Brain function distinguishes female carriers and non-carriers of familial risk for autism

BACKGROUND: Autism spectrum disorder (ASD) is characterized by high population-level heritability and a three-to-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed ( carrier ) females. METHODS: Using functional magnetic resonance imaging, we examined brain responses to passive viewing of point light displays-depicting biological versus non-biological motion-in a sample of undiagnosed adult females enriched for inherited susceptibility to ASD on the basis of affectation in their respective family pedigrees. Brain responses in carrier females were compared to responses in age-, SRS-, and IQ-matched non-carrier-females-i.e., females unrelated to individuals with ASD. We conducted a hypothesis-driven analysis focused on previously published regions of interest as well as exploratory, brain-wide analyses designed to characterize more fully the rich responses to this paradigm. RESULTS: We observed robust responses to biological motion. Notwithstanding, the 12 regions implicated by prior research did not exhibit the hypothesized interaction between group (carriers vs. controls) and point light displays (biological vs. non-biological motion). Exploratory, brain-wide analyses identified this interaction in three novel regions. Post hoc analyses additionally revealed significant variations in the time course of brain activation in 20 regions spanning occipital and temporal cortex, indicating group differences in response to point light displays (irrespective of the nature of motion) for exploration in future studies. LIMITATIONS: We were unable to successfully eye-track all participants, which prevented us from being able to control for potential differences in eye gaze position. CONCLUSIONS: These methods confirmed pronounced neural signatures that differentiate brain responses to biological and scrambled motion. Our sample of undiagnosed females enriched for family genetic loading enabled discovery of numerous contrasts between carriers and non-carriers of risk of ASD that may index variations in visual attention and motion processing related to genetic susceptibility and inform our understanding of mechanisms incurred by inherited liability for ASD

Analysis of matrisome expression patterns in murine and human dorsal root ganglia

The extracellular matrix (ECM) is a dynamic structure of molecules that can be divided into six different categories and are collectively called the matrisome. The ECM plays pivotal roles in physiological processes in many tissues, including the nervous system. Intriguingly, alterations in ECM molecules/pathways are associated with painful human conditions and murine pain models. Nevertheless, mechanistic insight into the interplay of normal or defective ECM and pain is largely lacking. The goal of this study was to integrate bulk, single-cell, and spatial RNA sequencing (RNAseq) datasets to investigate the expression and cellular origin of matrisome genes in male and female murine and human dorsal root ganglia (DRG). Bulk RNAseq showed that about 65% of all matrisome genes were expressed in both murine and human DRG, with proportionally more core matrisome genes (glycoproteins, collagens, and proteoglycans) expressed compared to matrisome-associated genes (ECM-affiliated genes, ECM regulators, and secreted factors). Single cell RNAseq on male murine DRG revealed the cellular origin of matrisome expression. Core matrisome genes, especially collagens, were expressed by fibroblasts whereas matrisome-associated genes were primarily expressed by neurons. Cell–cell communication network analysis with CellChat software predicted an important role for collagen signaling pathways in connecting vascular cell types and nociceptors in murine tissue, which we confirmed by analysis of spatial transcriptomic data from human DRG. RNAscope in situ hybridization and immunohistochemistry demonstrated expression of collagens in fibroblasts surrounding nociceptors in male and female human DRG. Finally, comparing human neuropathic pain samples with non-pain samples also showed differential expression of matrisome genes produced by both fibroblasts and by nociceptors. This study supports the idea that the DRG matrisome may contribute to neuronal signaling in both mouse and human, and that dysregulation of matrisome genes is associated with neuropathic pain

Understandings of cervical screening in sexual minority women: A Q-methodological study

Discursive perspectives argue that cervical screening carries social and moral meaning. Overlooked by research into the health needs of sexual minority women, previous literature that has examined uptake of cervical screening has instead targeted increasing attendance via information and service provision. In order to explore the diversity of meanings that British sexual minority women have about cervical screening, the Q-sorts of 34 sexual minority women were factor analysed by-person and rotated to simple structure using Varimax. The five factors are interpreted and discussed relative to competing discourses on information provision within cervical screening. The five accounts are labelled 'cervical screening is': an essential health check that women have the right to refuse; a woman's health entitlement; a vital test but degrading experience; a sensible thing to do; and an unnecessary imposition for some women. Critical approaches to informed choice are explored with attention to recent developments in cervical cancer prevention. Findings highlighting the need for affirmation of diversity within healthcare are considered in relation to existing criteria for UK national screening programmes

Leaf the kids outdoors : approaches and enquiries in quantifying natural environments for health

