191 research outputs found

    Public perceptions of expert disagreement: Bias and incompetence or a complex and random world?

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    30 page PDFExpert disputes can present laypeople with several challenges including trying to understand why such disputes occur. In an online survey of the U.S. public, we used a psychometric approach to elicit perceptions of expert disputes for 56 forecasts sampled from seven domains (climate change, crime, economics, environment, health, politics, terrorism). People with low education, or with low self-reported knowledge of the topic, were most likely to attribute expert disputes to expert incompetence. People with higher self-reported knowledge tended to attribute disputes to expert bias due to financial or ideological reasons. The more highly educated and cognitively able were most likely to attribute disputes to natural factors, such as the irreducible complexity and randomness of the phenomenon. We highlight several important implications of these results for scientists and risk managers and argue for further research on how people perceive and grapple with expert disputes.We would like to acknowledge the generous support of the National Science Foundation: This material is based upon work supported by NSF under Grant Nos. #1231231 (Robin Gregory, PI; Nathan Dieckmann co-PI) and #0925008 (Nathan Dieckmann, PI) to Decision Research. All views expressed in this paper are those of the authors alone

    Prognostic value of a modified surprise question designed for use in the emergency department setting.

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    OBJECTIVE: Few reliable and valid prognostic tools are available to help emergency physicians identify patients who might benefit from early palliative approaches. We sought to determine if responses to a modified version of the surprise question, Would you be surprised if this patient died in the next 30 days could predict in-hospital mortality and resource utilization for hospitalized emergency department patients. METHODS: For this observational study, emergency physicians responded to the modified surprise question with each admission over a five-month study period. Logistic regression analyses were completed and standard test characteristics evaluated. RESULTS: 6,122 visits were evaluated. Emergency physicians responded negatively to the modified surprise question in 918 (15.1%). Test characteristics for in-hospital mortality were: sensitivity 32%, specificity 85%, positive predictive value 6%, negative predictive value 98%. The risk of intensive care unit use (relative risk [RR], 1.87; 95% confidence interval [CI], 1.45 to 2.40), use of \u27comfort measures\u27 orders (RR, 3.43; 95% CI, 2.81 to 4.18), palliative-care consultation (RR, 3.06; 95% CI, 2.62 to 3.56), and in-hospital mortality (RR, 2.18; 95% CI, 1.72 to 2.76) were greater for patients with negative responses. CONCLUSION: The modified surprise question is a simple trigger for palliative care needs, accurately identifying those at greater risk for in-hospital mortality and resource utilization. With a negative predictive value of 98%, affirmative responses to the modified surprise question provide reassurance that in-hospital death is unlikely

    Prognostic value of a modified surprise question designed for use in the emergency department setting

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    Objective Few reliable and valid prognostic tools are available to help emergency physicians identify patients who might benefit from early palliative approaches. We sought to determine if responses to a modified version of the surprise question, “Would you be surprised if this patient died in the next 30 days” could predict in-hospital mortality and resource utilization for hospitalized emergency department patients. Methods For this observational study, emergency physicians responded to the modified surprise question with each admission over a five-month study period. Logistic regression analyses were completed and standard test characteristics evaluated. Results 6,122 visits were evaluated. Emergency physicians responded negatively to the modified surprise question in 918 (15.1%). Test characteristics for in-hospital mortality were: sensitivity 32%, specificity 85%, positive predictive value 6%, negative predictive value 98%. The risk of intensive care unit use (relative risk [RR], 1.87; 95% confidence interval [CI], 1.45 to 2.40), use of ‘comfort measures’ orders (RR, 3.43; 95% CI, 2.81 to 4.18), palliative-care consultation (RR, 3.06; 95% CI, 2.62 to 3.56), and in-hospital mortality (RR, 2.18; 95% CI, 1.72 to 2.76) were greater for patients with negative responses. Conclusion The modified surprise question is a simple trigger for palliative care needs, accurately identifying those at greater risk for in-hospital mortality and resource utilization. With a negative predictive value of 98%, affirmative responses to the modified surprise question provide reassurance that in-hospital death is unlikely

    Genetic Manipulation of Schistosoma haematobium, the Neglected Schistosome

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    More people are infected with Schistosoma haematobium than other major human schistosomes yet it has been less studied because of difficulty in maintaining the life cycle in the laboratory. S. haematobium might be considered the ‘neglected schistosome’ since minimal information on the genome and proteome of S. haematobium is available, in marked contrast to the other major schistosomes. In this report we describe tools and protocols to investigate the genome and genetics of this neglected schistosome. We cultured developmental stages of S. haematobium, and investigated the utility of introducing gene probes into the parasites to silence two model genes. One of these, firefly luciferase, was a reporter gene whereas the second was a schistosome gene encoding a surface protein, termed Sh-tsp-2. We observed that both genes could be silenced – a phenomenon known as experimental RNA interference (RNAi). These findings indicated that the genome of S. haematobium will be amenable to genetic manipulation investigations designed to determine the function and importance of genes of this schistosome and to investigate for novel anti-parasite treatments

    Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

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    We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

    A randomized controlled trial of tai chi for long-term low back pain (TAI CHI): Study rationale, design, and methods

