2,598 research outputs found

    Intersectionality in Queer Activism: A Case Study

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    This paper explores the relationships between intersectionality and queer activism through a case study of the Louisville, Kentucky LGBTQ+ organization The Fairness Campaign. Intersectionality has been increasingly explored by academia, but rarely ventures beyond the “big three” categorical divisions of race, gender, and class; even rarer are studies of the practical application of intersectionality in activism, particularly queer activism. Through analysis of secondary data, I examine the ways in which intersectionality has, consciously or not, played a part in the history of the Fairness Campaign, as well as its role in the future of the organization

    Finding Benefit and Feeling Strain in Parenting a Child with Autism Spectrum Disorder

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    Female caregivers of children with Autism Spectrum Disorder, often report higher levels of stress, anxiety, and depression which are often related to increased levels of caregiver strain, as well as the frequency and severity of child problem behaviors (CPB). Despite negative aspects of caring for a child with ASD, caregivers have also found benefit. The current study extended the caregiver benefit finding (CBF) and caregiver strain literature by exploring the role that these variables play in the mental health of female caregivers of children with ASD (n = 259), by assessing caregiver strain as a mediator between CPB and caregiver distress, examining CBF as a moderator between caregiver strain and distress, and assessing a moderated mediation of CPB, caregiver strain, caregiver distress, and CBF. Results suggest that caregiver strain is a significant mediator between CPB and caregiver distress, however CBF was not found to be a moderator, and thus the moderated mediation was not supported. CBF was a significant predictor for caregiver distress. Findings inform theoretical applications within the ASD sample and provide implications for future research in the development of interventions to enhance functioning in female caregivers

    Main Concept, Sequencing, and Story Grammar Analyses of Cinderella Narratives in a Large Sample of Persons with Aphasia

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    Recently, a multilevel analytic approach called Main Concept, Sequencing, and Story Grammar (MSSG) was presented along with preliminary normative information. MSSG analyses leverage the strong psychometrics and rich procedural knowledge of both main concept analysis and story grammar component coding, complementing it with easy-to-obtain sequencing information for a rich understanding of discourse informativeness and macrostructure. This study is the next critical step for demonstrating the clinical usefulness of MSSG’s six variables (main concept composite, sequencing, main concept+sequencing, essential story grammar components, total episodic components, and episodic complexity) for persons with aphasia (PWAs). We present descriptive statistical information for MSSG variables for a large sample of PWAs and compare their performance to a large sample of persons not brain injured (PNBIs). We observed significant differences between PWAs and PNBIs for all MSSG variables. These differences occurred at the omnibus group level and for each aphasia subtype, even for PWAs with very mild impairment that is not detected with standardized aphasia assessment. Differences between PWAs and PNBIs were also practically significant, with medium to large effect sizes observed for nearly all aphasia subtypes and MSSG variables. This work deepens our understanding of discourse informativeness and macrostructure in PWAs and further develops an efficient tool for research and clinical use. Future research should investigate ways to expand MSSG analyses and to improve sensitivity and specificity

    Genome-by-Trauma Exposure Interactions in Adults With Depression in the UK Biobank

