WorldWideScience

Sample records for bcr providing biospecimen

  1. Knowledge and willingness to provide research biospecimens among foreign-born Latinos using safety-net clinics.

    Science.gov (United States)

    Loffredo, Christopher A; Luta, Gheorghe; Wallington, Sherrie; Makgoeng, Solomon B; Selsky, Claire; Mandelblatt, Jeanne S; Adams-Campbell, Lucile L

    2013-08-01

    Latinos tend to be under-represented in cancer research and in bio-repositories. We conducted a Spanish-language, interviewer-administered cross-sectional survey of 331 foreign-born Latinos from Central and South America attending safety-net clinics in order to describe factors associated with knowledge about and intention to provide bio-specimens for research purposes. We used logistic regression and multiple imputation methods to evaluate associations between socio-cultural measures, medical trust, demographics, as well as knowledge about and intentions to provide bio-specimens. Almost half (47 %) of respondents knew what bio-specimens were, and 67 % said that they would provide a specimen after being given information about what this involved; this increased to 72 % among those with prior knowledge. Controlling for covariates, Latinos with a high school education and above were more likely to know what a bio-specimen was and to say they would provide bio-specimens than were those with lower levels of education [adjusted OR (aOR) 2.85, 95 % CI 1.37-5.96; and 3.49, 95 % CI 1.41-8.63, p ≤ 0.01, respectively]. Those with greater social integration were more likely to know about bio-specimens than those with less integration (aOR 2.54, 95 % CI 1.45-4.46, p = 0.001). Higher endorsement of family values was independently associated with intent to give bio-specimens (aOR 1.11, 95 % CI 1.02-1.20, p = 0.017 per five-point increase in "familism" score). Medical mistrust was not related to intentions to provide specimens. Our results suggest that interventions to increase willingness to provide bio-specimens could leverage trusted clinics or social networks and should consider individuals' education and socio-cultural perspectives.

  2. Biospecimen Core Resource - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The purpose of this notice is to notify the community that the National Cancer Institute's (NCI’s) Office of Cancer Clinical Proteomics Research (OCCPR) is seeking sources to establish a Biospecimen Core Resource (BCR), capable of receiving, qualifying, processing, and distributing annotated biospecimens.

  3. New Funding Opportunity: Biospecimen Core Resource - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The purpose of this notice is to notify the community that the National Cancer Institute's (NCI’s) Office of Cancer Clinical Proteomics Research (OCCPR) is seeking sources to establish a Biospecimen Core Resource (BCR), capable of receiving, qualifying, processing, and distributing annotated biospecimens.

  4. Biospecimen Core Resource - TCGA

    Science.gov (United States)

    The Cancer Genome Atlas (TCGA) Biospecimen Core Resource centralized laboratory reviews and processes blood and tissue samples and their associated data using optimized standard operating procedures for the entire TCGA Research Network.

  5. Biospecimen Reporting for Improved Study Quality (BRISQ)

    Energy Technology Data Exchange (ETDEWEB)

    National Cancer Institute; Jewell, Ph.D., Scott D.; Seijo, M.S., Edward; Kelly, Ph.D., Andrea; Somiari, Ph.D., Stella; B.Chir., M.B.; McShane, Ph.D., Lisa M.; Clark, M.D., Douglas; Greenspan, M.D., Renata; Hayes, M.D., Daniel F.; Hainaut, Ph.D., M.S., Pierre; Kim, Paula; Mansfield, Ph.D., Elizabeth; Potapova, Ph.D., Olga; Riegman, Ph.D., Peter; Rubinstein, Ph.D., Yaffa; Weier, Ph.D., Heinz-Ulrich; Zhu, Ph.D., Claire; Moore, Ph.D., Helen M.; Vaught, Ph.D., Jim; Watson, Peter

    2010-09-02

    Human biospecimens are subjected to collection, processing, and storage that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research that uses human tissues, it is crucial that information on the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen-related research and to help reassure patient contributors and the advocacy community that their contributions are valued and respected.

  6. Biospecimen Reporting for Improved Study Quality

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Ph.D., Helen M.; Kelly, Ph.D., Andrea B.; Jewell, Ph.D., Scott D.; McShane, Ph.D., Lisa M.; Clark, M.D., Douglas P.; Greenspan, M.D., Renata; Hayes, M.D., Daniel F.; Hainaut, Ph.D., Pierre; Kim, Paula; Mansfield, Ph.D., Elizabeth A.; Potapova, Ph.D., Olga; Riegman, Ph.D., Peter; Rubinstein, Ph.D., Yaffa; Seijo, M.S., Edward; Somiari, Ph.D., Stella; Chir., B; Weier, Ph.D., Heinz-Ulrich; Zhu, Ph.D., Claire; Vaught, Ph.D., Jim; Watson,M.B., Peter

    2010-12-27

    Human biospecimens are subjected to collection, processing, and storage that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research that uses human tissues, it is crucial that information on the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen-related research and to help reassure patient contributors and the advocacy community that their contributions are valued and respected.

  7. Biospecimen Reporting for Improved Study Quality (BRISQ)

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Ph.D., Helen M.; Kelly Ph.D., Andrea; Jewell Ph.D., Scott D.; McShane Ph.D., Lisa M.; Clark M.D., Douglas P.; Greenspan M.D., Renata; Hayes M.D., Daniel F.; Hainaut Ph.D.,, Pierre; Kim, Paula; Mansfield Ph.D., Elizabeth; Potapova Ph.D., Olga; Riegman Ph.D., Peter; Rubinstein Ph.D., Yaffa; Seijo M.S., Edward; Somiari Ph.D., Stella; Watson M.B., Peter; Weier Ph.D., Heinz-Ulrich; Zhu Ph.D., Claire; Vaught Ph.D., Jim

    2011-04-26

    Human biospecimens are subject to a number of different collection, processing, and storage factors that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research utilizing human tissues it is critical that information regarding the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications around biospecimen-related research and help reassure patient contributors and the advocacy community that the contributions are valued and respected.

  8. Review: The procurement, storage and quality assurance of frozen blood and tissue biospecimens

    Directory of Open Access Journals (Sweden)

    Manoj S. Charde

    2014-05-01

    Full Text Available The preserved frozen biospecimens are ideal for evaluating the genome, transcriptome, and proteome. Here we present a current overview of experimental data regarding procurement, storage, and quality assurance that can informthe handling of frozen biospecimens. Degradation of frozen biospecimens can be affected by collecting methodology, premortem agonal changes and warm ischemic time during surgery.  Tissue storage at− 80 °C can preserve DNA and protein but RNA show degradation at 5 years, therefore storage at − 150 °C provides significant advantages.  Histologic quality assurance of tissue biospecimens is typically performed at the time of surgery but should also be conducted on the aliquot to be distributed because of tissue heterogeneity.Additional qualityassurance testing should be dictated by the anticipated downstream applications.

  9. Biospecimen Repository Access and Data Sharing (BRADS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — BRADS is a repository for data and biospecimens from population health research initiatives and clinical or interventional trials designed and implemented by NICHD’s...

  10. The Future of Biobanking: A Conceptual Look at How Biobanks Can Respond to the Growing Human Biospecimen Needs of Researchers.

    Science.gov (United States)

    Somiari, Stella B; Somiari, Richard I

    2015-01-01

    Biobanking of human biological specimens has evolved from the simple private collection of often poorly annotated residual clinical specimens, to well annotated and organized collections setup by commercial and not-for-profit organizations. The activities of biobanks is now the focus of international and government agencies in recognition of the need to adopt best practices and provide scientific, ethical and legal guidelines for the industry. The demand for more, high quality and clinically annotated biospecimens will increase, primarily due to the unprecedented level of genomic, post genomic and personalized medicine research activities going on. Demand for more biospecimens provides new challenges and opportunities for developing strategies to build biobanking into a business that is better able to supply the biospecimen needs of the future. A paradigm shift is required particularly in organization and funding, as well as in how and where biospecimens are collected, stored and distributed. New collection sites, organized as Research Ready Hospitals (RRHs) and new public-private partnership models are needed for sustainability and increased biospecimen availability. Biobanks will need to adopt industry-wide standard operating procedures, better and "non-destructive" methods for quality assessment, less expensive methods for sample storage/distribution, and objective methods to manage scarce biospecimens. Ultimately, the success of future biobanks will rely greatly on the success of public-private partnerships, number and diversity of available biospecimens, cost management and the realization that an effective biobank is one that provides high quality and affordable biospecimens to drive research that leads to better health and quality of life for all.

  11. A practical tool for modeling biospecimen user fees.

    Science.gov (United States)

    Matzke, Lise; Dee, Simon; Bartlett, John; Damaraju, Sambasivarao; Graham, Kathryn; Johnston, Randal; Mes-Masson, Anne-Marie; Murphy, Leigh; Shepherd, Lois; Schacter, Brent; Watson, Peter H

    2014-08-01

    The question of how best to attribute the unit costs of the annotated biospecimen product that is provided to a research user is a common issue for many biobanks. Some of the factors influencing user fees are capital and operating costs, internal and external demand and market competition, and moral standards that dictate that fees must have an ethical basis. It is therefore important to establish a transparent and accurate costing tool that can be utilized by biobanks and aid them in establishing biospecimen user fees. To address this issue, we built a biospecimen user fee calculator tool, accessible online at www.biobanking.org . The tool was built to allow input of: i) annual operating and capital costs; ii) costs categorized by the major core biobanking operations; iii) specimen products requested by a biobank user; and iv) services provided by the biobank beyond core operations (e.g., histology, tissue micro-array); as well as v) several user defined variables to allow the calculator to be adapted to different biobank operational designs. To establish default values for variables within the calculator, we first surveyed the members of the Canadian Tumour Repository Network (CTRNet) management committee. We then enrolled four different participants from CTRNet biobanks to test the hypothesis that the calculator tool could change approaches to user fees. Participants were first asked to estimate user fee pricing for three hypothetical user scenarios based on their biobanking experience (estimated pricing) and then to calculate fees for the same scenarios using the calculator tool (calculated pricing). Results demonstrated significant variation in estimated pricing that was reduced by calculated pricing, and that higher user fees are consistently derived when using the calculator. We conclude that adoption of this online calculator for user fee determination is an important first step towards harmonization and realistic user fees.

  12. A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

    Science.gov (United States)

    2014-10-01

    1 Award Number: W81XWH-10-1-0818 TITLE: A Medical Center Network for Optimized Lung Cancer Biospecimen Banking PRINCIPAL...Biospecimen Resource Network: A medical center network for optimized lung cancer biospecimen banking 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-10-1-0818... audit sampling the source forms of 15 randomly selected patients from each Resource Site. The purpose of the audit was make certain required clinical

  13. International efforts to develop biospecimen best practices.

    Science.gov (United States)

    Vaught, Jimmie B; Caboux, Elodie; Hainaut, Pierre

    2010-04-01

    Variables introduced during the processes involved in biospecimen collection, processing, storage, and analysis are among the potential sources of bias in biomarker research. International efforts are under way to develop best practices to standardize biospecimen handling protocols. In general, documents on best practices address three major recurring themes: technical best practices on infrastructure and specimen handling, recommendations on informatics and data management, and recommendations on ethical, legal, and social issues. There are many areas of agreement among various international efforts, but no single set of practices has emerged as a unifying document. The ethical, legal, and social issues are particularly difficult to harmonize due to the many country-specific issues that are governed by a variety of local and federal rules and regulations. Given the increasingly international nature of research involving biomarkers and biospecimens, it will be necessary to continue to cooperate in the development of harmonized evidence-based best practices. Several international organizations including the International Cancer Genome Consortium are engaged in such efforts.

  14. Preanalytical Variables Affecting the Integrity of Human Biospecimens in Biobanking

    DEFF Research Database (Denmark)

    Ellervik, Christina; Vaught, Jim

    2015-01-01

    of a study will depend on the integrity of the biospecimens. Preanalytical preparations should be planned with consideration of the effect on downstream analyses. Currently such preanalytical variables are not routinely documented in the biospecimen research literature. Future studies using biobanked......BACKGROUND: Most errors in a clinical chemistry laboratory are due to preanalytical errors. Preanalytical variability of biospecimens can have significant effects on downstream analyses, and controlling such variables is therefore fundamental for the future use of biospecimens in personalized...... medicine for diagnostic or prognostic purposes. CONTENT: The focus of this review is to examine the preanalytical variables that affect human biospecimen integrity in biobanking, with a special focus on blood, saliva, and urine. Cost efficiency is discussed in relation to these issues. SUMMARY: The quality...

  15. Biospecimen quality program in the biobank of the Norwegian Institute of Public Health

    Directory of Open Access Journals (Sweden)

    Liv Paltiel

    2012-04-01

    Full Text Available Background: The biological material collected, processed and stored in biobanks are important research tools and it is important to minimize preanalytical variations to provide researchers with high quality biological material that will give reproducible results. Methods: To minimize the preanalytical variations caused by sample collection, processing and storage, we have established a biospecimen quality program. It consists of quality assurance aspects as well as quality control programs to measure adherence to protocols and sample integrity. The quality control program includes measurements and evaluation of the DNA quality and quantity before storage, i.e. concentration, purity, fragmentation and PCR success, and long term storage programs for plasma, urine and RNA. Conclusions: The Biobank at the Norwegian Institute of Public Health has established a biospecimen quality program that ensures high quality specimens and provides the documentation required to use the biomaterial in a best possible way.

  16. Study of Womens Health Across the Nation (SWAN) Biospecimen Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The SWAN Repository is the biospecimen bank of the SWAN study. All stored specimens are from the 3,302 SWAN participants, collected across the 14 clinic visits...

  17. The State of Cloud-Based Biospecimen and Biobank Data Management Tools.

    Science.gov (United States)

    Paul, Shonali; Gade, Aditi; Mallipeddi, Sumani

    2017-03-16

    Biobanks are critical for collecting and managing high-quality biospecimens from donors with appropriate clinical annotation. The high-quality human biospecimens and associated data are required to better understand disease processes. Therefore, biobanks have become an important and essential resource for healthcare research and drug discovery. However, collecting and managing huge volumes of data (biospecimens and associated clinical data) necessitate that biobanks use appropriate data management solutions that can keep pace with the ever-changing requirements of research. To automate biobank data management, biobanks have been investing in traditional Laboratory Information Management Systems (LIMS). However, there are a myriad of challenges faced by biobanks in acquiring traditional LIMS. Traditional LIMS are cost-intensive and often lack the flexibility to accommodate changes in data sources and workflows. Cloud technology is emerging as an alternative that provides the opportunity to small and medium-sized biobanks to automate their operations in a cost-effective manner, even without IT personnel. Cloud-based solutions offer the advantage of heightened security, rapid scalability, dynamic allocation of services, and can facilitate collaboration between different research groups by using a shared environment on a "pay-as-you-go" basis. The benefits offered by cloud technology have resulted in the development of cloud-based data management solutions as an alternative to traditional on-premise software. After evaluating the advantages offered by cloud technology, several biobanks have started adopting cloud-based tools. Cloud-based tools provide biobanks with easy access to biospecimen data for real-time sharing with clinicians. Another major benefit realized by biobanks by implementing cloud-based applications is unlimited data storage on the cloud and automatic backups for protecting any data loss in the face of natural calamities.

  18. Predictors of biospecimen donation in the Black Women’s Health Study

    Science.gov (United States)

    Adams-Campbell, Lucile L.; Dash, Chiranjeev; Palmer, Julie R.; Wiedemeier, Manuela V.; Russell, Cordelia W.; Rosenberg, Lynn; Cozier, Yvette C.

    2016-01-01

    Purpose Although African-Americans experience higher cancer morbidity and mortality rates compared to their White counterparts, their participation in biospecimen research is lower than that of their white peers. This study investigated the prevalence and predictors of biospecimen donation in a large, cohort study of Black women. Methods The BWHS is a follow-up study of U.S. Black women aged 21–69 years enrolled through postal health questionnaires. Between January 2004 and December 2007, participants were sent a consent form with a postage-paid return envelope, and a mouthwash collection kit. Univariate and age- and educational status-adjusted logistic regression models were used to estimate the association of socio-demographic, lifestyle and medical factors with donation of biospecimens. Results Buccal cells with consent forms were obtained from 26,790 women, for a response rate of 51 %. The strongest predictors of biospecimen donation were age: response increased from 48.6 % among those aged <40 to 63.1 % among those aged 60 and older [RR 1.30 (95 % CI 1.27, 1.34)]; multivitamin use [RR (95 % CI) 1.32 (1.30, 1.34)]; physician visit in the previous 2 years [RR (95 % CI) 1.61 (1.58, 1.65)], and a history of breast [RR (95 % CI) 1.59 (1.56, 1.63)], colon [RR (95 % CI) 1.18 (1.16, 1.20)], and cervical [RR (95 % CI) 1.63 (1.60, 1.67)] cancer screening. Conclusions We found that 51 % of women in the geographically-dispersed Black Women’s Health Study cohort were willing to provide mouthwash samples to be used for genetic analyses. The response in this study is encouraging given published findings of low overall participation rates of African-Americans in genetic studies. PMID:27106577

  19. A Federated Network for Translational Cancer Research Using Clinical Data and Biospecimens.

    Science.gov (United States)

    Jacobson, Rebecca S; Becich, Michael J; Bollag, Roni J; Chavan, Girish; Corrigan, Julia; Dhir, Rajiv; Feldman, Michael D; Gaudioso, Carmelo; Legowski, Elizabeth; Maihle, Nita J; Mitchell, Kevin; Murphy, Monica; Sakthivel, Mayurapriyan; Tseytlin, Eugene; Weaver, JoEllen

    2015-12-15

    Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the Text Information Extraction System (TIES) Cancer Research Network, a federated network that facilitates data and biospecimen sharing among member institutions. Member sites can access pathology data that are de-identified and processed with the TIES natural language processing system, which creates a repository of rich phenotype data linked to clinical biospecimens. TIES incorporates multiple security and privacy best practices that, combined with legal agreements, network policies, and procedures, enable regulatory compliance. The TIES Cancer Research Network now provides integrated access to investigators at all member institutions, where multiple investigator-driven pilot projects are underway. Examples of federated search across the network illustrate the potential impact on translational research, particularly for studies involving rare cancers, rare phenotypes, and specific biologic behaviors. The network satisfies several key desiderata including local control of data and credentialing, inclusion of rich phenotype information, and applicability to diverse research objectives. The TIES Cancer Research Network presents a model for a national data and biospecimen network.

  20. The CAS Bio-specimen Centers in Sound Progress

    Institute of Scientific and Technical Information of China (English)

    LI Liangqian; QIAO Gexia; YAO Yijian

    2010-01-01

    @@ Bio-specimen centers, including herbaria and zoological museums, are the most integrated places for the storage of specimens, which are real samples and the most important vouchers for taxonomic and biodiversity studies.The information carried by the specimens is of substantial reference for research on species distribution, history, status, phylogeny and evolution, etc.

  1. TRWG developmental pathway for biospecimen-based assessment modalities

    Energy Technology Data Exchange (ETDEWEB)

    Translational Research Working Group; Srivastava, Sudhir; Gray, Joe W.; Reid, Brian J.; Grad, Oren; Greenwood, Addison; Hawk, Ernest T.

    2008-09-03

    The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of NCI's investment in translational research and envision its future. The TRWG conceptualized translational research as a set of six developmental processes or pathways focused on various clinical goals. One of those pathways describes the development of biospecimen-based assays that utilize biomarkers for the detection, diagnosis, prognosis, and assessment of response to cancer treatment. The biospecimen-based assessment modality (BM) pathway was conceived not as comprehensive description of the corresponding real-world processes, but rather as a tool designed to facilitate movement of a candidate assay through the translational process to the point where it can be handed off for definitive clinical testing. This paper introduces the pathway in the context of prior work and discusses key challenges associated with the biomarker development process in light of the pathway.

  2. Factors associated with willingness to participate in biospecimen research among Chinese Americans.

    Science.gov (United States)

    Gao, Wanzhen; Ma, Grace X; Tan, Yin; Fang, Carolyn; Weaver, JoEllen; Jin, Ming; Lai, Philip

    2014-04-01

    A paucity of information exists on the recruitment of Asian Americans for biospecimen research. Although studies show that Chinese Americans are at high risk for hepatitis B virus (HBV) infection, little is known about their willingness to participate in HBV-related biospecimen research and how knowledge, attitudes, and cultural factors impact their willingness to participate. The study was guided by Community-Based Participatory Research principles. Data were derived from an assessment study on HBV-related biospecimen research participation among Chinese Americans in the Philadelphia region. The assessment was conducted with 415 Chinese Americans recruited from eight Chinese community-based organizations. Cultural beliefs, knowledge, and attitudes toward biospecimen research were examined for associations with their willingness to participate in biospecimen banking research. Overall, 192 (46.3%) of 415 participants who completed the assessment indicated they were willing to participate if they were invited to donate blood to be frozen and stored for future HBV biospecimen studies. Cultural variables significant in bivariate analysis included collectivism, knowledge about biospecimen research, and Yin-Yang beliefs. Fatalism and individualism were not associated with participation willingness. In multivariate analysis, age, health care attitudes, and trust were significantly associated with willingness to participate in biospecimen banking research. Asian American communities have little knowledge of biospecimen banking and will benefit from educational campaigns that emphasize collective benefits and attitudes towards and trust in the health care system. Understanding cultural factors is important for improving Chinese Americans' knowledge, awareness, and intentions of participation in biospecimen research. Similar efforts need to be undertaken to develop culturally appropriate educational intervention programs to increase participation in biospecimen research

  3. Assays for Qualification and Quality Stratification of Clinical Biospecimens Used in Research: A Technical Report from the ISBER Biospecimen Science Working Group.

    Science.gov (United States)

    Betsou, Fay; Bulla, Alexandre; Cho, Sang Yun; Clements, Judith; Chuaqui, Rodrigo; Coppola, Domenico; De Souza, Yvonne; De Wilde, Annemieke; Grizzle, William; Guadagni, Fiorella; Gunter, Elaine; Heil, Stacey; Hodgkinson, Verity; Kessler, Joseph; Kiehntopf, Michael; Kim, Hee Sung; Koppandi, Iren; Shea, Katheryn; Singh, Rajeev; Sobel, Marc; Somiari, Stella; Spyropoulos, Demetri; Stone, Mars; Tybring, Gunnel; Valyi-Nagy, Klara; Van den Eynden, Gert; Wadhwa, Lalita

    2016-10-01

    This technical report presents quality control (QC) assays that can be performed in order to qualify clinical biospecimens that have been biobanked for use in research. Some QC assays are specific to a disease area. Some QC assays are specific to a particular downstream analytical platform. When such a qualification is not possible, QC assays are presented that can be performed to stratify clinical biospecimens according to their biomolecular quality.

  4. Synthetic antigens reveal dynamics of BCR endocytosis during inhibitory signaling.

    Science.gov (United States)

    Courtney, Adam H; Bennett, Nitasha R; Zwick, Daniel B; Hudon, Jonathan; Kiessling, Laura L

    2014-01-17

    B cells detect foreign antigens through their B cell antigen receptor (BCR). The BCR, when engaged by antigen, initiates a signaling cascade. Concurrent with signaling is endocytosis of the BCR complex, which acts to downregulate signaling and facilitate uptake of antigen for processing and display on the cell surface. The relationship between signaling and BCR endocytosis is poorly defined. Here, we explore the interplay between BCR endocytosis and antigens that either promote or inhibit B cell activation. Specifically, synthetic antigens were generated that engage the BCR alone or both the BCR and the inhibitory co-receptor CD22. The lectin CD22, a member of the Siglec family, binds sialic acid-containing glycoconjugates found on host tissues, inhibiting BCR signaling to prevent erroneous B cell activation. At low concentrations, antigens that can cocluster the BCR and CD22 promote rapid BCR endocytosis; whereas, slower endocytosis occurs with antigens that bind only the BCR. At higher antigen concentrations, rapid BCR endocytosis occurs upon treatment with either stimulatory or inhibitory antigens. Endocytosis of the BCR, in response to synthetic antigens, results in its entry into early endocytic compartments. Although the CD22-binding antigens fail to activate key regulators of antigen presentation (e.g., Syk), they also promote BCR endocytosis, indicating that inhibitory antigens can be internalized. Together, our observations support a functional role for BCR endocytosis in downregulating BCR signaling. The reduction of cell surface BCR levels in the absence of B cell activation should raise the threshold for BCR subsequent activation. The ability of the activating synthetic antigens to trigger both signaling and entry of the BCR into early endosomes suggests strategies for targeted antigen delivery.

  5. BCR Routing for Intermittently Connected Mobile Ad hoc Networks

    Directory of Open Access Journals (Sweden)

    S. RAMESH

    2014-03-01

    Full Text Available The Wireless and the Mobile Networks appear to provide a wide range of applications. Following these, the Mobile Ad hoc Networks (MANET aid in wide development of many applications. The achievement of the real world applications are attained through effective routing. The Intermittently Connected Mobile Ad hoc Network (ICMANET is a sparse network where a full connectivity is never possible. ICMANET is a disconnected MANET and is also a Delay Tolerant Network (DTN that sustains for higher delays. The routing in a disseminated network is a difficult task. A new routing scheme called Bee Colony Routing (BCR is been proposed with a motto of achieving optimal result in delivering the data packet towards the destined node. BCR is proposed with the basis of Bee Colony Optimization technique (BCO. The routing in ICMNAET is done by means of Bee routing protocol. This paper enchants a novel routing methodology for data transmission in ICMANET.

  6. 76 FR 38191 - New Proposed Collection; Comment Request; Biospecimen and Physical Measures Formative Research...

    Science.gov (United States)

    2011-06-29

    ... Physical Measures Formative Research Methodology Studies for the National Children's Study SUMMARY: In...: Title: Biospecimen and Physical Measures Formative Research Methodology Studies for the National... fulfill the requirements of the Children's Health Act, the results of formative research tests will...

  7. 76 FR 23609 - New Proposed Collection; Comment Request; Biospecimen and Physical Measures Formative Research...

    Science.gov (United States)

    2011-04-27

    ... Physical Measures Formative Research Methodology Studies for the National Children's Study SUMMARY: In... approval. Proposed Collection: Title: Biospecimen and Physical Measures Formative Research Methodology... fulfill the requirements of the Children's Health Act, the results of formative research tests will...

  8. Standard Preanalytical Coding for Biospecimens : Review and Implementation of the Sample PREanalytical Code (SPREC)

    NARCIS (Netherlands)

    Lehmann, Sabine; Guadagni, Fiorella; Moore, Helen; Ashton, Garry; Barnes, Michael; Benson, Erica; Clements, Judith; Koppandi, Iren; Coppola, Domenico; Demiroglu, Sara Yasemin; DeSouza, Yvonne; De Wilde, Annemieke; Duker, Jacko; Eliason, James; Glazer, Barbara; Harding, Keith; Jeon, Jae Pil; Kessler, Joseph; Kokkat, Theresa; Nanni, Umberto; Shea, Kathi; Skubitz, Amy; Somiari, Stella; Tybring, Gunnel; Gunter, Elaine; Betsou, Fotini

    2012-01-01

    The first version of the Standard PREanalytical Code (SPREC) was developed in 2009 by the International Society for Biological and Environmental Repositories (ISBER) Biospecimen Science Working Group to facilitate documentation and communication of the most important preanalytical quality parameters

  9. BCR-mediated apoptosis associated with negative selection of immature B cells is selectively dependent on Pten

    Institute of Scientific and Technical Information of China (English)

    Shuhua Cheng; Constance Yu Hsia; Biao Feng; Me-Ling Liou; Xiaoying Fang; Pier Paolo Pandolfi; Hsiou-Chi Liou

    2009-01-01

    The molecular basis of B cell receptor (BCR)-induced apoptosis during the negative selection of immature B cells is largely unknown. We use transitional immature B cells that are highly susceptible to BCR-induced apoptosis to show that Pten is selectively required for BCR-mediated initiation of the mitochondrial death pathway. Specifically,deleting Pten, but not other pro-apoptotic molecules, abrogates BCR-elicited apoptosis and improves viability in wild-type immature B cells. We further identify a physiologically and significantly higher intracellular Pten level in immature B cells, as compared to mature B cells, which is responsible for low AKT activity and the propensity towards death in immature B cells. Restoration of AKT activity using a constitutive form of AKT or reduction of Pten to a level comparable with that seen in mature B cells rescues immature B cells from BCR-induced apoptosis. Thus,we provide evidence that Pten is an essential mediator of BCR-induced cell death, and that differential regulation of intracellular Pten levels determines whether BCR ligation promotes cell death or survival. Our findings provide a valuable insight into the mechanisms underlying negative selection and clonal deletion of immature B cells.

  10. HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species.

    Science.gov (United States)

    Capasso, Melania; Bhamrah, Mandeep K; Henley, Tom; Boyd, Robert S; Langlais, Claudia; Cain, Kelvin; Dinsdale, David; Pulford, Karen; Khan, Mahmood; Musset, Boris; Cherny, Vladimir V; Morgan, Deri; Gascoyne, Randy D; Vigorito, Elena; DeCoursey, Thomas E; MacLennan, Ian C M; Dyer, Martin J S

    2010-03-01

    Voltage-gated proton currents regulate generation of reactive oxygen species (ROS) in phagocytic cells. In B cells, stimulation of the B cell antigen receptor (BCR) results in the production of ROS that participate in B cell activation, but the involvement of proton channels is unknown. We report here that the voltage-gated proton channel HVCN1 associated with the BCR complex and was internalized together with the BCR after activation. BCR-induced generation of ROS was lower in HVCN1-deficient B cells, which resulted in attenuated BCR signaling via impaired BCR-dependent oxidation of the tyrosine phosphatase SHP-1. This resulted in less activation of the kinases Syk and Akt, impaired mitochondrial respiration and glycolysis and diminished antibody responses in vivo. Our findings identify unanticipated functions for proton channels in B cells and demonstrate the importance of ROS in BCR signaling and downstream metabolism.

  11. World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: III. Fluid biospecimen collection, processing, and storage in endometriosis research

    DEFF Research Database (Denmark)

    Rahmioglu, Nilufer; Fassbender, Amelie; Vitonis, Allison F.;

    2014-01-01

    ObjectiveTo harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of fluid biospecimens relevant to endometriosis.......ObjectiveTo harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of fluid biospecimens relevant to endometriosis....

  12. Advancing Translational Space Research Through Biospecimen Sharing: Amplified Impact of Studies Utilizing Analogue Space Platforms

    Science.gov (United States)

    Staten, B.; Moyer, E.; Vizir, V.; Gompf, H.; Hoban-Higgins, T.; Lewis, L.; Ronca, A.; Fuller, C. A.

    2016-01-01

    Biospecimen Sharing Programs (BSPs) have been organized by NASA Ames Research Center since the 1960s with the goal of maximizing utilization and scientific return from rare, complex and costly spaceflight experiments. BSPs involve acquiring otherwise unused biological specimens from primary space research experiments for distribution to secondary experiments. Here we describe a collaboration leveraging Ames expertise in biospecimen sharing to magnify the scientific impact of research informing astronaut health funded by the NASA Human Research Program (HRP) Human Health Countermeasures (HHC) Element. The concept expands biospecimen sharing to one-off ground-based studies utilizing analogue space platforms (e.g., Hindlimb Unloading (HLU), Artificial Gravity) for rodent experiments, thereby significantly broadening the range of research opportunities with translational relevance for protecting human health in space and on Earth.

  13. Lessons from HeLa Cells: The Ethics and Policy of Biospecimens

    Science.gov (United States)

    Beskow, Laura M.

    2016-01-01

    Human biospecimens have played a crucial role in scientific and medical advances. Although the ethical and policy issues associated with biospecimen research have long been the subject of scholarly debate, the story of attention of a much broader audience. The story has been a catalyst for policy change, including major regulatory changes proposed in the United States surrounding informed consent. These proposals are premised in part on public opinion data, necessitating a closer look at what such data tell us. The development of biospecimen policy should be informed by many considerations—one of which is public input, robustly gathered, on acceptable approaches that optimize shared interests, including access for all to the benefits of research. There is a need for consent approaches that are guided by realistic aspirations and a balanced view of autonomy within an expanded ethical framework. PMID:26979405

  14. [Research and development of medical case database: a novel medical case information system integrating with biospecimen management].

    Science.gov (United States)

    Pan, Shiyang; Mu, Yuan; Wang, Hong; Wang, Tong; Huang, Peijun; Ma, Jianfeng; Jiang, Li; Zhang, Jie; Gu, Bing; Yi, Lujiang

    2010-04-01

    To meet the needs of management of medical case information and biospecimen simultaneously, we developed a novel medical case information system integrating with biospecimen management. The database established by MS SQL Server 2000 covered, basic information, clinical diagnosis, imaging diagnosis, pathological diagnosis and clinical treatment of patient; physicochemical property, inventory management and laboratory analysis of biospecimen; users log and data maintenance. The client application developed by Visual C++ 6.0 was used to implement medical case and biospecimen management, which was based on Client/Server model. This system can perform input, browse, inquest, summary of case and related biospecimen information, and can automatically synthesize case-records based on the database. Management of not only a long-term follow-up on individual, but also of grouped cases organized according to the aim of research can be achieved by the system. This system can improve the efficiency and quality of clinical researches while biospecimens are used coordinately. It realizes synthesized and dynamic management of medical case and biospecimen, which may be considered as a new management platform.

  15. Induction of autophagy by Imatinib sequesters Bcr-Abl in autophagosomes and down-regulates Bcr-Abl protein.

    LENUS (Irish Health Repository)

    Elzinga, Baukje M

    2013-06-01

    Chronic Myeloid Leukemia (CML) is a disease of hematopoietic stem cells which harbor the chimeric gene Bcr-Abl. Expression levels of this constitutively active tyrosine kinase are critical for response to tyrosine kinase inhibitor treatment and also disease progression, yet the regulation of protein stability is poorly understood. We have previously demonstrated that imatinib can induce autophagy in Bcr-Abl expressing cells. Autophagy has been associated with the clearance of large macromolecular signaling complexes and abnormal proteins, however, the contribution of autophagy to the turnover of Bcr-Abl protein in imatinib treated cells is unknown. In this study, we show that following imatinib treatment, Bcr-Abl is sequestered into vesicular structures that co-localize with the autophagy marker LC3 or GABARAP. This association is inhibited by siRNA mediated knockdown of autophagy regulators (Beclin 1\\/ATG7). Pharmacological inhibition of autophagy also reduced Bcr-Abl\\/LC3 co-localization in both K562 and CML patient cells. Bcr-Abl protein expression was reduced with imatinib treatment. Inhibition of both autophagy and proteasome activity in imatinib treated cells was required to restore Bcr-Abl protein levels to those of untreated cells. This ability to down-regulate Bcr-Abl protein levels through the induction of autophagy may be an additional and important feature of the activity of imatinib.

  16. Comparative study of DNA damage, cell cycle and apoptosis in human K562 and CCRF-CEM leukemia cells: role of BCR/ABL in therapeutic resistance.

    Science.gov (United States)

    Pytel, Dariusz; Wysocki, Tomasz; Majsterek, Ireneusz

    2006-09-01

    The Philadelphia translocation t(9;22) resulting in the bcr/abl fusion gene is the pathogenic principle of almost 95% of human chronic myelogenous leukemia (CML). Imatinib mesylate (STI571) is a specific inhibitor of the BCR/ABL fusion tyrosine kinase that exhibits potent antileukemic effects in CML. BCR/ABL-positive K562 and -negative CCRF-CEM human leukemia cells were investigated. MTT survival assay and clonogenic test of the cell proliferation ability were used to estimate resistance against idarubicin. DNA damage after cell treatment with the drug at the concentrations from 0.001 to 3 microM with or without STI571 pre-treatment were examined by the alkaline comet assay. We found that the level of DNA damages was lower in K562 cells after STI571 pre-treatment. It is suggested that BCR/ABL activity may promote genomic instability, moreover K562 cells were found to be resistant to the drug treatment. Further, we provided evidence of apoptosis inhibition in BCR/ABL-positive cells using caspase-3 activity colorimetric assay and DAPI nuclear staining for chromatin condensation. We suggest that these processes associated with cell cycle arrest in G2/M checkpoint detected in K562 BCR/ABL-positive compared to CCRF-CEM cells without BCR/ABL expression might promote clone selection resistance to drug treatment.

  17. Transferred BCR/ABL DNA from K562 extracellular vesicles causes chronic myeloid leukemia in immunodeficient mice.

    Directory of Open Access Journals (Sweden)

    Jin Cai

    Full Text Available Our previous study showed that besides mRNAs and microRNAs, there are DNA fragments within extracellular vesicles (EVs. The BCR/ABL hybrid gene, involved in the pathogenesis of chronic myeloid leukemia (CML, could be transferred from K562 EVs to neutrophils and decrease their phagocytic activity in vitro. Our present study provides evidence that BCR/ABL DNAs transferred from EVs have pathophysiological significance in vivo. Two months after injection of K562 EVs into the tail vein of Sprague-Dawley (SD rats, they showed some characteristics of CML, e.g., feeble, febrile, and thin, with splenomegaly and neutrophilia but with reduced neutrophil phagocytic activity. These findings were also observed in immunodeficient NOD/SCID mice treated with K562 EVs; BCR/ABL mRNA and protein were found in their neutrophils. The administration of actinomycin D, an inhibitor of de novo mRNA synthesis, prevented the abnormalities caused by K562 EVs in NOD/SCID mice related to CML, including neutrophilia and bone marrow hyperplasia. As a specific inhibitor of tyrosine kinases, imatinib blocked the activity of tyrosine kinases and the expression of phospho-Crkl, induced by the de novo BCR/ABL protein caused by K562 EVs bearing BCR/ABL DNA. Our current study shows the pathophysiological significance of transferred tumor gene from EVs in vivo, which may represent an important mechanism for tumorigenesis, tumor progression, and metastasis.

  18. Targeting Hedgehog signaling pathway and autophagy overcomes drug resistance of BCR-ABL-positive chronic myeloid leukemia.

    Science.gov (United States)

    Zeng, Xian; Zhao, Hui; Li, Yubin; Fan, Jiajun; Sun, Yun; Wang, Shaofei; Wang, Ziyu; Song, Ping; Ju, Dianwen

    2015-01-01

    The frontline tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, drug resistance is the major clinical challenge in the treatment of CML. The Hedgehog (Hh) signaling pathway and autophagy are both related to tumorigenesis, cancer therapy, and drug resistance. This study was conducted to explore whether the Hh pathway could regulate autophagy in CML cells and whether simultaneously regulating the Hh pathway and autophagy could induce cell death of drug-sensitive or -resistant BCR-ABL(+) CML cells. Our results indicated that pharmacological or genetic inhibition of Hh pathway could markedly induce autophagy in BCR-ABL(+) CML cells. Autophagic inhibitors or ATG5 and ATG7 silencing could significantly enhance CML cell death induced by Hh pathway suppression. Based on the above findings, our study demonstrated that simultaneously inhibiting the Hh pathway and autophagy could markedly reduce cell viability and induce apoptosis of imatinib-sensitive or -resistant BCR-ABL(+) cells. Moreover, this combination had little cytotoxicity in human peripheral blood mononuclear cells (PBMCs). Furthermore, this combined strategy was related to PARP cleavage, CASP3 and CASP9 cleavage, and inhibition of the BCR-ABL oncoprotein. In conclusion, this study indicated that simultaneously inhibiting the Hh pathway and autophagy could potently kill imatinib-sensitive or -resistant BCR-ABL(+) cells, providing a novel concept that simultaneously inhibiting the Hh pathway and autophagy might be a potent new strategy to overcome CML drug resistance.

  19. Leveraging a clinical research information system to assist biospecimen data and workflow management: a hybrid approach

    Science.gov (United States)

    2011-01-01

    Background Large multi-center clinical studies often involve the collection and analysis of biological samples. It is necessary to ensure timely, complete and accurate recording of analytical results and associated phenotypic and clinical information. The TRIBE-AKI Consortium http://www.yale.edu/tribeaki supports a network of multiple related studies and sample biorepository, thus allowing researchers to take advantage of a larger specimen collection than they might have at an individual institution. Description We describe a biospecimen data management system (BDMS) that supports TRIBE-AKI and is intended for multi-center collaborative clinical studies that involve shipment of biospecimens between sites. This system works in conjunction with a clinical research information system (CRIS) that stores the clinical data associated with the biospecimens, along with other patient-related parameters. Inter-operation between the two systems is mediated by an interactively invoked suite of Web Services, as well as by batch code. We discuss various challenges involved in integration. Conclusions Our experience indicates that an approach that emphasizes inter-operability is reasonably optimal in allowing each system to be utilized for the tasks for which it is best suited. PMID:21884570

  20. Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Churchman, Michelle L; Low, Jonathan; Qu, Chunxu; Paietta, Elisabeth M; Kasper, Lawryn H; Chang, Yunchao; Payne-Turner, Debbie; Althoff, Mark J; Song, Guangchun; Chen, Shann-Ching; Ma, Jing; Rusch, Michael; McGoldrick, Dan; Edmonson, Michael; Gupta, Pankaj; Wang, Yong-Dong; Caufield, William; Freeman, Burgess; Li, Lie; Panetta, John C; Baker, Sharyn; Yang, Yung-Li; Roberts, Kathryn G; McCastlain, Kelly; Iacobucci, Ilaria; Peters, Jennifer L; Centonze, Victoria E; Notta, Faiyaz; Dobson, Stephanie M; Zandi, Sasan; Dick, John E; Janke, Laura; Peng, Junmin; Kodali, Kiran; Pagala, Vishwajeeth; Min, Jaeki; Mayasundari, Anand; Williams, Richard T; Willman, Cheryl L; Rowe, Jacob; Luger, Selina; Dickins, Ross A; Guy, R Kiplin; Chen, Taosheng; Mullighan, Charles G

    2015-09-14

    Alterations of IKZF1, encoding the lymphoid transcription factor IKAROS, are a hallmark of high-risk acute lymphoblastic leukemia (ALL), however the role of IKZF1 alterations in ALL pathogenesis is poorly understood. Here, we show that in mouse models of BCR-ABL1 leukemia, Ikzf1 and Arf alterations synergistically promote the development of an aggressive lymphoid leukemia. Ikzf1 alterations result in acquisition of stem cell-like features, including self-renewal and increased bone marrow stromal adhesion. Retinoid receptor agonists reversed this phenotype, partly by inducing expression of IKZF1, resulting in abrogation of adhesion and self-renewal, cell cycle arrest, and attenuation of proliferation without direct cytotoxicity. Retinoids potentiated the activity of dasatinib in mouse and human BCR-ABL1 ALL, providing an additional therapeutic option in IKZF1-mutated ALL.

  1. Allosteric Inhibition of Bcr-Abl Kinase by High Affinity Monobody Inhibitors Directed to the Src Homology 2 (SH2)-Kinase Interface.

    Science.gov (United States)

    Wojcik, John; Lamontanara, Allan Joaquim; Grabe, Grzegorz; Koide, Akiko; Akin, Louesa; Gerig, Barbara; Hantschel, Oliver; Koide, Shohei

    2016-04-15

    Bcr-Abl is a constitutively active kinase that causes chronic myelogenous leukemia. We have shown that a tandem fusion of two designed binding proteins, termed monobodies, directed to the interaction interface between the Src homology 2 (SH2) and kinase domains and to the phosphotyrosine-binding site of the SH2 domain, respectively, inhibits the Bcr-Abl kinase activity. Because the latter monobody inhibits processive phosphorylation by Bcr-Abl and the SH2-kinase interface is occluded in the active kinase, it remained undetermined whether targeting the SH2-kinase interface alone was sufficient for Bcr-Abl inhibition. To address this question, we generated new, higher affinity monobodies with single nanomolar KD values targeting the kinase-binding surface of SH2. Structural and mutagenesis studies revealed the molecular underpinnings of the monobody-SH2 interactions. Importantly, the new monobodies inhibited Bcr-Abl kinase activity in vitro and in cells, and they potently induced cell death in chronic myelogenous leukemia cell lines. This work provides strong evidence for the SH2-kinase interface as a pharmacologically tractable site for allosteric inhibition of Bcr-Abl.

  2. CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells.

    Directory of Open Access Journals (Sweden)

    Shweta Jain

    Full Text Available Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID, signifying class switch recombination (CSR. Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response.

  3. BCR-ABL DERIVED PEPTIDE VACCINES FOR CHRONIC MYELOID LEUKAEMIA

    Directory of Open Access Journals (Sweden)

    M. Bocchia

    2012-01-01

    Full Text Available Chronic Myeloid Leukemia (CML is a myeloproliferative pluripotent stem cell disorder characterized by the presence of a cytogenetic hallmark, the Philadelphia (Ph chromosome, and accounts for 15% of adult leukemias. The disease progresses from a chronic phase through an accelerated phase to a blast phase and its natural course accounts for a median 4 years survival1. The Ph chromosome is derived by a reciprocal translocation termed t(9;22 in which the c-abl oncogene has moved from chromosome 9 into the breakpoint cluster region (bcr, within the bcr gene on chromosome 22, resulting in a chimeric bcr-abl fusion gene that encodes a 210 KD protein (p210 with constitutive tyrosine kinase activity. Two major alternative chimeric p210 can result from this fusion gene: p210-b2a2 where the junction occurs between bcr exon 2 (b2 and abl exon 2 (a2 and p210-b3a2 where the the junction occurs between bcr exon 3 (b3 and abl exon 2 (a2. About 40% of CML patients harbor the p210-b2a2 and about 60% of them show the p210-b3a2.

  4. Conservation and distribution of the benzalkonium chloride resistance cassette bcrABC in Listeria monocytogenes.

    Science.gov (United States)

    Dutta, Vikrant; Elhanafi, Driss; Kathariou, Sophia

    2013-10-01

    Analysis of a panel of 116 Listeria monocytogenes strains of diverse serotypes and sources (clinical, environment of food processing plants, and food) revealed that all but one of the 71 benzalkonium chloride-resistant (BC(r)) isolates harbored bcrABC, previously identified on a large plasmid (pLM80) of the 1998-1999 hot dog outbreak strain H7858. In contrast, bcrABC was not detected among BC-susceptible (BC(s)) isolates. The bcrABC sequences were highly conserved among strains of different serotypes, but variability was noted in sequences flanking bcrABC. The majority of the BC(r) isolates had either the pLM80-type of organization of the bcrABC region or appeared to harbor bcrABC on the chromosome, adjacent to novel sequences. Transcription of bcrABC was induced by BC (10 μg/ml) in strains of different serotypes and diverse bcrABC region organization. These findings reveal widespread dissemination of bcrABC across BC(r) L. monocytogenes strains regardless of serotype and source, while also suggesting possible mechanisms of bcrABC dissemination across L. monocytogenes genomes.

  5. INHIBITION OF APOPTOSIS BY bcr-abl FUSION GENE IN K562 CELLS

    Institute of Scientific and Technical Information of China (English)

    WANG Chun-hong; SUN Bing-zhong; YUAN Yue-chuan

    1999-01-01

    Objective: To investigate the effect of bcr-abl fusion gene on CML cell apoptosis. Methods: Apoptosis of exvivo cultured K562 cells were observed after exposure to synthetic 18 mer antisense oligodeoxynucleotide complementary to the bcr-abl junction (b3a2). Results: Apoptosis of K562 cells was significantly increased associated with inhibition of bcr-abl expression. Conclusion: bcr-abl fusion gene formation due to chromosome translocation may be the major mechanism of CML via inhibition of apoptosis.

  6. Statistical design for biospecimen cohort size in proteomics-based biomarker discovery and verification studies.

    Science.gov (United States)

    Skates, Steven J; Gillette, Michael A; LaBaer, Joshua; Carr, Steven A; Anderson, Leigh; Liebler, Daniel C; Ransohoff, David; Rifai, Nader; Kondratovich, Marina; Težak, Živana; Mansfield, Elizabeth; Oberg, Ann L; Wright, Ian; Barnes, Grady; Gail, Mitchell; Mesri, Mehdi; Kinsinger, Christopher R; Rodriguez, Henry; Boja, Emily S

    2013-12-01

    Protein biomarkers are needed to deepen our understanding of cancer biology and to improve our ability to diagnose, monitor, and treat cancers. Important analytical and clinical hurdles must be overcome to allow the most promising protein biomarker candidates to advance into clinical validation studies. Although contemporary proteomics technologies support the measurement of large numbers of proteins in individual clinical specimens, sample throughput remains comparatively low. This problem is amplified in typical clinical proteomics research studies, which routinely suffer from a lack of proper experimental design, resulting in analysis of too few biospecimens to achieve adequate statistical power at each stage of a biomarker pipeline. To address this critical shortcoming, a joint workshop was held by the National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), and American Association for Clinical Chemistry (AACC) with participation from the U.S. Food and Drug Administration (FDA). An important output from the workshop was a statistical framework for the design of biomarker discovery and verification studies. Herein, we describe the use of quantitative clinical judgments to set statistical criteria for clinical relevance and the development of an approach to calculate biospecimen sample size for proteomic studies in discovery and verification stages prior to clinical validation stage. This represents a first step toward building a consensus on quantitative criteria for statistical design of proteomics biomarker discovery and verification research.

  7. Transformation of an Unclassified Myeloproliferative Neoplasm with a Rare BCR-JAK2 Fusion Transcript Resulting from the Translocation (9;22)(p24;q11)

    Science.gov (United States)

    Chamseddine, A. N.; Etancelin, P.; Penther, D.; Parmentier, F.; Kuadjovi, C.; Camus, V.; Contentin, N.; Lenain, P.; Bastard, C.; Tilly, H.; Jardin, F.

    2015-01-01

    BCR-ABL1 negative myeloproliferative neoplasms (MPNs) are known to contain alterations of the tyrosine kinase JAK2 (located on 9p24) that result in constitutive activation of the encoded protein. JAK2 fusions are reported in acute and chronic leukemias of myeloid and lymphoid phenotypes. Here, we report an unclassified case of MPN (MPN-U) showing a t(9;22)(p24;q11), which generates a BCR-JAK2 fusion gene by fusing the BCR at intron 13 to JAK2 at intron 17 on the derivative chromosome 22. Most reported JAK2 fusions cases reveal an aggressive clinical course and long-term remissions have only been achieved after allogeneic stem cell transplantation (ASCT). To the best of our knowledge, this is the thirteenth case reported worldwide to describe a BCR-JAK2 fusion transcript in MPN-U. The present report revealed a sustained complete clinical, hematologic, and cytogenetic remission 35 months after diagnosis and ~24 months after ASCT. Regarding BCR-ABL1  negative MPN patients this case report provides strong support for a role of JAK2 activation in the oncogenesis and suggests a possible diagnostic and therapeutic target that should be investigated. PMID:25789185

  8. Transformation of an Unclassified Myeloproliferative Neoplasm with a Rare BCR-JAK2 Fusion Transcript Resulting from the Translocation (9;22(p24;q11

    Directory of Open Access Journals (Sweden)

    A. N. Chamseddine

    2015-01-01

    Full Text Available BCR-ABL1 negative myeloproliferative neoplasms (MPNs are known to contain alterations of the tyrosine kinase JAK2 (located on 9p24 that result in constitutive activation of the encoded protein. JAK2 fusions are reported in acute and chronic leukemias of myeloid and lymphoid phenotypes. Here, we report an unclassified case of MPN (MPN-U showing a t(9;22(p24;q11, which generates a BCR-JAK2 fusion gene by fusing the BCR at intron 13 to JAK2 at intron 17 on the derivative chromosome 22. Most reported JAK2 fusions cases reveal an aggressive clinical course and long-term remissions have only been achieved after allogeneic stem cell transplantation (ASCT. To the best of our knowledge, this is the thirteenth case reported worldwide to describe a BCR-JAK2 fusion transcript in MPN-U. The present report revealed a sustained complete clinical, hematologic, and cytogenetic remission 35 months after diagnosis and ~24 months after ASCT. Regarding BCR-ABL1  negative MPN patients this case report provides strong support for a role of JAK2 activation in the oncogenesis and suggests a possible diagnostic and therapeutic target that should be investigated.

  9. BCR and its mutants, the reciprocal t(9;22-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility

    Directory of Open Access Journals (Sweden)

    Puccetti Elena

    2006-11-01

    Full Text Available Abstract Background The reciprocal (9;22 translocation fuses the bcr (breakpoint cluster region gene on chromosome 22 to the abl (Abelson-leukemia-virus gene on chromosome 9. Depending on the breakpoint on chromosome 22 (the Philadelphia chromosome – Ph+ the derivative 9+ encodes either the p40(ABL/BCR fusion transcript, detectable in about 65% patients suffering from chronic myeloid leukemia, or the p96(ABL/BCR fusion transcript, detectable in 100% of Ph+ acute lymphatic leukemia patients. The ABL/BCRs are N-terminally truncated BCR mutants. The fact that BCR contains Rho-GEF and Rac-GAP functions strongly suggest an important role in cytoskeleton modeling by regulating the activity of Rho-like GTPases, such as Rho, Rac and cdc42. We, therefore, compared the function of the ABL/BCR proteins with that of wild-type BCR. Methods We investigated the effects of BCR and ABL/BCRs i. on the activation status of Rho, Rac and cdc42 in GTPase-activation assays; ii. on the actin cytoskeleton by direct immunofluorescence; and iii on cell motility by studying migration into a three-dimensional stroma spheroid model, adhesion on an endothelial cell layer under shear stress in a flow chamber model, and chemotaxis and endothelial transmigration in a transwell model with an SDF-1α gradient. Results Here we show that both ABL/BCRs lost fundamental functional features of BCR regarding the regulation of small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells. Conclusion Our data presented here describe for the first time an analysis of the biological function of the reciprocal t(9;22 ABL/BCR fusion proteins in comparison to their physiological counterpart BCR.

  10. Naïve and memory B cells exhibit distinct biochemical responses following BCR engagement.

    Science.gov (United States)

    Moens, Leen; Kane, Alisa; Tangye, Stuart G

    2016-09-01

    Immunological memory is characterized by the rapid reactivation of memory B cells that produce large quantities of high-affinity antigen-specific antibodies. This contrasts the response of naïve B cells, and the primary immune response, which is much slower and of lower affinity. Memory responses are critical for protection against infectious diseases and form the basis of most currently available vaccines. Although we have known about the phenomenon of long-lived memory for centuries, the biochemical differences underlying these diverse responses of naïve and memory B cells is incompletely resolved. Here we investigated the nature of B-cell receptor (BCR) signaling in human splenic naïve, IgM(+) memory and isotype-switched memory B cells following multivalent BCR crosslinking. We observed comparable rapid and transient phosphorylation kinetics for proximal (phosphotyrosine and spleen tyrosine kinase) and propagation (B-cell linker, phospholipase Cγ2) signaling components in these different B-cell subsets. However, the magnitude of activation of downstream components of the BCR signaling pathway were greater in memory compared with naïve cells. Although no differences were observed in the magnitude of Ca(2+) mobilization between subsets, IgM(+) memory B cells exhibited a more rapid Ca(2+) mobilization and a greater depletion of the Ca(2+) endoplasmic reticulum stores, while IgG(+) memory B cells had a prolonged Ca(2+) uptake. Collectively, our findings show that intrinsic signaling features of B-cell subsets contribute to the robust response of human memory B cells over naïve B cells. This has implications for our understanding of memory B-cell responses and provides a framework to modulate these responses in the setting of vaccination and immunopathologies, such as immunodeficiency and autoimmunity.

  11. Targeting the SH2-Kinase Interface in Bcr-Abl Inhibits Leukemogenesis

    OpenAIRE

    Grebien, Florian; Hantschel, Oliver; Wojcik, John; Kaupe, Ines; Kovacic, Boris; Wyrzucki, Arkadiusz M.; Gish, Gerald D.; Cerny-Reiterer, Sabine; Koide, Akiko; Beug, Hartmut; Pawson, Tony; Valent, Peter; Koide, Shohei; Superti-Furga, Giulio

    2011-01-01

    Summary Chronic myelogenous leukemia (CML) is caused by the constitutively active tyrosine kinase Bcr-Abl and treated with the tyrosine kinase inhibitor (TKI) imatinib. However, emerging TKI resistance prevents complete cure. Therefore, alternative strategies targeting regulatory modules of Bcr-Abl in addition to the kinase active site are strongly desirable. Here, we show that an intramolecular interaction between the SH2 and kinase domains in Bcr-Abl is both necessary and sufficient for hig...

  12. Inverse regulation of bridging integrator 1 and BCR-ABL1 in chronic myeloid leukemia.

    Science.gov (United States)

    Trino, Stefania; De Luca, Luciana; Simeon, Vittorio; Laurenzana, Ilaria; Morano, Annalisa; Caivano, Antonella; La Rocca, Francesco; Pietrantuono, Giuseppe; Bianchino, Gabriella; Grieco, Vitina; Signorino, Elisabetta; Fragasso, Alberto; Bochicchio, Maria Teresa; Venturi, Claudia; Rosti, Gianantonio; Martinelli, Giovanni; Del Vecchio, Luigi; Cilloni, Daniela; Musto, Pellegrino

    2016-01-01

    Endocytosis is the major regulator process of tyrosine kinase receptor (RTK) functional activities. Bridging integrator 1 (BIN1) is a key protein involved in RTK intracellular trafficking. Here, we report, by studying 34 patients with chronic myeloid leukemia (CML) at diagnosis, that BIN1 gene is downregulated in CML as compared to healthy controls, suggesting an altered endocytosis of RTKs. Rab interactor 1 (RIN1), an activator of BIN1, displayed a similar behavior. Treatment of 57 patients by tyrosine kinase inhibitors caused, along with BCR-ABL1 inactivation, an increase of BIN1 and RIN1 expression, potentially restoring endocytosis. There was a significant inverse correlation between BIN1-RIN1 and BCR-ABL1 expression. In vitro experiments on both CML and nontumorigenic cell lines treated with Imatinib confirmed these results. In order to provide another proof in favor of BIN1 and RIN1 endocytosis function in CML, we demonstrated that Imatinib induced, in K562 cell line, BIN1-RIN1 upregulation accompanied by a parallel AXL receptor internalization into cytoplasmic compartment. This study shows a novel deregulated mechanism in CML patients, indicating BIN1 and RIN1 as players in the maintenance of the abnormal RTK signaling in this hematological disease.

  13. Biospecimen Sharing Among Hispanic Women in a Safety-Net Clinic: Implications for the Precision Medicine Initiative

    Science.gov (United States)

    Nodora, Jesse N.; Komenaka, Ian K.; Bouton, Marcia E.; Ohno-Machado, Lucila; Schwab, Richard; Kim, Hyeon-eui; Farcas, Claudiu; Perez, Giovanna

    2017-01-01

    Biospecimen donation is key to the Precision Medicine Initiative, which pioneers a model for accelerating biomedical research through individualized care. Personalized medicine should be made available to medically underserved populations, including the large and growing US Hispanic population. We present results of a study of 140 Hispanic women who underwent a breast biopsy at a safety-net hospital and were randomly assigned to receive information and request for consent for biospecimen and data sharing by the patient’s physician or a research assistant. Consent rates were high (97.1% and 92.9% in the physician and research assistant arms, respectively) and not different between groups (relative risk [RR] = 1.05, 95% confidence interval [CI] = 0.96 to 1.10). Consistent with a small but growing literature, we show that perceptions of Hispanics’ unwillingness to participate in biospecimen sharing for research are not supported by data. Safety-net clinics and hospitals offer untapped possibilities for enhancing participation of underserved populations in the exciting Precision Medicine Initiative. PMID:27688295

  14. Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation

    DEFF Research Database (Denmark)

    Satpathy, Shankha; Wagner, Sebastian A; Beli, Petra;

    2015-01-01

    ) and to investigate the dynamics of downstream phosphorylation and ubiquitylation signaling. We identify most of the previously known components of BCR signaling, as well as many proteins that have not yet been implicated in this system. BCR activation leads to rapid tyrosine phosphorylation and ubiquitylation...

  15. Detection of p190BCR-ABL AND p210BCR-ABL fusion transcripts in patients with chronic myeloid leukemia (CML using qualitative RT-PCR

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    Aya Bonilla, Carlos Alberto

    2014-10-01

    Full Text Available Introduction: Chronic myelogenous leukemia (CML is characterized by the presence of the Philadelphia chromosome (Ph, resulting from the balanced reciprocal translocation t(9;22(q34;q11. This marker chromosome is found less frequently in patients suffering from acute lymphoblastic leukemia. Objective: To determine the frequency of BCR-ABL gene fusions encoding the p210BCR-ABL y p190 BCR-ABL transcripts in Colombian patients diagnosed with CML in different stages of the disease and/or its treatment. Materials and methods: Cross sectional, descriptive study of thirty one CML patients (aged 15-78. Analysis was carried out through qualitative nested PCR for the isoforms P210 BCR-ABL (b3a2 e b2a2 and P190 BCR-ABL (e1a2, and based on peripheral blood samples. Results: In 29 of the 31 patients (93.6% transcript p210BCR-ABL was detected; b2a2 and b3a2 gene fusions and the coexpression b3a2 y b2a2 were identified in 55.2% (16/29, 34.5% (10/29 and 10.3% (3/29 of the cases, respectively. Conclusion: b2a2 gene fusion was the most frequent in this CML population.

  16. Combination of bortezomib and mitotic inhibitors down-modulate Bcr-Abl and efficiently eliminates tyrosine-kinase inhibitor sensitive and resistant Bcr-Abl-positive leukemic cells.

    Science.gov (United States)

    Bucur, Octavian; Stancu, Andreea Lucia; Goganau, Ioana; Petrescu, Stefana Maria; Pennarun, Bodvael; Bertomeu, Thierry; Dewar, Rajan; Khosravi-Far, Roya

    2013-01-01

    Emergence of resistance to Tyrosine-Kinase Inhibitors (TKIs), such as imatinib, dasatinib and nilotinib, in Chronic Myelogenous Leukemia (CML) demands new therapeutic strategies. We and others have previously established bortezomib, a selective proteasome inhibitor, as an important potential treatment in CML. Here we show that the combined regimens of bortezomib with mitotic inhibitors, such as the microtubule-stabilizing agent Paclitaxel and the PLK1 inhibitor BI2536, efficiently kill TKIs-resistant and -sensitive Bcr-Abl-positive leukemic cells. Combined treatment activates caspases 8, 9 and 3, which correlate with caspase-induced PARP cleavage. These effects are associated with a marked increase in activation of the stress-related MAP kinases p38MAPK and JNK. Interestingly, combined treatment induces a marked decrease in the total and phosphorylated Bcr-Abl protein levels, and inhibits signaling pathways downstream of Bcr-Abl: downregulation of STAT3 and STAT5 phosphorylation and/or total levels and a decrease in phosphorylation of the Bcr-Abl-associated proteins CrkL and Lyn. Moreover, we found that other mitotic inhibitors (Vincristine and Docetaxel), in combination with bortezomib, also suppress the Bcr-Abl-induced pro-survival signals and result in caspase 3 activation. These results open novel possibilities for the treatment of Bcr-Abl-positive leukemias, especially in the imatinib, dasatinib and nilotinib-resistant CML cases.

