Sample records for potential assessment progress

  1. An Argument for Formative Assessment with Science Learning Progressions

    ERIC Educational Resources Information Center

    Alonzo, Alicia C.

    2018-01-01

    Learning progressions--particularly as defined and operationalized in science education--have significant potential to inform teachers' formative assessment practices. In this overview article, I lay out an argument for this potential, starting from definitions for "formative assessment practices" and "learning progressions"…

  2. Scanning laser Doppler imaging may predict disease progression of localized scleroderma in children and young adults.

    PubMed

    Shaw, L J; Shipley, J; Newell, E L; Harris, N; Clinch, J G; Lovell, C R

    2013-07-01

    Localized scleroderma is a rare but potentially disfiguring and disabling condition. Systemic treatment should be started early in those with active disease in key functional and cosmetic sites, but disease activity is difficult to determine clinically. Superficial blood flow has been shown to correlate with disease activity in localized scleroderma. To examine whether superficial blood flow measured by laser Doppler imaging (LDI) has the potential to predict disease progression and therefore select patients for early systemic treatment. A group of 20 individuals had clinical assessment and scanning LDI blood-flow measurements of 32 affected body sites. After a mean follow-up of 8.7 months their clinical outcome was compared with the results of the initial LDI assessment. Eleven out of 15 patients with an assessment of active LDI had progressed clinically, and 16 out of the 17 scans with inactive LDI assessment had not progressed, giving a positive predictive value of 73% and a negative predictive value of 94%. We believe that LDI can be a useful tool in predicting disease progression in localized scleroderma, and it may help clinicians to decide which patients to treat early. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

  3. Designing the National Assessment of Educational Progress to Serve a Wider Community of Users: A Position Paper.

    ERIC Educational Resources Information Center

    Bock, R. Darrell

    Efforts have been made to increase the dissemination and use of data generated by the National Assessment of Educational Progress (NAEP). Potential users include those concerned with curriculum and methods evaluation, public policymakers, and researchers. NAEP can provide data for curriculum evaluation, including item analysis data which assist in…

  4. Gaining Momentum, Losing Ground. Progress Report, 2008

    ERIC Educational Resources Information Center

    Business Roundtable, 2008

    2008-01-01

    This report presents an update of the progress of Tapping America's Potential (TAP), a coalition of 15 of the nation's leading business organizations, and assesses three years' progress since 2005 in working towards the goal of doubling the number of students earning bachelor's degrees in science, technology, engineering and math (STEM) by 2015.…

  5. NAEP Reconfigured: An Integrated Redesign of the National Assessment of Educational Progress. Working Paper Series.

    ERIC Educational Resources Information Center

    Johnson, Eugene G.; Lazer, Stephen; O'Sullivan, Christine Y.

    Chapters in this report outline the potential plans for the redesign of the National Assessment of Educational Progress (NAEP). It is argued that any successful redesign must consider the NAEP as a whole. This report reviews overall NAEP designs and discusses the implications that each of the designs has for various functional areas. The following…

  6. When dementia progresses quickly: a practical approach to the diagnosis and management of rapidly progressive dementia.

    PubMed

    Day, Gregory S; Tang-Wai, David F

    2014-01-01

    Making a diagnosis of rapidly progressive dementia requires practical adaptation of the skills used to assess patients with chronic causes of cognitive impairment. An expedited assessment, commensurate with the accelerated pace of the disease, is required to identify the cause of symptoms amidst a myriad of possibilities. Features upon history, physical examination and cognitive assessment that support specific diagnoses are reviewed, and a stratified approach to testing is presented. The use of readily-accessible investigations is prioritized, acknowledging the implications and applications of novel diagnostic tests. The coordinated use of clinical and laboratory measures are promoted as a means of facilitating rapid evaluation, with the ultimate goal of identifying patients with potentially reversible causes of rapidly progressive dementia.

  7. Review and Oversight of the 1998 Reading Results of the National Assessment of Educational Progress (NAEP)--The Nation's Report Card. Hearing before the Subcommittee on Oversight and Investigations of the Committee on Education and the Workforce. United States House of Representatives, One Hundred Sixth Congress, First Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Committee on Education and the Workforce.

    This document presents the transcript (and written statements) of a congressional hearing on the potential politicization of the National Assessment of Educational Progress (NAEP) and the trustworthiness of the scores that the states received during the 1998 reading assessment. It addresses whether Vice President Al Gore's "release" of…

  8. [Research progress and development trend of quantitative assessment techniques for urban thermal environment.

    PubMed

    Sun, Tie Gang; Xiao, Rong Bo; Cai, Yun Nan; Wang, Yao Wu; Wu, Chang Guang

    2016-08-01

    Quantitative assessment of urban thermal environment has become a focus for urban climate and environmental science since the concept of urban heat island has been proposed. With the continual development of space information and computer simulation technology, substantial progresses have been made on quantitative assessment techniques and methods of urban thermal environment. The quantitative assessment techniques have been developed to dynamics simulation and forecast of thermal environment at various scales based on statistical analysis of thermal environment on urban-scale using the historical data of weather stations. This study reviewed the development progress of ground meteorological observation, thermal infrared remote sensing and numerical simulation. Moreover, the potential advantages and disadvantages, applicability and the development trends of these techniques were also summarized, aiming to add fundamental knowledge of understanding the urban thermal environment assessment and optimization.

  9. Novel Applications of Radionuclide Imaging in Peripheral Vascular Disease

    PubMed Central

    Stacy, Mitchel R.; Sinusas, Albert J.

    2015-01-01

    Peripheral vascular disease (PVD) is a progressive atherosclerotic disease that leads to stenosis or occlusion of blood vessels supplying the lower extremities. Current diagnostic imaging techniques commonly focus on evaluation of anatomy or blood flow at the macrovascular level and do not permit assessment of the underlying pathophysiology associated with disease progression or treatment response. Molecular imaging with radionuclide-based approaches, such as PET and SPECT, can offer novel insight into PVD by providing non-invasive assessment of biological processes such as angiogenesis and atherosclerosis. This review discusses emerging radionuclide-based imaging approaches that have potential clinical applications in the evaluation of PVD progression and treatment. PMID:26590787

  10. 75 FR 9232 - Measuring Progress on Food Safety: Current Status and Future Directions; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-01

    ... for assessing progress in food safety and associated methodological issues and to discuss potential.... The FoodNet also conducts special studies to determine risk factors for acquiring those illnesses... production, studies on the prevalence of specific pathogens in specific classes of food, and studies of...

  11. Improving Cardiac Action Potential Measurements: 2D and 3D Cell Culture.

    PubMed

    Daily, Neil J; Yin, Yue; Kemanli, Pinar; Ip, Brian; Wakatsuki, Tetsuro

    2015-11-01

    Progress in the development of assays for measuring cardiac action potential is crucial for the discovery of drugs for treating cardiac disease and assessing cardiotoxicity. Recently, high-throughput methods for assessing action potential using induced pluripotent stem cell (iPSC) derived cardiomyocytes in both two-dimensional monolayer cultures and three-dimensional tissues have been developed. We describe an improved method for assessing cardiac action potential using an ultra-fast cost-effective plate reader with commercially available dyes. Our methods improve dramatically the detection of the fluorescence signal from these dyes and make way for the development of more high-throughput methods for cardiac drug discovery and cardiotoxicity.

  12. An Update on the Progress of the Extended One-Generation Reproductive Protocol

    EPA Science Inventory

    Consistent with a more science-based approach assessing potential adverse effects of pesticides, the ILSI-HESI Agricultural Chemical Safety Assessment (ACSA) Technical Committee, proposed a new tiered toxicity testing strategy. This approach utilizes fewer animals and provides an...

  13. Workshop overview: approaches to the assessment of the allergenic potential of food from genetically modified crops.

    PubMed

    Ladics, Gregory S; Holsapple, Michael P; Astwood, James D; Kimber, Ian; Knippels, Leon M J; Helm, Ricki M; Dong, Wumin

    2003-05-01

    There is a need to assess the safety of foods deriving from genetically modified (GM) crops, including the allergenic potential of novel gene products. Presently, there is no single in vitro or in vivo model that has been validated for the identification or characterization of potential food allergens. Instead, the evaluation focuses on risk factors such as source of the gene (i.e., allergenic vs. nonallergenic sources), physicochemical and genetic comparisons to known allergens, and exposure assessments. The purpose of this workshop was to gather together researchers working on various strategies for assessing protein allergenicity: (1) to describe the current state of knowledge and progress that has been made in the development and evaluation of appropriate testing strategies and (2) to identify critical issues that must now be addressed. This overview begins with a consideration of the current issues involved in assessing the allergenicity of GM foods. The second section presents information on in vitro models of digestibility, bioinformatics, and risk assessment in the context of clinical prevention and management of food allergy. Data on rodent models are presented in the next two sections. Finally, nonrodent models for assessing protein allergenicity are discussed. Collectively, these studies indicate that significant progress has been made in developing testing strategies. However, further efforts are needed to evaluate and validate the sensitivity, specificity, and reproducibility of many of these assays for determining the allergenicity potential of GM foods.

  14. Future Perspectives for Management of Stage A Heart Failure.

    PubMed

    Tanaka, Hidekazu

    2018-05-07

    Patients with Stage A heart failure (HF) show no HF symptoms but have related comorbid diseases with a high risk of progressing to HF. Screening for comorbid diseases warrants closer attention because of the growing interest in addressing Stage A HF as the best means of preventing eventual progression to overt HF such as Stages C and D. The identification of individuals of Stage A HF is potentially useful for the implementation of HF-prevention strategies; however, not all Stage A HF patients develop left ventricular (LV) structural heart disease or symptomatic HF, which lead to advanced HF stages. Therefore, Stage A HF requires management with the long-term goal of avoiding HF development; likewise, Stage B HF patients are ideal targets for HF prevention. Although the early detection of subclinical LV dysfunction is, thus, essential for delaying the progression to HF, the assessment of subclinical LV dysfunction can be challenging. Global longitudinal strain (GLS) as assessed by speckle-tracking echocardiography has recently been reported to be a sensitive marker of early subtle LV myocardial abnormalities, helpful for the prediction of the outcomes for various cardiac diseases, and superior to conventional echocardiographic indices. GLS reflects LV longitudinal myocardial systolic function, and can be assessed usually by means of two-dimensional speckle-tracking. This article reviews the importance of the assessment of subclinical LV dysfunction in Stage A HF patients by means of GLS, and its current potential to prevent progression to later stage HF.

  15. The National Assessment Approach to Objectives and Exercise Development.

    ERIC Educational Resources Information Center

    Ward, Barbara

    The National Assessment of Educational Progress (NAEP) item development procedures, possible improvements or alternatives to these procedures, and methods used to control potential sources of errors of interpretation are described. Current procedures call for the assessment of 9-, 13- and 17-year-olds in subject areas typically taught in schools.…

  16. New secondary batteries utilizing electronically conductive polymer cathodes

    NASA Technical Reports Server (NTRS)

    Martin, Charles R.; White, Ralph E.

    1989-01-01

    The objectives of this project are to characterize the transport properties in electronically conductive polymers and to assess the utility of these films as cathodes in lithium/polymer secondary batteries. During this research period, progress has been made in a literature survey of the historical background, methods of preparation, the physical and chemical properties, and potential technological applications of polythiophene. Progress has also been made in the characterization of polypyrrole flat films and fibrillar films. Cyclic voltammetry and potential step chronocoulometry were used to gain information on peak currents and potentials switching reaction rates, charge capacity, and charge retention. Battery charge/discharge studies were also performed.

  17. Needs and challenges for assessing the environmental impacts of engineered nanomaterials (ENMs)

    PubMed Central

    Romero-Franco, Michelle; Godwin, Hilary A; Bilal, Muhammad

    2017-01-01

    The potential environmental impact of nanomaterials is a critical concern and the ability to assess these potential impacts is top priority for the progress of sustainable nanotechnology. Risk assessment tools are needed to enable decision makers to rapidly assess the potential risks that may be imposed by engineered nanomaterials (ENMs), particularly when confronted by the reality of limited hazard or exposure data. In this review, we examine a range of available risk assessment frameworks considering the contexts in which different stakeholders may need to assess the potential environmental impacts of ENMs. Assessment frameworks and tools that are suitable for the different decision analysis scenarios are then identified. In addition, we identify the gaps that currently exist between the needs of decision makers, for a range of decision scenarios, and the abilities of present frameworks and tools to meet those needs. PMID:28546894

  18. Importance of investigating epigenetic alterations for industry and regulators: An appraisal of current efforts by the Health and Environmental Sciences Institute.

    PubMed

    Miousse, Isabelle R; Currie, Richard; Datta, Kaushik; Ellinger-Ziegelbauer, Heidrun; French, John E; Harrill, Alison H; Koturbash, Igor; Lawton, Michael; Mann, Derek; Meehan, Richard R; Moggs, Jonathan G; O'Lone, Raegan; Rasoulpour, Reza J; Pera, Renee A Reijo; Thompson, Karol

    2015-09-01

    Recent technological advances have led to rapid progress in the characterization of epigenetic modifications that control gene expression in a generally heritable way, and are likely involved in defining cellular phenotypes, developmental stages and disease status from one generation to the next. On November 18, 2013, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) held a symposium entitled "Advances in Assessing Adverse Epigenetic Effects of Drugs and Chemicals" in Washington, D.C. The goal of the symposium was to identify gaps in knowledge and highlight promising areas of progress that represent opportunities to utilize epigenomic profiling for risk assessment of drugs and chemicals. Epigenomic profiling has the potential to provide mechanistic information in toxicological safety assessments; this is especially relevant for the evaluation of carcinogenic or teratogenic potential and also for drugs that directly target epigenetic modifiers, like DNA methyltransferases or histone modifying enzymes. Furthermore, it can serve as an endpoint or marker for hazard characterization in chemical safety assessment. The assessment of epigenetic effects may also be approached with new model systems that could directly assess transgenerational effects or potentially sensitive stem cell populations. These would enhance the range of safety assessment tools for evaluating xenobiotics that perturb the epigenome. Here we provide a brief synopsis of the symposium, update findings since that time and then highlight potential directions for future collaborative efforts to incorporate epigenetic profiling into risk assessment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Early progressive encephalopathy in boys and MECP2 mutations.

    PubMed

    Kankirawatana, P; Leonard, H; Ellaway, C; Scurlock, J; Mansour, A; Makris, C M; Dure, L S; Friez, M; Lane, J; Kiraly-Borri, C; Fabian, V; Davis, M; Jackson, J; Christodoulou, J; Kaufmann, W E; Ravine, D; Percy, A K

    2006-07-11

    MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.

  20. A Road Map for Learning Progressions Research in Geography

    ERIC Educational Resources Information Center

    Huynh, Niem Tu; Solem, Michael; Bednarz, Sarah Witham

    2015-01-01

    This article provides an overview of learning progressions (LP) and assesses the potential of this line of research to improve geography education. It presents the merits and limitations of three of the most common approaches used to conduct LP research and draws on one approach to propose a first draft of a LP on map reading and interpretation.…

  1. 18F-FDG PET imaging for identifying the dynamics of intestinal disease caused by SFTSV infection in a mouse model.

    PubMed

    Hayasaka, Daisuke; Nishi, Kodai; Fuchigami, Takeshi; Shiogama, Kazuya; Onouchi, Takanori; Shimada, Satoshi; Tsutsumi, Yutaka; Morita, Kouichi

    2016-01-05

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that causes fever, enteritis, thrombocytopenia, and leucopenia and can be fatal in up to 30% of cases. However, the mechanism of severe disease is not fully understood. Molecular imaging approaches, such as positron-emission tomography (PET), are functional in vivo imaging techniques that provide real-time dynamics of disease progression, assessments of pharmacokinetics, and diagnoses for disease progression. Molecular imaging also potentially provides useful approaches to explore the pathogenesis of viral infections. Thus, the purpose of this study was to image the pathological features of SFTSV infection in vivo by PET imaging. In a mouse model, we showed that 18F-FDG accumulations clearly identified the intestinal tract site as a pathological site. We also demonstrated that 18F-FDG PET imaging can assess disease progression and response to antiserum therapy within the same individual. This is the first report demonstrating a molecular imaging strategy for SFTSV infection. Our results provide potentially useful information for preclinical studies such as the elucidation of the mechanism of SFTSV infection in vivo and the assessment of drugs for SFTS treatment.

  2. Teacher Effectiveness in the Formative Use of a Mathematical Assessment

    ERIC Educational Resources Information Center

    Collette, Lisa Audrey

    2012-01-01

    In current research literature, formative assessment has been identified as having the potential for tracking student progress to ensure high-stakes test preparedness. Formative assessment has several shades of meaning. This study defines it as an ongoing process that utilizes all of the moment-by-moment day-by-day pieces of data that can be…

  3. Assessment in Gifted Education: A Review of the Literature from 2005 to 2016

    ERIC Educational Resources Information Center

    Cao, Thuy Hong; Jung, Jae Yup; Lee, Jihyun

    2017-01-01

    Assessment is a crucial component of gifted education. Not only does it facilitate the recognition of the potential and specific needs of gifted students, it also monitors the progress and growth of gifted students, and allows for the evaluation of gifted education programs. In the present review, we synthesize the literature on assessment in…

  4. Assessment approaches in massive open online courses: Possibilities, challenges and future directions

    NASA Astrophysics Data System (ADS)

    Xiong, Yao; Suen, Hoi K.

    2018-03-01

    The development of massive open online courses (MOOCs) has launched an era of large-scale interactive participation in education. While massive open enrolment and the advances of learning technology are creating exciting potentials for lifelong learning in formal and informal ways, the implementation of efficient and effective assessment is still problematic. To ensure that genuine learning occurs, both assessments for learning (formative assessments), which evaluate students' current progress, and assessments of learning (summative assessments), which record students' cumulative progress, are needed. Providers' more recent shift towards the granting of certificates and digital badges for course accomplishments also indicates the need for proper, secure and accurate assessment results to ensure accountability. This article examines possible assessment approaches that fit open online education from formative and summative assessment perspectives. The authors discuss the importance of, and challenges to, implementing assessments of MOOC learners' progress for both purposes. Various formative and summative assessment approaches are then identified. The authors examine and analyse their respective advantages and disadvantages. They conclude that peer assessment is quite possibly the only universally applicable approach in massive open online education. They discuss the promises, practical and technical challenges, current developments in and recommendations for implementing peer assessment. They also suggest some possible future research directions.

  5. NAEP Design.

    ERIC Educational Resources Information Center

    National Opinion Research Center, Chicago, IL.

    To fulfill its mandate and its potential the National Assessment of Educational Progress (NAEP) must be a multi-content annual assessment of priority learning areas. This report describes a procedure under which measures of attainment can be charted over time in a broad range of skill domains, on item-invariant item response theory scales, using…

  6. Landscape assessment for tourism

    Treesearch

    Clare A. Gunn

    1979-01-01

    Increased development of landscapes for tourism now creates problems of integrating the many parts. Accomplishments at the site scale have not been matched with equal progress at the regional scale. This concept, and its example of application, shows promise of assisting regions in assessing their potential of landscapes before development. With such a concept, not...

  7. Clinical synovitis in a particular joint is associated with progression of erosions and joint space narrowing in that same joint, but not in patients initially treated with infliximab.

    PubMed

    Klarenbeek, N B; Güler-Yüksel, M; van der Heijde, D M F M; Hulsmans, H M J; Kerstens, P J S M; Molenaar, T H E; de Sonnaville, P B J; Huizinga, T W J; Dijkmans, B A C; Allaart, C F

    2010-12-01

    To assess the relationship between joint tenderness, swelling and joint damage progression in individual joints and to evaluate the influence of treatment on these relationships. First-year data of the Behandel Strategieën (BeSt) study were used, in which patients recently diagnosed as having rheumatoid arthritis (RA) were randomly assigned into four different treatment strategies. Baseline and 1-year x-rays of the hands and feet were assessed using the Sharp-van der Heijde score (SHS). With generalised estimating equations, 3-monthly assessments of tender and swollen joints of year 1 were related to erosion progression, joint space narrowing (JSN) progression and total SHS progression at the individual joint level (definition > 0.5 SHS units) in year 1, corrected for potential confounders and within-patient correlation for multiple joints per patient. During year 1, 59% of all 13 959 joints analysed were ever tender and 45% ever swollen, 2.1% showed erosion progression, 1.9% JSN progression and 3.6% SHS progression. Swelling and tenderness were both independently associated with erosion and JSN progression with comparable OR, although with higher OR in the hands than in the feet. Local swelling and tenderness were not associated with local damage progression in patients initially treated with infliximab. Clinical signs of synovitis are associated with erosion and JSN progression in individual joints after 1 year in RA. A disconnect between synovitis and joint damage progression was observed at joint level in patients who were treated with methotrexate and infliximab as initial treatment, confirming the disconnect between synovitis and the development of joint damage in tumour necrosis factor blockers seen at patient level.

  8. Does nailfold capillaroscopy help predict future outcomes in systemic sclerosis? A systematic literature review.

    PubMed

    Paxton, Dolcie; Pauling, John D

    2018-02-14

    Nailfold capillaroscopy (NC) is an important diagnostic tool in systemic sclerosis (SSc). Confirmation of NC as a prognostic factor could facilitate earlier intervention and slow disease progression in SSc. We undertook a systematic literature review to evaluate the prognostic value of NC in predicting SSc disease progression. Standardised searches of EMBASE and MEDLINE were undertaken to identify longitudinal studies of adult subjects with SSc reporting the prognostic value of NC for any aspect of disease progression and/or survival. Non-English, non-original research, animal studies, non-adult studies and non-full length reports were excluded from the analysis (PROSPERO 2017:CRD42017071719). Wide heterogeneity in study design, prognostic factor measurement and study outcomes necessitated a qualitative data synthesis. The "QUality In Prognosis Studies" (QUIPS) risk-of-bias tool was used to assess study quality. Study selection, data extraction and risk-of-bias assessment were each undertaken independently by 2 reviewers and consensus reached where necessary. Of 942 retrieved articles, 18 studies fulfilled the inclusion criteria. The majority of studies (17/18, 94%) reported positive associations between baseline NC appearances (using a variety of qualitative, semi-quantitative and quantitative NC endpoints) and clinical outcomes including digital ulcer (DU) occurrence/healing, survival, disease progression (using domains of Medsger disease severity scale), calcinosis, skin progression, pulmonary arterial hypertension (PAH), and/or a composite analysis of "cardiovascular events". Application of the QUIPS tool identified a moderate-high risk of potential bias in 6/18 studies for study participation, 3/18 studies for study attrition, 10/18 for prognostic factor measurement, 5/18 for outcome measurement, 13/18 for confounders and 13/18 for statistical analyses. Study quality limited the strength of the conclusions drawn from these studies. The most important source of potential bias across the studies was insufficient adjustment for potential confounders; such as existing DU disease in studies evaluating future DU occurrence. Recent work suggests NC evolution is an important predictor of disease progression in SSc. High levels of potential bias relating to study confounding and statistical analysis make it difficult to draw conclusions regarding the prognostic role of NC in SSc. There is strong evidence supporting an association between NC abnormalities (particularly capillary loss) and disease severity (particularly vascular manifestations such as DU, calcinosis and PAH). Evolution of NC appearances may represent a more important predictor of disease progression which could have important implications for the future use of NC in the routine longitudinal assessment and management of SSc. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Progress toward determining the potential of ODS alloys for gas turbine applications

    NASA Technical Reports Server (NTRS)

    Dreshfield, R. L.; Hoppin, G., III; Sheffler, K.

    1983-01-01

    The Materials for Advanced Turbine Engine (MATE) Program managed by the NASA Lewis Research Center is supporting two projects to evaluate the potential of oxide dispersion strengthened (ODS) alloys for aircraft gas turbine applications. One project involves the evaluation of Incoloy (TM) MA-956 for application as a combustor liner material. An assessment of advanced engine potential will be conducted by means of a test in a P&WA 2037 turbofan engine. The other project involves the evaluation of Inconel (TM) MA 6000 for application as a high pressure turbine blade material and includes a test in a Garrett TFE 731 turbofan engine. Both projects are progressing toward these engine tests in 1984.

  10. Characterizing risk assessments for the development of occupational exposure limits for engineered nanomaterials.

    PubMed

    Schulte, P A; Kuempel, E D; Drew, N M

    2018-06-01

    The commercialization of engineered nanomaterials (ENMs) began in the early 2000's. Since then the number of commercial products and the number of workers potentially exposed to ENMs is growing, as is the need to evaluate and manage the potential health risks. Occupational exposure limits (OELs) have been developed for some of the first generation of ENMs. These OELs have been based on risk assessments that progressed from qualitative to quantitative as nanotoxicology data became available. In this paper, that progression is characterized. It traces OEL development through the qualitative approach of general groups of ENMs based primarily on read-across with other materials to quantitative risk assessments for nanoscale particles including titanium dioxide, carbon nanotubes and nanofibers, silver nanoparticles, and cellulose nanocrystals. These represent prototypic approaches to risk assessment and OEL development for ENMs. Such substance-by-substance efforts are not practical given the insufficient data for many ENMs that are currently being used or potentially entering commerce. Consequently, categorical approaches are emerging to group and rank ENMs by hazard and potential health risk. The strengths and limitations of these approaches are described, and future derivations and research needs are discussed. Critical needs in moving forward with understanding the health effects of the numerous EMNs include more standardized and accessible quantitative data on the toxicity and physicochemical properties of ENMs. Published by Elsevier Inc.

  11. Reform towards National Health Insurance in Malaysia: the equity implications.

    PubMed

    Yu, Chai Ping; Whynes, David K; Sach, Tracey H

    2011-05-01

    This paper assesses the potential equity impact of Malaysia's projected reform of its current tax financed system towards National Health Insurance (NHI). The Kakwani's progressivity index was used to assess the equity consequences of the new NHI system (with flat rate NHI scheme) compared to the current tax financed system. It was also used to model a proposed system (with a progressive NHI scheme) that can generate the same amount of funding more equitably. The new NHI system would be less equitable than the current tax financed system, as evident from the reduction of Kakwani's index to 0.168 from 0.217. The new flat rate NHI scheme, if implemented, would reduce the progressivity of the health finance system because it is a less progressive finance source than that of general government revenue. We proposed a system with a progressive NHI scheme that generates the same amount of funding whilst preserving the equity at the Kakwani's progressivity index of 0.213. A NHI system with a progressive NHI scheme is proposed to be implemented to raise health funding whilst preserving the equity in health care financing. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  12. Pupil Performance, Absenteeism and School Drop-out: A Multi-dimensional Analysis.

    ERIC Educational Resources Information Center

    Smyht, Emer

    1999-01-01

    Assesses whether second-level schools in Ireland are equally effective regarding examination performance, absenteeism, and potential dropouts, using multivariate analyses of data from 15- and 16-year-olds in 116 schools. Absenteeism and potential dropout rates are lower in schools that enhance pupils' academic progress. (Contains 22 references.)…

  13. Can HMG Co-A reductase inhibitors (“statins”) slow the progression of age-related macular degeneration? The Age-Related Maculopathy Statin Study (ARMSS)

    PubMed Central

    Guymer, Robyn H; Dimitrov, Peter N; Varsamidis, Mary; Lim, Lyndell L; Baird, Paul N; Vingrys, Algis J; Robman, Luba

    2008-01-01

    Age-related macular degeneration (AMD) is responsible for the majority of visual impairment in the Western world. The role of cholesterol-lowering medications, HMG Co-A reductase inhibitors or statins, in reducing the risk of AMD or of delaying its progression has not been fully investigated. A 3-year prospective randomized controlled trial of 40 mg simvastatin per day compared to placebo in subjects at high risk of AMD progression is described. This paper outlines the primary aims of the Age-Related Maculopathy Statin Study (ARMSS), and the methodology involved. Standardized clinical grading of macular photographs and comparison of serial macular digital photographs, using the International grading scheme, form the basis for assessment of primary study outcomes. In addition, macular function is assessed at each visit with detailed psychophysical measurements of rod and cone function. Information collected in this study will assist in the assessment of the potential value of HMG Co-A reductase inhibitors (statins) in reducing the risk of AMD progression. PMID:18982929

  14. Calculator Use on NAEP: A Look at Fourth- and Eighth-Grade Mathematics Achievement

    ERIC Educational Resources Information Center

    Walcott, Crystal; Stickles, Paula R.

    2012-01-01

    This article summarizes research conducted on calculator block items from the 2007 fourth- and eighth-grade National Assessment of Educational Progress Main Mathematics. Calculator items from the assessment were categorized into two categories: problem-solving items and noncomputational mathematics concept items. A calculator has the potential to…

  15. Improving Workplace-Based Assessment and Feedback by an E-Portfolio Enhanced with Learning Analytics

    ERIC Educational Resources Information Center

    van der Schaaf, Marieke; Donkers, Jeroen; Slof, Bert; Moonen-van Loon, Joyce; van Tartwijk, Jan; Driessen, Eric; Badii, Atta; Serban, Ovidiu; Ten Cate, Olle

    2017-01-01

    Electronic portfolios (E-portfolios) are crucial means for workplace-based assessment and feedback. Although E-portfolios provide a useful approach to view each learner's progress, so far options for personalized feedback and potential data about a learner's performances at the workplace often remain unexploited. This paper advocates that…

  16. Primary progressive aphasia: a clinical approach.

    PubMed

    Marshall, Charles R; Hardy, Chris J D; Volkmer, Anna; Russell, Lucy L; Bond, Rebecca L; Fletcher, Phillip D; Clark, Camilla N; Mummery, Catherine J; Schott, Jonathan M; Rossor, Martin N; Fox, Nick C; Crutch, Sebastian J; Rohrer, Jonathan D; Warren, Jason D

    2018-06-01

    The primary progressive aphasias are a heterogeneous group of focal 'language-led' dementias that pose substantial challenges for diagnosis and management. Here we present a clinical approach to the progressive aphasias, based on our experience of these disorders and directed at non-specialists. We first outline a framework for assessing language, tailored to the common presentations of progressive aphasia. We then consider the defining features of the canonical progressive nonfluent, semantic and logopenic aphasic syndromes, including 'clinical pearls' that we have found diagnostically useful and neuroanatomical and other key associations of each syndrome. We review potential diagnostic pitfalls and problematic presentations not well captured by conventional classifications and propose a diagnostic 'roadmap'. After outlining principles of management, we conclude with a prospect for future progress in these diseases, emphasising generic information processing deficits and novel pathophysiological biomarkers.

  17. Using a modified Learning Potential Assessment Device and Mediated Learning Experiences to Assess Minority Student Progress and Program Goals in an Undergraduate Research Based Geoscience Program Serving American Indians

    NASA Astrophysics Data System (ADS)

    Mitchell, L. W.

    2002-12-01

    During the initiation of a new program at the University of North Dakota designed to promote American Indians to engage in geoscience research and complete geoscience related degrees, an evaluation procedure utilizing a modified Learning Potential Assessment Device (LPAD) and Mediated Learning Experiences (MLE) to assess minority student progress was implemented. The program, called Indians Into Geosciences (INGEOS), utilized a modified form of the Learning Potential Assessment Device first to assess cultural factors, determination, and other baseline information, and second, utilized a series of Mediated Learning Experiences to enhance minority students' opportunities in a culturally appropriate, culturally diverse, and scientifically challenging manner in an effort to prepare students for competitive research careers in the geosciences. All of the LPADs and MLEs corresponded directly to the three goals or eight objectives of INGEOS. The three goals of the INGEOS program are: 1) increasing the number of American Indians earning degrees at all levels, 2) engaging American Indians in challenging and technically based scientific research, and 3) preparing American Indians for successful geoscience careers through multicultural community involvement. The eight objectives of the INGEOS program, called the Eight Points of Success, are: 1) spiritual health, 2) social health, 3) physical health, 4) mental health, 5) financial management, 6) research involvement, 7) technical exposure, and 8) multicultural community education. The INGEOS program goals were evaluated strictly quantitatively utilizing a variety of data sources such as grade point averages, number of credits earned, research project information, and developed products. The INGEOS Program goals reflected a combined quantitative score of all participants, whereas the objectives reflected qualitative measures and are specific for each INGEOS participant. Initial results indicate that those participants which show progress through Mediated Learning Experiences within all of the Eight Points of Success, have a higher likelihood of contributing to all three of the INGEOS programs goals.

  18. Elevated Levels of Innate Immune Modulators in Lymph Nodes and Blood Are Associated with More-Rapid Disease Progression in Simian Immunodeficiency Virus-Infected Monkeys▿

    PubMed Central

    Durudas, Andre; Milush, Jeffrey M.; Chen, Hui-Ling; Engram, Jessica C.; Silvestri, Guido; Sodora, Donald L.

    2009-01-01

    Cytokines and chemokines are critical for establishing tissue-specific immune responses and play key roles in modulating disease progression in simian immunodeficiency virus (SIV)-infected macaques and human immunodeficiency virus (HIV)-infected humans. The goal here was to characterize the innate immune response at different tissue sites and to correlate these responses to clinical outcome, initially focusing on rhesus macaques orally inoculated with SIV and monitored until onset of simian AIDS. Cytokine and chemokine mRNA transcripts were assessed at lymph nodes (LN) and peripheral blood cells utilizing quantitative real-time PCR at different time points postinfection. The mRNA expression of four immune modulators—alpha interferon (IFN-α), oligoadenylate synthetase (OAS), CXCL9, and CXCL10—was positively associated with disease progression within LN tissue. Elevated cytokine/chemokine expression in LN did not result in any observed beneficial outcome since the numbers of CXCR3+ cells were not increased, nor were the SIV RNA levels decreased. In peripheral blood, increased OAS and CXCL10 expression were elevated in SIV+ monkeys that progress the fastest to simian AIDS. Our results indicate that higher IFN-α, OAS, CXCL9, and CXCL10 mRNA expression in LN was associated with rapid disease progression and a LN environment that may favor SIV replication. Furthermore, higher expression of CXCL10 and OAS in peripheral blood could potentially serve as a diagnostic marker for hosts that are likely to progress to AIDS. Understanding the expression patterns of key innate immune modulators will be useful in assessing the disease state and potential rates of disease progression in HIV+ patients, which could lead to novel therapy and vaccine approaches. PMID:19759147

  19. Elevated levels of innate immune modulators in lymph nodes and blood are associated with more-rapid disease progression in simian immunodeficiency virus-infected monkeys.

    PubMed

    Durudas, Andre; Milush, Jeffrey M; Chen, Hui-Ling; Engram, Jessica C; Silvestri, Guido; Sodora, Donald L

    2009-12-01

    Cytokines and chemokines are critical for establishing tissue-specific immune responses and play key roles in modulating disease progression in simian immunodeficiency virus (SIV)-infected macaques and human immunodeficiency virus (HIV)-infected humans. The goal here was to characterize the innate immune response at different tissue sites and to correlate these responses to clinical outcome, initially focusing on rhesus macaques orally inoculated with SIV and monitored until onset of simian AIDS. Cytokine and chemokine mRNA transcripts were assessed at lymph nodes (LN) and peripheral blood cells utilizing quantitative real-time PCR at different time points postinfection. The mRNA expression of four immune modulators-alpha interferon (IFN-alpha), oligoadenylate synthetase (OAS), CXCL9, and CXCL10-was positively associated with disease progression within LN tissue. Elevated cytokine/chemokine expression in LN did not result in any observed beneficial outcome since the numbers of CXCR3(+) cells were not increased, nor were the SIV RNA levels decreased. In peripheral blood, increased OAS and CXCL10 expression were elevated in SIV(+) monkeys that progress the fastest to simian AIDS. Our results indicate that higher IFN-alpha, OAS, CXCL9, and CXCL10 mRNA expression in LN was associated with rapid disease progression and a LN environment that may favor SIV replication. Furthermore, higher expression of CXCL10 and OAS in peripheral blood could potentially serve as a diagnostic marker for hosts that are likely to progress to AIDS. Understanding the expression patterns of key innate immune modulators will be useful in assessing the disease state and potential rates of disease progression in HIV(+) patients, which could lead to novel therapy and vaccine approaches.

  20. Use of the Progressive Aphasia Severity Scale (PASS) in monitoring speech and language status in PPA

    PubMed Central

    Sapolsky, Daisy; Domoto-Reilly, Kimiko; Dickerson, Bradford C.

    2014-01-01

    Background Primary progressive aphasia (PPA) is a devastating neurodegenerative syndrome involving the gradual development of aphasia, slowly impairing the patient’s ability to communicate. Pharmaceutical treatments do not currently exist and intervention often focuses on speech-language behavioral therapies, although further investigation is warranted to determine how best to harness functional benefits. Efforts to develop pharmaceutical and behavioral treatments have been hindered by a lack of standardized methods to monitor disease progression and treatment efficacy. Aims Here we describe our current approach to monitoring progression of PPA, including the development and applications of a novel clinical instrument for this purpose, the Progressive Aphasia Severity Scale (PASS). We also outline some of the issues related to initial evaluation and longitudinal monitoring of PPA. Methods & Procedures In our clinical and research practice we perform initial and follow-up assessments of PPA patients using a multi-faceted approach. In addition to standardized assessment measures, we use the PASS to rate presence and severity of symptoms across distinct domains of speech, language, and functional and pragmatic aspects of communication. Ratings are made using the clinician’s best judgment, integrating information from patient test performance in the office as well as a companion’s description of routine daily functioning. Outcomes & Results Monitoring symptom characteristics and severity with the PASS can assist in developing behavioral therapies, planning treatment goals, and counseling patients and families on clinical status and prognosis. The PASS also has potential to advance the implementation of PPA clinical trials. Conclusions PPA patients display heterogeneous language profiles that change over time given the progressive nature of the disease. The monitoring of symptom progression is therefore crucial to ensure that proposed treatments are appropriate at any given stage, including speech-language therapy and potentially pharmaceutical treatments once these become available. Because of the discrepancy that can exist between a patient’s daily functioning and standardized test performance, we believe a comprehensive assessment and monitoring battery must include performance-based instruments, interviews with the patient and partner, questionnaires about functioning in daily life, and measures of clinician judgment. We hope that our clinician judgment-based rating scale described here will be a valuable addition to the PPA assessment and monitoring battery. PMID:25419031

  1. Non invasive blood flow assessment in diabetic foot ulcer using laser speckle contrast imaging technique

    NASA Astrophysics Data System (ADS)

    Jayanthy, A. K.; Sujatha, N.; Reddy, M. Ramasubba; Narayanamoorthy, V. B.

    2014-03-01

    Measuring microcirculatory tissue blood perfusion is of interest for both clinicians and researchers in a wide range of applications and can provide essential information of the progress of treatment of certain diseases which causes either an increased or decreased blood flow. Diabetic ulcer associated with alterations in tissue blood flow is the most common cause of non-traumatic lower extremity amputations. A technique which can detect the onset of ulcer and provide essential information on the progress of the treatment of ulcer would be of great help to the clinicians. A noninvasive, noncontact and whole field laser speckle contrast imaging (LSCI) technique has been described in this paper which is used to assess the changes in blood flow in diabetic ulcer affected areas of the foot. The blood flow assessment at the wound site can provide critical information on the efficiency and progress of the treatment given to the diabetic ulcer subjects. The technique may also potentially fulfill a significant need in diabetic foot ulcer screening and management.

  2. Bioassays for Evaluating Water Quality-Technical Brief

    EPA Pesticide Factsheets

    Bioassays are a potential solution for assessing complex samples since they screen for total bioactivity for a given pathway or mode of action (MOA), such as estrogen receptor activation, in the samples. EPA has made considerable progress in the developmen

  3. A study of progress of labour using intrapartum translabial ultrasound, assessing head station, direction, and angle of descent.

    PubMed

    Tutschek, B; Braun, T; Chantraine, F; Henrich, W

    2011-01-01

    Intrapartum translabial ultrasound (ITU) has the potential to objectively and quantitatively assess the progress of labour. The relationships between the different ITU parameters and their development during normal term labour have not been studied. Observational study. University teaching hospital. Labouring women with normal term fetuses in cephalic presentation. Intrapartum translabial ultrasound measurements for 'head station', 'head direction', and 'angle of descent' (AoD) were taken in 50 labouring women, compared, studied for repeatability, and correlated with the progress of labour. Reproducibility and correlation of ITU parameters and their pattern of changes during labour. All three ITU parameters were clinically well reproducible. AoD and head station were interchangeable, and could be calculated from each other. Head station and head direction changed in a typical pattern along the birth canal. Time to delivery correlated with ITU head station. Intrapartum translabial ultrasound is a simple technique that improves the understanding of normal and abnormal labour, enables the objective measurement of birth progress and provides a more scientific basis for assessing labour. © 2010 The Authors Journal compilation © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.

  4. Core principles of assessment in competency-based medical education.

    PubMed

    Lockyer, Jocelyn; Carraccio, Carol; Chan, Ming-Ka; Hart, Danielle; Smee, Sydney; Touchie, Claire; Holmboe, Eric S; Frank, Jason R

    2017-06-01

    The meaningful assessment of competence is critical for the implementation of effective competency-based medical education (CBME). Timely ongoing assessments are needed along with comprehensive periodic reviews to ensure that trainees continue to progress. New approaches are needed to optimize the use of multiple assessors and assessments; to synthesize the data collected from multiple assessors and multiple types of assessments; to develop faculty competence in assessment; and to ensure that relationships between the givers and receivers of feedback are appropriate. This paper describes the core principles of assessment for learning and assessment of learning. It addresses several ways to ensure the effectiveness of assessment programs, including using the right combination of assessment methods and conducting careful assessor selection and training. It provides a reconceptualization of the role of psychometrics and articulates the importance of a group process in determining trainees' progress. In addition, it notes that, to reach its potential as a driver in trainee development, quality care, and patient safety, CBME requires effective information management and documentation as well as ongoing consideration of ways to improve the assessment system.

  5. Application of Diffusion Tensor Imaging Parameters to Detect Change in Longitudinal Studies in Cerebral Small Vessel Disease.

    PubMed

    Zeestraten, Eva Anna; Benjamin, Philip; Lambert, Christian; Lawrence, Andrew John; Williams, Owen Alan; Morris, Robin Guy; Barrick, Thomas Richard; Markus, Hugh Stephen

    2016-01-01

    Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI's potential as surrogate marker for SVD.

  6. The UN Decade for Women.

    ERIC Educational Resources Information Center

    Reynolds, Nancy C.

    1983-01-01

    The events of the UN Decade for Women are reviewed. The Third World Conference on Women, to be held in 1985, is seen as a forum to assess progress achieved and to look to the future needs and potential of women throughout the world. (MLW)

  7. Waste Isolation Safety Assessment Program. Technical progress report for FY-1978

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brandstetter, A.; Harwell, M.A.; Howes, B.W.

    1979-07-01

    Associated with commercial nuclear power production in the United States is the generation of potentially hazardous radioactive wastes. The Department of Energy (DOE) is seeking to develop nuclear waste isolation systems in geologic formations that will preclude contact with the biosphere of waste radionuclides in concentrations which are sufficient to cause deleterious impact on humans or their environments. Comprehensive analyses of specific isolation systems are needed to assess the expectations of meeting that objective. The Waste Isolation Safety Assessment Program (WISAP) has been established at the Pacific Northwest Laboratory (operated by Battelle Memorial Institute) for developing the capability of makingmore » those analyses. Progress on the following tasks is reported: release scenario analysis, waste form release rate analysis, release consequence analysis, sorption-desorption analysis, and societal acceptance analysis. (DC)« less

  8. Architecture for Integrated Medical Model Dynamic Probabilistic Risk Assessment

    NASA Technical Reports Server (NTRS)

    Jaworske, D. A.; Myers, J. G.; Goodenow, D.; Young, M.; Arellano, J. D.

    2016-01-01

    Probabilistic Risk Assessment (PRA) is a modeling tool used to predict potential outcomes of a complex system based on a statistical understanding of many initiating events. Utilizing a Monte Carlo method, thousands of instances of the model are considered and outcomes are collected. PRA is considered static, utilizing probabilities alone to calculate outcomes. Dynamic Probabilistic Risk Assessment (dPRA) is an advanced concept where modeling predicts the outcomes of a complex system based not only on the probabilities of many initiating events, but also on a progression of dependencies brought about by progressing down a time line. Events are placed in a single time line, adding each event to a queue, as managed by a planner. Progression down the time line is guided by rules, as managed by a scheduler. The recently developed Integrated Medical Model (IMM) summarizes astronaut health as governed by the probabilities of medical events and mitigation strategies. Managing the software architecture process provides a systematic means of creating, documenting, and communicating a software design early in the development process. The software architecture process begins with establishing requirements and the design is then derived from the requirements.

  9. Market assessment overview

    NASA Technical Reports Server (NTRS)

    Habib-Agahi, H.

    1981-01-01

    Market assessment, refined with analysis disaggregated from a national level to the regional level and to specific market applications, resulted in more accurate and detailed market estimates. The development of an integrated set of computer simulations, coupled with refined market data, allowed progress in the ability to evaluate the worth of solar thermal parabolic dish systems. In-depth analyses of both electric and thermal market applications of these systems are described. The following market assessment studies were undertaken: (1) regional analysis of the near term market for parabolic dish systems; (2) potential early market estimate for electric applications; (3) potential early market estimate for industrial process heat/cogeneration applications; and (4) selection of thermal and electric application case studies for fiscal year 1981.

  10. An Innovative Approach to Integrated Training for Smallholder Dairying

    ERIC Educational Resources Information Center

    Chagunda, Mizeck Gift Gibson; Munthali, David Pusi; Gondwe, Timothy N.; Wood, Bethan; Roberts, David J.

    2014-01-01

    Purpose: This paper assesses an integrated approach in smallholder dairy training through a partnership between Malawi and Scotland. Design/ methodology/ approach: Acute staff shortages and inadequate expertise hamper progress in Malawi's smallholder dairy production despite its potential to substantially contribute to sustainable household…

  11. Minireview: Epigenetics of Obesity and Diabetes in Humans

    PubMed Central

    Slomko, Howard; Heo, Hye J.

    2012-01-01

    Understanding the determinants of human health and disease is overwhelmingly complex, particularly for common, late-onset, chronic disorders, such as obesity and diabetes. Elucidating the genetic and environmental factors that influence susceptibility to disruptions in energy homeostasis and metabolic regulation remain a challenge, and progress will entail the integration of multiple assessments of temporally dynamic environmental exposures in the context of each individual's genotype. To meet this challenge, researchers are increasingly exploring the epigenome, which is the malleable interface of gene-environment interactions. Epigenetic variation, whether innate or induced, contributes to variation in gene expression, the range of potential individual responses to internal and external cues, and risk for metabolic disease. Ultimately, advancement in our understanding of chronic disease susceptibility in humans will depend on refinement of exposure assessment tools and systems biology approaches to interpretation. In this review, we present recent progress in epigenetics of human obesity and diabetes, existing challenges, and the potential for new approaches to unravel the complex biology of metabolic dysregulation. PMID:22253427

  12. Minireview: Epigenetics of obesity and diabetes in humans.

    PubMed

    Slomko, Howard; Heo, Hye J; Einstein, Francine H

    2012-03-01

    Understanding the determinants of human health and disease is overwhelmingly complex, particularly for common, late-onset, chronic disorders, such as obesity and diabetes. Elucidating the genetic and environmental factors that influence susceptibility to disruptions in energy homeostasis and metabolic regulation remain a challenge, and progress will entail the integration of multiple assessments of temporally dynamic environmental exposures in the context of each individual's genotype. To meet this challenge, researchers are increasingly exploring the epigenome, which is the malleable interface of gene-environment interactions. Epigenetic variation, whether innate or induced, contributes to variation in gene expression, the range of potential individual responses to internal and external cues, and risk for metabolic disease. Ultimately, advancement in our understanding of chronic disease susceptibility in humans will depend on refinement of exposure assessment tools and systems biology approaches to interpretation. In this review, we present recent progress in epigenetics of human obesity and diabetes, existing challenges, and the potential for new approaches to unravel the complex biology of metabolic dysregulation.

  13. Health Assessment Questionnaire disability progression in early rheumatoid arthritis: Systematic review and analysis of two inception cohorts

    PubMed Central

    Norton, Sam; Fu, Bo; Scott, David L.; Deighton, Chris; Symmons, Deborah P.M.; Wailoo, Allan J.; Tosh, Jonathan; Lunt, Mark; Davies, Rebecca; Young, Adam; Verstappen, Suzanne M.M

    2014-01-01

    Objective The Health Assessment Questionnaire is widely used for patients with inflammatory polyarthritis (IP) and its subset, rheumatoid arthritis (RA). In this study, we evaluated the progression of HAQ scores in RA (i) by systematically reviewing the published literature on the methods used to assess changes in functional disability over time and (ii) to study in detail HAQ progression in two large prospective observational studies from the UK. Methods Data from two large inception cohorts, ERAS and NOAR, were studied to determine trajectories of HAQ progression over time by applying latent class growth models (LCGMs) to each dataset separately. Age, sex, baseline DAS28, symptom duration, rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status (SES) were included as potential predictors of HAQ trajectory subgroup membership. Results The literature search identified 49 studies showing that HAQ progression has mainly been based on average changes in the total study population. In the HAQ progression study, a LCGM with four HAQ trajectory subgroups was selected as providing the best fit in both cohorts. In both the cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987 ACR criteria, higher DAS28 and lower SES were associated with increased likelihood of membership of subgroups with worse HAQ progression. Conclusion Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR cohorts. The fact that the subgroups identified were nearly identical supports their validity. Identifying distinct groups of patients who are at risk of poor functional outcome may help to target therapy to those who are most likely to benefit. PMID:24925692

  14. Is there a causal link between knee loading and knee osteoarthritis progression? A systematic review and meta-analysis of cohort studies and randomised trials

    PubMed Central

    Henriksen, Marius; Creaby, Mark W; Lund, Hans; Juhl, Carsten; Christensen, Robin

    2014-01-01

    Objective We performed a systematic review, meta-analysis and assessed the evidence supporting a causal link between knee joint loading during walking and structural knee osteoarthritis (OA) progression. Design Systematic review, meta-analysis and application of Bradford Hill's considerations on causation. Data sources We searched MEDLINE, Scopus, AMED, CINAHL and SportsDiscus for prospective cohort studies and randomised controlled trials (RCTs) from 1950 through October 2013. Study eligibility criteria We selected cohort studies and RCTs in which estimates of knee joint loading during walking were used to predict structural knee OA progression assessed by X-ray or MRI. Data analyses Meta-analysis was performed to estimate the combined OR for structural disease progression with higher baseline loading. The likelihood of a causal link between knee joint loading and OA progression was assessed from cohort studies using the Bradford Hill guidelines to derive a 0–4 causation score based on four criteria and examined for confirmation in RCTs. Results Of the 1078 potentially eligible articles, 5 prospective cohort studies were included. The studies included a total of 452 patients relating joint loading to disease progression over 12–72 months. There were very serious limitations associated with the methodological quality of the included studies. The combined OR for disease progression was 1.90 (95% CI 0.85 to 4.25; I2=77%) for each one-unit increment in baseline knee loading. The combined causation score was 0, indicating no causal association between knee loading and knee OA progression. No RCTs were found to confirm or refute the findings from the cohort studies. Conclusions There is very limited and low-quality evidence to support for a causal link between knee joint loading during walking and structural progression of knee OA. Trial registration number CRD42012003253 PMID:25031196

  15. Is there a causal link between knee loading and knee osteoarthritis progression? A systematic review and meta-analysis of cohort studies and randomised trials.

    PubMed

    Henriksen, Marius; Creaby, Mark W; Lund, Hans; Juhl, Carsten; Christensen, Robin

    2014-07-15

    We performed a systematic review, meta-analysis and assessed the evidence supporting a causal link between knee joint loading during walking and structural knee osteoarthritis (OA) progression. Systematic review, meta-analysis and application of Bradford Hill's considerations on causation. We searched MEDLINE, Scopus, AMED, CINAHL and SportsDiscus for prospective cohort studies and randomised controlled trials (RCTs) from 1950 through October 2013. We selected cohort studies and RCTs in which estimates of knee joint loading during walking were used to predict structural knee OA progression assessed by X-ray or MRI. Meta-analysis was performed to estimate the combined OR for structural disease progression with higher baseline loading. The likelihood of a causal link between knee joint loading and OA progression was assessed from cohort studies using the Bradford Hill guidelines to derive a 0-4 causation score based on four criteria and examined for confirmation in RCTs. Of the 1078 potentially eligible articles, 5 prospective cohort studies were included. The studies included a total of 452 patients relating joint loading to disease progression over 12-72 months. There were very serious limitations associated with the methodological quality of the included studies. The combined OR for disease progression was 1.90 (95% CI 0.85 to 4.25; I(2)=77%) for each one-unit increment in baseline knee loading. The combined causation score was 0, indicating no causal association between knee loading and knee OA progression. No RCTs were found to confirm or refute the findings from the cohort studies. There is very limited and low-quality evidence to support for a causal link between knee joint loading during walking and structural progression of knee OA. CRD42012003253. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification

    PubMed Central

    Korolev, Igor O.; Symonds, Laura L.; Bozoki, Andrea C.

    2016-01-01

    Background Individuals with mild cognitive impairment (MCI) have a substantially increased risk of developing dementia due to Alzheimer's disease (AD). In this study, we developed a multivariate prognostic model for predicting MCI-to-dementia progression at the individual patient level. Methods Using baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139) and those who did not (n = 120) during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI) data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework. Results Cognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87). Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex). Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions. Conclusions We developed an accurate prognostic model for predicting MCI-to-dementia progression over a three-year period. The model utilizes widely available, cost-effective, non-invasive markers and can be used to improve patient selection in clinical trials and identify high-risk MCI patients for early treatment. PMID:26901338

  17. Application of Diffusion Tensor Imaging Parameters to Detect Change in Longitudinal Studies in Cerebral Small Vessel Disease

    PubMed Central

    Zeestraten, Eva Anna; Benjamin, Philip; Lambert, Christian; Lawrence, Andrew John; Williams, Owen Alan; Morris, Robin Guy; Barrick, Thomas Richard; Markus, Hugh Stephen

    2016-01-01

    Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI’s potential as surrogate marker for SVD. PMID:26808982

  18. Exercise Training in Progressive Multiple Sclerosis: A Comparison of Recumbent Stepping and Body Weight-Supported Treadmill Training.

    PubMed

    Pilutti, Lara A; Paulseth, John E; Dove, Carin; Jiang, Shucui; Rathbone, Michel P; Hicks, Audrey L

    2016-01-01

    Background: There is evidence of the benefits of exercise training in multiple sclerosis (MS); however, few studies have been conducted in individuals with progressive MS and severe mobility impairment. A potential exercise rehabilitation approach is total-body recumbent stepper training (TBRST). We evaluated the safety and participant-reported experience of TBRST in people with progressive MS and compared the efficacy of TBRST with that of body weight-supported treadmill training (BWSTT) on outcomes of function, fatigue, and health-related quality of life (HRQOL). Methods: Twelve participants with progressive MS (Expanded Disability Status Scale scores, 6.0-8.0) were randomized to receive TBRST or BWSTT. Participants completed three weekly sessions (30 minutes) of exercise training for 12 weeks. Primary outcomes included safety assessed as adverse events and patient-reported exercise experience assessed as postexercise response and evaluation of exercise equipment. Secondary outcomes included the Multiple Sclerosis Functional Composite, the Modified Fatigue Impact Scale, and the Multiple Sclerosis Quality of Life-54 questionnaire scores. Assessments were conducted at baseline and after 12 weeks. Results: Safety was confirmed in both exercise groups. Participants reported enjoying both exercise modalities; however, TBRST was reviewed more favorably. Both interventions reduced fatigue and improved HRQOL (P ≤ .05); there were no changes in function. Conclusions: Both TBRST and BWSTT seem to be safe, well tolerated, and enjoyable for participants with progressive MS with severe disability. Both interventions may also be efficacious for reducing fatigue and improving HRQOL. TBRST should be further explored as an exercise rehabilitation tool for patients with progressive MS.

  19. Use magnetic resonance imaging to assess articular cartilage

    PubMed Central

    Wang, Yuanyuan; Wluka, Anita E.; Jones, Graeme; Ding, Changhai

    2012-01-01

    Magnetic resonance imaging (MRI) enables a noninvasive, three-dimensional assessment of the entire joint, simultaneously allowing the direct visualization of articular cartilage. Thus, MRI has become the imaging modality of choice in both clinical and research settings of musculoskeletal diseases, particular for osteoarthritis (OA). Although radiography, the current gold standard for the assessment of OA, has had recent significant technical advances, radiographic methods have significant limitations when used to measure disease progression. MRI allows accurate and reliable assessment of articular cartilage which is sensitive to change, providing the opportunity to better examine and understand preclinical and very subtle early abnormalities in articular cartilage, prior to the onset of radiographic disease. MRI enables quantitative (cartilage volume and thickness) and semiquantitative assessment of articular cartilage morphology, and quantitative assessment of cartilage matrix composition. Cartilage volume and defects have demonstrated adequate validity, accuracy, reliability and sensitivity to change. They are correlated to radiographic changes and clinical outcomes such as pain and joint replacement. Measures of cartilage matrix composition show promise as they seem to relate to cartilage morphology and symptoms. MRI-derived cartilage measurements provide a useful tool for exploring the effect of modifiable factors on articular cartilage prior to clinical disease and identifying the potential preventive strategies. MRI represents a useful approach to monitoring the natural history of OA and evaluating the effect of therapeutic agents. MRI assessment of articular cartilage has tremendous potential for large-scale epidemiological studies of OA progression, and for clinical trials of treatment response to disease-modifying OA drugs. PMID:22870497

  20. Remission of proteinuria in primary glomerulonephritis: we know the goal but do we know the price?

    PubMed

    Philibert, David; Cattran, Daniel

    2008-10-01

    Membranous nephropathy, focal segmental glomerulosclerosis and IgA nephropathy are the most commonly recognized types of primary glomerulonephritis that progress to end-stage renal disease. Persistent proteinuria is a major determinant of such progression. Reduction of proteinuria slows progression of renal disease and improves renal survival, but many of the agents used to reduce proteinuria carry a considerable risk of toxicity. The assessment of benefit versus risk of these medications can be further complicated by the temporal disconnect between the onset of benefit and of serious adverse events. In addition, relapses are common in these disorders and there is often a need for retreatment. Such retreatment might lead to repeated and/or prolonged drug exposure and to the oversight or underestimation of the cumulative dose of these agents because of the potentially extended interval between relapses. Consequently, it is very important to constantly review each patient's status and take into account their age, comorbid conditions and cumulative drug exposure when assessing treatment options. The potentially delayed development of adverse events also emphasizes the need for long-term surveillance of patients who receive immunosuppressive treatment for glomerular disease, often well beyond their drug exposure period and even when the treatment has been successful.

  1. POTENTIAL UTILITY OF SALIVA BIOMONITORING FOR ASSESSING ORGANOPHOSPHATE INSECTICIDE DOSIMETRY AND ESTERASE INHIBITION. (R828608)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  2. 18F-AV-1451 positron emission tomography in Alzheimer's disease and progressive supranuclear palsy.

    PubMed

    Passamonti, Luca; Vázquez Rodríguez, Patricia; Hong, Young T; Allinson, Kieren S J; Williamson, David; Borchert, Robin J; Sami, Saber; Cope, Thomas E; Bevan-Jones, W Richard; Jones, P Simon; Arnold, Robert; Surendranathan, Ajenthan; Mak, Elijah; Su, Li; Fryer, Tim D; Aigbirhio, Franklin I; O'Brien, John T; Rowe, James B

    2017-03-01

    The ability to assess the distribution and extent of tau pathology in Alzheimer's disease and progressive supranuclear palsy in vivo would help to develop biomarkers for these tauopathies and clinical trials of disease-modifying therapies. New radioligands for positron emission tomography have generated considerable interest, and controversy, in their potential as tau biomarkers. We assessed the radiotracer 18F-AV-1451 with positron emission tomography imaging to compare the distribution and intensity of tau pathology in 15 patients with Alzheimer's pathology (including amyloid-positive mild cognitive impairment), 19 patients with progressive supranuclear palsy, and 13 age- and sex-matched controls. Regional analysis of variance and a support vector machine were used to compare and discriminate the clinical groups, respectively. We also examined the 18F-AV-1451 autoradiographic binding in post-mortem tissue from patients with Alzheimer's disease, progressive supranuclear palsy, and a control case to assess the 18F-AV-1451 binding specificity to Alzheimer's and non-Alzheimer's tau pathology. There was increased 18F-AV-1451 binding in multiple regions in living patients with Alzheimer's disease and progressive supranuclear palsy relative to controls [main effect of group, F(2,41) = 17.5, P < 0.0001; region of interest × group interaction, F(2,68) = 7.5, P < 0.00001]. More specifically, 18F-AV-1451 binding was significantly increased in patients with Alzheimer's disease, relative to patients with progressive supranuclear palsy and with control subjects, in the hippocampus and in occipital, parietal, temporal, and frontal cortices (t's > 2.2, P's < 0.04). Conversely, in patients with progressive supranuclear palsy, relative to patients with Alzheimer's disease, 18F-AV-1451 binding was elevated in the midbrain (t = 2.1, P < 0.04); while patients with progressive supranuclear palsy showed, relative to controls, increased 18F-AV-1451 uptake in the putamen, pallidum, thalamus, midbrain, and in the dentate nucleus of the cerebellum (t's > 2.7, P's < 0.02). The support vector machine assigned patients' diagnoses with 94% accuracy. The post-mortem autoradiographic data showed that 18F-AV-1451 strongly bound to Alzheimer-related tau pathology, but less specifically in progressive supranuclear palsy. 18F-AV-1451 binding to the basal ganglia was strong in all groups in vivo. Postmortem histochemical staining showed absence of neuromelanin-containing cells in the basal ganglia, indicating that off-target binding to neuromelanin is an insufficient explanation of 18F-AV-1451 positron emission tomography data in vivo, at least in the basal ganglia. Overall, we confirm the potential of 18F-AV-1451 as a heuristic biomarker, but caution is indicated in the neuropathological interpretation of its binding. Off-target binding may contribute to disease profiles of 18F-AV-1451 positron emission tomography, especially in primary tauopathies such as progressive supranuclear palsy. We suggest that 18F-AV-1451 positron emission tomography is a useful biomarker to assess tau pathology in Alzheimer's disease and to distinguish it from other tauopathies with distinct clinical and pathological characteristics such as progressive supranuclear palsy. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  3. Sequential chemical-biological processes for the treatment of industrial wastewaters: review of recent progresses and critical assessment.

    PubMed

    Guieysse, Benoit; Norvill, Zane N

    2014-02-28

    When direct wastewater biological treatment is unfeasible, a cost- and resource-efficient alternative to direct chemical treatment consists of combining biological treatment with a chemical pre-treatment aiming to convert the hazardous pollutants into more biodegradable compounds. Whereas the principles and advantages of sequential treatment have been demonstrated for a broad range of pollutants and process configurations, recent progresses (2011-present) in the field provide the basis for refining assessment of feasibility, costs, and environmental impacts. This paper thus reviews recent real wastewater demonstrations at pilot and full scale as well as new process configurations. It also discusses new insights on the potential impacts of microbial community dynamics on process feasibility, design and operation. Finally, it sheds light on a critical issue that has not yet been properly addressed in the field: integration requires complex and tailored optimization and, of paramount importance to full-scale application, is sensitive to uncertainty and variability in the inputs used for process design and operation. Future research is therefore critically needed to improve process control and better assess the real potential of sequential chemical-biological processes for industrial wastewater treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Microbicides: Topical Prevention against HIV

    PubMed Central

    Shattock, Robin J.; Rosenberg, Zeda

    2012-01-01

    Microbicides represent a potential intervention strategy for preventing HIV transmission. Vaginal microbicides would meet the need for a discreet method that women could use to protect themselves against HIV. Although early-generation microbicides failed to demonstrate efficacy, newer candidates are based on more potent antiretroviral (ARV) products. Positive data from the CAPRISA 004 trial of tenofovir gel support use in women and represent a turning point for the field. This article reviews current progress in development of ARV-based microbicides. We discuss the consensus on selection criteria, the potential for drug resistance, rationale for drug combinations, and the use of pharmacokinetic (PK)/pharmacodynamic (PD) assessment in product development. The urgent need for continued progress in development of formulations for sustained delivery is emphasized. Finally, as the boundaries between different prevention technologies become increasingly blurred, consideration is given to the potential synergy of diverse approaches across the prevention landscape. PMID:22355798

  5. Assessing Decline: Visualising Progression in Huntington's Disease using a Clinical Dashboard with Enroll-HD Data.

    PubMed

    Walker, Thomas; Ghosh, Boyd; Kipps, Christopher

    2017-01-01

    In Huntington's disease (HD), it remains unclear how symptom severity and rate of symptomatic change relates to age and CAG repeat number (CAGn). It is often difficult for clinicians to assess whether an affected individual's symptoms are progressing at a similar rate to their affected peers, limiting their ability to intervene at the most appropriate time. To develop a clinical dashboard that compares an individual's total motor score (TMS), total functional capacity (TFC) and symbol digit modality test (SDMT) scores against a global cohort, controlling for age and CAGn. The dashboard could then be used by clinicians to identify individuals progressing at a disproportionate rate to his or her peers. Annualised longitudinal clinical assessment scores from the Enroll-HD dataset were used to generate decline trajectories of the global cohort, allowing cross-sectional (TMS n = 734; TFC n = 734; SDMT n = 694) and longitudinal (TMS n = 270; TFC n = 270; SDMT n = 247) comparison with individual clinical symptom rating scores, to assess decline relative to affected peers. An electronic dashboard with a dynamic output display was created that rapidly compares clinical symptom rating scores of a specific individual against affected peers from a global cohort of comparable CAGn. This study shows the potential for use of multi-centre trial data in allowing comparison of the individual to a larger group to facilitate improved decision-making for individual patients. Visualisation of these metrics via a clinical dashboard demonstrates how it may aid identification of those with disproportionate decline, offering potential for intervention at specific critical points in the disease course.

