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Sample records for association recommended targets

  1. Attainment of Canadian Diabetes Association recommended targets in patients with type 2 diabetes

    Science.gov (United States)

    McCrate, Farah; Godwin, Marshall; Murphy, Laura

    2010-01-01

    OBJECTIVE To examine the degree to which targets for diabetes (blood pressure [BP], glycated hemoglobin [HbA1c], and low-density lipoprotein cholesterol [LDL-C]) are achieved in family practices and how these results compare with family physicians’ perceptions of how well targets are being achieved. DESIGN Chart audit and physician survey. SETTING Newfoundland and Labrador. PARTICIPANTS Patients with type 2 diabetes and their family physicians. INTERVENTIONS The charts of 20 patients with type 2 diabetes were randomly chosen from each of 8 family physician practices in St John’s, Nfld, and data were abstracted. All family physicians in the province were surveyed using a modified Dillman method. MAIN OUTCOME MEASURES The most recent HbA1c, LDL-C, and BP measurements listed in each audited chart; surveyed family physicians’ knowledge of the recommended targets for HbA1c, LDL-C, and BP and their estimates of what percentage of their patients were at those recommended targets. RESULTS The chart audit revealed that 20.6% of patients were at the recommended target for BP, 48.1% were at the recommended target for HbA1c, and 17.5% were at the recommended target for LDL-C. When targets were examined collectively, only 2.5% of patients were achieving targets in all 3 areas. The survey found that most family physicians were aware of the recommended targets for BP, LDL-C, and HbA1c. However, their estimates of the percentages of patients in their practices achieving these targets appeared high (59.3% for BP, 58.2% for HbA1c, and 48.4% for LDL-C) compared with the results of the chart audit. CONCLUSION The findings of the chart audit are consistent with other published reports, which have illustrated that a large majority of patients with diabetes fall short of reaching recommended targets for BP, blood glucose, and lipid levels. Although family physicians are knowledgeable about recommended targets, there is a gap between knowledge and clinical outcomes. The reasons for

  2. Target tracking in the recommender space: Toward a new recommender system based on Kalman filtering

    CERN Document Server

    Nowakowski, Samuel; Boyer, Anne

    2010-01-01

    In this paper, we propose a new approach for recommender systems based on target tracking by Kalman filtering. We assume that users and their seen resources are vectors in the multidimensional space of the categories of the resources. Knowing this space, we propose an algorithm based on a Kalman filter to track users and to predict the best prediction of their future position in the recommendation space.

  3. Treating Rheumatoid Arthritis to Target : multinational recommendations assessment questionnaire

    NARCIS (Netherlands)

    Haraoui, Boulos; Smolen, Josef S.; Aletaha, Daniel; Breedveld, Ferdinand C.; Burmester, Gerd; Codreanu, Catalin; Da Silva, Jose Pereira; de Wit, Maarten; Dougados, Maxime; Durez, Patrick; Emery, Paul; Fonseca, Joao Eurico; Gibofsky, Allan; Gomez-Reino, Juan; Graninger, Winfried; Hamuryudan, Vedat; Jannaut Pena, Maria Jose; Kalden, Joachim; Kvien, Tore K.; Laurindo, Ieda; Martin-Mola, Emilio; Montecucco, Carlomaurizio; Santos Moreno, Pedro; Pavelka, Karel; Poor, Gyula; Cardiel, Mario H.; Stanislawska-Biernat, Ewa; Takeuchi, Tsutomu; van der Heijde, Desiree

    2011-01-01

    Aim To measure the level of agreement and application of 10 international recommendations for treating rheumatoid arthritis (RA) to a target of remission/low disease activity. Methods A 10-point Likert scale (1=fully disagree, 10=fully agree) measured the level of agreement with each of 10

  4. Association Rule Mining for Web Recommendation

    Directory of Open Access Journals (Sweden)

    R. Suguna

    2012-10-01

    Full Text Available Web usage mining is the application of web mining to discover the useful patterns from the web in order to understand and analyze the behavior of the web users and web based applications. It is theemerging research trend for today’s researchers. It entirely deals with web log files which contain the user website access information. It is an interesting thing to analyze and understand the user behaviorabout the web access. Web usage mining normally has three categories: 1. Preprocessing, 2. Pattern Discovery and 3. Pattern Analysis. This paper proposes the association rule mining algorithms for betterWeb Recommendation and Web Personalization. Web recommendation systems are considered as an important role to understand customers’ behavior, interest, improving customer convenience, increasingservice provider profits and future needs.

  5. Treat-to-target (T2T) recommendations for gout.

    Science.gov (United States)

    Kiltz, U; Smolen, J; Bardin, T; Cohen Solal, A; Dalbeth, N; Doherty, M; Engel, B; Flader, C; Kay, J; Matsuoka, M; Perez-Ruiz, F; da Rocha Castelar-Pinheiro, G; Saag, K; So, A; Vazquez Mellado, J; Weisman, M; Westhoff, T H; Yamanaka, H; Braun, J

    2017-04-01

    The treat-to-target (T2T) concept has been applied successfully in several inflammatory rheumatic diseases. Gout is a chronic disease with a high burden of pain and inflammation. Because the pathogenesis of gout is strongly related to serum urate levels, gout may be an ideal disease in which to apply a T2T approach. Our aim was to develop international T2T recommendations for patients with gout. A committee of experts with experience in gout agreed upon potential targets and outcomes, which was the basis for the systematic literature search. Eleven rheumatologists, one cardiologist, one nephrologist, one general practitioner and one patient met in October 2015 to develop T2T recommendations based on the available scientific evidence. Levels of evidence, strength of recommendations and levels of agreement were derived. Although no randomised trial was identified in which a comparison with standard treatment or an evaluation of a T2T approach had been performed in patients with gout, indirect evidence was provided to focus on targets such as normalisation of serum urate levels. The expert group developed four overarching principles and nine T2T recommendations. They considered dissolution of crystals and prevention of flares to be fundamental; patient education, ensuring adherence to medications and monitoring of serum urate levels were also considered to be of major importance. This is the first application of the T2T approach developed for gout. Since no publication reports a trial comparing treatment strategies for gout, highly credible overarching principles and level D expert recommendations were created and agreed upon. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. Olmesartan vs ramipril in the treatment of hypertension and associated clinical conditions in the elderly: a reanalysis of two large double-blind, randomized studies at the light of the most recent blood pressure targets recommended by guidelines.

    Science.gov (United States)

    Omboni, Stefano; Malacco, Ettore; Mallion, Jean-Michel; Volpe, Massimo

    2015-01-01

    In this paper, we present the results of a reanalysis of the data of two large randomized, double-blind, parallel group studies with a similar design, comparing the efficacy of an angiotensin-receptor blocker (olmesartan medoxomil) with that of an angiotensin-converting enzyme inhibitor (ramipril), by applying two different blood pressure targets recently recommended by hypertension guidelines for all patients, irrespective of the presence of diabetes (olmesartan was not negatively affected by age, sex, hypertension type, diabetes status or other concomitant clinical conditions, or cardiovascular risk factors. In most cases, olmesartan provided better blood pressure control than ramipril. Olmesartan was significantly more effective than ramipril in male patients, in younger patients (aged 65-69 years), in those with metabolic syndrome, obesity, dyslipidemia, preserved renal function, diastolic ± systolic hypertension, and, in general, in patients with a high or very high cardiovascular risk. Interestingly, patients previously untreated or treated with two or more antihypertensive drugs showed a significantly larger response with olmesartan than with ramipril. Thus, our results confirm the good efficacy of olmesartan in elderly hypertensives even when new blood pressure targets for antihypertensive treatment are considered. Such results may be relevant for the clinical practice, providing some hint on the possible different response of elderly hypertensive patients to two different drugs acting on the renin-angiotensin system, when patients are targeted according to the blood pressure levels recommended by recent hypertension guidelines.

  7. Olmesartan vs ramipril in the treatment of hypertension and associated clinical conditions in the elderly: a reanalysis of two large double-blind, randomized studies at the light of the most recent blood pressure targets recommended by guidelines

    Science.gov (United States)

    Omboni, Stefano; Malacco, Ettore; Mallion, Jean-Michel; Volpe, Massimo

    2015-01-01

    In this paper, we present the results of a reanalysis of the data of two large randomized, double-blind, parallel group studies with a similar design, comparing the efficacy of an angiotensin-receptor blocker (olmesartan medoxomil) with that of an angiotensin-converting enzyme inhibitor (ramipril), by applying two different blood pressure targets recently recommended by hypertension guidelines for all patients, irrespective of the presence of diabetes (hypertensive patients (hypertension type, diabetes status or other concomitant clinical conditions, or cardiovascular risk factors. In most cases, olmesartan provided better blood pressure control than ramipril. Olmesartan was significantly more effective than ramipril in male patients, in younger patients (aged 65–69 years), in those with metabolic syndrome, obesity, dyslipidemia, preserved renal function, diastolic ± systolic hypertension, and, in general, in patients with a high or very high cardiovascular risk. Interestingly, patients previously untreated or treated with two or more antihypertensive drugs showed a significantly larger response with olmesartan than with ramipril. Thus, our results confirm the good efficacy of olmesartan in elderly hypertensives even when new blood pressure targets for antihypertensive treatment are considered. Such results may be relevant for the clinical practice, providing some hint on the possible different response of elderly hypertensive patients to two different drugs acting on the renin–angiotensin system, when patients are targeted according to the blood pressure levels recommended by recent hypertension guidelines. PMID:26491273

  8. [Immunisation schedule of the Spanish Association of Paediatrics: 2014 recommendations].

    Science.gov (United States)

    Moreno-Pérez, D; Alvarez García, F J; Arístegui Fernández, J; Cilleruelo Ortega, M J; Corretger Rauet, J M; García Sánchez, N; Hernández Merino, A; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa Del Castillo, L; Ruiz-Contreras, J

    2014-01-01

    The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on safety, effectiveness and efficiency of vaccines. The present schedule includes levels of recommendation. We have graded, as routine vaccinations, those that the CAV-AEP consider all children should receive; as recommended those that fit the profile for universal childhood immunisation and would ideally be given to all children, but that can be prioritised according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in special situations. Immunisation schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Based on the latest epidemiological trends, CAV-AEP recommends the administration of the first dose of MMR and varicella vaccines at age 12 months, with the second dose at age 2-3 years; the administration of DTaP or Tdap vaccine at age 4-6 years, always followed by another Tdap dose at 11-12 years; and the three meningococcal C scheme at 2 months, 12 months and 12 years of age. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-12 years must be increased. Universal vaccination against varicella in the second year of life is an effective strategy, and the immediate public availability of the vaccine is requested in order to guarantee the right of healthy children to be vaccinated. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. The recently authorised meningococcal B vaccine has opened a chapter of hope in the

  9. Olmesartan vs ramipril in the treatment of hypertension and associated clinical conditions in the elderly: a reanalysis of two large double blind, randomized studies at the light of the most recent blood pressure targets recommended by guidelines

    Directory of Open Access Journals (Sweden)

    Omboni S

    2015-10-01

    Full Text Available Stefano Omboni,1 Ettore Malacco,2 Jean-Michel Mallion,3 Massimo Volpe4,5 1Clinical Research Unit, Italian Institute of Telemedicine, Solbiate Arno, Varese, Italy; 2Department of Internal Medicine, Ospedale L Sacco, University of Milan, Milan, Italy; 3Cardiology and Arterial Hypertension, CHU de Grenoble, Grenoble, France; 4Division of Cardiology, II Faculty of Medicine, University of Rome “La Sapienza”, Sant’Andrea Hospital, Rome, Italy; 5IRCCS Neuromed, Pozzilli, Isernia, Italy Abstract: In this paper, we present the results of a reanalysis of the data of two large randomized, double-blind, parallel group studies with a similar design, comparing the efficacy of an angiotensin-receptor blocker (olmesartan medoxomil with that of an angiotensin-converting enzyme inhibitor (ramipril, by applying two different blood pressure targets recently recommended by hypertension guidelines for all patients, irrespective of the presence of diabetes (<140/90 mmHg, and for elderly hypertensive patients (<150/90 mmHg. The efficacy of olmesartan was not negatively affected by age, sex, hypertension type, diabetes status or other concomitant clinical conditions, or cardiovascular risk factors. In most cases, olmesartan provided better blood pressure control than ramipril. Olmesartan was significantly more effective than ramipril in male patients, in younger patients (aged 65–69 years, in those with metabolic syndrome, obesity, dyslipidemia, preserved renal function, diastolic ± systolic hypertension, and, in general, in patients with a high or very high cardiovascular risk. Interestingly, patients previously untreated or treated with two or more antihypertensive drugs showed a significantly larger response with olmesartan than with ramipril. Thus, our results confirm the good efficacy of olmesartan in elderly hypertensives even when new blood pressure targets for antihypertensive treatment are considered. Such results may be relevant for the clinical

  10. [Immunisation schedule of the Spanish Association of Paediatrics: 2013 recommendations].

    Science.gov (United States)

    Moreno-Pérez, D; Álvarez García, F J; Arístegui Fernández, J; Barrio Corrales, F; Cilleruelo Ortega, M J; Corretger Rauet, J M; González-Hachero, J; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa Del Castillo, L; Ruiz-Contreras, J

    2013-01-01

    The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on the safety, effectiveness and efficiency of vaccines. The present schedule includes levels of recommendation. We have graded as routine vaccinations those that the CAV-AEP consider all children should receive; as recommended those that fit the profile for universal childhood immunisation and would ideally be given to all children, but that can be prioritised according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in situations of risk. Immunisation schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Nevertheless, the achievement of a unified immunisation schedule in all regions of Spain is a top priority for the CAV-AEP. Based on the latest epidemiological trends, CAV-AEP follows the innovations proposed in the last year's schedule, such as the administration of the first dose of the MMR and the varicella vaccines at age 12 months and the second dose at age 2-3 years, as well as the administration of the Tdap vaccine at age 4-6 years, always followed by another dose at 11-14 years of age, preferably at 11-12 years. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-14 years, preferably at 11-12 years, must increase. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule. Universal vaccination against varicella in the second year of life is an effective strategy and therefore a desirable objective. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. Finally, it

  11. Immunization schedule of the Spanish Association of Pediatrics: 2012 recommendations.

    Science.gov (United States)

    Moreno-Pérez, D; Alvarez García, F J; Aristegui Fernández, J; Barrio Corrales, F; Cilleruelo Ortega, M J; Corretger Rauet, J M; González-Hachero, J; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa del Castillo, L; Ruiz-Contreras, J

    2012-01-01

    The Advisory Committee on Vaccines of the Spanish Association of Pediatrics (CAV-AEP) updates the immunization schedule every year, taking into account epidemiological data as well as evidence on the effectiveness and efficiency of vaccines. The present schedule includes grades of recommendation. We have graded as routine vaccinations those that the CAV-AEP believes all children should receive; as recommended those that fit the profile for universal childhood immunization and would ideally be given to all children, but that can be prioritized according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in situations of risk. Immunization schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Nevertheless, the achievement of a unified immunization schedule in all regions of Spain is a top priority for the CAV-AEP. Based on the latest epidemiological trends, the main changes introduced to the schedule are the administration of the first dose of the MMR and the varicella vaccines at age 12 months (12-15 months) and the second dose at age 2-3 years, as well as the administration of the Tdap vaccine at age 4-6 years, always followed by another dose at 11-14 years of age. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-14 years must increase. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunization schedule. Universal vaccination against varicella in the second year of life is an effective strategy and therefore a desirable objective. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. Finally, it emphasizes the need to bring incomplete vaccinations up to date following the catch

  12. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 - executive summary.

    Science.gov (United States)

    Jacobson, Terry A; Ito, Matthew K; Maki, Kevin C; Orringer, Carl E; Bays, Harold E; Jones, Peter H; McKenney, James M; Grundy, Scott M; Gill, Edward A; Wild, Robert A; Wilson, Don P; Brown, W Virgil

    2014-01-01

    Various organizations and agencies have issued recommendations for the management of dyslipidemia. Although many commonalities exist among them, material differences are present as well. The leadership of the National Lipid Association (NLA) convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel and includes: (1) background and conceptual framework for formulation of the NLA Expert Panel recommendations; (2) screening and classification of lipoprotein lipid levels in adults; (3) targets for intervention in dyslipidemia management; (4) atherosclerotic cardiovascular disease risk assessment and treatment goals based on risk category; (5) atherogenic cholesterol-non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol-as the primary targets of therapy; and (6) lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia.

  13. Targeting Net Zero Energy at Fort Carson: Assessment and Recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, K.; Markel, T.; Simpson, M.; Leahey, J.; Rockenbaugh, C.; Lisell, L.; Burman, K.; Singer, M.

    2011-10-01

    The U.S. Army's Fort Carson installation was selected to serve as a prototype for net zero energy assessment and planning. NREL performed the comprehensive assessment to appraise the potential of Fort Carson to achieve net zero energy status through energy efficiency, renewable energy, and electric vehicle integration. This report summarizes the results of the assessment and provides energy recommendations. This study is part of a larger cross-laboratory effort that also includes an assessment of renewable opportunities at seven other DoD Front Range installations, a microgrid design for Fort Carson critical loads and an assessment of regulatory and market-based barriers to a regional secure smart grid.

  14. Targeted and comprehensive space-environment sensors: description and recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, Geoffrey; O' Brien, Paul; Mazur, Joe; Ginet, Gregory

    2009-01-01

    We discuss the roles of the two classes of space-environment sensors on operational space systems: (1) Targeted sensors capable of measuring the environment and effects at a level sufficient for providing situational awareness for the host spacecraft and (2) Comprehensive sensors capable of providing detailed environment measurements that can be mapped to a broad region of near-Earth space, providing global situational awareness and quantitative characterization of the environment. Our purpose is to show the usefulness of a heterogeneous architecture with both classes of sensors for the near-term and long-term needs of National Security Space

  15. Recommendations

    Science.gov (United States)

    Brazelton, G. Blue; Renn, Kristen A.; Stewart, Dafina-Lazarus

    2015-01-01

    In this chapter, the editors provide a summary of the information shared in this sourcebook about the success of students who have minoritized identities of sexuality or gender and offer recommendations for policy, practice, and further research.

  16. [Immunisation schedule of the Spanish Association of Paediatrics: 2017 recommendations].

    Science.gov (United States)

    Moreno-Pérez, David; Álvarez García, Francisco José; Arístegui Fernández, Javier; Cilleruelo Ortega, María José; Corretger Rauet, José María; García Sánchez, Nuria; Hernández Merino, Ángel; Hernández-Sampelayo Matos, Teresa; Merino Moína, Manuel; Ortigosa Del Castillo, Luis; Ruiz-Contreras, Jesús

    2017-02-01

    The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV- AEP) annually publishes the immunisation schedule which, in our opinion, is considered optimal for children resident in Spain, taking into account the evidence available on current vaccines. Pneumococcal and varicella immunisation in early childhood is already included in all funded vaccines present in the regional immunisation programmes. Furthermore, this committee establishes recommendations on vaccines not included in official calendars (non-funded immunisations), such as rotavirus, meningococcal B, and meningococcal ACWY. As regards funded immunisations, 2+1 strategy (2, 4, 11-12 months) with hexavalent (DTaP-IPV-Hib-HB) and 13-valent pneumococcal vaccines is recommended. Administration of the 6-year booster dose with DTaP is recommended, as well as a poliomyelitis dose for children who had received the 2+1 scheme, with the Tdap vaccine for adolescents and pregnant women between 27 and 32 weeks gestation. The two-dose scheme should be used for MMR (12 months and 2-4 years) and varicella (15 months and 2-4 years). Coverage of human papillomavirus vaccination in girls aged 12 with a two-dose scheme (0, 6 months) should be improved. Information and recommendations for male adolescents about potential beneficial effects of the tetravalent HPV vaccine should also be provided. ACWY meningococcal vaccine is the optimal choice in adolescents. For recommended unfunded immunisations, the CAV-AEP recommends the administration of meningococcal B vaccine, due to the current availability in Spanish community pharmacies, with a 3+1 scheme. CAV-AEP requests the incorporation of this vaccine in the funded unified schedule. Vaccination against rotavirus is recommended in all infants. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Treating rheumatoid arthritis to target: recommendations of an international task force

    Science.gov (United States)

    Smolen, Josef S; Aletaha, Daniel; Bijlsma, Johannes W J; Breedveld, Ferdinand C; Boumpas, Dimitrios; Burmester, Gerd; Combe, Bernard; Cutolo, Maurizio; de Wit, Maarten; Dougados, Maxime; Emery, Paul; Gibofsky, Alan; Gomez-Reino, Juan Jesus; Haraoui, Boulos; Kalden, Joachim; Keystone, Edward C; Kvien, Tore K; McInnes, Iain; Martin-Mola, Emilio; Montecucco, Carlomaurizio; Schoels, Monika; van der Heijde, Desirée

    2010-01-01

    Background Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). Objective To develop recommendations for achieving optimal therapeutic outcomes in RA. Methods A task force of rheumatologists and a patient developed a set of recommendations on the basis of evidence derived from a systematic literature review and expert opinion; these were subsequently discussed, amended and voted upon by >60 experts from various regions of the world in a Delphi-like procedure. Levels of evidence, strength of recommendations and levels of agreement were derived. Results The treat-to-target activity resulted in 10 recommendations. The treatment aim was defined as remission with low disease activity being an alternative goal in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with appropriate therapeutic adaptation to reach the desired state within 3 to a maximum of 6 months was recommended. Follow-up examinations ought to employ composite measures of disease activity which include joint counts. Additional items provide further details for particular aspects of the disease. Levels of agreement were very high for many of these recommendations (≥9/10). Conclusion The 10 recommendations are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA based on evidence and expert opinion. PMID:20215140

  18. [Immunisation schedule of the Spanish Association of Paediatrics: 2016 recommendations].

    Science.gov (United States)

    Moreno-Pérez, D; Álvarez García, F J; Arístegui Fernández, J; Cilleruelo Ortega, M J; Corretger Rauet, J M; García Sánchez, N; Hernández Merino, A; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa del Castillo, L; Ruiz-Contreras, J

    2016-01-01

    The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) annually publishes the immunisation schedule which, in our opinion, estimates optimal for children resident in Spain, considering available evidence on current vaccines. We acknowledge the effort of the Ministry of Health during the last year in order to optimize the funded unified Spanish vaccination schedule, with the recent inclusion of pneumococcal and varicella vaccination in early infancy. Regarding the funded vaccines included in the official unified immunization schedule, taking into account available data, CAV-AEP recommends 2+1 strategy (2, 4 and 12 months) with hexavalent (DTPa-IPV-Hib-HB) vaccines and 13-valent pneumococcal conjugate vaccine. Administration of Tdap and poliomyelitis booster dose at the age of 6 is recommended, as well as Tdap vaccine for adolescents and pregnant women, between 27-36 weeks gestation. The two-dose scheme should be used for MMR (12 months and 2-4 years) and varicella (15 months and 2-4 years). Coverage of human papillomavirus vaccination in girls aged 11-12 with a two dose scheme (0, 6 months) should be improved. Information for male adolescents about potential beneficial effects of this immunisation should be provided as well. Regarding recommended unfunded immunisations, CAV-AEP recommends the administration of meningococcal B vaccine, due to the current availability in Spanish communitary pharmacies, with a 3+1 scheme (3, 5, 7 and 13-15 months). CAV-AEP requests the incorporation of this vaccine in the funded unified schedule. Vaccination against rotavirus is recommended in all infants. Annual influenza immunisation and vaccination against hepatitis A are indicated in population groups considered at risk.

  19. A new Recommender system based on target tracking: a Kalman Filter approach

    CERN Document Server

    Nowakowski, Samuel; Boyer, Anne

    2010-01-01

    In this paper, we propose a new approach for recommender systems based on target tracking by Kalman filtering. We assume that users and their seen resources are vectors in the multidimensional space of the categories of the resources. Knowing this space, we propose an algorithm based on a Kalman filter to track users and to predict the best prediction of their future position in the recommendation space.

  20. Recommendations for using standardised phenotypes in genetic association studies

    Directory of Open Access Journals (Sweden)

    Naylor Melissa G

    2009-07-01

    Full Text Available Abstract Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity. These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

  1. [Immunisation schedule of the Spanish Association of Paediatrics: 2015 recommendations].

    Science.gov (United States)

    Moreno-Pérez, D; Álvarez García, F J; Arístegui Fernández, J; Cilleruelo Ortega, M J; Corretger Rauet, J M; García Sánchez, N; Hernández Merino, A; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa Del Castillo, L; Ruiz-Contreras, J

    2015-01-01

    The Advisory Committee on Vaccines of the Spanish Association of Paediatrics updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on the safety, effectiveness and efficiency of current vaccines, including levels of recommendation. In our opinion, this is the optimal vaccination calendar for all children resident in Spain. Regarding the vaccines included in the official unified immunization schedule, the Committee emphasizes the administration of the first dose of hepatitis B either at birth or at 2 months of life; the recommendation of the first dose of MMR and varicella vaccine at the age of 12 months, with the second dose at the age of 2-3 years; DTaP or Tdap vaccine at the age of 6 years, followed by another Tdap booster dose at 11-12 years old; Tdap strategies for pregnant women and household contacts of the newborn, and immunization against human papillomavirus in girls aged 11-12 years old with a 2 dose scheme (0, 6 months). The Committee reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule, the same as it is being conducted in Western European countries. The recently authorised meningococcal B vaccine, currently blocked in Spain, exhibits the profile of a universal vaccine. The Committe insists on the need of having the vaccine available in communitary pharmacies. It has also proposed the free availability of varicella vaccines. Their efectiveness and safety have been confirmed when they are administred from the second year of life. Vaccination against rotavirus is recommended in all infants. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. Copyright © 2014. Published by Elsevier Espana.

  2. Optimal blood pressure targets in 2014 - Does the guideline recommendation match the evidence base?

    Science.gov (United States)

    Alviar, C L; Bangalore, S; Messerli, F H

    2015-01-01

    Various scientific societies have recently published practice guidelines for the diagnosis and management of arterial hypertension with no clear consensus on a blood pressure target. This article reviews those recommendations and critically examines if they are based on sound evidence. Copyright © 2015 SEHLELHA. Published by Elsevier Espana. All rights reserved.

  3. Integrated Web Recommendation Model with Improved Weighted Association Rule Mining

    Directory of Open Access Journals (Sweden)

    S.A.Sahaaya Arul Mary

    2013-04-01

    Full Text Available World Wide Web plays a significant role in human life. It requires a technological improvement to satisfy the user needs. Web log data is essential for improving the performance of the web. It contains large,heterogeneous and diverse data. Analyzing g the web log data is a tedious process for Web developers, Web designers, technologists and end users. In this work, a new weighted association mining algorithm is developed to identify the best association rules that are useful for web site restructuring and recommendation that reduces false visit and improve users’ navigation behavior. The algorithm finds the frequent item set from a large uncertain database. Frequent scanning of database in each time is the problem with the existing algorithms which leads to complex output set and time consuming process. Theproposed algorithm scans the database only once at the beginning of the process and the generated frequent item sets, which are stored into the database. The evaluation parameters such as support, confidence, lift and number of rules are considered to analyze the performance of proposed algorithm and traditional association mining algorithm. The new algorithm produced best result that helps the developer to restructure their website in a way to meet the requirements of the end user within short time span.

  4. TATR (Tactical Air Target Recommender): A Prototype Expert System for Tactical Air Targeting

    Science.gov (United States)

    1984-08-01

    1 2 F-l6X/2 3 F-16X/2 0.85 0.95 0. 77 0. 12 0.16 0.18 REFERENCES 1. Callero, M., D. Gorlin , F. Hayes-Roth, and L. Jamison, Toward an Expert...for Tactical Air Targeting, The Rand Corporation, N -1796-ARPA, January 1982. 3. Fain, J., D. Gorlin , F. Hayes-Roth, S. Rosenschein, H. Sowizral... Gorlin , S. Rosenschein, H. Sowizral, and D. Waterman, Rationale and Motivation for ROSIE, The Rand Corporation, N-1648-ARPA, November 1981. 6. Hayes

  5. E-commerce Website Recommender System Based on Dissimilarity and Association Rule

    OpenAIRE

    MingWang Zhang; ShuWen Yang; LiFeng Zhang

    2013-01-01

    By analyzing the current electronic commerce recommendation algorithm analysis, put forward a kind to use dissimilarity clustering and association recommendation algorithm, the algorithm realized web website shopping user data clustering by use of the dissimilarity, and then use the association rules algorithm for clustering results of association recommendation, experiments show that the algorithm compared with traditional clustering association algorithm of iteration times decrease, improve...

  6. Letters of Recommendation: Association with Interviewers' Perceptions and Preferences.

    Science.gov (United States)

    Young, VyVy N

    2017-06-01

    Objective Letters of recommendation (LORs) are an inescapable aspect of the application process. Standardized LORs (SLORs) have been developed and compared with traditional narrative LORs (NLORs). This study investigated whether there was a difference in degree of association between LOR types and face-to-face interviews. Interviewer preference for LOR was anonymously surveyed. Study Design Survey. Setting Single-institution otolaryngology residency program, 1 year before and 4 years after introduction of SLORs. Subjects and Methods Residency interviewers indicated on a visual analog scale how well their impression of an applicant compared between the LOR and the face-to-face interview. Interviewers assessed each applicant, each year, based on LOR type. Results Of 2573 assessments, 964 were collected (37.5% response rate), including 927 responses related to NLORs, 561 to SLORs, and 316 to medical student performance evaluations (ie, dean's letters). The average association of VAS scores between LORs and interviews ranged from 72 to 81 across years and LOR types. Sixty-one percent of interviewers preferred NLORs, and 13% preferred SLORs. Reasons for these preferences included more information provided in NLORs versus faster read time with SLORs. Conclusions Interviewers' perceptions of applicants based on LORs and face-to-face interviews were comparable across LOR types over the last 5 years. For many reasons, the general utility of the LOR remains questionable, and the continued need for it should be critically assessed.

  7. Treating rheumatoid arthritis to target: Revision of the 2014 International Expert Group Recommendations

    Directory of Open Access Journals (Sweden)

    N. T. Vatutin

    2016-01-01

    Full Text Available The paper presents a new edition (2014 of basic approaches to therapy of rheumatoid arthritis (RA based on the principle of «Treat to target », which has been elaborated by the experts of the European League Against Rheumatism (EULAR and the American College of Rheumatology (ACR. The revised recommendations consider the results of numerous randomized controlled and cohort studies, as well as the data of an extensive systematic review of the literature. The new 2014 version contains 4 basic principles and 10 recommendations for the management of patients with RA. When making the updated recommendations, the experts took into account particularly issues, such as criteria for defining a remission, the need to minimize comorbidities in patients with RA and to individualize its therapy, as well as their working ability. The basic principles in the management of patients with RA, by using a treat-to-target strategy, are discussed in detail and the rewording of the main points of the 2010 recommendations and their new edition are substantiated.

  8. Diet and inflammatory bowel disease: review of patient-targeted recommendations.

    Science.gov (United States)

    Hou, Jason K; Lee, Dale; Lewis, James

    2014-10-01

    Patients have strong beliefs about the role of diet in the cause of inflammatory bowel disease (IBD) and in exacerbating or alleviating ongoing symptoms from IBD. The rapid increase in the incidence and prevalence of IBD in recent decades strongly suggests an environmental trigger for IBD, one of which may be dietary patterns. There are several pathways where diet may influence intestinal inflammation, such as direct dietary antigens, altering the gut microbiome, and affecting gastrointestinal permeability. However, data that altering diet can change the natural history of IBD are scarce, and evidence-based dietary guidelines for patients with IBD are lacking. Patients, therefore, seek nonmedical resources for dietary guidance, such as patient support groups and unverified sources on the Internet. The aim of this review is to identify patient-targeted dietary recommendations for IBD and to critically appraise the nutritional value of these recommendations. We review patient-targeted dietary information for IBD from structured Internet searches and popular defined diets. Patient-targeted dietary recommendations focus on food restrictions and are highly conflicting. High-quality dietary intervention studies are needed to facilitate creation of evidence-based dietary guidelines for patients with IBD. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Only a fraction of patients with ischaemic diseases or diabetes are treated to recommended target values for plasma lipids

    DEFF Research Database (Denmark)

    Siggaard-Andersen, Niels; Freiberg, Jacob J; Nordestgaard, Børge G

    2012-01-01

    We tested the hypothesis that individuals in the general population with and without ischaemic cardiovascular disease, or with diabetes, are treated to recommended target values for plasma lipids.......We tested the hypothesis that individuals in the general population with and without ischaemic cardiovascular disease, or with diabetes, are treated to recommended target values for plasma lipids....

  10. Only a fraction of patients with ischaemic diseases or diabetes are treated to recommended target values for plasma lipids

    DEFF Research Database (Denmark)

    Siggaard-Andersen, Niels; Freiberg, Jacob J; Nordestgaard, Børge G

    2012-01-01

    We tested the hypothesis that individuals in the general population with and without ischaemic cardiovascular disease, or with diabetes, are treated to recommended target values for plasma lipids.......We tested the hypothesis that individuals in the general population with and without ischaemic cardiovascular disease, or with diabetes, are treated to recommended target values for plasma lipids....

  11. Recommendations for managing cutaneous disorders associated with advancing age

    Directory of Open Access Journals (Sweden)

    Humbert P

    2016-02-01

    literature from 2004 to 2014 using PubMed was performed by a working group of six European dermatologists with clinical and research experience in dermatology. Basic topical therapy can restore and protect skin barrier function, which relieves problems associated with xerosis, prevents aggravating moisture-associated skin damage, and enhances quality of life. In conclusion, the authors provide physicians with practical recommendations to assist them in implementing basic skin care for the elderly in an integrated care approach.Keywords: elderly, skin, cosmetic management

  12. E-commerce Website Recommender System Based on Dissimilarity and Association Rule

    Directory of Open Access Journals (Sweden)

    MingWang Zhang

    2013-07-01

    Full Text Available By analyzing the current electronic commerce recommendation algorithm analysis, put forward a kind to use dissimilarity clustering and association recommendation algorithm, the algorithm realized web website shopping user data clustering by use of the dissimilarity, and then use the association rules algorithm for clustering results of association recommendation, experiments show that the algorithm compared with traditional clustering association algorithm of iteration times decrease, improve operational efficiency, to prove the method by use of the actual users purchase the recommended, and evidence of the effectiveness of the algorithm in recommendation.  

  13. Using Fuzzy Association Rules to Design E-commerce Personalized Recommendation System

    OpenAIRE

    Guofang Kuang; Yuanchen Li

    2013-01-01

    In order to improve the efficiency of fuzzy association rule mining, the paper defines the redundant fuzzy association rules, and strong fuzzy association rules redundant nature. As much as possible for more information in the e-commerce environment, and in the right form is a prerequisite for personalized recommendation. Personalized recommendation technology is a core issue of e-commerce automated recommendation system. Higher complexity than ordinary association rules algorithm fuzzy assoc...

  14. Factors associated with knowledge of personal gestational weight gain recommendations.

    Science.gov (United States)

    Ledoux, Tracey; Van Den Berg, Patricia; Leung, Patrick; Berens, Pamela D

    2015-08-13

    Excess adiposity (obesity and excess gestational weight gain, GWG) during pregnancy (EADP) increases risk for gestational diabetes, preeclampsia, and child and maternal obesity. Personal GWG goals predict total GWG. Some estimates suggest only 30% of pregnant women have personal GWG goals that are congruent with Institute of Medicine GWG recommendations. The primary purpose of this study was to determine the extent to which perceived pre-pregnancy weight status, healthcare provider advice, knowledge of EADP risks, and value for healthy GWG predicted knowledge of GWG recommendations. The secondary purpose was to determine sources of GWG information among pregnant women. Pregnant women with a confirmed singleton pregnancy completed a one-time survey in obstetric clinic waiting rooms. Logistic regression analysis was used. 246 predominantly African American, low income, overweight/obese women completed surveys. Average age was 25 (SD 5.3) and gestation age ranged from 7 to 40 weeks. Knowledge of pre-pregnancy weight status was the only unique predictor of GWG recommendation knowledge (B = .642, p = .03). The top three sources of GWG information were physicians, internet, and books. The least frequently reported sources of GWG information were other healthcare providers, community programs, and television. In low income diverse overweight/obese pregnant women, accurate pre-pregnancy weight status perception was the only significant unique predictor of knowledge of GWG recommendations. Physicians were the preferred source of GWG information. Clinicians should have frequent, ongoing conversations about weight status with women before, during, and after pregnancy.

  15. Improved Personalized Recommendation Based on Causal Association Rule and Collaborative Filtering

    Science.gov (United States)

    Lei, Wu; Qing, Fang; Zhou, Jin

    2016-01-01

    There are usually limited user evaluation of resources on a recommender system, which caused an extremely sparse user rating matrix, and this greatly reduce the accuracy of personalized recommendation, especially for new users or new items. This paper presents a recommendation method based on rating prediction using causal association rules.…

  16. Using Fuzzy Association Rules to Design E-commerce Personalized Recommendation System

    Directory of Open Access Journals (Sweden)

    Guofang Kuang

    2013-09-01

    Full Text Available In order to improve the efficiency of fuzzy association rule mining, the paper defines the redundant fuzzy association rules, and strong fuzzy association rules redundant nature. As much as possible for more information in the e-commerce environment, and in the right form is a prerequisite for personalized recommendation. Personalized recommendation technology is a core issue of e-commerce automated recommendation system. Higher complexity than ordinary association rules algorithm fuzzy association rules, the low efficiency become a bottleneck in the practical application of fuzzy association rules algorithm. The paper presents using fuzzy association rules to design E-commerce personalized recommendation system. The experimental results show that the new algorithm to improve the efficiency of the implementation.

  17. Association Rule Analysis for Tour Route Recommendation and Application to Wctsnop

    Science.gov (United States)

    Fang, H.; Chen, C.; Lin, J.; Liu, X.; Fang, D.

    2017-09-01

    The increasing E-tourism systems provide intelligent tour recommendation for tourists. In this sense, recommender system can make personalized suggestions and provide satisfied information associated with their tour cycle. Data mining is a proper tool that extracting potential information from large database for making strategic decisions. In the study, association rule analysis based on FP-growth algorithm is applied to find the association relationship among scenic spots in different cities as tour route recommendation. In order to figure out valuable rules, Kulczynski interestingness measure is adopted and imbalance ratio is computed. The proposed scheme was evaluated on Wangluzhe cultural tourism service network operation platform (WCTSNOP), where it could verify that it is able to quick recommend tour route and to rapidly enhance the recommendation quality.

  18. Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology.

    Science.gov (United States)

    Barnes, Thomas R E

    2011-05-01

    These guidelines from the British Association for Psychopharmacology address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting, involving experts in schizophrenia and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from the participants and interested parties, and cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. The practice recommendations presented are based on the available evidence to date, and seek to clarify which interventions are of proven benefit. It is hoped that the recommendations will help to inform clinical decision making for practitioners, and perhaps also serve as a source of information for patients and carers. They are accompanied by a more detailed qualitative review of the available evidence. The strength of supporting evidence for each recommendation is rated.