  17. Expression of BCR/ABL p210 from a Knockin Allele Enhances Bone Marrow Engraftment without Inducing Neoplasia

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    Samantha B. Foley

    2013-10-01

    Full Text Available Chronic myeloid leukemia (CML and some acute lymphoblastic leukemias are characterized by the t(9;22 chromosome, which encodes the BCR/ABL oncogene. Multiple mouse models of CML express BCR/ABL at high levels from non-Bcr promoters, resulting in the development of leukemias. In contrast, a significant fraction of healthy humans have been found to have BCR/ABL-positive hematopoietic cells. To bridge the gap between the information derived from current mouse models and nonleukemic humans with the BCR/ABL oncogene, we generated a knockin model with BCR/ABL p210 expressed from the Bcr locus. Unlike previous models, expression of BCR/ABL from the knockin allele did not induce leukemia. BCR/ABL mutant cells did exhibit favorable bone marrow engraftment compared to control cells. These data suggest that BCR/ABL expression alone is insufficient to induce disease. This model allows for inducible spatial and temporal control of BCR/ABL expression for analysis of early steps in the pathogenesis of BCR/ABL-expressing leukemias.

  18. Ibrutinib inhibits pre-BCR(+) B-cell acute lymphoblastic leukemia progression by targeting BTK and BLK.

    Science.gov (United States)

    Kim, Ekaterina; Hurtz, Christian; Koehrer, Stefan; Wang, Zhiqiang; Balasubramanian, Sriram; Chang, Betty Y; Müschen, Markus; Davis, R Eric; Burger, Jan A

    2017-03-02

    Targeting B-cell receptor (BCR) signaling is a successful therapeutic strategy in mature B-cell malignancies. Precursor BCR (pre-BCR) signaling, which is critical during normal B lymphopoiesis, also plays an important role in pre-BCR(+) B cell acute lymphoblastic leukemia (B-ALL). Here, we investigated the activity and mechanism of action of the BTK inhibitor ibrutinib in preclinical models of B-ALL. Pre-BCR(+) ALL cells were exquisitely sensitive to ibrutinib at therapeutically relevant drug concentrations. In pre-BCR(+) ALL, ibrutinib thwarted autonomous and induced pre-BCR signaling, resulting in deactivation of PI3K/Akt signaling. Ibrutinib modulated the expression of pre-BCR regulators (PTPN6, CD22, CD72, and PKCβ) and substantially reduced BCL6 levels. Ibrutinib inhibited ALL cell migration toward CXCL12 and beneath marrow stromal cells and reduced CD44 expression. CRISPR-Cas9 gene editing revealed that both BTK and B lymphocyte kinase (BLK) are relevant targets of ibrutinib in pre-BCR(+) ALL. Consequently, in mouse xenograft models of pre-BCR(+) ALL, ibrutinib treatment significantly prolonged survival. Combination treatment of ibrutinib with dexamethasone or vincristine demonstrated synergistic activity against pre-BCR(+) ALL. These data corroborate ibrutinib as a promising targeted agent for pre-BCR(+) ALL and highlight the importance of ibrutinib effects on alternative kinase targets.

  19. Blockade of Y177 and Nuclear Translocation of Bcr-Abl Inhibits Proliferation and Promotes Apoptosis in Chronic Myeloid Leukemia Cells.

    Science.gov (United States)

    Li, Qianyin; Huang, Zhenglan; Gao, Miao; Cao, Weixi; Xiao, Qin; Luo, Hongwei; Feng, Wenli

    2017-03-02

    The gradual emerging of resistance to imatinib urgently calls for the development of new therapy for chronic myeloid leukemia (CML). The fusion protein Bcr-Abl, which promotes the malignant transformation of CML cells, is mainly located in the cytoplasm, while the c-Abl protein which is expressed in the nucleus can induce apoptosis. Based on the hetero-dimerization of FKBP (the 12-kDa FK506- and rapamycin-binding protein) and FRB (the FKBP-rapamycin binding domain of the protein kinase, mTOR) mediated by AP21967, we constructed a nuclear transport system to induce cytoplasmic Bcr-Abl into nuclear. In this study, we reported the construction of the nuclear transport system, and we demonstrated that FN3R (three nuclear localization signals were fused to FRBT2098L with a FLAG tag), HF2S (two FKBP domains were in tandem and fused to the SH2 domain of Grb2 with an HA tag) and Bcr-Abl form a complexus upon AP21967. Bcr-Abl was imported into the nucleus successfully by the nuclear transport system. The nuclear transport system inhibited CML cell proliferation through mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 5 (STAT5) pathways mainly by HF2S. It was proven that nuclear located Bcr-Abl induced CML cell (including imatinib-resistant K562G01 cells) apoptosis by activation of p73 and its downstream molecules. In summary, our study provides a new targeted therapy for the CML patients even with Tyrosine Kinase Inhibitor (TKI)-resistance.

  20. Blockade of Y177 and Nuclear Translocation of Bcr-Abl Inhibits Proliferation and Promotes Apoptosis in Chronic Myeloid Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Qianyin Li

    2017-03-01

    Full Text Available The gradual emerging of resistance to imatinib urgently calls for the development of new therapy for chronic myeloid leukemia (CML. The fusion protein Bcr-Abl, which promotes the malignant transformation of CML cells, is mainly located in the cytoplasm, while the c-Abl protein which is expressed in the nucleus can induce apoptosis. Based on the hetero-dimerization of FKBP (the 12-kDa FK506- and rapamycin-binding protein and FRB (the FKBP-rapamycin binding domain of the protein kinase, mTOR mediated by AP21967, we constructed a nuclear transport system to induce cytoplasmic Bcr-Abl into nuclear. In this study, we reported the construction of the nuclear transport system, and we demonstrated that FN3R (three nuclear localization signals were fused to FRBT2098L with a FLAG tag, HF2S (two FKBP domains were in tandem and fused to the SH2 domain of Grb2 with an HA tag and Bcr-Abl form a complexus upon AP21967. Bcr-Abl was imported into the nucleus successfully by the nuclear transport system. The nuclear transport system inhibited CML cell proliferation through mitogen-activated protein kinase (MAPK and signal transducer and activator of transcription 5 (STAT5 pathways mainly by HF2S. It was proven that nuclear located Bcr-Abl induced CML cell (including imatinib-resistant K562G01 cells apoptosis by activation of p73 and its downstream molecules. In summary, our study provides a new targeted therapy for the CML patients even with Tyrosine Kinase Inhibitor (TKI-resistance.

  1. The Study on BCR/ABL Fusion Gene in Adult Acute Lymphoblastic Leukemia

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In order to assess the significance of BCR/ABC fusion gene in adult acute lymphoblastic Leukemia (ALL), 28 patients who were diagnosed as ALL were enrolled to detect BCR/ABC gene using nested-RT PCR. The results showed that 9 cases (31.25%) were BCR/ABL positive ,and expressed P210 subtype. A mong them 7 cases were B-ALL, and one was T-ALL. The diagnosis was proved by monoclonal antibodies recognition by indirect immunofluorescence. Adult patients with BCR/ABL positive ALL were significantly older (p<0. 01) and had higher WBC count (p<0. 01) as compared with BCR/ABL-negative patients. There was no significant difference in sex, hemoglobin and splenomegaly between two group (p>0. 05). The induc tion failure rate was high in BCR/ABL positive patients and those who achieved complete remission usually relapsed earlier. In conclusion, adult ALL patients with BCR/ABL-positive have poorer prognosis.

  2. BCR/ABL stimulates WRN to promote survival and genomic instability

    Science.gov (United States)

    Slupianek, Artur; Poplawski, Tomasz; Jozwiakowski, Stanislaw K.; Cramer, Kimberly; Pytel, Dariusz; Stoczynska, Ewelina; Nowicki, Michal O.; Blasiak, Janusz; Skorski, Tomasz

    2010-01-01

    BCR/ABL-transformed chronic myeloid leukemia (CML) cells accumulate numerous DNA double-strand breaks (DSBs) induced by reactive oxygen species (ROS) and genotoxic agents. To repair these lesions BCR/ABL stimulate unfaithful DSB repair pathways, homologous recombination repair (HRR), non-homologous end-joining (NHEJ) and single-strand annealing (SSA). Here we show that BCR/ABL enhances the expression and increase nuclear localization of WRN (mutated in Werner syndrome), which is required for processing DSB ends during the repair. Other fusion tyrosine kinases (FTKs) such as TEL/ABL, TEL/JAK2, TEL/PDGFβR, and NPM/ALK also elevate WRN. BCR/ABL induces WRN mRNA and protein expression in part by c-MYC -mediated activation of transcription and Bcl-xL –dependent inhibition of caspase-dependent cleavage, respectively. WRN is in complex with BCR/ABL resulting in WRN tyrosine phosphorylation and stimulation of its helicase and exonuclease activities. Activated WRN protects BCR/ABL-positive cells from the lethal effect of oxidative and genotoxic stresses, which causes DSBs. In addition, WRN promotes unfaithful recombination-dependent repair mechanisms HRR and SSA, and enhances the loss of DNA bases during NHEJ in leukemia cells. In summary, we postulate that BCR/ABL-mediated stimulation of WRN modulates the efficiency and fidelity of major DSB repair mechanisms to protect leukemia cells from apoptosis and to facilitate genomic instability. PMID:21123451

  3. BCR/ABL stimulates WRN to promote survival and genomic instability.

    Science.gov (United States)

    Slupianek, Artur; Poplawski, Tomasz; Jozwiakowski, Stanislaw K; Cramer, Kimberly; Pytel, Dariusz; Stoczynska, Ewelina; Nowicki, Michal O; Blasiak, Janusz; Skorski, Tomasz

    2011-02-01

    BCR/ABL-transformed chronic myeloid leukemia (CML) cells accumulate numerous DNA double-strand breaks (DSB) induced by reactive oxygen species (ROS) and genotoxic agents. To repair these lesions BCR/ABL stimulate unfaithful DSB repair pathways, homologous recombination repair (HRR), nonhomologous end-joining (NHEJ), and single-strand annealing (SSA). Here, we show that BCR/ABL enhances the expression and increase nuclear localization of WRN (mutated in Werner syndrome), which is required for processing DSB ends during the repair. Other fusion tyrosine kinases (FTK), such as TEL/ABL, TEL/JAK2, TEL/PDGFβR, and NPM/ALK also elevate WRN. BCR/ABL induces WRN mRNA and protein expression in part by c-MYC-mediated activation of transcription and Bcl-xL-dependent inhibition of caspase-dependent cleavage, respectively. WRN is in complex with BCR/ABL resulting in WRN tyrosine phosphorylation and stimulation of its helicase and exonuclease activities. Activated WRN protects BCR/ABL-positive cells from the lethal effect of oxidative and genotoxic stresses, which causes DSBs. In addition, WRN promotes unfaithful recombination-dependent repair mechanisms HRR and SSA, and enhances the loss of DNA bases during NHEJ in leukemia cells. In summary, we postulate that BCR/ABL-mediated stimulation of WRN modulates the efficiency and fidelity of major DSB repair mechanisms to protect leukemia cells from apoptosis and to facilitate genomic instability.

  4. Molecular measurement of BCR-ABL transcript variations in chronic myeloid leukemia patients in cytogenetic remission

    Directory of Open Access Journals (Sweden)

    Costa Juliana

    2010-11-01

    Full Text Available Abstract Background The monitoring of BCR-ABL transcript levels by real-time quantitative polymerase chain reaction (RT-qPCR has become important to assess minimal residual disease (MRD and standard of care in the treatment of chronic myeloid leukemia (CML. In this study, we performed a prospective, sequential analysis using RT-qPCR monitoring of BCR-ABL gene rearrangements in blood samples from 91 CML patients in chronic phase (CP who achieved complete cytogenetic remission (CCyR and major molecular remission (MMR throughout imatinib treatment. Methods The absolute level of BCR-ABL transcript from peripheral blood was serially measured every 4 to 12 weeks by RT-qPCR. Only level variations > 0.5%, according to the international scale, was considered positive. Sequential cytogenetic analysis was also performed in bone marrow samples from all patients using standard protocols. Results Based on sequential analysis of BCR-ABL transcripts, the 91 patients were divided into three categories: (A 57 (62.6% had no variation on sequential analysis; (B 30 (32.9% had a single positive variation result obtained in a single sample; and (C 4 (4.39% had variations of BCR-ABL transcripts in at least two consecutive samples. Of the 34 patients who had elevated levels of transcripts (group B and C, 19 (55.8% had a BCR-ABL/BCR ratio, 13 (38.2% patients had a 1% to 10% increase and 2 patients had a >10% increase of RT-qPCR. The last two patients had lost a CCyR, and none of them showed mutations in the ABL gene. Transient cytogenetic alterations in Ph-negative cells were observed in five (5.5% patients, and none of whom lost CCyR. Conclusions Despite an increase levels of BCR-ABL/BCR ratio variations by RT-qPCR, the majority of CML patients with MMR remained in CCyR. Thus, such single variations should neither be considered predictive of subsequent failure and nor an indication for altering imatinib dose or switching to second generation therapy. Changing of

  5. Improved coiled-coil design enhances interaction with Bcr-Abl and induces apoptosis.

    Science.gov (United States)

    Dixon, Andrew S; Miller, Geoffrey D; Bruno, Benjamin J; Constance, Jonathan E; Woessner, David W; Fidler, Trevor P; Robertson, James C; Cheatham, Thomas E; Lim, Carol S

    2012-01-01

    The oncoprotein Bcr-Abl drives aberrant downstream activity through trans-autophosphorylation of homo-oligomers in chronic myelogenous leukemia (CML).(1, 2) The formation of Bcr-Abl oligomers is achieved through the coiled-coil domain at the N-terminus of Bcr.(3, 4) We have previously reported a modified version of this coiled-coil domain, CCmut2, which exhibits disruption of Bcr-Abl oligomeric complexes and results in decreased proliferation of CML cells and induction of apoptosis.(5) A major contributing factor to these enhanced capabilities is the destabilization of the CCmut2 homodimers, increasing the availability to interact with and inhibit Bcr-Abl. Here, we included an additional mutation (K39E) that could in turn further destabilize the mutant homodimer. Incorporation of this modification into CCmut2 (C38A, S41R, L45D, E48R, Q60E) generated what we termed CCmut3, and resulted in further improvements in the binding properties with the wild-type coiled-coil domain representative of Bcr-Abl [corrected]. A separate construct containing one revert mutation, CCmut4, did not demonstrate improved oligomeric properties and indicated the importance of the L45D mutation. CCmut3 demonstrated improved oligomerization via a two-hybrid assay as well as through colocalization studies, in addition to showing similar biologic activity as CCmut2. The improved binding between CCmut3 and the Bcr-Abl coiled-coil may be used to redirect Bcr-Abl to alternative subcellular locations with interesting therapeutic implications.

  6. Lack of bcr and abr promotes hypoxia-induced pulmonary hypertension in mice.

    Directory of Open Access Journals (Sweden)

    Min Yu

    Full Text Available BACKGROUND: Bcr and Abr are GTPase activating proteins that specifically downregulate activity of the small GTPase Rac in restricted cell types in vivo. Rac1 is expressed in smooth muscle cells, a critical cell type involved in the pathogenesis of pulmonary hypertension. The molecular mechanisms that underlie hypoxia-associated pulmonary hypertension are not well-defined. METHODOLOGY/PRINCIPAL FINDINGS: Bcr and abr null mutant mice were compared to wild type controls for the development of pulmonary hypertension after exposure to hypoxia. Also, pulmonary arterial smooth muscle cells from those mice were cultured in hypoxia and examined for proliferation, p38 activation and IL-6 production. Mice lacking Bcr or Abr exposed to hypoxia developed increased right ventricular pressure, hypertrophy and pulmonary vascular remodeling. Perivascular leukocyte infiltration in the lungs was increased, and under hypoxia bcr-/- and abr-/- macrophages generated more reactive oxygen species. Consistent with a contribution of inflammation and oxidative stress in pulmonary hypertension-associated vascular damage, Bcr and Abr-deficient animals showed elevated endothelial leakage after hypoxia exposure. Hypoxia-treated pulmonary arterial smooth muscle cells from Bcr- or Abr-deficient mice also proliferated faster than those of wild type mice. Moreover, activated Rac1, phosphorylated p38 and interleukin 6 were increased in these cells in the absence of Bcr or Abr. Inhibition of Rac1 activation with Z62954982, a novel Rac inhibitor, decreased proliferation, p38 phosphorylation and IL-6 levels in pulmonary arterial smooth muscle cells exposed to hypoxia. CONCLUSIONS: Bcr and Abr play a critical role in down-regulating hypoxia-induced pulmonary hypertension by deactivating Rac1 and, through this, reducing both oxidative stress generated by leukocytes as well as p38 phosphorylation, IL-6 production and proliferation of pulmonary arterial smooth muscle cells.

  7. A Requirement for SOCS-1 and SOCS-3 Phosphorylation in Bcr-Abl-Induced Tumorigenesis

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    Xiaoxue Qiu

    2012-06-01

    Full Text Available Suppressors of cytokine signaling 1 and 3 (SOCS-1 and SOCS-3 are inhibitors of the Janus tyrosine kinase (JAK/signal transducers and activators of transcription (STAT pathway and function in a negative feedback loop during cytokine signaling. Abl transformation is associated with constitutive activation of JAK/STAT-dependent signaling. However, the mechanism by which Abl oncoproteins bypass SOCS inhibitory regulation remains poorly defined. Here, we demonstrate that coexpression of Bcr-Abl with SOCS-1 or SOCS-3 results in tyrosine phosphorylation of these SOCS proteins. Interestingly, SOCS-1 is highly tyrosine phosphorylated in one of five primary chronic myelogenous leukemia samples. Bcr-Abl-dependent tyrosine phosphorylation of SOCS-1 and SOCS-3 occurs mainly on Tyr 155 and Tyr 204 residues of SOCS-1 and on Tyr 221 residue of SOCS-3. We observed that phosphorylation of these SOCS proteins was associated with their binding to Bcr-Abl. Bcr-Abl-dependent phosphorylation of SOCS-1 and SOCS-3 diminished their inhibitory effects on the activation of JAK and STAT5 and thereby enhanced JAK/STAT5 signaling. Strikingly, disrupting the tyrosine phosphorylation of SOCS-1 or SOCS-3 impaired the expression of Bcl-XL protein and sensitized K562 leukemic cells to undergo apoptosis. Moreover, selective mutation of tyrosine phosphorylation sites of SOCS-1 or SOCS-3 significantly blocked Bcr-Abl-mediated tumorigenesis in nude mice and inhibited Bcr-Abl-mediated murine bone marrow transformation. Together, these results reveal a mechanism of how Bcr-Abl may overcome SOCS-1 and SOCS-3 inhibition to constitutively activate the JAK/STAT-dependent signaling, and suggest that Bcr-Abl may critically requires tyrosine phosphorylation of SOCS-1 and SOCS-3 to mediate tumorigenesis when these SOCS proteins are present in cells.

  8. Evaluation of Morpholino Antisense Oligos’ Role on BCR-ABL Gene Silencing in the K562 Cell Line

    Directory of Open Access Journals (Sweden)

    Bahman Delalat

    2010-01-01

    Full Text Available Objective: Chronic myeloid leukemia (CML develops when a hematopoietic stem cellacquires the BCR/ABL fusion gene. This causes these transformed hematopoietic cellsto have a greater than normal proliferation rate. Scientists attempt to improve the CMLtreatment process by silencing the BCR/ABL oncogene. In this work, we used morpholinoantisense oligos to silence the BCR/ABL oncogene.Materials and Methods: In this study, the K562 was used as a BCR/ABL fusion-genepositive cell line and the Jurkat cell line as a control. We explored the inhibiting capacityof morpholino antisense oligos in the the expression of the BCR/ABL oncogene andstudied their p210 BCR/ABL suppression, inhibition of cell proliferation and stimulation ofapoptosis in the K562 cells after 24 and 48 hours. Endo-Porter was used for delivery ofmorpholino antisense oligos into cell cytosols. Meanwhile, flow cytometric analysis wasperformed in order to determine the appropriate concentration of morpholino antisenseoligos.Results: Prolonged exposure of the K562 cell line to the morpholino antisense oligostargeted against the BCR-ABL gene showed proliferation inhibition as its main feature.After western blotting, we found that complete silencing of BCR/ABL was achieved, butflow cytometric analysis showed no broad apoptosis.Conclusion: The results indicate that the Morpholino antisense oligo is able to inhibitp210 BCR/ABL; however, it cannot induce broad apoptosis due to co-silencing of BCR.

  9. Role of Bcr1-activated genes Hwp1 and Hyr1 in Candida albicans oral mucosal biofilms and neutrophil evasion.

    Science.gov (United States)

    Dwivedi, Prabhat; Thompson, Angela; Xie, Zhihong; Kashleva, Helena; Ganguly, Shantanu; Mitchell, Aaron P; Dongari-Bagtzoglou, Anna

    2011-01-25

    Candida albicans triggers recurrent infections of the oropharyngeal mucosa that result from biofilm growth. Prior studies have indicated that the transcription factor Bcr1 regulates biofilm formation in a catheter model, both in vitro and in vivo. We thus hypothesized that Bcr1 plays similar roles in the formation of oral mucosal biofilms and tested this hypothesis in a mouse model of oral infection. We found that a bcr1/bcr1 mutant did not form significant biofilm on the tongues of immunocompromised mice, in contrast to reference and reconstituted strains that formed pseudomembranes covering most of the tongue dorsal surface. Overexpression of HWP1, which specifies an epithelial adhesin that is under the transcriptional control of Bcr1, partly but significantly rescued the bcr1/bcr1 biofilm phenotype in vivo. Since HWP1 overexpression only partly reversed the biofilm phenotype, we investigated whether additional mechanisms, besides adhesin down-regulation, were responsible for the reduced virulence of this mutant. We discovered that the bcr1/bcr1 mutant was more susceptible to damage by human leukocytes when grown on plastic or on the surface of a human oral mucosa tissue analogue. Overexpression of HYR1, but not HWP1, significantly rescued this phenotype. Furthermore a hyr1/hyr1 mutant had significantly attenuated virulence in the mouse oral biofilm model of infection. These discoveries show that Bcr1 is critical for mucosal biofilm infection via regulation of epithelial cell adhesin and neutrophil function.

  10. Biospecimen Retrieval from NASA's Rodent Research-1: Maximizing Science Return from Flight Missions

    Science.gov (United States)

    Choi, S. Y.; Chen, Y.- C.; Reyes, A.; Verma, V.; Dinh, M.; Globus, R. K.

    2016-01-01

    Rodent Research (RR)-1 was conducted to validate flight hardware, operations, and science capabilities that were developed to support long duration missions on the International Space Station. After 37 days in microgravity twenty mice were euthanized and frozen on orbit. Upon return to Earth the carcasses were dissected and yielded 32 different types of tissues from each mouse and over 3200 tissue aliquots. Many tissues were distributed to the Space Life and Physical Sciences (SLPS) Biospecimen Sharing Program (BSP) Principal Investigators (PIs) through the Ames Life Science Data Archive (ALSDA). A second round of dissections was performed to collect additional tissues from the remaining carcasses thawed for a second time for additional BSP PIs. Tissues retrieved included vaginal walls, aorta, pelvis, brown adipose tissue, tail, spine and forearms. Although the analyses are still in progress, some of the PIs have reported that the quality of the tissues was acceptable for their study. In a separate experiment we tested the RNA quality of the tissues that were dissected from frozen carcasses that were subjected to euthanasia, freezing, first and second thaw dissections. Timelines simulated the on-orbit RR-1 procedures to assess the quality of the tissues retrieved from the second thaw dissections. We analyzed the RIN values of select tissues including kidney, brain, white adipose tissue (WAT) and brown adipose tissue (BAT). Overall the RIN values from the second thaw were lower compared to those from the first by about a half unit; however, the tissues yielded RNA that are acceptable quality for some quantitative gene expression assays. Interestingly, RIN values of brain tissues were 8.4+/-0.6 and 7.9+/-0.7 from first and second round dissections, respectively (n=5). Kidney and WAT yielded RIN values less than 8 but they can still be used for qPCR. BAT yielded higher quality RNA (8.2+/-0.5) than WAT (5.22+/-0.9), possibly due to the high fat content. Together, these

  11. Modeling the influence of stromal microenvironment in the selection of ENU-induced BCR-ABL1 mutants by tyrosine kinase inhibitors.

    Science.gov (United States)

    Aggoune, Djamel; Tosca, Lucie; Sorel, Nathalie; Bonnet, Marie-Laure; Dkhissi, Fatima; Tachdjian, Gérard; Bennaceur-Griscelli, Annelise; Chomel, Jean-Claude; Turhan, Ali G

    2014-01-01

    Tyrosine kinase inhibitors (TKIs) have profoundly changed the natural history of chronic myeloid leukemia (CML). However, acquired resistance to imatinib, dasatinib or nilotinib (1(st) and 2(nd) generation TKIs), due in part to BCR-ABL1 kinase mutations, has been largely described. These drugs are ineffective on the T315I gatekeeper substitution, which remains sensitive to 3(rd) generation TKI ponatinib. It has recently been suggested that the hematopoietic niche could protect leukemic cells from targeted therapy. In order to investigate the role of a stromal niche in mutation-related resistance, we developed a niche-based cell mutagenesis assay. For this purpose, ENU (N-ethyl-N-nitrosourea)-exposed UT-7 cells expressing non-mutated or T315I-mutated BCR-ABL1 were cultured with or without murine MS-5 stromal cells and in the presence of imatinib, dasatinib, nilotinib, or ponatinib. In the assays relative to 1(st) and 2(nd) generation TKIs, which were performed on non-mutated BCR-ABL1 cells, our data highlighted the increasing efficacy of the latter, but did not reveal any substantial effect of the niche. In ponatinib assays performed on both non-mutated and T315I-mutated BCR-ABL1 cells, an increased number of resistant clones were observed in the presence of MS-5. Present data suggested that T315I mutants need either compound mutations (e.g. E255K/T315I) or a stromal niche to escape from ponatinib. Using array-comparative genomic hybridization experiments, we found an increased number of variations (involving some recurrent chromosome regions) in clones cultured on MS-5 feeder. Overall, our study suggests that the hematopoietic niche could play a crucial role in conferring resistance to ponatinib, by providing survival signals and favoring genetic instability.

  12. Targeting the SH2-Kinase Interface in Bcr-Abl Inhibits Leukemogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Grebien, Florian; Hantschel, Oliver; Wojcik, John; Kaupe, Ines; Kovacic, Boris; Wyrzucki, Arkadiusz M.; Gish, Gerald D.; Cerny-Reiterer, Sabine; Koide, Akiko; Beug, Hartmut; Pawson, Tony; Valent, Peter; Koide, Shohei; Superti-Furga, Giulio (AAS); (Mount Sinai Hospital); (Med U. Vienna); (UC); (IMP-CNRS)

    2012-10-25

    Chronic myelogenous leukemia (CML) is caused by the constitutively active tyrosine kinase Bcr-Abl and treated with the tyrosine kinase inhibitor (TKI) imatinib. However, emerging TKI resistance prevents complete cure. Therefore, alternative strategies targeting regulatory modules of Bcr-Abl in addition to the kinase active site are strongly desirable. Here, we show that an intramolecular interaction between the SH2 and kinase domains in Bcr-Abl is both necessary and sufficient for high catalytic activity of the enzyme. Disruption of this interface led to inhibition of downstream events critical for CML signaling and, importantly, completely abolished leukemia formation in mice. Furthermore, disruption of the SH2-kinase interface increased sensitivity of imatinib-resistant Bcr-Abl mutants to TKI inhibition. An engineered Abl SH2-binding fibronectin type III monobody inhibited Bcr-Abl kinase activity both in vitro and in primary CML cells, where it induced apoptosis. This work validates the SH2-kinase interface as an allosteric target for therapeutic intervention.

  13. Expression patterns of WT-1 and Bcr-Abl measured by TaqMan quantitative real-time RT-PCR during follow-up of leukemia patients with the Ph chromosome

    Institute of Scientific and Technical Information of China (English)

    CHEN Zi-xing陈子兴; Jaspal Kaeda; Sue Saunders; John M Goldman

    2004-01-01

    Background This study was designed to quantitatively measure WT-1 expression levels in patients with chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) during follow-up and to clarify the value of WT-1 as a molecular marker in minimal residual disease monitoring.Methods The TaqMan quantitative real-time RT-PCR method was established by using cloned WT-1 cDNA or synthesized oligonucleotides resembling WT-1 cDNA fragments in limit dilution as template until a stable and reliable standard curve was obtained. In a 25-month follow-up, the transcriptional levels of WT-1, Bcr-Abl, and Abl gene, were quantitatively measured in bone marrow cells from 25 CML or acute lymphoblastic leukemia (ALL) patients with the Ph chromosome. In addition, the expression of these genes in 40 samples of normal peripheral blood was also examined using the same method. The ratios of WT-1/Abl and Bcr-Abl/Abl were both plotted, and the two expression patterns were compared as well as their clinical significance.Results The levels of WT-1 expression in normal peripheral blood were detectable. In CML and Ph positive ALL patients, WT-1 expression levels changed in parallel with the Bcr-Abl expression pattern as the disease progressed or responded to effective treatment.Conclusion WT-1 expression provides a novel molecular marker in addition to Bcr-Abl for monitoring minimal residual disease (MRD) and targeting therapy in Ph chromosome-positive leukemia patients.

  14. Oridonin Triggers Chaperon-mediated Proteasomal Degradation of BCR-ABL in Leukemia

    Science.gov (United States)

    Huang, Huilin; Weng, Hengyou; Dong, Bowen; Zhao, Panpan; Zhou, Hui; Qu, Lianghu

    2017-01-01

    Inducing degradation of oncoproteins by small molecule compounds has the potential to avoid drug resistance and therefore deserves to be exploited for new therapies. Oridonin is a natural compound with promising antitumor efficacy that can trigger the degradation of oncoproteins; however, the direct cellular targets and underlying mechanisms remain unclear. Here we report that oridonin depletes BCR-ABL through chaperon-mediated proteasomal degradation in leukemia. Mechanistically, oridonin poses oxidative stress in cancer cells and directly binds to cysteines of HSF1, leading to the activation of this master regulator of the chaperone system. The resulting induction of HSP70 and ubiquitin proteins and the enhanced binding to CHIP E3 ligase hence target BCR-ABL for ubiquitin-proteasome degradation. Both wild-type and mutant forms of BCR-ABL can be efficiently degraded by oridonin, supporting its efficacy observed in cultured cells as well as mouse tumor xenograft assays with either imatinib-sensitive or -resistant cells. Collectively, our results identify a novel mechanism by which oridonin induces rapid degradation of BCR-ABL as well as a novel pharmaceutical activator of HSF1 that represents a promising treatment for leukemia. PMID:28128329

  15. Frequency of BCR-ABL Transcript Types in Syrian CML Patients

    Directory of Open Access Journals (Sweden)

    Sulaf Farhat-Maghribi

    2016-01-01

    Full Text Available Background. In Syria, CML patients are started on tyrosine kinase inhibitors (TKIs and monitored until complete molecular response is achieved. BCR-ABL mRNA transcript type is not routinely identified, contrary to the recommendations. In this study we aimed to identify the frequency of different BCR-ABL transcripts in Syrian CML patients and highlight their significance on monitoring and treatment protocols. Methods. CML patients positive for BCR-ABL transcripts by quantitative RT-PCR were enrolled. BCR-ABL transcript types were investigated using a home-made PCR method that was adapted from published protocols and optimized. The transcript types were then confirmed using a commercially available research kit. Results. Twenty-four transcripts were found in 21 patients. The most common was b2a2, followed by b3a2, b3a3, and e1a3 present solely in 12 (57.1%, 3 (14.3%, 2 (9.5%, and 1 (4.8%, respectively. Three samples (14.3% contained dual transcripts. While b3a2 transcript was apparently associated with warning molecular response to imatinib treatment, b2a2, b3a3, and e1a3 transcripts collectively proved otherwise (P=0.047. Conclusion. It might be advisable to identify the BCR-ABL transcript type in CML patients at diagnosis, using an empirically verified method, in order to link the detected transcript with the clinical findings, possible resistance to treatment, and appropriate monitoring methods.

  16. Activity of the Aurora kinase inhibitor VX-680 against Bcr/Abl-positive acute lymphoblastic leukemias.

    Science.gov (United States)

    Fei, Fei; Stoddart, Sonia; Groffen, John; Heisterkamp, Nora

    2010-05-01

    The emergence of resistance to tyrosine kinase inhibitors due to point mutations in Bcr/Abl is a challenging problem for Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) patients, especially for those with the T315I mutation, against which neither nilotinib or dasatinib shows significant activity. VX-680 is a pan-Aurora kinase inhibitor active against all Bcr/Abl proteins but has not been extensively examined in preclinical models of Ph-positive ALL. Here, we have tested VX-680 for the treatment of Bcr/Abl-positive ALL when leukemic cells are protected by the presence of stroma. Under these conditions, VX-680 showed significant effects on primary human Ph-positive ALL cells both with and without the T315I mutation, including ablation of tyrosine phosphorylation downstream of Bcr/Abl, decreased viability, and induction of apoptosis. However, drug treatment of human Ph-positive ALL cells for 3 days followed by drug removal allowed the outgrowth of abnormal cells 21 days later, and on culture of mouse Bcr/Abl ALL cells on stroma with lower concentrations of VX-680, drug-resistant cells emerged. Combined treatment of human ALL cells lacking the T315I mutation with both VX-680 and dasatinib caused significantly more cytotoxicity than each drug alone. We suggest that use of VX-680 together with a second effective drug as first-line treatment for Ph-positive ALL is likely to be safer and more useful than second-line treatment with VX-680 as monotherapy for drug-resistant T315I Ph-positive ALL.

  17. Prospective molecular monitoring of BCR/ABL transcript in children with Ph+ acute lymphoblastic leukaemia unravels differences in treatment response.

    Science.gov (United States)

    Cazzaniga, Giovanni; Lanciotti, Marina; Rossi, Vincenzo; Di Martino, Daniela; Aricò, Maurizio; Valsecchi, Maria Grazia; Basso, Giuseppe; Masera, Giuseppe; Micalizzi, Concetta; Biondi, Andrea

    2002-11-01

    Children with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) represent a subgroup at very high risk for treatment failure, despite intensive chemotherapy. However, recent retrospective studies showed that Ph+ childhood ALL is a heterogeneous disease with regard to treatment response. We have prospectively monitored, by reverse transcription polymerase chain reaction (RT-PCR) during follow-up, the presence of the BCR/ABL fusion transcript in Ph+ ALL children diagnosed in the Italian multicentre Associazione Italiana Ematologia Oncologia Pediatrica ALL-AIEOP-95 therapy protocol. To our knowledge, this is the first report on the evaluation of minimal residual disease (MRD) in childhood Ph+ ALL prospectively enrolled in an intensive, Berlin-Frankfurt-Munster (BFM)-type treatment protocol. Twenty-seven of 36 (75.0%) Ph+ patients consecutively enrolled into the high-risk group of the AIEOP-ALL protocol between May 1995 and October 1999 were successfully analysed. Twenty were good responders to the pre-phase of prednisone/intrathecal methotrexate treatment (PGR) and seven were poor responders (PPR). Within the PPR group, the RT-PCR monitoring constantly showed positivity for the BCR/ABL fusion transcript and all the patients died of disease progression. In contrast, highly sensitive qualitative RT-PCR monitoring revealed heterogeneity within the PGR group of Ph+ childhood ALL patients. Three different subgroups could be defined, according to the clearance of Ph+ cells within the first 5 months of treatment. This provides useful information on the capability of chemotherapy to reduce the leukaemic clone, with prognostic implications.

  18. Antileukemia effects of xanthohumol in Bcr/Abl-transformed cells involve nuclear factor-kappaB and p53 modulation.

    Science.gov (United States)

    Monteghirfo, Stefano; Tosetti, Francesca; Ambrosini, Claudia; Stigliani, Sara; Pozzi, Sarah; Frassoni, Francesco; Fassina, Gianfranco; Soverini, Simona; Albini, Adriana; Ferrari, Nicoletta

    2008-09-01

    The oncogenic Bcr-Abl tyrosine kinase activates various signaling pathways including phosphoinositide 3-kinase/Akt and nuclear factor-kappaB that mediate proliferation, transformation, and apoptosis resistance in Bcr-Abl+ myeloid leukemia cells. The hop flavonoid xanthohumol inhibits tumor growth by targeting the nuclear factor-kappaB and Akt pathways and angiogenesis. Here, we show that xanthohumol has in vitro activity against Bcr-Abl+ cells and clinical samples and retained its cytotoxicity when imatinib mesylate-resistant K562 cells were examined. Xanthohumol inhibition of K562 cell viability was associated with induction of apoptosis, increased p21 and p53 expression, and decreased survivin levels. We show that xanthohumol strongly inhibited Bcr-Abl expression at both mRNA and protein levels and show that xanthohumol caused elevation of intracellular reactive oxygen species and that the antioxidant N-acetylcysteine blunted xanthohumol-induced events. Further, we observed that xanthohumol inhibits leukemia cell invasion, metalloprotease production, and adhesion to endothelial cells, potentially preventing in vivo life-threatening complications of leukostasis and tissue infiltration by leukemic cells. As structural mutations and/or gene amplification in Bcr-Abl can circumvent an otherwise potent anticancer drug such as imatinib, targeting Bcr-Abl expression as well as its kinase activity could be a novel additional therapeutic approach for the treatment of Bcr-Abl+ myeloid leukemia.

  19. MicroRNA-320a acts as a tumor suppressor by targeting BCR/ABL oncogene in chronic myeloid leukemia.

    Science.gov (United States)

    Xishan, Zhu; Ziying, Lin; Jing, Du; Gang, Liu

    2015-01-01

    Accumulating evidences demonstrated that the induction of epithelial-mesenchymal transition (EMT) and aberrant expression of microRNAs (miRNAs) are associated with tumorigenesis, tumor progression, metastasis and relapse in cancers, including chronic myeloid leukemia (CML). We found that miR-320a expression was reduced in K562 and in CML cancer stem cells. Moreover, we found that miR-320a inhibited K562 cell migration, invasion, proliferation and promoted apoptosis by targeting BCR/ABL oncogene. As an upstream regulator of BCR/ABL, miR-320a directly targets BCR/ABL. The enhanced expression of miR-320a inhibited the phosphorylation of PI3K, AKT and NF-κB; however, the expression of phosphorylated PI3K, AKT and NF-κB were restored by the overexpression of BCR/ABL. In K562, infected with miR-320a or transfected with SiBCR/ABL, the protein levels of fibronectin, vimentin, and N-cadherin were decreased, but the expression of E-cadherin was increased. The expression of mesenchymal markers in miR-320a-expressing cells was restored to normal levels by the restoration of BCR/ABL expression. Generally speaking, miR-320a acts as a novel tumor suppressor gene in CML and miR-320a can decrease migratory, invasive, proliferative and apoptotic behaviors, as well as CML EMT, by attenuating the expression of BCR/ABL oncogene.

  20. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

    DEFF Research Database (Denmark)

    Nicolini, Franck Emmanuel; Basak, Grzegorz W; Soverini, Simona;

    2011-01-01

    T315I(+) Philadelphia chromosome-positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABL(T315I) mutations. Median follow...... myeloid leukemia. The occurrence of chronic GVHD had a positive impact on overall survival (P = .047). Transplant-related mortality rates were low. Multivariate analysis identified only blast phase at transplantation (hazard ratio 3.68, P = .0011) and unrelated stem cell donor (hazard ratio 2.98, P = .011......) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABL(T315I) mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors....

  1. Susceptibility of Ph-positive all to TKI therapy associated with Bcr-Abl rearrangement patterns: a retrospective analysis.

    Directory of Open Access Journals (Sweden)

    Yu Jing

    Full Text Available BACKGROUND: Tyrosine kinase inhibitors (TKIs have demonstrated success in the treatment of acute lymphoblastic leukemia (ALL in patients that express BCR-ABL rearrangements (Philadelphia chromosome [Ph]. The current study aimed to assess the efficacy of TKIs and prognostic factors in the treatment of adults with Ph+-ALL. METHODS: In this multicenter retrospective study, the relationship between Ph+-ALL and treatment outcomes among Chinese patients receiving TKI-containing induction/consolidation chemotherapy was examined. A total of 86 Ph+-ALL patients were included and followed for 3.85 (0.43-9.30 years. Overall survival (OS and event-free survival (EFS were analyzed. RESULTS: A total of 86 Ph+-ALL patients (40 females and 46 males; median age: 34.0 years were enrolled, including those with BCR/ABL transcripts 190 (n = 52, 210 (n = 25, and 230 (n = 2; BCR/ABL isoform determination was not available for 7 patients. Mortality was influenced by variable BCR/ABL transcripts and TKI administration, and BCR/ABL transcripts, hematopoietic stem cell transplantation (HSCT, and TKI administration were associated with the occurrence of events. The OS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKI administration (P = 0.008, the EFS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKIs (P = 0.012, and also higher than those with TKI salvage administration (P = 0.004. BCR/ABL transcripts 210 showed preferable OS and EFS compared with BCR/ABL transcripts 190 and 230 (P<0.05 for each. CONCLUSIONS: The susceptibility of Ph+-ALL to TKI associated with the patterns of BCR-ABL rearrangement is demonstrated for the first time, thus adding another risk-stratifying molecular prognostic tool for the management of patients with Ph+-ALL.

  2. Detection of BCR-ABL Fusion mRNA Using Reverse Transcriptase Loop-mediated Isothermal Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Dugan, L C; Hall, S; Kohlgruber, A; Urbin, S; Torres, C; Wilson, P

    2011-12-08

    RT-PCR is commonly used for the detection of Bcr-Abl fusion transcripts in patients diagnosed with chronic myelogenous leukemia, CML. Two fusion transcripts predominate in CML, Br-Abl e13a2 and e14a2. They have developed reverse transcriptase isothermal loop-mediated amplification (RT-LAMP) assays to detect these two fusion transcripts along with the normal Bcr transcript.

  3. LMC y detección del gen de fusión BCR/ABL

    Directory of Open Access Journals (Sweden)

    C. G. Artigas Allaire

    2006-04-01

    Full Text Available La anormalidad citogenética más común en la leucemia mieloide crónica (LMC es el cromosoma Philadelphia producida por la translocación t(9:22, cuya expresión molecular es el gen de fusión BCR-ABL, que codifica una proteína con actividad tirosinquinasa.

  4. On Tachyons in Generic Orbifolds of $\\BC^r$ and Gauged Linear Sigma Models

    OpenAIRE

    Sarkar, Tapobrata

    2006-01-01

    We study some aspects of Gauged Linear Sigma Models corresponding to orbifold singularities of the form $\\BC^r/\\Gamma$, for $r=2,3$ and $\\Gamma = \\BZ_n$ and $\\BZ_n\\times \\BZ_m$. These orbifolds might be tachyonic in general. We compute expressions for the multi parameter sigma model Lagrangians for these orbifolds, in terms of their toric geometry data. Using this, we analyze some aspects of the phases of generic orbifolds of $\\BC^r$.

  5. Autophagy induction by Bcr-Abl-expressing cells facilitates their recovery from a targeted or nontargeted treatment.

    LENUS (Irish Health Repository)

    Crowley, Lisa C

    2012-01-31

    Although Imatinib has transformed the treatment of chronic myeloid leukemia (CML), it is not curative due to the persistence of resistant cells that can regenerate the disease. We have examined how Bcr-Abl-expressing cells respond to two mechanistically different therapeutic agents, etoposide and Imatinib. We also examined Bcr-Abl expression at low and high levels as elevated expression has been associated with treatment failure. Cells expressing low levels of Bcr-Abl undergo apoptosis in response to the DNA-targeting agent (etoposide), whereas high-Bcr-Abl-expressing cells primarily induce autophagy. Autophagic populations engage a delayed nonapoptotic death; however, sufficient cells evade this and repopulate following the withdrawal of the drug. Non-Bcr-Abl-expressing 32D or Ba\\/F3 cells induce both apoptosis and autophagy in response to etoposide and can recover. Imatinib treatment induces both apoptosis and autophagy in all Bcr-Abl-expressing cells and populations rapidly recover. Inhibition of autophagy with ATG7 and Beclin1 siRNA significantly reduced the recovery of Imatinib-treated K562 cells, indicating the importance of autophagy for the recovery of treated cells. Combination regimes incorporating agents that disrupt Imatinib-induced autophagy would remain primarily targeted and may improve response to the treatment in CML.

  6. shRNA library screening identifies nucleocytoplasmic transport as a mediator of BCR-ABL1 kinase-independent resistance.

    Science.gov (United States)

    Khorashad, Jamshid S; Eiring, Anna M; Mason, Clinton C; Gantz, Kevin C; Bowler, Amber D; Redwine, Hannah M; Yu, Fan; Kraft, Ira L; Pomicter, Anthony D; Reynolds, Kimberly R; Iovino, Anthony J; Zabriskie, Matthew S; Heaton, William L; Tantravahi, Srinivas K; Kauffman, Michael; Shacham, Sharon; Chenchik, Alex; Bonneau, Kyle; Ullman, Katharine S; O'Hare, Thomas; Deininger, Michael W

    2015-03-12

    The mechanisms underlying tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML) patients lacking explanatory BCR-ABL1 kinase domain mutations are incompletely understood. To identify mechanisms of TKI resistance that are independent of BCR-ABL1 kinase activity, we introduced a lentiviral short hairpin RNA (shRNA) library targeting ∼5000 cell signaling genes into K562(R), a CML cell line with BCR-ABL1 kinase-independent TKI resistance expressing exclusively native BCR-ABL1. A customized algorithm identified genes whose shRNA-mediated knockdown markedly impaired growth of K562(R) cells compared with TKI-sensitive controls. Among the top candidates were 2 components of the nucleocytoplasmic transport complex, RAN and XPO1 (CRM1). shRNA-mediated RAN inhibition or treatment of cells with the XPO1 inhibitor, KPT-330 (Selinexor), increased the imatinib sensitivity of CML cell lines with kinase-independent TKI resistance. Inhibition of either RAN or XPO1 impaired colony formation of CD34(+) cells from newly diagnosed and TKI-resistant CML patients in the presence of imatinib, without effects on CD34(+) cells from normal cord blood or from a patient harboring the BCR-ABL1(T315I) mutant. These data implicate RAN in BCR-ABL1 kinase-independent imatinib resistance and show that shRNA library screens are useful to identify alternative pathways critical to drug resistance in CML.

  7. Biodegradable charged polyester-based vectors (BCPVs) as an efficient non-viral transfection nanoagent for gene knockdown of the BCR-ABL hybrid oncogene in a human chronic myeloid leukemia cell line

    Science.gov (United States)

    Yang, Chengbin; Panwar, Nishtha; Wang, Yucheng; Zhang, Butian; Liu, Maixian; Toh, Huiting; Yoon, Ho Sup; Tjin, Swee Chuan; Chong, Peter Han Joo; Law, Wing-Cheung; Chen, Chih-Kuang; Yong, Ken-Tye

    2016-04-01

    First-line therapy of chronic myelogenous leukemia (CML) has always involved the use of BCR-ABL tyrosine-kinase inhibitors which is associated with an abnormal chromosome called Philadelphia chromosome. Although the overall survival rate has been improved by the current therapeutic regime, the presence of resistance has resulted in limited efficacy. In this study, an RNA interference (RNAi)-based therapeutic regime is proposed with the aim to knockdown the BCR-ABL hybrid oncogene using small interfering RNA (siRNA). The siRNA transfection rates have usually been limited due to the declining contact probability among polyplexes and the non-adherent nature of leukemic cells. Our work aims at addressing this limitation by using a biodegradable charged polyester-based vector (BCPV) as a nanocarrier for the delivery of BCR-ABL-specific siRNA to the suspension culture of a K562 CML cell line. BCR-ABL siRNAs were encapsulated in the BCPVs by electrostatic force. Cell internalization was facilitated by the BCPV and assessed by confocal microscopy and flow cytometry. The regulation of the BCR-ABL level in K562 cells as a result of RNAi was analyzed by real-time polymerase chain reaction (RT-PCR). We observed that BCPV was able to form stable nanoplexes with siRNA molecules, even in the presence of fetal bovine serum (FBS), and successfully assisted in vitro siRNA transfection in the non-adherent K562 cells. As a consequence of downregulation of BCR-ABL, BCPV-siRNA nanoplexes inhibited cell proliferation and promoted cell apoptosis. All results were compared with a commercial transfection reagent, Lipofectamine2000™, which served as a positive control. More importantly, this class of non-viral vector exhibits biodegradable features and negligible cytotoxicity, thus providing a versatile platform to deliver siRNA to non-adherent leukemia cells with high transfection efficiency by effectively overcoming extra- and intra-cellular barriers. Due to the excellent in vitro

  8. AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance

    Energy Technology Data Exchange (ETDEWEB)

    O’Hare, Thomas; Shakespeare, William C.; Zhu, Xiaotian; Eide, Christopher A.; Rivera, Victor M.; Wang, Frank; Adrian, Lauren T.; Zhou, Tianjun; Huang, Wei-Sheng; Xu, Qihong; Metcalf, III, Chester A.; Tyner, Jeffrey W.; Loriaux, Marc M.; Corbin, Amie S.; Wardwell, Scott; Ning, Yaoyu; Keats, Jeffrey A.; Wang, Yihan; Sundaramoorthi, Raji; Thomas, Mathew; Zhou, Dong; Snodgrass, Joseph; Commodore, Lois; Sawyer, Tomi K.; Dalgarno, David C.; Deininger, Michael W.N.; Druker, Brian J.; Clackson, Tim; (OHSU- Cancer Instit.); (ARIAD)

    2010-09-07

    Inhibition of BCR-ABL by imatinib induces durable responses in many patients with chronic myeloid leukemia (CML), but resistance attributable to kinase domain mutations can lead to relapse and a switch to second-line therapy with nilotinib or dasatinib. Despite three approved therapeutic options, the cross-resistant BCR-ABL{sup T315I} mutation and compound mutants selected on sequential inhibitor therapy remain major clinical challenges. We report design and preclinical evaluation of AP24534, a potent, orally available multitargeted kinase inhibitor active against T315I and other BCR-ABL mutants. AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABL{sup T315I}-driven tumor growth in mice, and completely abrogated resistance in cell-based mutagenesis screens. Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML.

  9. Acute promyelocytic leukaemia in patients originating in Latin America is associated with an increased frequency of the bcr1 subtype of the PML/RARalpha fusion gene.

    Science.gov (United States)

    Douer, Dan; Santillana, Sergio; Ramezani, Laleh; Samanez, Cesar; Slovak, Marilyn L; Lee, Ming S; Watkins, Kristy; Williams, Tony; Vallejos, Carlos

    2003-08-01

    The PML/RARalpha fusion gene in acute promyelocytic leukaemia (APL) has three subtypes based on the breakpoint site of the PML gene: long (bcr1), short (bcr3) and variable (bcr2) subtypes. The PML/RARalpha fusion protein is involved in the pathogenesis of APL and the breakpoint site of the PML gene might be associated with aetiological factor(s). Because APL is over-represented in patients that originate in Latin America (Latinos), we evaluated whether the distribution of the PML/RARalpha fusion mRNA in this population is different to that reported in non-Latinos. Among 52 APL patients (28 from Mexico and Central America diagnosed in Los Angeles and 24 from Peru, South America), bcr1, bcr2 and bcr3 expression was 75%, 10% and 15% respectively. However, bcr1 breakpoints were significantly higher compared with non-Latino patients (340/654, 52%) reported in four studies. Often bcr1 and bcr2 are reported together; 862 (60%) of 1429 non-Latino APL patients reported in nine studies were either bcr1 or bcr2, compared with 44 (85%) in our 52 Latino patients. This difference was also statistically significant when our patients were compared to each of the individual studies from USA and Europe, but not for a small series from China and Japan. These results suggest that the overrepresentation of APL among Latin American patients can be accounted for by an increase of a single subtype--bcr1, and the breakage sites in the PML gene may not be random but possibly influenced by genetic and/or environmental factor(s).

  10. Sensitivity of imatinib-resistant T315I BCR-ABL CML to a synergistic combination of ponatinib and forskolin treatment.

    Science.gov (United States)

    Oaxaca, Derrick M; Yang-Reid, Sun Ah; Ross, Jeremy A; Rodriguez, Georgialina; Staniswalis, Joan G; Kirken, Robert A

    2016-09-01

    Tyrosine kinase inhibitors (TKIs) have dramatically improved the life expectancy of patients suffering from chronic myeloid leukemia (CML); however, patients will eventually develop resistance to TKI therapy or adverse side effects due to secondary off-target mechanisms associated with TKIs. CML patients exhibiting TKI resistance are at greater risk of developing an aggressive and drug-insensitive disease. Drug-resistant CML typically arises in response to spontaneous mutations within the drug binding sites of the targeted oncoproteins. To better understand the mechanism of drug resistance in TKI-resistant CML patients, the BCR-ABL transformed cell line KCL22 was grown with increasing concentrations of imatinib for a period of 6 weeks. Subsequently, a drug-resistant derivative of the parental KCL22 cell line harboring the T315I gatekeeper mutation was isolated and investigated for TKI drug sensitivity via multi-agent drug screens. A synergistic combination of ponatinib- and forskolin-reduced cell viability was identified in this clinically relevant imatinib-resistant CML cell line, which also proved efficacious in other CML cell lines. In summary, this study provides new insight into the biological underpinnings of BCR-ABL-driven CML and potential rationale for investigating novel treatment strategies for patients with T315I CML.

  11. Contrasting the ethical perspectives of biospecimen research among individuals with familial risk for hereditary cancer and biomedical researchers: implications for researcher training.

    Science.gov (United States)

    Quinn, Gwendolyn P; Koskan, Alexis; Sehovic, Ivana; Pal, Tuya; Meade, Cathy; Gwede, Clement K

    2014-07-01

    While ethical concerns about participating in biospecimen research have been previously identified, few studies have reported the concerns among individuals with familial risk for hereditary cancer (IFRs). At the same time, biomedical researchers often lack training in discussing such concerns to potential donors. This study explores IFRs' and biomedical researchers' perceptions of ethical concerns about participating in biobanking research. In separate focus groups, IFRs and biomedical researchers participated in 90-min telephone focus groups. Focus group questions centered on knowledge about laws that protect the confidentiality of biospecimen donors, understanding of informed consent and study procedures, and preferences for being recontacted about potential incidental discovery and also study results. A total of 40 IFRs and 32 biomedical researchers participated in the focus groups. Results demonstrated discrepancies between the perceptions of IFRs and researchers. IFRs' concerns centered on health information protection; potential discrimination by insurers and employers; and preferences for being recontacted upon discovery of gene mutations or to communicate study results. Researchers perceived that participants understood laws protecting donors' privacy and (detailed study information outlined in the informed consent process), study outcomes were used to create a training tool kit to increase researchers' understanding of IFRs' concerns about biobanking.

  12. A Tissue Retrieval and Postharvest Processing Regimen for Rodent Reproductive Tissues Compatible with Long-Term Storage on the International Space Station and Postflight Biospecimen Sharing Program

    Directory of Open Access Journals (Sweden)

    Vijayalaxmi Gupta

    2015-01-01

    Full Text Available Collection and processing of tissues to preserve space flight effects from animals after return to Earth is challenging. Specimens must be harvested with minimal time after landing to minimize postflight readaptation alterations in protein expression/translation, posttranslational modifications, and expression, as well as changes in gene expression and tissue histological degradation after euthanasia. We report the development of a widely applicable strategy for determining the window of optimal species-specific and tissue-specific posteuthanasia harvest that can be utilized to integrate into multi-investigator Biospecimen Sharing Programs. We also determined methods for ISS-compatible long-term tissue storage (10 months at −80°C that yield recovery of high quality mRNA and protein for western analysis after sample return. Our focus was reproductive tissues. The time following euthanasia where tissues could be collected and histological integrity was maintained varied with tissue and species ranging between 1 and 3 hours. RNA quality was preserved in key reproductive tissues fixed in RNAlater up to 40 min after euthanasia. Postfixation processing was also standardized for safe shipment back to our laboratory. Our strategy can be adapted for other tissues under NASA’s Biospecimen Sharing Program or similar multi-investigator tissue sharing opportunities.

  13. A tissue retrieval and postharvest processing regimen for rodent reproductive tissues compatible with long-term storage on the international space station and postflight biospecimen sharing program.

    Science.gov (United States)

    Gupta, Vijayalaxmi; Holets-Bondar, Lesya; Roby, Katherine F; Enders, George; Tash, Joseph S

    2015-01-01

    Collection and processing of tissues to preserve space flight effects from animals after return to Earth is challenging. Specimens must be harvested with minimal time after landing to minimize postflight readaptation alterations in protein expression/translation, posttranslational modifications, and expression, as well as changes in gene expression and tissue histological degradation after euthanasia. We report the development of a widely applicable strategy for determining the window of optimal species-specific and tissue-specific posteuthanasia harvest that can be utilized to integrate into multi-investigator Biospecimen Sharing Programs. We also determined methods for ISS-compatible long-term tissue storage (10 months at -80°C) that yield recovery of high quality mRNA and protein for western analysis after sample return. Our focus was reproductive tissues. The time following euthanasia where tissues could be collected and histological integrity was maintained varied with tissue and species ranging between 1 and 3 hours. RNA quality was preserved in key reproductive tissues fixed in RNAlater up to 40 min after euthanasia. Postfixation processing was also standardized for safe shipment back to our laboratory. Our strategy can be adapted for other tissues under NASA's Biospecimen Sharing Program or similar multi-investigator tissue sharing opportunities.

  14. Rapid Collection of Biospecimens by Automated Identification of Patients Eligible for Pharmacoepigenetic Studies

    OpenAIRE

    Sun, Yan V.; Davis, Robert L.

    2013-01-01

    Epigenetics plays an important role in regulating gene expression, and can be modified by environmental factors and physiological conditions. Studying epigenetics is a promising approach to potentially improving the diagnosis, prevention and treatment of human diseases, and to providing personalized medical care. However, the role of epigenetics in the development of diseases is not clear because epigenetic markers may be both mediators and outcomes of human diseases. It is particularly compl...

  15. [Guidelines for molecular monitoring of BCR-ABL1 in chronic myeloid leukemia patients by RT-qPCR].

    Science.gov (United States)

    Larripa, Irene; Ruiz, María Sol; Gutiérrez, Marina; Bianchini, Michele

    2017-01-01

    Current clinical guidelines for managing chronic myeloid leukemia include molecular monitoring of BCR-ABL1 transcript quantitative reverse-transcription PCR. Despite the proven prognostic significance of molecular response, it is not widely appreciated that quantitative reverse-transcription PCR potentially produces highly variable data, which may affect the validity of results, making comparability between different laboratories difficult. Therefore, standardized reporting of BCR-ABL1 measurements is needed for optimal clinical management. An approach to achieve comparable BCR-ABL1 values is the use of an international reporting scale. Conversion to the international scale is achieved by the application of laboratory specific conversion factor that is obtained by using validated secondary reference calibrators. Moreover, with the aim to mitigate the interlaboratory imprecision of quantitative BCR-ABL1 measurements and to facilitate local laboratory results interpretation and reporting, we decide to prepare laboratory guidelines that will further facilitate interlaboratory comparative studies and independent quality-assessment programs, which are of paramount importance for worldwide standardization of BCR-ABL1 monitoring results, in particular for those most isolated laboratories, with not easy access to commercial kits or sample interchange programs.

  16. Guidelines for molecular monitoring of BCR-ABL1 in chronic myeloid leukemia patients by RT-qPCR

    Directory of Open Access Journals (Sweden)

    Irene Larripa

    2017-02-01

    Full Text Available Current clinical guidelines for managing chronic myeloid leukemia include molecular monitoring of BCR-ABL1 transcript quantitative reverse-transcription PCR. Despite the proven prognostic significance of molecular response, it is not widely appreciated that quantitative reverse-transcription PCR potentially produces highly variable data, which may affect the validity of results, making comparability between different laboratories difficult. Therefore, standardized reporting of BCR-ABL1 measurements is needed for optimal clinical management. An approach to achieve comparable BCR-ABL1 values is the use of an international reporting scale. Conversion to the international scale is achieved by the application of laboratory specific conversion factor that is obtained by using validated secondary reference calibrators. Moreover, with the aim to mitigate the interlaboratory imprecision of quantitative BCR-ABL1 measurements and to facilitate local laboratory results interpretation and reporting, we decide to prepare laboratory guidelines that will further facilitate interlaboratory comparative studies and independent quality-assessment programs, which are of paramount importance for worldwide standardization of BCR-ABL1 monitoring results, in particular for those most isolated laboratories, with not easy access to commercial kits or sample interchange programs

  17. Characterization of CLL exosomes reveals a distinct microRNA signature and enhanced secretion by activation of BCR signaling.

    Science.gov (United States)

    Yeh, Yuh-Ying; Ozer, Hatice Gulcin; Lehman, Amy M; Maddocks, Kami; Yu, Lianbo; Johnson, Amy J; Byrd, John C

    2015-05-21

    Multiple studies show that chronic lymphocytic leukemia (CLL) cells are heavily dependent on their microenvironment for survival. Communication between CLL cells and the microenvironment is mediated through direct cell contact, soluble factors, and extracellular vesicles. Exosomes are small particles enclosed with lipids, proteins, and small RNAs that can convey biological materials to surrounding cells. Our data herein demonstrate that CLL cells release significant amounts of exosomes in plasma that exhibit abundant CD37, CD9, and CD63 expression. Our work also pinpoints the regulation of B-cell receptor (BCR) signaling in the release of CLL exosomes: BCR activation by α-immunoglobulin (Ig)M induces exosome secretion, whereas BCR inactivation via ibrutinib impedes α-IgM-stimulated exosome release. Moreover, analysis of serial plasma samples collected from CLL patients on an ibrutinib clinical trial revealed that exosome plasma concentration was significantly decreased following ibrutinib therapy. Furthermore, microRNA (miR) profiling of plasma-derived exosomes identified a distinct exosome microRNA signature, including miR-29 family, miR-150, miR-155, and miR-223 that have been associated with CLL disease. Interestingly, expression of exosome miR-150 and miR-155 increases with BCR activation. In all, this study successfully characterized CLL exosomes, demonstrated the control of BCR signaling in the release of CLL exosomes, and uncovered a disease-relevant exosome microRNA profile.