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    <p>Abstract</p> <p>Background</p> <p>Low back pain persisting for longer than 3 months is a common and costly condition for which many current treatments have low-moderate success rates at best. Exercise is among the more successful treatments for this condition, however, the type and dosage of exercise that elicits the best results is not clearly defined. Tai chi is a gentle form of low intensity exercise that uses controlled movements in combination with relaxation techniques and is currently used as a safe form of exercise for people suffering from other chronic pain conditions such as arthritis. To date, there has been no scientific evaluation of tai chi as an intervention for people with back pain. Thus the aim of this study will be to examine the effects of a tai chi exercise program on pain and disability in people with long-term low back pain.</p> <p>Methods and design</p> <p>The study will recruit 160 healthy individuals from the community setting to be randomised to either a tai chi intervention group or a wait-list control group. Individuals in the tai chi group will attend 2 tai chi sessions (40 minutes)/week for 8 weeks followed by 1 tai chi session/week for 2 weeks. The wait-list control will continue their usual health care practices and have the opportunity to participate in the tai chi program once they have completed the follow-up assessments. The primary outcome will be bothersomeness of back symptoms measured with a 0–10 numerical rating scale. Secondary outcomes include, self-reports of pain-related disability, health-related quality of life and global perceived effect of treatment. Statistical analysis of primary and secondary outcomes will be based on the intention to treat principle. Linear mixed models will be used to test for the effect of treatment on outcome at 10 weeks follow up. This trial has received ethics approval from The University of Sydney Human Research Ethics Committee. HREC Approval No.10452</p> <p>Discussion</p> <p>This study will be the first trial in this area and the information on its effectiveness will allow patients, clinicians and treatment funders to make informed choices regarding this treatment.</p> <p>Trial Registration</p> <p>This trial has been registered with Australian New Zealand Clinical Trials Registry. <b>ACTRN12608000270314</b></p

    PubChem3D: a new resource for scientists

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    <p>Abstract</p> <p>Background</p> <p>PubChem is an open repository for small molecules and their experimental biological activity. PubChem integrates and provides search, retrieval, visualization, analysis, and programmatic access tools in an effort to maximize the utility of contributed information. There are many diverse chemical structures with similar biological efficacies against targets available in PubChem that are difficult to interrelate using traditional 2-D similarity methods. A new layer called PubChem3D is added to PubChem to assist in this analysis.</p> <p>Description</p> <p>PubChem generates a 3-D conformer model description for 92.3% of all records in the PubChem Compound database (when considering the parent compound of salts). Each of these conformer models is sampled to remove redundancy, guaranteeing a minimum (non-hydrogen atom pair-wise) RMSD between conformers. A diverse conformer ordering gives a maximal description of the conformational diversity of a molecule when only a subset of available conformers is used. A pre-computed search per compound record gives immediate access to a set of 3-D similar compounds (called "Similar Conformers") in PubChem and their respective superpositions. Systematic augmentation of PubChem resources to include a 3-D layer provides users with new capabilities to search, subset, visualize, analyze, and download data.</p> <p>A series of retrospective studies help to demonstrate important connections between chemical structures and their biological function that are not obvious using 2-D similarity but are readily apparent by 3-D similarity.</p> <p>Conclusions</p> <p>The addition of PubChem3D to the existing contents of PubChem is a considerable achievement, given the scope, scale, and the fact that the resource is publicly accessible and free. With the ability to uncover latent structure-activity relationships of chemical structures, while complementing 2-D similarity analysis approaches, PubChem3D represents a new resource for scientists to exploit when exploring the biological annotations in PubChem.</p

    Helminth Genomics: The Implications for Human Health

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    More than two billion people (one-third of humanity) are infected with parasitic roundworms or flatworms, collectively known as helminth parasites. These infections cause diseases that are responsible for enormous levels of morbidity and mortality, delays in the physical development of children, loss of productivity among the workforce, and maintenance of poverty. Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation. Draft genome sequences of the filarial worm Brugia malayi and two of the human schistosomes, Schistosoma japonicum and S. mansoni, are now available, among others. These genome data will provide the basis for a comprehensive understanding of the molecular mechanisms involved in helminth nutrition and metabolism, host-dependent development and maturation, immune evasion, and evolution. They are likely also to predict new potential vaccine candidates and drug targets. In this review, we present an overview of these efforts and emphasize the potential impact and importance of these new findings

    Apoptotic Effects of Antilymphocyte Globulins on Human Pro-inflammatory CD4+CD28− T-cells

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    BACKGROUND: Pro-inflammatory, cytotoxic CD4(+)CD28(-) T-cells with known defects in apoptosis have been investigated as markers of premature immuno-senescence in various immune-mediated diseases. In this study we evaluated the influence of polyclonal antilymphocyte globulins (ATG-Fresenius, ATG-F) on CD4(+)CD28(-) T-cells in vivo and in vitro. PRINCIPAL FINDINGS: Surface and intracellular three colour fluorescence activated cell sorting analyses of peripheral blood mononuclear cells from 16 consecutive transplant recipients and short-term cell lines were performed. In vivo, peripheral levels of CD3(+)CD4(+)CD28(-) T-cells decreased from 3.7 ± 7.1% before to 0 ± 0% six hours after ATG-F application (P = 0.043) in 5 ATG-F treated but not in 11 control patients (2.9 ± 2.9% vs. 3.9 ± 3.0%). In vitro, ATG-F induced apoptosis even in CD4(+)CD28(-) T-cells, which was 4.3-times higher than in CD4(+)CD28(+) T-cells. ATG-F evoked apoptosis was partially reversed by the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) and prednisolon-21-hydrogensuccinate. ATG-F triggered CD25 expression and production of pro-inflammatory cytokines, and induced down-regulation of the type 1 chemokine receptors CXCR-3, CCR-5, CX3CR-1 and the central memory adhesion molecule CD62L predominately in CD4(+)CD28(-) T-cells. CONCLUSION: In summary, in vivo depletion of peripheral CD3(+)CD4(+)CD28(-) T-cells by ATG-F in transplant recipients was paralleled in vitro by ATG-F induced apoptosis. CD25 expression and chemokine receptor down-regulation in CD4(+)CD28(-) T-cells only partly explain the underlying mechanism
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