Assessing Depression and Attributional Styles as Determinants of Engagement in Digital Behavior Change Interventions

Digital behavior change interventions are capable of promoting significant change in health behaviors, but often suffer high disengagement and nonusage dropout. The purpose of this dissertation was to determine if depressive symptoms or pessimistic attributional styles negatively influenced proximal engagement behaviors among users of study websites or smartphone apps. Three different interventions were assessed across the three Aims. Aim One used structural equation modeling to determine if CES-D scores were indirectly associated with 6-month weight change outcomes through mediating latent constructs for engagement and adherence among adults (N=338) in a 12-month eHealth intervention. CES-D scores were negatively associated with both engagement and adherence, which were positively associated with 6-month weight loss, contributing to a significant negative indirect effect. Additionally, CES-D scores predicted significantly higher risk of users disengaging from the website over time. Aim Two applied mixed effects modeling to estimate participants’ (N=52) likelihood of viewing messages as a function of the number of goals they were currently failing in an mHealth microrandomized pilot, and a generalization of log-linear regression analysis to assess the likelihood of reading consecutive program messages following receipt of goal-discrepant messages, and if these relationships were moderated by CES-D scores, net of other covariates. The more goals participants were failing, the less likely they were to read any program messages sent. Additionally, receipt of goal discrepant messages was associated with a significantly lower likelihood of participants reading the next program message sent, compared to neutral messages or no message; however, these relationships did not appear to be influenced by CES-D scores. Aim Three compared the CES-D indicating depressive symptoms and the DAQ indicating pessimistic attributional styles for their potential to predict lower engagement following goal-discrepant feedback using mixed effects regression among a subsample of participants (N=132) in an ongoing mHealth intervention. Both scales were associated with lower odds of reading the next program message sent following receipt of goal-discrepant feedback, and higher odds of disengagement, but no effects on app page views between messages. These results provide some support for tailoring message content based on psychological indicators to reduce negative influences on program engagement.Doctor of Philosoph

Global change and the future of avian diversity

Biodiversity in the Anthropocene is declining at an alarming rate. Both ecological and evolutionary components of biodiversity are critical for determining the processes that have led to the biogeographic patterns of biodiversity we see today, as well as understanding the impacts of global change on communities and ecosystems. Here, I use unique trait datasets, and phylogenetic relationships, to explore extant and future patterns of avian biodiversity. In the first part of this Thesis, I interrogate global-scale biogeographic patterns of avian diversity, by using avian traits to reveal how species fill and expand niche space. I show that evolutionary history, rather than contemporary environment, drives patterns of extant global trait diversity. In the second part I assess the impact of species extinctions on this diversity and examine whether the loss of trait and phylogenetic diversity is greater than predicted by species loss alone. I find that not only is trait homogenisation expected across the whole Avian class, but that this is borne out spatially, with the majority of biome and ecoregion assemblages predicted to experience a significant reduction in morphological diversity with important consequences for ecosystem functioning. Finally, given that Anthropogenic land-use change is experienced most intensely in the tropics, I move from a broad to local spatial scales, and highlight that the protection of secondary forests should be seen as a priority for the conservation of tropical biodiversity. Overall, this Thesis helps to further our understanding of the origins of biodiversity, and in the face of global change, its conservation

Addressing the false positive MRI phenotype in prostate cancer diagnosis and management

Multiparametric magnetic resonance imaging (mpMRI) is set to dominate the diagnosis and active surveillance of prostate cancer. However, false positive MRIs confound clinical decision-making and prompt unwarranted biopsies that carry morbidity risks. This is a significant issue: NICE currently recommends pre-biopsy MRI in men with suspected prostate cancer and, as 80,000 patients undergo biopsy every year in England and Wales, between 12,600 to 17,300 are expected to be biopsy-negative. Furthermore, MRI in active surveillance (AS) is strongly recommended by NICE for risk stratification at baseline and for the detection of oncological progression. However, MRI-based AS is new and it is still unknown when observed dynamic MRI changes reflect true transition to clinically significant disease. Recognising this on imaging is important for optimising clinical decisions and reducing the overall number of biopsies during AS. In this thesis it will be shown that MRI lesions seen in biopsy-naïve individuals with clinically significant cancer are larger, more conspicuous and more diffusion-restricted compared to phenotypes seen in men without significant disease. Furthermore, in men with indeterminate MRI phenotypes, PSA density and index lesion ADC predict the presence of significant cancer through a logistic regression model (mean cross-validated AUC: 0.77 [95% CI: 0.67–0.87]) and could help men avoid unnecessary biopsies. It is also shown that false positive MRI phenotypes in such men arise in prostatic regions with increased overall cellularity and expanded epithelium, while assuming either focal or diffuse patterns. In addition, it is demonstrated that MRI-based AS can be safely used to monitor men with insignificant disease, as approximately 84.7% (95% CI: 82.0–87.6) and 71.8% (95% CI: 68.2–75.6) of patients remain on AS at 3 and 5 years (with those with MRI-visible disease at baseline exiting earlier). Finally, it will be shown that progressing MRI lesions during imaging-based AS have two distinct histological phenotypes: one characterised by increased overall cellularity and expansion of epithelial areas (typically seen with transition to higher grade cancer) and another by moderate, standalone stromal hyperplasia seen in cases of pathological stability, not ideally requiring biopsy. This finding could lead to the development of radiological metrics that distinguish the two progression types and spare men from unnecessary biopsies in AS contexts