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    IMPORTANCE: Self-reported trauma exposure has consistently been found to be a risk factor for major depressive disorder (MDD), and several studies have reported interactions with genetic liability. To date, most studies have examined gene-environment interactions with trauma exposure using genome-wide variants (single-nucleotide variations [SNVs]) or polygenic scores, both typically capturing less than 3% of phenotypic risk variance. OBJECTIVE: To reexamine genome-by-trauma interaction associations using genetic measures using all available genotyped data and thus, maximizing accounted variance. DESIGN, SETTING, AND PARTICIPANTS: The UK Biobank study was conducted from April 2007 to May 1, 2016 (follow-up mental health questionnaire). The current study used available cross-sectional genomic and trauma exposure data from UK Biobank. Participants who completed the mental health questionnaire and had available genetic, trauma experience, depressive symptoms, and/or neuroticism information were included. Data were analyzed from April 1 to August 30, 2021. EXPOSURES: Trauma and genome-by-trauma exposure interactions. MAIN OUTCOMES AND MEASURES: Measures of self-reported depression, neuroticism, and trauma exposure with whole-genome SNV data are available from the UK Biobank study. Here, a mixed-model statistical approach using genetic, trauma exposure, and genome-by-trauma exposure interaction similarity matrices was used to explore sources of variation in depression and neuroticism. RESULTS: Analyses were conducted on 148 129 participants (mean [SD] age, 56 [7] years) of which 76 995 were female (52.0%). The study approach estimated the heritability (SE) of MDD to be approximately 0.160 (0.016). Subtypes of self-reported trauma exposure (catastrophic, adult, childhood, and full trauma) accounted for a significant proportion of the variance of MDD, with heritability (SE) ranging from 0.056 (0.013) to 0.176 (0.025). The proportion of MDD risk variance accounted for by significant genome-by-trauma interaction revealed estimates (SD) ranging from 0.074 (0.006) to 0.201 (0.009). Results from sex-specific analyses found genome-by-trauma interaction variance estimates approximately 5-fold greater for MDD in male participants (0.441 [0.018]) than in female participants (0.086 [0.009]). CONCLUSIONS AND RELEVANCE: This cross-sectional study used an approach combining all genome-wide SNV data when exploring genome-by-trauma interactions in individuals with MDD; findings suggest that such interactions were associated with depression manifestation. Genome-by-trauma interaction accounts for greater trait variance in male individuals, which points to potential differences in depression etiology between the sexes. The methodology used in this study can be extrapolated to other environmental factors to identify modifiable risk environments and at-risk groups to target with interventions

    Finding and Resolving Security Misusability with Misusability Cases

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    Although widely used for both security and usability concerns, scenarios used in security design may not necessarily inform the design of usability, and vice- versa. One way of using scenarios to bridge security and usability involves explicitly describing how design deci- sions can lead to users inadvertently exploiting vulnera- bilities to carry out their production tasks. This paper describes how misusability cases, scenarios that describe how design decisions may lead to usability problems sub- sequently leading to system misuse, address this problem. We describe the related work upon which misusability cases are based before presenting the approach, and illus- trating its application using a case study example. Finally, we describe some findings from this approach that further inform the design of usable and secure systems

    Lifestyle and Genetic Factors Modify Parent-of-Origin Effects on the Human Methylome

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    BACKGROUND: parent-of-origin effects (POE) play important roles in complex disease and thus understanding their regulation and associated molecular and phenotypic variation are warranted. Previous studies mainly focused on the detection of genomic regions or phenotypes regulated by POE. Understanding whether POE may be modified by environmental or genetic exposures is important for understanding of the source of POE-associated variation, but only a few case studies addressing modifiable POE exist. METHODS: in order to understand this high order of POE regulation, we screened 101 genetic and environmental factors such as ‘predicted mRNA expression levels’ of DNA methylation/imprinting machinery genes and environmental exposures. POE-mQTL-modifier interaction models were proposed to test the potential of these factors to modify POE at DNA methylation using data from Generation Scotland: The Scottish Family Health Study(N=2315). FINDINGS: a set of vulnerable/modifiable POE-CpGs were identified (modifiable-POE-regulated CpGs, N=3). Four factors, ‘lifetime smoking status’ and ‘predicted mRNA expression levels’ of TET2, SIRT1 and KDM1A, were found to significantly modify the POE on the three CpGs in both discovery and replication datasets. We further identified plasma protein and health-related phenotypes associated with the methylation level of one of the identified CpGs. INTERPRETATION: the modifiable POE identified here revealed an important yet indirect path through which genetic background and environmental exposures introduce their effect on DNA methylation, motivating future comprehensive evaluation of the role of these modifiers in complex diseases. FUNDING: NSFC (81971270),H2020-MSCA-ITN(721815), Wellcome (204979/Z/16/Z,104036/Z/14/Z), MRC (MC_UU_00007/10, MC_PC_U127592696), CSO (CZD/16/6,CZB/4/276, CZB/4/710), SFC (HR03006), EUROSPAN (LSHG-CT-2006-018947), BBSRC (BBS/E/D/30002276), SYSU, Arthritis Research UK, NHLBI, NIH

    Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank

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    Background: Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants. Methods: In the present analysis, three cohort studies (ntotal = 48,002) were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS), the English Longitudinal Study of Ageing (ELSA), and the UK Biobank. A genome-wide haplotype-based meta-analysis of cognitive ability was performed, as well as a targeted meta-analysis of several gene coding regions. Results: None of the assessed haplotypes provided evidence of a statistically significant association with cognitive ability in either the individual cohorts or the meta-analysis. Within the meta-analysis, the haplotype with the lowest observed P-value overlapped with the D-amino acid oxidase activator (DAOA) gene coding region. This coding region has previously been associated with bipolar disorder, schizophrenia and Alzheimer’s disease, which have all been shown to impact upon cognitive ability. Another potentially interesting region highlighted within the current genome-wide association analysis (GS:SFHS: P = 4.09 x 10-7), was the butyrylcholinesterase (BCHE) gene coding region. The protein encoded by BCHE has been shown to influence the progression of Alzheimer’s disease and its role in cognitive ability merits further investigation. Conclusions: Although no evidence was found for any haplotypes with a statistically significant association with cognitive ability, our results did provide further evidence that the genetic variants contributing to the variance of cognitive ability are likely to be of small effect

    Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment

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    Veterans of Operation Desert Storm/Desert Shield - the 1991 Gulf War (GW) - are a unique population who returned from theater with multiple health complaints and disorders. Studies in the U.S. and elsewhere have consistently concluded that approximately 25-32% of this population suffers from a disorder characterized by symptoms that vary somewhat among individuals and include fatigue, headaches, cognitive dysfunction, musculoskeletal pain, and respiratory, gastrointestinal and dermatologic complaints. Gulf War illness (GWI) is the term used to describe this disorder. In addition, brain cancer occurs at increased rates in subgroups of GW veterans, as do neuropsychological and brain imaging abnormalities. Chemical exposures have become the focus of etiologic GWI research because nervous system symptoms are prominent and many neurotoxicants were present in theater, including organophosphates (OPs), carbamates, and other pesticides; sarin/cyclosarin nerve agents, and pyridostigmine bromide (PB) medications used as prophylaxis against chemical warfare attacks. Psychiatric etiologies have been ruled out. This paper reviews the recent literature on the health of 1991 GW veterans, focusing particularly on the central nervous system and on effects of toxicant exposures. In addition, it emphasizes research published since 2008, following on an exhaustive review that was published in that year that summarizes the prior literature (RACGWI, 2008). We conclude that exposure to pesticides and/or to PB are causally associated with GWI and the neurological dysfunction in GW veterans. Exposure to sarin and cyclosarin and to oil well fire emissions are also associated with neurologically based health effects, though their contribution to development of the disorder known as GWI is less clear. Gene-environment interactions are likely to have contributed to development of GWI in deployed veterans. The health consequences of chemical exposures in the GW and other conflicts have been called "toxic wounds" by veterans. This type of injury requires further study and concentrated treatment research efforts that may also benefit other occupational groups with similar exposure-related illnesses

    Logic integration of mRNA signals by an RNAi-based molecular computer

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    Synthetic in vivo molecular ‘computers’ could rewire biological processes by establishing programmable, non-native pathways between molecular signals and biological responses. Multiple molecular computer prototypes have been shown to work in simple buffered solutions. Many of those prototypes were made of DNA strands and performed computations using cycles of annealing-digestion or strand displacement. We have previously introduced RNA interference (RNAi)-based computing as a way of implementing complex molecular logic in vivo. Because it also relies on nucleic acids for its operation, RNAi computing could benefit from the tools developed for DNA systems. However, these tools must be harnessed to produce bioactive components and be adapted for harsh operating environments that reflect in vivo conditions. In a step toward this goal, we report the construction and implementation of biosensors that ‘transduce’ mRNA levels into bioactive, small interfering RNA molecules via RNA strand exchange in a cell-free Drosophila embryo lysate, a step beyond simple buffered environments. We further integrate the sensors with our RNAi ‘computational’ module to evaluate two-input logic functions on mRNA concentrations. Our results show how RNA strand exchange can expand the utility of RNAi computing and point toward the possibility of using strand exchange in a native biological setting
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