International Telemetering Conference Proceedings / October 18-21, 2004 / Town & Country Resort, San Diego, California / Because all video compression schemes introduce artifacts into the compressed video images, degradation occurs. These artifacts, generated by a wavelet-based compression scheme, will vary with the compression ratio and input imagery, but do show some consistent patterns across applications. There are a number of design trade-offs that can be made to mitigate the effect of these artifacts. By understanding the artifacts introduced by video compression and being able to anticipate the amount of image degradation, the video compression can be configured in a manner optimal to the application under consideration in telemetry.

Abstract The primary objective of this study was to determine the isotopic variation of the sedimentary organic carbon (£_13Corg) in the sediment samples of the gravity core 17950-2. The core was retrieved from the northern South China Sea during ¡§Monitoring Monsoon¡¨ cruise onboard R/V Sonne in 1994. The £_13Corg data were further compared with other proxies, such as foraminiferal £_18O and £_13C, TOC wt%, and CaCO3 wt% to decipher the late Quaternary evolution of climate change from the South China Sea for the last 200 ky. Prior to 65 ka, the £_13Corg, calibrated TOC wt% (TOC ex wt%), and Terrestrial wt% fluctuated synchronously. The increased TOC ex wt% and Terrestrial wt% were consistent with the enriched £_13Corg, implying the enhanced productivity due to the increased terrestrial input. The enhanced glacial productivity could have been caused by the increase in terrestrial input and mixed layer by wind-driven upwelling. The South China Sea, however, is a nitrogen-limited basin. The enhanced nitrogen fixation induced by increased dust input can also be a potential candidate that is responsible for the elevated productivity during glacials. Theoretically, the £_13Corg is utilized as a powerful tool to determine the carbon ratio between marine and terrestrial origin in the shelf area and reconstruct the pCO2 history of the low-productivity open ocean. According to TOC ex wt%, the productivity of the northern South China Sea were significantly higher in glacials than interglacials. Therefore, the variation of pCO2 of the northern South China Sea can not be reconstructed properly based on £_13Corg record solely .

In ihrer stammesgeschichtlichen Entwicklung haben, neben Säugetieren, Vögeln und Insekten, auch Froschlurche ein umfangreiches Repertoire an akustischen Signalen zur Identifizierung arteigener Individuen und anlocken potenzieller Paarungspartner entwickelt. Diese sogenannten Anzeigerufe sind dabei für jede Art einzigartig. Beobachtungen zeigen aber, dass es neben dieser Artspezifität, auch Ähnlichkeiten in den Anzeigerufen zwischen nicht näher verwandten Arten existieren. Es stellt sich daher die Frage woher diese Ähnlichkeiten stammen. Stellen diese Ähnlichkeiten eine Anpassung an die Bedingungen der Lebensräume dar (konvergente Evolution) oder sind sie ein Ergebnis der stammesgeschichtlichen Entwicklung der Arten (divergente Evolution). Zur Klärung dieser Frage habe ich Anzeigerufe von ca. 1500 Arten aus den unterschiedlichsten Lebensräumen unseres Planten gesammelt und ausgewertet. Eine Korrelation der gemessenen akustischen Eigenschaften (z. B. dominante Frequenz) mit der Phylogenie der Amphibien sollte dabei klären, inwieweit die Phylogenie mit diesen akustischen Eigenschaften verknüpft ist. Vergleiche zwischen verschiedenen Kategorien aus Morphologie, Verhalten und Lebensraum in Bezug auf die akustischen Eigenschaften wiederum sollten mögliche Anpassungen der akustischen Eigenschaften herausstellen. Es stellte sich am Ende heraus, dass einige akustische Eigenschaften (z. B. dominante Frequenz) sowohl ein Ergebnis einer divergenten Evolution sind, als auch einer konvergenten Evolution. Zusätzlich war es mir möglich die Anzeigerufe in separate Gilden einzuteilen, die ähnliche strukturellen Eigenschaften aufweisen. Gilden in die Arten unabhängig von ihren verwandtschaftlichen Beziehungen eingeordnet werden können. Ein Werkzeug was Vergleiche zwischen Arten anhand ihrer Akustik vereinfacht und die Möglichkeit gibt zu verstehen wie Arten die Bedingungen ihrer Lebensräume auf ähnliche akustische Weise nutzen. / Beside mammals, birds and insects also anurans developed at their evolutionary history a wide repertoire of acoustic signals to identify conspecific individuals and to attract possible mating partners. These so-called advertisement calls are unique to every single species. However, beside this species-specific uniqueness we can also observe astonishing similarities among advertisement calls of not close related species. Therefore, there is the question of where these similarities came from. Are these similarities adaptations to conditions to similar biology’s and environments and so a result of a convergent evolution or these similarities arose by the anuran phylogeny and represent a divergent evolution? To answer these questions I collected and measured advertisement calls of ca. 1500 anuran species around the globe of different living habitats. A correlation between phylogeny and acoustic properties (e.g. dominant frequency) could show the influence of the phylogeny at the evolved acoustic traits. Comparisons among different categories of morphology, behaviour and habitat concerning the acoustic traits could show possible adaptations. The result of my research showed that some structural and spectral properties are a consequence of the phylogenetic history as well as an adaptation to conditions of biology and environment. Both, the divergent and the convergent evolution place a role in these cases. Additional I managed to introduce a system to order anuran advertisement calls into distinct guilds. These guilds show how different species uses their acoustic properties in a similar matter. An additional tool to make comparisons among species easier and to understand how anuran uses environments in a similar acoustic way.

