203 research outputs found

    Food Security, Depression and Quality of Life in Northern Plains Indians

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    Major health disparities, high levels of poverty and food insecurity exist in many Native American and Alaskan Native (AI/AN) communities. Relatively little research has been done on these issues and possible relationships between them. A research program was designed with the objective of exploring the relationships between these various issues, if any existed, in one sub-group of AI/AN. In the study, the incidence of food insecurity was determined in a convenience sample of Northern Plains Indians (NPI) and correlated with measures of physical and mental health, body composition, quality of life, cultural identification and dietary intakes. Participants were 458 adult attendees at summer powwows and health fairs held at 5 reservations and 3 tribal colleges in North Dakota and western Minnesota. Participants completed various measurements and assessments and pertinent health and demographic data were recorded. Observed incidences of “food insecurity” overall and “very low food security” in particular (26.4% and 10.4%, respectively) were in sharp contrast to recently reported rates for North Dakota (8.7% and 3.4%) and the U.S. population as a whole (14.7% and 5.6%). In this manuscript, analysis revealed a positive relationship between food insecurity and depression and a negative relationship between food insecurity and quality of life. The findings emphasize the need to address food insecurity when designing research and service programs to address depression in AI/AN populations

    Comparing Adult Cannabis Treatment-Seekers Enrolled in a Clinical Trial with National Samples of Cannabis Users in the United States

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    Background—Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment Episodes Data Set – Admissions. Methods—Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. Results—Results showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users. Conclusions—These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings

    Implementation, Evalution and Maintenance of a Social-Emotional Skills Training Program for Children with an Autism Spectrum Disorder in a Specialist School Setting

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    Socialization difficulties in children with an Autism Spectrum Disorder (ASD) are often associated with peer rejection and impaired academic achievement. Schools might appear to offer an ideal setting for social-emotional skills (SES) instruction. However, common challenges to successful implementation of school-based programs include inadequate staffing and resourcing, and a lack of ASD-specific staff training. This paper describes how barriers to program implementation were overcome in a project evaluating the Secret Agent Society (SAS) SES training intervention within Autism Spectrum Australia (Aspect) specialist classes. Questionnaire data was collected from school staff over a one-year period. Findings supported the effectiveness of the adoption process used, and suggest that SAS was feasible and acceptable to school staff

    Different functions of rape myth use in court: findings from a trial observation study

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    This study examines rape myth use in eight English rape trials and assesses attempts by trial participants to combat it. Trial notes, based on observations, were analyzed using thematic analysis. Rape myths were used in three identifiable ways: to distance the case from the “real rape” stereotype, to discredit the complainant, and to emphasize the aspects of the case that were consistent with rape myths. Prosecution challenges to the myths were few, and judges rarely countered the rape myths. This study provides new insights by demonstrating the ways that rape myths are utilized to manipulate jurors’ interpretations of the evidenc

    Detection of metastases using circulating tumour DNA in uveal melanoma

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    Background: Approximately 50% of uveal melanoma (UM) patients will develop metastatic disease depending on the genetic features of the primary tumour. Patients need 3–12 monthly scans, depending on their prognosis, which is costly and often non-specific. Circulating tumour DNA (ctDNA) quantification could serve as a test to detect and monitor patients for early signs of metastasis and therapeutic response. Methods: We assessed ctDNA as a biomarker in three distinct UM cohorts using droplet-digital PCR: (A) a retrospective analysis of primary UM patients to predict metastases; (B) a prospective analysis of UM patients after resolution of their primary tumour for early detection of metastases; and (C) monitoring treatment response in metastatic UM patients. Results: Cohort A: ctDNA levels were not associated with the development of metastases. Cohort B: ctDNA was detected in 17/25 (68%) with radiological diagnosis of metastases. ctDNA was the strongest predictor of overall survival in a multivariate analysis (HR = 15.8, 95% CI 1.7–151.2, p = 0.017). Cohort C: ctDNA monitoring of patients undergoing immunotherapy revealed a reduction in the levels of ctDNA in patients with combination immunotherapy. Conclusions: Our proof-of-concept study shows the biomarker feasibility potential of ctDNA monitoring in for the clinical management of uveal melanoma patients