  18. BCR-ABL1 kinase inhibits uracil DNA glycosylase UNG2 to enhance oxidative DNA damage and stimulate genomic instability

    Science.gov (United States)

    Slupianek, Artur; Falinski, Rafal; Znojek, Pawel; Stoklosa, Tomasz; Flis, Sylwia; Doneddu, Valentina; Pytel, Dariusz; Synowiec, Ewelina; Blasiak, Janusz; Bellacosa, Alfonso; Skorski, Tomasz

    2013-01-01

    Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of CML-CP. Unfortunately, 25% of TKI-naive patients and 50–90% of TKI-responding patients carry CML clones expressing TKI resistant BCR-ABL1 kinase mutants. We reported that CML-CP leukemia stem and progenitor cell populations accumulate high amounts of reactive oxygen species (ROS), which may result in accumulation of uracil derivatives in genomic DNA. Unfaithful and/or inefficient repair of these lesions generates TKI resistant point mutations in BCR-ABL1 kinase. Using an array of specific substrates and inhibitors/blocking antibodies we found that uracil-DNA glycosylase UNG2 were inhibited in BCR-ABL1 –transformed cell lines and CD34+ CML cells. The inhibitory effect was not accompanied by downregulation of nuclear expression and/or chromatin association of UNG2. The effect was BCR-ABL1 kinase-specific because several other fusion tyrosine kinases did not reduce UNG2 activity. Using UNG2-specific inhibitor UGI we found that reduction of UNG2 activity increased the number of uracil derivatives in genomic DNA detected by modified comet assay and facilitated accumulation of ouabain-resistant point mutations in reporter gene Na+/K+ATPase. In conclusion, we postulate that BCR-ABL1 kinase-mediated inhibition of UNG2 contributes to accumulation of point mutations responsible for TKI-resistance causing the disease relapse, and perhaps also other point mutations facilitating malignant progression of CML. PMID:23047475

  19. The impact of multiple low-level BCR-ABL1 mutations on response to ponatinib

    Science.gov (United States)

    Yeung, David T. O.; Yeoman, Alexandra L.; Altamura, Haley K.; Jamison, Bronte A.; Field, Chani R.; Hodgson, J. Graeme; Lustgarten, Stephanie; Rivera, Victor M.; Hughes, Timothy P.; Branford, Susan

    2016-01-01

    The third-generation tyrosine kinase inhibitor (TKI) ponatinib shows activity against all common BCR-ABL1 single mutants, including the highly resistant BCR-ABL1-T315I mutant, improving outcome for patients with refractory chronic myeloid leukemia (CML). However, responses are variable, and causal baseline factors have not been well-studied. The type and number of low-level BCR-ABL1 mutations present after imatinib resistance has prognostic significance for subsequent treatment with nilotinib or dasatinib as second-line therapy. We therefore investigated the impact of low-level mutations detected by sensitive mass-spectrometry before ponatinib initiation (baseline) on treatment response in 363 TKI-resistant patients enrolled in the PONATINIB for Chronic Myeloid Leukemia Evaluation and Ph+ Acute Lymphoblastic Leukemia trial, including 231 patients in chronic phase (CP-CML). Low-level mutations were detected in 53 patients (15%, including low-level T315I in 14 patients); most, however, did not undergo clonal expansion during ponatinib treatment and, moreover, no specific individual mutations were associated with inferior outcome. We demonstrate however, that the number of mutations detectable by mass spectrometry after TKI resistance is associated with response to ponatinib treatment and could be used to refine the therapeutic approach. Although CP-CML patients with T315I (63/231, 27%) had superior responses overall, those with multiple mutations detectable by mass spectrometry (20, 32%) had substantially inferior responses compared with those with T315I as the sole mutation detected (43, 68%). In contrast, for CP-CML patients without T315I, the inferior responses previously observed with nilotinib/dasatinib therapy for imatinib-resistant patients with multiple mutations were not seen with ponatinib treatment, suggesting that ponatinib may prove to be particularly advantageous for patients with multiple mutations detectable by mass spectrometry after TKI resistance

  20. Molecular Imaging of Bcr-Abl Phosphokinase in a Xenograft Model*

    OpenAIRE

    Wu, Ji Yuan; David J. Yang; Angelo, Laura S.; Kohanim, Saady; Kurzrock, Razelle

    2009-01-01

    The purpose of this study was to determine whether the Bcr-Abl tyrosine kinase can be assessed by gamma imaging using an 111Indium-labeled anti-phosphotyrosine antibody, and if the response to treatment with imatinib could be detected using this imaging technique. Anti-phosphotyrosine antibody (APT) was labeled with indium (111In) using ethylenedicysteine (EC) as a chelator. To determine if 111In-EC-APT could assess a non-receptor tyrosine kinase, xenografts of the human chronic myelogenous l...

  1. Rapid Collection of Biospecimens by Automated Identification of Patients Eligible for Pharmacoepigenetic Studies

    Directory of Open Access Journals (Sweden)

    Yan V. Sun

    2013-09-01

    Full Text Available Epigenetics plays an important role in regulating gene expression, and can be modified by environmental factors and physiological conditions. Studying epigenetics is a promising approach to potentially improving the diagnosis, prevention and treatment of human diseases, and to providing personalized medical care. However, the role of epigenetics in the development of diseases is not clear because epigenetic markers may be both mediators and outcomes of human diseases. It is particularly complicated to study pharmacoepigenetics, as medication use may modify the epigenetic profile. To address the challenges facing pharmacoepigenetic research of human diseases, we developed a novel design to rapidly identify, contact, and recruit participants and collect specimens for longitudinal studies of pharmacoepigenetics. Using data in real-time from electronic medical record systems, we can identify patients recently start on new medications and who also have a blood test. Prior to disposal of the leftover blood by the clinical laboratory, we are able to contact and recruit these patients, enabling us to use both their leftover baseline blood sample as well as leftover specimens at future tests. With treatment-naïve and follow-up specimens, this system is able to study both epigenetic markers associated with disease without treatment effect as well as treatment-related epigenetic changes.

  2. Janus kinase 2 mutations in cases with BCR-ABL-negative chronic myeloproliferative disorders from Turkey

    Science.gov (United States)

    Yildiz, Ismail; Yokuş, Osman; Gedik, Habip

    2017-01-01

    Objective: We aimed to investigate the frequency of Janus kinase 2 (JAK2) mutations in cases with chronic myeloproliferative disorders (CMDs), and the relationship between the presence of JAK2 mutation and leukocytosis and splenomegaly, retrospectively. Materials and Methods: Patients, who were diagnosed with BCR-ABL-negative CMDs according to diagnosis criteria of the World Health Organization and followed up at the hematology clinic between 2013 and 2015, were investigated in terms of the frequency of JAK2 mutation in cases with CMDs, and the relationship between the presence of JAK2 mutation and leukocytosis and splenomegaly, retrospectively. Results: In total, 100 patients, who were diagnosed with BCR-ABL-negative CMDs, were evaluated retrospectively. The mean age of the patients with JAK2 positivity was significantly higher compared to patients with negative. JAK2-positivity rates in the age groups were significantly different. Gender, diagnosis, splenomegaly, and leukocytosis were not statistically different for JAK2 positivity between the groups. Conclusion: JAK2 V617F mutation is more commonly seen in older age as a risk for complications related to CDMS. Splenomegaly and leukocytosis are not associated with JAK2 V617F mutation. PMID:28182037

  3. BCR and Endosomal TLR Signals Synergize to Increase AID Expression and Establish Central B Cell Tolerance.

    Science.gov (United States)

    Kuraoka, Masayuki; Snowden, Pilar B; Nojima, Takuya; Verkoczy, Laurent; Haynes, Barton F; Kitamura, Daisuke; Kelsoe, Garnett

    2017-02-14

    Activation-induced cytidine deaminase (AID) is required to purge autoreactive immature and transitional-1 (immature/T1) B cells at the first tolerance checkpoint, but how AID selectively removes self-reactive B cells is unclear. We now show that B cell antigen receptor (BCR) and endosomal Toll-like receptor (TLR) signals synergize to elicit high levels of AID expression in immature/T1 B cells. This synergy is restricted to ligands for endocytic TLR and requires phospholipase-D activation, endosomal acidification, and MyD88. The first checkpoint is significantly impaired in AID- or MyD88-deficient mice and in mice doubly heterozygous for AID and MyD88, suggesting interaction of these factors in central B cell tolerance. Moreover, administration of chloroquine, an inhibitor of endosomal acidification, results in a failure to remove autoreactive immature/T1 B cells in mice. We propose that a BCR/TLR pathway coordinately establishes central tolerance by hyper-activating AID in immature/T1 B cells that bind ligands for endosomal TLRs.

  4. Microstructure and Wear Analysis of FeBCr Based Coating Deposited by HVOF Method

    Directory of Open Access Journals (Sweden)

    M.S. Priyan

    2014-06-01

    Full Text Available Thermally sprayed coatings that are based on FeBCr-related alloy powders are widely used to improve properties such as the surface hardness and wear resistance of a variety of coated metal substrate materials. Gray cast iron is widely used in the automobile industry due to its low cost and performance. In this work Gray cast iron substrate is coated with FeBCr alloy powder to improve its performance. The microstructure and micro abrasive wear performance of both the uncoated substrates and the coated substrates were characterized by optical microscopy as well as by Scanning Electron Microscope (SEM. In addition, X-ray Diffraction (XRD was undertaken in the partial characterization of the coating. The densely layered coating had porosity levels that were below 2.5 % and a high surface hardness, of the order of 980 HV0.1. The coating exhibited excellent wear resistance when subjected to the ball-cratering test method. The low coefficients of friction of hard coating on the substrate were recorded. The wear performance of the coating was nearly 82 % better than that of the substrate, with a 0.05 N load, even under severe three body abrasive conditions.

  5. A Non-ATP Competitive Inhibitor of BCR-ABL for the Therapy of Imatinib-Resistant Cmls

    Science.gov (United States)

    2008-05-01

    10% SDS-PAGE and analyzed for indicated proteins by infrared labeled secondary antibodies and scanning with Odyssey scanner ( LiCor Technology). pBcr...proteins by infrared labeled secondary antibodies and scanning with Odyssey scanner ( LiCor Technology). 10 treated 32D/T315I-BCR-ABL cells with increasing...with Odyssey scanner ( LiCor Technology). V G 0.5 1.0 2.5 5.0 0.5 1.0 2.5 5.0 (µM

  6. DMPD: Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin-1during B-cell development. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14962188 Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokin...ng) (.svg) (.html) (.csml) Show Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin...-1during B-cell development. PubmedID 14962188 Title Mechanisms of selection media

  7. BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia.

    Science.gov (United States)

    Zabriskie, Matthew S; Eide, Christopher A; Tantravahi, Srinivas K; Vellore, Nadeem A; Estrada, Johanna; Nicolini, Franck E; Khoury, Hanna J; Larson, Richard A; Konopleva, Marina; Cortes, Jorge E; Kantarjian, Hagop; Jabbour, Elias J; Kornblau, Steven M; Lipton, Jeffrey H; Rea, Delphine; Stenke, Leif; Barbany, Gisela; Lange, Thoralf; Hernández-Boluda, Juan-Carlos; Ossenkoppele, Gert J; Press, Richard D; Chuah, Charles; Goldberg, Stuart L; Wetzler, Meir; Mahon, Francois-Xavier; Etienne, Gabriel; Baccarani, Michele; Soverini, Simona; Rosti, Gianantonio; Rousselot, Philippe; Friedman, Ran; Deininger, Marie; Reynolds, Kimberly R; Heaton, William L; Eiring, Anna M; Pomicter, Anthony D; Khorashad, Jamshid S; Kelley, Todd W; Baron, Riccardo; Druker, Brian J; Deininger, Michael W; O'Hare, Thomas

    2014-09-08

    Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph(+)) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph(+) leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome.

  8. Application of BCR-ABL in chronic myelogenous leukemia%BCR-ABL探针在慢性粒细胞白血病中的应用

    Institute of Scientific and Technical Information of China (English)

    李娟; 陆莉; 蒲育栋; 杨柳; 赵丽

    2009-01-01

    目的 用常规细胞遗传学(conventional cytogenetics,CC)和荧光原位杂交(fluorescence chromosomal in situ hybridization,FISH)技术检测Ph染色体.方法 常规细胞遗传学分析(CC),荧光原位杂交(FISH)技术.结果 7例患者4例Ph染色体阴性,其中2例分别伴有t(18;22)和t(17;22)异常,其余2例为异基因造血干细胞移植后正常核型.一例培养后无中期分裂相.2例Ph染色体阳性,FISH结果bcr/abl(+)细胞检出率分别为63.87%,84.51%,7.56%,4.0%,74.45%,67%,47%.结论 常规细胞遗传学与荧光原位杂交技术相结合对CML患者诊断治疗过程中肿瘤负荷动态检测有显著意义.

  9. A multiple reaction monitoring (MRM method to detect Bcr-Abl kinase activity in CML using a peptide biosensor.

    Directory of Open Access Journals (Sweden)

    Tzu-Yi Yang

    Full Text Available The protein kinase Bcr-Abl plays a major role in the pathogenesis of chronic myelogenous leukemia (CML, and is the target of the breakthrough drug imatinib (Gleevec™. While most patients respond well to imatinib, approximately 30% never achieve remission or develop resistance within 1-5 years of starting imatinib treatment. Evidence from clinical studies suggests that achieving at least 50% inhibition of a patient's Bcr-Abl kinase activity (relative to their level at diagnosis is associated with improved patient outcomes, including reduced occurrence of resistance and longer maintenance of remission. Accordingly, sensitive assays for detecting Bcr-Abl kinase activity compatible with small amounts of patient material are desirable as potential companion diagnostics for imatinib. Here we report the detection of Bcr-Abl activity and inhibition by imatinib in the human CML cell line K562 using a cell-penetrating peptide biosensor and multiple reaction monitoring (MRM on a triple quadrupole mass spectrometer. MRM enabled reproducible, selective detection of the peptide biosensor at fmol levels from aliquots of cell lysate equivalent to ~15,000 cells. This degree of sensitivity will facilitate the miniaturization of the entire assay procedure down to cell numbers approaching 15,000, making it practical for translational applications in patient cells in which the limited amount of available patient material often presents a major challenge.

  10. Mutations of Cx43 that affect B cell spreading in response to BCR signaling

    Directory of Open Access Journals (Sweden)

    Letitia Falk

    2014-07-01

    Full Text Available The gap junction (GJ protein connexin 43 (Cx43 is both necessary and sufficient for B cell receptor (BCR-mediated cell spreading. To address how Cx43 mediates this effect, we blocked its function genetically, by expressing mutants of Cx43, and pharmacologically, by using chemical inhibitors. While various point mutations of Cx43 inhibited B cell spreading, treatment with channel blocking drugs did not, suggesting that this response was independent of channel function. The critical region of Cx43 appears to be the cytoplasmic carboxyl-terminal (CT domain, which has previously been shown to be important for B cell spreading. Consistent with this, mutations of either tyrosine 247 or 265 found in the CT were sufficient to inhibit spreading. Thus Cx43 may influence B cell spreading by mechanisms requiring protein binding to, or modification of, these sites in the CT tail.

  11. Transcription Factors Efg1 and Bcr1 Regulate Biofilm Formation and Virulence during Candida albicans-Associated Denture Stomatitis.

    Science.gov (United States)

    Yano, Junko; Yu, Alika; Fidel, Paul L; Noverr, Mairi C

    2016-01-01

    Denture stomatitis (DS) is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. The disease is caused by Candida albicans, which readily colonizes and form biofilms on denture materials. While evidence for biofilms on abiotic and biotic surfaces initiating Candida infections is accumulating, a role for biofilms in DS remains unclear. Using an established model of DS in immunocompetent animals, the purpose of this study was to determine the role of biofilm formation in mucosal damage during pathogenesis using C. albicans or mutants defective in morphogenesis (efg1-/-) or biofilm formation (bcr1-/-). For in vivo analyses, rats fitted with custom dentures, consisting of fixed and removable parts, were inoculated with wild-type C. albicans, mutants or reconstituted strains and monitored weekly for fungal burden (denture and palate), body weight and tissue damage (LDH) for up to 8 weeks. C. albicans wild-type and reconstituted mutants formed biofilms on dentures and palatal tissues under in vitro, ex vivo and in vivo conditions as indicated by microscopy demonstrating robust biofilm architecture and extracellular matrix (ECM). In contrast, both efg1-/- and bcr1-/- mutants exhibited poor biofilm growth with little to no ECM. In addition, quantification of fungal burden showed reduced colonization throughout the infection period on dentures and palates of rats inoculated with efg1-/-, but not bcr1-/-, compared to controls. Finally, rats inoculated with efg1-/- and bcr1-/- mutants had minimal palatal tissue damage/weight loss while those inoculated with wild-type or reconstituted mutants showed evidence of tissue damage and exhibited stunted weight gain. These data suggest that biofilm formation is associated with tissue damage during DS and that Efg1 and Bcr1, both central regulators of virulence in C. albicans, have pivotal roles in pathogenesis of DS.

  12. BCR-ABL1 kinase inhibits uracil DNA glycosylase UNG2 to enhance oxidative DNA damage and stimulate genomic instability.

    Science.gov (United States)

    Slupianek, A; Falinski, R; Znojek, P; Stoklosa, T; Flis, S; Doneddu, V; Pytel, D; Synowiec, E; Blasiak, J; Bellacosa, A; Skorski, T

    2013-03-01

    Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia in chronic phase (CML-CP). Unfortunately, 25% of TKI-naive patients and 50-90% of patients developing TKI-resistance carry CML clones expressing TKI-resistant BCR-ABL1 kinase mutants. We reported that CML-CP leukemia stem and progenitor cell populations accumulate high amounts of reactive oxygen species, which may result in accumulation of uracil derivatives in genomic DNA. Unfaithful and/or inefficient repair of these lesions generates TKI-resistant point mutations in BCR-ABL1 kinase. Using an array of specific substrates and inhibitors/blocking antibodies we found that uracil DNA glycosylase UNG2 were inhibited in BCR-ABL1-transformed cell lines and CD34(+) CML cells. The inhibitory effect was not accompanied by downregulation of nuclear expression and/or chromatin association of UNG2. The effect was BCR-ABL1 kinase-specific because several other fusion tyrosine kinases did not reduce UNG2 activity. Using UNG2-specific inhibitor UGI, we found that reduction of UNG2 activity increased the number of uracil derivatives in genomic DNA detected by modified comet assay and facilitated accumulation of ouabain-resistant point mutations in reporter gene Na(+)/K(+)ATPase. In conclusion, we postulate that BCR-ABL1 kinase-mediated inhibition of UNG2 contributes to accumulation of point mutations responsible for TKI resistance causing the disease relapse, and perhaps also other point mutations facilitating malignant progression of CML.

  13. Transcription Factors Efg1 and Bcr1 Regulate Biofilm Formation and Virulence during Candida albicans-Associated Denture Stomatitis.

    Directory of Open Access Journals (Sweden)

    Junko Yano

    Full Text Available Denture stomatitis (DS is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. The disease is caused by Candida albicans, which readily colonizes and form biofilms on denture materials. While evidence for biofilms on abiotic and biotic surfaces initiating Candida infections is accumulating, a role for biofilms in DS remains unclear. Using an established model of DS in immunocompetent animals, the purpose of this study was to determine the role of biofilm formation in mucosal damage during pathogenesis using C. albicans or mutants defective in morphogenesis (efg1-/- or biofilm formation (bcr1-/-. For in vivo analyses, rats fitted with custom dentures, consisting of fixed and removable parts, were inoculated with wild-type C. albicans, mutants or reconstituted strains and monitored weekly for fungal burden (denture and palate, body weight and tissue damage (LDH for up to 8 weeks. C. albicans wild-type and reconstituted mutants formed biofilms on dentures and palatal tissues under in vitro, ex vivo and in vivo conditions as indicated by microscopy demonstrating robust biofilm architecture and extracellular matrix (ECM. In contrast, both efg1-/- and bcr1-/- mutants exhibited poor biofilm growth with little to no ECM. In addition, quantification of fungal burden showed reduced colonization throughout the infection period on dentures and palates of rats inoculated with efg1-/-, but not bcr1-/-, compared to controls. Finally, rats inoculated with efg1-/- and bcr1-/- mutants had minimal palatal tissue damage/weight loss while those inoculated with wild-type or reconstituted mutants showed evidence of tissue damage and exhibited stunted weight gain. These data suggest that biofilm formation is associated with tissue damage during DS and that Efg1 and Bcr1, both central regulators of virulence in C. albicans, have pivotal roles in pathogenesis of DS.

  14. Colorimetric assessment of BCR-ABL1 transcripts in clinical samples via gold nanoprobes.

    Science.gov (United States)

    Vinhas, Raquel; Correia, Cláudia; Ribeiro, Patricia; Lourenço, Alexandra; Botelho de Sousa, Aida; Fernandes, Alexandra R; Baptista, Pedro V

    2016-07-01

    Gold nanoparticles functionalized with thiolated oligonucleotides (Au-nanoprobes) have been used in a range of applications for the detection of bioanalytes of interest, from ions to proteins and DNA targets. These detection strategies are based on the unique optical properties of gold nanoparticles, in particular, the intense color that is subject to modulation by modification of the medium dieletric. Au-nanoprobes have been applied for the detection and characterization of specific DNA sequences of interest, namely pathogens and disease biomarkers. Nevertheless, despite its relevance, only a few reports exist on the detection of RNA targets. Among these strategies, the colorimetric detection of DNA has been proven to work for several different targets in controlled samples but demonstration in real clinical bioanalysis has been elusive. Here, we used a colorimetric method based on Au-nanoprobes for the direct detection of the e14a2 BCR-ABL fusion transcript in myeloid leukemia patient samples without the need for retro-transcription. Au-nanoprobes directly assessed total RNA from 38 clinical samples, and results were validated against reverse transcription-nested polymerase chain reaction (RT-nested PCR) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The colorimetric Au-nanoprobe assay is a simple yet reliable strategy to scrutinize myeloid leukemia patients at diagnosis and evaluate progression, with obvious advantages in terms of time and cost, particularly in low- to medium-income countries where molecular screening is not routinely feasible. Graphical abstract Gold nanoprobe for colorimetric detection of BCR-ABL1 fusion transcripts originating from the Philadelphia chromosome.

  15. The NDR/LATS kinase Cbk1 controls the activity of the transcriptional regulator Bcr1 during biofilm formation in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Pilar Gutiérrez-Escribano

    Full Text Available In nature, many microorganisms form specialized complex, multicellular, surface-attached communities called biofilms. These communities play critical roles in microbial pathogenesis. The fungal pathogen Candida albicans is associated with catheter-based infections due to its ability to establish biofilms. The transcription factor Bcr1 is a master regulator of C. albicans biofilm development, although the full extent of its regulation remains unknown. Here, we report that Bcr1 is a phosphoprotein that physically interacts with the NDR kinase Cbk1 and undergoes Cbk1-dependent phosphorylation. Mutating the two putative Cbk1 phosphoacceptor residues in Bcr1 to alanine markedly impaired Bcr1 function during biofilm formation and virulence in a mouse model of disseminated candidiasis. Cells lacking Cbk1, or any of its upstream activators, also had reduced biofilm development. Notably, mutating the two putative Cbk1 phosphoacceptor residues in Bcr1 to glutamate in cbk1Δ cells upregulated the transcription of Bcr1-dependent genes and partially rescued the biofilm defects of a cbk1Δ strain. Therefore, our data uncovered a novel role of the NDR/LATS kinase Cbk1 in the regulation of biofilm development through the control of Bcr1.

  16. CCR7 is involved in BCR-ABL/STAP-2-mediated cell growth in hematopoietic Ba/F3 cells.

    Science.gov (United States)

    Kubo, Kaori; Iwakami, Masashi; Muromoto, Ryuta; Inagaki, Takuya; Kitai, Yuichi; Kon, Shigeyuki; Sekine, Yuichi; Oritani, Kenji; Matsuda, Tadashi

    2015-08-07

    Chronic myeloid leukemia is a clonal disease characterized by the presence of the Philadelphia chromosome and its oncogenic product, BCR-ABL, which activates multiple pathways involved in cell survival, growth promotion, and disease progression. We previously reported that in murine hematopoietic Ba/F3 cells, signal transducing adaptor protein-2 (STAP-2) binds to BCR-ABL and up-regulates BCR-ABL phosphorylation, leading to enhanced activation of its downstream signaling molecules. The binding of STAP-2 to BCR-ABL also influenced the expression levels of chemokine receptors, such as CXCR4 and CCR7. For the induction of CCR7 expression, signals mediated by the MAPK/ERK pathway were critical in Ba/F3 cells expressing BCR-ABL and STAP-2. In addition, STAP-2 cooperated with BCR-ABL to induce the production of CCR7 ligands, CCL19 and CCL21. Our results demonstrate a contribution of CCR7 to STAP-2-dependent enhancement of BCR-ABL-mediated cell growth in Ba/F3 cells.

  17. Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-κB signaling and depleting Bcr-Abl

    Directory of Open Access Journals (Sweden)

    Cao Qi

    2010-05-01

    Full Text Available Abstract Background Chronic myelogenous leukemia (CML is characterized by the chimeric tyrosine kinase Bcr-Abl. Bcr-Abl-T315I is the notorious point mutation that causes resistance to imatinib and the second generation tyrosine kinase inhibitors, leading to poor prognosis. CML blasts have constitutive p65 (RelA NF-κB transcriptional activity, and NF-κB may be a potential target for molecular therapies in CML that may also be effective against CML cells with Bcr-Abl-T315I. Results In this report, we discovered that pristimerin, a quinonemethide triterpenoid isolated from Celastraceae and Hippocrateaceae, inhibited growth and induced apoptosis in CML cells, including the cells harboring Bcr-Abl-T315I mutation. Additionally, pristimerin inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Pristimerin blocked the TNFα-induced IκBα phosphorylation, translocation of p65, and expression of NF-κB-regulated genes. Pristimerin inhibited two steps in NF-κB signaling: TAK1→IKK and IKK→IκBα. Pristimerin potently inhibited two pairs of CML cell lines (KBM5 versus KBM5-T315I, 32D-Bcr-Abl versus 32D-Bcr-Abl-T315I and primary cells from a CML patient with acquired resistance to imatinib. The mRNA and protein levels of Bcr-Abl in imatinib-sensitive (KBM5 or imatinib-resistant (KBM5-T315I CML cells were reduced after pristimerin treatment. Further, inactivation of Bcr-Abl by imatinib pretreatment did not abrogate the TNFα-induced NF-κB activation while silencing p65 by siRNA did not affect the levels of Bcr-Abl, both results together indicating that NF-κB inactivation and Bcr-Abl inhibition may be parallel independent pathways. Conclusion To our knowledge, this is the first report to show that pristimerin is effective in vitro and in vivo against CML cells, including those with the T315I mutation. The mechanisms may involve inhibition of NF-κB and Bcr-Abl. We concluded that pristimerin could be a lead compound for

  18. Detection of BCR/ABL Fusion Gene by Fluorescence In Situ Hybridization and Its Clinical Application%荧光原位杂交技术检测BCR/ABL融合基因的临床应用

    Institute of Scientific and Technical Information of China (English)

    周瑞莲; 莫耀禧; 蓝梅; 林金盈

    2011-01-01

    This study was aimed to investigate the clinical value of detecting BCR/ABL fusion gene by fluorescence in situ hybridization (FISH). The conventional cytogenetic test and detection of BCR/ABL fusion gene by FISH for bone marrow of patients with newly diagnosed chronic myeloproliferative disease or myelodysplastic and myeloproliferative disorders, acute lymphocytic leukemia and chronic myelogeneous leukemia (CML) after allogeneic hematopoietic stem cell transplantation were carried out. The results showed that ( 1 ) out of 46 newly diagnosed as chronic myeloproliferative dsease or myelodysplastic and myeloproliferative disorders, 22 cases were diagnosed as CML, the FISH detection showed all positive (100% ), while cytogenetic test showed 86.4% (19/22) positive, in the other 24 patients who were diagnosed as other chronic myeloproliferative disease or myelodysplastic and myeloproliferative disorders, BCR/ABL fusion gene all were be detected as regative 100% by FISH, while the cytogenetic test of bone marrow in 3 cases supported the diagnosis of CML, and the diagnosis of myelodysplastic disorder in 1 case; (2) in 3 out of 7 acute lymphocytic leukemia cases the BCR/ABL fusion gene could not be detected by FISH; (3) the BCR/ABL fusion gene could be detected by FISH in 2 cases of CML received allogeneic hematopoietic stem cell transplantation, with abnormal threshold 6.5% and 1. 2% respectively. It is concluded that the detection of BCR/ABL fusion gene by FISH is sensitive and reliable, which is very important for the diagnosis and differential dignosis of chronic myeloproliferative disorders, myelodysplastic and myeloproliferative disease, as well as definite diagnosis of Ph* acute lymphoblastic leukemia. This method also has an important significance for monitor of minimal residual disease in CML patients received allogeneic hematopoietic stem cell transplantation.%本研究探讨应用荧光原位杂交技术( FISH)检测BCR/ABL融合基因在临床中的应用价

  19. Ability of 3 extraction methods (BCR, Tessier and protease K) to estimate bioavailable metals in sediments from Huelva estuary (Southwestern Spain).

    Science.gov (United States)

    Rosado, Daniel; Usero, José; Morillo, José

    2016-01-15

    The bioavailable fraction of metals (Zn, Cu, Cd, Mn, Pb, Ni, Fe, and Cr) in sediments of the Huelva estuary and its littoral of influence has been estimated carrying out the most popular methods of sequential extraction (BCR and Tessier) and a biomimetic approach (protease K extraction). Results were compared to enrichment factors found in Arenicola marina. The linear correlation coefficients (R(2)) obtained between the fraction mobilized by the first step of the BCR sequential extraction, by the sum of the first and second steps of the Tessier sequential extraction, and by protease K, and enrichment factors in A. marina, are at their highest for protease K extraction (0.709), followed by BCR first step (0.507) and the sum of the first and second steps of Tessier (0.465). This observation suggests that protease K represents the bioavailable fraction more reliably than traditional methods (BCR and Tessier), which have a similar ability.

  20. Kriging analysis of geochemical data obtained by sequential extraction procedure (BCR)

    Science.gov (United States)

    Fajkovic, Hana; Pitarević Svedružić, Lovorka; Prohić, Esad; Rončević, Sanda; Nemet, Ivan

    2015-04-01

    Field examination and laboratory analysis were performed to establish whether nonsanitary landfill Bastijunski brig has a negative influence on Vransko Lake, situated only 1500 m away. Vransko Lake is Croatia's largest natural lake, and it is a part of the Nature Park and ornithological reserve, which indicates its high biodiversity. Therefore it is necessary to understand the environmental processes and complex sediment/water interface. Lake sediments are considered to be a good "sinkhole'and are often the final recipients of anthropogenic and natural pollutants through adsorption onto the organic or clay fraction in sediments. Geochemical investigation were obtained throughout more than 50 lake sediments cores situated in different parts of the lake Speciation of heavy metals by modified BCR sequential extraction procedure with the addition of a first step of sequential extraction procedure by Tessier and analysis of residual by aqua regia were used to determine the amounts of selected elements (Al, Cd, Cr, Co, Cu, Fe, Mn, Ni, Pb, Zn) in different fractions. With such approach it is possible to determine which element will be extracted from sediment/soil in a different environmental conditions and can be valuable tool for interpretation of the mobile fraction of the elements, considered bioavailability, that present threat to biota in a case of a contaminant concentration magnification. All sediment and soil samples were analyzed by inductively coupled plasma atomic emission spectrometry. More accurate interpretation of data is an advantage of BCR sequential extraction procedure while high number of the data together with point data type could be considered as a drawback. Due to high amount of data, graphical presentation is advisable while interpolation tool is a first choice for point type of data, as it makes predictions for defined area based on the measurements. Distribution maps of analysed elements were obtained by kriging as a geostatistical method and

  1. ON012380: A Non-ATP Competitive Inhibitor of BCR-ABL for the Therapy of Imatinib-Resistant CMLs

    Science.gov (United States)

    2010-05-01

    diverse client proteins. Biopolymers 2009. 41. Tsuruma R, Ohbayashi N, Kamitani S, et al. Physical and functional interactions between STAT3 and...compounds to significantly inhibit the proliferation of K562 and Ba/F3:JAK2V617F cells suggests that this scaffold could be a promising lead for the... scaffold could be a promising lead for the development of anticancer agents that are able to block BCR-ABL phosphorylation in leuke- mic cells. 2010

  2. Quantification of BCR-ABL mRNA in Plasma/Serum of Patients with Chronic Myelogenous Leukemia

    Directory of Open Access Journals (Sweden)

    Miwako Narita, Anri Saito, Aya Kojima, Minami Iwabuchi, Naoya Satoh, Takayoshi Uchiyama, Akie Yamahira, Tatsuo Furukawa, Hirohito Sone, Masuhiro Takahashi

    2012-01-01

    Full Text Available Quantification of tumor-associated mRNA extracted from blood cells/tissues containing tumor cells is used for evaluation of treatment efficacy or residual tumor cell burden in tumors including leukemia. However, this method using tumor cell-containing blood/tissue is difficult to evaluate the whole tumor cell burden in the body. In order to establish an efficient method to evaluate the whole tumor cell burden in the body, we tried to quantify tumor-associated mRNA existing in plasma/serum instead of leukemia cell-containing blood cells in patients with chronic myelogenous leukemia (CML and compared the levels of BCR-ABL mRNA between plasma/serum and peripheral blood cells. mRNA of BCR-ABL, WT1 or GAPDH (control molecule was detected by real-time RT-PCR using RNA extracted from plasma/serum of almost all the patients with CML. Copy numbers of BCR-ABL mRNA were significantly correlated between plasma/serum and peripheral blood cells. However, levels of BCR-ABL mRNA extracted from serum were low compared with those extracted with peripheral blood cells. The present findings suggest that although real-time RT-PCR of mRNA existing in plasma/serum could be used for evaluating the whole tumor cell burden in the body, it's required to establish an efficient method to quantify plasma/serum mRNA by nature without degrading during the procedure.

  3. Structural Mechanism of the Pan-BCR-ABL Inhibitor Ponatinib (AP24534): Lessons for Overcoming Kinase Inhibitor Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Tianjun; Commodore, Lois; Huang, Wei-Sheng; Wang, Yihan; Thomas, Mathew; Keats, Jeff; Xu, Qihong; Rivera, Victor M.; Shakespeare, William C.; Clackson, Tim; Dalgarno, David C.; Zhu, Xiaotian (ARIAD)

    2012-01-20

    The BCR-ABL inhibitor imatinib has revolutionized the treatment of chronic myeloid leukemia. However, drug resistance caused by kinase domain mutations has necessitated the development of new mutation-resistant inhibitors, most recently against the T315I gatekeeper residue mutation. Ponatinib (AP24534) inhibits both native and mutant BCR-ABL, including T315I, acting as a pan-BCR-ABL inhibitor. Here, we undertook a combined crystallographic and structure-activity relationship analysis on ponatinib to understand this unique profile. While the ethynyl linker is a key inhibitor functionality that interacts with the gatekeeper, virtually all other components of ponatinib play an essential role in its T315I inhibitory activity. The extensive network of optimized molecular contacts found in the DFG-out binding mode leads to high potency and renders binding less susceptible to disruption by single point mutations. The inhibitory mechanism exemplified by ponatinib may have broad relevance to designing inhibitors against other kinases with mutated gatekeeper residues.

  4. Inhibiting CARD11 translation during BCR activation by targeting the eIF4A RNA helicase.

    Science.gov (United States)

    Steinhardt, James J; Peroutka, Raymond J; Mazan-Mamczarz, Krystyna; Chen, Qing; Houng, Simone; Robles, Carol; Barth, Rolf N; DuBose, Joseph; Bruns, Brandon; Tesoriero, Ronald; Stein, Deborah; Fang, Raymond; Hanna, Nader; Pasley, Jason; Rodriguez, Carlos; Kligman, Mark D; Bradley, Matthew; Rabin, Joseph; Shackelford, Stacy; Dai, Bojie; Landon, Ari L; Scalea, Thomas; Livak, Ferenc; Gartenhaus, Ronald B

    2014-12-11

    Human diffuse large B-cell lymphomas (DLBCLs) often aberrantly express oncogenes that generally contain complex secondary structures in their 5' untranslated region (UTR). Oncogenes with complex 5'UTRs require enhanced eIF4A RNA helicase activity for translation. PDCD4 inhibits eIF4A, and PDCD4 knockout mice have a high penetrance for B-cell lymphomas. Here, we show that on B-cell receptor (BCR)-mediated p70s6K activation, PDCD4 is degraded, and eIF4A activity is greatly enhanced. We identified a subset of genes involved in BCR signaling, including CARD11, BCL10, and MALT1, that have complex 5'UTRs and encode proteins with short half-lives. Expression of these known oncogenic proteins is enhanced on BCR activation and is attenuated by the eIF4A inhibitor Silvestrol. Antigen-experienced immunoglobulin (Ig)G(+) splenic B cells, from which most DLBCLs are derived, have higher levels of eIF4A cap-binding activity and protein translation than IgM(+) B cells. Our results suggest that eIF4A-mediated enhancement of oncogene translation may be a critical component for lymphoma progression, and specific targeting of eIF4A may be an attractive therapeutic approach in the management of human B-cell lymphomas.

  5. 血液病患者bcr/abl融合基因、Ph染色体异同浅谈

    Institute of Scientific and Technical Information of China (English)

    王旭萍

    2011-01-01

    @@ CML特异性费城染色体(Philadephia,Ph)是由t(9:22)(q34:11)易位形成.9号染色体原癌基因abl(Abelson protooncogene)易位至22号染色体的断裂点簇集区(breakpoint duster region,ber),发生重排,产生bcr/abl融合基因,引起CML的始动突变.融合基因bcr/abl几乎见于所有的慢性粒细胞性白血病、25%-50%的急性B系淋巴细胞性白血病(ALL)和约5%的急性粒细胞性白血病中J,本文统计了进行染色体和bcr/abl融合基因检查的初诊血液病66例,对其骨髓细胞染色体核型及ber/~1融合基因进行分析.

  6. Migration of antibody secreting cells towards CXCL12 depends on the isotype that forms the BCR

    Science.gov (United States)

    Achatz-Straussberger, Gertrude; Zaborsky, Nadja; Königsberger, Sebastian; Luger, Elke O.; Lamers, Marinus; Crameri, Reto; Achatz, Gernot

    2010-01-01

    Truncation of the cytoplasmic tail of membrane-bound IgE in vivo results in lower serum IgE levels, decreased numbers of IgE-secreting plasma cells and the abrogation of specific secondary immune responses. Here we present mouse strain KN1 that expresses a chimeric ε-γ1 BCR, consisting of the extracellular domains of the ε gene and the trans-membrane and cytoplasmic domains of the γ1 gene. Thus, differences in the IgE immune response of KN1 mice reflect the influence of the “γ1-mediated signalling” of mIgE bearing B cells. KN1 mice show an increased serum IgE level, resulting from an elevated number of IgE-secreting cells. Although the primary IgE immune response in KN1 mice is inconspicuous, the secondary response is far more robust. Most strikingly, IgE-antibody secreting cells with “γ1-signalling history” migrate more efficiently towards the chemokine CXCL12, which guides plasmablasts to plasma cell niches, than IgE-antibody secreting cells with WT “ε-signalling history”. We conclude that IgE plasmablasts have an intrinsic, lower chance to contribute to the long-lived plasma cell pool than IgG1 plasmablasts. PMID:18925577

  7. Papel da P190 BCR-ABL como parâmetro de recaída na leucemia mielóide crônica P190 BCR-ABL role in myeloid chronic leukemia relapse

    Directory of Open Access Journals (Sweden)

    Gabriela V. Andrade

    2008-08-01

    Full Text Available A leucemia mielóide crônica (LMC é uma desordem hematológica mieloproloferativa clonal causada por uma mutação em uma célula-tronco pluripotente, resultando na proliferação e acúmulo de células mielóides e seus progenitores. O cromossomo Philadelphia é o resultado de uma translocação recíproca de material genético entre os genes abl (Abelson murine leukemia no cromossomo 9, e o bcr (breakpoint cluster region no cromossomo 22, resultando na formação do gene quimérico BCR-ABL. Neste trabalho, 45 pacientes foram acompanhados de forma seqüencial, de acordo com as avaliações periódicas individuais, e 360 amostras foram selecionadas e analisadas pela técnica da reação em cadeia da polimerase (PCR através da técnica qualitativa para as isoformas características da P210BCR-ABL (b3a2 e b2a2 e P190BCR-ABL (e1a2. No nosso estudo no pré-TMO, observou-se uma prevalência das isoformas características da LMC (b3a2 e/ou b2a2, fato imprescindível para que o paciente fosse acompanhado dentro do protocolo da LMC. A isoforma e1a2, característica da LLA, foi detectada em 11 pacientes em conjunto com essas isoformas. A detecção do transcrito e1a2 foi avaliada quanto ao seu provável papel na LMC, e foi um dos parâmetros de avaliação deste estudo.Chronic myeloid leukemia (CML is a myeloproliferative clonal disorder caused by a mutation in a stem cell, resulting in the proliferation and accumulation of myeloid cells and their progenitors. The Philadelphia chromosome (Ph1 is a result of a mutual translocation of genetic material between the abl gene (Abelson murine leukemia in chromosome 9 and bcr gene (breakpoint cluster region in chromosome 22, resulting in the formation of the chimerical gene, BCR-ABL. In this work 45 patients were sequentially followed up in individual periodic evaluations, and 360 samples were selected and analyzed by PCR using the qualitative technique for isoforms characteristic of P210CR-ABL (b3a2 and b2a2

  8. Outcomes of Children With BCR-ABL1–Like Acute Lymphoblastic Leukemia Treated With Risk-Directed Therapy Based on the Levels of Minimal Residual Disease

    Science.gov (United States)

    Roberts, Kathryn G.; Pei, Deqing; Campana, Dario; Payne-Turner, Debbie; Li, Yongjin; Cheng, Cheng; Sandlund, John T.; Jeha, Sima; Easton, John; Becksfort, Jared; Zhang, Jinghui; Coustan-Smith, Elaine; Raimondi, Susana C.; Leung, Wing H.; Relling, Mary V.; Evans, William E.; Downing, James R.; Mullighan, Charles G.; Pui, Ching-Hon

    2014-01-01

    Purpose BCR-ABL1–like acute lymphoblastic leukemia (ALL) is a recently identified B-cell ALL (B-ALL) subtype with poor outcome that exhibits a gene expression profile similar to BCR-ABL1-positive ALL but lacks the BCR-ABL1 fusion protein. We examined the outcome of children with BCR-ABL1–like ALL treated with risk-directed therapy based on minimal residual disease (MRD) levels during remission induction. Patients and Methods Among 422 patients with B-ALL enrolled onto the Total Therapy XV study between 2000 and 2007, 344 had adequate samples for gene expression profiling. Next-generation sequencing and/or analysis of genes known to be altered in B-ALL were performed in patients with BCR-ABL1–like ALL who had available material. Outcome was compared between patients with and those without BCR-ABL1–like ALL. Results Forty (11.6%) of the 344 patients had BCR-ABL1–like ALL. They were significantly more likely to be male, have Down syndrome, and have higher MRD levels on day 19 and at the end of induction than did other patients with B-ALL. Among 25 patients comprehensively studied for genetic abnormalities, 11 harbored a genomic rearrangement of CRLF2, six had fusion transcripts responsive to ABL tyrosine kinase inhibitors or JAK inhibitors, and seven had mutations involving the Ras signaling pathway. There were no significant differences in event-free survival (90.0% ± 4.7% [SE] v 88.4% ± 1.9% at 5 years; P = .41) or in overall survival (92.5% ± 4.2% v 95.1% ± 1.3% at 5 years; P = .41) between patients with and without BCR-ABL1–like ALL. Conclusion Patients who have BCR-ABL1–like ALL with poor initial treatment response can be salvaged with MRD-based risk-directed therapy and may benefit from identification of kinase-activating lesions for targeted therapies. PMID:25049327

  9. Frequency of p190 and p210 BCR-ABL rearrangements and survival in Brazilian adult patients with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ilana de França Azevedo

    2014-10-01

    Full Text Available Objective: This study investigated the occurrence of the p190 and p210 break point clusterregion-Abelson (BCR-ABL rearrangements in adults with acute lymphoblastic leukemia and possible associations with clinical and laboratory characteristics and survival. Methods: Forty-one over 18-year-old patients with acute lymphoblastic leukemia of both genders followed-up between January 2008 and May 2012 were included in this study. Clinical and laboratory data were obtained from the medical charts of the patients. Reverse transcription polymerase chain reaction (RT-PCR using specific primers was employed to identify molecular rearrangements. Results: At diagnosis, the median age was 33 years, and there was a predominance of males (61%. The most common immunophenotype was B lineage (76%. BCR-ABL rearrangements was detected in 14 (34% patients with the following distribution: p190 (28%, p210 (50% and double positive (22%. Overall survival of patients with a mean/median of 331/246 days of follow up was 39%, respectively, negative BCR-ABL (44% and positive BCR-ABL (28%. Conclusion: These results confirm the high frequency of BCR-ABL rearrangements and the low survival rate of adult Brazilian patients with acute lymphoblastic leukemia.

  10. Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL– and mutant FLT3-expressing cells

    Science.gov (United States)

    Weisberg, Ellen; Banerji, Lolita; Wright, Renee D.; Barrett, Rosemary; Ray, Arghya; Moreno, Daisy; Catley, Laurence; Jiang, Jingrui; Hall-Meyers, Elizabeth; Sauveur-Michel, Maira; Stone, Richard; Galinsky, Ilene; Fox, Edward; Kung, Andrew L.

    2008-01-01

    Mediators of PI3K/AKT signaling have been implicated in chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Studies have shown that inhibitors of PI3K/AKT signaling, such as wortmannin and LY294002, are able to inhibit CML and AML cell proliferation and synergize with targeted tyrosine kinase inhi-bitors. We investigated the ability of BAG956, a dual PI3K/PDK-1 inhibitor, to be used in combination with inhibitors of BCR-ABL and mutant FLT3, as well as with the mTOR inhibitor, rapamycin, and the rapamycin derivative, RAD001. BAG956 was shown to block AKT phosphorylation induced by BCR-ABL–, and induce apoptosis of BCR-ABL–expressing cell lines and patient bone marrow cells at concentrations that also inhibit PI3K signaling. Enhancement of the inhibitory effects of the tyrosine kinase inhibitors, imatinib and nilotinib, by BAG956 was demonstrated against BCR-ABL expressing cells both in vitro and in vivo. We have also shown that BAG956 is effective against mutant FLT3-expressing cell lines and AML patient bone marrow cells. Enhancement of the inhibitory effects of the tyrosine kinase inhibitor, PKC412, by BAG956 was demonstrated against mutant FLT3-expressing cells. Finally, BAG956 and rapamycin/RAD001 were shown to combine in a nonantagonistic fashion against BCR-ABL– and mutant FLT3-expressing cells both in vitro and in vivo. PMID:18184863

  11. PESV对K562细胞BCR/ABL融合基因及凋亡调控因子Bcl-2、Bad表达的影响%The Effects of PESV on the Expression of BCR/ABL Fusion Gene and Bcl-2, Bad of Apoptosis Regulators on the K562 Cells

    Institute of Scientific and Technical Information of China (English)

    于文俊; 杨文华; 杨向东; 史哲新; 王兴丽; 郝征; 张佳

    2012-01-01

    Objective: To investigate the PESV of K562 cells BCR / ABL fusion gene and apoptosis regulators bcl-2 and bad expression. Methods: K562 cells were cultured in vitro, by PESV for different times, the apoptosis rate by flow cytometry, fluorescence quantitative RT-PCR detection of BCR / ABL, Bcl-2, Bad mRNA level changes. Results: Compared with the control group, PESV treated K562 cells, apoptosis increased, BCR / ABL fusion gene reduced expression, anti-apoptotic gene Bcl-2 mRNA expression decreased, pro-apoptotic gene Bad mRNA expression. Conclusion: PESV reduced in K562 cells can reduce the BCR / ABL fusion gene, may regulate the expression of Bcl-2 and Bad, inhibit proliferation of K562 cells and promote their apoptosis.%目的:探讨PESV对K562细胞BCR/ABL融合基因及凋亡调控因子bcl-2和bad表达的影响.方法:将体外培养K562细胞,经PESV处理不同时间后,流式细胞术检测细胞凋亡率,荧光定量RT-PCR检测BCR/ABL、Bcl-2、Bad mRNA水平变化.结果:与对照组相比,PESV处理后K562细胞,凋亡率增加,BCR/ABL融合基因表达降低,抗凋亡相关基因Bcl-2 mRNA表达降低,促凋亡基因Bad mRNA表达增加.结论:PESV能降低降低K562细胞BCR/ABL融合基因的表达,可能通过调节Bcl-2和Bad表达,抑制K562细胞增殖,促进其凋亡.

  12. Fluorescent in-situ hybridization (FISH for BCR/ABL in chronic myeloid leukemia after bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Lopes Ferrari Chauffaille

    2001-01-01

    Full Text Available CONTEXT: Identification of Philadelphia chromosome or BCR/ABL gene rearrangement in chronic myeloid leukemia is important at diagnosis as well as after treatment. OBJECTIVE: To compare the results of karyotyping using fluorescent in-situ hybridization (FISH upon diagnosis and 1 year after bone marrow transplantation in 12 patients. TYPE OF STUDY: Diagnostic test and residual disease detection. SETTING: Hematology and Hemotherapy Department, Federal University of São Paulo/Escola Paulista de Medicina, São Paulo, Brazil. SAMPLE: 12 patients with chronic myeloid leukemia at diagnosis and 1 year after bone marrow transplantation. DIAGNOSTIC TEST: Karyotyping was done in the usual way and the BCR/ABL gene-specific probe was used for FISH. MAIN MEASUREMENTS: Disease at diagnosis and residual. RESULTS: At diagnosis, 10 patients presented t(9;22(q34.1;q11 as well as positive FISH. Two cases did not have metaphases but FISH was positive. After bone marrow transplantation, 8 patients presented normal karyotype, 1 had persistence of identifiable Philadelphia chromosome and 3 had no metaphases. Two cases showed complete chimera and 2 had donor and host cells simultaneously. FISH was possible in all cases after bone marrow transplantation and confirmed the persistence of identifiable Philadelphia chromosome clone in one patient, and identified another that did not present metaphases for analysis. Cases that showed mixed chimera in karyotype were negative for BCR/ABL by FISH. CONCLUSION: The applicability of FISH is clear, particularly for residual disease detection. Classical and molecular cytogenetics are complementary methods.

  13. Speciation of heavy metals by modified BCR sequential extraction procedure in different depths of sediments from Sungai Buloh, Selangor, Malaysia

    Energy Technology Data Exchange (ETDEWEB)

    Nemati, Keivan, E-mail: keivan_nemati@yahoo.com [Environmental Research Group, Department of Chemistry, University of Malaya (UM), Kuala Lumpur 50603 (Malaysia); Bakar, Nor Kartini Abu; Abas, Mhd. Radzi; Sobhanzadeh, Elham [Environmental Research Group, Department of Chemistry, University of Malaya (UM), Kuala Lumpur 50603 (Malaysia)

    2011-08-15

    Highlights: {yields} A BCR sequential extraction procedure was applied for measurement of heavy metals in Sungai Buloh sediments in different depths. {yields} The amounts of CF and percentage of RAC was measured in this study too. {yields} Highest CF was obtained for Cd, Co, Pb and Zn in these samples. {yields} Zn at S3 and Cd at S3-S7 showed a high risk for the sediment samples. There were no elements of very high risk conditions in the selected samples. - Abstract: The sequential extraction procedure proposed by the European Standard, Measurements and Testing (SM and T) program, formerly the Community Bureau of Reference (BCR), was applied for partitioning of heavy metals (HMs) in river sediments collected along the course of Sungai Buloh and the Straits of Malacca in Selangor, Malaysia. Eight elements (V, Pb, Cd, Cr, Co, Ni, Cu and Zn) from seven stations (S1-S7) and at different depths were analyzed using the modified BCR Sequential Extraction Procedure (SEP) in combination with ICP-MS to obtain the metal distribution patterns in this region. The results showed that heavy metal contaminations at S2 and S3 was more severe than at other sampling sites, especially for Zn, Cu, Ni and Pb. Nevertheless, the element concentrations from top to bottom layers decreased predominantly. The samples from the Straits of Malacca (S4-S7) the highest contamination factors obtained were for Co, Zn and Pb while the lowest were found for V and Cr, similar to Sungai Buloh sediments. The sediments showed a low risk for V, Cr, Cu and Pb with RAC values of less than 10%, but medium risk for Co, Zn (except S3), Cd at S1 and S2 and Ni at S1, S3 and S5. Zn at S3 and Cd at S3-S7 showed high risk to our sediment samples. There is not any element of very high risk conditions in the selected samples.

  14. Medicare Provider Data - Hospice Providers

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Hospice Utilization and Payment Public Use File provides information on services provided to Medicare beneficiaries by hospice providers. The Hospice PUF...

  15. Molecular monitoring of BCR-ABL transcripts in patients with chronic myelogenous leukemia: is high sensitivity of clinical value?

    Science.gov (United States)

    Norkin, Maxim; Schiffer, Charles A

    2010-04-01

    Monitoring of disease response during treatment with tyrosine kinase inhibitors of patients with chronic myelogenous leukemia dramatically changed after the introduction of real-time PCR, which allows quantification of BCR-ABL transcript levels with high sensitivity and precision. However, its role in patients who have achieved complete cytogenetic response is not entirely clear; incorrect interpretation of results could lead to unnecessary changes from an effective treatment. This review discusses the current evidence regarding the benefits, uncertainties, and potential drawbacks of molecular monitoring in patients with chronic myelogenous leukemia in chronic phase.

  16. Total uncertainty budget calculation for the determination of mercury in incineration ash (BCR 176R) by atomic fluorescence spectrometry.

    Science.gov (United States)

    Tirez, Kristof; Beutels, Filip; Brusten, Wilfried; Noten, Bart; De Brucker, Nicole

    2002-11-01

    The mercury mass fraction has been determined by atomic fluorescence spectrometry (AFS) in the framework of the project "Certification of a reference material (trace elements in fly ash) in replacement of BCR CRM 176". Calculation of the uncertainty budget, as described in this manuscript, emphasizes a practical and realistic approach to estimation of uncertainty components on the basis of statistical assumptions. GUM Workbench software was used, and resulted in a mercury mass fraction of 1.58+/-0.11 mg kg(-1) (with coverage factor k=2.2, 95% probability) related to dry mass, submitted in the certification exercise. The calculated total uncertainty budget applies to analogous samples analyzed by this procedure.

  17. Detection of residual bcr/abl translocation by polymerase chain reaction in chronic myeloid leukaemia patients after bone-marrow transplantation.

    Science.gov (United States)

    Gabert, J; Thuret, I; Lafage, M; Carcassonne, Y; Maraninchi, D; Mannoni, P

    1989-11-11

    The polymerase chain reaction was used to evaluate minimum residual disease in chronic myelogenous leukaemia (CML) patients after bone-marrow transplantation, by amplification of the transcript of the specific bcr/abl hybrid gene. Strict precautions were taken to avoid contamination. Peripheral blood cells from 22 patients transplanted for haematological malignant disorders were analysed. The results were clearcut for positive controls (patients with CML in relapse) and negative controls (patients with malignant disorders other than CML). In 11 of 12 CML patients in clinical and cytogenetic remission the bcr/abl transcript was detected 3 months to 6 years after transplantation. Thus, it appears that cells expressing the bcr/abl mRNA are not eradicated from the blood of CML patients in complete clinical remission even years after bone-marrow transplantation.

  18. Detection of a rare BCR-ABL tyrosine kinase fusion protein in H929 multiple myeloma cells using immunoprecipitation (IP)-tandem mass spectrometry (MS/MS).

    Science.gov (United States)

    Breitkopf, Susanne B; Yuan, Min; Pihan, German A; Asara, John M

    2012-10-02

    Hypothesis directed proteomics offers higher throughput over global analyses. We show that immunoprecipitation (IP)-tandem mass spectrometry (LC-MS/MS) in H929 multiple myeloma (MM) cancer cells led to the discovery of a rare and unexpected BCR-ABL fusion, informing a therapeutic intervention using imatinib (Gleevec). BCR-ABL is the driving mutation in chronic myeloid leukemia (CML) and is uncommon to other cancers. Three different IP-MS experiments central to cell signaling pathways were sufficient to discover a BCR-ABL fusion in H929 cells: phosphotyrosine (pY) peptide IP, p85 regulatory subunit of phosphoinositide-3-kinase (PI3K) IP, and the GRB2 adaptor IP. The pY peptides inform tyrosine kinase activity, p85 IP informs the activating adaptors and receptor tyrosine kinases (RTKs) involved in AKT activation and GRB2 IP identifies RTKs and adaptors leading to ERK activation. Integration of the bait-prey data from the three separate experiments identified the BCR-ABL protein complex, which was confirmed by biochemistry, cytogenetic methods, and DNA sequencing revealed the e14a2 fusion transcript. The tyrosine phosphatase SHP2 and the GAB2 adaptor protein, important for MAPK signaling, were common to all three IP-MS experiments. The comparative treatment of tyrosine kinase inhibitor (TKI) drugs revealed only imatinib, the standard of care in CML, was inhibitory to BCR-ABL leading to down-regulation of pERK and pS6K and inhibiting cell proliferation. These data suggest a model for directed proteomics from patient tumor samples for selecting the appropriate TKI drug(s) based on IP and LC-MS/MS. The data also suggest that MM patients, in addition to CML patients, may benefit from BCR-ABL diagnostic screening.

  19. Biosensing of BCR/ABL fusion gene using an intensity-interrogation surface plasmon resonance imaging system

    Science.gov (United States)

    Wu, Jiangling; Huang, Yu; Bian, Xintong; Li, DanDan; Cheng, Quan; Ding, Shijia

    2016-10-01

    In this work, a custom-made intensity-interrogation surface plasmon resonance imaging (SPRi) system has been developed to directly detect a specific sequence of BCR/ABL fusion gene in chronic myelogenous leukemia (CML). The variation in the reflected light intensity detected from the sensor chip composed of gold islands array is proportional to the change of refractive index due to the selective hybridization of surface-bound DNA probes with target ssDNA. SPRi measurements were performed with different concentrations of synthetic target DNA sequence. The calibration curve of synthetic target sequence shows a good relationship between the concentration of synthetic target and the change of reflected light intensity. The detection limit of this SPRi measurement could approach 10.29 nM. By comparing SPRi images, the target ssDNA and non-complementary DNA sequence are able to be distinguished. This SPRi system has been applied for assay of BCR/ABL fusion gene extracted from real samples. This nucleic acid-based SPRi biosensor therefore offers an alternative high-effective, high-throughput label-free tool for DNA detection in biomedical research and molecular diagnosis.

  20. BCR Signaling Inhibitors: an Overview of Toxicities Associated with Ibrutinib and Idelalisib in Patients with Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Falchi, Lorenzo; Baron, Jessica M; Orlikowski, Carrie Anne; Ferrajoli, Alessandra

    2016-01-01

    The B-cell receptor (BCR) signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in treatment-naïve CLL patients. Both ibrutinib and idelalisib are well tolerated by most patients, including older, frailer individuals. Toxicities are usually mild and self-resolving. Clinicians must, however, be aware of a number of peculiar adverse events, the effects of which can be severe enough to limit the clinical use of these agents. In this review, we survey the salient aspects of the pharmacology and clinical experience with the use of BCR signaling inhibitors for the treatment of patients with CLL. We next focus on both the most common and the most clinically significant toxicities associated with these drugs.

  1. Speciation of heavy metals by modified BCR sequential extraction procedure in different depths of sediments from Sungai Buloh, Selangor, Malaysia.

    Science.gov (United States)

    Nemati, Keivan; Abu Bakar, Nor Kartini; Abas, Mhd Radzi; Sobhanzadeh, Elham

    2011-08-15

    The sequential extraction procedure proposed by the European Standard, Measurements and Testing (SM&T) program, formerly the Community Bureau of Reference (BCR), was applied for partitioning of heavy metals (HMs) in river sediments collected along the course of Sungai Buloh and the Straits of Malacca in Selangor, Malaysia. Eight elements (V, Pb, Cd, Cr, Co, Ni, Cu and Zn) from seven stations (S1-S7) and at different depths were analyzed using the modified BCR Sequential Extraction Procedure (SEP) in combination with ICP-MS to obtain the metal distribution patterns in this region. The results showed that heavy metal contaminations at S2 and S3 was more severe than at other sampling sites, especially for Zn, Cu, Ni and Pb. Nevertheless, the element concentrations from top to bottom layers decreased predominantly. The samples from the Straits of Malacca (S4-S7) the highest contamination factors obtained were for Co, Zn and Pb while the lowest were found for V and Cr, similar to Sungai Buloh sediments. The sediments showed a low risk for V, Cr, Cu and Pb with RAC values of less than 10%, but medium risk for Co, Zn (except S3), Cd at S1 and S2 and Ni at S1, S3 and S5. Zn at S3 and Cd at S3-S7 showed high risk to our sediment samples. There is not any element of very high risk conditions in the selected samples.

  2. A target-disease network model of second-generation BCR-ABL inhibitor action in Ph+ ALL.

    Directory of Open Access Journals (Sweden)

    Uwe Rix

    Full Text Available Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL is in part driven by the tyrosine kinase bcr-abl, but imatinib does not produce long-term remission. Therefore, second-generation ABL inhibitors are currently in clinical investigation. Considering different target specificities and the pronounced genetic heterogeneity of Ph+ ALL, which contributes to the aggressiveness of the disease, drug candidates should be evaluated with regard to their effects on the entire Ph+ ALL-specific signaling network. Here, we applied an integrated experimental and computational approach that allowed us to estimate the differential impact of the bcr-abl inhibitors nilotinib, dasatinib, Bosutinib and Bafetinib. First, we determined drug-protein interactions in Ph+ ALL cell lines by chemical proteomics. We then mapped those interactions along with known genetic lesions onto public protein-protein interactions. Computation of global scores through correlation of target affinity, network topology, and distance to disease-relevant nodes assigned the highest impact to dasatinib, which was subsequently confirmed by proliferation assays. In future, combination of patient-specific genomic information with detailed drug target knowledge and network-based computational analysis should allow for an accurate and individualized prediction of therapy.

