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Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
OBJECTIVES/SPECIFIC AIMS: This study aims to identify genetic biomarkers of GDM and facilitate the understanding of its molecular underpinnings. METHODS/STUDY POPULATION: We identified a cohort of mothers diagnosed with GDM in our longitudinal birth study by mining Electronic Health Records of participants utilizing PheCode map with ICD-9 and ICD-10 codes. We verified each case using ACOG’s GDM diagnosis criteria. RESULTS/ANTICIPATED RESULTS: Whole genome sequencing (WGS) data were available for 111 confirmed cases (out of 205) and 706 controls (out of 1,429) from different ancestries (412 EUR, 256 AMR, 56 EAS, 26 SAS and 18 AFR; 49 OTHER). SAS had the highest incidence of GDM at 38.46% and EUR had the lowest at 6.55%. We performed logistic regression using computed ancestry, age and BMI as covariates to determine if any variants are associated with GDM. The top variant (rs139014401) was found in an intron of DFFB gene, which is p53-bound and regulates DNA fragmentation during apoptosis. We will investigate the robustness of 49 identified variants and will separate the cohort by ancestry to detect population-specific differences in the top loci. DISCUSSION/SIGNIFICANCE OF IMPACT: Identification of molecular biomarkers in GDM across different ancestral backgrounds will address a gap in current GDM research. Findings may enhance screening and enable clinicians to identify those at risk for developing GDM earlier in the pregnancy. Early management of mothers at risk may lead to better health outcomes for mother and baby.
OBJECTIVES/SPECIFIC AIMS: The aims of this study are 2-fold: (1) to determine if maternal schistosomiasis affects maternal immunity to tetanus and/or transplacental transfer of antitetanus toxoid (TT) immunoglobulin G (IgG) from mother to infant and (2) determine the influence of maternal schistosomiasis on infant BCG vaccine immunogenicity. METHODS/STUDY POPULATION: The study will utilize blood samples from a historic cohort of 100 mother-infant pairs from Kisumu, Kenya, a schistosomiasis-endemic area. For the first aim, we will evaluate maternal schistosomal circulating anodic antigen, which has improved sensitivity and specificity to detect active schistosomiasis from serum, and antisoluble egg antigen IgG positivity compared with quantitative maternal anti-TT IgG at delivery and anti-TT IgG cord blood to maternal blood ratio (cord:maternal ratio). For the second aim, we will evaluate association between maternal schistosomiasis as detected by circulating anodic antigen and antisoluble egg antigen IgG at delivery and infant BCG-specific Th1-cytokine positive CD4+ cells at 10 weeks following BCG vaccination at birth. RESULTS/ANTICIPATED RESULTS: We hypothesize that active maternal schistosomiasis will be associated with decreased maternal anti-TT IgG and reduced efficiency of transplacental transfer, as measured by infant cord blood to maternal blood ratio of anti-TT IgG. We also expect that maternal schistosomiasis will be associated with decreased infant immunogenicity to BCG vaccine. DISCUSSION/SIGNIFICANCE OF IMPACT: This is a formative study on infant vaccine immunity using laboratory methodology not previously applied. Understanding infant immunity in the setting of maternal schistosomiasis will inform vaccination strategies and tailor vaccine development in schistosome-endemic areas such as Kenya, where neither TB nor neonatal tetanus have been eradicated. Additionally, our results will inform public health policies to consider integration of antischistosomal agents in antenatal care.
Although the rumen fluke, Calicophoron daubneyi is now very common and widespread throughout Western Europe, reports of clinical cases are still rare. This study explores the epidemiological background to a severe rumen fluke outbreak in 6-month-old heifers on a dairy farm in Ireland. Sequence analysis of the cytochrome oxidase subunit 1 (Cox1) gene of the rumen fluke metacercariae on pasture failed to identify predominant, possibly pathogenic subtypes. However, estimates of metacercarial load indicated that the animals were exposed to a daily dose of about 5334 C. daubneyi metacercariae for a period of 3 weeks resulting in the build-up of very large numbers of immature worms in the small intestine. It is hypothesized that specific environmental conditions may favour this parasite over its competitor, the liver fluke, Fasciola hepatica, possibly by allowing it to emerge earlier. The possibility that C. daubneyi may be better adapted to the Irish climate than F. hepatica together with the fact that selective treatment against F. hepatica effectively frees the niche for C. daubneyi, may result in the gradual replacement of F. hepatica by C. daubneyi.
This paper presents a framework for the interactions between the processes of mapping and rerepresentation within analogy making. Analogical reasoning systems for use in design tasks require representations that are open to being reinterpreted. The framework, interpretation-driven mapping, casts the process of constructing an analogical relationship as requiring iterative, parallel interactions between mapping and interpreting. This paper argues that this interpretation-driven approach focuses research on a fundamental problem in analogy making: how do the representations that make new mappings possible emerge during the mapping process? The framework is useful for both describing existing analogy-making models and designing future ones. The paper presents a computational model informed by the framework Idiom, which learns ways to reinterpret the representations of objects as it maps between them. The results of an implementation in the domain of visual analogy are presented to demonstrate its feasibility. Analogies constructed by the system are presented as examples. The interpretation-driven mapping framework is then used to compare representational change in Idiom to that in three previously published systems.
The planet was once much more forested. As human populations have grown, the forests have been cleared to make way for crops and livestock. This conversion from forest to agriculture started in Neolithic times (Brown 1997) but accelerated during the European colonisation of North America and other territories. Since the 1970s, it has continued apace in the tropics. The need to produce food is not the only cause of deforestation: humans have always used timber as fuel and as a raw material for construction. They will continue to do so, whilst new threats are likely to emerge: for example, in recent years tropical forests and woodlands have been cleared to make way for biofuel crops and plantations. These changes are causing widespread concern, as they may bring short-term benefits at the expense of the sustained provision of ecosystem goods and services (Foley et al. 2007).
