18,592 research outputs found
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The Epidemiology and Genetic Architecture of Vitamin D Deficiency in African Children
Vitamin D deficiency is a common public health problem worldwide. However, little is known about the epidemiology of vitamin D deficiency in Africa. In this thesis, I aimed to determine: 1) the prevalence of and risk factors associated with vitamin D deficiency in studies conducted in Africa; 2) the prevalence and predictors of vitamin D deficiency in African children; 3) the association between vitamin D and iron deficiency in African children; and 4) genetic variants that influence vitamin D status in Africans.
In a systematic review and meta-analyses of previous vitamin D studies in Africa, the average prevalence of low vitamin D status was 18.5%, 34.2% and 59.5% using cut-offs of 25-hydroxyvitamin D (25(OH)D) levels of <30 nmol/L, <50 nmol/L and <75 nmol/L, respectively. Populations at risk of vitamin D deficiency included newborns, women, and people living in high latitudes or urban areas.
In an epidemiological study of young children living in Africa, the prevalence of low vitamin D status was 0.6%, 7.8% and 44.5% using cut-offs of 25(OH)D levels of GC2 variant of the group-specific component (GC) gene, which encodes vitamin D binding protein.
Vitamin D deficiency was also associated with 80% higher odds of iron deficiency in these children. Adjusted regression models revealed that vitamin D deficiency was associated with higher ferritin and hepcidin levels suggesting lower iron status, and reduced sTfR and transferrin levels and increased TSAT and serum iron levels suggesting improved iron status.
Genome-wide association study (GWAS) in Africans revealed genetic variants that influence vitamin D status in vitamin D metabolism genes: DHCR7/NADSYN1, CYP2R1 and GC. However, the majority of SNPs from previous European GWASs did not replicate in the current GWAS.
Findings from this thesis indicate that vitamin D deficiency is prevalent in many African populations and should be considered in public health strategies in Africa
Learning to listen: downstream effects of listening training on employees' relatedness, burnout, and turnover intentions
Abstract: The present work focuses on listening training as an example of a relational human resource practice that can improve human resource outcomes: Relatedness to colleagues, burnout, and turnover intentions. In two quasiâfield experiments, employees were assigned to either a group listening training or a control condition. Both immediately after training and after 3 weeks later, receiving listening training was shown to be linked to higher feelings of relatedness with colleagues, lower burnout, and lower turnover intentions. These findings suggest that listening training can be harnessed as a powerful human resource management tool to cultivate stronger relationships at work. The implications for Relational Coordination Theory, HighâQuality Connections Theory, and SelfâDetermination Theory are discussed
Image classification over unknown and anomalous domains
A longstanding goal in computer vision research is to develop methods that are simultaneously applicable to a broad range of prediction problems. In contrast to this, models often perform best when they are specialized to some task or data type. This thesis investigates the challenges of learning models that generalize well over multiple unknown or anomalous modes and domains in data, and presents new solutions for learning robustly in this setting.
Initial investigations focus on normalization for distributions that contain multiple sources (e.g. images in different styles like cartoons or photos). Experiments demonstrate the extent to which existing modules, batch normalization in particular, struggle with such heterogeneous data, and a new solution is proposed that can better handle data from multiple visual modes, using differing sample statistics for each.
While ideas to counter the overspecialization of models have been formulated in sub-disciplines of transfer learning, e.g. multi-domain and multi-task learning, these usually rely on the existence of meta information, such as task or domain labels. Relaxing this assumption gives rise to a new transfer learning setting, called latent domain learning in this thesis, in which training and inference are carried out over data from multiple visual domains, without domain-level annotations. Customized solutions are required for this, as the performance of standard models degrades: a new data augmentation technique that interpolates between latent domains in an unsupervised way is presented, alongside a dedicated module that sparsely accounts for hidden domains in data, without requiring domain labels to do so.
