Fjords contain a significant quantity of sediments deposited in coastal zones over the last ~100,000 years. Studies of Northern Hemisphere fjords have shown that a large part of the high concentration of sedimentary organic matter (OMsed) is terrestrial in origin (OMterr), composed of a modern detrital fraction and an old mineral-associated fraction (OMfossil). These results suggest that fjords are disproportionately responsible, on a per area basis, for the burial of organic matter in coastal zones. This study, after a rigorous examination of CuO and GDGT biomarker methods used to quantify terrestrial organic matter in coastal environments, demonstrated this hypothesis in a Southern Hemisphere fjord system, Fiordland, New Zealand. CuO analysis of Doubtful Sound surface sediments indicated a large contribution of vascular plant material to fjord sediments. The BIT Index correlated strongly with both delta13C and C/N values in Doubtful Sound surface sediments, indicated that it may accurately trace the relative proportions of marine and soil organic matter (OMsoil) in Fiordland. However, a detailed analysis of the conversion of the BIT Index to quantitative estimates of terrestrial (soil) organic matter revealed that these values are overestimates. Reconstructions of the BIT Index and tetraethers in cores from two locations on the Louisiana continental shelf demonstrated the influence of the crenarchaeol term on BIT Index-based terrestrial organic matter estimates. The differences in the applicability of the BIT Index to these two coastal environments was most likely due to large seasonal changes in productivity on the Louisiana Continental Shelf as well as higher marine relative to terrestrial inputs. Six cores were reconstructed for contributions from marine OM (OMmar), OMfossil, and OMterrestrial representing the last ~500 years of sedimentation. Spatial variations were larger than temporal variations, owing to negligible development and deforestation in the region. OMterr was the dominant fraction in all but one core, and OMfossil inputs were significant. Additionally, source reconstructions from a variety of biomarkers indicated that Landslides deliver large volumes of detrital organic matter to fjord sediments. These results confirm that fjords bury quantitatively significant volumes of organic carbon on a global scale.

The present thesis is based on four studies focusing on alcohol consumption among Swedish adolescents, and therewith related psychosocial and genetic factors. One main objective was to study the reasons for drinking alcohol among different population - representative samples of adolescents in order to identify motives for drinking. Relationships between these drinking motives, alcohol consumption, and alcohol - related problems were also investigated. Three motives emerged from this study: social - enhancement, coping and dominance. The association with alcohol consumption and alcohol - related problems was positive for social - enhancement and coping motives, but negative for the dominance motive. A significant heritability of alcohol use disorders has been demonstrated by family, adoption and twin studies. Environmental influences have also been acknowledged to play an important role in the development of alcohol use disorders. Moreover, the interaction between genetic and environmental factors is likely to influence the risk - resilience for alcohol use disorders. In view of this knowledge, plausible candidate polymorphisms were considered in gene - environment interaction models. An effect of the genetic polymorphisms was only present when a G x E model was considered. A genetic variant of the clock gene Period2, in an interaction with sleep problems, was studied in relation to alcohol consumption among adolescents. High alcohol consumption was associated with the AA genotype of the PER2 SNP10870 polymorphism, in an interaction with several and frequent sleep problems, among adolescent boys. A genetic variant in the opioid µ receptor 1 gene, in an interaction with alcohol consumption, was studied in relation to depressive symptoms. Depressive symptoms were predicted by the G allele of the OPRM1 A118G polymorphism, in an interaction with high alcohol consumption, among adolescent girls. Additionally, the PER2 SNP10870 and the OPRM1 A118G polymorphisms were studied in a sample of severely alcoholic females. Furthermore, alcohol consumption was assessed by using different instruments, such as biomarkers and surveys. Comparisons were carried out to identify the most suitable method to assess alcohol consumption among adolescents. Questionnaire and interview seemed more suitable tools than biomarkers in this regard.The results eventually support the importance of psychosocial and genetic influences, and their interaction effect on alcohol consumption among adolescents.

