Alien Registration- Devlin, Amy (Lewiston, Androscoggin County)

https://digitalmaine.com/alien_docs/29613/thumbnail.jp

Peat Bog Wildfire Smoke Exposure in Rural North Carolina Is Associated with Cardiopulmonary Emergency Department Visits Assessed through Syndromic Surveillance

Background: In June 2008, burning peat deposits produced haze and air pollution far in excess of National Ambient Air Quality Standards, encroaching on rural communities of eastern North Carolina. Although the association of mortality and morbidity with exposure to urban air pollution is well established, the health effects associated with exposure to wildfire emissions are less well understood. Objective: We investigated the effects of exposure on cardiorespiratory outcomes in the population affected by the fire. Methods: We performed a population-based study using emergency department (ED) visits reported through the syndromic surveillance program NC DETECT (North Carolina Disease Event Tracking and Epidemiologic Collection Tool). We used aerosol optical depth measured by a satellite to determine a high-exposure window and distinguish counties most impacted by the dense smoke plume from surrounding referent counties. Poisson log-linear regression with a 5-day distributed lag was used to estimate changes in the cumulative relative risk (RR). Results: In the exposed counties, significant increases in cumulative RR for asthma [1.65 (95% confidence interval, 1.25–2.1)], chronic obstructive pulmonary disease [1.73 (1.06–2.83)], and pneumonia and acute bronchitis [1.59 (1.07–2.34)] were observed. ED visits associated with cardiopulmonary symptoms [1.23 (1.06–1.43)] and heart failure [1.37 (1.01–1.85)] were also significantly increased. Conclusions: Satellite data and syndromic surveillance were combined to assess the health impacts of wildfire smoke in rural counties with sparse air-quality monitoring. This is the first study to demonstrate both respiratory and cardiac effects after brief exposure to peat wildfire smoke

A Mixed Bag: Critical Reflections On The Revised Ethical Principles For Judges

In 2021 the Canadian Judicial Council completed a multi-year review and update of Ethical Principles for Judges (EPJ), the ethical and professional guidance for all federally-appointed judges in Canada. The revisions address issues such as case management and settlement conferences, technological competence and the use of social media, interactions with self-represented litigants, professional development for judges, confidentiality, and the return of former judges to the practice of law. In this article, five directors of the Canadian Association for Legal Ethics/Association canadienne pour l’éthique juridique analyze the revised EPJ and offer their observations. The article covers five important topics. On impartiality, it explains the ways in which the revised EPJ represents a significant evolution in the understanding of this important concept. The article then critically examines the absence of any reference to Reconciliation. On judicial involvement with the community, it argues that the revised EPJ may lead judges to disengage from community activities to an unwarranted degree and critiques the scope of new provisions requiring judges to avoid visible signals of support for causes or views. On judicial technological competence, the article endorses new obligations but cautions that these developments will have to be supported by significant resources to provide appropriate training and guidance on best practices. On confidentiality and return to practice, the article welcomes the new provisions while highlighting some additional issues including avenues for enforcement

Spleen Tyrosine Kinase (Syk) Regulates Systemic Lupus Erythematosus (SLE) T Cell Signaling

Engagement of the CD3/T cell receptor complex in systemic lupus erythematosus (SLE) T cells involves Syk rather than the zeta-associated protein. Because Syk is being considered as a therapeutic target we asked whether Syk is central to the multiple aberrantly modulated molecules in SLE T cells. Using a gene expression array, we demonstrate that forced expression of Syk in normal T cells reproduces most of the aberrantly expressed molecules whereas silencing of Syk in SLE T cells normalizes the expression of most abnormally expressed molecules. Protein along with gene expression modulation for select molecules was confirmed. Specifically, levels of cytokine IL-21, cell surface receptor CD44, and intracellular molecules PP2A and OAS2 increased following Syk overexpression in normal T cells and decreased after Syk silencing in SLE T cells. Our results demonstrate that levels of Syk affect the expression of a number of enzymes, cytokines and receptors that play a key role in the development of disease pathogenesis in SLE and provide support for therapeutic targeting in SLE patients