  19. Treating axial and peripheral spondyloarthritis, including psoriatic arthritis, to target: results of a systematic literature search to support an international treat-to-target recommendation in spondyloarthritis

    Science.gov (United States)

    Schoels, M M; Braun, J; Dougados, M; Emery, P; Fitzgerald, O; Kavanaugh, A; Kvien, T K; Landewé, R; Luger, T; Mease, P; Olivieri, I; Reveille, J; Ritchlin, C; Rudwaleit, M; Sieper, J; Smolen, J S; de Wit, M; van der Heijde, D

    2014-01-01

    Background Current recommendations for the management of axial spondyloarthritis (SpA) and psoriatic arthritis are to monitor disease activity and adjust therapy accordingly. However, treatment targets and timeframes of change have not been defined. An international expert panel has been convened to develop ‘treat-to-target’ recommendations, based on published evidence and expert opinion. Objective To review evidence on targeted treatment for axial and peripheral SpA, as well as for psoriatic skin disease. Methods We performed a systematic literature search covering Medline, Embase and Cochrane, conference abstracts and studies in http://www.clinicaltrials.gov. Results Randomised comparisons of targeted versus routine treatment are lacking. Some studies implemented treatment targets before escalating therapy: in ankylosing spondylitis, most trials used a decrease in Bath Ankylosing Spondylitis Disease Activity Index; in psoriatic arthritis, protocols primarily considered a reduction in swollen and tender joints; in psoriasis, the Modified Psoriasis Severity Score and the Psoriasis Area and Severity Index were used. Complementary evidence correlating these factors with function and radiographic damage at follow-up is sparse and equivocal. Conclusions There is a need for randomised trials that investigate the value of treat-to-target recommendations in SpA and psoriasis. Several trials have used thresholds of disease activity measures to guide treatment decisions. However, evidence on the effect of these data on long-term outcome is scarce. The search data informed the expert committee regarding the formulation of recommendations and a research agenda. PMID:23740234

  20. Safety of American Heart Association-recommended minimum exercise for desmosomal mutation carriers

    NARCIS (Netherlands)

    Sawant, Abhishek C; Te Riele, Anneline S J M; Tichnell, Crystal; Murray, Brittney; Bhonsale, Aditya; Tandri, Harikrishna; Judge, Daniel P; Calkins, Hugh; James, Cynthia A

    2016-01-01

    BACKGROUND: Endurance exercise is associated with adverse outcomes in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Exercise recommendations for family members remain undetermined. OBJECTIVE: The purposes of this study were to determine if (1) endurance exercise (

  1. Safety of American Heart Association-recommended minimum exercise for desmosomal mutation carriers

    NARCIS (Netherlands)

    Sawant, Abhishek C; Te Riele, Anneline S J M; Tichnell, Crystal; Murray, Brittney; Bhonsale, Aditya; Tandri, Harikrishna; Judge, Daniel P; Calkins, Hugh; James, Cynthia A

    2016-01-01

    BACKGROUND: Endurance exercise is associated with adverse outcomes in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Exercise recommendations for family members remain undetermined. OBJECTIVE: The purposes of this study were to determine if (1) endurance exercise (

  2. Factors Associated with Osteoporosis Screening and Recommendations for Osteoporosis Screening in Older Adults

    OpenAIRE

    Nayak, Smita; Roberts, Mark S.; Greenspan, Susan L

    2009-01-01

    ABSTRACT BACKGROUND Osteoporosis screening rates are low, and it is unclear which patient factors are associated with screening and physician recommendations for screening. OBJECTIVE To identify patient characteristics associated with osteoporosis screening recommendations and receipt of screening in older adults. DESIGN Cross-sectional mailed survey. PARTICIPANTS Women and men ≥60 years old living in or near western Pennsylvania. MEASUREMENTS Sociodemographic characteristics and osteoporosis...

  3. Associated factors for recommending HBV vaccination to children among Georgian health care workers

    Directory of Open Access Journals (Sweden)

    Butsashvili Maia

    2012-12-01

    Full Text Available Abstract Background Most cases of hepatitis B virus (HBV infection and subsequent liver diseases can be prevented with universal newborn HBV vaccination. The attitudes of health care workers about HBV vaccination and their willingness to recommend vaccine have been shown to impact HBV vaccination coverage and the prevention of vertical transmission of HBV. The purpose of this study was to ascertain the factors associated with health care worker recommendations regarding newborn HBV vaccination. Methods A cross-sectional study of prevalence and awareness of hepatitis B and hepatitis B vaccine was conducted among randomly selected physicians and nurses employed in seven hospitals in Georgia in 2006 and 2007. Self-administered questionnaires included a module on recommendations for HBV, HCV and HIV. Results Of the 1328 participants included in this analysis, 36% reported recommending against hepatitis B vaccination for children, including 33% of paediatricians. Among the 70.6% who provided a reason for not recommending HBV vaccine, the most common concern was an adverse vaccine event. Unvaccinated physicians and nurses were more likely to recommend against HBV vaccine (40.4% vs 11.4%, PR 3.54; 95% CI: 2.38, 5.29. Additionally, health care worker age was inversely correlated with recommendations for HBV vaccine with older workers less likely to recommend it. Conclusion Vaccinating health care workers against HBV may provide a dual benefit by boosting occupational safety as well as strengthening universal coverage programs for newborns.

  4. Design and Realization of user Behaviors Recommendation System Based on Association rules under Cloud Environment

    Directory of Open Access Journals (Sweden)

    Wei Dai

    2013-07-01

    Full Text Available This study introduces the basal principles of association rules, properties and advantages of Map Reduce model and Hbase in Hadoop ecosystem. And giving design steps of the user's actions recommend system in detail, many time experiences proves that the exploration combined association rules theory with cloud computing is successful and effective.

  5. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis.

    Science.gov (United States)

    Yates, M; Watts, R A; Bajema, I M; Cid, M C; Crestani, B; Hauser, T; Hellmich, B; Holle, J U; Laudien, M; Little, M A; Luqmani, R A; Mahr, A; Merkel, P A; Mills, J; Mooney, J; Segelmark, M; Tesar, V; Westman, K; Vaglio, A; Yalçındağ, N; Jayne, D R; Mukhtyar, C

    2016-09-01

    In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. Intrapersonal, behavioral, and environmental factors associated with meeting recommended physical activity among rural Latino youth.

    Science.gov (United States)

    Perry, Cynthia K; Saelens, Brian E; Thompson, Beti

    2011-11-01

    This study aimed to identify intrapersonal, behavioral, and environmental factors associated with engaging in recommended levels of physical activity among rural Latino middle school youth. Data were from an anonymous survey of 773 Latino youth (51% female) about level of and barriers and motivators to physical activity, risk behaviors, and park use. Logistic regression models identified factors correlated with meeting recommended levels of physical activity (5 days or more 3 60 min/day). Thirty-four percent of girls and 41% of boys reported meeting this physical activity recommendation. Participation in an organized after school activity (p physical education (PE) classes 5 days a week (p physical activity level. Making PE available 5 days a week and creating opportunities for organized after school physical activity programs may increase the number of rural Latino middle school youth who meet recommended physical activity level.

  7. Treat-to-target in systemic lupus erythematosus : recommendations from an international task force

    NARCIS (Netherlands)

    van Vollenhoven, Ronald F.; Mosca, Marta; Bertsias, George; Isenberg, David; Kuhn, Annegret; Lerstrom, Kirsten; Aringer, Martin; Bootsma, Hendrika; Boumpas, Dimitrios; Bruce, Ian N.; Cervera, Ricard; Clarke, Ann; Costedoat-Chalumeau, Nathalie; Czirjak, Laszlo; Derksen, Ronald; Doerner, Thomas; Gordon, Caroline; Graninger, Winfried; Houssiau, Frederic; Inanc, Murat; Jacobsen, Soren; Jayne, David; Jedryka-Goral, Anna; Levitsky, Adrian; Levy, Roger; Mariette, Xavier; Morand, Eric; Navarra, Sandra; Neumann, Irmgard; Rahman, Anisur; Rovensky, Jozef; Smolen, Josef; Vasconcelos, Carlos; Voskuyl, Alexandre; Voss, Anne; Zakharova, Helena; Zoma, Asad; Schneider, Matthias

    2014-01-01

    The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidan

  8. National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2.

    Science.gov (United States)

    Jacobson, Terry A; Maki, Kevin C; Orringer, Carl E; Jones, Peter H; Kris-Etherton, Penny; Sikand, Geeta; La Forge, Ralph; Daniels, Stephen R; Wilson, Don P; Morris, Pamela B; Wild, Robert A; Grundy, Scott M; Daviglus, Martha; Ferdinand, Keith C; Vijayaraghavan, Krishnaswami; Deedwania, Prakash C; Aberg, Judith A; Liao, Katherine P; McKenney, James M; Ross, Joyce L; Braun, Lynne T; Ito, Matthew K; Bays, Harold E; Brown, W Virgil; Underberg, James A

    2015-01-01

    An Expert Panel convened by the National Lipid Association previously developed a consensus set of recommendations for the patient-centered management of dyslipidemia in clinical medicine (part 1). These were guided by the principle that reducing elevated levels of atherogenic cholesterol (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) reduces the risk for atherosclerotic cardiovascular disease. This document represents a continuation of the National Lipid Association recommendations developed by a diverse panel of experts who examined the evidence base and provided recommendations regarding the following topics: (1) lifestyle therapies; (2) groups with special considerations, including children and adolescents, women, older patients, certain ethnic and racial groups, patients infected with human immunodeficiency virus, patients with rheumatoid arthritis, and patients with residual risk despite statin and lifestyle therapies; and (3) strategies to improve patient outcomes by increasing adherence and using team-based collaborative care.

  9. Recommendation System Based On Association Rules For Distributed E-Learning Management Systems

    Science.gov (United States)

    Mihai, Gabroveanu

    2015-09-01

    Traditional Learning Management Systems are installed on a single server where learning materials and user data are kept. To increase its performance, the Learning Management System can be installed on multiple servers; learning materials and user data could be distributed across these servers obtaining a Distributed Learning Management System. In this paper is proposed the prototype of a recommendation system based on association rules for Distributed Learning Management System. Information from LMS databases is analyzed using distributed data mining algorithms in order to extract the association rules. Then the extracted rules are used as inference rules to provide personalized recommendations. The quality of provided recommendations is improved because the rules used to make the inferences are more accurate, since these rules aggregate knowledge from all e-Learning systems included in Distributed Learning Management System.

  10. Evidence-based recommendations for the development of obesity prevention programs targeted at preschool children.

    Science.gov (United States)

    Summerbell, C D; Moore, H J; Vögele, C; Kreichauf, S; Wildgruber, A; Manios, Y; Douthwaite, W; Nixon, C A; Gibson, E L

    2012-03-01

    The ToyBox intervention was developed using an evidence-based approach, using the findings of four reviews. These reviews included three critical and narrative reviews of educational strategies and psychological approaches explaining young children's acquisition and formation of energy-balance related behaviours, and the management of these behaviours, and also a systematic review of behavioural models underpinning school-based interventions in preschool and school settings for the prevention of obesity in children aged 4-6 years. This paper summarises and translates the findings from these reviews into practical evidence based recommendations for researchers and policy-makers to consider when developing and implementing interventions for the prevention of overweight and obesity in young (aged 4-6 years) children. The recommendations focus on two behaviours, physical activity and sedentary behaviour, and healthy eating, and include general recommendations, intervention approaches, interventions content, and simple messages. The review also briefly examines the role that the commercial sector plays in hindering or facilitating attempts to create healthy food environments for children. This paper also recognises that childhood obesity is not an issue for the education sector alone; it needs to be tackled at a multi sectoral level, recognizing the particularly important role of local governments, nongovernment organizations and the media.

  11. The health belief model and factors associated with adherence to treatment recommendations for positional plagiocephaly.

    Science.gov (United States)

    Lam, Sandi; Luerssen, Thomas G; Hadley, Caroline; Daniels, Bradley; Strickland, Ben A; Brookshier, Jim; Pan, I-Wen

    2017-03-01

    OBJECTIVE This study aimed to examine factors associated with adherence to recommended treatment among pediatric patients with positional skull deformity by reviewing a single-institution experience (2007-2014) with the treatment of positional plagiocephaly. METHODS A retrospective chart review was conducted. Risk factors, treatment for positional head shape deformity, and parent-reported adherence were recorded. Univariate and multivariate analyses were used to assess the impact of patient clinical and demographic characteristics on adherence. RESULTS A total of 991 patients under age 12 months were evaluated for positional skull deformity at the Texas Children's Hospital Cranial Deformity Clinic between 2007 and 2014. According to an age- and risk factor-based treatment algorithm, patients were recommended for repositioning, physical therapy, or cranial orthosis therapy or crossover from repositioning/physical therapy into cranial orthosis therapy. The patients' average chronological age at presentation was 6.2 months; 69.3% were male. The majority were white (40.7%) or Hispanic (32.6%); 38.7% had commercial insurance and 37.9% had Medicaid. The most common initial recommended treatment was repositioning or physical therapy; 85.7% of patients were adherent to the initial recommended treatment. Univariate analysis showed differences in adherence rates among subgroups. Children's families with Medicaid were less likely to be adherent to treatment recommendations (adherence rate, 80.2%). Families with commercial insurance were more likely to be adherent to the recommended treatment (89.6%). Multivariate logistic regression confirmed that factors associated with parent-reported adherence to recommended treatment included primary insurance payer, diagnosis (plagiocephaly vs brachycephaly), and the nature of the recommended treatment. Families were less likely to be adherent if they had Medicaid, a child with a diagnosis of brachycephaly, or were initially recommended

  12. Targeting Net Zero Energy at Marine Corps Base Kaneohe Bay, Hawaii: Assessment and Recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Burman, K.; Kandt, A.; Lisell, L.; Booth, S.; Walker, A.; Roberts, J.; Falcey, J.

    2011-11-01

    DOD's U.S. Pacific Command has partnered with the U.S. Department of Energy's (DOE) National Renewable Energy Laboratory (NREL) to assess opportunities for increasing energy security through renewable energy and energy efficiency in Hawaii installations. NREL selected Marine Corps Base Hawaii (MCBH), Kaneohe Bay to receive technical support for net zero energy assessment and planning funded through the Hawaii Clean Energy Initiative (HCEI). NREL performed a comprehensive assessment to appraise the potential of MCBH Kaneohe Bay to achieve net zero energy status through energy efficiency, renewable energy, and electric vehicle integration. This report summarizes the results of the assessment and provides energy recommendations.

  13. Applications for human rights relief and the recommendations of the Japan Federations of Bar Associations.

    Science.gov (United States)

    Kuramochi, Takeshi

    2005-01-01

    Between the enactment of Japan's "Organ Transplantation Law" (OTL) in 1997 and the end of October 2003, there were 27 (30 now) legal declarations of brain death, and organs were donated from 26 (29) of those. During this period, four applications for human rights relief were made against organ donation facilities by Takayoshi Okamoto and others. One of these remains under investigation, but the Japanese Federation of Bar Associations (JFBA) has offered recommendations relating to the other three. The purpose of this report lies in examining these applications and recommendations.

  14. Recommendations on Chronic Constipation (Including Constipation Associated with Irritable Bowel Syndrome Treatment

    Directory of Open Access Journals (Sweden)

    Pierre Paré

    2007-01-01

    Full Text Available While chronic constipation (CC has a high prevalence in primary care, there are no existing treatment recommendations to guide health care professionals. To address this, a consensus group of 10 gastroenterologists was formed to develop treatment recommendations. Although constipation may occur as a result of organic disease, the present paper addresses only the management of primary CC or constipation associated with irritable bowel syndrome. The final consensus group was assembled and the recommendations were created following the exact process outlined by the Canadian Association of Gastroenterology for the following areas: epidemiology, quality of life and threshold for treatment; definitions and diagnostic criteria; lifestyle changes; bulking agents and stool softeners; osmotic agents; prokinetics; stimulant laxatives; suppositories; enemas; other drugs; biofeedback and behavioural approaches; surgery; and probiotics. A treatment algorithm was developed by the group for CC and constipation associated with irritable bowel syndrome. Where possible, an evidence-based approach and expert opinions were used to develop the statements in areas with insufficient evidence. The nature of the underlying pathophysiology for constipation is often unclear, and it can be tricky for physicians to decide on an appropriate treatment strategy for the individual patient. The myriad of treatment options available to Canadian physicians can be confusing; thus, the main aim of the recommendations and treatment algorithm is to optimize the approach in clinical care based on available evidence.

  15. Identifying factors associated with concordance with the American College of Rheumatology rheumatoid arthritis treatment recommendations.

    Science.gov (United States)

    Harrold, Leslie R; Reed, George W; Kremer, Joel M; Curtis, Jeffrey R; Solomon, Daniel H; Hochberg, Marc C; Kavanaugh, Arthur; Saunders, Katherine C; Shan, Ying; Spruill, Tanya M; Pappas, Dimitrios A; Greenberg, Jeffrey D

    2016-04-26

    Factors associated with care concordant with the American College of Rheumatology (ACR) recommendations for the use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) are unknown. We identified a national cohort of biologic-naive patients with RA with visits between December 2008 and February 2013. Treatment acceleration (initiation or dose escalation of biologic and nonbiologic DMARDs) in response to moderate to high disease activity (using the Clinical Disease Activity Index) was assessed. The population was divided into two subcohorts: (1) methotrexate (MTX)-only users and (2) multiple nonbiologic DMARD users. In both subcohorts, we compared the characteristics of patients who received care consistent with the ACR recommendations (e.g., prescriptions for treatment acceleration) and their providers with the characteristics of those who did not at the conclusion of one visit and over two visits, using logistic regression and adjusting for clustering of patients by rheumatologist. Our study included 741 MTX monotherapy and 995 multiple nonbiologic DMARD users cared for by 139 providers. Only 36.2 % of MTX monotherapy users and 39.6 % of multiple nonbiologic DMARD users received care consistent with the recommendations after one visit, which increased over two visits to 78.3 % and 76.2 %, respectively (25-30 % achieved low disease activity by the second visit without DMARD acceleration). Increasing time since the ACR publication on RA treatment recommendations was not associated with improved adherence. Allowing two encounters for treatment acceleration was associated with an increase in care concordant with the recommendations; however, time since publication was not.

  16. Data association based on target signal classification information

    Institute of Scientific and Technical Information of China (English)

    Guo Lei; Tang Bin; Liu Gang

    2008-01-01

    In most of the passive tracking systems, only the target kinematical information is used in the measurement-to-track association, which results in error tracking in a multitarget environment, where the tar-gets are too close to each other. To enhance the tracking accuracy, the target signal classification information (TSCI) should be used to improve the data association. The TSCI is integrated in the data association process using the JPDA (joint probabilistie data association). The use of the TSCI in the data association can improve discrimination by yielding a purer track and preserving continuity. To verify the validity of the application of TSCI,two simulation experiments are done on an air target-tracing problem, that is, one using the TSCI and the other not using the TSCI. The final comparison shows that the use of the TSCI can effectively improve tracking accuracy.

  17. The benefits associated with volunteering among seniors: a critical review and recommendations for future research.

    Science.gov (United States)

    Anderson, Nicole D; Damianakis, Thecla; Kröger, Edeltraut; Wagner, Laura M; Dawson, Deirdre R; Binns, Malcolm A; Bernstein, Syrelle; Caspi, Eilon; Cook, Suzanne L

    2014-11-01

    There is an urgent need to identify lifestyle activities that reduce functional decline and dementia associated with population aging. The goals of this article are to review critically the evidence on the benefits associated with formal volunteering among older adults, propose a theoretical model of how volunteering may reduce functional limitations and dementia risk, and offer recommendations for future research. Database searches identified 113 papers on volunteering benefits in older adults, of which 73 were included. Data from descriptive, cross-sectional, and prospective cohort studies, along with 1 randomized controlled trial, most consistently reveal that volunteering is associated with reduced symptoms of depression, better self-reported health, fewer functional limitations, and lower mortality. The extant evidence provides the basis for a model proposing that volunteering increases social, physical, and cognitive activity (to varying degrees depending on characteristics of the volunteer placement) which, through biological and psychological mechanisms, leads to improved functioning; we further propose that these volunteering-related functional improvements should be associated with reduced dementia risk. Recommendations for future research are that studies (a) include more objective measures of psychosocial, physical, and cognitive functioning; (b) integrate qualitative and quantitative methods in prospective study designs; (c) explore further individual differences in the benefits associated with volunteering; (d) include occupational analyses of volunteers' specific jobs in order to identify their social, physical, and cognitive complexity; (e) investigate the independent versus interactive health benefits associated with volunteering relative to engagement in other forms of activity; and (f) examine the relationship between volunteering and dementia risk.

  18. Methodological recommendations for cognition trials in bipolar disorder by the International Society for Bipolar Disorders Targeting Cognition Task Force.

    Science.gov (United States)

    Miskowiak, K W; Burdick, K E; Martinez-Aran, A; Bonnin, C M; Bowie, C R; Carvalho, A F; Gallagher, P; Lafer, B; López-Jaramillo, C; Sumiyoshi, T; McIntyre, R S; Schaffer, A; Porter, R J; Torres, I J; Yatham, L N; Young, A H; Kessing, L V; Vieta, E

    2017-09-12

    To aid the development of treatment for cognitive impairment in bipolar disorder, the International Society for Bipolar Disorders (ISBD) convened a task force to create a consensus-based guidance paper for the methodology and design of cognition trials in bipolar disorder. The task force was launched in September 2016, consisting of 18 international experts from nine countries. A series of methodological issues were identified based on literature review and expert opinion. The issues were discussed and expanded upon in an initial face-to-face meeting, telephone conference call and email exchanges. Based upon these exchanges, recommendations were achieved. Key methodological challenges are: lack of consensus on how to screen for entry into cognitive treatment trials, define cognitive impairment, track efficacy, assess functional implications, and manage mood symptoms and concomitant medication. Task force recommendations are to: (i) enrich trials with objectively measured cognitively impaired patients; (ii) generally select a broad cognitive composite score as the primary outcome and a functional measure as a key secondary outcome; and (iii) include remitted or partly remitted patients. It is strongly encouraged that trials exclude patients with current substance or alcohol use disorders, neurological disease or unstable medical illness, and keep non-study medications stable. Additional methodological considerations include neuroimaging assessments, targeting of treatments to illness stage and using a multimodal approach. This ISBD task force guidance paper provides the first consensus-based recommendations for cognition trials in bipolar disorder. Adherence to these recommendations will likely improve the sensitivity in detecting treatment efficacy in future trials and increase comparability between studies. © 2017 The Authors Bipolar Disorders Published by John Wiley & Sons Ltd.

  19. Mentoring during surgical training: consensus recommendations for mentoring programmes from the Association of Surgeons in Training.

    Science.gov (United States)

    Sinclair, P; Fitzgerald, J E F; McDermott, F D; Derbyshire, L; Shalhoub, J

    2014-11-01

    Mentoring has been present within surgical training for many years, albeit in different forms. There is evidence that formal mentoring can improve patient outcomes and facilitate learning and personal growth in the mentee. The Association of Surgeons in Training (ASiT) is an independent educational charity working to promote excellence in surgical training. This document recommends the introduction of a structured mentoring programme, which is readily accessible to all surgical trainees. A review of the available evidence--including an ASiT-led survey of its membership--highlights the desire of surgical trainees to have a mentor, whilst the majority do not have access to one. There is also limited training for those in mentoring roles. In response, ASiT have implemented a pilot mentoring scheme, with surgical trainees acting both as mentors and mentees. Based on the existing literature, survey data and pilot experience, ASiT formalises in this document consensus recommendations for mentoring in surgical training.

  20. Recommendation on Design, Execution, and Reporting of Animal Atherosclerosis Studies: A Scientific Statement From the American Heart Association.

    Science.gov (United States)

    Daugherty, Alan; Tall, Alan R; Daemen, Mat J A P; Falk, Erling; Fisher, Edward A; García-Cardeña, Guillermo; Lusis, Aldons J; Owens, A Phillip; Rosenfeld, Michael E; Virmani, Renu

    2017-09-01

    Animal studies are a foundation for defining mechanisms of atherosclerosis and potential targets of drugs to prevent lesion development or reverse the disease. In the current literature, it is common to see contradictions of outcomes in animal studies from different research groups, leading to the paucity of extrapolations of experimental findings into understanding the human disease. The purpose of this statement is to provide guidelines for development and execution of experimental design and interpretation in animal studies. Recommendations include the following: (1) animal model selection, with commentary on the fidelity of mimicking facets of the human disease; (2) experimental design and its impact on the interpretation of data; and (3) standard methods to enhance accuracy of measurements and characterization of atherosclerotic lesions. © 2017 American Heart Association, Inc.

  1. A Hybrid Web Recommendation System based on the Improved Association Rule Mining Algorithm

    OpenAIRE

    Wanaskar, Ujwala; Vij, Sheetal; Mukhopadhyay, Debajyoti

    2013-01-01

    As the growing interest of web recommendation systems those are applied to deliver customized data for their users, we started working on this system. Generally the recommendation systems are divided into two major categories such as collaborative recommendation system and content based recommendation system. In case of collaborative recommen-dation systems, these try to seek out users who share same tastes that of given user as well as recommends the websites according to the liking given us...

  2. COLLABORATIVE WEB RECOMMENDATION SYSTEMS BASED ON AN EFFECTIVE FUZZY ASSOCIATION RULE MINING ALGORITHM (FARM)

    OpenAIRE

    Dr. P. THAMBIDURAI; A.KUMAR,

    2010-01-01

    With increasing popularity of the web-based systems that are applied in many different areas, they tend to deliver customized informationfor their users by means of utilization of recommendation methods. This recommendation system is mainly classified into two groups:Content-based recommendation and collaborative recommendation system. Content based recommendation tries to recommend web sites similar to those web sites the user has liked, whereas collaborative ecommendation tries to find som...

  3. Targeting Neuroblastoma Cell Surface Proteins: Recommendations for Homology Modeling of hNET, ALK, and TrkB

    Science.gov (United States)

    Haddad, Yazan; Heger, Zbyněk; Adam, Vojtech

    2017-01-01

    Targeted therapy is a promising approach for treatment of neuroblastoma as evident from the large number of targeting agents employed in clinical practice today. In the absence of known crystal structures, researchers rely on homology modeling to construct template-based theoretical structures for drug design and testing. Here, we discuss three candidate cell surface proteins that are suitable for homology modeling: human norepinephrine transporter (hNET), anaplastic lymphoma kinase (ALK), and neurotrophic tyrosine kinase receptor 2 (NTRK2 or TrkB). When choosing templates, both sequence identity and structure quality are important for homology modeling and pose the first of many challenges in the modeling process. Homology modeling of hNET can be improved using template models of dopamine and serotonin transporters instead of the leucine transporter (LeuT). The extracellular domains of ALK and TrkB are yet to be exploited by homology modeling. There are several idiosyncrasies that require direct attention throughout the process of model construction, evaluation and refinement. Shifts/gaps in the alignment between the template and target, backbone outliers and side-chain rotamer outliers are among the main sources of physical errors in the structures. Low-conserved regions can be refined with loop modeling method. Residue hydrophobicity, accessibility to bound metals or glycosylation can aid in model refinement. We recommend resolving these idiosyncrasies as part of “good modeling practice” to obtain highest quality model. Decreasing physical errors in protein structures plays major role in the development of targeting agents and understanding of chemical interactions at the molecular level. PMID:28163672

  4. Targeting Neuroblastoma Cell Surface Proteins: Recommendations for Homology Modeling of hNET, ALK, and TrkB.

    Science.gov (United States)

    Haddad, Yazan; Heger, Zbyněk; Adam, Vojtech

    2017-01-01

    Targeted therapy is a promising approach for treatment of neuroblastoma as evident from the large number of targeting agents employed in clinical practice today. In the absence of known crystal structures, researchers rely on homology modeling to construct template-based theoretical structures for drug design and testing. Here, we discuss three candidate cell surface proteins that are suitable for homology modeling: human norepinephrine transporter (hNET), anaplastic lymphoma kinase (ALK), and neurotrophic tyrosine kinase receptor 2 (NTRK2 or TrkB). When choosing templates, both sequence identity and structure quality are important for homology modeling and pose the first of many challenges in the modeling process. Homology modeling of hNET can be improved using template models of dopamine and serotonin transporters instead of the leucine transporter (LeuT). The extracellular domains of ALK and TrkB are yet to be exploited by homology modeling. There are several idiosyncrasies that require direct attention throughout the process of model construction, evaluation and refinement. Shifts/gaps in the alignment between the template and target, backbone outliers and side-chain rotamer outliers are among the main sources of physical errors in the structures. Low-conserved regions can be refined with loop modeling method. Residue hydrophobicity, accessibility to bound metals or glycosylation can aid in model refinement. We recommend resolving these idiosyncrasies as part of "good modeling practice" to obtain highest quality model. Decreasing physical errors in protein structures plays major role in the development of targeting agents and understanding of chemical interactions at the molecular level.

  5. Recommendations for the design of laboratory studies on non-target arthropods for risk assessment of genetically engineered plants.

    Science.gov (United States)

    Romeis, Jörg; Hellmich, Richard L; Candolfi, Marco P; Carstens, Keri; De Schrijver, Adinda; Gatehouse, Angharad M R; Herman, Rod A; Huesing, Joseph E; McLean, Morven A; Raybould, Alan; Shelton, Anthony M; Waggoner, Annabel

    2011-02-01

    This paper provides recommendations on experimental design for early-tier laboratory studies used in risk assessments to evaluate potential adverse impacts of arthropod-resistant genetically engineered (GE) plants on non-target arthropods (NTAs). While we rely heavily on the currently used proteins from Bacillus thuringiensis (Bt) in this discussion, the concepts apply to other arthropod-active proteins. A risk may exist if the newly acquired trait of the GE plant has adverse effects on NTAs when they are exposed to the arthropod-active protein. Typically, the risk assessment follows a tiered approach that starts with laboratory studies under worst-case exposure conditions; such studies have a high ability to detect adverse effects on non-target species. Clear guidance on how such data are produced in laboratory studies assists the product developers and risk assessors. The studies should be reproducible and test clearly defined risk hypotheses. These properties contribute to the robustness of, and confidence in, environmental risk assessments for GE plants. Data from NTA studies, collected during the analysis phase of an environmental risk assessment, are critical to the outcome of the assessment and ultimately the decision taken by regulatory authorities on the release of a GE plant. Confidence in the results of early-tier laboratory studies is a precondition for the acceptance of data across regulatory jurisdictions and should encourage agencies to share useful information and thus avoid redundant testing.

  6. How to treat ANCA‑associated vasculitis: practical messages from 2016 EULAR/ERA‑EDTA recommendations.

    Science.gov (United States)

    Sznajd, Jan; Mukhtyar, Chetan

    2016-10-28

    The European League against Rheumatism (EULAR) with the European Renal Association - European Dialysis and Transplant Association recently published an update of 2009 EULAR recommendations with a focus on the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). In this article, we discuss the following key messages for clinical practice derived from these recommendations: 1) biopsy should be performed if possible to confirm new diagnosis or relapse; 2) glucocorticoid therapy is an extremely important adjunct to the management of AAV, but it is also responsible for the majority of adverse effects; the dose should be tapered to 7.5 to 10 mg/d at 3 to 5 months; 3) cyclophosphamide or rituximab are the mainstay of remission induction; 4) patients with major relapse should be treated like those with new disease, but rituximab is the preferred option in those patients who relapse after prior cyclophosphamide; 5) minor relapse should not be treated with glucocorticoid alone, and a change in immunosuppressive regimen should be considered; 6) rituximab can be used not only for remission induction but also for maintenance; 7) maintenance therapy should continue for at least 2 years, after which gradual taper could be considered; 8) while ANCA are extremely useful for diagnosis and rising ANCA levels seem to be associated with relapse, serial monitoring should not guide treatment decisions; 9) monitoring of AAV patients should be holistic with a structured assessment tool and monitoring for effects related to the vasculitis as well as treatment; 10) management should be either at or in conjunction with an expert center; and 11) patients should be involved in decision making and have access to educational resources.

  7. Association between meeting the WCRF/AICR cancer prevention recommendations and colorectal cancer incidence: results from the VITAL cohort.

    Science.gov (United States)

    Hastert, Theresa A; White, Emily

    2016-11-01

    In 2007, the World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) published eight recommendations regarding body weight, physical activity, and dietary behaviors aimed at reducing cancer incidence worldwide. In this paper, we assess whether meeting the WCRF/AICR recommendations is associated with lower colorectal cancer (CRC) incidence; evaluate whether particular recommendations are most strongly associated with lower CRC incidence; and assess whether associations differ by sex. We operationalized six of the recommendations (related to body weight, physical activity, energy density, plant foods, red and processed meat, and alcohol) and examined their association with CRC incidence over 7.6 years of follow-up in the prospective VITamins And Lifestyle Study cohort. Participants included 66,920 adults aged 50-76 years at baseline (2000-2002) with no history of CRC and with complete data for the recommendations evaluated. Incident colorectal cancers (n = 546) were tracked through 2009. Compared with meeting no recommendations, meeting 1-3 recommendations was associated with 34-45 % lower CRC incidence, and meeting 4-6 was associated with 58 % lower incidence (95 % CI 34 %, 74 %) in fully adjusted analyses. The recommendations most strongly associated with lower CRC risk for women were related to body fatness and red and processed meat, while for men these were alcohol intake and red and processed meat. Differences by sex were statistically significant (p alcohol. Meeting the WCRF/AICR recommendations, particularly those related to alcohol, body weight, and red and processed meat, could substantially reduce CRC incidence; however, associations differ by sex.

  8. Assessing drug target association using semantic linked data.

    Directory of Open Access Journals (Sweden)

    Bin Chen

    Full Text Available The rapidly increasing amount of public data in chemistry and biology provides new opportunities for large-scale data mining for drug discovery. Systematic integration of these heterogeneous sets and provision of algorithms to data mine the integrated sets would permit investigation of complex mechanisms of action of drugs. In this work we integrated and annotated data from public datasets relating to drugs, chemical compounds, protein targets, diseases, side effects and pathways, building a semantic linked network consisting of over 290,000 nodes and 720,000 edges. We developed a statistical model to assess the association of drug target pairs based on their relation with other linked objects. Validation experiments demonstrate the model can correctly identify known direct drug target pairs with high precision. Indirect drug target pairs (for example drugs which change gene expression level are also identified but not as strongly as direct pairs. We further calculated the association scores for 157 drugs from 10 disease areas against 1683 human targets, and measured their similarity using a [Formula: see text] score matrix. The similarity network indicates that drugs from the same disease area tend to cluster together in ways that are not captured by structural similarity, with several potential new drug pairings being identified. This work thus provides a novel, validated alternative to existing drug target prediction algorithms. The web service is freely available at: http://chem2bio2rdf.org/slap.

  9. Assessing drug target association using semantic linked data.

    Science.gov (United States)

    Chen, Bin; Ding, Ying; Wild, David J

    2012-01-01

    The rapidly increasing amount of public data in chemistry and biology provides new opportunities for large-scale data mining for drug discovery. Systematic integration of these heterogeneous sets and provision of algorithms to data mine the integrated sets would permit investigation of complex mechanisms of action of drugs. In this work we integrated and annotated data from public datasets relating to drugs, chemical compounds, protein targets, diseases, side effects and pathways, building a semantic linked network consisting of over 290,000 nodes and 720,000 edges. We developed a statistical model to assess the association of drug target pairs based on their relation with other linked objects. Validation experiments demonstrate the model can correctly identify known direct drug target pairs with high precision. Indirect drug target pairs (for example drugs which change gene expression level) are also identified but not as strongly as direct pairs. We further calculated the association scores for 157 drugs from 10 disease areas against 1683 human targets, and measured their similarity using a [Formula: see text] score matrix. The similarity network indicates that drugs from the same disease area tend to cluster together in ways that are not captured by structural similarity, with several potential new drug pairings being identified. This work thus provides a novel, validated alternative to existing drug target prediction algorithms. The web service is freely available at: http://chem2bio2rdf.org/slap.

  10. National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report.

    Science.gov (United States)

    Jacobson, Terry A; Ito, Matthew K; Maki, Kevin C; Orringer, Carl E; Bays, Harold E; Jones, Peter H; McKenney, James M; Grundy, Scott M; Gill, Edward A; Wild, Robert A; Wilson, Don P; Brown, W Virgil

    2015-01-01

    The leadership of the National Lipid Association convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. An Executive Summary of those recommendations was previously published. This document provides support for the recommendations outlined in the Executive Summary. The major conclusions include (1) an elevated level of cholesterol carried by circulating apolipoprotein B-containing lipoproteins (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol [LDL-C], termed atherogenic cholesterol) is a root cause of atherosclerosis, the key underlying process contributing to most clinical atherosclerotic cardiovascular disease (ASCVD) events; (2) reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle and drug therapies; (3) the intensity of risk-reduction therapy should generally be adjusted to the patient's absolute risk for an ASCVD event; (4) atherosclerosis is a process that often begins early in life and progresses for decades before resulting a clinical ASCVD event. Therefore, both intermediate-term and long-term or lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies; (5) for patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk; (6) nonlipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus; and (7) the measurement and monitoring of atherogenic cholesterol levels remain an important part of a comprehensive ASCVD prevention strategy.

  11. Adverse Effects Associated with Protein Intake above the Recommended Dietary Allowance for Adults.

    Science.gov (United States)

    Delimaris, Ioannis

    2013-01-01

    Background. While high-protein consumption-above the current recommended dietary allowance for adults (RDA: 0.8 g protein/kg body weight/day)-is increasing in popularity, there is a lack of data on its potential adverse effects. Objective. To determine the potential disease risks due to high protein/high meat intake obtained from diet and/or nutritional supplements in humans. Design. Review. Subjects. Healthy adult male and female subjects. Method. In order to identify relevant studies, the electronic databases, Medline and Google Scholar, were searched using the terms:"high protein diet," "protein overconsumption," "protein overuse," and "high meat diet." Papers not in English were excluded. Further studies were identified by citations in retrieved papers. Results. 32 studies (21 experimental human studies and 11 reviews) were identified. The adverse effects associated with long-term high protein/high meat intake in humans were (a) disorders of bone and calcium homeostasis, (b) disorders of renal function, (c) increased cancer risk, (d) disorders of liver function, and (e) precipitated progression of coronary artery disease. Conclusions. The findings of the present study suggest that there is currently no reasonable scientific basis in the literature to recommend protein consumption above the current RDA (high protein diet) for healthy adults due to its potential disease risks. Further research needs to be carried out in this area, including large randomized controlled trials.

  12. Understanding and using the brief Implicit Association Test: recommended scoring procedures.

    Directory of Open Access Journals (Sweden)

    Brian A Nosek

    Full Text Available A brief version of the Implicit Association Test (BIAT has been introduced. The present research identified analytical best practices for overall psychometric performance of the BIAT. In 7 studies and multiple replications, we investigated analytic practices with several evaluation criteria: sensitivity to detecting known effects and group differences, internal consistency, relations with implicit measures of the same topic, relations with explicit measures of the same topic and other criterion variables, and resistance to an extraneous influence of average response time. The data transformation algorithms D outperformed other approaches. This replicates and extends the strong prior performance of D compared to conventional analytic techniques. We conclude with recommended analytic practices for standard use of the BIAT.