  3. Role of the three-dimensional distribution of abl and bcr genes in the formation of bcr/abl fusion gene in interphase neucleus%间期细胞核中abl和bcr基因的三维空间分布在bcr/abl融合基因形成中的作用

    Institute of Scientific and Technical Information of China (English)

    张青; 周淑芸; 刘晓力; 牛超; 徐岚; 陈赛娟

    2002-01-01

    目的从生物体视学角度分析bcr/abl融合基因的形成机制.方法应用荧光原位杂交和激光共聚焦扫描显微镜技术,观察γ-射线对IM9细胞中的bcr和abl基因在间期核内三维空间分布的影响.结果abl和bcr基因在间期核内有其特定的分布区域,且该分布区域在细胞周期中呈规律性的动态变化.放射性照射会使abl和bcr基因之间的距离缩短.结论abl和bcr基因在间期细胞核内的易接近性是bcr/abl融合基因形成的因素之一.

  4. Detection of BCR/ABL Fusion Gene in Interphase Cens with Bi-labelling Hybridization in Situ%双标记原位杂交法检测间期细胞BCR/ABL融合基因

    Institute of Scientific and Technical Information of China (English)

    袁长吉; 王建伟; 李舜华; 易永林

    2003-01-01

    目的:应用双标记原位杂交方法检测BCR/ABL融合基因.方法:BCR基因探针用地高辛标记,碱性磷酸酶显色;ABL基因用3H-dATP标记,核子乳胶放射自显影.结果:检测9例初治的慢性粒细胞白血病(CML)病人均为阳性,阳性细胞比例为93%;检测CML来源的K562细胞株阳性细胞占98.8%;正常人假阳性率为0.75%.结论:该方法简便、快速,适用于CML微小残留病的检测.

  5. A novel Lyn-protein kinase Cδ/ε-protein kinase D axis is activated in B cells by signalosome-independent alternate pathway BCR signaling.

    Science.gov (United States)

    Guo, Benchang; Rothstein, Thomas L

    2013-06-01

    BCR signaling initiates multiple activities critical for B-cell function. Recently, we identified an alternate BCR signaling pathway, induced by IL-4, that is signalosome-independent, unlike the classical signalosome-dependent pathway, and that leads to activation of the MAP kinase, ERK. Here we questioned whether alternate pathway signaling extends to other key downstream events, especially protein kinase D (PKD) activation. We found that in murine spleen-derived B cells the IL-4-induced alternate pathway for BCR signaling results in PKD and PKD substrate phosphorylation, and that alternate pathway phosphorylation of HDAC5/7 and other key substrates requires PKD. Furthermore, we found that tyrosine phosphorylation of PKCδ/ε occurs as a result of alternate but not classical pathway signaling and is required for phosphorylation of PKD and PKD substrates. This result identifies PKCδ/ε tyrosine phosphorylation as a unique outcome of the alternate pathway. The alternate pathway is mediated by Lyn that is not required for classical pathway signaling and we found that Lyn associates directly with PKCδ/ε and is required for phosphorylation of PKCδ/ε and of PKD. These findings indicate that IL-4 influences B-cell activation by inducing a novel signaling pathway from BCR to Lyn to PKCδ/ε to PKD.

  6. 66例血液病患者bcr/abl融合基因、Ph染色体结果分析

    Institute of Scientific and Technical Information of China (English)

    刘永林; 虞玉群; 陈益民; 张丽; 彭来君; 施丽华; 谈潘莉; 钱丽丽; 胡正军; 陈婷停

    2011-01-01

    @@ CML特异性费城染色体(Philadephia,Ph)是由t(9:22)(q34:11)易位形成.9号染色体原癌基因abl(Abelson protooncogene)易位至22号染色体的断裂点簇集区(breakpointcluster region,bcr),发生重排,产生ber/abl融合基因,引起CML的始动突变.融合基因bcr/abl几乎见于所有的慢性粒细胞性白血病、25%~50%的急性B系淋巴细胞性白血病(ALL)和约5%的急性粒细胞性白血病中,本文统计了进行染色体和bcr/abl融合基因检查的初诊血液病66例,对其骨髓细胞染色体核型及bcr/abl融合基因进行分析.

  7. Rapid Evolution to Blast Crisis Associated with a Q252H ABL1 Kinase Domain Mutation in e19a2 BCR-ABL1 Chronic Myeloid Leukaemia

    Directory of Open Access Journals (Sweden)

    Sarah L. McCarron

    2013-01-01

    Full Text Available A minority of chronic myeloid leukaemia (CML patients express variant transcripts of which the e19a2 BCR-ABL1 fusion is the most common. Instances of tyrosine kinase inhibitor (TKI resistance in e19a2 BCR-ABL1 CML patients have rarely been reported. A case of e19a2 BCR-ABL1 CML is described in whom imatinib resistance, associated with a Q252H ABL1 kinase domain mutation, became apparent soon after initiation of TKI therapy. The patient rapidly transformed to myeloid blast crisis (BC with considerable bone marrow fibrosis and no significant molecular response to a second generation TKI. The clinical course was complicated by comorbidities with the patient rapidly succumbing to advanced disease. This scenario of Q252H-associated TKI resistance with rapid BC transformation has not been previously documented in e19a2 BCR-ABL1 CML. This case highlights the considerable challenges remaining in the management of TKI-resistant BC CML, particularly in the elderly patient.

  8. Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era.

    Directory of Open Access Journals (Sweden)

    Zafar Iqbal

    Full Text Available BACKGROUND: BCR-ABL kinase domain mutations are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CML patients. Recent studies indicate the presence of pre-existing BCR-ABL mutations in a higher percentage of CML patients when CD34+ stem/progenitor cells are investigated using sensitive techniques, and these mutations are associated with imatinib resistance and disease progression. However, such studies were limited to smaller number of patients. METHODS: We investigated BCR-ABL kinase domain mutations in CD34+ cells from 100 chronic-phase CML patients by multiplex allele-specific PCR and sequencing at diagnosis. Mutations were re-investigated upon manifestation of imatinib resistance using allele-specific PCR and direct sequencing of BCR-ABL kinase domain. RESULTS: Pre-existing BCR-ABL mutations were detected in 32/100 patients and included F311L, M351T, and T315I. After a median follow-up of 30 months (range 8-48, all patients with pre-existing BCR-ABL mutations exhibited imatinib resistance. Of the 68 patients without pre-existing BCR-ABL mutations, 24 developed imatinib resistance; allele-specific PCR and BCR-ABL kinase domain sequencing detected mutations in 22 of these patients. All 32 patients with pre-existing BCR-ABL mutations had the same mutations after manifestation of imatinib-resistance. In imatinib-resistant patients without pre-existing BCR-ABL mutations, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients except T315I and Y253F mutations responded to imatinib dose escalation. CONCLUSION: Pre-existing BCR-ABL mutations can be detected in a substantial number of chronic-phase CML patients by sensitive allele-specific PCR technique using CD34+ cells. These mutations are associated with imatinib resistance if affecting drug binding directly or indirectly. After the recent approval of nilotinib, dasatinib, bosutinib and ponatinib for treatment of chronic myeloid

  9. Efficacy of Dasatinib in Treatment of Imatinib-Resistant BCR/ABL Positive Leukemia%达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病的临床研究

    Institute of Scientific and Technical Information of China (English)

    朱雨; 潘良琴; 钱思轩; 宋萍; 于慧; 张苏江; 葛峥; 洪鸣; 田甜

    2013-01-01

    本研究评价达沙替尼治疗原发或继发伊马替尼耐药的BCR/ABL阳性白血病的疗效和安全性.对27例原发或继发伊马替尼耐药的慢性髓系白血病(CML)或Ph阳性急性淋巴细胞白血病(Ph+ ALL)患者,给予达沙替尼100-140 mg/d口服治疗,评估疗效、总体生存和耐受情况.结果表明:27例伊马替尼耐药的BCR/ABL阳性白血病中位达沙替尼治疗时间8(1-66)个月,中位随访时间54(3-75)个月.27例接受达沙替尼治疗的患者中,88.8%获得完全血液学反应(CHR),44.4%获得主要细胞遗传学反应(mCyR),37%获得完全遗传学反应(CCyR),18.5%获得主要分子学反应(MMR).伊马替尼耐药的进展期(CML-AP、CML-BC、骨髓复发Ph+ ALL)患者接受达沙替尼治疗获CCyR率低于疾病稳定期(CML-CP、骨髓缓解Ph+ ALL)患者(P=0.0377),且3-4级不良反应发生率明显增高.达沙替尼治疗后获得CCyR的患者生存期(OS)较未达CCyR者明显延长(63个月vs9个月,P=0.0126).达沙替尼治疗后最常见的3-4级不良反应包括血液学反应如血小板减少(51.8%)、中性粒细胞减少(48.1%)、贫血(33.3%)和非血液学反应如胸腔积液(18.5%)、肺部感染(18.5%)、心包积液(11.1%).3-4级不良反应主要发生在疾病进展期时改服达沙替尼者,均发生于服药12个月内.结论:达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病有效,且在疾病稳定期改服达沙替尼疗效和耐受性更好.%This study was aimed to evaluate the efficacy and safety of dasatinib in BCR/ABL positive leukemia patients with primary or secondary resistance to imatinib.27 patients with primary or secondary imatinib-resistant chronic myelogenous leukemia (CML) or Philadelphia chromosome positive acute lymphocytic leukemia (Ph + ALL) received 100-140 mg/d dasatinib orally.Their overall survival and tolerance were evaluated.The results showed that the median duration of dasatinib therapy was 8 (1-66) months in the 27

  10. A Non-ATP-Competitive Dual Inhibitor of JAK2 and BCR-ABL Kinases: Elucidation of a Novel Therapeutic Spectrum Based on Substrate Competitive Inhibition.

    Science.gov (United States)

    Jatiani, Shashidhar S; Cosenza, Stephen C; Reddy, M V Ramana; Ha, Ji Hee; Baker, Stacey J; Samanta, Ajoy K; Olnes, Matthew J; Pfannes, Loretta; Sloand, Elaine M; Arlinghaus, Ralph B; Reddy, E Premkumar

    2010-04-01

    Here we report the discovery of ON044580, an α-benzoyl styryl benzyl sulfide that possesses potent inhibitory activity against two unrelated kinases, JAK2 and BCR-ABL, and exhibits cytotoxicity to human tumor cells derived from chronic myelogenous leukemia (CML) and myelodysplasia (MDS) patients or cells harboring a mutant JAK2 kinase. This novel spectrum of activity is explained by the non-ATP-competitive inhibition of JAK2 and BCR-ABL kinases. ON044580 inhibits mutant JAK2 kinase and the proliferation of JAK2(V617F)-positive leukemic cells and blocks the IL-3-mediated phosphorylation of JAK2 and STAT5. Interestingly, this compound also directly inhibits the kinase activity of both wild-type and imatinib-resistant (T315I) forms of the BCR-ABL kinase. Finally, ON044580 effectively induces apoptosis of imatinib-resistant CML patient cells. The apparently unrelated JAK2 and BCR-ABL kinases share a common substrate, STAT5, and such substrate competitive inhibitors represent an alternative therapeutic strategy for development of new inhibitors. The novel mechanism of kinase inhibition exhibited by ON044580 renders it effective against mutant forms of kinases such as the BCR-ABL(T315I) and JAK2(V617F). Importantly, ON044580 selectively reduces the number of aneuploid cells in primary bone marrow samples from monosomy 7 MDS patients, suggesting another regulatory cascade amenable to this agent in these aberrant cells. Data presented suggest that this compound could have multiple therapeutic applications including monosomy 7 MDS, imatinib-resistant CML, and myeloproliferative neoplasms that develop resistance to ATP-competitive agents.

  11. Linkage of data from diverse data sources (LDS): a data combination model provides clinical data of corresponding specimens in biobanking information system.

    Science.gov (United States)

    Eminaga, Okyaz; Özgür, Enver; Semjonow, Axel; Herden, Jan; Akbarov, Ilgar; Tok, Ali; Engelmann, Udo; Wille, Sebastian

    2013-10-01

    To provide sufficient clinical data for corresponding specimens from diverse databases established before the implementation of biobanks for research purposes with respect to data privacy regulations. For this purpose, we developed a data model called "linkage of data from diverse data sources (LDS)". The data model was developed to merge clinical data from an existing local database with biospecimen repository data in our serum bank for uro-oncology. This concept combines two data models based on XML: the first stores information required to connect multiple data sources and retrieve clinical data, and the second provides a data architecture to acquire clinical and repository data. All data were anonymized and encrypted using the Advanced Encryption Standard. X.509 certificates were applied to secure data access. Furthermore, we tested the feasibility of implementing these models in the information management system for biobanking. The data concept can provide clinical and repository data of biospecimens. Only authorized receivers can access these data. Sensitive and personal data are not accessible by the data receivers. The data receiver cannot backtrack to the individual donor using the data model. The acquired data can be converted into a text file format supported by familiar statistical software. Supplementary tools were implemented to generate and view XML documents based on these data models. This data model provides an effective approach to distribute clinical and repository data from different data sources to enable data analysis compliant with data privacy regulations.

  12. Arsenic Mobility and Availability in Sediments by Application of BCR Sequential Extractions Method; Movilidad y Disponibilidad de Arsenico en Sedimentos Mediante la Aplicacion del Metodo de Extracciones Secuenciales BCR

    Energy Technology Data Exchange (ETDEWEB)

    Larios, R.; Fernandez, R.; Rucandio, M. I.

    2011-05-13

    Arsenic is a metalloid found in nature, both naturally and due to anthropogenic activities. Among them, mining works are an important source of arsenic release to the environment. Asturias is a region where important mercury mines were exploited, and in them arsenic occurs in para genesis with mercury minerals. The toxicity and mobility of this element depends on the chemical species it is found. Fractionation studies are required to analyze the mobility of this metalloid in soils and sediments. Among them, the proposed by the Bureau Community of Reference (BCR) is one of the most employed. This method attempts to divide up, by operationally defined stages, the amount of this element associated with carbonates (fraction 1), iron and manganese oxy hydroxides (fraction 2), organic matter and sulphides (fraction 3), and finally as the amount associated residual fraction to primary and secondary minerals, that is, from the most labile fractions to the most refractory ones. Fractionation of arsenic in sediments from two mines in Asturias were studied, La Soterrana and Los Rueldos. Sediments from La Soterrana showed high levels of arsenic in the non-residual phases, indicating that the majority of arsenic has an anthropogenic origin. By contrast, in sediments from Los Rueldos most of the arsenic is concentrated in the residual phase, indicating that this element remains bound to very refractory primary minerals, as is also demonstrated by the strong correlation of arsenic fractionation and the fractionation of elements present in refractory minerals, such as iron, aluminum and titanium. (Author) 51 refs.

  13. Multidimensional single-cell analysis of BCR signaling reveals proximal activation defect as a hallmark of chronic lymphocytic leukemia B cells.

    Directory of Open Access Journals (Sweden)

    M Lia Palomba

    Full Text Available PURPOSE: Chronic Lymphocytic Leukemia (CLL is defined by a perturbed B-cell receptor-mediated signaling machinery. We aimed to model differential signaling behavior between B cells from CLL and healthy individuals to pinpoint modes of dysregulation. EXPERIMENTAL DESIGN: We developed an experimental methodology combining immunophenotyping, multiplexed phosphospecific flow cytometry, and multifactorial statistical modeling. Utilizing patterns of signaling network covariance, we modeled BCR signaling in 67 CLL patients using Partial Least Squares Regression (PLSR. Results from multidimensional modeling were validated using an independent test cohort of 38 patients. RESULTS: We identified a dynamic and variable imbalance between proximal (pSYK, pBTK and distal (pPLCγ2, pBLNK, ppERK phosphoresponses. PLSR identified the relationship between upstream tyrosine kinase SYK and its target, PLCγ2, as maximally predictive and sufficient to distinguish CLL from healthy samples, pointing to this juncture in the signaling pathway as a hallmark of CLL B cells. Specific BCR pathway signaling signatures that correlate with the disease and its degree of aggressiveness were identified. Heterogeneity in the PLSR response variable within the B cell population is both a characteristic mark of healthy samples and predictive of disease aggressiveness. CONCLUSION: Single-cell multidimensional analysis of BCR signaling permitted focused analysis of the variability and heterogeneity of signaling behavior from patient-to-patient, and from cell-to-cell. Disruption of the pSYK/pPLCγ2 relationship is uncovered as a robust hallmark of CLL B cell signaling behavior. Together, these observations implicate novel elements of the BCR signal transduction as potential therapeutic targets.

  14. Rapid detection of BCR-ABL fusion genes using a novel combined LUX primer, in-cell RT-PCR and flow cytometric method.

    Science.gov (United States)

    Shi, Yan; Li, Li-Zhen; Sun, Jian-Zhi; Zhang, Ti; Peng, Jun; Xu, Cong-Gao

    2008-01-01

    Currently, quantitative and semiquantitative assays for minimal residual disease detection include fluorescence in situ hybridisation, multiparameter flow cytometric immunophenotyping and real-time quantitative polymerase chain reaction (RQ-PCR). We have developed a new approach to detect hybrid breakpoint cluster region and Abelson proto-oncogene (BCR-ABL) transcripts inside suspension cells using in situ RT-PCR and light upon extension (LUX) primer, followed by rapid quantitative analysis with flow cytometry. After cellular permeabilization and fixation of single cell suspension, the neoplastic mRNA was reverse transcribed and amplified by PCR with LUX primer. The results demonstrated that a strong positive yellow-green signal was observed in 99-100% cells of K562 cell line, only the red nucleus was detected in NB4 cell line and normal controls. The technique has been utilised to study 12 patients with chronic myeloid leukemia, and the results were compared with those of BCR-ABL fusion mRNA by RT-PCR and BCR-ABL fusion gene of the interphase cells by fluorescence in situ hybridization (FISH). In the five diagnosed patients, 90-98% cells were strongly positive. Four patients, including three patients treated with interferon-alpha and hydroxyurea and one patient treated with imatinib mesylate, had 26-82.5% positive cells. Three patients treated with imatinib mesylate were negative. The in situ RT-PCR results demonstrated complete concordance with the results of I-FISH and RT-PCR. A fluorescence signal was detectable at 1/10(4) cells and became negative below this threshold with flow cytometry. The results of the present study suggest that (1) LUX primers can be used to efficiently detect BCR-ABL fusion mRNA by in-cell RT-PCR; (2) the novel technique is a specific and sensitive way of detecting fusion gene with potential clinical usefulness.

  15. A generalized quantitative antibody homeostasis model: regulation of B-cell development by BCR saturation and novel insights into bone marrow function

    Science.gov (United States)

    Prechl, József

    2017-01-01

    In a pair of articles, we present a generalized quantitative model for the homeostatic function of clonal humoral immune system. In this first paper, we describe the cycles of B-cell expansion and differentiation driven by B-cell receptor engagement. The fate of a B cell is determined by the signals it receives via its antigen receptor at any point of its lifetime. We express BCR engagement as a function of apparent affinity and free antigen concentration, using the range of 10−14–10−3 M for both factors. We assume that for keeping their BCR responsive, B cells must maintain partial BCR saturation, which is a narrow region defined by [Ag]≈KD. To remain in this region, B cells respond to changes in [Ag] by proliferation or apoptosis and modulate KD by changing BCR structure. We apply this framework to various niches of B-cell development such as the bone marrow, blood, lymphoid follicles and germinal centers. We propose that clustered B cells in the bone marrow and in follicles present antigen to surrounding B cells by exposing antigen captured on complement and Fc receptors. The model suggests that antigen-dependent selection in the bone marrow results in (1) effector BI cells, which develop in blood as a consequence of the inexhaustible nature of soluble antigens, (2) memory cells that survive in antigen rich niches, identified as marginal zone B cells. Finally, the model implies that memory B cells could derive survival signals from abundant non-cognate antigens. PMID:28265373

  16. Targeting of heme oxygenase-1 attenuates the negative impact of Ikaros isoform 6 in adult BCR-ABL1-positive B-ALL.

    Science.gov (United States)

    Lin, Xiaojing; Zou, Xingli; Wang, Ziming; Fang, Qin; Chen, Shuya; Huang, Jun; Zhe, Nana; Yu, Meisheng; Zhang, Yaming; Wang, Jishi

    2016-08-16

    The correlation between Heme oxygenase-1 (HO-1) and dominant-negative Ikaros isoform 6 (IK6) is unclear. Firstly, we detected that IK6 existed in 20 of 42 (47.6%) adult BCR-ABL1-positive B-lineage acute lymphoblastic leukemia (BCR-ABL1-positive B-ALL) by using reverse transcribed polymerase chain reaction (PCR) and nucleotide sequencing. IK6-positive patients had an unfavorable outcome compared with IK6-negative ones. Further study showed that the level of HO-1 expression was higher in IK6-positive patients' samples than that in IK6-negative ones. And there was a strong correlation between the expression of IK6 and HO-1. The growth of primary CD34+ leukemic cells derived from our IK6-positive patients' pool was prohibited by silencing HO-1, further promoting their apoptosis. Furthermore, primary CD34+ leukemic cells derived from IK6-positive patients shown poor responses to imatinib in comparison with wild-type (IK1) patients, suggesting that the expression of IK6 resisted to imatinib in adult BCR-ABL1-positive B-ALL. Importantly, inhibition of HO-1 also increased their sensitivity to tyrosine kinase inhibitors (TKIs). Finally, we found that IK6 activated downstream STAT5, and HO-1 was one of the downstream target genes of STAT5. In conclusion, HO-1 is an essential survival factor in BCR-ABL1-positive B-ALL with IK6, and targeting HO-1 can attenuate the negative impact of IK6.

  17. UV Differentially Induces Oxidative Stress, DNA Damage and Apoptosis in BCR-ABL1-Positive Cells Sensitive and Resistant to Imatinib

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    Ewelina Synowiec

    2015-08-01

    Full Text Available Chronic myeloid leukemia (CML cells express the active BCR-ABL1 protein, which has been targeted by imatinib in CML therapy, but resistance to this drug is an emerging problem. BCR-ABL1 induces endogenous oxidative stress promoting genomic instability and imatinib resistance. In the present work, we investigated the extent of oxidative stress, DNA damage, apoptosis and expression of apoptosis-related genes in BCR-ABL1 cells sensitive and resistant to imatinib. The resistance resulted either from the Y253H mutation in the BCR-ABL1 gene or incubation in increasing concentrations of imatinib (AR. UV irradiation at a dose rate of 0.12 J/(m2·s induced more DNA damage detected by the T4 pyrimidine dimers glycosylase and hOGG1, recognizing oxidative modifications to DNA bases in imatinib-resistant than -sensitive cells. The resistant cells displayed also higher susceptibility to UV-induced apoptosis. These cells had lower native mitochondrial membrane potential than imatinib-sensitive cells, but UV-irradiation reversed that relationship. We observed a significant lowering of the expression of the succinate dehydrogenase (SDHB gene, encoding a component of the complex II of the mitochondrial respiratory chain, which is involved in apoptosis sensing. Although detailed mechanism of imatinib resistance in AR cells in unknown, we detected the presence of the Y253H mutation in a fraction of these cells. In conclusion, imatinib-resistant cells may display a different extent of genome instability than their imatinib-sensitive counterparts, which may follow their different reactions to both endogenous and exogenous DNA-damaging factors, including DNA repair and apoptosis.

  18. 自身淬灭荧光定量PCR检测慢性粒细胞白血病bcr/abl mRNA%Quantification of bcr/abl mRNA in patients with chronic myeloid leukemia by using real-time quantitative fluorescence PCR with self-quenched primer

    Institute of Scientific and Technical Information of China (English)

    彭辉; 冯文莉; 王小中; 曾建明; 肖青; 潘健; 曹唯希; 罗云萍; 黄宗干

    2007-01-01

    目的 利用自身淬灭探针技术建立一种能检测慢性粒细胞白血病(CML)bcr/abl融合基因mRNA的实时荧光定量PCR方法,为CML的诊断、疗效观察以及微量残留白血病(MRD)的监测提供有效手段.方法 用逆转录PCR方法(RT-PCR)扩增K562细胞的bcr/abl融合基因,A-T克隆法构建定量标准模板;设计自身淬灭荧光引物(探针),建立自身淬灭荧光定量逆转录PCR方法(FQRT-PCR),并对该方法的线性检测范围、灵敏度、重复性、稳定性进行检测;然后检测临床白血病患者骨髓标本bcr/abl mRNA.结果 建立的FQ-RT-PCR方法可检测10 copies/μl的bcr/abl重组质粒,并能从105个正常细胞中检出1个白血病细胞,该方法的批内、批间变异系数(CV)分别为2.1%、6.1%,线性检测范围为102~109 copies/μl.25例CML患者bcr/abl融合基因mRNA表达量中位数为4.50×104[(0.45~89.00)×104]copies/μg RNA,其中11例慢性期初诊患者bcr/abl mRNA表达量中位数为5.45×104[(2.95~19.30)×104]copies/μg RNA,6例急变期患者bcr/abl mRNA表达量中位数为13.00×104[(4.10~89.00)×104]copies/μg RNA,8例慢性期治疗后复查患者bcr/ablmRNA表达量中位数为2.35×104[(0.45~5.12)×104]copies/μg RNA,CML急变期患者bcr/abl融合基因表达水平与慢性期患者之间差异有统计学意义(q=3.41,P<0.05).PCR产物经电泳分析,其中21例CML患者为b3a2型,4例CML患者为b2a2型;3例急性淋巴细胞白血病(ALL)患者中,1例有bcr/abl mRNA表达,为b2a2型.结论 所建立的基于自身淬灭探针技术的实时荧光定量PCR检测方法灵敏、特异、重复性好,结果用拷贝数表示,准确可靠,利于标准统一.可广泛用于CML的诊断、疗效观察以及MRD的监测.

  19. [Standardization of quantitative detection of BCR-ABL gene expression by RQ-PCR in patients with chronic myeloid leukemia in cooperation with European Leukemia Net].

    Science.gov (United States)

    Sacha, Tomasz; Zawada, Magdalena; Czekalska, Sylwia; Florek, Izabela; Mueller, Martin; Gniot, Michał; Jaźwiec, Bozena; Kyrcz-Krzemień, Sławomira; Leszczyńska, Aleksandra; Lewandowski, Krzysztof; Matiakowska, Karolina; Solarska, Iwona; Stokłosa, Tomasz; Skotnicki, Aleksander B

    2010-01-01

    Monitoring of chronic myeloid leukemia treatment efficacy requires very sensitive methods of BCR-ABL gene detection based on polymerase chain reaction (PCR). The lack of comparability of BCR-ABL mRNA quantification results generated by various methodologies in different laboratories was the cause of an international multicenter trial initiation with the participation of 133 laboratories in 24 European countries cooperating within the "EUTOS for CML" project. Pracownia Diagnostyki Molekularnej Kliniki Hematologii is taking part in standardisation rounds organised since 2005. The compatibility of methodology used in Pracownia with European Leukemia Net (ELN) standards was confirmed, and correction factor for the expression of RQ-PCR results in an international scale was calculated. Pracownia was charge by ELN with a task of conducting the standardisation in polish molecular biology laboratories. Test probes were prepared and sent to eight cooperating laboratories. The results obtained in six laboratories were concordant with results from laboratory in Krakow after conversion to international scale, therefore it was possible to calculate individual correction factors. The participation of polish laboratories in international standardization process created the opportunity for unification of BCR-ABL quantification methodologies with recommendations of international experts, and showed that the quality of analyses performed in majority of them was satisfactory enough to calculate correction factor and to express the RQ-PCR results in widely accepted international scale.

  20. An appraisal of conventional, microwave and ultrasound BCR extraction methods for the analysis of metals in sediments of Pančevo, Serbia

    Directory of Open Access Journals (Sweden)

    Relić D.

    2013-04-01

    Full Text Available We use conventional, microwave and ultrasound assisted sequential extraction, of defined time and power, techniques for extractions of Cd, Cu, Cr, Ni, Pb and Zn in sediments and certified material. We did not change the conditions of extractions through steps, cause we what to see is there difference in extraction results for the certified material and sediments. We use lower powers and time from microwave and ultrasound extraction in order to avoid additional heating and boiling of the samples. Steps 1–3 of the BCR (Community Bureau of Reference, excluding the hydrogen peroxide digestion in step 3, were completed in 16 h in the conventional, in 120 s with 90 W power of microwave and in 30 min of 42 kHz of an ultrasonic frequency. Digestion of organic matter with hydrogen peroxide was performed the same for all techniques. The fourth step, the pseudo-total content, was performed the same on samples remaining after performing the extraction of the previous three phases either conventionally, microwave-assisted or with ultrasound. The precision and accuracy of the proposed procedures were evaluated using a certified reference material BCR701. Acceptable accuracy for most of the metals was observed for all three steps of BCR protocol applying a 16 h total shaking period. Metals were determined with an acceptable accuracy after the pseudo-total step; expect Cr. Results obtained after the application of different techniques on sediments were comparable with ANOVA test for the 95 % of confidence level.

  1. Evaluating the mobility of toxic metals in untreated industrial wastewater sludge using a BCR sequential extraction procedure and a leaching test.

    Science.gov (United States)

    Kazi, T G; Jamali, M K; Kazi, G H; Arain, M B; Afridi, H I; Siddiqui, A

    2005-09-01

    The distribution and speciation of toxic metals in industrial wastewater sludge (IWS) was investigated. In this work, the modified BCR three-stage sequential extraction procedure was applied to the fractionation of Cr Pb Ni, and Cd in untreated industrial wastewater sludge from industrial sites in Hyderabad (Pakistan). The extracts were analyzed using electrothermal atomic absorption spectrometry. The procedure was evaluated using a certified reference material for soil mixed with sewage sludge BCR 483. The results from the partitioning study indicate that more easily mobilized forms (acid exchangeable) of Cd were dominant. The oxidizable fraction was dominant for all four toxic metals. Metal recovery was good, with metal recovered through the extractant steps and the total metal determined after microwave digestion. Lixiviation tests (DIN 38414-S4) were used to evaluate the leaching of toxic species from IWS, and it was observed that levels of leachable toxic metals were low compared to the amount of metal extracted in the exchangeable fraction of the BCR protocol.

  2. Coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites for the detection of BCR/ABL fusion gene

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xueping [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Wang, Li [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Department of Medical Laboratory, Chongqing Emergency Medical Center (Chongqing The Fourth Hospital), Chongqing, 400016 (China); Sheng, Shangchun [The No.2 Peoples' Hospital of Yibin, Sichuan, 644000 (China); Wang, Teng; Yang, Juan [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Xie, Guoming, E-mail: guomingxie@cqmu.edu.cn [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Feng, Wenli, E-mail: fengwlcqmu@sina.com [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China)

    2015-08-19

    This article described a novel method by coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites (GS/PANI/AuNPs) for highly sensitive and specific detection of BCR/ABL fusion gene (bcr/abl) in chronic myeloid leukemia (CML). DNA circuit known as catalyzed hairpin assembly (CHA) is enzyme-free and can be simply operated to achieve exponential amplification, which has been widely employed in biosensing. However, application of CHA has been hindered by the need of specially redesigned sequences for each single-stranded DNA input. Herein, a transducer hairpin (HP) was designed to obtain a universal DNA circuit with favorable signal-to-background ratio. To further improve signal amplification, GS/PANI/AuNPs with excellent conductivity and enlarged effective area were introduced into this DNA circuit. Consequently, by combining the advantages of CHA and GS/PANI/AuNPs, bcr/abl could be detected in a linear range from 10 pM to 20 nM with a detection limit of 1.05 pM. Moreover, this protocol showed excellent specificity, good stability and was successfully applied for the detection of real sample, which demonstrated its great potential in clinical application. - Highlights: • A transducer hairpin was designed to improve the versatility of DNA circuit. • GS/PANI/AuNPs were introduced to the DNA circuit for further signal amplification. • The established biosensor displayed high sensitivity and good specificity.

  3. Low expression of miR-196b enhances the expression of BCR-ABL1 and HOXA9 oncogenes in chronic myeloid leukemogenesis.

    Directory of Open Access Journals (Sweden)

    Yue Liu

    Full Text Available MicroRNAs (miRNAs can function as tumor suppressors or oncogene promoters during tumor development. In this study, low levels of expression of miR-196b were detected in patients with chronic myeloid leukemia. Bisulfite genomic sequencing PCR and methylation-specific PCR were used to examine the methylation status of the CpG islands in the miR-196b promoter in K562 cells, patients with leukemia and healthy individuals. The CpG islands showed more methylation in patients with chronic myeloid leukemia compared with healthy individuals (P<0.05, which indicated that low expression of miR-196b may be associated with an increase in the methylation of CpG islands. The dual-luciferase reporter assay system demonstrated that BCR-ABL1 and HOXA9 are the target genes of miR-196b, which was consistent with predictions from bioinformatics software analyses. Further examination of cell function indicated that miR-196b acts to reduce BCR-ABL1 and HOXA9 protein levels, decrease cell proliferation rate and retard the cell cycle. A low level of expression of miR-196b can cause up-regulation of BCR-ABL1 and HOXA9 expression, which leads to the development of chronic myeloid leukemia. MiR-196b may represent an effective target for chronic myeloid leukemia therapy.

  4. Immunologic evaluation of peptides derived from BCR/ABL-out-of-frame fusion protein in HLA A2.1 transgenic mice.

    Science.gov (United States)

    Casnici, Claudia; Volpe, Gisella; Crotta, Katia; Lattuada, Donatella; Saglio, Giuseppe; Marelli, Ornella

    2012-05-01

    Philadelphia chromosome-positive chronic myelogenous leukemia and acute lymphocytic leukemia express, besides the main BCR/ABL transcripts, novel BCR/ABL transcripts derived from alternative splicing between BCR exons 1, 13, or 14 with ABL exons 4 and 5. Their translational products present at C-terminus an amino acid portion derived from out-of-frame (OOF) reading of the ABL gene. The presence of OOF-peptide-specific T cells in chronic myelogenous leukemia patients was demonstrated and a first study in in vivo model demonstrated that OOF ABL portion was immunogenic in human leukcocyte antigen (HLA)-A2.1 transgenic mice. Here we immunized HLA A2.1 mice with novel peptides designed on the ABL OOF sequence, containing epitopes with high affinity for HLA A2.1 molecule. The specific immune response, cellular and humoral, obtained ex vivo against HLA A2.1-positive human chronic myelogenous leukemia cells using peptide 22-53 and the cytotoxic activity induced by peptide 32mer confirm the possibility to use the ABL OOF portion as target to evoke a specific and multiple immune response in Philadelphia positive leukemic patients in cytogenetic remission.

  5. Effects of modified zeolite on the removal and stabilization of heavy metals in contaminated lake sediment using BCR sequential extraction.

    Science.gov (United States)

    Wen, Jia; Yi, Yuanjie; Zeng, Guangming

    2016-08-01

    Sediment can be applied on land as a soil conditioner. However, toxic substances such as heavy metals within the sediment often lead to soil contamination if no proper management is conducted prior to land application. In order to reduce the bioavailable portion of heavy metals such as Pb, Cu, Zn and Cd, zeolite as a kind of stabilizer was investigated on the effect of metal stabilization in sediment. Zeolite was firstly modified and screened to get the best condition for removal of heavy metals. Results showed that the granulated zeolite with NaCl conditioning had the highest CEC and metal sorption. Using BCR sequential extraction, the selected modified zeolite effectively stabilized Pb, Cu, Zn and Cd in sediment to different extents. It was most suitable for Cd stabilization by reducing its acid exchangeable fraction while increasing the contents of the reducible and residual fractions. Modified zeolite also immobilized Cu, Zn and Pb in sediment by enhancing one stable fraction while decreasing the acid exchangeable fraction.

  6. Evaluation of Mobility, Bioavailability and Toxicity of Pb and Cd in Contaminated Soil Using TCLP, BCR and Earthworms

    Directory of Open Access Journals (Sweden)

    Maria Luiza F. M. Kede

    2014-11-01

    Full Text Available The objective of the present study was to investigate the reduction of mobility, availability and toxicity found in soil contaminated with lead (Pb and cadmium (Cd from Santo Amaro Municipality, Bahia, Brazil using two combined methods, commonly tested separately according to the literature: metal mobilization with phosphates and phytoextraction. The strategy applied was the treatment with two sources of phosphates (separately and mixed followed by phytoremediation with vetiver grass (Vetiveria zizanioides (L.. The treatments applied (in triplicates were: T1—potassium dihydrogen phosphate (KH2PO4; T2—reactive natural phosphate fertilizer (NRP and; T3—a mixture 1:1 of KH2PO4 and NRP. After this step, untreated and treated soils were planted with vetiver grass. The extraction procedures and assays applied to contaminated soil before and after the treatments included metal mobility test (TCLP; sequential extraction with BCR method; toxicity assays with Eisenia andrei. The soil-to-plant transfer factors (TF for Pb and Cd were estimated in all cases. All treatments with phosphates followed by phytoremediation reduced the mobility and availability of Pb and Cd, being KH2PO4 (T1 plus phytoremediation the most effective one. Soil toxicity however, remained high after all treatments.

  7. Evaluation of mobility, bioavailability and toxicity of Pb and Cd in contaminated soil using TCLP, BCR and earthworms.

    Science.gov (United States)

    Kede, Maria Luiza F M; Correia, Fabio V; Conceição, Paulo F; Junior, Sidney F Salles; Marques, Marcia; Moreira, Josino C; Pérez, Daniel V

    2014-11-07

    The objective of the present study was to investigate the reduction of mobility, availability and toxicity found in soil contaminated with lead (Pb) and cadmium (Cd) from Santo Amaro Municipality, Bahia, Brazil using two combined methods, commonly tested separately according to the literature: metal mobilization with phosphates and phytoextraction. The strategy applied was the treatment with two sources of phosphates (separately and mixed) followed by phytoremediation with vetiver grass (Vetiveria zizanioides (L.)). The treatments applied (in triplicates) were: T1-potassium dihydrogen phosphate (KH2PO4); T2-reactive natural phosphate fertilizer (NRP) and; T3-a mixture 1:1 of KH2PO4 and NRP. After this step, untreated and treated soils were planted with vetiver grass. The extraction procedures and assays applied to contaminated soil before and after the treatments included metal mobility test (TCLP); sequential extraction with BCR method; toxicity assays with Eisenia andrei. The soil-to-plant transfer factors (TF) for Pb and Cd were estimated in all cases. All treatments with phosphates followed by phytoremediation reduced the mobility and availability of Pb and Cd, being KH2PO4 (T1) plus phytoremediation the most effective one. Soil toxicity however, remained high after all treatments.

  8. Speciation of Heavy Metals by Modified BCR Sequential Extraction in Soils Contaminated by Phosphogypsum in Sfax, Tunisia

    Directory of Open Access Journals (Sweden)

    Ahmed Wali

    2015-01-01

    Full Text Available The accumulation of trace metals in soil is a serious environmental problem that creates a hazard when metals are transferred to water or plants. To understand the mobility and bioavailability of trace metals, the concentrations and distributions of trace metals must be established for different physical and chemical phases of the soil. We determined the concentrations of trace metals (Zn, Pb, Cu, Cr, Co, Ni, Mn, and Fe in soil using the sequential extraction method recommended by Community Bureau of Reference (BCR and analysed chemical properties, such as the pH, cation exchange capacity, total organic carbon, electrical conductivity, and calcium carbonate. Our results revealed higher concentrations of trace metals in topsoil samples (0–20 cm than in subsoil samples (20–40 cm and 40–60 cm for most metals at four sites. Zn in the topsoil was mostly associated with the non-resistant fraction at all sites. Approximately 60% more Pb was bound to the non-residual, exchangeable and reducible fractions at all sites, and soil depths. Cr, Cu, Ni and Fe were mainly in the residual fraction, whereas Mn was largely present in the non-resistant fraction. The global contamination factor of trace metals decreased with soil depth. The mobility and bioavailability were greatest for Zn, followed by Cu and Pb. DOI: http://dx.doi.org/10.5755/j01.erem.70.4.7807

  9. A BCR-ABL1 cutoff of 1.5% at 3 months, determined by the GeneXpert system, predicts an optimal response in patients with chronic myeloid leukemia

    Science.gov (United States)

    García-Gutiérrez, Valentín; Gómez-Casares, María T.; Puerta, José M.; Alonso-Domínguez, Juan M.; Osorio, Santiago; Hernández-Boluda, Juan C.; Collado, Rosa; Ramírez, María J.; Ibáñez, Fátima; Martín, María L.; Rodríguez-Gambarte, Juan D.; Martínez-Laperche, Carolina; Gómez, Montse; Fiallo, Dolly V.; Redondo, Sara; Rodríguez, Alicia; Ruiz-Nuño, Concepción; Steegmann, Juan L.

    2017-01-01

    In chronic myeloid leukemia (CML) patients, 3-month BCR-ABL1 levels have consistently been correlated with further outcomes. Monitoring molecular responses in CML using the GeneXpert (Cepheid) platform has shown an optimal correlation with standardized RQ-PCR (IS) when measuring BCR-ABL1 levels lower than 10%, as it is not accurate for values over 10%. The aim of the present study was to determine the predictive molecular value at three months on different outcome variables using the Xpert BCR-ABL1 MonitorTM assay (Xpert BCR-ABL1). We monitored 125 newly diagnosed consecutive CML patients in the chronic phase (CML-CP) using an automated method: Xpert BCR-ABL1. Only 5% of patients did not achieve an optimal response at 3 months, and the 10% BCR-ABL1 cutoff defined by RQ-PCR (IS) methods was unable to identify significant differences in the probabilities of achieving a complete cytogenetic response (CCyR) (50% vs. 87%, p = 0.1) or a major molecular response (MMR) (60% vs. 80%, p = 0.29) by 12 months. In contrast, a cutoff of 1.5% more accurately identified differences in the probabilities of achieving CCyR (98% vs. 54%, p<0.001) and MMR (88% vs. 56%, p<0.001) by 12 months, as well as probabilities of treatment changes (p = 0.005). Therefore, when using the Xpert BCR-ABL1 assay, a cutoff of 1.5% at 3 months could with high probability identify patients able to achieve an optimal response at 12 months. PMID:28278193

  10. STUDY ON QUANTITATIVE SPECIATION, BY BCR METHOD, OF ZINC CONTENT FROM RIVER SEDIMENTS

    Directory of Open Access Journals (Sweden)

    Georgiana Vasile

    2008-06-01

    Full Text Available The present work presents the results obtained during investigation of the zinc content of the water and river sediments in an area polluted by mining activities, to provide information on the mobility and availability of this element. Sediment and water samples have been collected from significant sites in a former mining area in which with some sterile pits, which represent a major environmental hazard.

  11. miR-29b suppresses CML cell proliferation and induces apoptosis via regulation of BCR/ABL1 protein

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yajuan; Wang, Haixia; Tao, Kun [Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated of Ministry of Education, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016 (China); Xiao, Qing [Department of Hematology, The First Affiliated Hospital, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016 (China); Huang, Zhenglan; Zhong, Liang; Cao, Weixi [Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated of Ministry of Education, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016 (China); Wen, Jianping [Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5 (Canada); Feng, Wenli, E-mail: fengwlcqmu@sina.com [Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated of Ministry of Education, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016 (China)

    2013-05-01

    MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally and are critical for many cellular pathways. Recent evidence has shown that aberrant miRNA expression profiles and unique miRNA signaling pathways are present in many cancers. Here, we demonstrate that miR-29b is markedly lower expressed in CML patient samples. Bioinformatics analysis reveals a conserved target site for miR-29b in the 3′-untranslated region (UTR) of ABL1. miR-29b significantly suppresses the activity of a luciferase reporter containing ABL1-3′UTR and this activity is not observed in cells transfected with mutated ABL1-3′UTR. Enforced expression of miR-29b in K562 cells inhibits cell growth and colony formation ability thereby inducing apoptosis through cleavage of procaspase 3 and PARP. Furthermore, K562 cells transfected with a siRNA targeting ABL1 show similar growth and apoptosis phenotypes as cells overexpression of miR-29b. Collectively, our results suggest that miR-29b may function as a tumor suppressor by targeting ABL1 and BCR/ABL1. - Highlights: ► miR-29b expression was downregulated in CML patients. ► ABL1 was identified as a direct target gene of miR-29b. ► Enforced expression of miR-29b inhibits cell proliferation and induces apoptosis. ► miR-29b might be a therapeutic target to CML.

  12. Pharmacophore modeling of nilotinib as an inhibitor of ATP-binding cassette drug transporters and BCR-ABL kinase using a three-dimensional quantitative structure-activity relationship approach.

    Science.gov (United States)

    Shukla, Suneet; Kouanda, Abdul; Silverton, Latoya; Talele, Tanaji T; Ambudkar, Suresh V

    2014-07-07

    Nilotinib (Tasigna) is a tyrosine kinase inhibitor approved by the FDA to treat chronic phase chronic myeloid leukemia patients. It is also a transport substrate of the ATP-binding cassette (ABC) drug efflux transporters ABCB1 (P-glycoprotein, P-gp) and ABCG2 (BCRP), which may have an effect on the pharmacokinetics and toxicity of this drug. The goal of this study was to identify pharmacophoric features of nilotinib in order to potentially develop specific inhibitors of BCR-ABL kinase with minimal interactions with ABC drug transporters. Three-dimensional pharmacophore modeling and quantitative structure-activity relationship (QSAR) studies were carried out on a series of nilotinib analogues to identify chemical features that contribute to inhibitory activity of nilotinib against BCR-ABL kinase activity, P-gp, and ABCG2. Twenty-five derivatives of nilotinib were synthesized and were then tested to measure their activity to inhibit BCR-ABL kinase and to inhibit the function of ABC drug transporters. A set of in vitro experiments including kinase activity and cell-based transport assays and photolabeling of P-gp and ABCG2 with a transport substrate, [(125)I]-iodoarylazido-prazosin (IAAP), were carried out in isolated membranes to evaluate the potency of the derivatives to inhibit the function of ABC drug transporters and BCR-ABL kinase. Sixteen, fourteen, and ten compounds were selected as QSAR data sets, respectively, to generate PHASE v3.1 pharmacophore models for BCR-ABL kinase, ABCG2, and P-gp inhibitors. The IC50 values of these derivatives against P-gp, ABCG2, or BCR-ABL kinase were used to generate pharmacophore features required for optimal interactions with these targets. A seven-point pharmacophore (AADDRRR) for BCR-ABL kinase inhibitory activity, a six-point pharmacophore (ADHRRR) for ABCG2 inhibitory activity, and a seven-point pharmacophore (AADDRRR) for P-gp inhibitory activity were generated. The derived models clearly demonstrate high predictive power

  13. Otimização das condições de pré-redução do As(V em extratos do método BCR para quantificação de arsênio por HG-AAS Optimization of pre-reduction conditions of as(V in BCR extracts to quantify arsenic by HG-AAS

    Directory of Open Access Journals (Sweden)

    Eduardo Vinícius Vieira Varejão

    2009-08-01

    Full Text Available A determinação de As por espectrometria de absorção atômica com geração de hidretos (HG-AAS constitui um método simples, sensível, preciso e de baixo custo. Entretanto, essa técnica requer a pré-redução das espécies de As(V, o que se obtém através do uso de agentes redutores como o KI. Em extratos contendo agentes oxidantes, a pré-redução do As é comprometida, como acontece em extratos obtidos pela aplicação do método BCR (acrônimo francês para Community Bureau of Reference para a extração sequencial de As em sedimentos. O objetivo deste trabalho foi avaliar as condições de redução do As(V a As(III, de modo a permitir o uso da HG-AAS para a quantificação do arsênio em extratos obtidos a partir do método BCR. Foram avaliadas condições reacionais utilizando KI, L-cisteína e ácido ascórbico. Para cada uma das etapas de extração do método BCR, diferentes condições de pré-redução possibilitaram a detecção quantitativa do As presente. O uso do método BCR para a extração de arsênio em amostras de sedimentos contaminadas e a aplicação das condições de pré-redução do As(V selecionadas, seguida pela detecção por HG-AAS, forneceram percentagens de recuperação entre 91 e 99 %.The determination of As by hydride generation atomic absorption spectroscopy (HG-AAS is a simple, sensitive, precise and low-cost method. However, this technique requires the pre-reduction of the existing As(V species, which is obtained by the use of reducing agents such as KI. In extracts containing oxidizing agents, the pre-reduction of As is impaired, as it occurs in extracts obtained by the BCR (French acronym for Community Bureau of Reference method for the sequential extraction of As in sediments. The objective of this study was to evaluate the conditions for the reduction of As(V to As(III in a way that allows the use of HG-AAS for the quantification of arsenic in extracts obtained using the BCR method. Reaction

  14. Attomolar electrochemical detection of the BCR/ABL fusion gene based on an amplifying self-signal metal nanoparticle-conducting polymer hybrid composite.

    Science.gov (United States)

    Avelino, Karen Y P S; Frias, Isaac A M; Lucena-Silva, Norma; Gomes, Renan G; de Melo, Celso P; Oliveira, Maria D L; Andrade, César A S

    2016-12-01

    In the last ten years, conjugated polymers started to be used in the immobilization of nucleic acids via non-covalent interactions. In the present study, we describe the construction and use of an electrochemical DNA biosensor based on a nanostructured polyaniline-gold composite, specifically developed for the detection of the BCR/ABL chimeric oncogene. This chromosome translocation is used as a biomarker to confirm the clinical diagnosis of both chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). The working principle of the biosensor rests on measuring the conductivity resulting from the non-covalent interactions between the hybrid nanocomposite and the DNA probe. The nanostructured platform exhibits a large surface area that enhances the conductivity. Positive cases, which result from the hybridization between DNA probe and targeted gene, induce changes in the amperometric current and in the charge transfer resistance (RCT) responses. Atomic force microscopy (AFM) images showed changes in the genosensor surface after exposure to cDNA sample of patient with leukemia, evidencing the hybridization process. This new hybrid sensing-platform displayed high specificity and selectivity, and its detection limit is estimated to be as low as 69.4 aM. The biosensor showed excellent analytical performance for the detection of the BCR/ABL oncogene in clinical samples of patients with leukemia. Hence, this electrochemical sensor appears as a simple and attractive tool for the molecular diagnosis of the BCR/ABL oncogene even in early-stage cases of leukemia and for the monitoring of minimum levels of residual disease.

  15. The CRISPR/Cas9 system efficiently reverts the tumorigenic ability of BCR/ABL in vitro and in a xenograft model of chronic myeloid leukemia.

    Science.gov (United States)

    García-Tuñón, Ignacio; Hernández-Sánchez, María; Ordoñez, José Luis; Alonso-Pérez, Veronica; Álamo-Quijada, Miguel; Benito, Rocio; Guerrero, Carmen; Hernández-Rivas, Jesús María; Sánchez-Martín, Manuel

    2017-02-09

    CRISPR/Cas9 technology was used to abrogate p210 oncoprotein expression in the Boff-p210 cell line, a pro-B line derived from interlukin-3-dependent Baf/3, that shows IL-3-independence arising from the constitutive expression of BCR-ABL p210. Using this approach, pools of Boff-p210-edited cells and single edited cell-derived clones were obtained and functionally studied in vitro. The loss of p210 expression in Boff-p210 cells resulted in the loss of ability to grow in the absence of IL-3, as the Baf/3 parental line, showing significantly increased apoptosis levels. Notably, in a single edited cell-derived clone carrying a frame-shift mutation that prevents p210 oncoprotein expression, the effects were even more drastic, resulting in cell death. These edited cells were injected subcutaneously in immunosuppressed mice and tumor growth was followed for three weeks. BCR/ABL-edited cells developed smaller tumors than those originating from unedited Boff-p210 parental cells. Interestingly, the single edited cell-derived clone was unable to develop tumors, similar to what is observed with the parental Baf/3 cell line.CRISPR/Cas9 genomic editing technology allows the ablation of the BCR/ABL fusion gene, causing an absence of oncoprotein expression, and blocking its tumorigenic effects in vitro and in the in vivo xenograft model of CML. The future application of this approach in in vivo models of CML will allow us to more accurately assess the value of CRISPR/Cas9 technology as a new therapeutic tool that overcomes resistance to the usual treatments for CML patients.

  16. Comparative quantitative analysis of BCR-ABL transcripts with the T315I mutant clone by polymerase chain reaction (PCR)-Invader method.

    Science.gov (United States)

    Tadokoro, Kenichi; Ishikawa, Maho; Suzuki, Makoto; Saito, Tomoyoshi; Suzuki, Yoshie; Yamaguchi, Toshikazu; Yagasaki, Fumiharu

    2011-09-01

    Drug resistance is a serious complication in the treatment of chronic myeloid leukemia (CML). The most common and best-characterized mechanism of secondary imatinib resistance in CML is the development of kinase domain mutations in the BCR-ABL gene. Second-generation tyrosine kinase inhibitors, such as dasatinib or nilotinib, overcome most of these mutations, but they are not effective against the T315I mutant. To determine whether these mutations contribute to clinical resistance, it is necessary to monitor the ratio of the mutant and wild-type forms. Here, we developed a polymerase chain reaction (PCR)-Invader assay for comparative quantitative analysis (qPI assay) of BCR-ABL transcripts with the T315I mutant clone. T315I ratios were calculated for the wild-type and mutant fold-over-zero (FOZ) values. In examination with 2 kinds of plasmids containing wild-type or T315I mutant PCR amplicons, mutant FOZ values were detected down to 1% of the total. The results of 12 serial samples from 2 patients (case A: Philadelphia-positive acute lymphoblastic leukemia and case B: CML) with the T315I mutant clone were compared with those of direct sequencing or 2 kinds of allele-specific oligonucleotide (ASO)-PCR. All samples showed the T315I mutation by qPI assay and ASO-PCR, and 10 samples showed it by direct sequencing. Significant correlation (correlation coefficient; r2 = 0.951) was noted between the qPI assay and quantitative ASO-PCR to analyze T315I mutant ratios. Thus, the qPI assay is a useful method for evaluating the T315I mutant clone in BCR-ABL transcripts.

  17. BCR/ABL DCDF-FISH信号特征与染色体核型的关系及其在慢性粒细胞白血病中的意义%Significance of BCR/ABL DCDF-FISH signal pattern and karyotype in chronic myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    杜庆华; 应逸; 陈晓燕

    2010-01-01

    目的 探讨慢性粒细胞白血病(CML)BCR/ABL DCCF-FISH的信号特点及其与染色体核型的关系.结果 使用BCR/ABL的DCDF探针对65例慢性粒细胞白血病骨髓标本进行荧光原位杂交及染色体核型检查.结果 65例CML核型43例Ph阳性,1例阴性,其余21例未行核性检查或无可分析分裂相;FISH结果65例均为BCR/ABL阳性,其中9例伴ASS基因缺失,5例复杂易位,1例+Ph伴ASS基因缺失.结论 传统核型与DCDF-FISH,应互相结合,方可对遗传学特征作出更准确分析.%Objective To investigate the relation between the BCR/ABL DCDF-FISH signal pattern and karyotype in chronic myeloid leukemia(CML). Methods 65 cases of CML were performed FISH and karyotyping. Results In 65 cases CML. 43 cases were Ph positive, 1 case was Ph negative, 21 cases had no performed karyotyping analysis. All of 65 cases were FISH positive,9 cases with ASS gene deletion, 5 cases with complex variant translocation, 1 case with (+) Ph and ASS gene deletion. Conclusion More precise analysis can be got by combining the result of FISH and karyotyping.

  18. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

    DEFF Research Database (Denmark)

    Nicolini, Franck E; Mauro, Michael J; Martinelli, Giovanni;

    2009-01-01

    The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP......), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation...

  19. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F+ HEL Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Axel Weber

    2015-03-01

    Full Text Available Signal transducers and activators of transcription (Stats play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML and Jak2(V617F in other myeloproliferative diseases (MPD. We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl+ K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL

  20. Study of the water-rock interaction in Tsengwenshi groundwater system (southern Taiwan) using BCR sequential extraction procedure

    Science.gov (United States)

    Teng, J. Y.

    2012-04-01

    The heavy metals in groundwater seriously risk the human wealth, agriculture and the aquaculture, especially, if the water is the major source of daily use. Generally, in spite of anthropogenic source, the heavy metals in groundwater are released during water-rock interaction. However, there are many mineral phases being capable of releasing heavy metals. It would need a sequential extraction procedure to identify the source mineral phase in the aquifer. In addition, the geochemical reactions after the release of heavy metals are also important to modify the concentrations. In this study, the rare earth elements are used to be a natural tracer for this purpose. The study area, Tsengwenshi watershed in southern Taiwan, is an alluvial fan with all kinds of land uses and is notorious of arsenic contamination. The groundwaters sampled in this study show that arsenic is enriched in deep aquifer (depth>150m), which is composed of sediments deposited in the last glacial period (18 ka). Based on this conceptual model, the results of BCR sequential extraction procedure are categorized into shallow aquifer (depthheavy metals in two groups can be subsequently obtained to take account of extensive water-rock interaction in the groundwater system. The results show that arsenic and other heavy metals are mostly binding with Fe-Mn oxides. To compare the ratios between deep and shallow aquifers for all heavy metals, the pattern of groundwaters does not show the similar type with those of extracted phases from soils. It is believed that the released heavy metals were strongly modified by the geochemical reactions during the transportation in the groundwater system. In addition, the analysis results of the rare earth elements demonstrates that almost all groundwaters with high arsenic do not have Ce negative anomaly; and, on the contrary, those with low arsenic are generally characterized by strong negative anomaly. Generally, the Ce negative anomaly is a prominent indicator of

  1. 伴不典型BCR-ABL融合基因的慢性髓性白血病的临床和实验研究%A clinical and laboratory study of chronic myeloid leukemia with atypical BCR-ABL fusion gene subtypes

    Institute of Scientific and Technical Information of China (English)

    桂晓敏; 潘金兰; 仇惠英; 岑建农; 薛永权; 陈苏宁; 沈宏杰; 姚利; 张俊

    2014-01-01

    目的 探讨伴不典型BCR-ABL融合基因亚型el4a3和e19a2型慢性髓性白血病(CML)的临床和实验室特点.方法 对2004至2012年染色体核型分析有t(9;22) (q34;q11),荧光原位杂交(FISH)证实为BCR-ABL融合基因阳性,而常规实时定量PCR(RQ-PCR)检测常见BCR-ABL融合基因(b3a2、b2a2和e1a2)阴性的6例CML患者,重新设计引物进行PCR扩增,并将扩增产物测序,以明确不典型BCR-ABL融合基因类型.对BCR-ABL融合基因扩增产物进行突变检测.对患者的临床资料进行回顾性分析.结果 6例患者PCR扩增产物经测序分析,其中5例为e14a3型,1例为e19a2型.5例e14a3型CML患者中,男4例,女1例,中位年龄48岁,慢性期4例,加速期1例;1例e19a2型患者为女性,40岁,CML慢性期,PLT>1 000× 109/L.5例e14a3型CML患者中4例在羟基脲或IFN治疗无效后予以伊马替尼(IM)治疗,1例行造血干细胞移植(HSCT).前4例患者中1例因有E255K突变而对IM耐药,改用达沙替尼后获完全细胞遗传学反应(CCyR);1例在IM治疗获CCyR后3个月复发并急变,最终死亡;2例IM治疗后获CCyR,目前状态稳定,仍处于CCyR,尽管其中1例伴有I293T突变.行HSCT治疗患者目前处于CCyR.1例e19a2型CML患者羟基脲治疗后获得完全血液学反应,后改用IM治疗,很快获得CCyR.结论 伴不典型BCR-ABL融合基因的CML发病率极低,酪氨酸激酶抑制剂或HSCT都可以取得疗效,常规RQ-PCR可能漏检少见的不典型BCR-ABL融合基因亚型.%Objective To explore the clinical and laboratory features of chronic myeloid leukemia (CML) with atypical e14a3 and e19a2 BCR-ABL fusion gene subtypes.Methods We retrospectively analyzed a cohort of CML patients with Ph chromosome positive confirmed by cytogenetic and FISH but classical el3a3 (b2a2),e14a2 (b3a2)and ela2 fusion transcripts negative identified by conventional realtime quantification RT-PCR (RQ-PCR).Further RQ-PCR was done with the forward primer and reverse primer designed to

  2. 荧光原位杂交在慢性粒细胞白血病细胞BCR/ABL融合基因检测中的应用及其意义%The detection of BCR/ABL fusion gene by interphase fluorescence in situ hybridization in patients with chronic myeloid leukemia and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    张济; 李君君; 颜家运; 邹礼衡; 刘静

    2012-01-01

    目的:探讨荧光原位杂交(FISH)技术检测慢性粒细胞白血病(CML)骨髓和外周血细胞的BCR /ABL融合基因的临床价值.方法:应用FISH 对正常对照组及CML患者骨髓和外周血细胞BCR/ ABL融合基因进行检测和分析.结果:慢性期CML 患者骨髓和外周血细胞该融合基因阳性细胞率分别为(61.9 ± 22.3)%和(68.4 ± 19.8)%,加速期为(77.2 ± 16.7)% 和(86.8 ± 12.1)%,急变期为(80.6 ± 17.5)%和(81.4 ± 18.0)%,两者细胞中BCR/ABL 基因的阳性率未见统计学差异(P>0.05),且骨髓和外周血细胞之间融合基因阳性细胞比率呈直线正相关.同时发现在完全临床缓解患者中,经伊马替尼治疗的CML 患者(71.4%)较经干扰素和羟基脲联合治疗者(10.0%)有更高的分子生物学缓解(P 0.05). A significant correlation was found between the BCR/ABL positive cells in peripheral blood and in bone marrow samples. Moreover, the higher rate of complete molecular remission was achieved by treating with imatinib than with interferon and hydroxyurea during complete remission phase (P < 0.05). Conclusions Detecting BCR/ABL fusion gene in peripheral blood and bone marrow samples by FISH are beneficial to diagnosis, treatment and minimal residual disease monitor in CML.

  3. Accurate determination of arsenic in arsenobetaine standard solutions of BCR-626 and NMIJ CRM 7901-a by neutron activation analysis coupled with internal standard method.

    Science.gov (United States)

    Miura, Tsutomu; Chiba, Koichi; Kuroiwa, Takayoshi; Narukawa, Tomohiro; Hioki, Akiharu; Matsue, Hideaki

    2010-09-15

    Neutron activation analysis (NAA) coupled with an internal standard method was applied for the determination of As in the certified reference material (CRM) of arsenobetaine (AB) standard solutions to verify their certified values. Gold was used as an internal standard to compensate for the difference of the neutron exposure in an irradiation capsule and to improve the sample-to-sample repeatability. Application of the internal standard method significantly improved linearity of the calibration curve up to 1 microg of As, too. The analytical reliability of the proposed method was evaluated by k(0)-standardization NAA. The analytical results of As in AB standard solutions of BCR-626 and NMIJ CRM 7901-a were (499+/-55)mgkg(-1) (k=2) and (10.16+/-0.15)mgkg(-1) (k=2), respectively. These values were found to be 15-20% higher than the certified values. The between-bottle variation of BCR-626 was much larger than the expanded uncertainty of the certified value, although that of NMIJ CRM 7901-a was almost negligible.