  6. The Spaces and Ethics of Organic Food

    ERIC Educational Resources Information Center

    Clarke, Nick; Cloke, Paul; Barnett, Clive; Malpass, Alice

    2008-01-01

    Initial assessments of the potential for organic food systems have offered an optimistic interpretation of the progressive political and ethical characteristics involved. This positive gloss has prompted a stream of critique emphasising the need to explore the ambiguities and disconnections inherent therein. In this paper, we consider the case of…

  7. The Human Service Scale: A New Measure for Evaluation

    ERIC Educational Resources Information Center

    Reagles, Kenneth W.; Butler, Alfred S.

    1976-01-01

    The Human Service Scale is an assessment instrument for measuring the progress of the rehabilitation client and the effectiveness of rehabilitation programs. The theory behind the scale is based on Maslow's hierarchy of human needs. The development and some potential uses of the scale are discussed. (EC)

  8. Canada's Composite Learning Index: A Path Towards Learning Communities

    ERIC Educational Resources Information Center

    Cappon, Paul; Laughlin, Jarrett

    2013-01-01

    In the development of learning cities/communities, benchmarking progress is a key element. Not only does it permit cities/communities to assess their current strengths and weaknesses, it also engenders a dialogue within and between cities/communities on the means of enhancing learning conditions. Benchmarking thereby is a potentially motivational…

  9. The Benefits of Implementing a Feedback Informed Treatment System within Counselor Education Curriculum

    ERIC Educational Resources Information Center

    Yates, Chad M.; Holmes, Courtney M.; Coe Smith, Jane C.; Nielson, Tiffany

    2016-01-01

    Counselor education departments have a unique opportunity to implement feedback informed treatment (FIT) systems that serve as continual assessment procedures by informing counselors, clients, supervisors and educators about client functioning and progress toward goals. These systems hold potential benefits within counselor training such as a…

  10. Forest productivity: producing goods and services for people

    Treesearch

    Thomas R. Crow; Daniel C. Dey; Don Riemenschneider

    2006-01-01

    Presents the progress made by North Central Research Station scientists working in the Forest Productivity Integrated Research and Development Program over the past several years. We discuss policy relevant research on assessing productivity, modeling potential, productivity, and improving productivity within the conceptual framework for research and development in the...

  11. Challenges on the Path to Implementation

    ERIC Educational Resources Information Center

    Martineau, Joseph A.; Wyse, Adam E.

    2015-01-01

    This article is a commentary of a paper by Derek C. Briggs and Frederick A. Peck, "Using Learning Progressions to Design Vertical Scales That Support Coherent Inferences about Student Growth," which describes an elegant potential framework for at least beginning to address three priorities in large-scale assessment that have not been…

  12. CD133 expression in oral lichen planus correlated with the risk for progression to oral squamous cell carcinoma.

    PubMed

    Sun, Lili; Feng, Jinqiu; Ma, Lihua; Liu, Wei; Zhou, Zengtong

    2013-12-01

    Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk for progression to oral squamous cell carcinoma (OSCC). The objective of this study to determine protein expression of cancer stem cell marker CD133 in tissue samples of patients with OLP and evaluate the correlation between CD133 expression and the risk of progression to OSCC. In this longitudinal case-control study, a total of 110 patients with OLP who received a mean follow-up of 56 months were enrolled, including 100 patients who did not progress to OSCC and 10 patients who had progressed to OSCC. CD133 expression was determined using immunohistochemistry in samples from these patients. Analysis of 10 cases of normal oral mucosa and 6 cases of postmalignant OSCC form previously diagnosed OLP was also performed. The results showed that CD133 expression was observed in 29% cases of nonprogressing OLP and in 80% cases of progressing OLP (P = .002). CD133 was not expressed in normal oral mucosa, but it positively expressed in the 100% cases of OSCC. Logistic regression analysis revealed that the risk of malignant progression in the patients with CD133-positive expression was significantly higher than those with CD133 negativity (odds ratio, 9.79; 95% confidence interval, 1.96-48.92; P = .005). Collectively, CD133 expression was significantly associated with malignant progression in a longitudinal series of patients with OLP. Our findings suggested that CD133 may serve as a novel candidate biomarker for risk assessment of malignant potential of OLP. © 2013.

  13. Sensory-motor problems in Autism

    PubMed Central

    Whyatt, Caroline; Craig, Cathy

    2013-01-01

    Despite being largely characterized as a social and cognitive disorder, strong evidence indicates the presence of significant sensory-motor problems in Autism Spectrum Disorder (ASD). This paper outlines our progression from initial, broad assessment using the Movement Assessment Battery for Children (M-ABC2) to subsequent targeted kinematic assessment. In particular, pronounced ASD impairment seen in the broad categories of manual dexterity and ball skills was found to be routed in specific difficulties on isolated tasks, which were translated into focused experimental assessment. Kinematic results from both subsequent studies highlight impaired use of perception-action coupling to guide, adapt and tailor movement to task demands, resulting in inflexible and rigid motor profiles. In particular difficulties with the use of temporal adaption are shown, with “hyperdexterity” witnessed in ballistic movement profiles, often at the cost of spatial accuracy and task performance. By linearly progressing from the use of a standardized assessment tool to targeted kinematic assessment, clear and defined links are drawn between measureable difficulties and underlying sensory-motor assessment. Results are specifically viewed in-light of perception-action coupling and its role in early infant development suggesting that rather than being “secondary” level impairment, sensory-motor problems may be fundamental in the progression of ASD. This logical and systematic process thus allows a further understanding into the potential root of observable motor problems in ASD; a vital step if underlying motor problems are to be considered a fundamental aspect of autism and allow a route of non-invasive preliminary diagnosis. PMID:23882194

  14. Novel Application of Stem Cell-Derived Neurons to Evaluate the Time-and Dose-Dependent Progression of Excitotoxic Injury

    DTIC Science & Technology

    2013-05-14

    enzymes . At sufficiently high doses of glutamate, this process culminates in excitogenic cell death [1]. Treatments to mitigate neuronal damage during...To evaluate the potential for therapeutic screening, we assessed the effect of several small molecule antagonists on excitotoxicity in a moderate...C. Current clamp recordings showing repeated overshooting action potentials are evoked by injection of a 75 pA current. D. Voltage-clamp recordings

  15. Using GeoRePORT to report socio-economic potential for geothermal development

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Young, Katherine R.; Levine, Aaron

    The Geothermal Resource Portfolio Optimization and Reporting Tool (GeoRePORT, http://en.openei.org/wiki/GeoRePORT) was developed for reporting resource grades and project readiness levels, providing the U.S. Department of Energy a consistent and comprehensible means of evaluating projects. The tool helps funding organizations (1) quantitatively identify barriers, (2) develop measureable goals, (3) objectively evaluate proposals, including contribution to goals, (4) monitor progress, and (5) report portfolio performance. GeoRePORT assesses three categories: geological, technical, and socio-economic. Here, we describe GeoRePORT, then focus on the socio-economic assessment and its applications for assessing deployment potential in the U.S. Socio-economic attributes include land access, permitting, transmission, and market.

  16. Assessing MODIS-based Products and Techniques for Detecting Gypsy Moth Defoliation

    NASA Technical Reports Server (NTRS)

    Spruce, Joseph P.; Hargrove, William; Smoot, James C.; Prados, Don; McKellip, Rodney; Sader, Steven A.; Gasser, Jerry; May, George

    2008-01-01

    The project showed potential of MODIS and VIIRS time series data for contributing defoliation detection products to the USFS forest threat early warning system. This study yielded the first satellite-based wall-to-wall 2001 gypsy moth defoliation map for the study area. Initial results led to follow-on work to map 2007 gypsy moth defoliation over the eastern United States (in progress). MODIS-based defoliation maps offer promise for aiding aerial sketch maps either in planning surveys and/or adjusting acreage estimates of annual defoliation. More work still needs to be done to assess potential of technology for "now casts"of defoliation.

  17. The role of inflammation in lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and its potential impact on medical therapy.

    PubMed

    Ficarra, Vincenzo; Rossanese, Marta; Zazzara, Michele; Giannarini, Gianluca; Abbinante, Maria; Bartoletti, Riccardo; Mirone, Vincenzo; Scaglione, Francesco

    2014-12-01

    A chronic prostatic inflammation seems to play a crucial role in benign prostatic hyperplasia (BPH) pathogenesis and progression. Therefore, inflammation could represent a new potential target for medical therapy of lower urinary tract symptoms (LUTS) due to BPH (LUTS/BPH). This review article analyzes the evidence supporting the role of inflammation in the onset and progression of BPH, and it assesses the potential impact of previous mechanisms on medical therapy of LUTS/BPH. Literature data support the role of inflammation as a relevant factor in the pathogenesis of BPH. Indeed, several data favour the role of infiltrating lymphocytes in the development and progression of prostate adenoma as an effect of a self-maintaining remodeling process. Although available drugs commonly used in the treatment of LUTS/BPH do not exhibit an anti-inflammatory activity, it seems to be obvious considering the inflammation as a new target in the treatment of LUTS/BPH. Drugs currently investigated for the treatment of prostatic inflammation include the hexanic lipidosterolic extract of Serenoa repens, nonsteroidal anti-inflammatory drugs, and vitamin D receptor agonists.

  18. The importance of total kidney volume in evaluating progression of polycystic kidney disease

    PubMed Central

    Grantham, Jared J.; Torres, Vicente E.

    2017-01-01

    The rate at which autosomal dominant polycystic kidney disease (ADPKD) progresses to end-stage renal disease varies widely and is determined by genetic and non-genetic factors. The ability to determine the prognosis of children and young adults with ADPKD is important for the effective life-long management of the disease and to enable the efficacy of emerging therapies to be determined. Total kidney volume (TKV) reflects the sum volume of hundreds of individual cysts with potentially devastating effects on renal function. The sequential measurement of TKV has been advanced as a dynamic biomarker of disease progression, yet doubt remains among nephrologists and regulatory agencies as to its usefulness. Here, we review the mechanisms that lead to an increase in TKV in ADPKD, and examine the evidence supporting the conclusion that TKV provides a metric of disease progression that can be used to assess the efficacy of potential therapeutic regimens in children and adults with ADPKD. Moreover, we propose that TKV can be used to monitor treatment efficacy in patients with normal levels of renal function, before the pathologic processes of ADPKD cause extensive fibrosis and irreversible loss of functioning renal tissue. PMID:27694979

  19. An assessment of laser velocimetry in hypersonic flow

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Although extensive progress has been made in computational fluid mechanics, reliable flight vehicle designs and modifications still cannot be made without recourse to extensive wind tunnel testing. Future progress in the computation of hypersonic flow fields is restricted by the need for a reliable mean flow and turbulence modeling data base which could be used to aid in the development of improved empirical models for use in numerical codes. Currently, there are few compressible flow measurements which could be used for this purpose. In this report, the results of experiments designed to assess the potential for laser velocimeter measurements of mean flow and turbulent fluctuations in hypersonic flow fields are presented. Details of a new laser velocimeter system which was designed and built for this test program are described.

  20. Progress in modelling agricultural impacts of and adaptations to climate change.

    PubMed

    Rötter, R P; Hoffmann, M P; Koch, M; Müller, C

    2018-06-01

    Modelling is a key tool to explore agricultural impacts of and adaptations to climate change. Here we report recent progress made especially referring to the large project initiatives MACSUR and AgMIP; in particular, in modelling potential crop impacts from field to global using multi-model ensembles. We identify two main fields where further progress is necessary: a more mechanistic understanding of climate impacts and management options for adaptation and mitigation; and focusing on cropping systems and integrative multi-scale assessments instead of single season and crops, especially in complex tropical and neglected but important cropping systems. Stronger linking of experimentation with statistical and eco-physiological crop modelling could facilitate the necessary methodological advances. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Electrical injury and amyotrophic lateral sclerosis: a systematic review of the literature

    PubMed Central

    Abhinav, Kumar; Al‐Chalabi, Ammar; Hortobagyi, Tibor; Leigh, P Nigel

    2007-01-01

    Electrical injury may act as a potential precipitating or risk factor for amyotrophic lateral sclerosis (ALS). A systematic review of the literature was undertaken to assess the relationship between electrical injury and the development of ALS. Information for the review was obtained using five medical databases, and from manual searching of individual papers. Patients presenting with a neurological syndrome after electrical injury, including lightning, were included and classified into four categories: ALS; progressive upper motor neurone (UMN) syndrome; progressive lower motor neurone (LMN) syndrome; and non‐progressive syndrome. Linear regression and χ2testing were used for analysis of the data. 96 individuals, comprising 44 with ALS, 1 with a progressive UMN syndrome, 7 with a progressive LMN syndrome and 44 with a non‐progressive syndrome, were identified from 31 papers with publication dates between 1906 and 2002. The median interval between electrical injury and disease onset was 2.25 years for all progressive syndromes and just over 1 week for the non‐progressive syndrome. The more severe the shock (excluding lightning), the more likely individuals were to have a non‐progressive motor syndrome. A non‐progressive spinal cord syndrome is associated with more severe electrical injury. Overall, the evidence reviewed does not support a causal relationship between ALS and electric shock. PMID:17098839

  2. Methodology for assessing the probability of corrosion in concrete structures on the basis of half-cell potential and concrete resistivity measurements.

    PubMed

    Sadowski, Lukasz

    2013-01-01

    In recent years, the corrosion of steel reinforcement has become a major problem in the construction industry. Therefore, much attention has been given to developing methods of predicting the service life of reinforced concrete structures. The progress of corrosion cannot be visually assessed until a crack or a delamination appears. The corrosion process can be tracked using several electrochemical techniques. Most commonly the half-cell potential measurement technique is used for this purpose. However, it is generally accepted that it should be supplemented with other techniques. Hence, a methodology for assessing the probability of corrosion in concrete slabs by means of a combination of two methods, that is, the half-cell potential method and the concrete resistivity method, is proposed. An assessment of the probability of corrosion in reinforced concrete structures carried out using the proposed methodology is presented. 200 mm thick 750 mm  ×  750 mm reinforced concrete slab specimens were investigated. Potential E corr and concrete resistivity ρ in each point of the applied grid were measured. The experimental results indicate that the proposed methodology can be successfully used to assess the probability of corrosion in concrete structures.

  3. NAEP Reporting Practices: Investigating District-Level and Market-Basket Reporting. The Compass Series.

    ERIC Educational Resources Information Center

    DeVito, Pasquale J., Ed.; Koenig, Judith A., Ed.

    A committee of the National Research Council studied the desirability, feasibility, and potential impact of two reporting practices for National Assessment of Educational Progress (NAEP) results: district-level reporting and market-basket reporting. NAEP's sponsors believe that reporting district-level NAEP results would support state and local…

  4. The Debate over National Testing. ERIC Digest.

    ERIC Educational Resources Information Center

    Boston, Carol

    This digest presents various views of the federal role in testing and offers a brief examination of the National Assessment of Educational Progress (NAEP), the "nation's report card," in its national sample format and its state administration, which critics fear has the potential to become a de facto national test if selected as the…

  5. Educational Awareness of Biotechnology Issues among Undergraduate Students at the United Arab Emirates University

    ERIC Educational Resources Information Center

    AbuQamar, Synan; Alshannag, Qasim; Sartawi, Abdelaziz; Iratni, Rabah

    2015-01-01

    Due to its valuable benefits and potential risks, there is a progressing debate among opponents and proponents of biotechnology in recent decades. Previous studies have shown that lack of knowledge about biotechnology remains the concern about genetically modified organisms/food (GMO/GMF). This study assessed levels of educational awareness…

  6. Predicting progress in Picture Exchange Communication System (PECS) use by children with autism.

    PubMed

    Pasco, Greg; Tohill, Christina

    2011-01-01

    The Picture Exchange Communication System (PECS) is a widely used communication intervention for non-verbal children with autism spectrum disorder. Findings for the benefits of PECS have almost universally been positive, although there is very limited information about the characteristics of PECS users that determine the amount of progress that they are likely to make. To explore the utility of using children's developmental age to predict the subsequent degree of progress using PECS. In a retrospective study, 23 non-verbal 5- and 6-year-old children with autism spectrum disorder attending a special school were assessed to determine their highest level of PECS ability. They were then allocated to one of two groups depending on whether or not they had mastered PECS phase III. All participants had been assessed using the Psycho-Educational Profile-Revised (PEP-R) on entry to the school and before being introduced to PECS. Total developmental age scores were examined to determine whether they accurately predicted membership of the two PECS ability groups. All the 16 children who had mastered PECS phase III had total developmental age scores of 16 months or above, whilst six of the seven children who had not progressed beyond phase III scored below 16 months--the other child had a score of 16 months. The assessment of the developmental level of potential PECS users may provide valuable predictive information for speech-and-language therapists and other professionals in relation to the likely degree of progress and in setting realistic and achievable targets. © 2010 Royal College of Speech & Language Therapists.

  7. Technical Feasibility Aspects of the Geothermal Resource Reporting Methodology (GRRM)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Badgett, Alex; Young, Katherine R; Dobson, Patrick F.

    This paper reviews the technical assessment of the Geothermal Research Reporting Methodology (GRRM, http://en.openei.org/wiki/GRRM) being developed for reporting geothermal resources and project progress. The goal of the methodology is to provide the U.S. Department of Energy's Geothermal Technologies Office (GTO) with a consistent and comprehensible means of evaluating the impacts of its funding programs. The GRRM is designed to provide uniform assessment criteria for geothermal resource grades and developmental phases of geothermal resource exploration and development. This resource grade system provides information on twelve attributes of geothermal resource locations (e.g., temperature, permeability, land access) to indicate potential for geothermal development.more » The GTO plans to use these Protocols to help quantitatively identify the greatest barriers to geothermal development, develop measureable program goals that will have the greatest impact to geothermal deployment, objectively evaluate proposals based (in part) on a project's ability to contribute to program goals, monitor project progress, and report on GTO portfolio performance. The GRRM assesses three areas of geothermal potential: geological, socio-economic, and technical. Previous work and publications have discussed the work done on the geological aspects of this methodology (Young et al. 2015c); this paper details the development of the technical assessment of the GRRM. Technical development attributes considered include: reservoir management, drilling, logistics, and power conversion.« less

  8. Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis

    PubMed Central

    Kiiski, Hanni S. M.; Ní Riada, Sinéad; Lalor, Edmund C.; Gonçalves, Nuno R.; Nolan, Hugh; Whelan, Robert; Lonergan, Róisín; Kelly, Siobhán; O'Brien, Marie Claire; Kinsella, Katie; Bramham, Jessica; Burke, Teresa; Ó Donnchadha, Seán; Hutchinson, Michael; Tubridy, Niall; Reilly, Richard B.

    2016-01-01

    Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis. PMID:26726800

  9. High doses of biotin in chronic progressive multiple sclerosis: a pilot study.

    PubMed

    Sedel, Frédéric; Papeix, Caroline; Bellanger, Agnès; Touitou, Valérie; Lebrun-Frenay, Christine; Galanaud, Damien; Gout, Olivier; Lyon-Caen, Olivier; Tourbah, Ayman

    2015-03-01

    No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. Uncontrolled, non-blinded proof of concept study 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalization of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalization of the Choline/Creatine ratio. One patient with left homonymous hemianopia kept on improving from 2 to 16 months following treatment׳s onset. Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment׳s onset. These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Urinary Liver-Type Fatty Acid–Binding Protein and Progression of Diabetic Nephropathy in Type 1 Diabetes

    PubMed Central

    Panduru, Nicolae M.; Forsblom, Carol; Saraheimo, Markku; Thorn, Lena; Bierhaus, Angelika; Humpert, Per M.; Groop, Per-Henrik

    2013-01-01

    OBJECTIVE Diabetic nephropathy (DN) has mainly been considered a glomerular disease, although tubular dysfunction may also play a role. This study assessed the predictive value for progression of a tubular marker, urinary liver-type fatty acid–binding protein (L-FABP), at all stages of DN. RESEARCH DESIGN AND METHODS At baseline, 1,549 patients with type 1 diabetes had an albumin excretion rate (AER) within normal reference ranges, 334 had microalbuminuria, and 363 had macroalbuminuria. Patients were monitored for a median of 5.8 years (95% CI 5.7–5.9). In addition, 208 nondiabetic subjects were studied. L-FABP was measured by ELISA and normalized with urinary creatinine. Different Cox proportional hazard models for the progression at every stage of DN were used to evaluate the predictive value of L-FABP. The potential benefit of using L-FABP alone or together with AER was assessed by receiver operating characteristic curve analyses. RESULTS L-FABP was an independent predictor of progression at all stages of DN. As would be expected, receiver operating characteristic curves for the prediction of progression were significantly larger for AER than for L-FABP, except for patients with baseline macroalbuminuria, in whom the areas were similar. Adding L-FABP to AER in the models did not significantly improve risk prediction of progression in favor of the combination of L-FABP plus AER compared with AER alone. CONCLUSIONS L-FABP is an independent predictor of progression of DN irrespective of disease stage. L-FABP used alone or together with AER may not improve the risk prediction of DN progression in patients with type 1 diabetes, but further studies are needed in this regard. PMID:23378622

  11. Plasma D-dimer as a predictor of the progression of abdominal aortic aneurysm.

    PubMed

    Vele, E; Kurtcehajic, A; Zerem, E; Maskovic, J; Alibegovic, E; Hujdurovic, A

    2016-11-01

    Essentials D-dimer could provide important information about abdominal aortic aneurysm (AAA) progression. The greatest diameter of the infrarenal aorta and the value of plasma D-dimer were determined. AAA progression is correlated with increasing plasma D-dimer levels. The increasing value of plasma D-dimer could be a predictor of aneurysm progression. Background The natural course of abdominal aortic aneurysm (AAA) is mostly asymptomatic and unpredictable. D-dimer could provide potentially important information about subsequent AAA progression. Objectives The aims of this study were to establish the relationship between the progression of an abdominal aortic aneurysm (AAA) and plasma D-dimer concentration over a 12-month period and determine the value of plasma D-dimer in patients with sub-aneurysmal aortic dilatation. Patients/Methods This was a prospective observational study that involved 33 patients with an AAA, 30 patients with sub-aneurysmal aortic dilatation and 30 control subjects. The greatest diameter of the infrarenal aorta, which was assessed by ultrasound, and the value of plasma D-dimer were determined for all subjects at baseline assessment, as well as after 12 months for those with an AAA. Results A positive correlation was found between the diameter of an AAA and plasma D-dimer concentration at the baseline and the control measurement stages. There was a strong positive correlation between AAA progression and increasing plasma D-dimer concentration over a 12-month period. Among patients with sub-aneurysmal aortic dilatation (n = 30), the value of plasma D-dimer was higher compared with matched controls (n = 30). Conclusions There is a strongly positive correlation between AAA progression and increasing plasma D-dimer concentration. The value of plasma D-dimer is higher in patients with sub-aneurysmal aortic dilatation than in control subjects. © 2016 International Society on Thrombosis and Haemostasis.

  12. Alignment and the States: Three Approaches to Aligning the National Assessment of Educational Progress with State Assessments, Other Assessments, and Standards

    ERIC Educational Resources Information Center

    Vockley, Martha; Lang, Vockley

    2009-01-01

    Since 1969, the National Assessment of Educational Progress (NAEP) has been the common yardstick for measuring the progress of students' education over time across the country. Teachers, principals, parents, policymakers, and researchers all use NAEP results to assess progress and develop ways to improve education in America. To make the…

  13. Health risk assessment: WTE (waste-to-energy) vs. peanut butter

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Michaels, R.A.

    1988-10-01

    The degree to which society will come to accept potential health risks associated with municipal waste-to-energy plants depends on three factors: the reliability with which exposure and adverse health effects associated with facility emissions can be described, quantified, and gradually reduced; the relative magnitude of the risks compared with those of other waste management options, especially landfilling and recycling; and the relative magnitude of the risks compared with those of more familiar activities, such as driving, flying, smoking, and eating peanut butter sandwiches. Progress in risk assessment has already improved quantification of human exposure to emissions through the food chain,more » as well as through other pathways within the general categories of inhalation, ingestion, and dermal contact. Where does this progress leave municipal refuse incineration relative to other risks This article explores that issue.« less

  14. [KIM-1 and NGAL as potential biomarkers for the diagnosis and cancer progression].

    PubMed

    Marchewka, Zofia; Tacik, Aneta; Piwowar, Agnieszka

    2016-04-18

    On the basis of scientific literature, there is growing evidence that KIM-1 and NGAL are interesting and promising biomarkers not only in acute and chronic inflammatory processes but also in oncogenesis. There are a number of studies which investigate their possible use in diagnosis, treatment and monitoring of therapy effectiveness. The results of recent research suggests that they may play an important role in standard oncology practice. Simultaneous measurement of KIM-1 and NGAL in urine can play a crucial role in carcinogenesis assessment and cancer progression. In the future, they can become rapid diagnostic indicators, which allow one to determine cancer subtype leading to biopsy replacement and therapy improvement. In the present work, beside biochemical characteristics of KIM-1 and NGAL, we will also discuss their role in the diagnosis and assessment of development of cancer.

  15. Progress Towards the Development of a Fathead Minnow Embryo Test and Comparison to the Zebrafish Embryo Test for Assessing Acute Fish Toxicity

    EPA Science Inventory

    The Zebrafish Embryo Test (ZFET) for acute fish toxicity is a well developed method nearing adoption as an OECD Test Guideline. Early drafts of the test guideline (TG) envisioned a suite of potential test species to be covered including zebrafish, fathead minnow, Japanese Medaka...

  16. NAEP Scores Put Spotlight on Standards: Flat Math Results Also Spur Calls for Teaching Reforms

    ERIC Educational Resources Information Center

    Cavanagh, Sean

    2009-01-01

    Fourth grade math scores stagnated for the first time in two decades on a prominent nationwide test, prompting calls for new efforts to improve teacher content knowledge and stirring discussion of the potential benefits of setting more-uniform academic standards across states. The results on the National Assessment of Educational Progress,…

  17. Relations between the CCSS and RTI in Literacy and Language

    ERIC Educational Resources Information Center

    Wixson, Karen K.; Lipson, Marjorie Y.

    2012-01-01

    Initiatives such as Response to Intervention (RTI) and the Common Core State Standards for English Language Arts (CCSS-ELA) have the potential to positively impact progress toward the goal of literacy for all. Because the CCSS-ELA will guide the content of the curriculum, instruction and assessment in the large number of adopting states, they will…

  18. Test-Enhanced Learning: The Potential for Testing to Promote Greater Learning in Undergraduate Science Courses

    ERIC Educational Resources Information Center

    Brame, Cynthia J.; Biel, Rachel

    2015-01-01

    Testing within the science classroom is commonly used for both formative and summative assessment purposes to let the student and the instructor gauge progress toward learning goals. Research within cognitive science suggests, however, that testing can also be a learning event. We present summaries of studies that suggest that repeated retrieval…

  19. Mesotrypsin promotes malignant growth of breast cancer cells through shedding of CD109

    PubMed Central

    Hockla, Alexandra; Radisky, Derek C.

    2010-01-01

    Serine proteases have been implicated in many stages of cancer development, facilitating tumor cell growth, invasion, and metastasis, and naturally occurring serine protease inhibitors have shown promise as potential anticancer therapeutics. Optimal design of inhibitors as potential therapeutics requires the identification of the specific serine proteases involved in disease progression and the functional targets responsible for the tumor-promoting properties. Here, we use the HMT-3522 breast cancer progression series grown in 3D organotypic culture conditions to find that serine protease inhibitors cause morphological reversion of the malignant T4-2 cells, assessed by inhibition of proliferation and formation of acinar structures with polarization of basal markers, implicating serine protease activity in their malignant growth behavior. We identify PRSS3/mesotrypsin upregulation in T4-2 cells as compared to their nonmalignant progenitors, and show that knockdown of PRSS3 attenuates, and treatment with recombinant purified mesotrypsin enhances, the malignant growth phenotype. Using proteomic methods, we identify CD109 as the functional proteolytic target of mesotrypsin. Our study identifies a new mediator and effector of breast cancer growth and progression. PMID:20035377

  20. High-risk carotid plaque: lessons learned from histopathology.

    PubMed

    Kolodgie, Frank D; Yahagi, Kazuyuki; Mori, Hiroyoshi; Romero, Maria E; Trout, Hugh H; Finn, Aloke V; Virmani, Renu

    2017-03-01

    The pathophysiology and natural history of atherosclerotic carotid disease is predicated on a more extensive knowledge of lesion progression gained in the studies conducted in the coronary arteries, and these will be reviewed. While the precise sequence of lesion progression leading to carotid plaque vulnerability and cerebrovascular events remain less well understood, specific early and more advanced progressive lesion morphologies associated with stroke risk have been characterized. Of late, there has been a conscious effort for stroke prevention in symptomatic and asymptomatic patients to move beyond luminal stenosis as the only guidance to predict future cerebrovascular events. Driving this strategy are recent advances in medical imaging modalities to assess carotid atherosclerosis vulnerability particularly involving molecular imaging, which is now positioned at the forefront to provide a more detailed and mechanistic assessment of stroke risk. As such, we will spotlight the pathology of high-risk carotid plaques in patients with symptomatic and asymptomatic carotid disease with further reference into more recent mechanistic insights involving a recognized macrophage-mediated inflammatory change, intraplaque neoangiogenesis/hemorrhage, hypoxia, and microcalcification, as potential morphologic indicators of stroke risk. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. The kinetics of feline leukaemia virus shedding in experimentally infected cats are associated with infection outcome.

    PubMed

    Cattori, Valentino; Tandon, Ravi; Riond, Barbara; Pepin, Andrea C; Lutz, Hans; Hofmann-Lehmann, Regina

    2009-01-13

    Feline leukaemia virus (FeLV) infection in felids results mainly from oronasal exposure to infectious saliva and nasal secretions, but the potential for viral transmission through faeces and urine has not been completely characterized. In order to assess and compare potential FeLV transmission routes, we determined the viral kinetics in plasma, saliva, faeces and urine during early experimental FeLV infection (up to week 15 post-exposure) in specific pathogen-free cats. In addition to monitoring p27 antigen levels measured by ELISA, we evaluated the presence of infectious particles by cell culture assays and quantified viral RNA loads by a quantitative real-time TaqMan polymerase chain reaction. RNA load was associated with infection outcome (high load-progressive infection; low load-regressive infection) not only in plasma, but also in saliva, faeces and urine. Infectious virus was isolated from the saliva, faeces and urine of infected cats with progressive infection as early as 3-6 weeks post-infection, but usually not in cats with regressive infection. In cats with progressive infection, therefore, not only saliva but also faeces and to some extent urine might represent potential FeLV transmission routes. These results should be taken into account when modelling FeLV-host interactions and assessing FeLV transmission risk. Moreover, during early FeLV infection, detection of viral RNA in saliva may be used as an indicator of recent virus exposure, even in cats without detectable antigenaemia/viraemia. To determine the clinically relevant outcome of FeLV infection in exposed cats, however, p27 antigen levels in the peripheral blood should be measured.

  2. Research outcomes and recommendations for the assessment of progression in cancer clinical trials from a PhRMA working group.

    PubMed

    Stone, A M; Bushnell, W; Denne, J; Sargent, D J; Amit, O; Chen, C; Bailey-Iacona, R; Helterbrand, J; Williams, G

    2011-08-01

    Progression free survival (PFS) is increasingly used as a primary end-point in oncology clinical trials. This paper provides recommendations for optimal trial design, conduct and analysis in situations where PFS has the potential to be an acceptable end-point for regulatory approval. These recommendations are based on research performed by the Pharmaceutical Research and Manufacturers Association (PhRMA) sponsored PFS Working Group, including the re-analysis of 28 randomised Phase III trials from 12 companies/institutions. (1) In the assessment of PFS, there is a critical distinction between measurement error that results from random variation, which by itself tends to attenuate treatment effect, versus bias which increases the probability of a false negative or false positive finding. Investigator bias can be detected by auditing a random sample of patients by blinded, independent, central review (BICR). (2) ITT analyses generally resulted in smaller treatment effects (HRs closer to 1) than analyses that censor patients for potentially informative events (such as starting other anti-cancer therapy). (3) Interval censored analyses (ICA) are more robust to time-evaluation bias than the log-rank test. A sample based BICR audit may be employed in open or partially blinded trials and should not be required in true double-blind trials. Patients should be followed until progression even if they have discontinued treatment to be consistent with the ITT principle. ICAs should be a standard sensitivity analysis to assess time-evaluation bias. Implementation of these recommendations would standardize and in many cases simplify phase III oncology clinical trials that use a PFS primary end-point. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Moving the Agenda on Noncommunicable Diseases: Policy Implications of Mobile Phone Surveys in Low and Middle-Income Countries.

    PubMed

    Pariyo, George W; Wosu, Adaeze C; Gibson, Dustin G; Labrique, Alain B; Ali, Joseph; Hyder, Adnan A

    2017-05-05

    The growing burden of noncommunicable diseases (NCDs), for example, cardiovascular diseases and chronic respiratory diseases, in low- and middle-income countries (LMICs) presents special challenges for policy makers, due to resource constraints and lack of timely data for decision-making. Concurrently, the increasing ubiquity of mobile phones in LMICs presents possibilities for rapid collection of population-based data to inform the policy process. The objective of this paper is to highlight potential benefits of mobile phone surveys (MPS) for developing, implementing, and evaluating NCD prevention and control policies. To achieve this aim, we first provide a brief overview of major global commitments to NCD prevention and control, and subsequently explore how countries can translate these commitments into policy action at the national level. Using the policy cycle as our frame of reference, we highlight potential benefits of MPS which include (1) potential cost-effectiveness of using MPS to inform NCD policy actions compared with using traditional household surveys; (2) timeliness of assessments to feed into policy and planning cycles; (3) tracking progress of interventions, hence assessment of reach, coverage, and distribution; (4) better targeting of interventions, for example, to high-risk groups; (5) timely course correction for suboptimal or non-effective interventions; (6) assessing fairness in financial contribution and financial risk protection for those affected by NCDs in the spirit of universal health coverage (UHC); and (7) monitoring progress in reducing catastrophic medical expenditure due to chronic health conditions in general, and NCDs in particular. We conclude that MPS have potential to become a powerful data collection tool to inform policies that address public health challenges such as NCDs. Additional forthcoming assessments of MPS in LMICs will inform opportunities to maximize this technology. ©George W Pariyo, Adaeze C Wosu, Dustin G Gibson, Alain B Labrique, Joseph Ali, Adnan A Hyder. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 05.05.2017.

  4. Apoptosis induction and anti-cancer activity of LeciPlex formulations.

    PubMed

    Dhawan, Vivek V; Joshi, Ganesh V; Jain, Ankitkumar S; Nikam, Yuvraj P; Gude, Rajiv P; Mulherkar, Rita; Nagarsenker, Mangal S

    2014-10-01

    Cationic agents have been reported to possess anti-neoplastic properties against various cancer cell types. However, their complexes with lipids appear to interact differently with different cancer cells. The purpose of this study was to (i) design and generate novel cationic lecithin nanoparticles, (ii) assess and understand the mechanism underlying their putative cytotoxicity and (iii) test their effect on cell cycle progression in various cancer-derived cell lines. In addition, we aimed to evaluate the in vivo potential of these newly developed nanoparticles in oral anti-cancer delivery. Cationic lecithin nanoparticles were generated using a single step nanoprecipitation method and they were characterized for particle size, zeta potential, stability and in vitro release. Their cytotoxic potential was assessed using a sulforhodamine B assay, and their effect on cell cycle progression was evaluated using flow cytometry. The nanoparticle systems were also tested in vivo for their anti-tumorigenic potential. In contrast to cationic agents alone, the newly developed nanoformulations showed a specific toxicity against cancer cells. The mechanism of toxic cell death included apoptosis, S and G2/M cell cycle phase arrest, depending on the type of cationic agent and the cancer-derived cell line used. Both blank and drug-loaded systems exhibited significant anti-cancer activity, suggesting a synergistic anti-tumorigenic effect of the drug and its delivery system. Both in vitro and in vivo data indicate that cationic agents themselves exhibit broad anti-neoplastic activities. Complex formation of the cationic agents with phospholipids was found to provide specificity to the anti-cancer activity. These formulations thus possess potential for the design of effective anti-cancer delivery systems.

  5. Methodology for Assessing the Probability of Corrosion in Concrete Structures on the Basis of Half-Cell Potential and Concrete Resistivity Measurements

    PubMed Central

    2013-01-01

    In recent years, the corrosion of steel reinforcement has become a major problem in the construction industry. Therefore, much attention has been given to developing methods of predicting the service life of reinforced concrete structures. The progress of corrosion cannot be visually assessed until a crack or a delamination appears. The corrosion process can be tracked using several electrochemical techniques. Most commonly the half-cell potential measurement technique is used for this purpose. However, it is generally accepted that it should be supplemented with other techniques. Hence, a methodology for assessing the probability of corrosion in concrete slabs by means of a combination of two methods, that is, the half-cell potential method and the concrete resistivity method, is proposed. An assessment of the probability of corrosion in reinforced concrete structures carried out using the proposed methodology is presented. 200 mm thick 750 mm  ×  750 mm reinforced concrete slab specimens were investigated. Potential E corr and concrete resistivity ρ in each point of the applied grid were measured. The experimental results indicate that the proposed methodology can be successfully used to assess the probability of corrosion in concrete structures. PMID:23766706

  6. Hepatocyte growth factor is associated with progression of atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

    PubMed

    Bell, Elizabeth J; Decker, Paul A; Tsai, Michael Y; Pankow, James S; Hanson, Naomi Q; Wassel, Christina L; Larson, Nicholas B; Cohoon, Kevin P; Budoff, Matthew J; Polak, Joseph F; Stein, James H; Bielinski, Suzette J

    2018-05-01

    Hepatocyte growth factor (HGF) has previously been associated with risk of stroke, coronary heart disease, and atherosclerosis. We hypothesized that higher circulating HGF is associated with greater progression of measures of atherosclerosis: coronary artery calcium (CAC) and carotid plaque. Participants aged 45-84 years from the prospective cohort study Multi-Ethnic Study of Atherosclerosis had HGF measured at baseline (between 2000 and 2002) and were followed for progression of atherosclerosis for up to 12 years. CAC was measured at all five exams using the Agatston method. Mixed-effects models were used to examine the association of HGF and CAC progression among 6695 participants with available data. Relative risk regression was used to assess the association between HGF and new or additional carotid plaque between exams 1 and 5 in 3400 participants with available data. All point estimates were adjusted for potential confounding variables. Each standard deviation higher HGF at baseline was associated with 2.9 Agatston units/year greater CAC progression (95% CI: 1.6-4.2, p < 0.0001), and the magnitude of this association differed by race/ethnicity (p value for interaction by race = 0.003). Each standard deviation higher HGF at baseline was associated with a 4% higher risk of new or additional carotid plaque (95% CI: 1.01-1.08, p = 0.005). Higher levels of HGF were significantly associated with greater progression of atherosclerosis in this large and diverse population. Circulating HGF continues to show promise as a potential clinical biomarker for cardiovascular disease. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Emotional recognition of dynamic facial expressions before and after cochlear implantation in adults with progressive deafness.

    PubMed

    Ambert-Dahan, Emmanuèle; Giraud, Anne-Lise; Mecheri, Halima; Sterkers, Olivier; Mosnier, Isabelle; Samson, Séverine

    2017-10-01

    Visual processing has been extensively explored in deaf subjects in the context of verbal communication, through the assessment of speech reading and sign language abilities. However, little is known about visual emotional processing in adult progressive deafness, and after cochlear implantation. The goal of our study was thus to assess the influence of acquired post-lingual progressive deafness on the recognition of dynamic facial emotions that were selected to express canonical fear, happiness, sadness, and anger. A total of 23 adults with post-lingual deafness separated into two groups; those assessed either before (n = 10) and those assessed after (n = 13) cochlear implantation (CI); and 13 normal hearing (NH) individuals participated in the current study. Participants were asked to rate the expression of the four cardinal emotions, and to evaluate both their emotional valence (unpleasant-pleasant) and arousal potential (relaxing-stimulating). We found that patients with deafness were impaired in the recognition of sad faces, and that patients equipped with a CI were additionally impaired in the recognition of happiness and fear (but not anger). Relative to controls, all patients with deafness showed a deficit in perceiving arousal expressed in faces, while valence ratings remained unaffected. The current results show for the first time that acquired and progressive deafness is associated with a reduction of emotional sensitivity to visual stimuli. This negative impact of progressive deafness on the perception of dynamic facial cues for emotion recognition contrasts with the proficiency of deaf subjects with and without CIs in processing visual speech cues (Rouger et al., 2007; Strelnikov et al., 2009; Lazard and Giraud, 2017). Altogether these results suggest there to be a trade-off between the processing of linguistic and non-linguistic visual stimuli. Copyright © 2017. Published by Elsevier B.V.

  8. Progressive disease in glioblastoma: Benefits and limitations of semi-automated volumetry

    PubMed Central

    Alber, Georgina; Bette, Stefanie; Kaesmacher, Johannes; Boeckh-Behrens, Tobias; Gempt, Jens; Ringel, Florian; Specht, Hanno M.; Meyer, Bernhard; Zimmer, Claus

    2017-01-01

    Purpose Unambiguous evaluation of glioblastoma (GB) progression is crucial, both for clinical trials as well as day by day routine management of GB patients. 3D-volumetry in the follow-up of GB provides quantitative data on tumor extent and growth, and therefore has the potential to facilitate objective disease assessment. The present study investigated the utility of absolute changes in volume (delta) or regional, segmentation-based subtractions for detecting disease progression in longitudinal MRI follow-ups. Methods 165 high resolution 3-Tesla MRIs of 30 GB patients (23m, mean age 60.2y) were retrospectively included in this single center study. Contrast enhancement (CV) and tumor-related signal alterations in FLAIR images (FV) were semi-automatically segmented. Delta volume (dCV, dFV) and regional subtractions (sCV, sFV) were calculated. Disease progression was classified for every follow-up according to histopathologic results, decisions of the local multidisciplinary CNS tumor board and a consensus rating of the neuro-radiologic report. Results A generalized logistic mixed model for disease progression (yes / no) with dCV, dFV, sCV and sFV as input variables revealed that only dCV was significantly associated with prediction of disease progression (P = .005). Delta volume had a better accuracy than regional, segmentation-based subtractions (79% versus 72%) and a higher area under the curve by trend in ROC curves (.83 versus .75). Conclusion Absolute volume changes of the contrast enhancing tumor part were the most accurate volumetric determinant to detect progressive disease in assessment of GB and outweighed FLAIR changes as well as regional, segmentation-based image subtractions. This parameter might be useful in upcoming objective response criteria for glioblastoma. PMID:28245291

  9. Magnetic resonance imaging of disease progression and resolution in a transgenic mouse model of pulmonary fibrosis.

    PubMed

    Cleveland, Zackary I; Zhou, Yu M; Akinyi, Teckla G; Dunn, R Scott; Davidson, Cynthia R; Guo, Jinbang; Woods, Jason C; Hardie, William D

    2017-04-01

    Pulmonary fibrosis contributes to morbidity and mortality in a range of diseases, and there are no approved therapies for reversing its progression. To understand the mechanisms underlying pulmonary fibrosis and assess potential therapies, mouse models are central to basic and translational research. Unfortunately, metrics commonly used to assess murine pulmonary fibrosis require animals to be grouped and euthanized, increasing experimental difficulty and cost. We examined the ability of magnetic resonance imaging (MRI) to noninvasively assess lung fibrosis progression and resolution in a doxycycline (Dox) regulatable, transgenic mouse model that overexpresses transforming growth factor-α (TGF-α) under control of a lung-epithelial-specific promoter. During 7 wk of Dox treatment, fibrotic lesions were readily observed as high-signal tissue. Mean weighted signal and percent signal volume were found to be the most robust MRI-derived measures of fibrosis, and these metrics correlated significantly with pleural thickness, histology scores, and hydroxyproline content ( R  = 0.75-0.89). When applied longitudinally, percent high signal volume increased by 1.5% wk -1 ( P < 0.001) and mean weighted signal increased at a rate of 0.0065 wk -1 ( P = 0.0062). Following Dox treatment, lesions partially resolved, with percent high signal volume decreasing by -3.2% wk -1 ( P = 0.0034) and weighted mean signal decreasing at -0.015 wk -1 ( P = 0.0028). Additionally, longitudinal MRI revealed dynamic remodeling in a subset of lesions, a previously unobserved behavior in this model. These results demonstrate MRI can noninvasively assess experimental lung fibrosis progression and resolution and provide unique insights into its pathobiology. Copyright © 2017 the American Physiological Society.

  10. Technical adequacy of growth estimates from a computer adaptive test: Implications for progress monitoring.

    PubMed

    Van Norman, Ethan R; Nelson, Peter M; Parker, David C

    2017-09-01

    Computer adaptive tests (CATs) hold promise to monitor student progress within multitiered systems of support. However, the relationship between how long and how often data are collected and the technical adequacy of growth estimates from CATs has not been explored. Given CAT administration times, it is important to identify optimal data collection schedules to minimize missed instructional time. We used simulation methodology to investigate how the duration and frequency of data collection influenced the reliability, validity, and precision of growth estimates from a math CAT. A progress monitoring dataset of 746 Grade 4, 664 Grade 5, and 400 Grade 6 students from 40 schools in the upper Midwest was used to generate model parameters. Across grades, 53% of students were female and 53% were White. Grade level was not as influential as the duration and frequency of data collection on the technical adequacy of growth estimates. Low-stakes decisions were possible after 14-18 weeks when data were collected weekly (420-540 min of assessment), 20-24 weeks when collected every other week (300-360 min of assessment), and 20-28 weeks (150-210 min of assessment) when data were collected once a month, depending on student grade level. The validity and precision of growth estimates improved when the duration and frequency of progress monitoring increased. Given the amount of time required to obtain technically adequate growth estimates in the present study, results highlight the importance of weighing the potential costs of missed instructional time relative to other types of assessments, such as curriculum-based measures. Implications for practice, research, as well as future directions are also discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. Prediction of functional loss in glaucoma from progressive optic disc damage.

    PubMed

    Medeiros, Felipe A; Alencar, Luciana M; Zangwill, Linda M; Bowd, Christopher; Sample, Pamela A; Weinreb, Robert N

    2009-10-01

    To evaluate the ability of progressive optic disc damage detected by assessment of longitudinal stereophotographs to predict future development of functional loss in those with suspected glaucoma. The study included 639 eyes of 407 patients with suspected glaucoma followed up for an average of 8.0 years with annual standard automated perimetry visual field and optic disc stereophotographs. All patients had normal and reliable standard automated perimetry results at baseline. Conversion to glaucoma was defined as development of 3 consecutive abnormal visual fields during follow-up. Presence of progressive optic disc damage was evaluated by grading longitudinally acquired simultaneous stereophotographs. Other predictive factors included age, intraocular pressure, central corneal thickness, pattern standard deviation, and baseline stereophotograph grading. Hazard ratios for predicting visual field loss were obtained by extended Cox models, with optic disc progression as a time-dependent covariate. Predictive accuracy was evaluated using a modified R(2) index. Progressive optic disc damage had a hazard ratio of 25.8 (95% confidence interval, 16.0-41.7) and was the most important risk factor for development of visual field loss with an R(2) of 79%. The R(2)s for other predictive factors ranged from 6% to 26%. Presence of progressive optic disc damage on stereophotographs was a highly predictive factor for future development of functional loss in glaucoma. These findings suggest the importance of careful monitoring of the optic disc appearance and a potential role for longitudinal assessment of the optic disc as an end point in clinical trials and as a reference for evaluation of diagnostic tests in glaucoma.

  12. A Case Report of Successful Treatment of Recalcitrant Childhood Localized Scleroderma with Infliximab and Leflunomide.

    PubMed

    Ferguson, Ian D; Weiser, Peter; Torok, Kathryn S

    2015-01-01

    Herein we report successful treatment of an adolescent Caucasian female with severe progressive localized scleroderma (mixed subtype, including generalized morphea and linear scleroderma of the trunk/limb) using infliximab and leflunomide. The patient demonstrated improvement after the first 9 months of therapy based on her clinical examination, objective measures, and patient and parent global assessments. Infliximab is a potential treatment option for pediatric localized scleroderma patients who have progression of disease or who are unable to tolerate the side effect profile of more standard systemic therapy. Larger longitudinal studies or case series are needed to confirm and further investigate infliximab's role in localized scleroderma.

  13. "Watching time tick by…": Decision making for Duchenne muscular dystrophy trials.

    PubMed

    Peay, Holly L; Scharff, Hadar; Tibben, Aad; Wilfond, Benjamin; Bowie, Janice; Johnson, Joanna; Nagaraju, Kanneboyina; Escolar, Diana; Piacentino, Jonathan; Biesecker, Barbara B

    2016-01-01

    This interview study explored clinicians' perspectives and parents' decision making about children's participation in Duchenne muscular dystrophy (DMD) clinical trials. Data from semi-structured interviews conducted with clinicians and parents in U.S. or Canada were assessed using thematic analysis. Eleven clinicians involved in ten trials and fifteen parents involved in six trials were interviewed. Parents described benefit-risk assessments using information from advocacy, peers, professionals, and sponsors. Strong influence was attributed to the progressive nature of DMD. Most expected direct benefit. Few considered the possibility of trial failure. Most made decisions to participate before the informed consent (IC) process, but none-the-less perceived informed choice with little to lose for potential gain. Clinicians described more influence on parental decisions than attributed by parents. Clinicians felt responsible to facilitate IC while maintaining hope. Both clinicians and parents reported criticisms about the IC process and regulatory barriers. The majority of parents described undertaking benefit-risk assessments that led to informed choices that offered psychological and potential disease benefits. Parents' high expectations influenced their decisions while also reflecting optimism. Clinicians felt challenged in balancing parents' expectations and likely outcomes. Prognosis-related pressures coupled with decision making prior to IC suggest an obligation to ensure educational materials are understandable and accurate, and to consider an expanded notion of IC timeframes. Anticipatory guidance about potential trial failure might facilitate parents' deliberations while aiding clinicians in moderating overly-optimistic motivations. Regulators and industry should appreciate special challenges in progressive disorders, where doing nothing was equated with doing harm. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. GIS-based preliminary wind-hydrogen energy assessment: A case study for Pakistan

    NASA Astrophysics Data System (ADS)

    Hussain Siyal, Shahid; Hopper, Miles; Lefvert, Adrian; Mentis, Dimitris; Korkovelos, Alexandros; Lopez De Briñas Gorosabel, Oier; Varela González, Cristina; Howells, Mark

    2017-04-01

    While the world is making progress on incorporating renewables in the electricity grid, the transport sector is still widely locked into using gasoline and diesel fuels. Simultaneously, wind energy is encountering resistance due to its intermittent nature. Wind to hydrogen energy conversion poses a solution to this problem, using wind powered electrolysis to produce hydrogen which can fuel the transport sector. In this report a preliminary assessment for wind to hydrogen energy conversion potential of Pakistan was made considering two different turbines; Vestas V82 and V112. Using available wind speed data, processed in ArcGIS, the hydrogen potential was calculated. Finally, the economic feasibility and potential environmental savings were assessed. From the results it was concluded that Pakistan has a good potential for wind to hydrogen conversion, with 63,807 and 80,232 ktons of hydrogen per year from the V82 and V112 turbines. This corresponds to 2,105 and 2,647 TWh of energy per year respectively. Only using 2% of that potential could give emissions savings of up to 11.43 and 14.37 MtCO2-eq, which would give good reason for more in-depth studies to evaluate the feasibility of a project in Pakistan.

  15. Quantitative evaluation of redox ratio and collagen characteristics during breast cancer chemotherapy using two-photon intrinsic imaging.

    PubMed

    Wu, Shulian; Huang, Yudian; Tang, Qinggong; Li, Zhifang; Horng, Hannah; Li, Jiatian; Wu, Zaihua; Chen, Yu; Li, Hui

    2018-03-01

    Preoperative neoadjuvant treatment in locally advanced breast cancer is recognized as an effective adjuvant therapy, as it improves treatment outcomes. However, the potential complications remain a threat, so there is an urgent clinical need to assess both the tumor response and changes in its microenvironment using non-invasive and precise identification techniques. Here, two-photon microscopy was employed to detect morphological alterations in breast cancer progression and recession throughout chemotherapy. The changes in structure were analyzed based on the autofluorescence and collagen of differing statuses. Parameters, including optical redox ratio, the ratio of second harmonic generation and auto-fluorescence signal, collagen density, and collagen shape orientation, were studied. Results indicate that these parameters are potential indicators for evaluating breast tumors and their microenvironment changes during progression and chemotherapy. Combined analyses of these parameters could provide a quantitative, novel method for monitoring tumor therapy.

  16. Progressive Dysarthria and Augmentative and Alternative Communication in Conversation: Establishing the Reliability of the Dysarthria-in-Interaction Profile

    ERIC Educational Resources Information Center

    Bloch, Steven; Tuomainen, Jyrki

    2017-01-01

    Background: The Dysarthria-in-Interaction Profile's potential contribution to the clinical assessment of dysarthria-in-conversation has been outlined in the literature, but its consistency of use across different users has yet to be reported. Aims: To establish the level of consistency across raters on four different interaction categories. That…

  17. Attention Training in Autism as a Potential Approach to Improving Academic Performance: A School-Based Pilot Study

    ERIC Educational Resources Information Center

    Spaniol, Mayra Muller; Shalev, Lilach; Kossyvaki, Lila; Mevorach, Carmel

    2018-01-01

    This study assessed the effectiveness of an attention intervention program (Computerized Progressive Attentional Training; CPAT) in improving academic performance of children with ASD. Fifteen 6-10 year olds with ASD attending a mainstream and a special school were assigned to an experimental (CPAT; n = 8) and active control (computer games; n =…

  18. Proteolytic roles of matrix metalloproteinase (MMP)-13 during progression of chronic periodontitis: initial evidence for MMP-13/MMP-9 activation cascade.

    PubMed

    Hernández Ríos, Marcela; Sorsa, Timo; Obregón, Fabián; Tervahartiala, Taina; Valenzuela, María Antonieta; Pozo, Patricia; Dutzan, Nicolás; Lesaffre, Emmanuel; Molas, Marek; Gamonal, Jorge

    2009-12-01

    Matrix metalloproteinases (MMP)-13 can initiate bone resorption and activate proMMP-9 in vitro, and both these MMPs have been widely implicated in tissue destruction associated with chronic periodontitis. We studied whether MMP-13 activity and TIMP-1 levels in gingival crevicular fluid (GCF) associated with progression of chronic periodontitis assessed clinically and by measuring carboxy-terminal telopeptide of collagen I (ICTP) levels. We additionally addressed whether MMP-13 could potentiate gelatinase activation in diseased gingival tissue. In this prospective study, GCF samples from subjects undergoing clinical progression of chronic periodontitis and healthy controls were screened for ICTP levels, MMP-13 activity and TIMP-1. Diseased gingival explants were cultured, treated or not with MMP-13 with or without adding CL-82198, a synthetic MMP-13 selective inhibitor, and assayed by gelatin zymography and densitometric analysis. Active sites demonstrated increased ICTP levels and MMP-13 activity (p<0.05) in progression subjects. The MMP-9 activation rate was elevated in MMP-13-treated explants (p<0.05) and MMP-13 inhibitor prevented MMP-9 activation. MMP-13 could be implicated in the degradation of soft and hard supporting tissues and proMMP-9 activation during progression of chronic periodontitis. MMP-13 and -9 can potentially form an activation cascade overcoming the protective TIMP-1 shield, which may become useful for diagnostic aims and a target for drug development.

  19. A method to detect progression of glaucoma using the multifocal visual evoked potential technique

    PubMed Central

    Wangsupadilok, Boonchai; Kanadani, Fabio N.; Grippo, Tomas M.; Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

    2010-01-01

    Purpose To describe a method for monitoring progression of glaucoma using the multifocal visual evoked potential (mfVEP) technique. Methods Eighty-seven patients diagnosed with open-angle glaucoma were divided into two groups. Group I, comprised 43 patients who had a repeat mfVEP test within 50 days (mean 0.9 ± 0.5 months), and group II, 44 patients who had a repeat test after at least 6 months (mean 20.7 ± 9.7 months). Monocular mfVEPs were obtained using a 60-sector pattern reversal dartboard display. Monocular and interocular analyses were performed. Data from the two visits were compared. The total number of abnormal test points with P < 5% within the visual field (total scores) and number of abnormal test points within a cluster (cluster size) were calculated. Data for group I provided a measure of test–retest variability independent of disease progression. Data for group II provided a possible measure of progression. Results The difference in the total scores for group II between visit 1 and visit 2 for the interocular and monocular comparison was significant (P < 0.05) as was the difference in cluster size for the interocular comparison (P < 0.05). Group I did not show a significant change in either total score or cluster size. Conclusion The change in the total score and cluster size over time provides a possible method for assessing progression of glaucoma with the mfVEP technique. PMID:18830654

  20. Noninvasive assessment of arterial function in children: clinical applications

    PubMed Central

    Aggoun, Y; Beghetti, M

    2002-01-01

    Non invasive methods to assess arterial function are widely used in adults. The development and progression of arterial vascular disease is a multifactorial process that can start early in life, thus even in a pediatric population. Risk factors for cardiovascular disease mediate their effects by altering the structure, properties and function of wall and endothelial components of the arterial blood vessels. The ability to detect and monitor sub-clinical damage, representing the cumulative and integrated influence of risk factors in impairing arterial wall integrity, holds potential to further refine cardiovascular risk stratification and enable early intervention to prevent or attenuate disease progression. Measurements that provide more direct information in relation to changes in arterial wall integrity clearly hold predictive and therapeutic potential. The aim of this current review will be to describe the non-invasive procedure used in children to investigate the mechanical properties of a great elastic artery, the common carotid, and the endothelial function of the brachial artery. The accuracy of recording noninvasively the blood pressure wave contour along the arterial tree has been improved by the technique of applanation tonometry. The results obtained with these methods in previous studies are described. PMID:22368620

  1. Novel Contrast Mechanisms at 3 Tesla and 7 Tesla

    PubMed Central

    Regatte, Ravinder R.; Schweitzer, Mark E.

    2013-01-01

    Osteoarthritis (OA) is the most common musculoskeletal degenerative disease, affecting millions of people. Although OA has been considered primarily a cartilage disorder associated with focal cartilage degeneration, it is accompanied by well-known changes in subchondral and trabecular bone, including sclerosis and osteophyte formation. The exact cause of OA initiation and progression remains under debate, but OA typically first affects weightbearing joints such as the knee. Magnetic resonance imaging (MRI) has been recognized as a potential tool for quantitative assessment of cartilage abnormalities due to its excellent soft tissue contrast. Over the last two decades, several new MR biochemical imaging methods have been developed to characterize the disease process and possibly predict the progression of knee OA. These new MR biochemical methods play an important role not only for diagnosis of disease at an early stage, but also for their potential use in monitoring outcome of various drug therapies (success or failure). Recent advances in multicoil radiofrequency technology and high field systems (3 T and above) significantly improve the sensitivity and specificity of imaging studies for the diagnosis of musculoskeletal disorders. The current state-of-the-art MR imaging methods are briefly reviewed for the quantitative biochemical and functional imaging assessment of musculoskeletal systems. PMID:18850506

  2. Evaluating Chagas disease progression and cure through blood-derived biomarkers: a systematic review.

    PubMed

    Requena-Méndez, Ana; López, Manuel Carlos; Angheben, Andrea; Izquierdo, Luis; Ribeiro, Isabela; Pinazo, Maria-Jesús; Gascon, Joaquim; Muñoz, José

    2013-09-01

    This article reviews the usefulness of various types of blood-derived biomarkers that are currently being studied to predict the progression of Chagas disease in patients with the indeterminate form, to assess the efficacy of antiparasitic drugs and to identify early cardiac and gastrointestinal damage. The authors used a search strategy based on MEDLINE, Cochrane Library Register for systematic review, EmBase, Global Health and LILACS databases. Out of 1716 screened articles, only 166 articles were eligible for final inclusion. The authors classified the biomarkers according to their biochemical structure and primary biological activity in four groups: i) markers of inflammation and cellular injury, ii) metabolic biomakers, iii) prothrombotic biomarkers and iv) markers derived from specific antigens of the parasite. Several potential biomarkers might have clinical potential for the detection of early cardiopathy. Such capacity is imperative in order to detect high-risk patients who require intensive monitoring and earlier therapy. Prospective studies with longer follow-ups are needed for the appraisal of biomarkers assessing clinical or microbiological cure after therapy. At the same time, studies evaluating more than one biomarker are useful to compare the efficacy among them given the lack of a recognized gold standard.

  3. Cognitive impairment in COPD: should cognitive evaluation be part of respiratory assessment?

    PubMed Central

    Gloeckl, Rainer; Vogiatzis, Ioannis; Kenn, Klaus

    2017-01-01

    Cognitive impairment is highly prevalent in patients with COPD and demonstrates multiple detrimental effects on many aspects of patient state and therapeutic outcomes. It is attributed to several overlapping pathophysiological factors, with the most common being the low level of oxygen saturation due to respiratory insufficiency. Despite the impact of cognitive impairment on clinical outcomes, the screening for coexisting cognitive deficits which may interfere with the successful progress of respiratory treatment is yet neglected. There is a special consideration that cognitive deficits should be taken into account when developing respiratory therapy plans. Cognitively impaired patients are likely to require more support and have need of an individualised respiratory care plan which can also be beneficial for their cognitive deficits. Pulmonary rehabilitation as a multidisciplinary approach could be prioritised for COPD patients with cognitive impairment. Educational aims To illustrate the common signs of cognitive impairment and define potential associations between lung and cognitive dysfunction. To illustrate the potential influence of cognitive deficits on the optimal progress of respiratory therapy. To illustrate the importance of cognitive evaluation as part of a comprehensive clinical assessment for patients suspected of suffering cognitive impairment. PMID:29184593

  4. [Research progress and trend on grassland agroecology].

    PubMed

    Ren, Jizhou; Li, Xianglin; Hou, Fujiang

    2002-08-01

    The connotation, progress, research frontiers and developmental trend of grassland agroecology are discussed in this paper. The interface theory, structure and function, coupling and discordance, and health assessment of grassland agroecosystems were recognized as the four research frontiers of the discipline. There exist three primary interfaces in a grassland agroecosystem, i.e., vegetation-site, grassland-animal and production-management. Research into a series of the ecological processes that occurred at these interfaces is the key to revealing the features of the system behavior. There are four sections in a grassland agroecosystem, i.e., pre-plant, plant, animal and post-biotic sections. System coupling and discordance are the two important concepts to describe interactions among the production sections. System coupling among the sections can lead to system improvement by exerting the potential of system capacity. Health of an ecosystem is a reflection of its structure and function, and health assessment is a measurement of its orderliness and service value.

  5. [The impact of psychological variables on the presentation and progress of asthma and patient's cognitive functions].

    PubMed

    Talarowska, Monika; Florkowski, Antoni; Gałecki, Piotr; Szemraj, Janusz; Zboralski, Krzysztof; Pietras, Tadeusz; Górski, Paweł

    2009-01-01

    Chronic respiratory system diseases become serious public health problem all over the world. The most prevalent are obstructive diseases (asthma and COPD). The prevalence of asthma is still high and concern patients representing wide range of age and socio-economic status. Despite progress in diagnostic and therapeutic options several studies showed that asthma has an impact on health-related quality of life and patients' coping. Asthma as chronic condition results in limitations of patients activity and social relations. Thus psychosocial variables, which may have an impact on asthma symptoms presentation and disease progress, should be considered. There are only few reports concerning cognitive functions in asthma. The aim of the study was to assess the potential impact of psychosocial factors on asthma symptoms presentation, and cognitive function in asthma patients.

  6. Estimating nitrogen loading and far-field dispersal potential from background sources and coastal finfish aquaculture: A simple framework and case study in Atlantic Canada

    NASA Astrophysics Data System (ADS)

    McIver, R.; Milewski, I.; Loucks, R.; Smith, R.

    2018-05-01

    Far-field nutrient impacts associated with finfish aquaculture have been identified as a topic of concern for regulators, managers, scientists, and the public for over two decades but disentangling aquaculture impacts from those caused by other natural and anthropogenic sources has impeded the development of monitoring metrics and management plans. We apply a bulk, steady-state nitrogen loading model (NLM) framework to estimate the annual input of Total Dissolved Nitrogen (TDN) from point and non-point sources to the watershed surrounding Port Mouton Bay, Nova Scotia (Canada). We then use the results of the NLM together with estimates of dissolved inorganic nitrogen (DIN) loading from a sea-cage trout farm in the Bay and progressive vector diagrams to illustrate potential patterns of DIN dispersal from the trout farm. Our estimated anthropogenic nitrogen contribution to Port Mouton Bay from all terrestrial and atmospheric sources is ∼211,703 kg TDN/year with atmospheric deposition accounting for almost all (98.6%). At a stocking level of ∼400,000 rainbow trout, the Port Mouton Bay sea-cage farm increases the annual anthropogenic TDN loading to the bay by 14.4% or 30,400 kg. Depending on current flow rates, nitrogen flux from the trout farm can be more than double the background concentrations of TDN near the farm site. Although it is unlikely that nitrogen loading from this single fish farm is saturating the DIN requirements of the entire bay, progressive vector diagrams suggest that the dispersal potential may be insufficient to mitigate potential symptoms of eutrophication associated with nitrogen fluxes. We present an accessible and user-friendly tool for managers to estimate baseline nutrient loading in relation to aquaculture and our use of progressive vector diagrams illustrate a practical and simple method for characterizing potential nutrient dispersal based on local conditions and spatial scales. Our study joins numerous studies which have highlighted the need for more effective monitoring and assessment methods to improve the detection of aquaculture effects at far-field scales and to assess those effects in relation to other natural and anthropogenic factors impacting coastal habitats.

  7. Pharmacokinetics and pharmacodynamics of MD1003 (high-dose biotin) in the treatment of progressive multiple sclerosis.