Evaluation of multiple data sources for predicting increased need for HIV prevention among cisgender women: Understanding missed opportunities for Pre-exposure Prophylaxis (PrEP)

Background: Ciswomen constitute a disproportionately low percentage of pre-exposure prophylaxis for HIV prevention (PrEP) users compared to men. Despite PrEP’s effectiveness, women are 5.25 times less likely to take PrEP than men. Identifying women who have increased reasons for HIV prevention and educating and offering PrEP to these women is crucial to reducing HIV transmission and overall health equity. However, the best method of identifying women at highest risk of acquiring HIV remains unknown. This study aimed to identify common HIV risk factors and data sources for identifying these common factors (e.g., electronic medical record data, open source neighborhood data), as well as potential intervention points and missed opportunities for PrEP linkage. Methods: We conducted an evaluation of multiple data sources: semi-structured qualitative interviews, electronic medical record (EMR) chart abstraction, and open source data abstraction. We accessed EMRs for enrolled participants and all participants signed a standard release of medical information (ROI) form for all institutions at which they had received medical care for the five-year period preceding their HIV diagnosis. Data were abstracted using a standardized procedure. Both structured and unstructured fields (i.e., narrative text of free notes) within the EMR were examined and included for analysis. Finally, open data sources (e.g., STI cases, HIV prevalence) were examined by community area of Chicago. Open data sources were used to examine several factors contributing to the overall Economic Hardship Index (EHI) score. We used these calculated scores to assess the economic hardship within participants’ neighborhoods. Results: A total of 18 cisgender women with HIV participated in our study. Participants were mostly Black/African American (55.6%) and young (median age of 34). Our analysis identified two main themes influencing HIV risk among participants: contextual factors and relationship factors. Further, potential pre-diagnosis intervention points and missed opportunities were identified during reproductive health/prenatal visits, behavioral/mental health visits, and routine STI testing. Our evaluation of multiple data sources included investigating the presence or absence of information in the EMR (STI history, HIV testing, substance use, etc.) as well as whether pertinent information could be gathered from open access sources. Conclusion: Ciswomen recently diagnosed with HIV identified many shared experiences, including syndemic conditions like mental illness and substance abuse, sex with men who have sex with men, and frequent moving in areas with high HIV incidence prior to their diagnosis. It is imperative that providers ask patients about social history, information about partners, and other key variables, in addition to the standardized questions. Findings can be used to better recognize ciswomen most vulnerable to HIV and offer PrEP to them, reducing HIV transmission.</p

Perspectives of healthcare providers in family planning centers on increasing pre-exposure prophylaxis uptake among women who have migrated from sub-Saharan Africa to France

Pre-exposure prophylaxis (PrEP) for HIV remains largely underused among women who have migrated from sub-Saharan Africa (WMSSA), despite their accounting for a significant proportion of new HIV diagnoses in France and Western European countries. To expand PrEP reach, we explored healthcare providers’ perspectives on PrEP implementation within family planning centers (FPCs) in the Paris region through focus groups. The focus group discussion guide and rapid content analysis were informed by the Consolidated Framework for Implementation Research (CFIR) 2.0, which uses five domains to capture implementation determinants (Innovation, Outer Setting, Inner Setting, Individuals, and Implementation Process). Twenty providers participated across five focus groups and one key informant interview (median age 45; 80% women, 70% physicians). Oral PrEP was seen as easy to prescribe, but providers advocated for choices beyond the daily pill for better acceptability. While providers recognized increased HIV prevention needs among WMSSA, they found low PrEP demand among women stemming from a lack of knowledge. Although providers acknowledged that PrEP aligned with FPC missions, they cited significant implementation barriers, including limited resources, staff shortages, insufficient on-site capacity, competing priorities, and physicians being the sole prescribers. Provider-level implementation challenges included insufficient training and discomfort in discussing HIV risk and PrEP with WMSSA. Recommendations for implementing PrEP within FPCs included provider training and mentorship, tailored information campaigns for WMSSA, flexible delivery processes, support groups for women, and authorizing midwives and nurses to prescribe PrEP. These results support the need for tailored and multi-level implementation strategies to increase PrEP uptake among WMSSA attending FPCs in France