  13. Evaluation of the Canadian Rheumatology Association Choosing Wisely recommendation concerning anti-nuclear antibody (ANA) testing.

    Science.gov (United States)

    Ferrari, Robert

    2015-09-01

    The objective of this study was to evaluate the Canadian Rheumatology Association Choosing Wisely recommendation concerning anti-nuclear antibody (ANA) testing. Patients with joint pain/stiffness/swelling were assessed to determine if ANA testing was indicated. An a priori threshold was set before ANA testing would be considered. Those who did not have ANA testing ordered were followed for 1 year to determine if any of them went on to have a diagnosis of systemic lupus erythematosus (SLE) or other connective tissue disease. A parallel study was conducted with a similar a priori threshold for the use of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody testing in the diagnosis of rheumatoid arthritis (RA), and again, patients were followed for 1 year. A total of 866 subjects were examined, 509 females (58.8 %) and 357 males (41.2 %). The mean age of the group was 47.5 ± 16.8 years. The mean duration of symptoms was 12.0 ± 5.6 weeks. Of the 866 subjects, 68 met an a priori threshold for ordering ANA, RF, and anti-CCP testing. Of these 68, there was a newly diagnosed case of SLE, 4 newly diagnosed cases of RA, and 3 cases of polymyalgia rheumatica. The remaining 798 subjects were followed for approximately 1 year and none developed evidence of SLE, RA, or other connective tissue disease. In the evaluation of non-specific musculoskeletal symptoms, setting an a priori threshold for ordering serology in keeping with the spirit of the Canadian Rheumatology Association Choosing Wisely recommendation for antibody testing results in a very low risk of missing a case of systemic lupus erythematosus or rheumatoid arthritis.

  14. Kaposi's sarcoma associated herpesvirus (KSHV entry into target cells

    Directory of Open Access Journals (Sweden)

    Sayan eChakraborty

    2012-01-01

    Full Text Available Herpesvirus infection of target cells is a complex process involving multiple host cell surface molecules (receptors and multiple viral envelope glycoproteins. Kaposi’s sarcoma associated herpesvirus (KSHV or HHV-8 infects a variety of in vivo target cells such as endothelial cells, B cells, monocytes, epithelial cells, and keratinocytes. KSHV also infects a diversity of in vitro target cells and establishes in vitro latency in many of these cell types. KSHV interactions with the host cell surface molecules and its mode of entry in the various target cells are critical for the understanding of KSHV pathogenesis. KSHV is the first herpesvirus shown to interact with adherent target cell integrins and this interaction initiates the host cell pre-existing signal pathways that are utilized for successful infection. This chapter discusses the various aspects of the early stage of KSHV infection of target cells, receptors used and issues that need to be clarified and future directions. The various signaling events triggered by KSHV infection and the potential role of signaling events in the different stages of infection are summarized providing the framework and starting point for further detailed studies essential to fully comprehend the pathogenesis of KSHV.

  15. Ethics Guide Recommendations for Organ-Donation-Focused Physicians: Endorsed by the Canadian Medical Association.

    Science.gov (United States)

    Shemie, Sam D; Simpson, Christy; Blackmer, Jeff; MacDonald, Shavaun; Dhanani, Sonny; Torrance, Sylvia; Byrne, Paul

    2017-05-01

    Donation physicians are specialists with expertise in organ and tissue donation and have been recognized internationally as a key contributor to improving organ and tissue donation services. Subsequent to a 2011 Canadian Critical Care Society-Canadian Blood Services consultation, the donation physician role has been gradually implemented in Canada. These professionals are generally intensive care unit physicians with an enhanced focus and expertise in organ/tissue donation. They must manage the dual obligation of caring for dying patients and their families while providing and/or improving organ donation services. In anticipation of actual, potential or perceived ethical challenges with the role, Canadian Blood Services in partnership with the Canadian Medical Association organized the development of an evidence-informed consensus process of donation experts and bioethicists to produce an ethics guide. This guide includes overarching principles and benefits of the DP role, and recommendations in regard to communication with families, role disclosure, consent discussions, interprofessional conflicts, conscientious objection, death determination, donation specific clinical practices in neurological determination of death and donation after circulatory death, end-of-life care, performance metrics, resources and remuneration. Although this report is intended to inform donation physician practices, it is recognized that the recommendations may have applicability to other professionals (eg, physicians in intensive care, emergency medicine, neurology, neurosurgery, pulmonology) who may also participate in the end-of-life care of potential donors in various clinical settings. It is hoped that this guidance will assist practitioners and their sponsoring organizations in preserving their duty of care, protecting the interests of dying patients, and fulfilling best practices for organ and tissue donation.

  16. Prevention and treatment of skin lesions associated with non-invasive mechanical ventilation. Recommendations of experts.

    Science.gov (United States)

    Raurell-Torredà, M; Romero-Collado, A; Rodríguez-Palma, M; Farrés-Tarafa, M; Martí, J D; Hurtado-Pardos, B; Peñarrubia-San Florencio, L; Saez-Paredes, P; Esquinas, A M

    In the last two decades, non-invasive mechanical ventilation (NIV) has been consolidated as an initial strategy for the management of respiratory failure in critical adult and paediatric patients. To identify risk factors and preventive strategies to reduce the incidence of skin lesions associated with clinical devices (LESADIC) related to NIV, as well as the most effective treatment for injuries that cannot be avoided. Review in the MEDLINE, CINAHL and Cochrane databases of studies published in the last 10years to reach consensus through an expert panel. Knowledge about how to measure correct mask size and protection of the skin with foam or hydrocolloids dressings are factors related to the incidence of LESADIC, as it conditions the degree of pressure-friction and shear that the interface exerts on the skin. The interface that causes fewer LESADIC and is better tolerated is the face mask. When there are injuries, the first thing is to remove the interface that causes pressure on damaged skin, recommending a Helmet(®) hood as an alternative, treating the infection, managing the exudate and stimulating perilesional skin. The mask of choice is the facial, always using foam or hydrocolloid dressings on the nasal bridge. Evaluate the condition of the skin under the interface and harness every 4hours (recommended) and 11hours (maximum). Evaluate the rotation strategy of the interface at 24hours if the NIV is still needed on an ongoing basis. Copyright © 2017 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Molecular epidemiology tools in the management of healthcare-associated infections: towards the definition of recommendations.

    Science.gov (United States)

    Boccia, Stefania; Pasquarella, Cesira; Colotto, Marco; Barchitta, Martina; Quattrocchi, Annalisa; Agodi, Antonella

    2015-01-01

    Healthcare-Associated Infections (HAIs) are an important cause of morbidity and mortality worldwide and have a significant economic impact for health systems. Molecular epidemiology tools have a central role in HAI prevention programs. In order to give an overview of their specific advantages and disadvantages we reported current and new molecular typing methods for HAI outbreak detection and epidemiological surveillance. The current review was drafted as a short version of a longer document written by the Public Health Genomics (GSP) working group, and the Italian Study Group of Hospital Hygiene (GISIO), entitled Molecular epidemiology of Healthcare Associated Infections: recommendations from the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI). This text considers various aspects related to HAIs: the role of genotyping and bioinformatics, the organizational levels of laboratories, as well as ethical and economic aspects. The use of molecular epidemiology represents a key tool in the management of HAIs, to be used as a complement to conventional control measures. The present contribution aims to increase knowledge on the proper use of such methods, given the major challenge HAI represents for National Health systems.

  18. An ecosystem services approach to pesticide risk assessment and risk management of non-target terrestrial plant: recommendations from a SETAC Europe workshop

    NARCIS (Netherlands)

    Arts, G.H.P.; Dollinger, M.; Kohlschmid, E.; Maltby, L.; Ochoa-Acuna, H.; Poulsen, V.

    2015-01-01

    The registration of plant protection products (PPPs) in the EU is under Regulation 1107/2009, which recommends a tiered approach to assessing the risk to non-target terrestrial plants (NTTPs). However, little information is provided on how to perform and implement higher tier studies or how to use t

  19. Stratification and monitoring of natalizumab-associated progressive multifocal leukoencephalopathy risk: recommendations from an expert group.

    Science.gov (United States)

    McGuigan, C; Craner, M; Guadagno, J; Kapoor, R; Mazibrada, G; Molyneux, P; Nicholas, R; Palace, J; Pearson, O R; Rog, D; Young, C A

    2016-02-01

    The use of natalizumab for highly active relapsing-remitting multiple sclerosis (MS) is influenced by the occurrence of progressive multifocal leukoencephalopathy (PML). Through measurement of the anti-JCV antibody index, and in combination with the presence or absence of other known risk factors, it may be possible to stratify patients with MS according to their risk of developing PML during treatment with natalizumab and detect early suspected PML using MRI including a diffusion-weighted imaging sequence. This paper describes a practical consensus guideline for treating neurologists, based on current evidence, for the introduction into routine clinical practice of anti-JCV antibody index testing of immunosuppressant-naïve patients with MS, either currently being treated with, or initiating, natalizumab, based on their anti-JCV antibody status. Recommendations for the frequency and type of MRI screening in patients with varying index-associated PML risks are also discussed. This consensus paper presents a simple and pragmatic algorithm to support the introduction of anti-JCV antibody index testing and MRI monitoring into standard PML safety protocols, in order to allow some JCV positive patients who wish to begin or continue natalizumab treatment to be managed with a more individualised analysis of their PML risk.

  20. Promoter-associated RNAs and promoter-targeted RNAs.

    Science.gov (United States)

    Yan, Bing-Xue; Ma, Jin-Xia

    2012-09-01

    The world of RNAs is much more complex than previously thought, and has rapidly emerged as one of the most actively researched topics in the life sciences. Recently, two findings in this field were reported and given special attention: promoter-associated RNAs (paRNAs), a novel class of RNAs with numerous potential functions; and promoter-targeted RNA-induced transcriptional gene regulation, a new regulatory mechanism to control transcription. In this review, we summarize the studies in these two areas, and outline the current understanding with respect to the potential biological functions of paRNAs, and the molecular mechanisms of promoter-targeted RNA-induced transcriptional gene silencing and activation. Additionally, we seek to integrate these two areas, as paRNAs may have potential biological links with promoter-targeted RNA-induced transcriptional gene regulation. Finally, we will discuss the significance of identifying paRNAs and the possible use of promoter-targeted RNAs in gene regulation and therapy.

  1. Cancer-associated fibroblasts as targets for immunotherapy.

    Science.gov (United States)

    Kakarla, Sunitha; Song, Xiao-Tong; Gottschalk, Stephen

    2012-11-01

    Immunotherapy for solid tumors has shown promise in preclinical as well as early clinical studies. However, its efficacy remains limited. The hindrance to achieving objective, long-lasting therapeutic responses in solid tumors is, in part, mediated by the dynamic nature of the tumor and its complex microenvironment. Tumor-directed therapies fail to eliminate components of the microenvironment, which can reinstate a tumorigenic milieu and contribute to recurrence. Cancer-associated fibroblasts (CAFs) form the most preponderant cell type in the solid tumor microenvironment. Given their pervasive role in facilitating tumor growth and metastatic dissemination, CAFs have emerged as attractive therapeutic targets in the tumor microenvironment. In this article, we highlight the cross-talk between CAFs and cancer cells, and discuss how targeting CAFs has the potential to improve current immunotherapy approaches for cancer.

  2. Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target

    Energy Technology Data Exchange (ETDEWEB)

    Togo, Shinsaku, E-mail: shinsaku@juntendo.ac.jp [Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo 113-8412 (Japan); Polanska, Urszula M. [CR-UK Stromal-Tumour Interaction Group, Paterson Institute for Cancer Research, The University of Manchester, Wilmslow Road, Manchester M20 4BX (United Kingdom); Horimoto, Yoshiya [Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8412 (Japan); Atopy Research Centre, Juntendo University School of Medicine, Tokyo 113-8412 (Japan); Department of Breast Oncology, Juntendo University School of Medicine, Tokyo 113-8412 (Japan); Orimo, Akira, E-mail: shinsaku@juntendo.ac.jp [CR-UK Stromal-Tumour Interaction Group, Paterson Institute for Cancer Research, The University of Manchester, Wilmslow Road, Manchester M20 4BX (United Kingdom); Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8412 (Japan); Atopy Research Centre, Juntendo University School of Medicine, Tokyo 113-8412 (Japan)

    2013-01-31

    Human carcinomas frequently exhibit significant stromal reactions such as the so-called “desmoplastic stroma” or “reactive stroma”, which is characterised by the existence of large numbers of stromal cells and extracellular matrix proteins. Carcinoma-associated fibroblasts (CAFs), which are rich in activated fibroblast populations exemplified by myofibroblasts, are among the predominant cell types present within the tumour-associated stroma. Increased numbers of stromal myofibroblasts are often associated with high-grade malignancies with poor prognoses in humans. CAF myofibroblasts possess abilities to promote primary tumour development, growth and progression by stimulating the processes of neoangiogenesis as well as tumour cell proliferation, survival, migration and invasion. Moreover, it has been demonstrated that CAFs serve as a niche supporting the metastatic colonisation of disseminated carcinoma cells in distant organs. Their contribution to primary and secondary malignancies makes these fibroblasts a potential therapeutic target and they also appear to be relevant to the development of drug resistance and tumour recurrence. This review summarises our current knowledge of tumour-promoting CAFs and discusses the therapeutic feasibility of targeting these cells as well as disrupting heterotypic interactions with other cell types in tumours that may improve the efficacy of current anti-tumour therapies.

  3. The association between a journal’s source of revenue and the drug recommendations made in the articles it publishes

    Science.gov (United States)

    Becker, Annette; Dörter, Fatma; Eckhardt, Kirsten; Viniol, Annika; Baum, Erika; Kochen, Michael M.; Lexchin, Joel; Wegscheider, Karl; Donner-Banzhoff, Norbert

    2011-01-01

    Background There is evidence to suggest that pharmaceutical companies influence the publication and content of research papers. Most German physicians rely on journals for their continuing medical education. We studied the influence of pharmaceutical advertising on the drug recommendations made in articles published in 11 German journals that focus on continuing medical education. Methods We conducted a cross-sectional study of all of the issues of 11 journals published in 2007. Only journals frequently read by general practitioners were chosen. Issues were screened for pharmaceutical advertisements and recommendations made in the editorial content for a specified selection of drugs. Each journal was rated on a five-point scale according to the strength with which it either recommended or discouraged the use of these drugs. We looked for differences in these ratings between free journals (i.e., those financed entirely by pharmaceutical advertising), journals with mixed sources of revenue and journals financed solely by subscription fees. The journals were also screened for the simultaneous appearance of advertisements and recommendations for the same drug within a certain period, which was adjusted for both journal and class of drug. Results We identified 313 issues containing at least one advertisement for the selected drugs and 412 articles in which drug recommendations were made. Free journals were more likely to recommend the specified drugs than journals with sources of revenue that were mixed or based solely on subscriptions. The simultaneous appearance of advertisements and recommendations for the same drug in the same issue of a journal showed an inconsistent association. Interpretation Free journals almost exclusively recommended the use of the specified drugs, whereas journals financed entirely with subscription fees tended to recommend against the use of the same drugs. Doctors should be aware of this bias in their use of material published in medical

  4. The association between a journal's source of revenue and the drug recommendations made in the articles it publishes.

    Science.gov (United States)

    Becker, Annette; Dörter, Fatma; Eckhardt, Kirsten; Viniol, Annika; Baum, Erika; Kochen, Michael M; Lexchin, Joel; Wegscheider, Karl; Donner-Banzhoff, Norbert

    2011-03-22

    There is evidence to suggest that pharmaceutical companies influence the publication and content of research papers. Most German physicians rely on journals for their continuing medical education. We studied the influence of pharmaceutical advertising on the drug recommendations made in articles published in 11 German journals that focus on continuing medical education. We conducted a cross-sectional study of all of the issues of 11 journals published in 2007. Only journals frequently read by general practitioners were chosen. Issues were screened for pharmaceutical advertisements and recommendations made in the editorial content for a specified selection of drugs. Each journal was rated on a five-point scale according to the strength with which it either recommended or discouraged the use of these drugs. We looked for differences in these ratings between free journals (i.e., those financed entirely by pharmaceutical advertising), journals with mixed sources of revenue and journals financed solely by subscription fees. The journals were also screened for the simultaneous appearance of advertisements and recommendations for the same drug within a certain period, which was adjusted for both journal and class of drug. We identified 313 issues containing at least one advertisement for the selected drugs and 412 articles in which drug recommendations were made. Free journals were more likely to recommend the specified drugs than journals with sources of revenue that were mixed or based solely on subscriptions. The simultaneous appearance of advertisements and recommendations for the same drug in the same issue of a journal showed an inconsistent association. Free journals almost exclusively recommended the use of the specified drugs, whereas journals financed entirely with subscription fees tended to recommend against the use of the same drugs. Doctors should be aware of this bias in their use of material published in medical journals that focus on continuing medical

  5. Dendritic cell targeting vaccine for HPV-associated cancer

    Science.gov (United States)

    Yin, Wenjie; Duluc, Dorothée; Joo, HyeMee; Oh, SangKon

    2017-01-01

    Dendritic cells (DCs) are major antigen presenting cells that can efficiently prime and activate cellular immune responses. Delivering antigens to in vivo DCs has thus been considered as a promising strategy that could allow us to mount T cell-mediated therapeutic immunity against cancers in patients. Successful development of such types of cancer vaccines that can target in vivo DCs, however, requires a series of outstanding questions that need to be addressed. These include the proper selection of which DC surface receptors, specific DC subsets and DC activators that can further enhance the efficacy of vaccines by promoting effector T cell infiltration and retention in tumors and their actions against tumors. Supplementing these areas of research with additional strategies that can counteract tumor immune evasion mechanisms is also expected to enhance the efficacy of such therapeutic vaccines against cancers. After more than a decade of study, we have concluded that antigen targeting to DCs via CD40 to evoke cellular responses is more efficient than targeting antigens to the same types of DCs via eleven other DC surface receptors tested. In recent work, we have further demonstrated that a prototype vaccine (anti-CD40-HPV16.E6/7, a recombinant fusion protein of anti-human CD40 and HPV16.E6/7 protein) for HPV16-associated cancers can efficiently activate HPV16.E6/7-specific T cells, particularly CD8+ T cells, from the blood of HPV16+ head-and-neck cancer patients. Moreover, anti-CD40-HPV16.E6/7 plus poly(I:C) can mount potent therapeutic immunity against TC-1 tumor expressing HPV16.E6/7 protein in human CD40 transgenic mice. In this manuscript, we thus highlight our recent findings for the development of novel CD40 targeting immunotherapeutic vaccines for HPV16-associated malignancies. In addition, we further discuss several of key questions that still remain to be addressed for enhancing therapeutic immunity elicited by our prototype vaccine against HPV16

  6. Cardiomyopathy Associated With Targeted Therapy for Breast Cancer.

    Science.gov (United States)

    Sivagnanam, Kamesh; Rahman, Zia U; Paul, Timir

    2016-02-01

    Chemotherapeutic agents directed against human epidermal growth factor receptor 2 (HER-2) have significantly improved the prognosis of patients who are positive for this receptor. However, cardiomyopathy remains as a common adverse effect of using these agents. Literature search was conducted via PubMed using the keywords of "Trastuzumab Cardiomyopathy," "Lapatinib Cardiomyopathy" and "Pertuzumab Cardiomyopathy," which provided 104 results. These articles were then screened for relevance to the targeted subject based on their title and abstracts. Case reports and articles that were not discussing any aspect of cardiomyopathy secondary to targeted therapy for breast cancer and articles not in English were eliminated. After elimination, a bibliography search among selected articles was done and a total of 46 articles were identified. The collected articles were then meticulously analyzed and summarized. The use of human epidermal growth factor receptor 2 (HER-2) receptor targeted chemotherapy in breast cancer is limited because of a higher incidence (19-22%) of cardiomyopathy. The incidence of cardiomyopathy is not dose dependent and in most cases it is reversible after discontinuation of the drug and treatment with heart failure medications. Severe adverse outcomes including death or permanent disability are rare. HER-2 targeted chemotherapy for breast cancer has a higher incidence of associated reversible cardiomyopathy. Patients should be monitored by serial echocardiography starting at the beginning of the treatment and followed by every 3 months until the completion of chemotherapy. Co-ordination between oncologists and cardiologists is needed to develop evidence-based protocols to prevent, identify, monitor and treat trastuzumab-induced cardiomyopathy. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  7. New cholesterol guidelines for the management of atherosclerotic cardiovascular disease risk: a comparison of the 2013 American College of Cardiology/American Heart Association cholesterol guidelines with the 2014 National Lipid Association recommendations for patient-centered management of dyslipidemia.

    Science.gov (United States)

    Adhyaru, Bhavin B; Jacobson, Terry A

    2015-05-01

    This review discusses the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults and compares it with the 2014 National Lipid Association (NLA) Recommendations for Patient-Centered Management of Dyslipidemia. The review discusses some of the distinctions between the guidelines, including how to determine a patient's atherosclerotic cardiovascular disease risk, the role of lipoprotein treatment targets, the importance of moderate- and high-intensity statin therapy, and the use of nonstatin therapy in light of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial.

  8. Evidence-based guidelines for the pharmacological treatment of anxiety disorders : recommendations from the British Association for Psychopharmacology

    NARCIS (Netherlands)

    Baldwin, DS; Anderson, IM; Nutt, DJ; Bandelow, B; Bond, A; Davidson, JRT; den Boer, JA; Fineberg, NA; Knapp, M; Scott, J; Wittchen, HU

    2005-01-01

    These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve

  9. Guideline-recommended use of asthma medication by children is associated with parental information and knowledge : the PIAMA birth cohort

    NARCIS (Netherlands)

    Wijga, Alet H.; Zuidgeest, Mira G. P.; Kerkhof, Marjan; Koppelman, Gerard H.; Smit, Henriette A.; de Jongste, Johan C.

    2014-01-01

    PurposeWe investigated the use of asthma medication by children and the association of use as recommended by guidelines with modifiable risk factors: parental attitudes, knowledge of asthma medication and information provided by health care providers. MethodsQuestionnaire data were obtained from par

  10. Guideline-recommended use of asthma medication by children is associated with parental information and knowledge : the PIAMA birth cohort

    NARCIS (Netherlands)

    Wijga, Alet H.; Zuidgeest, Mira G. P.; Kerkhof, Marjan; Koppelman, Gerard H.; Smit, Henriette A.; de Jongste, Johan C.

    PurposeWe investigated the use of asthma medication by children and the association of use as recommended by guidelines with modifiable risk factors: parental attitudes, knowledge of asthma medication and information provided by health care providers. MethodsQuestionnaire data were obtained from

  11. Evidence-based guidelines for the pharmacological treatment of anxiety disorders : recommendations from the British Association for Psychopharmacology

    NARCIS (Netherlands)

    Baldwin, DS; Anderson, IM; Nutt, DJ; Bandelow, B; Bond, A; Davidson, JRT; den Boer, JA; Fineberg, NA; Knapp, M; Scott, J; Wittchen, HU

    2005-01-01

    These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve

  12. 2014 Update of the Canadian Rheumatology Association/spondyloarthritis research consortium of Canada treatment recommendations for the management of spondyloarthritis. Part I: principles of the management of spondyloarthritis in Canada.

    Science.gov (United States)

    Rohekar, Sherry; Chan, Jon; Tse, Shirley M L; Haroon, Nigil; Chandran, Vinod; Bessette, Louis; Mosher, Dianne; Flanagan, Cathy; Keen, Kevin J; Adams, Karen; Mallinson, Michael; Thorne, Carter; Rahman, Proton; Gladman, Dafna D; Inman, Robert D

    2015-04-01

    The Canadian Rheumatology Association (CRA) and the Spondyloarthritis Research Consortium of Canada (SPARCC) have collaborated to update the recommendations for the management of spondyloarthritis (SpA). A working group was assembled and consisted of the SPARCC executive committee, rheumatologist leaders from SPARCC collaborating sites, Canadian rheumatologists from across the country with an interest in SpA (both academic and community), a rheumatology trainee with an interest in SpA, an epidemiologist/health services researcher, a member of the CRA executive, a member of the CRA therapeutics committee, and a patient representative from the Canadian Spondylitis Association. An extensive review was conducted of literature published from 2007 to 2014 involving the management of SpA. The working group created draft recommendations using multiple rounds of Web-based surveys and an in-person conference. A survey was sent to the membership of the CRA to obtain an extended review that was used to finalize the recommendations. Guidelines for the management of SpA were created. Part I focuses on the principles of management of SpA in Canada and includes 6 general management principles, 5 ethical considerations, target groups for treatment recommendations, 2 wait time recommendations, and recommendations for disease monitoring. Also included are 6 modifications for application to juvenile SpA. These recommendations were developed based on current literature and applied to a Canadian healthcare context. It is hoped that the implementation of these recommendations will promote best practices in the treatment of SpA.

  13. The Association of Teachers of Preventive Medicine's Recommendations for Postgraduate Education in Prevention.

    Science.gov (United States)

    Collins, Terence R.; And Others

    1991-01-01

    Detailed recommendations for integrating preventive medicine into residency education and the continuum of medical care are outlined, with the goal of putting the patient's health rather than disease process into the forefront of primary care. Suggestions are based on a guide assessing the effectiveness of 169 types of preventive intervention.…

  14. Implementing the Association of Teachers of Preventive Medicine's Recommendations into the Undergraduate Medical School Curriculum.

    Science.gov (United States)

    Altekruse, Joan; And Others

    1991-01-01

    Ideas for integrating preventive medicine into the undergraduate medical curriculum include options for curricula in quantitative skills, clinical preventive medicine, primary care rotation, community health services, and independent continuing education. Recommendations are based on a guide assessing the effectiveness of 169 types of preventive…

  15. Counselees' Expressed Level of Understanding of the Risk Estimate and Surveillance Recommendation are Not Associated with Breast Cancer Surveillance Adherence.

    Science.gov (United States)

    Albada, Akke; van Dulmen, Sandra; Dijkstra, Henrietta; Wieffer, Ivette; Witkamp, Arjen; Ausems, Margreet G E M

    2016-04-01

    We studied counselees' expressed understanding of the risk estimate and surveillance recommendation in the final consultation for breast cancer genetic counseling in relation with their risk perception, worry and cancer surveillance adherence 1 year post-counseling. Consecutive counselees were included from 2008 to 2010. Counselees with an indication for diagnostic DNA-testing for themselves or a breast cancer affected relative were requested to complete online questionnaires before and after counseling and one year after counseling (N = 152-124). Self-reported surveillance was compared to surveillance recommendations. Consultations were videotaped. Counselees' reactions to the risks and recommendations were coded. Statements about the risk perception and surveillance intentions of breast cancer unaffected counselees were transcribed. Associations with outcomes were explored. Almost all breast cancer unaffected counselees (>90 %) reacted to their risk estimate with an utterance indicating understanding and this reaction was not significantly associated with their post-visit risk perception alignment. Over one-third (38.6 %) overestimated their risk post-counseling. Few counselees (5.8 %) expressed surveillance intentions. One year after counseling, about three-quarters (74.0 %) of the breast cancer unaffected counselees had adhered to the surveillance recommendation. Almost one-quarter (23.3 %) had performed more mammograms/MRI scans than recommended, which was associated with prior mammography uptake (n = 47; X (2)  = 5.2; p = .02). Counselees' post-counseling overestimation of their risk, high levels of worry and high surveillance uptake were not reflected in their reactions to the counselor's information during the final visit.

  16. Recommendations for responsible monitoring and regulation of clinical software systems. American Medical Informatics Association, Computer-based Patient Record Institute, Medical Library Association, Association of Academic Health Science Libraries, American Health Information Management Association, American Nurses Association.

    Science.gov (United States)

    Miller, R A; Gardner, R M

    1997-01-01

    In mid-1996, the FDA called for discussions on regulation of clinical software programs as medical devices. In response, a consortium of organizations dedicated to improving health care through information technology has developed recommendations for the responsible regulation and monitoring of clinical software systems by users, vendors, and regulatory agencies. Organizations assisting in development of recommendations, or endorsing the consortium position include the American Medical Informatics Association, the Computer-based Patient Record Institute, the Medical Library Association, the Association of Academic Health Sciences Libraries, the American Health Information Management Association, the American Nurses Association, the Center for Healthcare Information Management, and the American College of Physicians. The consortium proposes four categories of clinical system risks and four classes of measured monitoring and regulatory actions that can be applied strategically based on the level of risk in a given setting. The consortium recommends local oversight of clinical software systems, and adoption by healthcare information system developers of a code of good business practices. Budgetary and other constraints limit the type and number of systems that the FDA can regulate effectively. FDA regulation should exempt most clinical software systems and focus on those systems posing highest clinical risk, with limited opportunities for competent human intervention.

  17. Proportion of children meeting recommendations for 24-hour movement guidelines and associations with adiposity in a 12-country study

    OpenAIRE

    Roman-Viñas, Blanca; Chaput, Jean-Philippe; Peter T. Katzmarzyk; Fogelholm, Mikael; Estelle V. Lambert; Maher, Carol; Maia, Jose; Olds, Timothy; Onywera, Vincent; Sarmiento, Olga L.; Standage, Martyn; Tudor-Locke, Catrine; Tremblay, Mark S; ,

    2016-01-01

    Background The Canadian 24-h movement guidelines were developed with the hope of improving health and future health outcomes in children and youth. The purpose of this study was to evaluate adherence to the 3 recommendations most strongly associated with health outcomes in new 24-h movement guidelines and their relationship with adiposity (obesity and body mass index z-score) across countries participating in the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE)...

  18. Adverse Effects Associated with Protein Intake above the Recommended Dietary Allowance for Adults

    OpenAIRE

    Delimaris, Ioannis

    2013-01-01

    Background. While high-protein consumption—above the current recommended dietary allowance for adults (RDA: 0.8 g protein/kg body weight/day)—is increasing in popularity, there is a lack of data on its potential adverse effects. Objective. To determine the potential disease risks due to high protein/high meat intake obtained from diet and/or nutritional supplements in humans. Design. Review. Subjects. Healthy adult male and female subjects. Method. In order to identify relevant studies, the e...

  19. Risk factors and current recommendations for prevention of infections associated with central venous catheters: a literature review

    Directory of Open Access Journals (Sweden)

    Danielle de Mendonça Henrique

    2014-04-01

    Full Text Available Backgound and Objectives: Infections related to central venous catheter (CVC use constitute an important a problem. It is estimated that approximately 90% of bloodstream infections (BSI are caused by CVC use. This study aims at reviewing the risk factors and current recommendations for prevention of infections associated with central venous catheter use. Methods: A total of 12 articles published in the last 5 years and indexed in the databases of the Latin American and Caribbean Literature on Health Sciences (LILACS, Nursing Database (BDENF, International Literature on Health Sciences (Medline/Pubmed were selected, as well as publications related to the recommendations for BSI prevention, such as: Institute for Healthcare Improvement (IHI, Centers for Disease Control and Prevention (CDC and the National Health Surveillance Agency (ANVISA. Results: Two categories were identified: prevention and control measures and risk factors for BSI associated with central venous catheter use. Conclusions: Some recommendations that were well-defined over the years have been questioned by some authors and continuing training and education of the multidisciplinary team are the most important factors for the prevention of bloodstream infections associated with CVC use.

  20. Dermatologic adverse events associated with chemotherapy and targeted anticancer therapy

    Directory of Open Access Journals (Sweden)

    Maria Kowalska

    2016-05-01

    Full Text Available Chemotherapeutic agents and drugs used for targeted tumor therapy often cause undesirable side effects of the skin which typically are toxic cutaneous reactions (toxicity grade 1 to 4. The first group of drugs that cause toxicities affecting the skin are inhibitors of epidermal growth factor receptor (EGFR. They cause a variety of skin changes (PRIDE syndrome, which are mainly manifested by papulopustular rash, also referred to as acneiform rash, occurring in 44–74% of patients. Another drug which causes cutaneous toxicities is inhibitor of CTLA4 (cytotoxic T lymphocyte-associated protein 4, which is represented by ipilimumab, used in the treatment of metastatic melanoma. The most common dermatological adverse event, observed in 40–64% of patients receiving ipilimumab, is generalized maculopapular rash with pruritus and dry skin, and in some cases vitiligo is also observed. BRAF and MEK inhibitors introduced for the treatment of advanced melanoma also cause skin rashes. BRAF inhibitors also affecting the proliferation of keratinocytes stimulate hypertrophic changes and cause the whole spectrum of lesions from benign and keratoacanthoma to squamous cell carcinoma. A hedgehog pathway inhibitor (vismodegib is used for the treatment of metastatic basal cell carcinoma. The most common adverse events it causes are reversible alopecia and dysgeusia, but it can also cause the development of keratoacanthoma and squamous cell carcinoma. Among the most common side effects of chemotherapy and targeted therapy are toxic changes within the hands and feet (hand-foot skin reaction – HFSR that early manifest as a neurological symptoms (numbness, paresthesia, and skin symptoms (erythematous swelling changes, blisters, hyperkeratosis occur later. Anti-cancer drugs can also cause serious skin diseases such as Stevens-Johnson syndrome (SJS, toxic epidermal necrolysis (TEN and DRESS (drug rash with eosinophilia and systemic symptoms, whose course and prognosis

  1. Association of adherence to lifestyle recommendations and risk of colorectal cancer

    DEFF Research Database (Denmark)

    Kirkegaard, Helene; Johnsen, Nina Føns; Christensen, Jane

    2010-01-01

    have been prevented. Results were similar for colon and rectal cancer, but only statistically significant for colon cancer. CONCLUSIONS: Adherence to the recommendations for physical activity, waist circumference, smoking, alcohol intake, and diet may reduce colorectal cancer risk considerably...... on physical activity, waist circumference, smoking, alcohol intake, and diet (dietary fibre, energy percentage from fat, red and processed meat, and fruits and vegetables)) modelled through Cox regression. RESULTS: During a median follow-up of 9.9 years, 678 men and women had colorectal cancer diagnosed......: Prospective cohort study. SETTING: General population of Copenhagen and Aarhus, Denmark. PARTICIPANTS: 55 487 men and women aged 50-64 years at baseline (1993-7), not previously diagnosed with cancer. MAIN OUTCOME MEASURE: Risk of colorectal cancer in relation to points achieved in the lifestyle index (based...

  2. Recommendations for use of marginal donors in heart transplantation: Brazilian Association of Organs Transplantation guideline.

    Science.gov (United States)

    Fiorelli, A I; Stolf, N A G; Pego-Fernandes, P M; Oliveira Junior, J L; Santos, R H B; Contreras, C A M; Filho, D D L; Dinkhuysen, J J; Moreira, M C V; Mejia, J A C; Castro, M C R

    2011-01-01

    The high prevalence of heart failure has increased the candidate list for heart transplantation; however, there is a shortage of viable donated organs, which is responsible for the high mortality of patients awaiting a transplantation. Because the marginal donor presents additional risk factors, it is not considered to be an ideal donor. The use of a marginal donor is only justified in situations when the risk of patient death due to heart disease is greater than that offered by the donor. These recommendations sought to expand the supply of donors, consequently increasing the transplant rate. We selected articles based on robust evidence to provide a substratum to develop recommendations for donors who exceed the traditional acceptance criteria. Recipient survival in the immediate postoperative period is intimately linked to allograft quality. Primary allograft failure is responsible for 38% to 40% of immediate deaths after heart transplantation: therefore; marginal donor selection must be more rigorous to not increase the surgical risk. The main donor risk factors with the respective evidence levels are: cancer in the donor (B), female donor (B), donor death due to hemorrhagic stroke (B), donor age above 50 years (relative risk [RR] = 1.5) (B), weight mismatch between donor and recipient 240 minutes (RR = 1.2) (B), left ventricular dysfunction with ejection fraction below 45% (B), and use of high doses of vasoactive drugs (dopamine > 15 mg/kg·min) (B). Factors that impact recipient mortality are: age over 50 years (RR = 1.5); allograft harvest at a distance; adult recipient weighing more than 20% of the donor; high doses of vasoactive drugs (dopamine greater than 15 mg/kg·min) and ischemic time >4 hours. The use of a marginal donor is only justified when it is able to increase life expectancy compared with clinical treatment, albeit the outcomes are interior to those using an ideal donor.

  3. Targeting TBP-associated factors in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Jennifer R Ribeiro

    2014-03-01

    Full Text Available As ovarian tumors progress, they undergo a process of dedifferentiation, allowing adaptive changes in growth and morphology that promote metastasis and chemoresistance. Herein, we outline a hypothesis that TATA-box binding protein (TBP associated factors (TAFs, which compose the RNA Polymerase II initiation factor, TFIID, contribute to regulation of dedifferentiation states in ovarian cancer. Numerous studies demonstrate that TAFs regulate differentiation and proliferation states; their expression is typically high in pluripotent cells and reduced upon differentiation. Strikingly, TAF2 exhibits copy number increases or mRNA overexpression in 73% of high grade serous ovarian cancers (HGSC. At the biochemical level, TAF2 directs TFIID to TATA-less promoters by contact with an Initiator element, which may lead to the deregulation of the transcriptional output of these tumor cells. TAF4, which is altered in 66% of HGSC, is crucial for the stability of the TFIID complex and helps drive dedifferentiation of mouse embryonic fibroblasts to induced pluripotent stem cells. Its ovary-enriched paralog, TAF4B, is altered in 26% of HGSC. Here, we show that Taf4b mRNA correlates with Cyclin D2 mRNA expression in human granulosa cell tumors. TAF4B may also contribute to regulation of tumor microenvironment due to its estrogen-responsiveness and ability to act as a cofactor for NFκB. Conversely, TAF9, a cofactor for p53 in regulating apoptosis, may act as a tumor suppressor in ovarian cancer, since it is downregulated or deleted in 98% of HGSC. We conclude that a greater understanding of mechanisms of transcriptional regulation that execute signals from oncogenic signaling cascades is needed in order to expand our understanding of the etiology and progression of ovarian cancer, and most importantly to identify novel targets for therapeutic intervention.

  4. Spanish adaptation of the recommendations for the appropriate use of social networks in urology of the European Association of Urology.

    Science.gov (United States)

    Rodríguez-Socarrás, M E; Gómez-Rivas, J; Álvarez-Maestro, M; Tortolero, L; Ribal, M J; Garcia Sanz, M; Roupret, M

    2016-09-01

    To adapt to Spanish the recommendations for the appropriate use of social media (SoMe) in the urological setting prepared by the European Association of Urology (EAU). The use of SoMe has become fairly popular in the international urological community. Due to the nature of the medical content shared among healthcare professionals through SoMe, however, there is the risk of medical and legal problems. For this reason, various international urological associations such as the American Urological Association, the British Association of Urological Surgeons and EAU have published their recommendations for the appropriate use of social media. Efforts have been made to adapt and summarise the recommendations of the EAU in Spanish and to publish them in Actas Urológicas Españolas (@actasurologicas), the official journal of the Spanish Urological Association (@InfoAEU) and the American Confederation of Urology (@CAU_URO). SoMe include well-known platforms such as Twitter, Facebook and YouTube, which have undoubtedly changed the way in which people communicate and interact. SoMe offer clear advantages for communicating between professionals, working in teams, disseminating knowledge and creating professional profiles and are increasingly used by patients and healthcare practitioners. The introduction of SoMe in the urological community has started a revolution in how scientific articles are shared, how people participate in congresses and how international urological associations communicate with their followers. However, SoMe is generally an open public setting, with potential risks for confidentiality and the doctor-patient relationship due to the nature of the shared information. The present recommendations include tools for creating professional profiles, protecting confidentiality and creating honest and responsible content. SoMe represents a fascinating area for the communication and dissemination of knowledge, with considerable applicability in health care and the

  5. Clustering of unhealthy lifestyle behaviors is associated with a low adherence to recommended preventive practices among COPD patients in Spain.