  4. Functionally deregulated AML1/RUNX1 cooperates with BCR-ABL to induce a blastic phase-like phenotype of chronic myelogenous leukemia in mice.

    Directory of Open Access Journals (Sweden)

    Kiyoko Yamamoto

    Full Text Available Patients in the chronic phase (CP of chronic myelogenous leukemia (CML have been treated successfully following the advent of ABL kinase inhibitors, but once they progress to the blast crisis (BC phase the prognosis becomes dismal. Although mechanisms underlying the progression are largely unknown, recent studies revealed the presence of alterations of key molecules for hematopoiesis, such as AML1/RUNX1. Our analysis of 13 BC cases revealed that three cases had AML1 mutations and the transcript levels of wild-type (wt. AML1 were elevated in BC compared with CP. Functional analysis of representative AML1 mutants using mouse hematopoietic cells revealed the possible contribution of some, but not all, mutants for the BC-phenotype. Specifically, K83Q and R139G, but neither R80C nor D171N mutants, conferred upon BCR-ABL-expressing cells a growth advantage over BCR-ABL-alone control cells in cytokine-free culture, and the cells thus grown killed mice upon intravenous transfer. Unexpectedly, wt.AML1 behaved similarly to K83Q and R139G mutants. In a bone marrow transplantation assay, K83Q and wt.AML1s induced the emergence of blast-like cells. The overall findings suggest the roles of altered functions of AML1 imposed by some, but not all, mutants, and the elevated expression of wt.AML1 for the disease progression of CML.

  5. Comparison between BCR sequential extraction and geo-accumulation method to evaluate metal mobility in sediments of Dongting Lake, Central China

    Science.gov (United States)

    Yao, Zhigang

    2008-02-01

    The form in which a metal exists strongly influences its mobility and thus, the effects on the environment. Operational methods of speciation analysis, such as the use of sequential extraction procedures, are commonly applied. The Dongting Lake, the second largest fresh-water lake in China, contains three China wetlands of international importance, the East Dongting Lake, South Dongting Lake, and West Dongting Lake. In this work, an optimized BCR sequential extraction procedure was used to assess the environmental risk of Cd, Cr, Cu, Ni, Pb and Zn in contaminated sediment of the Dongting Lake. The procedure was evaluated by using a certified reference material, BCR701. The results of the partitioning study indicated that in the lake sediments, more easily mobilized forms (acid exchangeable) were predominant for Cd, particularly in the samples from the East Dongting Lake. In contrast, the largest amount of Pb was associated with the iron and manganese oxide fractions and Cu, Zn, Cr, and Ni analyzed were mainly distributed in residual phase at an average percentage greater than 60% of the total metals. The potential risk to the lake’s water contamination was highest in the East Dongting Lake based on the calculated contamination factors. On the other hand, the total metal content was determined as well by inductively coupled plasma and mass spectrometry (ICP-MS) and assessed by using geo-accumulation index. The assessment results using geo-accumulation index were compared with the information on metal speciation. Both were correspondent with each other.

  6. INFLUENCE OF CHEMOTHERAPEUTANTS AND CYTOKINES ON GROWTH AND TRANSGENE EXPRESSION OF BONE MARROW CELLS FROM MT/P210bcr-ab1 TRANSGENIC MICE

    Institute of Scientific and Technical Information of China (English)

    CHEN Hanchun; Andrew Pierce; Tony Whetton

    1999-01-01

    Objective: To investigate the influence of chemotherapeutic agents and cytokines on growth of bone marrow cells from MT/p210 bcr-ab1 transgenic mice.Methods: The bone marrow cells of transgenic chronic myelogenous leukemia (CML) model mice carrying metallothionein (MT) promoter/enhancer, bcr-abl (p210)cDNA and SV40 splicing/poly (A) signal sequences were cultured in liquid and soft agar with hydroxyurea (Hu),5-fluorouracil (5-Fu), mouse stem cell factor (mSCF)and mouse interleukin-3 (mIL-3) independently or collectively. The cells and colonies were counted. The levels of transgene expression were detected by reverse transcriptase-polymerase chain reaction (RT-PCR).Results: The cell proliferation, colony formation and transgene expression of the bone marrow cells were stimulated with mSCF and mIL-3, but there was little growth without any growth factors, or when mSCF,mIL-3 and Hu or 5-Fu were added. Conclusion: The combined utilization of chemotherapeutants and cytokines is a potentially effective strategy of clinical treatment for CML.

  7. Estandarización de la TR-PCR para la detección de las fusiones génicas BCR-ABL en pacientes con leucemia Mieloide Crónica (LMC y Linfoide Aguda (LLA provenientes de HUSVP y Clíncia León XIII

    Directory of Open Access Journals (Sweden)

    Gonzálo Vásquez Palacio

    2006-04-01

    Full Text Available La translocación recíproca t(9:22(q34;q11 involucra el proto-oncogen ABL y el gen BCR, originando un gen de fusión BCR-ABL, que codifica una proteína con elevada actividad tirosina quinasa, implicada en la leucemogénesis.

  8. Increased acetylation of lysine 317/320 of p53 caused by BCR-ABL protects from cytoplasmic translocation of p53 and mitochondria-dependent apoptosis in response to DNA damage

    NARCIS (Netherlands)

    Kusio-Kobialka, Monika; Wolanin, Kamila; Podszywalow-Bartnicka, Paulina; Sikora, Ewa; Skowronek, Krzysztof; McKenna, Sharon L.; Ghizzoni, Massimo; Dekker, Frank J.; Piwocka, Katarzyna

    2012-01-01

    Chronic myeloid leukemia (CML) is a disorder of hematopoietic stem cells caused by the expression of BCR-ABL. Loss of p53 has not been implicated as important for the development of CML. Mutations in p53 protein are infrequent, however they correlate with the disease progression. The absence of p53

  9. Characterization of the CDR3 structure of the Vβ21 T cell clone in patients with P210(BCR-ABL)-positive chronic myeloid leukemia and B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Zha, Xianfeng; Chen, Shaohua; Yang, Lijian; Li, Bo; Chen, Yu; Yan, Xiaojuan; Li, Yangqiu

    2011-10-01

    The clonally expanded T cells identified in most cancer patients that respond to tumor-associated antigen such as P210(BCR-ABL) protein have definite, specific antitumor cytotoxicity. T cell receptor (TCR) Vβ CDR3 repertoire diversity was analyzed in patients with chronic myeloid leukemia (CML) and BCR-ABL(+) B-cell acute lymphoblastic leukemia (B-ALL) by GeneScan. A high frequency of oligoclonal expansion of the TCR Vβ21 subfamily was observed in the peripheral blood of CML and B-ALL patients. These clonally expanded Vβ21 T cells were correlated with the pathophysiologic process of CML. A conserved amino acid motif (SLxxV) was observed within the CDR3 region in only 3 patients with CML. Preferential usage of the Jβ segments was also observed in a minority of patients. The 3-dimensional structures of the CDR3 region containing the same motif or using the same Jβ segment displayed low similarity; on the contrary, the conformation of the CDR3 region containing no conserved motif in some T cell clones was highly similar. In conclusion, our findings indicate a high frequency of TCR Vβ21 subfamily expansion in p210(BCR-ABL)-positive CML and B-ALL patients. The characterization of the CDR3 structure was complex. Regrettably, at this time it was not possible to confirm that the Vβ21 T cell clones were derived from the stimulation of p210(BCR-ABL) protein.

  10. Which method better evaluates the molecular response in newly diagnosed chronic phase chronic myeloid leukemia patients with imatinib treatment, BCR-ABL(IS) or log reduction from the baseline level?

    Science.gov (United States)

    Qin, Ya-Zhen; Jiang, Qian; Jiang, Hao; Li, Jin-Lan; Li, Ling-Di; Zhu, Hong-Hu; Lai, Yue-Yun; Lu, Xi-Jing; Liu, Yan-Rong; Jiang, Bin; Huang, Xiao-Jun

    2013-09-01

    The molecular response of chronic myeloid leukemia (CML) patients to tyrosine kinase inhibitor treatment can be evaluated either by BCR-ABL mRNA levels on international scale (IS) or by log reduction from the baseline level of the laboratory. Both methods were compared in 248 newly diagnosed chronic phase CML patients treated with imatinib. The major molecular responses (MMR) obtained by both methods predict progression-free survival (PFS, all Plog reduction method, had the same PFS as MMR patients identified by both methods. The molecular responses of patients at 3 and 6 months, as evaluated by the two methods, have similar predictive values on their cytogenetic responses at 12 months and on their molecular responses at 18 months. Both ≤ 10%(IS) and ≥ 1 log reduction at 3 months and ≤ 1%(IS) at 6 months were significantly associated with PFS (P=0.0011, 0.0090, and 0.0064). The percentages of patients with BCR-ABL(IS) of ≤ 1%, >1-10%, and of >10% at 3 months and 6 months in the German CML Study IV were similar with those with corresponding BCR-ABL(IS) in our center, but was significantly different with those evaluated by the log reduction method. Therefore, the molecular response evaluated by BCR-ABL(IS) has similar trends in PFS and in response prediction, but can better differentiate patients than that by the log reduction method. Furthermore, the IS method allows comparison among molecular response results from different laboratories.

  11. Determination of lactate dehydrogenase (LDH and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia = Determinação da lactate desidrogenase (LDH e do transcrito Bcr-Abl em pacientes com leucemia mielóide crônica

    Directory of Open Access Journals (Sweden)

    Roberto Iemitsu Tatakihara

    2010-07-01

    Full Text Available Chronic myeloid leukemia (CML is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the Bcr-Abl (b3a2 transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L-1 and 589 U L-1. Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease. Leucemia mieloide crônica (LMC é uma desordem mieloproliferativa maligna que é originada de célula-tronco pluripotente caracterizada por expansão anormal, maligna de clones de células tronco da medula óssea na circulação. A grande maioria dos pacientes com LMC apresentam transcritos Bcr-Abl. Lactato desidrogenase (LDH,considerado um marcador bioquímico para crescimento tumoral, glicólise anaeróbica, e tem sido considerado um fator de pior prognóstico da LMC. Portanto, este estudo visa avaliar a concentraçãode LDH no plasma e a detecção do transcrito Bcr-Abl em 22 pacientes com LMC e 56 indivíduos saudáveis. Foram avaliados 22 pacientes com LMC e 56 doadores saudáveis. A

  12. BCR/ABL阴性骨髓增生性疾病患者JAK2-V617F点突变与外周血三系变化的相关性%Correlation between JAK2-V617F mutations and variation of peripheral blood cells among BCR/ABL-negative MPD patients

    Institute of Scientific and Technical Information of China (English)

    叶远馨; 宋兴勃; 周易; 应斌武; 陆小军

    2012-01-01

    目的 探讨BCR/ABL阴性骨髓增生性疾病患者JAK2-V617F突变的阳性率以及突变量与外周血三系变化的相关性.方法 对191例确诊为BCR/ABL阴性的骨髓增生性疾病患者进行JAK2-V617F突变检测,分别以外周血中红细胞、白细胞、血小板计数进行分类统计,分析不同类型的标本JAK2-V617F基因点突变的发生率及相对定量变化.结果 外周血红细胞、白细胞、血小板计数不同范围的标本JAK2-V617F突变阳性率有统计学差异.随着外周血红细胞、血小板计数增高,JAK2-V617F突变阳性率也随之增高,且以三系均增多者JAK2-V617F突变率为最高(92.86%).结论 BCR/ABL阴性的骨髓增生性疾病JAK2-V617F点突变发生率与外周血三系变化存在明显的相关性.外周血三系变化、尤其是红细胞计数与BCR/ABL阴性的骨髓增生性疾病JAK2-V617F突变的阳性率以及突变相对定量存在一定的相关性.%Objective To assess the correlation between JAK2-V617F mutation and complete blood counts among patients with BCR/ABL-negative myeloproliferative diseases (MPD).Methods One hundred and ninety one patients were recruited.Retrospectively,their laboratory data were analyzed for the counts of red blood cells (RBC),white blood cells (WBC) and platelets (PLT).And the incidence of JAK2-V617F mutation was determined.Results There was significant difference in the incidence of JAK2-V617F mutation between patients with different cell counts (P<0.01).The incidence of JAK2-V617F mutation has increased with the counts of RBC and PLT,which was the highest (92.86%) among those featuring simultaneous increase in all three series.Conclusion The incidence of JAK2-V617F mutation seems to be strongly associated with variation of peripheral blood cell counts among patients with BCR/ABL-negative MPD.Variation of peripheral blood cells,particularly RBC,may be correlated with the rate of JAK2-V617F mutation.

  13. Patan hospital experience in treating philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukemia patients with gleevec (imatinib mesylate; the first generation specific tyrosine kinase inhibitor

    Directory of Open Access Journals (Sweden)

    Zimmerman Mark

    2010-12-01

    Full Text Available Abstract Background Chronic Myeloid Leukemia (CML is caused by the abnormal fusion protein BCR-ABL1, a constitutively active tyrosine kinase and product of the Philadelphia chromosome. Gleevec (Imatinib mesylate is a selective inhibitor of this kinase. Treatment with this agent is known to result in hematologic, cytogenetic, and molecular responses. Patan hospital (Patan, Nepal is one of the Gleevec International Patient Assistance Program (GIPAP centers for patients with CML. Methods A total of 106 Philadelphia positive CML patients were enrolled in our center between Feb 2003 and Jun 2008, and 103 of them were eligible for cytogenetic and/or hematologic response analyses. Results Out of 103 patients, 27% patients underwent cytogenetic analysis. Imatinib induced major cytogenetic responses in 89% and complete hematologic responses in almost 100% of the patients with confirmed CML. After a mean follow up of 27 months, an estimated 90% of the patients on imatinib remained in hematologic remission and more than 90% of the patients are still alive. About 30% of patients developed some form of manageable myelosuppression. A few patients developed non-hematologic toxic side effects such as edema and hepatotoxicity. Conclusions Our study demonstrates that imatinib is safe to use in a developing country. Furthermore, we demonstrate that imatinib is very effective and induced long lasting responses in a high proportion of patients with Ph chromosome/BCR-ABL1 positive CML. Imatinib is well tolerated by our patients. The lack of cytogenetic analysis in the majority of our patients hindered our ability to detect inadequate responses to imatinib and adjust therapy appropriately.

  14. SPR Detection and Discrimination of the Oligonucleotides Related to the Normal and the Hybrid bcr-abl Genes by Two Stringency Control Strategies

    Science.gov (United States)

    Matsishin, M. J.; Ushenin, Iu. V.; Rachkov, A. E.; Solatkin, A. P.

    2016-01-01

    In this study, we applied two stringency control strategies for surface plasmon resonance (SPR) detection of DNA hybridization and discrimination of completely and partially complementary 24-mer sequences. These sequences are specific to the human normal bcr and the hybrid bcr-abl genes, protein products of which are responsible for some leukemia. SPR sensors based on resonance phenomena in nanoscale gold films are well suited for label-free, real-time investigations of the macromolecule interactions. Thermodynamic parameters obtained using the web server DINAMelt allowed supposing the possibility for realization (a) stringency control based on the ionic strength of the hybridization buffer and (b) stringency control based on the temperature elevation. The first one resulted in that the discrimination index of completely complementary and partially complementary oligonucleotides depending on the target concentration varied from 1.3 to 1.8 in 2 × SSC and from 2.0 to 2.9 in 0.5 × SSC. For implementation of the second stringency control strategy, SPR spectrometer measuring flow cell with built-in high-precision temperature control and regulation as well as corresponding software was created. It is shown that the duplexes formed by the immobilized probes mod-Ph and completely complementary oligonucleotides P1 remained without significant changes until ~50 °C, while the duplexes formed with partially complementary oligonucleotide Bcrex14 almost entirely disrupted at 40 °C. Thus, the absolutely effective thermodiscrimination of this pair of oligonucleotides was achieved in this temperature range (40-50 °C).

  15. Cell sorting enables interphase fluorescence in situ hybridization detection of low BCR-ABL1 producing stem cells in chronic myeloid leukaemia patients beyond deep molecular remission.

    Science.gov (United States)

    van Kooten Niekerk, Peter B; Petersen, Charlotte C; Nyvold, Charlotte G; Ommen, Hans B; Roug, Anne S; Nederby, Line; Hokland, Peter; Kjeldsen, Eigil

    2014-01-01

    The exact disease state of chronic myeloid leukaemia (CML) patients in deep molecular remission is unknown, because even the most sensitive quantitative reverse transcription polymerase chain reaction (qPCR) methods cannot identify patients prone to relapse after treatment withdrawal. To elucidate this, CD34(+) stem cell and progenitor cell subpopulations were isolated by fluorescence-activated cell sorting (FACS), and their content of residual Philadelphia positive (Ph(+) ) cells was evaluated in 17 CML patients (major molecular response, n = 6; 4-log reduction in BCR-ABL1 expression (MR(4) ), n = 11) using both sensitive qPCR and interphase fluorescence in situ hybridization (iFISH). Despite evaluating fewer cells, iFISH proved superior to mRNA-based qPCR in detecting residual Ph(+) stem cells (P = 0·005), and detected Ph(+) stem- and progenitor cells in 9/10 patients at frequencies of 2-14%. Moreover, while all qPCR(+) samples also were iFISH(+) , 9/33 samples were qPCR-/iFISH(+) , including all positive samples from MR(4) patients. Our findings show that residual Ph(+) cells are low BCR-ABL1 producers, and that DNA-based methods are required to assess the content of persisting Ph(+) stem cells in these patients. This approach demonstrates a clinically applicable manner of assessing residual disease at the stem cell level in CML patients in MR(4) , and may enable early and safe identification of candidates for tyrosine kinase inhibitor withdrawal.

  16. 用COLD-PCR方法提高BCR-ABL1激酶区耐药突变检测灵敏度%Application of COLD-PCR for improved detection of BCR-ABL1 kinase domain drug-resistant mutation

    Institute of Scientific and Technical Information of China (English)

    李庆; 刘红星; 孙慧; 王倩; 张之芬; 武焕玲; 李元堂; 陈永金; 田文君

    2013-01-01

    Objective To evaluate the feasibility of the co-amplification using a low denaturation temperature PCR (COLD-PCR) method in improving the detection of BCR-ABL1 fusion gene kinase domain drug-resistant mutation.Methods Conventional nested PCR (CN-PCR) and COLD-PCR protocol were designed to amplify full-length of BCR-ABL1 kinase domain.PCR products were purified and then Sanger sequenced to detect BCR-ABL1 kinase domain mutation (KDM).20 newly diagnosed CML patients and 32 Imatinib (IM) resistant patients were chosen and peripheral blood or bone marrow samples were collected.PCR products of the clinical specimens were purified and then cloned to evaluate the proportion of the KDM allele.Standard samples with different proportion of KDMs were prepared using T-A vectors with KDM and wild type BCR-ABL1 kinase domain sequence,and then CN-PCR,COLD-PCR and Sanger sequencing were performed to compare the detection sensitivity.Results In the 32 IM-resistant patients,23 were identified KDM-positive using CN-PCR and 28 KDM-positive using COLD-PCR.In the 20 newly diagnosed CML patients,none was identified KDM-positive using CN-PCR and 1 was identified carrying a lower proportion of KDM using COLD-PCR.For 16 different types of KDMs,COLD-PCR method could improve the detection sensitivity 4-12 times.Conclusion Detection sensitivity of BCR-ABL1 drug-resistant kinase domain mutation can be effectively improved by using COLD-PCR method and may contribute to early detection of resistance KDMs.%目的 探讨用低变性温度共扩增PCR(COLD-PCR)方法提高BCR-ABL1融合基因激酶区耐药突变检测灵敏度的可行性.方法 本研究为实验诊断研究.设计常规巢式PCR(CN-PCR)和COLD-PCR方案扩增BCR-ABL1激酶区全长,扩增产物纯化后用Sanger测序法检测激酶区突变(KDM).采集32例经伊马替尼(IM)治疗并出现耐药的慢性粒细胞性白血病(CML)患者和20例初诊CML患者外周血或骨髓标本,用上述2种方案检测标本中的KDM.

  17. Determination of lactate dehydrogenase (LDH and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia - doi: 10.4025/actascihealthsci.v32i2.6408 Determination of lactate dehydrogenase (LDH and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia - doi: 10.4025/actascihealthsci.v32i2.6408

    Directory of Open Access Journals (Sweden)

    Thiago Cezar Fujita

    2010-09-01

    Full Text Available Chronic myeloid leukemia (CML is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the Bcr-Abl (b3a2 transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L-1 and 589 U L-1. Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease.Chronic myeloid leukemia (CML is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed

  18. Overexpression or knock-down of runt-related transcription factor 1 affects BCR-ABL-induced proliferation and migration in vitro and leukemogenesis in vivo in mice

    Institute of Scientific and Technical Information of China (English)

    YANG Li-jun; YU Wei-dong; DU Jun-bao; CHAO Shuang; CHEN Min-xia; ZHAO He-hua; GUO Jing-zhu

    2009-01-01

    Background Runt-related transcription factor 1 (Runx1) plays a crucial role in hematogenesis and its dysfunction may contribute to leukemogenesis. However, it is not clear whether or not abnormal expression of Runx1 will induce leukemia and how the change of Runx1 expression level could affect BCR-ABL-induced leukemogenesis. In the present study, we aimed to analyze if abnormal expression of Runx1 in BaF3 cells alone would induce leukemogenesis. And we also wanted to know if abnormal expression of Runx1 in leukemic cells would affect leukemogenesis. Furthermore, we investigated whether overexpression or knock-down of Runx1 in BaF3 cells would induce leukemogenesis.Methods Plasmids containing full-length Runx1 cDNA were transduced into BaF3 cells and BaF3-P185wt cells (BCR-ABL transformed BaF3 cells) by electroporation. Plasmids containing a short hairpin RNA of Runx1 were transduced into BaF3 cells and BaF3-P185wt cells by electroporation. Runx1 expression level was quantified by Western blotting and quantitative real-time PCR. The effects of overexpression or knock-down of Runx1 on proliferation, apoptosis and migration of cells were detected in vitro. Then, using MSCV-P185wt-FGFP as a control, we transplanted MSCV-P185wt-Runx1 cells or MSCV-P185wt-shRNA cells into Balb/c mice through tail vein and observed tumorgenesis of the different phenotypes.Results In vitro analysis revealed that overexpression of Runx1 in P185wt cells could inhibit cell proliferation and slow down cell migration; while knock-down of Runx1 could promote cell proliferation and speed up cell migration. In vivo analysis indicated that mice transplanted with MSCV-P185wt-Runx1 survived longer than controls. In contrast, mice transplanted with MSCV-P185wt-shRNA survived shorter than the control group. Gross pathological analysis revealed that the MSCV-P185wt-Runx1 group had less severe splenomegaly and hepatomegaly compared to the control group, and the MSCV-P185wt-shRNA group had more severe

  19. Therapy Provider Phase Information

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Therapy Provider Phase Information dataset is a tool for providers to search by their National Provider Identifier (NPI) number to determine their phase for...

  20. Establishment and characterization of A novel Philadelphia-chromosome positive chronic myeloid leukemia cell line, TCC-S, expressing P210 and P190 BCR/ABL transcripts but missing normal ABL gene.

    Science.gov (United States)

    Van, Phan Nguyen Thanh; Xinh, Phan Thi; Kano, Yasuhiko; Tokunaga, Katsushi; Sato, Yuko

    2005-03-01

    A novel Philadelphia-chromosome positive (Ph+) cell line, TCC-S, has been established from a patient with Ph+ chronic myeloid leukemia (CML) in the blastic crisis. TCC-S cells were shown to express both P210 and P190 BCR/ABL transcripts by reverse transcriptase-polymerase chain reaction (PCR), although quantitative-PCR revealed that TCC-S cells mainly expressed P210 BCR/ABL transcript. Karyotype analysis revealed several triploid clones which constantly harbored two der(9)del(9) (p12)t(9;22) (q34;qll)s and two del(9) (q21)s. The der(9)del(9) (p12)t(9;22) (q34;q11) is rarely found in other CML cell lines. Moreover, to the best of our knowledge, del(9) (q21) resulting in missing of a restrict region including normal ABL gene has not been found among CML cell lines previously described. Thus, TCC-S cells with only BCR/ABL gene and no normal ABL gene may be a useful tool for functional study of ABL in Ph+ CML.

  1. Acute WT1-positive promyelocytic leukemia with hypogranular variant morphology, bcr-3 isoform of PML-RARα and Flt3-ITD mutation: a rare case report

    Directory of Open Access Journals (Sweden)

    Xi Zhang

    Full Text Available ABSTRACT CONTEXT: Acute promyelocytic leukemia (APL accounts for 8% to 10% of cases of acute myeloid leukemia (AML. Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD, and bcr-3 isoform of PML-RARα. Most importantly, we detected high level of Wilms’ tumor gene (WT1 in marrow blasts, through the reverse transcription polymerase chain reaction (RT-PCR. To date, no clear conclusions about an association between WT1 expression levels and APL have been reached. This patient successively received a combined treatment regimen consisting of hydroxycarbamide, arsenic trioxide and idarubicin plus cytarabine, which ultimately enabled complete remission. Unfortunately, he subsequently died of sudden massive hemoptysis because of pulmonary infection. CONCLUSION: Based on our findings and a review of the literature, abnormal functioning of WT1 may be a high-risk factor in cases of APL. Further studies aimed towards evaluating the impact of WT1 expression on the prognosis for APL patients are of interest.

  2. DFT+ U study of electronic structure and Curie temperature of A2 B ReO6 (A=Sr, Ca and B=Cr, Fe)

    Science.gov (United States)

    Lee, Alex; Marianetti, Chris

    Re-based double perovskites (DPs) have attracted much attention due to their high Curie temperature (TC) and colossal magneto resistance with large potential for spintronic applications. Here we investigate the electronic and magnetic properties of the Re-based DPs A2 B ReO6 (A=Sr, Ca and B=Cr, Fe) using density functional theory + U (DFT+ U) calculations. While monoclinic Ca2CrReO6 and Ca2FeReO6 (monoclinic) are insulating within GGA+ U, tetragonal Sr2CrReO6 (a0a0c0) and Sr2FeReO6 (a0a0c-) remain metallic. We show that both on-site interaction U and octahedral tilting are critical to obtain the insulating phases. The a0a0c- -phase of Sr2CrReO6 is most stable and insulating with nonzero U, suggesting that the high quality Sr2CrReO6 film on STO substrate can be a semiconductor as reported in recent experiments. We explain that the insulator-to-metal transition (MIT) of Ca2FeReO6 at 140K is predominantly due to a structural phase transition which drives the insulating state. Curie temperatures of Re-based DPs are calculated using the classical Monte Carlo simulations based on the Heisenberg model.

  3. Doxorubicin Differentially Induces Apoptosis, Expression of Mitochondrial Apoptosis-Related Genes, and Mitochondrial Potential in BCR-ABL1-Expressing Cells Sensitive and Resistant to Imatinib

    Directory of Open Access Journals (Sweden)

    Ewelina Synowiec

    2015-01-01

    Full Text Available Imatinib resistance is an emerging problem in the therapy of chronic myeloid leukemia (CML. Because imatinib induces apoptosis, which may be coupled with mitochondria and DNA damage is a prototype apoptosis-inducing factor, we hypothesized that imatinib-sensitive and -resistant CML cells might differentially express apoptosis-related mitochondrially encoded genes in response to genotoxic stress. We investigated the effect of doxorubicin (DOX, a DNA-damaging anticancer drug, on apoptosis and the expression of the mitochondrial NADH dehydrogenase 3 (MT-ND3 and cytochrome b (MT-CYB in model CML cells showing imatinib resistance caused by Y253H mutation in the BCR-ABL1 gene (253 or culturing imatinib-sensitive (S cells in increasing concentrations of imatinib (AR. The imatinib-resistant 253 cells displayed higher sensitivity to apoptosis induced by 1 μM DOX and this was confirmed by an increased activity of executioner caspases 3 and 7 in those cells. Native mitochondrial potential was lower in imatinib-resistant cells than in their sensitive counterparts and DOX lowered it. MT-CYB mRNA expression in 253 cells was lower than that in S cells and 0.1 μM DOX kept this relationship. In conclusion, imatinib resistance may be associated with altered mitochondrial response to genotoxic stress, which may be further exploited in CML therapy in patients with imatinib resistance.

  4. Induction of apoptosis by shikonin through a ROS/JNKmediated process in Bcr/Abl-positive chronic myelogenous leukemia (CML) cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This study examined the signaling events induced by shikonin that lead to the induction of apoptosis in Bcr/ Abl-positive chronic myelogenous leukemia (CML) cells (e.g., K562, LAMA84). Treatment of K562 cells with shikonin (e.g., 0.5 μM) resulted in profound induction of apoptosis accompanied by rapid generation of reactive oxygen species (ROS), striking activation of c-Jun-N-terminai kinase (JNK) and p38, marked release of the mitochondrial proteins cytochrome c and Smac/DIABLO, activation of caspase-9 and -3, and cleavage of PARP. Scavenging of ROS completely blocked all of the above-mentioned events (i.e., JNK and p38 phosphorylation, cytochrome c and Smac/DIABLO release, caspase and PARP cleavage, as well as the induction of apoptosis) following shikonin treatment. Inhibition of JNK and knock-down of JNKI significantly attenuated cytochrome c release, caspase cleavage and apoptosis, but did not affect shikonin-mediated ROS production. Additionally, inhibition of caspase activation completely blocked shikonin-induced apoptosis, but did not appreciably modify shikonin-mediated cytochrome c release or ROS generation. Altogether, these findings demonstrate that shikonin-induced oxidative injury operates at a proximal point in apoptotic signaling cascades, and subsequently activates the stress-related JNK pathway, triggers mitochondrial dysfunction, cytochrome c release, and caspase activation, and leads to apoptosis. Our data also suggest that shikonin may be a promising agent for the treatment of CML, as a generator of ROS.

  5. Dasatinib treatment based on BCR-ABL mutation detection in imatinib-resistant patients with chronic myeloid leukemia%BCR-ABL突变检测指导下的达沙替尼治疗伊马替尼耐药的慢性髓性白血病疗效分析

    Institute of Scientific and Technical Information of China (English)

    江倩; 秦亚溱; 赖悦云; 江浩; 石红霞

    2016-01-01

    Objective To evaluate the efficiency of dasatinib as the second-or third-line tyrosine kinase inhibitor(TKI)in imatinib-resistant patients with chronic myeloid leukemia(CML)based on BCR-ABL mutation detection. Methods 122 CML patients received dasatinib treatment, including 83 with imatinib-resistance and 39 with both imatinib-and nilotinib-resistance, 55 in the chronic-phase(CP), 21 in the accelerated-phase (AP) and 46 in the blast-phase (BP). Those harboring dasatinib highly-resistant mutations(T315I/A, F317L/V/C and V299L)were excluded based on BCR-ABL kinase domain mutation screening by Sanger sequencing at baseline. Hematologic, cytogenetic and molecular responses were evaluated regularly, and rates of progression-free-survival(PFS)and overall survival(OS)were analyzed. BCR-ABL mutation detection was performed once the patients failed on dasatinib. Results In the CP patients, the rates of complete hematological response (CHR), complete cytogenetic response (CCyR), major molecular response(MMR)and molecular response 4.5(MR4.5)were 92.7%, 53.7%, 29.6%and 14.8%, respectively. 4-year PFS and OS rates were 84.4%and 89.5%, respectively. In the AP patients, HR and CCyR rates were 81.0%and 35.0%;and 3-year PFS and OS rates were 56.1%and 59.3%, respectively. In the BP patients, HR and CCyR rates were 63.0%and 21.4%;and 1-year PFS and OS rates were 43.6%and 61.8%, respectively. Outcomes were similar when dasatinib was used as the second-line TKI or thethird-line TKI. Of the 75 patients who were resistant to dasatinib, 37(48.7%)developed new mutation(s), and T315I(59.5%)was the most common mutation type. The patients who already harbored mutation(s) before dasatinib therapy achieved similar responses and outcomes to those with no mutation at baseline. However, they had higher likelihood of developing additional mutations associated with resistance to dasatinib(65.7%vs 34.1%, P=0.006). Conclusions Dasatinib was proved to be effective in the treatment of imatinib

  6. Dependent rational providers.

    Science.gov (United States)

    Brothers, Kyle B

    2011-04-01

    Provider claims to conscientious objection have generated a great deal of heated debate in recent years. However, the conflicts that arise when providers make claims to the "conscience" are only a subset of the more fundamental challenges that arise in health care practice when patients and providers come into conflict. In this piece, the author provides an account of patient-provider conflict from within the moral tradition of St. Thomas Aquinas. He argues that the practice of health care providers should be understood as a form of practical reasoning and that this practical reasoning must necessarily incorporate both "moral" and "professional" commitments. In order to understand how the practical reasoning of provider should account for the needs and commitments of the patient and vice versa, he explores the account of dependence provided by Alasdair MacIntyre in his book Dependent Rational Animals. MacIntyre argues that St. Thomas' account of practical reasoning should be extended and adapted to account for the embodied vulnerability of all humans. In light of this insight, providers must view patients not only as the subjects of their moral reflection but also as fellow humans upon whom the provider depends for feedback on the effectiveness and relevance of her practical reasoning. The author argues that this account precludes responsive providers from adopting either moral or professional conclusions on the appropriateness of interventions outside the individual circumstances that arise in particular situations. The adoption of this orientation toward patients will neither eradicate provider-patient conflict nor compel providers to perform interventions to which they object. But this account does require that providers attend meaningfully to the suffering of patients and seek feedback on whether their intervention has effectively addressed that suffering.

  7. Provider of Services File

    Data.gov (United States)

    U.S. Department of Health & Human Services — The POS file consists of two data files, one for CLIA labs and one for 18 other provider types. The file names are CLIA and OTHER. If downloading the file, note it...

  8. What HERA may provide?

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Hannes [DESY, Hamburg (Germany); De Roeck, Albert [CERN, Genf (Switzerland); Bartles, Jochen [Univ. Hamburg (DE). Institut fuer Theoretische Physik II] (and others)

    2008-09-15

    More than 100 people participated in a discussion session at the DIS08 workshop on the topic What HERA may provide. A summary of the discussion with a structured outlook and list of desirable measurements and theory calculations is given. (orig.)

  9. Internet Medline providers.

    Science.gov (United States)

    Vine, D L; Coady, T R

    1998-01-01

    Each database in this review has features that will appeal to some users. Each provides a credible interface to information available within the Medline database. The major differences are pricing and interface design. In this context, features that cost more and might seem trivial to the occasional searcher may actually save time and money when used by the professional. Internet Grateful Med is free, but Ms. Coady and I agree the availability of only three ANDable search fields is a major functional limitation. PubMed is also free but much more powerful. The command line interface that permits very sophisticated searches requires a commitment that casual users will find intimidating. Ms. Coady did not believe the feedback currently provided during a search was sufficient for sustained professional use. Paper Chase and Knowledge Finder are mature, modestly priced Medline search services. Paper Chase provides a menu-driven interface that is very easy to use, yet permits the user to search virtually all of Medline's data fields. Knowledge Finder emphasizes the use of natural language queries but fully supports more traditional search strategies. The impact of the tradeoff between fuzzy and Boolean strategies offered by Knowledge Finder is unclear and beyond the scope of this review. Additional software must be downloaded to use all of Knowledge Finders' features. Other providers required no software beyond the basic Internet browser, and this requirement prevented Ms. Coady from evaluating Knowledge Finder. Ovid and Silver Platter offer well-designed interfaces that simplify the construction of complex queries. These are clearly services designed for professional users. While pricing eliminates these for casual use, it should be emphasized that Medline citation access is only a portion of the service provided by these high-end vendors. Finally, we should comment that each of the vendors and government-sponsored services provided prompt and useful feedback to e

  10. Building Service Provider Capabilities

    DEFF Research Database (Denmark)

    Brandl, Kristin; Jaura, Manya; Ørberg Jensen, Peter D.

    In this paper we study whether and how the interaction between clients and the service providers contributes to the development of capabilities in service provider firms. In situations where such a contribution occurs, we analyze how different types of activities in the production process...... of the services, such as sequential or reciprocal task activities, influence the development of different types of capabilities. We study five cases of offshore-outsourced knowledge-intensive business services that are distinguished according to their reciprocal or sequential task activities in their production...... process. We find that clients influence the development of human capital capabilities and management capabilities in reciprocally produced services. While in sequential produced services clients influence the development of organizational capital capabilities and management capital capabilities....

  11. 达沙替尼治疗伊马替尼耐药的 BCR/ABL阳性白血病%Dasatinib in treatment of imatinib-resistant BCR/ABL positive leukemia

    Institute of Scientific and Technical Information of China (English)

    严红; 赵海军

    2014-01-01

    This study was aimed to evaluate the efficacy and safety of dasatinib in BCR /ABL positive leukemia patients with resistance to imatinib.Method 9 patients with imatinib -resistant chronic myelogenous leukemia ( CML) or Philadelphia chromosome positive acute lymphocytic leukemia (Ph+ALL) received 100~140 mg· d-1 dasatinib orally.Their overall survival and tolerance were evalua-ted.Results After the dasatinib treatment ,2 patients with CML in chronic phase achieved complete hematologic response ( CHR) ,one of them achieved complete cytogenetic response (CCyR);4 of 5 patients with CML in blast crisis achieved CHR and partly cytogenetic response (PCyR);one patient had no response .Treated with dasatinib,one patient with Ph +ALL,presented with E255V mutation,a-chieved CHR and PCyR .The other died of infection .Conlusion Receiving therapy of dasatinib , patients with resistance to imatinib could achieve CHR ,even PCyR .%目的:评价达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病的疗效和安全性。方法对9例伊马替尼耐药的慢性髓系白血病( CML)或Ph阳性急性淋巴细胞白血病( Ph+ALL)患者,给予达沙替尼100~140 mg· d-1口服治疗,评估疗效和耐受情况。结果9例伊马替尼耐药的BCR/ABL阳性白血病,2例CML-CP患者均获得CHR,1例达CCyR;5例CML-BC患者中4例获得CHR和PCyR,1例NR;2例Ph+ALL患者中1例检测到E255V突变,采用达沙替尼治疗达CHR和PCyR,1例诱导缓解时,同时行VDP方案化疗,继发严重感染死亡。结论达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病患者可获得血液学甚至细胞遗传学缓解,且耐受性好。

  12. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl{sup +} K562 and Jak2(V617F){sup +} HEL Leukemia Cells

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Axel [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany); Borghouts, Corina [Ganymed Pharmaceuticals AG, Mainz 55131 (Germany); Brendel, Christian [Boston Children’s Hospital, Division of Hematology/Oncology, Boston, MA 02115 (United States); Moriggl, Richard [Ludwig Boltzmann Institute for Cancer Research (LBI-CR), Vienna 1090 (Austria); Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd, E-mail: Groner@em.uni-frankfurt.de [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany)

    2015-03-19

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl{sup +} K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells

  13. Providing Compassion through Flow

    Directory of Open Access Journals (Sweden)

    Lydia Royeen

    2015-07-01

    Full Text Available Meg Kral, MS, OTR/L, CLT, is the cover artist for the Summer 2015 issue of The Open Journal of Occupational Therapy. Her untitled piece of art is an oil painting and is a re-creation of a photograph taken while on vacation. Meg is currently supervisor of outpatient services at Rush University Medical Center. She is lymphedema certified and has a specific interest in breast cancer lymphedema. Art and occupational therapy serve similar purposes for Meg: both provide a sense of flow. She values the outcomes, whether it is a piece of art or improved functional status

  14. Polymorphism Analysis of 5′ Promotor Region of BCR Gene%BCR基因5′启动子区多态性分析

    Institute of Scientific and Technical Information of China (English)

    田红; 郑维扬; 付永贵; 林蒋海; 吕凤娟; 周淑芸

    2004-01-01

    背景与目的:bcr-abl融合基因被认为是慢性髓系白血病(chronic myelogenous leukemia,CML)的分子标志,该融合基因的表达受 bcr基因启动子的调控.本实验目的是研究 bcr基因启动子区的多态性,并探讨其与 CML之间可能存在的联系.方法:采用 PCR方法扩增 bcr基因 5′启动子区 1.13 kb的序列范围,通过测序获得了 30例 CML和 19例对照的启动子区序列.应用软件和在线工具对启动子序列进行转录因子结合位点分析和重复序列分析.结果:在所研究片段范围内共发现 4处新的单核苷酸多态性(single nucleotide polymorphism,SNP)和 3处与参考序列不一致的碱基变异.其中 2处 SNPs和 1处碱基插入位于转录因子结合位点中或邻近几个碱基内.各多态性基因频率在 CML和对照人群中无统计学差异.结论:bcr基因的 5′启动子区存在一定的序列多态性,主要为 SNPs,未能证实其与 CML之间存在相关性,但部分 SNPs的定位使其有可能对基因的转录和表达产生影响.

  15. What HERA May Provide?

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Hannes; /DESY; De Roeck, Albert; /CERN; Bartels, Jochen; /Hamburg U., Inst. Theor. Phys. II; Behnke, Olaf; Blumlein, Johannes; /DESY; Brodsky, Stanley; /SLAC /Durham U., IPPP; Cooper-Sarkar, Amanda; /Oxford U.; Deak, Michal; /DESY; Devenish, Robin; /Oxford U.; Diehl, Markus; /DESY; Gehrmann, Thomas; /Zurich U.; Grindhammer, Guenter; /Munich, Max Planck Inst.; Gustafson, Gosta; /CERN /Lund U., Dept. Theor. Phys.; Khoze, Valery; /Durham U., IPPP; Knutsson, Albert; /DESY; Klein, Max; /Liverpool U.; Krauss, Frank; /Durham U., IPPP; Kutak, Krzysztof; /DESY; Laenen, Eric; /NIKHEF, Amsterdam; Lonnblad, Leif; /Lund U., Dept. Theor. Phys.; Motyka, Leszek; /Hamburg U., Inst. Theor. Phys. II /Birmingham U. /Southern Methodist U. /DESY /Piemonte Orientale U., Novara /CERN /Paris, LPTHE /Hamburg U. /Penn State U.

    2011-11-10

    More than 100 people participated in a discussion session at the DIS08 workshop on the topic What HERA may provide. A summary of the discussion with a structured outlook and list of desirable measurements and theory calculations is given. The HERA accelerator and the HERA experiments H1, HERMES and ZEUS stopped running in the end of June 2007. This was after 15 years of very successful operation since the first collisions in 1992. A total luminosity of {approx} 500 pb{sup -1} has been accumulated by each of the collider experiments H1 and ZEUS. During the years the increasingly better understood and upgraded detectors and HERA accelerator have contributed significantly to this success. The physics program remains in full swing and plenty of new results were presented at DIS08 which are approaching the anticipated final precision, fulfilling and exceeding the physics plans and the previsions of the upgrade program. Most of the analyses presented at DIS08 were still based on the so called HERA I data sample, i.e. data taken until 2000, before the shutdown for the luminosity upgrade. This sample has an integrated luminosity of {approx} 100 pb{sup -1}, and the four times larger statistics sample from HERA II is still in the process of being analyzed.

  16. BCR-ABL1: Test

    Science.gov (United States)

    ... molecular genetic test, and/or fluorescence in situ hybridization (FISH) . These help establish the initial diagnosis of ... Health Professionals ©2001 - by American Association for Clinical Chemistry • Contact Us | Terms of Use | Privacy We comply ...

  17. Frequency of the ETV6-RUNX1, BCR-ABL1, TCF3-PBX1, and MLL-AFF1 fusion genes in Guatemalan pediatric acute lymphoblastic leukemia patients and their ethnic associations.

    Science.gov (United States)

    Carranza, Claudia; Granados, Lilian; Morales, Oneida; Jo, Wendy; Villagran, Swuanny; Tinti, Damaris; Villegas, Mauricio; Antillón, Federico; Torselli, Silvana; Silva, Gabriel

    2013-06-01

    Fusion genes involved in acute lymphoblastic leukemia (ALL) occur mostly due to genetic and environmental factors, and only a limited number of studies have reported any ethnic influence. This study assesses whether an ethnic influence has an effect on the frequency of any of the four fusion genes: BCR-ABL1, ETV6-RUNX1, TCF3-PBX1, and MLL-AFF1 found in ALL. To study this ethnic influence, mononuclear cells were obtained from bone marrow samples from 143 patients with ALL. We performed RNA extraction and reverse transcription, then assessed the quality of the cDNA by amplifying the ABL1 control gene, and finally evaluated the presence of the four transcripts by multiplex polymerase chain reaction. We found 10 patients who had the BCR-ABL1 fusion gene (7%); 3 patients (2%) were TCF3-PBX1 positive; and 6 patients (4.5%) were ETV6-RUNX1 positive. The incidence of this last fusion gene is quite low when compared to the values reported in most countries. The low incidence of the ETV6-RUNX1 fusion gene found in Guatemala matches the incidence rates that have been reported in Spain and Indian Romani. Since it is known that an ethnic resemblance exists among these three populations, as shown by ancestral marker studies, the ALL data suggests an ethnic influence on the occurrence and frequency of this particular fusion gene.

  18. Persistence of BCR/ABL mRNA-expressing bone-marrow cells in patients with chronic myelogenous leukemia in complete cytogenetic remission induced by interferon-alpha therapy.

    Science.gov (United States)

    Eberlé, F; Toiron, Y; Camerlo, J; Lafage, M; Sainty, D; Arnoulet, C; Raineri, V; Gabert, J; Maraninchi, D; Mannoni, P

    1995-06-01

    Complete hematologic and cytogenetic responses can be obtained with interferon-alpha (IFN-alpha) in 15-25% of the patients with chronic myelogenous leukemia (CML). In these patients, reverse-transcription polymerase chain reaction (RT-PCR) can be used to evaluate minimal residual disease. We studied 12 patients who remained Philadelphia-negative for a median period of 21 months on IFN-alpha therapy. Using RT-PCR, the specific transcript was found in all bone marrow (BM) samples. Ten patients still exhibiting a persistent residual clone remained in cytogenetic remission for a median period of 14 months. As we observed a dissociation between bcr-abl expression in BM and peripheral blood (PB) cells, and given the known fluctuations of the bcr-abl PCR results, we suggest that PB negative results should be confirmed on BM specimens. Alternatively, it remains to be demonstrated whether longitudinal monitoring of residual disease would benefit from quantitative PCR or double fluorescence in situ hybridization.

  19. Synthesis, magnetic properties and Moessbauer spectroscopy for the pyrochlore family Bi{sub 2}BB Prime O{sub 7} with B=Cr and Fe and B Prime =Nb, Ta and Sb

    Energy Technology Data Exchange (ETDEWEB)

    Blanco, Maria C. [INFIQC (CONICET), Dpto. de Fisicoquimica, Fac. de Ciencias Quimicas, U.N.C., Cordoba (X5000HUA) (Argentina); Franco, Diego G. [INFIQC (CONICET), Dpto. de Fisicoquimica, Fac. de Ciencias Quimicas, U.N.C., Cordoba (X5000HUA) (Argentina); Centro Atomico Bariloche - CNEA, Av. E. Bustillo 9500, S.C. de Bariloche (8500), R.N. (Argentina); Jalit, Yamile; Pannunzio Miner, Elisa V. [INFIQC (CONICET), Dpto. de Fisicoquimica, Fac. de Ciencias Quimicas, U.N.C., Cordoba (X5000HUA) (Argentina); Berndt, Graciele; Paesano, Andrea [Departamento de Fisica, Universidade Estadual de Maringa, Parana (Brazil); Nieva, Gladys [Centro Atomico Bariloche - CNEA, Av. E. Bustillo 9500, S.C. de Bariloche (8500), R.N. (Argentina); Carbonio, Raul E., E-mail: carbonio@mail.fcq.unc.edu.ar [INFIQC (CONICET), Dpto. de Fisicoquimica, Fac. de Ciencias Quimicas, U.N.C., Cordoba (X5000HUA) (Argentina)

    2012-08-15

    The samples Bi{sub 2}BB Prime O{sub 7}, with B=Cr and Fe and B Prime =Nb, Ta and Sb were prepared by solid state method. The crystallographic structure was investigated on the basis of X-ray powder diffraction data. Rietveld refinements show that the crystal structure is cubic, space group Fd-3m. The Bi{sup 3+} cation on the eight-coordinate pyrochlore A-site shows displacive disorder, as a consequence of its lone pair electron configuration. There is also a considerable A-site disorder shown by Rietveld Analysis and confirmed in the case of the iron containing samples with Moessbauer spectroscopy. The magnetic measurements show paramagnetic behavior at all temperatures for the Cr oxides. The Fe pyrochlores show antiferromagnetic order around 10 K.

  20. RT-PCR ANALYSIS OF E2A-PBX1, TEL-AML1, BCR-ABL AND MLL-AF4 FUSION GENE TRANSCRIPTS IN B-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Iuliu-Cristian Ivanov

    2013-11-01

    Full Text Available Acute lymphoblastic leukemia represents a heterogeneous group of hematological malignancies, defined by clonal proliferation of lymphoid cells. Immunophenotyping by flow cytometry and molecular analysis for the detection of genetic anomalies are clinical standard procedures for diagnosis, sub-classification and post-therapeutic evaluation. Samples from 105 patients diagnosed with acute lymphoblastic leukemia were immunophenotyped at diagnosis and were investigated by molecular analysis in order to identify the occurrence of four fusion genes: MLL-AF4, TEL-AML-1, BCR-ABL-p190, E2A-PBX-1. There were no associations found between the immunophenotype and the presence of any fusion genes evaluated. Both methods in combination remain a prerequisite for an improved subclassification of hematological malignancies, therapeutic decision, and evaluation of treatment response.

  1. Monitoring of bcr/abl Fusion Gene by Interphase-Dual-Color and Dual-Fusion Fluorescence in situ Hybridization in CML after Allo-HSCT%间期双色双融合荧光原位杂交监测慢性髓系白血病异基因造血干细胞移植后bcr/abl融合基因

    Institute of Scientific and Technical Information of China (English)

    钱思轩; 李建勇; 张闰; 洪鸣; 仇海荣; 李丽; 徐卫; 盛瑞兰; 吴汉新

    2006-01-01

    本研究探讨bcr/abl双色双融合荧光原位杂交(DD-FISH)的敏感性及临床应用价值.对19例慢性髓细胞白血病(CML)异基因造血干细胞移植(allo-HSCT)后微小残留病灶(MRD)用DD-FISH进行监测,同时与常规细胞遗传学(CC)、逆转录-聚合酶链反应(RT-PCR)结果相比较.样本取自骨髓,少数来源于骨髓片或外周血.结果表明:14例CML患者在Allo-HSCT后CC显示持续正常供者核型,RT-PCR转为阴性,移植2月后均为完全供者嵌合(DC),DD-FISH检测结果持续为阴性,平均随访11.25月,MRD无增加.1例CC及RT-PCR阴性,而性染色体FISH为混合嵌合,DD-FISH阳性,监测无MRD增加,临床未治疗,疾病稳定.3例骨髓复发患者的DD-FISH及性染色体FISH均提示MRD明显增加,RT-PCR转为阳性,却只有1例CC异常,供者淋巴细胞输注(DLI)及甲磺酸伊马替尼治疗后均为DC,DD-FISH阴性,RT-PCR阴性.1例骨活检证实髓外复发患者骨髓或外周血样本的DD-FISH、CC及PCR均阴性,供受者完全嵌合.结论:间期双色双融合FISH可应用于CML异基因造血干细胞移植后MRD的监测,其操作简易快速,灵敏度高,且骨髓或外周血均可采用.动态监测能及时发现扩大的白血病细胞克隆.

  2. Internet Provider Facilities, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Internet Provider Facilities dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable...

  3. BCR-ABL融合基因T315I突变的白血病行异基因HSCT的疗效及复发后的治疗分析%Curative effectiveness of allogeneic stem cell transplantation and treatment of recurrence in patients harboring T315I BCR-ABL mutated leukemias

    Institute of Scientific and Technical Information of China (English)

    桂晓敏; 仇惠英; 潘金兰; 周敏; 鲍协炳; 陈苏宁; 孙爱宁; 吴德沛; 岑建农

    2014-01-01

    Objective To retrospectively analyze the curative effectiveness of allogeneic stem cell transplantation (allo-SCT) for the leukemia patients with the T315I mutation,and to discuss the treatments for the relapsing patients after allo-SCT.Method Through observing 10 leukemia patients harboring a T315I BCR-ABL mutation who underwent allo-SCT,we analyzed the remission rate,recurrence rate and long-term survival situation of these patients and explored the treatments for relapsing patients after allo-SCT.Result Of 10 patients,4 patients were female and 6 were male.The median age was 29 years (range,18-49).Before HSCT,5 were given imatinib,3 nilotinib and 2 dasatinib,respectively.Ten patients (100%) obtained complete remission (CR) and the median remission time was 23 days (range,14-56).During the follow-up period,1 case of CML and 3 cases of Ph+-ALL (40%) obtained CR.The survival time was 75 to 741 days.In the 6 dead patients,1 died of upper gastrointestinal hemorrhage on the day 137 after allo-SCT; 2 died of graft versus host disease on the day 53 and 617 respectively after allo-SCT; 1 case of CML and 2 cases of Ph+ ALL relapsed on the day 27,50 and 130 respectively after allo-SCT,and 2 of them died on the day 5 and 40 respectively after relapse,and 1 recurrent case did not obtain remission after chemotherapy and died on the day 97 after relapse.Conclusion The allo-SCT can be used to treat the leukemia patients with T315I mutation,and high remission rate can be obtained,tut there is the high risk of recurrence.The patients with recurrent leukemia can take further relevant treatment to prolong survival time.%目的 分析BCR-ABL融合基因T315I突变的白血病患者接受异基因造血干细胞移植(HSCT)的资料,探讨移植疗效及复发后的治疗.方法 观察10例伴T315I突变的费城染色体阳性(Ph+)的急性淋巴细胞白血病(ALL)和慢性粒细胞白血病(CML)接受异基因HSCT后缓解率、复发率以及长期存活情况,分析这

  4. HMO partnering: the provider dilemma.

    Science.gov (United States)

    Ayers, J; Benson, L; Bonhag, R

    1996-10-01

    While the growth of HMOs has slowed patient visits to doctors, it also has created a deluge of press clippings. On July 16, 1996, three articles on the subject appeared in the Wall Street Journal, front section. The headlines painted a vivid picture of the forces acting on HMOs and providers alike (Figure 1). The articles portended more change for healthcare. The "shake-out," a term applied to industries in serious transformation, brings shedding of excess capacity and loss of jobs and income. Providers, in particular, find themselves in a difficult dilemma. They must not only cut costs as reimbursement drops, but also retain patients with good outcomes and high quality service. Patient retention means keeping the individual patient from switching to another provider and keeping the insurer's group of patients as an authorized provider for that insurer. The relationship between provider and HMO lies at the heart of the provider dilemma. The HMO structure, which shifts financial risk for care, is quickly setting the standard, for healthcare pricing, medical standards, and management practices. Understanding and responding to HMO needs are vital to competitive advantage and survival. The article discusses the inherent dilemma of HMO and provider partnering and suggests provider responses.

  5. Babesiosis for Health Care Providers

    Centers for Disease Control (CDC) Podcasts

    2012-04-25

    This podcast will educate health care providers on diagnosing babesiosis and providing patients at risk with tick bite prevention messages.  Created: 4/25/2012 by Center for Global Health, Division of Parasitic Diseases and Malaria.   Date Released: 4/25/2012.

  6. First Case of Biphenotypic/bilineal (B/myeloid, B/monocytic) Mixed Phenotype Acute Leukemia with t(9;22)(q34;q11.2);BCR-ABL1.

    Science.gov (United States)

    Kim, Hyeong Nyeon; Hur, Mina; Kim, Hanah; Ji, Misuk; Moon, Hee-Won; Yun, Yeo-Min; Lee, Mark Hong

    2016-07-01

    Mixed phenotype acute leukemia (MPAL) includes biphenotypic leukemia, bilineal leukemia, or its combination by the 2008 WHO classification. A few cases of combined biphenotypic/bilineal MPAL have been reported so far; they all had biphenotypic expressions in only one of the two distinct leukemic populations. A 43-year-old female presented with leukocytosis and bicytopenia. Her complete blood counts were: hemoglobin, 6.9 g/dL; white blood cells, 62.8×10(9)/L; and platelets, 83×10(9)/L. Neither lymphadenopathy nor organomegaly was observed. Blasts and promonocytes/monoblasts were increased in her peripheral blood (42%) and bone marrow (60.1%). Flow cytometric analysis revealed two distinct populations of leukemic cells, which expressed CD11c, CD19, and cytoplasmic CD79a in common. Additionally, the first population expressed CD10 and CD117 (B/myeloid), and the second one expressed CD14 and CD20 (B/monocytic). She had a karyotype of 46,XX,inv(9)(p12q13),t(9;22)(q34;q11.2)[20] and BCR/ABL1 rearrangement. To the best of our knowledge, this is the first reported case of biphenotypic/bilineal MPAL with B/myeloid and B/monocytic expressions.

  7. Switching to second-generation tyrosine kinase inhibitor improves the response and outcome of frontline imatinib-treated patients with chronic myeloid leukemia with more than 10% of BCR-ABL/ABL ratio at 3 months

    Science.gov (United States)

    Casado, Luis-Felipe; García-Gutiérrez, José-Valentín; Massagué, Isabel; Giraldo, Pilar; Pérez-Encinas, Manuel; de Paz, Raquel; Martínez-López, Joaquín; Bautista, Guiomar; Osorio, Santiago; Requena, María-José; Palomera, Luis; Peñarrubia, María-Jesús; Calle, Carmen; Hernández-Rivas, José-Ángel; Burgaleta, Carmen; Maestro, Begoña; García-Ormeña, Nuria; Steegmann, Juan-Luis

    2015-01-01

    Chronic myeloid leukemia patients display heterogeneous responses to imatinib. Survival depends on baseline clinical characteristics (including prognostic scoring systems) and on early response (such as >10% BCR-ABL/ABL ratio at 3 months of therapy). The results of switching to second-generation tyrosine kinase inhibitors (2GTKIs) may contain a bias since, in the majority of these studies, patients who switch treatment due to intolerance or failure are censored or excluded. We analyzed the Spanish Registry data on switching in an intention-to-treat analysis of patients in standard clinical practice. Switching to 2GTKIs improves responses from 45% to 75% of complete cytogenetic response (CCyR) and from 15% to 45% of major molecular response (MMR) in the group without molecular response 1 (MR1) at 3 months and from 70% to 87% in CCyR and from 52% to 87% in MMR in the group with MR1. The final response rate is poorer in the group with no MR1 at 3 months. Nevertheless, the differences in the rates of response were not translated into differences in major events (transformations or deaths), and the final progression-free survival and overall survival were similar. PMID:25756742

  8. TERRAIN, PROVIDENCE COUNTY, RHODE ISLAND

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — The Providence AOI consists of the costal portion of the county, and meshes up seamlessly with the Kent county AOI directly south. Ground Control is collected...

  9. Medicare Referring Provider DMEPOS PUF

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset, which is part of CMSs Medicare Provider Utilization and Payment Data, details information on Durable Medical Equipment, Prosthetics, Orthotics and...

  10. Lodging Update: Providence, Rhode Island

    Directory of Open Access Journals (Sweden)

    Ragel Roginsky

    2013-04-01

    Full Text Available Each quarter, Pinnacle Advisory Group prepares an analysis of the New England lodging industry, which provides a regional summary and then focuses in depth on a particular market. These reviews look at recent and proposed supply changes, factors affecting demand and growth rates, and the effects of interactions between such supply and demand trends. In this issue, the authors spotlight the lodging market in Providence, Rhode Island.

  11. Ancillary Services Provided from DER

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, J.B.

    2005-12-21

    Distributed energy resources (DER) are quickly making their way to industry primarily as backup generation. They are effective at starting and then producing full-load power within a few seconds. The distribution system is aging and transmission system development has not kept up with the growth in load and generation. The nation's transmission system is stressed with heavy power flows over long distances, and many areas are experiencing problems in providing the power quality needed to satisfy customers. Thus, a new market for DER is beginning to emerge. DER can alleviate the burden on the distribution system by providing ancillary services while providing a cost adjustment for the DER owner. This report describes 10 types of ancillary services that distributed generation (DG) can provide to the distribution system. Of these 10 services the feasibility, control strategy, effectiveness, and cost benefits are all analyzed as in the context of a future utility-power market. In this market, services will be provided at a local level that will benefit the customer, the distribution utility, and the transmission company.

  12. Ecosystem services provided by waterbirds.

    Science.gov (United States)

    Green, Andy J; Elmberg, Johan

    2014-02-01

    Ecosystem services are ecosystem processes that directly or indirectly benefit human well-being. There has been much recent literature identifying different services and the communities and species that provide them. This is a vital first step towards management and maintenance of these services. In this review, we specifically address the waterbirds, which play key functional roles in many aquatic ecosystems, including as predators, herbivores and vectors of seeds, invertebrates and nutrients, although these roles have often been overlooked. Waterbirds can maintain the diversity of other organisms, control pests, be effective bioindicators of ecological conditions, and act as sentinels of potential disease outbreaks. They also provide important provisioning (meat, feathers, eggs, etc.) and cultural services to both indigenous and westernized societies. We identify key gaps in the understanding of ecosystem services provided by waterbirds and areas for future research required to clarify their functional role in ecosystems and the services they provide. We consider how the economic value of these services could be calculated, giving some examples. Such valuation will provide powerful arguments for waterbird conservation.

  13. Twitter for travel medicine providers.

    Science.gov (United States)

    Mills, Deborah J; Kohl, Sarah E

    2016-03-01

    Travel medicine practitioners, perhaps more so than medical practitioners working in other areas of medicine, require a constant flow of information to stay up-to-date, and provide best practice information and care to their patients. Many travel medicine providers are unaware of the popularity and potential of the Twitter platform. Twitter use among our travellers, as well as by physicians and health providers, is growing exponentially. There is a rapidly expanding body of published literature on this information tool. This review provides a brief overview of the ways Twitter is being used by health practitioners, the advantages that are peculiar to Twitter as a platform of social media, and how the interested practitioner can get started. Some key points about the dark side of Twitter are highlighted, as well as the potential benefits of using Twitter as a way to disseminate accurate medical information to the public. This article will help readers develop an increased understanding of Twitter as a tool for extracting useful facts and insights from the ever increasing volume of health information.