Associations of Serum Inflammatory Biomarkers During Pregnancy With Placental Pathology and Placental Gene Expression at Delivery

Problem: We sought to investigate whether maternal inflammatory cytokines during pregnancy are associated with histologic inflammatory or vascular lesions in the placenta and/or correlated with gene expression patterns in the placenta. Method of Study: We leveraged data from a large randomized controlled trial (RCT) at a single site. Maternal serum was collected in the second and third trimesters, and a composite inflammatory score was created using five measured biomarkers (CRP, IL-6, IL-1ra, IL-10, and TNF-α). Placentas were collected at delivery for histological analysis and four major patterns of placental injury were characterized. Fresh small chorionic villous biopsies were collected for placental genome-wide mRNA profiling. Transcripts showing >2-fold differential expression over the 4-SD range of circulating inflammatory biomarkers were reported, adjusting for potential confounders. Results: The primary analysis included 601 participants. A one standard deviation increase in the third-trimester inflammatory composite was associated with increased odds of chronic inflammation in the placenta (OR: 1.23, 95% CI 1.01, 1.51;). This was driven primarily by elevations in IL-10 (OR: 1.37; 99% CI: 1.06, 1.77). Higher maternal IL-10 in circulation was associated with bioinformatic indications of reduced pro-inflammatory gene regulation pathways in the placenta (AP1 decreased 25%, p = 0.003; NF-kB decreased 53%, p = 0.003) and indications of increased STAT family signaling pathways which mediate signaling through the IL-10 receptor (increased 73%, p = 0.002). Conclusions: Our results indicate that elevated maternal circulating IL-10 during pregnancy is associated with chronic inflammatory lesions in the placenta at delivery. Additionally, higher levels of circulating IL-10 are associated with upregulated STAT signaling pathways in placental tissues.</p

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Increasing providers’ PrEP prescription for Black cisgender women: A qualitative study to improve provider knowledge and competency via PrEP training

Background: Awareness and uptake of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) remains low among Black/African American cisgender women, partly due to low self-reported PrEP knowledge and comfort among primary care providers. Ensuring providers are trained on PrEP is crucial, as increased PrEP knowledge is associated with higher rates of PrEP prescription. Objective: We aimed to develop a PrEP training for providers to improve their self-efficacy in discussing and prescribing PrEP for Black women, with the ultimate goal of increasing PrEP awareness and utilization among Black women. Design: In this qualitative study, we conducted focus groups with medical providers at three federally qualified health centers in the Southern and Midwestern United States to identify themes informing the development of a provider PrEP training. Methods: Providers were asked for input on content/design of PrEP training. Transcripts underwent rapid qualitative analysis using the Stanford Lightning Report Method. Themes were identified and presented under the domains of the Consolidated Framework for Implementation Research. Results: Ten providers completed four focus groups. Themes included the individual characteristics of providers (low comfort initiating PrEP discussions, particularly among White providers) and the outer setting of client attitudes (perceptions of potential provider bias/racism, varying levels of concern about HIV acquisition). Opportunities were identified to maximize the benefit of training design (e.g., developing case scenarios to enhance providers' cultural competency with Black women and PrEP knowledge). Conclusion: This comprehensive PrEP training features both didactic material and interactive role-plays to equip providers with the clinical knowledge for prescribing PrEP while building their competency discussing PrEP with Black women. This training is particularly important for providers who have racial or gender discordance with Black women and express lower comfort discussing PrEP with these clients. Provider training could lead to minimizing racial- and gender-based inequities in PrEP use.</p

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre