10,076 research outputs found

    Unraveling the effect of sex on human genetic architecture

    Get PDF
    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

    Balancing the urban stomach: public health, food selling and consumption in London, c. 1558-1640

    Get PDF
    Until recently, public health histories have been predominantly shaped by medical and scientific perspectives, to the neglect of their wider social, economic and political contexts. These medically-minded studies have tended to present broad, sweeping narratives of health policy's explicit successes or failures, often focusing on extraordinary periods of epidemic disease viewed from a national context. This approach is problematic, particularly in studies of public health practice prior to 1800. Before the rise of modern scientific medicine, public health policies were more often influenced by shared social, cultural, economic and religious values which favoured maintaining hierarchy, stability and concern for 'the common good'. These values have frequently been overlooked by modern researchers. This has yielded pessimistic assessments of contemporary sanitation, implying that local authorities did not care about or prioritise the health of populations. Overly medicalised perspectives have further restricted historians' investigation and use of source material, their interpretation of multifaceted and sometimes contested cultural practices such as fasting, and their examination of habitual - and not just extraordinary - health actions. These perspectives have encouraged a focus on reactive - rather than preventative - measures. This thesis contributes to a growing body of research that expands our restrictive understandings of pre-modern public health. It focuses on how public health practices were regulated, monitored and expanded in later Tudor and early Stuart London, with a particular focus on consumption and food-selling. Acknowledging the fundamental public health value of maintaining urban foodways, it investigates how contemporaries sought to manage consumption, food production waste, and vending practices in the early modern City's wards and parishes. It delineates the practical and political distinctions between food and medicine, broadly investigates the activities, reputations of and correlations between London's guild and itinerant food vendors and licensed and irregular medical practitioners, traces the directions in which different kinds of public health policy filtered up or down, and explores how policies were enacted at a national and local level. Finally, it compares and contrasts habitual and extraordinary public health regulations, with a particular focus on how perceptions of and actual food shortages, paired with the omnipresent threat of disease, impacted broader aspects of civic life

    The applied psychology of addictive orientations : studies in a 12-step treatment context.

    Get PDF
    The clinical data for the studies was collected at The PROMIS Recovery Centre, a Minnesota Model treatmentc entre for addictions,w hich encouragesth e membership and use of the 12 step Anonymous Fellowships, and is abstinence based. The area of addiction is contextualised in a review chapter which focuses on research relating to the phenomenon of cross addiction. A study examining the concept of "addictive orientations" in male and female addicts is described, which develops a study conductedb y StephensonM, aggi, Lefever, & Morojele (1995). This presents study found a four factor solution which appeared to be subdivisions of the previously found Hedonism and Nurturance factors. Self orientated nurturance (both food dimensions, shopping and caffeine), Other orientated nurturance (both compulsive helping dimensions and work), Sensation seeking hedonism (Drugs, prescription drugs, nicotine and marginally alcohol), and Power related hedonism (Both relationship dimensions, sex and gambling. This concept of "addictive orientations" is further explored in a non-clinical population, where again a four factor solution was found, very similar to that in the clinical population. This was thought to indicate that in terms of addictive orientation a pattern already exists in this non-clinical population and that consideration should be given to why this is the case. These orientations are examined in terms of gender differences. It is suggested that the differences between genders reflect power-related role relationships between the sexes. In order to further elaborate the significance and meaning behind these orientations, the next two chapters look at the contribution of personality variables and how addictive orientations relate to psychiatric symptomatology. Personality variables were differentially, and to a considerable extent predictably involved with the four factors for both males and females.Conscientiousness as positively associated with "Other orientated Nurturance" and negatively associated with "Sensation seeking hedonism" (particularly for men). Neuroticism had a particularly strong association with the "Self orientated Nurturance" factor in the female population. More than twice the symptomatology variance was explained by the factor scores for females than it was for males. The most important factorial predictors for psychiatric symptomatology were the "Power related hedonism" factor for males, and "Self oriented nurturance" for females. The results are discussed from theoretical and treatment perspectives

