39 research outputs found

    Mutational Analysis in Pediatric Thyroid Cancer and Correlations with Age, Ethnicity, and Clinical Presentation.

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    BackgroundWell-differentiated thyroid cancer (WDTC) incidence in pediatrics is rising, most being papillary thyroid carcinoma (PTC). The objective of the study was to assess the prevalence of different mutations in pediatric WDTC and correlate the genotype with the clinical phenotype.MethodsThis is a single-center retrospective study. Thyroid tissue blocks from 42 consecutive pediatric WDTC patients who underwent thyroidectomy between 2001 and 2013 were analyzed at Quest Diagnostics for BRAF(V600E), RAS mutations (N,K,H), and RET/PTC and PAX8/PPARγ rearrangements, using validated molecular methods. Thyroid carcinomas included PTC, follicular thyroid carcinoma (FTC), and follicular variant of PTC (FVPTC).ResultsThirty-nine samples (29 females) were genotyped. The mean age at diagnosis was 14.7 years (range 7.9-18.4 years), and most were Hispanic (56.4%) or Caucasian (35.9%). The mean follow-up period was 2.9 years. Mutations were noted in 21/39 (53.8%), with both BRAF(V600E) (n = 9), and RET/PTC (n = 6) detected only in PTC. Mutations were detected in 2/5 FTC (PAX8/PPARγ and NRAS) and 3/6 FVPTC cases (PAX8/PPARγ). Of 28 PTC patients, 57.1% had mutations: 32.1% with BRAF(V600E), 21.4% with RET/PTC, and 3.6% with NRAS. Of patients with BRAF(V600E), 77.8% were Hispanic and 88.9% were >15 years, while all RET/PTC-positive patients were ≤15 years (p = 0.003). Tumor size, lymph node involvement, and distant metastasis at diagnosis (or soon after (131)I ablation) did not vary significantly based on the mutation.ConclusionsBRAF(V600E) was the most common mutation, especially in older and Hispanic adolescents. A larger, ethnically diverse pediatric cohort followed long term will enable the genotypic variability, clinical presentation, and response to therapy to be better assessed

    Evaluation of the benefits and risks of introducing Ebola community care centers, Sierra Leone.

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    In some parts of western Africa, Ebola treatment centers (ETCs) have reached capacity. Unless capacity is rapidly scaled up, the chance to avoid a generalized Ebola epidemic will soon diminish. The World Health Organization and partners are considering additional Ebola patient care options, including community care centers (CCCs), small, lightly staffed units that could be used to isolate patients outside the home and get them into care sooner than otherwise possible. Using a transmission model, we evaluated the benefits and risks of introducing CCCs into Sierra Leone's Western Area, where most ETCs are at capacity. We found that use of CCCs could lead to a decline in cases, even if virus transmission occurs between CCC patients and the community. However, to prevent CCC amplification of the epidemic, the risk of Ebola virus-negative persons being exposed to virus within CCCs would have to be offset by a reduction in community transmission resulting from CCC use

    Financing of International Collective Action for Epidemic and Pandemic Preparedness.