    PubMed

    Peyro Saint Paul, Laure; Debruyne, Danièle; Bernard, Delphine; Mock, Donald M; Defer, Gilles L

    2016-01-01

    Multiple sclerosis (MS) is a chronic, potentially highly disabling neurological disorder. No disease-modifying treatments are approved in the progressive and not active forms of the disease. High doses of biotin were tested in an open-label pilot study involving 23 patients with progressive MS and reported positive results. A randomized, double-blind, placebo-controlled trial in 154 progressive MS patients confirmed the beneficial effect of MD1003 (high-dose biotin) on reversing or stabilizing disability progression, with a good safety profile. It is proposed that MD1003 in progressive MS 1) increases energy production in demyelinated axons and/or 2) enhances myelin synthesis in oligodendrocytes. Biotin is highly bioavailable; absorption and excretion are rapid. The major route of elimination is urinary excretion. A high oral dose of biotin seems generally well tolerated but a few important safety concerns were identified: 1) teratogenicity in one species and 2) interference with some biotin-based laboratory immunoassays. The animal toxicity data are limited at such high doses. Further preclinical studies would be useful to address the mechanism of action of MD1003. Assessment of clinical benefit duration in responders will be also very important to set. Results of randomized, placebo-controlled trial are reassuring and provide hope for the treatment of progressive MS.

  8. Department of Defense Landfill Database: A Collection of DoD-Wide Landfill Data for the Assessment of Implementing the Flex Energy Powerstation for Landfill Gas to Energy Projects

    DTIC Science & Technology

    2011-06-01

    Microturbine. Given the approximate nature of the source data and the gas production models , this material can only be used for a preliminary assessment...methane generation rate, k, used in the first order decay model can vary widely from landfill to landfill and are partly dependent on waste composition...State Status (active/closed/ closure in progress) Gross Power Generation Potential (kW) 345 ARMY WHITE SANDS MISSLE RANGE DONA ANA NM ACTIVE

  9. Driving and Dementia: A Review of the Literature

    PubMed Central

    Brown, Laura B.; Ott, Brian R.

    2012-01-01

    The purpose of this article is to review the literature on the ability of individuals with dementia to drive an automobile. Based on a review of the literature, several factors were identified that may be useful in differentiating between people with dementia who presently remain safe drivers from those who have progressed to impaired driving. These factors include disease duration and severity, sex, patient self-assessment, family assessment, neuropsychological measures, findings on road evaluations, and driving simulator testing. The approach of the physician to driving and dementia is addressed, including in-office screening, referral for on-road driving assessments, and the potential for physician reporting to state agencies. PMID:15533995

  10. Tracing the Assessment Triangle with Learning Progression-Aligned Assessments in Mathematics

    ERIC Educational Resources Information Center

    Lai, Emily R.; Kobrin, Jennifer L.; DiCerbo, Kristen E.; Holland, Laura R.

    2017-01-01

    We describe an application of the assessment triangle, using a learning progression as the "cognition" vertex. We summarize two studies to evaluate whether evidence of student performance is consistent with our progression. In Study 1, we conducted think alouds using draft assessment activities and evaluated responses in relation to the…

  11. Overexpression of periostin and distinct mesothelin forms predict malignant progression in a rat cholangiocarcinoma model

    PubMed Central

    Manzanares, Miguel Á.; Campbell, Deanna J.W.; Maldonado, Gabrielle T.

    2017-01-01

    Periostin and mesothelin have each been suggested to be predictors of poor survival for patients with intrahepatic cholangiocarcinoma, although the clinical prognostic value of both of these biomarkers remains uncertain. The aim of the current study was to investigate these biomarkers for their potential to act as tumor progression factors when assessed in orthotopic tumor and three‐dimensional culture models of rat cholangiocarcinoma progression. Using our orthotopic model, we demonstrated a strong positive correlation between tumor and serum periostin and mesothelin and increasing liver tumor mass and associated peritoneal metastases that also reflected differences in cholangiocarcinoma cell aggressiveness and malignant grade. Periostin immunostaining was most prominent in the desmoplastic stroma of larger sized more aggressive liver tumors and peritoneal metastases. In comparison, mesothelin was more highly expressed in the cholangiocarcinoma cells; the slower growing more highly differentiated liver tumors exhibited a luminal cancer cell surface immunostaining for this biomarker, and the rapidly growing less differentiated liver and metastatic tumor masses largely showed cytoplasmic mesothelin immunoreactivity. Two molecular weight forms of mesothelin were identified, one at ∼40 kDa and the other, a more heavily glycosylated form, at ∼50 kDa. Increased expression of the 40‐kDa mesothelin over that of the 50 kDa form predicted increased malignant progression in both the orthotopic liver tumors and in cholangiocarcinoma cells of different malignant potential in three‐dimensional culture. Moreover, coculturing of cancer‐associated myofibroblasts with cholangiocarcinoma cells promoted overexpression of the 40‐kDa mesothelin, which correlated with enhanced malignant progression in vitro. Conclusion: Periostin and mesothelin are useful predictors of tumor progression in our rat desmoplastic cholangiocarcinoma models. This supports their relevance to human intrahepatic cholangiocarcinoma. (Hepatology Communications 2018;2:155–172) PMID:29404524

  12. Patients and animal models of CNGβ1-deficient retinitis pigmentosa support gene augmentation approach

    PubMed Central

    Petersen-Jones, Simon M.; Occelli, Laurence M.; Winkler, Paige A.; Lee, Winston; Sparrow, Janet R.; Tsukikawa, Mai; Boye, Sanford L.; Chiodo, Vince; Capasso, Jenina E.; Becirovic, Elvir; Schön, Christian; Seeliger, Mathias W.; Levin, Alex V.; Hauswirth, William W.

    2017-01-01

    Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene augmentation using adeno-associated virus vectors robustly sustained the rescue of rod function and preserved retinal structure in the dog model. Together, our results reveal an early loss of rod function in CNGB1-deficient patients and a wide window for therapeutic intervention. Moreover, the identification of potential biomarkers of outcome measures, availability of relevant animal models, and robust functional rescue from gene augmentation therapy support future work to move CNGB1-RP therapies toward clinical trials. PMID:29202463

  13. Laboratory Experiments on Bentonite Samples: FY16 Progress

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ruth M. Tinnacher; Tournassat, Christophe; James A. Davis

    2016-08-22

    The primary goal of this study is to improve the understanding of U(VI) sorption and diffusion behavior in sodium-montmorillonite in order to support the development of realistic conceptual models describing these processes in performance assessment models while (1) accounting for potential changes in system conditions over time and space, (2) avoiding overly conservative transport predictions, and (3) using a minimum number of fitting parameters.

  14. The Aims and Objectives of the Monitoring the Future Study and Progress toward Fulfilling Them as of 2001. Monitoring the Future Occasional Paper 52.

    ERIC Educational Resources Information Center

    Johnston, Lloyd D.; O'Malley, Patrick M.; Schulenberg, John E.; Bachman, Jerald G.

    Monitoring the Future is an ongoing program of research intended to assess the changing lifestyles, values, and preferences of American youth. This publication, from the occasional paper series, describes a study that monitors drug use and potential explanatory factors among American secondary school students, college students, and young adults.…

  15. A Progress Conference Survey: Assessment of the First Enrollment Experience of the Educational Opportunity Program (GROUPS) Students. Indiana Studies in Higher Education Number 36.

    ERIC Educational Resources Information Center

    Brigman, S. Leelan

    A survey was conducted at Indiana University-Bloomington to provide (1) normative data for identifying common adjustment problems of the first enrollment experience of 265 of the Educational Opportunity Program (GROUPS) students, and (2) student evaluations of potential areas of the program that need administrative attention and/or redesigning. a…

  16. Polygenic risk accelerates the developmental progression to heavy, persistent smoking and nicotine dependence: Evidence from a 4-Decade Longitudinal Study

    PubMed Central

    Moffitt, Terrie E; Baker, Timothy B; Biddle, Andrea K; Evans, James P; Harrington, HonaLee; Houts, Renate; Meier, Madeline; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Caspi, Avshalom

    2013-01-01

    OBJECTIVE To test how genomic loci identified in genome-wide association studies (GWAS) influence the developmental progression of smoking behavior. DESIGN A 38-year prospective longitudinal study of a representative birth-cohort. SETTING The Dunedin Multidisciplinary Health and Development Study, New Zealand. PARTICIPANTS N=1037 male and female study members. MAIN EXPOSURES We assessed genetic risk with a multi-locus genetic risk score (GRS). The GRS was composed of single-nucleotide polymorphisms identified in three meta-analyses of GWAS of smoking quantity phenotypes. OUTCOME MEASURES Smoking initiation, conversion to daily smoking, progression to heavy smoking, nicotine dependence (Fagerstrom Test of Nicotine Dependence), and cessation difficulties were evaluated at eight assessments spanning ages 11-38 years. RESULTS Genetic risk score was unrelated to smoking initiation. However, individuals at higher genetic risk were more likely to convert to daily smoking as teenagers, progressed more rapidly from smoking initiation to heavy smoking, persisted longer in smoking heavily, developed nicotine dependence more frequently, were more reliant on smoking to cope with stress, and were more likely to fail in their cessation attempts. Further analysis revealed that two adolescent developmental phenotypes—early conversion to daily smoking and rapid progression to heavy smoking--mediated associations between the genetic risk score and mature phenotypes of persistent heavy smoking, nicotine dependence, and cessation failure. The genetic risk score predicted smoking risk over and above family history. CONCLUSIONS Initiatives that disrupt the developmental progression of smoking behavior among adolescents may mitigate genetic risks for developing adult smoking problems. Future genetic research may maximize discovery potential by focusing on smoking behavior soon after smoking initiation and by studying young smokers. PMID:23536134

  17. The Role of BPTF in Melanoma Progression and in Response to BRAF-Targeted Therapy

    PubMed Central

    Dar, Altaf A.; Nosrati, Mehdi; Bezrookove, Vladimir; de Semir, David; Majid, Shahana; Thummala, Suresh; Sun, Vera; Tong, Schuyler; Leong, Stanley P. L.; Minor, David; Billings, Paul R.; Soroceanu, Liliana; Debs, Robert; Miller, James R.; Sagebiel, Richard W.

    2015-01-01

    Background: Bromodomain PHD finger transcription factor (BPTF) plays an important role in chromatin remodeling, but its functional role in tumor progression is incompletely understood. Here we explore the oncogenic effects of BPTF in melanoma. Methods: The consequences of differential expression of BPTF were explored using shRNA-mediated knockdown in several melanoma cell lines. Immunoblotting was used to assess the expression of various proteins regulated by BPTF. The functional role of BPTF in melanoma progression was investigated using assays of colony formation, invasion, cell cycle, sensitivity to selective BRAF inhibitors, and in xenograft models of melanoma progression (n = 12 mice per group). The biomarker role of BPTF in melanoma progression was assessed using fluorescence in situ hybridization and immunohistochemical analyses. All statistical tests were two-sided. Results: shRNA-mediated BPTF silencing suppressed the proliferative capacity (by 65.5%) and metastatic potential (by 66.4%) of melanoma cells. Elevated BPTF copy number (mean ≥ 3) was observed in 28 of 77 (36.4%) melanomas. BPTF overexpression predicted poor survival in a cohort of 311 melanoma patients (distant metastasis-free survival P = .03, and disease-specific survival P = .008), and promoted resistance to BRAF inhibitors in melanoma cell lines. Metastatic melanoma tumors progressing on BRAF inhibitors contained low BPTF-expressing, apoptotic tumor cell subclones, indicating the continued presence of drug-responsive subclones within tumors demonstrating overall resistance to anti-BRAF agents. Conclusions: These studies demonstrate multiple protumorigenic functions for BPTF and identify it as a novel target for anticancer therapy. They also suggest the combination of BPTF targeting with BRAF inhibitors as a novel therapeutic strategy for melanomas with mutant BRAF. PMID:25713167

  18. Longitudinal DSC-MRI for Distinguishing Tumor Recurrence From Pseudoprogression in Patients With a High-grade Glioma.

    PubMed

    Boxerman, Jerrold L; Ellingson, Benjamin M; Jeyapalan, Suriya; Elinzano, Heinrich; Harris, Robert J; Rogg, Jeffrey M; Pope, Whitney B; Safran, Howard

    2017-06-01

    For patients with high-grade glioma on clinical trials it is important to accurately assess time of disease progression. However, differentiation between pseudoprogression (PsP) and progressive disease (PD) is unreliable with standard magnetic resonance imaging (MRI) techniques. Dynamic susceptibility contrast perfusion MRI (DSC-MRI) can measure relative cerebral blood volume (rCBV) and may help distinguish PsP from PD. A subset of patients with high-grade glioma on a phase II clinical trial with temozolomide, paclitaxel poliglumex, and concurrent radiation were assessed. Nine patients (3 grade III, 6 grade IV), with a total of 19 enhancing lesions demonstrating progressive enhancement (≥25% increase from nadir) on postchemoradiation conventional contrast-enhanced MRI, had serial DSC-MRI. Mean leakage-corrected rCBV within enhancing lesions was computed for all postchemoradiation time points. Of the 19 progressively enhancing lesions, 10 were classified as PsP and 9 as PD by biopsy/surgery or serial enhancement patterns during interval follow-up MRI. Mean rCBV at initial progressive enhancement did not differ significantly between PsP and PD (2.35 vs. 2.17; P=0.67). However, change in rCBV at first subsequent follow-up (-0.84 vs. 0.84; P=0.001) and the overall linear trend in rCBV after initial progressive enhancement (negative vs. positive slope; P=0.04) differed significantly between PsP and PD. Longitudinal trends in rCBV may be more useful than absolute rCBV in distinguishing PsP from PD in chemoradiation-treated high-grade gliomas with DSC-MRI. Further studies of DSC-MRI in high-grade glioma as a potential technique for distinguishing PsP from PD are indicated.

  19. Leisure time physical activity assessment of American adults through an analysis of time diaries collected in 1981.

    PubMed Central

    Brooks, C M

    1987-01-01

    One of the 1990 Health Objectives established by the U.S. Department of Health and Human Services is for 60 per cent of adults 18-65 years of age to be participating regularly in vigorous physical exercise. Unfortunately, no valid and practical measurement system is available that will allow assessment of leisure time physical activity participation of large populations. Consequently, not only is it difficult to assess progress toward the 1990 goal, an accurate baseline from which to measure potential progress does not exist. This paper presents a time diary technique for measuring aggregate population physical activity participation and utilizes actual time diaries collected from adults by the Institute for Social Research in 1981 to arrive at a possible baseline. The results indicated that time diaries are a viable method for assessing aggregate physical activity behavior of large populations. American Adults were quite sedentary in 1981. Over a period of one week, 31% undertook no leisure time physical activity. Only 14 per cent expended more than 1600 kcals/week in leisure time physical activity, and 10 per cent met the DHHS physical activity requirements. PMID:3826464

  20. Potential use of metabolic breath tests to assess liver disease and prognosis: has the time arrived for routine use in the clinic?

    PubMed

    Stravitz, R Todd; Ilan, Yaron

    2017-03-01

    The progression of liver disease may be unique among organ system diseases in that progressive fibrosis compromises not only the sufficiency of hepatocyte mass but also impairs blood flow to the liver, resulting in porto-systemic shunting. Although liver biopsy as an assessment of fibrosis has become the key biomarker of and target for new therapies, it is invasive and subject to sampling error, and cannot quantify metabolic function or porto-systemic shunting. Measurement of the hepatic venous pressure gradient accommodates some of the deficiencies of biopsy but requires expertise not widely available and misses minor changes in hepatocellular mass and thereby information about metabolic function. Thus, an unmet need in clinical hepatology remains unfulfilled: a noninvasive biomarker which quantitates both the hepatocellular insufficiency and porto-systemic shunting inherent in progressive hepatic fibrosis. Ideally, such a biomarker should correlate with clinical endpoints including liver-related survival and cirrhotic complications, be performed at the point-of-care, and be affordable and easy to use. This review, an expert opinion, summarizes background and recent data suggesting that metabolic breath tests may now meet these requirements and have a valid place in clinical hepatology to supplant the time-honoured assessment of hepatic fibrosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Geothermal Resource Reporting Metric (GRRM) Developed for the U.S. Department of Energy's Geothermal Technologies Office

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Young, Katherine R.; Wall, Anna M.; Dobson, Patrick F.

    This paper reviews a methodology being developed for reporting geothermal resources and project progress. The goal is to provide the U.S. Department of Energy's (DOE) Geothermal Technologies Office (GTO) with a consistent and comprehensible means of evaluating the impacts of its funding programs. This framework will allow the GTO to assess the effectiveness of research, development, and deployment (RD&D) funding, prioritize funding requests, and demonstrate the value of RD&D programs to the U.S. Congress and the public. Standards and reporting codes used in other countries and energy sectors provide guidance to develop the relevant geothermal methodology, but industry feedback andmore » our analysis suggest that the existing models have drawbacks that should be addressed. In order to formulate a comprehensive metric for use by the GTO, we analyzed existing resource assessments and reporting methodologies for the geothermal, mining, and oil and gas industries, and sought input from industry, investors, academia, national labs, and other government agencies. Using this background research as a guide, we describe a methodology for evaluating and reporting on GTO funding according to resource grade (geological, technical and socio-economic) and project progress. This methodology would allow GTO to target funding, measure impact by monitoring the progression of projects, or assess geological potential of targeted areas for development.« less

  2. A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease.

    PubMed

    Snow, Barry J; Rolfe, Fiona L; Lockhart, Michelle M; Frampton, Christopher M; O'Sullivan, John D; Fung, Victor; Smith, Robin A J; Murphy, Michael P; Taylor, Kenneth M

    2010-08-15

    Multiple lines of evidence point to mitochondrial oxidative stress as a potential pathogenic cause for Parkinson's disease (PD). MitoQ is a powerful mitochondrial antioxidant. It is absorbed orally and concentrates within mitochondria where it has been shown to protect against oxidative damage. We enrolled 128 newly diagnosed untreated patients with PD in a double-blind study of two doses of MitoQ compared with placebo to explore the hypothesis that, over 12 months, MitoQ would slow the progression of PD as measured by clinical scores, particularly the Unified Parkinson Disease Rating Scale. We showed no difference between MitoQ and placebo on any measure of PD progression. MitoQ does not slow the progression of PD, and this finding should be taken into account when considering the oxidative stress hypothesis for the pathogenesis of PD.

  3. Applying Item Response Theory Methods to Design a Learning Progression-Based Science Assessment

    ERIC Educational Resources Information Center

    Chen, Jing

    2012-01-01

    Learning progressions are used to describe how students' understanding of a topic progresses over time and to classify the progress of students into steps or levels. This study applies Item Response Theory (IRT) based methods to investigate how to design learning progression-based science assessments. The research questions of this study are: (1)…

  4. Genome-wide screening of indicator genes for assessing the potential carcinogenic risk of Nanjing city drinking water.

    PubMed

    Zhang, Rui; Cheng, Shupei; Li, Aimin; Sun, Jie; Zhang, Yan; Zhang, Xuxiang

    2011-07-01

    Effects of all pollutants existing in the Nanjing city drinking water (DWNC) on mouse gene transcription levels were measured to assess the DWNC carcinogenic risks and to identify candidate indicator genes for assessing and early warning the cancer risks. Transcriptional expression levels of 14,000 hepatic genes for the treatment group mice (Mus musculus, ICR) fed with DWNC for 90 days were detected using the GeneChip(®) Mouse Genome 430A 2.0 array. The analysis indicated that the transcriptional levels of 294 genes were up-regulated and 542 ones were down-regulated. Of these genes, 12 ones identified to be involved in at least five different types of cancers were further analyzed. An interrogation by Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that three (including ITGAV, CCND1 and SMAD2) of the 12 genes were mapped to pathway in cancer. Gene Ontology (GO) function annotation also showed that they were associated with the functional categories of cell cycle regulation, adhesion, apoptosis, signal transduction and so on which are closely implicated in tumorigenesis and progression. The correlations between the aberrant expressions of them and the genesis and progression of cancers have been further documented by a number of scientific researches. These results might demonstrate that the potential toxicity and carcinogenic risks were associated with DWNC. Moreover, ITGAV, CCND1 and SMAD2 were identified as the most likely candidate indicator genes for the assessment of the combined carcinogenic risk of all pollutants existing in DWNC.

  5. From the Margins to the Spotlight: Diverse Deaf and Hard of Hearing Student Populations and Standardized Assessment Accessibility.

    PubMed

    Cawthon, Stephanie

    2015-01-01

    Designing assessments and tests is one of the more challenging aspects of creating an accessible learning environment for students who are deaf or hard of hearing (DHH), particularly for deaf students with a disability (DWD). Standardized assessments are a key mechanism by which the educational system in the United States measures student progress, teacher effectiveness, and the impact of school reform. The diversity of student characteristics within DHH and DWD populations is only now becoming visible in the research literature relating to standardized assessments and their use in large-scale accountability reforms. The purpose of this article is to explore the theoretical frameworks surrounding assessment policy and practice, current research related to standardized assessment and students who are DHH and DWD, and potential implications for practice within both the assessment and instruction contexts.

  6. A fuzzy logic expert system for evaluating policy progress towards sustainability goals.

    PubMed

    Cisneros-Montemayor, Andrés M; Singh, Gerald G; Cheung, William W L

    2017-12-16

    Evaluating progress towards environmental sustainability goals can be difficult due to a lack of measurable benchmarks and insufficient or uncertain data. Marine settings are particularly challenging, as stakeholders and objectives tend to be less well defined and ecosystem components have high natural variability and are difficult to observe directly. Fuzzy logic expert systems are useful analytical frameworks to evaluate such systems, and we develop such a model here to formally evaluate progress towards sustainability targets based on diverse sets of indicators. Evaluation criteria include recent (since policy enactment) and historical (from earliest known state) change, type of indicators (state, benefit, pressure, response), time span and spatial scope, and the suitability of an indicator in reflecting progress toward a specific objective. A key aspect of the framework is that all assumptions are transparent and modifiable to fit different social and ecological contexts. We test the method by evaluating progress towards four Aichi Biodiversity Targets in Canadian oceans, including quantitative progress scores, information gaps, and the sensitivity of results to model and data assumptions. For Canadian marine systems, national protection plans and biodiversity awareness show good progress, but species and ecosystem states overall do not show strong improvement. Well-defined goals are vital for successful policy implementation, as ambiguity allows for conflicting potential indicators, which in natural systems increases uncertainty in progress evaluations. Importantly, our framework can be easily adapted to assess progress towards policy goals with different themes, globally or in specific regions.

  7. Potential of MR spectroscopy for assessment of glioma grading.

    PubMed

    Bulik, Martin; Jancalek, Radim; Vanicek, Jiri; Skoch, Antonin; Mechl, Marek

    2013-02-01

    Magnetic resonance spectroscopy (MRS) is an imaging diagnostic method based that allows non-invasive measurement of metabolites in tissues. There are a number of metabolites that can be identified by standard brain proton MRS but only a few of them has a clinical significance in diagnosis of gliomas including N-acetylaspartate, choline, creatine, myo-inositol, lactate, and lipids. In this review, we describe potential of MRS for grading of gliomas. Low-grade gliomas are generally characterized by a relatively high concentration of N-acetylaspartate, low level of choline and absence of lactate and lipids. The increase in creatine concentration indicates low-grade gliomas with earlier progression and malignant transformation. Progression in grade of a glioma is reflected in the progressive decrease in the N-acetylaspartate and myo-inositol levels on the one hand and elevation in choline level up to grade III on the other. Malignant transformation of the glial tumors is also accompanied by the presence of lactate and lipids in MR spectra of grade III but mainly grade IV gliomas. It follows that MRS is a helpful method for detection of glioma regions with aggressive growth or upgrading due to favorable correlation of the choline and N-acetylaspartate levels with histopathological proliferation index Ki-67. Thus, magnetic resonance spectroscopy is also a suitable method for the targeting of brain biopsies. Gliomas of each grade have some specific MRS features that can be used for improvement of the diagnostic value of conventional magnetic resonance imaging in non-invasive assessment of glioma grade. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  8. Might Progress Assessments Hinder Equitable Progress? Evidence from England

    ERIC Educational Resources Information Center

    Alcott, Benjamin

    2017-01-01

    Prior research has highlighted the importance of educational achievement throughout school in predicting subsequent progression to higher education in England. However, progress assessments may not only demonstrate students' prior academic achievement but also influence their future achievement. I compare students who have received different…

  9. Progression of Late-Onset Stargardt Disease.

    PubMed

    Lambertus, Stanley; Lindner, Moritz; Bax, Nathalie M; Mauschitz, Matthias M; Nadal, Jennifer; Schmid, Matthias; Schmitz-Valckenberg, Steffen; den Hollander, Anneke I; Weber, Bernhard H F; Holz, Frank G; van der Wilt, Gert Jan; Fleckenstein, Monika; Hoyng, Carel B

    2016-10-01

    Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression as an outcome measure. We performed a retrospective cohort study collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt, defined by clinical phenotype, at least one ABCA4 mutation, and age at disease onset ≥ 45 years. We analyzed RPE atrophy progression on fundus autofluorescence and near-infrared reflectance imaging using semiautomated software and a linear mixed model. We performed sample size calculations to assess the power in a simulated 2-year interventional study and assessed visual endpoints using time-to-event analysis. Over time, progression of RPE atrophy was observed (mean: 0.22 mm/year, 95% confidence interval [CI]: 0.19-0.27). By including only patients with bilateral RPE atrophy in a future trial, 32 patients are needed to reach a power of 83.9% (95% CI: 83.1-84.6), assuming a fixed therapeutic effect size of 30%. We found a median interval between disease onset and visual acuity decline to 20/32, 20/80, and 20/200 of 2.74 (95% CI: 0.54-4.41), 10.15 (95% CI: 6.13-11.38), and 11.38 (95% CI: 6.13-13.34) years, respectively. We show that RPE atrophy represents a robust biomarker to monitor disease progression in future therapeutic trials. In contrast, the variability in terms of the course of visual acuity was high.

  10. Examining Progress across Time with Practical Assessments in Ensemble Settings

    ERIC Educational Resources Information Center

    Crochet, Lorrie S.; Green, Susan K.

    2012-01-01

    This article provides the rationale for effective music assessment that tracks individual progress across time and offers examples to illustrate assessment of a range of music-learning goals. Gauging progress across time helps students become more mastery-oriented, while showing more effort and positive attitudes. As instruction and assessment…

  11. Prognostic and predictive potential molecular biomarkers in colon cancer.

    PubMed

    Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I

    2011-01-01

    An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

  12. The Shoulder Objective Practical Assessment Tool: Evaluation of a New Tool Assessing Residents Learning in Diagnostic Shoulder Arthroscopy.

    PubMed

    Talbot, Christopher L; Holt, Edward M; Gooding, Benjamin W T; Tennent, Thomas D; Foden, Philip

    2015-08-01

    To design and validate an objective practical assessment tool for diagnostic shoulder arthroscopy that would provide residents with a method to evaluate their progression in this field of surgery and to identify specific learning needs. We designed and evaluated the shoulder Objective Practical Assessment Tool (OPAT). The shoulder OPAT was designed by us, and scoring domains were created using a Delphi process. The shoulder OPAT was trialed by members of the British Elbow & Shoulder Society Education Committee for internal consistency and ease of use before being offered to other trainers and residents. Inter-rater reliability and intrarater reliability were calculated. One hundred forty orthopaedic residents, of varying seniority, within 5 training regions in the United Kingdom, were questioned regarding the tool. A pilot study of 6 residents was undertaken. Internal consistency was 0.77 (standardized Cronbach α). Inter-rater reliability was 0.60, and intrarater reliability was 0.82. The Spearman correlation coefficient (r) between the global summary score for the shoulder OPAT and the current assessment tool used in postgraduate training for orthopaedic residents undertaking diagnostic shoulder arthroscopy equaled 0.74. Of the residents, 82% agreed or strongly agreed when asked if the shoulder OPAT would be a useful tool in monitoring progression and 72% agreed or strongly agreed with the introduction of the shoulder OPAT within the orthopaedic domain. This study shows that the shoulder OPAT fulfills several aspects of reliability and validity when tested. Despite the inter-rater reliability being 0.60, we believe that the shoulder OPAT has the potential to play a role alongside the current assessment tool in the training of orthopaedic residents. The shoulder OPAT can be used to assess residents during shoulder arthroscopy and has the potential for use in medical education, as well as arthroscopic skills training in the operating theater. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  13. Detecting glaucomatous change in visual fields: Analysis with an optimization framework.

    PubMed

    Yousefi, Siamak; Goldbaum, Michael H; Varnousfaderani, Ehsan S; Belghith, Akram; Jung, Tzyy-Ping; Medeiros, Felipe A; Zangwill, Linda M; Weinreb, Robert N; Liebmann, Jeffrey M; Girkin, Christopher A; Bowd, Christopher

    2015-12-01

    Detecting glaucomatous progression is an important aspect of glaucoma management. The assessment of longitudinal series of visual fields, measured using Standard Automated Perimetry (SAP), is considered the reference standard for this effort. We seek efficient techniques for determining progression from longitudinal visual fields by formulating the problem as an optimization framework, learned from a population of glaucoma data. The longitudinal data from each patient's eye were used in a convex optimization framework to find a vector that is representative of the progression direction of the sample population, as a whole. Post-hoc analysis of longitudinal visual fields across the derived vector led to optimal progression (change) detection. The proposed method was compared to recently described progression detection methods and to linear regression of instrument-defined global indices, and showed slightly higher sensitivities at the highest specificities than other methods (a clinically desirable result). The proposed approach is simpler, faster, and more efficient for detecting glaucomatous changes, compared to our previously proposed machine learning-based methods, although it provides somewhat less information. This approach has potential application in glaucoma clinics for patient monitoring and in research centers for classification of study participants. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Early Detection of Progressive Adolescent Idiopathic Scoliosis: A Severity Index.

    PubMed

    Skalli, Wafa; Vergari, Claudio; Ebermeyer, Eric; Courtois, Isabelle; Drevelle, Xavier; Kohler, Remi; Abelin-Genevois, Kariman; Dubousset, Jean

    2017-06-01

    Early detection of progressive adolescent idiopathic scoliosis (AIS) was assessed based on 3D quantification of the deformity. Based on 3D quantitative description of scoliosis curves, the aim is to assess a specific phenotype that could be an early detectable severity index for progressive AIS. Early detection of progressive scoliosis is important for adapted treatment to limit progression. However, progression risk assessment is mainly based on the follow up, waiting for signs of rapid progression that generally occur during the growth peak. Sixty-five mild scoliosis (16 boys, 49 girls, Cobb Angle between 10 and 20°) with a Risser between 0 and 2 were followed from their first examination until a decision was made by the clinician, either considering the spine as stable at the end of growth (26 patients) or planning to brace because of progression (39 patients). Calibrated biplanar x-rays were performed and 3D reconstructions of the spine allowed calculating six local parameters related to main curve deformity. For progressive curve 3D phenotype assessment, data were compared with those previously assessed for 30 severe scoliosis (Cobb Angle > 35°), 17 scoliosis before brace (Cobb Angle > 29°) and 53 spines of nonscoliosis subjects. A predictive discriminant analysis was performed to assess similarity of mild scoliosis curves either to those of scoliosis or nonscoliosis spines, yielding a severity index (S-index). S-index value at first examination was compared with clinical outcome. At the first exam, 53 out of 65 predictions (82%) were in agreement with actual clinical outcome. Approximately, 89% of the curves that were predicted as progressive proved accurate. Although still requiring large scale validation, results are promising for early detection of progressive curves. 2.

  15. [Progress on neuropsychology and event-related potentials in patients with brain trauma].

    PubMed

    Dong, Ri-xia; Cai, Wei-xiong; Tang, Tao; Huang, Fu-yin

    2010-02-01

    With the development of information technology, as one of the research frontiers in neurophysiology, event-related potentials (ERP) is concerned increasingly by international scholars, which provides a feasible and objective method for exploring cognitive function. There are many advances in neuropsychology due to new assessment tool for the last years. The basic theories in the field of ERP and neuropsychology were reviewed in this article. The research and development in evaluating cognitive function of patients with syndrome after brain trauma were focused in this review, and the perspectives for the future research of ERP was also explored.

  16. Assessment of Options for Enhancing Surface Ship Acquisition.

    DTIC Science & Technology

    1996-03-01

    propulsion control, cargo handling, and the ship’s self defense capability. Cost growth was 50 percent even with a reduction from 9 ships to 5. For...technology, high - value weapon and sensor systems Cargo Arrangements Every area of ship densely packed with equipment, cables, pipes, ventilation...acquisition reform has a high potential to improve the outcomes of ship acquisition programs. Progress has been made in the reduction of military

  17. Sexual Assault Prevention and Response Website Analysis

    DTIC Science & Technology

    2014-09-01

    IRR inter-rater reliability KPI key performance indicator N17 U.S Navy 21st Century Sailor Office NASASV National Association of Services Against...determine if progress is being made to achieve the desired goal; this is typically done by establishing key performance indicators 22 ( KPI ). After...defining the KPIs , organizations must prioritize the potential solutions and devise a plan for making small incremental changes to accurately assess the

  18. A Summary of Models and Standards-Based Applications for Grade-to-Grade Growth on Statewide Assessments and Implications for Students with Disabilities. Research Report. ETS RR-10-14

    ERIC Educational Resources Information Center

    Buzick, Heather M.; Laitusis, Cara Cahalan

    2010-01-01

    Recently growth-based approaches to accountability have received considerable attention because they have the potential to reward schools and teachers for improving student performance over time by measuring the progress of students at all levels of the performance spectrum (including those who have not yet reached proficiency on state…

  19. The supercam instrument on the NASA Mars 2020 mission: optical design and performance

    NASA Astrophysics Data System (ADS)

    Perez, R.; Parès, Laurent P.; Newell, R.; Robinson, S.; Bernardi, P.; Réess, J.-M.; Caïs, Ph.; McCabe, K.; Maurice, S.; Wiens, R. C.

    2017-09-01

    NASA is developing the MARS 2020 mission, which includes a rover that will land and operate on the surface of Mars. MARS 2020, scheduled for launch in July, 2020, is designed to conduct an assessment of Mars' past habitability, search for potential biosignatures, demonstrate progress toward the future return of samples to Earth, and contribute to NASA's Human Exploration and Space Technology Programs.

  20. Understanding Optimal Military Decision Making: Year 2 Progress Report

    DTIC Science & Technology

    2014-01-01

    measures. ARMY RELEVANCY AND MILITARY APPLICATION AREAS Objectively defining, measuring, and developing a means to assess military optimal decision making...has the potential to enhance training and refine procedures supporting more efficient learning and task accomplishment. Through the application of...26.79 (12.39) 7.94 (62.38) N/A = Not applicable ; as it is not possible to calculate this particular variable. Table 2. Descriptive statistics of

  1. Previous Bladder Cancer History in Patients with High-Risk, Non-muscle-invasive Bladder Cancer Correlates with Recurrence and Progression: Implications of Natural History.

    PubMed

    Mitrakas, Lampros P; Zachos, Ioannis V; Tzortzis, Vassileios P; Gravas, Stavros A; Rouka, Erasmia C; Dimitropoulos, Konstantinos I; Vandoros, Gerasimos P; Karatzas, Anastasios D; Melekos, Michael D; Papavassiliou, Athanasios G

    2015-07-01

    The purpose of this study was to assess the correlation of previous bladder cancer history with the recurrence and progression of patients with high-risk non-muscle-invasive bladder cancer treated with adjuvant Bacillus Calmette-Guérin (BCG) and to evaluate their natural history. Patients were divided into two groups based on the existence of previous bladder cancer (primary, non-primary). A logistic regression analysis was used to identify the possible differences in the probabilities of recurrence and progression with respect to tumor history, while potential differences due to gender, tumor size (> 3 cm, < 3 cm), stage (pTa, T1), concomitant carcinoma in situ (pTis) and number of tumors (single, multiple) were also assessed. Univariate and multivariate models were employed. In addition, Kaplan-Meier survival analysis was used to compare recurrence- and progression-free survival between the groups. A total of 192 patients were included (144 with primary and 48 with non-primary tumors). The rates of recurrence and progression for patients with primary tumors were 27.8% and 12.5%, respectively. The corresponding percentages for patients with non-primary tumors were 77.1% and 33.3%, respectively. The latter group of patients displayed significantly higher probabilities of recurrence (p=0.000; 95% confidence interval [CI], 4.067 to 18.804) and progression (p=0.002; 95% CI, 1.609 to 7.614) in a univariate logistic regression analysis. Previous bladder cancer history remained significant in the multivariate model accounting for history, age, gender, tumor size , number of tumors, stage and concomitant pTis (p=0.000; 95% CI, 4.367 to 21.924 and p=0.002; 95% CI, 1.611 to 8.182 for recurrence and progression respectively). Kaplan-Meier curves revealed that the non-primary group hadreduced progression- and recurrence-free survival. Previous non-muscle-invasive bladder cancer history correlates significantly with recurrence and progression in patients with high-risk non-muscle-invasive disease treated with adjuvant BCG.

  2. A narrative overview of the current status of MRI of the hip and its relevance for osteoarthritis research - what we know, what has changed and where are we going?

    PubMed

    Crema, M D; Watts, G J; Guermazi, A; Kim, Y-J; Kijowski, R; Roemer, F W

    2017-01-01

    To review and discuss the role of magnetic resonance imaging (MRI) in the context of hip osteoarthritis (OA) research. The content of this narrative review, based on an extensive PubMed database research including English literature only, describes the advances in MRI of the hip joint and its potential usefulness in hip OA research, reviews the relevance of different MRI features in regard to symptomatic and structural progression in hip OA, and gives an outlook regarding future use of MRI in hip OA research endeavors. Recent technical advances have helped to overcome many of the past difficulties related to MRI assessment of hip OA. MRI-based morphologic scoring systems allow for detailed assessment of several hip joint tissues and, in combination with the recent advances in MRI, may increase reproducibility and sensitivity to change. Compositional MRI techniques may add to our understanding of disease onset and progression. Knowledge about imaging pitfalls and anatomical variants is crucial to avoid misinterpretation. In comparison to research on knee OA, the associations between MRI features and the incidence and progression of disease as well as with clinical symptoms have been little explored. Anatomic alterations of the hip joint as seen in femoro-acetabular impingement (FAI) seem to play a role in the onset and progression of structural damage. With the technical advances occurring in recent years, MRI may play a major role in investigating the natural history of hip OA and provide an improved method for assessment of the efficacy of new therapeutic approaches. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  3. Vectra DA for the objective measurement of disease activity in patients with rheumatoid arthritis.

    PubMed

    Segurado, O G; Sasso, E H

    2014-01-01

    Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.

  4. Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial.

    PubMed

    Höglinger, Günter U; Huppertz, Hans-Jürgen; Wagenpfeil, Stefan; Andrés, María V; Belloch, Vincente; León, Teresa; Del Ser, Teodoro

    2014-04-01

    It is believed that glycogen synthase kinase-3 hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) trial assessed the glycogen synthase kinase-3 inhibitor tideglusib as potential treatment. For the magnetic resonance imaging (MRI) substudy reported here, we assessed the progression of brain atrophy. TAUROS was a multinational, phase 2, double-blind, placebo-controlled trial in patients with mild-to-moderate PSP who were treated with oral tideglusib (600 mg or 800 mg daily) or with placebo for 1 year. A subset of patients underwent baseline and 52-week MRI. Automated, observer-independent, atlas-based, and mask-based volumetry was done on high-resolution, T1-weighted, three-dimensional data. For primary outcomes, progression of atrophy was compared both globally (brain, cerebrum) and regionally (third ventricle, midbrain, pons) between the active and placebo groups (Bonferroni correction). For secondary outcomes, 15 additional brain structures were explored (Benjamini & Yekutieli correction). In total, MRIs from 37 patient were studied (placebo group, N = 9; tideglusib 600 mg group, N = 19; tideglusib 800 mg group, N = 9). The groups compared well in their demographic characteristics. Clinical results showed no effect of tideglusib over placebo. Progression of atrophy was significantly lower in the active group than in the placebo group for the brain (mean ± standard error of the mean: -1.3% ± 1.4% vs. -3.1% ± 2.3%, respectively), cerebrum (-1.3% ± 1.5% vs. -3.2% ± 2.1%, respectively), parietal lobe (-1.6% ± 1.9% vs. -4.1% ± 3.0%, respectively), and occipital lobe (-0.3% ± 1.8% vs. -2.7% ± 3.2%, respectively). A trend toward reduced atrophy also was observed in the frontal lobe, hippocampus, caudate nucleus, midbrain, and brainstem. In patients with PSP, tideglusib reduced the progression of atrophy in the whole brain, particularly in the parietal and occipital lobes. © 2014 International Parkinson and Movement Disorder Society.

  5. Portfolio: a comprehensive method of assessment for postgraduates in oral and maxillofacial surgery.

    PubMed

    Kadagad, Poornima; Kotrashetti, S M

    2013-03-01

    Post graduate learning and assessment is an important responsibility of an academic oral and maxillofacial surgeon. The current method of assessment for post graduate training include formative evaluation in the form of seminars, case presentations, log books and infrequently conducted end of year theory exams. End of the course theory and practical examination is a summative evaluation which awards the degree to the student based on grades obtained. Oral and maxillofacial surgery is mainly a skill based specialty and deliberate practice enhances skill. But the traditional system of assessment of post graduates emphasizes their performance on the summative exam which fails to evaluate the integral picture of the student throughout the course. Emphasis on competency and holistic growth of the post graduate student during training in recent years has lead to research and evaluation of assessment methods to quantify students' progress during training. Portfolio method of assessment has been proposed as a potentially functional method for post graduate evaluation. It is defined as a collection of papers and other forms of evidence that learning has taken place. It allows the collation and integration of evidence on competence and performance from different sources to gain a comprehensive picture of everyday practice. The benefits of portfolio assessment in health professions education are twofold: it's potential to assess performance and its potential to assess outcomes, such as attitudes and professionalism that are difficult to assess using traditional instruments. This paper is an endeavor for the development of portfolio method of assessment for post graduate student in oral and maxillofacial surgery.

  6. Geography Assessment and Exercise Specifications for the 1994 National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    American Inst. for Research, Washington, DC. Washington Research Center.

    This document lists and outlines the specific educational objectives of the content of the 1994 National Assessment of Educational Progress's Geography Assessment. The document is divided into two sections: "Assessment Specifications" and "Exercise Specifications." The "Assessment Specifications" provide an overall…

  7. Evaluative studies in nuclear medicine research. Progress report, October 1, 1979-June 30, 1980

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Potchen, E.J.

    Effort since the last progress report (September 1979) has been directed toward assessing the potential short and long term benefits of continued development and application and medical research of emission computed tomograhy (ECT). This report contains a review of existing ECT technology, including functional descriptions of current and proposed image systems, for both sngle-photon ECT (SPECT) and positron ECT (PECT) approaches. Medical research and clinical topics to which ECT has been, or may be, applied are presented. One such area of investigation involves the effects of stroke. The application of ECT to laboratory research, and to clinical diagnosis and prognosis,more » of stroke may result in improved management of the disease. An illustration of the potential savings in the cost of management of stroke due to the effects of applied ECT research is included. The results represent a compilation of data collected from conversations with, and conference presentations by, ECT users, researchers and image system designers, and from a review of the literature.« less

  8. Effect of pulsed progressive fluoroscopy on reduction of radiation dose in the cardiac catheterization laboratory

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Holmes, D.R. Jr.; Wondrow, M.A.; Gray, J.E.

    1990-01-01

    The increased application of therapeutic interventional cardiology procedures is associated with increased radiation exposure to physicians, patients and technical personnel. New advances in imaging techniques have the potential for reducing radiation exposure. A progressive scanning video system with a standard vascular phantom has been shown to decrease entrance radiation exposure. The effect of this system on reducing actual radiation exposure to physicians and technicians was assessed from 1984 through 1987. During this time, progressive fluoroscopy was added sequentially to all four adult catheterization laboratories; no changes in shielding procedures were made. During this time, the case load per physician increasedmore » by 63% and the number of percutaneous transluminal coronary angioplasty procedures (a high radiation procedure) increased by 244%. Despite these increases in both case load and higher radiation procedures, the average radiation exposure per physician declined by 37%. During the same time, the radiation exposure for technicians decreased by 35%. Pulsed progressive fluoroscopy is effective for reducing radiation exposure to catheterization laboratory physicians and technical staff.« less

  9. Human and animal health risk assessments of chemicals in the food chain: Comparative aspects and future perspectives

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dorne, J.L.C.M., E-mail: jean-lou.dorne@efsa.europa.eu; Fink-Gremmels, J.

    Chemicals from anthropogenic and natural origins enter animal feed, human food and water either as undesirable contaminants or as part of the components of a diet. Over the last five decades, considerable efforts and progress to develop methodologies to protect humans and animals against potential risks associated with exposure to such potentially toxic chemicals have been made. This special issue presents relevant methodological developments and examples of risk assessments of undesirable substances in the food chain integrating the animal health and the human health perspective and refers to recent Opinions of the Scientific Panel on Contaminants in the Food Chainmore » (CONTAM) of the European Food Safety Authority (EFSA). This introductory review aims to give a comparative account of the risk assessment steps used in human health and animal health risk assessments for chemicals in the food chain and provides a critical view of the data gaps and future perspectives for this cross-disciplinary field. - Highlights: ► Principles of human and animal health risk assessment. ► Data gaps for each step of animal health risk assessment. ► Implications of animal risk assessment on human risk assessment. ► Future perspectives on chemical risk assessment.« less

  10. 3-Dimensional magnetic resonance spectroscopic imaging at 3 Tesla for early response assessment of glioblastoma patients during external beam radiation therapy.

    PubMed

    Muruganandham, Manickam; Clerkin, Patrick P; Smith, Brian J; Anderson, Carryn M; Morris, Ann; Capizzano, Aristides A; Magnotta, Vincent; McGuire, Sarah M; Smith, Mark C; Bayouth, John E; Buatti, John M

    2014-09-01

    To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested. Published by Elsevier Inc.

  11. 3-Dimensional Magnetic Resonance Spectroscopic Imaging at 3 Tesla for Early Response Assessment of Glioblastoma Patients During External Beam Radiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Muruganandham, Manickam; Clerkin, Patrick P.; Smith, Brian J.

    Purpose: To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials: Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al.more » MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results: After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Conclusion: Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested.« less

  12. Measuring Disease Progression in Early Parkinson Disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) Experience

    PubMed Central

    Parashos, Sotirios A.; Luo, Sheng; Biglan, Kevin M.; -Wollner, Ivan Bodis; He, Bo; Liang, Grace S.; Ross, G. Webster; Tilley, Barbara C.; Shulman, Lisa M.

    2014-01-01

    Importance Optimizing assessments of rate of progression in Parkinson Disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents. Objective To examine the value of measures of impairment, disability, and quality of life in assessing progression in early Parkinson disease. Design, Setting, and Participants Inception cohort analysis of data from 413 early, untreated PD patients, who were enrolled in two multicenter, randomized, double-blind clinical trials. Intervention Participants were randomized into five treatments: 67 received creatine, 66 minocycline, 71 Coenzyme Q10, 71 GPI-1485, and 138 placebo. We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment. Main Outcome Measure Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression. Results After adjusting for baseline confounding variables Unified Parkinson Disease Rating Scale (UPDRS) II, UPDRS III, modified Rankin score (mRS), level of education, and treatment group, the rate of change of the following measurements was assessed: UPDRS II, UPDRS III, Schwab and England ADL (S&E), Total Functional Capacity (TFC), Parkinson’s Disease Quality of Life Questionnaire – 39 (PDQ39) ADL and Summary Index (SI), Short Form -12v2 Health Survey (SF12) Physical Summary (PS), and SF12 Mental Summary (MS). Variables reaching statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid worsening of UPDRS II (HR 1.15, 95% C.I. 1.08 – 1.22 for 1 scale unit change per 6 months), UPDRS III (HR 1.09; 95% C.I. 1.06 – 1.13 for 1 scale unit change per 6 months), and S&E (HR 1.29 95% C.I. 1.12 – 1.48 for 5 percentage point change per 6 months), was associated with earlier need for symptomatic therapy. Conclusions and Relevance In early PD, UPDRS II and III, and S&E can be used to measure disease progression, while the PDQ39 ADL, PDQ39 SI, TFC, SF12 PH, and SF12 MH are not sensitive to change. Trial Registration clinicaltrials.gov identifiers NCT00063193 and NCT00076492 PMID:24711047

  13. Refining a learning progression of energy

    NASA Astrophysics Data System (ADS)

    Yao, Jian-Xin; Guo, Yu-Ying; Neumann, Knut

    2017-11-01

    This paper presents a revised learning progression for the energy concept and initial findings on diverse progressions among subgroups of sample students. The revised learning progression describes how students progress towards an understanding of the energy concept along two progress variables identified from previous studies - key ideas about energy and levels of conceptual development. To assess students understanding with respect to the revised learning progression, we created a specific instrument, the Energy Concept Progression Assessment (ECPA) based on previous work on assessing students' understanding of energy. After iteratively refining the instrument in two pilot studies, the ECPA was administered to a total of 4550 students (Grades 8-12) from schools in two districts in a major city in Mainland China. Rasch analysis was used to examine the validity of the revised learning progression and explore factors explaining different progressions. Our results confirm the validity of the four conceptual development levels. In addition, we found that although following a similar progression pattern, students' progression rate was significantly influenced by environmental factors such as school type. In the discussion of our findings, we address the non-linear and complex nature of students' progression in understanding energy. We conclude with illuminating our research's implication for curriculum design and energy teaching.

  14. The Present and Future of Robotic Technology in Rehabilitation

    PubMed Central

    Laut, Jeffrey; Porfiri, Maurizio; Raghavan, Preeti

    2016-01-01

    Robotic technology designed to assist rehabilitation can potentially increase the efficiency of and accessibility to therapy by assisting therapists to provide consistent training for extended periods of time, and collecting data to assess progress. Automatization of therapy may enable many patients to be treated simultaneously and possibly even remotely, in the comfort of their own homes, through telerehabilitation. The data collected can be used to objectively assess performance and document compliance as well as progress. All of these characteristics can make therapists more efficient in treating larger numbers of patients. Most importantly for the patient, it can increase access to therapy which is often in high demand and rationed severely in today’s fiscal climate. In recent years, many consumer grade low-cost and off-the-shelf devices have been adopted for use in therapy sessions and methods for increasing motivation and engagement have been integrated with them. This review paper outlines the effort devoted to the development and integration of robotic technology for rehabilitation. PMID:28603663

  15. Evaluation of the Achievement Levels for Mathematics and Reading on the National Assessment of Educational Progress

    ERIC Educational Resources Information Center

    National Academies Press, 2016

    2016-01-01

    Since 1969, the National Assessment of Educational Progress (NAEP) has been providing policymakers, educators, and the public with reports on academic performance and progress of the nation's students. The assessment is given periodically in a variety of subjects: mathematics, reading, writing, science, the arts, civics, economics, geography, U.S.…

  16. Conceptualizing and Exemplifying Science Teachers' Assessment Expertise

    NASA Astrophysics Data System (ADS)

    Geaney Lyon, Edward

    2013-05-01

    Although research in science education has led to new assessment forms and functions, the reality is that little work has been done to unpack and capture what it means for a teacher to develop expertise at assessing science. The purpose of this paper is two-fold. First, I suggest a conceptualization of assessment expertise that is organized around three dimensions: (a) designing aligned and theoretically cohesive assessment (Design), (b) using assessment to support students' science learning (Use), and (c) equitably assessing language minorities (Equity). The second purpose is to suggest and exemplify various levels of teaching expertise across the three conceptual dimensions using written assessment plans gathered from a study on secondary science pre-service teachers' assessment growth. The contribution of this paper lies in its further conceptual development of assessment expertise, instantiated in a rubric, which can spark discussion about how to capture the range of assessment practices that might be found in science classrooms as well as move toward a potential learning progression of assessment expertise.

  17. Vaccines for Viral Hemorrhagic Fevers – Progress and Shortcomings

    PubMed Central

    Falzarano, Darryl; Feldmann, Heinz

    2013-01-01

    With a few exceptions, vaccines for viruses that cause hemorrhagic fever remain unavailable or lack well-documented efficacy. In the past decade this has not been due to a lack of the ability to develop vaccine platforms against highly pathogenic viruses, but rather the lack of will/interest to invest in platforms that have the potential to become successful vaccines. The two exceptions to this are vaccines against Dengue virus and Rift Valley Fever virus, which recently have seen significant progress in putting forward new and improved vaccines, respectively. Experimental vaccines for filoviruses and Lassa virus do exist but are hindered by a lack of financial interest and only partially or ill-defined correlates/mechanisms of protection that could be assessed in clinical trials. PMID:23773330

  18. Towards optimizing the sequence of bevacizumab and nitrosoureas in recurrent malignant glioma.

    PubMed

    Wiestler, Benedikt; Radbruch, Alexander; Osswald, Matthias; Combs, Stephanie E; Jungk, Christine; Winkler, Frank; Bendszus, Martin; Unterberg, Andreas; Platten, Michael; Wick, Wolfgang; Wick, Antje

    2014-03-01

    Studies on the monoclonal VEGF-A antibody bevacizumab gave raise to questions regarding the lack of an overall survival benefit, the optimal timing in the disease course and potential combination and salvage therapies. We retrospectively assessed survival, radiological progression type on bevacizumab and efficacy of salvage therapies in 42 patients with recurrent malignant gliomas who received bevacizumab and nitrosourea sequentially. 15 patients received bevacizumab followed by nitrosourea at progression and 27 patients vice versa. Time to treatment failure, defined as time from initiation of one to failure of the other treatment, was similar in both groups (9.6 vs. 9.2 months, log rank p = 0.19). Progression-free survival on nitrosoureas was comparable in both groups, while progression-free survival on bevacizumab was longer in the group receiving bevacizumab first (5.3 vs. 4.1 months, log rank p = 0.03). Survival times were similar for patients with grade III (n = 9) and grade IV (n = 33) tumors. Progression-free survival on bevacizumab for patients developing contrast-enhancing T1 progression was longer than for patients who displayed a non-enhancing T2 progression. However, post-progression survival times after bevacizumab failure were not different. Earlier treatment with bevacizumab was not associated with better outcome in this series. The fact that earlier as compared to later bevacizumab treatment does not result in a different time to treatment failure highlights the challenge for first-line or recurrence trials with bevacizumab to demonstrate an overall survival benefit if crossover of bevacizumab-naïve patients after progression occurs.

  19. Occupational Attainment as Risk Factor for Progression from Mild Cognitive Impairment to Alzheimer's Disease: A CREDOS Study.

    PubMed

    Myung, Woojae; Lee, Chunsoo; Park, Jin Hong; Woo, Sook-Young; Kim, Seonwoo; Kim, Sangha; Chung, Jae Won; Kang, Hyo Shin; Lim, Shinn-Won; Choi, Junbae; Na, Duk L; Kim, Seong Yoon; Lee, Jae-Hong; Han, Seol-Heui; Choi, Seong Hye; Kim, Sang Yun; Carroll, Bernard J; Kim, Doh Kwan

    2017-01-01

    High occupational attainment has been known as a marker of cognitive reserve. Previous studies in the general population have shown that high occupational attainment is associated with reduced risk of Alzheimer's disease (AD). However, few studies have assessed the effect of occupational attainment on the clinical course of mild cognitive impairment (MCI). In this study, we evaluated whether individuals with high occupational attainment show more frequent progression from MCI to AD. Participants (n = 961) with MCI were recruited from a nationwide, hospital-based multi-center cohort, and were followed for up to 60 months (median: 17.64, interquartile range [12.36, 29.28]). We used Cox regression for competing risks to analyze the effect of occupational attainment on development of AD, treating dementia other than AD as a competing risk. Among the 961 individuals with MCI, a total of 280 (29.1%) converted to dementia during the follow-up period. The risk of progression to AD was higher in the individuals with high occupational attainment after controlling for potential confounders (hazard ratio = 1.83, 95% confidence interval = 1.25-2.69, p = 0.002). High occupational attainment in individuals with MCI is an independent risk factor for higher progression rate of MCI to AD. This result suggests that the protective effect of high occupational attainment against cognitive decline disappears in the MCI stage, and that careful assessment of occupational history can yield important clinical information for prognosis in individuals with MCI.

  20. Metamorphic III–V Solar Cells: Recent Progress and Potential

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Garcia, Ivan; France, Ryan M.; Geisz, John F.

    Inverted metamorphic multijunction solar cells have been demonstrated to be a pathway to achieve the highest photovoltaic (PV) conversion efficiencies. Attaining high-quality lattice-mismatched (metamorphic) semiconductor devices is challenging. However, recent improvements to compositionally graded buffer epitaxy and junction structures have led to the achievement of high-quality metamorphic solar cells exhibiting internal luminescence efficiencies over 90%. For this high material quality, photon recycling is significant, and therefore, the optical environment of the solar cell becomes important. In this paper, we first present recent progress and performance results for 1- and 0.7-eV GaInAs solar cells grown on GaAs substrates. Then, an electroopticalmore » model is used to assess the potential performance improvements in current metamorphic solar cells under different realizable design scenarios. The results show that the quality of 1-eV subcells is such that further improving its electronic quality does not produce significant Voc increases in the four-junction inverted metamorphic subcells, unless a back reflector is used to enhance photon recycling, which would significantly complicate the structure. Conversely, improving the electronic quality of the 0.7-eV subcell would lead to significant Voc boosts, driving the progress of four-junction inverted metamorphic solar cells.« less

  1. Assessment Program Technical Progress Report, 1996-1997.

    ERIC Educational Resources Information Center

    McCown, Laurie; Fanning, Erin; Eickmeyer, Barbara

    Coconino Community College (CCC) annually assesses its institutional effectiveness to demonstrate its commitment to improving programs and services to students. The 1996-97 Assessment Program Technical Progress Report records the assessment and institutional activities enacted during the academic year, detailing the assessment model, timelines,…

  2. Draft report: Results of stainless steel canister corrosion studies and environmental sample investigations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bryan, Charles R.; Enos, David

    2014-09-01

    This progress report describes work being done at Sandia National Laboratories (SNL) to assess the localized corrosion performance of container/cask materials used in the interim storage of used nuclear fuel. The work involves both characterization of the potential physical and chemical environment on the surface of the storage canisters and how it might evolve through time, and testing to evaluate performance of the canister materials under anticipated storage conditions.

  3. Development of Monitors for Assessing Exposure of Military Personnel to Toxic Chemicals.

    DTIC Science & Technology

    2000-01-01

    Residues " S ampler Preparation 7 Transfer and Analysis 7 Temperature Effects on PIMS Sampling Rate 8 Environmental Air Sampling 8 Results and...of exposure and potential toxicity to personnel. While progress has been made in improving active water and air sampling technology, such devices...streams, 3) the apparatus is also applicable for use in air sampling deployments in indoor and outdoor scenarios, and 4) the apparatus is commercially

  4. The therapeutic potential of plant-derived vaccines and antibodies.

    PubMed

    Rodgers, P B; Hamilton, W D; Adair, J R

    1999-03-01

    The production of recombinant proteins in plants is reviewed with a particular focus on plant-derived vaccines and antibodies for human healthcare. Issues relating to foreign gene expression, such as protein yield, localisation and glycosylation are also considered. Emphasis is placed on reporting progress with preclinical and clinical evaluation of plant-derived vaccines and antibodies. An assessment is made of the likely future direction of research and development in this area.

  5. [Sustainable development of the three economic patterns in China: The application of genuine progress indicator in the sustainability assessment of six typical cities.

    PubMed

    Li, Jing; Huang, Lu; Yan, Li Jiao

    2016-06-01

    Three economic patterns, i.e., Zhujiang Model, Wenzhou Model and Sunan Model, were all generated in the developed areas of China. Sustainability assessment of those areas plays an important role in guiding future development of the economy of China. Genuine progress indicator (GPI) was adopted in this study to evaluate the sustainability of 6 typical cities (Guangzhou, Shenzhen, Wenzhou, Suzhou, Wuxi, and Changzhou) of the three economic patterns from 1995 to 2012. During the study period, the values of GDP for the six cities had experienced exponential growth, while the values of GPI started to increase since 2005 after a relatively constant period between 1995 and 2005. The gap between GPI and GDP had been widening from a historical perspective. Zhujiang Model made great progress in economic growth, however, the economic, social, and environmental costs were evident. It should tackle income inequality, traffic jam, and environmental pollution to reach sustainability. The development of Wenzhou Model slowed down in the late pe-riod, with inadequate potential to develop. Its income inequality was tough, social and economic development was slow, and the economic development pattern needed to be urgently changed. Sunan Model had a higher value of GPI and the potential to reach sustainability, with remarkable growth of economy, median level of the GPI costs, and steady improvement of social development, although its natural resources were depleted. Three economic patterns should focus on the three dimensions of sustainability (economy, environment, and society), and Zhujiang Model and Wenzhou Model needed to be more active to search for transition of their development.

  6. Optimizing clinical benefit with targeted treatment in mRCC: "Tumor growth rate" as an alternative clinical endpoint.

    PubMed

    Milella, Michele

    2016-06-01

    Tumor growth rate (TGR), usually defined as the ratio between the slope of tumor growth before the initiation of treatment and the slope of tumor growth during treatment, between the nadir and disease progression, is a measure of the rate at which tumor volume increases over time. In patients with metastatic renal cell carcinoma (mRCC), TGR has emerged as a reliable alternative parameter to allow a quantitative and dynamic evaluation of tumor response. This review presents evidence on the correlation between TGR and treatment outcomes and discusses the potential role of this tool within the treatment scenario of mRCC. Current evidence, albeit of retrospective nature, suggests that TGR might represent a useful tool to assess whether treatment is altering the course of the disease, and has shown to be significantly associated with progression-free survival and overall survival. Therefore, TGR may represent a valuable endpoint for clinical trials evaluating new molecularly targeted therapies. Most importantly, incorporation of TGR in the assessment of individual patients undergoing targeted therapies may help clinicians decide if a given agent is no longer able to control disease growth and whether continuing therapy beyond RECIST progression may still produce clinical benefit. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. The Nation's Report Card: Mathematics 2011. National Assessment of Educational Progress at Grades 4 and 8. NCES 2012-458

    ERIC Educational Resources Information Center

    National Center for Education Statistics, 2011

    2011-01-01

    This report presents results of the 2011 National Assessment of Educational Progress (NAEP) in mathematics at grades 4 and 8. Nationally representative samples of 209,000 fourth-graders and 175,200 eighth-graders participated in the 2011 National Assessment of Educational Progress (NAEP) in mathematics. At each grade, students responded to…

  8. One Year Later: Assessing Our Progress | NOAA Gulf Spill Restoration

    Science.gov Websites

    Archive Home One Year Later: Assessing Our Progress One Year Later: Assessing Our Progress oil in the wake Restoration Area A year ago, the Deepwater Horizon drilling rig sank, starting an oil spill that became the samples, surveyed thousands of miles of shoreline for oil, posted more than 60 work plans and other data

  9. Computational Methods to Assess the Production Potential of Bio-Based Chemicals.

    PubMed

    Campodonico, Miguel A; Sukumara, Sumesh; Feist, Adam M; Herrgård, Markus J

    2018-01-01

    Elevated costs and long implementation times of bio-based processes for producing chemicals represent a bottleneck for moving to a bio-based economy. A prospective analysis able to elucidate economically and technically feasible product targets at early research phases is mandatory. Computational tools can be implemented to explore the biological and technical spectrum of feasibility, while constraining the operational space for desired chemicals. In this chapter, two different computational tools for assessing potential for bio-based production of chemicals from different perspectives are described in detail. The first tool is GEM-Path: an algorithm to compute all structurally possible pathways from one target molecule to the host metabolome. The second tool is a framework for Modeling Sustainable Industrial Chemicals production (MuSIC), which integrates modeling approaches for cellular metabolism, bioreactor design, upstream/downstream processes, and economic impact assessment. Integrating GEM-Path and MuSIC will play a vital role in supporting early phases of research efforts and guide the policy makers with decisions, as we progress toward planning a sustainable chemical industry.

  10. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yeung, Timothy P C; Robarts Research Institute, The University of Western Ontario, Ontario, Canada, N6A 5B7; Department of Medical Biophysics, The University of Western Ontario, Ontario, Canada, N6A 5C1

    Introduction: This study aimed to explore the potential for computed tomography (CT) perfusion and 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting sites of future progressive tumour on a voxel-by-voxel basis after radiotherapy and chemotherapy. Methods: Ten patients underwent pre-radiotherapy magnetic resonance (MR), FDG-PET and CT perfusion near the end of radiotherapy and repeated post-radiotherapy follow-up MR scans. The relationships between these images and tumour progression were assessed using logistic regression. Cross-validation with receiver operating characteristic (ROC) analysis was used to assess the value of these images in predicting sites of tumour progression. Results: Pre-radiotherapy MR-defined gross tumour; near-end-of-radiotherapy CT-defined enhancingmore » lesion; CT perfusion blood flow (BF), blood volume (BV) and permeability-surface area (PS) product; FDG-PET standard uptake value (SUV); and SUV:BF showed significant associations with tumour progression on follow-up MR imaging (P < 0.0001). The mean sensitivity (±standard deviation), specificity and area under the ROC curve (AUC) of PS were 0.64 ± 0.15, 0.74 ± 0.07 and 0.72 ± 0.12 respectively. This mean AUC was higher than that of the pre-radiotherapy MR-defined gross tumour and near-end-of-radiotherapy CT-defined enhancing lesion (both AUCs = 0.6 ± 0.1, P ≤ 0.03). The multivariate model using BF, BV, PS and SUV had a mean AUC of 0.8 ± 0.1, but this was not significantly higher than the PS only model. Conclusion: PS is the single best predictor of tumour progression when compared to other parameters, but voxel-based prediction based on logistic regression had modest sensitivity and specificity.« less

  11. A language-based sum score for the course and therapeutic intervention in primary progressive aphasia.

    PubMed

    Semler, Elisa; Anderl-Straub, Sarah; Uttner, Ingo; Diehl-Schmid, Janine; Danek, Adrian; Einsiedler, Beate; Fassbender, Klaus; Fliessbach, Klaus; Huppertz, Hans-Jürgen; Jahn, Holger; Kornhuber, Johannes; Landwehrmeyer, Bernhard; Lauer, Martin; Muche, Rainer; Prudlo, Johannes; Schneider, Anja; Schroeter, Matthias L; Ludolph, Albert C; Otto, Markus

    2018-04-25

    With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions. We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials. Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures. Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies.