    Science.gov (United States)

    de Miguel-Díez, Javier; Jiménez-García, Rodrigo; Hernández-Barrera, Valentín; Maestu, Luis Puente; Aparicio, Irene Jarana; Ramos, Alicia Oliva; López de Andrés, Ana; Carrasco-Garrido, Pilar

    2014-08-01

    To analyze clustering of unhealthy lifestyle behavior and its relationship with non-adherence to recommended clinical preventive care services among Spanish COPD patients. Cross-sectional study including 2,575 COPD subjects from the 2006 Spanish National Health Survey (NHS) and 2009 European Health Survey for Spain (EHISS). Subjects were asked about the following recommended preventive practices: uptake of blood pressure (BP) measurement, lipid profile, influenza vaccination and dental examination. Lifestyle behaviors included: smoking status, physical activity, alcohol consumption and obesity. Logistic regression models were built to assess the association between clustering of unhealthy lifestyle and the uptake of preventive activities. Blood pressure measurement in the previous 6 months and a blood lipid test in the last year had not been taken by 11.74% and 23.26% of the subjects, respectively, in 2006 NHS and by 11.16% and 16.33% of the subjects, respectively, in EHISS 2009. Then, 36.36% percent had not been vaccinated and 70.61% had not received dental examination in 2006 NHS and these percentages decreased to 27.33% and 66.22%, respectively, in 2009 EHISS. A higher number of unhealthy lifestyle behaviors increased the probability of not being vaccinated and not having a dental examination. Clustering of unhealthy lifestyle behaviors is linearly associated with a greater number of preventive measures unfulfilled. Compliance with healthy lifestyles and adherence to recommended clinical preventive services is under desirable levels among Spanish COPD patients. Patients with lifestyles considered as "worse" are those who also have lower uptake of recommended preventive activities.

  6. Cinacalcet and achievement of the NKF/K-DOQI recommended target values for bone and mineral metabolism in real-world clinical practice--the ECHO observational study

    DEFF Research Database (Denmark)

    Urena, P.; Jacobson, S.H.; Zitt, E.

    2009-01-01

    /dl) at baseline, despite being prescribed conventional therapies. The proportions of patients achieving the recommended [NKF-K/DOQI(TM) (KDOQI(TM))] targets increased from baseline [4%, 39%, 40% and 46% for iPTH, phosphorus, calcium and calcium-phosphorus product (Ca x P), respectively] to Month 12 (28%, 48%, 51......% and 68%, respectively). At Month 12, 18% of patients had achieved the combined target for iPTH + Ca x P compared with 2% at baseline. Most patients (65%) received ... sevelamer; use of calcium-based phosphate binders increased by 5.6%. There was no unexpected safety or tolerability concerns. CONCLUSION: This analysis of current European clinical practice shows that-consistent with findings from randomized controlled trials and retrospective observational studies...

  7. General Report & Recommendations in Predictive, Preventive and Personalised Medicine 2012: White Paper of the European Association of Predictive, Preventive and Personalised Medicine

    Directory of Open Access Journals (Sweden)

    Golubnitschaja Olga

    2012-11-01

    Full Text Available Abstract This report is the collective product of word-leading experts working in the branches of integrative medicine by predictive, preventive and personalised medicine (PPPM under the coordination of the European Association for Predictive, Preventive and Personalised Medicine. The general report has been prepared as the consortium document proposed at the EPMA World Congress 2011 which took place in Bonn, Germany. This forum analyzed the overall deficits and trends relevant for the top-science and daily practice in PPPM focused on the patient. Follow-up consultations resulted in a package of recommendations for consideration by research units, educators, healthcare industry, policy-makers, and funding bodies to cover the current knowledge deficit in the field and to introduce integrative approaches for advanced diagnostics, targeted prevention, treatments tailored to the person and cost-effective healthcare.

  8. Fluctuations in Echo Level Associated with Changes in Target Aspect and Target Frequency Response (abstract only)

    NARCIS (Netherlands)

    Zampolli, M.; Ainslie, M.A.; Zon, T. van

    2011-01-01

    Ping-to-ping variations in echo level can be caused by time variations in sonar parameters (source level, orientation), target aspect, relative and absolute motion of sonar and target, and time varying environment (e.g. surface waves). Quantifying and understanding such fluctuations are important,

  9. Fluctuations in Echo Level Associated with Changes in Target Aspect and Target Frequency Response (abstract only)

    NARCIS (Netherlands)

    Zampolli, M.; Ainslie, M.A.; Zon, T. van

    2011-01-01

    Ping-to-ping variations in echo level can be caused by time variations in sonar parameters (source level, orientation), target aspect, relative and absolute motion of sonar and target, and time varying environment (e.g. surface waves). Quantifying and understanding such fluctuations are important, s

  10. A Comprehensive Review of the Literature Supporting Recommendations From the Canadian Diabetes Association for the Use of a Plant-Based Diet for Management of Type 2 Diabetes.

    Science.gov (United States)

    Rinaldi, Sylvia; Campbell, Emily E; Fournier, John; O'Connor, Colleen; Madill, Janet

    2016-10-01

    Type 2 diabetes mellitus is considered one of the fastest growing diseases in Canada, representing a serious public health concern. Thus, clinicians have begun targeting modifiable risk factors to manage type 2 diabetes, including dietary patterns such as a plant-based diets (PBDs). The Canadian Diabetes Association has included PBDs among the recommended dietary patterns to be used in medical nutrition therapy for persons with type 2 diabetes. To support knowledge translation, this review summarizes the current literature relating to PBDs and the prevalence of type 2 diabetes, its clinical applications and its acceptability in the management of type 2 diabetes as well as its application in community settings. This comprehensive review seeks to close the literature gap by providing background and rationale to support the use of PBDs as medical nutrition therapy. Within this review is support from large observational studies, which have shown that PBDs were associated with lower prevalence of type 2 diabetes. As well, intervention studies have shown that PBDs were just as effective, if not more effective, than other diabetes diets in improving body weight, cardiovascular risk factors, insulin sensitivity, glycated hemoglobin levels, oxidative stress markers and renovascular markers. Furthermore, patient acceptability was comparable to other diabetes diets, and PBDs reduced the need for diabetes medications. Diabetes education centres in Canada could improve patients' perceptions of PBDs by developing PBD-focused education and support as well as providing individualized counselling sessions addressing barriers to change. The development of more standardized and user-friendly PBD practice guidelines could overcome the disparity in recommendations and, thereby, increase how frequently practitioners recommend PBDs. Based on current published research, PBDs lend support in the management of type 2 diabetes.

  11. On family-based genome-wide association studies with large pedigrees: observations and recommendations

    OpenAIRE

    Fardo, David W.; Zhang, Xue; Ding, Lili; He, Hua; Kurowski, Brad; Alexander, Eileen S.; Mersha, Tesfaye B.; Pilipenko, Valentina; Kottyan, Leah; Nandakumar, Kannabiran; Martin, Lisa

    2014-01-01

    Family based association studies are employed less often than case-control designs in the search for disease-predisposing genes. The optimal statistical genetic approach for complex pedigrees is unclear when evaluating both common and rare variants. We examined the empirical power and type I error rates of 2 common approaches, the measured genotype approach and family-based association testing, through simulations from a set of multigenerational pedigrees. Overall, these results suggest that ...

  12. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    McAlindon, T. E.; Driban, J. B.; Henrotin, Y.;

    2015-01-01

    The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct...... and index knee, describing interventions, patient-reported and physical performance measures, structural outcome measures, biochemical biomarkers, and reporting recommendations. In summary, the working group identified 25 recommendations that represent the current best practices regarding clinical trials...... that target symptom or structure modification among individuals with knee OA. These updated recommendations incorporate novel technologies (e.g., magnetic resonance imaging (MRI)) and strategies to address the heterogeneity of knee OA....

  13. Recommendations for high-risk clinical target volume definition with computed tomography for three-dimensional image-guided brachytherapy in cervical cancer patients.

    Science.gov (United States)

    Ohno, Tatsuya; Wakatsuki, Masaru; Toita, Takafumi; Kaneyasu, Yuko; Yoshida, Ken; Kato, Shingo; Li, Noriko; Tokumaru, Sunao; Ikushima, Hitoshi; Uno, Takashi; Noda, Shin-Ei; Kazumoto, Tomoko; Harima, Yoko

    2016-11-10

    Our purpose was to develop recommendations for contouring the computed tomography (CT)-based high-risk clinical target volume (CTVHR) for 3D image-guided brachytherapy (3D-IGBT) for cervical cancer. A 15-member Japanese Radiation Oncology Study Group (JROSG) committee with expertise in gynecological radiation oncology initiated guideline development for CT-based CTVHR (based on a comprehensive literature review as well as clinical experience) in July 2014. Extensive discussions occurred during four face-to-face meetings and frequent email communication until a consensus was reached. The CT-based CTVHR boundaries were defined by each anatomical plane (cranial-caudal, lateral, or anterior-posterior) with or without tumor progression beyond the uterine cervix at diagnosis. Since the availability of magnetic resonance imaging (MRI) with applicator insertion for 3D planning is currently limited, T2-weighted MRI obtained at diagnosis and just before brachytherapy without applicator insertion was used as a reference for accurately estimating the tumor size and topography. Furthermore, utilizing information from clinical examinations performed both at diagnosis and brachytherapy is strongly recommended. In conclusion, these recommendations will serve as a brachytherapy protocol to be used at institutions with limited availability of MRI for 3D treatment planning.

  14. Advancing nursing home practice: the International Association of Geriatrics and Gerontology Recommendations.

    Science.gov (United States)

    Tolson, Debbie; Morley, John E; Rolland, Yves; Vellas, Bruno

    2011-01-01

    Recognition of the urgent need to improve the provision of long-term care, as well as the known variations in standards of nursing home care around the world, prompted the International Association of Geriatrics and Gerontology (IAGG), in association with the World Health Organization (WHO), to form a task force. This task force was charged with the identification of the key concerns, research priorities, and actions that would enhance the care provided to older people in nursing homes. Nurses are equipped with the knowledge to take a leadership role in the IAGG/WHO initiative, and the task force eagerly seeks their input.

  15. The Books Recommend Service System Based on Improved Algorithm for Mining Association Rules

    Institute of Scientific and Technical Information of China (English)

    王萍

    2009-01-01

    The Apriori algorithm is a classical method of association rules mining. Based on analysis of this theory, the paper provides an improved Apriori algorithm. The paper puts foward with algorithm combines HASH table technique and reduction of candidate item sets to en-hance the usage efficiency of resources as well as the individualized service of the data library.

  16. Recommended documentation of evapotranspiration measurements and associated weather data and a review of requirements for accuracy

    Science.gov (United States)

    More and more evapotranspiration (ET) models, ET crop coefficients, and associated measurements of ET are reported in the literature. These measurements base from a range of measurement systems including lysimeters, eddy covariance, Bowen ratio, water balance (gravimetric, neutron meter, other soil ...

  17. Undermining and bullying in surgical training: A review and recommendations by the Association of Surgeons in Training.

    Science.gov (United States)

    Wild, J R L; Ferguson, H J M; McDermott, F D; Hornby, S T; Gokani, V J

    2015-11-01

    The 2012 General Medical Council National Trainees' Survey found that 13% of UK trainees had experienced undermining or bullying in the workplace. The Association of Surgeons in Training subsequently released a position statement raising concerns stemming from these findings, including potential compromise to patient safety. This article considers the impact of such behaviour on the NHS, and makes recommendations for creating a positive learning environment within the NHS at national, organisational, and local levels. The paper also discusses the nature of issues within the UK, and pathways through which trainees can seek help.

  18. Is statin-associated cognitive impairment clinically relevant? A narrative review and clinical recommendations.

    Science.gov (United States)

    Rojas-Fernandez, Carlos H; Cameron, Jean-Christy F

    2012-04-01

    To explore the impact of statin use on cognition. A literature search was performed using MEDLINE (1950-November 2011), EMBASE (1980-November 2011), and the Cochrane Library (1960-November 2011) using the search terms "cognition/drug effects," "delirium, dementia, amnestic, cognitive disorders/chemically induced," "memory disorders/chemically induced," "hydroxymethylglutaryl-CoA reductase inhibitors/adverse effects," and "hydroxymethylglutaryl-CoA reductase inhibitors." A bibliographic search on included references was also conducted. Studies were included for analysis if they were conducted in humans and examined the impact of statin use on cognition as either a primary or secondary endpoint; case reports and case series were also included for analysis. Reports of statin-associated cognitive impairment were found primarily in observational studies (eg, case reports/series). One randomized controlled trial demonstrated that simvastatin impaired some measures of cognition compared to placebo. Conversely, in the majority of randomized controlled trials and observational studies, statins were found to have either a neutral or beneficial effect on cognition. Preliminary data suggest that statins that are less lipophilic (ie, pravastatin and rosuvastatin) may be less likely to contribute to cognitive impairment due to limited penetration across the blood-brain barrier. These drugs would be a logical alternative in cases where cognitive impairment secondary to another statin is suspected. Despite several reports of statin-associated cognitive impairment, this adverse effect remains a rare occurrence among the totality of the literature. If statin-associated cognitive impairment is suspected, a trial discontinuation can reveal a temporal relationship. Switching from lipophilic to hydrophilic statins may resolve cognitive impairment. The vascular benefits and putative cognitive benefits outweigh the risk of cognitive impairment associated with statin use; therefore, the

  19. Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson's Disease

    Institute of Scientific and Technical Information of China (English)

    Xiao-Houg Wang; Lin Zhang; Laura Sperry; John Olichney; Sarah Tomaszewski Farias; Kiarash Shahlaie; Norika Malhado Chang

    2015-01-01

    Objective: This review examines the evidence that deep brain stimulation (DBS) has extensive impact on nonmotor symptoms (NMSs) of patients with Parkinson's disease (PD).Data Sources: We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus intemus (GPi), subthalamic nucleus (STN), and ventral intermediate thalamic nucleus.Study Selection: We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances.For psychological symptoms and cognitive impairment, we tried to use more reliable proofs: Random, control, multicenter, large sample sizes, and long period follow-up clinical studies.We categorized the NMSs into four groups: those that would improve definitively following DBS;those that are not significantly affected by DBS;those that remain controversial on their surgical benefit;and those that can be worsened by DBS.Results: In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results;Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS;The impact of DBS on behavioral addictions and dysphagia is still uncertain.Conclusions: As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients.

  20. Guidelines for preventing health-care--associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee.

    Science.gov (United States)

    Tablan, Ofelia C; Anderson, Larry J; Besser, Richard; Bridges, Carolyn; Hajjeh, Rana

    2004-03-26

    This report updates, expands, and replaces the previously published CDC "Guideline for Prevention of Nosocomial Pneumonia". The new guidelines are designed to reduce the incidence of pneumonia and other severe, acute lower respiratory tract infections in acute-care hospitals and in other health-care settings (e.g., ambulatory and long-term care institutions) and other facilities where health care is provided. Among the changes in the recommendations to prevent bacterial pneumonia, especially ventilator-associated pneumonia, are the preferential use of oro-tracheal rather than naso-tracheal tubes in patients who receive mechanically assisted ventilation, the use of noninvasive ventilation to reduce the need for and duration of endotracheal intubation, changing the breathing circuits of ventilators when they malfunction or are visibly contaminated, and (when feasible) the use of an endotracheal tube with a dorsal lumen to allow drainage of respiratory secretions; no recommendations were made about the use of sucralfate, histamine-2 receptor antagonists, or antacids for stress-bleeding prophylaxis. For prevention of health-care--associated Legionnaires disease, the changes include maintaining potable hot water at temperatures not suitable for amplification of Legionella spp., considering routine culturing of water samples from the potable water system of a facility's organ-transplant unit when it is done as part of the facility's comprehensive program to prevent and control health-care--associated Legionnaires disease, and initiating an investigation for the source of Legionella spp. when one definite or one possible case of laboratory-confirmed health-care--associated Legionnaires disease is identified in an inpatient hemopoietic stem-cell transplant (HSCT) recipient or in two or more HSCT recipients who had visited an outpatient HSCT unit during all or part of the 2-10 day period before illness onset. In the section on aspergillosis, the revised recommendations

  1. Target-Based Maintenance of Privacy Preserving Association Rules

    Science.gov (United States)

    Ahluwalia, Madhu V.

    2011-01-01

    In the context of association rule mining, the state-of-the-art in privacy preserving data mining provides solutions for categorical and Boolean association rules but not for quantitative association rules. This research fills this gap by describing a method based on discrete wavelet transform (DWT) to protect input data privacy while preserving…

  2. In vivo Target Residence Time and Kinetic Selectivity: The Association Rate Constant as Determinant.

    Science.gov (United States)

    de Witte, Wilhelmus E A; Danhof, Meindert; van der Graaf, Piet H; de Lange, Elizabeth C M

    2016-10-01

    It is generally accepted that, in conjunction with pharmacokinetics, the first-order rate constant of target dissociation is a major determinant of the time course and duration of in vivo target occupancy. Here we show that the second-order rate constant of target association can be equally important. On the basis of the commonly used mathematical models for drug-target binding, it is shown that a high target association rate constant can increase the (local) concentration of the drug, which decreases the rate of decline of target occupancy. The increased drug concentration can also lead to increased off-target binding and decreased selectivity. Therefore, the kinetics of both target association and dissociation need to be taken into account in the selection of drug candidates with optimal pharmacodynamic properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Association between guideline recommended drugs and death in older adults with multiple chronic conditions: population based cohort study.

    Science.gov (United States)

    Tinetti, Mary E; McAvay, Gail; Trentalange, Mark; Cohen, Andrew B; Allore, Heather G

    2015-10-02

    To estimate the association between guideline recommended drugs and death in older adults with multiple chronic conditions. Population based cohort study. Medicare Current Beneficiary Survey cohort, a nationally representative sample of Americans aged 65 years or more. 8578 older adults with two or more study chronic conditions (atrial fibrillation, coronary artery disease, chronic kidney disease, depression, diabetes, heart failure, hyperlipidemia, hypertension, and thromboembolic disease), followed through 2011. Drugs included β blockers, calcium channel blockers, clopidogrel, metformin, renin-angiotensin system (RAS) blockers; selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs); statins; thiazides; and warfarin. Adjusted hazard ratios for death among participants with a condition and taking a guideline recommended drug relative to participants with the condition not taking the drug and among participants with the most common combinations of four conditions. Over 50% of participants with each condition received the recommended drugs regardless of coexisting conditions; 1287/8578 (15%) participants died during the three years of follow-up. Among cardiovascular drugs, β blockers, calcium channel blockers, RAS blockers, and statins were associated with reduced mortality for indicated conditions. For example, the adjusted hazard ratio for β blockers was 0.59 (95% confidence interval 0.48 to 0.72) for people with atrial fibrillation and 0.68 (0.57 to 0.81) for those with heart failure. The adjusted hazard ratios for cardiovascular drugs were similar to those with common combinations of four coexisting conditions, with trends toward variable effects for β blockers. None of clopidogrel, metformin, or SSRIs/SNRIs was associated with reduced mortality. Warfarin was associated with a reduced risk of death among those with atrial fibrillation (adjusted hazard ratio 0.69, 95% confidence interval 0.56 to 0.85) and

  4. Targeting danger-associated molecular patterns after myocardial infarction

    NARCIS (Netherlands)

    van Hout, Geert; Arslan, Fatih; Pasterkamp, Gerard; Hoefer, Imo E

    2016-01-01

    INTRODUCTION: Myocardial infarction (MI) provokes an intense inflammatory response that can lead to left ventricular adverse remodeling and heart failure (HF). The prognosis of HF patients is poor and related to a decreased quality of life and considerable health care costs. Hence, targeting the ear

  5. Mammalian target of rapamycin inhibitor-associated stomatitis

    NARCIS (Netherlands)

    Boers-Doets, C.B.; Raber-Durlacher, J.E.; Treister, N.S.; Epstein, J.B.; Arends, A.B.P.; Wiersma, D.R.; Lalla, R.V.; Logan, R.M.; van Erp, N.R.P.; Gelderblom, H.

    2013-01-01

    With the recent introduction of inhibitors of mammalian target of rapamycin (mTOR) in oncology, distinct cutaneous and oral adverse events have been identified. In fact, stomatitis and rash are documented as the most frequent and potentially dose-limiting side effects. Clinically, mTOR inhibitor-ass

  6. European Association of Urology (@Uroweb) recommendations on the appropriate use of social media.

    Science.gov (United States)

    Rouprêt, Morgan; Morgan, Todd M; Bostrom, Peter J; Cooperberg, Matthew R; Kutikov, Alexander; Linton, Kate D; Palou, Joan; Martínez-Piñeiro, Luis; van der Poel, Henk; Wijburg, Carl; Winterbottom, Andrew; Woo, Henry H; Wirth, Manfred P; Catto, James W F

    2014-10-01

    Social media use is becoming common in medical practice. Although primarily used in this context to connect physicians, social media allows users share information, to create an online profile, to learn and keep knowledge up to date, to facilitate virtual attendance at medical conferences, and to measure impact within a field. However, shared content should be considered permanent and beyond the control of its author, and typical boundaries, such as the patient-physician interaction, become blurred, putting both parties at risk. The European Association of Urology brought together a committee of stakeholders to create guidance on the good practice and standards of use of social media. These encompass guidance about defining an online profile; managing accounts; protecting the reputations of yourself and your organization; protecting patient confidentiality; and creating honest, responsible content that reflects your standing as a physician and your membership within this profession.

  7. Higher adherence to a diet score based on American Heart Association recommendations is associated with lower odds of allostatic load and metabolic syndrome in Puerto Rican adults.

    Science.gov (United States)

    Mattei, Josiemer; Bhupathiraju, Shilpa; Tucker, Katherine L

    2013-11-01

    A score based on diet and lifestyle recommendations from the AHA has been associated with cardiovascular risk factors. We aimed to assess whether the diet components alone were associated with metabolic syndrome (MetS) and allostatic load (AL; a composite measure of 10 physiologically dysregulated variables). The diet score ranged from 0 to 90 and included intake components for dietary fats, fruits and vegetables, whole grains, salt, added sugars, and alcohol and was tested in a cross-sectional analysis of 1318 Puerto Rican adults (aged 45-75 y; 72% women) living in Boston, MA. The mean ± SD diet score was 28.0 ± 9.9 for men and 30.0 ± 10.1 for women. Replicating findings from a previous study in this cohort that used both the diet and lifestyle components, we observed associations between the diet-only score and insulin, waist circumference, and HDL cholesterol. We found novel significant associations between the continuous diet score and AL components, namely an inverse association with urinary cortisol and a positive association with serum dehydroepiandrosterone sulfate in women as well as an inverse association with urinary norepinephrine in men (all P diet score units were associated with 22% (95% CI: 1, 38; P = 0.043) lower odds of having ≥6 (vs. ≤2) dysregulated AL components in women. In men, every 10 diet score units were associated with lower odds of MetS (OR: 0.69; 95% CI: 0.52, 0.93; P = 0.016). Following AHA recommendations for a healthy diet may protect against the development of components of MetS and AL in Puerto Rican adults.

  8. Practice guidelines for perioperative transesophageal echocardiography: Recommendations of the Indian association of cardiovascular thoracic anesthesiologists

    Directory of Open Access Journals (Sweden)

    Kanchi Muralidhar

    2013-01-01

    Full Text Available Transoesophageal Echocardiography (TEE is now an integral part of practice of cardiac anaesthesiology. Advances in instrumentation and the information that can be obtained from the TEE examination has proceeded at a breath-taking pace since the introduction of this technology in the early 1980s. Recognizing the importance of TEE in the management of surgical patients, the American Societies of Anesthesiologists (ASA and the Society of Cardiac Anesthesiologists, USA (SCA published practice guidelines for the clinical application of perioperative TEE in 1996. On a similar pattern, Indian Association of Cardiac Anaesthesiologists (IACTA has taken the task of putting forth guidelines for transesophageal echocardiography (TEE to standardize practice across the country. This review assesses the risks and benefits of TEE for several indications or clinical scenarios. The indications for this review were drawn from common applications or anticipated uses as well as current clinical practice guidelines published by various society practicing Cardiac Anaesthesia and cardiology . Based on the input received, it was determined that the most important parts of the TEE examination could be displayed in a set of 20 cross sectional imaging planes. These 20 cross sections would provide also the format for digital acquisition and storage of a comprehensive TEE examination. Because variability exists in the precise anatomic orientation between the heart and the esophagus in individual patients, an attempt was made to provide specific criteria based on identifiable anatomic landmarks to improve the reproducibility and consistency of image acquisition for each of the standard cross sections.

  9. Standardised reporting protocol for endoscopic resection for Barrett oesophagus associated neoplasia: expert consensus recommendations.

    Science.gov (United States)

    Kumarasinghe, M P; Brown, I; Raftopoulos, S; Bourke, M J; Charlton, A; de Boer, W B; Eckstein, R; Epari, K; Gill, A J; Lam, A K; Price, T; Streutker, C; Lauwers, G Y

    2014-10-01

    Endoscopic resection (ER) is considered the therapy of choice for intraepithelial neoplasia associated with visible lesions and T1a adenocarcinoma. Pathologists are bound to encounter specimens collected via these techniques more frequently in their practice. A standardised protocol for handling, grossing, and assessing ER specimens should be adopted to ensure that all prognostic information and characteristics influencing treatment are included in reports (see Supplementary Video Abstract, http://links.lww.com/PAT/A22). The entire specimen should be appropriately oriented, processed and assessed. An ER specimen will commonly show intraepithelial neoplasia or invasive carcinoma. There are essential features that should be recorded if invasive carcinoma is found as they dictate further management and follow-up. These features are the margin status, depth of invasion, degree of differentiation and presence or absence of lymphovascular invasion. Important features such as duplication of muscularis mucosae should be recognised to avoid misinterpretation of depth of invasion. Key diagnostic and prognostic elements that are essential for optimal clinical decisions have been included in the reporting format proposed by the Structured Pathology Reporting committee of the Royal College of Pathologists of Australasia (RCPA).

  10. Factors associated with compliance with recommendations for liver cancer screening in Korea: a nationwide survey in Korea.

    Science.gov (United States)

    Park, Boyoung; Choi, Kui Son; Suh, Mina; Shin, Ji-Yeon; Jun, Jae Kwan

    2013-01-01

    To investigate the factors associated with compliance with recommendations regarding liver cancer screening intervals and methods among individuals at high-risk for liver cancer in the Republic of Korea. We used data from the fourth Korean National Health and Nutrition Examination Survey (KNHANES IV), a representative cross-sectional nationwide survey conducted between 2007 and 2009. The liver cancer screening rate and factors associated with compliance with recommended screening intervals (6 months) and methods (both abdominal ultrasonography and serum alpha-fetoprotein testing) among individuals at high risk for liver cancer such as hepatitis B virus (HBV) carriers were investigated. Out of 24,871 KNHANES IV participants, 604 HBV carriers aged ≥ 20 years were included in our analysis. 39.6% of our study sample reported attending liver cancer screening at least once in their lifetime, 12.3% had attended within the previous 6 months, and 14.6% were screened using both recommended methods. Older age was associated with increased compliance with screening intervals (P-trend 0.011) and methods (40-49 year: OR = 3.25, 95% CI: 1.62-6.51; 50-59 years: OR = 3.09, 95% CI: 1.44-6.66; 60-69 years: OR = 3.17, 95% CI: 1.28-7.82). Unawareness of HBV infection status was negatively related to compliance with screening intervals and methods (OR = 0.30, 95% CI: 0.17-0.53; OR = 0.45, 95% CI: 0.26-0.79). Female sex (OR = 0.45, 95% CI: 0.25-0.78), lower household income (P-trend 0.011), and routine and manual occupations (OR = 0.46, 95% CI: 0.22-0.97) were associated with decreased compliance with screening methods. The liver cancer screening rate among high-risk individuals is much less suboptimal. Considering that those unaware of their HBV infection status got regular and complete liver cancer screening much less often, efforts should be made not only to decrease sociodemographic disparities, but also to better identify the high-risk population.

  11. Consultant outcomes publication and surgical training: Consensus recommendations by the association of surgeons in training.

    Science.gov (United States)

    Mohan, Helen M; Gokani, Vimal J; Williams, Adam P; Harries, Rhiannon L

    2016-11-01

    Consultant Outcomes Publication (COP) has the longest history in cardiothoracic surgery, where it was introduced in 2005. Subsequently COP has been broadened to include all surgical specialties in NHS England in 2013-14. The Association of Surgeons in Training (ASiT) fully supports efforts to improve patient care and trust in the profession and is keen to overcome potential unintended adverse effects of COP. Identification of these adverse effects is the first step in this process: Firstly, there is a risk that COP may lead to reluctance by consultants to provide trainees with the necessary appropriate primary operator experience to become skilled consultant surgeons for the future. Secondly, COP may lead to inappropriately cautious case selection. This adjusted case mix affects both patients who are denied operations, and also limits the complexity of the case mix to which surgical trainees are exposed. Thirdly, COP undermines efforts to train surgical trainees in non-technical skills and human factors, simply obliterating the critical role of the multidisciplinary team and organisational processes in determining outcomes. This tunnel vision masks opportunities to improve patient care and outcomes at a unit level. It also misinforms the public as to the root causes of adverse events by failing to identify care process deficiencies. Finally, for safe surgical care, graduate retention and morale is important - COP may lead to high calibre trainees opting out of surgical careers, or opting to work abroad. The negative effects of COP on surgical training and trainees must be addressed as high quality surgical training and retention of high calibre graduates is essential for excellent patient care. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  12. An ecosystem services approach to pesticide risk assessment and risk management of non-target terrestrial plants: recommendations from a SETAC Europe workshop.

    Science.gov (United States)

    Arts, Gertie H P; Dollinger, Margit; Kohlschmid, Eva; Maltby, Lorraine; Ochoa-Acuña, Hugo; Poulsen, Véronique

    2015-02-01

    The registration of plant protection products (PPPs) in the EU is under Regulation 1107/2009, which recommends a tiered approach to assessing the risk to non-target terrestrial plants (NTTPs). However, little information is provided on how to perform and implement higher tier studies or how to use them to refine the risk assessments. Therefore, a stakeholder workshop was organized to consolidate current knowledge and expertise to aid the further development of testing and assessment procedures for NTTPs. This brief communication highlights the agreed recommendations of the workshop, which relate to the three main themes, i.e. specific protection goals, risk assessment and mitigation. The participants of the workshop adopted the European Food Safety Authority (EFSA) approach of using an ecosystem services framework for identifying specific protection goals. First, delivery and protection of ecosystem services were discussed for in-crop, in-field and off-crop, and off-field areas. Second, lower and higher tier risk assessment methods, including modelling approaches, were evaluated. Third, options for risk mitigation of spray drift and run-off were discussed and evaluated. Several important knowledge gaps were identified, and specific data collation and literature-based tasks were actioned to begin to address them. A full workshop report is planned for the fall of 2014.

  13. Recommendations from multi-disciplinary focus groups on cascade testing and genetic counseling for fragile X-associated disorders.

    Science.gov (United States)

    McConkie-Rosell, Allyn; Abrams, Liane; Finucane, Brenda; Cronister, Amy; Gane, Louise W; Coffey, Sarah M; Sherman, Stephanie; Nelson, Lawrence M; Berry-Kravis, Elizabeth; Hessl, David; Chiu, Sufen; Street, Natalie; Vatave, Ajay; Hagerman, Randi J

    2007-10-01

    The purpose of this paper is to report the outcome of a collaborative project between the Fragile X Research and Treatment Center at the Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute at the University of California at Davis, the National Fragile X Foundation (NFXF), and the Centers for Disease Control and Prevention (CDC). The objective of this collaboration was to develop and disseminate protocols for genetic counseling and cascade testing for the multiple disorders associated with the fragile X mental retardation 1 (FMR1) mutation. Over the last several years, there has been increasing insight into the phenotypic range associated with both the premutation and the full mutation of the FMR1 gene. To help develop recommendations related to screening for fragile X-associated disorders, four, two day advisory focus group meetings were conducted, each with a different theme. The four themes were: (1) fragile X-associated tremor/ataxia syndrome (FXTAS); (2) premature ovarian failure (POF) and reproductive endocrinology; (3) psychiatric, behavioral and psychological issues; and (4) population screening and related ethical issues.

  14. Trust for intelligent recommendation

    CERN Document Server

    Bhuiyan, Touhid

    2013-01-01

    Recommender systems are one of the recent inventions to deal with the ever-growing information overload in relation to the selection of goods and services in a global economy. Collaborative Filtering (CF) is one of the most popular techniques in recommender systems. The CF recommends items to a target user based on the preferences of a set of similar users known as the neighbors, generated from a database made up of the preferences of past users. In the absence of these ratings, trust between the users could be used to choose the neighbor for recommendation making. Better recommendations can b

  15. Physical activity and exercise recommendations for stroke survivors: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

    Science.gov (United States)

    Billinger, Sandra A; Arena, Ross; Bernhardt, Julie; Eng, Janice J; Franklin, Barry A; Johnson, Cheryl Mortag; MacKay-Lyons, Marilyn; Macko, Richard F; Mead, Gillian E; Roth, Elliot J; Shaughnessy, Marianne; Tang, Ada

    2014-08-01

    This scientific statement provides an overview of the evidence on physical activity and exercise recommendations for stroke survivors. Evidence suggests that stroke survivors experience physical deconditioning and lead sedentary lifestyles. Therefore, this updated scientific statement serves as an overall guide for practitioners to gain a better understanding of the benefits of physical activity and recommendations for prescribing exercise for stroke survivors across all stages of recovery. Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statement Oversight Committee and the American Heart Association's Manuscript Oversight Committee. The writers used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and indicate gaps in current knowledge. Physical inactivity after stroke is highly prevalent. The assessed body of evidence clearly supports the use of exercise training (both aerobic and strength training) for stroke survivors. Exercise training improves functional capacity, the ability to perform activities of daily living, and quality of life, and it reduces the risk for subsequent cardiovascular events. Physical activity goals and exercise prescription for stroke survivors need to be customized for the individual to maximize long-term adherence. The recommendation from this writing group is that physical activity and exercise prescription should be incorporated into the management of stroke survivors. The promotion of physical activity in stroke survivors should emphasize low- to moderate-intensity aerobic activity, muscle-strengthening activity, reduction of sedentary behavior, and risk management for secondary prevention of stroke. © 2014 American Heart Association, Inc.

  16. Performance evaluation of three computed radiography systems using methods recommended in American Association of Physicists in Medicine Report 93

    Directory of Open Access Journals (Sweden)

    Wilbroad Muhogora

    2011-01-01

    Full Text Available The performances of three clinical computed radiography (CR systems, (Agfa CR 75 (with CRMD 4.0 image plates, Kodak CR 850 (with Kodak GP plates and Kodak CR 850A (with Kodak GP plates were evaluated using six tests recommended in American Association of Physicists in Medicine Report 93. The results indicated variable performances with majority being within acceptable limits. The variations were mainly attributed to differences in detector formulations, plate readers′ characteristics, and aging effects. The differences of the mean low contrast scores between the imaging systems for three observers were statistically significant for Agfa and Kodak CR 850A (P=0.009 and for Kodak CR systems (P=0.006 probably because of the differences in ages. However, the differences were not statistically significant between Agfa and Kodak CR 850 (P=0.284 suggesting similar perceived image quality. The study demonstrates the need to implement quality control program regularly.

  17. The non-medical workforce and its role in surgical training: Consensus recommendations by the Association of Surgeons in Training.

    Science.gov (United States)

    Gokani, Vimal J; Peckham-Cooper, Adam; Bunting, David; Beamish, Andrew J; Williams, Adam; Harries, Rhiannon L

    2016-11-01

    Changes in the delivery of the healthcare structure have led to the expansion of the non-medical workforce (NMW). The non-medical practitioner in surgery (a healthcare professional without a medical degree who undertakes specialist training) is a valuable addition to a surgical firm. However, there are a number of challenges regarding the successful widespread implementation of this role. This paper outlines a number of these concerns, and makes recommendations to aid the realisation of the non-medical practitioner as a normal part of the surgical team. In summary, the Association of Surgeons in Training welcomes the development of the non-medical workforce as part of the surgical team in order to promote enhanced patient care and improved surgical training opportunities. However, establishing a workforce of independent/semi-independent practitioners who compete for the same training opportunities as surgeons in training may threaten the UK surgical training system, and therefore the care of our future patients.

  18. Achievement of recommended glucose and blood pressure targets in patients with type 2 diabetes and hypertension in clinical practice – study rationale and protocol of DIALOGUE

    Directory of Open Access Journals (Sweden)

    Gitt Anselm K

    2012-12-01

    Full Text Available Abstract Background Patients with type 2 diabetes have 2–4 times greater risk for cardiovascular morbidity and mortality than those without, and this is even further aggravated if they also suffer from hypertension. Unfortunately, less than one third of hypertensive diabetic patients meet blood pressure targets, and more than half fail to achieve target HbA1c values. Thus, appropriate blood pressure and glucose control are of utmost importance. Since treatment sometimes fails in clinical practice while clinical trials generally suggest good efficacy, data from daily clinical practice, especially with regard to the use of newly developed anti-diabetic and anti-hypertensive compounds in unselected patient populations, are essential. The DIALOGUE registry aims to close this important gap by evaluating different treatment approaches in hypertensive type 2 diabetic patients with respect to their effectiveness and tolerability and their impact on outcomes. In addition, DIALOGUE is the first registry to determine treatment success based on the new individualized treatment targets recommended by the ADA and the EASD. Methods DIALOGUE is a prospective observational German multicentre registry and will enrol 10,000 patients with both diabetes and hypertension in up to 700 sites. After a baseline visit, further documentations are scheduled at 6, 12 and 24 months. There are two co-primary objectives referring to the most recent guidelines for the treatment of diabetes and hypertension: 1 individual HbA1c goal achievement with respect to anti-diabetic pharmacotherapy and 2 individual blood pressure goal achievement with different antihypertensive treatments. Among the secondary objectives the rate of major cardio-vascular and cerebro-vascular events (MACCE and the rate of hospitalizations are the most important. Conclusion The registry will be able to gain insights into the reasons for the obvious gap between the demonstrated efficacy and safety of anti

  19. Detecting slowly moving infrared targets using temporal filtering and association strategy

    Institute of Scientific and Technical Information of China (English)

    Jing-li GAO; Cheng-lin WEN; Zhe-jing BAO; Mei-qin LIU

    2016-01-01

    The special characteristics of slowly moving infrared targets, such as containing only a few pixels, shapeless edge, low signal-to-clutter ratio, and low speed, make their detection rather difficult, especially when immersed in complex backgrounds. To cope with this problem, we propose an effective infrared target detection algorithm based on temporal target detection and association strategy. First, a temporal target detection model is developed to segment the interested targets. This model contains mainly three stages, i.e., temporal fi ltering, temporal target fusion, and cross-product fi ltering. Then a graph matching model is presented to associate the targets obtained at different times. The association relies on the motion characteristics and appearance of targets, and the association operation is performed many times to form continuous trajectories which can be used to help disambiguate targets from false alarms caused by random noise or clutter. Experimental results show that the proposed method can detect slowly moving infrared targets in complex backgrounds accurately and robustly, and has superior detection performance in comparison with several recent methods.