  14. Service Provider DevOps

    OpenAIRE

    John, Wolfgang; Marchetto, Guido; Németh, Felicián; Sköldström, Pontus; Steinert, Rebecca; Meirosu, Catalin; Papafili, Ioanna; Pentikousis, Kostas

    2017-01-01

    Although there is consensus that software defined networking and network functions virtualization overhaul service provisioning and deployment, the community still lacks a definite answer on how carrier-grade operations praxis needs to evolve. This article presents what lies beyond the first evolutionary steps in network management, identifies the challenges in service verification, observability, and troubleshooting, and explains how to address them using our Service Provider DevOps (SP-DevO...

  15. The synthetic heat shock protein 90 (Hsp90) inhibitor EC141 induces degradation of Bcr-Abl p190 protein and apoptosis of Ph-positive acute lymphoblastic leukemia cells.

    Science.gov (United States)

    Tong, Wei-Gang; Estrov, Zeev; Wang, Yongtao; O'Brien, Susan; Faderl, Stefan; Harris, David M; Van Pham, Quin; Hazan-Halevy, Inbal; Liu, Zhiming; Koch, Patricia; Kantarjian, Hagop; Keating, Michael J; Ferrajoli, Alessandra

    2011-12-01

    The prognosis of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is poor. Chemotherapy is rarely curative and tyrosine kinase inhibitors (TKIs) induce only transient responses. Heat shock protein 90 (Hsp90) is a chaperone protein that is important in signal transduction, cell cycle control, and transcription regulation in both normal and leukemia cells. In the current study, we tested the growth inhibitory and apoptotic effects of a novel Hsp90 inhibitor, EC141 on the Ph+ ALL lines Z-119, Z-181, and Z-33, as well as primary bone marrow-derived blasts from patients with newly diagnosed Ph+ ALL. We found that EC141 inhibited the growth of Ph+ ALL cells in a concentration-dependent manner with IC(50) ranged from 1 to 10 nM. EC141 also inhibited the proliferation of primary bone marrow-derived blasts using the ALL blast colony assay. EC141 down-regulated Hsp90 and up-regulated Hsp70 protein levels, inhibited CrkL phosphorylation, and induced degradation of Bcr-Abl p190 protein through ubiquitin-dependent proteasomal pathway. Furthermore, exposure of Ph+ ALL cells to EC141 resulted in activation of caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and induction of apoptosis. In conclusion, our data suggest that EC141 is a potent Hsp90 inhibitor with activity against Ph+ ALL. Further studies to investigate the anticancer effect of EC141 either as a single agent, or in combination in Ph+ ALL and other hematological malignancies are warranted.

  16. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib

    Science.gov (United States)

    Shah, Neil P.; Kim, Dong-Wook; Kantarjian, Hagop; Rousselot, Philippe; Llacer, Pedro Enrique Dorlhiac; Enrico, Alicia; Vela-Ojeda, Jorge; Silver, Richard T.; Khoury, Hanna Jean; Müller, Martin C.; Lambert, Alexandre; Matloub, Yousif; Hochhaus, Andreas

    2010-01-01

    Background Dasatinib 100 mg once daily achieves intermittent BCR-ABL kinase inhibition and is approved for chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib. To better assess durability of response to and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here. Design and Methods In a phase 3 study, 670 chronic-phase chronic myeloid leukemia patients with resistance, intolerance, or suboptimal response to imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140 mg once-daily, or 70 mg twice-daily. Results Data from a 2-year minimum follow-up demonstrate that dasatinib 100 mg once daily achieves major cytogenetic response and complete cytogenetic response rates comparable to those in the other treatment arms, and reduces the frequency of key side effects. Comparable 2-year progression-free survival and overall survival rates were observed (80% and 91%, respectively, for 100 mg once daily, and 75%–76% and 88%–94%, respectively, in other arms). Complete cytogenetic responses were achieved rapidly, typically by 6 months. In patients treated with dasatinib 100 mg once daily for 6 months without complete cytogenetic response, the likelihood of achieving such a response by 2 years was 50% for patients who had achieved a partial cytogenetic response, and only 8% or less for patients with minor, minimal, or no cytogenetic response. Less than 3% of patients suffered disease transformation to accelerated or blast phase. Conclusions Intermittent kinase inhibition can achieve rapid and durable responses, indistinguishable from those achieved with more continuous inhibition. PMID:20139391

  17. Collection of Biospecimen & Clinical Information in Patients w/ Gastrointestinal Cancers

    Science.gov (United States)

    2012-05-24

    Gastrointestinal Neoplasms; Gynecologic Cancers; Gynecologic Cancers Cervical Cancer; Gastric (Stomach) Cancer; Gastro-Esophageal(GE) Junction Cancer; Gastrointenstinal Stromal Tumor (GIST); Colon/Rectal Cancer; Colon/Rectal Cancer Colon Cancer; Colon/Rectal Cancer Rectal Cancer; Colon/Rectal Cancer Anal Cancer; Anal Cancer; Hepatobiliary Cancers; Hepatobiliary Cancers Liver; Pancreatic Cancer

  18. A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

    Science.gov (United States)

    2015-10-01

    Squamous Cell Carcinoma Stage IB Y N 0.8 60 50 25 3 4 1.84 3 4 . 17 1 Yes - Current Smoker 52 None None V0099 Carcinoid Tumor: Typical Stage IA Y N...Carcinoma Stage IIIA Y N 1.8 75 50 5 5 1.3 5 .33 Yes - Current Smoker 60 None None V0233 Squamous Cell Carcinoma Stage IA Y N 0.32 90 50 5 1 4 .70 2 4 . 17 ...No - Quit Smoking 60 AR Second- hand smoke Second- hand smoke V0289 Squamous Cell Carcinoma Stage IA Y N 0.22 90 50 0 2 1.35 6 . 17 2 Yes - Current

  19. Impact of biospecimens handling on biomarker research in breast cancer

    Directory of Open Access Journals (Sweden)

    Callari Maurizio

    2009-11-01

    Full Text Available Abstract Background Gene expression profiling is moving from the research setting to the practical clinical use. Gene signatures able to correctly identify high risk breast cancer patients as well as to predict response to treatment are currently under intense investigation. While technical issues dealing with RNA preparation, choice of array platforms, statistical analytical tools are taken into account, the tissue collection process is seldom considered. The time elapsed between surgical tissue removal and freezing of samples for biological characterizations is rarely well defined and/or recorded even for recently stored samples, despite the publications of standard operating procedures for biological sample collection for tissue banks. Methods Breast cancer samples from 11 patients were collected immediately after surgical removal and subdivided into aliquots. One was immediately frozen and the others were maintained at room temperature for respectively 2, 6 and 24 hrs. RNA was extracted and gene expression profile was determined using cDNA arrays. Phosphoprotein profiles were studied in parallel. Results Delayed freezing affected the RNA quality only in 3 samples, which were not subjected to gene profiling. In the 8 breast cancer cases with apparently intact RNA also in sample aliquots frozen at delayed times, 461 genes were modulated simply as a function of freezing timing. Some of these genes were included in gene signatures biologically and clinically relevant for breast cancer. Delayed freezing also affected detection of phosphoproteins, whose pattern may be crucial for clinical decision on target-directed drugs. Conclusion Time elapsed between surgery and freezing of samples appears to have a strong impact and should be considered as a mandatory variable to control for clinical implications of inadequate tissue handling.

  20. Wind Turbine Providing Grid Support

    DEFF Research Database (Denmark)

    2011-01-01

    A variable speed wind turbine is arranged to provide additional electrical power to counteract non-periodic disturbances in an electrical grid. A controller monitors events indicating a need to increase the electrical output power from the wind turbine to the electrical grid. The controller...... is arranged to control the wind turbine as follows: after an indicating event has been detected, the wind turbine enters an overproduction period in which the electrical output power is increased, wherein the additional electrical output power is taken from kinetic energy stored in the rotor and without...... changing the operation of the wind turbine to a more efficient working point.; When the rotational speed of the rotor reaches a minimum value, the wind turbine enters a recovery period to re-accelerate the rotor to the nominal rotational speed while further contributing to the stability of the electrical...

  1. Providing Southern Perspectives on CSR

    DEFF Research Database (Denmark)

    Jeppesen, Søren; Kothuis, Bas

    The article seeks to contribute to the SMEs and CSR literature in developing countries by providing; a) a ‘Southern’ SME perspective, which includes the voices of managers and workers, b) a perspective of CSR, which opens up to informal CSR practices that SMEs undertake, and c) an analysis...... of the key institutional issues affecting the CSR practices of SMEs. It presents perceptions of CSR practices among 21 SMEs in the garment industry in South Africa, based on 40 interviews with managers and 19 interviews with workers through the use of qualitative and quantitative interview frameworks....... It highlights a high degree of similarities between managers and workers, though knowledge of (cognitive level) the concept ‘CSR’ differ considerably. Informal practices are widespread and of key importance to the SMEs, expressed by managers and workers alike. History, industry and manager-workers relations...

  2. Using of Automatic Metadata Providing

    Directory of Open Access Journals (Sweden)

    P. Šimek

    2013-12-01

    Full Text Available The paper deals with the necessity of systemic solution for metadata providing by local archives into central repositories and its subsequent implementatiton by the Department of Information Technologies, Faculty of Economics and Management, Czech University of Life Sciences in Prague, for the needs of the agrarian WWW AGRIS portal. The system supports the OAI-PMH (Open Archive Initiative – Protocol for Metadata Harvesting protocol, several metadata formats and thesauri and meets the quality requirements: functionality, high level of reliability, applicability, sustainability and transferability. The SW application for the OAI-PMH requests’ servicing is run in the setting of the WWW Apache server using an efficient PHP framework Nette and database dibi layer.

  3. Combined shift and methanation in a fluidized-bed reactor. Quarterly progress report, 1 October-31 December 1979. BCR report L-1061

    Energy Technology Data Exchange (ETDEWEB)

    Streeter, R C

    1980-01-01

    Construction of a new bench-scale methanation reactor is in progress. This system will provide the capability of adding steam to the feed gas. A bench-scale activity test, employing four samples of a Ni/Mo catalyst, was conducted using the existing life test system. Results showed that a spent catalyst sample containing 18 percent carbon was still as active as the fresh, as-received catalyst, thus confirming an earlier observation based on the results of PEDU Test No. 37. The activity of one sample that was previously heated at 450 C to remove the carbon seemed abnormally low. However, the results were inconclusive, and this sample will be tested further. No PEDU tests were scheduled. Some planned modifications to the PEDU reactor system are being delayed due to late delivery of a water injection pump and malfunctioning of new ball valves intended for installation on the catalyst sampling system. Arrangements have been made with Dr. Calvin Bartholomew of Brigham Young University to undertake continued studies on carbon deposition and catalyst regeneration. A research proposal submitted by Dr. Bartholomew has been reviewed and approved, and the BYU work is expected to commence early in January 1980.

  4. Batch Covariance Relaxation (BCR) Adaptive Processing.

    Science.gov (United States)

    1981-08-01

    IR&D Final Report 7263-001F, March 15, 1980. [2] Hestenes, M. R. and Steifel, E., "Methods of Conjugate Gradients for Solving Linear Systems," Journal ...Wilkinson, J. H., "Notes on the Solution of Algebraic Linear Simultaneous Equations," Quarterly Journal of Mechanics and Applied Mathematics, pp. 149-173...00 0 In F- P0 -a -- -~e -2 - - -4 - o 0 p.. to I ~ a I I PzN N oin g I ’ l g 1 C 0I ~ Nw c gL Il* . a* . * p. 4r I-in a a4i * Csea OCI I2e Co , lk. lX

  5. Insure Kids Now (IKN) (Dental Care Providers)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Insure Kids Now (IKN) Dental Care Providers in Your State locator provides profile information for oral health providers participating in Medicaid and Children's...

  6. Medicare Provider Data - Part D Prescriber

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Part D Prescriber Public Use File (PUF) provides information on prescription drugs prescribed by individual physicians and other health care providers and paid...

  7. Discussing Diabetes with Your Healthcare Provider

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Diabetes Discussing Diabetes with Your Healthcare Provider Past Issues / Fall 2009 Table of Contents Diabetes Medicines—Always Discuss Them with Your Healthcare Provider ...

  8. Identifiable Data Files - Medicare Provider Analysis and ...

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Medicare Provider Analysis and Review (MEDPAR) File contains data from claims for services provided to beneficiaries admitted to Medicare certified inpatient...

  9. Medicare Provider Data - Physician and Other Supplier

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Physician and Other Supplier Public Use File (Physician and Other Supplier PUF) provides information on services and procedures provided to Medicare...

  10. Medicare Provider Payment Data - Skilled Nursing Facilities

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Skilled Nursing Facility Utilization and Payment Public Use File (Skilled Nursing Facility PUF) provides information on services provided to Medicare...

  11. Institutional Provider and Beneficiary Summary PUF

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS IPBS PUFs are aggregated files in which each record summarizes information for a particular institutional provider. An institutional provider refers to a...

  12. 5 CFR 890.910 - Provider information.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Provider information. 890.910 Section 890.910 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS..., and FEHB Benefit Payments § 890.910 Provider information. The hospital provider information used...

  13. 48 CFR 445.302 - Providing facilities.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Providing facilities. 445.302 Section 445.302 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE CONTRACT MANAGEMENT GOVERNMENT PROPERTY Providing Government Property to Contractors 445.302 Providing facilities....

  14. 48 CFR 645.302 - Providing facilities.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Providing facilities. 645.302 Section 645.302 Federal Acquisition Regulations System DEPARTMENT OF STATE CONTRACT MANAGEMENT GOVERNMENT PROPERTY Providing Government Property to Contractors 645.302 Providing facilities....

  15. Co-providing: understanding the logistics.

    Science.gov (United States)

    Dickerson, Pamela S

    2011-11-01

    Continuing nursing education providers have sometimes said that they don't want to co-provide because "it's too much trouble" or they "won't be able to control what happens" or because they don't understand the process. This column clarifies the logistics of the co-provider relationship.

  16. 75 FR 48273 - Technical Service Provider Assistance

    Science.gov (United States)

    2010-08-10

    ... provisions by expanding the definition Technical Service Provider Assistance, which contained an error in the omission of ``Indian Tribe'' in the definition of Technical Service Provider. DATES: Effective Date: This... page 6846, in the third column, the Technical Service Provider definition reads ``Technical...

  17. Moral Distress in Pediatric Healthcare Providers.

    Science.gov (United States)

    Trotochaud, Karen; Coleman, Joyce Ramsey; Krawiecki, Nicolas; McCracken, Courtney

    2015-01-01

    Pediatric providers across professions and clinical settings experience moral distress. Higher moral distress correlates with intent to leave for all professionals. Physicians as professional group had the highest moral distress. Intensive care nurses had the highest moral distress for nurses. While all providers describe distressing scenarios as disturbing, physicians report situations as occurring more frequently. The most distressing situations include requests for aggressive treatments not in child's best interest, poor team communication and lack of provider continuity. Understanding moral distress as experienced by all pediatric providers is needed to create interventions with a goal of reducing provider turnover.

  18. Competition of Wireless Providers for Atomic Users

    CERN Document Server

    Gajić, Vojislav; Rimoldi, Bixio

    2010-01-01

    We study a problem where wireless service providers compete for heterogenous wireless users. The users differ in their utility functions as well as in the perceived quality of service of individual providers. We model the interaction of an arbitrary number of providers and users as a two-stage multi-leader-follower game. We prove existence and uniqueness of the subgame perfect Nash equilibrium for a generic channel model and a wide class of users' utility functions. We show that the competition of resource providers leads to a globally optimal outcome under mild technical conditions. Most users will purchase the resource from only one provider at the unique subgame perfect equilibrium. The number of users who connect to multiple providers at the equilibrium is always smaller than the number of providers. We also present a decentralized algorithm that globally converges to the unique system equilibrium with only local information under mild conditions on the update rates.

  19. Data Service Provider Cost Estimation Tool

    Science.gov (United States)

    Fontaine, Kathy; Hunolt, Greg; Booth, Arthur L.; Banks, Mel

    2011-01-01

    The Data Service Provider Cost Estimation Tool (CET) and Comparables Database (CDB) package provides to NASA s Earth Science Enterprise (ESE) the ability to estimate the full range of year-by-year lifecycle cost estimates for the implementation and operation of data service providers required by ESE to support its science and applications programs. The CET can make estimates dealing with staffing costs, supplies, facility costs, network services, hardware and maintenance, commercial off-the-shelf (COTS) software licenses, software development and sustaining engineering, and the changes in costs that result from changes in workload. Data Service Providers may be stand-alone or embedded in flight projects, field campaigns, research or applications projects, or other activities. The CET and CDB package employs a cost-estimation-by-analogy approach. It is based on a new, general data service provider reference model that provides a framework for construction of a database by describing existing data service providers that are analogs (or comparables) to planned, new ESE data service providers. The CET implements the staff effort and cost estimation algorithms that access the CDB and generates the lifecycle cost estimate for a new data services provider. This data creates a common basis for an ESE proposal evaluator for considering projected data service provider costs.

  20. Home care providers to the rescue

    DEFF Research Database (Denmark)

    Hansen, Steen Møller; Brøndum, Stig; Thomas, Grethe

    2015-01-01

    AIM: To describe the implementation of a novel first-responder programme in which home care providers equipped with automated external defibrillators (AEDs) were dispatched in parallel with existing emergency medical services in the event of a suspected out-of-hospital cardiac arrest (OHCA......). METHODS: We evaluated a one-year prospective study that trained home care providers in performing cardiopulmonary resuscitation (CPR) and using an AED in cases of suspected OHCA. Data were collected from cardiac arrest case files, case files from each provider dispatch and a survey among dispatched...... providers. The study was conducted in a rural district in Denmark. RESULTS: Home care providers were dispatched to 28 of the 60 OHCAs that occurred in the study period. In ten cases the providers arrived before the ambulance service and subsequently performed CPR. AED analysis was executed in three cases...

  1. Identifying Mentors' Observations for Providing Feedback

    Science.gov (United States)

    Hudson, Peter

    2016-01-01

    Mentors' feedback can assist preservice teachers' development; yet feedback tends to be variable from one mentor to the next. What do mentors observe for providing feedback? In this study, 24 mentors observed a final-year preservice teacher through a professionally video-recorded lesson and provided written notes for feedback. They observed the…

  2. Organizational culture associated with provider satisfaction

    Science.gov (United States)

    Scammon, Debra L.; Tabler, Jennifer; Brunisholz, Kimberly; Gren, Lisa H.; Kim, Jaewhan; Tomoaia-Cotisel, Andrada; Day, Julie; Farrell, Timothy W.; Waitzman, Norman J.; Magill, Michael K.

    2014-01-01

    Objectives Assess 1) provider satisfaction with specific elements of PCMH; 2) clinic organizational cultures; 3) associations between provider satisfaction and clinic culture. Methods Cross sectional study with surveys conducted in 2011 with providers and staff in 10 primary care clinics implementing their version of a PCMH: Care by Design™. Measures included the Organizational Culture Assessment Instrument (OCAI) and the American Medical Group Association provider satisfaction survey. Results Providers were most satisfied with quality of care (M=4.14; scale=1–5) and interactions with patients (M=4.12) and least satisfied with time spent working (M=3.47), paper work (M =3.45) and compensation (M=3.35). Culture profiles differed across clinics with family/clan and hierarchical the most common. Significant correlations (p ≤ 0.05) between provider satisfaction and clinic culture archetypes included: family/clan negatively correlated with administrative work; entrepreneurial positively correlated with the Time Spent Working dimension; market/rational positively correlated with how practices were facing economic and strategic challenges; and hierarchical negatively correlated with Relationships with Staff and Resource dimensions. Discussion Provider satisfaction is an important metric for assessing experiences with features of a PCMH model. Conclusions Identification of clinic-specific culture archetypes and archetype associations with provider satisfaction can help inform practice redesign. Attention to effective methods for changing organizational culture is recommended. PMID:24610184

  3. Provider Services Network Project. Draft Final Report.

    Science.gov (United States)

    Urban and Rural Systems Associates, San Francisco, CA.

    This draft report on the development and testing of a child care Provider Services Network (PSN) model in Santa Clara County, California, includes a handbook (Manual to Optimize a PSN) designed to provide the State Department of Education and regional or local child care coordinating agencies with information needed to develop PSN optimization…

  4. Extensive IT outsourcing: advice from providers.

    Science.gov (United States)

    Smith, Mike; Whiting, Stacilee

    2007-01-01

    In summary, providers are reporting some benefits related to resources and knowledge, improved service levels/performance and stronger IT staff/leadership. Also, on average, providers are reporting satisfactory experiences with application support and CIO outsourcing. However, not all of their expectations are being met, and some providers have discontinued outsourcing due to unmet expectations. Clearly, outsourcing is an option one must research in depth--it is not for everyone. When one evaluates the results of extensive IT outsourcing, it becomes easier to see what outsourcing mix and firm may be a good match for your organization's needs and expected outcomes. As you decide upon the outsourcing mix and firm that is right for you, providers advise you to pay special attention to contractual arrangements. With adequate research and contractual provisions, organizations can find the outsourcing mix that is right for them.

  5. Elder Care for Alzheimer's: Choosing a Provider

    Science.gov (United States)

    ... elder care center for a loved one with Alzheimer's. What should I look for when considering a ... provide an opportunity for your loved one with Alzheimer's to receive assistance and therapeutic activities in a ...

  6. New Zika Vaccine Candidate Provides Powerful Protection

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_163384.html New Zika Vaccine Candidate Provides Powerful Protection Made without live ... HealthDay News) -- A single dose of an experimental Zika vaccine protected mice and monkeys from the virus, ...

  7. Medicare Referring Provider (DMEPOS) Data CY2013

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Centers for Medicare and Medicaid Services (CMS) released a new dataset, the Referring Provider Durable Medical Equipment, Prosthetics, Orthotics and Supplies...

  8. Provider Customer Service Program - Performance Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — CMS is continuously analyzing performance and quality of the Provider Customer Service Programs (PCSPs) of the contractors and will be identifying trends and making...

  9. Medicare Provider Utilization and Payment Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — CMS has released a series of publicly available data files that summarize the utilization and payments for procedures, services, and prescription drugs provided to...

  10. Medicare Provider Analysis and Review (MEDPAR)

    Data.gov (United States)

    U.S. Department of Health & Human Services — MEDPAR files contain information on Medicare beneficiaries using hospital inpatient services. The data is provided by the state and the Diagnosis Related Groups...

  11. Concrete "Waffle" Provides Laser Beam Accuracy

    Science.gov (United States)

    Building Design and Construction, 1978

    1978-01-01

    A massive concrete "waffle," riding on a bed of specially treated gravel and sand inside another building, provides the structural rigidity needed by the University of Rochester's Laboratory for Laser Energetics. (Author)

  12. National Provider Identifier Standard - Data Dissemination

    Data.gov (United States)

    U.S. Department of Health & Human Services — The National Plan and Provider Enumeration System, NPPES, downloadable file, also referred to as the NPI Downloadable File, contains FOIA disclosable NPPES health...

  13. Medicare Provider Utilization and Payment Data - Inpatient

    Data.gov (United States)

    U.S. Department of Health & Human Services — The data provided here include hospital-specific charges for the more than 3,000 U.S. hospitals that receive Medicare Inpatient Prospective Payment System (IPPS)...

  14. Medicare Referring Provider DMEPOS PUF CY2013

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset, which is part of CMSs Medicare Provider Utilization and Payment Data, details information on Durable Medical Equipment, Prosthetics, Orthotics and...

  15. Topological Trends of Internet Content Providers

    CERN Document Server

    Shavitt, Yuval

    2012-01-01

    The Internet is constantly changing, and its hierarchy was recently shown to become flatter. Recent studies of inter-domain traffic showed that large content providers drive this change by bypassing tier-1 networks and reaching closer to their users, enabling them to save transit costs and reduce reliance of transit networks as new services are being deployed, and traffic shaping is becoming increasingly popular. In this paper we take a first look at the evolving connectivity of large content provider networks, from a topological point of view of the autonomous systems (AS) graph. We perform a 5-year longitudinal study of the topological trends of large content providers, by analyzing several large content providers and comparing these trends to those observed for large tier-1 networks. We study trends in the connectivity of the networks, neighbor diversity and geographical spread, their hierarchy, the adoption of IXPs as a convenient method for peering, and their centrality. Our observations indicate that co...

  16. Obstetric Provider Maldistribution: Georgia, USA, 2011.

    Science.gov (United States)

    Spelke, Bridget; Zertuche, Adrienne D; Rochat, Roger

    2016-07-01

    Objectives In 2010, Georgia had the nation's highest maternal mortality rate, sixteenth highest infant mortality rate, and a waning obstetrician/gynecologist (ob/gyn) workforce. Statewide ob/gyn workforce data, however, masked obstetric-specific care shortages and regional variation in obstetric services. The Georgia Maternal and Infant Health Research Group thereby assessed each Georgia region's obstetric provider workforce to identify service-deficient areas. Methods We identified 63 birthing facilities in the 82 Primary Care Service Areas (PCSAs) outside metropolitan Atlanta and interviewed nurse managers and others to assess the age, sex, and expected departure year of each delivering professional. Using accepted annual delivery rates of 155 per obstetrician (OB), 100 per certified nurse midwife (CNM), and 70 per family medicine physician (FP) we converted obstetric providers into "OB equivalents" to standardize obstetric services available in any given area. Using facility births and computed OB equivalents (contemporary and 2020 estimates), we calculated current and projected average annual births per provider (AABP) for each PCSA, categorizing its obstetric provider workforce as "adequate" (AABP  166). We mapped results using ArcGIS. Results Of 82 surveyed PCSAs, 52 % (43) were deficient in obstetric care; 16 % (13) had a shortage and 37 % (30) lacked obstetric providers entirely. There were no delivering FPs in 89 % (73) of PCSAs and no CNMs in 70 % (56). If Georgia fails to recruit delivering providers, 72 % (58/77) of PCSAs will have deficient or no obstetric care by 2020. Conclusions Obstetric provider shortages in Georgia hinder access to prenatal and delivery services. Care-deficient areas will expand if recruitment and retention of delivering professionals does not improve.

  17. Quality Business Service Provider in Community Enterprise

    Directory of Open Access Journals (Sweden)

    Chalard Chantarasombat

    2012-01-01

    Full Text Available Problem statement: The development of community enterprises focuses on the development of service providers for commercial industries and community enterprises and it is necessary to create and extend the development according to the changing global conditions. The department of industrial promotion and industry promotion center region 5, Khon Kaen must create and develop the quality of service providers in community enterprises as an exclusive course to find a model and development guideline in effective operations that is efficient and appropriate according to the particular community. Approach: The objectives of this research were: (1 to recruit and select at least 15 individuals to participate in the training of service providers in community enterprise in Kalasin province. (2 To define the structure, content, create a curriculum and development of service providers in community enterprise. (3 To develop the participants basic skills training, create motivation, learning experience through on the job training and business management and capability in the diagnosing the cause of problems. (4 To develop the participants understanding of community product standards and provide advice and consultation on the preparation and application of manufacturing standard certification of community products, community enterprise management and provide advice in the implementation of management standards of community enterprises. (5 Satisfaction of the participants training in service providers in community enterprise. Results: 29 people applied for the training program and 26 passed evaluation which was higher than the target of 15 individuals. The theoretical training courses prior to the training had an overall average of 5.06 and after the training had an average of 15.80, the average progress was 10.74. The exercise training through on the job training was regarded as a vocational skill and hand an average of 5.27 before the training. After the

  18. Logistic service providers and sustainable physical distribution

    Directory of Open Access Journals (Sweden)

    Stef Weijers

    2012-06-01

    Full Text Available Background: Logistic Service Providers main concern was to ensure reliability for a low price (Christopher, 2005. Dutch Logistic Service Providers still have these two aspects at the top of their list, but also have to take in a new aspect: sustainability. 88% Of the investigated Logistic Service Providers have included sustainability in the company's goals. These Logistic Service Providers have developed different strategies to achieve a higher level of sustainability. This paper presents the results of a study into what Logistic Service Providers say what they are doing, or intend to do, to improve sustainability for their transport services. In this way insight is given in the attitude of Dutch Logistic Service Providers towards sustainability and how they intend to translate this into business practise: internal solutions or new methods incorporating external partners. Methods: Various methods of the investigations were used, among which the analysis of the statements about the sustainabilityon the websites of various companies as well as the questionnaire per Internet. The research covered 50 largest logistics companies operating in the Netherlands and 60 companies that competed for the award "Lean and Green" advertised in the Netherlands. In addition, the Internet survey was answered by 41 companies that belong to the network of our university. Results: The investigation has shown that sustainability is handled by the logistics company as an integral part of the corporate strategy. In contrast, shippers depend in the choice of logistics services primarily on such classical aspects as the reliability or the price and the sustainability play a minor role. Conclusions: Trying to find methods to improve the sustainability, Dutch logistics service providers, in the first place, look for solutions that increase the efficiency and therefore the cost reduction potential. Solutions, which require the involvement of clients, were less often

  19. Dasatinib targets B-lineage cells but does not provide an effective therapy for myeloproliferative disease in c-Cbl RING finger mutant mice.

    Directory of Open Access Journals (Sweden)

    Johanna M Duyvestyn

    Full Text Available This study aimed to determine whether the multi-kinase inhibitor dasatinib would provide an effective therapy for myeloproliferative diseases (MPDs involving c-Cbl mutations. These mutations, which occur in the RING finger and linker domains, abolish the ability of c-Cbl to function as an E3 ubiquitin ligase and downregulate activated protein tyrosine kinases. Here we analyzed the effects of dasatinib in a c-Cbl RING finger mutant mouse that develops an MPD with a phenotype similar to the human MPDs. The mice are characterized by enhanced tyrosine kinase signaling resulting in an expansion of hematopoietic stem cells, multipotent progenitors and cells within the myeloid lineage. Since c-Cbl is a negative regulator of c-Kit and Src signaling we reasoned that dasatinib, which targets these kinases, would be an effective therapy. Furthermore, two recent studies showed dasatinib to be effective in inhibiting the in vitro growth of cells from leukemia patients with c-Cbl RING finger and linker domain mutations. Surprisingly we found that dasatinib did not provide an effective therapy for c-Cbl RING finger mutant mice since it did not suppress any of the hematopoietic lineages that promote MPD development. Thus we conclude that dasatinib may not be an appropriate therapy for leukemia patients with c-Cbl mutations. We did however find that dasatinib caused a marked reduction of pre-B cells and immature B cells which correlated with a loss of Src activity. This study is therefore the first to provide a detailed characterization of in vivo effects of dasatinib in a hematopoietic disorder that is driven by protein tyrosine kinases other than BCR-ABL.

  20. Dasatinib Targets B-Lineage Cells but Does Not Provide an Effective Therapy for Myeloproliferative Disease in c-Cbl RING Finger Mutant Mice

    Science.gov (United States)

    Duyvestyn, Johanna M.; Taylor, Samuel J.; Dagger, Samantha A.; Orandle, Marlene; Morse, Herbert C.; Thien, Christine B. F.; Langdon, Wallace Y.

    2014-01-01

    This study aimed to determine whether the multi-kinase inhibitor dasatinib would provide an effective therapy for myeloproliferative diseases (MPDs) involving c-Cbl mutations. These mutations, which occur in the RING finger and linker domains, abolish the ability of c-Cbl to function as an E3 ubiquitin ligase and downregulate activated protein tyrosine kinases. Here we analyzed the effects of dasatinib in a c-Cbl RING finger mutant mouse that develops an MPD with a phenotype similar to the human MPDs. The mice are characterized by enhanced tyrosine kinase signaling resulting in an expansion of hematopoietic stem cells, multipotent progenitors and cells within the myeloid lineage. Since c-Cbl is a negative regulator of c-Kit and Src signaling we reasoned that dasatinib, which targets these kinases, would be an effective therapy. Furthermore, two recent studies showed dasatinib to be effective in inhibiting the in vitro growth of cells from leukemia patients with c-Cbl RING finger and linker domain mutations. Surprisingly we found that dasatinib did not provide an effective therapy for c-Cbl RING finger mutant mice since it did not suppress any of the hematopoietic lineages that promote MPD development. Thus we conclude that dasatinib may not be an appropriate therapy for leukemia patients with c-Cbl mutations. We did however find that dasatinib caused a marked reduction of pre-B cells and immature B cells which correlated with a loss of Src activity. This study is therefore the first to provide a detailed characterization of in vivo effects of dasatinib in a hematopoietic disorder that is driven by protein tyrosine kinases other than BCR-ABL. PMID:24718698

  1. Teaching antenatal counseling skills to neonatal providers.

    Science.gov (United States)

    Stokes, Theophil A; Watson, Katie L; Boss, Renee D

    2014-02-01

    Counseling a family confronted with the birth of a periviable neonate is one of the most difficult tasks that a neonatologist must perform. The neonatologist's goal is to facilitate an informed, collaborative decision about whether life-sustaining therapies are in the best interest of this baby. Neonatologists are trained to provide families with a detailed account of the morbidity and mortality data they believe are necessary to facilitate a truly informed decision. Yet these complicated and intensely emotional conversations require advanced communication and counseling skills that our current fellowship-training strategies are not adequately providing. We review educational models for training neonatology fellows to provide antenatal counseling at the threshold of viability. We believe that training aimed at teaching these skills should be incorporated into the neonatal-perinatal medicine fellowship. The optimal approaches for teaching these skills remain uncertain, and there is a need for continued innovation and outcomes-based research.

  2. Homeless women's experiences of service provider encounters.

    Science.gov (United States)

    Biederman, Donna J; Nichols, Tracy R

    2014-01-01

    Service providers are gatekeepers to health-sustaining services and resources, although little is known about service encounters from the perspective of homeless women. We conducted in-depth semistructured interviews with 15 homeless women to better understand their experiences of service encounters. Using a phenomenological method, 160 significant statements were extracted from participant transcripts; more positive than negative interactions were reported. The 10 themes that emerged fall along a dehumanizing/humanizing continuum primarily separated by the power participants experienced in the interaction and the trust they felt in the service provider. Implications for nursing practice and research are offered.

  3. MDP challenges from a software provider's perspective

    Science.gov (United States)

    Ohara, Shuichiro

    2014-10-01

    This industry faces new challenges every day. It gets tougher as process nodes shrink and the data complexity and volume increase. We are a mask data preparation (MDP) software provider, and have been providing MDP systems to mask shops since 1990. As the industry has, MDP software providers also have been facing new challenges over time, and the challenges get tougher as process nodes shrink and the data complexity and volume increase. We discuss such MDP challenges and solutions in this paper from a MDP software provider's perspective. The data volume continuously increases, and it is caused by shrinking the process node. In addition, resolution enhancement techniques (RET) such as optical proximity correction (OPC) and inverse lithography technique (ILT) induce data complexity, and it contributes considerably to the increase in data volume. The growth of data volume and complexity brings challenges to MDP system, such as the computing speed, shot count, and mask process correction (MPC). New tools (especially mask writers) also bring new challenges. Variable-shaped E-beam (VSB) mask writers demand fracturing less slivers and lower figure counts for CD accuracy and write time requirements respectively. Now multibeam mask writers are under development and will definitely bring new challenges.

  4. Providing Career Guidance for Young Women.

    Science.gov (United States)

    Colby, Pamela G.

    This module is directed at personnel working or planning to work in the areas of guidance, counseling, placement and follow-through in junior and senior high school settings, grades 7-12. The module topic is career guidance for young women of junior and senior high school age, aand the focus will be on providing nonbiased career guidance which…

  5. 78 FR 14034 - Health Insurance Providers Fee

    Science.gov (United States)

    2013-03-04

    ... techniques or other forms of information technology; and Estimates of capital or start-up costs and costs of... the 111th Congress, JCS-2-11 (March 2011) (JCT General Explanation) at 330. A State health department... select a person as the designated entity on Form 8963, ``Report of Health Insurance Provider...

  6. Outpatient provider concentration and commercial colonoscopy prices.

    Science.gov (United States)

    Pozen, Alexis

    2015-01-01

    The objective was to evaluate the magnitude of various contributors to outpatient commercial colonoscopy prices, including market- and provider-level factors, especially market share. We used adjudicated fee-for-service facility claims from a large commercial insurer for colonoscopies occurring in hospital outpatient department or ambulatory surgery center from October 2005 to December 2012. Claims were matched to provider- and market-level data. Linear fixed effects regressions of negotiated colonoscopy price were run on provider, system, and market characteristics. Markets were defined as counties. There were 178,433 claims from 169 providers (104 systems). The mean system market share was 76% (SD = 0.34) and the mean real (deflated) price was US$1363 (SD = 374), ranging from US$169 to US$2748. For every percentage point increase in a system or individual facility's bed share, relative price increased by 2 to 4 percentage points; this result was stable across a number of specifications. Market population and price were also consistently positively related, though this relation was small in magnitude. No other factor explained price as strongly as market share. Price variation for colonoscopy was driven primarily by market share, of particular concern as the number of mergers increases in wake of the recession and the Affordable Care Act. Whether variation is justified by better quality care requires further research to determine whether quality is subsumed in prices.

  7. Medical Services: Nonphysician Health Care Providers

    Science.gov (United States)

    2007-11-02

    of osteopathy ). (2) PAs may write routine orders on inpatients, using DA Form 4256 (Doctor’s Orders). (3) When required, inpatient treatment...of medicine or osteopathy , who are authorized and responsible for determining, starting, or altering the regimen of medical treatment provided to a

  8. 42 CFR 410.134 - Provider qualifications.

    Science.gov (United States)

    2010-10-01

    ... Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical Nutrition Therapy § 410.134 Provider qualifications. For Medicare Part B coverage of MNT, only a registered dietitian or nutrition professional...

  9. 44 CFR 206.393 - Providing assistance.

    Science.gov (United States)

    2010-10-01

    ... HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE Fire Suppression Assistance § 206.393 Providing assistance. Following the Assistant Administrator for the Disaster Assistance Directorate's... requested by the State. For each fire or fire situation, the State shall prepare a separate Fire...

  10. Messer to provide helium for LHC

    CERN Document Server

    2008-01-01

    Over the course of the next few years, industrial gas specialist The Messer Group, through its Swiss subsidiary Messer Schweiz AG, is to provide a 160,000kg supply of helium to the European Organisation for Nuclear Research (CERN) for the operation of the world's largest particle accelerator.

  11. Messer to provide helium for LHC project

    CERN Multimedia

    2008-01-01

    Over the course of the next few years, industrial gas specialist The Messer Group, through its Swiss subsidiary Messer Schweiz AG, is to provide a 160,000kg supply of helium to the European Organisation for Nuclear Research (CERN) for the operation of the world's largest particle accelerator.

  12. Outpatient Provider Concentration and Commercial Colonoscopy Prices

    Directory of Open Access Journals (Sweden)

    Alexis Pozen PhD

    2015-04-01

    Full Text Available The objective was to evaluate the magnitude of various contributors to outpatient commercial colonoscopy prices, including market- and provider-level factors, especially market share. We used adjudicated fee-for-service facility claims from a large commercial insurer for colonoscopies occurring in hospital outpatient department or ambulatory surgery center from October 2005 to December 2012. Claims were matched to provider- and market-level data. Linear fixed effects regressions of negotiated colonoscopy price were run on provider, system, and market characteristics. Markets were defined as counties. There were 178 433 claims from 169 providers (104 systems. The mean system market share was 76% (SD = 0.34 and the mean real (deflated price was US$1363 (SD = 374, ranging from US$169 to US$2748. For every percentage point increase in a system or individual facility’s bed share, relative price increased by 2 to 4 percentage points; this result was stable across a number of specifications. Market population and price were also consistently positively related, though this relation was small in magnitude. No other factor explained price as strongly as market share. Price variation for colonoscopy was driven primarily by market share, of particular concern as the number of mergers increases in wake of the recession and the Affordable Care Act. Whether variation is justified by better quality care requires further research to determine whether quality is subsumed in prices.

  13. Promoting wellness of peer providers through coaching.

    Science.gov (United States)

    Brice, George H; Swarbrick, Margaret A; Gill, Kenneth J

    2014-01-01

    Peer wellness coaching is workforce innovation that empowers individuals with mental and substance use disorders to achieve recovery. This article briefly describes how this approach can help peer providers develop self-care skills to improve job tenure and promote satisfaction. Promising results of this new approach are presented.

  14. Providing nursing care in a children's hospice.

    Science.gov (United States)

    Day, Alison

    Children who are admitted to hospices need specialist treatment that enables them to enjoy their childhood as much as possible while they receive the care they require. Their parents also have particular needs. During Children's Hospice Week, which started on September 21, the Association of Children's Hospices aims to raise awareness of the work done by children's hospices and the services they provide.

  15. GEAR UP: Providing Opportunities or Conflict?

    Science.gov (United States)

    Walsh, Rachael

    2008-01-01

    Since 1965 the federal government has attempted to provide low socioeconomic status students with equal access to postsecondary education through the Higher Education Act and its multiplicative programmatic efforts. Implemented as one such program in 1998, the Gaining Early Awareness and Readiness for Undergraduate Programs, or GEAR UP, has been…

  16. How Do Health Care Providers Diagnose Vaginitis?

    Science.gov (United States)

    ... the treatments? Are there complications? Does it affect pregnancy? How is it prevented? NICHD Research Information Clinical Trials Resources and Publications How do health care providers diagnose vaginitis? Skip sharing on social media links Share this: Page Content To find out ...

  17. Accessibility of MOOCs: Understanding the Provider Perspective

    Science.gov (United States)

    Iniesto, Francisco; McAndrew, Patrick; Minocha, Shailey; Coughlan, Tim

    2016-01-01

    Massive Online Open Courses (MOOCs) have become an accepted way to make learning opportunities available at large scale and with low cost to the learner. However, only if these are made accessible will they be able to offer flexibility of learning and benefits to all, irrespective of disability. Experience in providing accessible online learning…

  18. PROVIDES: A Complete Veterinary Medical Information System

    OpenAIRE

    Pollock, Roy V.H.; Fredericks, Thomas A.

    1988-01-01

    The desirable attributes of a computer-based diagnostic aid are proposed. These include ease of use, ready accessibility, sound reasoning, completeness, the ability to justify its recommendations, and a system for updating. These principles are illustrated by examples from the authors' diagnostic system (PROVIDES).

  19. Management services organizations: providing economies of scale.

    Science.gov (United States)

    Schaffer, C L

    1998-09-01

    Effective information management and other shared costs can reduce agencies' operating expenses as well as make new products available while providing opportunities to gain a competitive advantage. By taking a close look at ways of controlling documentation, such as the use of a management services organization for information system/computer-based management, agencies can prepare for the challenges of the next century.

  20. 78 FR 71476 - Health Insurance Providers Fee

    Science.gov (United States)

    2013-11-29

    ... under subchapter L, an entity providing health insurance under Medicare Advantage, Medicare Part D, or... entities from the DOL reporting requirements under 29 CFR 2520.101-2 governing MEWAs. The reasons... entity's status as an ECE is only relevant for reporting during a limited period of time. For...

  1. Training To Provide for Healthy Rural Aging.

    Science.gov (United States)

    Troisi, Joseph

    2001-01-01

    Most of the world's rapidly expanding aging population is in rural areas of developing countries. Geriatric training programs should include social, economic, and psychological aspects of aging as well as medical, and should focus on enabling primary health caregivers to care for older people in their environments. Efforts to provide rural…

  2. The $500,000 deduction limitation for remuneration provided by certain health insurance providers. Final regulations.

    Science.gov (United States)

    2014-09-23

    This document contains final regulations on the application of the $500,000 deduction limitation for remuneration provided by certain health insurance providers under section 162(m)(6) of the Internal Revenue Code (Code). These regulations affect certain health insurance providers providing remuneration that exceeds the deduction limitation.

  3. 荧光原位杂交技术可早期有效的预测慢性粒细胞性白血病的预后%Fluorescence in-situ hybridization can provide the early and effective prediction for the prognosis of chronic myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    彭友帆; 刘洋; 张朝霞

    2015-01-01

    目的:本研究探讨荧光原位杂交技术(FISH)在甲磺酸伊马替尼(IM)治疗慢性粒细胞性白血病(CML)长期预后中的早期预测价值。方法选取60例 IM治疗阶段的 CML 患者骨髓标本,运用骨髓细胞形态学(BM)、FISH、逆转录-聚合酶链反应(RT-PCR)以及常规染色体分析方法(CC)对入组的 CML 患者每3~6个月进行48个月疗效观察。结果运用 FISH 技术在第3个月、第6个月以及第12个月检测融合基因 Bcr-abl 阳性细胞<10%的病例,其在第12个月具有较高的细胞遗传学完全缓解(CCR),同时,在第36个月和第48个月所观察的大多数患者均获得了无事件生存,与 Bcr-abl 阳性细胞百分数>10%的患者组比较,差异具有统计学意义(P <0.05)。相似的,运用 RT-PCR 和 CC 在第3个月和第6个月检测 Bcr-Abl mRNA 以及阳性分裂相百分数,两组病例在第36个月和第48个月的无事件生存率(EFS)差异无统计学意义(P >0.05),仅在第12个月差异具有统计学意义(P <0.05)。结论FISH 分析技术可以为 CML 的长期预后提供早期有效的预测。%Objective To investigate the early predictive significance of fluorescence in-situ hybridization (FISH) in the long-term prognosis of treating chronic myeloid leukemia(CML)by imatinib(IM).Methods A total of 60 patients with CML undergoing IMtreatment were enrolled,their bone marrow specimens were collected,and they were observed per 3-6 months for 48 months for treatment efficiency by bone marrow cell morphology(BM),FISH,reverse transcription polymerase chain reaction (RT-PCR)and karyotyping (CC).Results Applying FISH to detect the patients showed that BCR-ABL positive cell 1 0%,there was statistical significance (P 0.05),and there was statistical significance only in the 1 2th month (P <0.05).Conclusions FISH is able to provide the early and effective prediction for the long-term prognosis

  4. Informed consent - Providing information about prenatal examinations

    DEFF Research Database (Denmark)

    Dahl, Katja; Kesmodel, Ulrik; Hvidman, Lone

    Prenatal care has gradually moved away from paternalism, to a state where patient autonomy and information is vital. It is known from other health care settings that the way information is presented affects understanding.The objective is to summarize current knowledge on aspects of informing...... pregnant women about prenatal examinations. Women's knowledge, decisional conflict, satisfaction and anxiety will be explored as compared with different ways and different groups of health professionals providing information. To what extent information empowers informed decision making will be explored......, individual sessions and by way of written materials. None of the interventions leads to a raise in anxiety scores or influence up-take rates. Satisfaction with information provided is found unrelated to level of knowledge, but associated with having expectations for information met. Information does not seem...

  5. Providing Scalable Data Services in Ubiquitous Networks

    CERN Document Server

    Malik, Tanu; Patil, Sanket; Chaudhary, Amitabh; Venkatasubramanian, Venkat

    2010-01-01

    Topology is a fundamental part of a network that governs connectivity between nodes, the amount of data flow and the efficiency of data flow between nodes. In traditional networks, due to physical limitations, topology remains static for the course of the network operation. Ubiquitous data networks (UDNs), alternatively, are more adaptive and can be configured for changes in their topology. This flexibility in controlling their topology makes them very appealing and an attractive medium for supporting "anywhere, any place" communication. However, it raises the problem of designing a dynamic topology. The dynamic topology design problem is of particular interest to application service providers who need to provide cost-effective data services on a ubiquitous network. In this paper we describe algorithms that decide when and how the topology should be reconfigured in response to a change in the data communication requirements of the network. In particular, we describe and compare a greedy algorithm, which is of...

  6. The EU as an international security provider

    DEFF Research Database (Denmark)

    Rodt, Annemarie Peen; Wolff, Stefan; Whitman, Richard

    2015-01-01

    This contribution develops a framework of analysis that covers the actors involved in the policy making process of international security provision, the dynamics of this process itself, its outcomes (concrete strategies and policies) and their impact. Our efforts to establish such a framework...... of analysis, which could serve as the foundation for a mid-range theory of the EU as an international security provider, will examine the relevance of, and apply, existing theories of international relations/international security and foreign policy analysis to the specific case of the EU. The framework...... that will emerge from this analysis will then be tested and applied empirically in the following contributions that focus on how particular policies are formulated and implemented, and that analyse, in single and comparative case studies, the impact and effectiveness of the EU as an international security provider....

  7. Providing contact cards for relatives following bereavement.

    Science.gov (United States)

    Clarke, K; Pearson, N

    This article describes the implementation of a Welsh Assembly Government policy to improve customer service and provide an opportunity for relatives to seek further information about the death of a loved one in an acute hospital setting. A new relative-centred pathway has been developed. It offers a single point of contact for recently bereaved relatives and provides an opportunity to discuss any concerns or anxieties in relation to the care and/or treatment in the final hours of their loved one's life. The pathway includes a contact card with the name and number of a designated person and is a more informal, empathetic and person-centred service than the formal complaint process.

  8. Client Provider Collaboration for Service Bundling

    Directory of Open Access Journals (Sweden)

    LETIA, I. A.

    2008-04-01

    Full Text Available The key requirement for a service industry organization to reach competitive advantages through product diversification is the existence of a well defined method for building service bundles. Based on the idea that the quality of a service or its value is given by the difference between expectations and perceptions, we draw the main components of a frame that aims to support the client and the provider agent in an active collaboration meant to co-create service bundles. Following e3-value model, we structure the supporting knowledge around the relation between needs and satisfying services. We deal with different perspectives about quality through an ontological extension of Value Based Argumentation. The dialog between the client and the provider takes the form of a persuasion whose dynamic object is the current best configuration. Our approach for building service packages is a demand driven approach, allowing progressive disclosure of private knowledge.

  9. Airborne Internet Providing Tethered Balloon System

    Directory of Open Access Journals (Sweden)

    Suvriti Dhawan1

    2015-12-01

    Full Text Available In this paper we shall introduce a new system for providing wireless network communication over a specified area using ’lighter than air’ balloons. This technology will replace the existing fiber optic network system. This will be done by using a tethered balloon along with the payload (containing a receiver, a transmitter and a radio communication device.This payload will be suspended from the ground at an altitude (depending on the area of coverage required. Users under this area will be able to access this system directly for internet connectivity. This system can be used over large areas like universities, companies and societies to provide internet facility to their users through Wi-Fi or over an area where the user is specified (commercial purposes. Currently Google is working on similar idea called the ’Google Loon’ in which they use high altitude balloons which float at an altitude twice as high as air planes and the weather. They recently tested this system over New-Zealand by providing internet to their pilot testers on ground. Their balloons not being stationary, move with directional winds and have to be replaced one after the other to maintain consistency. This can be a huge problem over the areas where upper atmospheric winds are not in favorable direction. We can resolve this problem by using our stationary tethered balloon system which can communicate with the loon balloons to provide internet facility over a desired area. Moreover when our balloon will communicate with the loon balloon it will increase the coverage area as the loon balloon has to communicate to a point which is above the ground. Our system will not only replace the existing fiber optic system but it will also be selfsustaining i.e. It will generate its own power using solar panels.

  10. Logistics Service Providers in the Czech Republic

    OpenAIRE

    HRNEČKOVÁ, Kateřina

    2010-01-01

    The main purpose of the thesis is to analyze the developement of providing logistics services in the Czech Republic and analyze the current situation and expected trends in the near future. The thesis presents the implementation process of logistics outsourcing and follows up the influence of the outsourcing at the level of logistics costs. Manufacturing companies see in logistics the potential tool to improve the efficiency in their operations and they include the logistics in their strategi...

  11. Service Providers Rush to Capital Markets

    Institute of Scientific and Technical Information of China (English)

    ISABELDING

    2004-01-01

    Chinese Service Providers (SPs) are finding it hard to resist the lure of the overseas capital market and many are rushing towards listing. On March 4, Shanghai-based Linktone Ltd,under the trading name LTON, became the first Chinese SP to list on the Nasdaq stock market. Through its IPO, the company offered a total of 6.14 million American Depositary Receipts and raised US$84.7 million.

  12. Providing Real Research Opoportunities to Undergraduates

    Science.gov (United States)

    Ragozzine, Darin

    2016-01-01

    The current approach to undergraduate education focuses on teaching classes which provide the foundational knowledge for more applied experiences such as scientific research. Like most programs, Florida Institute of Technology (Florida Tech or FIT) strongly encourages undergraduate research, but is dominated by content-focused courses (e.g., "Physical Mechanics"). Research-like experiences are generally offered through "lab" classes, but these are almost always reproductions of past experiments: contrived, formulaic, and lacking the "heart" of real (i.e., potentially publishable) scientific research. Real research opportunities 1) provide students with realistic insight into the actual scientific process; 2) excite students far more than end-of-chapter problems; 3) provide context for the importance of learning math, physics, and astrophysics concepts; and 4) allow unique research progress for well-chosen problems. I have provided real research opportunities as an "Exoplanet Lab" component of my Introduction to Space Science (SPS1020) class at Florida Tech, generally taken by first-year majors in our Physics, Astronomy & Astrophysics, Planetary Science, and Astrobiology degree programs. These labs are a hybrid between citizen science (e.g., PlanetHunters) and simultaneously mentoring ~60 undergraduates in similar small research projects. These projects focus on problems that can be understood in the context of the course, but which benefit from "crowdsourcing". Examples include: dividing up the known planetary systems and developing a classification scheme and organizing them into populations (Fall 2013); searching through folded light curves to discover new exoplanets missed by previous pipelines (Fall 2014); and fitting n-body models to all exoplanets with known Transit Timing Variations to estimate planet masses (Fall 2015). The students love the fact that they are doing real potentially publishable research: not many undergraduates can claim to have discovered

  13. JSTOR: Providing New Access to Old Research

    OpenAIRE

    K.M. Guthrie

    1998-01-01

    Much has transpired in a short period of time. The JSTOR database now includes well over two million pages from 47 core journals in 11 academic disciplines. Additional journal content is being digitized at a rate of approximately 100,000 pages per month. More than 250 libraries in the United States and Canada have become participating institutions, providing support for the creation, maintenance and growth of this database. Outside of North America, we have recently announced the establishmen...

  14. ACCOUNTING TREATMENTS USED FOR ACCOUNTING SERVICES PROVIDERS

    OpenAIRE

    ŢOGOE GRETI DANIELA; AVRAM MARIOARA; AVRAM COSTIN DANIEL

    2014-01-01

    The theme of our research is the ways of keeping accounting entities that are the object of the provision of services in the accounting profession. This paper aims to achieve a parallel between the ways of organizing financial records - accounting provided by freelancers and companies with activity in the financial - accounting. The first step in our scientific research is to establish objectives chosen area of scientific knowledge. Our scientific approach seeks to explain thr...

  15. ACCOUNTING TREATMENTS USED FOR ACCOUNTING SERVICES PROVIDERS

    Directory of Open Access Journals (Sweden)

    ŢOGOE GRETI DANIELA

    2014-08-01

    Full Text Available The theme of our research is the ways of keeping accounting entities that are the object of the provision of services in the accounting profession. This paper aims to achieve a parallel between the ways of organizing financial records - accounting provided by freelancers and companies with activity in the financial - accounting. The first step in our scientific research is to establish objectives chosen area of scientific knowledge. Our scientific approach seeks to explain through a thorough and detailed approach as different sides (conceptual and practical looking projections of accounting issues related to regulatory developments and practices in the field. This paper addresses various concepts, accounting treatments, and books and accounting documents used both freelancers in providing accounting services and legal persons authorized accounting profession. In terms of methodology and research perspective, the whole scientific approach combined with quantitative and qualitative research theoretical perspective (descriptive-conceptual with practice perspective (empirical analyzing the main contributions of various authors (Romanian and foreign to knowledge in the field. Following the survey believe that the amendments to the national legislation will support entities providing accounting services, by cutting red tape on Administrative Burdens, and consequently will increase profitability and increase service quality.

  16. Provider volume and outcomes for oncological procedures.

    LENUS (Irish Health Repository)

    Killeen, S D

    2012-02-03

    BACKGROUND: Oncological procedures may have better outcomes if performed by high-volume providers. METHODS: A review of the English language literature incorporating searches of the Medline, Embase and Cochrane collaboration databases was performed. Studies were included if they involved a patient cohort from 1984 onwards, were community or population based, and assessed health outcome as a dependent variable and volume as an independent variable. The studies were also scored quantifiably to assess generalizability with respect to any observed volume-outcome relationship and analysed according to organ system; numbers needed to treat were estimated where possible. RESULTS: Sixty-eight relevant studies were identified and a total of 41 were included, of which 13 were based on clinical data. All showed either an inverse relationship, of variable magnitude, between provider volume and mortality, or no volume-outcome effect. All but two clinical reports revealed a statistically significant positive relationship between volume and outcome; none demonstrated the opposite. CONCLUSION: High-volume providers have a significantly better outcome for complex cancer surgery, specifically for pancreatectomy, oesphagectomy, gastrectomy and rectal resection.

  17. Intraoperative patient information handover between anesthesia providers

    Science.gov (United States)

    Choromanski, Dominik; Frederick, Joel; McKelvey, George Michael; Wang, Hong

    2014-01-01

    Abstract Currently, no reported studies have evaluated intraoperative handover among anesthesia providers. Studies on anesthetic handover in the US recovery room setting observed that handover processes are insufficient and, in many instances, significant intraoperative events are disregarded. An online survey tool was sent to anesthesia providers at US anesthesia residency programs nationwide (120 out of the 132 US programs encompassing around 4500 residents and their academic MDAs) and a smaller survey selection of CRNAs (10 institutions about 300 CRNAs in the metropolitan area of Detroit, MI, USA) to collect information on handover practices. The response rate to this survey (n = 216) was comprised of approximately 5% (n = 71) of the resident population in US anesthesia programs, 5% (n = 87) of MDAs , and 20% (n = 58) of the CRNAs. Out of all respondents (n = 212), 49.1 % had no hand-over protocol at their institution and 88% of respondents who did have institutional handover protocols believed them insufficient for effective patient handover. In addiiton, 84.8% of all responders reported situations where there was insufficient information received during a patient handover. Only 7% of the respondents reported never experiencing complications or mismanagement due to poor or incomplete hand-overs. In contrast, 60% reported rarely having complications, 31% reported sometimes having complications, and 3% reported frequent complications. In conclusion, handover transition of patient care is a vulnerable and potentially life-threatening event in the operating room. Our preliminary study suggests that current intraoperatvive handover practices among anesthesia providers are suboptimal and that national patient handover guidelines are required to improve patient safety. PMID:25332710

  18. Zika Virus: Critical Information for Emergency Providers.

    Science.gov (United States)

    Shastry, Siri; Koenig, Kristi L; Hirshon, Jon Mark

    2016-08-01

    Zika virus is an arbovirus of the Flaviviridae family. It is primarily a minimally symptomatic mosquito-borne infection. However, with Zika's 2015 to 2016 introduction into the Western Hemisphere and its dramatic and rapid spread, it has become a public health concern, in large part due to congenital abnormalities associated with infection in pregnant women. In early 2016, the World Health Organization declared the microcephaly and other neurologic conditions associated with Zika virus infection a public health emergency of international concern. This article discusses the current epidemiologic and clinical understanding of Zika virus, focusing on critical information needed by emergency providers.

  19. [In-patient smoker? - Providing appropriate intervention].

    Science.gov (United States)

    Pamplona, Paula

    2007-01-01

    Tobacco use is the most avoidable cause of death. Other than provoking multiple diseases requiring hospitalisation, Tobacco Use is also a disease requiring management in the hospital setting, not only in terms of controlling the withdrawal symptoms of the patient, who has been abruptly prohibited from smoking, but also for fulfilling legislation which prohibits tobacco use in the health services, the only efficient way of preventing exposure of non-smokers to environmental tobacco smoke. Treating the in-patient smoker in an appropriate way also provides a window of opportunity for promoting not just a temporary but a complete smoking cessation.

  20. Supercomputing Centers and Electricity Service Providers

    DEFF Research Database (Denmark)

    Patki, Tapasya; Bates, Natalie; Ghatikar, Girish

    2016-01-01

    Supercomputing Centers (SCs) have high and variable power demands, which increase the challenges of the Electricity Service Providers (ESPs) with regards to efficient electricity distribution and reliable grid operation. High penetration of renewable energy generation further exacerbates this pro......Supercomputing Centers (SCs) have high and variable power demands, which increase the challenges of the Electricity Service Providers (ESPs) with regards to efficient electricity distribution and reliable grid operation. High penetration of renewable energy generation further exacerbates...... this problem. In order to develop a symbiotic relationship between the SCs and their ESPs and to support effective power management at all levels, it is critical to understand and analyze how the existing relationships were formed and how these are expected to evolve. In this paper, we first present results...... from a detailed, quantitative survey-based analysis and compare the perspectives of the European grid and SCs to the ones of the United States (US). We then show that contrary to the expectation, SCs in the US are more open toward cooperating and developing demand-management strategies with their ESPs...

  1. Building a safe care-providing robot.

    Science.gov (United States)

    Fotoohi, Leila; Gräser, Axel

    2011-01-01

    A service robot especially a care-providing robot, works in the vicinity of a human body and is sometimes even in direct contact with it. Conventional safety methods and precautions in industrial robotics are not applicable to such robots. This paper presents a safety approach for designing the safe care-providing robot FRIEND. The approach is applied in each step of design iteratively to identify and assess the potential hazards during design. The steps are explained briefly in this work. The main contribution of this paper is verification of safety requirements using the Ramadge-Wonham (RW) framework. The greater complexity of the tasks the robot will perform, the more complex is the identification of safety requirements. Use of this framework led us to analyze the requirements and verify them formally, systematically and on a modular basis. In our approach human-robot interaction (HRI) is also modeled by a set of uncontrolled events that may happen any time during operation. Subsequently the safety requirements are modified to consider these interactions. As a result the safety module behaves like a controller, running in parallel with the system, which maintains the system safe and works according to the safety requirements by enabling the admissible sequences of events.

