuve. La zone distale de lobes est quant à elle située au débouché d’une large vallée qui canalise les écoulements turbiditiques. Des analyses sédimentaires (granulométrie, XRF, DRX) et géochimiques (%Corg, δ13Corg, palynofaciès, n-alcanes et tétraéthers) ont été réalisées sur neuf carottes Küllenberg prélevées dans différents environnements de dépôt du système. L’objectif est d’étudier la teneur en matière organique et son origine en fonction du mode de dépôt des sédiments et de comprendre la dynamique spatio-temporelle de son accumulation sédimentaire. Les analyses réalisées ont permis de révéler une binarité marquée dans les modes d’accumulation au sein de ce système. Les sédiments silto-argileux issus d’une sédimentation hémipélagique apportent peu de carbone organique continental mais une quantité importante de carbone organique marin qui forme des agrégats organo-minéraux avec les minéraux argileux de smectite exportés par le fleuve. Les écoulements turbiditiques sableux permettent quant à eux de faire transiter jusque dans les lobes distaux de fortes concentrations de débris végétaux très bien conservés. Ces séquences turbiditiques peuvent entrainer des enrichissements marqués en carbone organique continental (>5% TOC) au niveau des levées des chenaux turbiditiques et des dépôts sableux de lobes et constituent le principal mode de dépôt de Corg dans ces éléments architecturaux. La teneur en matière organique est également très fortement modulée par les variations glacio eustatiques. Durant les périodes de bas niveau marin relatif, l’accumulation organique est bien plus forte que durant les périodes de haut niveau marin. Ces fluctuations s’expliquent par l’effet combiné d’une plus forte productivité marine enregistrée en période glaciaire et d’un transfert sédimentaire entre le continent et le domaine profond très intensifié grâce au bas niveau marin. L’activité du système turbiditique est en effet dépendante de la connexion entre le système fluviatile et les têtes de canyons qui n’est possible que lorsque le niveau marin est bas. Bien que l’export de carbone continental vers l’océan dans ce système soit fort, les estimations du taux de préservation du carbone continental exporté par le fleuve montrent que la majorité du carbone est reminéralisé dans l’océan. Les taux de sédimentation relativement faibles sur l’ensemble du système du fait de la prédominance de la sédimentation hémipélagique sur la sédimentation turbiditique ne permettent pas une préservation optimale de la matière organique. / The Ogooué deep-sea turbidite system is located on the Gabonese margin and extends up to 500 km off the coastline. A dense vegetation due to the wet equatorial climate prevails on the Ogooue drainage basin and a strong primary productivity is observed in the waters of the Gulf of Guinea. These two features make the Ogooue system a good example to study the characteristics of organic carbon accumulation on a river-dominated ocean margin. A morpho-bathymetric analysis of the area combined with a study of seismic lines allowed us to define the architecture and the dynamic of the system. It is composed of an area where numerous meandering channels are localized and fed in sediments by several aligned canyons. The canyons heads incise the shelf but do not extend to the present-day Ogooué delta. Terminal depositional lobes are present at the exit of a large valley that funnels turbidity currents. Sedimentary (grain size, XRF, XRD) and geochemical (%Corg, δ13Corg, palynofacies, n-alkanes and GDGTs) analysis were performed on nine Küllenberg cores taken in different sedimentary environments of the system. These analyses aim at defining the Corg content of the cores as well as its origin and to link these parameters with the sedimentation type. The temporal and spatial repartition of carbon accumulation was also considered. Results show that hemipelagic sedimentation appears as quite inefficient to transport terrigenous organic carbon but is effective to bury marine organic carbon that forms aggregates with the smectite clay particles supplied by the river. Conversely, the sandy turbidites transport high quantity of terrigenous Corg to the deep sea areas. This Corg appears mostly under the form of well-preserved plant debris. These organic-rich turbidites (>5% TOC) form the main way of deposition of organic carbon in the levees of the turbidite channels and in the terminal lobes. Organic carbon accumulation is also strongly controlled by glacio eustatic variations. Low sea-level periods are characterized by very high organic carbon accumulation compared with high sea-level periods. Theses variations are the results of the combination of a higher marine productivity during glacials and a more intense export of terrigenous particles (both mineral and organic) during sea-level lowstand. The turbidite system activity is indeed governed by the connection between the canyons ‘heads and the riverine delta. This connection occurs only during lowstand. However, even though the export of organic carbon in the system is strong, the estimated preservation rates attest that most of the terrigenous organic carbon is mineralized in the ocean and not buried in the sediments. Globally low sedimentation rate on the whole system and the domination of hemipelagic over turbiditic sedimentation do not allow a better preservation of the organic material.