Over the past few decades there has been an increased interest in how urban natural environments (NEs) affect health, particularly with the migration of people into cities and subsequent densification. Recently, there has been an increase in studies on associations between NEs and childhood health and development, but, to date, no systematic assessment of evidence level exists, especially not within the context of different NE exposure measurements. The focus of this research is to determine which NE measurements have been used in childhood health and development research and to assess if associations and the relative level of evidence changes with different NE metrics. Additionally, this thesis seeks to evaluate possible risk of misclassification of NE exposure due to temporal alignment issues between NE exposure and health data by analyzing general and local vegetation change in Metro Vancouver over a 15-year period. The most common NE metrics identified in the systematic review (Chapter 2) were remote sensing derived metrics, such as the normalized difference vegetation index (NDVI) and land use/land cover datasets. These metrics were also most consistently associated to health outcomes, particularly birth outcomes and decreased ADHD symptoms. Overall, there was considerable heterogeneity within NE metrics, suggesting that more research is needed before conclusions on evidence level can be made. Through modeling NDVI over time with the Theil-Sen estimator, it was found that vegetation remained relatively stable throughout the Metro Vancouver region, an exception being in localized areas of the southeast. Additionally, large amounts of variation were found in NDVI between years, suggesting that direct comparison of NDVI between years is not advisable. To minimize the risk of misclassification in exposure, datasets should be aligned temporally. Ultimately, this thesis discusses and highlights the importance of careful consideration of measurement selection for NE exposure in health studies. While confirming some evidence for childhood health benefits through NE exposure, the thesis concludes that, to date, research has insufficiently considered optimal selection of NE metric and the impact of vegetation change over time. These are important consideration for improving evidence-based decisions for healthy urban planning and should be considered in future studies.Forestry, Faculty ofGraduat

The Canadian Environmental Quality Index (Can-EQI): Development and calculation of an index to assess spatial variation of environmental quality in Canada’s 30 largest cities

Background: Multiple characteristics of the urban environment have been shown to influence population health and health-related behaviours, though the distribution and combined effects of these characteristics on health is less understood. A composite measure of multiple environmental conditions would allow for comparisons among different urban areas; however, this measure is not available in Canada. Objectives: To develop an index of environmental quality for Canada’s largest urban areas and to assess the influence of population size on index values. Methods: We conducted a systematic search of potential datasets and consulted with experts to refine and select datasets for inclusion. We identified and selected nine datasets across five domains (outdoor air pollution, natural environments, built environments, radiation, and climate/weather). Datasets were chosen based on known impacts on human health across the life course, complete geographic coverage of the cities of interest, and temporal alignment with the 2016 Canadian census. Each dataset was then summarized into dissemination areas (DAs). The Canadian Environmental Quality Index (Can-EQI) was created by summing decile ranks of each variable based on hypothesized relationships to health outcomes. Results: We selected 30 cities with a population of more than 100,000 people which included 28,026 DAs and captured approximately 55% of the total Canadian population. Can-EQI scores ranged from 21.1 to 88.9 out of 100, and in Canada’s largest cities were 10.2 (95% CI: −10.7, −9.7) points lower than the smallest cities. Mapping the Can-EQI revealed high geographic variability within and between cities. Discussion: Our work demonstrates a valuable methodology for exploring variations in environmental conditions in Canada’s largest urban areas and provides a means for exploring the role of environmental factors in explaining urban health inequalities and disparities. Additionally, the Can-EQI may be of value to municipal planners and decision makers considering the allocation of investments to improve urban conditions

Pesticide residues in the Great Barrier Reef

Australia’s Great Barrier Reef (GBR) is one of the world’s most iconic World Heritage-listed ecosystems but is currently under threat from a range of environmental insults including climate change and pollution. Recent research has shown that herbicides from agricultural runoff have been found in the GBR lagoon at concentrations capable of harming keystone marine plants. The agricultural sector and state and national governments have responded by encouraging the implementation of improved management practices across the GBR catchment area

Dynamics of herbicide transport and partitioning under event flow conditions in the lower Burdekin region, Australia

This study examined the temporal variability in herbicide delivery to the Great Barrier Reef (GBR) lagoon (Australia) from one of the GBR catchment's major sugarcane growing regions. Annual loads of measured herbicides were consistently in the order of 200+ kg. Atrazine, it's degradate desethylatrazine, and diuron contributed approximately 90% of annual herbicide load, with early 'first-flush' events accounting for the majority of herbicide loads leaving the catchment. Assessment of herbicide water–sediment partitioning in flood runoff highlighted the majority of herbicides were transported in predominantly dissolved form, although a considerable fraction of diuron was transported in particulate-bound form (ca. 33%). Diuron was also the herbicide demonstrating the highest concentrations and frequency of detection in sediments collected from catchment waterways and adjacent estuarine–marine environments, an outcome aligning with previous research. Herbicide physico-chemical properties appear to play a crucial role in partitioning between water column and sediment habitat types in GBR receiving ecosystems