A visual and curatorial approach to clinical variant prioritization and disease gene discovery in genome-wide diagnostics

Background: Genome-wide data are increasingly important in the clinical evaluation of human disease. However, the large number of variants observed in individual patients challenges the efficiency and accuracy of diagnostic review. Recent work has shown that systematic integration of clinical phenotype data with genotype information can improve diagnostic workflows and prioritization of filtered rare variants. We have developed visually interactive, analytically transparent analysis software that leverages existing disease catalogs, such as the Online Mendelian Inheritance in Man database (OMIM) and the Human Phenotype Ontology (HPO), to integrate patient phenotype and variant data into ranked diagnostic alternatives. Methods: Our tool, “OMIM Explorer” (http://www.omimexplorer.com), extends the biomedical application of semantic similarity methods beyond those reported in previous studies. The tool also provides a simple interface for translating free-text clinical notes into HPO terms, enabling clinical providers and geneticists to contribute phenotypes to the diagnostic process. The visual approach uses semantic similarity with multidimensional scaling to collapse high-dimensional phenotype and genotype data from an individual into a graphical format that contextualizes the patient within a low-dimensional disease map. The map proposes a differential diagnosis and algorithmically suggests potential alternatives for phenotype queries—in essence, generating a computationally assisted differential diagnosis informed by the individual’s personal genome. Visual interactivity allows the user to filter and update variant rankings by interacting with intermediate results. The tool also implements an adaptive approach for disease gene discovery based on patient phenotypes. Results: We retrospectively analyzed pilot cohort data from the Baylor Miraca Genetics Laboratory, demonstrating performance of the tool and workflow in the re-analysis of clinical exomes. Our tool assigned to clinically reported variants a median rank of 2, placing causal variants in the top 1 % of filtered candidates across the 47 cohort cases with reported molecular diagnoses of exome variants in OMIM Morbidmap genes. Our tool outperformed Phen-Gen, eXtasy, PhenIX, PHIVE, and hiPHIVE in the prioritization of these clinically reported variants. Conclusions: Our integrative paradigm can improve efficiency and, potentially, the quality of genomic medicine by more effectively utilizing available phenotype information, catalog data, and genomic knowledge

Jaguar (Panthera onca) food habits in Atlantic rain forest of southeastern Brazil

Between January and December 1996, the food habits of a relict population of jaguars were studied in 220 km(2) Linhares Forest Preserve, which comprises much of the remaining old-growth Atlantic Forest of Espirito Santo, Brazil. Fecal analysis indicated opportunistic feeding on 24 prey species (N = 101 scats). Mammals represented 87 percent of the total items, followed by reptiles (9.8%) and birds (2.8%). Considering prey weight, 23.4 percent of the items weighed 1-3 kg, 40.5 percent were 3-10 kg, and 27.7 percent weighed more than 10 kg. Analysis of relative prey frequency and biomass indicated that the diet was concentrated in two prey types: long-nosed armadillo and white-lipped peccary. Literature data suggest that forest jaguars rely on the same mammal prey over their entire geographic range

Expanding Landscapes: Intersections between Writing Center Work and Other Academic Fields

This presentation explores the intersections between writing center work and math education, counseling psychology, and speech/hearing sciences. The four fields share more similarities than first expected, such as prioritizing relational approaches and maintaining client agency. Implications for writing centers include the need to adjust consultant education to overtly explore such overlaps in order to increase new consultants’ confidence and circumvent potential problems caused by differing assumptions

Effect of parenteral infusion of fish oil-based lipid emulsion on systemic inflammatory cytokines and lung eicosanoid levels in experimental acute pancreatitis

Aim: we evaluated the effect of short-term FOLE infusion before experimental induction of AP on systemic cytokine and lung eicosanoid profiles.Methods: Lewis rats (n = 72) received parenteral infusion of FOLE (FO group) or saline (SS group), or remained without parenteral infusion (CG group) for 48 h. Thereafter, AP was induced by retrograde injection of sodium taurocholate into the pancreatic duct. Animals were sacrificed after 2, 12 and 24 h. Blood and lung samples were collected to assess serum inflammatory cytokines (Luminex) and tissue eicosanoids (ELISA), respectively.Results: serum TNF-α increased over time and serum IL-10 decreased from 12 to 24 h in CG group. In SS group serum TNF-α increased from 12 to 24 h (p = 0.039) and serum IL-10 decreased over time. Both CG and SS groups exhibited increased IL-6/IL-10 ratio (p = 0.040). From 12 to 24 h animals from FO group showed decreased serum IL-1 (p < 0.001), IL-4 (p < 0.002) and IL-6 (p = 0.050), and a trend towards increased IL-10 (p = 0.060). All experimental groups showed a trend towards increased PGE2 and decreased LTB4 in the lung at 24 compared with 12 hConclusion: parenteral infusion of FOLE for 48 h before the induction of experimental AP appears to favorably influence the cytokine response without affecting lung eicosanoids at the time points measured. The use of FOLE to prevent and treat AP following major surgery needs to be further explore