  2. Green roofs provide habitat for urban bats

    Directory of Open Access Journals (Sweden)

    K.L. Parkins

    2015-07-01

    Full Text Available Understanding bat use of human-altered habitat is critical for developing effective conservation plans for this ecologically important taxon. Green roofs, building rooftops covered in growing medium and vegetation, are increasingly important conservation tools that make use of underutilized space to provide breeding and foraging grounds for urban wildlife. Green roofs are especially important in highly urbanized areas such as New York City (NYC, which has more rooftops (34% than green space (13%. To date, no studies have examined the extent to which North American bats utilize urban green roofs. To investigate the role of green roofs in supporting urban bats, we monitored bat activity using ultrasonic recorders on four green and four conventional roofs located in highly developed areas of NYC, which were paired to control for location, height, and local variability in surrounding habitat and species diversity. We then identified bat vocalizations on these recordings to the species level. We documented the presence of five of nine possible bat species over both roof types: Lasiurus borealis, L. cinereus, L. noctivagans, P. subflavus,andE. fuscus. Of the bat calls that could be identified to the species level, 66% were from L. borealis. Overall levels of bat activity were higher over green roofs than over conventional roofs. This study provides evidence that, in addition to well documented ecosystem benefits, urban green roofs contribute to urban habitat availability for several North American bat species.

  3. Social capital and trust in providers.

    Science.gov (United States)

    Ahern, Melissa M; Hendryx, Michael S

    2003-10-01

    Trust in providers has been in decline in recent decades. This study attempts to identify sources of trust in characteristics of health care systems and the wider community. The design is cross-sectional. Data are from (1) the 1996 Household Survey of the Community Tracking Study, drawn from 24 Metropolitan Statistical Areas; (2) a 1996 multi-city broadcast media marketing database including key social capital indicators; (3) Interstudy; (4) the American Hospital Association; and (5) the American Medical Association. Independent variables include individual socio-demographic variables, HMO enrollment, community-level health sector variables, and social capital. The dependent variable is self-reported trust in physicians. Data are merged from the various sources and analyzed using SUDAAN. Subjects include adults in the Household Survey who responded to the items on trust in physicians (N=17,653). Trust in physicians is independently predicted by community social capital (p<0.001). Trust is also negatively related to HMO enrollment and to many individual characteristics. The effect of HMOs is not uniform across all communities. Social capital plays a role in how health care is perceived by citizens, and how health care is delivered by providers. Efforts to build trust and collaboration in a community may improve trust in physicians, health care quality, access, and preserve local health care control.

  4. Private provider participation in statewide immunization registries

    Directory of Open Access Journals (Sweden)

    Cowan Anne E

    2006-02-01

    Full Text Available Abstract Background Population-based registries have been promoted as an effective method to improve childhood immunization rates, yet rates of registry participation in the private sector are low. We sought to describe, through a national overview, the perspectives of childhood immunization providers in private practice regarding factors associated with participation or non-participation in immunization registries. Methods Two mailed surveys, one for 264 private practices identified as registry non-participants and the other for 971 identified as registry participants, from 15 of the 31 states with population-based statewide immunization registries. Frequency distributions were calculated separately for non-participants and participants regarding the physician-reported factors that influenced decisions related to registry participation. Pearson chi-square tests of independence were used to assess associations among categorical variables. Results Overall response rate was 62% (N = 756. Among non-participants, easy access to records of vaccines provided at other sites (N = 101, 68% and printable immunization records (N = 82, 55% were most often cited as "very important" potential benefits of a registry, while the most commonly cited barriers to participation were too much cost/staff time (N = 36, 38% and that the practice has its own system for recording and monitoring immunizations (N = 35, 37%. Among registry participants, most reported using the registry to input data on vaccines administered (N = 326, 87% and to review immunization records of individual patients (N = 302, 81%. A minority reported using it to assess their practice's immunization coverage (N = 110, 29% or generate reminder/recall notices (N = 54, 14%. Few participants reported experiencing "significant" problems with the registry; the most often cited was cost/staff time to use the registry (N = 71, 20%. Conclusion Most registry participants report active participation with few

  5. Development of Model for Providing Feasible Scholarship

    Directory of Open Access Journals (Sweden)

    Harry Dhika

    2016-05-01

    Full Text Available The current work focuses on the development of a model to determine a feasible scholarship recipient on the basis of the naiv¨e Bayes’ method using very simple and limited attributes. Those attributes are the applicants academic year, represented by their semester, academic performance, represented by their GPa, socioeconomic ability, which represented the economic capability to attend a higher education institution, and their level of social involvement. To establish and evaluate the model performance, empirical data are collected, and the data of 100 students are divided into 80 student data for the model training and the remaining of 20 student data are for the model testing. The results suggest that the model is capable to provide recommendations for the potential scholarship recipient at the level of accuracy of 95%.

  6. Providing Virtual Execution Environments: A Twofold Illustration

    CERN Document Server

    Grehant, Xavier

    2008-01-01

    Platform virtualization helps solving major grid computing challenges: share resource with flexible, user-controlled and custom execution environments and in the meanwhile, isolate failures and malicious code. Grid resource management tools will evolve to embrace support for virtual resource. We present two open source projects that transparently supply virtual execution environments. Tycoon has been developed at HP Labs to optimise resource usage in creating an economy where users bid to access virtual machines and compete for CPU cycles. SmartDomains provides a peer-to-peer layer that automates virtual machines deployment using a description language and deployment engine from HP Labs. These projects demonstrate both client-server and peer-to-peer approaches to virtual resource management. The first case makes extensive use of virtual machines features for dynamic resource allocation. The second translates virtual machines capabilities into a sophisticated language where resource management components can b...

  7. New consumer services provided by smart metering

    Directory of Open Access Journals (Sweden)

    Daminov Ildar

    2015-01-01

    Full Text Available This paper focuses on the issues of smart metering market and considers different services provided by smart metering from consumer point of view. Firstly, smart metering deployment challenges emerging and conventional tariffs, which modify a consumer behavior and thus, the entire electric energy market can be optimized since the customer is motivated to consume less energy. Secondly, the authors illustrate changes in electricity quality, which have an impact on consumer relations with utility. Additionally, two main indices of grid resilience – SAIDI and SAIFI – are exemplified to reveal the improvement potential of smart metering implementation in certain regions of Russia that also influence the consumer. Finally, in-home display and privacy problem directly reflect the consumer’s behavior, thus the private life rights should not be violated as they are guaranteed by law.

  8. Providing better indoor environmental quality brings economicbenefits

    Energy Technology Data Exchange (ETDEWEB)

    Fisk, William; Seppanen, Olli

    2007-06-01

    This paper summarizes the current scientific evidence that improved indoor environmental quality can improve work performance and health. The review indicates that work and school work performance is affected by indoor temperature and ventilation rate. Pollutant source removal can sometimes improve work performance. Based on formal statistical analyses of existing research results, quantitative relationships are provided for the linkages of work performance with indoor temperature and outdoor air ventilation rate. The review also indicates that improved health and related financial savings are obtainable from reduced indoor tobacco smoking, prevention and remediation of building dampness, and increased ventilation. Example cost-benefit analyses indicate that many measures to improve indoor temperature control and increase ventilation rates will be highly cost effective, with benefit-cost ratios as high as 80 and annual economic benefits as high as $700 per person.

  9. International Entry Modes for Digital Product Providers

    DEFF Research Database (Denmark)

    Rask, Morten

    Often internationalization of the firm refers to the process of increasing involvement in international operations. In relation to e-business many authors have argued that e-business will change the internationalization processes. E-business is about digitalization of processes, products and actors...... and many think that because these digitalisations, the importance of localization diminish, especially for what we call digital product providers that sells digitized products and services. The empirical foundation of this paper consists of an inductive explorative case-study that serves as a challenger...... (Fredsted, 2003). The case study gives insight into one of the few international marketplaces. Scanmarket has expanded to the English, German, American and Swedish markets. Essentially the case raises the question: "To what extent does the Internet supersede firms' need for local, physical presence?"...

  10. Perioperative Care of Prisoners: Providing Safe Care.

    Science.gov (United States)

    Smith, Francis Duval

    2016-03-01

    Correctional nurses are trained to care for prisoners in a controlled security environment; however, when a convict is transferred to a noncorrectional health care facility, the nurses there are often unfamiliar with custody requirements or how to safely care for these patients. The care of prisoners outside of prison has not been adequately investigated, and a gap exists between research and nursing education and practice. Nurses rarely have to consider how providing care for a prisoner in custody affects their practice, the potential dissonance between routine nursing care and the requirements to maintain security, or that care of prisoners in unsecured clinical areas places the nurse and other personnel at risk for physical assault or prisoner escape. Educating perioperative nurses in the care of prisoners in a public hospital environment is important for the provision of safe care and prevention of physical and emotional repercussions to personnel.

  11. Multicultural Nursing: Providing Better Employee Care.

    Science.gov (United States)

    Rittle, Chad

    2015-12-01

    Living in an increasingly multicultural society, nurses are regularly required to care for employees from a variety of cultural backgrounds. An awareness of cultural differences focuses occupational health nurses on those differences and results in better employee care. This article explores the concept of culturally competent employee care, some of the non-verbal communication cues among cultural groups, models associated with completing a cultural assessment, and how health disparities in the workplace can affect delivery of employee care. Self-evaluation of the occupational health nurse for personal preferences and biases is also discussed. Development of cultural competency is a process, and occupational health nurses must develop these skills. By developing cultural competence, occupational health nurses can conduct complete cultural assessments, facilitate better communication with employees from a variety of cultural backgrounds, and improve employee health and compliance with care regimens. Tips and guidelines for facilitating communication between occupational health nurses and employees are also provided.

  12. Multiagency Initiative to Provide Greenhouse Gas Information

    Science.gov (United States)

    Boland, Stacey W.; Duren, Riley M.

    2009-11-01

    Global Greenhouse Gas Information System Workshop; Albuquerque, New Mexico, 20-22 May 2009; The second Greenhouse Gas Information System (GHGIS) workshop brought together 74 representatives from 28 organizations including U.S. government agencies, national laboratories, and members of the academic community to address issues related to the understanding, operational monitoring, and tracking of greenhouse gas emissions and carbon offsets. The workshop was held at Sandia National Laboratories and organized by an interagency collaboration among NASA centers, Department of Energy laboratories, and the U.S. National Oceanic and Atmospheric Administration. It was motivated by the perceived need for an integrated interagency, community-wide initiative to provide information about greenhouse gas sources and sinks at policy-relevant temporal and spatial scales. Such an initiative could significantly enhance the ability of national and regional governments, industry, and private citizens to implement and evaluate effective climate change mitigation policies.

  13. Do drug advertisements provide therapeutic information?

    Science.gov (United States)

    Stimson, G V

    1977-03-01

    In this study of advertisements appearing in medical periodicals and by direct mail advertising to general practitioners, Dr. Stimson, a sociologist, concludes that from what is intended to provide therapeutic information hardly any therapeutic information is provided. He reminds the reader of the safeguards which surround all drug advertising by law and by the code of practice of the Association of the British Pharmaceutical Industry but these safeguards do not appear to control real or potential sins of omission. Frequently in these advertisements the literature relating to the drug is quoted but Dr. Stimson found that it was difficult to trace all the papers quoted in different types of medical library. (Some references quoted were to unpublished papers but surely the blame should be shared in this situation?) Dr. Stimson also gives a vivid and fascinating glimpse of what he calls the 'images and stereotypes' of the patients who, it is claimed, would benefit from the drug being advertised. Certainly most general practitioners must be aware that when they prescribe that image is displaced by an individual but the portrait gallery is indeed depressing. However, to balance these advertisements drug companies issue data sheets which must be more informative than advertisements and conform to regulations in their format. Unfortunately data sheets are only issued every 15 months whereas the 'average general practitioner is potentially exposed to 1,300 advertisements every month'. In other words, the data sheet and not the advertisement should be the guideline but it arrives too infrequently to offset the lack of therapeutic information contained in advertisements.

  14. PROVIDING BUDGET CREDITS TO RUSSIAN REGIONS

    Directory of Open Access Journals (Sweden)

    L. A. Gelyakhova

    2016-01-01

    Full Text Available The state budget of the Russian Federation can be called the primary means of accumulating financial resources in the country. Giving cash is seen as a measure to prevent the country's financial crisis. Public lending is its basic form. Nevertheless, in spite of the scientific and practical significance of the Russian Federation Public Credit, the issue has not been studied. These circumstances suggest that there are many unresolved issues in the field of public credit Russian Federation.Relevance of the topic of this article is revealed when considering the peculiarities of the legal regulation of public credit of the Russian Federation. In this article the author attempts to develop a series of recommendations to improve legislation at both the federal and regional levels. The growth of the budget deficit in the Russian Federation determines the need to find all the possible sources of financing, the most important of which acts as a budget loan, which refers to "funds provided by the budget to another budget of the budget system, the legal entity (except for state (municipal institutions, a foreign state, foreign legal entity on a returnable and paid basis "(art. 6 of the Budget Code of the Russian Federation [1]. 

  15. PROVIDING R-TREE SUPPORT FOR MONGODB

    Directory of Open Access Journals (Sweden)

    L. Xiang

    2016-06-01

    Full Text Available Supporting large amounts of spatial data is a significant characteristic of modern databases. However, unlike some mature relational databases, such as Oracle and PostgreSQL, most of current burgeoning NoSQL databases are not well designed for storing geospatial data, which is becoming increasingly important in various fields. In this paper, we propose a novel method to provide R-tree index, as well as corresponding spatial range query and nearest neighbour query functions, for MongoDB, one of the most prevalent NoSQL databases. First, after in-depth analysis of MongoDB’s features, we devise an efficient tabular document structure which flattens R-tree index into MongoDB collections. Further, relevant mechanisms of R-tree operations are issued, and then we discuss in detail how to integrate R-tree into MongoDB. Finally, we present the experimental results which show that our proposed method out-performs the built-in spatial index of MongoDB. Our research will greatly facilitate big data management issues with MongoDB in a variety of geospatial information applications.

  16. Family benefits - Obligation to provide information

    CERN Multimedia

    HR Department

    2015-01-01

    Pursuant to Article R V 1.38 of the Staff Regulations, members of the personnel are reminded that they are required to inform the Organization in writing, within 30 calendar days, of any change in their family situation (marriage, partnership, birth of a child, etc.) and of the amount of any financial benefit of a similar nature to those provided for in the Staff Regulations (e.g. family allowance, child allowance, infant allowance, non-resident allowance or international indemnity) to which they or a member of their family may be entitled from a source other than CERN.   The procedures to be followed are available in the Admin e-guide: https://admin-eguide.web.cern.ch/en/procedure/change-family-situation Members of the personnel are also reminded that any false declaration or failure to make a declaration with a view to deceiving others or achieving a gain resulting in a loss of funds or reputation for CERN constitutes fraud and may lead to disciplinary action in accordance with Article S ...

  17. Dental practice satisfaction with preferred provider organizations

    Directory of Open Access Journals (Sweden)

    Schilling Elizabeth A

    2007-11-01

    Full Text Available Abstract Background Despite their increasing share of the dental insurance market, little is known about dental practices' satisfaction with preferred provider organizations (PPOs. This analysis examined practice satisfaction with dental PPOs and the extent to which satisfaction was a function of communications from the plan, claims handling and compensation. Methods Data were collected through telephone surveys with dental practices affiliated with MetLife between January 2002 and December 2004. Each respondent was asked a series of questions related to their satisfaction with a systematically selected PPO with which they were affiliated. Six different PPO plans had sufficient observations to allow for comparative analysis (total n = 4582. Multiple imputation procedures were used to adjust for item non-response. Results While the average level of overall satisfaction with the target plan fell between "very satisfied" and "satisfied," regression models revealed substantial differences in overall satisfaction across the 6 PPOs (p Conclusion Results demonstrate the importance of compensation to dental practice satisfaction with PPOs. However, these results also highlight the critical role of service-related factors in differentiating plans and suggest that there are important non-monetary dimensions of PPO performance that can be used to recruit and retain practices.

  18. Contingency management: perspectives of Australian service providers.

    Science.gov (United States)

    Cameron, Jacqui; Ritter, Alison

    2007-03-01

    Given the very positive and extensive research evidence demonstrating efficacy and effectiveness of contingency management, it is important that Australia explore whether contingency management has a role to play in our own treatment context. Qualitative interviews were conducted with 30 experienced alcohol and drug practitioners, service managers and policy-makers in Victoria. Interviewees were selected to represent the range of drug treatment services types and included rural representation. A semi-structured interview schedule, covering their perceptions and practices of contingency management was used. All interviews were transcribed verbatim and analysed using N2 qualitative data analysis program. The majority of key informants were positively inclined toward contingency management, notwithstanding some concerns about the philosophical underpinnings. Concerns were raised in relation to the use of monetary rewards. Examples of the use of contingency management provided by key informants demonstrated an over-inclusive definition: all the examples did not adhere to the key principles of contingency management. This may create problems if a structured contingency management were to be introduced in Australia. Contingency management is an important adjunctive treatment intervention and its use in Australia has the potential to enhance treatment outcomes. No unmanageable barriers were identified in this study.

  19. Providing effective supervision in clinical neuropsychology.

    Science.gov (United States)

    Stucky, Kirk J; Bush, Shane; Donders, Jacobus

    2010-01-01

    A specialty like clinical neuropsychology is shaped by its selection of trainees, educational standards, expected competencies, and the structure of its training programs. The development of individual competency in this specialty is dependent to a considerable degree on the provision of competent supervision to its trainees. In clinical neuropsychology, as in other areas of professional health-service psychology, supervision is the most frequently used method for teaching a variety of skills, including assessment, report writing, differential diagnosis, and treatment. Although much has been written about the provision of quality supervision in clinical and counseling psychology, very little published guidance is available regarding the teaching and provision of supervision in clinical neuropsychology. The primary focus of this article is to provide a framework and guidance for the development of suggested competency standards for training of neuropsychological supervisors, particularly at the residency level. In this paper we outline important components of supervision for neuropsychology trainees and suggest ways in which clinicians can prepare for supervisory roles. Similar to Falender and Shafranske (2004), we propose a competency-based approach to supervision that advocates for a science-informed, formalized, and objective process that clearly delineates the competencies required for good supervisory practice. As much as possible, supervisory competencies are related to foundational and functional competencies in professional psychology, as well as recent legislative initiatives mandating training in supervision. It is our hope that this article will foster further discussion regarding this complex topic, and eventually enhance training in clinical neuropsychology.

  20. Providing R-Tree Support for Mongodb

    Science.gov (United States)

    Xiang, Longgang; Shao, Xiaotian; Wang, Dehao

    2016-06-01

    Supporting large amounts of spatial data is a significant characteristic of modern databases. However, unlike some mature relational databases, such as Oracle and PostgreSQL, most of current burgeoning NoSQL databases are not well designed for storing geospatial data, which is becoming increasingly important in various fields. In this paper, we propose a novel method to provide R-tree index, as well as corresponding spatial range query and nearest neighbour query functions, for MongoDB, one of the most prevalent NoSQL databases. First, after in-depth analysis of MongoDB's features, we devise an efficient tabular document structure which flattens R-tree index into MongoDB collections. Further, relevant mechanisms of R-tree operations are issued, and then we discuss in detail how to integrate R-tree into MongoDB. Finally, we present the experimental results which show that our proposed method out-performs the built-in spatial index of MongoDB. Our research will greatly facilitate big data management issues with MongoDB in a variety of geospatial information applications.

  1. The effect of provider- and workflow-focused strategies for guideline implementation on provider acceptance

    Directory of Open Access Journals (Sweden)

    Ramanujam Rangaraj

    2009-10-01

    Full Text Available Abstract Background The effective implementation of clinical practice guidelines (CPGs depends critically on the extent to which the strategies that are deployed for implementing the guidelines promote provider acceptance of CPGs. Such implementation strategies can be classified into two types based on whether they primarily target providers (e.g., academic detailing, grand rounds presentations or the work context (e.g., computer reminders, modifications to forms. This study investigated the independent and joint effects of these two types of implementation strategies on provider acceptance of CPGs. Methods Surveys were mailed to a national sample of providers (primary care physicians, physician assistants, nurses, and nurse practitioners and quality managers selected from Veterans Affairs Medical Centers (VAMCs. A total of 2,438 providers and 242 quality managers from 123 VAMCs participated. Survey items measured implementation strategies and provider acceptance (e.g., guideline-related knowledge, attitudes, and adherence for three sets of CPGs--chronic obstructive pulmonary disease, chronic heart failure, and major depressive disorder. The relationships between implementation strategy types and provider acceptance were tested using multi-level analytic models. Results For all three CPGs, provider acceptance increased with the number of implementation strategies of either type. Moreover, the number of workflow-focused strategies compensated (contributing more strongly to provider acceptance when few provider-focused strategies were used. Conclusion Provider acceptance of CPGs depends on the type of implementation strategies used. Implementation effectiveness can be improved by using both workflow-focused as well as provider-focused strategies.

  2. Are Anesthesia Providers Ready for Hypnosis? Anesthesia Providers' Attitudes Toward Hypnotherapy.

    Science.gov (United States)

    Stone, Alexander B; Sheinberg, Rosanne; Bertram, Amanda; Seymour, Anastasia Rowland

    2016-04-01

    This study sought to measure current attitudes toward hypnosis among anesthesia providers using an in-person survey distributed at a single grand rounds at a single academic teaching hospital. One hundred twenty-six anesthesia providers (anesthesiologists and nurse anesthetists) were included in this study. A 10-question Institutional Review Board (IRB)-approved questionnaire was developed. One hundred twenty-six (73% of providers at the meeting) anesthesia providers completed the survey. Of the respondents, 54 (43%) were anesthesiologists, 42 (33%) were trainees (interns/residents/fellows) in anesthesia, and 30 (24%) were nurse anesthetists. Over 70% of providers, at each level of training, rated their knowledge of hypnosis as either below average or having no knowledge. Fifty-two (42%) providers agreed or strongly agreed that hypnotherapy has a place in the clinical practice of anesthesia, while 103 (83%) believed that positive suggestion has a place in the clinical practice of anesthesia (p hypnosis were that it is too time consuming (41%) and requires special training (34%). Only three respondents (2%) believed that there were no reasons for using hypnosis in their practice. These data suggest that there is a self-reported lack of knowledge about hypnosis among anesthesia providers, although many anesthesia providers are open to the use of hypnosis in their clinical practice. Anesthesia providers are more likely to support the use of positive suggestion in their practice than hypnosis. Practical concerns should be addressed if hypnosis and therapeutic verbal techniques are to gain more widespread use.

  3. Attitudes of Healthcare Providers towards Providing Contraceptives for Unmarried Adolescents in Ibadan, Nigeria.

    Directory of Open Access Journals (Sweden)

    Ezihe Loretta Ahanonu

    2014-03-01

    Full Text Available This study sought to assess the attitude of Healthcare Providers towards providing contraceptives for unmarried adolescents in four Local Government Areas in Ibadan, Nigeria.A cross-sectional descriptive study was conducted among 490 Healthcare Providers in 24 randomly selected healthcare facilities using self-administered, pre-tested questionnaires.More than half (57.5% of the respondents perceived the provision of contraceptives for unmarried adolescents as promoting sexual promiscuity. The attitude of 42.7% of them was informed by the Nigerian culture which does not support premarital sex. About half (51.7%, reported that unmarried adolescents should be asked to abstain from sex rather than providing them with contraceptives. Over a third (44.2% reported that providers should not provide services for both married and unmarried adolescents.Many healthcare providers have unfavourable attitudes towards the provision of contraceptives for unmarried adolescents. There is a need for further training of Healthcare Providers to address this situation.

  4. A Providence History Mystery: Discover the History of Providence through Architecture. Second Edition.

    Science.gov (United States)

    Jordan, Amy, Ed.

    This workbook, a part of the Providence (Rhode Island) Preservation Society's preservation education curriculum for elementary school students, is designed to help students appreciate the significance and the beauty of Providence's architectural heritage. (Other materials in this program are a handbook entitled, "A New Look at Old…

  5. Parenting provided by adults with mental retardation.

    Science.gov (United States)

    Dowdney, L; Skuse, D

    1993-01-01

    Studies assessing the quality of parenting provided by adults with mental retardation present conflicting conclusions. Some consider the majority to be doing reasonably well, whilst others report frequently unsatisfactory caretaking. There are a number of reasons for such different views. First, inconsistent selection criteria make it hard to compare across studies. In particular, sample composition will be influenced by the recruitment source. For example, if parents have been chosen from voluntary educational programmes a rather different picture is likely to be found than if they have been selected from individuals known to, or referred by, statutory agencies. On the whole, authors working with subjects from the former source have been rather more optimistic than those working with parents referred because there were already serious concerns about parenting difficulties or about delayed child development. Secondly, the majority of studies have used poorly defined global measures of parenting, with variable criteria of what constitutes adequate care. Some have concentrated on physical care and hygiene, whilst others have looked for the presence of affection and warmth. A child's reception into care as the sole measure of the quality of parenting is an unsatisfactory criterion because parental retardation has itself occasionally been used as the basis for removal of a child into care, even in the absence of other evidence of neglect or abuse. Thirdly, methodological flaws are found in studies that have used observational assessments of parenting. Such studies have suggested mothers with mental retardation tend to lack interactive skills (such as high levels of praise and imitation, and low restrictiveness) which are known to be associated with optimal child development. Control groups have often not been matched on social and other variables which might be expected to exert a significant influence upon parenting practices. In addition, the generalisability of

  6. Providing Data Access for Interdisciplinary Research

    Science.gov (United States)

    Hooper, R. P.; Couch, A.

    2012-12-01

    Developing an interdisciplinary understanding of human and environmental interactions with water requires access to a variety of data kinds collected by various organizations. The CUAHSI Hydrologic Information System (HIS) is a standards-based, services-oriented architecture designed for time-series data. Such data represents an important type of data in water studies. Through the efforts of HIS, a standard transmission language, WaterML2, has been adopted by the Open Geospatial Consortium and is under consideration by the World Meteorologic Organization as an international standards. Web services have also been developed to retrieve data and metadata. HIS is completed with a metadata catalog, hosted by San Diego Supercomputing Center, which indexes more than 20 million time series provided from over 90 different services. This catalog is supported through a hierarchically organized controlled vocabulary that is open for community input and mediation. Data publishers include federal agencies, universities, state agencies, and non-profit organizations such as watershed associations. Accessing data from such a broad spectrum of sources through a uniform service standard promises to truly transform the way in which hydrologic research is done. CUAHSI HIS is a large-scale prototype at this time, but a proposal is under consideration by the National Science Foundation to operationalize HIS through a data facility, tentatively called the CUAHSI Water Data Center. Establishing HIS is an important step to enable research into human-environment interactions with water, but it is only one step. Other data structures will need to be made accessible and interoperable to support this research. Some data—such as two-dimensional GIS coverages—already have widely used standards for transmission and sharing. The US Federal government has long operated a clearinghouse for federal geographic data that is now being augmented with other services such as ArcGIS OnLine. Other data

  7. Informal sector providers in Bangladesh: how equipped are they to provide rational health care?

    Science.gov (United States)

    Ahmed, Syed Masud; Hossain, Md Awlad; Chowdhury, Mushtaque Raja

    2009-11-01

    In Bangladesh, there is a lack of knowledge about the large body of informal sector practitioners, who are the major providers of health care to the poor, especially in rural areas, knowledge which is essential for designing a need-based, pro-poor health system. This paper addresses this gap by presenting descriptive data on their professional background including knowledge and practices on common illnesses and conditions from a nationwide, population-based health-care provider survey undertaken in 2007. The traditional healers (43%), traditional birth attendants (TBAs, 22%), and unqualified allopathic providers (village doctors and drug sellers, 16%) emerged as major providers in the health care scenario of Bangladesh. Community health workers (CHWs) comprised about 7% of the providers. The TBAs/traditional healers had sector, instead of ignoring, recognize the importance of the informal providers for the health care of the poor. Consequently, their capacity should be developed through training, supportive supervision and regulatory measures so as to accommodate them in the mainstream health system until constraints on the supply of qualified and motivated health care providers into the system can be alleviated.

  8. Measuring stigma among abortion providers: assessing the Abortion Provider Stigma Survey instrument.

    Science.gov (United States)

    Martin, Lisa A; Debbink, Michelle; Hassinger, Jane; Youatt, Emily; Eagen-Torkko, Meghan; Harris, Lisa H

    2014-01-01

    We explored the psychometric properties of 15 survey questions that assessed abortion providers' perceptions of stigma and its impact on providers' professional and personal lives referred to as the Abortion Provider Stigma Survey (APSS). We administered the survey to a sample of abortion providers recruited for the Providers' Share Workshop (N = 55). We then completed analyses using Stata SE/12.0. Exploratory factor analysis, which resulted in 13 retained items and identified three subscales: disclosure management, resistance and resilience, and discrimination. Stigma was salient in abortion provider's lives: they identified difficulties surrounding disclosure (66%) and felt unappreciated by society (89%). Simultaneously, workers felt they made a positive contribution to society (92%) and took pride in their work (98%). Paired t-test analyses of the pre- and post-Workshop APSS scores showed no changes in the total score. However, the Disclosure Management subscale scores were significantly lower (indicating decreased stigma) for two subgroups of participants: those over the age of 30 and those with children. This analysis is a promising first step in the development of a quantitative tool for capturing abortion providers' experiences of and responses to pervasive abortion stigma.

  9. HUBBLE PROVIDES COMPLETE VIEW OF JUPITER'S AURORAS

    Science.gov (United States)

    2002-01-01

    NASA's Hubble Space Telescope has captured a complete view of Jupiter's northern and southern auroras. Images taken in ultraviolet light by the Space Telescope Imaging Spectrograph (STIS) show both auroras, the oval- shaped objects in the inset photos. While the Hubble telescope has obtained images of Jupiter's northern and southern lights since 1990, the new STIS instrument is 10 times more sensitive than earlier cameras. This allows for short exposures, reducing the blurring of the image caused by Jupiter's rotation and providing two to five times higher resolution than earlier cameras. The resolution in these images is sufficient to show the 'curtain' of auroral light extending several hundred miles above Jupiter's limb (edge). Images of Earth's auroral curtains, taken from the space shuttle, have a similar appearance. Jupiter's auroral images are superimposed on a Wide Field and Planetary Camera 2 image of the entire planet. The auroras are brilliant curtains of light in Jupiter's upper atmosphere. Jovian auroral storms, like Earth's, develop when electrically charged particles trapped in the magnetic field surrounding the planet spiral inward at high energies toward the north and south magnetic poles. When these particles hit the upper atmosphere, they excite atoms and molecules there, causing them to glow (the same process acting in street lights). The electrons that strike Earth's atmosphere come from the sun, and the auroral lights remain concentrated above the night sky in response to the 'solar wind,' as Earth rotates underneath. Earth's auroras exhibit storms that extend to lower latitudes in response to solar activity, which can be easily seen from the northern U. S. But Jupiter's auroras are caused by particles spewed out by volcanoes on Io, one of Jupiter's moons. These charged particles are then magnetically trapped and begin to rotate with Jupiter, producing ovals of auroral light centered on Jupiter's magnetic poles in both the day and night skies

  10. Provider practice models in ambulatory oncology practice: analysis of productivity, revenue, and provider and patient satisfaction.

    Science.gov (United States)

    Buswell, Lori A; Ponte, Patricia Reid; Shulman, Lawrence N

    2009-07-01

    Physicians, nurse practitioners, and physician assistants often work in teams to deliver cancer care in ambulatory oncology practices. This is likely to become more prevalent as the demand for oncology services rises, and the number of providers increases only slightly.

  11. Health service providers in Somalia: their readiness to provide malaria case-management

    Directory of Open Access Journals (Sweden)

    Moonen Bruno

    2009-05-01

    Full Text Available Abstract Background Studies have highlighted the inadequacies of the public health sector in sub-Saharan African countries in providing appropriate malaria case management. The readiness of the public health sector to provide malaria case-management in Somalia, a country where there has been no functioning central government for almost two decades, was investigated. Methods Three districts were purposively sampled in each of the two self-declared states of Puntland and Somaliland and the south-central region of Somalia, in April-November 2007. A survey and mapping of all public and private health service providers was undertaken. Information was recorded on services provided, types of anti-malarial drugs used and stock, numbers and qualifications of staff, sources of financial support and presence of malaria diagnostic services, new treatment guidelines and job aides for malaria case-management. All settlements were mapped and a semi-quantitative approach was used to estimate their population size. Distances from settlements to public health services were computed. Results There were 45 public health facilities, 227 public health professionals, and 194 private pharmacies for approximately 0.6 million people in the three districts. The median distance to public health facilities was 6 km. 62.3% of public health facilities prescribed the nationally recommended anti-malarial drug and 37.7% prescribed chloroquine as first-line therapy. 66.7% of public facilities did not have in stock the recommended first-line malaria therapy. Diagnosis of malaria using rapid diagnostic tests (RDT or microscopy was performed routinely in over 90% of the recommended public facilities but only 50% of these had RDT in stock at the time of survey. National treatment guidelines were available in 31.3% of public health facilities recommended by the national strategy. Only 8.8% of the private pharmacies prescribed artesunate plus sulphadoxine/pyrimethamine, while 53

  12. Obstetric Provider Trainees in Georgia: Characteristics and Attitudes About Practice in Obstetric Provider Shortage Areas.

    Science.gov (United States)

    Smulian, Elizabeth A; Zahedi, Leilah; Hurvitz, Julie; Talbot, Abigail; Williams, Audra; Julian, Zoë; Zertuche, Adrienne D; Rochat, Roger

    2016-07-01

    Objectives In Georgia, 52 % of the primary care service areas outside metropolitan Atlanta have a deficit of obstetric providers. This study was designed to identify factors associated with the likelihood of Georgia's obstetric trainees (obstetrics and gynecology (OB/GYN) residents and certified nurse midwifery (CNM) students) to practice in areas of Georgia that lack obstetric providers and services, i.e. rural Georgia. Methods Pilot-tested electronic and paper surveys were distributed to all of Georgia's OB/GYN residents (N = 95) and CNM students (N = 28). Mixed-methods survey questions assessed characteristics, attitudes, and incentives that might be associated with trainee desire to practice in areas of Georgia that lack obstetric providers and services. Surveys also gathered information about concerns that may prevent trainees from practicing in shortage areas. Univariate and bivariate analyses were performed, and qualitative themes were abstracted from open-ended questions. Results The survey response rate was 87.8 % (108/123). Overall, 24.4 % (19/78) of residents and 53.6 % (15/28) of CNM students expressed interest in practicing in rural Georgia, and both residents and CNM students were more likely to desire to practice in rural Georgia with the offer of any of six financial incentives (P < 0.001). Qualitative themes highlighted trainees' strong concerns about Georgia's political environment as it relates to reproductive healthcare. Conclusions Increasing state-level, rurally-focused financial incentive programs and emphasizing the role of CNMs may alleviate obstetric provider shortages in Georgia.

  13. Price transparency for MRIs increased use of less costly providers and triggered provider competition.

    Science.gov (United States)

    Wu, Sze-jung; Sylwestrzak, Gosia; Shah, Christiane; DeVries, Andrea

    2014-08-01

    To encourage patients to select high-value providers, an insurer-initiated price transparency program that focused on elective advanced imaging procedures was implemented. Patients having at least one outpatient magnetic resonance imaging (MRI) scan in 2010 or 2012 were divided according to their membership in commercial health plans participating in the program (the intervention group) or in nonparticipating commercial health plans (the reference group) in similar US geographic regions. Patients in the intervention group were informed of price differences among available MRI facilities and given the option of selecting different providers. For those patients, the program resulted in a $220 cost reduction (18.7 percent) per test and a decrease in use of hospital-based facilities from 53 percent in 2010 to 45 percent in 2012. Price variation between hospital and nonhospital facilities for the intervention group was reduced by 30 percent after implementation. Nonparticipating members residing in intervention areas also observed price reductions, which indicates increased price competition among providers. The program significantly reduced imaging costs. This suggests that patients select lower-price facilities when informed about available alternatives.

  14. Research and Practice Communications Between Oral Health Providers and Prenatal Health Providers: A Bibliometric Analysis.

    Science.gov (United States)

    Skvoretz, John; Dyer, Karen; Daley, Ellen; Debate, Rita; Vamos, Cheryl; Kline, Nolan; Thompson, Erika

    2016-08-01

    Objectives We aimed to examine scholarly collaboration between oral health and prenatal providers. Oral disease is a silent epidemic with significant public health implications for pregnant women. Evidence linking poor oral health during pregnancy to adverse pregnancy and birth outcomes requires oral health and prenatal providers to communicate on the prevention, treatment and co-management matters pertaining to oral health issues among their pregnant patients. The need for inter-professional collaboration is highlighted by guidelines co-endorsed by the American College of Obstetricians and Gynecologists and the American Dental Association, stressing the importance of oral health care during pregnancy. Methods To assess if interdisciplinary communication occurs between oral health and prenatal disciplines, we conducted a network analysis of research on pregnancy-related periodontal disease. Results Social Network analysis allowed us to identify communication patterns between communities of oral health and prenatal professionals via scientific journals. Analysis of networks of citations linking journals in different fields reveals a core-periphery pattern dominated by oral health journals with some participation from medicine journals. However, an analysis of dyadic ties of citation reveals statistically significant "inbreeding" tendencies in the citation patterns: both medical and oral health journals tend to cite their own kind at greater-than-chance levels. Conclusions Despite evidence suggesting that professional collaboration benefits patients' overall health, findings from this research imply that little collaboration occurs between these two professional groups. More collaboration may be useful in addressing women's oral-systemic health concerns that result in adverse pregnancy outcomes.

  15. 42 CFR 489.102 - Requirements for providers.

    Science.gov (United States)

    2010-10-01

    ... (CONTINUED) STANDARDS AND CERTIFICATION PROVIDER AGREEMENTS AND SUPPLIER APPROVAL Advance Directives § 489..., providers of personal care services), hospices, and religious nonmedical health care institutions must... the personal care services provider. The personal care provider may furnish advance...

  16. 76 FR 54474 - Submission for OMB Review; Comment Request New proposed collection, Biospecimen and Physical...

    Science.gov (United States)

    2011-09-01

    ... 60 days for public comment. Two written comments and two verbal comments were received. The verbal..., Analysis and Communication, National Institute of Child Health and Human Development, 31 Center Drive Room 2A18, Bethesda, Maryland, 20892, or call a non-toll free number (301) 496-1877 or E-mail your...

  17. The Establishment of the Pfizer-Canine Comparative Oncology and Genomics Consortium Biospecimen Repository

    Directory of Open Access Journals (Sweden)

    Christina Mazcko

    2015-07-01

    Full Text Available The Canine Comparative Oncology and Genomics Consortium (CCOGC was formed in 2004 in an effort to capitalize on the generation of a domestic dog genome sequence assembly [1], which created new opportunities to investigate canine cancers at the molecular level [2]. [...

  18. The Establishment of an Inflammatory Breast Cancer Registry and Biospecimen Repository

    Science.gov (United States)

    2005-08-01

    0100 (SWOG 8814 ) trial. In this trial, 1,477 postmenopausal breast cancer patients were random ised to Tamoxifen, chemotherapy plus Tamoxifen (CAFT-T...results from intergroup trial 0100(SWOG- 8814 ). Proc. Am. Soc. Clin. Oncol 2002;21. (66) Osborne CK, Kitten L, Arteaga CL: Antagonism of chemotherapy...indicated, p=.Ol); OS similar 8313 [54] Node (+), Yes, main 531(11%) No (1984-1990) HR (-) trial report 8814 [55] Postmenopa Yes, follow- 1,558(9

  19. Cable Provider Facilities, Cable Provider Facilities, Published in Not Provided, 1:4800 (1in=400ft) scale, Warren County Emergency Services.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Cable Provider Facilities dataset, published at 1:4800 (1in=400ft) scale, was produced all or in part from Hardcopy Maps information as of Not Provided. It is...

  20. 47 CFR 10.320 - Provider alert gateway requirements.

    Science.gov (United States)

    2010-10-01

    ... alert gateway if a validation fails. (c) Security. The CMS provider gateway must support standardized IP... CMS provider gateways. (a) General. The CMS provider gateway must provide secure, redundant, and reliable connections to receive Alert Messages from the Federal alert gateway. Each CMS provider...

  1. 78 FR 19949 - The $500,000 Deduction Limitation for Remuneration Provided by Certain Health Insurance Providers

    Science.gov (United States)

    2013-04-02

    ... Deduction Limitation for Remuneration Provided by Certain Health Insurance Providers; Proposed Rule #0;#0... Remuneration Provided by Certain Health Insurance Providers AGENCY: Internal Revenue Service (IRS), Treasury... application of the $500,000 deduction limitation for remuneration provided by certain health...

  2. Childcare Providers: Work Stress and Personal Well-Being

    Science.gov (United States)

    Faulkner, Monica; Gerstenblatt, Paula; Lee, Ahyoung; Vallejo, Viana; Travis, Dnika

    2016-01-01

    Childcare providers face multiple work-related stressors. Small studies of childcare providers have suggested that providers have high levels of depression compared to the general population. However, unlike other caregiving professions, the research examining childcare providers is sparse, and there is little information to inform practices and…

  3. Attitudes regarding the safety of health care provider attire.

    Science.gov (United States)

    Garvin, Kanishka W; Lipira, Lauren; Neradilek, Moni; Fox, Anna; Ali, Fatima; Pottinger, Paul S

    2014-11-01

    The majority of medical providers, nurses, and patients agree that appearance is important for patient care. However, at our institution, concerns regarding providers' white coats as fomites are expressed primarily by providers and nurses, not by patients. We provide a framework for approaching this important issue through a structured quality-improvement process.

  4. 42 CFR 424.545 - Provider and supplier appeal rights.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Provider and supplier appeal rights. 424.545... Maintaining Medicare Billing Privileges § 424.545 Provider and supplier appeal rights. (a) General. A prospective provider or supplier that is denied enrollment in the Medicare program, or a provider or...

  5. 29 CFR 825.125 - Definition of health care provider.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Definition of health care provider. 825.125 Section 825.125... Definition of health care provider. (a) The Act defines “health care provider” as: (1) A doctor of medicine... providing health care services. (b) Others “capable of providing health care services” include only:...

  6. Hog and Pig Houses, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Hog and Pig Houses dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection;...

  7. Television Transmitter Locations, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Television Transmitter Locations dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable...

  8. Search for an Emergency Contraception Provider in the United States

    Science.gov (United States)

    ... contraception provider. Concerned about cost? Click here . ---------- Emergency contraceptive pills are stocked by all major pharmacy chains, but ... birth control pills you can use as emergency contraceptive pills. You can search for a provider in the ...

  9. Broadcast Service Areas, Cable, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Broadcast Service Areas, Cable dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable...

  10. Irrigated Lands and Features, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Irrigated Lands and Features dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable...

  11. State Boundaries, Published in Not Provided, Hubie's School of Learning.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This State Boundaries dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection; The...

  12. Agriculture, Fruit and Orchards, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Agriculture, Fruit and Orchards dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable...

  13. Provider Specific Data for Public Use in SAS Format

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Fiscal Intermediary maintains the Provider Specific File (PSF). The file contains information about the facts specific to the provider that affects computations...

  14. Television Stations, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Television Stations dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection;...

  15. Hydrography, Published in Not Provided, Chautauqua County/Elk County.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Hydrography dataset as of Not Provided. Data by this publisher are often provided in State Plane coordinate system; in a Lambert Conformal-conic projection;...

  16. Postmarket Drug Safety Information for Patients and Providers

    Science.gov (United States)

    ... Drug Safety Information for Patients and Providers Postmarket Drug Safety Information for Patients and Providers Share Tweet Linkedin Pin ... 2007 (FDAAA), this website contains links to postmarket drug safety information to improve transparency and communication to patients and ...

  17. Address Points, Published in Not Provided, Shield Engineering, Inc..

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Address Points dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection; The...

  18. Telephone Switching Facilities, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Telephone Switching Facilities dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable...

  19. Poultry Houses, Published in Not Provided, US Army.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Poultry Houses dataset as of Not Provided. Data by this publisher are often provided in Not Applicable coordinate system; in a Not Applicable projection; The...

  20. Government Buildings, Leased, Published in Not Provided, The Keith Corporation.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Government Buildings, Leased dataset as of Not Provided. Data by this publisher are often provided in Not Sure coordinate system; in a Not Sure projection; The...

  1. Providing a computing environment for a high energy physics workshop

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, C.; Butler, J.; Carter, T.; DeMar, P.; Fagan, D.; Gibbons, R.; Grigaliunas, V.; Haibeck, M.; Haring, P.; Horvath, C.; Hughart, N.; Johnstad, H.; Jones, S.; Kreymer, A.; LeBrun, P.; Lego, A.; Leninger, M.; Loebel, L.; McNamara, S.; Nguyen, T.; Nicholls, J.; O' Reilly, C.; Pabrai, U.; Pfister, J.; Ritchie, D.; Roberts, L.; Sazama, C.; Wohlt, D. (Fermi National Accelerator Lab., Batavia, IL (USA)); Carven, R. (Wiscons

    1989-12-01

    Although computing facilities have been provided at conferences and workshops remote from the host institution for some years, the equipment provided has rarely been capable of providing for much more than simple editing and electronic mail. This report documents the effort involved in providing a local computing facility with world-wide networking capability for a physics workshop so that we and others can benefit from the knowledge gained through the experience.

  2. 20 CFR 220.45 - Providing evidence of disability.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Providing evidence of disability. 220.45... DETERMINING DISABILITY Evidence of Disability § 220.45 Providing evidence of disability. (a) General. The claimant for a disability annuity is responsible for providing evidence of the claimed disability and...

  3. Outsourcing customer support : The role of provider customer focus

    NARCIS (Netherlands)

    Wuyts, S.H.K.; Rindfleisch, A.; Citrin, A.

    2015-01-01

    An increasing number of firms are outsourcing customer support to external service providers. This creates a triadic setting in which an outsourcing provider serves end customers on behalf of its clients. While outsourcing presents an opportunity to serve customers, service providers differ in their

  4. 42 CFR 431.51 - Free choice of providers.

    Science.gov (United States)

    2010-10-01

    ... provided in § 431.55; or (4) Limiting the providers who are available to furnish targeted case management services defined in § 440.169 of this chapter to target groups that consist solely of individuals with... providers of case management services for eligible individuals with developmental disabilities or...

  5. Lessons from VET Providers Delivering Degrees: Case Studies. Support Document

    Science.gov (United States)

    Callan, Victor J.; Bowman, Kaye

    2015-01-01

    The recent growth in the number of registered vocational education and training (VET) providers delivering associate degrees and bachelor degrees in their own right has been well publicized. However, little is known about why these VET providers have made this transition, what support is being provided to their staff and students, and how the…

  6. Provider-sponsored HMOs: make, buy, or joint venture?

    Science.gov (United States)

    Clay, S B

    1997-03-01

    Providers can sponsor their own HMOs in one of three ways: by creating their own HMO, by joint venturing with an existing HMO, or by purchasing an existing HMO. When selecting the best option, providers must consider various market conditions. Managed care penetration in the area, potential competitive responses of existing HMOs, market demand, provider reputation, and provider marketing ability will all influence the feasibility of each option. Providers also must examine their own organizational identity, their ability to raise the necessary capital to start an HMO, their managed care expertise and risk contracting experience, and their information systems capabilities.

  7. Internet health information in the patient-provider dialogue.

    Science.gov (United States)

    Hong, Traci

    2008-10-01

    A patient discussing Internet health information with a health care provider (referred to as "patient-provider communication about Internet health information") can contribute positively to health outcomes. Although research has found that once Internet access is achieved, there are no ethnic differences in Internet health information seeking, it is unclear if there are ethnic differences in patient-provider communication about Internet health information. To help fill this gap in the literature, the National Cancer Institute's Health Information National Trends Survey 2005 was analyzed with Stata 9. Two sets of logistic regression analyses were conducted, one for a subsample of Internet users (n = 3,244) and one for a subsample of Internet users who are first-generation immigrants (n = 563). The dependent variable was patient-provider communication about Internet health information, which assessed whether survey participants had discussed online health information with a health care provider. The predictor variables included trust of health care provider, trust of online health information, Internet use, health care coverage, frequency of visits to health care provider, health status, and demographics. Among all Internet users, Whites had higher levels of patient-provider communication about Internet health information than Blacks and Asians. Similarly, among Internet users who are immigrants, Whites had higher levels of patient-provider communication about Internet health information than Blacks and Asians. While the digital divide is narrowing in terms of Internet access, racial differences in patient-provider communication about Internet health information may undermine the potential benefits of the information age.

  8. 34 CFR 386.34 - What assurances must be provided by a grantee that intends to provide scholarships?

    Science.gov (United States)

    2010-07-01

    ... intends to provide scholarships? 386.34 Section 386.34 Education Regulations of the Offices of the... Award? § 386.34 What assurances must be provided by a grantee that intends to provide scholarships? A grantee under this part that intends to grant scholarships for any academic year beginning after June...

  9. Management of behavioral health provider networks in private health plans.

    Science.gov (United States)

    Garnick, Deborah W; Horgan, Constance M; Reif, Sharon; Merrick, Elizabeth L; Hodgkin, Dominic

    2008-01-01

    We explored the techniques used by private health plans or by their contracted managed behavioral healthcare organizations (MBHOs) to maintain networks of behavioral health providers. In particular, we focused on differences by health plans' product types (health maintenance organization, point-of-service plan, or preferred provider organization) and contracting arrangements (MBHO contracts, comprehensive contracts, or no contracts). More than 94% of products selected providers using credentialing standards, particular specialists, or geographic coverage. To retain providers viewed as high quality, 54% offer reduced administrative burden and 44% higher fees. Only 16% reported steerage to a core group of highest-quality providers and few reported an annual bonus or guaranteed volume of referrals. Some standard activities are common, but some health plans are adopting other approaches to retain higher-quality providers.

  10. Development of an educational module on provider self-care.

    Science.gov (United States)

    Meadors, Patrick; Lamson, Angela; Sira, Natalia

    2010-01-01

    Intensive care providers who care for traumatized populations often face multiple traumas for extended periods and are vulnerable to developing lasting symptoms of compassion fatigue and secondary traumatization. Symptoms are often not recognizable until compassion fatigue or secondary traumatization negatively affects the providers' ability to care for their patients. More attention needs to be given to the care of the provider to ensure high-quality patient care, decrease turnover in the profession, and increase productivity. This article provides a framework for the development of an educational module for healthcare providers' self-care. This educational module created the opportunity to share with providers (a) how to explore their own professional experience; (b) how to recognize the different symptoms of compassion fatigue, primary traumatization, and secondary traumatization; (c) factors related to grief reactions; and (d) personal and professional strategies to decrease compassion fatigue and secondary traumatization.

  11. Metagenomes provide valuable comparative information on soil microeukaryotes

    DEFF Research Database (Denmark)

    Jacquiod, Samuel Jehan Auguste; Stenbæk, Jonas; Santos, Susana

    2016-01-01

    , providing microbiologists with substantial amounts of accessible information. We took advantage of public metagenomes in order to investigate microeukaryote communities in a well characterized grassland soil. The data gathered allowed the evaluation of several factors impacting the community structure...... has been identified. Our analyses suggest that publicly available metagenome data can provide valuable information on soil microeukaryotes for comparative purposes when handled appropriately, complementing the current view provided by ribosomal amplicon sequencing methods....

  12. Human Trafficking: The Role of the Health Care Provider

    OpenAIRE

    Dovydaitis, Tiffany

    2010-01-01

    Human trafficking is a major public health problem, both domestically and internationally. Health care providers are often the only professionals to interact with trafficking victims who are still in captivity. The expert assessment and interview skills of providers contribute to their readiness to identify victims of trafficking. The purpose of this article is to provide clinicians with knowledge on trafficking and give specific tools that they may use to assist victims in the clinical setti...

  13. Healthcare provider moral distress as a leadership challenge.

    Science.gov (United States)

    Bell, Jennifer; Breslin, Jonathan M

    2008-01-01

    Healthcare leaders are responsible for using strategies to promote an organizational ethical climate. However, these strategies are limited in that they do not directly address healthcare provider moral distress. Since healthcare provider moral distress and the establishment of a positive ethical climate are both linked to an organization's ability to retain healthcare professionals and increase their level of job satisfaction, leaders have a corollary responsibility to address moral distress. We recommend that leaders should provide access to ethics education and resources, offer interventions such as ethics debriefings, establish ethics committees, and/or hire a bioethicist to develop ethics capacity and to assist with addressing healthcare provider moral distress.

  14. External Service Providers to the National Security Technology Incubator

    Energy Technology Data Exchange (ETDEWEB)

    None

    2008-02-28

    This report documents the identification and assessment of external service providers to the National Security Technology Incubator (NSTI) program for southern New Mexico. The NSTI is being developed as part of the National Security Preparedness Project (NSPP), funded by a Department of Energy (DOE)/National Nuclear Security Administration (NNSA) grant to Arrowhead Center, New Mexico State University. This report contains 1) a summary of the services to be provided by NSTI; 2) organizational descriptions of external service providers; and 3) a comparison of NSTI services and services offered by external providers.

  15. Full amnesty could encourage provider self-disclosure.

    Science.gov (United States)

    Mustokoff, M M; Nagele, R L; Swichar, J L

    2000-07-01

    The Federal government's current policy toward healthcare providers that voluntarily disclose improprieties has been ineffective because it offers no guarantee of immunity from prosecution. To be successful, a self-disclosure program must offer real incentives to providers to come forward. The government's self-disclosure programs with respect to tax, environmental, and antitrust laws provide models for an effective amnesty program. The success of these three programs, and particularly of the antitrust program, suggests that healthcare providers would be encouraged to come forward and disclose improprieties if, under certain specific conditions, the OIG and DOJ offered a guarantee of full amnesty to the entity and its officers, directors, and employees.

  16. Providing Formative Feedback: Language Technologies for Lifelong Learning CONSPECT tool

    NARCIS (Netherlands)

    Berlanga, Adriana

    2011-01-01

    Berlanga, A. J. (2011). Providing Formative Feedback: Language Technologies for Lifelong Learning CONSPECT tool. Presentation given at the Onderwijslunch, University of Maastricht. January, 18, 2011, Maastricht, The Netherlands.

  17. Providing Formative Feedback; Language Technologies for Lifelong Learning

    NARCIS (Netherlands)

    Berlanga, Adriana; Stoyanov, Slavi

    2010-01-01

    Berlanga, A. J., & Stoyanov, S. (2010, 24 November). Providing Formative Feedback; Language Technologies for Lifelong Learning. Presentation at a LTfLL workshop validation session, Heerlen, The Netherlands.

  18. Consumer satisfaction with primary care provider choice and associated trust

    Directory of Open Access Journals (Sweden)

    Balkrishnan Rajesh

    2006-10-01

    Full Text Available Abstract Background Development of managed care, characterized by limited provider choice, is believed to undermine trust. Provider choice has been identified as strongly associated with physician trust. Stakeholders in a competitive healthcare market have competing agendas related to choice. The purpose of this study is to analyze variables associated with consumer's satisfaction that they have enough choice when selecting their primary care provider (PCP, and to analyze the importance of these variables on provider trust. Methods A 1999 randomized national cross-sectional telephone survey conducted of United States residential households, who had a telephone, had seen a medical professional at least twice in the past two years, and aged ≥ 20 years was selected for secondary data analyses. Among 1,117 households interviewed, 564 were selected as the final sample. Subjects responded to a core set of questions related to provider trust, and a subset of questions related to trust in the insurer. A previously developed conceptual framework was adopted. Linear and logistic regressions were performed based on this framework. Results Results affirmed 'satisfaction with amount of PCP choice' was significantly (p Conclusion This study confirmed the association of 'satisfaction with amount of PCP choice' with provider trust. Results affirmed 'enough PCP choice' was a strong predictor of provider trust. 'Second opinion on PCP' may indicate distrust in the provider. Data such as 'trust in providers in general' and 'the role of provider performance information' in choice, though import in PCP choice, were not available for analysis and should be explored in future studies. Results have implications for rethinking the relationships among consumer choice, consumer behaviors in making trade-offs in PCP choice, and the role of healthcare experiences in 'satisfaction with amount of PCP choice' or 'provider trust.'

  19. Framing the future: sme logistics service providers and scenario planning

    NARCIS (Netherlands)

    Glöckner, Hans-Heinrich; Pieters, Reinder; Weijers, Stef; Woodburn, Allan

    2013-01-01

    In recent years, the transport industry has encountered numerous challenges. It experienced strong growth, but also many uncertainties. In many cases, logistics service providers were forced to change their strategy. So, the question for logistics service providers arises “how to deal best with unce

  20. Using Turnitin to Provide Feedback on L2 Writers' Texts

    Science.gov (United States)

    Kostka, Ilka; Maliborska, Veronika

    2016-01-01

    Second language (L2) writing instructors have varying tools at their disposal for providing feedback on students' writing, including ones that enable them to provide written and audio feedback in electronic form. One tool that has been underexplored is Turnitin, a widely used software program that matches electronic text to a wide range of…

  1. Predictors of radiation exposure to providers during percutaneous nephrolithotomy

    Directory of Open Access Journals (Sweden)

    David L Wenzler

    2017-01-01

    Conclusion: Increased stone burden, partial or staghorn calculi, surgery and fluoroscopy duration, and absence of preexisting access were associated with high provider radiation exposure. Radiation safety awareness is essential to minimize exposure and to protect the patient and all providers from potential radiation injury.

  2. Early Intervention Provider Use of Child Caregiver-Teaching Strategies

    Science.gov (United States)

    Campbell, Philippa H.; Coletti, Catherine Ehret

    2013-01-01

    The purpose of this study was to identify the extent to which multidiscipline early intervention providers identified and demonstrated caregiver-teaching strategies. A total of 78 providers submitted 205 videotaped segments to illustrate 1 of 5 caregiver-teaching strategies (i.e., demonstration; caregiver practice with feedback; guided practice;…

  3. A joint venture in providing home care and community service.

    Science.gov (United States)

    Reifsteck, S

    1987-01-01

    General discussion of a joint venture providing home care and community service including future possibilities, business and financial aspects and demand is presented. The author then provides a group practice joint venture model including descriptions of operating structure, contract arrangements and management.

  4. 8 CFR 204.302 - Role of service providers.

    Science.gov (United States)

    2010-01-01

    ... facilitator that is not authorized under 8 CFR part 292 to engage in representation before USCIS. (c... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Role of service providers. 204.302 Section... PETITIONS Intercountry Adoption of a Convention Adoptee § 204.302 Role of service providers. (a) Who...

  5. EV and HP Providing Ancillary Services in the Nordic Region

    DEFF Research Database (Denmark)

    Liu, Zhaoxi; Wu, Qiuwei

    This report covers the analysis of the electric vehicle (EV) and heat pump (HP) providing ancillary services to the power system of the Nordic region including Denmark, Finland, Norway and Sweden. The analysis is to investigate the feasibility of EVs and HPs to serve as demand as frequency reserve...... (DFR) providers in the distribution power system in the four mentioned Nordic countries....

  6. Understanding Emotional Development: Helping Early Childhood Providers Better Support Families

    Science.gov (United States)

    Edwards, Nicole Megan

    2012-01-01

    This article is intended to provide early childhood providers with a concise overview of emerging emotional development in young children (birth-5), the important role of primary caregivers, and the link between parenting, emotional development, and behavior. Specific suggestions that have been shared with urban Head Start mothers are offered,…

  7. 5 CFR 9701.407 - Monitoring performance and providing feedback.

    Science.gov (United States)

    2010-01-01

    ... feedback. 9701.407 Section 9701.407 Administrative Personnel DEPARTMENT OF HOMELAND SECURITY HUMAN... performance and providing feedback. In applying the requirements of the performance management system and its... organization; and (b) Provide timely periodic feedback to employees on their actual performance with respect...

  8. A Novel Trust Service Provider for Internet Based Commerce Applications.

    Science.gov (United States)

    Siyal, M. Y.; Barkat, B.

    2002-01-01

    Presents a framework for enhancing trust in Internet commerce. Shows how trust can be provided through a network of Trust Service Providers (TSp). Identifies a set of services that should be offered by a TSp. Presents a distributed object-oriented implementation of trust services using CORBA, JAVA and XML. (Author/AEF)

  9. Rolls-Royce Becomes Provider for West-East Pipeline

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ Rolls-Royce, a leading provider of gas turbines for global energy markets, announced on February that it has won the contract to provide Rolls-Royce pipeline compression equipment for China's West-East Gas Pipeline Project (WEPP). The contract is valued at over US$150 million.

  10. The consumer-provider relationship in the dental industry.

    Science.gov (United States)

    Griffith, Andrew S; Abratt, Russell

    2013-01-01

    This article explains how a consumer's level of trust and commitment to his or her dental service provider factors into the relationship between the consumer and the dental professional. Very little research has been done that describes the complexity of this relationship. This article documents the complexity of and influences on that relationship by providing an interaction model of this relationship.

  11. Safe Passages: Providing Online Support to Beginning Teachers.

    Science.gov (United States)

    DeWert, Marjorie Helsel; Babinski, Leslie M.; Jones, Brett D.

    2003-01-01

    Examined the use of online collaborative consultation in providing social, emotional, practical, and professional support to beginning teachers. Beginning and experienced teachers and teacher educators communicated via an email list over 6 months. Qualitative and quantitative data indicated that these discussions provided teachers opportunities to…

  12. Providers' response to child eating behaviors: A direct observation study.

    Science.gov (United States)

    Tovar, Alison; Vaughn, Amber E; Fallon, Megan; Hennessy, Erin; Burney, Regan; Østbye, Truls; Ward, Dianne S

    2016-10-01

    Child care providers play an important role in feeding young children, yet little is known about children's influence on providers' feeding practices. This qualitative study examines provider and child (18 months -4 years) feeding interactions. Trained data collectors observed 200 eating occasions in 48 family child care homes and recorded providers' responses to children's meal and snack time behaviors. Child behaviors initiating provider feeding practices were identified and practices were coded according to higher order constructs identified in a recent feeding practices content map. Analysis examined the most common feeding practices providers used to respond to each child behavior. Providers were predominately female (100%), African-American (75%), and obese (77%) and a third of children were overweight/obese (33%). Commonly observed child behaviors were: verbal and non-verbal refusals, verbal and non-verbal acceptance, being "all done", attempts for praise/attention, and asking for seconds. Children's acceptance of food elicited more autonomy supportive practices vs. coercive controlling. Requests for seconds was the most common behavior, resulting in coercive controlling practices (e.g., insisting child eat certain food or clean plate). Future interventions should train providers on responding to children's behaviors and helping children become more aware of internal satiety and hunger cues.