  12. HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer

    PubMed Central

    Kitchen, Mark O; Bryan, Richard T; Emes, Richard D; Luscombe, Christopher J; Cheng, KK; Zeegers, Maurice P; James, Nicholas D; Gommersall, Lyndon M; Fryer, Anthony A

    2018-01-01

    Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG) were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease. PMID:29343995

  13. Corpus callosum damage predicts disability progression and cognitive dysfunction in primary-progressive MS after five years.

    PubMed

    Bodini, Benedetta; Cercignani, Mara; Khaleeli, Zhaleh; Miller, David H; Ron, Maria; Penny, Sophie; Thompson, Alan J; Ciccarelli, Olga

    2013-05-01

    We aim to identify specific areas of white matter (WM) and grey matter (GM), which predict disability progression and cognitive dysfunction after five years in patients with primary-progressive multiple sclerosis (PPMS). Thirty-two patients with early PPMS were assessed at baseline and after five years on the Expanded Disability Status Scale (EDSS), and EDSS step-changes were calculated. At year five, a subgroup of 25 patients and 31 healthy controls underwent a neuropsychological assessment. Baseline imaging consisted of dual-echo (proton density and T2-weighted), T1-weighted volumetric, and diffusion tensor imaging. Fractional anisotropy (FA) maps were created, and fed into tract-based spatial statistics. To compensate for the potential bias introduced by WM lesions, the T1 volumes underwent a lesion-filling procedure before entering a voxel-based morphometry protocol. To investigate whether FA and GM volume predicted EDSS step-changes over five years and neuropsychological tests scores at five years, voxelwise linear regression analyses were performed. Lower FA in the splenium of the corpus callosum (CC) predicted a greater progression of disability over the follow-up. Lower FA along the entire CC predicted worse verbal memory, attention and speed of information processing, and executive function at five years. GM baseline volume did not predict any clinical variable. Our findings highlight the importance of damage to the interhemispheric callosal pathways in determining physical and cognitive disability in PPMS. Disruption of these pathways, which interconnect motor and cognitive networks between the two hemispheres, may result in a disconnection syndrome that contributes to long-term physical and cognitive disability. Copyright © 2011 Wiley Periodicals, Inc.

  14. Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration.

    PubMed

    Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard; Seddon, Johanna M

    2017-09-01

    There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43-0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39-0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53-1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50-0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss.

  15. Assessing the bioaccumulation potential of ionizable organic ...

    EPA Pesticide Factsheets

    The objective of the present study is to review current knowledge regarding the bioaccumulation potential of IOCs, with a focus on the availability of empirical data for fish. Aspects of the bioaccumulation potential of IOCs in fish that can be characterized relatively well include the pH-dependence of gill uptake and elimination, uptake in the gut, and sorption to phospholipids (membrane-water partitioning). Key challenges include the lack of empirical data for biotransformation and binding in plasma. Fish possess a diverse array of proteins which may transport IOCs across cell membranes. Except in a few cases, however, the significance of this transport for uptake and accumulation of environmental contaminants is unknown. Two case studies are presented. The first describes modeled effects of pH and biotransformation on bioconcentration of organic acids and bases, while the second employs an updated model to investigate factors responsible for accumulation of perfluoroalkylated acids (PFAA). The PFAA case study is notable insofar as it illustrates the likely importance of membrane transporters in the kidney and highlights the potential value of read across approaches. Recognizing the current need to perform bioaccumulation hazard assessments and ecological and exposure risk assessment for IOCs, we provide a tiered strategy that progresses (as needed) from conservative assumptions (models and associated data) to more sophisticated models requiring chemical-speci

  16. Detection of halitosis in breath: Between the past, present, and future.

    PubMed

    Nakhleh, M K; Quatredeniers, M; Haick, H

    2017-06-16

    To develop a new generation of diagnostics for halitosis, replacing the subjective organoleptic assessment, a series of exhaled breath analyzers has been developed and assessed. All three devices rely on the assessment of exhaled volatile sulfuric compounds (VSCs), which are mainly generated in and emitted from the oral cavity, contributing to the malodor. Portable, on-site and easy to use, these devices have potential for non-invasive diagnosis of halitosis. However, global assessment of exhaled VSCs alone has two main drawbacks: (i) the absence of VSCs does not rule out halitosis; (ii) non-sulfuric volatile compounds that could be biomarkers of systemic diseases, found in up to 15% of halitosis cases, are neglected. In this article, we review and discuss progress to date in the field of oral/exhaled volatile compounds as potential non-invasive diagnostics for halitosis. We will briefly describe the generation of these compounds both from local (oral) and distal (extra-oral) sources. In addition, we debate the different analytical approaches in use and discuss the potential value of bio-inspired artificially intelligent olfaction in diagnosing and classifying oral and systemic diseases by analyzing exhaled breath. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  17. Assessment of Operational Progress of NASA Langley Developed Windshield and Microphone for Infrasound

    DTIC Science & Technology

    2013-04-01

    Assessment of Operational Progress of NASA Langley Developed Windshield and Microphone for Infrasound by W.C. Kirkpatrick Alberts, II...Windshield and Microphone for Infrasound W.C. Kirkpatrick Alberts, II, Stephen M. Tenney, and John M. Noble Sensors and Electron Devices Directorate...2013 4. TITLE AND SUBTITLE Assessment of Operational Progress of NASA Langley Developed Windshield and Microphone for Infrasound 5a. CONTRACT

  18. Alzheimer's Disease Assessment: A Review and Illustrations Focusing on Item Response Theory Techniques.

    PubMed

    Balsis, Steve; Choudhury, Tabina K; Geraci, Lisa; Benge, Jared F; Patrick, Christopher J

    2018-04-01

    Alzheimer's disease (AD) affects neurological, cognitive, and behavioral processes. Thus, to accurately assess this disease, researchers and clinicians need to combine and incorporate data across these domains. This presents not only distinct methodological and statistical challenges but also unique opportunities for the development and advancement of psychometric techniques. In this article, we describe relatively recent research using item response theory (IRT) that has been used to make progress in assessing the disease across its various symptomatic and pathological manifestations. We focus on applications of IRT to improve scoring, test development (including cross-validation and adaptation), and linking and calibration. We conclude by describing potential future multidimensional applications of IRT techniques that may improve the precision with which AD is measured.

  19. The importance of formative assessment in science and engineering ethics education: some evidence and practical advice.

    PubMed

    Keefer, Matthew W; Wilson, Sara E; Dankowicz, Harry; Loui, Michael C

    2014-03-01

    Recent research in ethics education shows a potentially problematic variation in content, curricular materials, and instruction. While ethics instruction is now widespread, studies have identified significant variation in both the goals and methods of ethics education, leaving researchers to conclude that many approaches may be inappropriately paired with goals that are unachievable. This paper speaks to these concerns by demonstrating the importance of aligning classroom-based assessments to clear ethical learning objectives in order to help students and instructors track their progress toward meeting those objectives. Two studies at two different universities demonstrate the usefulness of classroom-based, formative assessments for improving the quality of students' case responses in computational modeling and research ethics.

  20. Ferret and pig models of cystic fibrosis: prospects and promise for gene therapy.

    PubMed

    Yan, Ziying; Stewart, Zoe A; Sinn, Patrick L; Olsen, John C; Hu, Jim; McCray, Paul B; Engelhardt, John F

    2015-03-01

    Large animal models of genetic diseases are rapidly becoming integral to biomedical research as technologies to manipulate the mammalian genome improve. The creation of cystic fibrosis (CF) ferrets and pigs is an example of such progress in animal modeling, with the disease phenotypes in the ferret and pig models more reflective of human CF disease than mouse models. The ferret and pig CF models also provide unique opportunities to develop and assess the effectiveness of gene and cell therapies to treat affected organs. In this review, we examine the organ disease phenotypes in these new CF models and the opportunities to test gene therapies at various stages of disease progression in affected organs. We then discuss the progress in developing recombinant replication-defective adenoviral, adeno-associated viral, and lentiviral vectors to target genes to the lung and pancreas in ferrets and pigs, the two most affected organs in CF. Through this review, we hope to convey the potential of these new animal models for developing CF gene and cell therapies.

  1. Sex differences and the role of dopamine receptors in the reward-enhancing effects of nicotine and bupropion.

    PubMed

    Barrett, Scott T; Geary, Trevor N; Steiner, Amy N; Bevins, Rick A

    2017-01-01

    Nicotine and bupropion have been demonstrated to enhance the value of other reinforcers, and this may partially account for nicotine reward and dependence. Evidence suggests that the sexes differ in their sensitivity to the primary and secondary reinforcing effects of nicotine and nicotine-associated stimuli. Whether the sexes also differ in sensitivity to the reward-enhancing effects of nicotine (and bupropion) is yet unclear. The present study evaluated potential sex differences in the enhancement effects of nicotine and bupropion using a reinforcer demand approach. Furthermore, we sought to investigate the role that D1- and D2-type dopamine receptors play in the reward-enhancing effects of nicotine and bupropion. Demand for sensory reinforcement was assessed in male and female rats responding on a progression of fixed ratio schedules. The effects of nicotine and 10 or 20 mg/kg bupropion on reinforcer demand were assessed within subjects. Subsequently, the effects of SCH-23390 and eticlopride were assessed on the enhancing effects of nicotine and bupropion on progressive ratio responding. Nicotine and bupropion enhanced demand metrics of reinforcement value in both sexes. Females were more sensitive to the enhancement effects of bupropion assessed by reinforcer demand and progressive ratio performance. D2-like dopamine receptor antagonism by eticlopride attenuated the enhancement effects of bupropion, but not of nicotine. Nicotine and bupropion both enhance reinforcement value in both sexes, though females may be more sensitive to the reward-enhancing effects of bupropion. D2- and possibly D1-type receptors appear to be involved in the reward-enhancing effects of bupropion, but not necessarily nicotine.

  2. The USGS national geothermal resource assessment: An update

    USGS Publications Warehouse

    Williams, C.F.; Reed, M.J.; Galanis, S.P.; DeAngelo, J.

    2007-01-01

    The U. S. Geological Survey (USGS) is working with the Department of Energy's (DOE) Geothermal Technologies Program and other geothermal organizations on a three-year effort to produce an updated assessment of available geothermal resources. The new assessment will introduce significant changes in the models for geothermal energy recovery factors, estimates of reservoir volumes, and limits to temperatures and depths for electric power production. It will also include the potential impact of evolving Enhanced Geothermal Systems (EGS) technology. An important focus in the assessment project is on the development of geothermal resource models consistent with the production histories and observed characteristics of exploited geothermal fields. New models for the recovery of heat from heterogeneous, fractured reservoirs provide a physically realistic basis for evaluating the production potential of both natural geothermal reservoirs and reservoirs that may be created through the application of EGS technology. Project investigators have also made substantial progress studying geothermal systems and the factors responsible for their formation through studies in the Great Basin-Modoc Plateau region, Coso, Long Valley, the Imperial Valley and central Alaska, Project personnel are also entering the supporting data and resulting analyses into geospatial databases that will be produced as part of the resource assessment.

  3. Genetic Analysis of Oncorhynchus Nerka : 1991 Annual Progress Report.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brannon, E.L.; Setter, A.L.; Welsh, T.L.

    1992-01-01

    The 1990 project to develop DNA assessment techniques for the purpose of determining relationships among populations of Oncorhynchus nerka demonstrated differences that had potential for such application. The work was continued in 1991 with specific application of the techniques to develop DNA probes that could be used in separating populations of 0. nerka associated with the lakes in the upper Salmon River, principally those in Redfish Lake. Research included sockeye-kokanee life history studies that might add supporting evidence for assessing the degree of difference or similarity among populations in the lake systems. This report summarizes the annual activities under themore » work plan.« less

  4. Chronic stress enhances progression of periodontitis via α1-adrenergic signaling: a potential target for periodontal disease therapy.

    PubMed

    Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan

    2014-10-17

    This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the α1-adrenergic receptor (α1-AR) and β2-adrenergic receptor (β2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of α1-AR and β2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1β, IL-6 and IL-8 were detected after pretreatment with the α1/β2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, α1-AR and β2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of α1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1β, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an α1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.

  5. Assessment of groundwater recharge potential zone using GIS approach in Purworejo regency, Central Java province, Indonesia

    NASA Astrophysics Data System (ADS)

    Aryanto, Daniel Eko; Hardiman, Gagoek

    2018-02-01

    Floods and droughts in Purworejo regency are an indication of problems in groundwater management. The current development progress has led to land conversion which has an impact on the problem of water infiltration in Purworejo regency. This study aims to determine the distribution of groundwater recharge potential zones by using geographic information system as the basis for ground water management. The groundwater recharge potential zone is obtained by overlaying all the thematic maps that affect the groundwater infiltration. Each thematic map is weighted according to its effect on groundwater infiltration such as land-use - 25%, rainfall - 20%, litology - 20%, soil - 15%, slope - 10%, lineament - 5%, and river density - 5% to find groundwater recharge potential zones. The groundwater recharge potential zones thus obtained were divided into five categories, viz., very high, high, medium, low and very low zones. The results of this study may be useful for better groundwater planning and management.

  6. Assessing Student Academic and Social Progress.

    ERIC Educational Resources Information Center

    Baird, Leonard L., Ed.

    Assessment of student progress in community colleges is necessary for several reasons; among them are accountability to the public, improvement of decision-making for both students and educators, and planning and evaluation of curricula. This sourcebook focuses on various types of student progress--vocational, social, academic, transfer--and on…

  7. Provider Agreement in the Assessment of Glaucoma Progression within a Team Model.

    PubMed

    Shah, Saumya; Choo, Clara; Odden, Jamie; Zhao, Bingying; Fang, Chengbo; Schornack, Muriel; Stalboerger, Gina; Bennett, Jeffrey R; Khanna, Cheryl L

    2018-06-04

    Glaucoma specialists and optometrists who work in a team model at a single institution utilize a common definition of glaucoma progression and treatment algorithm. The purpose of this study was to assess the consistency of agreement in identifying glaucoma progression among glaucoma specialists and optometrists of one team. 399 eyes of 200 patients age 18 or older with glaucoma were enrolled over two years. Clinical data, disc photographs, OCT, and visual fields were independently reviewed by two masked optometrists and two masked fellowship-trained glaucoma specialists. Each eye was judged as progression or no-progression of glaucomatous disease. The following were assessed: (1) agreement among optometrists; (2) agreement among glaucoma specialists; and (3) agreement among optometrists and glaucoma specialists. The frequency of use of testing modality to determine progression was also studied. Kappa statistics were used to evaluate agreements. Optometrists agreed with each other for 74.2% of the eyes assessed (κ=0.42), whereas glaucoma specialists agreed with each other for 78.7% of eyes (κ=0.39). All four providers agreed with each other for 54.4% of the eyes evaluated (κ=0.37). Providers had the highest agreement when the progression decision was based on disc hemorrhage (92%) and the lowest agreement when based on OCT progression analysis (36%). Compared to optometrists, glaucoma specialists used OCT (P= <0.01) more frequently to determine disease progression. Fair to moderate agreement levels were found among providers in their assessment of glaucoma progression, suggesting that a team approach to glaucoma management may be effective. Further work is needed to investigate ways to optimize consistency within the glaucoma team.

  8. An Introduction to NAEP: National Assessment of Educational Progress. NCES 2010-468

    ERIC Educational Resources Information Center

    National Center for Education Statistics, 2010

    2010-01-01

    The National Assessment of Educational Progress (NAEP) is a continuing and nationally representative assessment of what this nation's students know and can do. NAEP has often been called the "gold standard" of assessments because it is developed using the best thinking of assessment and content specialists, education experts, and…

  9. Assessing first-stage labor progression and its relationship to complications.

    PubMed

    Hamilton, Emily F; Warrick, Philip A; Collins, Kathleen; Smith, Samuel; Garite, Thomas J

    2016-03-01

    New labor curves have challenged the traditional understanding of the general pattern of dilation and descent in labor. They also revealed wide variation in the time to advance in dilation. An interval of arrest such as 4 hours did not fall beyond normal limits until dilation had reached 6 cm. Thus, the American College of Obstetricians and Gynecologists/Society for Maternal-Fetal Medicine first-stage arrest criteria, based in part on these findings, are applicable only in late labor. The wide range of time to dilate is unavoidable because cervical dilation has neither a precise nor direct relationship to time. Newer statistical techniques (multifactorial models) can improve precision by incorporating several factors that are related directly to labor progress. At each examination, the calculations adapt to the mother's current labor conditions. They produce a quantitative assessment that is expressed in percentiles. Low percentiles indicate potentially problematic labor progression. The purpose of this study was to assess the relationship between first-stage labor progress- and labor-related complications with the use of 2 different assessment methods. The first method was based on arrest of dilation definitions. The other method used percentile rankings of dilation or station based on adaptive multifactorial models. We included all 4703 cephalic-presenting, term, singleton births with electronic fetal monitoring and cord gases at 2 academic community referral hospitals in 2012 and 2013. We assessed electronic data for route of delivery, all dilation and station examinations, newborn infant status, electronic fetal monitoring tracings, and cord blood gases. The labor-related complication groups included 272 women with cesarean delivery for first-stage arrest, 558 with cesarean delivery for fetal heart rate concerns, 178 with obstetric hemorrhage, and 237 with neonatal depression, which left 3004 women in the spontaneous vaginal birth group. Receiver operating characteristic curves were constructed for each assessment method by measurement of the sensitivity for each complication vs the false-positive rate in the normal reference group. The duration of arrest at ≥6 cm dilation showed poor levels of discrimination for the cesarean delivery interventions (area under the curve, 0.55-0.65; P < .01) and no significant relationship to hemorrhage or neonatal depression. The dilation and station percentiles showed high discrimination for the cesarean delivery-related outcomes (area under the curve, 0.78-0.93; P < .01) and low discrimination for the clinical outcomes of hemorrhage and neonatal depression (area under the curve, 0.58-0.61; P < .01). Duration of arrest of dilation at ≥6 cm showed little or no discrimination for any of the complications. In comparison, percentile rankings that were based on the adaptive multifactorial models showed much higher discrimination for cesarean delivery interventions and better, but low discrimination for hemorrhage. Adaptive multifactorial models present a different method to assess labor progress. Rather than "pass/fail" criteria that are applicable only to dilation in late labor, they produce percentile rankings, assess 2 essential processes for vaginal birth (dilation and descent), and can be applied from 3 cm onward. Given the limitations of labor-progress assessment based solely on the passage of time and because of the extreme variation in decision-making for cesarean delivery for labor disorders, the types of mathematic analyses that are described in this article are logical and promising steps to help standardize labor assessment. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Changes in Nutritional Status after Deep Brain Stimulation of the Nucleus Basalis of Meynert in Alzheimer's Disease--Results of a Phase I Study.

    PubMed

    Noreik, M; Kuhn, J; Hardenacke, K; Lenartz, D; Bauer, A; Bührle, C P; Häussermann, P; Hellmich, M; Klosterkötter, J; Wiltfang, J; Maarouf, M; Freund, H-J; Visser-Vandewalle, V; Sturm, V; Schulz, R-J

    2015-10-01

    The progression of Alzheimer's disease (AD) is associated with impaired nutritional status. New methods, such as deep brain stimulation (DBS), are currently being tested to decrease the progression of AD. DBS is an approved method in the treatment of Parkinson's disease, and its suitability for the treatment of AD patients is currently under experimental investigation. To evaluate the advantages and disadvantages of this new treatment, it is important to assess potential side effects of DBS regarding the nucleus basalis of Meynert; this new treatment is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in AD. This study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status. A 1-year phase I proof-of-concept study. The Department of Psychiatry and Psychotherapy at the University of Cologne. We assessed a consecutive sample of patients with mild to moderate AD (n=6) who fulfilled the inclusion criteria and provided written informed consent. Bilateral low-frequency DBS of the nucleus basalis of Meynert. Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate. With a normal body mass index (BMI) at baseline (mean 23.75 kg/m²) and after 1 year (mean 24.59 kg/m²), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman's rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman's rho = -0.829, p = 0.042). Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies.

  11. The Interaction between Epigenetics, Nutrition and the Development of Cancer

    PubMed Central

    Bishop, Karen S.; Ferguson, Lynnette R.

    2015-01-01

    Unlike the genome, the epigenome can be modified and hence some epigenetic risk markers have the potential to be reversed. Such modifications take place by means of drugs, diet or environmental exposures. It is widely accepted that epigenetic modifications take place during early embryonic and primordial cell development, but it is also important that we gain an understanding of the potential for such changes later in life. These “later life” epigenetic modifications in response to dietary intervention are the focus of this paper. The epigenetic modifications investigated include DNA methylation, histone modifications and the influence of microRNAs. The epigenotype could be used not only to predict susceptibility to certain cancers but also to assess the effectiveness of dietary modifications to reduce such risk. The influence of diet or dietary components on epigenetic modifications and the impact on cancer initiation or progression has been assessed herein. PMID:25647662

  12. Late post-treatment radiographic changes 3 years following chemoradiation for glioma: the importance of histopathology.

    PubMed

    Galante, Joao R; Rodriguez, Fausto; Grossman, Stuart A; Strowd, Roy E

    2017-07-18

    Treatment-related changes can mimic brain tumor progression both clinically and radiographically. Distinguishing these two entities represents a major challenge in neuro-oncology. No single imaging modality is capable of reliably achieving such distinction. While histopathology remains the gold standard, definitive pathological criteria are also lacking which can further complicate such cases. We report a patient with high-grade glioma who, after initially presenting with histopathologically confirmed pseudoprogression 10 months following treatment, re-presented 3 years following concurrent chemoradiation with clinical and radiographic changes that were most consistent with progressive disease but for which histopathology revealed treatment effects without active glioma. This case highlights the potential late onset of treatment-related changes and underscores the importance of histopathologic assessment even years following initial therapy.

  13. Could Sirtuin Activities Modify ALS Onset and Progression?

    PubMed

    Tang, Bor Luen

    2017-10-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a complex etiology. Sirtuins have been implicated as disease-modifying factors in several neurological disorders, and in the past decade, attempts have been made to check if manipulating Sirtuin activities and levels could confer benefit in terms of neuroprotection and survival in ALS models. The efforts have largely focused on mutant SOD1, and while limited in scope, the results were largely positive. Here, the body of work linking Sirtuins with ALS is reviewed, with discussions on how Sirtuins and their activities may impact on the major etiological mechanisms of ALS. Moving forward, it is important that the potentially beneficial effect of Sirtuins in ALS disease onset and progression are assessed in ALS models with TDP-43, FUS, and C9orf72 mutations.

  14. Analyzing compound and project progress through multi-objective-based compound quality assessment.

    PubMed

    Nissink, J Willem M; Degorce, Sébastien

    2013-05-01

    Compound-quality scoring methods designed to evaluate multiple drug properties concurrently are useful to analyze and prioritize output from drug-design efforts. However, formalized multiparameter optimization approaches are not widely used in drug design. We rank molecules synthesized in drug-discovery projects using simple and aggregated desirability functions reflecting medicinal chemistry 'rules'. Our quality score deals transparently with missing data, a key requirement in drug-hunting projects where data availability is often limited. We further estimate confidence in the interpretation of such a compound-quality measure. Scores and associated confidences provide systematic insight in the quality of emerging chemical equity. Tracking quality of synthetic output over time yields valuable insight into the progress of drug-design teams, with potential applications in risk and resource management of a drug portfolio.

  15. Impact of universal interventions on social inequalities in physical activity among older adults: an equity-focused systematic review.

    PubMed

    Lehne, Gesa; Bolte, Gabriele

    2017-02-10

    Physical activity is one of the most important contributors to healthy aging. Public health strategies aiming to promote physical activity among older adults are increasingly being implemented. However, little is known about their impact on social inequalities. Purpose of the study was to analyze whether and how studies of interventions consider effects on social inequalities in physical activity among older adults. Nine electronic databases were searched to identify quantitative studies evaluating the effects of interventions on self-reported or objectively measured physical activity among the general population of older adults (≥50 years). English and German language peer-reviewed journal articles published between 2005 and 2015 were included. Using the PROGRESS-Plus framework, data on whether and how social factors were considered both for describing participants' baseline characteristics and for measuring intervention effects were systematically extracted. Studies examining differential intervention effects by at least one PROGRESS-Plus factor were quality assessed. Results were presented in narrative synthesis. Fifty-nine studies were included. Beside age and sex, 44 studies used at least 1 further PROGRESS-Plus factor for the description of participants' baseline characteristics. When measuring intervention effects, 22 studies considered PROGRESS-Plus factors as control variables. Eleven studies reported having analyzed potential effects on inequalities by testing interaction effects, stratifying effect analyses, or exploring associations between PROGRESS-Plus factors and increases in physical activity following an intervention. Effects were most often analyzed by gender/sex (n = 9) and age (n = 9), followed by education (n = 3), marital status (n = 2), and race/ethnicity (n = 2). Five studies pointed to gender/sex- or age-specific intervention effects, indicating that some interventions affect males and females, and younger and older individuals differently. Many studies evaluating the effects of interventions on physical activity among older adults have not exploited the potential for assessing effects on social inequalities so far. There is an urgent need for systematic application of appropriate methodological approaches and transparent reporting of social inequalities-related findings which can provide important indications for the design of those interventions most likely to be effective across all social groups of older adults. PROSPERO registration number: CRD42015025066.

  16. Mathematics Framework for the 2011 National Assessment of Educational Progress

    ERIC Educational Resources Information Center

    National Assessment Governing Board, 2010

    2010-01-01

    Since 1973, the National Assessment of Educational Progress (NAEP) has gathered information about student achievement in mathematics. Results of these periodic assessments, produced in print and web-based formats, provide valuable information to a wide variety of audiences. The NAEP Assessment in mathematics has two components that differ in…

  17. Tapered Roller Bearing Damage Detection Using Decision Fusion Analysis

    NASA Technical Reports Server (NTRS)

    Dempsey, Paula J.; Kreider, Gary; Fichter, Thomas

    2006-01-01

    A diagnostic tool was developed for detecting fatigue damage of tapered roller bearings. Tapered roller bearings are used in helicopter transmissions and have potential for use in high bypass advanced gas turbine aircraft engines. A diagnostic tool was developed and evaluated experimentally by collecting oil debris data from failure progression tests conducted using health monitoring hardware. Failure progression tests were performed with tapered roller bearings under simulated engine load conditions. Tests were performed on one healthy bearing and three pre-damaged bearings. During each test, data from an on-line, in-line, inductance type oil debris sensor and three accelerometers were monitored and recorded for the occurrence of bearing failure. The bearing was removed and inspected periodically for damage progression throughout testing. Using data fusion techniques, two different monitoring technologies, oil debris analysis and vibration, were integrated into a health monitoring system for detecting bearing surface fatigue pitting damage. The data fusion diagnostic tool was evaluated during bearing failure progression tests under simulated engine load conditions. This integrated system showed improved detection of fatigue damage and health assessment of the tapered roller bearings as compared to using individual health monitoring technologies.

  18. [The impact of electronic cigarettes usage on the endothelial function and the progression of atherosclerosis].

    PubMed

    Knura, Miłosz; Dragon, Jonasz; Łabuzek, Krzysztof; Okopień, Bogusław

    2018-01-23

    The exponetial growth in popularity of electronic cigarettes in the world markets intensifies the debate about their health effects. The smoking of traditional tabacoo products is a factor associated with the endothelium damage and progression of atherosclerosis. The elimination of the combustion process in electronic cigarettes allows to conclude that they are less harmful to a vascular endothelium than traditional tobacco products. E-cigarette aerosol contains many compounds that have an influence on initiation and progression of atherosclerosis. Nicotine protherogenic action is not fully explained. On one hand, nicotine modifies metabolic pathways leading to atherosclerosis, whereas epidemiological studies do not show an increased risk of cardiovascular disease in the population using nicotine replacement therapy or snuff. Acrolein, formaldehyde and the ultrafine particles generated during e-liquid heating have an impact on initiation and progression of atherosclerosis, but their level is lower than that of tobacco smoke. In order to assess accurately the longterm effects of e-cigarettes, it is necessary to conduct epidemiological studies measuring the effects of using e-cigarettes. It is claimed that the use of electronic cigarettes has a potential impact on the development of atherosclerosis, but is significantly lower than that of traditional cigarettes.

  19. SOARCA Peach Bottom Atomic Power Station Long-Term Station Blackout Uncertainty Analysis: Knowledge Advancement.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gauntt, Randall O.; Mattie, Patrick D.; Bixler, Nathan E.

    2014-02-01

    This paper describes the knowledge advancements from the uncertainty analysis for the State-of- the-Art Reactor Consequence Analyses (SOARCA) unmitigated long-term station blackout accident scenario at the Peach Bottom Atomic Power Station. This work assessed key MELCOR and MELCOR Accident Consequence Code System, Version 2 (MACCS2) modeling uncertainties in an integrated fashion to quantify the relative importance of each uncertain input on potential accident progression, radiological releases, and off-site consequences. This quantitative uncertainty analysis provides measures of the effects on consequences, of each of the selected uncertain parameters both individually and in interaction with other parameters. The results measure the modelmore » response (e.g., variance in the output) to uncertainty in the selected input. Investigation into the important uncertain parameters in turn yields insights into important phenomena for accident progression and off-site consequences. This uncertainty analysis confirmed the known importance of some parameters, such as failure rate of the Safety Relief Valve in accident progression modeling and the dry deposition velocity in off-site consequence modeling. The analysis also revealed some new insights, such as dependent effect of cesium chemical form for different accident progressions. (auth)« less

  20. A progressive 5-week exercise therapy program leads to significant improvement in knee function early after anterior cruciate ligament injury.

    PubMed

    Eitzen, Ingrid; Moksnes, Håvard; Snyder-Mackler, Lynn; Risberg, May Arna

    2010-11-01

    Prospective cohort study without a control group. Firstly, to present our 5-week progressive exercise therapy program in the early stage after anterior cruciate ligament (ACL) injury. Secondly, to evaluate changes in knee function after completion of the program for patients with ACL injury in general and also when classified as potential copers or noncopers, and, finally, to examine potential adverse events. Few studies concerning early-stage ACL rehabilitation protocols exist. Consequently, little is known about the tolerance for, and outcomes from, short-term exercise therapy programs in the early stage after injury. One-hundred patients were included in a 5-week progressive exercise therapy program, within 3 months after injury. Knee function before and after completion of the program was evaluated from isokinetic quadriceps and hamstrings muscle strength tests, 4 single-leg hop tests, 2 different self-assessment questionnaires, and a global rating of knee function. A 2-way mixed-model analysis of variance was conducted to evaluate changes from pretest to posttest for the limb symmetry index for muscle strength and single-leg hop tests, and the change in scores for the patient-reported questionnaires. In addition, absolute values and the standardized response mean for muscle strength and single-leg hop tests were calculated at pretest and posttest for the injured and uninjured limb. Adverse events during the 5-week period were recorded. The progressive 5-week exercise therapy program led to significant improvements (P<.05) in knee function from pretest to posttest both for patients classified as potential copers and noncopers. Standardized response mean values for changes in muscle strength and single-leg hop performance from pretest to posttest for the injured limb were moderate to strong (0.49-0.84), indicating the observed improvements to be clinically relevant. Adverse events occurred in 3.9% of the patients. Short-term progressive exercise therapy programs are well tolerated and should be incorporated in early-stage ACL rehabilitation, either to improve knee function before ACL reconstruction or as a first step in further nonoperative management. Therapy, level 2b.

  1. Deep brain stimulation of the pedunculopontine nucleus for treatment of gait and balance disorder in progressive supranuclear palsy: Effects of frequency modulations and clinical outcome.

    PubMed

    Galazky, Imke; Kaufmann, Jörn; Lorenzl, Stefan; Ebersbach, Georg; Gandor, Florin; Zaehle, Tino; Specht, Sylke; Stallforth, Sabine; Sobieray, Uwe; Wirkus, Edyta; Casjens, Franziska; Heinze, Hans-Jochen; Kupsch, Andreas; Voges, Jürgen

    2018-05-01

    The pedunculopontine nucleus has been suggested as a potential deep brain stimulation target for axial symptoms such as gait and balance impairment in idiopathic Parkinson's disease as well as atypical Parkinsonian disorders. Seven consecutive patients with progressive supranuclear palsy received bilateral pedunculopontine nucleus deep brain stimulation. Inclusion criteria comprised of the clinical diagnosis of progressive supranuclear palsy, a levodopa-resistant gait and balance disorder, age <75 years, and absence of dementia or major psychiatric co-morbidities. Effects of stimulation frequencies at 8, 20, 60 and 130 Hz on motor scores and gait were assessed. Motor scores were followed up for two years postoperatively. Activities of daily living, frequency of falls, health-related quality of life, cognition and mood at 12 months were compared to baseline parameters. Surgical and stimulation related adverse events were assessed. Bilateral pedunculopontine nucleus deep brain stimulation at 8 Hz significantly improved axial motor symptoms and cyclic gait parameters, while high frequency stimulation did not ameliorate gait and balance but improved hypokinesia. This improvement however did not translate into clinically relevant benefits. Frequency of falls was not reduced. Activities of daily living, quality of life and frontal cognitive functions declined, while mood remained unchanged. Bilateral pedunculopontine nucleus deep brain stimulation in progressive supranuclear palsy generates frequency-dependent effects with improvement of cyclic gait parameters at low frequency and amelioration of hypokinesia at high frequency stimulation. However, these effects do not translate into a clinically important improvement. Copyright © 2018. Published by Elsevier Ltd.

  2. Diminished disease progression rate in a chronic kidney disease population following the replacement of dietary water source with quality drinking water: A pilot study.

    PubMed

    Siriwardhana, Edirisinghe Arachchige Ranga Iroshanie Edirisinghe; Perera, Ponnamperuma Aratchige Jayasumana; Sivakanesan, Ramiah; Abeysekara, Tilak; Nugegoda, Danaseela Bandara; Weerakoon, Kosala; Siriwardhana, Dunusingha Asitha Surandika

    2018-05-01

    Environmental toxin/s is alleged to be the contributory factor for the chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka. The potential of drinking water as a medium for the nephrotoxic agents in the affected subjects has been comprehensively discoursed in the recent past. The present study was aimed to assess the effect of replacing the habitual drinking water on the kidney function of CKDu patients residing in the North Central Province of Sri Lanka: METHODS: An interventional study was carried out to assess the disease progression rate of a CKDu population whose habitual drinking water was replaced by bottled spring water certified by Sri Lanka Standard (SLS) for a period of 18 month along with a population of CKDu patients who continued with their usual drinking water. Kidney function of subjects in both groups were monitored in terms of blood pressure, serum creatinine, serum calcium, serum phosphorus, hemoglobin, estimated glomerular filtration rate and urinary protein at 6 months intervals during the intervention and follow up periods. Diminished disease progression rate was observed in CKDu patients in the intervention group when compared with the non- intervention group based on serum creatinine, Hb, estimated glomerular filtration rate and urinary protein levels. Extensive interventional studies are required to generalize effect of drinking water on CKDu population. The habitual drinking water is likely to be a contributory factor towards the progression of the disease. © 2017 Asian Pacific Society of Nephrology.

  3. Shortening the Miles to the Milestones: Connecting EPA-Based Evaluations to ACGME Milestone Reports for Internal Medicine Residency Programs.

    PubMed

    Choe, John H; Knight, Christopher L; Stiling, Rebekah; Corning, Kelli; Lock, Keli; Steinberg, Kenneth P

    2016-07-01

    The Next Accreditation System requires internal medicine training programs to provide the Accreditation Council for Graduate Medical Education (ACGME) with semiannual information about each resident's progress in 22 subcompetency domains. Evaluation of resident "trustworthiness" in performing entrustable professional activities (EPAs) may offer a more tangible assessment construct than evaluations based on expectations of usual progression toward competence. However, translating results from EPA-based evaluations into ACGME milestone progress reports has proven to be challenging because the constructs that underlay these two systems differ.The authors describe a process to bridge the gap between rotation-specific EPA-based evaluations and ACGME milestone reporting. Developed at the University of Washington in 2012 and 2013, this method involves mapping EPA-based evaluation responses to "milestone elements," the narrative descriptions within the columns of each of the 22 internal medicine subcompetencies. As faculty members complete EPA-based evaluations, the mapped milestone elements are automatically marked as "confirmed." Programs can maintain a database that tallies the number of times each milestone element is confirmed for a resident; these data can be used to produce graphical displays of resident progress along the internal medicine milestones.Using this count of milestone elements allows programs to bridge the gap between faculty assessments of residents based on rotation-specific observed activities and semiannual ACGME reports based on the internal medicine milestones. Although potentially useful for all programs, this method is especially beneficial to large programs where clinical competency committee members may not have the opportunity for direct observation of all residents.

  4. The Development of a Telemedicine Planning Framework Based on Needs Assessment.

    PubMed

    AlDossary, Sharifah; Martin-Khan, Melinda G; Bradford, Natalie K; Armfield, Nigel R; Smith, Anthony C

    2017-05-01

    Providing equitable access to healthcare services in rural and remote communities is an ongoing challenge that faces most governments. By increasing access to specialty expertise, telemedicine may be a potential solution to this problem. Regardless of its potential, many telemedicine initiatives do not progress beyond the research phase, and are not implemented into mainstream practice. One reason may be that some telemedicine services are developed without the appropriate planning to ascertain community needs and clinical requirements. The aim of this paper is to report the development of a planning framework for telemedicine services based on needs assessment. The presented framework is based on the key processes in needs assessment, Penchansky and Thomas's dimensions of access, and Bradshaw's types of need. This proposed planning framework consists of two phases. Phase one comprises data collection and needs assessment, and includes assessment of availability and expressed needs; accessibility; perception and affordability. Phase two involves prioritising the demand for health services, balanced against the known limitations of supply, and the implementation of an appropriate telemedicine service that reflects and meets the needs of the community. Using a structured framework for the planning of telemedicine services, based on need assessment, may help with the identification and prioritisation of community health needs.

  5. Targeting Net Zero Energy at Marine Corps Base Hawaii, Kaneohe Bay: Preprint

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Burman, K.; Kandt, A.; Lisell, L.

    2012-05-01

    This paper summarizes the results of an NREL assessment of Marine Corps Base Hawaii (MCBH), Kaneohe Bay to appraise the potential of achieving net zero energy status through energy efficiency, renewable energy, and hydrogen vehicle integration. In 2008, the U.S. Department of Defense's U.S. Pacific Command partnered with the U.S. Department of Energy's (DOE's) National Renewable Energy Laboratory (NREL) to assess opportunities for increasing energy security through renewable energy and energy efficiency at Hawaii military installations. DOE selected Marine Corps Base Hawaii (MCBH), Kaneohe Bay, to receive technical support for net zero energy assessment and planning funded through the Hawaiimore » Clean Energy Initiative (HCEI). NREL performed a comprehensive assessment to appraise the potential of MCBH Kaneohe Bay to achieve net zero energy status through energy efficiency, renewable energy, and hydrogen vehicle integration. This paper summarizes the results of the assessment and provides energy recommendations. The analysis shows that MCBH Kaneohe Bay has the potential to make significant progress toward becoming a net zero installation. Wind, solar photovoltaics, solar hot water, and hydrogen production were assessed, as well as energy efficiency technologies. Deploying wind turbines is the most cost-effective energy production measure. If the identified energy projects and savings measures are implemented, the base will achieve a 96% site Btu reduction and a 99% source Btu reduction. Using excess wind and solar energy to produce hydrogen for a fleet and fuel cells could significantly reduce energy use and potentially bring MCBH Kaneohe Bay to net zero. Further analysis with an environmental impact and interconnection study will need to be completed. By achieving net zero status, the base will set an example for other military installations, provide environmental benefits, reduce costs, increase energy security, and exceed its energy goals and mandates.« less

  6. The Potentials of Fas Receptors and Ligands in Monitoring HIV-1 Disease in Children in Yaoundé, Cameroon.

    PubMed

    Ikomey, G; Assoumou, M-C Okomo; Atashili, J; Mesembe, M; Mukwele, B; Lyonga, E; Eyoh, A; Kafando, A; Ndumbe, P M

    2016-09-01

    Difficulties in systematically monitoring HIV viral load in resource-limited settings prompt the search for alternate approaches. The authors aimed at assessing the correlation between the plasma levels of soluble forms of Fas receptors (Fas) and Fas ligands (FasL) with standard indicators of HIV disease progression in children. Twenty-two HIV-1-positive children were enrolled in Yaounde. CD4 counts, CD4% counts, plasma levels of Fas, FasL, and HIV-1 RNA levels were assayed. The correlation coefficients (P values) between FasL levels and each of HIV-1 viral load, CD4 counts, and CD4% were, respectively, .56 (.01), -.29 (.18), and .30 (.18). On the other hand, the respective correlation coefficients (P values) with Fas levels were .12 (.60), -.30 (.18), and -.29 (.19). The significant correlation between levels of HIV-1 viral load and FasL suggests that the latter needs to be further studied as a potential biomarker to monitor HIV-1 disease progression in children in resource-limited setting. © The Author(s) 2013.

  7. Measuring Progressions: Assessment Structures Underlying a Learning Progression

    ERIC Educational Resources Information Center

    Wilson, Mark

    2009-01-01

    This article describes some of the underlying conceptualizations that have gone into the work of the BEAR Center in the development of learning progressions. The core of all of these developments has been the construct map, which is the first building block in the BEAR Assessment System (BAS). After introducing the concept of a learning…

  8. Where Are We Now? Learning Progressions and Formative Assessment

    ERIC Educational Resources Information Center

    Gotwals, Amelia Wenk

    2018-01-01

    In this commentary, I consider the three empirical studies in this special issue based on two main aspects: (a) the nature of the learning progressions and (b) what formative assessment practice(s) were investigated. Specifically, I describe differences among the learning progressions in terms of scope and grain size. I also identify three…

  9. A new role for evoked potentials in MS? Repurposing evoked potentials as biomarkers for clinical trials in MS.

    PubMed

    Hardmeier, Martin; Leocani, Letizia; Fuhr, Peter

    2017-09-01

    Evoked potentials (EP) characterize signal conduction in selected tracts of the central nervous system in a quantifiable way. Since alteration of signal conduction is the main mechanism of symptoms and signs in multiple sclerosis (MS), multimodal EP may serve as a representative measure of the functional impairment in MS. Moreover, EP have been shown to be predictive for disease course, and thus might help to select patient groups at high risk of progression for clinical trials. EP can detect deterioration, as well as improvement of impulse propagation, independently from the mechanism causing the change. Therefore, they are candidates for biomarkers with application in clinical phase-II trials. Applicability of EP in multicenter trials has been limited by different standards of registration and assessment.

  10. Potential of thin-film solar cell module technology

    NASA Technical Reports Server (NTRS)

    Shimada, K.; Ferber, R. R.; Costogue, E. N.

    1985-01-01

    During the past five years, thin-film cell technology has made remarkable progress as a potential alternative to crystalline silicon cell technology. The efficiency of a single-junction thin-film cell, which is the most promising for use in flat-plate modules, is now in the range of 11 percent with 1-sq cm cells consisting of amorphous silicon, CuInSe2 or CdTe materials. Cell efficiencies higher than 18 percent, suitable for 15 percent-efficient flat plate modules, would require a multijunction configuration such as the CdTe/CuInSe2 and tandem amorphous-silicon (a-Si) alloy cells. Assessments are presented of the technology status of thin-film-cell module research and the potential of achieving the higher efficiencies required for large-scale penetration into the photovoltaic (PV) energy market.

  11. Both Predator and Prey

    PubMed Central

    Löw, Andreas; Lang, Peter J.; Smith, J. Carson; Bradley, Margaret M.

    2013-01-01

    This research examined the psychophysiology of emotional arousal anticipatory to potentially aversive and highly pleasant outcomes. Human brain reactions (event-related potentials) and body reactions (heart rate, skin conductance, the probe startle reflex) were assessed along motivational gradients determined by apparent distance from sites of potential punishment or reward. A predator-prey survival context was simulated using cues that signaled possible money rewards or possible losses; the cues appeared to loom progressively closer to the viewer, until a final step when a rapid key response could ensure reward or avoid a punishing loss. The observed anticipatory response patterns of heightened vigilance and physiological mobilization are consistent with the view that the physiology of emotion is founded on action dispositions that evolved in mammals to facilitate survival by dealing with threats or capturing life-sustaining rewards. PMID:18947351

  12. Distress improves after mindfulness training for progressive MS: A pilot randomised trial.

    PubMed

    Bogosian, A; Chadwick, P; Windgassen, S; Norton, S; McCrone, P; Mosweu, I; Silber, E; Moss-Morris, R

    2015-08-01

    Mindfulness-based interventions have been shown to effectively reduce anxiety, depression and pain in patients with chronic physical illnesses. We assessed the potential effectiveness and cost-effectiveness of a specially adapted Skype distant-delivered mindfulness intervention, designed to reduce distress for people affected by primary and secondary progressive MS. Forty participants were randomly assigned to the eight-week intervention (n = 19) or a waiting-list control group (n = 21). Participants completed standardised questionnaires to measure mood, impact of MS and symptom severity, quality of life and service costs at baseline, post-intervention and three-month follow-up. Distress scores were lower in the intervention group compared with the control group at post-intervention and follow-up (p < 0.05), effect size -0.67 post-intervention and -0.97 at follow-up. Mean scores for pain, fatigue, anxiety, depression and impact of MS were reduced for the mindfulness group compared with control group at post-therapy and follow-up; effect sizes ranged from -0.27 to -0.99 post-intervention and -0.29 to -1.12 at follow-up. There were no differences in quality-adjusted life years, but an 87.4% probability that the intervention saves on service costs and improves outcome. A mindfulness intervention delivered through Skype video conferences appears accessible, feasible and potentially effective and cost-effective for people with progressive MS. © The Author(s), 2015.

  13. MicroRNA, Proteins, and Metabolites as Novel Biomarkers for Prediabetes, Diabetes, and Related Complications

    PubMed Central

    Vaishya, Suniti; Sarwade, Rucha D.; Seshadri, Vasudevan

    2018-01-01

    Type 2 diabetes mellitus (T2DM) is no more a lifestyle disease of developed countries. It has emerged as a major health problem worldwide including developing countries. However, how diabetes could be detected at an early stage (prediabetes) to prevent the progression of disease is still unclear. Currently used biomarkers like glycated hemoglobin and assessment of blood glucose level have their own limitations. These classical markers can be detected when the disease is already established. Prognosis of disease at early stages and prediction of population at a higher risk require identification of specific markers that are sensitive enough to be detected at early stages of disease. Biomarkers which could predict the risk of disease in people will be useful for developing preventive/proactive therapies to those individuals who are at a higher risk of developing the disease. Recent studies suggested that the expression of biomolecules including microRNAs, proteins, and metabolites specifically change during the progression of T2DM and related complications, suggestive of disease pathology. Owing to their omnipresence in body fluids and their association with onset, progression, and pathogenesis of T2DM, these biomolecules can be potential biomarker for prognosis, diagnosis, and management of disease. In this article, we summarize biomolecules that could be potential biomarkers and their signature changes associated with T2DM and related complications during disease pathogenesis. PMID:29740397

  14. Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity

    PubMed Central

    Deep, Gagan; Kumar, Rahul; Jain, Anil K.; Dhar, Deepanshi; Panigrahi, Gati K.; Hussain, Anowar; Agarwal, Chapla; El-Elimat, Tamam; Sica, Vincent P.; Oberlies, Nicholas H.; Agarwal, Rajesh

    2016-01-01

    Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with higher expression/activity in prostate tumors and play critical role in PCa growth and progression. Here we report that NADPH oxidase (NOX) expression is directly associated with PCa progression in TRAMP mice, suggesting NOX as a potential chemoprevention target in controlling PCa. Accordingly, we assessed whether NOX activity in PCa cells could be inhibited by Graviola pulp extract (GPE) that contains unique acetogenins with strong anti-cancer effects. GPE (1–5 μg/ml) treatment strongly inhibited the hypoxia-induced NOX activity in PCa cells (LNCaP, 22Rv1 and PC3) associated with a decrease in the expression of NOX catalytic and regulatory sub-units (NOX1, NOX2 and p47phox). Furthermore, GPE-mediated NOX inhibition was associated with a strong decrease in nuclear HIF-1α levels as well as reduction in the proliferative and clonogenic potential of PCa cells. More importantly, GPE treatment neither inhibited NOX activity nor showed any cytotoxicity against non-neoplastic prostate epithelial PWR-1E cells. Overall, these results suggest that GPE could be useful in the prevention of PCa progression via inhibiting NOX activity. PMID:26979487

  15. Plenary: Progress in Regional Landslide Hazard Assessment—Examples from the USA

    USGS Publications Warehouse

    Baum, Rex L.; Schulz, William; Brien, Dianne L.; Burns, William J.; Reid, Mark E.; Godt, Jonathan W.

    2014-01-01

    Landslide hazard assessment at local and regional scales contributes to mitigation of landslides in developing and densely populated areas by providing information for (1) land development and redevelopment plans and regulations, (2) emergency preparedness plans, and (3) economic analysis to (a) set priorities for engineered mitigation projects and (b) define areas of similar levels of hazard for insurance purposes. US Geological Survey (USGS) research on landslide hazard assessment has explored a range of methods that can be used to estimate temporal and spatial landslide potential and probability for various scales and purposes. Cases taken primarily from our work in the U.S. Pacific Northwest illustrate and compare a sampling of methods, approaches, and progress. For example, landform mapping using high-resolution topographic data resulted in identification of about four times more landslides in Seattle, Washington, than previous efforts using aerial photography. Susceptibility classes based on the landforms captured 93 % of all historical landslides (all types) throughout the city. A deterministic model for rainfall infiltration and shallow landslide initiation, TRIGRS, was able to identify locations of 92 % of historical shallow landslides in southwest Seattle. The potentially unstable areas identified by TRIGRS occupied only 26 % of the slope areas steeper than 20°. Addition of an unsaturated infiltration model to TRIGRS expands the applicability of the model to areas of highly permeable soils. Replacement of the single cell, 1D factor of safety with a simple 3D method of columns improves accuracy of factor of safety predictions for both saturated and unsaturated infiltration models. A 3D deterministic model for large, deep landslides, SCOOPS, combined with a three-dimensional model for groundwater flow, successfully predicted instability in steep areas of permeable outwash sand and topographic reentrants. These locations are consistent with locations of large, deep, historically active landslides. For an area in Seattle, a composite of the three maps illustrates how maps produced by different approaches might be combined to assess overall landslide potential. Examples from Oregon, USA, illustrate how landform mapping and deterministic analysis for shallow landslide potential have been adapted into standardized methods for efficiently producing detailed landslide inventory and shallow landslide susceptibility maps that have consistent content and format statewide.

  16. Cariogenicity and acidogenicity of human milk, plain and sweetened bovine milk: an in vitro study.

    PubMed

    Prabhakar, A R; Kurthukoti, Ameet J; Gupta, Pranjali

    2010-01-01

    The objective of the present study was to determine the acidogenicity and cariogenicity of human breast milk and plain and sweetened packaged bovine milk. First all milk specimens were inoculated with a cariogenic strain of Streptococcus mutans (SM). The culture pH and number of colony forming units (cfus) was assessed. Second, the buffer capacity of all milk specimens was evaluated by mixing with acid. Finally, enamel windows were created on extracted primary maxillary incisors and colonized with SM. Enamel demineralization and caries progression were assessed visually, histologically, and radiographically at the end of twelve weeks. Plain and sweetened packaged bovine milk (BM) supported greater bacterial growth and caused more fermentation than human breast milk (HBM). The buffer capacity values for plain and sweetened bovine milk were highest; HBM, however had poor buffering capacity. The progression of the carious lesions into the dentin was most severe for the sweetened bovine milk. HBM and plain bovine milk are relatively cariogenic in an in vitro caries model in the absence of saliva. However, supplementation with sugar exponentially enhances the cariogenic potential of the natural milk.

  17. Promoting Learning and Achievement through Self-Assessment

    ERIC Educational Resources Information Center

    Andrade, Heidi; Valtcheva, Anna

    2009-01-01

    Criteria-referenced self-assessment is a process during which students collect information about their own performance or progress; compare it to explicitly stated criteria, goals, or standards; and revise accordingly. The authors argue that self-assessment must be a formative type of assessment, done on drafts of works in progress: It should not…

  18. Combined Vision and Wearable Sensors-based System for Movement Analysis in Rehabilitation.

    PubMed

    Spasojević, Sofija; Ilić, Tihomir V; Milanović, Slađan; Potkonjak, Veljko; Rodić, Aleksandar; Santos-Victor, José

    2017-03-23

    Traditional rehabilitation sessions are often a slow, tedious, disempowering and non-motivational process, supported by clinical assessment tools, i.e. evaluation scales that are prone to subjective rating and imprecise interpretation of patient's performance. Poor patient motivation and insufficient accuracy are thus critical factors that can be improved by new sensing / processing technologies. We aim to develop a portable and affordable system, suitable for home rehabilitation, which combines vision-based and wearable sensors. We introduce a novel approach for examining and characterizing the rehabilitation movements, using quantitative descriptors. We propose new Movement Performance Indicators (MPIs) that are extracted directly from sensor data and quantify the symmetry, velocity, and acceleration of the movement of different body/hand parts, and that can potentially be used by therapists for diagnosis and progress assessment. First, a set of rehabilitation exercises is defined, with the supervision of neurologists and therapists for the specific case of Parkinson's disease. It comprises full-body movements measured with a Kinect device and fine hand movements, acquired with a data glove. Then, the sensor data is used to compute 25 Movement Performance Indicators, to assist the diagnosis and progress monitoring (assessing the disease stage) in Parkinson's disease. A kinematic hand model is developed for data verification and as an additional resource for extracting supplementary movement information. Our results show that the proposed Movement Performance Indicators are relevant for the Parkinson's disease assessment. This is further confirmed by correlation of the proposed indicators with clinical tapping test and UPDRS clinical scale. Classification results showed the potential of these indicators to discriminate between the patients and controls, as well as between the stages that characterize the evolution of the disease. The proposed sensor system, along with the developed approach for rehabilitation movement analysis have a significant potential to support and advance traditional rehabilitation therapy. The main impact of our work is two-fold: (i) the proposition of an approach for supporting the therapists during the diagnosis and monitoring evaluations by reducing subjectivity and imprecision, and (ii) offering the possibility of the system to be used at home for rehabilitation exercises in between sessions with doctors and therapists.

  19. 75 FR 6012 - National Assessment of Educational Progress (NAEP) in Reading

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-05

    ... comment for evaluating and finalizing achievement levels definitions for the National Assessment of... comment and recommendations for improvements to the achievement levels definitions for the National Assessment of Educational Progress (NAEP) in reading. These achievement levels definitions describe the...

  20. Civics Framework for the 1998 National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    Center for Civic Education, Calabasas, CA.

    The material provides a comprehensive look at the design, goals, and methods to be used in the 1998 National Assessment of Educational Progress (NAEP) Civics Assessment. This assessment will attempt to gauge the civic knowledge and skills of the nation's 4th, 8th, and 12th grade students. To do well on the assessment, students will have to show…

  1. Civics Framework for the 2006 National Assessment of Educational Progress. NAEP Civics Project

    ERIC Educational Resources Information Center

    National Assessment Governing Board, 2007

    2007-01-01

    To gauge the civic knowledge and skills of the nation's 4th-, 8th-, and 12th-grade students, an assessment has been scheduled for 2006 by the National Assessment of Educational Progress (NAEP). This assessment will enable NAEP to report on trends in civics achievement from 1998 to 2006. The National Assessment Governing Board (NAGB), NAEP's…

  2. Plasma Switch Development.

    DTIC Science & Technology

    1984-06-08

    Appendix II), the progress to date will be detailed here. II° K -BEAM CONTROLLED SWITCH The EBCS is an opening switch concept that has the potential for...such plasma in ᝺ uis. To accurately assess the viability of this scheme, more effort than what was provided to date is required. 0 00 LL k CCj2 E - w...1962 e+A* -A +A (2) ... 2OOOz t~ -- whs A is, in enera, any positive molecular ion (simple or cluster ) of species A. We define the effective rate at

  3. Phage Therapy: Beyond Antibacterial Action.

    PubMed

    Górski, Andrzej; Jończyk-Matysiak, Ewa; Międzybrodzki, Ryszard; Weber-Dąbrowska, Beata; Łusiak-Szelachowska, Marzanna; Bagińska, Natalia; Borysowski, Jan; Łobocka, Małgorzata B; Węgrzyn, Alicja; Węgrzyn, Grzegorz

    2018-01-01

    Until recently, phages were considered as mere "bacteria eaters" with potential for use in combating antimicrobial resistance. The real value of phage therapy assessed according to the standards of evidence-based medicine awaits confirmation by clinical trials. However, the progress in research on phage biology has shed more light on the significance of phages. Accumulating data indicate that phages may also interact with eukaryotic cells. How such interactions could be translated into advances in medicine (especially novel means of therapy) is discussed herein.

  4. The Value of Addressing Patient Preferences.

    PubMed

    Allen, Jeff D; Stewart, Mark D; Roberts, Samantha A; Sigal, Ellen V

    2017-02-01

    Recent scientific progress is, in some cases, leading to transformative new medicines for diseases that previously had marginal or even no treatment options. This offers great promise for people affected by these diseases, but it has also placed stress on the health care system in terms of the growing cost associated with some new interventions. Effort has been taken to create tools to help patients and health care providers assess the value of new medical innovations. These tools may also provide the basis for assessing the price associated with new medical products. Given the growing expenditures in health care, value frameworks present an opportunity to evaluate new therapeutic options in the context of other treatments and potentially lead to a more economically sustainable health care system. In summary, the contribution to meaningful improvements in health outcomes is the primary focus of any assessment of the value of a new intervention. A component of such evaluations, however, should factor in timely access to new products that address an unmet medical need, as well as the magnitude of that beneficial impact. To achieve these goals, value assessment tools should allow for flexibility in clinical end points and trial designs, incorporate patient preferences, and continually evolve as new evidence, practice patterns, and medical progress advance. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  5. A Programme for Risk Assessment and Minimisation of Progressive Multifocal Leukoencephalopathy Developed for Vedolizumab Clinical Trials.

    PubMed

    Parikh, Asit; Stephens, Kristin; Major, Eugene; Fox, Irving; Milch, Catherine; Sankoh, Serap; Lev, Michael H; Provenzale, James M; Shick, Jesse; Patti, Mark; McAuliffe, Megan; Berger, Joseph R; Clifford, David B

    2018-05-08

    Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4β7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval regulatory requirement. The aim of this study was to describe the multiple risk minimisation elements that were incorporated in vedolizumab clinical trials in inflammatory bowel disease patients as part of the risk assessment and minimisation of PML programme for vedolizumab. A case evaluation algorithm was developed for sequential screening and diagnostic evaluation of subjects who met criteria that indicated a clinical suspicion of PML. An Independent Adjudication Committee provided an independent, unbiased opinion regarding the likelihood of PML. Although no cases were detected, all suspected PML events were thoroughly reviewed and successfully adjudicated, making it unlikely that cases were missed. We suggest that this programme could serve as a model for pragmatic screening for PML during the clinical development of new drugs.

  6. Gait and Cognition: A Complementary Approach to Understanding Brain Function and the Risk of Falling

    PubMed Central

    Montero-Odasso, Manuel; Verghese, Joe; Beauchet, Olivier; Hausdorff, Jeffrey M.

    2012-01-01

    Until recently, clinicians and researchers have performed gait assessments and cognitive assessments separately when evaluating older adults. Increasing evidence from clinical practice, epidemiological studies, and clinical trials shows that gait and cognition are inter-related in older adults. Quantifiable alterations in gait among older adults are associated with falls, dementia, and disability. At the same time, emerging evidence indicates that early disturbances in cognitive processes such as attention, executive function, and working memory are associated with slower gait and gait instability during single and dual-task testing, and that these cognitive disturbances assist in the prediction of future mobility loss, falls, and progression to dementia. This paper reviews the importance of the gait-cognition inter-relationship in aging and presents evidence that gait assessments can provide a window into the understanding of cognitive function and dysfunctions, and fall risk in older people in clinical practice. To this end, the benefits of dual-task gait assessments (e.g., walking while performing an attention-demanding task) as a marker of fall risk are summarized. Further, we also present a potential complementary approach for reducing the risk of falls by improving certain aspects of cognition through both non-pharmacological and pharmacological treatments. Untangling the relationship between early gait disturbances and early cognitive changes may be helpful for identifying older adults at higher risk of experiencing mobility decline, falls and the progression to dementia. PMID:23110433

  7. A prospective pilot study measuring muscle volumetric change in amyotrophic lateral sclerosis.

    PubMed

    Jenkins, Thomas M; Burness, Christine; Connolly, Daniel J; Rao, D Ganesh; Hoggard, Nigel; Mawson, Susan; McDermott, Christopher J; Wilkinson, Iain D; Shaw, Pamela J

    2013-09-01

    Our objective was to investigate the potential of muscle volume, measured with magnetic resonance (MR), as a biomarker to quantify disease progression in patients with amyotrophic lateral sclerosis (ALS). In this longitudinal pilot study, we first sought to determine the stability of volumetric muscle MR measurements in 11 control subjects at two time-points. We assessed feasibility of detecting atrophy in four patients with ALS, followed at three-month intervals for 12 months. Muscle power and MR volume were measured in thenar eminence (TEm), first dorsal interosseous (1DIO), tibialis anterior (TA) and tongue. Changes over time were assessed using linear regression models and t-tests. Results demonstrated that, in controls, no volumetric MR changes were seen (mean volume variation in all muscles < 5%, p > 0.1). In patients, between-subject heterogeneity was identified. Trends for volume loss were found in TEm (mean, - 26.84%, p = 0.056) and TA (- 8.29%, p = 0.077), but not in 1DIO (- 18.47%, p = 0.121) or tongue (< 5%, p = 0.367). In conclusion, volumetric muscle MR appears a stable measure in controls, and progressive volume loss was demonstrable in individuals with ALS in whom clinical weakness progressed. In this small study, subclinical atrophy was not demonstrable using muscle MR. Clinico-radiological discordance between muscle weakness and MR atrophy could reflect a contribution of upper motor neuron pathology.

  8. Improving outcomes for people with progressive cancer: interrupted time series trial of a needs assessment intervention.

    PubMed

    Waller, Amy; Girgis, Afaf; Johnson, Claire; Lecathelinais, Christophe; Sibbritt, David; Forstner, Dion; Liauw, Winston; Currow, David C

    2012-03-01

    Improving the effectiveness of cancer care delivery has become a major focus of research. This study assessed the uptake and impact of the Palliative Care Needs Assessment Guidelines and Needs Assessment Tool: Progressive Disease--Cancer (NAT: PD-C) on the outcomes of people with advanced cancer. Given widely varying survival in people with advanced cancer, an interrupted time series design was used, with data on unmet needs, depression, anxiety, and quality of life collected from 195 patients using telephone interviews every two months, for up to 18 months. Patients completed at least two baseline interviews before health professionals were academically detailed in the use of the Palliative Care Needs Assessment Guidelines and NAT: PD-C. Health professionals completed the NAT: PD-C with patients approximately monthly for the remainder of the study. Changes in patients' outcomes were compared prior to and following the introduction of the NAT: PD-C using general estimating equations. Moderate to high needs across all domains were frequently seen in the preintervention phase. The use of the NAT: PD-C was associated with a significant reduction in health system and information and patient care and support needs. These resources have the potential as an efficient and acceptable strategy for supporting needs-based cancer care. Further work is required to determine their unique contribution to improvements in patient outcomes. Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  9. Urine circulating-tumor DNA (ctDNA) detection of acquired EGFR T790M mutation in non-small-cell lung cancer: An outcomes and total cost-of-care analysis.

    PubMed

    Sands, Jacob; Li, Qianyi; Hornberger, John

    2017-08-01

    Third-generation tyrosine kinase inhibitors (TKIs) have proven effective in patients with the acquired EGFR T790M resistance mutation who progress on prior EGFR TKI therapy. Median progression-free survival (PFS) on a 3rd-gen TKI was 9-10 months for T790M+ patients compared to 2.8 months for T790M- patients. PFS is similar regardless of the specimen used to assess T790M, such as tissue, plasma, or urine ctDNA. This study aimed to assess the total cost of care of a urine-testing strategy (UTS) versus a tissue-testing strategy (TTS) for T790M detection, in patients with EGFR-mutation positive lung adenocarcinoma and progression on prior TKI therapy. Long-term outcomes and economic implications were assessed from a US payer perspective. Endpoints were PFS, overall survival (OS), medical resource use and related costs. We included published randomized drug trials and Medicare fee schedules. A state-transition analysis and Markov model tracked patients from stable disease to progression and death. Univariate and multivariate sensitivity analyses were performed to assess the robustness of findings and identify factors that most influenced outcomes and costs. UTS increased the rate of detection of patients with T790M mutation eligible for treatment with 3rd generation TKI by 7% compared with TTS; urine ctDNA testing detected T790M mutation in some patients for whom biopsy could not be performed or when tissue testing yielded indeterminate results. Due to enhanced targeting of TKI therapy, UTS increased PFS and OS by 0.44 and 0.35 months, respectively. UTS yields a savings of $1243-$1680 per patient due to avoidance of biopsy, potential biopsy-associated complications, and tissue-based molecular testing in approximately 55.6% of patients. Probability of T790M detection by tissue and cost of biopsy procedure were the most influential factors. UTS prolonged PFS/OS due to increased detection of T790M mutation and decreased biopsies and complication-related costs. Copyright © 2017. Published by Elsevier B.V.

  10. TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort

    PubMed Central

    Molnar, Christoph; Scherer, Almut; de Hooge, Manouk; Micheroli, Raphael; Exer, Pascale; Kissling, Rudolf O; Tamborrini, Giorgio; Wildi, Lukas M; Nissen, Michael J; Zufferey, Pascal; Bernhard, Jürg; Weber, Ulrich; Landewé, Robert B M; Ciurea, Adrian

    2018-01-01

    Objectives To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS). Methods Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis. Results A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97). Conclusion TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity. PMID:28939631

  11. Evaluation of biotechnology-derived novel proteins for the risk of food-allergic potential: advances in the development of animal models and future challenges.