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    The global pandemic response has typically followed cycles of panic followed by neglect. We are now, once again, in a phase of neglect, leaving the world highly vulnerable to massive loss of life and economic shocks from natural or human-made epidemics and pandemics. Quantifying the size of the losses caused by large-scale outbreaks is challenging because the epidemiological and economic research in this field is still at an early stage. Research on the 1918 influenza H1N1 pandemic and recent epidemics and pandemics has shown a range of estimated losses (panel).1; 2; 3; 4; 5; 6 ; 7 A limitation in assessing the economic costs of outbreaks is that they only capture the impact on income. Fan and colleagues8 recently addressed this limitation by estimating the “inclusive” cost of pandemics: the sum of the cost in lost income and a dollar valuation of the cost of early death. They found that for Ebola and severe acute respiratory syndrome (SARS), the true (“inclusive”) costs are two to three times the income loss. For extremely serious pandemics such as that of influenza in 1918, the inclusive costs are over five times income loss. The inclusive costs of the next severe influenza pandemic could be US570billioneachyearor07570 billion each year or 0·7% of global income (range 0·4–1·0%)8—an economic threat similar to that of global warming, which is expected to cost 0·2–2·0% of global income annually. Given the magnitude of the threat, we call for scaled-up financing of international collective action for epidemic and pandemic preparedness. Two planks of preparedness must be strengthened. The first is public health capacity—including human and animal disease surveillance—as a first line of defence.9 Animal surveillance is important since most emerging infectious diseases with outbreak potential originate in animals. Rigorous external assessment of national capabilities is critical; WHO developed the Joint External Evaluation (JEE) tool specifically for this purpose.10 Financing for this first plank will largely be through domestic resources, but supplementary donor financing to low-income, high-risk countries is also needed. The second plank is financing global efforts to accelerate research and development (R&D) of vaccines, drugs, and diagnostics for outbreak control, and to strengthen the global and regional outbreak preparedness and response system. These two international collective action activities are underfunded.11 Medical countermeasures against many emerging infectious diseases are currently missing. We need greater investment in development of vaccines, therapeutics, and diagnostics to prevent potential outbreaks from becoming humanitarian crises. The new Coalition for Epidemic Preparedness Innovations (CEPI), which aims to mobilise 1 billion over 5 years, is developing vaccines against known emerging infectious diseases as well as platforms for rapid development of vaccines against outbreaks of unknown origin. The WHO R&D Blueprint for Action to Prevent Epidemics12 is a new mechanism for coordinating and prioritising the development of drugs and diagnostics for emerging infectious diseases. Consolidating and enhancing donor support for these new initiatives would be an efficient way to channel resources aimed at improving global outbreak preparedness and response. Crucial components of the global and regional system for outbreak control include surge capacity (eg, the ability to urgently deploy human resources); providing technical guidance to countries in the event of an outbreak; and establishing a coordinated, interlinked global, regional, and national surveillance system. These activities are the remit of several essential WHO financing envelopes that all face major funding shortfalls. The Contingency Fund for Emergencies finances surge outbreak response for up to 3 months. The fund has a capitalisation target of 100millionofflexiblevoluntarycontributions,whichneedstobereplenishedwithabout100 million of flexible voluntary contributions, which needs to be replenished with about 25–50 million annually, depending on the extent of the outbreak in any given year. However, as of April 30, 2017, only 3765millionhadbeencontributed,withanadditional37·65 million had been contributed, with an additional 4 million in pledges.13 The WHO Health Emergencies and Health Systems Preparedness Programmes face an annual shortfall of 225millioninfundingtheirepidemicandpandemicpreventionandcontrolactivities.14Previoushealthemergencieshaveshownthatitcantaketimetoorganiseglobalcollectiveactionandprovidefinancingtothenationalandlocallevel.Insuchsituations,aglobalmechanismshouldofferarapidinjectionofliquiditytoaffectedcountries.TheWorldBank2˘7sPandemicEmergencyFinancingFacility(PEF)isaproposedglobalinsurancemechanismforpandemicemergencies.15Itaimstoprovidesurgefundingforresponseeffortstohelprespondtorare,highburdendiseaseoutbreaks,preventingthemfrombecomingmoredeadlyandcostlypandemics.ThePEFcurrentlyproposesacoverageof225 million in funding their epidemic and pandemic prevention and control activities.14 Previous health emergencies have shown that it can take time to organise global collective action and provide financing to the national and local level. In such situations, a global mechanism should offer a rapid injection of liquidity to affected countries. The World Bank\u27s Pandemic Emergency Financing Facility (PEF) is a proposed global insurance mechanism for pandemic emergencies.15 It aims to provide surge funding for response efforts to help respond to rare, high-burden disease outbreaks, preventing them from becoming more deadly and costly pandemics. The PEF currently proposes a coverage of 500 million for the insurance window; increasing the current coverage will require additional donor commitments. In addition, the PEF has a $50–100 million replenishable cash window. As the world\u27s health ministers meet this month for the World Health Assembly, we propose five key ways to help prevent mortality and economic shocks from disease outbreaks. First, to accelerate development of new technologies to control outbreaks, donors should expand their financing for CEPI and support the WHO R&D Blueprint for Action to Prevent Epidemics. Second, funding gaps in the WHO Contingency Fund for Emergencies and the WHO Health Emergencies Programme should be urgently filled and the PEF should be fully financed. Third, all nations should support their own and other countries\u27 national preparedness efforts, including committing to the JEE process. Fourth, we believe it would be valuable to create and maintain a regional and country-level pandemic risk and preparedness index. This index could potentially be used as a way to review preparedness in International Monetary Fund article IV consultations (regular country reports by staff to its Board). Finally, we call for a new global effort to develop long-term national, regional, and global investment plans to create a world secure from the threat of devastation from outbreaks. This article summarises the recommendations of a workshop held at the National Academy of Medicine, Washington, DC, USA, co-hosted by the Center for Policy Impact in Global Health at Duke University, Durham, NC, USA and the Coalition for Epidemic Preparedness Innovations, Oslo, Norway. Participants\u27 travel and accommodation were supported by the Center for Policy Impact in Global Health. BO is a consultant to Metabiota, a private company engaged in infectious disease risk modelling and analytical services. In this capacity, he has led the development of an index measuring national capacity to respond to epidemic and pandemic disease outbreaks