Aerobic Exercise for the Promotion of Healthy Aging: Changes in Brain Structure Assessed with New Methods

As the proportion of older individuals in the population increases, so does the scientific concern surrounding age-related deterioration of brain tissue and related cognitive decline. One modifiable lifestyle factor of interest in the pursuit to slow or even reverse age-related brain atrophy is aerobic exercise. A number of studies have already demonstrated that aerobic exercise in older age can induce maintenance (i.e., reduction of loss) of both gray and white matter volume, particularly in the frontal regions of the brain, which are vulnerable to shrinkage in older age. Other magnetic resonance imaging (MRI)-based techniques, such as quantitative MRI and diffusion-weighted MRI, have been used to measure age-related deterioration of gray and white matter integrity in both voxel-wise analyses as well as on the latent level, but whether these negative changes can be ameliorated through exercise has yet to be shown. The current dissertation includes three papers which used a number of both established and novel MRI-based metrics to quantify changes in brain tissue integrity resulting from aging, as well as to investigate whether these changes can be ameliorated through aerobic exercise. In Paper I (Wenger et al., 2022), we tested the reliability of quantitative MRI measures, namely longitudinal relaxation rate, effective transverse relaxation rate, proton density, and magnetization transfer saturation, by measuring them in a two-day, four-session design with repositioning in the scanner. Using the intra-class effect decomposition model, we found that magnetization transfer saturation could reliably detect individual differences, validating its use to investigate changes in brain structure longitudinally, as well as correlations with other variables of interest, such as change in cardiovascular fitness. In Paper II (Polk et al., 2022), we tested the effects of aerobic exercise on a latent factor of gray-matter structural integrity, comprising observed measures of gray-matter volume, magnetization transfer saturation, and mean diffusivity, in regions of interest that have previously shown volumetric effects of aerobic exercise. We found that gray-matter structural integrity was maintained in frontal and midline regions, and that change in gray-matter structural integrity in the right anterior cingulate cortex was positively correlated with change in cardiovascular fitness within exercising participants. These results suggest a causal relationship between aerobic exercise, cardiovascular fitness, and gray-matter structural integrity in this region. In Paper III (Polk et al., 2022), we tested the effects of aerobic exercise on white matter integrity, measured with both established and recently developed metrics. We were able to replicate findings from a previous study on the effects of aerobic exercise on white matter volume, and we also found change-change correlations between white matter volume and cardiovascular fitness as well as between white matter volume and performance on a test of perceptual speed. We also found unexpected exercise-induced changes in the diffusion weighted imaging-derived metrics of fractional anisotropy, mean diffusivity, fiber density, and fiber density and cross-section. Specifically, we found increases (or decreases in the case of mean diffusivity) within control participants and decreases (or increases in mean diffusivity) in exercisers. Furthermore, we found that percent change in fiber density and fiber density and cross-section correlated negatively with percent change in both cardiovascular fitness and cognitive performance. This casts doubt on the functional interpretation of these measures and suggests that the “more is better” principle may not be universally applicable when investigating age-related and exercise-induced changes in white matter integrity. In sum, this dissertation showed that regular at-home aerobic exercise, which may be more accessible for older individuals than supervised exercise, can be an effective tool to ameliorate age-related decreases in a latent measure of gray-matter structural integrity as well as white matter volume. It also illuminated potential limitations of other measures of white matter integrity in the context of aging and aerobic exercise, and calls for further research into these novel measures, especially when considering functional outcomes such as cognitive performance

Ischaemia reperfusion injury in subclinical chronic kidney disease: Protection targeting mitochondria