In addition, the thesis studies the problem of classifying previously unseen or anomalous modes in data, a fundamental problem in one-class learning, and anomaly detection in particular. While recent ideas have been focused on developing self-supervised solutions for the one-class setting, in this thesis new methods based on transfer learning are formulated. Extensive experimental evidence demonstrates that a transfer-based perspective benefits new problems that have recently been proposed in anomaly detection literature, in particular challenging semantic detection tasks
Political Islam and grassroots activism in Turkey : a study of the pro-Islamist Virtue Party's grassroots activists and their affects on the electoral outcomes
This thesis presents an analysis of the spectacular rise of political Islam in Turkey. It has two aims: first to understand the underlying causes of the rise of the Welfare Party which -later became the Virtue Party- throughout the 1990s, and second to analyse how grassroots activism influenced this process. The thesis reviews the previous literature on the Islamic fundamentalist movements, political parties, political party systems and concentrates on the local party organisations and their effects on the party's electoral performance. It questions the categorisation of Islamic fundamentalism as an appropriate label for this movement. An exploration of such movements is particularly important in light of the event of 11`x' September. After exploring existing theoretical and case studies into political Islam and party activism, I present my qualitative case study. I have used ethnographic methodology and done participatory observations among grassroots activists in Ankara's two sub-districts covering 105 neighbourhoods. I examined the Turkish party system and the reasons for its collapse. It was observed that as a result of party fragmentation, electoral volatility and organisational decline and decline in the party identification among the citizens the Turkish party system has declined. However, the WP/VP profited from this trend enormously and emerged as
the main beneficiary of this process. Empirical data is analysed in four chapters, dealing with the different aspects of the Virtue Party's local organisations and grassroots activists. They deal with change and continuity in the party, the patterns of participation, the routes and motives for becoming a party activist, the profile of party activists and the local party organisations. I explore what they do and how they do it. The analysis reveals that the categorisation of Islamic fundamentalism is misplaced and the rise of political Islam in Turkey cannot be explained as religious revivalism or the rise of Islamic fundamentalism. It is a political force that drives its strength from the urban poor which has been harshly affected by the IMF directed neoliberal economy policies. In conclusion, it is shown that the WP/VP's electoral chances were significantly improved by its very efficient and effective party organisations and highly committed grassroots activists
Unraveling the effect of sex on human genetic architecture
Sex is arguably the most important differentiating characteristic in most mammalian
species, separating populations into different groups, with varying behaviors, morphologies,
and physiologies based on their complement of sex chromosomes, amongst other factors. In
humans, despite males and females sharing nearly identical genomes, there are differences
between the sexes in complex traits and in the risk of a wide array of diseases. Sex provides
the genome with a distinct hormonal milieu, differential gene expression, and environmental
pressures arising from gender societal roles. This thus poses the possibility of observing
gene by sex (GxS) interactions between the sexes that may contribute to some of the
phenotypic differences observed. In recent years, there has been growing evidence of GxS,
with common genetic variation presenting different effects on males and females. These
studies have however been limited in regards to the number of traits studied and/or
statistical power. Understanding sex differences in genetic architecture is of great
importance as this could lead to improved understanding of potential differences in
underlying biological pathways and disease etiology between the sexes and in turn help
inform personalised treatments and precision medicine.
In this thesis we provide insights into both the scope and mechanism of GxS across the
genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK
Biobank. We found small yet widespread differences in genetic architecture across traits
through the calculation of sex-specific heritability, genetic correlations, and sex-stratified
genome-wide association studies (GWAS). We further investigated whether sex-agnostic
(non-stratified) efforts could potentially be missing information of interest, including sex-specific trait-relevant loci and increased phenotype prediction accuracies. Finally, we
studied the potential functional role of sex differences in genetic architecture through sex
biased expression quantitative trait loci (eQTL) and gene-level analyses.
Overall, this study marks a broad examination of the genetics of sex differences. Our findings
parallel previous reports, suggesting the presence of sexual genetic heterogeneity across
complex traits of generally modest magnitude. Furthermore, our results suggest the need to
consider sex-stratified analyses in future studies in order to shed light into possible sex-specific molecular mechanisms
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Evaluation of a Remote Implementation of the Well-Being Promotion Program with Middle School Students during COVID-19