    Public health, conflict and human rights: toward a collaborative research agenda

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    Although epidemiology is increasingly contributing to policy debates on issues of conflict and human rights, its potential is still underutilized. As a result, this article calls for greater collaboration between public health researchers, conflict analysts and human rights monitors, with special emphasis on retrospective, population-based surveys. The article surveys relevant recent public health research, explains why collaboration is useful, and outlines possible future research scenarios, including those pertaining to the indirect and long-term consequences of conflict; human rights and security in conflict prone areas; and the link between human rights, conflict, and International Humanitarian Law

    Do Frogs Get Their Kicks on Route 66? Continental U.S. Transect Reveals Spatial and Temporal Patterns of Batrachochytrium dendrobatidis Infection

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    The chytrid fungus Batrachochytrium dendrobatidis (Bd) has been devastating amphibians globally. Two general scenarios have been proposed for the nature and spread of this pathogen: Bd is an epidemic, spreading as a wave and wiping out individuals, populations, and species in its path; and Bd is endemic, widespread throughout many geographic regions on every continent except Antarctica. To explore these hypotheses, we conducted a transcontinental transect of United States Department of Defense (DoD) installations along U.S. Highway 66 from California to central Illinois, and continuing eastward to the Atlantic Seaboard along U.S. Interstate 64 (in sum from Marine Corps Base Camp Pendleton in California to Naval Air Station Oceana in Virginia). We addressed the following questions: 1) Does Bd occur in amphibian populations on protected DoD environments? 2) Is there a temporal pattern to the presence of Bd? 3) Is there a spatial pattern to the presence of Bd? and 4) In these limited human-traffic areas, is Bd acting as an epidemic (i.e., with evidence of recent introduction and/or die-offs due to chytridiomycosis), or as an endemic (present without clinical signs of disease)? Bd was detected on 13 of the 15 bases sampled. Samples from 30 amphibian species were collected (10% of known United States' species); half (15) tested Bd positive. There was a strong temporal (seasonal) component; in total, 78.5% of all positive samples came in the first (spring/early-summer) sampling period. There was also a strong spatial component—the eleven temperate DoD installations had higher prevalences of Bd infection (20.8%) than the four arid (<60 mm annual precipitation) bases (8.5%). These data support the conclusion that Bd is now widespread, and promote the idea that Bd can today be considered endemic across much of North America, extending from coast-to-coast, with the exception of remote pockets of naïve populations

    Patient-Reported oral health outcome measurement for children and adolescents

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    BACKGROUND: Oral health is an important component of daily functioning and well-being. A comprehensive patient-reported oral health measure is needed to gauge the impact of oral health status on children and adolescents. This study aims to develop oral health item banks and associated short-form surveys for children and adolescents 2–17 year olds. METHODS: Using children and adolescents, ages 2–17 years, selected from diverse dental sites in Greater Los Angeles Area, we propose to develop state-of-the-science methods to create oral health item banks to effectively measure oral health outcomes for children and adolescents. Methods include a literature review of existing measures, focus groups, cognitive interviews, drafting and field testing of survey items, and evaluation of the psychometric properties of the measures. RESULTS: Based on the systematic literature search and focus groups, we identified core (physical health, mental health, and social function domains) and peripheral (e.g., need and access) oral health domains. We then drafted survey items and revised them based on 66 cognitive interviews (27 children/adolescents and 39 parents) with 39 families. The revised items will be administered in a field test of 500 children and adolescents ages 2–17, and their parents. CONCLUSIONS: The qualitative methods used in the initial phases of the project (focus group and cognitive interviews) are the initial steps in the development of oral health item banks and associated short-form surveys for children and adolescents. The oral health items can potentially be used to create effective computerized adaptive test and/or create ad hoc short forms targeting specific areas of oral health to survey large populations of children with much less cost compared with traditional clinical oral health examination

    The Science Performance of JWST as Characterized in Commissioning

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    This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

    Field Investigations of Natural Disasters and Complex Emergencies

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    © 2008 by Oxford University Press, Inc. All rights reserved. This chapter discusses field investigations of disasters and emergencies. Topics covered include the historical development of field epidemiology in disasters and emergencies, role of the epidemiologist in disaster response, problems faced in the field, rapid quantitative needs assessment, and surveys
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