Habitat of juvenile Caribbean reef sharks, Carcharhinus perezi, at two oceanic insular marine protected areas in the southwestern Atlantic Ocean: Fernando de Noronha Archipelago and Atol das Rocas, Brazil

Habitat of juvenile Caribbean reef sharks, Carcharhinus perezi (Carcharhinidae), was identified using fishing surveys and capture of immature specimens at two Brazilian insular sites in the southwestern Atlantic Ocean, Fernando de Noronha Archipelago and Atol das Rocas. Standardized sampling at Fernando de Noronha indicated that parturition occurred from February to April and that a wide depth-range (at least 5-30 m) along the insular shelf was used by immature sharks throughout the year. The catch-per-unit effort of C. perezi was significantly higher inside than outside a marine protected area at this location, suggesting that these sharks are more common in parts of the reef least disturbed by human activities. More limited sampling at Atol das Rocas suggested that juvenile C. perezi occurred at similar depths and utilized similar substrate as sharks at Fernando de Noronha. These findings suggest that successful conservation and management of this economically important, protected species will need to include conservation of habitat around insular reef systems. © 2006 Elsevier B.V. All rights reserved

Individual and population benefits of marine reserves for reef sharks

No-take marine protected areas (MPAs) are a commonly applied tool to reduce human fishing impacts on marine and coastal ecosystems. However, conservation outcomes of MPAs for mobile and long-lived predators such as sharks are highly variable. Here, we use empirical animal tracking data from 459 individual sharks and baited remote underwater video surveys undertaken in 36 countries to construct an empirically supported individual-based model that estimates the conservation effectiveness of MPAs for five species of coral reef-associated sharks (Triaenodon obesus, Carcharhinus melanopterus, Carcharhinus amblyrhynchos, Carcharhinus perezi, and Ginglymostoma cirratum). We demonstrate how species-specific individual movement traits can contribute to fishing mortality of sharks found within MPAs as they move outside to adjacent fishing grounds. We discovered that the world's officially recorded coral reef-based managed areas (with a median width of 9.4 km) would need to be enforced as strict no-take MPAs and up to 5 times larger to expect protection of the majority of individuals of the five investigated reef shark species. The magnitude of this effect depended on local abundances and fishing pressure, with MPAs required to be 1.6-2.6 times larger to protect the same number of Atlantic and Caribbean species, which occur at lower abundances than similar species in the western Pacific. Furthermore, our model was used to quantify partially substantial reductions (>50%) in fishing mortality resulting from small increases in MPA size, allowing us to bridge a critical gap between traditional conservation planning and fisheries management. Overall, our results highlight the challenge of relying on abundance data alone to ensure that estimates of shark conservation impacts of MPAs follow the precautionary approach

Infusion time for fish oil-containing parenteral emulsions in surgery: A study on omega-3 fatty acid dynamics in rats

Objectives The aim of this study was to contribute to the design of specialized parenteral nutrition protocols in surgery by evaluating the dynamics of polyunsaturated fatty acid (PUFA) concentrations in different body pools after the infusion of fish oil–containing lipid emulsion (FOLE) in rats that had undergone surgical central venous catheterization (CVC). Methods After 5-d adaptation in metabolic cages, 78 male Lewis rats (300–450 g) fed a standard diet were sacrificed (baseline control) or had only CVC (surgical control) or also received a 72-h infusion of a parenteral lipid emulsion with or without fish oil. The catheterized animals were sacrificed 0 (T0), 2 (T2), 6 (T6), and 12 h (T12) after the infusion ended. Gas chromatography was used to determine the concentrations of eicosapentaenoic (EPA), docosahexaenoic (DHA), and arachidonic (ARA) acids and the ω-3 to ω-6 ratio in plasma, liver, and blood leukocytes. Kruskal–Wallis and Wilcoxon tests were applied to plasma and liver data and descriptive analysis to leukocyte data. Results Plasma, liver, and leukocytes exhibited almost undetectable EPA and DHA and detectable ARA concentrations at baseline. Immediately after FOLE infusion (T0), these PUFAs changed in all pools, resulting in a higher ratio of ω-3 to ω-6 compared with rats with no FOLE infusion (P < 0.05). All these changes decreased over time, with residual effects remaining until T6 in plasma, T12 in liver, and only until T2 in leukocytes. Conclusion Data from this study suggest that ω-3 PUFAs are cleared early after the end of FOLE infusion, mainly in leukocytes. This should be considered when FOLEs are applied for immunomodulatory purposes in surgery