<p>This thesis describes a multi-parameter biogeochemical investigation in a shallow hyper-eutrophic freshwater coastal lake, Zeekoevlei, in South Africa. The predominance of autochthonous algal-derived organic matter in lake sediments is indicated by low C/N, high H/C ratios and δ13Corganic values. Seepage from a nearby waste water treatment plant, rapid urbanization, raw sewage input and heavily fertilized farming in the catchments have caused enhanced productivity and is reflected by the changes in TOC concentrations, δ15N values, terrestrial to aquatic (n-alkane) ratio (TAR) and low carbon preference index (CPI) values. Eutrophic conditions were initiated in the lake with the start of recreational activities in early 1900s. Construction of dams and pondweed eradication in mid-1900s caused the transformation of the lake towards a hyper-eutrophic water body. Moreover, the aquatic macrophyte n-alkane proxy (Paq) values indicate the slow takeover by floating macrophytes after the eradication of submerged pondweeds in 1951. Low δ15N values and appearance of zeaxanthin indicate initiation of cyanobacterial bloom in the lake following pondweed eradication. Furthermore, the lake experienced intense cyanobacterial bloom after 1983 dredging. Although, cyanobacterial domination has decreased in recent years, hyper-eutrophic condition persists in the lake.</p><p>Chemical weathering process supplies major fraction of trace metals, whereas fertilizers, agricultural wastes, sewage effluents and road runoff constitute the anthropogenic fraction. Low industrialization in the catchments causes low metal pollution in waters. In addition, high pH and metal scavenging by planktons result low dissolved trace metal concentrations. Adsorption by CaCO3 and planktonic assimilation control trace metal and phosphorus (P) sedimentation. Lake sediments have low P retention capacity and P is released from surface sediments by wind-induced resuspension.</p>

<p><em>A Quick Test </em>(AQT)<em> Färg och Form</em> är ett test av snabb automatiserad benämning avsett att detektera kognitiva störningar. Det består av tre delar som var och en utgörs av 40 visuella stimuli som skall benämnas så snabbt som möjligt. Tidigare studier har indikerat att AQT skiljer personer med Alzheimers sjukdom från friska kontroller med högre precision än det ofta använda <em>Mini-Mental-Testet </em>(MMT). I denna studie undersöktes för första gången om AQT-resultat kunde predicera diagnosen hos en konsekutiv serie patienter vid en minnesklinik samt relationen mellan AQT-resultat och biomarkörer (likvorproteiner) för neurodegenerativ sjukdom. 492 svarsblanketter från <em>AQT Färg och Form</em> analyserades och diagnostisk prediktion samt korrelation med nivån av likvorproteiner fastställdes för de 374 första patienterna i serien. Resultaten tyder på att <em>AQT Färg och Form</em> kan vara känsligt för vissa lindriga kognitiva sviktsymptom som förekommer hos personer remitterade för minnesbesvär men inte alltid känsligt för lindriga grader av demens. AQT-data korrelerade måttligt med nivån av patologiska likvorproteiner, troligen avspeglande förhöjda nivåer i Alzheimergruppen. Ytterligare forskning på konsekutiva fallserier behövs för att fastställa testets diagnostiska diskriminationsförmåga i klinisk praxis.</p> / <p><em>A Quick Test </em>(AQT)<em> Color-Form </em>is a test that uses rapid automatized naming in order to identify cognitive impairment. It is divided into three parts, each of which consists of 40 stimuli that are to be named as quickly as possible. Previous studies have indicated that AQT separates patients with Alzheimer’s disease from normal controls with higher accuracy than the commonly used <em>Mini-Mental State Examination </em>(MMSE). The purpose of this study was to investigate, for the first time, whether AQT results collected from a consecutive series of patients at a Memory Clinic would be able to predict the diagnosis. Another aim was to study the possible relation between AQT results and Cerebrospinal Fluid (CSF) biomarkers for neurodegenerative diseases. 492 forms from <em>AQT Color-Form</em> tests were analyzed and diagnostic prediction and correlation with level of CSF biomarkers were determined for the first 374 patients. The results imply that <em>AQT Color-Form</em> may be sensitive to some symptoms of benign memory impairment that is found in patients admitted to a Memory Clinic, but that it is not always sensitive to mild degrees of dementia. Further research consecutive series of patients is needed in order to determine the diagnostic abilities of discrimination in clinical practice.</p>

This thesis describes a multi-parameter biogeochemical investigation in a shallow hyper-eutrophic freshwater coastal lake, Zeekoevlei, in South Africa. The predominance of autochthonous algal-derived organic matter in lake sediments is indicated by low C/N, high H/C ratios and δ13Corganic values. Seepage from a nearby waste water treatment plant, rapid urbanization, raw sewage input and heavily fertilized farming in the catchments have caused enhanced productivity and is reflected by the changes in TOC concentrations, δ15N values, terrestrial to aquatic (n-alkane) ratio (TAR) and low carbon preference index (CPI) values. Eutrophic conditions were initiated in the lake with the start of recreational activities in early 1900s. Construction of dams and pondweed eradication in mid-1900s caused the transformation of the lake towards a hyper-eutrophic water body. Moreover, the aquatic macrophyte n-alkane proxy (Paq) values indicate the slow takeover by floating macrophytes after the eradication of submerged pondweeds in 1951. Low δ15N values and appearance of zeaxanthin indicate initiation of cyanobacterial bloom in the lake following pondweed eradication. Furthermore, the lake experienced intense cyanobacterial bloom after 1983 dredging. Although, cyanobacterial domination has decreased in recent years, hyper-eutrophic condition persists in the lake. Chemical weathering process supplies major fraction of trace metals, whereas fertilizers, agricultural wastes, sewage effluents and road runoff constitute the anthropogenic fraction. Low industrialization in the catchments causes low metal pollution in waters. In addition, high pH and metal scavenging by planktons result low dissolved trace metal concentrations. Adsorption by CaCO3 and planktonic assimilation control trace metal and phosphorus (P) sedimentation. Lake sediments have low P retention capacity and P is released from surface sediments by wind-induced resuspension.