Screening complex biological specimens such as exhaled air, tissue, blood and urine to identify biomarkers in different forms of cancer has become increasingly popular over the last decade, mainly due to new instruments and improved bioinformatics. However, despite some progress, the identification of biomarkers has shown to be a difficult task with few new biomarkers (excluding recent genetic markers) being considered for introduction to clinical analysis. This review describes recent advances in gas chromatographic methods for the identification of biomarkers in the detection, diagnosis and treatment of cancer. It presents a general overview of cancer metabolism, the current biomarkers used for cancer diagnosis and treatment, a background to metabolic changes in tumors, an overview of current GC methods, and collectively presents the scope and outlook of GC methods in oncology.

In Sweden, close to 10 000 men are annually diagnosed with prostate cancer (PCa) and approximately 2400 men die of their disease each year. Today there is no reliable marker that can separate patients who will have an aggressive type of disease that requires treatment, from patients who will have a more indolent clinical course and can be left untreated. This further leads to the current problem of over treatment of men with PCa. Hence, there is an urgent need for reliable prognostic markers that can be used at time of diagnosis. With the discovery of recurrent gene rearrangements in PCa, most commonly ERG rearrangements, hope came that this aberration could play a role in diagnosis and/or prognosis of the disease. The aim of this thesis was to investigate the clinical implication of ERG rearrangements in the management of PCa. The work in this thesis supports the findings from previous studies, suggesting that the ERG rearrangement is a sign of a more aggressive type of cancer. The major findings are that in multifocal PCa, the ERG rearranged cancer foci are more prone to metastatic dissemination compared to foci without the ERG rearrangement and that patients harboring the ERG rearrangement have a faster disease progression leading up to earlier start of hormonal treatment. Furthermore, the results add an additional level of complexity in a subset of PCa tumors that harbor multiple gene rearrangements on the cellular level. The result also show that the newly available ERG antibody is highly predictive of ERG rearrangement and is appropriate to use when faced with limitations in tissue amounts. The findings in this thesis indicate that the ERG rearrangement has a potential role in the clinical management of PCa but further studies arerequired.

Atrial fibrillation (AF) confers an independent increased risk of stroke and death. The stroke risk is very heterogeneous and current risk stratification models based on clinical variables, such as the CHADS2 and CHA2DS2VASc score, only offer a modest discriminating value. The aims of this thesis were to study cardiac biomarkers, cardiac troponin and natriuretic peptides e.g. N-terminal prohormone-B-type natriuretic peptide (NT-proBNP), and describe levels in AF patients, investigate the association with stroke or systemic embolism, cardiovascular event, major bleeding and mortality, and to assess how levels of cardiac biomarkers change over time. Cardiac troponin was analyzed with contemporary assays and high sensitivity assays. The study populations consisted of patients with atrial fibrillation and one risk factor for stroke included in the RE-LY (n=6189) and the ARISTOTLE (n=14892) biomarker substudies. Median follow-up time was 2.2 years and 1.9 years, respectively. In a subset of participants (n=2514) data from repeated measurements was available at three months. Cardiac troponin was detectable in 57.0% with the contemporary assay and 99.4% with the high sensitivity assay. NT-proBNP was elevated in approximately three quarters of the participants. In Cox models adjusted for established risk factors the cardiac biomarkers levels was independently associated with stroke or systemic embolism, cardiovascular events, and mortality. Only cardiac troponin was associated with major bleeding. In ROC analyses the prediction of stroke or systemic embolism, cardiovascular events, and mortality increased significantly by addition of cardiac troponin or NT-proBNP to the models. Persistent detectable cardiac troponin (contemporary assay) and elevated NT-proBNP levels were found in a large number of participants. Persistent detectable or elevated levels conferred significantly higher risk for stroke or systemic embolism, cardiovascular events, and mortality. By using both cardiac biomarkers simultaneously the risk stratification improved even further for all outcomes. In conclusion the analyses for the first time display that elevation of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke, cardiovascular events and mortality. Persistent elevation of troponin and NT-proBNP indicate a worse prognosis than transient elevations or no elevations of either marker. The cardiac biomarkers added substantial improvements to existing risk stratification models.