The COVID-19 pandemic and pivot to emergency remote teaching changed the way in which many students access school-based mental health interventions. Furthermore, the effects of the pandemic heightened distress and decreased life satisfaction amongst many youth, increasing the need for schools to provide targeted mental health supports (Lazarus et al, 2021; Magson et al., 2021). Empirically supported Tier 2 mental health interventions exist (i.e., the Well-Being Promotion Program; Suldo, 2016), but little is known about how these interventions can be adapted and feasibly implemented in remote school contexts. This retrospective case study evaluated the implementation of a remote version of the Well-Being Promotion Program, a targeted positive psychology intervention, with eighth grade students during the COVID-19 pandemic. The study aimed to (1) to describe the co-design process through which a research-practice partnership modified the WBPP for remote delivery and (2) to explore the implementation strategies that influenced the feasibility of implementing the resulting digital version of the WBPP. The study used qualitative data (e.g., meeting notes, interviews and written feedback from providers, students, and caregivers) and quantitative data (e.g., pre-/post-measures, intervention integrity, attendance) to evaluate the co-design process and the feasibility of the adapted WBPP. Through co-design, the intervention was modified to be facilitated via videoconference, to use digital versions of WBPP materials, to use email to share with caregivers the handouts and a recorded version of the information session, to add additional sessions for data collection, and to adapt language to align with school vernacular. Using reflexive thematic analysis (Braun & Clarke, 2006; Braun et al., 2019), themes were constructed from the data to provide insight into the implementation strategies used by the research-practice partnership to influence feasibility. Findings suggest that (a) maintaining the structure of the WBPP, (b) using technology for remote implementation, (c) collaborating through the research-practice partnership, and (d) recognizing the effectiveness of intervention efforts influenced the feasibility of the remote implementation. Lessons learned from this case study suggest that research-practice partnerships can be critical for influencing the feasibility of intervention implementation in local school contexts, especially during novel situations such as the COVID-19 pandemic
Identification of Hindbrain Neural Substrates for Motor Initiation in the hatchling Xenopus laevis Tadpole
Animal survival profoundly depends on the ability to detect stimuli in the environment, process them and respond accordingly. In this respect, motor responses to a sensory stimulation evolved into a variety of coordinated movements, which involve the control of brain centres over spinal locomotor circuits. The hatchling Xenopus tadpole, even in its embryonic stage, is able to detect external sensory information and to swim away if the stimulus is considered noxious. To do so, the tadpole relies on well-known ascending sensory pathway, which carries the sensory information to the brain. When the stimulus is strong enough, descending interneurons are activated, leading to the excitation of spinal CPG neurons, which causes the undulatory movement of swimming. However, the activation of descending interneurons that marks the initiation of motor response appears after a long delay from the sensory stimulation. Furthermore, the long-latency response is variable in time, as observed in the slow-summating excitation measured in descending interneurons. These two features, i.e. long-latency and variability, cannot be explained by the firing time and pattern of the ascending sensory pathway of the Xenopus tadpole. Therefore, a novel neuronal population has been proposed to lie in the hindbrain of the tadpole, and being able to 'hold' the sensory information, thus accounting for the long and variable delay of swim initiation. In this work, the role of the hindbrain in the maintenance of the long and variable response to trunk skin stimulation is investigated in the Xenopustadpole at developmental stage 37/38. A multifaceted approach has been used to unravel the neuronal mechanisms underlying the delayed motor response, including behavioural experiments, electrophysiology analysis of fictive swimming, hindbrain extracellular recordings and imaging experiments. Two novel neuronal populations have been identified in the tadpole's hindbrain, which exhibit activation patterns compatible with the role of delaying the excitation of the spinal locomotor circuit. Future work on cellular properties and synaptic connections of these newly discovered populations might shed light on the mechanism of descending control active at embryonic stage. Identifying supraspinal neuronal populations in an embryonic organism could aid in understanding mechanisms of descending motor control in more complex vertebrates
Self-help/mutual aid groups in mental health : ideology, helping mechanisms and empowerment
In the last quarter of the twentieth century, self-help/mutual aid groups for mental health issues started to emerge in growing numbers, mainly in Western societies, offering and/or advocating for alternative non-traditional forms of support, and attracted the attention of many researchers and clinicians for their unique characteristics. Among the subjects of interest are typologies of groups, helping mechanisms and benefits from participation. However, there is lack of systematic research in the area and existing studies have been largely confined to the therapeutic value of these groups instead of acknowledging their
socio-political meaning and subsequent psychosocial benefits for their members like personal empowerment.
The present study was conducted during the transitional years from a Conservative to a newly elected Labour Government (1996 -1998), with subsequent policy shifts taking place in the welfare sector. The purpose of the study was to explore the potential of self-help groups as part of a broader new social movement, the service user movement, focussing on the English scene. It addressed this issue examining the relevance of a group typology based on political ideology and focus of change. To test the validity of this classification for members, a set of individual characteristics and group mechanisms as well as their change
through time were examined. The sample consisted of fourteen mental health selfhelp/mutual aid groups from London and South East England, with a variety of structural and organisational features. The methodology used was a combination of both quantitative (self-completion questionnaires) and qualitative techniques (analysis of written material, participant observation and interviews). Measurements were repeated after a one-year interval (Time 1N=67, Time 2 N=56).