    Listening to Rivers: Using sound to monitor rivers

    Get PDF
    From a babbling brook to a thunderous torrent, a rivers' soundscape can be described by many onomatopoeic words. Using sound produced sub-aerially by a river to calculate its stage is an entirely novel idea, designed to be used in an environment that is seldom monitored, headwater catchments. In these environments it is difficult to use traditional methods of automatic stage gauging, such as pressure transducers and ultrasonic depth monitors. I propose a cost-effective, simple to install sound monitor which can be simply placed beside a river that is making a noise. I develop a method of how to take the tempest that is river sound and filter it to a usable component using data collected from around the North East of England during Storm Ciara and Dennis, 2020. Understanding where river sound is generated from and the mechanisms behind it are key to developing sound monitoring which is why I use an experiment at a white water course to investigate the link between sound and river topography. Using an artificial channel and obstacles I investigate the link between obstacle height and configuration on the production of sound. To use river sound as a proxy for river stage, there has to be a process of how to setup and calibrate sound. I present a method of how one may go about setting up a sound monitor and the usage it may have in water resource management. Finally, I apply the method of sound filtering, river placement, and calibration at a catchment scale to determine its validity in river monitoring. Although novel, using sound to monitor a rivers' stage is practical and deployable

    Why people tolerate transgressive leaders: Social identity advancement, group prototypicality, and charisma

    Get PDF
    Transgressive leaders have the potential to cause widespread disruption and damage to organisations. Not only can leaders' misconduct have economic, legal, and social ramifications for organisational functioning, but national leaders who violate established rules may also threaten the social fabric of entire societies. Despite these implications, transgressive leadership is a rampant problem within groups and organisations, and such leaders are often treated sympathetically by in-group members. This thesis aimed to identify some of the social psychological constructs and mechanisms that encourage followers to tolerate the transgressive behaviours of their leaders. Across eight studies using a variety of methods, populations, and contexts, I demonstrate the role of group prototypicality, identity advancement, and charisma in upholding the lenient treatment of transgressive leaders. Overall, findings from this thesis suggest that leaders who are perceived as having the group's best interests at heart are treated more sympathetically following their transgression. In part, this is because advancing group interests contributes towards perceptions of group prototypicality and charisma, which subsequently also encourage followers to treat their leader lightly. Additionally, perceptions of identity advancement encourage followers to rationalise the transgressive behaviour of their leader by downplaying how unethical their misconduct is, which paves the way for continued support of transgressive leaders. The research in this thesis has theoretical implications for the social identity theory of leadership, subjective group dynamics theory, and the deviance credit model. This research also provides practical insights into the difficulties faced in managing or mitigating transgressive leadership, and point to potential mechanisms that may be targeted by future interventions in resolving such a key societal problem

