Abstracts from the NIHR INVOLVE Conference 2017

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Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Personalized, Health-Aware Recipe Recommendation: An Ensemble Topic Modeling Based Approach

The 4th International Workshop on Health Recommender Systems (HealthRecSys 2019), Copenhagen, Denmark, 20 September 2019Food choices are personal and complex and have a significant impact on our long-term health and quality of life. By helping users to make informed and satisfying decisions, Recommender Systems (RS) have the potential to support users in making healthier food choices. Intelligent users-modeling is a key challenge in achieving this potential. This paper investigates Ensemble Topic Modelling (EnsTM) based Feature Identification techniques for efficient user-modeling and recipe recommendation. It builds on findings in EnsTM to propose a reduced data representation format and a smart user-modeling strategy that makes capturing user-preference fast, efficient and interactive. This approach enables personalization, even in a cold-start scenario. We compared three EnsTM based variations through a user study with 48 participants, using a large-scale, real-world corpus of 230,876 recipes, and compare against a conventional Content Based (CB) approach. EnsTM based recommenders performed significantly better than the CB approach. Besides acknowledging multi-domain contents such as taste, demographics and cost, our proposed approach also considers user’s nutritional preference and assists them finding recipes under diverse nutritional categories. Furthermore, it provides excellent coverage and enables implicit understanding of user’s food practices. Subsequent analysis also exposed correlation between certain features and healthier lifestyle.Science Foundation IrelandInsight Research Centr

Environmental contaminants and biomarker responses in fish from the Rio Grande and its U.S. tributaries: Spatial and temporal trends

We collected, examined, and analyzed 368 fish of seven species from 10 sites on rivers of the Rio Grande Basin (RGB) during late 1997 and early 1998 to document temporal and geographic trends in the concentrations of accumulative contaminants and to assess contaminant effects on the fish. Sites were located on the mainstem of the Rio Grande and on the Arroyo Colorado and Pecos River in Texas (TX), New Mexico (NM), and Colorado. Common carp (Cyprinus carpio) and largemouth bass (Micropterus salmoides) were the targeted species. Fish were examined in the field for internal and external visible gross lesions, selected organs were weighed to compute ponderal and organosomatic indices, and samples of tissues and fluids were obtained and preserved for analysis of fish health and reproductive biomarkers. Whole fish from each station were composited by species and gender and analyzed for organochlorine chemical residues and elemental contaminants using instrumental methods, and for 2,3,7,8-tetrachloro dibenzo-p-dioxin-like activity (TCDD-EQ) using the H4IIE rat hepatoma cell bioassay. Overall, fish from lower RGB stations contained greater concentrations of organochlorine pesticide residues and appeared to be less healthy than those from sites in the central and upper parts of the basin, as indicated by a general gradient of residue concentrations and biomarker responses. A minimal number of altered biomarkers and few or no elevated contaminant concentrations were noted in fish from the upper RGB. The exception was elevated concentrations [up to 0.46 µg/g wet-weight (ww)] of total mercury (Hg) in predatory species from the Rio Grande at Elephant Butte Reservoir, NM, a condition documented in previous studies. Arsenic (As) and selenium (Se) concentrations were greatest in fish from sites in the central RGB; Se concentrations in fish from the Pecos River at Red Bluff Lake, TX and from the Rio Grande at Langtry, TX and Amistad International Reservoir, TX exceeded published fish and wildlife toxicity thresholds. In the lower RGB, residues of p,p\u27-DDT metabolites (≤ 1.69 Ag/g ww), chlordane-related compounds (≤ 0.21 Ag/g ww), dieldrin (≤ 0.0.05 Ag/g ww), and toxaphene (≤ 2.4 Ag/g ww) were detected in fish from most sites; maximum concentrations were in channel catfish (Ictalurus punctatus) from the Arroyo Colorado at Harlingen, TX. Concentrations of one or more residues exceeded toxicity thresholds for fish and wildlife in fish from this site and from the Rio Grande at Mission, TX and Brownsville, TX; however, concentrations were lower than those reported by previous studies. In addition, the proportional concentrations of p,p\u27-DDT at all sites were low, indicating weathered DDT rather than the influx of new material. Concentrations of total PCBs (\u3c 0.05 Ag/g ww) and TCDD-EQ (≤ 6 pg/g ww) were comparatively low in all samples. Hepatic ethoxyresorufin O-deethylase (EROD) activity in some fish was elevated relative to reference rates at most sites, but was generally lower than previously reported activity in fish from heavily contaminated locations. The comparatively low PCB and TCDD-EQ concentrations together with elevated EROD activity may reflect exposure to polycyclic aromatic hydrocarbons. Reproductive biomarkers were consistent with chronic contaminant exposure at lower RGB sites; comparatively large percentages of intersex male largemouth bass, relatively low gonadosomatic indices, and elevated plasma vitellogenin concentrations in male fish were noted at three of the four stations. Large percentages of atretic eggs were also observed in the ovaries of female common carp from the Rio Grande at Brownsville, TX. Although many of the conditions noted may have other causes in addition to contaminant exposure, the biomarker results for the lower RGB sites are consistent with subtle responses of fish to contaminants, an interpretation supported by the chemical data of this and other investigations