Since 1990 the world’s forests have shrunk from 28.6% to 27.6% of the land surface, with substantial shrinkage in the tropics and slight expansion in the temperate regions (calculated from FAO 2011). Overall, we expect to see a continuation of this trend as human populations continue to expand and economic development proceeds.
A clean hot-water drill was used to gain access to Subglacial Lake Whillans (SLW) in late January 2013 as part of the Whillans Ice Stream Subglacial Access Research Drilling (WISSARD) project. Over 3 days, we deployed an array of scientific tools through the SLW borehole: a downhole camera, a conductivity–temperature–depth (CTD) probe, a Niskin water sampler, an in situ filtration unit, three different sediment corers, a geothermal probe and a geophysical sensor string. Our observations confirm the existence of a subglacial water reservoir whose presence was previously inferred from satellite altimetry and surface geophysics. Subglacial water is about two orders of magnitude less saline than sea water (0.37–0.41 psu vs 35 psu) and two orders of magnitude more saline than pure drill meltwater (<0.002 psu). It reaches a minimum temperature of –0.55~C, consistent with depression of the freezing point by 7.019 MPa of water pressure. Subglacial water was turbid and remained turbid following filtration through 0.45 µm filters. The recovered sediment cores, which sampled down to 0.8 m below the lake bottom, contained a macroscopically structureless diamicton with shear strength between 2 and 6 kPa. Our main operational recommendation for future subglacial access through water-filled boreholes is to supply enough heat to the top of the borehole to keep it from freezing.
Haliclona indistincta has in some respects, a typical reproductive cycle for a marine haplosclerid sponge. We suggest that oocytes originate from archaeocytes and that spermatozoa originate from choanocytes. Oocytes were first seen in November and matured as eggs by May and June. Immature spermatic cysts were identified from February and mature cysts were present in May and June only. Of the individuals surveyed that had reproductive elements present (150/200), reproductive elements from a single sex were reported in over half of the specimens (59%) but there were also many hermaphrodites (41%). Embryos were first seen in June. Larvae were distributed throughout the mesohyl and were released from the end of June to the end of July. Three mobile larval stages and fusing of sibling larvae were observed. Post-settlement stages from early settlement to the development of oscula and excurrent canals are also shown. However, some elements of the larvae (uniform ciliation and no spicules at posterior pole) are not consistent with larvae from this genus.
OVERVIEW. The counseling needs of people with disabilities in African settings have received relatively little attention in the published literature, despite the fact that a majority of Africans, or their families, experience disability in their lifetimes. The disabilities arise mostly from avoidable causes such as inadequate health care systems, civil strife, marginal or failing national economies, and lack of enforcement of disability rights by national governments. This chapter addresses conceptions of disability from an African cultural heritage perspective and counseling interventions to address disability-related needs in those settings. Legal and professional issues that influence the availability of psychosocial services to people with disabilities in sub-Saharan Africa are considered. Counseling enhances health and quality of life in people of African descent with disabilities.
By the end of the chapter, the reader should be able to:
Define disability-related terms.
Explain the likely influence of culture on disability identity in an African cultural heritage setting.
Identify and describe the needs in people of African descent with disabilities that counseling services would meet.
Outline the typical counseling interventions that have been used in counseling people with disabilities in African settings and the rationale for their use.
Evaluate the role of community-based approaches in counseling people of African descent with disabilities.
Suggest and discuss ways in which counseling services for African cultural heritage people with disabilities could be enhanced.
In sub-Saharan Africa, over 22 million people are estimated to be co-infected with both helminths and HIV-1. Several studies have suggested that de-worming individuals with HIV-1 may delay HIV-1 disease progression, and that the benefit of de-worming may vary by individual helminth species. We conducted a systematic review and meta-analysis of the published literature to determine the effect of treatment of individual helminth infections on markers of HIV-1 progression (CD4 count and HIV viral load). There was a trend towards an association between treatment for Schistosoma mansoni and a decrease in HIV viral load (Weighted mean difference (WMD)=−0·10; 95% Confidence interval (CI): −0·24, 0·03), although this association was not seen for Ascaris lumbricoides, hookworm or Trichuris trichiura. Treatment of A. lumbricoides, S. mansoni, hookworm or T. trichiura was not associated with a change in CD4 count. While pooled data from randomized trials suggested clinical benefit of de-worming for individual helminth species, these effects decreased when observational data were included in the pooled analysis. While further trials are needed to confirm the role of anthelmintic treatment in HIV-1 co-infected individuals, providing anthelmintics to individuals with HIV-1 may be a safe, inexpensive and practical intervention to slow progression of HIV-1.
Since the pioneering text by Mathur and Epstein over 35 years ago, much of the work on this subject has been extended or superseded, producing an enormous body of scattered literature. This edited volume unifies the subject, pulling material together and underpinning it with fundamental theory to produce the only complete, up-to-date reference on all major areas of spouted bed research and practice. With contributions from internationally renowned research groups, this book guides the reader through new developments, insights and models. The hydrodynamic and reactor models of spouted and spout-fluid beds are examined, as well as such topics as particle segregation, heat and mass transfer, mixing and scale-up. Later chapters focus on drying, particle-coating and energy-related applications based on spouted and spout-fluid beds. This is a valuable resource for chemical and mechanical engineers in research and industry.