Actually, there is a strong incidence of psychiatric diseases, representing a 13% of total burden diseases and 450 million of people affected. The etiology of psychiatric diseases remains unknown. However, scientific evidences suggest a maldevelopment of nervous system (NS). The diagnosis is inaccurate, and international manuals (ICD-10 and DSM-IV) identify pathologies according to a list of symptoms but no underlying biological cause of disease. The aim of the thesis is to identify potential biomarkers -related to the development of NS- in peripheral blood of psychiatric patients diagnosed as different mental diseases, such as autism spectrum disorders (ASD), schizophrenia and bipolar disorders. It is intended to contribute with the improvement of diagnostic, prognostic and treatment of subjects. The thesis is divided into 4 chapters: 1) study of neurotrophins in ASD, where the results show the relationship of this family of molecules with the disease, 2) study of Latrophilin-3 (LPHN3) in the TEA, which was obtained in association with lower cognitive level of ASD, 3) study of the Eph-receptor A4 in the pathology of schizophrenia and bipolar disorder, results of which show no association, and finally 4) study of Ankyrin-3 (ANK3) in schizophrenia and bipolar disorder, which shown a relationship with bipolar disorder but not with schizophrenia. / Actualment, hi ha una forta incidència de les patologies psiquiàtriques, representant un 13% del total de les malalties i 450 milions de persones afectades. L’etiologia de les patologies psiquiàtriques és desconeguda. Tot i així, evidències científiques suggereixen un mal desenvolupament del sistema nerviós (SN). El diagnòstic és poc precís, i els manuals internacionals (ICD-10 i DSM-IV) identifiquen les patologies d’acord a un llistat de símptomes, però sense cap causa biològica subjacent de la patologia. L’objectiu de la tesi és la identificació de biomarcadors potencials –relacionats en el desenvolupament del SN- en sang perifèrica de pacients diagnosticats amb diferents patologies mentals, com ara els trastorns de l’espectre autista (TEA), esquizofrènia i desordres bipolars. És pretén contribuir amb la millora del diagnòstic, el pronòstic i el tractament de les persones que les pateixen. La tesi s’estructura en 4 capítols: 1) estudi de les neurotrofines en els TEA, on els resultats evidencien la relació d’aquesta família de molècules amb la patologia, 2) estudi de la Latrofilina-3 (LPHN3) en els TEA, on s’ha obtingut associació amb el nivell cognitiu més baix dels TEA, 3) estudi del receptor EPH A4 en les patologies d’esquizofrènia i desordres bipolars, resultats del qual no mostren associació i, per últim 4) estudi de la Ankirina-3 (ANK3) en l’esquizofrènia i els desordres bipolars, en el qual si que es troba una relació amb els desordres bipolars, però no amb l’esquizofrènia. / Actualmente, hay una fuerte incidencia de las patologías psiquiátricas, representando un 13% del total de las enfermedades y 450 millones de personas afectadas. La etiología de las patologías psiquiátricas es desconocida. Aún así, evidencias científicas sugieren un mal desarrollo del sistema nervioso (NS). El diagnóstico es poco preciso, y los manuales internacionales (ICD-10 y DSM-IV) identifican las patologías de acuerdo a un listado de síntomas, pero sin ninguna causa biológica subyacente de la patología. El objetivo de la tesis es la identificación de biomarcadores potenciales –relacionados con el desarrollo del SN- en sangre periférica de pacientes diagnosticados con diferentes patologías mentales, como son los trastornos del espectro autista (TEA), esquizofrenia y desordenes bipolares. Se pretende contribuir en la mejora del diagnóstico, el pronóstico i el tratamiento de las personas que las padecen. La tesis se estructura en 4 capítulos: 1) estudio de las neurotrofinas en los trastornos del espectro autista (TEA), en el cual los resultados evidencian la relación de esta familia de moléculas con la patología, 2) estudio de la Latrofilina-3 (LPHN3) en los TEA, donde se ha obtenido una asociación con el nivel cognitivo más bajo de los TEA, 3) estudio del receptor EPH A4 en las patologías de la esquizofrenia y los desordenes bipolares, resultados del cual no muestran asociación y, por último 4) estudio de la Ankirina-3 (ANK3) en la esquizofrenia y los desordenes bipolares, en el cual si que se ha encontrado una relación con los desordenes bipolares, pero no con la esquizofrenia.

This study investigates the risk of arsenic (As) exposure from staple diet to the communities in rural Bengal, even when they have been supplied with As safe drinking water. The results indicate that average accumulation of As in rice grain increases with decrease of grain size [extra-long slender (ELS): 0.04 mg kg-1; long slender (LS): 0.10 mg kg-1; medium slender (MS): 0.16 mg kg-1 and short bold (SB): 0.33 mg kg-1], however people living in the rural villages mostly prefer brown colored SB type of rice because of its lower cost. Among the vegetables generally consumed in rural villages, the accumulation of As is highest in the leafy type of vegetables (0.21 mg kg-1), compared to non-leafy (0.07 mg kg-1) and root  vegetables (0.10 mg kg-1). Arsenic predominantly accumulates in rice (&gt;90%) and vegetables (almost 100%) in inorganic species [As(III &amp; V)]. The estimates of exposure via dietary and drinking water routes show that when people are consuming water with As concentration &lt;10 μg L-1, the total daily intake of inorganic As (TDI-iAs) exceeds the previous provisional tolerable daily intake (PTDI) value of 2.1 μg day-1 kg-1 BW, recommended by World Health Organization (WHO) in 35% of the cases due to consumption of rice. Considerably high concentration of As in urine and saliva despite drinking of As safe water (&lt;10 μg L-1) further supports that dietary intake of As, mainly through consumption of rice could be alternative pathway of As exposure among the population. When the level of As concentration in drinking water is above 10 μg L-1, the TDI-iAs exceeds the previous  PTDI for all the participants. These results imply that when rice consumption is a significant contributor to the TDI-iAs, supplying water with As concentration at current national drinking water standard for India and Bangladesh (50 μg L-1) would place many people above the safety threshold of PTDI. When As concentration in drinking water exceeds 50 μg L-1 As exposure through drinking water largely predominates over the exposure through dietary intake. It is found that the consumption of vegetables in rural Bengal does not pose  significant health threat to the population independently. It is also revealed that cooking of rice with high volume of As safe (&lt;10 μg L-1) water can decrease both total and inorganic As content in cooked rice. However, the assessment of As exposure risk indicates that despite such lowering in As concentrations, still consumption of cooked rice is a significant pathway of As exposure to the population in rural Bengal. This study suggests that any effort to mitigate the As exposure of the villagers in Bengal must consider the risk of As exposure from rice consumption together with drinking water. / <p>QC 20130919</p> / EAECA-EURINDIA 2009-1665

A Quick Test (AQT) Färg och Form 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 Mini-Mental-Testet (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 AQT Färg och Form analyserades och diagnostisk prediktion samt korrelation med nivån av likvorproteiner fastställdes för de 374 första patienterna i serien. Resultaten tyder på att AQT Färg och Form 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. / A Quick Test (AQT) Color-Form 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 Mini-Mental State Examination (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 AQT Color-Form tests were analyzed and diagnostic prediction and correlation with level of CSF biomarkers were determined for the first 374 patients. The results imply that AQT Color-Form 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.