  20. Online Aggressor/Targets, Aggressors, and Targets: A Comparison of Associated Youth Characteristics

    Science.gov (United States)

    Ybarra, Michele L.; Mitchell, Kimberly J.

    2004-01-01

    Background: While most youth report positive experiences and activities online, little is known about experiences of Internet victimization and associated correlates of youth, specifically in regards to Internet harassment. Methods: The Youth Internet Safety Survey is a cross-sectional, nationally representative telephone survey of young regular…

  1. Higher adherence to Mediterranean diet prior to pregnancy is associated with decreased risk for deviation from the maternal recommended gestational weight gain.

    Science.gov (United States)

    Koutelidakis, Antonios E; Alexatou, Olga; Kousaiti, Savvina; Gkretsi, Elisavet; Vasios, George; Sampani, Anastasia; Tolia, Maria; Kiortsis, Dimitrios N; Giaginis, Constantinos

    2017-06-14

    The present retrospective study was conducted on 1482 women in order to evaluate whether their pre-pregnancy adherence to the Mediterranean diet may affect maternal gestational weight gain (GWG). For this purpose, the study population was classified according to the Institute of Medicine (IOM) recommendations concerning GWG. Pre-pregnancy adherence to the Mediterranean diet was assessed with 11 food patterns groups based on their contribution in the Mediterranean diet pyramid. Women with high adherence to the Mediterranean diet were more frequently characterised by GWG inside the IOM recommendations. In multivariate analysis, women with low Mediterranean diet adherence were almost twice at risk in presenting deflection from recommended GWG regardless of various confounding factors. These findings suggested that high pre-pregnancy adherence to the Mediterranean diet may be associated with reduced risk for GWG outside the IOM recommendations. However, larger prospective studies are strongly recommended in order for more precise conclusions to be drawn.

  2. Breast cancer screening: updated recommendations of the Brazilian College of Radiology and Diagnostic Imaging, Brazilian Breast Disease Society, and Brazilian Federation of Gynecological and Obstetrical Associations

    Science.gov (United States)

    Urban, Linei Augusta Brolini Dellê; Chala, Luciano Fernandes; Bauab, Selma di Pace; Schaefer, Marcela Brisighelli; dos Santos, Radiá Pereira; Maranhão, Norma Medicis de Albuquerque; Kefalas, Ana Lucia; Kalaf, José Michel; Ferreira, Carlos Alberto Pecci; Canella, Ellyete de Oliveira; Peixoto, João Emílio; de Amorim, Heverton Leal Ernesto; de Camargo Junior, Helio Sebastião Amâncio

    2017-01-01

    Objective To present the current recommendations for breast cancer screening in Brazil, as devised by the Brazilian College of Radiology and Diagnostic Imaging, the Brazilian Breast Disease Society, and the Brazilian Federation of Gynecological and Obstetrical Associations. Materials and methods We analyzed scientific studies available in the Medline and Lilacs databases. In the absence of evidence, the recommendations reflected the consensus of a panel of experts. Recommendations Annual mammography screening is recommended for women 40-74 years of age. Among women ≥ 75 years of age, annual mammography screening should be reserved for those with an expected survival > 7 years. Complementary ultrasound should be considered for women with dense breasts. Complementary magnetic resonance imaging is recommended for women at high risk. When available, an advanced form of mammography known as tomosynthesis can be considered as a means of screening for breast cancer. PMID:28894332

  3. Non-exchangeability of running vs. other exercise in their association with adiposity, and its implications for public health recommendations.

    Directory of Open Access Journals (Sweden)

    Paul T Williams

    Full Text Available PURPOSE: Current physical activity recommendations assume that different activities can be exchanged to produce the same weight-control benefits so long as total energy expended remains the same (exchangeability premise. To this end, they recommend calculating energy expenditure as the product of the time spent performing each activity and the activity's metabolic equivalents (MET, which may be summed to achieve target levels. The validity of the exchangeability premise was assessed using data from the National Runners' Health Study. METHODS: Physical activity dose was compared to body mass index (BMI and body circumferences in 33,374 runners who reported usual distance run and pace, and usual times spent running and other exercises per week. MET hours per day (METhr/d from running was computed from: a time and intensity, and b reported distance run (1.02 MET • hours per km. RESULTS: When computed from time and intensity, the declines (slope±SE per METhr/d were significantly greater (P<10(-15 for running than non-running exercise for BMI (slopes±SE, male: -0.12 ± 0.00 vs. 0.00±0.00; female: -0.12 ± 0.00 vs. -0.01 ± 0.01 kg/m(2 per METhr/d and waist circumference (male: -0.28 ± 0.01 vs. -0.07±0.01; female: -0. 31±0.01 vs. -0.05 ± 0.01 cm per METhr/d. Reported METhr/d of running was 38% to 43% greater when calculated from time and intensity than distance. Moreover, the declines per METhr/d run were significantly greater when estimated from reported distance for BMI (males: -0.29 ± 0.01; females: -0.27 ± 0.01 kg/m(2 per METhr/d and waist circumference (males: -0.67 ± 0.02; females: -0.69 ± 0.02 cm per METhr/d than when computed from time and intensity (cited above. CONCLUSION: The exchangeability premise was not supported for running vs. non-running exercise. Moreover, distance-based running prescriptions may provide better weight control than time-based prescriptions for running or other activities. Additional longitudinal studies

  4. Study on the Customer targeting using Association Rule Mining

    Directory of Open Access Journals (Sweden)

    Surendiran.R

    2010-10-01

    Full Text Available Data mining is one of the widest area where many researches takes place to mine desired and hidden data. There are many different approaches to find the hidden data. This paper deals with Frequent Pattern growth algorithm which follows association rule concept togroup the required data items. Using this method of mining time can be reduced to a greater extent. This paper contains implementation of a real time system; the implementation is about making a survey on the group of people and their mobile connection’s service providers.End result contains the set of people from a particular age group with their support and confidence for the service provider they have chosen. Based on which any decisions can be made by service providers to enhance their business and attain many customers.

  5. TARGET:?

    National Research Council Canada - National Science Library

    James M Acton

    2014-01-01

      By 2003. as military planners had become worried that the country's long-range conventional weapons, such as cruise missiles, might be too slow to reach hypothetical distant targets that needed to be struck urgently...

  6. Pathways Targeted by Antidiabetes Drugs Are Enriched for Multiple Genes Associated With Type 2 Diabetes Risk

    NARCIS (Netherlands)

    Segre, Ayellet V.; Wei, Nancy; Altshuler, David; Florez, Jose C.; Wijmenga, T. N.; Ostaptchouk, J. V.

    2015-01-01

    Genome-wide association studies (GWAS) have uncovered >65 common variants associated with type 2 diabetes (T2D); however, their relevance for drug development is not yet clear. Of note, the first two T2D-associated loci (PPARG and KCNJ11/ABCC8) encode known targets of antidiabetes medications. We th

  7. Validation of static IMRT. TG-119 recommendations of the American Association of Physicists in Medicine; Validacion de IMRT estatica. Recomendaciones TG-119 de la AAPM

    Energy Technology Data Exchange (ETDEWEB)

    Gomez Barrado, A.; Sanchez Jimenez, E.; Sanchez-Reyes, A.

    2013-07-01

    The implementation of radiotherapy by intensity modulated (IMRT) requires a series of previous checks that ensure the quality of the treatments. There are several national and international recommendations, and of which we highlight the conclusions of the Task Group 119 from the American Association of Physicists in Medicine (AAPM). This work describes the implementation and results of the tests proposed in the recommendations of the AAPM TG-1191, to validate an improved model of our linear accelerator (LINAC) in our Planner system. (Author)

  8. Unrelated adult stem cell donor medical suitability: recommendations from the World Marrow Donor Association Clinical Working Group Committee.

    Science.gov (United States)

    Lown, R N; Philippe, J; Navarro, W; van Walraven, S M; Philips-Johnson, L; Fechter, M; Pawson, R; Bengtsson, M; Beksac, M; Field, S; Yang, H; Shaw, B E

    2014-07-01

    The World Marrow Donor Association (WMDA) fosters collaboration between international registries to facilitate the exchange of hematopoietic stem cell products for unrelated stem cell donor transplantation. As indications for hematopoietic SCT grow, the movement of products across the world will increase. Although competent authorities may regulate products within their country, there is a need to protect the best interests of donors and recipients by identifying universal donor medical suitability criteria. Within this report the WMDA provides a background to unrelated adult donor and recipient safety, recommends a common framework for assessing the health of unrelated adult donors at each stage of the donation pathway and presents a novel mechanism for sharing international consensus criteria for individual medical and lifestyle conditions. Wherever possible, these criteria are evidence-based. By establishing a donor medical suitability working group, the WMDA has developed a process through which donor centers and registries may request a consensus opinion on conditions not already listed, as well as challenge existing criteria. Guidance from the WMDA is intended to complement, not supersede, guidance from national competent authorities and international regulatory bodies.

  9. Music, music therapy and dementia: a review of literature and the recommendations of the Italian Psychogeriatric Association.

    Science.gov (United States)

    Raglio, A; Bellelli, G; Mazzola, P; Bellandi, D; Giovagnoli, A R; Farina, E; Stramba-Badiale, M; Gentile, S; Gianelli, M V; Ubezio, M C; Zanetti, O; Trabucchi, M

    2012-08-01

    This study reviews the most recent (from 2000 to 2011) Clinical Controlled Trials (CCT) and Randomized Controlled Trials (RCT) concerning the use of music and music-therapy (MT) in the context of dementia and related issues. Studies which explored the efficacy of music and MT on behavioral and psychological symptoms of dementia (BPSD) are prevalent, while those aiming at assessing a potential effect of these approaches on cognitive and physiological aspects are scant. Although with some limitations, the results of these studies are consistent with the efficacy of MT approach on BPSD. In this context, the ability of the music therapist to directly interact with the patients appears to be crucial for the success of the intervention. This review was endorsed by the Italian Psychogeriatric Association (AIP) and represents its view about the criteria to select appropriate music and MT approaches in the field of dementia. Accordingly, we have developed a list of recommendations to facilitate the current use of these techniques in the context of non-pharmacological treatments for patients with dementia.

  10. Pathways targeted by antidiabetes drugs are enriched for multiple genes associated with type 2 diabetes risk.

    Science.gov (United States)

    Segrè, Ayellet V; Wei, Nancy; Altshuler, David; Florez, Jose C

    2015-04-01

    Genome-wide association studies (GWAS) have uncovered >65 common variants associated with type 2 diabetes (T2D); however, their relevance for drug development is not yet clear. Of note, the first two T2D-associated loci (PPARG and KCNJ11/ABCC8) encode known targets of antidiabetes medications. We therefore tested whether other genes/pathways targeted by antidiabetes drugs are associated with T2D. We compiled a list of 102 genes in pathways targeted by marketed antidiabetic medications and applied Gene Set Enrichment Analysis (MAGENTA [Meta-Analysis Gene-set Enrichment of variaNT Associations]) to this gene set, using available GWAS meta-analyses for T2D and seven quantitative glycemic traits. We detected a strong enrichment of drug target genes associated with T2D (P = 2 × 10(-5); 14 potential new associations), primarily driven by insulin and thiazolidinedione (TZD) targets, which was replicated in an independent meta-analysis (Metabochip). The glycemic traits yielded no enrichment. The T2D enrichment signal was largely due to multiple genes of modest effects (P = 4 × 10(-4), after removing known loci), highlighting new associations for follow-up (ACSL1, NFKB1, SLC2A2, incretin targets). Furthermore, we found that TZD targets were enriched for LDL cholesterol associations, illustrating the utility of this approach in identifying potential side effects. These results highlight the potential biomedical relevance of genes revealed by GWAS and may provide new avenues for tailored therapy and T2D treatment design. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  11. Randomized Trial of Central Nervous System–Targeted Antiretrovirals for HIV-Associated Neurocognitive Disorder

    Science.gov (United States)

    Ellis, Ronald J.; Letendre, Scott; Vaida, Florin; Haubrich, Richard; Heaton, Robert K.; Sacktor, Ned; Clifford, David B.; Best, Brookie M.; May, Susanne; Umlauf, Anya; Cherner, Mariana; Sanders, Chelsea; Ballard, Craig; Simpson, David M.; Jay, Cheryl; McCutchan, J. Allen

    2014-01-01

    Background. Antiretroviral (ARV) medications differentially penetrate across the blood-brain barrier into central nervous system (CNS) tissues, potentially influencing their effectiveness in treating brain infection. Methods. This randomized controlled clinical trial (RCT) called for 120 participants at 5 study sites to be randomized 1:1 to CNS-targeted (CNS-T) or non–CNS-T ART. Entry clinical factors such as ARV experience were balanced across arms using an adaptive randomization approach. The primary outcome, change in neurocognitive performance, was measured as the difference in global deficit score (GDS) from baseline to week 16. Results. The study was terminated early on the recommendation of its data safety monitoring board on the basis of slow accrual and a low likelihood of detecting a difference in the primary outcome. No safety concerns were identified. Of 326 participants screened, 59 met entry criteria and were randomized. The primary intent-to-treat analysis included 49 participants who completed week 16. These comprised 39 men and 10 women with a mean age of 44 years (SD, 10 years), and median nadir and current CD4+ T-cell counts of 175 cells/µL and 242 cells/µL, respectively. The proportional improvement in GDS from baseline was nonsignificantly larger (7%; 95% confidence interval [CI], −31% to 62%) in the CNS-T arm than in the non-CNS-T arm, representing a treatment effect size of 0.09 (95% CI, −.48 to .65). Prespecified secondary analysis showed a trend interaction (P = .087), indicating that participants who had baseline plasma virologic suppression may have benefited from CNS-T. Conclusions. This study found no evidence of neurocognitive benefit for a CNS-T strategy in HIV-associated neurocognitive disorders. A benefit for a subgroup or small overall benefits could not be excluded. Clinical Trials Registration NCT00624195. PMID:24352352

  12. Is adherence to diet, physical activity, and body weight cancer prevention recommendations associated with colorectal cancer incidence in African American women?

    Science.gov (United States)

    Nomura, Sarah J O; Dash, Chiranjeev; Rosenberg, Lynn; Yu, Jeffrey; Palmer, Julie R; Adams-Campbell, Lucile L

    2016-07-01

    The purpose of this study was to evaluate whether adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations was associated with colorectal cancer incidence in the Black Women's Health Study (BWHS). In this ongoing prospective cohort of African American women (analytic cohort n = 49,103), 354 incident colorectal cancers were diagnosed between baseline (1995) and 2011. Adherence scores for seven WCRF/AICR recommendations (adherent = 1 point, non-adherent level 1 = 0.5 points, non-adherent level 2 = 0 points) were created using questionnaire data and summed to an overall adherence score (maximum = 7). Recommendation adherence and colorectal cancer incidence were evaluated using baseline and time-varying data in Cox regression models. At baseline, 8.5 % of women adhered >4 recommendations. In time-varying analyses, the HR was 0.98 (95 % CI 0.84-1.15) per 0.5 point higher score and 0.51 (95 % CI 0.23-1.10) for adherence to >4 compared to Adherence to individual recommendations was not associated with colorectal cancer risk. Results were similar in models that considered baseline exposures only. Adherence to cancer prevention recommendations was low and not associated with colorectal cancer risk among women in the BWHS. Research in diverse populations is essential to evaluate the validity of existing recommendations, and assess whether there are alternative recommendations that are more beneficial for cancer prevention in specific populations.

  13. Counselees' Expressed Level of Understanding of the Risk Estimate and Surveillance Recommendation are Not Associated with Breast Cancer Surveillance Adherence

    NARCIS (Netherlands)

    Albada, Akke; van Dulmen, Sandra; Dijkstra, Henrietta; Wieffer, Ivette; Witkamp, Arjen; Ausems, Margreet G E M

    We studied counselees' expressed understanding of the risk estimate and surveillance recommendation in the final consultation for breast cancer genetic counseling in relation with their risk perception, worry and cancer surveillance adherence 1 year post-counseling. Consecutive counselees were

  14. Counselees' Expressed Level of Understanding of the Risk Estimate and Surveillance Recommendation are Not Associated with Breast Cancer Surveillance Adherence

    NARCIS (Netherlands)

    Albada, A.; Dulmen, S. van; Dijkstra, H.; Wieffer, I.; Witkamp, A.; Ausems, M.G.

    2016-01-01

    We studied counselees' expressed understanding of the risk estimate and surveillance recommendation in the final consultation for breast cancer genetic counseling in relation with their risk perception, worry and cancer surveillance adherence 1 year post-counseling. Consecutive counselees were

  15. Counselees’ expressed level of understanding of the risk estimate and surveillance recommendation are not associated with breast cancer surveillance adherence.

    NARCIS (Netherlands)

    Albada, A.; Dulmen, S. van; Dijkstra, H.; Wieffer, I.; Witkamp, A.; Ausems, M.G.E.M.

    2016-01-01

    We studied counselees’ expressed understanding of the risk estimate and surveillance recommendation in the final consultation for breast cancer genetic counseling in relation with their risk perception, worry and cancer surveillance adherence 1 year post-counseling. Consecutive counselees were

  16. Factors Associated With Adherence to Blood Pressure Measurement Recommendations at Pediatric Primary Care Visits, Minnesota and Colorado, 2007–2010

    OpenAIRE

    2015-01-01

    Introduction Elevated blood pressure in childhood may predict increased cardiovascular risk in young adulthood. The Task Force on the Diagnosis, Evaluation and Treatment of High Blood pressure in Children and Adolescents recommends that blood pressure be measured in children aged 3 years or older at all health care visits. Guidelines from both Bright Futures and the Expert Panel of Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents recommend annual ...

  17. [Update of recommendations for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology].

    Science.gov (United States)

    Reyes-García, Rebeca; García-Martín, Antonia; Varsavsky, Mariela; Rozas-Moreno, Pedro; Cortés-Berdonces, María; Luque-Fernández, Inés; Gómez Sáez, José Manuel; Vidal Casariego, Alfonso; Romero Muñoz, Manuel; Guadalix Iglesias, Sonsoles; Fernández García, Diego; Jódar Gimeno, Esteban; Muñoz Torres, Manuel

    2015-05-01

    To update previous recommendations developed by the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition for the evaluation and treatment of osteoporosis associated to different endocrine and nutritional diseases. Members of the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition. Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date between 18 October 2011 and 30 October 2014 were included. The recommendations were discussed and approved by all members of the Working Group. This update summarizes the new data regarding evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  18. Targeted enhancement of cortical-hippocampal brain networks and associative memory.

    Science.gov (United States)

    Wang, Jane X; Rogers, Lynn M; Gross, Evan Z; Ryals, Anthony J; Dokucu, Mehmet E; Brandstatt, Kelly L; Hermiller, Molly S; Voss, Joel L

    2014-08-29

    The influential notion that the hippocampus supports associative memory by interacting with functionally distinct and distributed brain regions has not been directly tested in humans. We therefore used targeted noninvasive electromagnetic stimulation to modulate human cortical-hippocampal networks and tested effects of this manipulation on memory. Multiple-session stimulation increased functional connectivity among distributed cortical-hippocampal network regions and concomitantly improved associative memory performance. These alterations involved localized long-term plasticity because increases were highly selective to the targeted brain regions, and enhancements of connectivity and associative memory persisted for ~24 hours after stimulation. Targeted cortical-hippocampal networks can thus be enhanced noninvasively, demonstrating their role in associative memory.

  19. A Meta-Path-Based Prediction Method for Human miRNA-Target Association

    Directory of Open Access Journals (Sweden)

    Jiawei Luo

    2016-01-01

    Full Text Available MicroRNAs (miRNAs are short noncoding RNAs that play important roles in regulating gene expressing, and the perturbed miRNAs are often associated with development and tumorigenesis as they have effects on their target mRNA. Predicting potential miRNA-target associations from multiple types of genomic data is a considerable problem in the bioinformatics research. However, most of the existing methods did not fully use the experimentally validated miRNA-mRNA interactions. Here, we developed RMLM and RMLMSe to predict the relationship between miRNAs and their targets. RMLM and RMLMSe are global approaches as they can reconstruct the missing associations for all the miRNA-target simultaneously and RMLMSe demonstrates that the integration of sequence information can improve the performance of RMLM. In RMLM, we use RM measure to evaluate different relatedness between miRNA and its target based on different meta-paths; logistic regression and MLE method are employed to estimate the weight of different meta-paths. In RMLMSe, sequence information is utilized to improve the performance of RMLM. Here, we carry on fivefold cross validation and pathway enrichment analysis to prove the performance of our methods. The fivefold experiments show that our methods have higher AUC scores compared with other methods and the integration of sequence information can improve the performance of miRNA-target association prediction.

  20. Recommended Levels of Physical Activity Are Associated with Reduced Risk of the Metabolic Syndrome in Mexican-Americans

    Science.gov (United States)

    Wu, Shenghui; Fisher-Hoch, Susan P.; Reininger, Belinda; McCormick, Joseph B.

    2016-01-01

    Purpose To measure the association between physical activity and the metabolic syndrome risk in Mexican-Americans. Methods Participants were drawn from the Cameron County Hispanic Cohort (n = 3,414), a randomly selected Mexican-American cohort in Texas on the US-Mexico border. Moderate and vigorous physical activity was assessed using reliable and validated instruments. The metabolic syndrome was defined as having 3 or more metabolic abnormalities. Results One thousand five hundred and twenty-four participants of the cohort (45.02%) were found to have the metabolic syndrome. Compared to participants who did not meet US physical activity guidelines, participants who met physical activity guidelines of 150 moderate and vigorous minutes per week (≥ 600 MET adjusted minutes) had 36% lower risk for the metabolic syndrome (OR = 0.64; 95% CI: 0.42–0.98), and participants with total minutes per week of moderate and vigorous/strenuous activity greater than 743 MET adjusted minutes had 37% lower risk for the metabolic syndrome (OR = 0.63; 95% CI: 0.42–0.94) compared with their counterparts, after adjusting for age, gender, annual household income, body mass index, smoking and alcohol drinking status, total portions of fruit and vegetable intake, census tracts and blocks, and survey version for physical activity. Conclusions Meeting or exceeding physical activity guidelines significantly was inversely associated with the risk for the metabolic syndrome in Mexican-Americans. Improving levels of physical activity appears to be an effective target for the metabolic syndrome prevention and control among Mexican-Americans independent of other factors. PMID:27054324

  1. Recommender Systems

    CERN Document Server

    Lü, Linyuan; Yeung, Chi Ho; Zhang, Yi-Cheng; Zhang, Zi-Ke; Zhou, Tao

    2012-01-01

    The ongoing rapid expansion of the Internet greatly increases the necessity of effective recommender systems for filtering the abundant information. Extensive research for recommender systems is conducted by a broad range of communities including social and computer scientists, physicists, and interdisciplinary researchers. Despite substantial theoretical and practical achievements, unification and comparison of different approaches are lacking, which impedes further advances. In this article, we review recent developments in recommender systems and discuss the major challenges. We compare and evaluate available algorithms and examine their roles in the future developments. In addition to algorithms, physical aspects are described to illustrate macroscopic behavior of recommender systems. Potential impacts and future directions are discussed. We emphasize that recommendation has a great scientific depth and combines diverse research fields which makes it of interests for physicists as well as interdisciplinar...

  2. Limbic, associative, and motor territories within the targets for deep brain stimulation: potential clinical implications.

    Science.gov (United States)

    Sudhyadhom, Atchar; Bova, Frank J; Foote, Kelly D; Rosado, Christian A; Kirsch-Darrow, Lindsey; Okun, Michael S

    2007-07-01

    The use of deep brain stimulation (DBS) has recently been expanding for the treatment of many neurologic disorders such as Parkinson disease, dystonia, essential tremor, Tourette's syndrome, cluster headache, epilepsy, depression, and obsessive compulsive disorder. The target structures for DBS include specific segregated territories within limbic, associative, or motor regions of very small subnuclei. In this review, we summarize current clinical techniques for DBS, the cognitive/mood/motor outcomes, and the relevant neuroanatomy with respect to functional territories within specific brain targets. Future development of new techniques and technology that may include a more direct visualization of "motor" territories within target structures may prove useful for avoiding side effects that may result from stimulation of associative and limbic regions. Alternatively, newer procedures may choose and specifically target non-motor territories for chronic electrical stimulation.

  3. Transcription factor-microRNA-target gene networks associated with ovarian cancer survival and recurrence.

    Science.gov (United States)

    Delfino, Kristin R; Rodriguez-Zas, Sandra L

    2013-01-01

    The identification of reliable transcriptome biomarkers requires the simultaneous consideration of regulatory and target elements including microRNAs (miRNAs), transcription factors (TFs), and target genes. A novel approach that integrates multivariate survival analysis, feature selection, and regulatory network visualization was used to identify reliable biomarkers of ovarian cancer survival and recurrence. Expression profiles of 799 miRNAs, 17,814 TFs and target genes and cohort clinical records on 272 patients diagnosed with ovarian cancer were simultaneously considered and results were validated on an independent group of 146 patients. Three miRNAs (hsa-miR-16, hsa-miR-22*, and ebv-miR-BHRF1-2*) were associated with both ovarian cancer survival and recurrence and 27 miRNAs were associated with either one hazard. Two miRNAs (hsa-miR-521 and hsa-miR-497) were cohort-dependent, while 28 were cohort-independent. This study confirmed 19 miRNAs previously associated with ovarian cancer and identified two miRNAs that have previously been associated with other cancer types. In total, the expression of 838 and 734 target genes and 12 and eight TFs were associated (FDR-adjusted P-value cancer survival and recurrence, respectively. Functional analysis highlighted the association between cellular and nucleotide metabolic processes and ovarian cancer. The more direct connections and higher centrality of the miRNAs, TFs and target genes in the survival network studied suggest that network-based approaches to prognosticate or predict ovarian cancer survival may be more effective than those for ovarian cancer recurrence. This study demonstrated the feasibility to infer reliable miRNA-TF-target gene networks associated with survival and recurrence of ovarian cancer based on the simultaneous analysis of co-expression profiles and consideration of the clinical characteristics of the patients.

  4. Transcription factor-microRNA-target gene networks associated with ovarian cancer survival and recurrence.

    Directory of Open Access Journals (Sweden)

    Kristin R Delfino

    Full Text Available The identification of reliable transcriptome biomarkers requires the simultaneous consideration of regulatory and target elements including microRNAs (miRNAs, transcription factors (TFs, and target genes. A novel approach that integrates multivariate survival analysis, feature selection, and regulatory network visualization was used to identify reliable biomarkers of ovarian cancer survival and recurrence. Expression profiles of 799 miRNAs, 17,814 TFs and target genes and cohort clinical records on 272 patients diagnosed with ovarian cancer were simultaneously considered and results were validated on an independent group of 146 patients. Three miRNAs (hsa-miR-16, hsa-miR-22*, and ebv-miR-BHRF1-2* were associated with both ovarian cancer survival and recurrence and 27 miRNAs were associated with either one hazard. Two miRNAs (hsa-miR-521 and hsa-miR-497 were cohort-dependent, while 28 were cohort-independent. This study confirmed 19 miRNAs previously associated with ovarian cancer and identified two miRNAs that have previously been associated with other cancer types. In total, the expression of 838 and 734 target genes and 12 and eight TFs were associated (FDR-adjusted P-value <0.05 with ovarian cancer survival and recurrence, respectively. Functional analysis highlighted the association between cellular and nucleotide metabolic processes and ovarian cancer. The more direct connections and higher centrality of the miRNAs, TFs and target genes in the survival network studied suggest that network-based approaches to prognosticate or predict ovarian cancer survival may be more effective than those for ovarian cancer recurrence. This study demonstrated the feasibility to infer reliable miRNA-TF-target gene networks associated with survival and recurrence of ovarian cancer based on the simultaneous analysis of co-expression profiles and consideration of the clinical characteristics of the patients.

  5. Is popularity associated with aggression toward socially preferred or marginalized targets?

    Science.gov (United States)

    Peets, Kätlin; Hodges, Ernest V E

    2014-08-01

    This study was designed to test whether aggression toward easy or challenging targets is more likely to be associated with popularity. More specifically, we tested two alternative hypotheses with a sample of 224 adolescents (12- and 13-year-olds): (a) whether aggression toward highly disliked peers is associated with popularity (the easy target hypothesis) or (b) whether aggression toward highly liked peers is associated with popularity (the challenging target hypothesis). Support was found only for the challenging target hypothesis. In particular, our results indicate that aggressiveness toward peers who are liked by many others has social benefits in the form of greater popularity (particularly for highly preferred adolescents) without social costs (i.e., is unrelated to social preference). In contrast, aggressiveness toward peers who are disliked by many others is associated with lower social preference but bears no association with popularity. These results highlight the importance of studying contextualized aggression in order to understand the conditions under which aggression is most, and least, likely to be associated with social power and dominance.

  6. Optimization neural net for multiple-target data association: real-time optical lab results

    Science.gov (United States)

    Yee, Mark L.; Casasent, David P.

    1991-08-01

    The Hopfield neural network was first used for optimization in solving the famous Traveling Salesman Problem. A similar approach has been applied to the solution of another problem, namely, data association for multiple targets. Simulation data are presented which demonstrate the network''s ability to successfully determine the optimum data association solutions, with target noise present. Simulations also indicate the ability to solve the problem on a low accuracy (analog optical) processor. Optical implementation issues are discussed, and an optical architecture is presented with laboratory results.

  7. US adolescents and MyPyramid: Associations between fast-food consumption and lower likelihood of meeting recommendations

    Science.gov (United States)

    The goals of this study were to determine the effect of fast food consumption on adolescents’ food group intakes and likelihood of meeting recommendations outlined in USDA’s MyPyramid Food Guidance System. Two days of 24-hour recall data from 1,956 adolescents 12-19 years of age collected in What W...

  8. Recommended Wilderness

    Data.gov (United States)

    National Park Service, Department of the Interior — Recommended wilderness is an Arcview shapefile representing the porposed wilderness areas throughout the park. The boundaries for this data set were digitized by...

  9. Recommender systems

    CERN Document Server

    Kembellec, Gérald; Saleh, Imad

    2014-01-01

    Acclaimed by various content platforms (books, music, movies) and auction sites online, recommendation systems are key elements of digital strategies. If development was originally intended for the performance of information systems, the issues are now massively moved on logical optimization of the customer relationship, with the main objective to maximize potential sales. On the transdisciplinary approach, engines and recommender systems brings together contributions linking information science and communications, marketing, sociology, mathematics and computing. It deals with the understan

  10. Point association analysis of vessel target detection with SAR, HFSWR and AIS

    Institute of Scientific and Technical Information of China (English)

    JI Yonggang; ZHANG Jie; MENG Junmin; WANG Yiming

    2014-01-01

    A space-borne synthetic aperture radar (SAR), a high frequency surface wave radar (HFSWR), and a ship automatic identification system (AIS) are the main remote sensors for vessel monitoring in a wide range. These three sensors have their own advantages and weaknesses, and they can complement each other in some situations. So it would improve the capability of vessel target detection to use multiple sensors in-cluding SAR, HFSWR, and AIS to identify non-cooperative vessel targets from the fusion results. During the fusion process of multiple sensors’ detection results, point association is one of the key steps, and it can affect the accuracy of the data fusion and the efficiency of a non-cooperative target’s recognition. This study investigated the point association analyses of vessel target detection under different conditions: space-borne SAR paired with AIS, as well as HFSWR, paired with AIS , and the characteristics of the SAR and the HFSWR and their capability of vessel target detection. Then a point association method of multiple sensors was proposed. Finally, the thresholds selection of key parameters in the points association (including range threshold, radial velocity threshold, and azimuth threshold) were investigated, and their influences on final association results were analyzed.

  11. Universalism under siege? Exploring the association between targeting, child benefits and child poverty across 26 countries.

    Science.gov (United States)

    Van Lancker, Wim; Van Mechelen, Natascha

    2015-03-01

    The long-standing wisdom that universally designed benefits outperform targeted benefits in terms of poverty reduction has come under siege. Recent empirical studies tend to find that targeting is not necessarily associated anymore with lower levels of poverty reduction. In this study, we investigate for a broad set of European countries (1) the relationship between child benefits and child poverty reduction; (2) whether a universal or targeted approach is more effective in reducing child poverty; and (3) the causal mechanisms explaining the link between (1) and (2). In doing so, we take into account the general characteristics of the child benefit system, the size of the redistributive budget and the generosity of benefit levels. In contrast to previous studies, we construct an indicator of targeting that captures the design instead of the outcomes of child benefit systems. We find that targeting towards lower incomes is associated with higher levels of child poverty reduction, conditional on the direction of targeting and the characteristics of the benefit system.

  12. Enteropeptidase: a gene associated with a starvation human phenotype and a novel target for obesity treatment.

    Directory of Open Access Journals (Sweden)

    Sandrine Braud

    Full Text Available BACKGROUND: Obesity research focuses essentially on gene targets associated with the obese phenotype. None of these targets have yet provided a viable drug therapy. Focusing instead on genes that are involved in energy absorption and that are associated with a "human starvation phenotype", we have identified enteropeptidase (EP, a gene associated with congenital enteropeptidase deficiency, as a novel target for obesity treatment. The advantages of this target are that the gene is expressed exclusively in the brush border of the intestine; it is peripheral and not redundant. METHODOLOGY/PRINCIPAL FINDINGS: Potent and selective EP inhibitors were designed around a boroarginine or borolysine motif. Oral administration of these compounds to mice restricted the bioavailability of dietary energy, and in a long-term treatment it significantly diminished the rate of increase in body weight, despite ad libitum food intake. No adverse reactions of the type seen with lipase inhibitors, such as diarrhea or steatorrhea, were observed. This validates EP as a novel, druggable target for obesity treatment. CONCLUSIONS: In vivo testing of novel boroarginine or borolysine-based EP inhibitors validates a novel approach to the treatment of obesity.

  13. Capsid modification of adeno-associated virus and tumor targeting gene therapy

    Institute of Scientific and Technical Information of China (English)

    XU ZengHu; ZHOU XiuMei; SHI WenFang; QIAN QiJun

    2008-01-01

    Targeting is critical for successful tumor gene therapy. The adeno-associated virus (AAV) has aroused wide concern due to its excellent advantages over other viral vectors in gene therapy. AAV has a broad infection spectrum, which also results in poor specificity towards tissues or cells and low transduction efficiency. Therefore, it is imperative to improve target and transduction efficiency in AAV-mediated gene therapy. Up to now, researchers have developed many strategies to modify AAV capsids for improving targeting or retargeting only desired cells. These strategies include not only traditional chemical modification, phage display technology, modification of AAV capsid genome, chimeric vectors and so on, but also many novel strategies involved in marker rescue strategy, direct evolution of capsid proteins, direct display random peptides on AAV capsid, AAVP (AAV-Phage), and etc. This review will summarize the advances of researches on the capsid modification of AAV to target malignant cells.

  14. Is popularity associated with aggression toward socially preferred or marginalized targets?

    NARCIS (Netherlands)

    Peets, Kätlin; Hodges, Ernest V E

    2014-01-01

    This study was designed to test whether aggression toward easy or challenging targets is more likely to be associated with popularity. More specifically, we tested two alternative hypotheses with a sample of 224 adolescents (12- and 13-year-olds): (a) whether aggression toward highly disliked peers

  15. Paired associative stimulation targeting the tibialis anterior muscle using either mono or biphasic transcranial magnetic stimulation

    DEFF Research Database (Denmark)

    Mrachacz-Kersting, Natalie; Stevenson, Andrew James Thomas

    2017-01-01

    Paired associative stimulation (PAS) protocols induce plastic changes within the motor cortex. The objectives of this study were to investigate PAS effects targeting the tibialis anterior (TA) muscle using a biphasic transcranial magnetic stimulation (TMS) pulse form and, to determine whether...

  16. A High Diet Quality Based on Dietary Recommendations Is Not Associated with Lower Incidence of Type 2 Diabetes in the Malmö Diet and Cancer Cohort

    Directory of Open Access Journals (Sweden)

    Emmanuel Mandalazi

    2016-06-01

    Full Text Available A high diet quality index based on Swedish nutrition recommendations has previously been associated with reduced risk of cardiovascular disease and mortality in the Malmö Diet and Cancer (MDC cohort. The aim of the present study was to investigate whether this diet quality index was associated with the risk for type 2 diabetes. Of 26,868 participants (44–74 years in the MDC cohort study, 3838 type 2 diabetes cases were identified from registers during 17 years of follow-up. A diet quality index (from a modified diet history method was constructed based on adherence to the recommended intakes of saturated fat, polyunsaturated fat, fish, fiber, fruit and vegetables, and sucrose. After adjusting for potential confounders, we observed no significant association between the diet quality index and type 2 diabetes risk. The HR for the highest vs. lowest index category was 1.06 (95% CI: 0.94, 1.20; p-trend = 0.56. Because of the protective associations shown for cardiovascular disease and mortality, the specific dietary components that were chosen to represent adherence to the recommendations may be less applicable to type 2 diabetes risk.

  17. Centralized Fuzzy Data Association Algorithm of Three-sensor Multi-target Tracking System

    Directory of Open Access Journals (Sweden)

    Zhaofeng Su

    2014-02-01

    Full Text Available For improving the effect of multi-target tracking in dense target and clutter scenario, a centralized fuzzy optimal assignment algorithm (CMS-FOA of three-sensor multi-target system is proposed. And on the base of this, a generalized probabilistic data association algorithm (CMS-FOAGPDA based on CMS-FOA algorithm is presented. The fusion algorithm gets effective 3-tuple of measurement set by using components of several satisfactory solutions of the fuzzy optimal assignment problem and then uses generalized probabilistic data association algorithm to calculate the update states of targets. Simulation results show that, in the aspect of multi-target tracking accuracy, CMS-FOA algorithm is superior to the optimal assignment (CMS-OA algorithm based on state estimate and CMS-FOAGPDA algorithm is better than CMS-FOA algorithm. But considering the time spent, CMS-FOA algorithm spends a minimum of time and CMS-FOAGPDA algorithm is exactly on the contrary. Therefore, compared with CMS-OA algorithm, the two algorithms presented in the study each has its advantages and should be chosen according to the needs of the actual application when in use.

  18. Estimating Probabilities in Recommendation Systems

    CERN Document Server

    Sun, Mingxuan; Kidwell, Paul

    2010-01-01

    Recommendation systems are emerging as an important business application with significant economic impact. Currently popular systems include Amazon's book recommendations, Netflix's movie recommendations, and Pandora's music recommendations. In this paper we address the problem of estimating probabilities associated with recommendation system data using non-parametric kernel smoothing. In our estimation we interpret missing items as randomly censored observations and obtain efficient computation schemes using combinatorial properties of generating functions. We demonstrate our approach with several case studies involving real world movie recommendation data. The results are comparable with state-of-the-art techniques while also providing probabilistic preference estimates outside the scope of traditional recommender systems.