In 2009, two large genome wide association studies (GWAS) found associations between common single nucleotide polymorphisms (SNPs) at three loci (CLU, PICALM and CR1) and Alzheimer’s disease (AD) risk. The causal variants underlying these associations and how these impact on AD susceptibility remain unclear. Target enrichment and next generation sequencing (NGS) were used to completely resequence the three associated loci in 96 AD patients in an attempt to uncover potentially causative and rare variants that may explain the observed association signals. A pipeline was developed for the handling of pooled NGS data following a comparison of several different combinations of programs. 33 exonic SNPs were found within the three genes, along with over 1000 non-coding variants. To identify the variants most likely to be affecting AD risk, a two pronged approach was adopted. The variants were imputed in a large case-control cohort (2067 cases, 7376 controls) to test for association with AD, and the likely functional consequences of the variants were assessed using in silico resources. Several of the analysed variants showed suggestive or significant association with AD in the imputed data, and/or were predicted to have consequences on the function or regulation of the genes, suggesting avenues for future research in AD genetics. The whole method of pooled, targeted NGS and prioritisation using imputed data for association testing and in silico resources for functional analysis represents a new strategy for tracking down the illusive causation of GWAS signals.

This thesis explores doctors’ and medical students’ attitudes toward older patients in UK hospital settings. There have been regular and strong assertions in the grey literature and the news media that negative attitudes toward older patients may contribute to the inequality of healthcare service provision and treatment for older patients, compared to younger patients (those aged under 65 years), in UK hospital settings. However, much of the evidence does not investigate or explore these attitudes using a theoretical framework of attitudes outlined in the scientific research literature. This thesis comprises three studies. Firstly, a systematic search and review (Study 1) was undertaken in order to determine how attitudes toward older patients had been explored to date in the English-language, scientific research literature. Results demonstrated that previous studies had focused on attitude measurement rather than exploring the content of attitudes toward older patients. In fact, there was little evidence that previous research had ever explored these attitudes, despite the number of studies attempting to measure them. Furthermore, the review indicated the lack of research emanating from UK settings. In Study 2, attitudes toward older patients and their care were explored in twenty-five in-depth interviews with medical students and doctors in a UK NHS Hospital trust. Data were thematically analysed and findings indicated that attitudes toward older patients and their care could be conceptualised as: (1) attitudes toward older patients and their healthcare needs, and (2) attitudes toward providing care for older patients (e.g. the social and organisational barriers and facilitators). Within these two domains, the themes, subthemes and nodes, which represent attitude content with increasing levels of specificity, are presented. The findings from Study 2 mark one of the first attempts in this research area to explore and describe the content of attitudes in line with a theoretical framework of attitudes. The final study, Study 3, explored the devaluation and unpopularity of the specialty of geriatric medicine as a future career choice in a sample of junior doctors. Having identified, in Study 