    PubMed

    Ahuja, Varun; Quatchadze, Maria; Ahuja, Vaishali; Stelter, Daniela; Albrecht, Achim; Stahlmann, Ralf

    2010-12-01

    Increasing concern from the public about the safety of genetically modified food has made critical to have suitable methods for recognizing associated potential hazards. Hierarchical approaches to allergenicity determination were proposed, and these include evaluation of the structural and sequence homology and serological identity of novel proteins with existing allergens, measuring the resistance to proteolytic digestion and assessment of sensitizing potential using animal models. Allergic individuals have a predisposed (i.e. atopic) genetic background, and a close resemblance to this setup is therefore desirable in animal models, which is possible by using a strain of an animal species that is prone for allergic disorders. So far, none of the animal model has been validated for the purpose of hazard identification in the context of safety assessment. However, the available knowledge suggests that the judicious use of an appropriate animal model could provide important information about the allergic potential of novel proteins. This paper provides an up-to-date review of the progress made in the field of development of in vivo models in this direction and the further goals that have to be achieved.

  12. CCNE1 amplification is associated with aggressive potential in endometrioid endometrial carcinomas.

    PubMed

    Nakayama, Kentaro; Rahman, Mohammed Tanjimur; Rahman, Munmun; Nakamura, Kohei; Ishikawa, Masako; Katagiri, Hiroshi; Sato, Emi; Ishibashi, Tomoka; Iida, Kouji; Ishikawa, Noriyuki; Kyo, Satoru

    2016-02-01

    The clinicopathological significance of amplification was investigated of the gene encoding cyclin E (CCNE1) and we assessed whether CCNE1 was a potential target in endometrioid endometrial carcinomas. CCNE1 amplification and CCNE1 or F-box and WD repeat domain-containing 7 (FBXW7) expression in endometrial endometrioid carcinoma was assessed by immunohistochemistry and fluorescence in situ hybridization. CCNE1 knockdown by small interfering RNA (siRNA) was used to assess the CCNE1 function. The results showed that CCNE1 amplification was present in 9 (8.3%) of 108 endometrial carcinomas. CCNE1 amplification was correlated with high histological grade (Grade 3; p=0.0087) and lymphovascular space invasion (p=0.0258). No significant association was observed between CCNE1 amplification and FIGO stage (p=0.851), lymph node metastasis (p=0.078), body mass index (p=0.265), deep myometrial invasion (p=0.256), menopausal status (p=0.289) or patient age (p=0.0817). CCNE1 amplification was significantly correlated with shorter progression-free and overall survival (p=0.0081 and 0.0073, respectively). CCNE1 protein expression or loss of FBXW7 expression in endometrial endometrioid carcinoma tended to be correlated with shorter progression-free and overall survival; however, this difference was not statistically significant. Multivariate analysis showed that CCNE1 amplification was an independent prognostic factor for overall survival but not for progression-free survival (P=0.0454 and 0.2175, respectively). Profound growth inhibition was observed in siRNA-transfected cancer cells with endogenous CCNE1 overexpression compared with that in cancer cells having low CCNE1 expression. CCNE1 amplification was independent of p53, HER2, MLH1 and ARID1A expression but dependent on PTEN expression in endometrial carcinomas. These findings indicated that CCNE1 amplification was critical for the survival of endometrial endometrioid carcinomas. Furthermore, the effects of CCNE1 knockdown were dependent on the CCNE1 expression status, suggesting that CCNE1-targeted therapy may be beneficial for patients with endometrial endometrioid carcinoma having CCNE1 amplification.

  13. CCNE1 amplification is associated with aggressive potential in endometrioid endometrial carcinomas

    PubMed Central

    NAKAYAMA, KENTARO; RAHMAN, MOHAMMED TANJIMUR; RAHMAN, MUNMUN; NAKAMURA, KOHEI; ISHIKAWA, MASAKO; KATAGIRI, HIROSHI; SATO, EMI; ISHIBASHI, TOMOKA; IIDA, KOUJI; ISHIKAWA, NORIYUKI; KYO, SATORU

    2016-01-01

    The clinicopathological significance of amplification was investigated of the gene encoding cyclin E (CCNE1) and we assessed whether CCNE1 was a potential target in endometrioid endometrial carcinomas. CCNE1 amplification and CCNE1 or F-box and WD repeat domain-containing 7 (FBXW7) expression in endometrial endometrioid carcinoma was assessed by immunohistochemistry and fluorescence in situ hybridization. CCNE1 knockdown by small interfering RNA (siRNA) was used to assess the CCNE1 function. The results showed that CCNE1 amplification was present in 9 (8.3%) of 108 endometrial carcinomas. CCNE1 amplification was correlated with high histological grade (Grade 3; P=0.0087) and lymphovascular space invasion (P=0.0258). No significant association was observed between CCNE1 amplification and FIGO stage (P=0.851), lymph node metastasis (P=0.078), body mass index (P=0.265), deep myometrial invasion (P=0.256), menopausal status (P=0.289) or patient age (P=0.0817). CCNE1 amplification was significantly correlated with shorter progression-free and overall survival (P=0.0081 and 0.0073, respectively). CCNE1 protein expression or loss of FBXW7 expression in endometrial endometrioid carcinoma tended to be correlated with shorter progression-free and overall survival; however, this difference was not statistically significant. Multivariate analysis showed that CCNE1 amplification was an independent prognostic factor for overall survival but not for progression-free survival (P=0.0454 and 0.2175, respectively). Profound growth inhibition was observed in siRNA-transfected cancer cells with endogenous CCNE1 overexpression compared with that in cancer cells having low CCNE1 expression. CCNE1 amplification was independent of p53, HER2, MLH1 and ARID1A expression but dependent on PTEN expression in endometrial carcinomas. These findings indicated that CCNE1 amplification was critical for the survival of endometrial endometrioid carcinomas. Furthermore, the effects of CCNE1 knockdown were dependent on the CCNE1 expression status, suggesting that CCNE1-targeted therapy may be beneficial for patients with endometrial endometrioid carcinoma having CCNE1 amplification. PMID:26647729

  14. Evoked-potential changes following discrimination learning involving complex sounds

    PubMed Central

    Orduña, Itzel; Liu, Estella H.; Church, Barbara A.; Eddins, Ann C.; Mercado, Eduardo

    2011-01-01

    Objective Perceptual sensitivities are malleable via learning, even in adults. We trained adults to discriminate complex sounds (periodic, frequency-modulated sweep trains) using two different training procedures, and used psychoacoustic tests and evoked potential measures (the N1-P2 complex) to assess changes in both perceptual and neural sensitivities. Methods Training took place either on a single day, or daily across eight days, and involved discrimination of pairs of stimuli using a single-interval, forced-choice task. In some participants, training started with dissimilar pairs that became progressively more similar across sessions, whereas in others training was constant, involving only one, highly similar, stimulus pair. Results Participants were better able to discriminate the complex sounds after training, particularly after progressive training, and the evoked potentials elicited by some of the sounds increased in amplitude following training. Significant amplitude changes were restricted to the P2 peak. Conclusion Our findings indicate that changes in perceptual sensitivities parallel enhanced neural processing. Significance These results are consistent with the proposal that changes in perceptual abilities arise from the brain’s capacity to adaptively modify cortical representations of sensory stimuli, and that different training regimens can lead to differences in cortical sensitivities, even after relatively short periods of training. PMID:21958655

  15. New developments in the treatment of multiple myeloma - clinical utility of daratumumab.

    PubMed

    McEllistrim, Cian; Krawczyk, Janusz; O'Dwyer, Michael E

    2017-01-01

    Multiple myeloma is a clonal disorder of plasma cells that is currently considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1 monoclonal antibody that targets CD38, and has antimyeloma effects through several mechanisms. Single-agent trials show surprising activity in heavily pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have demonstrated significantly improved progression-free survival with acceptable toxicity. In this review, we discuss the mechanism of action, pharmacology and pharmacokinetics of daratumumab and review the available clinical data in detail. We examine how daratumumab interferes with transfusion testing due to the expression of CD38 on the red blood cells, leading to potential difficulties releasing blood products. Daratumumab also affects disease assessments in multiple myeloma, including serum protein electrophoresis, immunofixation and flow cytometry. Strategies to mitigate these effects are discussed. The optimal use of daratumumab has yet to be decided, and several trials are ongoing in the relapsed and upfront setting. We discuss the potential upfront role of this exciting therapy, which has significant potential for increased minimal residual disease negativity and improved progression-free survival even in high-risk groups.

  16. New developments in the treatment of multiple myeloma – clinical utility of daratumumab

    PubMed Central

    McEllistrim, Cian; Krawczyk, Janusz; O’Dwyer, Michael E

    2017-01-01

    Multiple myeloma is a clonal disorder of plasma cells that is currently considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1 monoclonal antibody that targets CD38, and has antimyeloma effects through several mechanisms. Single-agent trials show surprising activity in heavily pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have demonstrated significantly improved progression-free survival with acceptable toxicity. In this review, we discuss the mechanism of action, pharmacology and pharmacokinetics of daratumumab and review the available clinical data in detail. We examine how daratumumab interferes with transfusion testing due to the expression of CD38 on the red blood cells, leading to potential difficulties releasing blood products. Daratumumab also affects disease assessments in multiple myeloma, including serum protein electrophoresis, immunofixation and flow cytometry. Strategies to mitigate these effects are discussed. The optimal use of daratumumab has yet to be decided, and several trials are ongoing in the relapsed and upfront setting. We discuss the potential upfront role of this exciting therapy, which has significant potential for increased minimal residual disease negativity and improved progression-free survival even in high-risk groups. PMID:28442888

  17. 75 FR 34440 - National Assessment Governing Board: Proposed Information Collection

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ... through the use of automated collection techniques or other forms of information technology; and (5... Institutions). Use: The congressionally authorized National Assessment of Educational Progress (NAEP) reports... under the National Assessment of Educational Progress Authorization Act (Pub. L. 107-279). Among the...

  18. Arterial stiffness is an independent predictor for albuminuria progression among Asians with type 2 diabetes-A prospective cohort study.

    PubMed

    Zhang, Xiao; Low, Serena; Sum, Chee Fang; Tavintharan, Subramaniam; Yeoh, Lee Ying; Liu, Jianjun; Li, Na; Ang, Keven; Lee, Simon Bm; Tang, Wern Ee; Lim, Su Chi

    2017-06-01

    Albuminuria progression has been associated with renal deterioration in type 2 diabetes (T2DM). Central arterial stiffness can aggravate systemic vasculopathy by propagating elevated systolic and pulse pressures forward, thereby accentuating global vascular injury. We aim to investigate whether central arterial stiffness is an independent predictor for albuminuria progression in a multi-ethnic T2DM Asian cohort in Singapore. In a prospective cohort, 1012 T2DM patients were assessed at baseline and after a median follow-up of 3.1years. 880 patients with baseline normo- (urinary albumin-to-creatinine ratio (ACR)<30mg/g, n=579) and microalbuminuria (ACR=30-299mg/g, n=301) were divided into progression and non-progression groups according to ACR changes. Progression was defined as transition from normo- to microalbuminuria, micro- to macroalbuminuria, or normo- to macroalbuminuria. Central arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV) using applanation tonometry method. Stepwise multiple regression analysis was used to determine the predictor(s) for albuminuria progression. Albuminuria progression occurred in 178 patients (20.2%). Baseline PWV was higher in progression (10.1±2.9m/s) than non-progression group (9.2±2.4m/s, p<0.001). 1-SD increase in baseline PWV was associated with albuminuria progression (OR=1.457, 95% CI, 1.236-1.718, p<0.001). Stepwise regression analysis identified that baseline PWV (OR=1.241, 95% CI, 1.033-1.490, p=0.021), BMI (OR=1.046, 95% CI, 1.012-1.080, p=0.008), nature log-transformed estimated glomerular filtration rate (LneGFR) (OR=0.320, 95% CI, 0.192-0.530, p=0.010) and LnACR (OR=1.344, 95% CI, 1.187-1.522, p=0.008) are predictors for albuminuria progression. Increased central arterial stiffness at baseline predicted future progression of albuminuria. Our results suggest the potential benefit of ameliorating central arterial stiffness to retard albuminuria progression in T2DM. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Development and Validation of the Learning Progression-Based Assessment of Modern Genetics in a High School Context

    ERIC Educational Resources Information Center

    Todd, Amber; Romine, William L.; Cook Whitt, Katahdin

    2017-01-01

    We describe the development, validation, and use of the "Learning Progression-Based Assessment of Modern Genetics" (LPA-MG) in a high school biology context. Items were constructed based on a current learning progression framework for genetics (Shea & Duncan, 2013; Todd & Kenyon, 2015). The 34-item instrument, which was tied to…

  20. MRI-based biomechanical parameters for carotid artery plaque vulnerability assessment.

    PubMed

    Speelman, Lambert; Teng, Zhongzhao; Nederveen, Aart J; van der Lugt, Aad; Gillard, Jonathan H

    2016-03-01

    Carotid atherosclerotic plaques are a major cause of ischaemic stroke. The biomechanical environment to which the arterial wall and plaque is subjected to plays an important role in the initiation, progression and rupture of carotid plaques. MRI is frequently used to characterize the morphology of a carotid plaque, but new developments in MRI enable more functional assessment of carotid plaques. In this review, MRI based biomechanical parameters are evaluated on their current status, clinical applicability, and future developments. Blood flow related biomechanical parameters, including endothelial wall shear stress and oscillatory shear index, have been shown to be related to plaque formation. Deriving these parameters directly from MRI flow measurements is feasible and has great potential for future carotid plaque development prediction. Blood pressure induced stresses in a plaque may exceed the tissue strength, potentially leading to plaque rupture. Multi-contrast MRI based stress calculations in combination with tissue strength assessment based on MRI inflammation imaging may provide a plaque stress-strength balance that can be used to assess the plaque rupture risk potential. Direct plaque strain analysis based on dynamic MRI is already able to identify local plaque displacement during the cardiac cycle. However, clinical evidence linking MRI strain to plaque vulnerability is still lacking. MRI based biomechanical parameters may lead to improved assessment of carotid plaque development and rupture risk. However, better MRI systems and faster sequences are required to improve the spatial and temporal resolution, as well as increase the image contrast and signal-to-noise ratio.

  1. Map of the spirit: Diagnosis and treatment of spiritual disease.

    PubMed

    Cantwell, Michael F

    2008-01-01

    Holistic medicine presupposes that the body, mind, and spirit all influence health. At present, however, we lack any overarching paradigm for assessing and treating the spiritual aspect of disease. Map of the Spirit presents a potentially universal framework of human spiritual development. In this framework, spiritual progress is determined by the balance between 2 forces-Seeking (forward-tending force) and Resistance (force opposing Seeking). Greater Seeking and lower Spiritual Satisfaction predispose toward greater Spiritual Stress, which adds to patients' overall stress and, thereby, influences their health. Addressing Spiritual Stress may improve patients' physical and psychological symptoms. This framework also proposes 4 universal and sequential stages of human spiritual development-Pre-awareness, Awareness, Commitment, and Union. Spiritual experiences, classified into 3 distinct types-Awareness, Commitment, and Union Experiences-are the principal markers between these spiritual stages. Map of the Spirit presents a potentially universal and easy-to-apply framework for assessing (1) how important spirituality is to patients' health, (2) where patients are spiritually, and (3) when and how best to intervene to facilitate their spiritual development and potentially improve their overall health.

  2. Probabilistic Assessment of Fracture Progression in Composite Structures

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.; Minnetyan, Levon; Mauget, Bertrand; Huang, Dade; Addi, Frank

    1999-01-01

    This report describes methods and corresponding computer codes that are used to evaluate progressive damage and fracture and to perform probabilistic assessment in built-up composite structures. Structural response is assessed probabilistically, during progressive fracture. The effects of design variable uncertainties on structural fracture progression are quantified. The fast probability integrator (FPI) is used to assess the response scatter in the composite structure at damage initiation. The sensitivity of the damage response to design variables is computed. The methods are general purpose and are applicable to stitched and unstitched composites in all types of structures and fracture processes starting from damage initiation to unstable propagation and to global structure collapse. The methods are demonstrated for a polymer matrix composite stiffened panel subjected to pressure. The results indicated that composite constituent properties, fabrication parameters, and respective uncertainties have a significant effect on structural durability and reliability. Design implications with regard to damage progression, damage tolerance, and reliability of composite structures are examined.

  3. Exposure to Violence in the Community Predicts Friendships with Academically Disengaged Peers During Middle Adolescence.

    PubMed

    Schwartz, David; Kelly, Brynn M; Mali, Luiza V; Duong, Mylien T

    2016-09-01

    Adolescents who have been exposed to violence in the community often experience subsequent difficulties with academic achievement. Because competence in the classroom is a salient developmental task during the adolescent years, outcomes in this critical context can then have broader implications for social and psychological functioning. In the current study, we tested a hypothesized progression in which the association between violence exposure and deficient achievement is presumed to potentiate friendships with academically disengaged peers. We followed 415 urban adolescents (53 % girls; average age of 14.6 years) for a one-year period, with two annual assessment of psychosocial functioning. Exposure to violence in the community and academic engagement were assessed with a self-report inventory; reciprocated friendships were assessed with a peer interview; and achievement was indexed based on a review of school records. Consistent with our hypotheses, neighborhood violence was associated with deficient classroom achievement. Poor achievement, in turn, mediated associations between community violence exposure and low academic engagement among friends. Our findings highlight pathways though which exposure to community violence potentially predicts later dysfunction.

  4. Results and Interpretations of the 1990 through 2000 Mathematics Assessment of the National Assessment of Educational Progress

    ERIC Educational Resources Information Center

    Kloosterman, Peter, Ed.; Lester, Frank K., Jr., Ed.

    2004-01-01

    Often referred to as "The Nation's Report Card," the mathematics assessments of the National Assessment of Educational Progress (NAEP) have come to be regarded by many policymakers as the primary yardstick by which to judge our schools' success in meeting national expectations. This monograph reports and interprets trends in NAEP…

  5. Economics Framework for the 2006 National Assessment of Educational Progress

    ERIC Educational Resources Information Center

    Buckles, Stephen; Melican, Claire

    2006-01-01

    This document provides a guide for the development of the 2006 National Assessment of Educational Progress (NAEP) Economics Assessment. The framework is designed to assess the outcomes of student education in and understanding of economics in grade 12 as part of NAEP. Economic literacy is defined as the ability to identify, analyze, and evaluate…

  6. Results from the Fourth Mathematics Assessment of the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    Lindquist, Mary Montgomery, Ed.

    The National Assessment of Educational Progress (NAEP) completed its fourth mathematics assessment during the 1985-86 school year and finished the analyses of the results in 1988. This monograph, prepared by an interpretive team of the National Council of Teachers of Mathematics, represents a comprehensive discussion of the results of the fourth…

  7. The 2008 National Assessment of Educational Progress (NAEP): A Visual Arts Replication Study

    ERIC Educational Resources Information Center

    Heid, Karen

    2016-01-01

    The 2008 National Assessment of Educational Progress (NAEP) Arts Assessment was administered to selected 8th grade students throughout the nation, and in 2009 the results from that administration were publicly reported. In the spring of 2010, building on the format and structure of the 2008 national assessment, the researcher administered a…

  8. Music-evoked emotions in schizophrenia.

    PubMed

    Abe, Daijyu; Arai, Makoto; Itokawa, Masanari

    2017-07-01

    Previous studies have reported that people with schizophrenia have impaired musical abilities. Here we developed a simple music-based assay to assess patient's ability to associate a minor chord with sadness. We further characterize correlations between impaired musical responses and psychiatric symptoms. We exposed participants sequentially to two sets of sound stimuli, first a C-major progression and chord, and second a C-minor progression and chord. Participants were asked which stimulus they associated with sadness, the first set, the second set, or neither. The severity of psychiatric symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). Study participants were 29 patients diagnosed with schizophrenia and 29 healthy volunteers matched in age, gender and musical background. 37.9% (95% confidence interval [CI]:19.1-56.7) of patients with schizophrenia associated the minor chord set as sad, compared with 97.9% (95%CI: 89.5-103.6) of controls. Four patients were diagnosed with treatment-resistant schizophrenia, and all four failed to associate the minor chord with sadness. Patients who did not recognize minor chords as sad had significantly higher scores on all PANSS subscales. A simple test allows music-evoked emotions to be assessed in schizophrenia patient, and may show potential relationships between music-evoked emotions and psychiatric symptoms. Copyright © 2016. Published by Elsevier B.V.

  9. Examining the Predictive Validity of a Dynamic Assessment of Decoding to Forecast Response Tier 2 to Intervention

    PubMed Central

    Cho, Eunsoo; Compton, Donald L.; Fuchs, Doug; Fuchs, Lynn S.; Bouton, Bobette

    2013-01-01

    The purpose of this study was to examine the role of a dynamic assessment (DA) of decoding in predicting responsiveness to Tier 2 small group tutoring in a response-to-intervention model. First-grade students (n=134) who did not show adequate progress in Tier 1 based on 6 weeks of progress monitoring received Tier 2 small-group tutoring in reading for 14 weeks. Student responsiveness to Tier 2 was assessed weekly with word identification fluency (WIF). A series of conditional individual growth curve analyses were completed that modeled the correlates of WIF growth (final level of performance and growth). Its purpose was to examine the predictive validity of DA in the presence of 3 sets of variables: static decoding measures, Tier 1 responsiveness indicators, and pre-reading variables (phonemic awareness, rapid letter naming, oral vocabulary, and IQ). DA was a significant predictor of final level and growth, uniquely explaining 3% – 13% of the variance in Tier 2 responsiveness depending on the competing predictors in the model and WIF outcome (final level of performance or growth). Although the additional variances explained uniquely by DA were relatively small, results indicate the potential of DA in identifying Tier 2 nonresponders. PMID:23213050

  10. Examining the predictive validity of a dynamic assessment of decoding to forecast response to tier 2 intervention.

    PubMed

    Cho, Eunsoo; Compton, Donald L; Fuchs, Douglas; Fuchs, Lynn S; Bouton, Bobette

    2014-01-01

    The purpose of this study was to examine the role of a dynamic assessment (DA) of decoding in predicting responsiveness to Tier 2 small-group tutoring in a response-to-intervention model. First grade students (n = 134) who did not show adequate progress in Tier 1 based on 6 weeks of progress monitoring received Tier 2 small-group tutoring in reading for 14 weeks. Student responsiveness to Tier 2 was assessed weekly with word identification fluency (WIF). A series of conditional individual growth curve analyses were completed that modeled the correlates of WIF growth (final level of performance and growth). Its purpose was to examine the predictive validity of DA in the presence of three sets of variables: static decoding measures, Tier 1 responsiveness indicators, and prereading variables (phonemic awareness, rapid letter naming, oral vocabulary, and IQ). DA was a significant predictor of final level and growth, uniquely explaining 3% to 13% of the variance in Tier 2 responsiveness depending on the competing predictors in the model and WIF outcome (final level of performance or growth). Although the additional variances explained uniquely by DA were relatively small, results indicate the potential of DA in identifying Tier 2 nonresponders. © Hammill Institute on Disabilities 2012.

  11. Processes regulating progressive nitrogen limitation under elevated carbon dioxide: a meta-analysis

    NASA Astrophysics Data System (ADS)

    Liang, Junyi; Qi, Xuan; Souza, Lara; Luo, Yiqi

    2016-05-01

    The nitrogen (N) cycle has the potential to regulate climate change through its influence on carbon (C) sequestration. Although extensive research has explored whether or not progressive N limitation (PNL) occurs under CO2 enrichment, a comprehensive assessment of the processes that regulate PNL is still lacking. Here, we quantitatively synthesized the responses of all major processes and pools in the terrestrial N cycle with meta-analysis of CO2 experimental data available in the literature. The results showed that CO2 enrichment significantly increased N sequestration in the plant and litter pools but not in the soil pool, partially supporting one of the basic assumptions in the PNL hypothesis that elevated CO2 results in more N sequestered in organic pools. However, CO2 enrichment significantly increased the N influx via biological N fixation and the loss via N2O emission, but decreased the N efflux via leaching. In addition, no general diminished CO2 fertilization effect on plant growth was observed over time up to the longest experiment of 13 years. Overall, our analyses suggest that the extra N supply by the increased biological N fixation and decreased leaching may potentially alleviate PNL under elevated CO2 conditions in spite of the increases in plant N sequestration and N2O emission. Moreover, our syntheses indicate that CO2 enrichment increases soil ammonium (NH4+) to nitrate (NO3-) ratio. The changed NH4+/NO3- ratio and subsequent biological processes may result in changes in soil microenvironments, above-belowground community structures and associated interactions, which could potentially affect the terrestrial biogeochemical cycles. In addition, our data synthesis suggests that more long-term studies, especially in regions other than temperate ones, are needed for comprehensive assessments of the PNL hypothesis.

  12. Tectal gliomas: assessment of malignant progression, clinical management, and quality of life in a supposedly benign neoplasm.

    PubMed

    Mohme, Malte; Fritzsche, Friederike S; Mende, Klaus C; Matschke, Jakob; Löbel, Ulrike; Kammler, Gertrud; Westphal, Manfred; Emami, Pedram; Martens, Tobias

    2018-06-01

    OBJECTIVE Tectal gliomas constitute a rare and inhomogeneous group of lesions with an uncertain clinical course. Because these supposedly benign tumors are frequently followed up by observation over many years, the authors undertook this analysis of their own case series in an effort to demonstrate that the clinical course is highly variable and that there is a potential for a progressive biology. METHODS Clinical data analysis of 23 cases of tectal glioma (involving 9 children and 14 adults) was performed retrospectively. Radiographic data were analyzed longitudinally and MR images were evaluated for tumor volume, contrast enhancement, and growth progression. Quality of life was assessed using the EORTC BN20 and C30 questionnaires during follow-up in a subgroup of patients. RESULTS The patients' mean age at diagnosis was 29.2 years. The main presenting symptom at diagnosis was hydrocephalus (80%). Six patients were treated by primary tumor resection (26.1%), 3 patients underwent biopsy followed by resection (13.1%), and 3 patients underwent biopsy only (13.1%). For additional treatment of hydrocephalus, 14 patients (60.9%) received shunts and/or endoscopic third ventriculostomy. Radiographic tumor progression was observed in 47.9% of the 23 cases. The mean time between diagnosis and growth progression was 51.5 months, and the mean time to contrast enhancement was 69.7 months. Histopathological analysis was obtained in 12 cases (52.2%), resulting in 5 cases of high-grade glioma (3 cases of glioblastoma multiforme [GBM], grade IV, and 2 of anaplastic astrocytoma, grade III), 5 cases of pilocytic astrocytoma, 1 diffuse astrocytoma, and 1 ganglioglioma. Malignant progression was observed in 2 cases, with 1 case progressing from a diffuse astrocytoma (grade II) to a GBM (grade IV) within a period of 13 years. Quality-of-life measurements demonstrated distinct functional deficits compared to a healthy sample as well as glioma control cohorts. CONCLUSIONS Analysis of this case series shows that a major subpopulation of tectal gliomas show progression and malignant transformation in children as well as in adolescents. These tumors therefore cannot be considered inert lesions and require histological confirmation and close follow-up. Quality-of-life questionnaires show that tectal glioma patients might benefit from special psychological support in emotional, social, and cognitive functionality.

  13. The effectiveness of Robot-Assisted Gait Training versus conventional therapy on mobility in severely disabled progressIve MultiplE sclerosis patients (RAGTIME): study protocol for a randomized controlled trial.

    PubMed

    Straudi, Sofia; Manfredini, Fabio; Lamberti, Nicola; Zamboni, Paolo; Bernardi, Francesco; Marchetti, Giovanna; Pinton, Paolo; Bonora, Massimo; Secchiero, Paola; Tisato, Veronica; Volpato, Stefano; Basaglia, Nino

    2017-02-27

    Gait and mobility impairments affect the quality of life (QoL) of patients with progressive multiple sclerosis (MS). Robot-assisted gait training (RAGT) is an effective rehabilitative treatment but evidence of its superiority compared to other options is lacking. Furthermore, the response to rehabilitation is multidimensional, person-specific and possibly involves functional reorganization processes. The aims of this study are: (1) to test the effectiveness on gait speed, mobility, balance, fatigue and QoL of RAGT compared to conventional therapy (CT) in progressive MS and (2) to explore changes of clinical and circulating biomarkers of neural plasticity. This will be a parallel-group, randomized controlled trial design with the assessor blinded to the group allocation of participants. Ninety-eight (49 per arm) progressive MS patients (EDSS scale 6-7) will be randomly assigned to receive twelve 2-h training sessions over a 4-week period (three sessions/week) of either: (1) RAGT intervention on a robotic-driven gait orthosis (Lokomat, Hocoma, Switzerland). The training parameters (torque of the knee and hip drives, treadmill speed, body weight support) are set during the first session and progressively adjusted during training progression or (2) individual conventional physiotherapy focusing on over-ground walking training performed with the habitual walking device. The same assessors will perform outcome measurements at four time points: baseline (before the first intervention session); intermediate (after six training sessions); end of treatment (after the completion of 12 sessions); and follow-up (after 3 months from the end of the training program). The primary outcome is gait speed, assessed by the Timed 25-Foot Walk Test. We will also assess walking endurance, balance, depression, fatigue and QoL as well as instrumental laboratory markers (muscle metabolism, cerebral venous hemodynamics, cortical activation) and circulating laboratory markers (rare circulating cell populations pro and anti-inflammatory cytokines/chemokines, growth factors, neurotrophic factors, coagulation factors, other plasma proteins suggested by transcriptomic analysis and metabolic parameters). The RAGT training is expected to improve mobility compared to the active control intervention in progressive MS. Unique to this study is the analysis of various potential markers of plasticity in relation with clinical outcomes. ClinicalTrials.gov, identifier: NCT02421731 . Registered on 19 January 2015 (retrospectively registered).

  14. 76 FR 2348 - National Assessment Governing Board: Proposed Information Collection

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-13

    ... collection techniques or other forms of information technology; and (5) estimates of capital or start-up... congressionally authorized National Assessment of Educational Progress (NAEP) reports to the public on the... Assessment of Educational Progress Authorization Act (Pub. L. 107-279). Among the Board's responsibilities is...

  15. Assessment Program Technical Progress Report, 1997-1998.

    ERIC Educational Resources Information Center

    Eickmeyer, Barbara; Hill, Stephen

    This Assessment Program Progress Report (APPR) records the institutional activities that have taken place at Coconino Community College (CCC) during the 1997-98 academic year. It presents models, timelines, accomplishments, and opportunities for improvement in the assessment practices at CCC. Implementation and outcomes information is included for…

  16. Benefits of State-by-State Comparisons.

    ERIC Educational Resources Information Center

    Phillips, Gary W.

    1991-01-01

    Suggests that the National Assessment of Educational Progress's (NAEP) Trial State Assessment (TSA) will provide reliable and valid state-by-state comparisons of what students have learned and will assess their progress over time. The TSA will also provide information on home learning environments, instructional practices, educational resources,…

  17. Longitudinal assessment of childhood optic gliomas: relationship between flicker visual evoked potentials and magnetic resonance imaging findings.

    PubMed

    Falsini, Benedetto; Ziccardi, Lucia; Lazzareschi, Ilaria; Ruggiero, Antonio; Placentino, Luca; Dickmann, Anna; Liotti, Lucia; Piccardi, Marco; Balestrazzi, Emilio; Colosimo, Cesare; Di Rocco, Concezio; Riccardi, Riccardo

    2008-05-01

    The aim of this study was to evaluate longitudinally functional and neuro-radiologic findings in childhood optic gliomas (OG), by comparing flicker visual evoked potentials (F-VEPs) with brain magnetic resonance imaging (MRI) changes. Fourteen children (age range: 1-13 years) with OGs underwent serial F-VEP, MRI and neuro-ophthalmic examinations over a 38 month (median, range: 6-76) follow-up. F-VEPs were elicited by 8 Hz sine-wave flicker stimuli presented in a mini-Ganzfeld. Contrast-enhanced MRI examinations were performed. Results of both tests were blindly assessed by independent evaluators. F-VEPs were judged to be improved, stable or worsened if changes in the amplitude and/or phase angle of the response exceeded the limits of test-retest variability (+/-90th percentile) established for the same patients. MRI results were judged to show regression, stabilization or progression of OG based on its changes in size (+/-20%) or extension. Two to seven pairs of F-VEP/MRI examinations per patient (median: 4) were collected. Based on a total of 38 pairs of F-VEP/MRI examinations, both tests agreed in showing worsening (progression), stabilization and improvement (regression) in 5, 15 and 10 cases, respectively. In 3 cases, F-VEPs showed a worsening and MRI a stabilization, while in 5 cases F-VEPs showed an improvement and MRI a stabilization. Agreement between F-VEP and MRI changes was 78.9% (95% CI: +/- 37%, K statistics = 0.67, P < 0.001). The results indicate that longitudinal F-VEP changes can predict changes in MRI-assessed OG size and extension, providing a non-invasive functional assay, complementary to neuro-imaging, for OG follow-up.

  18. Alcohol use of diabetes patients: the need for assessment and intervention.

    PubMed

    Engler, Patricia A; Ramsey, Susan E; Smith, Robert J

    2013-04-01

    It is well known that diabetes self-care behaviors are critical to disease progression. Unfortunately, many patients do not adhere to diabetes self-care recommendations despite their importance. Alcohol use has been identified as a barrier to diabetes self-care adherence. Excessive alcohol consumption not only negatively impacts diabetes self-care adherence but also affects the course of diabetes. Diabetes patients who are at-risk drinkers are likely to have poor diabetes treatment adherence, leading to increased morbidity and mortality. Alcohol consumption by diabetes patients is often inadequately assessed and addressed in their medical care. Brief interventions to reduce at-risk drinking have been well validated in a variety of patient populations and offer the potential to improve diabetes treatment adherence and outcome. Assessment and treatment of at-risk drinking could be readily incorporated into routine diabetes care. Strategies for brief assessment of and intervention for at-risk drinking are offered.

  19. Assessing the self-development potential of a pharmacy management practitioner through self-assessment survey.

    PubMed

    Granko, Robert P; Wolfe, Adam S; Kelley, Lindsey R; Morton, Carolyn S; Delgado, Osmel

    2015-01-15

    The self-development potential of pharmacy management practitioners related to self-management, team development, and network management was assessed. A survey instrument consisting of 12 self-assessment questions and 11 questions about demographics was distributed to pharmacy management practitioners to assess their abilities to manage themselves, their teams, and their networks. The tool was distributed by e-mail hyperlink to 190 potential respondents. Only surveys from respondents who had a pharmacy degree and direct supervisory capacity were analyzed. Respondents rated their progress toward meeting the three imperatives on a scale of 1-5. Responses to the questions were analyzed as ordinal data, with median responses used for assessment. A total of 160 responses were received via e-mail, 149 (93%) of which met the inclusion criteria. About half of all respondents were practicing at institutions of 600 beds or more and supervised at least five employees. The majority of respondents identified their abilities to manage themselves, their teams, and their networks as areas of strength but also acknowledged that using all three of these skills on a daily basis was an area of opportunity. Respondents generally identified management of their network as an area needing work. The majority of survey respondents identified their skills in self-, team, and network management as areas of strength. Respondents generally identified management of their network as an area needing work. Respondents also identified the use of all three imperatives on a daily basis as an area of opportunity for improvement. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  20. Road Maps for Learning: A Guide to the Navigation of Learning Progressions

    ERIC Educational Resources Information Center

    Black, Paul; Wilson, Mark; Yao, Shih-Ying

    2011-01-01

    The overall aim of this article is to analyze the relationships between the roles of assessment in pedagogy, the interactions between curriculum assessment and pedagogy, and the study of pupils' progression in learning. It is argued that well-grounded evidence of pupils' progressions in learning is crucial to the work of teachers, so that a method…

  1. Assessing the Crop-Water Status in Almond (Prunus dulcis Mill.) Trees via Thermal Imaging Camera Connected to Smartphone.

    PubMed

    García-Tejero, Iván Francisco; Ortega-Arévalo, Carlos José; Iglesias-Contreras, Manuel; Moreno, José Manuel; Souza, Luciene; Tavira, Simón Cuadros; Durán-Zuazo, Víctor Hugo

    2018-03-31

    Different tools are being implemented in order to improve the water management in agricultural irrigated areas of semiarid environments. Thermography has been progressively introduced as a promising technique for irrigation scheduling and the assessing of crop-water status, especially when deficit irrigation is being implemented. However, an important limitation is related to the cost of the actual cameras, this being a severe limitation to its practical usage by farmers and technicians. This work evaluates the potential and the robustness of a thermal imaging camera that is connected to smartphone (Flir One) recently developed by Flir Systems Inc. as a first step to assess the crop water status. The trial was developed in mature almond ( Prunus dulcis Mill.) trees that are subjected to different irrigation treatments. Thermal information obtained by the Flir One camera was deal with the thermal information obtained with a conventional Thermal Camera (Flir SC660) with a high resolution, and subsequently, confronted with other related plant physiological parameters (leaf water potential, Ψ leaf , and stomatal conductance, g s ). Thermal imaging camera connected to smartphone provided useful information in estimating the crop-water status in almond trees, being a potential promising tool to accelerate the monitoring process and thereby enhance water-stress management of almond orchards.

  2. Assessing the Crop-Water Status in Almond (Prunus dulcis Mill.) Trees via Thermal Imaging Camera Connected to Smartphone

    PubMed Central

    García-Tejero, Iván Francisco; Ortega-Arévalo, Carlos José; Iglesias-Contreras, Manuel; Moreno, José Manuel; Souza, Luciene; Tavira, Simón Cuadros; Durán-Zuazo, Víctor Hugo

    2018-01-01

    Different tools are being implemented in order to improve the water management in agricultural irrigated areas of semiarid environments. Thermography has been progressively introduced as a promising technique for irrigation scheduling and the assessing of crop-water status, especially when deficit irrigation is being implemented. However, an important limitation is related to the cost of the actual cameras, this being a severe limitation to its practical usage by farmers and technicians. This work evaluates the potential and the robustness of a thermal imaging camera that is connected to smartphone (Flir One) recently developed by Flir Systems Inc. as a first step to assess the crop water status. The trial was developed in mature almond (Prunus dulcis Mill.) trees that are subjected to different irrigation treatments. Thermal information obtained by the Flir One camera was deal with the thermal information obtained with a conventional Thermal Camera (Flir SC660) with a high resolution, and subsequently, confronted with other related plant physiological parameters (leaf water potential, Ψleaf, and stomatal conductance, gs). Thermal imaging camera connected to smartphone provided useful information in estimating the crop-water status in almond trees, being a potential promising tool to accelerate the monitoring process and thereby enhance water-stress management of almond orchards. PMID:29614740

  3. Assessing Teachers' Competencies to Read and Interpret Graphs from Learning Progress Assessment: Results from Tests and Interviews

    ERIC Educational Resources Information Center

    Zeuch, Nina; Förster, Natalie; Souvignier, Elmar

    2017-01-01

    Learning progress assessment (LPA) provides formative information about effectiveness of instructional decisions. Learning curves are usually presented as graphical illustrations. However, little is known about teachers understanding and interpreting of graphically presented information. An instrument to measure competencies in reading graphs from…

  4. Mathematics Framework for the 2013 National Assessment of Educational Progress

    ERIC Educational Resources Information Center

    National Assessment Governing Board, 2012

    2012-01-01

    Since 1973, the National Assessment of Educational Progress (NAEP) has gathered information about student achievement in mathematics. Results of these periodic assessments, produced in print and web-based formats, provide valuable information to a wide variety of audiences. They inform citizens about the nature of students' comprehension of the…

  5. National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    National Center for Education Statistics (ED), Washington, DC.

    The National Center for Education Statistics (NCES) recently unveiled a new Web site about the National Assessment of Educational Progress (NAEP), the "Nation's Report Card." This site (http://nces.ed.gov/nationsreportcard) provides easy access to a wealth of assessment information about the condition of education in the United States,…

  6. Civics Framework for the 2010 National Assessment of Educational Progress

    ERIC Educational Resources Information Center

    National Assessment Governing Board, 2009

    2009-01-01

    The National Assessment of Educational Progress (NAEP) is a survey mandated by the U.S. Congress to collect and report information about student achievement in various academic subjects, such as mathematics, science, reading, writing, history, geography, and civics. The National Assessment Governing Board sets policy and the overall dimensions…

  7. Evaluation of the National Assessment of Educational Progress: Next Steps

    ERIC Educational Resources Information Center

    Noell, Jay; Ginsburg, Alan

    2009-01-01

    The report, "Evaluation of the National Assessment of Educational Progress", provides a number of recommendations for addressing validity concerns about NAEP. This article identifies actions that could be taken by the Congress, the National Center for Education Statistics, and the National Assessment Governing Board--which share responsibility for…

  8. Study of Exclusion and Assessibility of Students with Disabilities in the 1994 Trial State Assessment (TSA) of the National Assessment of Educational Progress (NAEP).

    ERIC Educational Resources Information Center

    Stancavage, Fran; And Others

    The National Assessment of Educational Progress (NAEP), a survey of national trends in educational achievement, is attempting to expand its inclusion of students with disabilities or limitations that have previously caused them to be excluded from the assessment. The study described was a precursor to the 1996 changes in NAEP inclusion procedures.…

  9. Quantification of plasma exosome is a potential prognostic marker for esophageal squamous cell carcinoma.

    PubMed

    Matsumoto, Yasunori; Kano, Masayuki; Akutsu, Yasunori; Hanari, Naoyuki; Hoshino, Isamu; Murakami, Kentaro; Usui, Akihiro; Suito, Hiroshi; Takahashi, Masahiko; Otsuka, Ryota; Xin, Hu; Komatsu, Aki; Iida, Keiko; Matsubara, Hisahiro

    2016-11-01

    Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established. Fluorescence imaging was performed on tumors and plasma exosomes harvested from mice. GFP-positive small vesicles were confirmed in the plasma obtained from TE2-CD63-GFP tumor-bearing mice. Patient plasma was collected in Chiba University Hospital (n=86). Exosomes were extracted from 100 µl of the plasma and quantified by acetylcholinesterase (AChE) activity. The relationship between exosome quantification and the patient clinical characteristics was assessed. The quantification of exosomes isolated from the patient plasma revealed that esophageal cancer patients (n=66) expressed higher exosome levels than non-malignant patients (n=20) (P=0.0002). Although there was no correlation between the tumor progression and the exosome levels, exosome number was the independent prognostic marker and low levels of exosome predicted a poor prognosis (P=0.03). In conclusion, exosome levels may be useful as an independent prognostic factor for ESCC patients.

  10. Meta-analysis of the predictive value of DNA aneuploidy in malignant transformation of oral potentially malignant disorders.

    PubMed

    Alaizari, Nader A; Sperandio, Marcelo; Odell, Edward W; Peruzzo, Daiane; Al-Maweri, Sadeq A

    2018-02-01

    DNA aneuploidy is an imbalance of chromosomal DNA content that has been highlighted as a predictor of biological behavior and risk of malignant transformation. To date, DNA aneuploidy in oral potentially malignant diseases (OPMD) has been shown to correlate strongly with severe dysplasia and high-risk lesions that appeared non-dysplastic can be identified by ploidy analysis. Nevertheless, the prognostic value of DNA aneuploidy in predicting malignant transformation of OPMD remains to be validated. The aim of this meta-analysis was to assess the role of DNA aneuploidy in predicting malignant transformation in OPMD. The questions addressed were (i) Is DNA aneuploidy a useful marker to predict malignant transformation in OPMD? (ii) Is DNA diploidy a useful negative marker of malignant transformation in OPMD? These questions were addressed using the PECO method. Five studies assessing aneuploidy as a risk marker of malignant change were pooled into the meta-analysis. Aneuploidy was found to be associated with a 3.12-fold increased risk to progress into cancer (RR=3.12, 95% CI 1.86-5.24). Based on the five studies meta-analyzed, "no malignant progression" was more likely to occur in DNA diploid OPMD by 82% when compared to aneuploidy (RR=0.18, 95% CI 0.08-0.41). In conclusion, aneuploidy is a useful marker of malignant transformation in OPMD, although a diploid result should be interpreted with caution. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. U.S. History Framework for the 2006 National Assessment of Educational Progress

    ERIC Educational Resources Information Center

    US Department of Education, 2006

    2006-01-01

    This document provides a guide for the development of the 2006 National Assessment of Education Progress (NAEP) U.S. History Assessment. NAEP measures the U.S. history knowledge and skills of students in grades 4, 8, and 12. According to the NAEP U.S. history framework, the assessment should be organized around three dimensions: historical themes,…

  12. The Nation's Report Card: Science 2011. National Assessment of Educational Progress at Grade 8. NCES 2012-465

    ERIC Educational Resources Information Center

    National Center for Education Statistics, 2012

    2012-01-01

    This report presents results of the National Assessment of Educational Progress (NAEP) U.S. science assessment in 2011. A representative sample of 122,000 eighth-graders participated in the 2011 NAEP science assessment, which is designed to measure students' knowledge and abilities in the areas of physical science, life science, and Earth and…

  13. National Assessment of Educational Progress Grade 12 Preparedness Research College Course Content Analysis Study: Final Report

    ERIC Educational Resources Information Center

    Educational Policy Improvement Center, 2014

    2014-01-01

    The National Assessment Governing Board is an independent, bipartisan organization that sets policy for the National Assessment of Educational Progress (NAEP). The Governing Board established the NAEP Program of 12th Grade Preparedness Research to assess what NAEP can report on the academic preparedness of 12th grade students entering college and…

  14. "Here we're all in the same boat"--a qualitative study of group based rehabilitation for sick-listed citizens with chronic pain.

    PubMed

    Andersen, Lotte Nygaard; Kohberg, Maria; Herborg, Lene Gram; Søgaard, Karen; Roessler, Kirsten Kaya

    2014-08-01

    Musculoskeletal pain impacts upon everyday life. A degree of chronicity may pose an increased risk of sickness absence. One of two rehabilitative interventions, "Tailored Physical Activity" or "Chronic Pain Self-Management Program", was offered to sick-listed citizens who experienced pain. The objectives of this paper were to: (1) Assess what factors are experienced as problematic for sick-listed citizens in everyday life with chronic pain, and (2) Evaluate the significance of two distinct rehabilitative interventions on the future everyday lives of sick-listed citizens. Seven semi-structured interviews with sick-listed citizens were analyzed using a phenomenological-hermeneutical approach. Results were discussed by applying the theoretical framework of Antonovsky's salutogenetic model and Yaloms principles for group psychology. The potential for development of citizen's coping is evaluated based on Roessler's notion of progression. The analysis revealed four main themes: (1) Living with pain and unemployment; (2) "Putting my foot down" and "asking for help"; (3) Significance of the group, including instructors, and; (4) Aspects significant to progression. Unemployment is a major life event that promotes stress and can be accompanied by problems related to depressed mood, acceptance of the life situation, feelings of not being useful, feelings of losing control and identity conflicts. Group characteristics that gave a significant basis for progression in the self-management program are both emotional and instrumental, while the physical training program offers a "here-and-now"-experience and motivation to participate. This study indicates that the self-management program could potentially improve coping while the physical activity program revealed one example of a means of progression. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  15. Cryopreservation of stallion spermatozoa using different cryoprotectants and combinations of cryoprotectants.

    PubMed

    Wu, Zhuangyuan; Zheng, Xinbiao; Luo, Yongming; Huo, Fei; Dong, Hong; Zhang, Guoting; Yu, Weihao; Tian, Fang; He, Liangjun; Chen, Jingbo

    2015-12-01

    The present study investigates the effects of five cryoprotectants (CPAs) and cryoprotectant combinations on the post-thaw total motility, progressive motility, viability, mitochondrial membrane potential and acrosome integrity in stallion spermatozoa. In Experiment 1, the objective was to compare the impact of different concentrations (2.5%, 3.5% and 5%) of a single CPA, including glycerol (Gly), ethylene glycol (EG), dimethyl sulphoxide (DMSO), methyl formamide (MF), and dimethylformamide (DMF) for stallion spermatozoa cryopreservation. In Experiment 2, two or more CPAs were used to assess whether this improved post-thaw spermatozoa quality. Gly, MF and DMF, were used to prepare seven combinations of freezing extender with different mixtures of cryoprotectant, and the 3.5% Gly, MF and DMF were used as a control group. The results show that post-thaw total motility, progressive motility, viability, and mitochondrial membrane potential for all concentrations of EG and DMSO were less than the 3.5% and 5% Gly and MF and 2.5% and 3.5% DMF (P<0.05). Use of the 3.5% concentration resulted in the greater post-thaw total motility and progressive motility than the 2.5% and 5% concentrations for all CPAs. The results for the use of different combinations of cryoprotectant indicate there are differences in progressive motility and viability. The viability with the use of Gly(2/3)+MF(1/3) was 44.65% and was greater than the Gly(1/3)+MF(1/3)+DMF(1/3) (30.96%), MF(2/3)+DMF(1/3) (35.05%), Gly (32.21%) and MF(33.76%) (P<0.05). The progressive motility with the use of the MF(2/3)+Gly(1/3) combination was 36.0% and was greater than in the DMF (25.0%) and MF(2/3)+DMF(1/3) (22.7%) (P<0.05). These results suggest that using the appropriate cryoprotectant combination instead of a single cryoprotectant can improve horse spermatozoa cryopreservation. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Ferret and Pig Models of Cystic Fibrosis: Prospects and Promise for Gene Therapy

    PubMed Central

    Yan, Ziying; Stewart, Zoe A.; Sinn, Patrick L.; Olsen, John C.; Hu, Jim; McCray, Paul B.

    2015-01-01

    Abstract Large animal models of genetic diseases are rapidly becoming integral to biomedical research as technologies to manipulate the mammalian genome improve. The creation of cystic fibrosis (CF) ferrets and pigs is an example of such progress in animal modeling, with the disease phenotypes in the ferret and pig models more reflective of human CF disease than mouse models. The ferret and pig CF models also provide unique opportunities to develop and assess the effectiveness of gene and cell therapies to treat affected organs. In this review, we examine the organ disease phenotypes in these new CF models and the opportunities to test gene therapies at various stages of disease progression in affected organs. We then discuss the progress in developing recombinant replication-defective adenoviral, adeno-associated viral, and lentiviral vectors to target genes to the lung and pancreas in ferrets and pigs, the two most affected organs in CF. Through this review, we hope to convey the potential of these new animal models for developing CF gene and cell therapies. PMID:25675143

  17. The National Institutes of Health Center for Human Immunology, Autoimmunity, and Inflammation: history and progress.

    PubMed

    Dickler, Howard B; McCoy, J Philip; Nussenblatt, Robert; Perl, Shira; Schwartzberg, Pamela A; Tsang, John S; Wang, Ena; Young, Neil S

    2013-05-01

    The Center for Human Immunology, Autoimmunity, and Inflammation (CHI) is an exciting initiative of the NIH intramural program begun in 2009. It is uniquely trans-NIH in support (multiple institutes) and leadership (senior scientists from several institutes who donate their time). Its goal is an in-depth assessment of the human immune system using high-throughput multiplex technologies for examination of immune cells and their products, the genome, gene expression, and epigenetic modulation obtained from individuals both before and after interventions, adding information from in-depth clinical phenotyping, and then applying advanced biostatistical and computer modeling methods for mining these diverse data. The aim is to develop a comprehensive picture of the human "immunome" in health and disease, elucidate common pathogenic pathways in various diseases, identify and validate biomarkers that predict disease progression and responses to new interventions, and identify potential targets for new therapeutic modalities. Challenges, opportunities, and progress are detailed. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  18. Reduced cellularity of bone marrow in multiple sclerosis with decreased MSC expansion potential and premature ageing in vitro.

    PubMed

    Redondo, Juliana; Sarkar, Pamela; Kemp, Kevin; Virgo, Paul F; Pawade, Joya; Norton, Aimie; Emery, David C; Guttridge, Martin G; Marks, David I; Wilkins, Alastair; Scolding, Neil J; Rice, Claire M

    2017-05-01

    Autologous bone-marrow-derived cells are currently employed in clinical studies of cell-based therapy in multiple sclerosis (MS) although the bone marrow microenvironment and marrow-derived cells isolated from patients with MS have not been extensively characterised. To examine the bone marrow microenvironment and assess the proliferative potential of multipotent mesenchymal stromal cells (MSCs) in progressive MS. Comparative phenotypic analysis of bone marrow and marrow-derived MSCs isolated from patients with progressive MS and control subjects was undertaken. In MS marrow, there was an interstitial infiltrate of inflammatory cells with lymphoid (predominantly T-cell) nodules although total cellularity was reduced. Controlling for age, MSCs isolated from patients with MS had reduced in vitro expansion potential as determined by population doubling time, colony-forming unit assay, and expression of β-galactosidase. MS MSCs expressed reduced levels of Stro-1 and displayed accelerated shortening of telomere terminal restriction fragments (TRF) in vitro. Our results are consistent with reduced proliferative capacity and ex vivo premature ageing of bone-marrow-derived cells, particularly MSCs, in MS. They have significant implication for MSC-based therapies for MS and suggest that accelerated cellular ageing and senescence may contribute to the pathophysiology of progressive MS. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding for this study was provided by the Medical Research Council, UK (grant no. MR/K004166/1). The ACTiMuS study is sup-ported by the Silverman Family Foundation, Multiple Sclerosis Trust, Rosetree’s Trust, Catholic Bishops of England and Wales and Friends of Frenchay and SIAMMS-II by the Sir Halley Stewart Trust. C.M.R., P.S., and K.K. received support from the Burden Neurological Institute.

  19. EPA releases progress report on hydraulic fracturing study

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2013-01-01

    The U.S. Environmental Protection Agency (EPA) provided a 21 December progress report on its ongoing national study about the potential impacts of hydraulic fracturing on drinking water resources. The agency said that a draft of the congressionally requested study will be released in 2014 for public and peer review and that its progress report does not draw conclusions about the potential impacts of hydraulic fracturing, often referred to as fracking.

  20. Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis.

    PubMed

    Ashrafian, Houman; O'Flaherty, Linda; Adam, Julie; Steeples, Violetta; Chung, Yuen-Li; East, Phil; Vanharanta, Sakari; Lehtonen, Heli; Nye, Emma; Hatipoglu, Emine; Miranda, Melroy; Howarth, Kimberley; Shukla, Deepa; Troy, Helen; Griffiths, John; Spencer-Dene, Bradley; Yusuf, Mohammed; Volpi, Emanuela; Maxwell, Patrick H; Stamp, Gordon; Poulsom, Richard; Pugh, Christopher W; Costa, Barbara; Bardella, Chiara; Di Renzo, Maria Flavia; Kotlikoff, Michael I; Launonen, Virpi; Aaltonen, Lauri; El-Bahrawy, Mona; Tomlinson, Ian; Pollard, Patrick J

    2010-11-15

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by mutations in the Krebs cycle enzyme fumarate hydratase (FH). It has been proposed that "pseudohypoxic" stabilization of hypoxia-inducible factor-α (HIF-α) by fumarate accumulation contributes to tumorigenesis in HLRCC. We hypothesized that an additional direct consequence of FH deficiency is the establishment of a biosynthetic milieu. To investigate this hypothesis, we isolated primary mouse embryonic fibroblast (MEF) lines from Fh1-deficient mice. As predicted, these MEFs upregulated Hif-1α and HIF target genes directly as a result of FH deficiency. In addition, detailed metabolic assessment of these MEFs confirmed their dependence on glycolysis, and an elevated rate of lactate efflux, associated with the upregulation of glycolytic enzymes known to be associated with tumorigenesis. Correspondingly, Fh1-deficient benign murine renal cysts and an advanced human HLRCC-related renal cell carcinoma manifested a prominent and progressive increase in the expression of HIF-α target genes and in genes known to be relevant to tumorigenesis and metastasis. In accord with our hypothesis, in a variety of different FH-deficient tissues, including a novel murine model of Fh1-deficient smooth muscle, we show a striking and progressive upregulation of a tumorigenic metabolic profile, as manifested by increased PKM2 and LDHA protein. Based on the models assessed herein, we infer that that FH deficiency compels cells to adopt an early, reversible, and progressive protumorigenic metabolic milieu that is reminiscent of that driving the Warburg effect. Targets identified in these novel and diverse FH-deficient models represent excellent potential candidates for further mechanistic investigation and therapeutic metabolic manipulation in tumors. Copyright © 2010 AACR.

  1. Combinatorial markers of mild cognitive impairment conversion to Alzheimer's disease--cytokines and MRI measures together predict disease progression.

    PubMed

    Furney, Simon J; Kronenberg, Deborah; Simmons, Andrew; Güntert, Andreas; Dobson, Richard J; Proitsi, Petroula; Wahlund, Lars Olof; Kloszewska, Iwona; Mecocci, Patrizia; Soininen, Hilkka; Tsolaki, Magda; Vellas, Bruno; Spenger, Christian; Lovestone, Simon

    2011-01-01

    Progression of people presenting with Mild Cognitive Impairment (MCI) to dementia is not certain and it is not possible for clinicians to predict which people are most likely to convert. The inability of clinicians to predict progression limits the use of MCI as a syndrome for treatment in prevention trials and, as more people present with this syndrome in memory clinics, and as earlier diagnosis is a major goal of health services, this presents an important clinical problem. Some data suggest that CSF biomarkers and functional imaging using PET might act as markers to facilitate prediction of conversion. However, both techniques are costly and not universally available. The objective of our study was to investigate the potential added benefit of combining biomarkers that are more easily obtained in routine clinical practice to predict conversion from MCI to Alzheimer's disease. To explore this we combined automated regional analysis of structural MRI with analysis of plasma cytokines and chemokines and compared these to measures of APOE genotype and clinical assessment to assess which best predict progression. In a total of 205 people with MCI, 77 of whom subsequently converted to Alzheimer's disease, we find biochemical markers of inflammation to be better predictors of conversion than APOE genotype or clinical measures (Area under the curve (AUC) 0.65, 0.62, 0.59 respectively). In a subset of subjects who also had MRI scans the combination of serum markers of inflammation and MRI automated imaging analysis provided the best predictor of conversion (AUC 0.78). These results show that the combination of imaging and cytokine biomarkers provides an improvement in prediction of MCI to AD conversion compared to either datatype alone, APOE genotype or clinical data and an accuracy of prediction that would have clinical utility.

  2. Advancing bioluminescence imaging technology for the evaluation of anticancer agents in the MDA-MB-435-HAL-Luc mammary fat pad and subrenal capsule tumor models.

    PubMed

    Zhang, Cathy; Yan, Zhengming; Arango, Maria E; Painter, Cory L; Anderes, Kenna

    2009-01-01

    Tumors grafted s.c. or under the mammary fat pad (MFP) rarely develop efficient metastasis. By applying bioluminescence imaging (BLI) technology, the MDA-MB-435-HAL-Luc subrenal capsule (SRC) model was compared with the MFP model for disease progression, metastatic potential, and response to therapy. The luciferase-expressing MDA-MB-435-HAL-Luc cell line was used in both MFP and SRC models. BLI technology allowed longitudinal assessment of disease progression and the therapeutic response to PD-0332991, Avastin, and docetaxel. Immunohistochemical analysis of Ki67 and CD31 staining in the primary tumors was compared in these models. Caliper measurement was used in the MFP model to validate the BLI quantification of primary tumors. The primary tumors in MDA-MB-435-HAL-Luc MFP and SRC models displayed comparable growth rates and vascularity. However, tumor-bearing mice in the SRC model developed lung metastases much earlier (4 weeks) than in the MFP model (>7 weeks), and the metastatic progression contributed significantly to the survival time. In the MFP model, BLI and caliper measurements were comparable for quantifying palpable tumors, but BLI offered an advantage for detecting the primary tumors that fell below a palpable threshold and for visualizing metastases. In the SRC model, BLI allowed longitudinal assessment of the antitumor and antimetastatic effects of PD-0332991, Avastin, and docetaxel, and the results correlated with the survival benefits of these agents. The MDA-MB-435-HAL-Luc SRC model and the MFP model displayed differences in disease progression. BLI is an innovative approach for developing animal models and creates opportunities for improving preclinical evaluations of anticancer agents.

  3. Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN.

    PubMed

    Kilday, John-Paul; Caldarelli, Massimo; Massimi, Luca; Chen, Robert Hsin-Hung; Lee, Yi Yen; Liang, Muh-Lii; Parkes, Jeanette; Naiker, Thuran; van Veelen, Marie-Lise; Michiels, Erna; Mallucci, Conor; Pettorini, Benedetta; Meijer, Lisethe; Dorfer, Christian; Czech, Thomas; Diezi, Manuel; Schouten-van Meeteren, Antoinette Y N; Holm, Stefan; Gustavsson, Bengt; Benesch, Martin; Müller, Hermann L; Hoffmann, Anika; Rutkowski, Stefan; Flitsch, Joerg; Escherich, Gabriele; Grotzer, Michael; Spoudeas, Helen A; Azquikina, Kristian; Capra, Michael; Jiménez-Guerra, Rolando; MacDonald, Patrick; Johnston, Donna L; Dvir, Rina; Constantini, Shlomi; Kuo, Meng-Fai; Yang, Shih-Hung; Bartels, Ute

    2017-10-01

    Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear. We report the retrospective experiences of several global centers using intracystic interferon-alpha. European Société Internationale d'Oncologie Pédiatrique and International Society for Pediatric Neurosurgery centers were contacted to submit a datasheet capturing pediatric patients with cystic craniopharyngiomas who had received intracystic interferon-alpha. Patient demographics, administration schedules, adverse events, and outcomes were obtained. Progression was clinical or radiological (cyst reaccumulation, novel cysts, or solid growth). Fifty-six children (median age, 6.3 y) from 21 international centers were identified. Median follow-up from diagnosis was 5.1 years (0.3-17.7 y). Lesions were cystic (n = 22; 39%) or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%) patients before interferon use. In such cases, further progression was delayed by intracystic interferon compared with the preceding therapy for cystic lesions (P = 0.0005). Few significant attributable side effects were reported. Progression post interferon occurred in 42 patients (median 14 mo; 0-8 y), while the estimated median time to definitive therapy post interferon was 5.8 (1.8-9.7) years. Intracystic interferon-alpha can delay disease progression and potentially offer a protracted time to definitive surgery or radiotherapy in pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile compared with other therapeutic modalities-important factors for this developing age group. A prospective, randomized international clinical trial assessment is warranted. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  4. Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration

    PubMed Central

    Merle, Bénédicte M. J.; Silver, Rachel E.; Rosner, Bernard; Seddon, Johanna M.

    2017-01-01

    Purpose There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Methods Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. Results There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43–0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39–0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53–1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50–0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. Conclusions A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss. PMID:28892825

  5. Sustainability Indicators and Metrics

    EPA Science Inventory

    Sustainability is about preserving human existence. Indicators and metrics are absolutely necessary to provide at least a semi-quantitative assessment of progress towards or away from sustainability. Otherwise, it becomes impossible to objectively assess whether progress is bei...

  6. Glaucoma progression detection: agreement, sensitivity, and specificity of expert visual field evaluation, event analysis, and trend analysis.

    PubMed

    Antón, Alfonso; Pazos, Marta; Martín, Belén; Navero, José Manuel; Ayala, Miriam Eleonora; Castany, Marta; Martínez, Patricia; Bardavío, Javier

    2013-01-01

    To assess sensitivity, specificity, and agreement among automated event analysis, automated trend analysis, and expert evaluation to detect glaucoma progression. This was a prospective study that included 37 eyes with a follow-up of 36 months. All had glaucomatous disks and fields and performed reliable visual fields every 6 months. Each series of fields was assessed with 3 different methods: subjective assessment by 2 independent teams of glaucoma experts, glaucoma/guided progression analysis (GPA) event analysis, and GPA (visual field index-based) trend analysis. Kappa agreement coefficient between methods and sensitivity and specificity for each method using expert opinion as gold standard were calculated. The incidence of glaucoma progression was 16% to 18% in 3 years but only 3 cases showed progression with all 3 methods. Kappa agreement coefficient was high (k=0.82) between subjective expert assessment and GPA event analysis, and only moderate between these two and GPA trend analysis (k=0.57). Sensitivity and specificity for GPA event and GPA trend analysis were 71% and 96%, and 57% and 93%, respectively. The 3 methods detected similar numbers of progressing cases. The GPA event analysis and expert subjective assessment showed high agreement between them and moderate agreement with GPA trend analysis. In a period of 3 years, both methods of GPA analysis offered high specificity, event analysis showed 83% sensitivity, and trend analysis had a 66% sensitivity.

  7. Evaluation of Overall Response Rate and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Immunotherapy Trials.

    PubMed

    Mushti, Sirisha L; Mulkey, Flora; Sridhara, Rajeshwari

    2018-05-15

    Purpose: With the approval of immunotherapies for a variety of indications, methods to assess treatment benefit addressing the response patterns observed are important. We evaluated RECIST criteria-based overall response rate (ORR) and progression-free survival (PFS) as potential surrogate endpoints of overall survival (OS), and explored a modified definition of PFS by altering the threshold percentage determining disease progression to assess the association with survival benefit in immunotherapy trials. Experimental Design: Thirteen randomized, multicenter, active-control trials containing immunotherapeutic agents submitted to the FDA were analyzed. Associations between treatment effects of ORR, PFS, modified PFS, and OS were evaluated at individual and trial levels. Patient-level responder analysis was performed for PFS and OS. Results: The coefficient of determination ( R ²) measured the strength of associations, where values near 1 imply surrogacy and values close to 0 suggest no association. At the trial level, the association between hazard ratios (HR) of PFS and OS was R 2 = 0.1303, and between the odds ratio (OR) of ORR and HR of OS was R 2 = 0.1277. At the individual level, the Spearman rank correlation coefficient between PFS and OS was 0.61. Trial-level associations between modified PFS and OS ranged between 0.07 and 0.1, and individual-level correlations were approximately 0.6. HRs of PFS and OS for responders versus nonresponders were 0.129 [95% confidence interval (CI), 0.11-0.15] and 0.118 (95% CI, 0.11-0.13), respectively. Conclusions: Although responders exhibited longer survival and PFS than nonresponders, the trial-level and individual-level associations were weak between PFS/ORR and OS. Modifications to PFS did not improve associations. Clin Cancer Res; 24(10); 2268-75. ©2018 AACR See related commentary by Korn and Freidlin, p. 2239 . ©2018 American Association for Cancer Research.