Environmental contaminants and biomarker responses in fish from the Columbia River and its tributaries: Spatial and temporal trends

Fish were collected from 16 sites on rivers in the Columbia River Basin (CRB) from September 1997 to April 1998 to document temporal and spatial trends in the concentrations of accumulative contaminants and to assess contaminant effects on the fish. Sites were located on the mainstem of the Columbia River and on the Snake, Willamette, Yakima, Salmon, and Flathead Rivers. Common carp (Cyprinus carpio), black bass (Micropterus sp.), and large-scale sucker (Catostomus macrocheilus) were the targeted species. Fish were field-examined for external and internal lesions, selected organs were weighed to compute somatic indices, and tissue and fluid samples were preserved for fish health and reproductive biomarker analyses. Composite samples of whole fish, grouped by species and gender, from each site were analyzed for organochlorine and elemental contaminants using instrumental methods and for 2,3,7,8-tetrachloro dibenzo-p-dioxin-like activity (TCDD-EQ) using the H4IIE rat hepatoma cell bioassay. Overall, pesticide concentrations were greatest in fish from lower CRB sites and elemental concentrations were greatest in fish from upper CRB sites. These patterns reflected land uses. Lead (Pb) concentrations in fish from the Columbia River at Northport and Grand Coulee, Washington (WA) exceeded fish and wildlife toxicity thresholds (\u3e 0.4 μg/g). Selenium (Se) concentrations in fish from the Salmon River at Riggins, Idaho (ID), the Columbia River at Vernita Bridge, WA, and the Yakima River at Granger, WA exceeded toxicity thresholds for piscivorous wildlife (\u3e 0.6 μg/g). Mercury (Hg) concentrations in fish were elevated throughout the basin but were greatest (\u3e0.4 μg/g) in predatory fish from the Salmon River at Riggins, ID, the Yakima River at Granger, WA, and the Columbia River at Warrendale, Oregon (OR). Residues of p,p′-DDE were greatest (\u3e0.8 μg/g) in fish from agricultural areas of the Snake, Yakima, and Columbia River basins but were not detected in upper CRB fish. Other organochlorine pesticides did not exceed toxicity thresholds in fish or were detected infrequently. Total polychlorinated biphenyls (PCBs; \u3e0.11 μg/g) and TCDD-EQs (\u3e5 pg/g) exceeded wildlife guidelines in fish from the middle and lower CRB, and ethoxyresorufin O-deethylase (EROD) activity was also elevated at many of the same sites. Temporal trend analysis indicated decreasing or stable concentrations of Pb, Se, Hg, p,p′-DDE, and PCBs at most sites where historical data were available. Altered biomarkers were noted in fish throughout the CRB. Fish from some stations had responded to chronic contaminant exposure as indicated by fish health and reproductive biomarker results. Although most fish from some sites had grossly visible external or internal lesions, histopathological analysis determined these to be inflammatory responses associated with helminth or myxosporidian parasites. Many largescale sucker from the Columbia River at Northport and Grand Coulee, WA had external lesions and enlarged spleens, which were likely associated with infections. Intersex male smallmouth bass (Micropterus dolomieu) were found in the Snake River at Lewiston, ID and the Columbia River at Warrendale, OR. Male bass, carp, and largescale sucker containing low concentrations of vitellogenin were common in the CRB, and comparatively high concentrations (\u3e0.3 mg/mL) were measured in male fish from the Flathead River at Creston, Montana, the Snake River at Ice Harbor Dam, WA, and the Columbia River at Vernita Bridge, WA and Warrendale, OR. Results from our study and other investigations indicate that continued monitoring in the CRB is warranted to identify consistently degraded sites and those with emerging problems

Chemical contaminants, health indicators, and reproductive biomarker responses in fish from rivers in the Southeastern United States