Background and aims: sCKD is a stage of chronic kidney disease is where the serum creatinine is normal despite extensive cortical damage. This stage is usually unrecognised but likely precedes most overt CKD. To date, no pharmacological treatments for prevention or amelioration of IRI induced renal injury on a background of sCKD has been studied. Using an established rodent model of sCKD, we investigated the efficacy of mitochondrial protection by NAD+ boosting with either nicotinamide (NAM) or nicotinamide riboside (NR) in combination with a plastiquinone conjugated to membrane penetrating rhodamine cation, SkQR1, in ameliorating ischaemia-reperfusion-induced, IRI, acute kidney injury, AKI. In order to validate gene expression, we initially determined the optimum housekeeper gene for reverse transcriptase quantitative PCR (RT-qPCR) studies in the rodent animal model. Methods: The optimum housekeeper gene was determined using RNA from kidney samples from 56 Sprague Dawley (SD) rats with nephrotoxic or IRI kidney injury or a combination of insults as well as control rats. Ten candidate reference genes were investigated and a 3-way mixed effects model was developed for analysis. sCKD was established using an adenine model in 5 groups (N=6) of SD rats. Efficacy of preventative treatment against IRI-AKI on a background of sCKD was determined in these groups receiving either none, single or combined rescue treatment with NAM, NR or SkQR1. A further 18 weight-matched control rats were sham operated with or without background sCKD. Kidney function and functional reserve (KFR) were measured by fluorescein isothiocyanate (FITC) sinistrin clearance and histology and nephroprotection pathways were compared up to 6 weeks post IRI. Results: The optimum housekeeper gene combination for RT-qPCR studies was the geometric mean of PABN1×ACTB. KFR was lower in sCKD consistent with histology at day 56 despite a normal serum creatinine. Treatment with NAM, NR and SkQR1 protected KFR, reduced histological damage, maintained mitochondrial density, endothelial density and renal blood volume by study endpoint (day 98). Modulation of Sirtuin 1, nuclear localised peroxisome proliferator-activated receptor-gamma coactivator 1 alpha and nuclear factor erythroid 2–related factor 2 pathway was the likely mechanism of nephroprotection using these preventative treatments. Conclusion: Treatment with NAM or NR and SkQR1 protect against IRI in the context of prior sCKD

Rapid biodiversity monitoring of freshwater ponds using environmental DNA : traversing the aquatic-terrestrial boundary in pondscapes

Environmental DNA (eDNA) analysis is transforming biodiversity monitoring in aquatic ecosystems with immense potential to inform their conservation and management. eDNA analysis is rapid, non-invasive, cost-efficient, and often more accurate and sensitive than conventional monitoring tools for single species detection and community survey. Ponds are extremely diverse yet understudied freshwater habitats that require novel tools to enable comprehensive, systematic, long-term monitoring. eDNA monitoring could radically improve assessments of pond biodiversity, but the applications and methodical constraints of this tool in ponds are largely unexplored. In this thesis, eDNA analysis was examined as a tool for monitoring biodiversity associated with ponds, including aquatic, semi-aquatic, and terrestrial taxa. eDNA analysis using metabarcoding was shown to have comparable detection sensitivity for Triturus cristatus to targeted eDNA analysis using quantitative PCR, depending on species detection thresholds applied. Using the community data generated by this method comparison, eDNA metabarcoding was validated as a tool for ecological hypothesis testing, specifically biotic and abiotic determinants of T. cristatus and vertebrate species richness. A novel eDNA assay was designed and validated for targeted survey of the threatened Carassius carassius, a fish species characteristic of ponds. Furthermore, eDNA metabarcoding was compared to established methods of freshwater invertebrate assessment, and all methods used to evaluate the impact of stocking C. carassius for conservation purposes. Finally, eDNA metabarcoding was vindicated as a tool to monitor semi-aquatic and terrestrial mammals associated with ponds, and investigate the spatiotemporal distribution of their eDNA signals in these water bodies as a function of behaviour. These results combined emphasise the biological and scientific importance of ponds, and the prospects of eDNA analysis - targeted and community approaches - for enhanced conservation, management, monitoring, and research of these valuable ecosystems

Evolutionary genomics : statistical and computational methods

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward

International Conference on Civil Infrastructure and Construction (CIC 2020)

This is the proceedings of the CIC 2020 Conference, which was held under the patronage of His Excellency Sheikh Khalid bin Khalifa bin Abdulaziz Al Thani in Doha, Qatar from 2 to 5 February 2020. The goal of the conference was to provide a platform to discuss next-generation infrastructure and its construction among key players such as researchers, industry professionals and leaders, local government agencies, clients, construction contractors and policymakers. The conference gathered industry and academia to disseminate their research and field experiences in multiple areas of civil engineering. It was also a unique opportunity for companies and organizations to show the most recent advances in the field of civil infrastructure and construction. The conference covered a wide range of timely topics that address the needs of the construction industry all over the world and particularly in Qatar. All papers were peer reviewed by experts in their field and edited for publication. The conference accepted a total number of 127 papers submitted by authors from five different continents under the following four themes: Theme 1: Construction Management and Process Theme 2: Materials and Transportation Engineering Theme 3: Geotechnical, Environmental, and Geo-environmental Engineering Theme 4: Sustainability, Renovation, and Monitoring of Civil InfrastructureThe list of the Sponsors are listed at page 1