  8. Is the Autism Treatment Evaluation Checklist a Useful Tool for Monitoring Progress in Children with Autism Spectrum Disorders?

    ERIC Educational Resources Information Center

    Magiati, I.; Moss, J.; Yates, R.; Charman, T.; Howlin, P.

    2011-01-01

    Background: There are few well validated brief measures that can be used to assess the general progress of young children with autism spectrum disorders (ASD) over time. In the present study, the Autism Treatment Evaluation Checklist (ATEC) was used as part of a comprehensive assessment battery to monitor the progress of 22 school-aged children…

  9. Region- and age-dependent alterations of glial-neuronal metabolic interactions correlate with CNS pathology in a mouse model of globoid cell leukodystrophy.

    PubMed

    Meisingset, Tore Wergeland; Ricca, Alessandra; Neri, Margherita; Sonnewald, Ursula; Gritti, Angela

    2013-07-01

    Globoid cell leukodystrophy (GLD) or Krabbe disease is a lysosomal storage disorder caused by genetic defects in the expression and activity of galactosylceramidase, a key enzyme in the catabolism of myelin-enriched sphingolipids. While there are several histologic, biochemical, and functional studies on GLD, correlations between morphologic and biochemical alterations in central nervous system (CNS) tissues during disease progression are lacking. Here, we combined immunohistochemistry and metabolic analysis using (1)H and (13)C magnetic resonance (MR) spectra of spinal cord, cerebellum, and forebrain to investigate glial-neuronal metabolic interactions and dysfunction in a GLD murine model that recapitulates the human pathology. In order to assess the temporal- and region-dependent disease progression and the potential metabolic correlates, we investigated CNS tissues at mildly symptomatic and fully symptomatic stages of the disease. When compared with age-matched controls, GLD mice showed glucose hypometabolism, alterations in neurotransmitter content, N-acetylaspartate, N-acetylaspartylglutamate, and osmolytes levels. Notably, age- and region-dependent patterns of metabolic disturbances were in close agreement with the progression of astrogliosis, microglia activation, apoptosis, and neurodegeneration. We suggest that MR spectroscopy could be used in vivo to monitor disease progression, as well as ex vivo and in vivo to provide criteria for the outcome of experimental therapies.

  10. Astaxanthin protects against early burn-wound progression in rats by attenuating oxidative stress-induced inflammation and mitochondria-related apoptosis

    PubMed Central

    Fang, Quan; Guo, Songxue; Zhou, Hanlei; Han, Rui; Wu, Pan; Han, Chunmao

    2017-01-01

    Burn-wound progression can occur in the initial or peri-burn area after a deep burn injury. The stasis zone has a higher risk of deterioration mediated by multiple factors but is also considered salvageable. Astaxanthin (ATX), which is extracted from some marine organisms, is a natural compound with a strong antioxidant effect that has been reported to attenuate organ injuries caused by traumatic injuries. Hence, we investigated the potential effects of ATX on preventing early burn-wound progression. A classic “comb” burn rat model was established in this study for histological and biological assessments, which revealed that ATX, particularly higher doses, alleviated histological deterioration in the stasis zone. Additionally, we observed dose-dependent improvements in oxidative stress and the release of inflammatory mediators after ATX treatment. Furthermore, ATX dose-dependently attenuated burn-induced apoptosis in the wound areas, and this effect was accompanied by increases in Akt and Bad phosphorylation and a downregulation of cytochrome C and caspase expression. In addition, the administration of Ly 294002 further verified the effect of ATX. In summary, we demonstrated that ATX protected against early burn-wound progression in a rat deep-burn model. This protection might be mediated by the attenuation of oxidative stress-induced inflammation and mitochondria-related apoptosis. PMID:28128352

  11. Chemoprevention of Barrett's Esophagus and Esophageal Adenocarcinoma.

    PubMed

    Bresalier, Robert S

    2018-06-12

    Barrett's esophagus is common in Western countries, but progression to esophageal adenocarcinoma is uncommon. Chemoprevention therefore needs to consider whether benefits outweigh risks given an otherwise healthy population. This will depend on the particular population at risk and the relative safety of a potential preventive agent. Most evidence regarding the potential benefit of chemoprevention of Barrett's esophagus and prevention of progression to esophageal adenocarcinoma is based on observational studies such as case-control and cohort studies. Given the potential benefits and relatively low risks, patients with BE should receive once-daily PPI therapy, but routine use of twice-daily PPI is not recommended unless necessitated by poor control of reflux symptoms or esophagitis. Recent data suggest that the inverse associations between aspirin/NSAID use and esophageal adenocarcinoma may be the result of reducing neoplastic progression (from metaplasia to dysplasia and carcinoma) rather than initiation of Barrett's esophagus. While substantial associative data suggest a potential benefit of aspirin and nonaspirin NSAIDs in reducing the risk of progression of Barrett's esophagus, the low risk of progression and the potential risks (gastrointestinal bleeding, complicated ulcer disease, hemorrhagic stroke) do not warrant routine use, unless dictated by cardiovascular risk. Chemoprevention after mucosal ablation in those at highest risk of post-ablation recurrence (dysplastic Barrett's) is currently under investigation.

  12. Fishing in acid waters: A vulnerability assessment of the Norwegian fishing industry in the face of increasing ocean acidification.

    PubMed

    Heinrich, Luise; Krause, Torsten

    2017-07-01

    Ocean acidification (OA) describes a change in the ocean's carbonate chemistry. Whereas its chemical processes are largely understood, the biological and socioeconomic consequences particularly in relation to fisheries are less known. Norway is a major fishing nation worldwide and is potentially affected by OA. To improve the understanding of the socioeconomic consequences of OA, we conducted a risk assessment among the Norwegian counties using a modified version of a risk assessment framework introduced in the Intergovernmental Panel on Climate Change's "Special Report: Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation," which considers risk to be the sum of hazard, exposure, and vulnerability. Our results show that about 13 of 19 counties are likely to experience moderate to high risk from OA. We highlight that the success of integrated risk assessments highly depends on the availability of detailed environmental, economic, and societal data. In the case of Norway, modeling data regarding the progress of OA, improved information on potential biological impacts on a larger number of species, and statistical data on social variables are required. We conclude that although still in its infancy, integrated risk assessments are important prerequisites for any form of interdisciplinary research on OA and the development of successful response strategies. Integr Environ Assess Manag 2017;13:778-789. ©2016 SETAC. © 2016 SETAC.

  13. Progressive multiple sclerosis, cognitive function, and quality of life.

    PubMed

    Højsgaard Chow, Helene; Schreiber, Karen; Magyari, Melinda; Ammitzbøll, Cecilie; Börnsen, Lars; Romme Christensen, Jeppe; Ratzer, Rikke; Soelberg Sørensen, Per; Sellebjerg, Finn

    2018-02-01

    Patients with progressive multiple sclerosis (MS) often have cognitive impairment in addition to physical impairment. The burden of cognitive and physical impairment progresses over time, and may be major determinants of quality of life. The aim of this study was to assess to which degree quality of life correlates with physical and cognitive function in progressive MS. This is a retrospective study of 52 patients with primary progressive ( N  = 18) and secondary progressive MS ( N  = 34). Physical disability was assessed using the Expanded Disability Status Scale, Timed 25 Foot Walk (T25FW) test and 9-Hole Peg Test (9HPT). Cognitive function was assessed using Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test, and Trail Making Test B (TRAIL-B). In addition, quality of life was assessed by the Short Form 36 (SF-36) questionnaire. Only measures of cognitive function correlated with the overall SF-36 quality of life score and the Mental Component Summary score from the SF-36. The only physical measure that correlated with a measure of quality of life was T25FW test, which correlated with the Physical Component Summary from the SF-36. We found no other significant correlations between the measures of cognitive function and the overall physical measures but interestingly, we found a possible relationship between the 9HPT score for the nondominant hand and the SDMT and TRAIL-B. Our findings support inclusion of measures of cognitive function in the assessment of patients with progressive MS as these correlated closer with quality of life than measures of physical impairment.

  14. Placement, Progress, and Promotion: ESL Assessment in California's Adult Schools

    ERIC Educational Resources Information Center

    Gonzalves, Lisa

    2017-01-01

    In California adult schools, standardized language assessments are typically administered to adult English as a second language (ESL) students upon enrollment; students then take these same state-approved tests throughout the academic year to demonstrate progress. As these tests assess only listening and reading skills, schools may use their own…

  15. African Americans and Mathematics Outcomes on National Assessment of Educational Progress: Parental and Individual Influences

    ERIC Educational Resources Information Center

    Noble, Richard, III; Morton, Crystal Hill

    2013-01-01

    This study investigated within group differences between African American female and male students who participated in the 2009 National Assessment of Educational Progress mathematics assessment. Using results from participating states, we compare average scale scores of African American students based on home regulatory environment and interest…

  16. The National Assessment: A Critical Review and a New Direction

    ERIC Educational Resources Information Center

    Cunningham, William G.

    1976-01-01

    The National Assessment of Educational Progress (NAEP) is a national census-like survey of the knowledge, skills, understanding, and attitudes of certain groups of young Americans. Evaluates the NAEP's contribution to educational progress and its areas in need of improvement. (Author/RK) Aspect of National Assessment (NAEP) dealt with in this…

  17. Application of the National Assessment of Educational Progress Philosophy in San Bernardino City Unified School District.

    ERIC Educational Resources Information Center

    Bonney, Lewis A.

    the steps taken by a large urban school district to develop and implement an objectives-based curriculum with criterion-referenced assessment of student progress are described. These steps include: goal setting, development of curriculum objectives, construction of assessment exercises, matrix sampling in test administration, and reporting of…

  18. Assessing and Monitoring Student Progress in an E-Learning Personnel Preparation Environment.

    ERIC Educational Resources Information Center

    Meyen, Edward L.; Aust, Ronald J.; Bui, Yvonne N.; Isaacson, Robert

    2002-01-01

    Discussion of e-learning in special education personnel preparation focuses on student assessment in e-learning environments. It includes a review of the literature, lessons learned by the authors from assessing student performance in e-learning environments, a literature perspective on electronic portfolios in monitoring student progress, and the…

  19. Neural basis of the potentiated inhibition of repeated haloperidol and clozapine treatment on the phencyclidine-induced hyperlocomotion

    PubMed Central

    Zhao, Changjiu; Sun, Tao; Li, Ming

    2012-01-01

    Clinical observations suggest that antipsychotic effect starts early and increases progressively over time. This time course of antipsychotic effect can be captured in a rat phencyclidine (PCP)-induced hyperlocomotion model, as repeated antipsychotic treatment progressively increases its inhibition of the repeated PCP-induced hyperlocomotion. Although the neural basis of acute antipsychotic action has been studied extensively, the system that mediates the potentiated effect of repeated antipsychotic treatment has not been elucidated. In the present study, we investigated the neuroanatomical basis of the potentiated action of haloperidol (HAL) and clozapine (CLZ) treatment in the repeated PCP-induced hyperlocomotion. Once daily for five consecutive days, adult Sprague-Dawley male rats were first injected with HAL (0.05 mg/kg, sc), CLZ (10.0 mg/kg, sc) or saline, followed by an injection of PCP (3.2 mg/kg, sc) or saline 30 min later, and motor activity was measured for 90 min after the PCP injection. C-Fos immunoreactivity was assessed either after the acute (day 1) or repeated (day 5) drug tests. Behaviorally, repeated HAL or CLZ treatment progressively increased the inhibition of PCP-induced hyperlocomotion throughout the five days of drug testing. Neuroanatomically, both acute and repeated treatment of HAL significantly increased PCP-induced c-Fos expression in the nucleus accumbens shell (NAs) and the ventral tegmental area (VTA), but reduced it in the central amygdaloid nucleus (CeA). Acute and repeated CLZ treatment significantly increased PCP-induced c-Fos expression in the ventral part of lateral septal nucleus (LSv) and VTA, but reduced it in the medial prefrontal cortex (mPFC). More importantly, the effects of HAL and CLZ in these brain areas underwent a time-dependent reduction from day 1 to day 5. These findings suggest that repeated HAL achieves its potentiated inhibition of the PCP-induced hyperlocomotion by acting on the NAs, CeA and VTA, while CLZ does so by acting on the mPFC, LSv and VTA. PMID:22476004

  20. NAEP 1996 Science State Report for Connecticut. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  1. NAEP 1996 Science State Report for Mississippi. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  2. NAEP 1996 Science State Report for Indiana. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  3. NAEP 1996 Science State Report for Wisconsin. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  4. NAEP 1996 Science State Report for Nevada. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  5. NAEP 1996 Science State Report for North Carolina. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  6. NAEP 1996 Science State Report for Georgia. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  7. NAEP 1996 Science State Report for Texas. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  8. NAEP 1996 Science State Report for Colorado. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  9. NAEP 1996 Science State Report for Delaware. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  10. NAEP 1996 Science State Report for Hawaii. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  11. NAEP 1996 Science State Report for New Hampshire. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  12. NAEP 1996 Science State Report for Alabama. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  13. NAEP 1996 Science State Report for Florida. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  14. NAEP 1996 Science State Report for West Virginia. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  15. NAEP 1996 Science State Report for Arizona. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  16. NAEP 1996 Science State Report for Maine. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  17. NAEP 1996 Science State Report for Wyoming. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  18. NAEP 1996 Science State Report for Tennessee. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  19. Content and Alignment of State Writing Standards and Assessments as Predictors of Student Writing Achievement: An Analysis of 2007 National Assessment of Educational Progress Data

    ERIC Educational Resources Information Center

    Troia, Gary A.; Olinghouse, Natalie G.; Zhang, Mingcai; Wilson, Joshua; Stewart, Kelly A.; Mo, Ya; Hawkins, Lisa

    2018-01-01

    We examined the degree to which content of states' writing standards and assessments (using measures of content range, frequency, balance, and cognitive complexity) and their alignment were related to student writing achievement on the 2007 National Assessment of Educational Progress (NAEP), while controlling for student, school, and state…

  20. The Nation's Report Card: Writing 2011. National Assessment of Educational Progress at Grades 8 and 12. NCES 2012-470

    ERIC Educational Resources Information Center

    National Center for Education Statistics, 2012

    2012-01-01

    This report presents results of the 2011 National Assessment of Educational Progress (NAEP) in writing at grades 8 and 12. In this new national writing assessment sample, 24,100 eighth-graders and 28,100 twelfth-graders engaged with writing tasks and composed their responses on computer. The assessment tasks reflected writing situations common to…

  1. A Preliminary Report of National Estimates from the National Assessment of Educational Progress, 1992 Mathematics Assessment.

    ERIC Educational Resources Information Center

    Elliott, Emerson J., Comp.

    This report contains preliminary results from the 1992 mathematics assessment by the National Assessment of Educational Progress (NAEP) of nationally representative samples of about 26,000 4th, 8th and 12th grade students in 1,500 public schools and private schools in 44 states; and compares data to findings from the 1990 NAEP mathematics tests.…

  2. Political Knowledge and Attitudes, 1971-1972. A Special Social Studies Report from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    Marriner, Gerald L.; Crane, Robert

    The National Assessment of Educational Progress is an information-gathering project which surveys the educational attainments of 9, 13, and 17-year-olds and adults in ten subject areas, with two areas assessed every year. The results of the 1971-72 assessment of political knowledge and attitudes are summarized in this report. Chapters 1-4 present…

  3. Microglia activation in multiple sclerosis black holes predicts outcome in progressive patients: an in vivo [(11)C](R)-PK11195-PET pilot study.

    PubMed

    Giannetti, Paolo; Politis, Marios; Su, Paul; Turkheimer, Federico; Malik, Omar; Keihaninejad, Shiva; Wu, Kit; Reynolds, Richard; Nicholas, Richard; Piccini, Paola

    2014-05-01

    The pathophysiological correlates and the contribution to persisting disability of hypointense T1-weighted MRI lesions, black holes (BH), in multiple sclerosis (MS) are still unclear. In order to study the in vivo functional correlates of this MRI finding, we used 11C-PK11195 PET (PK-PET) to investigate changes in microglial activity. Ten relapsing and 9 progressive MS subjects had a PK-PET scan and a MRI scan alongside a full clinical assessment, including the expanded disability status scale (EDSS) for evaluation of disability. We studied the PK binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BPND) in T1 BHs. Out of a total of 1242 BHs identified, 947 were PK enhancing. The PKBPND was correlated with the EDSS (r=0.818; p<0.05) only in the progressive group. In the relapsing patients there was an inverse correlation between PKBPND and BH total lesion volume in whole brain (r=-0.781; p<0.05). When progressive patients were grouped according to the disability outcome at 2years from the PK-PET scan, the total PKBPND in BHs was found to be a significant outcome predictor of disability (p<0.01). Our findings show that relapsing and progressive patients have heterogeneous patterns of PKBPND in T1 BHs and indicate that BHs are not just "holes" representing loss of axons and myelin, but display inflammatory activity in the form of activated microglia. The significant association between PKBPND, neurological impairment and outcome in progressive subjects supports a role for activated microglia in disability progression. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. The role of early magnetic resonance imaging in predicting survival on bevacizumab for recurrent glioblastoma: Results from a prospective clinical trial (CABARET).

    PubMed

    Field, Kathryn M; Phal, Pramit M; Fitt, Greg; Goh, Christine; Nowak, Anna K; Rosenthal, Mark A; Simes, John; Barnes, Elizabeth H; Sawkins, Kate; Cher, Lawrence M; Hovey, Elizabeth J; Wheeler, Helen

    2017-09-15

    Bevacizumab has been associated with prolonged progression-free survival for patients with recurrent glioblastoma; however, not all derive a benefit. An early indicator of efficacy or futility may allow early discontinuation for nonresponders. This study prospectively assessed the role of early magnetic resonance imaging (eMRI) and its correlation with subsequent routine magnetic resonance imaging (MRI) results and survival. Patients were part of a randomized phase 2 clinical trial (CABARET) comparing bevacizumab with bevacizumab plus carboplatin for recurrent glioblastoma. eMRI was conducted after 4 weeks in the trial (after 2 treatments with bevacizumab [10 mg/kg every 2 weeks]). The results were compared with the results of the subsequent 8-week MRI standard. For 119 of 122 patients, eMRI was available, and 111 had subsequent MRI for comparison. Thirty-six (30%) had an early radiological response, and 17 (14%) had progressive disease. The concordance between eMRI and 8-week MRI was moderate (κ = 0.56), with most providing the same result (n = 79 [71%]). There was strong evidence that progression-free survival and overall survival were predicted by the eMRI response (both P values < .001). The median survival was 8.6 months for an eMRI response, 6.6 months for stable disease, and 3.7 months for progressive disease; the hazard ratio (progressive disease vs stable disease) was 3.4 (95% confidence interval, 1.9-6.0). Landmark analyses showed that eMRI progression was a strong predictor of mortality independent of other potential baseline predictors. In this study, early progression on MRI appears to be a robust marker of a poor prognosis for patients on bevacizumab. Cancer 2017;123:3576-82. © 2017 American Cancer Society. © 2017 American Cancer Society.

  5. 3D-MR Spectroscopic Imaging at 3Tesla for Early Response Assessment of Glioblastoma Patients during External Beam Radiation Therapy

    PubMed Central

    Muruganandham, Manickam; Clerkin, Patrick P; Smith, Brian J; Anderson, Carryn M; Morris, Ann; Capizzano, Aristides A; Magnotta, Vincent; McGuire, Sarah M; Smith, Mark C; Bayouth, John E; Buatti, John M

    2014-01-01

    Purpose To evaluate the utility of 3D-MR proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium enhanced MR images at simulation and at boost treatment planning after 17-20 fractions of radiotherapy. All patients received standard radiotherapy with temozolomide and follow-up with every two month MR scans. Progression free survival was defined using MacDonald criteria. MRSI images obtained at initial simulation were analyzed for choline / N-acetylaspartate ratios (Cho/NAA) on a voxel by voxel basis with abnormal activity defined as Cho/NAA ≥ 2. These images were compared on anatomically matched MRSI data collected after 3 weeks of radiotherapy. Changes in Cho/NAA between pre-therapy and 3rd week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results After 8.6 months (median follow-up), 50% of patients had progressed based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (p< 0.01). Patients with an increase in mean or median Cho/NAA values at the 3rd week RT scan had a significantly greater chance of early progression (p <0.01). An increased Cho/NAA at the 3rd week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval 1.10-6.71, p= 0.03). Most patients received the prescription dose of RT to the Cho/NAA ≥ 2 volume, which was where recurrence most often occurred. Conclusion Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested. PMID:24986746

  6. Bone resorptive activity in symptomatic and asymptomatic apical lesions of endodontic origin.

    PubMed

    Salinas-Muñoz, M; Garrido-Flores, M; Baeza, M; Huamán-Chipana, P; García-Sesnich, J; Bologna, R; Vernal, R; Hernández, M

    2017-11-01

    The aim of this study is to assess the levels and diagnostic accuracy of a set of bone resorption biomarkers, including TRAP-5, RANKL, and OPG in symptomatic and asymptomatic apical lesions and controls. Apical tissues from symptomatic and asymptomatic apical periodontitis patients and periodontal ligaments from healthy teeth extracted for orthodontic reasons were processed for tissue homogenization and the levels of TRAP-5, RANKL, and OPG were determined by multiplex assay. Marker levels were analyzed by Kruskal Wallis test, and diagnostic accuracy was analyzed with ROC curves. Higher levels of RANKL, OPG, and RANKL/OPG ratio were determined in both types of apical lesions compared to healthy periodontal ligament, whereas higher TRAP-5 levels were found only in symptomatic apical lesions (p < 0.05). OPG, RANKL, and RANKL/OPG ratio showed diagnostic potential to identify apical lesions versus healthy controls (AUC = 0.69, p < 0.05); while TRAP-5 showed a potential to discriminate symptomatic versus asymptomatic apical periodontitis (AUC = 0.71, p < 0.05) and healthy controls (AUC = 0.83, p < 0.05). Apical lesions showed higher RANKL and OPG levels than healthy tissues. TRAP-5 levels were the highest in symptomatic apical lesions, suggesting that these represent a progressive state, and showed diagnostic potential. Clinically symptomatic apical periodontitis might represent biologically progressive apical lesions based on TRAP5 levels. TRAP5 has diagnostic potential to identify these lesions, representing a candidate prognostic biomarker.

  7. Prevalence of obesity in paediatric psoriasis and its impact on disease severity and progression.

    PubMed

    Ergun, Tulin; Seckin Gencosmanoglu, Dilek; Karakoc-Aydiner, Elif; Salman, Andac; Tekin, Burak; Bulbul-Baskan, Emel; Alpsoy, Erkan; Cakıroglu, Aylin; Onsun, Nahide

    2017-11-01

    The current literature suggests there is a possible connection between paediatric psoriasis and obesity. However, there is a paucity of research on the influence of increased adiposity on the severity of paediatric psoriasis and disease progression. We aimed to compare the prevalence of being overweight or obese in paediatric psoriasis patients and controls and assess the potential impact of being overweight/obese on disease severity and progression of disease. This multicentre prospective case-control study included 289 psoriasis patients (aged < 18 years) treated and followed up by one of the four university hospitals in Turkey. The control group consisted of 151 consecutive age-matched and sex-matched children who lacked a personal or family history of psoriasis. The participants' characteristics, psoriasis-related parametres (e.g., initial subtype, psoriasis area and severity index, presence of psoriatic arthritis) and body mass index were determined. The difference between the prevalence of being overweight/obese among psoriatics (28%) and the control group (19%) was significant (P = 0.024). Being overweight/obese had no significant impact on disease severity and unresponsiveness to topical treatment. Within a median follow-up time of 12 months, 23% of our patients with localised disease at disease onset progressed to generalised disease. The impact of being overweight/obese on disease progression was found to be non-significant; however, disease duration was found to have a significant impact on disease progression (P = 0.026). Although it is not associated with disease severity and course, increased bodyweight may be a health problem for psoriatic children. © 2016 The Australasian College of Dermatologists.

  8. Clinical benefit of continuing crizotinib therapy after initial disease progression in Chinese patients with advanced ALK-rearranged non-small-cell lung cancer.

    PubMed

    Hong, Xiangchan; Chen, Qi; Ding, Lingyu; Liang, Ying; Zhou, Ningning; Fang, Wenfeng; Chen, Xinru; Wu, Haiying

    2017-06-20

    Although most patients with ALK-positive non-small-cell lung cancer (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients may be beneficial. In this study, we investigated whether Chinese patients with advanced ALK-positive NSCLC benefit from CBPD, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2). Data on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively. The impact of continued crizotinib therapy on the patients' PFS2 time was assessed after adjusting for potential confounding factors. With initial crizotinib therapy, the objective response rate (ORR) and median PFS time (PFS1) in the 33 patients were 63.6% and 8.6 months, respectively. With continued crizotinib therapy after documentation of PD, the median PFS2 for all 33 patients was 16 weeks, and in those with CNS progression but systemic disease control it was 30 weeks. Patients who received local therapy after disease progression had a significantly longer PFS2 compared with those who did not (P = 0.039). Multivariable Cox regression analysis showed that the PFS1 with initial crizotinib treatment and local therapy were independent predictors of PFS2. This study provides further evidence of the benefit of continuing crizotinib therapy in Chinese patients with progressive ALK-positive NSCLC. Patients with a longer PFS1 and those who received local brain therapy would have a longer period of continuing crizotinib.

  9. PROSPERA: a randomized, controlled trial evaluating rasagiline in progressive supranuclear palsy.

    PubMed

    Nuebling, Georg; Hensler, Mira; Paul, Sabine; Zwergal, Andreas; Crispin, Alexander; Lorenzl, Stefan

    2016-08-01

    To date, pharmacological treatment options for progressive supranuclear palsy (PSP), a neurodegenerative tauopathy, are limited. The MAO-B inhibitor rasagiline has shown neuroprotective effects in preclinical models of neurodegeneration. To evaluate the safety, tolerability and therapeutic effect of rasagiline on symptom progression in PSP. In this 1-year randomized, double-blind, placebo-controlled trial, 44 patients fulfilling the NINDS-PSP criteria were randomized to 1 mg/d rasagiline or placebo. The combined primary endpoint included symptom progression as measured by the PSP rating scale (PSP-RS) and the requirement of L-dopa rescue medication. Secondary endpoints included Schwab and England Activities of Daily Living (SEADL), Montgomery-Åsberg Depression Rating Scale, Mini Mental State Examination, Frontal Assessment Battery and posturographic measurements. Of the 44 patients randomized, 26 completed the trial per protocol. Rasagiline was well tolerated, with a slight increase of known side effects (hallucinations, ventricular extrasystoles). No effect on the primary endpoint (p = 0.496) was detected. Symptom progression averaged at 11.2 (rasagiline) and 10.8 (placebo) points per year (ΔPSP-RS). No difference was seen in SEADL, depression, cognitive function, frontal executive function and posturographic measurements. Post hoc analyses of PSP-RS subdomains indicate a potential beneficial effect in the "limb motor" subdomain, whereas performance appeared lower in the "mentation" and "history" subdomains in the treatment group. While rasagiline is well tolerated in PSP, a beneficial effect on overall symptom progression was not detected. Post hoc analyses suggest the implementation of more specific endpoints in future studies.

  10. Corneal markers of diabetic neuropathy.

    PubMed

    Pritchard, Nicola; Edwards, Katie; Shahidi, Ayda M; Sampson, Geoff P; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

    2011-01-01

    Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies. This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new noninvasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and noncontact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

  11. MR/PET Imaging of the Cardiovascular System.

    PubMed

    Robson, Philip M; Dey, Damini; Newby, David E; Berman, Daniel; Li, Debiao; Fayad, Zahi A; Dweck, Marc R

    2017-10-01

    Cardiovascular imaging has largely focused on identifying structural, functional, and metabolic changes in the heart. The ability to reliably assess disease activity would have major potential clinical advantages, including the identification of early disease, differentiating active from stable conditions, and monitoring disease progression or response to therapy. Positron emission tomography (PET) imaging now allows such assessments of disease activity to be acquired in the heart, whereas magnetic resonance (MR) scanning provides detailed anatomic imaging and tissue characterization. Hybrid MR/PET scanners therefore combine the strengths of 2 already powerful imaging modalities. Simultaneous acquisition of the 2 scans also provides added benefits, including improved scanning efficiency, motion correction, and partial volume correction. Radiation exposure is lower than with hybrid PET/computed tomography scanning, which might be particularly beneficial in younger patients who may need repeated scans. The present review discusses the expanding clinical literature investigating MR/PET imaging, highlights its advantages and limitations, and explores future potential applications. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Variability in pesticides residues--the US experience.

    PubMed

    Suhre, F B

    2000-07-01

    The evolution of US Environmental Protection Agency's (EPA) process for estimating potential health risks from pesticide residues in or on food is examined in light of changes in US Legislation and the variability of residue data and assumptions used to estimate dietary exposure. In the 86 years since enactment of the Insecticide Act, pesticide laws have become progressively more health-based. Passage of the 1996 Food Quality Protection Act (FQPA) requires EPA to place particular emphasis on assessing potential risk from pesticides to infants and children. Primary factors affecting the actual pesticide residues in food include frequency of application, percentage of crop treated, and the interval from treatment to harvest. Primary factors affecting the estimated pesticide residues in food include the source of the residue data, calculation techniques for non-detected residues, and the availability of data reflecting post-harvest treatments. Risk assessors must thoroughly consider these factors when assessing dietary risk to pesticides. Risk managers will need to consider these factors as a means of mitigating dietary risk from pesticides.

  13. The impact of HIV status, HIV disease progression, and post-traumatic stress symptoms on the health-related quality of life of Rwandan women genocide survivors.

    PubMed

    Gard, Tracy L; Hoover, Donald R; Shi, Qiuhu; Cohen, Mardge H; Mutimura, Eugene; Adedimeji, Adebola A; Anastos, Kathryn

    2013-10-01

    We examined whether established associations between HIV disease and HIV disease progression on worse health-related quality of life (HQOL) were applicable to women with severe trauma histories, in this case Rwandan women genocide survivors, the majority of whom were HIV-infected. Additionally, this study attempted to clarify whether post-traumatic stress symptoms were uniquely associated with HQOL or confounded with depression. The Rwandan Women's Interassociation Study and Assessment was a longitudinal prospective study of HIV-infected and uninfected women. At study entry, 922 women (705 HIV+ and 217 HIV-) completed measures of symptoms of post-traumatic stress and HQOL as well as other demographic, clinical, and behavioral characteristics. Even after controlling for potential confounders and mediators, HIV+ women, in particular those with the lowest CD4 counts, scored significantly worse on HQOL and overall quality of life (QOL) than did HIV- women. Even after controlling for depression and HIV disease progression, women with more post-traumatic stress symptoms scored worse on HQOL and overall QOL than women with fewer post-traumatic stress symptoms. This study demonstrated that post-traumatic stress symptoms were independently associated with HQOL and overall QOL, independent of depression and other confounders or potential mediators. Future research should examine whether the long-term impact of treatment on physical and psychological symptoms of HIV and post-traumatic stress symptoms would generate improvement in HQOL.

  14. Early disturbances in multimodal evoked potentials as a prognostic factor for long-term disability in relapsing-remitting multiple sclerosis patients.

    PubMed

    London, Frédéric; El Sankari, Souraya; van Pesch, Vincent

    2017-04-01

    The aim of this study was to investigate whether early alterations in evoked potentials (EPs) have a prognostic value in relapsing-remitting multiple sclerosis (RRMS). We retrospectively selected 108 early MS patients with a neurological follow-up ranging from 5 to 15years, in whom multimodal EPs (visual, brainstem auditory, somatosensory and motor) were performed at diagnosis. A conventional ordinal score was used to quantify the observed abnormalities. The extent of change in the composite EP score was well correlated to the Expanded Disability Status Scale (EDSS) at ten years (Y 10 ) and up to 15years (Y 11-15 ) after disease onset. Analysis of the predictive value of the EP score showed an increased risk of disability progression at Y 10 and Y 11-15 of 60% (p<0.0001) and 73% (p<0.0001) respectively in patients with an EP score >4. Conversely, the risk of disability progression at Y 10 and Y 11-15 associated with a lower EP score (⩽4) was reduced to 16% and 20% respectively. Our data support the good predictive value for long-term disability progression of multimodal EPs performed early after disease onset in RRMS patients. This study, performed in a homogeneous RRMS cohort with long term follow-up, demonstrates the value of an early comprehensive neurophysiological assessment as a marker for future disability. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  15. Translating airway biomarker information into practice: from theoretical science to applied medicine.

    PubMed

    Ameredes, Bill T

    2011-04-01

    Biomarkers ranging from simple to sophisticated have been used by man for many years of his existence. The main use for biomarkers over that time has been to assess relative states health and well-being, including the presence of functional limitations that presage debilitation and even death. In recent years, there has been intense interest in the development of non-invasive biomarkers to accurately predict disease state and progression, as well as potential drug therapy to assist in early mitigation of morbidity and possibly, forestall premature mortality. The development of biomarkers of airway status has followed a similar pattern, and in recent years, several biomarkers have followed the progression from basic and pre-clinical development, to clinical/translational application, and finally to potential clinical therapeutic application. Inherent in this progression is the refinement of technology that has allowed measurement of these biomarkers in a fast, convenient, and reliable fashion, such that they can be obtainable within a clinical practice setting, to allow the physician to make treatment decisions for diseases such as asthma and COPD. While the clinical therapeutic application of airway biomarkers such as exhaled nitric oxide and β(2)-adrenoreceptor Arg-16 polymorphism are still in their infancy, they have followed this common pathway of development, and now will require some years of application to demonstrate their true utility as predictive biomarkers of airway status and treatment response. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Prioritizing Arctic Observations with Limited Resources

    NASA Astrophysics Data System (ADS)

    Kelly, B.; Starkweather, S.

    2012-12-01

    U.S. Federal agencies recently completed a five-year research plan for the Arctic including plans to enhance efforts toward an Arctic Observing Network (AON). Following on numerous national and international planning efforts, the five-year plan identifies nine priority areas including enhancing observing system design, assessing priorities of local residents, and improving data access. AON progress to date has been realized through bottom-up funding decisions and some top-down design optimization approaches, which have resulted in valuable yet ad hoc progress towards Arctic research imperatives. We suggest that advancing AON beyond theoretical design and ad hoc efforts with the engagement of multiple U.S. Federal agencies will require a structured, input-based planning approach to prioritization that recognizes budget realities. Completing a long list of worthy observing efforts appears to be unsustainable and inadequate in responding to the rapid changes taking place in the Arctic. Society would be better served by more rapid implementation of sustained, long-term observations focused on those climate feedbacks with the greatest potential negative impacts. Several emerging theoretical frameworks have pointed to the need to enhance iterative, capacity-building dialog between observationalists, modelers, and stakeholders as a way to identify these broadest potential benefits. We concur and suggest that those dialogs need to be facilitated and sustained over long periods. Efforts to isolate observational programs from process research are, we believe, impeding progress. At the same time, we note that bottom-up funding decisions, while useful for prioritizing process research, are less appropriate to building observing systems.

  17. MicroRNAs for osteosarcoma in the mouse: a meta-analysis

    PubMed Central

    Chang, Junli; Yao, Min; Li, Yimian; Zhao, Dongfeng; Hu, Shaopu; Cui, Xuejun; Liu, Gang; Shi, Qi; Wang, Yongjun; Yang, Yanping

    2016-01-01

    Osteosarcoma (OS) is the most common primary malignant bone carcinoma with high morbidity that happens mainly in children and young adults. As the key components of gene-regulatory networks, microRNAs (miRNAs) control many critical pathophysiological processes, including initiation and progression of cancers. The objective of this study is to summarize and evaluate the potential of miRNAs as targets for prevention and treatment of OS in mouse models, and to explore the methodological quality of current studies. We searched PubMed, Web of Science, Embase, Wan Fang Database, VIP Database, China Knowledge Resource Integrated Database, and Chinese BioMedical since their beginning date to 10 May 2016. Two reviewers separately screened the controlled studies, which estimate the effects of miRNAs on osteosarcoma in mice. A pair-wise analysis was performed. Thirty six studies with enough randomization were selected and included in the meta-analysis. We found that blocking oncogenic or restoring decreased miRNAs in cancer cells could significantly suppress the progression of OS in vivo, as assessed by tumor volume and tumor weight. This meta-analysis suggests that miRNAs are potential therapeutic targets for OS and correction of the altered expression of miRNAs significantly suppresses the progression of OS in mouse models, however, the overall methodological quality of studies included here was low, and more animal studies with the rigourous design must be carried out before a miRNA-based treatment could be translated from animal studies to clinical trials. PMID:27852052

  18. The Impact of HIV Status, HIV Disease Progression and Post-Traumatic Stress Symptoms on the Health-Related Quality of Life of Rwandan Women Genocide Survivors

    PubMed Central

    Gard, Tracy L.; Hoover, Donald R.; Shi, Qiuhu; Cohen, Mardge H.; Mutimura, Eugene; Adedimeji, Adebola A.; Anastos, Kathryn

    2014-01-01

    Purpose We examined whether established associations between HIV disease and HIV disease progression on worse health-related quality of life (HQOL) were applicable to women with severe trauma histories, in this case Rwandan women genocide survivors, the majority of whom were HIV infected. Additionally, this study attempted to clarify whether post-traumatic stress symptoms were uniquely associated with HQOL or confounded with depression. Methods The Rwandan Women’s Interassociation Study and Assessment (RWISA) was a longitudinal prospective study of HIV-infected and uninfected women. At study entry 922 women (705 HIV+ and 217 HIV−) completed measures of symptoms of post-traumatic stress and HQOL as well as other demographic, clinical and behavioral characteristics. Results Even after controlling for potential confounders and mediators, HIV+ women, in particular those with the lowest CD4 counts, scored significantly worse on HQOL and overall QOL than did HIV− women. Even after controlling for depression and HIV disease progression, women with more post-traumatic stress symptoms scored worse on HQOL and overall QOL than women with fewer post-traumatic stress symptoms. Conclusions This study demonstrated that post-traumatic stress symptoms were independently associated with HQOL and overall QOL, independent of depression and other confounders or potential mediators. Future research should examine whether the long term impact of treatment on physical and psychological symptoms of HIV and post-traumatic stress symptoms would generate improvement in HQOL. PMID:23271207

  19. The Validation of a Case-Based, Cumulative Assessment and Progressions Examination

    PubMed Central

    Coker, Adeola O.; Copeland, Jeffrey T.; Gottlieb, Helmut B.; Horlen, Cheryl; Smith, Helen E.; Urteaga, Elizabeth M.; Ramsinghani, Sushma; Zertuche, Alejandra; Maize, David

    2016-01-01

    Objective. To assess content and criterion validity, as well as reliability of an internally developed, case-based, cumulative, high-stakes third-year Annual Student Assessment and Progression Examination (P3 ASAP Exam). Methods. Content validity was assessed through the writing-reviewing process. Criterion validity was assessed by comparing student scores on the P3 ASAP Exam with the nationally validated Pharmacy Curriculum Outcomes Assessment (PCOA). Reliability was assessed with psychometric analysis comparing student performance over four years. Results. The P3 ASAP Exam showed content validity through representation of didactic courses and professional outcomes. Similar scores on the P3 ASAP Exam and PCOA with Pearson correlation coefficient established criterion validity. Consistent student performance using Kuder-Richardson coefficient (KR-20) since 2012 reflected reliability of the examination. Conclusion. Pharmacy schools can implement internally developed, high-stakes, cumulative progression examinations that are valid and reliable using a robust writing-reviewing process and psychometric analyses. PMID:26941435

  20. Progress assessed with the Mayo-Portland Adaptability Inventory in 604 participants in 4 types of post-inpatient rehabilitation brain injury programs.

    PubMed

    Eicher, Vicki; Murphy, Mary Pat; Murphy, Thomas F; Malec, James F

    2012-01-01

    To compare progress in 4 types of post-inpatient rehabilitation brain injury programs. Quasiexperimental observational cohort study. Community and residential. Individuals (N=604) with acquired brain injury. Four program types within the Pennsylvania Association of Rehabilitation Facilities were compared: intensive outpatient and community-based rehabilitation (IRC; n=235), intensive residential rehabilitation (IRR; n=78), long-term residential supported living (SLR; n=246), and long-term community-based supported living (SLC; n=45). With the use of a commercial web-based data management system developed with federal grant support, progress was examined on 2 consecutive assessments. Mayo-Portland Adaptability Inventory (MPAI-4). Program types differed in participant age (F=10.69, P<.001), sex (χ(2)=22.38, P<.001), time from first to second assessment (F=20.71, P<.001), initial MPAI-4 score (F=6.89, P<.001), and chronicity (F=13.43, P<.001). However, only initial MPAI-4 score and chronicity were significantly associated with the second MPAI-4 rating. On average, SLR participants were 9.1 years postinjury compared with 5.1 years for IRR, 6.0 years for IRC, and 6.8 years for SLC programs. IRR participants were more severely disabled per MPAI-4 total score on admission than the other groups. Controlling for these variables, program types varied significantly on second MPAI-4 total score (F=5.14, P=.002). Both the IRR and IRC programs resulted in significant functional improvement across assessments. In contrast, both the SLR and SLC programs demonstrated relatively stable MPAI-4 scores. Results are consistent with stated goals of the programs; that is, intensive programs resulted in functional improvements, whereas supported living programs produced stable functioning. Further studies using data from this large, multiprovider measurement collaboration will potentially provide the foundation for developing outcome expectations for various types of postacute brain injury programs. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  1. Refining the approach to vaccines against influenza A viruses with pandemic potential

    PubMed Central

    Czako, Rita; Subbarao, Kanta

    2015-01-01

    Vaccination is the most effective strategy for prevention and control of influenza. Timely production and deployment of seasonal influenza vaccines is based on an understanding of the epidemiology of influenza and on global disease and virologic surveillance. Experience with seasonal influenza vaccines guided the initial development of pandemic influenza vaccines. A large investment in pandemic influenza vaccines in the last decade has resulted in much progress and a body of information that can now be applied to refine the established paradigm. Critical and complementary considerations for pandemic influenza vaccines include improved assessment of the pandemic potential of animal influenza viruses, proactive development and deployment of pandemic influenza vaccines, and application of novel platforms and strategies for vaccine production and administration. PMID:26587050

  2. Concentration analysis of breast tissue phantoms with terahertz spectroscopy

    PubMed Central

    Truong, Bao C. Q.; Fitzgerald, Anthony J.; Fan, Shuting; Wallace, Vincent P.

    2018-01-01

    Terahertz imaging has been previously shown to be capable of distinguishing normal breast tissue from its cancerous form, indicating its applicability to breast conserving surgery. The heterogeneous composition of breast tissue is among the main challenges to progressing this potential research towards a practical application. In this paper, two concentration analysis methods are proposed for analyzing phantoms mimicking breast tissue. The dielectric properties and the double Debye parameters were used to determine the phantom composition. The first method is wholly based on the conventional effective medium theory while the second one combines this theoretical model with empirical polynomial models. Through assessing the accuracy of these methods, their potential for application to quantifying breast tissue pathology was confirmed. PMID:29541525

  3. Measuring disease progression in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience.

    PubMed

    Parashos, Sotirios A; Luo, Sheng; Biglan, Kevin M; Bodis-Wollner, Ivan; He, Bo; Liang, Grace S; Ross, G Webster; Tilley, Barbara C; Shulman, Lisa M

    2014-06-01

    Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents. To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD. Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials. Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment. Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression. After adjusting for baseline confounding variables with regard to the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson's Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95% CI, 1.06-1.13] for 1 scale unit change per 6 months), and the Schwab and England Independence Scale score (hazard ratio, 1.29 [95% CI, 1.12-1.48] for 5 percentage point change per 6 months) was associated with earlier need for symptomatic therapy. AND RELEVANCE In early PD, the UPDRS Part II score and Part III score and the Schwab and England Independence Scale score can be used to measure disease progression, whereas the 39-item Parkinson's Disease Questionnaire and summary index, Total Functional Capacity scale, and the 12-item Short Form Health Survey Physical Summary and Mental Summary are not sensitive to change. clinicaltrials.gov Identifiers: NCT00063193 and NCT00076492.

  4. A novel approach to assess the spontaneous gastrointestinal bleeding risk of antithrombotic agents using Apc(min/+) mice.

    PubMed

    Wei, Huijun; Shang, Jin; Keohane, CarolAnn; Wang, Min; Li, Qiu; Ni, Weihua; O'Neill, Kim; Chintala, Madhu

    2014-06-01

    Assessment of the bleeding risk of antithrombotic agents is usually performed in healthy animals with some form of vascular injury to peripheral organs to induce bleeding. However, bleeding observed in patients with currently marketed antithrombotic drugs is typically spontaneous in nature such as intracranial haemorrhage (ICH) and gastrointestinal (GI) bleeding, which happens most frequently on top of preexisting pathologies such as GI ulcerations and polyps. Apc(min/+) mice are reported to develop multiple adenomas through the entire intestinal tract and display progressive anaemia.In this study, we evaluated the potential utility of Apc(min/+) mice as a model for assessing spontaneous GI bleeding with antithrombotic agents. Apc(min/+) mice exhibited progressive blood loss starting at the age of nine weeks. Despite the increase in bleeding, Apc(min/+) mice were in a hypercoagulable state and displayed an age-dependent increase in thrombin generation and circulating fibrinogen as well as a significant decrease in clotting times. We evaluated the effect of warfarin, dabigatran etexilate, apixaban and clopidogrel in this model by administering them in diet or in the drinking water to mice for 1-4 weeks. All of these marketed drugs significantly increased GI bleeding in Apc(min/+) mice, but not in wild-type mice. Although different exposure profiles of these antithrombotic agents make it challenging to compare the bleeding risk of compounds, our results indicate that the Apc(min/+) mouse may be a sensitive preclinical model for assessing the spontaneous GI bleeding risk of novel antithrombotic agents.

  5. Self-Awareness and Self-Monitoring of Cognitive and Behavioral Deficits in Behavioral Variant Frontotemporal Dementia, Primary Progressive Aphasia and Probable Alzheimer’s Disease

    PubMed Central

    Banks, Sarah; Weintraub, Sandra

    2008-01-01

    Lack of insight is a core diagnostic criterion for behavioral variant frontotemporal dementia (bvFTD), and is believed to be intact in the early stages of primary progressive aphasia (PPA). In other neurological conditions, symptom-specific insight has been noted, with behavioral symptoms appearing especially vulnerable to reduced insight. Different components of insight, self-awareness and self-monitoring, are also often considered separate phenomena. The current study compared insight in patients with PPA, bvFTD, and probable Alzheimer’s disease (PrAD) and a group of cognitively intact control subjects. Additionally, differences in insight for the domains primarily affected by the three types of dementia, namely, Behavior, Naming, and Memory, were assessed, and self-awareness and self-monitoring were compared. A total of 55 participants were enrolled. Participants were asked to complete self-estimate scales demonstrating their perceived ability immediately prior to, and immediately following a test in each domain of interest. Results indicated that PPA and normal control groups performed very similarly on control (Weight and Eyesight) and cognitive domains, whereas bvFTD and PrAD patients were unable to accurately assess Memory. All three diagnostic groups failed to accurately assess their behavioral symptoms, suggesting that this domain is vulnerable to loss of insight across diagnoses. Naming ability, in contrast, was either accurately assessed or underestimated in all groups. Finally, there were no notable differences between self-awareness and self-monitoring, potential explanations for this are examined. PMID:18194832

  6. Routes for breaching and protecting genetic privacy

    PubMed Central

    Erlich, Yaniv; Narayanan, Arvind

    2014-01-01

    We are entering an era of ubiquitous genetic information for research, clinical care and personal curiosity. Sharing these datasets is vital for progress in biomedical research. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we present an overview of genetic privacy breaching strategies. We outline the principles of each technique, point to the underlying assumptions, and assess its technological complexity and maturation. We then review potential mitigation methods for privacy-preserving dissemination of sensitive data and highlight different cases that are relevant to genetic applications. PMID:24805122

  7. Independent Engineering Assessment of the Army’s Transportation Plan for BRAC Recommendation #133 Project Fort Belvoir - Mark Center, Virginia

    DTIC Science & Technology

    2011-11-30

    does not display a currently valid OMB control number. 1. REPORT DATE 30 NOV 2011 2. REPORT TYPE 3. DATES COVERED 00-00-2011 to 00-00-2011 4...Appropriate site variables (for purposes of accurate modeling); • Potential queues caused by the access control facility to the south parking...to LoS D LoS Control Delay/Vehicle (sec) Qualitative Description A ≤10 Good progression, few stops, and short cycle lengths B >10 - 20 Good

  8. Single photon emission tomography using 99mTc-HM-PAO in the investigation of dementia.

    PubMed Central

    Neary, D; Snowden, J S; Shields, R A; Burjan, A W; Northen, B; MacDermott, N; Prescott, M C; Testa, H J

    1987-01-01

    Single photon emission tomographic imaging of the brain using 99mTc HM-PAO was carried out in patients with a clinical diagnosis of Alzheimer's disease, non-Alzheimer frontal-lobe dementia, and progressive supranuclear palsy. Independent assessment of reductions in uptake revealed posterior hemisphere abnormalities in the majority of the Alzheimer group, and selective anterior hemisphere abnormalities in both other groups. The findings were consistent with observed patterns of mental impairment. The imaging technique has potential value in the differential diagnosis of primary cerebral atrophy. Images PMID:3499484

  9. Application of Advanced Nondestructive Evaluation Techniques for Cylindrical Composite Test Samples

    NASA Technical Reports Server (NTRS)

    Martin, Richard E.; Roth, Donald J.; Salem, Jonathan A.

    2013-01-01

    Two nondestructive methods were applied to composite cylinder samples pressurized to failure in order to determine manufacturing quality and monitor damage progression under load. A unique computed tomography (CT) image processing methodology developed at NASA Glenn Research was used to assess the condition of the as-received samples while acoustic emission (AE) monitoring was used to identify both the extent and location of damage within the samples up to failure. Results show the effectiveness of both of these methods in identifying potentially critical fabrication issues and their resulting impact on performance.

  10. Recent progress in Precambrian paleobiology

    NASA Technical Reports Server (NTRS)

    Schopf, J. W.

    1986-01-01

    Ongoing studies at UCLA include the following: (1) investigations in Archean and Proterozoic sequences of various locations; (2) laboratory and field studies of modern microbial biocoenoses (analogues of Precambrian microbial communities) especially those at Laguna Mormona, Baja California, Mexico; (3) development of new laboratory techniques for the separation and concentration of minute cellularly preserved fossils for isotopic and organic geochemical analyses; and (4) assembly of a computerized database for assessment of the timing and nature of major events occurring during Precambrian biotic evolution, and of the potential applicability of ancient microbiotas to problems of global biostratigraphy and biogeography.

  11. Routes for breaching and protecting genetic privacy.

    PubMed

    Erlich, Yaniv; Narayanan, Arvind

    2014-06-01

    We are entering an era of ubiquitous genetic information for research, clinical care and personal curiosity. Sharing these data sets is vital for progress in biomedical research. However, a growing concern is the ability to protect the genetic privacy of the data originators. Here, we present an overview of genetic privacy breaching strategies. We outline the principles of each technique, indicate the underlying assumptions, and assess their technological complexity and maturation. We then review potential mitigation methods for privacy-preserving dissemination of sensitive data and highlight different cases that are relevant to genetic applications.

  12. New approaches to molecular cancer therapeutics.

    PubMed

    Collins, Ian; Workman, Paul

    2006-12-01

    Cancer drug development is leading the way in exploiting molecular biological and genetic information to develop "personalized" medicine. The new paradigm is to develop agents that target the precise molecular pathology driving the progression of individual cancers. Drug developers have benefited from decades of academic cancer research and from investment in genomics, genetics and automation; their success is exemplified by high-profile drugs such as Herceptin (trastuzumab), Gleevec (imatinib), Tarceva (erlotinib) and Avastin (bevacizumab). However, only 5% of cancer drugs entering clinical trials reach marketing approval. Cancer remains a high unmet medical need, and many potential cancer targets remain undrugged. In this review we assess the status of the discovery and development of small-molecule cancer therapeutics. We show how chemical biology approaches offer techniques for interconnecting elements of the traditional linear progression from gene to drug, thereby providing a basis for increasing speed and success in cancer drug discovery.

  13. Model-Based Phenotypic Signatures Governing the Dynamics of the Stem and Semi-differentiated Cell Populations in Dysplastic Colonic Crypts.

    PubMed

    Nikolov, Svetoslav; Santos, Guido; Wolkenhauer, Olaf; Vera, Julio

    2018-02-01

    Mathematical modeling of cell differentiated in colonic crypts can contribute to a better understanding of basic mechanisms underlying colonic tissue organization, but also its deregulation during carcinogenesis and tumor progression. Here, we combined bifurcation analysis to assess the effect that time delay has in the complex interplay of stem cells and semi-differentiated cells at the niche of colonic crypts, and systematic model perturbation and simulation to find model-based phenotypes linked to cancer progression. The models suggest that stem cell and semi-differentiated cell population dynamics in colonic crypts can display chaotic behavior. In addition, we found that clinical profiling of colorectal cancer correlates with the in silico phenotypes proposed by the mathematical model. Further, potential therapeutic targets for chemotherapy resistant phenotypes are proposed, which in any case will require experimental validation.

  14. The wave and tidal resource of Scotland

    NASA Astrophysics Data System (ADS)

    Neill, Simon; Vogler, Arne; Lewis, Matt; Goward-Brown, Alice

    2017-04-01

    As the marine renewable energy industry evolves, in parallel with an increase in the quantity of available data and improvements in validated numerical simulations, it is occasionally appropriate to re-assess the wave and tidal resource of a region. This is particularly true for Scotland - a leading nation that the international community monitors for developments in the marine renewable energy industry, and which has witnessed much progress in the sector over the last decade. With 7 leased wave and 17 leased tidal sites, Scotland is well poised to generate significant levels of electricity from its abundant natural marine resources. In this review of Scotland's wave and tidal resource, I present the theoretical and technical resource, and provide an overview of commercial progress. I also discuss issues that affect future development of the marine energy seascape in Scotland, applicable to other regions of the world, including the potential for developing lower energy sites, and grid connectivity.

  15. The Role of Audiologic Evaluation in Progressive Audiologic Tinnitus Management

    PubMed Central

    Henry, James A.; Zaugg, Tara L.; Myers, Paula J.; Schechter, Martin A.

    2008-01-01

    Progressive Audiologic Tinnitus Management (PATM) is based on the premise that tinnitus is managed most efficiently using a hierarchy of clinical services that address different levels of need. PATM includes five levels of management: (a) triage; (b) audiologic evaluation; (c) group education; (d) tinnitus evaluation; and (e) individualized management. This article provides an overview of PATM and focuses on the procedures that make up the Level 2 Audiologic Evaluation. The evaluation is conducted to assess the potential need for medical, audiologic (hearing loss, tinnitus, hyperacusis), and/or mental health services. The Tinnitus Handicap Inventory, Hearing Handicap Inventory, and Tinnitus and Hearing Survey are used to differentiate effects of tinnitus and hearing loss. If indicated, patients are interviewed with the Tinnitus-Impact Screening Interview. Patients requiring amplification receive hearing aids. Often, management of hearing loss at Level 2 addresses any problems that were attributed to the tinnitus, which obviates further tinnitus-specific intervention. PMID:18628281

  16. Assessment of TRPM7 functions by drug-like small molecules.

    PubMed

    Chubanov, Vladimir; Ferioli, Silvia; Gudermann, Thomas

    2017-11-01

    Transient receptor potential cation channel subfamily M member 7 (TRPM7) is a plasma membrane ion channel linked to a cytosolic protein kinase domain. Genetic inactivation of this bi-functional protein revealed its crucial role in Ca 2+ signalling, Mg 2+ metabolism, immune responses, cell motility, proliferation and differentiation. Malfunctions of TRPM7 are associated with anoxic neuronal death, cardiac fibrosis, tumour progression and macrothrombocytopenia. Recently, several groups have identified small organic compounds acting as inhibitors or activators of the TRPM7 channel. In follow-up studies, the identified TRPM7 modulators were successfully used to uncover new cellular functions of TRPM7 in situ including a crucial role of TRPM7 in Ca 2+ signaling and Ca 2+ dependent cellular processes. Hence, TRPM7 has been defined as a promising drug target. Here, we summarize the progress in this quickly developing field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Alcohol studies and science: trapped in the velvet cage of medical research? An editorial.

    PubMed

    Roman, Paul M

    2014-01-01

    This article offers the author's assessment of the progress in research on alcohol related to alcohol misuse and alcohol use disorders. The historical background of alcohol-problem research is reviewed in the context of defining problems for study and the pattern by which research is funded. Progress in terms of cumulative research has been affected by the lack of central authority and the National Institutes of Health structure within which almost all funding for alcohol research in the United States has occurred. Problems are traced to the particular history and nature of alcohol-problem research, the continuing prominence of moral elements, and particular features of the treatment of alcohol use disorders. Although the scope of activity and production of publications in alcohol research has expanded greatly during the past 75 years, there is a potential shortfall in the cumulative research that has led to solutions to major problems associated with alcohol.

  18. Mapping longitudinal stream connectivity in the North St. Vrain Creek watershed of Colorado

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wohl, Ellen; Rathburn, Sara; Chignell, Stephen

    We use reach-scale stream gradient as an indicator of longitudinal connectivity for water, sediment, and organic matter in a mountainous watershed in Colorado. Stream reaches with the highest gradient tend to have narrow valley bottoms with limited storage space and attenuation of downstream fluxes, whereas stream reaches with progressively lower gradients have progressively more storage and greater attenuation. We compared the distribution of stream gradient to stream-reach connectivity rankings that incorporated multiple potential control variables, including lithology, upland vegetation, hydroclimatology, road crossings, and flow diversions. We then assessed connectivity rankings using different weighting schemes against stream gradient and against field-basedmore » understanding of relative connectivity within the watershed. Here, we conclude that stream gradient, which is simple to map using publicly available data and digital elevation models, is the most robust indicator of relative longitudinal connectivity within the river network.« less

  19. Use of dispersion modelling for Environmental Impact Assessment of biological air pollution from composting: Progress, problems and prospects.

    PubMed

    Douglas, P; Hayes, E T; Williams, W B; Tyrrel, S F; Kinnersley, R P; Walsh, K; O'Driscoll, M; Longhurst, P J; Pollard, S J T; Drew, G H

    2017-12-01

    With the increase in composting asa sustainable waste management option, biological air pollution (bioaerosols) from composting facilities have become a cause of increasing concern due to their potential health impacts. Estimating community exposure to bioaerosols is problematic due to limitations in current monitoring methods. Atmospheric dispersion modelling can be used to estimate exposure concentrations, however several issues arise from the lack of appropriate bioaerosol data to use as inputs into models, and the complexity of the emission sources at composting facilities. This paper analyses current progress in using dispersion models for bioaerosols, examines the remaining problems and provides recommendations for future prospects in this area. A key finding is the urgent need for guidance for model users to ensure consistent bioaerosol modelling practices. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Inefficient Or Insufficient Encoding As Potential Primary Deficit In Neurodevelopmental Performance Among Children with OSA

    PubMed Central

    Spruyt, Karen; Capdevila, Oscar Sans; Kheirandish-Gozal, Leila; Gozal, David

    2010-01-01

    Memory (M) impairments have been suggested in pediatric Obstructive Sleep Apnea along with attention and executive (AE), language (L) and visuospatial (V) dysfunctions. NEPSY assessment of children aged 5–9-years who were either healthy (n= 43), or who had OSA without L, V, AE (OSA−, n= 22) or with L (n=6), V (n=1), AE (n=3) (OSA+, n=10) dysfunctions revealed no gross memory problems in OSA; however, over the 3 learning trials of cross-modal association learning of name with face, the OSA− progressively improved performance, whereas the OSA+ failed to progress. No within-group differences between immediate and delayed memory tasks were apparent. The data suggest the presence of slower information processing, and/or secondary memory problems, in the absence of retrieval or recall impairments among a subset of children with OSA. We hypothesize that inefficient/insufficient encoding may account for the primary deficit. PMID:20183722

  1. Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma.

    PubMed

    De Paz, Dante; Kao, Huang-Kai; Huang, Yenlin; Chang, Kai-Ping

    2017-08-10

    Prognosis of advanced oral squamous cell carcinoma remains a challenge for clinicians despite progress in its diagnosis and treatment over the past decades. In this review, we assessed clinicopathological factors and potential biomarkers along with their prognostic relevance in an attempt to develop optimal treatment strategies for these patients. In addition to several pathologic factors that have been proposed to improve prognostic stratification and treatment planning in the eighth edition of the American Joint Committee staging manual on cancer, we reviewed some other imaging and clinicopathological parameters demonstrated to be closely associated with patient prognosis, along with the biomarkers related to novel target or immune therapy. Evaluation of current literature regarding the prognostic stratification used in contemporary clinicopathological studies and progress in the development of targeted or immune therapy may help these patients benefit from tailored and personalized treatment and obtain better oncological results.

  2. Mapping longitudinal stream connectivity in the North St. Vrain Creek watershed of Colorado

    DOE PAGES

    Wohl, Ellen; Rathburn, Sara; Chignell, Stephen; ...

    2016-05-06

    We use reach-scale stream gradient as an indicator of longitudinal connectivity for water, sediment, and organic matter in a mountainous watershed in Colorado. Stream reaches with the highest gradient tend to have narrow valley bottoms with limited storage space and attenuation of downstream fluxes, whereas stream reaches with progressively lower gradients have progressively more storage and greater attenuation. We compared the distribution of stream gradient to stream-reach connectivity rankings that incorporated multiple potential control variables, including lithology, upland vegetation, hydroclimatology, road crossings, and flow diversions. We then assessed connectivity rankings using different weighting schemes against stream gradient and against field-basedmore » understanding of relative connectivity within the watershed. Here, we conclude that stream gradient, which is simple to map using publicly available data and digital elevation models, is the most robust indicator of relative longitudinal connectivity within the river network.« less

  3. Simulation for Prediction of Entry Article Demise (SPEAD): An Analysis Tool for Spacecraft Safety Analysis and Ascent/Reentry Risk Assessment

    NASA Technical Reports Server (NTRS)

    Ling, Lisa

    2014-01-01

    For the purpose of performing safety analysis and risk assessment for a potential off-nominal atmospheric reentry resulting in vehicle breakup, a synthesis of trajectory propagation coupled with thermal analysis and the evaluation of node failure is required to predict the sequence of events, the timeline, and the progressive demise of spacecraft components. To provide this capability, the Simulation for Prediction of Entry Article Demise (SPEAD) analysis tool was developed. The software and methodology have been validated against actual flights, telemetry data, and validated software, and safety/risk analyses were performed for various programs using SPEAD. This report discusses the capabilities, modeling, validation, and application of the SPEAD analysis tool.

  4. Ultrasonic histogram assessment of early response to concurrent chemo-radiotherapy in patients with locally advanced cervical cancer: a feasibility study.

    PubMed

    Xu, Yan; Ru, Tong; Zhu, Lijing; Liu, Baorui; Wang, Huanhuan; Zhu, Li; He, Jian; Liu, Song; Zhou, Zhengyang; Yang, Xiaofeng

    To monitor early response for locally advanced cervical cancers undergoing concurrent chemo-radiotherapy (CCRT) by ultrasonic histogram. B-mode ultrasound examinations were performed at 4 time points in thirty-four patients during CCRT. Six ultrasonic histogram parameters were used to assess the echogenicity, homogeneity and heterogeneity of tumors. I peak increased rapidly since the first week after therapy initiation, whereas W low , W high and A high changed significantly at the second week. The average ultrasonic histogram progressively moved toward the right and converted into more symmetrical shape. Ultrasonic histogram could be served as a potential marker to monitor early response during CCRT. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Add+VantageMR® Assessments: A Case Study of Teacher and Student Gains

    ERIC Educational Resources Information Center

    Briand, Cathy

    2013-01-01

    This case study analyzes the effect of the Add+VantageMRRTM (AVMR) program on a teacher's pedagogy and on her students' progress in mathematics. AVMR, a professional development program in early mathematics, trains teachers to assess their students' progress and apply those insights to their teaching pedagogy. The AVMR assessment uses a…

  6. On the Correspondence between Preference Assessment Outcomes and Progressive-Ratio Schedule Assessments of Stimulus Value

    ERIC Educational Resources Information Center

    DeLeon, Iser G.; Frank, Michelle A.; Gregory, Meagan K.; Allman, Melissa J.