Largemouth bass (Micropterus salmoides) and common carp (Cyprinus carpio)were collected from 13 sites located in the Mobile (MRB), Apalachicola–Flint–Chattahoochee (ARB), Savannah (SRB), and Pee Dee (PRB) River Basins to document spatial trends in accumulative chemical contaminants, health indicators, and reproductive biomarkers. Organochlorine residues, 2,3,7,8-tetrachlorodibenzo-p-dioxin-like activity (TCDD-EQ), and elemental contaminants were measured in composite samples of whole fish, grouped by species and gender, from each site. Mercury (Hg) and polychlorinated biphenyls (PCBs) were the primary contaminants of concern. Concentrations of Hg in bass samples from all basins exceeded toxicity thresholds for piscivorous mammals (\u3e0.1 μg/g ww), juvenile and adult fish (\u3e0.2 μg/g ww), and piscivorous birds (\u3e0.3 μg/g ww). Total PCB concentrations in samples from the MRB, ARB, and PRB were \u3e480 ng/gww and may be a risk to piscivorous wildlife. Selenium concentrations also exceeded toxicity thresholds (\u3e0.75 μg/gww) in MRB and ARB fish. Concentrations of other formerly used (total chlordanes, dieldrin, endrin, aldrin, mirex, and hexachlorobenzene) and currently used (pentachlorobenzene, pentachloroanisole, dacthal, endosulfan, γ-hexachlorocyclohexane, and methoxychlor) organochlorine residues were generally low or did not exceed toxicity thresholds for fish and piscivorous wildlife. TCDD-EQs exceeded wildlife dietary guidelines (\u3e5 pg/g ww) in MRB and PRB fish. Hepatic ethoxyresorufin O-deethylase (EROD) activity was generally greatest in MRB bass and carp. Altered fish health indicators and reproductive biomarker were noted in individual fish, but mean responses were similar among basins. The field necropsy and histopathological examination determined that MRB fish were generally in poorer health than those from the other basins, primarily due to parasitic infestations. Tumors were found in few fish (n=5; 0.01%); ovarian tumors of smooth muscle origin were found in two ARB carp from the same site. Intersex gonads were identified in 47male bass (42%) representing 12 sites and may indicate exposure to potential endocrine disrupting compounds. Comparatively high vitellogenin concentrations (N0.35 mg/mL) in male fish from the MRB, SRB, and PRB indicate exposure to estrogenic or anti-androgenic chemicals

Similarities in Maternal Weight and Birth Weight Across Pregnancies and Across Sisters

Objectives The current study examined how prepregnancy body mass index (BMI), gestational weight gain, and birth weight cluster between births within women and between women who are sisters. Methods Using data from the National Longitudinal Survey of Youth 1979 cohort, we utilized nested, multivariable hierarchical linear models to examine the correlation of these three outcomes between births (n = 6006) to women (n = 3605) and sisters (n = 3170) so that we can quantify the clustering by sibship and by woman for these three pregnancy-related outcomes. Results After controlling for confounding covariates, prepregnancy BMI (intraclass correlation (ICC) 0.24, 95% CI 0.16, 0.32), gestational weight gain (ICC 0.23, 95% CI 0.16, 0.31), and infant's birthweight (ICC 0.07, 95% CI 0.003, 0.13) were correlated between sisters. Additionally, all three outcomes were significantly correlated between births for each sister, suggesting that prepregnancy BMI (ICC 0.82, 95% CI 0.81, 0.83), gestational weight gain (ICC 0.45, 95% CI 0.42, 0.49), and birth weight (ICC 0.31, 95% CI 0.28, 0.35) track between pregnancies in the same woman. Conclusions for Practice The observed clustering both within women and between sisters suggests that shared genetic and environmental factors among sisters play a role in pregnancy outcomes above and beyond that of women's own genetic and environmental factors. Findings suggest that asking a woman about her sisters' pregnancy outcomes could provide insight into the possible outcomes for her current pregnancy. Future research should test if collecting such a family history and providing tailored clinical recommendations accordingly would be useful

Contaminant Concentrations and Ciomarker Responses of Piscivorous and Benthivorous Fish in the Colorado River Basin

The Large River Monitoring Network (LRMN) of the Biomonitoring of Environmental Status and Trends (BEST) Program measured tissue concentrations of selected contaminants and evaluated biomarker responses in black bass (Micropterus sp.), common carp (Cyprinus carpio), and channel catfish (Ictalurus punctatus) at 14 locations within Colorado River Basin (CDRB) in 2003. Major tributaries including the Yampa, Green, Gunnison, San Juan, and Gila Rivers were also sampled. Organic and inorganic contaminants were measured in whole-body composite fish samples, and the H4IIE bioassay determined dioxin-like activity in these samples. Fish health indicators (condition factor, somatic indices), immune system indicators (macrophage aggregate parameters), various molecular biomarkers (EROD, vitellogenin), and reproductive indicators (steroid hormones, gonadal histology) were measured in individual fish. Mean microsomal EROD activity was greatest in carp (\u3e9 pmol/min/mg) from Phoenix, AZ, in channel catfish (\u3e10 pmol/min/mg) from Vernal, UT and Grand Junction, CO, and in Bass (\u3e60 pmol/min/mg) from Vernal, UT. Fish health indicators including macrophage aggregates and oocyte atresia indicated poor health of carp in the Lake Mead area. High health assessment index (HAI) values in bass, channel catfish, and carp collected throughout the CDRB were attributed to abnormalities of the liver, kidney, and spleen. Histological examination of the gonads revealed several intersex fish. Previous contaminant studies in this basin have a wide range of focus from high concentrations of selenium in irrigation return flows to emerging contaminants downstream of Las Vegas. Other concerns include dropping water levels in the lower Colorado River and the reestablishment of endangered species within the CDRB. The goal of this BEST LRMN project is to help characterize fish health and contaminant concerns in the CDRB