759–5 Use of an Interactive Electronic Whiteboard to Teach Clinical Cardiology Decision Analysis to Medical Students

We used innovative state-of-the-art computer and collaboration technologies to teach first-year medical students an analytic methodology to solve difficult clinical cardiology problems to make informed medical decisions. Clinical examples included the decision to administer thrombolytic therapy considering the risk of hemorrhagic stroke, and activity recommendations for athletes at risk for sudden death. Students received instruction on the decision-analytic approach which integrates pathophysiology, treatment efficacy, diagnostic test interpretation, health outcomes, patient preferences, and cost-effectiveness into a decision-analytic model.The traditional environment of a small group and blackboard was significantly enhanced by using an electronic whiteboard, the Xerox LiveBoard™. The LiveBoard features an 80486-based personal computer, large (3’×4’) display, and wireless pens for input. It allowed the integration of decision-analytic software, statistical software, digital slides, and additional media. We developed TIDAL (Team Interactive Decision Analysis in the Large-screen environment), a software package to interactively construct decision trees, calculate expected utilities, and perform one- and two-way sensitivity analyses using pen and gesture inputs. The Live Board also allowed the novel incorporation of Gambler, a utility assessment program obtained from the New England Medical Center. Gambler was used to obtain utilities for outcomes such as non-disabling hemorrhagic stroke. The interactive nature of the LiveBoard allowed real-time decision model development by the class, followed by instantaneous calculation of expected utilities and sensitivity analyses. The multimedia aspect and interactivity were conducive to extensive class participation.Ten out of eleven students wanted decision-analytic software available for use during their clinical years and all students would recommend the course to next year's students. We plan to experiment with the electronic collaboration features of this technology and allow groups separated by time or space to collaborate on decisions and explore the models created

Impact of Point-of-Care Testing on the Management of Sexually Transmitted Infections in South Africa: Evidence from the HVTN702 Human Immunodeficiency Virus Vaccine Trial.

BACKGROUND: Alternative approaches to syndromic management are needed to reduce rates of sexually transmitted infections (STIs) in resource-limited settings. We investigated the impact of point-of-care (POC) versus central laboratory-based testing on STI treatment initiation and STI adverse event (STI-AE) reporting. METHODS: We used Kaplan-Meier and Cox regression models to compare times to treatment initiation and STI-AE reporting among HVTN702 trial participants in South Africa. Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) were diagnosed POC at eThekwini clinic and in a central laboratory at Verulam/Isipingo clinics. All clinics used POC assays for Trichomonas vaginalis (TV) testing. RESULTS: Among 959 women (median age, 23 [interquartile range, 21-26] years), median days (95% confidence interval [95%CI]) to NG/CT treatment initiation and NG/CT-AE reporting were 0.20 (.16-.25) and 0.24 (.19-.27) at eThekwini versus 14.22 (14.12-15.09) and 15.12 (13.22-21.24) at Verulam/Isipingo (all P .05). Cox regression analysis revealed that NG/CT treatment initiation (adjusted hazard ratio [aHR], 39.62 [95%CI, 15.13-103.74]) and NG/CT-AE reporting (aHR, 3.38 [95%CI, 2.23-5.13]) occurred faster at eThekwini versus Verulam/Isipingo, while times to TV treatment initiation (aHR, 0.93 [95%CI, .59-1.48]) and TV-AE reporting (aHR, 1.38 [95%CI, .86-2.21]) were similar. CONCLUSIONS: POC testing led to prompt STI management with potential therapeutic and prevention benefits, highlighting its utility as a diagnostic tool in resource-limited settings

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Molecular Species Identification with Rich Floristic Sampling: DNA Barcoding the Pteridophyte Flora of Japan

BACKGROUND: DNA barcoding is expected to be an effective identification tool for organisms with heteromorphic generations such as pteridophytes, which possess a morphologically simple gametophyte generation. Although a reference data set including complete coverage of the target local flora/fauna is necessary for accurate identification, DNA barcode studies including such rich taxonomic sampling on a countrywide scale are lacking. METHODOLOGY/PRINCIPAL FINDINGS: The Japanese pteridophyte flora (733 taxa including subspecies and varieties) was used to test the utility of two plastid DNA barcode regions (rbcL and trnH-psbA) with the intention of developing an identification system for native gametophytes. DNA sequences were obtained from each of 689 (94.0%) taxa for rbcL and 617 (84.2%) taxa for trnH-psbA. Mean interspecific divergence values across all taxon pairs (K2P genetic distances) did not reveal a significant difference in rate between trnH-psbA and rbcL, but mean K2P distances of each genus showed significant heterogeneity according to systematic position. The minimum fail rate of taxon discrimination in an identification test using BLAST (12.52%) was obtained when rbcL and trnH-psbA were combined, and became lower in datasets excluding infraspecific taxa or apogamous taxa, or including sexual diploids only. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the overall effectiveness of DNA barcodes for species identification in the Japanese pteridophyte flora. Although this flora is characterized by a high occurrence of apogamous taxa that pose a serious challenge to identification using DNA barcodes, such taxa are limited to a small number of genera, and only minimally detract from the overall success rate. In the case that a query sequence is matched to a known apogamous genus, routine species identification may not be possible. Otherwise, DNA barcoding is a practical tool for identification of most Japanese pteridophytes, and is especially anticipated to be helpful for identification of non-hybridizing gametophytes