2, that geriatric medicine was not highly regarded in a range of doctors and medical students, Study 3 aimed to ascertain whether this was due to the organisational and working environment or due to older patient-related factors in a recently-qualified sample of doctors. The findings indicated that organisational and work-related factors serve to discourage junior doctors from pursuing geriatric medicine, rather than factors related to the older patients treated on geriatric wards. This thesis contributes to the research literature in two main ways. Firstly, this thesis outlines the research gaps in the worldwide English-language scientific research. Secondly, this thesis presents a conceptualisation of doctors’ and medical students’ attitudes toward older patients in a UK hospital setting. Importantly, this conceptualisation provides research that is relevant to UK settings and is in line with a theoretical framework of attitudes that has been identified from the scientific research literature. The strengths and limitations of this work are discussed.

Alzheimer’s disease (AD) is the commonest form of dementia and is characterised with neuropathological hallmarks such as aggregated amyloid plaques and hyper-phosphorylated tau protein. One type of AD is autosomal dominant AD (ADAD) which is caused by highly penetrant variants in one of three genes (APP, PSEN1 and PSEN2), other cases of AD are described as sporadic and can have a late onset of disease symptoms (> 65 years of age) or early onset (≤ 65 years or age). Late-onset Alzheimer’s disease (LOAD) is estimated to be 70% heritable and is common. Conversely sporadic early-onset Alzheimer’s disease (sEOAD) is estimated to 90% heritable but is relatively rare. The difference in prevalence between the two types of AD has resulted in genome wide association studies focusing on LOAD with sEOAD receiving little attention. Here we use an Illumina human exome genotyping chip customised with neurodegenerative markers (NeuroX) to genotype the coding region of sEOAD samples in a hope to elucidate the genetic aetiology of sEOAD. Sanger sequencing exons 16 and 17 of APP was conducted in a sEOAD cohort (n=451) to screen for variants known to cause ADAD; 9% (n=4) of the cohort were heterozygous for known causative variants and where subsequently removed from the sEOAD NeuroX genotyping data before analyses. Screening also highlighted an intronic 6bp deletion downstream of exon 17 in APP with a non-significant increased minor allele frequency (MAF) in sEOAD, however it did not appear to influence splicing of exon 17. Screening the sEOAD cohort for other variants known to cause neurodegenerative disease was conducted using the NeuroX genotyping data (n=408) which identified two samples with variants in PARK2, these variants are thought to contribute susceptibility to Parkinson’s disease (PD) suggesting these variants might elicit risk for multiple diseases. A further study with increased power would ascertain if the 6bp deletion and PARK2 variants are associated with sEOAD. Statistical analyses of the sEOAD NeuroX genotypes highlighted many variants, genes and pathways that could be contributing to susceptibility to disease; however no tests reached significance after adjusting for multiple testing. The genes most associated (PDZK1, DCLK3, SLC33A1 and BLOC1S2) appear to be biologically relevant and would be ideal candidates for further study. Additionally, just under half of the variants that are significant associated with LOAD were genotyped on the NeuroX and two of these were significantly associated with sEOAD after correcting for multiple testing (rs3851179 and rs3764650). The genotypes of all the variants highlighted would need to be verified before their functionalities were investigated further.