Chronic kidney disease (CKD) is a major cause of illness in dogs, and it is commonly caused by glomerular diseases that result in proteinuria and a progressive decline in renal function. Despite the importance of glomerular lesions, tubulointerstitial fibrosis identified by histologic evaluation of renal biopsies correlates best with renal function. However, performing a renal biopsy is invasive. Most current non-invasive tests for renal function lack adequate sensitivity and specificity for renal disease. Proteinuria can be both a sensitive and specific marker for renal damage. However, its evaluation in veterinary medicine beyond determination of the magnitude of proteinuria (e.g., urine protein:creatinine ratio (UPC)) is limited. Therefore, in this report, further evaluation of the UPC was performed to aid in the monitoring of renal disease progression and response to treatment. In addition, qualitative evaluation of proteinuria was performed in dogs with progressive CKD in order to identify better non-invasive markers for tubulointerstitial injury. The day-to-day variability of the UPC was determined utilizing data obtained from female dogs that are carriers for X-linked hereditary nephropathy (XLHN). Despite an unchanging magnitude of proteinuria in these dogs, substantial variation in their UPC was observed. Using these results, guidelines were suggested to help assess whether disease progression or treatment leads to a significant change in UPC. Qualitative characterization of proteinuria in dogs with CKD was performed using urine from male dogs affected with XLHN, and results were correlated with clinical and histologic findings concerning renal function and damage. The two discovery proteomic techniques utilized (chromatographic chip array and two-dimensional gel electrophoresis) revealed several proteins that have not previously been implicated as markers for canine CKD, providing a basis for future studies. Specific assays for urinary biomarkers of renal injury were used to serially evaluate renal function in these dogs. All proteins evaluated proved to be sensitive markers for renal damage. However, only retinol binding protein provided clear evidence for renal disease progression. These results will provide the foundation for future studies aimed at monitoring urinary biomarkers in dogs with CKD, which will ultimately help veterinarians better diagnose and monitor proteinuric renal disease.

Rapid tropical glacier retreat over the last 50 years has been well documented, and has received significant media attention. Many studies suggest these changes are due to rising global surface air temperatures, however disentangling the effects of temperature and precipitation has hampered scientific consensus. Furthermore, because of the shortness of the instrumental record, it is difficult to assess the larger significance of the climate changes associated with the decline of tropical glaciers. Here, we present a locally calibrated, independent temperature reconstruction for the past 1,500 years from Laguna Chingaza, Colombia based on distributions of branched Glycerol Dialkyl Glycerol Tetraethers (brGDGTs) in order to assess the controls on long term temperature variability in the tropical Andes, and their relationship with growth and demise of Andean glaciers. Comparison of reconstructed temperatures with the instrumental record suggests that our proxy record faithfully records decadal to century scale trends in temperature. The largest temperature decline over the last 1,500 years was a decrease of 2.5 ± 0.3 °C during the Little Ice Age (LIA), reaching lowest temperatures during the mid-17th century, and is broadly consistent with terrestrial temperature reconstructions throughout the tropics and the higher latitudes. The structure and timing of temperature changes at Laguna Chingaza are remarkably similar to recent terrestrial temperature reconstructions from elsewhere in the tropics, including sites in the tropical Pacific and equatorial Africa, suggesting that these changes are widespread in the tropics. Together, these records suggest that warming over the last few decades is unprecedented over the last 1,500 years, including the Medieval Climate Anomaly (800-1150 AD). Comparison of these temperature changes with records of Andean glacier limits suggests that temperature is the dominant driver of glacial retreat, particularly over the past few decades. Additionally, paleotemperatures inferred from LIA and recent glacial equilibrium line altitudes (ELAs) underestimate past changes in temperature when compared with brGDGTs reconstructions, suggesting that changes in precipitation complicate the use of glacier ELAs to reconstruct past temperatures. The coupling of temperature and ice extent in South America suggests that with projected future warming, the health of tropical glaciers could be in jeopardy, significantly impacting the communities and ecosystems that depend on them. / text