  19. Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins

    Science.gov (United States)

    Boonstra, Martin C.; de Geus, Susanna W.L.; Prevoo, Hendrica A.J.M.; Hawinkels, Lukas J.A.C.; van de Velde, Cornelis J.H.; Kuppen, Peter J.K.; Vahrmeijer, Alexander L.; Sier, Cornelis F.M.

    2016-01-01

    Tumor targeting is a booming business: The global therapeutic monoclonal antibody market accounted for more than $78 billion in 2012 and is expanding exponentially. Tumors can be targeted with an extensive arsenal of monoclonal antibodies, ligand proteins, peptides, RNAs, and small molecules. In addition to therapeutic targeting, some of these compounds can also be applied for tumor visualization before or during surgery, after conjugation with radionuclides and/or near-infrared fluorescent dyes. The majority of these tumor-targeting compounds are directed against cell membrane-bound proteins. Various categories of targetable membrane-bound proteins, such as anchoring proteins, receptors, enzymes, and transporter proteins, exist. The functions and biological characteristics of these proteins determine their location and distribution on the cell membrane, making them more, or less, accessible, and therefore, it is important to understand these features. In this review, we evaluate the characteristics of cancer-associated membrane proteins and discuss their overall usability for cancer targeting, especially focusing on imaging applications.

  20. An update on the association between setting quantified road safety targets and road fatality reduction.

    Science.gov (United States)

    Allsop, Richard E; Sze, N N; Wong, S C

    2011-05-01

    This note is intended to rectify estimates provided in a previous paper (Wong et al., 2006) of the short-term effectiveness in terms of road fatality reduction of the setting of quantified road safety targets using data from 14 OECD countries during the period 1980-1999. This work is important in measuring the association between target setting and road safety improvement, because such targets are intended to serve as a useful tool to motivate timely road safety measures by the road authorities and others. The estimates to be rectified were based on before-and-after analysis using a comparison group of countries for each country that had set a target. This note first provides a correction to the qualification test for the inclusion of a country in any particular comparison group. It then presents the numerical effects of this correction on the estimates of the effectiveness of setting quantified road safety targets, both in individual countries and across the whole group of countries that set targets in the relevant period. Finally, impacts on the findings of the previous paper are discussed, with the conclusion that the changes in those of the numerical estimates that are affected do not alter the main message of the paper.

  1. 关联规则评分预测的协同过滤推荐算法%Collaborative Filtering Recommendation Algorithm Based on Association Rule Score Prediction

    Institute of Scientific and Technical Information of China (English)

    王竹婷

    2016-01-01

    协同过滤算法是目前应用于电子商务个性化推荐系统中的一种最成功的推荐算法。为缓解因数据稀疏性问题导致的算法推荐质量下降,将关联规则分析引入协同过滤算法中,预测部分未评分项目的评分值,再运用传统的基于用户的协同过滤算法实施推荐。实验结果表明:与传统的协同过滤算法相比,采用关联规则预测评分可以一定程度提高算法推荐质量。%Collaborative filtering algorithm is one of the most successful recommendation algorithms ap-plied to the personalized recommendation system of E-commerce.In order to alleviate the problem of the algorithm recommendation quality decline that caused by the data sparse,the association rule anal-ysis is introduced into the collaborative filtering algorithm,which predicts the item ratings of the non rating items,and then uses the traditional user_based collaborative filtering algorithm to implement the recommendation.The experimental results show that compared with the traditional collaborative filte-ring algorithm,the algorithm uses association rules to predict the item ratings can improve the recom-mended quality.

  2. [Recommendations of the Chilean Association for Digestive Endoscopy for the management of gastric pre-malignant lesions].

    Science.gov (United States)

    Rollán, Antonio; Cortés, Pablo; Calvo, Alfonso; Araya, Raúl; Bufadel, María Ester; González, Robinson; Heredia, Carolina; Muñoz, Pablo; Squella, Freddy; Nazal, Roberto; Gatica, María de Los Ángeles; Gobelet, Jaquelina; Estay, René; Pisano, Raúl; Contreras, Luis; Osorio, Ingrid; Estela, Ricardo; Fluxá, Fernando; Parra-Blanco, Adolfo

    2014-09-01

    An expert panel analyzed the available evidence and reached a consensus to release 24 recommendations for primary and secondary prevention of gastric cancer (CG) in symptomatic patients, with indication for upper GI endoscopy. The main recommendations include (1) Search for and eradicate H. pylori infection in all cases. (2) Systematic gastric biopsies (Sydney protocol) in all patients over 40 years of age or first grade relatives of patient with CG, to detect gastric atrophy, intestinal metaplasia or dysplasia. (3) Incorporate the OLGA system (Operative Link on Gastritis Assessment) to the pathological report, to categorize the individual risk of CG. (4) Schedule endoscopic follow-up according to the estimated risk of CG, namely annual for OLGA III- IV, every 3 years for OLGA I- II or persistent H. pylori infection, every 5 years for CG relatives without other risk factors and no follow-up for OLGA 0, H. pylori (-). (4) Establish basic human and material resources for endoscopic follow-up programs, including some essential administrative processes, and (5) Suggest the early CG/total CG diagnosis ratio of each institution and the proportion of systematic recording of endoscopic images, as quality indicators. These measures are applicable using currently available resources, they can complement any future screening programs for asymptomatic population and may contribute to improve the prognosis of CG in high-risk populations.

  3. Sodium channel genes in pain-related disorders: phenotype-genotype associations and recommendations for clinical use

    NARCIS (Netherlands)

    Waxman, S.G.; Merkies, I.S.; Gerrits, M.M.; Dib-Hajj, S.D.; Lauria, G.; Cox, J.J.; Wood, J.N.; Woods, C.G.; Drenth, J.P.H.; Faber, C.G.

    2014-01-01

    Human studies have firmly implicated voltage-gated sodium channels in human pain disorders, and targeted and massively parallel genomic sequencing is beginning to be used in clinical practice to determine which sodium channel variants are involved. Missense substitutions of SCN9A, the gene encoding

  4. Membrane-Associated RING-CH proteins associate with Bap31 and target CD81 and CD44 to lysosomes.

    Directory of Open Access Journals (Sweden)

    Eric Bartee

    Full Text Available Membrane-associated RING-CH (MARCH proteins represent a family of transmembrane ubiquitin ligases modulating intracellular trafficking and turnover of transmembrane protein targets. While homologous proteins encoded by gamma-2 herpesviruses and leporipoxviruses have been studied extensively, limited information is available regarding the physiological targets of cellular MARCH proteins. To identify host cell proteins targeted by the human MARCH-VIII ubiquitin ligase we used stable isotope labeling of amino-acids in cell culture (SILAC to monitor MARCH-dependent changes in the membrane proteomes of human fibroblasts. Unexpectedly, we observed that MARCH-VIII reduced the surface expression of Bap31, a chaperone that predominantly resides in the endoplasmic reticulum (ER. We demonstrate that Bap31 associates with the transmembrane domains of several MARCH proteins and controls intracellular transport of MARCH proteins. In addition, we observed that MARCH-VIII reduced the surface expression of the hyaluronic acid-receptor CD44 and both MARCH-VIII and MARCH-IV sequestered the tetraspanin CD81 in endo-lysosomal vesicles. Moreover, gene knockdown of MARCH-IV increased surface levels of endogenous CD81 suggesting a constitutive involvement of this family of ubiquitin ligases in the turnover of tetraspanins. Our data thus suggest a role of MARCH-VIII and MARCH-IV in the regulated turnover of CD81 and CD44, two ubiquitously expressed, multifunctional proteins.

  5. Membrane-Associated RING-CH proteins associate with Bap31 and target CD81 and CD44 to lysosomes.

    Science.gov (United States)

    Bartee, Eric; Eyster, Craig A; Viswanathan, Kasinath; Mansouri, Mandana; Donaldson, Julie G; Früh, Klaus

    2010-12-02

    Membrane-associated RING-CH (MARCH) proteins represent a family of transmembrane ubiquitin ligases modulating intracellular trafficking and turnover of transmembrane protein targets. While homologous proteins encoded by gamma-2 herpesviruses and leporipoxviruses have been studied extensively, limited information is available regarding the physiological targets of cellular MARCH proteins. To identify host cell proteins targeted by the human MARCH-VIII ubiquitin ligase we used stable isotope labeling of amino-acids in cell culture (SILAC) to monitor MARCH-dependent changes in the membrane proteomes of human fibroblasts. Unexpectedly, we observed that MARCH-VIII reduced the surface expression of Bap31, a chaperone that predominantly resides in the endoplasmic reticulum (ER). We demonstrate that Bap31 associates with the transmembrane domains of several MARCH proteins and controls intracellular transport of MARCH proteins. In addition, we observed that MARCH-VIII reduced the surface expression of the hyaluronic acid-receptor CD44 and both MARCH-VIII and MARCH-IV sequestered the tetraspanin CD81 in endo-lysosomal vesicles. Moreover, gene knockdown of MARCH-IV increased surface levels of endogenous CD81 suggesting a constitutive involvement of this family of ubiquitin ligases in the turnover of tetraspanins. Our data thus suggest a role of MARCH-VIII and MARCH-IV in the regulated turnover of CD81 and CD44, two ubiquitously expressed, multifunctional proteins.

  6. Provider beliefs associated with cervical cancer screening interval recommendations: A pilot study in Federally Qualified Health Centers

    Directory of Open Access Journals (Sweden)

    Katherine B. Roland

    2015-01-01

    Conclusion: Messages that promote the benefits of longer screening intervals after a normal co-test, the natural history of human papillomavirus and cervical cancer, and low risk of developing cancer with a longer interval may be useful to promote evidence-based screening in this population of Federally Qualified Health Center providers. Dissemination of targeted messages through professional journals and specialty organizations should be considered.

  7. Efficient gene targeting mediated by a lentiviral vector-associated meganuclease.

    Science.gov (United States)

    Izmiryan, Araksya; Basmaciogullari, Stéphane; Henry, Adrien; Paques, Frédéric; Danos, Olivier

    2011-09-01

    Gene targeting can be achieved with lentiviral vectors delivering donor sequences along with a nuclease that creates a locus-specific double-strand break (DSB). Therapeutic applications of this system would require an appropriate control of the amount of endonuclease delivered to the target cells, and potentially toxic sustained expression must be avoided. Here, we show that the nuclease can be transferred into cells as a protein associated with a lentiviral vector particle. I-SceI, a prototypic meganuclease from yeast, was incorporated into the virions as a fusion with Vpr, an HIV accessory protein. Integration-deficient lentiviral vectors containing the donor sequences and the I-SceI fusion protein were tested in reporter cells in which targeting events were scored by the repair of a puromycin resistance gene. Molecular analysis of the targeted locus indicated a 2-fold higher frequency of the expected recombination event when the nuclease was delivered as a protein rather than encoded by a separate vector. In both systems, a proportion of clones displayed multiple integrated copies of the donor sequences, either as tandems at the targeted locus or at unrelated loci. These integration patterns were dependent upon the mode of meganuclease delivery, suggesting distinct recombination processes.

  8. An integrative genomic and transcriptomic analysis reveals potential targets associated with cell proliferation in uterine leiomyomas

    DEFF Research Database (Denmark)

    Cirilo, Priscila Daniele Ramos; Marchi, Fábio Albuquerque; Barros Filho, Mateus de Camargo

    2013-01-01

    BACKGROUND: Uterine Leiomyomas (ULs) are the most common benign tumours affecting women of reproductive age. ULs represent a major problem in public health, as they are the main indication for hysterectomy. Approximately 40-50% of ULs have non-random cytogenetic abnormalities, and half of ULs may......: The integrated analysis identified the top 30 significant genes (Pindicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell...... and transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs....

  9. Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells.

    Science.gov (United States)

    Chen, Jiang; Ding, Jie; Wang, Ziwei; Zhu, Jian; Wang, Xuejian; Du, Jiyi

    2017-03-21

    This study aims to identify downstream target genes regulated by lysine-specific demethylase 1 (LSD1) in colon cancer cells and investigate the molecular mechanisms of LSD1 influencing invasion and metastasis of colon cancer. We obtained the expression changes of downstream target genes regulated by small-interfering RNA-LSD1 and LSD1-overexpression via gene expression profiling in two human colon cancer cell lines. An Affymetrix Human Transcriptome Array 2.0 was used to identify differentially expressed genes (DEGs). We screened out LSD1-target gene associated with proliferation, metastasis, and invasion from DEGs via Gene Ontology and Pathway Studio. Subsequently, four key genes (CABYR, FOXF2, TLE4, and CDH1) were computationally predicted as metastasis-related LSD1-target genes. ChIp-PCR was applied after RT-PCR and Western blot validations to detect the occupancy of LSD1-target gene promoter-bound LSD1. A total of 3633 DEGs were significantly upregulated, and 4642 DEGs were downregulated in LSD1-silenced SW620 cells. A total of 4047 DEGs and 4240 DEGs were upregulated and downregulated in LSD1-overexpressed HT-29 cells, respectively. RT-PCR and Western blot validated the microarray analysis results. ChIP assay results demonstrated that LSD1 might be negative regulators for target genes CABYR and CDH1. The expression level of LSD1 is negatively correlated with mono- and dimethylation of histone H3 lysine4(H3K4) at LSD1- target gene promoter region. No significant mono-methylation and dimethylation of H3 lysine9 methylation was detected at the promoter region of CABYR and CDH1. LSD1- depletion contributed to the upregulation of CABYR and CDH1 through enhancing the dimethylation of H3K4 at the LSD1-target genes promoter. LSD1- overexpression mediated the downregulation of CABYR and CDH1expression through decreasing the mono- and dimethylation of H3K4 at LSD1-target gene promoter in colon cancer cells. CABYR and CDH1 might be potential LSD1-target genes in colon

  10. DNA vaccines targeting human papillomavirus-associated diseases: progresses in animal and clinical studies

    OpenAIRE

    Han, Kyusun Torque; Sin, Jeong-Im

    2013-01-01

    Human papillomavirus (HPV) infection is a major cause of cervical cancer and its precancerous diseases. Cervical cancer is the second deadliest cancer killer among women worldwide. Moreover, HPV is also known to be a causative agent of oral, pharyngeal, anal and genital cancer. Recent application of HPV structural protein (L1)-targeted prophylactic vaccines (Gardasil® and Cervarix®) is expected to reduce the incidence of HPV infection and cervical cancer, and possibly other HPV-associated can...

  11. Association between self-efficacy and dietary behaviours of American football players in the Polish Clubs in the light of dietary recommendations for athletes.

    Science.gov (United States)

    Gacek, Maria

    2015-01-01

    Personality traits associated with one's health beliefs and expectations constitute a determinant of dietary behaviours. The aim of the study was to analyse the dietary behaviours of young American football players in the Polish clubs and association thereof with their general self-efficacy level. The study included the group of 100 young men (20-30 years of age) who practiced American football on a professional basis in three Polish clubs. The study was based on an original dietary behaviour questionnaire derived from the Swiss Food Pyramid for Athletes and General Self-Efficacy Scale (GSES). Statistical analysis, conducted with Statistica 10.0 PL software, included intergroup comparisons with the Chi-square test. Having at least three meals per day (82%), consumption of such protein products as eggs and/or meat several times per week (68%) and including cereal products in every main meal (67%) turned out to be the most often followed qualitative recommendations of the Swiss Food Pyramid for Athletes in the group of American football players. Other, frequently followed dietary recommendations included remaining on a variable diet (75%), preference to mineral water and other non- sweetened beverages (69%), reduced intake of sweets and salted snacks (65%), energy drinks (64%) and fast food products (60%). The least frequently declared dietary behaviours included consuming recommended amounts of vegetables/fruits (48%) and wholegrain cereal products (45%), and reduced intake of animal fats (42%). Analysis of a relationship between specific dietary behaviours and general self-efficacy level showed that the athletes with higher levels of this trait consumed recommended daily amounts of vegetables (54% vs. 26%, p<0.01) and cereal products (87% vs. 50%, p<0.001), had recommended number of meals per day (96% vs. 70%, p<0.001) and ate regularly (76% vs. 24%, p<0.001) significantly more often than the persons characterized by lower self-efficacy levels. Players with higher

  12. Food and diet factors associated to child obesity: recommendations for preventing it in children under two years of age

    OpenAIRE

    Saavedra, José M.; Department of Pediatrics, Johns Hopkins University School of Medicine. Baltimore, EE. UU. Nestlé Nutrition. New Jersey, EE. UU. Gastroenterólogo pediatra.; Dattilo, Anne M.; Nestlé Nutrition. New Jersey, EE. UU. Nutricionista.

    2014-01-01

    Several factors leading to obesity have been identified, which start at very early stages of life. Although there are genetic contributors and socioeconomic and racial disparities in the prevalence of overweight and obesity, the problem is universal. Children’s weight has been associated to multiple specific diet factors and these, in turn, are associated to specific “parent feeding practices” (PAPP, Spanish abbreviation). Parents or caretakers determine patterns that are set at an early ...

  13. PKA-chromatin association at stress responsive target genes from Saccharomyces cerevisiae.

    Science.gov (United States)

    Baccarini, Leticia; Martínez-Montañés, Fernando; Rossi, Silvia; Proft, Markus; Portela, Paula

    2015-11-01

    Gene expression regulation by intracellular stimulus-activated protein kinases is essential for cell adaptation to environmental changes. There are three PKA catalytic subunits in Saccharomyces cerevisiae: Tpk1, Tpk2, and Tpk3 and one regulatory subunit: Bcy1. Previously, it has been demonstrated that Tpk1 and Tpk2 are associated with coding regions and promoters of target genes in a carbon source and oxidative stress dependent manner. Here we studied five genes, ALD6, SED1, HSP42, RPS29B, and RPL1B whose expression is regulated by saline stress. We found that PKA catalytic and regulatory subunits are associated with both coding regions and promoters of the analyzed genes in a stress dependent manner. Tpk1 and Tpk2 recruitment was completely abolished in catalytic inactive mutants. BCY1 deletion changed the binding kinetic to chromatin of each Tpk isoform and this strain displayed a deregulated gene expression in response to osmotic stress. In addition, yeast mutants with high PKA activity exhibit sustained association to target genes of chromatin-remodeling complexes such as Snf2-catalytic subunit of the SWI/SNF complex and Arp8-component of INO80 complex, leading to upregulation of gene expression during osmotic stress. Tpk1 accumulation in the nucleus was stimulated upon osmotic stress, while the nuclear localization of Tpk2 and Bcy1 showed no change. We found that each PKA subunit is transported into the nucleus by a different β-karyopherin pathway. Moreover, β-karyopherin mutant strains abolished the chromatin association of Tpk1 or Tpk2, suggesting that nuclear localization of PKA catalytic subunits is required for its association to target genes and properly gene expression.

  14. Economic assessment of nutritional recommendations.

    Science.gov (United States)

    Irz, Xavier; Leroy, Pascal; Réquillart, Vincent; Soler, Louis-Georges

    2015-01-01

    The effect of consumers' compliance with nutritional recommendations is uncertain because of potentially complex substitutions. To lift this uncertainty, we adapt a model of consumer behaviour under rationing to the case of linear nutritional constraints. Dietary adjustments are derived from information on consumer preferences, consumption levels, and nutritional contents of foods. A calibration exercise simulates, for different income groups, how the French diet would respond to various nutrition recommendations, and those behavioural adjustments are translated into health outcomes through the DIETRON epidemiological model. This allows for the ex-ante comparison of the efficiency, equity and health effects of ten nutritional recommendations. Although most recommendations impose significant taste costs on consumers, they are highly cost-effective, with the recommendations targeting salt, saturated fat, and fruits and vegetables (F&V) ranking highest in terms of efficiency. Most recommendations are also economically progressive, with the exception of that targeting F&V.

  15. Associations of Guideline Recommended Medications for Acute Coronary Syndromes With Fall-Related Hospitalizations and Cardiovascular Events in Older Women With Ischemic Heart Disease.

    Science.gov (United States)

    Peeters, Geeske; Tett, Susan E; Hollingworth, Samantha A; Gnjidic, Danijela; Hilmer, Sarah N; Dobson, Annette J; Hubbard, Ruth E

    2017-02-01

    Guidelines for acute coronary syndrome recommend statins, β-blockers, angiotensin-converting-enzyme inhibitors or renin-angiotensin system blockers, and antiplatelet agents for the secondary prevention of cardiovascular events. The aim was to examine associations between guideline recommended medications and fall-related hospitalizations and cardiovascular events in robust and frail older women. 2002-2011 surveys from the Australian Longitudinal Study on Women's Health linked with administrative hospital, pharmaceutical and death registry data (2003-mid-2011) were used. Eight hundred eighty-five women (82.7±2.7 years, range 76-90) had prior admission for ischemic heart disease and ≥1 claims for any of the four medication classes. Four hundred thirteen (46.7%) were robust and 472 (53.3%) were frail. Fall-related admissions; cardiovascular event-related admissions or death; and cardiovascular death were recorded. Associations between each of the exposures and outcomes were analyzed using survival analyses with noncardiovascular death as a competing risk. There were 192 fall-related admissions and 314 cardiovascular events including 82 deaths. Using four recommended classes (compared to using one) was associated with increased risks of fall-related admissions (hazard ratio [HR] = 2.57, 95% confidence interval [CI] = 1.24-5.33), but not with cardiovascular events (HR = 1.41, CI = 0.97-2.05) or cardiovascular death (HR = 0.68, CI = 0.35-1.34). Associations for fall-related admissions were stronger in frail participants (HR = 5.46, CI = 1.34-22.30) than robust (HR = 1.37, CI = 0.48-3.95). In older women with ischemic heart disease, the combination of the four recommended medication classes was associated with increased risk of falls, particularly among frail women, with no statistically significant gain in cardiovascular health. The risks of falls and consequential morbidity in women over 75 needs consideration when prescribing medications after myocardial infarction

  16. Identification of target genes of synovial sarcoma-associated fusion oncoprotein using human pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, Kazuo [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Ikeya, Makoto [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Fukuta, Makoto [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Woltjen, Knut [Department of Reprogramming Sciences, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Tamaki, Sakura; Takahara, Naoko; Kato, Tomohisa; Sato, Shingo [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Otsuka, Takanobu [Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Toguchida, Junya, E-mail: togjun@frontier.kyoto-u.ac.jp [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto (Japan)

    2013-03-22

    Highlights: ► We tried to identify targets of synovial sarcoma (SS)-associated SYT–SSX fusion gene. ► We established pluripotent stem cell (PSC) lines with inducible SYT–SSX gene. ► SYT–SSX responsive genes were identified by the induction of SYT–SSX in PSC. ► SS-related genes were selected from database by in silico analyses. ► 51 genes were finally identified among SS-related genes as targets of SYT–SSX in PSC. -- Abstract: Synovial sarcoma (SS) is a malignant soft tissue tumor harboring chromosomal translocation t(X; 18)(p11.2; q11.2), which produces SS-specific fusion gene, SYT–SSX. Although precise function of SYT–SSX remains to be investigated, accumulating evidences suggest its role in gene regulation via epigenetic mechanisms, and the product of SYT–SSX target genes may serve as biomarkers of SS. Lack of knowledge about the cell-of-origin of SS, however, has placed obstacle in the way of target identification. Here we report a novel approach to identify SYT–SSX2 target genes using human pluripotent stem cells (hPSCs) containing a doxycycline-inducible SYT–SSX2 gene. SYT–SSX2 was efficiently induced both at mRNA and protein levels within three hours after doxycycline administration, while no morphological change of hPSCs was observed until 24 h. Serial microarray analyses identified genes of which the expression level changed more than twofold within 24 h. Surprisingly, the majority (297/312, 95.2%) were up-regulated genes and a result inconsistent with the current concept of SYT–SSX as a transcriptional repressor. Comparing these genes with SS-related genes which were selected by a series of in silico analyses, 49 and 2 genes were finally identified as candidates of up- and down-regulated target of SYT–SSX, respectively. Association of these genes with SYT–SSX in SS cells was confirmed by knockdown experiments. Expression profiles of SS-related genes in hPSCs and human mesenchymal stem cells (hMSCs) were strikingly

  17. FP-tree association rules algorithm in recommendation system%基于FP-tree算法的推荐系统设计与实现

    Institute of Scientific and Technical Information of China (English)

    刘华; 张亚昕

    2015-01-01

    当前是信息爆炸的时代,推荐系统已成为解决当前网络信息超载的有效工具。文章针对网上书店的电子商务网站的销售特点,详细地设计了推荐系统,并利用挖掘技术中的FP-tree关联规则算法实现数据挖掘运算,很好的实现了在线推荐的系统功能。%This is the era of information explosion, recommendation system has become an effective tool for solving the current network information overload. Aiming at the characteristics of online bookstores sell e-commerce site, a detailed design of the recommendation system, and using mining techniques in FP-tree data mining association rules algorithm computation, to achieve a good online recommendation system functions.

  18. Does Evidence Support the American Heart Association's Recommendation to Screen Patients for Depression in Cardiovascular Care? An Updated Systematic Review

    NARCIS (Netherlands)

    Thombs, Brett D.; Roseman, Michelle; Coyne, James C.; de Jonge, Peter; Delisle, Vanessa C.; Arthurs, Erin; Levis, Brooke; Ziegelstein, Roy C.

    2013-01-01

    Objectives: To systematically review evidence on depression screening in coronary heart disease (CHD) by assessing the (1) accuracy of screening tools; (2) effectiveness of treatment; and (3) effect of screening on depression outcomes. Background: A 2008 American Heart Association (AHA) Science Advi

  19. Recommended dietary pattern to achieve adherence to the American Heart Association/American College of Cardiology (AHA/ACC) Guidelines

    Science.gov (United States)

    In 2013, the American Heart Association and American College of Cardiology published the "Guideline on Lifestyle Management to Reduce Cardiovascular Risk," which was based on a systematic review originally initiated by the National Heart, Lung, and Blood Institute. The guideline supports the America...

  20. Neural network data association with application to multiple-target tracking

    Science.gov (United States)

    Leung, Henry

    1996-03-01

    Data association is the process of relating sensor measurements in a data fusion system. It can be structured in a basic framework very similar to that of the classic traveling salesman problem. The derivation of the energy function is presented, and the solution is based on a modified Hopfield network which uses the Runge-Kutta method and Aiyer's network structure. The neural data association is then applied to the problem of multiple-target tracking (MTT). The proposed neural MTT system consists of a modified Hough transform track initiator, a Kalman filter state estimator and the Hopfield probabilistic data association. Real- life air surveillance data are used to evaluate the practicality of the neural MTT system, and the results show that the neural system works efficiently in real-life tracking environments.

  1. Association factors of target organ damage: analysis of 17 682 elderly hypertensive patients in China

    Institute of Scientific and Technical Information of China (English)

    CUI Hua; WANG Fan; FAN Li; HU Yi-xin; HU Guo-liang; LIU Lin; HONG Chang-ming

    2011-01-01

    Background Hypertensive target organ damage (TOD) is the main reason for mortality or disability in elderly hypertensive patients.The studies on TOD of hypertension in Asia,especially in Chinese elderly hypertensive patients,are very limited.The aim of this study was to evaluate the prevalence and correlative factors of TOD in older Chinese hypertensive inpatients.Methods This is a retrospective survey and data were collected from the computerized medical files of hypertensive inpatients from January of 1993 to December of 2008.The analysis was done on 17 682 inpatients,aged 60 years or older,with a diagnosis of essential hypertension (EH).The evidence of hypertensive TOD and associated factors with TOD were collected.Results The prevalence of any hypertensive target organ involvement among these subjects was high.In multivariable Logistic regressions adjusted for potentially confounding factors,older age,male gender,diabetes,EH grade 3,systolic blood pressure (SBP),and low-density lipoprotein cholesterol (LDL-C),were independently associated with coronary artery disease.Age,duration of EH,EH grade 3,SBP,pulse pressure (PP),and homocysteine (Hcy) were independently associated with cerebrovascular disease.Age,diabetes,duration of EH,EH grade 3,SBP,PP and estimated glomerular filtration rate (eGFR) were independently associated with chronic kidney disease.Male gender,EH grade 3 and SBP were independently associated with aortic dissection.Conclusions The prevalence of hypertensive TOD is high in older Chinese hypertensive inpatients.Various cardiovascular risk factors are associated with hypertensive TOD.The level of SBP and severe hypertension (grade 3 hypertension) are common independent risk factors of TOD.

  2. 一种基于后项不定长关联规则的Web个性化推荐方法%A Web Personalized Recommendation Method Based on Uncertain Consequent Association Rules

    Institute of Scientific and Technical Information of China (English)

    丁增喜; 王菊英; 王大玲; 鲍玉斌; 于戈

    2003-01-01

    Web usage mining plays an important part in supporting personalized recommendation on Web and association rule uncovers the interesting relations among items hidden in data. The paper gives an idea of association rule merging-deleting based on the analysis of association rule characteristics and implements it in the rule preparation before the Web personalized recommendation. Furthermore, based on the comparisons in precision, coverage and F1 of recommendation system and the rule numbers used in three kinds of association rules, a Web personalized recommendation method based on uncertain consequent is put forward. After integrative analysis of several recommendation methods, the method given in the paper can be thought as a good selection. At last several pageweighted techniques are introduced in the paper.

  3. Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors

    Science.gov (United States)

    Bhowmick, Tuhin; Ghosh, Soumitra; Dixit, Karuna; Ganesan, Varsha; Ramagopal, Udupi A.; Dey, Debayan; Sarma, Siddhartha P.; Ramakumar, Suryanarayanarao; Nagaraja, Valakunja

    2014-06-01

    The nucleoid-associated protein HU plays an important role in maintenance of chromosomal architecture and in global regulation of DNA transactions in bacteria. Although HU is essential for growth in Mycobacterium tuberculosis (Mtb), there have been no reported attempts to perturb HU function with small molecules. Here we report the crystal structure of the N-terminal domain of HU from Mtb. We identify a core region within the HU-DNA interface that can be targeted using stilbene derivatives. These small molecules specifically inhibit HU-DNA binding, disrupt nucleoid architecture and reduce Mtb growth. The stilbene inhibitors induce gene expression changes in Mtb that resemble those induced by HU deficiency. Our results indicate that HU is a potential target for the development of therapies against tuberculosis.

  4. TOA Estimation and Data Association for Through-Wall Tracking of Moving Targets

    Directory of Open Access Journals (Sweden)

    Rovňáková Jana

    2010-01-01

    Full Text Available Through-wall tracking of moving targets is of great interest for rescue, surveillance, and security operations. For its realization, the handheld ultrawideband radars with small antenna array provide a practical solution. The radar signal processing, which is hidden behind the estimation of the final target tracks, represents a complex process with several processing phases. In this paper, all phases for through wall tracking are outlined whereas the attention is devoted to the estimation of the correct input data for the localization phase. This is done by applying a new approach that combines the time of arrival (TOA estimation and the data-association into a single step. The properties of the proposed algorithm are illustrated by processing of real radar signals. Here, the obtained results confirm that the proposed algorithm has provided good, stable, and robust TOA estimation including deghosting task solution.

  5. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

    Science.gov (United States)

    Richards, Sue; Aziz, Nazneen; Bale, Sherri; Bick, David; Das, Soma; Gastier-Foster, Julie; Grody, Wayne W; Hegde, Madhuri; Lyon, Elaine; Spector, Elaine; Voelkerding, Karl; Rehm, Heidi L

    2015-05-01

    The American College of Medical Genetics and Genomics (ACMG) previously developed guidance for the interpretation of sequence variants.(1) In the past decade, sequencing technology has evolved rapidly with the advent of high-throughput next-generation sequencing. By adopting and leveraging next-generation sequencing, clinical laboratories are now performing an ever-increasing catalogue of genetic testing spanning genotyping, single genes, gene panels, exomes, genomes, transcriptomes, and epigenetic assays for genetic disorders. By virtue of increased complexity, this shift in genetic testing has been accompanied by new challenges in sequence interpretation. In this context the ACMG convened a workgroup in 2013 comprising representatives from the ACMG, the Association for Molecular Pathology (AMP), and the College of American Pathologists to revisit and revise the standards and guidelines for the interpretation of sequence variants. The group consisted of clinical laboratory directors and clinicians. This report represents expert opinion of the workgroup with input from ACMG, AMP, and College of American Pathologists stakeholders. These recommendations primarily apply to the breadth of genetic tests used in clinical laboratories, including genotyping, single genes, panels, exomes, and genomes. This report recommends the use of specific standard terminology-"pathogenic," "likely pathogenic," "uncertain significance," "likely benign," and "benign"-to describe variants identified in genes that cause Mendelian disorders. Moreover, this recommendation describes a process for classifying variants into these five categories based on criteria using typical types of variant evidence (e.g., population data, computational data, functional data, segregation data). Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends that clinical molecular genetic testing should be performed in a

  6. Expression patterns of microRNAs associated with CML phases and their disease related targets

    Directory of Open Access Journals (Sweden)

    Trněný Marek

    2011-04-01

    Full Text Available Abstract Background MicroRNAs are important regulators of transcription in hematopoiesis. Their expression deregulations were described in association with pathogenesis of some hematological malignancies. This study provides integrated microRNA expression profiling at different phases of chronic myeloid leukemia (CML with the aim to identify microRNAs associated with CML pathogenesis. The functions of in silico filtered targets are in this report annotated and discussed in relation to CML pathogenesis. Results Using microarrays we identified differential expression profiles of 49 miRNAs in CML patients at diagnosis, in hematological relapse, therapy failure, blast crisis and major molecular response. The expression deregulation of miR-150, miR-20a, miR-17, miR-19a, miR-103, miR-144, miR-155, miR-181a, miR-221 and miR-222 in CML was confirmed by real-time quantitative PCR. In silico analyses identified targeted genes of these miRNAs encoding proteins that are involved in cell cycle and growth regulation as well as several key signaling pathways such as of mitogen activated kinase-like protein (MAPK, epidermal growth factor receptor (EGFR, ERBB, transforming growth factor beta (TGFB1 and tumor protein p53 that are all related to CML. Decreased levels of miR-150 were detected in patients at diagnosis, in blast crisis and 67% of hematological relapses and showed significant negative correlation with miR-150 proved target MYB and with BCR-ABL transcript level. Conclusions This study uncovers microRNAs that are potentially involved in CML and the annotated functions of in silico filtered targets of selected miRNAs outline mechanisms whereby microRNAs may be involved in CML pathogenesis.

  7. Conditions of tumor-associated antigens as a proper target for therapeutic antibodies against solid cancers

    Directory of Open Access Journals (Sweden)

    Yoshikazu Kurosawa

    2011-01-01

    Full Text Available Since the success of rituximab and trastuzumab for treatment of non-Hodgkin’s lymphoma and breast cancer, respectively, a huge therapeutic potential of monoclonal antibodies (mAbs was realized and development of therapeutic mAbs has been widely tried against various cancers. However, the successful examples are still limited and therapeutic mAbs are not yet available for the majority of human cancers. We established a procedure for comprehensive identification of tumor-associated antigens (TAAs through the extensive isolation of human mAbs that may become therapeutic. Thirty-twoTAAs have been identified and 555 mAbs that bound to one of the TAAs have been isolated to date. Now we are trying to select TAAs as proper targets for therapy and candidate mAbs as drugs from among them. The immunohistochemical analysis using many fresh lung cancer specimens suggested probabilities of proper targets, and moreover, presence of cancer-specific epitopes that could be distinguished from normal epitopes on the same molecules by mAbs. For Abs to efficiently kill the cancer cells they should have the ability to induce immunological cytotoxicity such as ADCC and/or CDC. They should also be able to inhibit the function mediated by the target Ags. For clinical point of view, the continuous presence of the target molecule on the cell surface until cell death might be essential for successful treatment. Therefore, it will be required for targets TAAs to play essential roles in tumorigenesis. Otherwise the cancer cells that do not express them could selectively survive during treatment and finally become dominant. It was also suggested that even the same molecules could play different roles in tumorigenesis quite often in different patients. Therefore when we develop therapeutic Abs, we should obtain information about the conditions of patients including genetic background to whom the treatment will be effective. I will discuss how we can accomplish this purpose.

  8. [Clinical practice recommendations for diabetes in pregnancy (Diabetes and Pregnancy Study Group of the Austrian Diabetes Association)].

    Science.gov (United States)

    Kautzky-Willer, Alexandra; Harreiter, Jürgen; Weitgasser, Raimund; Lechleitner, Monika

    2016-04-01

    Twenty-six years ago the St. Vincent Declaration aimed for an achievement of a comparable pregnancy outcome in diabetic and non-diabetic women. However, current surveys clearly show that women with pre-gestational diabetes still feature a much higher risk of perinatal morbidity and even increased mortality. This fact is mostly ascribed to a persistently low rate of pregnancy planning and pre-pregnancy care with optimization of metabolic control prior to conception. In addition, obesity increases worldwide, contributing to a growing number of women with type 2 diabetes at a childbearing age, and a further deterioration in outcome in diabetic women. Development of diabetic embryopathy and fetopathy are known to be related to maternal glycemic control (target: normoglycemia and normal HbA1c, if possible without hypoglycemia). The risk for hypoglycemia is at its greatest in early pregnancy and decreases with the progression of pregnancy due to the hormonal changes leading to a marked increase of insulin resistance. Intensified insulin therapy with multiple daily insulin injections and pump treatment are equally effective in reaching good metabolic control during pregnancy. All women should be experienced in the management of their therapy and on stable glycemic control prior to the conception. In addition, thyroid dysfunction, hypertension as well as the presence of diabetic complications should be excluded before pregnancy or treated adequately in order to decrease the risk for a progression of complications during pregnancy as well as for maternal and fetal morbidity.

  9. Implementation of the updated 2015 Commission for Hospital Hygiene and Infection Prevention (KRINKO) recommendations “Prevention and control of catheter-associated urinary tract infections” in the hospitals in Frankfurt/Main, Germany

    OpenAIRE

    Heudorf, Ursel; Grünewald, Miriam; Otto, Ulla

    2016-01-01

    Aim: The Commission for Hospital Hygiene and Infection Prevention (KRINKO) updated the recommendations for the prevention of catheter-associated urinary tract infections in 2015. This article will describe the implementation of these recommendations in Frankfurt's hospitals in autumn, 2015.Material and methods : In two non-ICU wards of each of Frankfurt's 17 hospitals, inspections were performed using a checklist based on the new KRINKO recommendations. In one large hospital, a total of 5 wa...

  10. Three-cohort targeted gene screening reveals a non-synonymous TRKA polymorphism associated with schizophrenia

    DEFF Research Database (Denmark)

    van Schijndel, Jessica E; van Loo, Karen M J; van Zweeden, Martine;

    2009-01-01

    Schizophrenia is a complex neurodevelopmental disorder that is thought to be induced by an interaction between predisposing genes and environmental stressors. To identify predisposing genetic factors, we performed a targeted (mostly neurodevelopmental) gene approach involving the screening of 396...... selected non-synonymous single-nucleotide polymorphisms (SNPs) in three independent Caucasian schizophrenia case-control cohorts (USA, Denmark and Norway). A meta-analysis revealed ten non-synonymous SNPs that were nominally associated with schizophrenia, nine of which have not been previously linked...... for schizophrenia....