Findings showed that, indeed, political ideology of self-help/mutual aid groups provided the basis of a meaningful typology and constitutes a comprehensive way of categorising them. Group ideology was related to specific helping mechanisms and aspects of personal empowerment. Specifically, conservative and combined group members reported more expressive group processes like sharing of feelings and self-disclosure, while radical group members were more empowered and optimistic. Group identification was also associated with specific helping activities and aspects of empowerment in the three group categories. The psychosocial character of group types and the beneficial outcomes for members remained stable through time. In general, prolonged participation was reflected in greater member identification with the group and resulted in improved mental wellbeing, increased social support, companionship and optimism for the future
Studies of strategic performance management for classical organizations theory & practice
Nowadays, the activities of "Performance Management" have spread very broadly in actually every part of business and management. There are numerous practitioners and researchers from very different disciplines, who are involved in exploring the different contents of performance management. In this thesis, some relevant historic developments in performance management are first reviewed. This includes various theories and frameworks of performance management. Then several management science techniques are developed for assessing performance management, including new methods in Data Envelopment Analysis (DEA) and Soft System Methodology (SSM). A theoretical framework for performance management and its practical procedures (five phases) are developed for "classic" organizations using soft system thinking, and the relationship with the existing theories are explored. Eventually these results are applied in three case studies to verify our theoretical development. One of the main contributions of this work is to point out, and to systematically explore the basic idea that the effective forms and structures of performance management for an organization are likely to depend greatly on the organizational configuration, in order to coordinate well with other management activities in the organization, which has seemingly been neglected in the existing literature of performance management research in the sense that there exists little known research that associated particular forms of performance management with the explicit assumptions of organizational configuration. By applying SSM, this thesis logically derives some main functional blocks of performance management in 'classic' organizations and clarifies the relationships between performance management and other management activities. Furthermore, it develops some new tools and procedures, which can hierarchically decompose organizational strategies and produce a practical model of specific implementation steps for "classic" organizations. Our approach integrates popular types of performance management models. Last but not least, this thesis presents findings from three major cases, which are quite different organizations in terms of management styles, ownership, and operating environment, to illustrate the fliexbility of the developed theoretical framework
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Role of Cerebrovascular Cells in Tau Processing Following Traumatic Brain Injury
Repetitive exposure to mild traumatic brain injuries (r-mTBI) sustained through the participation in contact sports can lead to chronic post-concussive symptoms and the development of neurodegenerative diseases such as Alzheimerâs disease and Chronic Traumatic Encephalopathy (CTE). A primary hallmark of CTE is the accumulation of pathogenic tau in neurons and astrocytes that surround small blood vessels in the brain. Chronic exposure to r-mTBI leads to elevated levels of extracellular tau and pathogenic tau accumulation in neurons, ultimately resulting in neuronal death. While the mechanisms responsible for pathogenic tau elimination from the brain are unclear, our prior work demonstrated that cells associated with the cerebrovasculature can interact with extracellular tau and may contribute to the removal of extracellular tau from the brain.
In this thesis, I examined the mechanisms through which the cerebrovascular cells eliminate extracellular tau from the brain and how those processes are impacted by r-mTBI. I demonstrated that brain vascular mural cells (pericytes and smooth muscle cells) progressively degenerate following exposure to r-mTBI consistent with what is observed in individuals with AD. This mural cell dysfunction impairs the ability of the cerebrovessels to interact with tau. Furthermore, I found that the cerebrovasculature can eliminate extracellular tau from the brain through caveolae-mediated endothelial transcytosis, which is impaired following chronic exposure to r-mTBI. The diminished tau transit across the blood-brain barrier following brain injury may be a contributing factor in the pathogenic tau accumulation observed in CTE.
A significant genetic risk factor for neurodegenerative diseases including AD and CTE is possession of the E4 isoform of Apolipoprotein E (ApoE). Astrocytes are the predominant source of ApoE in the brain, though there is very little understanding regarding their interactions with extracellular tau, particularly after exposure to head trauma. While the ApoE4 isoform has been associated with increased tau accumulation and cerebrovascular dysfunction after TBI, investigations into these associations are limited. The current studies found that while astrocytes internalize and release tau back into the extracellular space under normal conditions, these processes become dysfunctional following r-mTBI leading to astrocytic tau accumulation, which is further exacerbated by the ApoE4 isoform.
In summary, I identified the factors responsible for the elimination of extracellular tau across the BBB, which are impaired after head trauma. Therapeutic interventions that restore these processes may ameliorate the chronic accumulation of tau associated with neurodegenerative disease. These findings may be particularly important for individuals with the ApoE4 isoform, who are more susceptible to the pathophysiological sequelae of tau accumulation, particularly after exposure to r-mTBI
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