    A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response

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    Functional genomics efforts face tradeoffs between number of perturbations examined and complexity of phenotypes measured. We bridge this gap with Perturb-seq, which combines droplet-based single-cell RNA-seq with a strategy for barcoding CRISPR-mediated perturbations, allowing many perturbations to be profiled in pooled format. We applied Perturb-seq to dissect the mammalian unfolded protein response (UPR) using single and combinatorial CRISPR perturbations. Two genome-scale CRISPR interference (CRISPRi) screens identified genes whose repression perturbs ER homeostasis. Subjecting ∼100 hits to Perturb-seq enabled high-precision functional clustering of genes. Single-cell analyses decoupled the three UPR branches, revealed bifurcated UPR branch activation among cells subject to the same perturbation, and uncovered differential activation of the branches across hits, including an isolated feedback loop between the translocon and IRE1α. These studies provide insight into how the three sensors of ER homeostasis monitor distinct types of stress and highlight the ability of Perturb-seq to dissect complex cellular responses.National Human Genome Research Institute (U.S.) (Grant P50HG006193

    Analysis of circulating tumour cells in early-stage uveal melanoma: Evaluation of tumour marker expression to increase capture

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    Background: The stratification of uveal melanoma (UM) patients into prognostic groups is critical for patient management and for directing patients towards clinical trials. Current classification is based on clinicopathological and molecular features of the tumour. Analysis of circulating tumour cells (CTCs) has been proposed as a tool to avoid invasive biopsy of the primary tumour. However, the clinical utility of such liquid biopsy depends on the detection rate of CTCs. Methods: The expression of melanoma, melanocyte, and stem cell markers was tested in a primary tissue microarray (TMA) and UM cell lines. Markers found to be highly expressed in primary UM were used to either immunomagnetically isolate or immunostain UM CTCs prior to treatment of the primary lesion. (3) Results: TMA and cell lines had heterogeneous expression of common melanoma, melanocyte, and stem cell markers. A multi-marker panel of immunomagnetic beads enabled isolation of CTCs in 37/43 (86%) patients with UM. Detection of three or more CTCs using the multi-marker panel, but not MCSP alone, was a significant predictor of shorter progression free (p = 0.040) and overall (p = 0.022) survival. Conclusions: The multi-marker immunomagnetic isolation protocol enabled the detection of CTCs in most primary UM patients. Overall, our results suggest that a multi-marker approach could be a powerful tool for CTC separation for non-invasive prognostication of UM

    The genome sequence of <i>Trypanosoma brucei gambiense</i>, causative agent of chronic Human African Trypanosomiasis

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    &lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; &lt;i&gt;Trypanosoma brucei gambiense&lt;/i&gt; is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a &lt;i&gt;T. b. brucei&lt;/i&gt; isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between &lt;i&gt;T. b. gambiense&lt;/i&gt; and the reference genome. We sought to identify features that were uniquely associated with &lt;i&gt;T. b. gambiense&lt;/i&gt; and its ability to infect humans.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and findings:&lt;/b&gt; An improved high-quality draft genome sequence for the group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with &lt;i&gt;T. b. brucei&lt;/i&gt; showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972. A comparison of the variant surface glycoproteins (VSG) in &lt;i&gt;T. b. brucei&lt;/i&gt; with all &lt;i&gt;T. b. gambiense&lt;/i&gt; sequence reads showed that the essential structural repertoire of VSG domains is conserved across &lt;i&gt;T. brucei&lt;/i&gt;.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This study provides the first estimate of intraspecific genomic variation within &lt;i&gt;T. brucei&lt;/i&gt;, and so has important consequences for future population genomics studies. We have shown that the &lt;i&gt;T. b. gambiense&lt;/i&gt; genome corresponds closely with the reference, which should therefore be an effective scaffold for any &lt;i&gt;T. brucei&lt;/i&gt; genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in &lt;i&gt;T. b. brucei&lt;/i&gt;, no &lt;i&gt;T. b. gambiense&lt;/i&gt;-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.&lt;/p&gt
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