  11. Paired associative stimulation targeting the tibialis anterior muscle using either mono or biphasic transcranial magnetic stimulation

    DEFF Research Database (Denmark)

    Mrachacz-Kersting, Natalie; Stevenson, Andrew James Thomas

    2017-01-01

    a reduced intensity of this pulse would lead to significant changes as has been reported for hand muscles using a monophasic TMS pulse. Three interventions were investigated: (1) suprathreshold PAbi-PAS (n = 11); (2) suprathreshold PAmono-PAS (n = 11) where PAS was applied using a biphasic or monophasic......Paired associative stimulation (PAS) protocols induce plastic changes within the motor cortex. The objectives of this study were to investigate PAS effects targeting the tibialis anterior (TA) muscle using a biphasic transcranial magnetic stimulation (TMS) pulse form and, to determine whether...

  12. Improving the Medical Curriculum in Predoctoral Dental Education: Recommendations From the American Association of Oral and Maxillofacial Surgeons Committee on Predoctoral Education and Training.

    Science.gov (United States)

    Dennis, Matthew J; Bennett, Jeffrey D; DeLuke, Dean M; Evans, Erik W; Hudson, John W; Nattestad, Anders; Ness, Gregory M; Yeung, Allison

    2017-02-01

    Dental procedures are often performed on patients who present with some level of medical fragility. In many dental schools, the exercise of taking a medical history is all too often a transcription of information to the dental chart, with little emphasis on the presurgical risk assessment and the development of a treatment plan appropriate to the medical status of the dental patient. Changes in dentistry, driven by an increasingly medically complex population of dental patients, combined with treatment advances rooted in the biomedical sciences necessitate the adaptation of our dental education to include a stronger background in systemic health. Many predoctoral educators in the American Association of Oral and Maxillofacial Surgeons (AAOMS) have expressed concern about the medical preparedness of our dental students; therefore, the AAOMS and its Committee on Predoctoral Education and Training have provided recommendations for improving the medical curriculum in predoctoral dental education, including a strengthening of training in clinical medicine and biomedical sciences, with specific recommendations for improved training of our dental students and dental faculty. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  13. Recommendations of «not-to-do»: Proposals of the Spanish Association of Surgeons to the project «Commitment to quality of scientific societies».

    Science.gov (United States)

    Soria-Aledo, Víctor; Romero Simó, Manuel; Balibrea, José M; Badia, Josep M

    2016-10-01

    The initiative of the Spanish Ministry of Health «Commitment to quality of scientific societies», aims to reduce unnecessary interventions of healthcare professionals. The Spanish Association of Surgeons has selected 22 experts from the different sections that have participated in the identification of 26 proposals «do not do» to be ordered by the expected impact its implementation would have according to the GRADE methodology. From these proposals, the Delphi technique was used to select 5 recommendations presented in more detail in this article. The 5 selected recommendations are: Do not perform cholecystectomy in patients with asymptomatic cholelithiasis; do not keep bladder catheterization more than 48hours; do not extend antibiotic prophylaxis treatments more than 24hours after a surgical procedure; do not perform routine antibiotic prophylaxis for uncomplicated clean and no prosthetic surgery; and do not use antibiotics postoperatively after uncomplicated appendicitis. The Spanish Association of Surgeons's participation in this campaign has allowed a reflection on those activities that do not add value in the field of surgery and it is expected that the spread of this process serves to reduce its performance. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. 2013 ambulatory blood pressure monitoring recommendations for the diagnosis of adult hypertension, assessment of cardiovascular and other hypertension-associated risk, and attainment of therapeutic goals.

    Science.gov (United States)

    Hermida, Ramón C; Smolensky, Michael H; Ayala, Diana E; Portaluppi, Francesco

    2013-04-01

    Correlation between systolic (SBP) and diastolic (DBP) blood pressure (BP) level and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is much greater for ambulatory BP monitoring (ABPM) than daytime office measurements. The 2013 ABPM guidelines specified herein are based on ABPM patient outcomes studies and constitute a substantial revision of current knowledge. The asleep SBP mean and sleep-time relative SBP decline are the most significant predictors of CVD events, both individually as well as jointly when combined with other ABPM-derived prognostic markers. Thus, they should be preferably used to diagnose hypertension and assess CVD and other associated risks. Progressive decrease by therapeutic intervention of the asleep BP mean is the most significant predictor of CVD event-free interval. The 24-h BP mean is not recommended to diagnose hypertension because it disregards the more valuable clinical information pertaining to the features of the 24-h BP pattern. Persons with the same 24-h BP mean may display radically different 24-h BP patterns, ranging from extreme-dipper to riser types, representative of markedly different risk states. Classification of individuals by comparing office with either the 24-h or awake BP mean as "masked normotensives" (elevated clinic BP but normal ABPM), which should replace the terms of "isolated office" or "white-coat hypertension", and "masked hypertensives" (normal clinic BP but elevated ABPM) is misleading and should be avoided because it disregards the clinical significance of the asleep BP mean. Outcome-based ABPM reference thresholds for men, which in the absence of compelling clinical conditions are 135/85 mmHg for the awake and 120/70 mmHg for the asleep SBP/DBP means, are lower by 10/5 mmHg for SBP/DBP in uncomplicated, low-CVD risk, women and lower by 15/10 mmHg for SBP/DBP in male and female high-risk patients, e.g., with diabetes, chronic kidney disease (CKD), and/or past CVD

  15. Targeting of SMN to Cajal bodies is mediated by self-association.

    Science.gov (United States)

    Morse, Robert; Shaw, Debra J; Todd, Adrian G; Young, Philip J

    2007-10-01

    The childhood autosomal recessive disorder spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron (SMN) gene. SMN localizes diffusely in the cytoplasm and in distinct nuclear structures called Cajal bodies. Cajal bodies are believed to be the storage and processing sites of several ribonucleoproteins. Here, using a novel panel of SMN exon deletion constructs, we report a systematic analysis of internal targeting domains in the SMN protein. We demonstrate that the peptides encoded by exons 2b, 3 and 6 perform an integral role in the cellular targeting of SMN. In addition, we identify a nine amino acid motif within the highly conserved sequences of the exon 2b encoded domain that mediates Cajal body targeting and self-association. Deletion of this domain dramatically affects SMN activity and results in a dominant-negative clone. These results identify critical domains within the SMN protein and have an impact on our understanding of the SMN protein with regards to SMA as well as cellular biology.

  16. Targeted Imaging of Tumor-Associated Macrophages by Cyanine 7-Labeled Mannose in Xenograft Tumors

    Directory of Open Access Journals (Sweden)

    Chong Jiang MD

    2017-01-01

    Full Text Available Mannose receptor is considered as a hallmark of M2-oriented tumor-associated macrophages (TAMs, but its utility in TAMs was rarely reported. Therefore, deoxymannose (DM, a high-affinity ligand of mannose receptor, was labeled with near-infrared dye cyanine 7 (Cy7, and its feasibility of targeted imaging on TAMs was evaluated in vitro and in vivo. The Cy7-DM was synthesized, and its binding affinity with induced TAMs in vitro, whole-body imaging in xenograft tumor mouse model in vivo, and the cellular localization in dissected tissues were evaluated. We demonstrated a high uptake of Cy7-DM by induced M2 macrophages and TAMs in tumor tissues. In vivo near-infrared live imaging visualized abundant TAMs in tumor lesions instead of inflammatory sites by Cy7-DM imaging, and the quantity of Cy7-DM signals in tumors was significantly higher than that shown in inflammatory sites from 1 to 8 hours of imaging. Our results suggest that mannose could rapidly and specifically target TAMs and is a promising candidate for targeted diagnosis of tumor with rich TAMs.

  17. Design of functional small interfering RNAs targeting amyotrophic lateral sclerosis-associated mutant alleles

    Institute of Scientific and Technical Information of China (English)

    GENG Chang-ming; DING Hong-liu

    2011-01-01

    Background RNA interference (RNAi) is a potential cure for amyotrophic lateral sclerosis (ALS) caused by dominant,gain-of-function superoxide dismutase 1 (SOD1) mutations. The success of such therapy relies on the functional small interfering RNAs (siRNAs) that can effectively deliver RNAi. This study aimed to design the functional siRNAs targeting ALS-associated mutant alleles.Methods A modified dual luciferase system containing human SOD1 mRNA target was established to quantify siRNA efficacy. Coupled with validated siRNAs identified in the literature, we analyzed the rationale of siRNA design and subsequently developed an asymmetry rule-based strategy for designing siRNA. We then further tested the effectiveness of this design strategy in converting a naturally symmetric siRNA into functional siRNAs with favorable asymmetry for gene silencing of SOD1 alleles.Results The efficacies of siRNAs could vary tremendously by one base-pair position change. Functional siRNAs could target the whole span of SOD1 mRNA coding sequence as well as non-coding region. While there is no distinguishable pattern of the distribution of nucleobases in these validated siRNAs, the high percent of GC count at the last two positions of siRNAs (P18 and P19) indicated a strong effect of asymmetry rule. Introducing a mismatch at position 1 of the 5' of antisense strand of siRNA successfully converted the inactive siRNA into functional siRNAs that silence SOD1 with desired efficacy.Conclusions Asymmetry rule-based strategy that incorporates a mismatch into siRNA most consistently enhances RNAi efficacy and guarantees producing functional siRNAs that successfully silence ALS-associated SOD1 mutant alleles regardless target positions. This strategy could also be useful to design siRNAs for silencing other disease-associated dominant, gain-of-function mutant genes.

  18. Mitochondria-Targeted Peptide Reverses Mitochondrial Dysfunction and Cognitive Deficits in Sepsis-Associated Encephalopathy.

    Science.gov (United States)

    Wu, Jing; Zhang, Mingqiang; Hao, Shuangying; Jia, Ming; Ji, Muhuo; Qiu, Lili; Sun, Xiaoyan; Yang, Jianjun; Li, Kuanyu

    2015-08-01

    Sepsis-associated encephalopathy (SAE) is associated with increased mortality, morbidity, and long-term cognitive impairments. Its pathophysiology remains to be determined and an effective pharmacologic treatment is lacking. The goal of this study was to investigate the effects of the mitochondria-targeted peptide SS-31 on mitochondrial function and cognitive deficits in SAE mice. C57BL/6 male mice were randomly divided into sham, sham + SS-31, cecal ligation and puncture (CLP), and CLP + SS-31 groups. Peptide SS-31 (5 mg/kg) was intraperitoneally administrated immediately after operation and afterwards once daily for six consecutive days. Surviving mice were subjected to behavioral tests and the hippocampus was collected for biochemical analysis 7 days after operation. The results showed that CLP resulted in high mortality rate and cognitive deficits, representative characteristics of SAE. A physiological mechanistic investigation revealed that mitochondrial function of hippocampus was severely impaired, coupled with reactive oxygen species (ROS) generation, triggering neuronal apoptosis and inflammation. Notably, administration of peptide SS-31 protected the integrity of mitochondria, reversed the mitochondrial dysfunction, inhibited the apoptosis resulting from the release of cytochrome c, diminished the response of inflammation, and ultimately reversed the behavior deficits in the SAE mice. In conclusion, our data demonstrate that daily treatment with mitochondria-targeted peptide SS-31 reduces mortality rate and ameliorates cognitive deficits, which is possibly through a mechanism of reversing mitochondrial dysfunction and partial inhibition of neuronal apoptosis and inflammation in the hippocampus of the SAE mice.

  19. Protective and risk factors associated with voice strain among teachers in Castile and Leon, Spain: recommendations for voice training.

    Science.gov (United States)

    Ubillos, Silvia; Centeno, Javier; Ibañez, Jaime; Iraurgi, Ioseba

    2015-03-01

    The aim of this research was to know the protective and risk factors associated with voice strain in teachers. A total of 675 teachers from Castille and León, Spain took part in the research within an age range between 23 and 66 years (from nursery school to university). A cross-sectional, descriptive, and analytic design was applied to data from a self-administered questionnaire. The research showed that 16.4% had suffered some voice disorder and a remarkable percentage had never received any kind of voice training. The bivariate and multivariate analyses show that the size of the classroom, being a primary school teacher, teaching physical education, the noise caused by the students in the classroom, the struggle to keep the order within the class, raising the voice, and bad sleep are risk factors in the voice disorders. Each learning stage features a different risk factor, namely in nursery school, the noise caused by the pupils; in primary education, raising the voice; and in secondary education, the struggle to keep the order within the class. All these risk factors are linked with each other. The preventive measures must provide adequate answers to the voice requirements for every subject and stage, and these preventive measures must be based on the educational psychology principles to help the teachers deal with the problems originated by the lack of authority or the noise made by the students, using the proper voice techniques. Copyright © 2015. Published by Elsevier Inc.

  20. [Use of sugars and sweeteners in children's diets. Recommendations of the Nutrition Committee of the Spanish Paediatric Association].

    Science.gov (United States)

    Gil-Campos, M; San José González, M A; Díaz Martín, J J

    2015-11-01

    The term «sweetener» refers to a food additive that imparts a sweet flavour and usually provides no or very low energy. It is used to sweeten foods, medicines and food supplements with no nutritional purposes. For years, no-calorie sweeteners have been used as substitutes for all or part of the sugar content in foods and beverages. In recent decades its consumption has risen to prevent tooth decay, or as an aid in weight control, obesity and diabetes and, in general, to achieve an optimal energy balance. However, consumption of sugary or sweetened food and soft drinks is high, making this situation of special interest in calorie intake and in the poor behavioural pattern of eating habits in children. In addition, questions remain among consumers about the risks to health associated with their use, whether they are artificial or natural. The «artificial sweeteners» are the group of greatest interest in research in order to demonstrate their safety and to provide firm data on their possible therapeutic effects. The aim of the present document is to increase information for paediatricians on the characteristics of different sweeteners, and to advise on the choice of sweeteners, based on their properties. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  1. Immunotherapeutic targeting of shared melanoma-associated antigens in a murine glioma model.

    Science.gov (United States)

    Prins, Robert M; Odesa, Sylvia K; Liau, Linda M

    2003-12-01

    Immune-based treatments for central nervous system gliomas have traditionally lagged behind those of more immunogenic tumors such as melanoma. The relative paucity of defined glioma-associated antigens that can be targeted by the immune system may partially account for this situation. Antigens present on melanomas have been extensively characterized, both in humans and in murine preclinical models. Melanocytes and astrocytes are both derived embryologically from the neural ectoderm. Their neoplastic counterparts, malignant melanomas and gliomas, have been shown in humans to share common antigens at the RNA level. However, little is known concerning whether gliomas can be targeted by immune-based strategies that prime T cells to epitopes from melanoma-associated antigens (MAAs). In this study, we provide evidence that two common murine glioma cell lines (GL26 and GL261) express the melanoma antigens gp100 and tyrosinase-related protein 2 (TRP-2). To understand the immunogenicity of murine gliomas to CD8(+) T cells, we examined the ability of a MAA-specific CTL cell line to lyse the glioma cells, as well as the in vivo expansion of MAA-specific CD8(+) T cells in animals harboring gliomas. Both glioma cell lines were lysed by a human gp100-specific CTL cell line in vitro. Mice harboring s.c. GL26 gliomas possessed TRP-2-specific CD8(+) T cells, providing further evidence that these gliomas express the protein products in the context of MHC class I. Furthermore, MAA peptide-pulsed dendritic cells could prime T cells that specifically recognize GL26 glioma cells in vitro. Lastly, mice that were prevaccinated with human gp100 and TRP-2 peptide-pulsed dendritic cells had significantly extended survival when challenged with tumor cells in the brain, resulting in >50% long-term survival. These results suggest that shared MAAs on gliomas can be targeted immunotherapeutically, pointing the way to a new potential treatment option for patients with malignant gliomas.

  2. Targeting tumor-associated antigens to the MHC class I presentation pathway.

    Science.gov (United States)

    Gross, G; Margalit, A

    2007-06-01

    There is little doubt that cytotoxic T lymphocytes (CTLs) can kill tumor cells in-vivo. However, most CTL-inducing immunization protocols examined so far in cancer patients have yielded only limited clinical benefits, underscoring the urge to improve current approaches for the effective induction of tumor-reactive CTLs. The tumor side of the immunological frontline is armed with large masses, high mutability and an arsenal of immune evasion and suppression mechanisms. Accordingly, the confronting CTLs should come in large numbers, recognize an assortment of MHC class I (MHC-I) bound tumor-associated peptides and be brought into action under effective immunostimulatory conditions. Naïve CTLs are activated to become effector cells in secondary lymphoid organs, following their productive encounter with MHC-I-bound peptides at the surface of dendritic cells (DCs). Therefore, many cancer vaccines under development focus on the optimization of peptide presentation by DCs at this critical stage. The elucidation of discrete steps and the subsequent identification of inherent bottlenecks in the MHC-I antigen presentation pathway have fueled elaborate efforts to enhance vaccine efficacy by the rational targeting of proteins or peptides, formulated into these vaccines, to this pathway. Protein- and gene-based strategies are accordingly devised to deliver tumor-associated peptides to selected cellular compartments, which are essential for the generation of functional CTL ligands. Many of these strategies target the conventional, endogenous route, while others harness the unique pathways that enable DCs to present exogenous antigens, known as cross-presentation. Here we dissect the intricate machinery that produces CTL ligands and examine how knowledge-based cancer vaccines can target the sequence of workstations, biochemical utensils and molecular intermediates comprising this production line.

  3. The axon-dendrite targeting of Kv3 (Shaw) channels is determined by a targeting motif that associates with the T1 domain and ankyrin G.

    Science.gov (United States)

    Xu, Mingxuan; Cao, Ruifeng; Xiao, Rui; Zhu, Michael X; Gu, Chen

    2007-12-19

    Kv3 (Shaw) channels regulate rapid spiking, transmitter release and dendritic integration of many central neurons. Crucial to functional diversity are the complex targeting patterns of channel proteins. However, the targeting mechanisms are not known. Here we report that the axon-dendrite targeting of Kv3.1 is controlled by a conditional interaction of a C-terminal axonal targeting motif (ATM) with the N-terminal T1 domain and adaptor protein ankyrin G. In cultured hippocampal neurons, although the two splice variants of Kv3.1, Kv3.1a and Kv3.1b, are differentially targeted to the somatodendritic and axonal membrane, respectively, the lysine-rich ATM is surprisingly common for both splice variants. The ATM not only directly binds to the T1 domain in a Zn2+-dependent manner, but also associates with the ankyrin-repeat domain of ankyrin G. However, the full-length channel proteins of Kv3.1b display stronger association to ankyrin G than those of Kv3.1a, suggesting that the unique splice domain at Kv3.1b C terminus influences ATM binding to T1 and ankyrin G. Because ankyrin G mainly resides at the axon initial segment, we propose that it may function as a barrier for axon-dendrite targeting of Kv3.1 channels. In support of this idea, disrupting ankyrin G function either by over-expressing a dominant-negative mutant or by siRNA knockdown decreases polarized axon-dendrite targeting of both Kv3.1a and Kv3.1b. We conclude that the conditional ATM masked by the T1 domain in Kv3.1a is exposed by the splice domain in Kv3.1b, and is subsequently recognized by ankyrin G to target Kv3.1b into the axon.

  4. Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets.

    Science.gov (United States)

    Khan, Sajid; Shukla, Samriddhi; Sinha, Sonam; Meeran, Syed Musthapa

    2013-12-01

    Obesity is the cause of a large proportion of breast cancer incidences and mortality in post-menopausal women. In obese people, elevated levels of various growth factors such as insulin and insulin-like growth factors (IGFs) are found. Elevated insulin level leads to increased secretion of estrogen by binding to the circulating sex hormone binding globulin (SHBG). The increased estrogen-mediated downstream signaling favors breast carcinogenesis. Obesity leads to altered expression profiles of various adipokines and cytokines including leptin, adiponectin, IL-6, TNF-α and IL-1β. The increased levels of leptin and decreased adiponectin secretion are directly associated with breast cancer development. Increased levels of pro-inflammatory cytokines within the tumor microenvironment promote tumor development. Efficacy of available breast cancer drugs against obesity-associated breast cancer is yet to be confirmed. In this review, we will discuss different adipokine- and cytokine-mediated molecular signaling pathways involved in obesity-associated breast cancer, available therapeutic strategies and potential therapeutic targets for obesity-associated breast cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Gender-Specific Associations between Perceived Neighbourhood Walkability and Meeting Walking Recommendations When Walking for Transport and Recreation for Czech Inhabitants over 50 Years of Age

    Directory of Open Access Journals (Sweden)

    Jana Pelclová

    2013-12-01

    Full Text Available Few studies have investigated the different effects that the built environment may have on the physical activity behaviours of men and women. Therefore, the aim of this study was to estimate the gender differences in meeting walking recommendations in relation to perceived neighbourhood walkability attributes within the active transportation and leisure-time domains for Czech inhabitants over 50 years of age. The sample included 1,417 men and 1,422 women who were randomly selected. The Abbreviated Neighbourhood Environment Walkability Scale (ANEWS was used to obtain information about the perceived environment. The self-administered long version of the IPAQ was used to assess physical activity levels. When walking for transport, men living in neighbourhoods with high street connectivity (OR = 1.47, CI = 1.04–2.9 and higher traffic and crime safety (OR = 1.28, CI = 1.02–1.6 and women living in neighbourhoods with high proximity (OR = 1.36, CI = 1.04–1.77 and high neighbourhood aesthetics (OR = 1.36, CI = 1.04–1.76 were more likely to meet recommended levels of walking. No environmental attributes were found to significantly influence the accomplishment of walking recommendations by men or women when walking for leisure. The study results indicate the gender-specific associations between transportation-related walking and the environment factors. The consideration of those factors in the design of gender-specific walking interventions for Czech inhabitants may help the interventions to be more effective in promotion of physical activity.

  6. Gender-specific associations between perceived neighbourhood walkability and meeting walking recommendations when walking for transport and recreation for Czech inhabitants over 50 years of age.

    Science.gov (United States)

    Pelclová, Jana; Frömel, Karel; Cuberek, Roman

    2013-12-30

    Few studies have investigated the different effects that the built environment may have on the physical activity behaviours of men and women. Therefore, the aim of this study was to estimate the gender differences in meeting walking recommendations in relation to perceived neighbourhood walkability attributes within the active transportation and leisure-time domains for Czech inhabitants over 50 years of age. The sample included 1,417 men and 1,422 women who were randomly selected. The Abbreviated Neighbourhood Environment Walkability Scale (ANEWS) was used to obtain information about the perceived environment. The self-administered long version of the IPAQ was used to assess physical activity levels. When walking for transport, men living in neighbourhoods with high street connectivity (OR = 1.47, CI = 1.04-2.9) and higher traffic and crime safety (OR = 1.28, CI = 1.02-1.6) and women living in neighbourhoods with high proximity (OR = 1.36, CI = 1.04-1.77) and high neighbourhood aesthetics (OR = 1.36, CI = 1.04-1.76) were more likely to meet recommended levels of walking. No environmental attributes were found to significantly influence the accomplishment of walking recommendations by men or women when walking for leisure. The study results indicate the gender-specific associations between transportation-related walking and the environment factors. The consideration of those factors in the design of gender-specific walking interventions for Czech inhabitants may help the interventions to be more effective in promotion of physical activity.

  7. Human Papillomavirus vaccination in general practice in France, three years after the implementation of a targeted vaccine recommendation based on age and sexual history.

    Science.gov (United States)

    Thierry, Pascale; Lasserre, Andrea; Rossignol, Louise; Kernéis, Solen; Blaizeau, Fanette; Stheneur, Chantal; Blanchon, Thierry; Levy-Bruhl, Daniel; Hanslik, Thomas

    2016-01-01

    In France, vaccination against human papilloma virus (HPV) was recommended in 2007 for all 14-year-old girls as well as "catch-up" vaccination for girls between 15-23 y of age either before or within one year of becoming sexually active. We evaluated the vaccine coverage according to the eligibility for vaccination in a sample of young girls aged 14 to 23 years, who were seen in general practices. A survey was proposed to 706 general practitioners (GPs) and carried out from July to September 2010. GPs, also called "family doctor," are physicians whose practice is not restricted to a specific field of medicine but instead covers a variety of medical problems in patients of all ages. Each participating GP included, retrospectively, the last female patient aged 14-17 y and the last female patient aged 18-23 y whom he had seen. A questionnaire collected information regarding the GP and the patients' characteristics. The vaccine coverage was determined according to the eligibility for vaccination, i.e. the coverage among younger women (14-17) and among those sexually active in the second age range (18-23). Sexual activity status was assessed by GP, according to information stated in the medical record. The 363 participating physicians (response rate 51.4%) included 712 patients (357 in the 14- to 17-year-old group and 355 in the 15- to 23-year-old group) in their responses. The rate of the vaccination coverage in the 14- to 17-year-old group was 55%. Among the girls in the 18- to 23-year-old group, 126 were eligible, and their vaccination coverage rate was 82%. The evaluation of the eligibility by the GPs was incorrect in 36% of the cases. Of the 712 patients, 6% of the girls had been vaccinated without a need for the vaccination, and 26% of the girls had not been vaccinated, although they needed to be vaccinated. Regarding the vaccine uptake, vaccination at the age of 14 was not as effective as vaccinating the older population for which vaccination was indicated as a

  8. Adherence index based on the AHA 2006 diet and lifestyle recommendations is associated with select cardiovascular disease risk factors in older Puerto Ricans.

    Science.gov (United States)

    Bhupathiraju, Shilpa N; Lichtenstein, Alice H; Dawson-Hughes, Bess; Tucker, Katherine L

    2011-03-01

    In 2006, the AHA released diet and lifestyle recommendations (AHA-DLR) for cardiovascular disease (CVD) risk reduction. The effect of adherence to these recommendations on CVD risk is unknown. Our objective was to develop a unique diet and lifestyle score based on the AHA-DLR and to evaluate this score in relation to available CVD risk factors. In a cross-sectional study of Puerto Rican adults aged 45-75 y living in the greater Boston area, information was available for the following variables: diet (semiquantitative FFQ), blood pressure, waist circumference (WC), 10-y risk of coronary heart disease (CHD) (Framingham risk score), and fasting plasma lipids, serum glucose, insulin, and C-reactive protein (CRP) concentrations. We developed a diet and lifestyle score (AHA-DLS) based on the AHA-DLR. The AHA-DLS had both internal consistency and content validity. It was associated with plasma HDL cholesterol (P = 0.001), serum insulin (P = 0.0003), and CRP concentrations (P = 0.02), WC (P lifestyle behaviors and CVD risk.

  9. Italian Association of Clinical Endocrinologists (AME) & Italian Association of Clinical Diabetologists (AMD) Position Statement : Diabetes mellitus and thyroid disorders: recommendations for clinical practice.

    Science.gov (United States)

    Guastamacchia, Edoardo; Triggiani, Vincenzo; Aglialoro, Alberto; Aiello, Antimo; Ianni, Lucia; Maccario, Mauro; Zini, Michele; Giorda, Carlo; Guglielmi, Rinaldo; Betterle, Corrado; Attanasio, Roberto; Borretta, Giorgio; Garofalo, Piernicola; Papini, Enrico; Castello, Roberto; Ceriello, Antonio

    2015-06-01

    Thyroid disease and diabetes mellitus, the most common disorders in endocrine practice, are not infrequently associated in the same subject. An altered thyroid function may affect glucose tolerance and worsen metabolic control in patients with diabetes. Thyrotoxicosis increases the risk of hyperglycemic emergencies, while a clinically relevant hypothyroidism may have a detrimental effect on glycemic control in diabetic patients. The association of alterations in thyroid function with diabetes mellitus may adversely affect the risk of cardiovascular and microvascular complications resulting from diabetes. Moreover, the treatments used for both diabetes and thyroid disease, respectively, can impact one other. Finally, multinodular goiter, but not thyroid carcinoma, was shown to be more prevalent in type 2 diabetes mellitus. Aim of the present Position Statement is to focus on the evidence concerning the association of thyroid disease and diabetes mellitus and to provide some practical suggestions for an updated clinical management.

  10. Competitive release and outbreaks of non-target pests associated with transgenic Bt cotton.

    Science.gov (United States)

    Zeilinger, Adam R; Olson, Dawn M; Andow, David A

    2016-06-01

    The adoption of transgenic Bt cotton has, in some cases, led to environmental and economic benefits through reduced insecticide use. However, the distribution of these benefits and associated risks among cotton growers and cotton-growing regions has been uneven due in part to outbreaks of non-target or secondary pests, thereby requiring the continued use of synthetic insecticides. In the southeastern USA, Bt cotton adoption has resulted in increased abundance of and damage from stink bug pests, Euschistus servus and Nezara viridula (Heteroptera: Pentatomidae). While the impact of increased stink bug abundance has been well-documented, the causes have remained unclear. We hypothesize that release from competition with Bt-susceptible target pests may drive stink bug outbreaks in Bt cotton. We first examined the evidence for competitive release of stink bugs through meta-analysis of previous studies. We then experimentally tested if herbivory by Bt-susceptible Helicoverpa zea increases stink bug leaving rates and deters oviposition on non-Bt cotton. Consistent with previous studies, we found differences in leaving rates only for E servus, but we found that both species strongly avoided ovipositing on H. zea-damaged plants. Considering all available evidence, competitive release of stink bug populations in Bt cotton likely contributes to outbreaks, though the relative importance of competitive release remains an open question. Ecological risk assessments of Bt crops and other transgenic insecticidal crops would benefit from greater understanding of the ecological mechanisms underlying non-target pest outbreaks and greater attention to indirect ecological effects more broadly.

  11. Hormonally up-regulated neu-associated kinase: A novel target for breast cancer progression.

    Science.gov (United States)

    Zambrano, Joelle N; Neely, Benjamin A; Yeh, Elizabeth S

    2017-05-01

    Hormonally up-regulated neu-associated Kinase (Hunk) is a protein kinase that was originally identified in the murine mammary gland and has been shown to be highly expressed in Human Epidermal Growth Factor Receptor 2 positive (HER2(+)/ErbB2(+)) breast cancer cell lines as well as MMTV-neu derived mammary tumor cell lines. However, the physiological role of Hunk has been largely elusive since its identification. Though Hunk is predicted to be a Serine/Threonine (Ser/Thr) protein kinase with homology to the SNF1/AMPK family of protein kinases, there are no known Hunk substrates that have been identified to date. Recent work demonstrates a role for Hunk in HER2(+)/ErbB2(+) breast cancer progression, including drug resistance to HER2/ErbB2 inhibitors, with Hunk potentially acting downstream of HER2/ErbB2 and the PI3K/Akt pathway. These studies have collectively shown that Hunk plays a vital role in promoting mammary tumorigenesis, as Hunk knockdown via shRNA in xenograft tumor models or crossing MMTV-neu or Pten-deficient genetically engineered mouse models into a Hunk knockout (Hunk-/-) background impairs mammary tumor growth in vivo. Because the majority of HER2(+)/ErbB2(+) breast cancer patients acquire drug resistance to HER2/ErbB2 inhibitors, the characterization of novel drug targets like Hunk that have the potential to simultaneously suppress tumorigenesis and potentially enhance efficacy of current therapeutics is an important facet of drug development. Therefore, work aimed at uncovering specific regulatory functions for Hunk that could contribute to this protein kinase's role in both tumorigenesis and drug resistance will be informative. This review focuses on what is currently known about this under-studied protein kinase, and how targeting Hunk may prove to be a potential therapeutic target for the treatment of breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Quality criteria in bariatric surgery: Consensus review and recommendations of the Spanish Association of Surgeons and the Spanish Society of Bariatric Surgery.

    Science.gov (United States)

    Sabench Pereferrer, Fátima; Domínguez-Adame Lanuza, Eduardo; Ibarzabal, Ainitze; Socas Macias, María; Valentí Azcárate, Víctor; García Ruiz de Gordejuela, Amador; García-Moreno Nisa, Francisca; González Fernández, Jesús; Vilallonga Puy, Ramón; Vilarrasa García, Nuria; Sánchez Santos, Raquel

    2017-01-01

    Bariatric surgery has proven to be highly effective in controlling obesity and metabolic syndrome; the results of this surgery are not only expressed in terms of weight loss, but also in terms of resolution of comorbidities, improved quality of life and complications. The different parameters used to measure these outcomes require uniformity and reference patterns. Therefore, it is essential to identify those indicators and quality criteria that are helpful in defining the «best practice» principles in bariatric surgery. In this regard, the Section of Obesity of the Spanish Association of Surgeons, in collaboration with the Spanish Society for Bariatric Surgery (SECO), present as an objective to identify the key points that define «quality» in this type of surgery. We describe the main indicators based on the published literature as well as the criteria for referral of the main comorbidities according to the evidence found and grades of recommendation.

  13. Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: update on recommendations from the British Association for Psychopharmacology.

    Science.gov (United States)

    Bolea-Alamañac, Blanca; Nutt, David J; Adamou, Marios; Asherson, Phillip; Bazire, Stephen; Coghill, David; Heal, David; Müller, Ulrich; Nash, John; Santosh, Paramala; Sayal, Kapil; Sonuga-Barke, Edmund; Young, Susan J

    2014-03-01

    Attention deficit hyperactivity disorder (ADHD) is a common condition with a high societal burden. The present guidelines summarise current literature, generating expert consensus recommendations for the treatment of ADHD in children and adults. These guidelines also provide a review of recent research in the fields of neuroimaging, neuropsychology and genetics of ADHD. Novel discoveries in these areas have informed physiological models for the disease. Since the publication of the previous British Association for Psychopharmacology guidelines in 2008, new drugs have been licensed and further compounds are being investigated. The publication of randomised controlled trials of psychological interventions has contributed to the range of treatment options for ADHD. As the disorder has been diagnosed more frequently there has been greater focus on comorbid conditions and how they impact treatment. Services have continued to develop for the treatment of ADHD in adults and care agreements have been introduced to facilitate access to treatment.

  14. Centrosome-associated regulators of the G2/M checkpoint as targets for cancer therapy

    Directory of Open Access Journals (Sweden)

    Broaddus Russell R

    2009-02-01

    Full Text Available Abstract In eukaryotic cells, control mechanisms have developed that restrain cell-cycle transitions in response to stress. These regulatory pathways are termed cell-cycle checkpoints. The G2/M checkpoint prevents cells from entering mitosis when DNA is damaged in order to afford these cells an opportunity to repair the damaged DNA before propagating genetic defects to the daughter cells. If the damage is irreparable, checkpoint signaling might activate pathways that lead to apoptosis. Since alteration of cell-cycle control is a hallmark of tumorigenesis, cell-cycle regulators represent potential targets for therapy. The centrosome has recently come into focus as a critical cellular organelle that integrates G2/M checkpoint control and repairs signals in response to DNA damage. A growing number of G2/M checkpoint regulators have been found in the centrosome, suggesting that centrosome has an important role in G2/M checkpoint function. In this review, we discuss centrosome-associated regulators of the G2/M checkpoint, the dysregulation of this checkpoint in cancer, and potential candidate targets for cancer therapy.

  15. Alveolar macrophages are the main target cells in feline calicivirus-associated pneumonia.

    Science.gov (United States)

    Monné Rodriguez, J M; Soare, T; Malbon, A; Blundell, R; Papoula-Pereira, R; Leeming, G; Köhler, K; Kipar, A

    2014-08-01

    Feline calicivirus (FCV) is a pathogen of felids and one of the most common causative agents of feline upper respiratory disease (URD). Reports of natural FCV pneumonia in the course of respiratory tract infections are sparse. Therefore, knowledge on the pathogenesis of FCV-induced lung lesions comes only from experimental studies. The aim of the present study was to assess the type and extent of pulmonary involvement in natural respiratory FCV infections of domestic cats and to identify the viral target cells in the lung. For this purpose, histology, immunohistochemistry and RNA-in situ hybridisation for FCV and relevant cell markers were performed on diagnostic post-mortem specimens collected after fatal URD, virulent systemic FCV or other conditions. All groups of cats exhibited similar acute pathological changes, dominated by multifocal desquamation of activated alveolar macrophages (AM) and occasional type II pneumocytes with fibrin exudation, consistent with diffuse alveolar damage (DAD). In fatal cases, this was generally seen without evidence of epithelial regeneration. In cats without clinical respiratory signs, type II pneumocyte hyperplasia was present alongside the other changes, consistent with the post-damage proliferative phase of DAD. FCV infected and replicated in AM and, to a lesser extent, type II pneumocytes. This study shows that lung involvement is an infrequent but important feature of FCV-induced URD. AM are the main viral target cell and pulmonary replication site, and their infection is associated with desquamation and activation, as well as death via apoptosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Chemically modified peptide scaffolds target the CFTR-associated ligand PDZ domain.

    Directory of Open Access Journals (Sweden)

    Jeanine F Amacher

    Full Text Available PDZ domains are protein-protein interaction modules that coordinate multiple signaling and trafficking pathways in the cell and that include active therapeutic targets for diseases such as cancer, cystic fibrosis, and addiction. Our previous work characterized a PDZ interaction that restricts the apical membrane half-life of the cystic fibrosis transmembrane conductance regulator (CFTR. Using iterative cycles of peptide-array and solution-binding analysis, we targeted the PDZ domain of the CFTR-Associated Ligand (CAL, and showed that an engineered peptide inhibitor rescues cell-surface expression of the most common CFTR disease mutation ΔF508. Here, we present a series of scaffolds containing chemically modifiable side chains at all non-motif positions along the CAL PDZ domain binding cleft. Concordant equilibrium dissociation constants were determined in parallel by fluorescence polarization, isothermal titration calorimetry, and surface plasmon resonance techniques, confirming robust affinity for each scaffold and revealing an enthalpically driven mode of inhibitor binding. Structural studies demonstrate a conserved binding mode for each peptide, opening the possibility of combinatorial modification. Finally, we diversified one of our peptide scaffolds with halogenated substituents that yielded modest increases in binding affinity. Overall, this work validates our approach and provides a stereochemical foundation for further CAL inhibitor design and screening.

  17. Chemically modified peptide scaffolds target the CFTR-associated ligand PDZ domain.

    Science.gov (United States)

    Amacher, Jeanine F; Zhao, Ruizhi; Spaller, Mark R; Madden, Dean R

    2014-01-01

    PDZ domains are protein-protein interaction modules that coordinate multiple signaling and trafficking pathways in the cell and that include active therapeutic targets for diseases such as cancer, cystic fibrosis, and addiction. Our previous work characterized a PDZ interaction that restricts the apical membrane half-life of the cystic fibrosis transmembrane conductance regulator (CFTR). Using iterative cycles of peptide-array and solution-binding analysis, we targeted the PDZ domain of the CFTR-Associated Ligand (CAL), and showed that an engineered peptide inhibitor rescues cell-surface expression of the most common CFTR disease mutation ΔF508. Here, we present a series of scaffolds containing chemically modifiable side chains at all non-motif positions along the CAL PDZ domain binding cleft. Concordant equilibrium dissociation constants were determined in parallel by fluorescence polarization, isothermal titration calorimetry, and surface plasmon resonance techniques, confirming robust affinity for each scaffold and revealing an enthalpically driven mode of inhibitor binding. Structural studies demonstrate a conserved binding mode for each peptide, opening the possibility of combinatorial modification. Finally, we diversified one of our peptide scaffolds with halogenated substituents that yielded modest increases in binding affinity. Overall, this work validates our approach and provides a stereochemical foundation for further CAL inhibitor design and screening.