    2009-01-01

    The current study examined whether stimuli of different preference levels would be associated with different amounts of work maintained by the stimuli, as determined through progressive-ratio schedule break points. Using a paired-choice preference assessment, stimuli were classified as high, moderate, or low preference for 4 individuals with…

  7. Sex Differences in Mathematics and Science Achievement: A Meta-Analysis of National Assessment of Educational Progress Assessments

    ERIC Educational Resources Information Center

    Reilly, David; Neumann, David L.; Andrews, Glenda

    2015-01-01

    Gender gaps in the development of mathematical and scientific literacy have important implications for the general public's understanding of scientific issues and for the underrepresentation of women in science, technology, engineering, and math. We subjected data from the National Assessment of Educational Progress to a meta-analysis to examine…

  8. Teachers' Use of Learning Progression-Based Formative Assessment in Water Instruction

    ERIC Educational Resources Information Center

    Covitt, Beth A.; Gunckel, Kristin L.; Caplan, Bess; Syswerda, Sara

    2018-01-01

    While learning progressions (LPs) hold promise as instructional tools, researchers are still in the early stages of understanding how teachers use LPs in formative assessment practices. We report on a study that assessed teachers' proficiency in using a LP for student ideas about hydrologic systems. Research questions were: (a) what were teachers'…

  9. Science Framework for the 2009 National Assessment of Educational Progress

    ERIC Educational Resources Information Center

    National Assessment Governing Board, 2008

    2008-01-01

    This document sets forth recommendations for the design of a new science assessment. The assessment resulting from this framework will start a new NAEP science trend (i.e., measure of student progress in science) beginning in 2009. This framework represents a unique opportunity to build on previous NAEP science work as well as key developments in…

  10. Interactions between biomaterials and the sclera: Implications on myopia progression

    NASA Astrophysics Data System (ADS)

    Su, James

    Myopia prevalence has steadily climbed worldwide in recent decades with the most dramatic impact in East Asian countries. Treatments such as eyeglasses, contact lenses, and laser surgery for the refractive error are widely available, but none cures the underlying cause. In progressive high myopia, invasive surgical procedures using a scleral buckle for mechanical support are performed since the patient is at risk of becoming blind. The treatment outcome is highly dependent on the surgeon's skills and the patient's myopia progression rate, with limited choices in buckling materials. This dissertation, in four main studies, represents efforts made to control high myopia progression through the exploration and development of biomaterials that influence scleral growth. First, mRNA expression levels of the chick scleral matrix metalloproteinases, tissue-inhibitor of matrix metalloproteinases, and transforming growth factor-beta 2 were assessed for temporal and defocus power effects. The first study elucidated the roles that these factors play in scleral growth regulation and suggested potential motifs that can be incorporated in future biomaterials design. Second, poly(vinyl-pyrrolidone) as injectable gels and poly(2-hydroxyethyl methacrylate) as solid strips were implanted in chicks to demonstrate the concept of posterior pole scleral reinforcements. This second study found that placing appropriate biomaterials at the posterior pole of the eye could directly influence scleral remodeling by interacting with the host cells. Both studies advanced the idea that scleral tissue remodeling could be potentially controlled by well-designed biomaterials. These findings led to the exploration of biomimetic hydrogels comprising enzymatically-degradable semi-interpenetrating polymer networks (edsIPNs) to determine their biocompatibility and effects on the chick posterior eye wall. This third study demonstrated the feasibility of stimulating scleral growth by applying biomimetic injectable materials. Fourth, the muscarinic antagonist drug, atropine, was encapsulated within the edsIPNs and delivered to the chick eye posterior pole to evaluate the local effect of atropine release. This fourth study offered an alternative method of ocular drug delivery for treatment of myopia, with the potential to elucidate the actual location of the inhibitive effect of atropine on myopia progression. In summary, this dissertation contributes to the design and use of biomaterials specific to myopia therapy and adds novel insights to scleral tissue engineering.

  11. Strontium ranelate, a promising disease modifying osteoarthritis drug.

    PubMed

    Han, Weiyu; Fan, Shicai; Bai, Xiaochun; Ding, Changhai

    2017-03-01

    The articular cartilage and subchondral bone may have potential crosstalk in the development and progression of osteoarthritis (OA). Strontium ranelate (SrR) has the ability to dissociate the bone remodeling process and to change the balance between bone resorption and bone formation. Its effect on subchondral bone makes it a potential disease- modifying osteoarthritis drug (DMOAD) in the treatment of OA. The aim of the current review is to summarize up-to-date pharmacological and clinical data of SrR for OA treatment. Areas covered: A literature search was performed on PubMed and European Medicines Agency (EMA) website for all publications and documents related to SrR and OA. References of related studies were searched by hand. Treatment with SrR, especially at the dosage of 2 g/day, was associated with reduced radiographic knee OA progression, and with meaningful clinical improvement. It was also significantly associated with decreased MRI-assessed cartilage volume loss (CVL) and bone marrow lesions (BMLs). Expert opinion: SrR could be a promising DMOAD particularly for OA patients with bone phenotypes. The clinical efficacy and side effects of SrR for OA treatment need to be further investigated in future clinical trials before clinical application.

  12. Intramuscular transplantation of bone marrow cells prolongs the lifespan of SOD1G93A mice and modulates expression of prognosis biomarkers of the disease.

    PubMed

    Rando, Amaya; Pastor, Diego; Viso-León, Mari Carmen; Martínez, Anna; Manzano, Raquel; Navarro, Xavier; Osta, Rosario; Martínez, Salvador

    2018-04-06

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscle weakness, paralysis and death. There is no effective treatment for ALS and stem cell therapy has arisen as a potential therapeutic approach. SOD1 mutant mice were used to study the potential neurotrophic effect of bone marrow cells grafted into quadriceps femoris muscle. Bone marrow intramuscular transplants resulted in increased longevity with improved motor function and decreased motoneuron degeneration in the spinal cord. Moreover, the increment of the glial-derived neurotrophic factor and neurotrophin 4 observed in the grafted muscles suggests that this partial neuroprotective effect is mediated by neurotrophic factor release at the neuromuscular junction level. Finally, certain neurodegeneration and muscle disease-specific markers, which are altered in the SOD1 G93A mutant mouse and may serve as molecular biomarkers for the early detection of ALS in patients, have been studied with encouraging results. This work demonstrates that stem cell transplantation in the muscle prolonged the lifespan, increased motoneuron survival and slowed disease progression, which was also assessed by genetic expression analysis.

  13. Wild Blueberries (Vaccinium myrtillus) Alleviate Inflammation and Hypertension Associated with Developing Obesity in Mice Fed with a High-Fat Diet

    PubMed Central

    Mykkänen, Otto T.; Huotari, Anne; Herzig, Karl-Heinz; Dunlop, Thomas W.; Mykkänen, Hannu; Kirjavainen, Pirkka V.

    2014-01-01

    Background Low-grade metabolic inflammation and hypertension are primary mechanisms involved in obesity-associated adverse health effects. Berries, especially Nordic wild blueberries (hereafter referred to as bilberries), represent an important source of dietary anthocyanins, a group of polyphenols with potential beneficial effects to combat obesity-associated metabolic disturbances. Methods The effects of 5% or 10% (w/w) of whole bilberries (BB) were studied on the development of obesity and its metabolic disturbances in C57BL mice fed with a high-fat diet (HFD) for three months. Cytokines, inflammatory cells, systolic blood pressure, glucose tolerance, insulin sensitivity, weight gain, body fat, food consumption and energy metabolism were assessed. Results Bilberries ameliorated type 1 pro-inflammatory responsiveness induced by HFD. This was indicated by the altered cytokine profile and the reduced prevalence of interferon gamma -producing T-cells, in particular T helper type 1 cells. Bilberries also prevented the progression of obesity associated long term increase in systolic blood pressure in mice. Conclusions Bilberries reduce the development of systemic inflammation and prevent the progression of chronic hypertension, thus supporting their potential role in alleviating the adverse health effects associated with developing obesity. PMID:25501421

  14. [Stem cells therapy in amyotrophic lateral sclerosis treatment. A critical view].

    PubMed

    Soler, Bernardita; Fadic, Ricardo; von Bernhardi, Rommy

    2011-04-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. At present, there are not curative therapies for ALS. Pathogenic and progression mechanisms suggest the existence of oxidative stress, abnormal intracellular protein aggregation, mitochondrial dysfunction, axonal transport impairment, impairment of trophic support, altered glial cell function, and glutamate excitoxicity. To evaluate therapeutic results with adult stem cell for ALS treatment. Stem cells represent a potential therapeutic strategy, because their biological mechanisms could act on several of the pathogenic mechanisms proposed for ALS. Bone marrow mesenchymal stem cells are especially interesting among adult stem cells. Mesenchymal stem cells can differentiate in all central nervous system cells and potentially replace them. Furthermore, they have immunomodulatory effects, secreting, especially in neuroinflammatory environments, neurotrophic and antiinflammatory factors. Studies in murine models of ALS show decrease of inflammation and disease progression, and increase on animal highly heterogeneous, suggest that mesenchymal stem cells transplant in ALS appears to be safe. However, they fail showing clinical improvement of patients. Additional preclinical studies are necessary to refine this therapeutic approach, to assess long term survival and differentiation of mesenchymal stem cells, dosing, biological activity and safety should be conducted before any planning further human testing occurs.

  15. Screening and validation of serum protein biomarkers for early postmenopausal osteoporosis diagnosis.

    PubMed

    Wang, Long; Hu, Ya-Qian; Zhao, Zhuo-Jie; Zhang, Hong-Yang; Gao, Bo; Lu, Wei-Guang; Xu, Xiao-Long; Lin, Xi-Sheng; Wang, Jin-Peng; Jie, Qiang; Luo, Zhuo-Jing; Yang, Liu

    2017-12-01

    Postmenopausal osteoporosis is one of the most prominent worldwide public health problems and the morbidity is increasing with the aging population. It has been demonstrated that early diagnosis and intervention delay the disease progression and improve the outcome. Therefore, searching for biomarkers that are able to identify postmenopausal women at high risk for developing osteoporosis is an effective way to improve the quality of life of patients, and alleviate social and economic burdens. In the present study, a protein array was used to identify potential biomarkers. The bone mineral densities of 10 rats were dynamically measured in an ovariectomized model by micro‑computed tomography assessment, and the early stage of osteoporosis was defined. Through the protein array‑based screening, the expression levels of six serum protein biomarkers in ovariectomized rats were observed to alter at the initiation stage of the postmenopausal osteoporosis. Fractalkine, tissue inhibitor of metalloproteinases‑1 and monocyte chemotactic protein‑1 were finally demonstrated to be increased in the serum of eight enrolled postmenopausal osteoporosis patients using ELISA assay and were correlated with the severity of progressive bone loss. These biomarkers may be explored as potential early biomarkers to readily evaluate and diagnose postmenopausal osteoporosis in the clinic.

  16. Phonological fluency strategy of switching differentiates relapsing-remitting and secondary progressive multiple sclerosis patients.

    PubMed

    Messinis, L; Kosmidis, M H; Vlahou, C; Malegiannaki, A C; Gatzounis, G; Dimisianos, N; Karra, A; Kiosseoglou, G; Gourzis, P; Papathanasopoulos, P

    2013-01-01

    The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensitivity and specificity of phonological versus semantic verbal fluency tasks in discriminating between those with a diagnosis of MS and healthy adults. We found that the overall rate of impaired verbal fluency in our MS sample was consistent with that in other studies. However, we found no differences between types of MS (SPMS, RRMS), on semantic or phonological fluency word production, or the strategies used to maximize semantic fluency. In contrast, we found that the number of switches differed significantly in the phonological fluency task between the SPMS and RRMS subtypes. The clinical utility of semantic versus phonological fluency in discriminating MS patients from healthy controls did not indicate any significant differences. Further, the strategies used to maximize performance did not differentiate MS subgroups or MS patients from healthy controls.

  17. NAEP 1996 Science Report for Department of Defense Dependents Schools. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  18. NAEP 1996 Science State Report for Department of Defense Dependents Schools, Grade 4. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    Ballator, Nada; O'Sullivan, Christine Y.; Jerry, Laura

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  19. Aligning Science Assessment Standards: Oklahoma and the 2009 National Assessment of Educational Progress (NAEP). Issues & Answers. REL 2007-No. 022

    ERIC Educational Resources Information Center

    Timms, Michael; Schneider, Steven; Lee, Cindy; Rolfhus, Eric

    2007-01-01

    This policy research document is intended for Oklahoma policymakers to use when examining possible changes to the state assessment's alignment with the National Assessment of Educational Progress (NAEP). The 2009 NAEP test is not yet in existence, so the purpose of this report is to give policymakers a head start in determining where they might,…

  20. Examining the Content and Context of the Common Core State Standards: A First Look at Implications for the National Assessment of Educational Progress

    ERIC Educational Resources Information Center

    Stancavage, Frances B., Ed.; Bohrnstedt, George W., Ed.

    2013-01-01

    Since its inception more than four decades ago, the National Assessment of Educational Progress (NAEP) has served as a key indicator of what the nation's students know and can do in academic subjects. NAEP assessments provide a mechanism for putting the achievements of students in all states on a common scale; the assessments also serve as…

  1. Racial differences in associations between baseline patterns of radiographic osteoarthritis and multiple definitions of progression of hip osteoarthritis: the Johnston County Osteoarthritis Project.

    PubMed

    Foley, Bridget; Cleveland, Rebecca J; Renner, Jordan B; Jordan, Joanne M; Nelson, Amanda E

    2015-12-18

    To identify baseline radiographic features that predict hip osteoarthritis (HOA) progression, and to explore differences in these associations by race. Radiographs from the community-based Johnston County OA Project were scored using Kellgren-Lawrence (KL) grade and for presence and location of joint space narrowing (JSN), osteophytes, and subchondral changes. Associations between these features and HOA progression (increase of at least 1 KL grade, interval hip replacement, range of motion [ROM, a reduction of ≥10° in internal rotation], or disability [increase of ≥0.2 in Health Assessment Questionnaire scores], or Any of these) were assessed using logistic regression, adjusting for age, gender, race, hip injury, BMI, education, smoking and follow-up time, accounting for multiple comparisons. Race interactions were assessed and analyses stratified as indicated. The sample (n = 1,422) included 40 % men and 26 % African American (AA) participants, with mean age 61 years and BMI 29 kg/m(2). The baseline frequency of radiographic hip OA (RHOA) between Caucasians and AAs was similar (23 %), although some radiographic features differed. AAs were more likely to have progression defined by ROM or disability or Any progression; Caucasians were more likely to have RHOA progression. JSN, subchondral sclerosis, and medial osteophytes were associated with increased RHOA progression overall; JSN was associated with disability progression only in AAs, while lateral osteophytes were associated with ROM progression only in Caucasians. AAs and Caucasians exhibited differences in the radiographic presentation and progression patterns of HOA, with AAs reporting progressive pain and disability, while Caucasians had more RHOA progression.

  2. Smoking and multiple sclerosis: A systematic review and meta-analysis using the Bradford Hill criteria for causation.

    PubMed

    Degelman, Michelle L; Herman, Katya M

    2017-10-01

    Despite being one of the most common neurological disorders globally, the cause(s) of multiple sclerosis (MS) remain unknown. Cigarette smoking has been studied with regards to both the development and progression of MS. The Bradford Hill criteria for causation can contribute to a more comprehensive evaluation of a potentially causal risk factor-disease outcome relationship. The objective of this systematic review and meta-analysis was to assess the relationship between smoking and both MS risk and MS progression, subsequently applying Hill's criteria to further evaluate the likelihood of causal associations. The Medline, EMBASE, CINAHL, PsycInfo, and Cochrane Library databases were searched for relevant studies up until July 28, 2015. A random-effects meta-analysis was conducted for three outcomes: MS risk, conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS), and progression from relapsing-remitting multiple sclerosis (RRMS) to secondary-progressive multiple sclerosis (SPMS). Dose-response relationships and risk factor interactions, and discussions of mechanisms and analogous associations were noted. Hill's criteria were applied to assess causality of the relationships between smoking and each outcome. The effect of second-hand smoke exposure was also briefly reviewed. Smoking had a statistically significant association with both MS risk (conservative: OR/RR 1.54, 95% CI [1.46-1.63]) and SPMS risk (HR 1.80, 95% CI [1.04-3.10]), but the association with progression from CIS to CDMS was non-significant (HR 1.13, 95% CI [0.73-1.76]). Using Hill's criteria, there was strong evidence of a causal role of smoking in MS risk, but only moderate evidence of a causal association between smoking and MS progression. Heterogeneity in study designs and target populations, inconsistent results, and an overall scarcity of studies point to the need for more research on second-hand smoke exposure in relation to MS prior to conducting a detailed meta-analysis. This first review to supplement systematic review and meta-analytic methods with Hill's criteria to analyze the smoking-MS association provides evidence supporting the causal involvement of smoking in the development and progression of MS. Smoking prevention and cessation programs and policies should consider MS as an additional health risk when aiming to reduce smoking prevalence in the population. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. SF Bay Delta TMDL Progress Assessment

    EPA Pesticide Factsheets

    EPA assessed the progress 14 TMDLs in the SF Bay Delta Estuary (SF Bay Delta) to determine if the actions called for in the TMDL were being accomplished and water quality was improving. Status and water quality reports can be found here.

  4. Developments in Neuropsychological and Neurophysiological Assessment: An Overview of Progress and Products of the JWGD3 (Joint Working Group on Drug Dependent Degradation) Level I Neuropsychology Task Area Group

    DTIC Science & Technology

    1986-01-01

    995AB.081 IDA303502 11. TITLE (Indclude Security Classafication) Developments in Neuropsychological and Neurophysiological Assessment: An overview of...progress and products of the JWGD3 Level I Neuropsychology Task Area Group 12. PERSONAL AU1TOR(S) Reeves, D.L.; Taube, S.L. 13a. TYPE OF REPORT I13b...Phone: (301) 588-0058 7 Developments in Neuropsychological and Neurophysiological Assessment An Overview of Progress and Products of the JWGD3 Level I

  5. Machine Learning and Data Mining for Comprehensive Test Ban Treaty Monitoring

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Russell, S; Vaidya, S

    2009-07-30

    The Comprehensive Test Ban Treaty (CTBT) is gaining renewed attention in light of growing worldwide interest in mitigating risks of nuclear weapons proliferation and testing. Since the International Monitoring System (IMS) installed the first suite of sensors in the late 1990's, the IMS network has steadily progressed, providing valuable support for event diagnostics. This progress was highlighted at the recent International Scientific Studies (ISS) Conference in Vienna in June 2009, where scientists and domain experts met with policy makers to assess the current status of the CTBT Verification System. A strategic theme within the ISS Conference centered on exploring opportunitiesmore » for further enhancing the detection and localization accuracy of low magnitude events by drawing upon modern tools and techniques for machine learning and large-scale data analysis. Several promising approaches for data exploitation were presented at the Conference. These are summarized in a companion report. In this paper, we introduce essential concepts in machine learning and assess techniques which could provide both incremental and comprehensive value for event discrimination by increasing the accuracy of the final data product, refining On-Site-Inspection (OSI) conclusions, and potentially reducing the cost of future network operations.« less

  6. A case-control study relating railroad worker mortality to diesel exhaust exposure using a threshold regression model.

    PubMed

    Lee, Mei-Ling Ting; Whitmore, G A; Laden, Francine; Hart, Jaime E; Garshick, Eric

    2009-01-01

    A case-control study of lung cancer mortality in U.S. railroad workers in jobs with and without diesel exhaust exposure is reanalyzed using a new threshold regression methodology. The study included 1256 workers who died of lung cancer and 2385 controls who died primarily of circulatory system diseases. Diesel exhaust exposure was assessed using railroad job history from the US Railroad Retirement Board and an industrial hygiene survey. Smoking habits were available from next-of-kin and potential asbestos exposure was assessed by job history review. The new analysis reassesses lung cancer mortality and examines circulatory system disease mortality. Jobs with regular exposure to diesel exhaust had a survival pattern characterized by an initial delay in mortality, followed by a rapid deterioration of health prior to death. The pattern is seen in subjects dying of lung cancer, circulatory system diseases, and other causes. The unique pattern is illustrated using a new type of Kaplan-Meier survival plot in which the time scale represents a measure of disease progression rather than calendar time. The disease progression scale accounts for a healthy-worker effect when describing the effects of cumulative exposures on mortality.

  7. Animal Welfare in Studies on Murine Tuberculosis: Assessing Progress over a 12-Year Period and the Need for Further Improvement

    PubMed Central

    Franco, Nuno Henrique; Correia-Neves, Margarida; Olsson, I. Anna S.

    2012-01-01

    There is growing concern over the welfare of animals used in research, in particular when these animals develop pathology. The present study aims to identify the main sources of animal distress and to assess the possible implementation of refinement measures in experimental infection research, using mouse models of tuberculosis (TB) as a case study. This choice is based on the historical relevance of mouse studies in understanding the disease and the present and long-standing impact of TB on a global scale. Literature published between 1997 and 2009 was analysed, focusing on the welfare impact on the animals used and the implementation of refinement measures to reduce this impact. In this 12-year period, we observed a rise in reports of ethical approval of experiments. The proportion of studies classified into the most severe category did however not change significantly over the studied period. Information on important research parameters, such as method for euthanasia or sex of the animals, were absent in a substantial number of papers. Overall, this study shows that progress has been made in the application of humane endpoints in TB research, but that a considerable potential for improvement remains. PMID:23110093

  8. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study.

    PubMed

    Richard, Edo; Gouw, Alida A; Scheltens, Philip; van Gool, Willem A

    2010-03-01

    White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.

  9. The progression rate of spinocerebellar ataxia type 2 changes with stage of disease.

    PubMed

    Monte, Thais Lampert; Reckziegel, Estela da Rosa; Augustin, Marina Coutinho; Locks-Coelho, Lucas D; Santos, Amanda Senna P; Furtado, Gabriel Vasata; de Mattos, Eduardo Preusser; Pedroso, José Luiz; Barsottini, Orlando Póvoas; Vargas, Fernando Regla; Saraiva-Pereira, Maria-Luiza; Camey, Suzi Alves; Leotti, Vanessa Bielefeldt; Jardim, Laura Bannach

    2018-01-25

    Spinocerebellar ataxia type 2 (SCA2) affects several neurological structures, giving rise to multiple symptoms. However, only the natural history of ataxia is well known, as measured during the study duration. We aimed to describe the progression rate of ataxia, by the Scale for the Assessment and Rating of Ataxia (SARA), as well as the progression rate of the overall neurological picture, by the Neurological Examination Score for Spinocerebellar Ataxias (NESSCA), and not only during the study duration but also in a disease duration model. Comparisons between these models might allow us to explore whether progression is linear during the disease duration in SCA2; and to look for potential modifiers. Eighty-eight evaluations were prospectively done on 49 symptomatic subjects; on average (SD), study duration and disease duration models covered 13 (2.16) months and 14 (6.66) years of individuals' life, respectively. SARA progressed 1.75 (CI 95%: 0.92-2.57) versus 0.79 (95% CI 0.45 to 1.14) points/year in the study duration and disease duration models. NESSCA progressed 1.45 (CI 95%: 0.74-2.16) versus 0.41 (95% CI 0.24 to 0.59) points/year in the same models. In order to explain these discrepancies, the progression rates of the study duration model were plotted against disease duration. Then an acceleration was detected after 10 years of disease duration: SARA scores progressed 0.35 before and 2.45 points/year after this deadline (p = 0.013). Age at onset, mutation severity, and presence of amyotrophy, parkinsonism, dystonic manifestations and cognitive decline at baseline did not influence the rate of disease progression. NESSCA and SARA progression rates were not constant during disease duration in SCA2: early phases of disease were associated with slower progressions. Modelling of future clinical trials on SCA2 should take this phenomenon into account, since disease duration might impact on inclusion criteria, sample size, and study duration. Our database is available online and accessible to future studies aimed to compare the present data with other cohorts.

  10. Processes regulating progressive nitrogen limitation under elevated carbon dioxide: a meta-analysis

    NASA Astrophysics Data System (ADS)

    Liang, J.; Qi, X.; Souza, L.; Luo, Y.

    2015-10-01

    Nitrogen (N) cycle has the potential to regulate climate change through its influence on carbon (C) sequestration. Although extensive researches have been done to explore whether or not progressive N limitation (PNL) occurs under CO2 enrichment, a comprehensive assessment of the processes that regulate PNL is still lacking. Here, we quantitatively synthesized the responses of all major processes and pools in terrestrial N cycle with meta-analysis of CO2 experimental data available in the literature. The results showed that CO2 enrichment significantly increased N sequestration in plant and litter pools but not in soil pool. Thus, the basis of PNL occurrence partially exists. However, CO2 enrichment also significantly increased the N influx via biological N fixation, but decreased the N efflux via leaching. In addition, no general diminished CO2 fertilization effect on plant growth over time was observed. Overall, our analyses suggest that the extra N supply by the increased biological N fixation and decreased leaching may potentially alleviate PNL under elevated CO2 conditions. Moreover, our synthesis showed that CO2 enrichment increased soil ammonium (NH4+) but decreased nitrate (NO3-). The different responses of NH4+ and NO3-, and the consequent biological processes, may result in changes in soil microenvironment, community structures and above-belowground interactions, which could potentially affect the terrestrial biogeochemical cycles and the feedback to climate change.

  11. Loyalty and positive word-of-mouth: patients and hospital personnel as advocates of a customer-centric health care organization.

    PubMed

    Ferguson, Ronald J; Paulin, Michele; Leiriao, Elizabeth

    2006-01-01

    The ability to attract and retain loyal customers depends on the successful implementation of a customer-centric strategy. Customer loyalty is an attitude about an organization and its' services that is manifested by intentions and behaviors of re-patronization and recommendation. In the context of many medical services, loyalty through repeat patronization is not pertinent, whereas loyalty through positive word-of mouth (WOM) recommendation can be a powerful marketing tool. The Shouldice Hospital, a well-known institution for the surgical correction of hernias, instituted a marketing plan to develop a stable base of patients by creating positive WOM advocacy. This study focused on the consequences of both hernia patient overall satisfaction (and overall service quality) and hospital personnel satisfaction on the level of positive WOM advocacy. Using a commitment ladder of positive WOM advocacy, respondents were divided into three categories described as passive supporters, active advocates and ambassador advocates. Patient assessments of overall satisfaction and service quality were significantly related to these progressive levels of WOM for recommending the hospital to potential patients. Similarly, the satisfaction of the hospital employees was also significantly related to these progressive levels of positive WOM about recommending the hospital to potential patients and to potential employees. High levels of satisfaction are required to create true ambassadors of a service organization.

  12. Environmental Biosciences Program Quarterly Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lawrence C. Mohr, M.D.

    2009-01-30

    Current research projects have focused Environmental Biosciences Program (EBP) talent and resources on providing the scientific basis for risk-based standards, risk-based decision making and the accelerated clean-up of widespread environmental hazards. These hazards include trichloroethylene, low-dose ionizing radiation (gamma and neutron) and alpha radiation from plutonium. Trichloroethylene research has been conducted as a joint collaborative effort with the University of Georgia. Work on the trichloroethylene research projects has been slowed as a result of funding uncertainties. The impact of these funding uncertainties has been discussed with the United States Department of Energy (DOE). Laboratory work has been completed on severalmore » trichloroethylene risk assessment projects, and these projects have been brought to a close. Plans for restructuring the performance schedule of the remaining trichloroethylene projects have been submitted to the department. A comprehensive manuscript on the scientific basis of trichloroethylene risk assessment is in preparation. Work on the low-dose radiation risk assessment projects is also progressing at a slowed rate as a result of funding uncertainties. It has been necessary to restructure the proponency and performance schedule of these projects, with the project on Low-Dose Radiation: Epidemiology Risk Models transferred to DOE Office of Science proponency under a separate funding instrument. Research on this project will continue under the provisions of the DOE Office of Science funding instrument, with progress reported in accordance with the requirements of that funding instrument. Progress on that project will no longer be reported in quarterly reports for DE-FC09-02CH11109. Following a meeting at the Savannah River Site on May 8, 2008, a plan was submitted for development of an epidemiological cohort study and prospective medical surveillance system for the assessment of disease rates among workers at the Savannah River Site (SRS). This project will be incorporated into the ongoing project on Population Health Risks in the Vicinity of the Savannah River Site. During a meeting at the SRS on October 21, 2008, a presentation was made on EBP participation in the development and operation of an Epidemiology Consortium at the SRS. A follow-up meeting with SRS officials is planned for 29 and 30 January 2009 at Medical University of South Carolina (MUSC).An epidemiology project on population health risk assessment is being conducted to assess health risks among populations in the vicinity of the SRS. This project is using the capabilities of the EBP GIS for the geographical assessment of cancer and non-cancer disease rates, as well as the potential association of population health risks with environmental exposures. Although funding uncertainties have slowed progress on some aspects of this project, it has not been necessary to restructure the performance schedule to date.« less

  13. Learning Progressions as Tools for Assessment and Learning

    ERIC Educational Resources Information Center

    Shepard, Lorrie A.

    2018-01-01

    This article addresses the teaching and learning side of the learning progressions literature, calling out for measurement specialists the knowledge most needed when collaborating with subject-matter experts in the development of learning progressions. Learning progressions are one of the strongest instantiations of principles from "Knowing…

  14. Relationship between synovial inflammatory cytokines and progression of osteoarthritis after hip arthroscopy: Experimental assessment.

    PubMed

    Fukushima, Kensuke; Inoue, Gen; Uchida, Kentaro; Fujimaki, Hisako; Miyagi, Masayuki; Nagura, Naoshige; Uchiyama, Katsufumi; Takahira, Naonobu; Takaso, Masashi

    2018-01-01

    Synovial membrane inflammation is the most commonly presenting finding during hip arthroscopy and may have a role in the pathomechanism of hip osteoarthritis (OA). The aim of this study was to determine the relationship between synovial cytokine levels and progression of OA after hip arthroscopy. We prospectively examined 20 patients (20 hips) who underwent arthroscopic hip surgery. For all patients, radiographs and severity of pain were evaluated preoperatively. During arthroscopy, we harvested a sample of the synovial membrane and determined the levels of six typical inflammatory cytokines with real-time polymerase chain reaction. We compared the levels of these cytokines in patients who showed OA progression and non-progression after hip arthroscopy. Although the average age of patients who showed OA progression postoperatively tended to be higher, there were no significant differences in characteristics involving clinical assessment between patients who showed OA progression and those who showed non-progression. Intraoperative tumour necrosis factor α (TNFα) expression was significantly higher in patients who showed OA progression postoperatively ( p = 0.042). Elevation of TNFα level might be a predictor of OA progression after hip arthroscopy.

  15. Response Assessment in Paediatric Phase I Trials According to RECIST Guidelines: Survival Outcomes, Patterns of Progression and Relevance of Changes in Tumour Measurements.

    PubMed

    Carceller, Fernando; Bautista, Francisco J; Fowkes, Lucy A; Marshall, Lynley V; Sirvent, Sara I; Chisholm, Julia C; Pearson, Andrew D J; Koh, Dow-Mu; Moreno, Lucas

    2016-08-01

    RECIST guidelines constitute the reference for radiological response assessment in most paediatric trials of anticancer agents. However, these criteria have not been validated in children. We evaluated the outcomes and patterns of progression of children/adolescents enrolled in phase I trials in two paediatric drug development units. Patients aged ≤21 assessed with RECIST (v1.0 or v1.1) were eligible. Clinico-radiological data were analysed using Mann-Whitney U and log-rank tests to correlate response categories and sum of longest diameters (SLD) with time-to-event variables and overall survival (OS). Sixty-one patients (71 enrolments) were evaluated; median age: 12.7 years (range, 3.1-20.9). Overall, 7% achieved complete/partial response (n = 5) and 31% disease stabilisation (n = 22). Median (95% CI) OS (in months) was 29.1 (27.6-30.6) with complete/partial response, 8.9 (2.0-15.8) with stable disease and 2.8 (2.3-3.3) with disease progression (P < 0.001); 32.6% patients with measurable disease presented exclusive progression of existing non-target lesions and/or new lesions. The change in SLD at best response showed a linear correlation with duration of response (r = -0.605; P = 0.004) and time on trial (r = -0.61; P = 0.003), but the change in SLD at progression did not correlate with time to progression (r = -0.219; P = 0.206). Response assessment according to RECIST correlated with OS in children/adolescents treated on phase I trials. The reduction in SLD at best response correlated with more prolonged responses. Tumour size did not constitute an optimal method to assess disease progression in one third of patients with measurable disease. Further refinement of current response assessment guidelines will enable the development of paediatric-specific radiological criteria. © 2016 Wiley Periodicals, Inc.

  16. NAEP 1996 Science Report for Department of Defense Domestic Dependent Elementary and Secondary Schools. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    O'Sullivan, Christine Y.; Jerry, Laura; Ballator, Nada; Herr, Fiona

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  17. NAEP 1996 Science State Report for Department of Defense Domestic Dependent Elementary and Secondary Schools, Grade 4. Findings from the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    Ballator, Nada; O'Sullivan, Christine Y.; Jerry, Laura

    In 1990, the National Assessment of Educational Progress (NAEP) included a Trial State Assessment (TSA); for the first time in the NAEP's history, voluntary state-by-state assessments were made. The sample was designed to represent the 8th grade public school population in a state or territory. In 1996, 44 states, the District of Columbia, Guam,…

  18. The Nation's Report Card [TM]: U.S. History 2010. National Assessment of Educational Progress at Grades 4, 8, and 12. With Highlighted Results from the 2009 High School Transcript Study. NCES 2011-468

    ERIC Educational Resources Information Center

    National Center for Education Statistics, 2011

    2011-01-01

    The 2010 National Assessment of Educational Progress (NAEP) U.S. history assessment measures how well fourth-, eighth-, and twelfth-graders are learning American history, and whether they can evaluate historical evidence and understand change and continuity over time. Comparing the results from the 2010 assessment to results from previous years…

  19. Modified stoke ankylosing spondylitis spinal score as an outcome measure to assess the impact of treatment on structural progression in ankylosing spondylitis.

    PubMed

    van der Heijde, Désirée; Braun, Jürgen; Deodhar, Atul; Baraliakos, Xenofon; Landewé, Robert; Richards, Hanno B; Porter, Brian; Readie, Aimee

    2018-05-30

    In ankylosing spondylitis (AS), structural damage that occurs as a result of syndesmophyte formation and ankylosis of the vertebral column is irreversible. Structural damage is currently assessed by conventional radiography and scoring systems that reliably assess radiographic structural damage are needed to capture the differential effects of drugs on structural damage progression. The validity of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) as a primary outcome measure in evaluating the effect of AS treatments on radiographic progression rates was assessed in this review. The mSASSS has not been used, to date, as a primary outcome measure in a prospective randomized controlled clinical trial of biologic therapy in AS. This review of the medical literature confirmed that the mSASSS is the most validated and widely used method for assessing radiographic progression in AS, correlating with worsening measures of disease signs and symptoms, spinal mobility and physical function, with a 2-year interval being required to ensure sufficient sensitivity to change.

  20. Assessing Progress toward Accreditation Related Objectives: Evidence regarding the Use of Self-Efficacy as an Outcome in the Advanced Concentration Research Curriculum

    ERIC Educational Resources Information Center

    Holden, Gary; Barker, Kathleen; Rosenberg, Gary; Onghena, Patrick

    2007-01-01

    Objective: Assessing the achievement of social work educational outcomes is a requirement of the Council on Social Work Education's Educational Policy and Standards (EPAS). The Evaluation Self-Efficacy Scale (ESE) was created to assess student progress in advanced concentration courses focused on evaluation and thereby provide data regarding…

  1. An Evaluation of the Value of Choice-Making Opportunities in Single-Operant Arrangements: Simple Fixed- and Progressive-Ratio Schedules

    ERIC Educational Resources Information Center

    Tiger, Jeffrey H.; Toussaint, Karen A.; Roath, Christopher T.

    2010-01-01

    The current study compared the effects of choice and no-choice reinforcement conditions on the task responding of 3 children with autism across 2 single-operant paradigm reinforcer assessments. The first assessment employed simple fixed-ratio (FR) schedules; the second used progressive-ratio (PR) schedules. The latter assessment identified the…

  2. A Summary Report of Iowa's Review of PreK-6 Reading Assessments for Universal Screening and Progress

    ERIC Educational Resources Information Center

    Iowa Department of Education, 2013

    2013-01-01

    This document contains summary information for the Iowa Department of Education's review of PreK-6th grade reading assessments for the purposes of Universal Screening and Progress Monitoring. It is intended to provide general information to help inform decisions about selecting assessments for use as a part of Iowa's Response to Intervention…

  3. Maine Assessment of Educational Progress, Report 2. Results Report 1: Citizenship and Writing, 1972.

    ERIC Educational Resources Information Center

    Maine State Dept. of Educational and Cultural Services, Augusta.

    The purpose of the Maine Assessment of Educational Progress (MAEP) in 1972 was to complete the first phase of a 10-year comprehensive needs assessment program involving students in public and non-public schools of the state. The total program is designed to provide specific information about knowledge, skills, understandings, and attitudes in 10…

  4. National Assessment of Educational Progress, Report 1--Science: National Results. Observations and Commentary of a Panel of Reviewers.

    ERIC Educational Resources Information Center

    National Assessment of Educational Progress, Ann Arbor, MI.

    Presented are five reviews of the National Assessment of Educational Progress results in science. Dr. Mildred Ballou discusses the objectives of the assessment by age level with concern over explanations for responses, social implications, and validity of testing exercises. Wilmer Cooksey comments on the results as viewed by the classroom teacher…

  5. The National Assessment of Educational Progress: Changes in Reporting and Dissemination for 1992 and Beyond.

    ERIC Educational Resources Information Center

    Fromboluti, Carol Sue

    Changes that have been made in reporting and disseminating information from the National Assessment of Educational Progress are discussed, focusing on those changes brought about by the first Trial State Assessment (TSA). The TSA collected data on the mathematics performance of students in grades 4, 8, and 12 in public and private schools in 40…

  6. Review of Recent Literature Relevant to the Environmental Effects of Marine and Hydrokinetic Energy Devices; Task 2.1.3: Effects on Aquatic Organisms - Fiscal Year 2012 Progress Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kropp, Roy K.

    2013-01-01

    A literature search was conducted by using the Web of Science® databases component of the ISI Web of KnowledgeSM to identify recent articles that would be useful to help assess the potential environmental effects of renewable energy development in the ocean, with emphasis on seabirds and fish. Several relatively recent general review articles that included possible effects on seabirds and fish were examined to begin the search process. From these articles, several general topics of potential environmental effects on seabirds and fish were derived. These topics were used as the primary search factors. Additional sources were identified by cross-checking themore » Web of Science databases for articles that cited the review articles. It also became clear that the potential effects frequently w« less

  7. Diagnosis of glaucoma and detection of glaucoma progression using spectral domain optical coherence tomography.

    PubMed

    Grewal, Dilraj S; Tanna, Angelo P

    2013-03-01

    With the rapid adoption of spectral domain optical coherence tomography (SDOCT) in clinical practice and the recent advances in software technology, there is a need for a review of the literature on glaucoma detection and progression analysis algorithms designed for the commercially available instruments. Peripapillary retinal nerve fiber layer (RNFL) thickness and macular thickness, including segmental macular thickness calculation algorithms, have been demonstrated to be repeatable and reproducible, and have a high degree of diagnostic sensitivity and specificity in discriminating between healthy and glaucomatous eyes across the glaucoma continuum. Newer software capabilities such as glaucoma progression detection algorithms provide an objective analysis of longitudinally obtained structural data that enhances our ability to detect glaucomatous progression. RNFL measurements obtained with SDOCT appear more sensitive than time domain OCT (TDOCT) for glaucoma progression detection; however, agreement with the assessments of visual field progression is poor. Over the last few years, several studies have been performed to assess the diagnostic performance of SDOCT structural imaging and its validity in assessing glaucoma progression. Most evidence suggests that SDOCT performs similarly to TDOCT for glaucoma diagnosis; however, SDOCT may be superior for the detection of early stage disease. With respect to progression detection, SDOCT represents an important technological advance because of its improved resolution and repeatability. Advancements in RNFL thickness quantification, segmental macular thickness calculation and progression detection algorithms, when used correctly, may help to improve our ability to diagnose and manage glaucoma.

  8. Hydra as a model organism to decipher the toxic effects of copper oxide nanorod: Eco-toxicogenomics approach.

    PubMed

    Murugadas, Anbazhagan; Zeeshan, Mohammed; Thamaraiselvi, Kaliannan; Ghaskadbi, Surendra; Akbarsha, Mohammad Abdulkader

    2016-07-15

    Nanotechnology has emerged as a powerful field of applied research. However, the potential toxicity of nano-materials is a cause of concern. A thorough toxicological investigation is required before a nanomaterial is evaluated for application of any kind. In this context, there is concerted effort to find appropriate test systems to assess the toxicity of nanomaterials. Toxicity of a nanomaterial greatly depends on its physicochemical properties and the biological system with which it interacts. The present research was carried out with a view to generate data on eco-toxicological impacts of copper oxide nanorod (CuO NR) in Hydra magnipapillata 105 at organismal, cellular and molecular levels. Exposure of hydra to CuO NR resulted in severe morphological alterations in a concentration- as well as duration-dependent manner. Impairment of feeding, population growth, and regeneration was also observed. In vivo and in vitro analyses revealed induction of oxidative stress, genotoxicity, and molecular machinery of apoptotic cell death, accompanied by disruption of cell cycle progression. Taken together, CuO nanorod is potentially toxic to the biological systems. Also, hydra offers potential to be used as a convenient model organism for aquatic ecotoxicological risk assessment of nanomaterials.

  9. Hydra as a model organism to decipher the toxic effects of copper oxide nanorod: Eco-toxicogenomics approach

    PubMed Central

    Murugadas, Anbazhagan; Zeeshan, Mohammed; Thamaraiselvi, Kaliannan; Ghaskadbi, Surendra; Akbarsha, Mohammad Abdulkader

    2016-01-01

    Nanotechnology has emerged as a powerful field of applied research. However, the potential toxicity of nano-materials is a cause of concern. A thorough toxicological investigation is required before a nanomaterial is evaluated for application of any kind. In this context, there is concerted effort to find appropriate test systems to assess the toxicity of nanomaterials. Toxicity of a nanomaterial greatly depends on its physicochemical properties and the biological system with which it interacts. The present research was carried out with a view to generate data on eco-toxicological impacts of copper oxide nanorod (CuO NR) in Hydra magnipapillata 105 at organismal, cellular and molecular levels. Exposure of hydra to CuO NR resulted in severe morphological alterations in a concentration- as well as duration-dependent manner. Impairment of feeding, population growth, and regeneration was also observed. In vivo and in vitro analyses revealed induction of oxidative stress, genotoxicity, and molecular machinery of apoptotic cell death, accompanied by disruption of cell cycle progression. Taken together, CuO nanorod is potentially toxic to the biological systems. Also, hydra offers potential to be used as a convenient model organism for aquatic ecotoxicological risk assessment of nanomaterials. PMID:27417574

  10. Quantitative assessment of smoking-induced emphysema progression in longitudinal CT screening for lung cancer

    NASA Astrophysics Data System (ADS)

    Suzuki, H.; Mizuguchi, R.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.; Moriyama, N.

    2015-03-01

    Computed tomography has been used for assessing structural abnormalities associated with emphysema. It is important to develop a robust CT based imaging biomarker that would allow quantification of emphysema progression in early stage. This paper presents effect of smoking on emphysema progression using annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in longitudinal screening for lung cancer. The percentage of LAV (LAV%) was measured after applying CT value threshold method and small noise reduction. Progression of emphysema was assessed by statistical analysis of the annual changes represented by linear regression of LAV%. This method was applied to 215 participants in lung cancer CT screening for five years (18 nonsmokers, 85 past smokers, and 112 current smokers). The results showed that LAV% is useful to classify current smokers with rapid progression of emphysema (0.2%/year, p<0.05). This paper demonstrates effectiveness of the proposed method in diagnosis and prognosis of early emphysema in CT screening for lung cancer.

  11. The complex association between the antioxidant defense system and clinical status in early psychosis

    PubMed Central

    García, Saínza; Alberich, Susana; Martínez-Cengotitabengoa, Mónica; Arango, Celso; Castro-Fornieles, Josefina; Parellada, Mara; Baeza, Inmaculada; Moreno, Carmen; Micó, Juan Antonio; Berrocoso, Esther; Graell, Montserrat; Otero, Soraya; Simal, Tatiana

    2018-01-01

    Oxidative stress is a pathophysiological mechanism potentially involved in psychiatric disorders. The objective of this study was to assess the relationship between total antioxidant status (TAS) and the functional status of patients with a first episode of psychosis at the onset of the disease. For this purpose, a sample of 70 patients aged between 9 and 17 years with a first episode of psychosis were followed up for a period of two years. Blood samples were drawn to measure TAS levels at three time points: at baseline, at one year, and at two years. Clinical symptoms and functioning were also assessed at the same time points using various scales. Linear regression analysis was performed to investigate the relationship between TAS and clinical status at each assessment, adjusting for potential confounding factors. The distribution of clinical variables was grouped in different percentiles to assess the dose-response in the relation between clinical variables and TAS. At baseline, patient's score on Children's Global Assessment Scale (CGAS) was directly and significantly associated with TAS with a monotonic increase in percentiles, and surprising this association was reversed after one and two years of follow-up with a monotonic decrease. In summary at the onset of the illness, TAS is positively related to clinical status, whereas as the illness progresses this correlation is reversed and becomes negative. This may be the result of an adaptive response. PMID:29698400

  12. Assessing Patient Activation among High-Need, High-Cost Patients in Urban Safety Net Care Settings.

    PubMed

    Napoles, Tessa M; Burke, Nancy J; Shim, Janet K; Davis, Elizabeth; Moskowitz, David; Yen, Irene H

    2017-12-01

    We sought to examine the literature using the Patient Activation Measure (PAM) or the Patient Enablement Instrument (PEI) with high-need, high-cost (HNHC) patients receiving care in urban safety net settings. Urban safety net care management programs serve low-income, racially/ethnically diverse patients living with multiple chronic conditions. Although many care management programs track patient progress with the PAM or the PEI, it is not clear whether the PAM or the PEI is an effective and appropriate tool for HNHC patients receiving care in urban safety net settings in the United States. We searched PubMed, EMBASE, Web of Science, and PsycINFO for articles published between 2004 and 2015 that used the PAM and between 1998 and 2015 that used the PEI. The search was limited to English-language articles conducted in the United States and published in peer-reviewed journals. To assess the utility of the PAM and the PEI in urban safety net care settings, we defined a HNHC patient sample as racially/ethnically diverse, low socioeconomic status (SES), and multimorbid. One hundred fourteen articles used the PAM. All articles using the PEI were conducted outside the U.S. and therefore were excluded. Nine PAM studies (8%) included participants similar to those receiving care in urban safety net settings, three of which were longitudinal. Two of the three longitudinal studies reported positive changes following interventions. Our results indicate that research on patient activation is not commonly conducted on racially and ethnically diverse, low SES, and multimorbid patients; therefore, there are few opportunities to assess the appropriateness of the PAM in such populations. Investigators expressed concerns with the potential unreliability and inappropriate nature of the PAM on multimorbid, older, and low-literacy patients. Thus, the PAM may not be able to accurately assess patient progress among HNHC patients receiving care in urban safety net settings. Assessing progress in the urban safety net care setting requires measures that account for the social and structural challenges and competing demands of HNHC patients.

  13. Forward-looking infrared imaging predicts ultimate burn depth in a porcine vertical injury progression model.

    PubMed

    Miccio, Joseph; Parikh, Shruti; Marinaro, Xavier; Prasad, Atulya; McClain, Steven; Singer, Adam J; Clark, Richard A F

    2016-03-01

    Current methods of assessing burn depth are limited and are primarily based on visual assessments by burn surgeons. This technique has been shown to have only 60% accuracy and a more accurate, simple, noninvasive method is needed to determine burn wound depth. Forward-looking infrared (FLIR) thermography is both noninvasive and user-friendly with the potential to rapidly assess burn depth. The purpose of this paper is to determine if early changes in burn temperature (first 3 days) can be a predictor of burn depth as assessed by vertical scarring 28 days after injury. While under general anesthesia, 20 burns were created on the backs of two female Yorkshire swine using a 2.5cm×2.5cm×7.5cm, 150g aluminum bar, for a total of 40 burns. FLIR imaging was performed at both early (1, 2 and 3 days) and late (7, 10, 14, 17, 21, 24 and 28 days) time points. Burns were imaged from a height of 12 inches from the skin surface. FLIR ExaminIR(©) software was used to examine the infrared thermographs. One hundred temperature points from burn edge to edge across the center of the burn were collected for each burn at all time points and were exported as a comma-separated values (CSV) file. The CSV file was processed and analyzed using a MATLAB program. The temperature profiles through the center of the burns generated parabola-like curves. The lowest temperature (temperature minimum) and a line midway between the temperature minimum and ambient skin temperature at the burn edges was defined and the area of the curve calculated (the "temperature half-area"). Half-area values 2 days after burn had higher correlations with scar depth than did the minimum temperatures. However, burns that became warmer from 1 day to 2 days after injury had a lower scar depth then burns that became cooler and this trend was best predicted by temperature minima. When data were analyzed as a diagnostic test for sensitivity and specificity using >3mm scarring, i.e. a full-thickness burn, as a clinically relevant criterion standard, temperature minima at 2 days after burn was found to be the most sensitive and specific test. FLIR imaging is a fast and simple tool that has been shown to predict burn wound outcome in a porcine vertical injury progression model. Data showed that more severe burn wounds get cooler between 1 and 2 days after burn. We found four analytic methods of FLIR images that were predictive of burn progression at 1 and 2 days after burn; however, temperature minima 2 days after burn appeared to be the best predictive test for injury progression to a full-thickness burn. Although these results must be validated in clinical studies, FLIR imaging has the potential to aid clinicians in assessing burn severity and thereby assisting in burn wound management. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  14. Reviewing effectiveness of ankle assessment techniques for use in robot-assisted therapy.

    PubMed

    Zhang, Mingming; Davies, T Claire; Zhang, Yanxin; Xie, Shane

    2014-01-01

    This article provides a comprehensive review of studies that investigated ankle assessment techniques to better understand those that can be used in the real-time monitoring of rehabilitation progress for implementation in conjunction with robot-assisted therapy. Seventy-six publications published between January 1980 and August 2013 were selected based on eight databases. They were divided into two main categories (16 qualitative and 60 quantitative studies): 13 goniometer studies, 18 dynamometer studies, and 29 studies about innovative techniques. A total of 465 subjects participated in the 29 quantitative studies of innovative measurement techniques that may potentially be integrated in a real-time monitoring device, of which 19 studies included less than 10 participants. Results show that qualitative ankle assessment methods are not suitable for real-time monitoring in robot-assisted therapy, though they are reliable for certain patients, while the quantitative methods show great potential. The majority of quantitative techniques are reliable in measuring ankle kinematics and kinetics but are usually available only for use in the sagittal plane. Limited studies determine kinematics and kinetics in all three planes (sagittal, transverse, and frontal) where motions of the ankle joint and the subtalar joint actually occur.

  15. A real-time PCR tool for the surveillance of zoonotic Onchocerca lupi in dogs, cats and potential vectors.

    PubMed

    Latrofa, Maria Stefania; Annoscia, Giada; Colella, Vito; Cavalera, Maria Alfonsa; Maia, Carla; Martin, Coralie; Šlapeta, Jan; Otranto, Domenico

    2018-04-01

    The ocular onchocercosis is caused by the zoonotic parasite Onchocerca lupi (Spirurida: Onchocercidae). A major hindrance to scientific progress is the absence of a reliable diagnostic test in affected individuals. Microscopic examination of skin snip sediments and the identification of adults embedded in ocular nodules are seldom performed and labour-intensive. A quantitative real-time PCR (qPCR) assay was herein standardized for the detection of O. lupi DNA and the results compared with microscopic examination and conventional PCR (cPCR). The specificity of qPCR and cPCR was assessed by processing the most common filarial nematodes infecting dogs, skin samples from O. lupi infected (n = 35 dogs) or uninfected animals (n = 21 dogs; n = 152 cats) and specimens of potential insect vector (n = 93 blackflies; n = 59 mosquitoes/midges). The analytical sensitivity of both assays was assessed using 10-fold serial dilutions of DNA from adult specimen and from a pool of microfilariae. The qPCR on skin samples revealed an analytical specificity of 100% and a sensitivity up to 8 x 10-1 fg/2μl O. lupi adult-DNA and up to 3.6 x 10-1 pg/2μl of mfs-DNA (corresponding to 1 x 10-2 mfs/2μl). Only 9.5% O. lupi-infected skin samples were positive for cPCR with a sensitivity of 8 x 10-1 pg/2μl of DNA. Out of 152 blackflies and mosquitoes/midges, eight specimens experimentally infected (n = 1 S. erythrocephalum; n = 1 S. ornatum; n = 6 Simulium sp.) were positive by qPCR. The qPCR assay herein standardized represents an important step forward in the diagnosis of zoonotic onchocercosis caused by O. lupi, especially for the detection and quantification of low number of mfs. This assay provides a fundamental contribution for the establishment of surveillance strategies aiming at assessing the presence of O. lupi in carnivores and in insect species acting as potential intermediate hosts. The O. lupi qPCR assay will enable disease progress monitoring as well as the diagnosis of apparently clinical healthy dogs and cats.

  16. Applying Item Response Theory methods to design a learning progression-based science assessment

    NASA Astrophysics Data System (ADS)

    Chen, Jing

    Learning progressions are used to describe how students' understanding of a topic progresses over time and to classify the progress of students into steps or levels. This study applies Item Response Theory (IRT) based methods to investigate how to design learning progression-based science assessments. The research questions of this study are: (1) how to use items in different formats to classify students into levels on the learning progression, (2) how to design a test to give good information about students' progress through the learning progression of a particular construct and (3) what characteristics of test items support their use for assessing students' levels. Data used for this study were collected from 1500 elementary and secondary school students during 2009--2010. The written assessment was developed in several formats such as the Constructed Response (CR) items, Ordered Multiple Choice (OMC) and Multiple True or False (MTF) items. The followings are the main findings from this study. The OMC, MTF and CR items might measure different components of the construct. A single construct explained most of the variance in students' performances. However, additional dimensions in terms of item format can explain certain amount of the variance in student performance. So additional dimensions need to be considered when we want to capture the differences in students' performances on different types of items targeting the understanding of the same underlying progression. Items in each item format need to be improved in certain ways to classify students more accurately into the learning progression levels. This study establishes some general steps that can be followed to design other learning progression-based tests as well. For example, first, the boundaries between levels on the IRT scale can be defined by using the means of the item thresholds across a set of good items. Second, items in multiple formats can be selected to achieve the information criterion at all the defined boundaries. This ensures the accuracy of the classification. Third, when item threshold parameters vary a bit, the scoring rubrics and the items need to be reviewed to make the threshold parameters similar across items. This is because one important design criterion of the learning progression-based items is that ideally, a student should be at the same level across items, which means that the item threshold parameters (d1, d 2 and d3) should be similar across items. To design a learning progression-based science assessment, we need to understand whether the assessment measures a single construct or several constructs and how items are associated with the constructs being measured. Results from dimension analyses indicate that items of different carbon transforming processes measure different aspects of the carbon cycle construct. However, items of different practices assess the same construct. In general, there are high correlations among different processes or practices. It is not clear whether the strong correlations are due to the inherent links among these process/practice dimensions or due to the fact that the student sample does not show much variation in these process/practice dimensions. Future data are needed to examine the dimensionalities in terms of process/practice in detail. Finally, based on item characteristics analysis, recommendations are made to write more discriminative CR items and better OMC, MTF options. Item writers can follow these recommendations to write better learning progression-based items.

  17. Spelling Strategies: Take Stock of Students' Spelling Progress.

    ERIC Educational Resources Information Center

    Gentry, J. Richard

    1998-01-01

    Presents four informal assessments that elementary teachers can use to compare students' spelling progress to typical midyear benchmarks. The assessments, which target K-6 students, emphasize alphabet recognition, phonemic awareness, attitude and consciousness about spelling, and spelling growth through writing samples. The paper includes a…

  18. Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment

    PubMed Central

    Germolec, Dori R.; Luebke, Robert W.; Johnson, Victor J.

    2016-01-01

    This overview is an update of the unit originally published in 2004. While the basic tenants of immunotoxicity have not changed in the past 10 years, several publications have explored the application of immunotoxicological data to the risk assessment process. Therefore, the goal of this unit is still to highlight relationships between xenobiotic-induced immunosuppression and risk of clinical diseases progression. In immunotoxicology, this may require development of models to equate moderate changes in markers of immune functions to potential changes in incidence or severity of infectious diseases. For most xenobiotics, exposure levels and disease incidence data are rarely available and safe exposure levels must be estimated based on observations from experimental models or human biomarker studies. Thus, it is important to establish a scientifically sound framework that allows accurate and quantitative interpretation of experimental or biomarker data in the risk assessment process. PMID:26828330

  19. Assessment of the Effects of High-Speed Aircraft in the Stratosphere: 1998

    NASA Technical Reports Server (NTRS)

    Kawa, S. Randolph; Anderson, James G.; Baughcum, Steven L.; Brock, Charles A.; Brune, William H.; Cohen, Ronald C.; Kinnison, Douglas E.; Newman, Paul A.; Rodriquez, Jose M.; Stolarski, Richard S.; hide

    1999-01-01

    This report assesses the potential atmospheric impacts of a proposed fleet of high-speed civil transport (HSCT) aircraft. The purpose of the report is to assess the effects of HSCT's on atmospheric composition and climate in order to provide a scientific basis for making technical, commercial, and environmental policy decisions regarding the HSCT fleet. The work summarized here was carried out as part of NASA's Atmospheric Effects of Aviation Project (a component of the High-Speed Research Program) as well as other NASA, U.S., and international research programs. The principal focus is on change in stratospheric ozone concentrations. The impact on climate change is also a concern. The report describes progress in understanding atmospheric processes, the current state of understanding of HSCT emissions, numerical model predictions of HSCT impacts, the principal uncertainties in atmospheric predictions, and the associated sensitivities in predicted effects of HSCT's.

  20. Assessment of the Effects of High-Speed Aircraft in the Stratosphere: 1998

    NASA Technical Reports Server (NTRS)

    Kawa, S. Randolph; Anderson, James G.; Baughcum, Steven L.; Brock, Charles A.; Brune, William H.; Cohen, Ronald C.; Kinnison, Douglas E.; Newman, Paul A.; Rodriguez, Jose M.; Stolarski, Richard S.; hide

    1999-01-01

    This report assesses the potential atmospheric impacts of a proposed fleet of high-speed civil transport (HSCT) aircraft. The purpose of the report is to assess the effects of HSCT's on atmospheric composition and climate in order to provide a scientific basis for making technical, commercial, and environmental policy decisions regarding the HSCT fleet. The work summarized here was carried out as part of NASA's Atmospheric Effects of Aviation Project (a component of the High-Speed Research Program) as well as other NASA, U.S., and international research programs. The principal focus is on change in stratospheric ozone concentrations. The impact on climate change is also a concern. The report describes progress in understanding atmospheric processes, the current state of understanding of HSCT emissions, numerical model predictions of HSCT impacts, the principal uncertainties in atmospheric predictions, and the associated sensitivities in predicted effects of HSCT'S.

  1. Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment.

    PubMed

    DeWitt, Jamie C; Germolec, Dori R; Luebke, Robert W; Johnson, Victor J

    2016-02-01

    This overview is an update of the unit originally published in 2004. While the basic tenets of immunotoxicity have not changed in the past 10 years, several publications have explored the application of immunotoxicological data to the risk assessment process. Therefore, the goal of this unit is still to highlight relationships between xenobiotic-induced immunosuppression and risk of clinical diseases progression. In immunotoxicology, this may require development of models to equate moderate changes in markers of immune functions to potential changes in incidence or severity of infectious diseases. For most xenobiotics, exposure levels and disease incidence data are rarely available, and safe exposure levels must be estimated based on observations from experimental models or human biomarker studies. Thus, it is important to establish a scientifically sound framework that allows accurate and quantitative interpretation of experimental or biomarker data in the risk assessment process. Copyright © 2016 John Wiley & Sons, Inc.

  2. TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort.

    PubMed

    Molnar, Christoph; Scherer, Almut; Baraliakos, Xenofon; de Hooge, Manouk; Micheroli, Raphael; Exer, Pascale; Kissling, Rudolf O; Tamborrini, Giorgio; Wildi, Lukas M; Nissen, Michael J; Zufferey, Pascal; Bernhard, Jürg; Weber, Ulrich; Landewé, Robert B M; van der Heijde, Désirée; Ciurea, Adrian

    2018-01-01

    To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS). Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis. A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97). TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Assessment of nutritional status in cancer--the relationship between body composition and pharmacokinetics.

    PubMed

    Prado, Carla M M; Maia, Yara L M; Ormsbee, Michael; Sawyer, Michael B; Baracos, Vickie E

    2013-10-01

    Several nutritional assessment tools have been used in oncology settings to monitor nutritional status and its associated prognostic significance. Body composition is fundamental for the assessment of nutritional status. Recently, the use of accurate and precise body composition tools has significantly added to the value of nutritional assessment in this clinical setting. Computerized tomography (CT) is an example of a technique which provides state-of-the-art assessment of body composition. With use of CT images, a great variability in body composition of cancer patients has been identified even in people with identical body weight or body mass index. Severe muscle depletion (sarcopenia) has emerged as a prevalent body composition phenotype which is predictive of poor functional status, shorter time to tumor progression, shorter survival, and higher incidence of dose-limiting toxicity. Variability in body composition of cancer patients may be a source of disparities in the metabolism of cytotoxic agents. Future clinical trials investigating dose reductions in patients with sarcopenia and dose-escalating studies based on pre-treatment body composition assessment have the potential to alter cancer treatment paradigms.

  4. Immunomodulatory properties of 1,2-dihydro-4-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide derivative VL15.

    PubMed

    Malfitano, Anna Maria; Laezza, Chiara; Bertini, Simone; Marasco, Daniela; Tuccinardi, Tiziano; Bifulco, Maurizio; Manera, Clementina

    2017-04-01

    1,2-Dihydro-4-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide derivative VL15 has been recently developed as a selective cannabinoid CB2 receptor compound. Given the high selectivity of this compound at the cannabinoid CB2 receptor and the well-known protective function of this receptor in neurological disorders with autoimmune component like multiple sclerosis, we assessed the immunomodulatory properties of VL15. We assessed on activated peripheral blood mononuclear cells), proliferation and viability, cell cycle progression and measured activation markers and the expression of phosphorylated proteins. We found that VL15 reduces PBMC proliferation slightly affecting cell vitality, blocks the cell cycle progression and down-regulates the levels of T cell activation markers as well as the expression of phosphorylated proteins, NF-kB, IKKαβ, IKBα, ERK and Akt. VL15 was also used in drug-permeability assays on Caco-2 cell line to evaluate its oral bioavailability and on MDCKII-hMDR1 cell lines to estimate its propensity to cross the blood-brain barrier by passive diffusion, in order to potentially maintain its efficiency on the infiltrating auto-reactive lymphocytes in the central nervous system. In these models, VL15 showed high intestinal absorption and good blood-brain barrier penetration. Our findings suggest that VL15, by controlling the immune response, might find potential application as orally administered drug in pathologies like multiple sclerosis. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  5. Recent advances in understanding idiopathic pulmonary fibrosis

    PubMed Central

    Daccord, Cécile; Maher, Toby M.

    2016-01-01

    Despite major research efforts leading to the recent approval of pirfenidone and nintedanib, the dismal prognosis of idiopathic pulmonary fibrosis (IPF) remains unchanged. The elaboration of international diagnostic criteria and disease stratification models based on clinical, physiological, radiological, and histopathological features has improved the accuracy of IPF diagnosis and prediction of mortality risk. Nevertheless, given the marked heterogeneity in clinical phenotype and the considerable overlap of IPF with other fibrotic interstitial lung diseases (ILDs), about 10% of cases of pulmonary fibrosis remain unclassifiable. Moreover, currently available tools fail to detect early IPF, predict the highly variable course of the disease, and assess response to antifibrotic drugs. Recent advances in understanding the multiple interrelated pathogenic pathways underlying IPF have identified various molecular phenotypes resulting from complex interactions among genetic, epigenetic, transcriptional, post-transcriptional, metabolic, and environmental factors. These different disease endotypes appear to confer variable susceptibility to the condition, differing risks of rapid progression, and, possibly, altered responses to therapy. The development and validation of diagnostic and prognostic biomarkers are necessary to enable a more precise and earlier diagnosis of IPF and to improve prediction of future disease behaviour. The availability of approved antifibrotic therapies together with potential new drugs currently under evaluation also highlights the need for biomarkers able to predict and assess treatment responsiveness, thereby allowing individualised treatment based on risk of progression and drug response. This approach of disease stratification and personalised medicine is already used in the routine management of many cancers and provides a potential road map for guiding clinical care in IPF. PMID:27303645

  6. Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles.

    PubMed

    Förster, Yvonne; Schmidt, Johannes R; Wissenbach, Dirk K; Pfeiffer, Susanne E M; Baumann, Sven; Hofbauer, Lorenz C; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

    2016-01-01

    Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis.

  7. Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles

    PubMed Central

    Wissenbach, Dirk K.; Pfeiffer, Susanne E. M.; Baumann, Sven; Hofbauer, Lorenz C.; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

    2016-01-01

    Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis. PMID:27441377

  8. Using health technology assessment to identify gaps in evidence and inform study design for comparative effectiveness research.

    PubMed

    Tunis, Sean R; Turkelson, Charles

    2012-12-01

    Health technology assessment (HTA) is primarily used as a tool to ensure that clinical and policy decisions are made with the benefit of a systematic analysis of all completed research. This article describes the progress and potential for HTA reports to improve the quality and relevance of future research and to better serve the information needs of patients, clinicians, payers, and other decision makers. We conducted a review of the current published literature and working papers describing past, ongoing, and future initiatives that rely on HTA reports to identify gaps in evidence and improve the design of future research. Although still in a developmental stage, significant progress is under way to improve methods for using HTA reports for the systematic identification of research gaps, prioritization of future research, and improvement of study designs. Several well-defined frameworks have been developed to assist those who produce HTA to become more effective in these additional domains of work. A recurring element of this work is the importance of meaningfully involving stakeholders in the process of defining future research needs and designing studies to address them. Patients, clinicians, and payers are important audiences for completed research and are now recognized as serving an important role in determining what future research is needed. There are substantial opportunities to improve the quality, relevance, and efficiency of clinical research. Recent efforts are beginning to demonstrate the potential to build on the work invested in developing HTA reports to provide a roadmap toward these objectives.