  13. Definitions of Multicultural Competence: Frontline Human Service Providers' Perspective

    Science.gov (United States)

    Caldwell, Leon D.; Tarver, Dolores D.; Iwamoto, Derek K.; Herzberg, Sarah E.; Cerda-Lizarraga, Patricia; Mack, Tabethah

    2008-01-01

    In this qualitative study, the authors explored definitions of multicultural competence given by 99 frontline human service providers. The providers had no formal training in counseling but served in a helping role. Seven thematic definitions emerged: color blindness, client focused, acknowledgment of cultural differences, textbook consistent,…

  14. Market Research Manual for Providers of Vocational Education and Training.

    Science.gov (United States)

    Tamblyn, Annette; Shelton, Diane

    This manual, which is intended for vocational education and training (VET) providers, does the following: explains fundamental market research concepts; highlights situations where market research can help VET providers with their planning and policy development; and illustrates the uses of market research in VET institutions. The following topics…

  15. How Childcare Providers Interpret "Reasonable Suspicion" of Child Abuse

    Science.gov (United States)

    Levi, Benjamin H.; Crowell, Kathryn; Walsh, Kerryann; Dellasega, Cheryl

    2015-01-01

    Background: Childcare providers are often "first responders" for suspected child abuse, and how they understand the concept of "reasonable suspicion" will influence their decisions regarding which warning signs warrant reporting. Objective: The purpose of this study was to investigate how childcare providers interpret the…

  16. Keeping consumers safe: food providers' perspectives on pureed food.

    Science.gov (United States)

    Keller, Heather H; Duizer, Lisa M

    2014-01-01

    Twelve focus groups were conducted in five sites with 80 allied health providers to identify their perspectives on providing pureed food to consumers. Thematic care analysis was completed to summarize and interpret these data. Providers' greatest concern was keeping consumers safe, and the right texture was prioritized over sensory appeal and acceptance. Providers recognized that these foods impacted the quality of life of consumers and worked to rationalize these diets with residents/patients and their families. In addition, offering foods they knew to be poorly accepted affected their self-concept as providers. As a result of these challenges, they did whatever they could in the kitchen and tableside to promote intake of pureed foods. Those in the "food chain" of pureed food provision suggested several ways to further improve these products. Greater communication between those who assist consumers with eating and those who produce the pureed food they consume is needed to promote acceptable pureed products.

  17. Human trafficking: the role of the health care provider.

    Science.gov (United States)

    Dovydaitis, Tiffany

    2010-01-01

    Human trafficking is a major public health problem, both domestically and internationally. Health care providers are often the only professionals to interact with trafficking victims who are still in captivity. The expert assessment and interview skills of providers contribute to their readiness to identify victims of trafficking. The purpose of this article is to provide clinicians with knowledge on trafficking and give specific tools that they may use to assist victims in the clinical setting. Definitions, statistics, and common health care problems of trafficking victims are reviewed. The role of the health care provider is outlined through a case study and clinical practice tools are provided. Suggestions for future research are also briefly addressed.

  18. Managing smarter: a decision support system for mental health providers.

    Science.gov (United States)

    Mohan, L; Muse, L; McInerney, C

    1998-11-01

    Financing of mental health care has changed radically, especially with managed care. Shrinking revenues have forced providers to look for creative ways in which to provide quality services at less expense. Delivery of quality services depends largely on the productive use of the provider's prime resource--the clinicians. Productivity was the focus of the PC-based decision support system developed for mental health providers in New York State. It enables administrators to track key indicators of productivity such as face-to-face time and non-face-to-face time against goals. Unmet goals can be pinpointed quickly, and clinicians' caseloads can be reviewed to determine the underlying causes. A key feature of the system is the conversion of raw data into actionable information to help in problem finding and problem solving. The system has been implemented in Ulster County, the pilot site for the project. The software can be customized easily to suit the data of other providers.

  19. Employee motivation in Product-Service-System providers

    DEFF Research Database (Denmark)

    Kreye, Melanie

    2016-01-01

    This research investigates how intrinsic and extrinsic motivation factors contribute to employee motivation in providers of Product-Service Systems (PSS). Employee motivation determines the quality of the delivered service and is thus an area of great importance for PSS providers. We present rich...... case-based data collected through semi-structured interviews, a survey and secondary sources. The analysis showed the particularly high importance of intrinsic and individual motivation factors such as the fulfilling nature of the work and skill development showing the ownership and pride service...... employees took in their work. Further, the organisation needs to set the context of high employee motivation by enabling flexibility and performance feedback. Our research contributes to the literature by providing a first empirical study of employee motivation in PSS providers and thus providing important...

  20. Providers' Perceptions of Challenges in Obstetrical Care for Somali Women

    Directory of Open Access Journals (Sweden)

    Jalana N. Lazar

    2013-01-01

    Full Text Available Background. This pilot study explored health care providers’ perceptions of barriers to providing health care services to Somali refugee women. The specific aim was to obtain information about providers’ experiences, training, practices and attitudes surrounding the prenatal care, delivery, and management of women with Female Genital Cutting (FGC. Methods. Individual semi-structured interviews were conducted with 14 obstetricians/gynecologists and nurse midwives in Columbus, Ohio. Results. While providers did not perceive FGC as a significant barrier in itself, they noted considerable challenges in communicating with their Somali patients and the lack of formal training or protocols guiding the management of circumcised women. Providers expressed frustration with what they perceived as Somali patients' resistance to obstetrical interventions and disappointment with a perception of mistrust from patients and their families. Conclusion. Improving the clinical encounter for both patients and providers entails establishing effective dialogue, enhancing clinical and cultural training of providers, improving health literacy, and developing trust through community engagement.

  1. Enhancing genomic laboratory reports: A qualitative analysis of provider review

    Science.gov (United States)

    Rahm, Alanna Kulchak; Stuckey, Heather; Green, Jamie; Feldman, Lynn; Zallen, Doris T.; Bonhag, Michele; Segal, Michael M.; Fan, Audrey L.; Williams, Marc S.

    2016-01-01

    This study reports on the responses of physicians who reviewed provider and patient versions of a genomic laboratory report designed to communicate results of whole genome sequencing. Semi‐structured interviews addressed concept communication, elements, and format of example genome reports. Analysis of the coded transcripts resulted in recognition of three constructs around communication of genome sequencing results: (1) Providers agreed that whole genomic sequencing results are complex and they welcomed a report that provided supportive interpretation information to accompany sequencing results; (2) Providers strongly endorsed a report that included active clinical guidance, such as reference to practice guidelines, if available; and (3) Providers valued the genomic report as a resource that would serve as the basis to facilitate communication of genome sequencing results with their patients and families. Providers valued both versions of the report, though they affirmed the need for a provider‐oriented report. Critical elements of the report included clear language to explain the result, as well as consolidated yet comprehensive prognostic information with clear guidance over time for the clinical care of the patient. Most importantly, it appears a report with this design has the potential not only to return results but also serves as a communication tool to help providers and patients discuss and coordinate care over time. © 2016 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc. PMID:26842872

  2. Privately Provided Accommodation Service Quality and Customer Satisfaction

    Directory of Open Access Journals (Sweden)

    Joshua Mugambwa

    2016-04-01

    Full Text Available Privately provided accommodation is a growing service in Uganda’s higher education sector due to education liberalization and demand for education. This research took a case study of Nsamizi Training Institute of Social Development (NTISD to determine the relationship between privately provided accommodation service quality and customer satisfaction. Specifically, the objectives of the study were (a to find out the relationship between security and NTISD students’ satisfaction with privately provided accommodation, and (b to find out the hierarchical level of importance of NTISD student satisfaction of the three service quality dimensions (reliability, security, and tangibles with privately provided accommodation. Using quantitative and qualitative modes of data analysis and a sample of 300 students from 20 private hostels, this study established a strong positive significant relationship between security and satisfaction regarding privately provided accommodation. This implies that accommodation service providers should increase the quality of security so as to increase the satisfaction of students regarding privately provided accommodation. The study established the hierarchical order of importance from the most important service quality dimension, respectively, as follows: reliability, security, and tangibles. Therefore, private accommodation service managers should pay extra attention to the dimensions in the same order.

  3. Trust Your Cloud Service Provider: User Based Crypto Model. Sitanaboina

    Directory of Open Access Journals (Sweden)

    Sri Lakshmi Parvathi

    2014-10-01

    Full Text Available In Data Storage as a Service (STaaS cloud computing environment, the equipment used for business operations can be leased from a single service provider along with the application, and the related business data can be stored on equipment provided by the same service provider. This type of arrangement can help a company save on hardware and software infrastructure costs, but storing the company’s data on the service provider’s equipment raises the possibility that important business information may be improperly disclosed to others [1]. Some researchers have suggested that user data stored on a service-provider’s equipment must be encrypted [2]. Encrypting data prior to storage is a common method of data protection, and service providers may be able to build firewalls to ensure that the decryption keys associated with encrypted user data are not disclosed to outsiders. However, if the decryption key and the encrypted data are held by the same service provider, it raises the possibility that high-level administrators within the service provider would have access to both the decryption key and the encrypted data, thus presenting a risk for the unauthorized disclosure of the user data. we in this paper provides an unique business model of cryptography where crypto keys are distributed across the user and the trusted third party(TTP with adoption of such a model mainly the CSP insider attack an form of misuse of valuable user data can be treated secured.

  4. Resilience and professional quality of life among military healthcare providers.

    Science.gov (United States)

    Leners, Colleen; Sowers, Ramona; Quinn Griffin, Mary T; Fitzpatrick, Joyce J

    2014-07-01

    The retention of qualified military healthcare providers is a top priority for Department of Defense (DoD) leaders. The purpose of this study is to examine the relationship between resilience and professional quality of life and to explore differences among providers who had been deployed and those who had never been deployed. Results indicated high resilience scores among all providers, and significant relationships between dimensions of professional quality of life and resilience. There were significant differences in professional quality of life based on deployment. Recommendations for future research are included, particularly as retention is an important issue for the DoD.

  5. Analysis of science textbook recommendations provided for students with disabilities.

    Science.gov (United States)

    Parmar, R S; Cawley, J F

    1993-05-01

    Teachers' manuals from three major elementary science textbook series were analyzed. These textbooks provided specific instructional recommendations for students with disabilities in mainstream classes. Findings reveal that (a) the textbooks did not provide recommendations for all categories of disabilities as defined in Public Law 94-142; (b) many recommendations did not specifically address the learning needs of the students for whom they were intended; and (c) there were no consistency in the nature of recommendations provided for any given category of disability. Results indicate that special education and mainstream teachers should monitor the usefulness of published materials that claim to meet the needs of students with disabilities.

  6. Regulatory requirements for providing adequate veterinary care to research animals.

    Science.gov (United States)

    Pinson, David M

    2013-09-01

    Provision of adequate veterinary care is a required component of animal care and use programs in the United States. Program participants other than veterinarians, including non-medically trained research personnel and technicians, also provide veterinary care to animals, and administrators are responsible for assuring compliance with federal mandates regarding adequate veterinary care. All program participants therefore should understand the regulatory requirements for providing such care. The author provides a training primer on the US regulatory requirements for the provision of veterinary care to research animals. Understanding the legal basis and conditions of a program of veterinary care will help program participants to meet the requirements advanced in the laws and policies.

  7. AN ADAPTIVE AQM TO PROVIDE DELAY GUARANTEES FOR DIFFERENTIATED SERVICES

    Institute of Scientific and Technical Information of China (English)

    Yang Zongkai; Liu Wei; He Jianhua; Chou Chuntung

    2005-01-01

    RIO(RED with IN and OUT) is the primary queue management mechanism proposed for assured forwarding in the DiffServ (Differentiated Service) framework. Although RIO can generally provide bandwidth guarantees, its queuing delay is sensitive to the traffic load. This paper presents a qualitative explanation for its origin. As a solution, an Adaptive RIO for Delay (ARIO-D) is proposed to provide guaranteed delay for multimedia traffic. Simulation results show that by trading loss for delay, ARIO-D can effectively improve the robustness of RIO under different and dynamic traffic, and provide stable and differentiated performance of queuing delay without any degradation in performance of throughput.

  8. Clinical trial participant characteristics and saliva and DNA metrics

    Directory of Open Access Journals (Sweden)

    Richards Julie

    2009-10-01

    Full Text Available Abstract Background Clinical trial and epidemiological studies need high quality biospecimens from a representative sample of participants to investigate genetic influences on treatment response and disease. Obtaining blood biospecimens presents logistical and financial challenges. As a result, saliva biospecimen collection is becoming more frequent because of the ease of collection and lower cost. This article describes an assessment of saliva biospecimen samples collected through the mail, trial participant demographic and behavioral characteristics, and their association with saliva and DNA quantity and quality. Methods Saliva biospecimens were collected using the Oragene® DNA Self-Collection Kits from participants in a National Cancer Institute funded smoking cessation trial. Saliva biospecimens from 565 individuals were visually inspected for clarity prior to and after DNA extraction. DNA samples were then quantified by UV absorbance, PicoGreen®, and qPCR. Genotyping was performed on 11 SNPs using TaqMan® SNP assays and two VNTR assays. Univariate, correlation, and analysis of variance analyses were conducted to observe the relationship between saliva sample and participant characteristics. Results The biospecimen kit return rate was 58.5% among those invited to participate (n = 967 and 47.1% among all possible COMPASS participants (n = 1202. Significant gender differences were observed with males providing larger saliva volume (4.7 vs. 4.5 ml, p = 0.019, samples that were more likely to be judged as cloudy (39.5% vs. 24.9%, p 0.21, P Conclusion Findings from this study show that demographic and behavioral characteristics of smoking cessation trial participants have significant associations with saliva and DNA metrics, but not with the performance of TaqMan® SNP or VNTR genotyping assays. Trial registration COMPASS; registered as NCT00301145 at clinicaltrials.gov.

  9. 42 CFR 413.64 - Payments to providers: Specific rules.

    Science.gov (United States)

    2010-10-01

    ..., subject to later audit. When an audit is made and the final liability of the program is determined, a... as to whether payment can be made to the provider under the PIP method without undue risk of...

  10. Communication: Provide Solid Foundation for Good Business Communications

    Science.gov (United States)

    Jackson, Deborah

    1977-01-01

    To help high school teachers provide their students with a solid foundation for business communication, the following are discussed: five educational fundamentals of business communication, the importance of pretesting, and several teaching suggestions. (SH)

  11. Challenging RSD clients’ preferences for foreign service providers

    Directory of Open Access Journals (Sweden)

    Christian Pangilinan

    2012-12-01

    Full Text Available Organisations that provide legal services to refugees and asylumseekers face the challenge of responding ethically to clients’ requeststo be assisted by foreigners as opposed to by nationals in countryoffices.

  12. How Do Health Care Providers Diagnose Bacterial Vaginosis (BV)?

    Science.gov (United States)

    ... and Publications How do health care providers diagnose bacterial vaginosis (BV)? Skip sharing on social media links Share ... menstruating. Centers for Disease Control and Prevention. (2010). Bacterial vaginosis: CDC fact sheet . Retrieved May 10, 2012, from ...

  13. Shared Savings Program ACO Provider-level RIF

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Centers for Medicare (CM) has created a set of standard analytical files that contain Shared Savings Program Accountable Care Organizations. Provider-level RIF...

  14. Find Ryan White HIV/AIDS Medical Care Providers

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Find Ryan White HIV/AIDS Medical Care Providers tool is a locator that helps people living with HIV/AIDS access medical care and related services. Users can...

  15. Provider in triage: is this a place for nurse practitioners?

    Science.gov (United States)

    Bahena, Diana; Andreoni, Colleen

    2013-01-01

    The role of nurse practitioners (NPs) in emergency care continues to evolve. A new and exciting role is the provider-in-triage (PIT) role. This innovative role has been implemented in many emergency departments (EDs) across the country. It was developed primarily as a front-end strategy to improve throughput of patients receiving emergency care. The PIT process uses a provider, physician, NP, or physician assistant in the triage area. Patient satisfaction, quality measures, and financial improvements have been attributed to using a PIT. The emergency NP is an optimal choice for this role. Advanced emergency nursing knowledge, skills, and decision making confer the NP a cost-effective provider to improve throughput in the ED while providing quality emergency care.

  16. The role of written provider communication in external client participation.

    Science.gov (United States)

    Dellande, Stephanie; Taylor, Gail Ayala

    2004-01-01

    In certain classes of services, the client's role in the service delivery process often extends beyond the face-to-face exchange. With compliance dependent services (CDS), the client is expected to continue to perform for him or herself once away from the service provider in order to ensure positive outcomes and customer satisfaction (Dellande and Gilly, 1998). This study examined the effectiveness of written provider communication in influencing client motivation and role clarity in CDS. Two exploratory investigations examining written provider communication were conducted. In study 1, written material of three different types of health care related CDS (dialysis, prenatal care and weight loss) were examined; in study 2, dialysis written material was further examined. The findings suggest that, in the majority of the materials examined, written provider communication does not seem to clearly communicate the consequences of noncompliance (a source of customer motivation). However, the materials examined were effective in clarifying the client's external service roles.

  17. How Do Health Care Providers Diagnose Klinefelter Syndrome?

    Science.gov (United States)

    ... and Publications How do health care providers diagnose Klinefelter syndrome (KS)? Skip sharing on social media links Share ... in 166 boys, adolescents and adults with nonmosaic Klinefelter syndrome: A Copenhagen experience. Acta Paediatrica , Jun;100(6), ...

  18. Customer-Provider Strategic Alignment: A Maturity Model

    Science.gov (United States)

    Luftman, Jerry; Brown, Carol V.; Balaji, S.

    This chapter presents a new model for assessing the maturity of a ­customer-provider relationship from a collaborative service delivery perspective: the Customer-Provider Strategic Alignment Maturity (CPSAM) Model. This model builds on recent research for effectively managing the customer-provider relationship in IT service outsourcing contexts and a validated model for assessing alignment across internal IT service units and their business customers within the same organization. After reviewing relevant literature by service science and information systems researchers, the six overarching components of the maturity model are presented: value measurements, governance, partnership, communications, human resources and skills, and scope and architecture. A key assumption of the model is that all of the components need be addressed to assess and improve customer-provider alignment. Examples of specific metrics for measuring the maturity level of each component over the five levels of maturity are also presented.

  19. Welcoming max: Increasing pediatric provider knowledge of service dogs.

    Science.gov (United States)

    Stace, Laura Britton

    2016-08-01

    Service dogs have been used in the adult population for decades. Recently, there has been a diversification in types of service dogs, specifically for the pediatric population. Although guide dogs and mobility dogs are accepted in society, autism assistance dogs, seizure alert and response dogs and diabetic alert dogs are relatively new. As pediatric service dogs attract more attention, pediatric providers need to be prepared to answer parental inquires regarding service dog use. The pediatric provider is well equipped to identify children who could benefit from a service dog intervention and should be able to make a referral to a reputable service dog provider. This article presents guidance on appropriate patient selection, making a service dog referral, and risks and benefits involved. Pediatric providers are ideally positioned to be leaders in implementing this evolving new assistive technology that can help to alleviate pediatric disabilities for both the patient and family.

  20. Indium adhesion provides quantitative measure of surface cleanliness

    Science.gov (United States)

    Krieger, G. L.; Wilson, G. J.

    1968-01-01

    Indium tipped probe measures hydrophobic and hydrophilic contaminants on rough and smooth surfaces. The force needed to pull the indium tip, which adheres to a clean surface, away from the surface provides a quantitative measure of cleanliness.

  1. OPPS Provider Summary for 30 Selected APC Groups - CY2011

    Data.gov (United States)

    U.S. Department of Health & Human Services — A provider level summary of Outpatient Prospective Payment System (OPPS) average estimated submitted charges and average Medicare Payments for 30 selected Ambulatory...

  2. IPPS Provider Summary for the Top 100 DRGs - FY2011

    Data.gov (United States)

    U.S. Department of Health & Human Services — A provider level summary of Inpatient Prospective Payment System (IPPS) discharges, average charges and average Medicare payments for the Top 100 Diagnosis-Related...

  3. Increasing the marketability and recognition of provider network joint ventures.

    Science.gov (United States)

    Sjobeck, S J

    1998-08-01

    Physicians have been developing provider network joint ventures to market their services jointly to managed care plans, employers, and other purchasers. Over the past few years, external market factors have produced a growing impact on these joint ventures. These external market factors include the Federal government's revised antitrust guidelines, National Committee for Quality Assurance activities, and state and Federal consumer protection laws. Simply responding to these forces may not increase a provider network's marketability unless the network can demonstrate its value in the terms and measurements accepted by the consumer, managed care plans, and provider networks. By doing so, a provider network can not only increase its marketability, but also increase its recognition in the market, improve its competitive advantage, and enhance its return on investment.

  4. Athena: Providing Insight into the History of the Universe

    Science.gov (United States)

    Murphy, Gloria A.

    2010-01-01

    The American Institute for Aeronautics and Astronautics has provided a Request for Proposal which calls for a manned mission to a Near-Earth Object. It is the goal of Team COLBERT to respond to their request by providing a reusable system that can be implemented as a solid stepping stone for future manned trips to Mars and beyond. Despite Team COLBERT consisting of only students in Aerospace Engineering, in order to achieve this feat, the team must employ the use of Systems Engineering. Tools and processes from Systems Engineering will provide quantitative and semi-quantitative tools for making design decisions and evaluating items such as budgets and schedules. This paper will provide an in-depth look at some of the Systems Engineering processes employed and will step through the design process of a Human Asteroid Exploration System.

  5. Attitudes of potential providers toward preconceptual cystic fibrosis carrier screening.

    NARCIS (Netherlands)

    Poppelaars, F.; Ader, H.J.; Cornel, M.C.; Henneman, L.; Hermens, R.P.M.G.; Wal, G. van der; Kate, L. ten

    2004-01-01

    To determine the attitudes of potential providers (general practitioners and Community Health Service workers) towards preconceptual cystic fibrosis (CF) carrier screening and to determine which factors are associated with a positive attitude. A survey was conducted among 200 general practitioners (

  6. How Do Health Care Providers Diagnose Neural Tube Defects?

    Science.gov (United States)

    ... and Publications How do health care providers diagnose neural tube defects? Skip sharing on social media links Share this: Page Content Neural tube defects are usually diagnosed before the infant is ...

  7. Using the National Provider Identifier for Health Care...

    Data.gov (United States)

    U.S. Department of Health & Human Services — The establishment in recent years of a National Provider Identifier (NPI) offers a new method for counting and categorizing physicians and other health care...

  8. Ecosystem services provided by pacific NW Estuaries: State of knowledge

    Science.gov (United States)

    Coastal regions in the United States are rapidly developing areas, with increasing urbanization and growing populations. Estuarine and nearshore coastal marine waters provide valuable ecosystem services to resident and transient human communities. In the Pacific Northwest (PNW)...

  9. NIH scientists provide new insight into rare kidney cancer

    Science.gov (United States)

    NIH scientists have discovered a unique feature of a rare, hereditary form of kidney cancer that may provide a better understanding of its progression and metastasis, possibly laying the foundation for the development of new targeted therapies.

  10. How Do Health Care Providers Diagnose Spina Bifida?

    Science.gov (United States)

    ... and Publications How do health care providers diagnose spina bifida? Skip sharing on social media links Share this: Page Content Doctors diagnose spina bifida before or after the infant is born. Spina ...

  11. How Do Health Care Providers Diagnose Osteogenesis Imperfecta?

    Science.gov (United States)

    ... ee-on-ik VILL-uhs ) sampling (CVS) or amniocentesis (pronounced am-nee-oh-sen-TEE-sis ). The ... tested for the presence of abnormal collagen. For amniocentesis, a health care provider takes a small amount ...

  12. Planning start-up: digital educational game solutions provider

    OpenAIRE

    Paschalis, Antreas; Ibironke, Fakinkunmi; Essa, Lubna; Alsatrawi, Ali Jawad

    2015-01-01

    Game-based learning is a growing field that provides education with a new perspective of teaching through games. Game based learning is still considered an emerging field due to problems that have been identified in its real applications in official education in classes. The research conducted shows a very attractive market ahead for game based learning around the world. However the businesses success in this domain lie in providing value proposition that addresses the real barriers faced tod...

  13. Biosimilars: Opportunities to Promote Optimization Through Payer and Provider Collaboration.

    Science.gov (United States)

    Manolis, Chronis H; Rajasenan, Kiran; Harwin, William; McClelland, Scott; Lopes, Maria; Farnum, Carolyn

    2016-09-01

    A panel was convened that consisted of 1 medical director, 2 pharmacy directors, and 2 oncologists, who represented the University of Pittsburgh Medical Center Health Plan, an integrated delivery network, and Florida Blue, a progressive regional health plan. This panel met in order to share ideas, discuss challenges, and develop practical solutions to promote optimal utilization in order to encourage collaboration between payers and providers to help ensure the success of biosimilar entrants into the marketplace. Live meetings were conducted in Orlando, Florida, and Pittsburgh, Pennsylvania, and were followed by virtual meetings to solidify ideas and concepts for this supplement. It is important for biosimilar manufacturers to identify potential payer, provider, and patient obstacles in order to develop strategic and tactical plans to preemptively address these potential obstacles. Gathering payer and provider insights will shed light on various issues such as access and reimbursement. Biosimilar manufacturers must be proactive in the education of payers, providers, and patients to ensure access to biosimilars. A strong factor emphasized among this group was that the assumption surrounding biosimilar development and use is the potential for health care cost savings. According to the panel, payers and providers must carefully consider economic implications and potential cost-effectiveness in order to increase the acceptance or understanding of biosimilars in clinical practice. The group identified 3 major challenges surrounding biosimilar adoption: (1) provider confidence in biosimilar education and clinical value, (2) provider confidence in reimbursement for new biosimilars, and (3) creating shared payer and provider cost-savings. After identification of the 3 challenges, the group posed potential solutions to help with biosimilar adoption.

  14. Final Service Provider DevOps concept and evaluation

    OpenAIRE

    Marchetto, Guido; Sisto, Riccardo; John, Wolfgang; Sköldström, Pontus; Pechenot, Bertrand; Németh, Felicián; Pelle, István; Kim, Juhoon; Cai, Xuejun; Fu, Chunyan; Meirosu, Catalin; Pentikousis, Kostas; Sharma, Sachin; Papafili, Ioanna; Spinoso, Serena

    2016-01-01

    This report presents the results of the UNIFY Service Provider DevOps activities. First, we present the final definition and assessment of the concept. SP-DevOps is realized by a combination of various functional components facilitating integrated service verification, efficient and programmable observability, and automated troubleshooting processes. Our assessment shows that SP-DevOps can help providers to reach a medium level of DevOps maturity and allows significant reduction in OPEX. Seco...

  15. Satisfaction with information provided to Danish cancer patients

    DEFF Research Database (Denmark)

    Ross, Lone; Petersen, Morten Aagaard; Johnsen, Anna Thit

    2013-01-01

    To validate five items (CPWQ-inf) regarding satisfaction with information provided to cancer patients from health care staff, assess the prevalence of dissatisfaction with this information, and identify factors predicting dissatisfaction.......To validate five items (CPWQ-inf) regarding satisfaction with information provided to cancer patients from health care staff, assess the prevalence of dissatisfaction with this information, and identify factors predicting dissatisfaction....

  16. Service Provider DevOps network capabilities and tools

    OpenAIRE

    Steinert, Rebecca; John, Wolfgang; Sköldström, Pontus; Pechenot, Bertrand; Gulyás, András; Pelle, István; Lévai, Tamás; Németh, Felicián; Kim, Juhoon; Meirosu, Catalin; Cai, Xuejun; Fu, Chunyan; Pentikousis, Kostas; Sharma, Sachin; Papafili, Ioanna

    2015-01-01

    This report provides an understanding of how the UNIFY Service Provider (SP)-DevOps concept can be applied and integrated with a combined cloud and transport network NFV architecture. Specifically, the report contains technical descriptions of a set of novel SP-DevOps tools and support functions that facilitate observability, troubleshooting, verification, and VNF development processes. The tools and support functions are described in detail together with their architectural mapping, giving a...

  17. An Open Service Provider Concept for Enterprise Complex Automation

    Science.gov (United States)

    Ivaschenko, A. V.; Sitnikov, P. V.; Tanonykhina, M. O.

    2017-01-01

    The paper introduces a solution for IT services representation and management in the integrated information space of distributed enterprises. It is proposed to develop an Open Service Provider as a software platform for interaction between IT services providers and their users. Implementation of the proposed concept and approach is illustrated by an after-sales customer support system for a large manufacturing corporation delivered by SEC “Open Code”.

  18. Veteran, Primary Care Provider, and Specialist Satisfaction With Electronic Consultation

    OpenAIRE

    2015-01-01

    Background Access to specialty care is challenging for veterans in rural locations. To address this challenge, in December 2009, the Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS) implemented an electronic consultation (e-consult) program to provide primary care providers (PCPs) and patients with enhanced specialty care access. Objective The aim of this quality improvement (QI) project evaluation was to: (1) assess satisfaction with the e-consult process, and (2) identify perceive...

  19. A survey of assistive technology service providers in the USA.

    Science.gov (United States)

    Arthanat, Sajay; Elsaesser, Linda-Jeanne; Bauer, Stephen

    2017-01-26

    This study investigates perspectives of assistive technology service (ATS) providers regarding their education and training, interdisciplinary standards of practice, use of a common language framework, funding policies, utilization of evidence and outcomes measurement. A survey underpinned by AT legislations and established guidelines for practice was completed by 318 certified AT providers. More than 30% of the providers reported their education and training as inadequate to fulfil four of the seven primary roles of ATS. Nearly 90% of providers expressed awareness of the International Classification of Functioning, Disability and Health (ICF) domains for interdisciplinary communication. However, only 45% felt that they could effectively utilize the ICF in their documentation. About 75% of the providers acknowledged the lack of a recognized standard for the provision of services. Prevailing inadequacies in funding were negatively impacting the quality of ATS, as expressed by 88% of respondents. Translation of evidence to practice was identified as a major challenge by 41% of service providers. Providers were predominantly documenting outcomes through informal interviews (54%) or non-standard instruments (26%). Findings support the need for strengthening professional curriculum, pre-service and in-service training and an established standard to support effective, interdisciplinary AT services and data collection to support public policy decisions. Implications for Rehabilitation This study validates the need to strengthen education and training of AT service providers by enhancing professional curriculum as well as their engagement in pre-service and in-service training activities. This study draws attention to health care funding policies and practices that critically impact the quality of AT services. This study signifies the need for an established interdisciplinary standard among AT professionals to support effective communication, service coordination and

  20. DTC-and-Me: Patient, Provider, Proteins and Regulators.

    Science.gov (United States)

    Steele, Fintan R; Gold, Larry

    2014-03-18

    The yet-unrealized potential for more "personalized" Direct-to-Consumer (DTC) tests to fundamentally alter the practice and economics of healthcare is undeniable. However, there are also many challenges to be met, including the herculean task of ensuring that the information provided by such tests is scientifically sound and, ideally, medically actionable. We consider recent events in DTC testing and suggest a "thought experiment" of an approach that could ultimately meet the needs of patients, providers and regulatory authorities.

  1. Provider Reimbursement Review Board annual report: fiscal year 1994.

    Science.gov (United States)

    1995-01-01

    The Provider Reimbursement Review Board (PRRB) is the first step in the administrative/judicial appeals process for Medicare payment disputes of $10,000 ($50,000 for group appeals) or more. This annual report provides information about the PRRB, its performance during the past fiscal year (FY), an assessment of current issues, and comments regarding the future. Tables and figures accompanying this report illustrate trends reported herein.

  2. Providing Nuclear Criticality Safety Analysis Education through Benchmark Experiment Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    John D. Bess; J. Blair Briggs; David W. Nigg

    2009-11-01

    One of the challenges that today's new workforce of nuclear criticality safety engineers face is the opportunity to provide assessment of nuclear systems and establish safety guidelines without having received significant experience or hands-on training prior to graduation. Participation in the International Criticality Safety Benchmark Evaluation Project (ICSBEP) and/or the International Reactor Physics Experiment Evaluation Project (IRPhEP) provides students and young professionals the opportunity to gain experience and enhance critical engineering skills.

  3. Sexual health service providers' perceptions of transgender youth in England.

    Science.gov (United States)

    Lefkowitz, Ayla R F; Mannell, Jenevieve

    2017-01-23

    Transgender youth often face difficulties when accessing sexual health services. However, few studies investigate health service providers' perceptions of transgender youth, and fewer focus on sexual health. To fill this gap, our study draws on social representations theory to examine sexual health service providers' perceptions of transgender youth and how this influences the provision of health services for this marginalised population in England. A thematic analysis of 20 semi-structured interviews with service providers, conducted between March and June 2014, resulted in five main themes centred on: binary representations of transgender; transgender as homosexuality; uncertain bodies; unstable mental states; and too young to know. Of the service providers interviewed, many understood transgender within a male/female binary, and perceived being transgender to be synonymous with being gay. There was confusion among service providers regarding transgender youths' sexual organs, and most of those interviewed saw transgender youth as mentally unstable and confused. Finally, many service providers perceived that transgender youth are too young to know that they are transgender and make decisions about their body. Some of these representations were potentially stigmatising and many conflicted with transgender youths' representations of themselves. Training by transgender people is recommended to help address these misunderstandings.

  4. Selecting a provider: what factors influence patients' decision making?

    Science.gov (United States)

    Abraham, Jean; Sick, Brian; Anderson, Joseph; Berg, Andrea; Dehmer, Chad; Tufano, Amanda

    2011-01-01

    Each year consumers make a variety of decisions relating to their healthcare. Some experts argue that stronger consumer engagement in decisions about where to obtain medical care is an important mechanism for improving efficiency in healthcare delivery and financing. Consumers' ability and motivation to become more active decision makers are affected by several factors, including financial incentives and access to information. This study investigates the set of factors that consumers consider when selecting a provider, including attributes of the provider and the care experience and the reputation of the provider. Additionally, the study evaluates consumers awareness and use of formal sources of provider selection information. Our results from analyzing data from a survey of 467 patients at four clinics in Minnesota suggest that the factors considered of greatest importance include reputation of the physician and reputation of the healthcare organization. Contractual and logistical factors also play a role, with respondents highlighting the importance of seeing a provider affiliated with their health plan and appointment availability. Few respondents indicated that advertisements or formal sources of quality information affected their decision making. The key implication for provider organizations is to carefully manage referral sources to ensure that they consistently meet the needs of referrers. Excellent service to existing patients and to the network of referring physicians yields patient and referrer satisfaction that is critical to attracting new patients. Finally, organizations more generally may want to explore the capabilities of new media and social networking sites for building reputation.

  5. Who Do Batswana Men Prefer: Male or Female Health Providers?

    Science.gov (United States)

    Letshwenyo-Maruatona, Sandra

    2015-12-14

    Sexual and reproductive health (SRH) services are rarely designed specifically to meet men's needs. There is a general consensus among clinicians that males need access to SRH services. Studies have reported that men are often hesitant to go to health facilities because they feel uncomfortable being served by female providers. The study sought to determine whether men who participate in SRH services have specific preference for the gender of health workers for consultation on different types of services. A mixed-method design was employed. A combination of stratified proportional sampling of facilities and criterion purposive sampling of participants were used. Questionnaires were used to collect data from 390 participants, which were complemented with 10 in-depth interviews. Chi-square analysis with post hoc comparisons were used to determine whether there were significant differences in gender preference for specific services. Based on the data, Batswana males did not have any gender preference of the health provider for consultation on SRH services. The gender of the provider is of minor importance compared with other characteristics such as competence and confidentiality. However, the gender of the provider seems to be more important to younger men for delivery, sexually transmitted infections, voluntary counselling, and testing services. Further research is needed because the study was conducted in the city and the participants' characteristics may be unique to an urban setting. Preferences for providers among demographic groups can be useful in informing resource prioritization and help direct program efforts to reach different subgroups of males.

  6. Provider barriers to telemental health: obstacles overcome, obstacles remaining.

    Science.gov (United States)

    Brooks, Elizabeth; Turvey, Carolyn; Augusterfer, Eugene F

    2013-06-01

    Many providers are hesitant to use telemental health technologies. When providers are queried, various barriers are presented, such as the clinician's skepticism about the effectiveness of telemental health (TMH), viewing telehealth technologies as inconvenient, or reporting difficulties with medical reimbursement. Provider support for TMH is critical to its diffusion because clinicians often serve as the initial gatekeepers to telehealth implementation and program success. In this article, we address provider concerns in three broad domains: (1) personal barriers, (2) clinical workflow and technology barriers, and (3) licensure, credentialing, and reimbursement barriers. We found evidence that, although many barriers have been discussed in the literature for years, advancements in TMH have rapidly reduced obstacles for its use. Improvements include extensive opportunities for training, a growing evidence base supporting positive TMH outcomes, and transformations in technologies that improve provider convenience and transmission quality. Recommendations for further change are discussed within each domain. In particular, it is important to grow and disseminate data underscoring the promise and effectiveness of TMH, integrate videoconferencing capabilities into electronic medical record platforms, expand TMH reimbursement, and modify licensure standards.

  7. Applying the balanced scorecard in healthcare provider organizations.

    Science.gov (United States)

    Inamdar, Noorein; Kaplan, Robert S; Bower, Marvin

    2002-01-01

    Several innovative healthcare executives have recently introduced a new business strategy implementation tool: the Balanced Scorecard. The scorecard's measurement and management system provides the following potential benefits to healthcare organizations: It aligns the organization around a more market-oriented, customer-focused strategy It facilitates, monitors, and assesses the implementation of the strategy It provides a communication and collaboration mechanism It assigns accountability for performance at all levels of the organization It provides continual feedback on the strategy and promotes adjustments to marketplace and regulatory changes. We surveyed executives in nine provider organizations that were implementing the Balanced Scorecard. We asked about the following issues relating to its implementation and effect: 1. The role of the Balanced Scorecard in relation to a well-defined vision, mission, and strategy 2. The motivation for adopting the Balanced Scorecard 3. The difference between the Balanced Scorecard and other measurement systems 4. The process followed to develop and implement the Balanced Scorecard 5. The challenges and barriers during the development and implementation process 6. The benefits gained by the organization from adoption and use. The executives reported that the Balanced Scorecard strategy implementation and performance management tool could be successfully applied in the healthcare sector, enabling organizations to improve their competitive market positioning, financial results, and customer satisfaction. This article concludes with guidelines for other healthcare provider organizations to capture the benefits of the Balanced Scorecard performance management system.

  8. Practice characteristics among dental anesthesia providers in the United States.

    Science.gov (United States)

    Boynes, Sean G; Moore, Paul A; Tan, Peter M; Zovko, Jayme

    2010-01-01

    General descriptions or "snapshots" of sedation/general anesthesia practices during dental care are very limited in reviewed literature. The objective of this study was to determine commonalities in dental sedation/anesthesia practices, as well as to accumulate subjective information pertaining to sedation/anesthesia care within the dental profession. This questionnaire-based survey was completed by participating anesthesia providers in the United States. A standardized questionnaire was sent via facsimile, or was delivered by mail, to 1500 anesthesia providers from a randomized list using an online database. Data from the returned questionnaires were entered onto an Excel spreadsheet and were imported into a JMP Statistical Discovery Software program for analyses. Quantitative evaluations were confined to summation of variables, an estimation of means, and a valid percent for identified variables. A total of 717 questionnaires were entered for data analysis (N=717). Data from this study demonstrate the wide variation that exists in sedation/anesthesia care and those providing its administration during dental treatment in the United States. The demographics of this randomized population show anesthesia providers involved in all disciplines of the dental profession, as well as significant variation in the types of modalities used for sedation/anesthesia care. Data from this study reveal wide variation in sedation/anesthesia care during dental treatment. These distinctions include representation of sedation/anesthesia providers across all disciplines of the dental profession, as well as variations in the techniques used for sedation/anesthesia care.

  9. Palliative care providers' perspectives on service and education needs.

    Science.gov (United States)

    Sellick, S M; Charles, K; Dagsvik, J; Kelley, M L

    1996-01-01

    To obtain the information necessary for coordinated regional program development, we examined (a) the multidisciplinary viewpoint of palliative care service provision and (b) the continuing education needs reported by non-physician service providers. Of 146 surveys distributed to care providers from multiple settings, 135 were returned. Respondents cited these problems: fragmented services, poor pain and symptom control, lack of education for providers, lack of public awareness, problems with the continuity and coordination of care, lack of respite, and lack of hospice beds. Stress management for caregivers, pain management, communication skills, and symptom assessment were rated as priorities in continuing education. Lectures, small group discussions, practicum, and regular medical centre rounds were the preferred learning formats, while costs and staff shortages were cited as educational barriers.

  10. Providence nighttime bracing, in treatment of adolescent idiopathic scoliosis

    DEFF Research Database (Denmark)

    Simony, A.; Beuschau, Inge; Quisth, Lena

    2015-01-01

    Introduction: Since 2008 the non-surgical treatment of adolescent idiopathic scoliosis (AIS) in the southern part of Denmark, went from full-time bracing with Boston brace, to Providence night-time bracing. Methods: Since 2008, skeletally immature patients diagnosed with AIS and a primary curve...... with apex at T7 or below, were treated with the Providence night-time brace. The patients were evaluated every 6 months, with standing x-rays. Compliance with the treatment was recorded during the study. Bracing was continued up to two years post menarche or, for males upon reaching the expected adult......, and the follow up was 12 months (8-37m). The SRS22r Function score was 4, 32, Mental Health 3, 81, SRS22r total 3, 9 and satisfaction with management 3, 90. The Pain domain was 3, 8. Conclusion: This study shows a good curve control with the Providence Night time brace and an acceptable 20 % curve progression...

  11. Integration between manufacturers and third party logistics providers?

    DEFF Research Database (Denmark)

    Mortensen, Ole; Lemoine, Olga W.

    2008-01-01

    information and communications technology (ICT) tools are used for support, and what types of services are supplied and are expected to be supplied by TPL providers in the future. Design/methodology/approach - A multiple case study of seven manufacturers and TPL providers is conducted. As the basis...... of the eight business processes studied. Further integration in the same processes is expected, based on ICT tools and with a focus on cost. ICT competences are primarily seen as a qualifier not a differentiator. Because the future TPL industry is expected to be characterised by more standardised services......, more segmented markets for the various services and more intense competition, the manufacturers do not expect increased dependence on the TPL providers. Research limitations/implications - Managerial and behavioural components are not part of this study and their effect on integration will require...

  12. WSAP: provide loss rate differentiation with active queue management

    Institute of Scientific and Technical Information of China (English)

    Zhang Miao; Wu Jianping; Xu Ke

    2005-01-01

    How to provide service differentiation in the Internet is a hot research topic. One proposal is to provide loss rate differentiation by assigning levels of dropprecedence to IP packets. This paper proposes a new Active Queue Management (AQM) mechanism, Weighted SAP (WSAP) to achieve this goal. WSAP is based on a new AQM algorithm called Simple Adaptive Proportional (SAP). WSAP can approximate proportional loss rate differentiation, while keeping high link utilization and short queuing delay. Compared with Weighted RED(WRED) and RED In and Out (RIO), WSAP is easier to configure and can provide better performance. Furthermore, an architecture for differentiated service is proposed. In the design of this architecture, more attention is paid to the characte of network traffic in the Internet and an attempt is made to preserve the Internet's oringinal design principles.

  13. Parental Vaccine Hesitancy: Clinical Implications for Pediatric Providers.

    Science.gov (United States)

    Barrows, Meagan A; Coddington, Jennifer A; Richards, Elizabeth A; Aaltonen, Pamela M

    2015-01-01

    Despite being recognized as one of the greatest public health achievements, vaccines are increasingly under scrutiny for a multitude of reasons. "Parental vaccine hesitancy," an emerging term in today's literature, encompasses a wide range of concerns regarding vaccines and is believed to be responsible for decreasing coverage of many childhood vaccines. The threat to herd immunity posed by poor vaccine uptake increases the risk for resurgence of vaccine-preventable diseases. Pediatric primary health care providers have an obligation to respond to the increasing prevalence of vaccine hesitancy by providing education related to vaccines to ensure the safety and health of the population. The purpose of this article is to examine the most common concerns surrounding vaccine hesitancy and outline strategies for pediatric providers to address concerns with parents in the clinical setting.

  14. Real-time water quality monitoring and providing water quality ...

    Science.gov (United States)

    EPA and the U.S. Geological Survey (USGS) have initiated the “Village Blue” research project to provide real-time water quality monitoring data to the Baltimore community and increase public awareness about local water quality in Baltimore Harbor and the Chesapeake Bay. The Village Blue demonstration project complements work that a number of state and local organizations are doing to make Baltimore Harbor “swimmable and fishable” 2 by 2020. Village Blue is designed to build upon EPA’s “Village Green” project which provides real-time air quality information to communities in six locations across the country. The presentation, “Real-time water quality monitoring and providing water quality information to the Baltimore Community”, summarizes the Village Blue real-time water quality monitoring project being developed for the Baltimore Harbor.

  15. Non-Linear Fusion of Observations Provided by Two Sensors

    Directory of Open Access Journals (Sweden)

    Monir Azmani

    2013-07-01

    Full Text Available When we try to make the best estimate of some quantity, the problem of combining results from different experiments is encountered. In multi-sensor data fusion, the problem is seen as combining observations provided by different sensors. Sensors provide observations and information on an unknown quantity, which can differ in precision. We propose a combined estimate that uses prior information. We consider the simpler aspects of the problem, so that two sensors provide an observation of the same quantity. The standard error of the observations is supposed to be known. The prior information is an interval that bounds the parameter of the estimate. We derive the proposed combined estimate methodology, and we show its efficiency in the minimum mean square sense. The proposed combined estimate is assessed using synthetic data, and an application is presented.

  16. Hospital selection of home infusion therapy companies as preferred providers.

    Science.gov (United States)

    Rich, D S; Ayers, N

    1992-07-01

    The process by which a hospital selected home infusion therapy providers is described. Administrators at a 379-bed teaching hospital decided to attempt to reduce the high mean length of stay by expanding the use of home infusion therapy. Direct diversification into this field by the hospital was not feasible, so it was decided to establish contractual agreements with providers. A task force was appointed to evaluate and choose vendors in the area and to increase the number of patient referrals. The task force examined reports on past experience with providers, price lists, the range and level of services offered, and the amount of free care given and visited the companies' facilities. The group designated three providers as preferred and two as unacceptable. The number of patients referred increased from 21 during the 12 months before the task force was convened to 46 in the first 9 months afterward, for a saving of 2198 patients days. After one year the task force met again to consider company requests for evaluation or reevaluation, establish a plan for publicizing the benefits of home infusion therapy, and replace the site visits with a requirement for accreditation by the Joint Commission. After two years, the task force developed provider-evaluation criteria to streamline the process and reflect the experience gained. The responsibility for reviewing providers was transferred to the P&T committee. When a direct venture into home infusion therapy is not fiscally desirable, contracting for services can still offer the advantages of reduced length of stay and decreased drug expenses.

  17. Informal rural healthcare providers in North and South India.

    Science.gov (United States)

    Gautham, Meenakshi; Shyamprasad, K M; Singh, Rajesh; Zachariah, Anshi; Singh, Rajkumari; Bloom, Gerald

    2014-07-01

    Rural households in India rely extensively on informal biomedical providers, who lack valid medical qualifications. Their numbers far exceed those of formal providers. Our study reports on the education, knowledge, practices and relationships of informal providers (IPs) in two very different districts: Tehri Garhwal in Uttarakhand (north) and Guntur in Andhra Pradesh (south). We mapped and interviewed IPs in all nine blocks of Tehri and in nine out of 57 blocks in Guntur, and then interviewed a smaller sample in depth (90 IPs in Tehri, 100 in Guntur) about market practices, relationships with the formal sector, and their knowledge of protocol-based management of fever, diarrhoea and respiratory conditions. We evaluated IPs' performance by observing their interactions with three patients per condition; nine patients per provider. IPs in the two districts had very different educational backgrounds-more years of schooling followed by various informal diplomas in Tehri and more apprenticeships in Guntur, yet their knowledge of management of the three conditions was similar and reasonably high (71% Tehri and 73% Guntur). IPs in Tehri were mostly clinic-based and dispensed a blend of allopathic and indigenous drugs. IPs in Guntur mostly provided door-to-door services and prescribed and dispensed mainly allopathic drugs. In Guntur, formal private doctors were important referral providers (with commissions) and source of new knowledge for IPs. At both sites, IPs prescribed inappropriate drugs, but the use of injections and antibiotics was higher in Guntur. Guntur IPs were well organized in state and block level associations that had successfully lobbied for a state government registration and training for themselves. We find that IPs are firmly established in rural India but their role has grown and evolved differently in different market settings. Interventions need to be tailored differently keeping in view these unique features.

  18. Sealing device for providing a seal in a turbomachine

    Science.gov (United States)

    Lacy, Benjamin Paul; Kottilingam, Srikanth Chandrudu; Porter, Christopher Donald; Schick, David Edward; Weber, David Wayne

    2016-08-16

    Sealing device for providing seals between adjacent components, and turbomachines utilizing such sealing devices, are provided. A sealing device includes a seal plate insertable between the adjacent components, the seal plate comprising a first face and an opposing second face. The sealing device further includes a plurality of pins extending from one of the first face or the second face, the plurality of pins configured to space the one of the first face or the second face from contact surfaces of the adjacent components.

  19. Provider-owned health plans: El Dorado or Armageddon?

    Science.gov (United States)

    McCarthy, E J

    1999-11-01

    The development of provider-owned health plans continues to be an important strategy of integrated delivery systems (IDSs). While HMO enrollment growth has continued, reaching almost 70 million people, average health plan profit margins have declined from 8 percent in 1994 to less than 1 percent in 1997. About 56 percent of HMOs lost money in 1998. The ability to successfully develop and operate a provider-owned HMO is affected by conditions inherent to the managed care industry, the level of cooperation among IDS business, units, and local market conditions.

  20. Female farmworkers' health during pregnancy: health care providers' perspectives.

    Science.gov (United States)

    Kelley, Maureen A; Flocks, Joan D; Economos, Jeannie; McCauley, Linda A

    2013-07-01

    Pregnant farmworkers and their fetuses are at increased risk of negative health outcomes due to environmental and occupational factors at their workplaces. Health care providers who serve farm communities can positively affect workers' health through the informed care they deliver. Yet, interviews with rural health care providers reveal limited knowledge about agricultural work or occupational and environmental health risks during pregnancy. Professional associations, government organizations, academic institutions, and practice settings must renew their efforts to ensure that environmental and occupational health education, especially as it relates to women and their children, is incorporated into academic and practice environments.

  1. Maverick Firms: An Exploratory Analysis of Mortgage Providers in Australia

    OpenAIRE

    Robert Breunig; Flavio Menezes

    2007-01-01

    This paper develops an empirical strategy to measure maverick-like behaviour. It applies the strategy to a dataset that contains interest rates charged by mortgage providers in Australia from January 2003 to October 2006. The Reserve Bank of Australia raised its cash rate five times in this period, which provides a natural setting to observe suppliers� responses. We examine suppliers� behaviour both in terms of the rates they charge and the time it takes them to change their rates as a re...

  2. Listeriosis and Toxoplasmosis in Pregnancy: Essentials for Healthcare Providers.

    Science.gov (United States)

    Pfaff, Nicole Franzen; Tillett, Jackie

    2016-01-01

    Listeriosis and toxoplasmosis are foodborne illnesses that can have long-term consequences when contracted during pregnancy. Listeriosis is implicated in stillbirth, preterm labor, newborn sepsis, and meningitis, among other complications. Toxoplasmosis is associated with blindness, cognitive delays, seizures, and hearing loss, among other significant disabilities. Healthcare providers who understand the fundamentals of Listeria and Toxoplasma infection will have the tools to identify symptoms and high-risk behaviors, educate women to make safer decisions, and provide anticipatory guidance if a pregnant woman would become infected with either of these foodborne illnesses.

  3. Can green roofs provide habitat for urban bees (Hymenoptera: Apidae?

    Directory of Open Access Journals (Sweden)

    Laurence Packer

    2009-01-01

    Full Text Available Increasing urbanization of many regions of the world has resulted in the decline of suitable habitat for wild flora and fauna. Green roofs have been suggested as a potential avenue to provide patches of good-quality habitat in highly developed regions. In this study, we surveyed green roofs for bee diversity and abundance to determine their potential as quality habitats in an urban area for these important pollinators. By comparing various biodiversity measures between green roofs and ground-level sites, we show that green roofs provide habitat to many bee species. Implications for pollinator conservation and urban agricultural production are discussed.

  4. Exploring Service-led Growth Trajectories for Analytical Equipment Providers

    DEFF Research Database (Denmark)

    Raja, Jawwad; Frandsen, Thomas; Mouritsen, Jan

    2016-01-01

    This paper examines the dilemmas encountered by advanced analytical equipment providers in developing service-led growth strategies to expand their business in pursuit of more attractive revenue models. It does so by adopting a case based research approach. The findings detail the capabilities...... and solutions-in different contexts, with a view to expanding markets and developing solution based business models, are discussed. It is argued that analytical equipment providers encounter dilemmas as managing these different trajectories implies different needs in terms of the technological sophistication...

  5. Treatment essentials and training for health care providers

    Directory of Open Access Journals (Sweden)

    Sunil M Jain

    2015-01-01

    Full Text Available The lack of awareness among health care providers (HCPs is one of the biggest challenges for the management of patients with type 1 diabetes mellitus (T1DM in India. Major challenges faced by HCPs include lack of awareness about the disease among general physicians and inadequately trained staff to deal with children with T1DM. The changing diabetes in children (CDiC program is helping in overcoming these barriers faced by HCPs. CDiC provides treatment, monitoring tools, and education to children affected with T1DM and has been instrumental is developing various education and awareness tools.

  6. Employee motivation in Product-Service-System providers

    DEFF Research Database (Denmark)

    Kreye, Melanie

    2016-01-01

    This research investigates how intrinsic and extrinsic motivation factors contribute to employee motivation in providers of Product-Service Systems (PSS). Employee motivation determines the quality of the delivered service and is thus an area of great importance for PSS providers. We present rich...... case-based data collected through semi-structured interviews, a survey and secondary sources. The analysis showed the particularly high importance of intrinsic and individual motivation factors such as the fulfilling nature of the work and skill development showing the ownership and pride service...

  7. Why don’t humanitarian organizations provide safe abortion services?

    OpenAIRE

    McGinn, Therese; Casey, Sara E

    2016-01-01

    Background Although sexual and reproductive health services have become more available in humanitarian settings over the last decade, safe abortion services are still rarely provided. The authors’ observations suggest that four reasons are typically given for this gap: ‘There’s no need’; ‘Abortion is too complicated to provide in crises’; ‘Donors don’t fund abortion services’; and ‘Abortion is illegal’. Discussion However, each of these reasons is based on false premises. Unsafe abortion is a...

  8. Depressive Symptoms and Unmitigated Communion in Support Providers

    NARCIS (Netherlands)

    Jin, Lihua; Van Yperen, Nico W.; Sanderman, Robbert; Hagedoorn, Mariet

    2010-01-01

    In this research, we argue and demonstrate that the association between enacted (un)supportive behaviour and depressive symptoms is a function of the providers' levels of unmitigated communion (UC). UC is characterized by overinvolvement in others' problems, self-neglect and externalized self-evalua

  9. The Effect of Providing Breakfast in Class on Student Performance

    Science.gov (United States)

    Imberman, Scott A.; Kugler, Adriana D.

    2014-01-01

    Many schools have recently experimented with moving breakfast from the cafeteria to the classroom. We examine whether such a program increases achievement, grades, and attendance rates. We exploit quasi-random timing of program implementation that allows for a difference-in-differences identification strategy. We find that providing breakfast in…

  10. Marketing in the business activity of logistics service providers

    Directory of Open Access Journals (Sweden)

    Marcin Świtała

    2013-09-01

    Full Text Available Background: This article is a discussion on the role of marketing in the activity of logistics service providers. The strong competition and changing purchasing preferences should motivate the transport, forwarding and logistics sector managers to apply the marketing approach in practice. Methods: Results of direct research, conducted among a targeted group of 100 companies from the transport, forwarding and logistics sector, constitute the source basis. The sample group was divided into three categories of logistics providers: 2PL, 3PL and 4PL. The statistical analysis was based on three different non-parametric tests (Kruskal-Wallis, Chi-square and V Kramer.  Results and conclusions:  Currently, marketing does not play a key role in the activity of logistics services providers. The prevailing opinion is that importance of marketing in the company is average. The respondents have assessed in a similar way their activity compared to the activities of the competition. However, it was found that with the increase of the level of specialization (2PL-4PL, the awareness of impact of marketing on the logistics services sector also increased. The logistics services providers, who offer a wide range of logistics services, asses their competitive position in a better light.  

  11. Development of a system to provide diagnostics-while-drilling.

    Energy Technology Data Exchange (ETDEWEB)

    Wise, Jack LeRoy; Jacobson, Ronald David; Finger, John Travis; Mansure, Arthur James; Knudsen, Steven Dell

    2003-06-01

    This report describes development of a system that provides high-speed, real-time downhole data while drilling. Background of the project, its benefits, major technical challenges, test planning, and test results are covered by relatively brief descriptions in the body of the report, with some topics presented in more detail in the attached appendices.

  12. CNLC Provides Well-Bore Technical Services Worldwide

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ BRIEF INTRODUCTION of CNLC China National Logging Corporation (CNLC), a subsidiary of CNPC Services & Engineering Ltd.,which provides well bore technical services at international market solely on behalf of CNPC, is a specialized service company mainly engaged in: 1. Wire-line logging, mud logging, well testing,well completion, perforating and other relevant engineering services.

  13. Enhancing Learning Capabilities by Providing Transparency in Business Simulators.

    Science.gov (United States)

    Groessler, Andreas; Maier, Frank H.; Milling, Peter M.

    2000-01-01

    Discussion of computer-based simulations for business focuses on adding transparency through system dynamics techniques. Describes an experiment that evaluated the relevance and the effects of providing structural transparency to users of business simulators and suggests further research. (Contains 51 references.) (LRW)

  14. Providing Access to Electronic Information Resources in Further Education

    Science.gov (United States)

    Banwell, Linda; Ray, Kathryn; Coulson, Graham; Urquhart, Christine; Lonsdale, Ray; Armstrong, Chris; Thomas, Rhian; Spink, Sin; Yeoman, Alison; Fenton, Roger; Rowley, Jennifer

    2004-01-01

    This article aims to provide a baseline for future studies on the provision and support for the use of digital or electronic information services (EIS) in further education. The analysis presented is based on a multi-level model of access, which encompasses access to and availability of information and communication technology (ICT) resources,…

  15. Providing Mental Health Services to Arab Americans: Recommendations and Considerations.

    Science.gov (United States)

    Erickson, Chris D.; Al-Timimi, Nada R.

    2001-01-01

    This paper presents background information on the cultural sociopathology of the Arab American experience. It discusses how, in order to effectively deliver services, mental health workers need to be aware of their own biases. It explores ways to provide culturally relevant mental health services to Arab Americans. (JDM)

  16. DEVELOPMENT PERSPECTIVES OF LOGISTICS SERVICES PROVIDERS IN POLAND

    Directory of Open Access Journals (Sweden)

    Ewa PŁACZEK

    2015-04-01

    Full Text Available The market of logistics services (TSL in Poland is new, yet already mature. There are a lot of diverse entities operating there that provide various types of logistics services. So far the major goal of business conducted by them has been to generate profit that ensured further development. However, currently a change in the attitude towards business that is aimed for example at management of the company value is observed. And thus the following question should be asked: „What activities are undertaken by logistics services providers for the purpose of achievement of success such as for example improvement of the company attractiveness or growth in the company value?”. To answer the question put in this way, the analysis of activities undertaken by providers of logistics services in Poland is performed. The article presents activities of logistics services providers that are the response to demands of the market – the customer, for the purpose of satisfaction of their individualised needs. We can consider them determinants of further operations that describe possible trends of development.

  17. How Do Health Care Providers Diagnose Fragile X Syndrome?

    Science.gov (United States)

    ... These symptoms may include delays in speech and language skills, social and emotional difficulties, and being sensitive to certain sensations. Children may also be delayed in or have problems with motor skills such as learning to walk. A health care provider can perform ...

  18. Hand Washing Practices Among Emergency Medical Services Providers

    Directory of Open Access Journals (Sweden)

    Joshua Bucher

    2015-10-01

    Full Text Available Introduction: Hand hygiene is an important component of infection control efforts. Our primary and secondary goals were to determine the reported rates of hand washing and stethoscope cleaning in emergency medical services (EMS workers, respectively. Methods: We designed a survey about hand hygiene practices. The survey was distributed to various national EMS organizations through e-mail. Descriptive statistics were calculated for survey items (responses on a Likert scale and subpopulations of survey respondents to identify relationships between variables. We used analysis of variance to test differences in means between the subgroups. Results: There were 1,494 responses. Overall, reported hand hygiene practices were poor among pre-hospital providers in all clinical situations. Women reported that they washed their hands more frequently than men overall, although the differences were unlikely to be clinically significant. Hygiene after invasive procedures was reported to be poor. The presence of available hand sanitizer in the ambulance did not improve reported hygiene rates but improved reported rates of cleaning the stethoscope (absolute difference 0.4, p=0.0003. Providers who brought their own sanitizer were more likely to clean their hands. Conclusion: Reported hand hygiene is poor amongst pre-hospital providers. There is a need for future intervention to improve reported performance in pre-hospital provider hand washing.

  19. 30 CFR 778.11 - Providing applicant and operator information.

    Science.gov (United States)

    2010-07-01

    ... SYSTEMS UNDER REGULATORY PROGRAMS PERMIT APPLICATIONS-MINIMUM REQUIREMENTS FOR LEGAL, FINANCIAL... applicant, must provide in the permit application— (1) A statement indicating whether you and your operator... executive officer, and director (or persons in similar positions), and every person who owns, of record,...

  20. Model of Providing Assistive Technologies in Special Education Schools.

    Science.gov (United States)

    Lersilp, Suchitporn; Putthinoi, Supawadee; Chakpitak, Nopasit

    2015-05-14

    Most students diagnosed with disabilities in Thai special education schools received assistive technologies, but this did not guarantee the greatest benefits. The purpose of this study was to survey the provision, use and needs of assistive technologies, as well as the perspectives of key informants regarding a model of providing them in special education schools. The participants were selected by the purposive sampling method, and they comprised 120 students with visual, physical, hearing or intellectual disabilities from four special education schools in Chiang Mai, Thailand; and 24 key informants such as parents or caregivers, teachers, school principals and school therapists. The instruments consisted of an assistive technology checklist and a semi-structured interview. Results showed that a category of assistive technologies was provided for students with disabilities, with the highest being "services", followed by "media" and then "facilities". Furthermore, mostly students with physical disabilities were provided with assistive technologies, but those with visual disabilities needed it more. Finally, the model of providing assistive technologies was composed of 5 components: Collaboration; Holistic perspective; Independent management of schools; Learning systems and a production manual for users; and Development of an assistive technology center, driven by 3 major sources such as Government and Private organizations, and Schools.