Late onset Alzheimer’s disease (LOAD) is the commonest form of dementia, affecting approximately 850,000 patients in the UK alone, predicted to exceed one million by 2025. The cause of LOAD is complex, but several large Genome Wide Association Studies have highlighted 21 genetic loci associated with this devastating disease and the ATP-Binding Cassette Protein, family A, member 7 (ABCA7) is one of these genetic loci. However, the exact reasons behind this association are still unknown, focusing work on identifying functional, pathogenic mutations within this locus. A total of 240 exonic variations within ABCA7 were therefore annotated in order to identify ones potentially altering the functionality of ABCA7. A total of five variants were predicted to be damaging by in silico annotation tools: rs3752233; rs59851484; rs3752237; rs114782266 and a novel mutation at genomic position 19:1056958. These were genotyped in the ARUK DNA Bank resource and three (rs59851484, rs3752239 and 19:1056958) showed tentative association with LOAD. However, lack of power in this study prevented any definitive associations from being formed. A further two variants were examined within functional cell assays. rs881768 had been predicted to affect the splicing of the ABCA7 protein and appeared to do so within minigene cellular assays. However, this did not appear to be the case when RNA from brain tissue harbouring this variation was examined. rs2020000 was examined through the dual luciferase assays, with the minor allele seeming to down regulate the reporter protein by approximately 30% (p < 0.02) in these in vitro assays. Functional variations within the ABCA7 locus do play a role in LOAD risk and improvements within functional databases and annotation programmes will assist in identifying these causative mutations, in order to put a halt to LOAD, as well as other destructive complex disorders.

Little is known about the molecular biology of late onset Alzheimer’s disease (LOAD), the most common dementia in the elderly. Genetic loci associated with LOAD have been identified through genome-wide association studies (GWAS). However, the functional variants responsible for the observed GWAS association at each of the loci remain unknown. The aim of this project was to identify and assess potential functional rare variants at three associated loci, CD2AP, EPHA1 and CD33. Target enriched, pooled sequencing of 96 post-mortem confirmed LOAD patient samples was used to identify 1273 variants within the three GWAS loci. Variants were prioritised using a combination of in silico functional annotation and putative disease association. Disease association was assessed through comparison to an independent, imputed LOAD GWAS dataset (2067 cases, 7376 controls). 18 coding and untranslated region variants and 9 noncoding variants were prioritised for further investigation. Potential splicing variants in CD2AP (6:47544253A > G) and EPHA1 (rs6967117) were assessed using minigene assays, although neither were found to influence splicing products in vivo. Five untranslated variants from the three genes and a frameshift variant in CD33 (rs201074739) were assessed for potential cis-regulatory consequences using allelic expression imbalance in brain tissues and B-lymphoblast cell lines. Only the frameshift variant displayed significant allelic expression imbalance and was found to be targeted for nonsense-mediated decay. None of the prioritised variants investigated were both functional and significantly associated with LOAD. However, pooled next generation sequencing using target enrichment successfully identified potential functional rare variants in CD2AP, EPHA1 and CD33. Rare variants do have a role to play in late onset Alzheimer’s disease. With the development of additional functional databases and improvements imputing rare variants from GWAS datasets, the combined prioritisation strategy used in this thesis will be useful for similar studies investigating causal GWAS variants.

No description available.

Groundwater tracing studies have shown a well-developed conduit system in the karst aquifer beneath the Buffalo Creek Watershed of Carter County, TN. Groundwater can quickly travel beneath topographic divides, transporting contaminants. Using GIS and field reconnaissance, two sites were selected for a two phase dye trace study. In May-June 2016 groundwater resurgences were located using activated carbon samplers, and in October-December 2016 flow velocities were measured using ISCO automatic water samplers. In study 1, a stream sinking in the back of Carter Saltpeter Cave was traced to its resurgence at Cave Springs Cave. In study 2, the dye mass centroid passed the resurgence 23.2 hours after injection. During study 1, dye injected into a sinkhole near the headwaters of Toll Branch rapidly diffused into multiple conduits. In study 2, dye from the Toll Branch site was not recovered, indicating that groundwater follows different flow paths dependent on water table level.