Genome Wide Analysis of Inbred Mouse Lines Identifies a Locus Containing Ppar-γ as Contributing to Enhanced Malaria Survival

The genetic background of a patient determines in part if a person develops a mild form of malaria and recovers, or develops a severe form and dies. We have used a mouse model to detect genes involved in the resistance or susceptibility to Plasmodium berghei malaria infection. To this end we first characterized 32 different mouse strains infected with P. berghei and identified survival as the best trait to discriminate between the strains. We found a locus on chromosome 6 by linking the survival phenotypes of the mouse strains to their genetic variations using genome wide analyses such as haplotype associated mapping and the efficient mixed-model for association. This new locus involved in malaria resistance contains only two genes and confirms the importance of Ppar-γ in malaria infection

Investigating the links between diagnostic uncertainty, emotional exhaustion, and turnover intention in General Practitioners working in the United Kingdom

BackgroundGeneral Practitioners (GPs) report high levels of burnout, job dissatisfaction, and turnover intention. The complexity of presenting problems to general practice makes diagnostic uncertainty a common occurrence that has been linked to burnout. The interrelationship between diagnostic uncertainty with other factors such as burnout, job satisfaction and turnover intention have not been previously examined.ObjectivesTo examine associations between diagnostic uncertainty, emotional exhaustion (EE), depersonalization (DP), job satisfaction, and turnover intention in GPs.MethodsSeventy general practices in England were randomly selected through the Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC). A total of 348 GPs within 67 these practices completed a 10-item online questionnaire which included questions on GP characteristics, work-life balance, job satisfaction, sickness presenteeism, diagnostic uncertainty, turnover intention as well as EE and DP. Associations between diagnostic uncertainty and each of EE, DP, job satisfaction, and turnover intention were evaluated in multivariate mixed-effect ordinal logistic regressions whilst adjusting for covariates, to account for the correlation in the three outcomes of interest.ResultsAlmost one-third of GPs (n = 101; 29%) reported experiencing >10% of diagnostic uncertainty in their day-to-day practice over the past year. GPs reporting greater diagnostic uncertainty had higher levels of EE [OR = 3.90; 95% CI = (2.54, 5.99)], job dissatisfaction [OR = 2.01; 95% CI = (1.30, 3.13)] and turnover intention [OR = 4.51; 95% CI = (2.86, 7.11)]. GPs with no sickness presenteeism had lower levels of EE [OR = 0.53; 95% CI = (0.35, 0.82)], job dissatisfaction [OR = 0.56; 95% CI = (0.35, 0.88)], and turnover intention [OR = 0.61; 95% CI = (0.41, 0.91)].ConclusionDiagnostic uncertainty may not only negatively impact on the wellbeing of GPs, but could also have adverse implications on workforce retention in primary care

Ευρετικές προσεγγίσεις του μοναδιάστατου προβλήματος πακετοποίησης

Article 59.1, of the International Code of Nomenclature for Algae, Fungi, and Plants (ICN; Melbourne Code), which addresses the nomenclature of pleomorphic fungi, became effective from 30 July 2011. Since that date, each fungal species can have one nomenclaturally correct name in a particular classification. All other previously used names for this species will be considered as synonyms. The older generic epithet takes priority over the younger name. Any widely used younger names proposed for use, must comply with Art. 57.2 and their usage should be approved by the Nomenclature Committee for Fungi (NCF). In this paper, we list all genera currently accepted by us in Dothideomycetes (belonging to 23 orders and 110 families), including pleomorphic and non-pleomorphic genera. In the case of pleomorphic genera, we follow the rulings of the current ICN and propose single generic names for future usage. The taxonomic placements of 1261 genera are listed as an outline. Protected names and suppressed names for 34 pleomorphic genera are listed separately. Notes and justifications are provided for possible proposed names after the list of genera. Notes are also provided on recent advances in our understanding of asexual and sexual morph linkages in Dothideomycetes. A phylogenetic tree based on four gene analyses supported 23 orders and 75 families, while 35 families still lack molecular data

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

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