    Biodiversity: ecosystem function relationships in southern African woodlands

    Get PDF
    A broad corpus of previous research has sought to understand the role of biodiversity as a driver of ecosystem structure and function. Although theory suggests that increased biodiversity should increase ecosystem function by niche complementarity among co-existing species, in natural systems wide variation in the biodiversity effect exists among vegetation types and along environmental gradients. In southern African woodlands and savannas, which experience disturbance by fire and herbivory, drought and extreme temperatures, it is unclear whether positive biodiversity effects should occur. In this thesis, I explore the ecology of southern African woodlands through the lens of the biodiversity-ecosystem function relationship, to improve our understanding of the role of tree diversity as a mediator of ecosystem function, its interactions with abiotic environment, and its effect on woodland structure. In temperate and wet tropical forests, where the majority of biodiversity-ecosystem function studies in natural woody vegetation have been conducted, the positive effect of niche complementarity hinges on the condition that conspecific competition is the limiting factor to ecosystem function. In highly disturbed and environmentally stressed systems however, this may not hold true. I conducted a regional study investigating the role of tree species diversity and structural diversity as mediators of woody biomass, using a plot network of 1235 plots spanning wide climatic and biogeographic gradients across southern Africa. Using Structural Equation Modelling, I determined that tree species diversity has a positive effect on biomass, operating mostly via its effect on structural diversity. I found that biodiversity itself increases with water availability, and that positive biodiversity effects only arise under sufficiently high stem density. To further understand the ecological mechanisms which drive positive biodiversity-productivity relationships, I explored the effects of tree species diversity and woodland demographic structure on patterns of land-surface phenology. I combined a dense plot-based tree census dataset across multiple deciduous Zambian woodland types with remotely sensed measures of greenness, to understand drivers of variation in pre-rain green-up, growing season length and productivity. I found that pre-rain green-up occurred earlier in more diverse sites, across all woodland types, while in non-miombo woodlands, species richness also increased post-rain senescence lag and season length. I also found that large-sized trees increase the degree of both pre-rain green-up and post-rain senescence lag, across vegetation types, with an effect size similar to that of species richness. Southern African woodlands occur as a complex mosaic of open grassy patches and closed canopy forest-like patches, driven by positive feedbacks of fire-induced tree mortality and grass growth, but the biotic mechanisms causing variation in canopy closure are unclear. I used terrestrial LiDAR at two sites, in Tanzania and Angola, to understand at fine spatial scale the effects of species composition and diversity on canopy architecture and canopy cover. Species diversity was found to allow increased spatial clumping of trees, which drove vertical canopy layer diversity and canopy height, demonstrating an indirect role of species diversity on canopy cover via stand structure. Taken together with the regional study of the biodiversity-ecosystem function relationship, these findings suggest a nuanced role of tree species diversity on ecosystem function, operating primarily via its effect on canopy structural diversity in southern African woodlands. I propose that higher diversity communities are more likely to produce forest-like closed canopy woodlands, with a higher upper limit on biomass, and are more likely to transition from savanna to closed canopy forest under conditions of atmospheric CO2 enrichment. Finally, in an effort to increase our understanding of the variation in diversity and structure of woodlands across southern Africa, I conducted a study of tree species biodiversity and woodland structure in Bicuar National Park, southwest Angola, with comparison to other woodlands around the miombo ecoregion. Much of the published plot data and woodland monitoring infrastructure in miombo woodlands is located in central and eastern regions of southern Africa, while woodlands in the west of the region, which occur entirely within Angola, remain poorly represented. I found that Bicuar National Park constitutes an important woodland refuge at the transition between dry miombo woodland and Baikiaea-Baphia woodlands. I recorded 27 tree species not recorded elsewhere in the miombo ecoregion outside the Huíla plateau. An additional study of one-off plots in areas previously disturbed by shifting cultivation, found that this disturbance increases tree species diversity, but ultimately reduces woody biomass, even after a period of regeneration, potentially representing a directional shift to a different stable vegetation type. Together, the findings of this thesis demonstrate multiple relationships among tree biodiversity, ecosystem structure, and ecosystem function, measured primarily through woody biomass and productivity, at multiple spatial scales. I conclude that incorporation of diversity and canopy structural information into earth system models, by scaling up plot data using cutting edge remotely sensed datasets, could improve predictions of how climate change and biodiversity change will impact the functioning of different vegetation types across southern Africa, with consequences for carbon cycle modelling, conservation management, and ecosystem service provision. Finally, I suggest that biodiversity loss of large archetypal miombo tree species will have the greatest impact on a number of ecosystem functions related to carbon cycling, raising concerns over the impacts of selective logging of these species

    The social and psychological work of metaphor: a corpus linguistic investigation

    Get PDF
    This thesis investigates the triangular relationship between metaphor use, community, and state of mind, to ask the question: what social and psychological work does metaphor do, in the computer-mediated discourse setting of an online forum. The thesis goes beyond the finding and grouping of metaphors for analysis to consider the pattern of metaphor use over time in terms of (i) surrounding language style; (ii) density of use; and (iii) use by different participant groups. In achieving its aim the thesis provides insights into (i) the effect of metaphor use in terms of state of mind; (ii) the role of metaphor in the characterisation of a community; and (iii) methods for considering linguistic metaphor in naturally occurring discourse in terms of its psychological effect, which also creates insights into metaphor theory. The primary novel contribution of the thesis is to combine an analysis of metaphor use with an analysis of the language style that surrounds it, using established research relating language style to state of mind to consider the social and psychological work that metaphor does. The primary prediction of the investigation is that where metaphor is used to characterise a concept, the surrounding language will be of a style that has been found to be associated with better mental health. This is related to and supported by the second novel contribution of the thesis, which is to consider the role of metaphor in the formation and evolution of a community over time, by considering change in density of metaphor and other key variables in the data as a whole, and for comparative participant groups. The third novel contribution of the thesis is that, alongside more established corpus linguistic techniques, new techniques from the fast-evolving areas of data science and natural language processing are explored and evaluated in terms of (i) finding metaphors in the corpora; (ii) analysing language style; and (iii) diachronic analysis. It is shown that use of the identified dominant metaphor themes in each community co-occurs with specific language styles associated with mental health, and that this work of metaphor evolves over time as a consensus which becomes normative within the group for a period, such that it shapes community members as well as being shaped by them, while the flexibility of metaphor still leaves that work open to further evolution. The adaptation and prominence of particular metaphor themes over time to do particular work in each forum also underpins the characterisation of it as a particular community
    • …
    corecore