  9. Darkness and near work: myopia and its progression in third-year law students.

    PubMed

    Loman, Jane; Quinn, Graham E; Kamoun, Layla; Ying, Gui-Shuang; Maguire, Maureen G; Hudesman, David; Stone, Richard A

    2002-05-01

    To evaluate myopia prevalence, myopia progression, and various potential myopia risk factors in third-year law students. Cross-sectional study and survey. One hundred seventy-nine third-year law students at the University of Pennsylvania. We administered a questionnaire to assess the prevalence of myopia, myopia progression, and risk factors, including near work, family history, and daily light/dark exposure. We conducted a screening eye examination to ascertain myopia status. Myopia was defined as the mean spherical equivalent of the two eyes of 5.6 hours of darkness per day (95% vs. 80%, P = 0.07). To account for possible confounding effects of risk factors with myopia progression, logistic regression with categorization of the continuous exposure variables (hours of near work, sleep, and darkness) above or below median values weakened the near work association (odds ratio 1.8, 95% confidence interval 0.5-6.7, P = 0.35) but continued to identify darkness association with daily hours of darkness (odds ratio 4.8, 95% confidence interval 1.0 >/= 23.3, P < 0.05). Among the 77 students with myopia onset before college, those with

  10. The use of genetically modified mice in cancer risk assessment: challenges and limitations.

    PubMed

    Eastmond, David A; Vulimiri, Suryanarayana V; French, John E; Sonawane, Babasaheb

    2013-09-01

    The use of genetically modified (GM) mice to assess carcinogenicity is playing an increasingly important role in the safety evaluation of chemicals. While progress has been made in developing and evaluating mouse models such as the Trp53⁺/⁻, Tg.AC and the rasH2, the suitability of these models as replacements for the conventional rodent cancer bioassay and for assessing human health risks remains uncertain. The objective of this research was to evaluate the use of accelerated cancer bioassays with GM mice for assessing the potential health risks associated with exposure to carcinogenic agents. We compared the published results from the GM bioassays to those obtained in the National Toxicology Program's conventional chronic mouse bioassay for their potential use in risk assessment. Our analysis indicates that the GM models are less efficient in detecting carcinogenic agents but more consistent in identifying non-carcinogenic agents. We identified several issues of concern related to the design of the accelerated bioassays (e.g., sample size, study duration, genetic stability and reproducibility) as well as pathway-dependency of effects, and different carcinogenic mechanisms operable in GM and non-GM mice. The use of the GM models for dose-response assessment is particularly problematic as these models are, at times, much more or less sensitive than the conventional rodent cancer bioassays. Thus, the existing GM mouse models may be useful for hazard identification, but will be of limited use for dose-response assessment. Hence, caution should be exercised when using GM mouse models to assess the carcinogenic risks of chemicals.

  11. The use of genetically modified mice in cancer risk assessment: Challenges and limitations*

    PubMed Central

    Eastmond, David A.; Vulimiri, Suryanarayana V.; French, John E.; Sonawane, Babasaheb

    2015-01-01

    The use of genetically modified (GM) mice to assess carcinogenicity is playing an increasingly important role in the safety evaluation of chemicals. While progress has been made in developing and evaluating mouse models such as the Trp53+/−, Tg.AC and the rasH2, the suitability of these models as replacements for the conventional rodent cancer bioassay and for assessing human health risks remains uncertain. The objective of this research was to evaluate the use of accelerated cancer bioassays with GM mice for assessing the potential health risks associated with exposure to carcinogenic agents. We compared the published results from the GM bioassays to those obtained in the National Toxicology Program’s conventional chronic mouse bioassay for their potential use in risk assessment. Our analysis indicates that the GM models are less efficient in detecting carcinogenic agents but more consistent in identifying non-carcinogenic agents. We identified several issues of concern related to the design of the accelerated bioassays (e.g., sample size, study duration, genetic stability and reproducibility) as well as pathway-dependency of effects, and different carcinogenic mechanisms operable in GM and non-GM mice. The use of the GM models for dose-response assessment is particularly problematic as these models are, at times, much more or less sensitive than the conventional rodent cancer bioassays. Thus, the existing GM mouse models may be useful for hazard identification, but will be of limited use for dose-response assessment. Hence, caution should be exercised when using GM mouse models to assess the carcinogenic risks of chemicals. PMID:23985072

  12. Early Cerebral Blood Volume Changes Predict Progression After Convection-Enhanced Delivery of Topotecan for Recurrent Malignant Glioma.

    PubMed

    Surapaneni, Krishna; Kennedy, Benjamin C; Yanagihara, Ted K; DeLaPaz, Robert; Bruce, Jeffrey N

    2015-07-01

    To assess whether early changes in enhancing tumor volume (eTV) and relative cerebral blood volume (rCBV) 1 month after convection-enhanced delivery of topotecan in patients with recurrent malignant glioma correlated with 6-month disease progression status. Sixteen patients were enrolled in a Phase Ib trial of convection-enhanced delivery of topotecan for recurrent malignant glioma. Each patient was evaluated with serial follow-up magnetic resonance imaging at baseline and at 4- to 8-week intervals. Changes at 1 month compared with baseline in eTV and rCBV were evaluated as potential predictors of 6-month progression status, classified as either progressive disease or nonprogressive disease. Relationships between percent changes in eTV and rCBV at 1 month with the probability of progressive disease at 6 months were estimated by the use of logistic regression analysis. Receiver operating characteristic curves for varying percent change thresholds in eTV and rCBV were evaluated by the use of 6-month progressive disease as the reference. There was a significant difference in the percent change in rCBV at 1 month in patients with progressive disease compared with those with nonprogressive disease at 6 months (+12% vs. -29%, P = 0.02). Logistic regression analysis demonstrated on average that a 10% increase in rCBV at 1 month after convection-enhanced delivery of topotecan was associated with 1.7 times the odds of developing progressive disease at 6 months (95% confidence interval [CI] 1.0-2.9 P = 0.05). Receiver operating characteristic analysis for determining progressive disease at 6 months showed a greater area under the curve with rCBV (0.867; 95% CI 0.66-1.00) than with change in enhancing tumor volume (0.767; 95% CI 0.51-1.00). In this selected population of patients with recurrent malignant glioma treated with convection-enhanced delivery of topotecan, early changes in rCBV at 4 weeks after therapy may help predict progression status at 6 months. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Epoch Analysis of On-Treatment Disability Progression Events over Time in the Tysabri Observational Program (TOP)

    PubMed Central

    Wiendl, Heinz; Butzkueven, Helmut; Kappos, Ludwig; Trojano, Maria; Pellegrini, Fabio; Paes, Dominic; Zhang, Annie; Belachew, Shibeshih

    2016-01-01

    Objective To evaluate the effect of natalizumab on disability progression beyond 2 years of treatment in clinical practice. Methods Analyses included the 496 relapsing-remitting multiple sclerosis (RRMS) patients among 5122 patients in the Tysabri Observational Program (TOP) who had completed 4 continuous years of natalizumab treatment and had baseline (study enrollment) and postbaseline Expanded Disability Status Scale (EDSS) assessments. Proportions of patients with 6-month or 12-month confirmed ≥1.0-point EDSS progression relative to baseline were compared in treatment months 1–24 and 25–48. Sensitivity analyses compared progression rates in months 13–24 and 25–36. Results Baseline characteristics appeared similar between the overall TOP population (N = 5122), patients who had completed 4 years of natalizumab treatment (n = 469), and patients eligible to complete 4 years in TOP who had discontinued natalizumab after 2 years of treatment (n = 514). Among 4-year completers, the proportion of patients with 6-month and 12-month confirmed EDSS progression decreased between months 1–24 and 25–48 of natalizumab treatment by 42% (from 10.9% to 6.3%; p < 0.01) and 52% (from 9.5% to 4.6%; p < 0.01), respectively. Few patients had 6-month or 12-month confirmed EDSS progression in both epochs (0.6% and 0.2%, respectively). Between months 13–24 and 25–36 of treatment, the proportion of patients with 6-month and 12-month confirmed EDSS progression decreased by 60% (from 7.5% to 3.0%; p < 0.01) and 58% (from 6.7% to 2.8%; p < 0.01), respectively. Significant reductions in disability progression events between months 13–24 and 25–36 were also observed in relapse-free patients. Conclusion In this observational study, the disability progression rate decreased further beyond 2 years of natalizumab treatment. Patients who responded well and remained on continuous natalizumab therapy for over 4 years had sustained and potentially enhanced reductions in EDSS progression over time. PMID:26771747

  14. Assessing the Progress of Gender Parity in Education through Achieving Millennium Development Goals: A Case Study of Quetta District Balochistan

    ERIC Educational Resources Information Center

    Rashid, Abdul; Bibi, Zainab; Din, Siraj ud

    2012-01-01

    Using secondary data of Government Schools and literacy department for 10 years that is 2000-2010, this paper assesses the progress on the issue of gender equality within the framework of education related Millennium Development Goals (MDG) in district Quetta. The assessment is based on the selected indicators of goals by applying descriptive…

  15. Examining the Relationships among Mathematics Coaches and Specialists, Student Achievement, and Disability Status: A Multilevel Analysis Using National Assessment of Educational Progress Data

    ERIC Educational Resources Information Center

    Harbour, Kristin E.; Adelson, Jill L.; Pittard, Caroline M.; Karp, Karen S.

    2018-01-01

    Using restricted-use data from the 2011 National Assessment of Educational Progress mathematics assessment, the current study examined the relationship between the presence of elementary mathematics coaches and specialists (MCSs) and the mathematics achievement of more than 190,000 fourth-grade students in more than 7,400 schools nationwide. In…

  16. The Governance of the National Assessment of Educational Progress: A Brief Review and Some Options. Report No. A-158-5.

    ERIC Educational Resources Information Center

    Boruch, Robert F.

    This report concerns the governance of the structure of the National Assessment of Educational Progress (NAEP), especially the law and the role of the Assessment Policy Committee (APC). The major sources of evidence include interviews with APC members and National Institute of Education (NIE) staff, minutes of APC meetings and historical documents…

  17. National Assessment of Educational Progress: 1983-84 Public-Use Data Tapes, Version 3.1. Users' Guide.

    ERIC Educational Resources Information Center

    Barone, John L.; And Others

    This document is the users' guide for Version 3.1 of the Public-Use data tapes compiled by the National Assessment of Educational Progress (NAEP), 1983-84. The Public-Use tapes are produced to allow outside researchers access to the NAEP data. The tapes accompanying this guide contain data assessing student achievement in reading and writing at…

  18. The Nation's Report Card: A First Look--2013 Mathematics and Reading. National Assessment of Educational Progress at Grades 4 and 8. NCES 2014-451

    ERIC Educational Resources Information Center

    National Center for Education Statistics, 2013

    2013-01-01

    The National Assessment of Educational Progress (NAEP) mathematics assessment measures students' knowledge and skills in mathematics and students' ability to apply their knowledge in problem-solving situations. At each grade, students responded to questions designed to measure what they know and can do across five mathematics content areas: number…

  19. 77 FR 20474 - Delegation of Authority; Delegation of Authority No. 24 to the Chief Operating Officer

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-04

    ... and performance planning, measurement, analysis, assessment of progress, and use of performance...; long- range budgeting and accounting; hiring and training employees; modernizing information technology..., measurement, analysis, regular assessment of progress and the use of performance information to improve...

  20. Assessment of Age-Related Differences in Functional Capacity Using the Virtual Reality Functional Capacity Assessment Tool (VRFCAT)

    PubMed Central

    Atkins, A.S.; Stroescu, I.; Spagnola, N.B.; Davis, V.G.; Patterson, T.D.; Narasimhan, M.; Harvey, P.D.; Keefe, R.S.E.

    2015-01-01

    Clinical trials for primary prevention and early intervention in preclinical AD require measures of functional capacity with improved sensitivity to deficits in healthier, non-demented individuals. To this end, the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) was developed as a direct performance-based assessment of functional capacity that is sensitive to changes in function across multiple populations. Using a realistic virtual reality environment, the VRFCAT assesses a subject's ability to complete instrumental activities associated with a shopping trip. The present investigation represents an initial evaluation of the VRFCAT as a potential co-primary measure of functional capacity in healthy aging and preclinical MCI/AD by examining test-retest reliability and associations with cognitive performance in healthy young and older adults. The VRFCAT was compared and contrasted with the UPSA-2-VIM, a traditional performance-based assessment utilizing physical props. Results demonstrated strong age-related differences in performance on each VRFCAT outcome measure, including total completion time, total errors, and total forced progressions. VRFCAT performance showed strong correlations with cognitive performance across both age groups. VRFCAT Total Time demonstrated good test-retest reliability (ICC=.80 in young adults; ICC=.64 in older adults) and insignificant practice effects, indicating the measure is suitable for repeated testing in healthy populations. Taken together, these results provide preliminary support for the VRFCAT as a potential measure of functionally relevant change in primary prevention and preclinical AD/MCI trials. PMID:26618145

  1. Clinical benefit of continuing crizotinib therapy after initial disease progression in Chinese patients with advanced ALK-rearranged non-small-cell lung cancer

    PubMed Central

    Hong, Xiangchan; Chen, Qi; Ding, Lingyu; Liang, Ying; Zhou, Ningning; Fang, Wenfeng; Chen, Xinru; Wu, Haiying

    2017-01-01

    Purpose Although most patients with ALK-positive non?small-cell lung cancer (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients may be beneficial. In this study, we investigated whether Chinese patients with advanced ALK-positive NSCLC benefit from CBPD, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2). Materials and Methods Data on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively. The impact of continued crizotinib therapy on the patients’ PFS2 time was assessed after adjusting for potential confounding factors. Results With initial crizotinib therapy, the objective response rate (ORR) and median PFS time (PFS1) in the 33 patients were 63.6% and 8.6 months, respectively. With continued crizotinib therapy after documentation of PD, the median PFS2 for all 33 patients was 16 weeks, and in those with CNS progression but systemic disease control it was 30 weeks. Patients who received local therapy after disease progression had a significantly longer PFS2 compared with those who did not (P = 0.039). Multivariable Cox regression analysis showed that the PFS1 with initial crizotinib treatment and local therapy were independent predictors of PFS2. Discussion This study provides further evidence of the benefit of continuing crizotinib therapy in Chinese patients with progressive ALK-positive NSCLC. Patients with a longer PFS1 and those who received local brain therapy would have a longer period of continuing crizotinib. PMID:28427213

  2. RUNX3 methylation in normal surrounding urothelium of patients with non-muscle-invasive bladder cancer: potential role in the prediction of tumor progression.

    PubMed

    Jeong, P; Min, B D; Ha, Y S; Song, P H; Kim, I Y; Ryu, K H; Kim, J H; Yun, S J; Kim, W J

    2012-11-01

    Previously, we reported a causal relationship between RUNX3 methylation and bladder tumor development. Thus, in order to clarify its role in tumorigenesis, this study aims to identify the function of RUNX3 methylation in normal adjacent urothelium of patients with non-muscle invasive bladder cancer (NMIBC). Tumor tissue and donor-matched normal adjacent tissue from 55 patients who underwent transurethral resection (TUR) were selected for the study, and RUNX3 promoter methylation was assessed using methylation-specific polymerase chain reaction (MS-PCR). RUNX3 promoter methylation occurred more frequently in tumor samples than in histologically normal urothelium in patients with NMIBC (P = 0.02). The methylation rates for the RUNX3 promoter in normal adjacent urothelium and tumor tissue were 47% and 69%, respectively. Interestingly, RUNX3 methylation in normal adjacent urothelium was associated with tumor number (P = 0.022) and progression (P = 0.035). Kaplan-Meier estimates revealed that RUNX3 methylation in normal urothelium showed a significant association with time to progression (P = 0.017) in NMIBC patients. Stratifying the patients into 'both methylation', 'one methylation' and 'no methylation' groups for tumors and normal urothelium revealed that no progression occurred in the 'no methylation' group during follow-up. Multivariate Cox regression analysis demonstrated that RUNX3 methylation in normal urothelium [hazards ratio (HR): 5.692, P = 0.042] was an independent predictor of progression. RUNX3 methylation was associated with transition from normal urothelium to bladder tumor. More importantly, RUNX3 methylation in normal adjacent urothelium may predict progression in NMIBC patients who have undergone TUR. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Recovery of polyclonal immunoglobulins one year after autologous stem cell transplantation as a long-term predictor marker of progression and survival in multiple myeloma.

    PubMed

    González-Calle, Verónica; Cerdá, Seila; Labrador, Jorge; Sobejano, Eduardo; González-Mena, Beatriz; Aguilera, Carmen; Ocio, Enrique María; Vidriales, María Belén; Puig, Noemí; Gutiérrez, Norma Carmen; García-Sanz, Ramón; Alonso, José María; López, Rosa; Aguilar, Carlos; de Coca, Alfonso García; Hernández, Roberto; Hernández, José Mariano; Escalante, Fernando; Mateos, María-Victoria

    2017-05-01

    Immunoparesis or suppression of polyclonal immunoglobulins is a very common condition in newly diagnosed myeloma patients. However, the recovery of polyclonal immunoglobulins in the setting of immune reconstitution after autologous stem cell transplantation and its effect on outcome has not yet been explored. We conducted this study in a cohort of 295 patients who had undergone autologous transplantation. In order to explore the potential role of immunoglubulin recovery as a dynamic predictor of progression or survival after transplantation, conditional probabilities of progression-free survival and overall survival were estimated according to immunoglobulin recovery at different time points using a landmark approach. One year after transplant, when B-cell reconstitution is expected to be completed, among 169 patients alive and progression free, 88 patients (52%) showed immunoglobulin recovery and 81 (48%) did not. Interestingly, the group with immunoglobulin recovery had a significantly longer median progression-free survival than the group with persistent immunoparesis (median 60.4 vs. 27.9 months, respectively; Hazard Ratio: 0.45, 95%Confidence Interval: 0.31-0.66; P <0.001), and improved overall survival (11.3 vs. 7.3 years; Hazard Ratio: 0.45, 95%Confidence Interval: 0.27-0.74; P =0.002). Furthermore, the percentage of normal plasma cells detected by flow cytometry in the bone marrow assessed at day 100 after transplantation was associated with the immunoglobulin recovery at that time and may predict immunoglobulin recovery in the subsequent months: nine months and one year. In conclusion, the recovery of polyclonal immunoglobulins one year after autologous transplantation in myeloma patients is an independent long-term predictor marker for progression and survival. Copyright© Ferrata Storti Foundation.

  4. Design of combination angiotensin receptor blocker and angiotensin-converting enzyme inhibitor for treatment of diabetic nephropathy (VA NEPHRON-D).

    PubMed

    Fried, Linda F; Duckworth, William; Zhang, Jane Hongyuan; O'Connor, Theresa; Brophy, Mary; Emanuele, Nicholas; Huang, Grant D; McCullough, Peter A; Palevsky, Paul M; Seliger, Stephen; Warren, Stuart R; Peduzzi, Peter

    2009-02-01

    Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) can slow the progression of diabetic nephropathy. Even with ACEI or ARB treatment, the proportion of patients who progress to end-stage renal disease (ESRD) remains high. Interventions that achieve more complete blockade of the renin-angiotensin system, such as combination ACEI and ARB, might be beneficial. This approach may decrease progression of nondiabetic kidney disease. In diabetic nephropathy, combination therapy decreases proteinuria, but its effect in slowing progression is unknown. In addition, the potential for hyperkalemia may limit the utility of combined therapy in this population. VA NEPHRON-D is a randomized, double-blind, multicenter clinical trial to assess the effect of combination losartan and lisinopril, compared with losartan alone, on the progression of kidney disease in 1850 patients with diabetes and overt proteinuria. The primary endpoints are time to (1) reduction in estimated GFR (eGFR) of > 50% (if baseline < 60 ml/min/1.73 m(2)); (2) reduction in eGFR of 30 ml/min/1.73 m(2) (if baseline > or = 60 ml/min/1.73 m(2)); (3) progression to ESRD (need for dialysis, renal transplant, or eGFR < 15 ml/min/1.73 m(2)); or (4) death. The secondary endpoint is time to change in eGFR or ESRD. Tertiary endpoints are cardiovascular events, slope of change in eGFR, and change in albuminuria at 1 yr. Specific safety endpoints are serious hyperkalemia (potassium > 6 mEq/L, requiring admission, emergency room visit, or dialysis), all-cause mortality, and other serious adverse events. This paper discusses the design and key methodological issues that arose during the planning of the study.

  5. A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.

    PubMed

    Critchley-Thorne, Rebecca J; Duits, Lucas C; Prichard, Jeffrey W; Davison, Jon M; Jobe, Blair A; Campbell, Bruce B; Zhang, Yi; Repa, Kathleen A; Reese, Lia M; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory; DeMarshall, Maureen; Foxwell, Tyler; Zaidi, Ali H; Lansing Taylor, D; Rustgi, Anil K; Bergman, Jacques J G H M; Falk, Gary W

    2016-06-01

    Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia. We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies. Data were collected from Barrett's esophagus patients at four institutions. Patients who progressed to HGD or EAC in ≥1 year (n = 79) were matched with patients who did not progress (n = 287). Biopsies were assigned randomly to training or validation sets. Immunofluorescence analyses were performed for 14 biomarkers and quantitative biomarker and morphometric features were analyzed. Prognostic features were selected in the training set and combined into classifiers. The top-performing classifier was assessed in the validation set. A 3-tier, 15-feature classifier was selected in the training set and tested in the validation set. The classifier stratified patients into low-, intermediate-, and high-risk classes [HR, 9.42; 95% confidence interval, 4.6-19.24 (high-risk vs. low-risk); P < 0.0001]. It also provided independent prognostic information that outperformed predictions based on pathology analysis, segment length, age, sex, or p53 overexpression. We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables. The test has the potential to improve upon histologic analysis as an objective method to risk stratify Barrett's esophagus patients. Cancer Epidemiol Biomarkers Prev; 25(6); 958-68. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Supply Chain Sustainability Analysis of Whole Algae Hydrothermal Liquefaction and Upgrading

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pegallapati, Ambica Koushik; Dunn, Jennifer B.; Frank, Edward D.

    2015-04-01

    The Department of Energy's Bioenergy Technology Office (BETO) collaborates with a wide range of institutions towards the development and deployment of biofuels and bioproducts. To facilitate this effort, BETO and its partner national laboratories develop detailed techno-economic assessments (TEA) of biofuel production technologies as part of the development of design cases and state of technology (SOT) analyses. A design case is a TEA that outlines a target case for a particular biofuel pathway. It enables preliminary identification of data gaps and research and development needs and provides goals and targets against which technology progress is assessed. On the other hand,more » an SOT analysis assesses progress within and across relevant technology areas based on actual experimental results relative to technical targets and cost goals from design cases and includes technical, economic, and environmental criteria as available. (SOT) analyses. A design case is a TEA that outlines a target case for a particular biofuel pathway. It enables preliminary identification of data gaps and research and development needs and provides goals and targets against which technology progress is assessed. On the other hand, an SOT analysis assesses progress within and across relevant technology areas based on actual experimental results relative to technical targets and cost goals from design cases and includes technical, economic, and environmental criteria as available. (SOT) analyses. A design case is a TEA that outlines a target case for a particular biofuel pathway. It enables preliminary identification of data gaps and research and development needs and provides goals and targets against which technology progress is assessed. On the other hand, an SOT analysis assesses progress within and across relevant technology areas based on actual experimental results relative to technical targets and cost goals from design cases and includes technical, economic, and environmental criteria as available.« less

  7. Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report

    PubMed Central

    Joachim, Nichole; Colijn, Johanna Maria; Kifley, Annette; Lee, Kristine E; Buitendijk, Gabriëlle H S; Klein, Barbara E K; Myers, Chelsea E; Meuer, Stacy M; Tan, Ava G; Holliday, Elizabeth G; Attia, John; Liew, Gerald; Iyengar, Sudha K; de Jong, Paulus T V M; Hofman, Albert; Vingerling, Johannes R; Mitchell, Paul; Klaver, Caroline C W; Klein, Ronald; Wang, Jie Jin

    2018-01-01

    Purpose To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. Design Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. Methods Retinal photography and interview with comprehensive questionnaires were conducted at each visit of three studies. AMD was assessed following the modified Wisconsin AMD grading protocol. Progression to bilateral any (early and late) or late AMD was assessed among participants with unilateral involvement only. Factors associated with the progression were assessed using logistic regression models while simultaneously adjusting for other significant risk factors. Results In any 5-year duration, 19–28% of unilateral any AMD cases became bilateral and 27–68% of unilateral late AMD became bilateral. Factors associated with the progression to bilateral involvement of any AMD were age (per year increase, adjusted OR 1.07), carrying risk alleles of the complement factor H and age-related maculopathy susceptibility 2 genes (compared with none, OR 1.76 for 1 risk allele and OR 3.34 for 2+ risk alleles), smoking (compared with non-smokers, OR 1.64 for past and OR 1.67 for current smokers), and the presence of large drusen area or retinal pigmentary abnormalities in the first eye. Conclusion One in four to one in five unilateral any AMD cases, and up to one in two unilateral late AMD cases, progressed to bilateral in 5 years. Known AMD risk factors, including smoking, are significantly associated with the progression to bilateral involvement. PMID:28108569

  8. Progress in Energy Storage Technologies: Models and Methods for Policy Analysis

    NASA Astrophysics Data System (ADS)

    Matteson, Schuyler W.

    Climate change and other sustainability challenges have led to the development of new technologies that increase energy efficiency and reduce the utilization of finite resources. To promote the adoption of technologies with social benefits, governments often enact policies that provide financial incentives at the point of purchase. In their current form, these subsidies have the potential to increase the diffusion of emerging technologies; however, accounting for technological progress can improve program success while decreasing net public investment. This research develops novel methods using experience curves for the development of more efficient subsidy policies. By providing case studies in the field of automotive energy storage technologies, this dissertation also applies the methods to show the impacts of incorporating technological progress into energy policies. Specific findings include learning-dependent tapering subsidies for electric vehicles based on the lithium-ion battery experience curve, the effects of residual learning rates in lead-acid batteries on emerging technology cost competitiveness, and a cascading diffusion assessment of plug-in hybrid electric vehicle subsidy programs. Notably, the results show that considering learning rates in policy development can save billions of dollars in public funds, while also lending insight into the decision of whether or not to subsidize a given technology.

  9. Information processing efficiency in patients with multiple sclerosis.

    PubMed

    Archibald, C J; Fisk, J D

    2000-10-01

    Reduced information processing efficiency, consequent to impaired neural transmission, has been proposed as underlying various cognitive problems in patients with Multiple Sclerosis (MS). This study employed two measures developed from experimental psychology that control for the potential confound of perceptual-motor abnormalities (Salthouse, Babcock, & Shaw, 1991; Sternberg, 1966, 1969) to assess the speed of information processing and working memory capacity in patients with mild to moderate MS. Although patients had significantly more cognitive complaints than neurologically intact matched controls, their performance on standard tests of immediate memory span did not differ from control participants and their word list learning was within normal limits. On the experimental measures, both relapsing-remitting and secondary-progressive patients exhibited significantly slowed information processing speed relative to controls. However, only the secondary-progressive patients had an additional decrement in working memory capacity. Depression, fatigue, or neurologic disability did not account for performance differences on these measures. While speed of information processing may be slowed early in the disease process, deficits in working memory capacity may appear only as there is progression of MS. It is these latter deficits, however, that may underlie the impairment of new learning that patients with MS demonstrate.

  10. The Progress of US Hospitals in Addressing Community Health Needs.

    PubMed

    Cramer, Geri Rosen; Singh, Simone R; Flaherty, Stephen; Young, Gary J

    2017-02-01

    To identify how US tax-exempt hospitals are progressing in regard to community health needs assessment (CHNA) implementation following the Patient Protection and Affordable Care Act. We analyzed data on more than 1500 tax-exempt hospitals in 2013 to assess patterns in CHNA implementation and to determine whether a hospital's institutional and community characteristics are associated with greater progress. Our findings show wide variation among hospitals in CHNA implementation. Hospitals operating as part of a health system as well as hospitals participating in a Medicare accountable care organization showed greater progress in CHNA implementation whereas hospitals serving a greater proportion of uninsured showed less progress. We also found that hospitals reporting the highest level of CHNA implementation progress spent more on community health improvement. Hospitals widely embraced the regulations to perform a CHNA. Less is known about how hospitals are moving forward to improve population health through the implementation of programs to meet identified community needs.

  11. Three-dimensional cultures modeling premalignant progression of human breast epithelial cells: role of cysteine cathepsins.

    PubMed

    Mullins, Stefanie R; Sameni, Mansoureth; Blum, Galia; Bogyo, Matthew; Sloane, Bonnie F; Moin, Kamiar

    2012-12-01

    The expression of the cysteine protease cathepsin B is increased in early stages of human breast cancer.To assess the potential role of cathepsin B in premalignant progression of breast epithelial cells, we employed a 3D reconstituted basement membrane overlay culture model of MCF10A human breast epithelial cells and isogenic variants that replicate the in vivo phenotypes of hyper plasia(MCF10AneoT) and atypical hyperplasia (MCF10AT1). MCF10A cells developed into polarized acinar structures with central lumens. In contrast, MCF10AneoT and MCF10AT1 cells form larger structures in which the lumens are filled with cells. CA074Me, a cell-permeable inhibitor selective for the cysteine cathepsins B and L,reduced proliferation and increased apoptosis of MCF10A, MCF10AneoT and MCF10AT1 cells in 3D culture. We detected active cysteine cathepsins in the isogenic MCF10 variants in 3D culture with GB111, a cell-permeable activity based probe, and established differential inhibition of cathepsin B in our 3D cultures. We conclude that cathepsin B promotes proliferation and premalignant progression of breast epithelial cells. These findings are consistent with studies by others showing that deletion of cathepsin B in the transgenic MMTV-PyMT mice, a murine model that is predisposed to development of mammary cancer, reduces malignant progression.

  12. White matter disease independently predicts progression from mild cognitive impairment to Alzheimer's disease in a clinic cohort.

    PubMed

    Prasad, Kalpana; Wiryasaputra, Lynn; Ng, Amanda; Kandiah, Nagaendran

    2011-01-01

    The contribution of vascular pathology to the rate of progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) remains unclear. To ascertain the relative roles of cerebral white matter disease and medial temporal atrophy (MTA) in predicting progression from MCI to AD. MCI patients with baseline MRI and ≥18 months of longitudinal follow-up were evaluated. DSM-IV-TR criteria were used to diagnose conversion to dementia. MTA and white matter hyperintensity (WMH) were quantified using the Scheltens scale and modified Fazekas scale. Of a total of 171 MCI patients, 79 patients with baseline MRI and longitudinal follow-up were studied. Twenty-three MCI patients who progressed to dementia (MCI-P) were identified corresponding to a 19.4% annual risk of conversion. In MCI-P patients, the mean Mini-Mental State Examination and Montreal Cognitive Assessment decline was 1.3 and 2.9 points, respectively. MTA, periventricular WMH and deep subcortical WMH were significantly greater in the MCI-P cohort. WMH was found to predict MCI-P with an odds ratio of 7.69 (p = 0.03). MTA and deep subcortical WMH independently predict conversion from MCI to AD. Optimization of vascular risk factors among patients with MCI can potentially reduce the conversion from MCI to AD. Copyright © 2011 S. Karger AG, Basel.

  13. APELA promotes tumour growth and cell migration in ovarian cancer in a p53-dependent manner.

    PubMed

    Yi, Yuyin; Tsai, Shu-Huei; Cheng, Jung-Chien; Wang, Evan Y; Anglesio, Michael S; Cochrane, Dawn R; Fuller, Megan; Gibb, Ewan A; Wei, Wei; Huntsman, David G; Karsan, Aly; Hoodless, Pamela A

    2017-12-01

    APELA is a small, secreted peptide that can function as a ligand for the G-protein coupled receptor, Apelin Receptor (APLNR, APJ). APELA plays an essential role in endoderm differentiation and cardiac development during embryogenesis. We investigated whether APELA exerts any functions in cancer progression. The Cancer Genome Atlas (TCGA) RNA sequencing datasets, microarray from an OCCC mouse model, and RNA isolated from fresh frozen and FFPE patient tissue were used to assess APELA expression. APELA knockout ovarian clear cell carcinoma (OCCC) cell lines were generated using CRISPR/Cas9. APELA was expressed in various ovarian cancer histotypes and was especially elevated in OCCC. Disruption of APELA expression in OCCC cell lines suppressed cell growth and migration, and altered cell-cycle progression. Moreover, addition of human recombinant APELA peptide to the OCCC cell line OVISE promoted cell growth and migration. Interestingly, OVISE cells do not express APLNR, suggesting that APELA can function through an APLNR-independent pathway. Furthermore, APELA affected cell growth and cell cycle progression in a p53-dependent manner. In addition, APELA knockdown induced p53 expression in cancer cell lines. Our findings uncover a potential oncogenic role for APELA in promoting ovarian tumour progression and provide a possible therapeutic strategy in ovarian cancer by targeting APELA. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. SNF Interim Storage Canister Corrosion and Surface Environment Investigations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bryan, Charles R.; Enos, David G.

    2015-09-01

    This progress report describes work being done at Sandia National Laboratories (SNL) to assess the localized corrosion performance of container/cask materials used in the interim storage of spent nuclear fuel (SNF). Of particular concern is stress corrosion cracking (SCC), by which a through-wall crack could potentially form in a canister outer wall over time intervals that are shorter than possible dry storage times. In order for SCC to occur, three criteria must be met. A corrosive environment must be present on the canister surface, the metal must susceptible to SCC, and sufficient tensile stress to support SCC must be presentmore » through the entire thickness of the canister wall. SNL is currently evaluating the potential for each of these criteria to be met.« less

  15. From Computer-interpretable Guidelines to Computer-interpretable Quality Indicators: A Case for an Ontology.

    PubMed

    White, Pam; Roudsari, Abdul

    2014-01-01

    In the United Kingdom's National Health Service, quality indicators are generally measured electronically by using queries and data extraction, resulting in overlap and duplication of query components. Electronic measurement of health care quality indicators could be improved through an ontology intended to reduce duplication of effort during healthcare quality monitoring. While much research has been published on ontologies for computer-interpretable guidelines, quality indicators have lagged behind. We aimed to determine progress on the use of ontologies to facilitate computer-interpretable healthcare quality indicators. We assessed potential for improvements to computer-interpretable healthcare quality indicators in England. We concluded that an ontology for a large, diverse set of healthcare quality indicators could benefit the NHS and reduce workload, with potential lessons for other countries.

  16. Heparin and cAMP modulators interact during pre-in vitro maturation to affect mouse and human oocyte meiosis and developmental competence.

    PubMed

    Zeng, Hai-tao; Ren, Zi; Guzman, Luis; Wang, Xiaoqian; Sutton-McDowall, Melanie L; Ritter, Lesley J; De Vos, Michel; Smitz, Johan; Thompson, Jeremy G; Gilchrist, Robert B

    2013-06-01

    Does heparin ablate the advantageous effects of cyclic adenosine mono-phosphate (cAMP) modulators during pre-in vitro maturation (IVM) and have a deleterious effect in standard oocyte IVM? Heparin interrupts energy metabolism and meiotic progression and adversely affects subsequent development of oocytes under conditions of elevated cAMP levels in cumulus-oocyte complexes (COCs) after pre-IVM treatment with forskolin. In animal IVM studies, artificial regulation of meiotic resumption by cAMP-elevating agents improves subsequent oocyte developmental competence. Heparin has no effect on spontaneous, FSH- or epidermal growth factor (EGF)-stimulated meiotic maturation. An in vitro cross-sectional study was conducted using immature mouse and human COCs. Depending on individual experimental design, COCs were treated during pre-IVM with or without heparin, in the presence or absence of forskolin and/or 3-isobutyl-1-methylxanthine (IBMX), and then COC function was assessed by various means. Forty-two women with polycystic ovaries (PCOs) or polycystic ovarian syndrome (PCOS) donated COCs after oocyte retrieval in a non-hCG-triggered IVM cycle. COCs were collected in pre-IVM treatments and then cultured for 40 h and meiotic progression was assessed. COCs from 21- to 24-day-old female CBA F1 mice were collected 46 h after stimulation with equine chorionic gonadotrophin. Following treatments, COCs were checked for meiotic progression. Effects on mouse oocyte metabolism were measured by assessing oocyte mitochondrial membrane potential using JC-1 staining and oocyte ATP content. Post-IVM mouse oocyte developmental competence was assessed by in vitro fertilization and embryo production. Blastocyst quality was evaluated by differential staining of inner cell mass (ICM) and trophectoderm (TE) layers. In the absence of heparin in pre-IVM culture, the addition of cAMP modulators did not affect human oocyte MII competence after 40 h. In standard IVM, heparin supplementation in pre-IVM did not affect MII competence; however, when heparin was combined with cAMP modulators, MII competence was significantly reduced from 65 to 15% (P < 0.05). In mouse experiments, heparin alone in pre-IVM significantly delayed germinal vesicle breakdown (GVBD) so that fewer GVBDs were observed at 0 and 1 h of IVM (P < 0.05), but not by 2 or 3 h of IVM. Combined treatment with IBMX and forskolin in the pre-IVM medium produced a large delay in GVBD such that no COCs exhibited GVBD in the first 1 h of IVM, and the addition of heparin in pre-IVM further significantly delayed the progression of GVBD (P < 0.05), in a dose-dependent manner (P < 0.01). Combined IBMX and forskolin treatment of mouse COCs during pre-IVM significantly increased mitochondrial membrane potential and ATP production in the oocyte at the end of pre-IVM (P < 0.05), and significantly improved fertilization, embryo development and quality (P < 0.05). However, heparin abolished the IBMX + forskolin-stimulated increase in mitochondrial membrane potential and ATP production (P < 0.05), and adversely affected embryonic cleavage, development rates and embryo quality (P < 0.05). This latter adverse combinational effect was negated when mouse COCs were collected in heparin and IBMX for 15 min, washed and then cultured for 45 min in IBMX and forskolin without heparin. Experiments in mice found that heparin ablation of the advantageous effects of cAMP modulators during pre-IVM was associated with altered oocyte metabolism, but the mechanism by which heparin affects metabolism remains unclear. This study has revealed a novel and unexpected interaction between heparin and cAMP modulators in pre-IVM in immature mouse and human oocytes, and established a means to collect oocytes using heparin while modulating oocyte cAMP to improve developmental potential.

  17. Common Progress Monitoring Graph Omissions: Missing Goal and Goal Line. Progress Monitoring Brief #2

    ERIC Educational Resources Information Center

    National Center on Response to Intervention, 2013

    2013-01-01

    Progress monitoring assessment is one of the four essential components of Response to Intervention (RTI), as defined by the National Center on Response to Intervention (NCRTI). Progress data allow teachers to evaluate the academic performance of students over time, quantify rates of improvement or responsiveness to instruction, and evaluate…

  18. Evaluation of the National Assessment of Educational Progress. Study Reports

    ERIC Educational Resources Information Center

    Buckendahl, Chad W.; Davis, Susan L.; Plake, Barbara S.; Sireci, Stephen G.; Hambleton, Ronald K.; Zenisky, April L.; Wells, Craig S.

    2009-01-01

    The "Evaluation of the National Assessment of Educational Progress: Study Reports" describes the special studies that comprised the design of the evaluation. In the Final Report, the authors presented a practical discussion of the evaluation studies to its primary, intended audience, namely policymakers. On this accompanying CD, readers…

  19. Health and Safety Research Division. Progress report, October 1, 1979-March 31, 1981

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1981-08-01

    Research progress for the period October 1, 1979 through March 31, 1981 is reported. Research conducted by the Office of Integrated Assessments and Policy Analysis, Health Studies Section, Technology Assessments Section, Biological and Radiation Physics Section, and Chemical Physics Section is summarized. (ACR)

  20. The Impact of the Measures of Academic Progress (MAP) Program on Student Reading Achievement

    ERIC Educational Resources Information Center

    Cordray, David S.; Pion, Georgine M.; Brandt, Chris; Molefe, Ayrin

    2013-01-01

    One of the most widely used commercially available systems incorporating benchmark assessment and training in differentiated instruction is the Northwest Evaluation Association's (NWEA) Measures of Academic Progress (MAP) program. The MAP program involves two components: (1) computer-adaptive assessments administered to students three to four…

  1. A regional consensus recommendation on brain atrophy as an outcome measure in multiple sclerosis.

    PubMed

    Alroughani, Raed; Deleu, Dirk; El Salem, Khalid; Al-Hashel, Jasem; Alexander, K John; Abdelrazek, Mohamed Assem; Aljishi, Adel; Alkhaboori, Jaber; Al Azri, Faisal; Al Zadjali, Nahida; Hbahbih, Majed; Sokrab, Tag Eldin; Said, Mohamed; Rovira, Àlex

    2016-11-24

    Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory and neurodegenerative processes leading to irreversible neurological impairment. Brain atrophy occurs early in the course of the disease at a rate greater than the general population. Brain volume loss (BVL) is associated with disability progression and cognitive impairment in patients with MS; hence its value as a potential target in monitoring and treating MS is discussed. A group of MS neurologists and neuro-radiologists reviewed the current literature on brain atrophy and discussed the challenges in assessing and implementing brain atrophy measurements in clinical practice. The panel used a voting system to reach a consensus and the votes were counted for the proposed set of questions for cognitive and brain atrophy assessments. The panel of experts was able to identify recent studies, which demonstrated the correlation between BVL and future worsening of disability and cognition. The current evidence revealed that reduction of BVL could be achieved with different disease-modifying therapies (DMTs). BVL provided a better treatment and monitoring strategy when it is combined to the composite measures of "no evidence of disease activity" (NEDA). The panel recommended a set of cognitive assessment tools and MRI methods and software applications that may help in capturing and measuring the underlying MS pathology with high degree of specificity. BVL was considered to be a useful measurement to longitudinally assess disease progression and cognitive function in patients with MS. Brain atrophy measurement was recommended to be incorporated into the concept of NEDA. Consequently, a consensus recommendation was reached in anticipation for implementation of the use of cognitive assessment and brain atrophy measurements on a regional level.

  2. Translational aspects of rectal evoked potentials: a comparative study in rats and humans

    PubMed Central

    Nissen, Thomas Dahl; Graversen, Carina; Coen, Steven J.; Hultin, Leif; Aziz, Qasim; Lykkesfeldt, Jens; Drewes, Asbjørn Mohr

    2013-01-01

    Inconsistencies between species has stunted the progress of developing new analgesics. To increase the success of translating results between species, improved comparable models are required. Twelve rats received rectal balloon distensions on 2 different days separated by 24.3 (SD 24.6) days. Rectal balloon distensions were also performed in 18 humans (mean age: 34 yr; range: 21–56 yr; 12 men) on two separate occasions, separated by 9.3 (SD 5.5) days. In rats, cerebral evoked potentials (CEPs) were recorded by use of implanted skull-electrodes to distension pressure of 80 mmHg. In humans surface electrodes and individualized pressure, corresponding to pain detection threshold, were used. Comparison of morphology was assessed by wavelet analysis. Within- and between-day reproducibility was assessed in terms of latencies, amplitudes, and frequency content. In rats CEPs showed triphasic morphology. No differences in latencies, amplitudes, and power distribution were seen within or between days (all P ≥ 0.5). Peak-to-peak amplitude between the first positive and negative potential were the most reproducible characteristic within and between days (evaluated by intraclass correlation coefficients, ICC) (ICC = 0.99 and ICC = 9.98, respectively). In humans CEPs showed a triphasic morphology. No differences in latencies, amplitudes, or power distribution were seen within or between days (all P ≥ 0.2). Latency to the second negative potential (ICC = 0.98) and the second positive potential (ICC = 0.95) was the most reproducible characteristic within and between days. A unique and reliable translational platform was established assessing visceral sensitivity in rats and humans, which may improve the translational process of developing new drugs targeting visceral pain. PMID:23703652

  3. Pharmacodynamic and Therapeutic Investigation of Focused Ultrasound-Induced Blood-Brain Barrier Opening for Enhanced Temozolomide Delivery in Glioma Treatment

    PubMed Central

    Liu, Hao-Li; Huang, Chiung-Yin; Chen, Ju-Yu; Wang, Hay-Yan Jack; Chen, Pin-Yuan; Wei, Kuo-Chen

    2014-01-01

    Focused ultrasound (FUS) exposure with the presence of microbubbles has been shown to transiently open the blood-brain barrier (BBB), and thus has potential to enhance the delivery of various kinds of therapeutic agents into brain tumors. The purpose of this study was to assess the preclinical therapeutic efficacy of FUS-BBB opening for enhanced temozolomide (TMZ) delivery in glioma treatment. FUS exposure with microbubbles was delivered to open the BBB of nude mice that were either normal or implanted with U87 human glioma cells. Different TMZ dose regimens were tested, ranging from 2.5 to 25 mg/kg. Plasma and brain samples were obtained at different time-points ranging from 0.5 to 4 hours, and the TMZ concentration within samples was quantitated via a developed LC-MS/MS procedure. Tumor progression was followed with T2-MRI, and animal survival and brain tissue histology were conducted. Results demonstrated that FUS-BBB opening caused the local TMZ accumulation in the brain to increase from 6.98 to 19 ng/mg. TMZ degradation time in the tumor core was found to increase from 1.02 to 1.56 hours. Improved tumor progression and animal survival were found at different TMZ doses (up to 15% and 30%, respectively). In conclusion, this study provides preclinical evidence that FUS-BBB opening increases the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting the potential for clinical application to improve current brain tumor treatment. PMID:25490097

  4. Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL.

    PubMed

    Thompson, Philip A; Wierda, William G

    2016-01-21

    Deep remission and prolonged disease-free survival can be achieved with first-line chemoimmunotherapy (CIT), such as combined fludarabine, cyclophosphamide, and rituximab, in the majority of patients with chronic lymphocytic leukemia (CLL). More modest results are reported with less intense regimens like obinutuzumab plus chlorambucil. Clinical assessment has limited sensitivity in detecting residual disease responsible for subsequent relapse, even including morphologic bone marrow (BM) evaluation. Multicolor flow cytometry and polymerase chain reaction (PCR)-based methods can detect minimal residual disease (MRD) to a sensitivity of ≥1:10,000 (10(-4)). Achieving BM MRD-negative complete remission (CR) is associated with superior progression-free survival (PFS) and overall survival; MRD status is the single best posttreatment predictor of long-term outcomes after CIT. Newer oral B-cell receptor signaling pathway inhibitors are highly effective at controlling disease, but best monotherapy responses are typically partial remission, and patients must remain on treatment to maintain disease control. Therapeutic progress is still needed for CLL. We propose that targeting MRD provides opportunity to realize this progress. Achieving BM MRD-negative CR is a prerequisite for long-term unmaintained disease-free survival and potential for cure. We review available methodologies for detecting MRD and correlations with posttreatment outcomes. We discuss the potential utility of MRD to direct individualized therapy. Finally, we discuss the importance of MRD-negative status as a surrogate marker for longer PFS in clinical studies to allow more rapid determination of clinical benefit. © 2016 by The American Society of Hematology.

  5. Live births from artificial insemination of microfluidic-sorted bovine spermatozoa characterized by trajectories correlated with fertility

    PubMed Central

    Nagata, Maria Portia B.; Endo, Kenji; Ogata, Kazuko; Yamanaka, Kenichi; Egashira, Junki; Katafuchi, Naoto; Yamanouchi, Tadayuki; Matsuda, Hideo; Goto, Yuki; Sakatani, Miki; Hojo, Takuo; Nishizono, Hirofumi; Yotsushima, Kenji; Takenouchi, Naoki; Hashiyada, Yutaka; Yamashita, Kenichi

    2018-01-01

    Selection of functional spermatozoa plays a crucial role in assisted reproduction. Passage of spermatozoa through the female reproductive tract requires progressive motility to locate the oocyte. This preferential ability to reach the fertilization site confers fertility advantage to spermatozoa. Current routine sperm selection techniques are inadequate and fail to provide conclusive evidence on the sperm characteristics that may affect fertilization. We therefore developed a selection strategy for functional and progressively motile bovine spermatozoa with high DNA integrity based on the ability to cross laminar flow streamlines in a diffuser-type microfluidic sperm sorter (DMSS). The fluid dynamics, with respect to microchannel geometry and design, are relevant in the propulsion of spermatozoa and, consequently, ultrahigh-throughput sorting. Sorted spermatozoa were assessed for kinematic parameters, acrosome reaction, mitochondrial membrane potential, and DNA integrity. Kinematic and trajectory patterns were used to identify fertility-related subpopulations: the rapid, straighter, progressive, nonsinuous pattern (PN) and the transitional, sinuous pattern (TS). In contrast to the conventional notion that the fertilizing spermatozoon is always vigorously motile and more linear, our results demonstrate that sinuous patterns are associated with fertility and correspond to truly functional spermatozoa as supported by more live births produced from predominant TS than PN subpopulation in the inseminate. Our findings ascertain the true practical application significance of microfluidic sorting of functional sperm characterized by sinuous trajectories that can serve as a behavioral sperm phenotype marker for fertility potential. More broadly, we foresee the clinical application of this sorting technology to assisted reproduction in humans. PMID:29555773

  6. Persistent, Biologically Meaningful Prostate Cancer After 1 Year of Androgen Ablation and Docetaxel Treatment

    PubMed Central

    Tzelepi, Vassiliki; Efstathiou, Eleni; Wen, Sijin; Troncoso, Patricia; Karlou, Maria; Pettaway, Curtis A.; Pisters, Louis L.; Hoang, Anh; Logothetis, Christopher J.; Pagliaro, Lance C.

    2011-01-01

    Purpose Clinicians are increasingly willing to treat prostate cancer within the primary site in the presence of regional lymph node or even limited distant metastases. However, no formal study on the merits of this approach has been reported. We used a preoperative clinical discovery platform to prioritize pathways for assessment as therapeutic targets and to test the hypothesis that the primary site harbors potentially lethal tumors after aggressive treatment. Patients and Methods Patients with locally advanced or lymph node–metastatic prostate cancer underwent 1 year of androgen ablation and three cycles of docetaxel therapy, followed by prostatectomy. All specimens were characterized for stage by accepted criteria. Expression of select molecular markers implicated in disease progression and therapy resistance was determined immunohistochemically and compared with that in 30 archived specimens from untreated patients with high-grade prostate cancer. Marker expression was divided into three groups: intracellular signaling pathways, stromal-epithelial interaction pathways, and angiogenesis. Results Forty patients were enrolled, 30 (75%) of whom underwent prostatectomy and two (5%) who underwent cystoprostatectomy. Twenty-nine specimens contained sufficient residual tumor for inclusion in a tissue microarray. Immunohistochemical analysis showed increased epithelial and stromal expression of CYP17, SRD5A1, and Hedgehog pathway components, and modulations of the insulin-like growth factor I pathway. Conclusion A network of molecular pathways reportedly linked to prostate cancer progression is activated after 1 year of therapy; biomarker expression suggests that potentially lethal cancers persist in the primary tumor and may contribute to progression. PMID:21606419

  7. Canine Models of Duchenne Muscular Dystrophy and Their Use in Therapeutic Strategies

    PubMed Central

    Kornegay, Joe N.; Bogan, Janet R.; Bogan, Daniel J.; Childers, Martin K.; Li, Juan; Nghiem, Peter; Detwiler, David A.; Larsen, C. Aaron; Grange, Robert W.; Bhavaraju-Sanka, Ratna K.; Tou, Sandra; Keene, Bruce P.; Howard, James F.; Wang, Jiahui; Fan, Zheng; Schatzberg, Scott J.; Styner, Martin A.; Flanigan, Kevin M.; Xiao, Xiao; Hoffman, Eric P.

    2013-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder in which the loss of dystrophin causes progressive degeneration of skeletal and cardiac muscle. Potential therapies that carry substantial risk, such as gene and cell-based approaches, must first be tested in animal models, notably the mdx mouse and several dystrophin-deficient breeds of dogs, including golden retriever muscular dystrophy (GRMD). Affected dogs have a more severe phenotype, in keeping with that of DMD, so may better predict disease pathogenesis and treatment efficacy. We and others have developed various phenotypic tests to characterize disease progression in the GRMD model. These biomarkers range from measures of strength and joint contractures to magnetic resonance imaging. Some of these tests are routinely used in clinical veterinary practice, while others require specialized equipment and expertise. By comparing serial measurements from treated and untreated groups, one can document improvement or delayed progression of disease. Potential treatments for DMD may be broadly categorized as molecular, cellular, or pharmacologic. The GRMD model has increasingly been used to assess efficacy of a range of these therapies. While some of these studies have largely provided general proof-of-concept for the treatment under study, others have demonstrated efficacy using the biomarkers discussed. Importantly, just as symptoms in DMD vary among patients, GRMD dogs display remarkable phenotypic variation. While confounding statistical analysis in preclinical trials, this variation offers insight regarding the role that modifier genes play in disease pathogenesis. By correlating functional and mRNA profiling results, gene targets for therapy development can be identified. PMID:22218699

  8. Environmental effects of ozone depletion and its interactions with climate change: progress report, 2015.

    PubMed

    2016-02-01

    The Environmental Effects Assessment Panel (EEAP) is one of three Panels that regularly informs the Parties (countries) to the Montreal Protocol on the effects of ozone depletion and the consequences of climate change interactions with respect to human health, animals, plants, biogeochemistry, air quality, and materials. The Panels provide a detailed assessment report every four years. The most recent 2014 Quadrennial Assessment by the EEAP was published as a special issue of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). The next Quadrennial Assessment will be published in 2018/2019. In the interim, the EEAP generally produces an annual update or progress report of the relevant scientific findings. The present progress report for 2015 assesses some of the highlights and new insights with regard to the interactive nature of the effects of UV radiation, atmospheric processes, and climate change.

  9. Evaluation of the implementation of entrepreneurial potential (on the example of the Republic of Tatarstan)

    NASA Astrophysics Data System (ADS)

    Guzelbaeva, G. T.; Rakhmatullina, D. K.; Akhmetshina, E. R.

    2017-12-01

    Increase in the number of small businesses and the lack of effectiveness of existing support at local and regional level have led to curb the development of entrepreneurial activity. The article presents the methodological tools for assessing the effectiveness, which allows to identify existing municipalities in the advantages and disadvantages for the implementation of entrepreneurial potential, including the effectiveness of state and municipal support measures, as well as calculate the degree of progress in the implementation of entrepreneurial potential. In order to evaluate the implementation of the business potential of the Republic of Tatarstan and the impact of their public support at the regional level was calculated indexes of business activity in the municipal districts (MD) of the republic. It should be noted that a major breakthrough in share of small and medium-sized businesses is important to the whole ecosystem. The method of evaluation of the implementation of entrepreneurial potential which is presented in this paper can be used by every competent organization to analyze and form the effective programs of the economic and finance development.

  10. Using the National Assessment of Educational Progress To Confirm State Test Results. A Report of the Ad Hoc Committee on Confirming Test Results.

    ERIC Educational Resources Information Center

    National Assessment Governing Board, Washington, DC.

    The National Assessment Governing Board has recognized the need to study associated policy and technical issues to ensure that the National Assessment of Educational Progress (NAEP) is ready to do the best job possible if called on to confirm the results of state achievement testing under the No Child Left Behind Act. This report describes the…

  11. A Bayesian Hierarchical Model for Large-Scale Educational Surveys: An Application to the National Assessment of Educational Progress. Research Report. ETS RR-04-38

    ERIC Educational Resources Information Center

    Johnson, Matthew S.; Jenkins, Frank

    2005-01-01

    Large-scale educational assessments such as the National Assessment of Educational Progress (NAEP) sample examinees to whom an exam will be administered. In most situations the sampling design is not a simple random sample and must be accounted for in the estimating model. After reviewing the current operational estimation procedure for NAEP, this…

  12. Closing the Achievement Gap for Economically Disadvantaged Students? Analyzing Change since No Child Left Behind Using State Assessments and the National Assessment of Educational Progress

    ERIC Educational Resources Information Center

    Blank, Rolf K.

    2011-01-01

    A critical state-level indicator of progress in public education is student achievement annual performance and change over time. The Council of Chief State School Officers (CCSSO) has been very active in tracking and reporting on student achievement results and using state assessment scores and other data to analyze achievement trends. A central…

  13. Differential Virulence and Disease Progression following Mycobacterium tuberculosis Complex Infection of the Common Marmoset (Callithrix jacchus)

    PubMed Central

    Via, Laura E.; Weiner, Danielle M.; Schimel, Daniel; Lin, Philana Ling; Dayao, Emmanuel; Tankersley, Sarah L.; Cai, Ying; Coleman, M. Teresa; Tomko, Jaime; Paripati, Praveen; Orandle, Marlene; Kastenmayer, Robin J.; Tartakovsky, Michael; Rosenthal, Alexander; Portevin, Damien; Eum, Seok Yong; Lahouar, Saher; Gagneux, Sebastien; Young, Douglas B.; Flynn, JoAnne L.

    2013-01-01

    Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades. PMID:23716617

  14. MRI predictors of treatment response for perianal fistulizing Crohn disease in children and young adults.

    PubMed

    Shenoy-Bhangle, Anuradha; Nimkin, Katherine; Goldner, Dana; Bradley, William F; Israel, Esther J; Gee, Michael S

    2014-01-01

    Magnetic resonance imaging (MRI) is considered the imaging standard for diagnosis and characterization of perianal complications associated with Crohn disease in children and adults. To define MRI criteria that could act as potential predictors of treatment response in fistulizing Crohn disease in children, in order to guide more informed study interpretation. We performed a retrospective database query to identify all children and young adults with Crohn disease who underwent serial MRI studies for assessment of perianal symptoms between 2003 and 2010. We examined imaging features of perianal disease including fistula number, type and length, presence and size of associated abscess, and disease response/progression on follow-up MRI. We reviewed imaging studies and electronic medical records. Statistical analysis, including logistic regression, was performed to associate MR imaging features with treatment response and disease progression. We included 36 patients (22 male, 14 female; age range 8-21 years). Of these, 32 had a second MRI exam and 4 had clinical evidence of complete response, obviating the need for repeat imaging. Of the parameters analyzed, presence of abscess, type of fistula according to the Parks classification, and multiplicity were not predictors of treatment outcome. Maximum length of the dominant fistula and aggregate fistula length in the case of multiple fistulae were the best predictors of treatment outcome. Maximum fistula length <2.5 cm was a predictor of treatment response, while aggregate fistula length ≥2.5 cm was a predictor of disease progression. Perianal fistula length is an important imaging feature to assess on MRI of fistulizing Crohn disease.

  15. Prevalent cartilage damage and cartilage loss over time are associated with incident bone marrow lesions in the tibiofemoral compartments: the MOST Study

    PubMed Central

    Crema, Michel D.; Felson, David T.; Roemer, Frank W.; Wang, Ke; Marra, Monica D.; Nevitt, Michael C.; Lynch, John A.; Torner, James; Lewis, Cora E.; Guermazi, Ali

    2012-01-01

    Objective To assess the association of prevalent cartilage damage and cartilage loss over time with incident bone marrow lesions (BMLs) in the same subregion of the tibiofemoral compartments as detected on magnetic resonance imaging (MRI). Methods The Multicenter Osteoarthritis Study is an observational study of individuals with or at risk for knee osteoarthritis (OA). Subjects whose baseline and 30-month follow-up MRIs were read for findings of OA were included. MRI was performed with a 1.0T extremity system. Tibiofemoral compartments were divided into 10 subregions. Cartilage morphology was scored from 0 to 6 and BMLs were scored from 0 to 3. Prevalent cartilage damage and cartilage loss over time were considered predictors of incident BMLs. Associations were assessed using logistic regression, with adjustments for potential confounders. Results Medially, incident BMLs were associated with baseline cartilage damage (adjusted odds ratio (OR) 3.9 [95% CI 3.0, 5.1]), incident cartilage loss (7.3 [95% CI 5.0, 10.7]) and progression of cartilage loss (7.6 [95% CI 5.1, 11.3]) Laterally, incident BMLs were associated with baseline cartilage damage (4.1 [95% CI 2.6, 6.3]), incident cartilage loss (6.0 [95% CI 3.1, 11.8]), and progression of cartilage loss (11.9 [95% CI 6.2, 23.0]). Conclusion Prevalent cartilage damage and cartilage loss over time are strongly associated with incident BMLs in the same subregion, supporting the significance of the close interrelation of the osteochondral unit in the progression of knee OA. PMID:23178289

  16. Leadership, infrastructure and capacity to support child injury prevention: can these concepts help explain differences in injury mortality rankings between 18 countries in Europe?

    PubMed

    MacKay, J Morag; Vincenten, Joanne A

    2012-02-01

    Mortality and morbidity rates, traditionally used indicators for child injury, are limited in their ability to explain differences in child injury between countries, are inadequate in capturing actions to address the problem of child injury and do not adequately identify progress made within countries. There is a need for a broader set of indicators to help better understand the success of countries with low rates of child injury, provide guidance and benchmarks for policy makers looking to make investments to reduce their rates of fatal and non-fatal child injury and allow monitoring of progress towards achieving these goals. This article describes an assessment of national leadership, infrastructure and capacity in the context of child injury prevention in 18 countries in Europe and explores the potential of these to be used as additional indicators to support child injury prevention practice. Partners in 18 countries coordinated data collection on 21 items relating to leadership, infrastructure and capacity. Responses were coded into an overall score and scores for each of the three areas and were compared with child injury mortality rankings using Spearman's rank correlation. Overall score and scores for leadership and capacity were significantly negatively correlated to child injury mortality ranking. Findings of this preliminary work suggest that these three policy areas may provide important guidance for the types of commitments that are needed in the policy arena to support advances in child safety and their assessment a way to measure progress.

  17. Non-surgical management methods of noncavitated carious lesions.

    PubMed

    Tellez, Marisol; Gomez, Juliana; Kaur, Sundeep; Pretty, Iain A; Ellwood, Roger; Ismail, Amid I

    2013-02-01

    To critically appraise all evidence related to the efficacy of nonsurgical caries preventive methods to arrest or reverse the progression of noncavitated carious lesions (NCCls). A detailed search of Medline (via OVID), Cochrane Collaboration, Scielo, and EMBASE identified 625 publications. After title and abstract review, 103 publications were selected for further review, and 29 were finally included. The final publications evaluated the following therapies: fluorides (F) in varying vehicles (toothpaste, gel, varnish, mouthrinse, and combination), chlorhexidine (CHX) alone or in combination with F, resin infiltration (I), sealants (S), xylitol (X) in varying vehicles (lozenges, gum, or in combination with F and/or xylitol), casein phosphopeptide amorphous calcium phosphate (CPP-ACP) or in combination with calcium fluoride phosphate. All included studies were randomized clinical trials, were conducted with human subjects and natural NCCls, and reported findings that can yield outcomes measures such as caries incidence/increments, percentage of progression and/or arrest, odds ratio progression test to control, fluorescence loss/mean values, changes in lesion area/volume and lesion depth. Data were extracted from the selected studies and checked for errors. The quality of the studies was evaluated by three different methods (ADA, Cochrane, author's consensus). Sample size for these trials ranged between 15 and 3903 subjects, with a duration between 2 weeks and 4.02 years. More than half of the trials assessed had moderate to high risk of bias or may be categorized as 'poor'. The great majority (65.5%) did not use intention to treat analysis, 21% did not use any blinding techniques, and 41% reported concealment allocation procedures. Slightly more than half of the trials (55%) factored in background exposure to other fluoride sources, and only 41% properly adjusted for potential confounders. Fluoride interventions (varnishes, gels, and toothpaste) seem to have the most consistent benefit in decreasing the progression and incidence of NCCls. Studies using xylitol, CHX, and CPP-ACP vehicles alone or in combination with fluoride therapy are very limited in number and in the majority of the cases did not show a statistically significant reduction. Sealants and resin infiltration studies point to a potential consistent benefit in slowing the progression or reversing NCCls.

  18. Molecular Imaging Markers to Track Huntington's Disease Pathology.

    PubMed

    Wilson, Heather; De Micco, Rosa; Niccolini, Flavia; Politis, Marios

    2017-01-01

    Huntington's disease (HD) is a progressive, monogenic dominant neurodegenerative disorder caused by repeat expansion mutation in the huntingtin gene. The accumulation of mutant huntingtin protein, forming intranuclear inclusions, subsequently leads to degeneration of medium spiny neurons in the striatum and cortical areas. Genetic testing can identify HD gene carriers before individuals develop overt cognitive, psychiatric, and chorea symptoms. Thus, HD gene carriers can be studied in premanifest stages to understand and track the evolution of HD pathology. While advances have been made, the precise pathophysiological mechanisms underlying HD are unclear. Magnetic resonance imaging (MRI) and positron emission tomography (PET) have been employed to understand HD pathology in presymptomatic and symptomatic disease stages. PET imaging uses radioactive tracers to detect specific changes, at a molecular level, which could be used as markers of HD progression and to monitor response to therapeutic treatments for HD gene expansion carriers (HDGECs). This review focuses on available PET techniques, employed in cross-sectional and longitudinal human studies, as biomarkers for HD, and highlights future potential PET targets. PET studies have assessed changes in postsynaptic dopaminergic receptors, brain metabolism, microglial activation, and recently phosphodiesterase 10A (PDE10A) as markers to track HD progression. Alterations in PDE10A expression are the earliest biochemical change identified in HD gene carriers up to 43 years before predicted symptomatic onset. Thus, PDE10A expression could be a promising marker to track HD progression from early premanifest disease stages. Other PET targets which have been less well investigated as biomarkers include cannabinoid, adenosine, and GABA receptors. Future longitudinal studies are required to fully validate these PET biomarkers for use to track disease progression from far-onset premanifest to manifest HD stages. PET imaging is a crucial neuroimaging tool, with the potential to detect early changes and validate sensitivity of biomarkers for tracking HD pathology. Moreover, continued development of novel PET tracers provides exciting opportunities to investigate new molecular targets, such as histamine and serotonin receptors, to further understand the mechanisms underlying HD pathology.

  19. Atmospheric Electrical Activity and the Prospects for Improving Short-Term, Weather Forcasting

    NASA Technical Reports Server (NTRS)

    Goodman, Steven J.

    2003-01-01

    How might lightning measurements be used to improve short-term (0-24 hr) weather forecasting? We examine this question under two different prediction strategies. These include integration of lightning data into short-term forecasts (nowcasts) of convective (including severe) weather hazards and the assimilation of lightning data into cloud-resolving numerical weather prediction models. In each strategy we define specific metrics of forecast improvement and a progress assessment. We also address the conventional observing system deficiencies and potential gap-filling information that can be addressed through the use of the lightning measurement.

  20. A data mining method to facilitate SAR transfer.

    PubMed

    Wassermann, Anne Mai; Bajorath, Jürgen

    2011-08-22

    A challenging practical problem in medicinal chemistry is the transfer of SAR information from one chemical series to another. Currently, there are no computational methods available to rationalize or support this process. Herein, we present a data mining approach that enables the identification of alternative analog series with different core structures, corresponding substitution patterns, and comparable potency progression. Scaffolds can be exchanged between these series and new analogs suggested that incorporate preferred R-groups. The methodology can be applied to search for alternative analog series if one series is known or, alternatively, to systematically assess SAR transfer potential in compound databases.

Top