  18. The scatter factor signaling pathways as therapeutic associated target in cancer treatment.

    Science.gov (United States)

    Accornero, P; Pavone, L M; Baratta, M

    2010-01-01

    Receptor tyrosine kinases (RTKs) are key regulators of critical cellular processes such as proliferation, differentiation, neo-vascularization, and tissue repair. In addition to their importance in the regulation of normal physiology, aberrant expression of certain RTKs has also been associated to the development and progression of many types of cancer. c-Met and RON are two RTKs with closely related sequences, structural homology, and similar functional properties. Both these receptors, once activated by their respective ligands, the Hepatocyte Growth Factor/Scatter Factor (HGF/SF1) and the Macrophage Stimulating Protein/Scatter Factor 2 (MSP/SF2), can induce cell migration, invasion and proliferation. Soon after its discovery in the mid-1980s, c-Met attracted a great interest because of its role in modulating cell motility. Moreover, the causal role for c-Met activating mutations in human cancer propelled an intensive drug discovery effort throughout academic institutions and pharmaceutical companies. While c-Met is now a well-accepted target for anticancer drug design, less is known about the role of RON in cancer and less has been done to target this receptor. In this review we will discuss the biological relevance of c-Met and RON, their deregulation in human cancers and the progress, so far, in identifying c-Met and RON signaling inhibitors. Finally, we will focus on the development of therapeutic strategies and drug efficacy studies based on interfering the scatter factor signaling pathways.

  19. Recommender systems in knowledge-mining

    Science.gov (United States)

    Volna, Eva

    2017-07-01

    The subject of the paper is to analyse the possibilities of application of recommender systems in the field of data mining. The work focuses on three basic types of recommender systems (collaborative, content-based and hybrid). The goal of the article is to evaluate which of these three concepts of recommender systems provides forecast with the lowest error rate in the domain of recommending movies. This target is fulfilled by the practical part of the work - at first, the own recommender system was designed and created, capable of obtaining movies recommendation from the database based on the user's preferences. Next, we verified experimentally which recommender system produces more accurate results.

  20. Targets and Mechanisms Associated with Protection from Severe Plasmodium falciparum Malaria in Kenyan Children

    DEFF Research Database (Denmark)

    Murungi, Linda M; Sondén, Klara; Llewellyn, David

    2016-01-01

    Severe malaria (SM) is a life-threatening complication of infection withPlasmodium falciparum Epidemiological observations have long indicated that immunity against SM is acquired relatively rapidly, but prospective studies to investigate its immunological basis are logistically challenging...... and have rarely been undertaken. We investigated the merozoite targets and antibody-mediated mechanisms associated with protection against SM in Kenyan children aged 0 to 2 years. We designed a unique prospective matched case-control study of well-characterized SM clinical phenotypes nested within...... a longitudinal birth cohort of children (n= 5,949) monitored over the first 2 years of life. We quantified immunological parameters in sera collected before the SM event in cases and their individually matched controls to evaluate the prospective odds of developing SM in the first 2 years of life. Anti-AMA1...

  1. Combined targeted treatment in early onset epilepsy associated with tuberous sclerosis

    Directory of Open Access Journals (Sweden)

    Romina Moavero

    2016-01-01

    Full Text Available Tuberous sclerosis is associated with epilepsy in up to 85% of cases, and in 2/3, the onset is within the first year of life. An early antiepileptic treatment is crucial to minimize the consequences of epilepsy on cognition and behavior. We present a case report of a child with tuberous sclerosis who presented with infantile spasms at the age of 6 months, immediately treated with vigabatrin. Because of the presence of a subependymal giant cell astrocytoma, he also received everolimus since 18 months of age. We might wonder if an earlier treatment could have produced a better outcome; in fact, despite a targeted combined treatment, he continues to suffer from sporadic focal motor seizures, and at the age of 40 months, he presents severe developmental delay with autism-like behavior.

  2. Chimeric adeno-associated virus and bacteriophage: a potential targeted gene therapy vector for malignant glioma.

    Science.gov (United States)

    Asavarut, Paladd; O'Neill, Kevin; Syed, Nelofer; Hajitou, Amin

    2014-01-01

    The incipient development of gene therapy for cancer has fuelled its progression from bench to bedside in mere decades. Of all malignancies that exist, gliomas are the largest class of brain tumors, and are renowned for their aggressiveness and resistance to therapy. In order for gene therapy to achieve clinical success, a multitude of barriers ranging from glioma tumor physiology to vector biology must be overcome. Many viral gene delivery systems have been subjected to clinical investigation; however, with highly limited success. In this review, the current progress and challenges of gene therapy for malignant glioma are discussed. Moreover, we highlight the hybrid adeno-associated virus and bacteriophage vector as a potential candidate for targeted gene delivery to brain tumors.

  3. Targeting the cancer-associated fibroblasts as a treatment in triple-negative breast cancer

    Science.gov (United States)

    Takai, Ken; Le, Annie; Weaver, Valerie M.; Werb, Zena

    2016-01-01

    Increased collagen expression in tumors is associated with increased risk of metastasis, and triple-negative breast cancer (TNBC) has the highest propensity to develop distant metastases when there is evidence of central fibrosis. Transforming growth factor-β (TGF-β) ligands regulated by cancer-associated fibroblasts (CAFs) promote accumulation of fibrosis and cancer progression. In the present study, we have evaluated TNBC tumors with enhanced collagen to determine whether we can reduce metastasis by targeting the CAFs with Pirfenidone (PFD), an anti-fibrotic agent as well as a TGF-β antagonist. In patient-derived xenograft models, TNBC tumors exhibited accumulated collagen and activated TGF-β signaling, and developed lung metastasis. Next, primary CAFs were established from 4T1 TNBC homograft tumors, TNBC xenograft tumors and tumor specimens of breast cancer patients. CAFs promoted primary tumor growth with more fibrosis and TGF-β activation and lung metastasis in 4T1 mouse model. We then examined the effects of PFD in vitro and in vivo. We found that PFD had inhibitory effects on cell viability and collagen production of CAFs in 2D culture. Furthermore, CAFs enhanced tumor growth and PFD inhibited the tumor growth induced by CAFs by causing apoptosis in the 3D co-culture assay of 4T1 tumor cells and CAFs. In vivo, PFD alone inhibited tumor fibrosis and TGF-β signaling but did not inhibit tumor growth and lung metastasis. However, PFD inhibited tumor growth and lung metastasis synergistically in combination with doxorubicin. Thus, PFD has great potential for a novel clinically applicable TNBC therapy that targets tumor-stromal interaction. PMID:27756881

  4. Rare Variants in Neurodegeneration Associated Genes Revealed by Targeted Panel Sequencing in a German ALS Cohort

    Directory of Open Access Journals (Sweden)

    Stefanie Krüger

    2016-10-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive fatal multisystemic neurodegenerative disorder caused by preferential degeneration of upper and lower motor neurons. To further delineate the genetic architecture of the disease, we used comprehensive panel sequencing in a cohort of 80 German ALS patients. The panel covered 39 confirmed ALS genes and candidate genes, as well as 238 genes associated with other entities of the neurodegenerative disease spectrum. In addition, we performed repeat length analysis for C9orf72. Our aim was to (1 identify potentially disease-causing variants, to (2 assess a proposed model of polygenic inheritance in ALS and to (3 connect ALS with other neurodegenerative entities.We identified 79 rare potentially pathogenic variants in 27 ALS associated genes in familial and sporadic cases. Five patients had pathogenic C9orf72 repeat expansions, a further four patients harbored intermediate length repeat expansions. Our findings demonstrate that a genetic background of the disease can actually be found in a large proportion of seemingly sporadic cases and that it is not limited to putative most frequently affected genes such as C9orf72 or SOD1. Assessing the polygenic nature of ALS, we identified 15 patients carrying at least two rare potentially pathogenic variants in ALS associated genes including pathogenic or intermediate C9orf72 repeat expansions. Multiple variants might influence severity or duration of disease or could account for intrafamilial phenotypic variability or reduced penetrance. However, we could not observe a correlation with age of onset in this study. We further detected potentially pathogenic variants in other neurodegeneration associated genes in 12 patients, supporting the hypothesis of common pathways in neurodegenerative diseases and linking ALS to other entities of the neurodegenerative spectrum. Most interestingly we found variants in GBE1 and SPG7 which might represent differential diagnoses

  5. Rare Variants in Neurodegeneration Associated Genes Revealed by Targeted Panel Sequencing in a German ALS Cohort.

    Science.gov (United States)

    Krüger, Stefanie; Battke, Florian; Sprecher, Andrea; Munz, Marita; Synofzik, Matthis; Schöls, Ludger; Gasser, Thomas; Grehl, Torsten; Prudlo, Johannes; Biskup, Saskia

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive fatal multisystemic neurodegenerative disorder caused by preferential degeneration of upper and lower motor neurons. To further delineate the genetic architecture of the disease, we used comprehensive panel sequencing in a cohort of 80 German ALS patients. The panel covered 39 confirmed ALS genes and candidate genes, as well as 238 genes associated with other entities of the neurodegenerative disease spectrum. In addition, we performed repeat length analysis for C9orf72. Our aim was to (1) identify potentially disease-causing variants, to (2) assess a proposed model of polygenic inheritance in ALS and to (3) connect ALS with other neurodegenerative entities. We identified 79 rare potentially pathogenic variants in 27 ALS associated genes in familial and sporadic cases. Five patients had pathogenic C9orf72 repeat expansions, a further four patients harbored intermediate length repeat expansions. Our findings demonstrate that a genetic background of the disease can actually be found in a large proportion of seemingly sporadic cases and that it is not limited to putative most frequently affected genes such as C9orf72 or SOD1. Assessing the polygenic nature of ALS, we identified 15 patients carrying at least two rare potentially pathogenic variants in ALS associated genes including pathogenic or intermediate C9orf72 repeat expansions. Multiple variants might influence severity or duration of disease or could account for intrafamilial phenotypic variability or reduced penetrance. However, we could not observe a correlation with age of onset in this study. We further detected potentially pathogenic variants in other neurodegeneration associated genes in 12 patients, supporting the hypothesis of common pathways in neurodegenerative diseases and linking ALS to other entities of the neurodegenerative spectrum. Most interestingly we found variants in GBE1 and SPG7 which might represent differential diagnoses. Based on our

  6. Rare Variants in Neurodegeneration Associated Genes Revealed by Targeted Panel Sequencing in a German ALS Cohort

    Science.gov (United States)

    Krüger, Stefanie; Battke, Florian; Sprecher, Andrea; Munz, Marita; Synofzik, Matthis; Schöls, Ludger; Gasser, Thomas; Grehl, Torsten; Prudlo, Johannes; Biskup, Saskia

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive fatal multisystemic neurodegenerative disorder caused by preferential degeneration of upper and lower motor neurons. To further delineate the genetic architecture of the disease, we used comprehensive panel sequencing in a cohort of 80 German ALS patients. The panel covered 39 confirmed ALS genes and candidate genes, as well as 238 genes associated with other entities of the neurodegenerative disease spectrum. In addition, we performed repeat length analysis for C9orf72. Our aim was to (1) identify potentially disease-causing variants, to (2) assess a proposed model of polygenic inheritance in ALS and to (3) connect ALS with other neurodegenerative entities. We identified 79 rare potentially pathogenic variants in 27 ALS associated genes in familial and sporadic cases. Five patients had pathogenic C9orf72 repeat expansions, a further four patients harbored intermediate length repeat expansions. Our findings demonstrate that a genetic background of the disease can actually be found in a large proportion of seemingly sporadic cases and that it is not limited to putative most frequently affected genes such as C9orf72 or SOD1. Assessing the polygenic nature of ALS, we identified 15 patients carrying at least two rare potentially pathogenic variants in ALS associated genes including pathogenic or intermediate C9orf72 repeat expansions. Multiple variants might influence severity or duration of disease or could account for intrafamilial phenotypic variability or reduced penetrance. However, we could not observe a correlation with age of onset in this study. We further detected potentially pathogenic variants in other neurodegeneration associated genes in 12 patients, supporting the hypothesis of common pathways in neurodegenerative diseases and linking ALS to other entities of the neurodegenerative spectrum. Most interestingly we found variants in GBE1 and SPG7 which might represent differential diagnoses. Based on our

  7. Latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus promotes angiogenesis through targeting notch signaling effector Hey1.

    Science.gov (United States)

    Wang, Xing; He, Zhiheng; Xia, Tian; Li, Xiaofan; Liang, Deguang; Lin, Xianzhi; Wen, Hao; Lan, Ke

    2014-04-01

    Notch signaling has been implicated in the pathogenesis of Kaposi sarcoma. Kaposi sarcoma is an angioproliferative neoplasm that originates from Kaposi sarcoma-associated herpesvirus (KSHV) infection. Previously, we showed that the KSHV LANA protein can stabilize intracellular Notch in KSHV-infected tumor cells and promote cell proliferation. However, whether Notch signaling functions in pathologic angiogenesis of Kaposi sarcoma remains largely unknown. Hey1, an essential downstream effector of the Notch signaling pathway, has been demonstrated to play a fundamental role in vascular development. In the present study, we performed whole transcriptome, paired-end sequencing on three patient-matched clinical Kaposi sarcoma specimens and their corresponding adjacent stroma samples, with an average depth of 42 million reads per sample. Dll4, Hey1, and HeyL displayed significant upregulation in Kaposi sarcoma. Further verification based on immunohistochemistry analysis demonstrated that Hey1 was indeed highly expressed in Kaposi sarcoma lesions. Using the Matrigel plug assay, we showed that downregulation of Hey1 and γ-secretase inhibitor treatment caused dramatic reduction in the formation of new blood vessels in mice. Interestingly, LANA was responsible for the elevated level of Hey1 through inhibition of its degradation. Importantly, Hey1 stabilized by LANA promoted the neoplastic vasculature. Taken together, our data suggest that hijacking of the proangiogenic property of Hey1 by LANA is an important strategy utilized by KSHV to achieve pathologic angiogenesis and that Hey1 is a potential therapeutic target in Kaposi sarcoma.

  8. Association of hypertension drug target genes with blood pressure and hypertension in 86,588 individuals.

    Science.gov (United States)

    Johnson, Andrew D; Newton-Cheh, Christopher; Chasman, Daniel I; Ehret, Georg B; Johnson, Toby; Rose, Lynda; Rice, Kenneth; Verwoert, Germaine C; Launer, Lenore J; Gudnason, Vilmundur; Larson, Martin G; Chakravarti, Aravinda; Psaty, Bruce M; Caulfield, Mark; van Duijn, Cornelia M; Ridker, Paul M; Munroe, Patricia B; Levy, Daniel

    2011-05-01

    We previously conducted genome-wide association meta-analysis of systolic blood pressure, diastolic blood pressure, and hypertension in 29,136 people from 6 cohort studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Here we examine associations of these traits with 30 gene regions encoding known antihypertensive drug targets. We find nominal evidence of association of ADRB1, ADRB2, AGT, CACNA1A, CACNA1C, and SLC12A3 polymorphisms with 1 or more BP traits in the Cohorts for Heart and Aging Research in Genomic Epidemiology genome-wide association meta-analysis. We attempted replication of the top meta-analysis single nucleotide polymorphisms for these genes in the Global BPgen Consortium (n=34,433) and the Women's Genome Health Study (n=23,019) and found significant results for rs1801253 in ADRB1 (Arg389Gly), with the Gly allele associated with a lower mean systolic blood pressure (β: 0.57 mm Hg; SE: 0.09 mm Hg; meta-analysis: P=4.7×10(-10)), diastolic blood pressure (β: 0.36 mm Hg; SE: 0.06 mm Hg; meta-analysis: P=9.5×10(-10)), and prevalence of hypertension (β: 0.06 mm Hg; SE: 0.02 mm Hg; meta-analysis: P=3.3×10(-4)). Variation in AGT (rs2004776) was associated with systolic blood pressure (β: 0.42 mm Hg; SE: 0.09 mm Hg; meta-analysis: P=3.8×10(-6)), as well as diastolic blood pressure (P=5.0×10(-8)) and hypertension (P=3.7×10(-7)). A polymorphism in ACE (rs4305) showed modest replication of association with increased hypertension (β: 0.06 mm Hg; SE: 0.01 mm Hg; meta-analysis: P=3.0×10(-5)). Two loci, ADRB1 and AGT, contain single nucleotide polymorphisms that reached a genome-wide significance threshold in meta-analysis for the first time. Our findings suggest that these genes warrant further studies of their genetic effects on blood pressure, including pharmacogenetic interactions.

  9. MicroRNA-421 inhibits breast cancer metastasis by targeting metastasis associated 1.

    Science.gov (United States)

    Pan, Yongqin; Jiao, Genlong; Wang, Cunchuan; Yang, Jingge; Yang, Wah

    2016-10-01

    Dysregulation of microRNAs is involved in the initiation and progression of several human cancers, including breast cancer, as strong evidence of miRNAs acting as oncogenes or tumour suppressor genes has been found. This study was performed to investigate the biological functions of microRNA-421 (miR-421) in breast cancer and the underlying mechanisms. The expression level of miR-421 was detected in 50 pairs of surgical specimens and human breast cancer cell lines. The results showed that miR-421 is downregulated in breast cancer tissues and metastatic cell lines. In addition, the decrease in miR-421 levels was significantly associated with lymph node metastasis, recurrence/metastasis, or pTNM stage. Functions of miR-421 in cell migration and invasion were assessed through its silencing and overexpression. The results showed that miR-421 knockdown promotes invasion and metastasis in MCF-7 cells and its overexpression suppresses invasion and metastasis in MDA-MB-231 cells. The specific target genes of miR-421 were predicted by TargetScan algorithm and determined by dual luciferase reporter assay, quantitative reverse transcriptase PCR, and western blot analysis. miR-421 could suppress luciferase activity of the reporter containing 3'-untranslated region of metastasis associated 1 (MTA1), a potent oncogene. miR-421 overexpression or knockdown had no effect on the mRNA expression of MTA1, but it could modulate MTA1 protein level. Furthermore, MTA1 knockdown receded the effect of miR-421 inhibitor on invasion and metastasis of MCF-7 cells, and its overexpression receded the effect of miR-421 on invasion and metastasis of MDA-MB-231 cells. Our findings clearly demonstrate that miR-421 suppresses breast cancer metastasis by directly inhibiting MTA1 expression. The present study provides a new insight into the tumour suppressor roles of miR-421 and suggests that miR-421/MTA1 pathway is a putative therapeutic target in breast cancer.

  10. Cost-Efficient and Sustainable Deployment of Renewable Energy Sources towards the 20% Target by 2020, and beyond. D5.3. Key recommendations from the RES4LESS roadmap

    Energy Technology Data Exchange (ETDEWEB)

    Dalla Longa, F. [ECN Policy Studies, Amsterdam (Netherlands); Raimundo, C. [IT Power, Bristol, Avon (United Kingdom)

    2012-12-15

    In its Directive 2009/28/EC the European Commission (EC) set an ambitious 20% target on the final consumption of energy from renewable sources (RES) in 2020 (European Commission, 2009). This EU-level target is divided into different domestic targets for each single Member State (MS). The MS-level targets do not always reflect the domestic RES potentials, creating a situation where certain MSs will have to deploy very expensive technologies in order to meet their target, while other countries are expected to reach their target at lower costs and even produce a RES surplus. In order to promote a more balanced distribution of costs, the Directive allows MSs to establish cooperation mechanisms. Three types of cooperation mechanisms are defined: a MS could buy the RES-credits associated with the surplus potential of other MSs via statistical transfers, could finance additional RES deployment in other MSs by engaging in joint projects, or could share (part of) its RES potential with other MSs by establishing joint support schemes.

  11. Summary recommendations for responsible monitoring and regulation of clinical software systems. American Medical Informatics Association, The Computer-based Patient Record Institute, The Medical Library Association, The Association of Academic Health Science Libraries, The American Health Information Management Association, and The American Nurses Association.

    Science.gov (United States)

    Miller, R A; Gardner, R M

    1997-11-01

    Clinical software systems are becoming ubiquitous. A growing literature documents how these systems can improve health care delivery, but concerns about patient safety must now be formally addressed. In 1996, the U.S. Food and Drug Administration (FDA) called for discussions on regulation of software programs as medical devices. In response, a consortium of organizations dedicated to improving health care through information technology developed recommendations for the responsible regulation and monitoring of clinical software systems by users, vendors, and regulatory agencies. These recommendations were revised and approved by the American Medical informatics Association Public Policy Committee and Board. Other organizations reviewed, modified, and approved the recommendations, and the Boards of Directors of most of the organizations in the consortium endorsed the guidelines. The consortium proposes four categories of clinical system risk and four classes of monitoring and regulatory action that can be applied on the basis of the risk level. The consortium recommends that most clinical software systems be supervised locally and that developers of health care information systems adopt a code of good business practices. Budgetary and other constraints limit the type and number of systems that the FDA can regulate effectively; therefore, the FDA should exempt most clinical software systems and focus on systems that pose high clinical risk and provide limited opportunity for competent human intervention.

  12. 基于WHO卫生人力战略目标的我国农村卫生人才政策研究%Policy Recommendation of Rural Health Workforce Building Based on WHO Health Workforce Strategy Target

    Institute of Scientific and Technical Information of China (English)

    尹爱田; 王文华; 杨文燕

    2012-01-01

    Based on public policy nature and barrier analysis of rural health workforce building, we establish a theoretical frame from WHO health workforce strategy targets. From the four aspects of idea, model, action, measure, the policy recommendations conclude management policy, regulation policy, medical education policy and health workforce supporting policy.%文章以农村卫生人才建设的公共政策属性和对农村卫生人才建设的障碍分析为基础,基于世界卫生组织卫生人力战略目标建立理论框架,从思路、模式、行动、措施4个维度,提出建立和完善农村卫生人才管理政策、规制政策、医学教育政策和卫生人才支持政策的建议.

  13. Gender-associated genes in filarial nematodes are important for reproduction and potential intervention targets.

    Directory of Open Access Journals (Sweden)

    Ben-Wen Li

    also striking gender differences in environmental information processing and cell communication pathways. Many proteins encoded by GA genes are secreted by Brugia malayi, and these encode immunomodulatory molecules such as antioxidants and host cytokine mimics. Expression of many GA genes has been recently reported to be suppressed by tetracycline, which blocks reproduction in female Brugia malayi. Our localization of GA transcripts in filarial reproductive organs supports the hypothesis that these genes encode proteins involved in reproduction. CONCLUSIONS/SIGNIFICANCE: Genome-wide expression profiling coupled with a robust bioinformatics analysis has greatly expanded our understanding of the molecular biology of reproduction in filarial nematodes. This study has highlighted key molecules and pathways associated with reproductive and other biological processes and identified numerous potential candidates for rational drug design to target reproductive processes.

  14. Activated mammalian target of rapamycin is associated with T regulatory cell insufficiency in nasal polyps

    Directory of Open Access Journals (Sweden)

    Shi Jianbo

    2009-02-01

    Full Text Available Abstract Background Decreased infiltration of Foxp3+ T regulatory cell (Treg is considered to be critical for the Th1/Th2 dysregulation of nasal polyps, while the cellular mechanism underlying Foxp3+ Treg insufficiency is currently not well defined. Methods We attempted to investigate the tissue expression of phosphorylated mammalian target of rapamycin (pmTOR and infiltration of Foxp3+ Tregs in 28 nasal polyps and 16 controls by histological staining. We also evaluated the effects of blocking the mTOR signaling pathway with rapamycin on T cell phenotype selection and Foxp3+CD4+ Tregs expansion in a tissue culture system. Results Significantly increased infiltration of pmTOR+ inflammatory cells and decreased infiltration of Foxp3+CD4+ Tregs into nasal polyps was observed, with an inverse association. In the tissue culture system, we detected significantly elevated Foxp3 expression and IL-10 production, as well as an increased percentage of Foxp3+ Tregs in nasal polyps after blocking the mTOR signaling pathway with rapamycin. Conclusion Here we demonstrate for the first time that the mTOR signaling pathway is associated with Foxp3+ Tregs insufficiency in nasal polyps. Inhibition of the mTOR signaling pathway may be helpful for enhancement of Foxp3+ Treg expansion, as well as modulation of T cell phenotype imbalances in nasal polyps.

  15. Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol

    OpenAIRE

    Patel, Reesha R.; Barbosa, Cindy; Brustovetsky, Tatiana; Brustovetsky, Nickolay; Cummins, Theodore R.

    2016-01-01

    Resurgent sodium currents arise from channel reopening during repolarisation, and are predicted to increase neuronal excitability. Patel et al. show that epilepsy-associated mutations in the voltage-gated sodium channel Nav1.6, but not Nav1.1, upregulate resurgent currents. Cannabidiol preferentially targets these currents, suggesting a strategy for reducing neuronal hyperexcitability associated with epilepsy.

  16. Molecular and vascular targets in the pathogenesis and management of the hypertension associated with preeclampsia.

    Science.gov (United States)

    Reslan, Ossama M; Khalil, Raouf A

    2010-10-01

    Normal pregnancy is associated with significant hemodynamic changes and vasodilation of the uterine and systemic circulation in order to meet the metabolic demands of the mother and developing fetus. Preeclampsia (PE) is one of the foremost complications of pregnancy and a major cause of maternal and fetal mortality. The pathophysiological mechanisms of PE have been elusive, but some parts of the puzzle have begun to unravel. Genetic factors such as leptin gene polymorphism, environmental and dietary factors such as Ca(2+) and vitamin D deficiency, and co-morbidities such as obesity and diabetes may increase the susceptibility of pregnant women to develop PE. An altered maternal immune response may also play a role in the development of PE. Although the pathophysiology of PE is unclear, most studies have implicated inadequate invasion of cytotrophoblasts into the uterine artery, leading to reduced uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia. Placental ischemia induces the release of biologically active factors such as growth factor inhibitors, anti-angiogenic factors, inflammatory cytokines, reactive oxygen species, hypoxia-inducible factors, and antibodies to vascular angiotensin II (AngII) receptor. These bioactive factors could cause vascular endotheliosis and consequent increase in vascular resistance and blood pressure, as well as glomerular endotheliosis with consequent proteinuria. The PE-associated vascular endotheliosis could be manifested as decreased vasodilator mediators such as nitric oxide, prostacyclin and hyperpolarizing factor and increased vasoconstrictor mediators such as endothelin-1, AngII and thromboxane A₂. PE could also involve enhanced mechanisms of vascular smooth muscle contraction including intracellular Ca(2+), and Ca(2+) sensitization pathways such as protein kinase C and Rho-kinase. PE-associated changes in the extracellular matrix composition and matrix metalloproteinases activity also promote vascular

  17. The Cross-Sectional Association between Consumption of the Recommended Five Food Group "Grain (Cereal)", Dietary Fibre and Anthropometric Measures among Australian Adults.

    Science.gov (United States)

    Fayet-Moore, Flavia; Petocz, Peter; McConnell, Andrew; Tuck, Kate; Mansour, Marie

    2017-02-18

    The Australian Dietary Guidelines recommended "grain (cereal)" core food group includes both refined and whole grain foods, but excludes those that are discretionary (i.e., cakes). We investigated the association between daily serves from the "grain (cereal)" group and its effect on fibre and adiposity. Data from Australian adults in the 2011-2012 National Nutrition and Physical Activity Survey were used (n = 9341). Participants were categorised by serves of core grain foods and general linear models were used to investigate the effect of demographic, socioeconomic, and dietary covariates on waist circumference, body mass index (BMI) and fibre intake. Compared to core grain avoiders (0 serves), high consumers (6+ serves/day) were: more likely male and socially advantaged, had a healthier dietary pattern, less likely dieting, overweight or obese, and were at lower risk of metabolic complications. After adjustment for age, sex and energy intake, there was an inverse relationship between core grain serves intake and BMI (p grain serves was significantly associated with higher fibre, but marginally clinically significant for lower adiposity.

  18. A Flexible Electronic Commerce Recommendation System

    Science.gov (United States)

    Gong, Songjie

    Recommendation systems have become very popular in E-commerce websites. Many of the largest commerce websites are already using recommender technologies to help their customers find products to purchase. An electronic commerce recommendation system learns from a customer and recommends products that the customer will find most valuable from among the available products. But most recommendation methods are hard-wired into the system and they support only fixed recommendations. This paper presented a framework of flexible electronic commerce recommendation system. The framework is composed by user model interface, recommendation engine, recommendation strategy model, recommendation technology group, user interest model and database interface. In the recommender strategy model, the method can be collaborative filtering, content-based filtering, mining associate rules method, knowledge-based filtering method or the mixed method. The system mapped the implementation and demand through strategy model, and the whole system would be design as standard parts to adapt to the change of the recommendation strategy.

  19. Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chantarawong, Wipa [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan); Inter Departmental Multidisciplinary Graduate Program in Bioscience, Faculty of Science, Kasetsart University, Bangkok (Thailand); Takeda, Kazuhisa; Sangartit, Weerapon; Yoshizawa, Miki [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan); Pradermwong, Kantimanee [Department of Zoology, Faculty of Science, Kasetsart University, Bangkok (Thailand); Shibahara, Shigeki, E-mail: shibahar@med.tohoku.ac.jp [Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai (Japan)

    2014-11-28

    Highlights: • In human melanocytes, cadmium decreases the expression of MITF-M and tyrosinase and their mRNAs. • In human melanoma cells, cadmium decreases the expression of MITF-M protein and tyrosinase mRNA. • Expression of MITF-H is less sensitive to cadmium toxicity in melanocyte-linage cells. • Cadmium does not decrease the expression of MITF-H in retinal pigment epithelial cells. • MITF-M is the molecular target of cadmium toxicity in melanocytes. - Abstract: Dietary intake of cadmium is inevitable, causing age-related increase in cadmium accumulation in many organs, including hair, choroid and retinal pigment epithelium (RPE). Cadmium has been implicated in the pathogenesis of hearing loss and macular degeneration. The functions of cochlea and retina are maintained by melanocytes and RPE, respectively, and the differentiation of these pigment cells is regulated by microphthalmia-associated transcription factor (MITF). In the present study, we explored the potential toxicity of cadmium in the cochlea and retina by using cultured human melanocytes and human RPE cell lines. MITF consists of multiple isoforms, including melanocyte-specific MITF-M and widely expressed MITF-H. Levels of MITF-M protein and its mRNA in human epidermal melanocytes and HMV-II melanoma cells were decreased significantly by cadmium. In parallel with the MITF reduction, mRNA levels of tyrosinase, the key enzyme of melanin biosynthesis that is regulated by MITF-M, were also decreased. In RPE cells, however, the levels of total MITF protein, constituting mainly MITF-H, were not decreased by cadmium. We thus identify MITF-M as the molecular target of cadmium toxicity in melanocytes, thereby accounting for the increased risk of disability from melanocyte malfunction, such as hearing and vision loss among people with elevated cadmium exposure.

  20. Genomic analyses of musashi1 downstream targets show a strong association with cancer-related processes.

    Science.gov (United States)

    de Sousa Abreu, Raquel; Sanchez-Diaz, Patricia C; Vogel, Christine; Burns, Suzanne C; Ko, Daijin; Burton, Tarea L; Vo, Dat T; Chennasamudaram, Soudhamini; Le, Shu-Yun; Shapiro, Bruce A; Penalva, Luiz O F

    2009-05-01

    Musashi1 (Msi1) is a highly conserved RNA-binding protein with pivotal functions in stem cell maintenance, nervous system development, and tumorigenesis. Despite its importance, only three direct mRNA targets have been characterized so far: m-numb, CDKN1A, and c-mos. Msi1 has been shown to affect their translation by binding to short elements located in the 3'-untranslated region. To better understand Msi1 functions, we initially performed an RIP-Chip analysis in HEK293T cells; this method consists of isolation of specific RNA-protein complexes followed by identification of the RNA component via microarrays. A group of 64 mRNAs was found to be enriched in the Msi1-associated population compared with controls. These genes belong to two main functional categories pertinent to tumorigenesis: 1) cell cycle, cell proliferation, cell differentiation, and apoptosis and 2) protein modification (including ubiquitination and ubiquitin cycle). To corroborate our findings, we examined the impact of Msi1 expression on both mRNA (transcriptomic) and protein (proteomic) expression levels. Genes whose mRNA levels were affected by Msi1 expression have a Gene Ontology distribution similar to RIP-Chip results, reinforcing Msi1 participation in cancer-related processes. The proteomics study revealed that Msi1 can have either positive or negative effects on gene expression of its direct targets. In summary, our results indicate that Msi1 affects a network of genes and could function as a master regulator during development and tumor formation.

  1. Tumor-associated macrophages as an emerging target against tumors: Creating a new path from bench to bedside.

    Science.gov (United States)

    Jinushi, Masahisa; Komohara, Yoshihiro

    2015-04-01

    Tumor-associated macrophages are a critical component of tumor microenvironments, which affect tumor growth, tumor angiogenesis, immune suppression, metastasis and chemoresistance. There is emerging evidence that many anticancer modalities currently used in the clinic have unique and distinct properties that modulate the recruitment, polarization and tumorigenic activities of macrophages in the tumor microenvironments. Educated tumor-associated macrophages significantly impact the clinical efficacies of and resistance to these anticancer modalities. Moreover, the development of drugs targeting tumor-associated macrophages, especially c-Fms kinase inhibitors and humanized antibodies targeting colony-stimulating factor-1 receptor, are in early clinical stages and show promising benefit for cancer patients. These experimental and clinical findings prompted us to further evaluate the potential targets that exhibit tumorigenic and immunosuppressive potential in a manner specific for tumor associated macrophages. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. User behaviour, best practice and the risks of non-target exposure associated with anticoagulant rodenticide use.

    Science.gov (United States)

    Tosh, David G; Shore, Richard F; Jess, Stephen; Withers, Alan; Bearhop, Stuart; Ian Montgomery, W; McDonald, Robbie A

    2011-06-01

    Usage of anticoagulant rodenticides (ARs) is an integral component of modern agriculture and is essential for the control of commensal rodent populations. However, the extensive deployment of ARs has led to widespread exposure of a range of non-target predatory birds and mammals to some compounds, in particular the second-generation anticoagulant rodenticides (SGARs). As a result, there has been considerable effort placed into devising voluntary best practice guidelines that increase the efficacy of rodent control and reduce the risk of non-target exposure. Currently, there is limited published information on actual practice amongst users or implementation of best practice. We assessed the behaviour of a typical group of users using an on-farm questionnaire survey. Most baited for rodents every year using SGARs. Most respondents were apparently aware of the risks of non-target exposure and adhered to some of the best practice recommendations but total compliance was rare. Our questionnaire revealed that users of first generation anticoagulant rodenticides rarely protected or checked bait stations, and so took little effort to prevent primary exposure of non-targets. Users almost never searched for and removed poisoned carcasses and many baited for prolonged periods or permanently. These factors are all likely to enhance the likelihood of primary and secondary exposure of non-target species.

  3. Generation and associative encoding in young and old adults: the effect of the strength of association between cues and targets on a cued recall task.

    Science.gov (United States)

    Taconnat, Laurence; Froger, Charlotte; Sacher, Mathilde; Isingrini, Michel

    2008-01-01

    The generation effect (i.e., better recall of the generated items than the read items) was investigated with a between-list design in young and elderly participants. The generation task difficulty was manipulated by varying the strength of association between cues and targets. Overall, strong associates were better recalled than weak associates. However, the results showed different generation effect patterns according to strength of association and age, with a greater generation effect for weak associates in younger adults only. These findings suggest that generating weak associates leads to more elaborated encoding, but that elderly adults cannot use this elaborated encoding as well as younger adults to recall the target words at test.

  4. Targeted PCR for Detection of Vaginal Bacteria Associated with Bacterial Vaginosis▿

    Science.gov (United States)

    Fredricks, David N.; Fiedler, Tina L.; Thomas, Katherine K.; Oakley, Brian B.; Marrazzo, Jeanne M.

    2007-01-01

    Several novel bacterial species have been detected in subjects with bacterial vaginosis (BV) by using broad-range PCR assays, but this approach is insensitive for detecting minority species. We developed a series of taxon-directed 16S rRNA gene PCR assays for more sensitive detection of key vaginal bacteria. We sought to determine the prevalence of each species in the vagina, its association with BV, and the utility of PCR for the microbiological diagnosis of BV. Targeted PCR assays were developed for 17 vaginal bacterial species and applied to 264 vaginal-fluid samples from 81 subjects with and 183 subjects without BV. The results were compared to those of two widely accepted methods for diagnosing BV, the use of clinical findings (Amsel criteria) and the interpretation of vaginal-fluid Gram stains (Nugent criteria). Leptotrichia/Sneathia, Atopobium vaginae, an Eggerthella-like bacterium, Megasphaera species, and three novel bacteria in the order Clostridiales are among the bacterial species significantly associated with BV. PCR detection of either a Megasphaera species or one of the Clostridiales bacteria yielded a sensitivity of 99% and a specificity of 89% for diagnosis of BV compared to the Amsel clinical criteria and a sensitivity of 95.9% and a specificity of 93.7% compared to the Nugent criteria (Gram stain). PCR detection of one or more fastidious bacterial species is a more reliable indicator of BV than detection of bacteria, such as Gardnerella vaginalis, previously linked to BV, highlighting the potential of PCR for the diagnosis of BV. PMID:17687006

  5. Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Michael Schmitt

    2007-01-01

    Full Text Available Leukemia associated antigens (LAAs are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL cloning, serological analysis of recombinant cDNA expression libraries (SEREX and mass spectrometry (MS. In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs, serial analysis of gene expression (SAGE and 2-dimensional gel electrophoresis (2-DE have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML. It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.Abbreviations: AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; ATRA: all-trans-retinoic acid; B-CLL: B-cell chronic lymphocytic leukemia; CT: cancer-testis; CTL: cytotoxic T-lymphocyte; FAB: French-American-British; HI: hypusination inhibitors; HSP: heat shock protein; ITD: internal tandem duplication; LAA: leukemia associated antigen; MDS: myelodysplastic syndrome; MGEA6: meningioma antigen 6; MPD: myeloproliferative disease; MS: mass spectrometry; NK: natural killer; PRAME: preferentially expressed antigen of melanoma; PRTN3: proteinase 3; RAGE-1: renal antigen 1; RHAMM: receptor for hyaluronic acid-mediated motility; RQ-PCR: real-time PCR; SAGE: serial analysis of gene expression; SCT: stem cell transplant; SEREX: serological analysis of recombinant cDNA expression libraries; SNPs: single nucleotide polymorphisms; UPD

  6. Targeting Oxygen-Sensing Prolyl Hydroxylase for Metformin-Associated Lactic Acidosis Treatment.

    Science.gov (United States)

    Oyaizu-Toramaru, Tomoko; Suhara, Tomohiro; Hayakawa, Noriyo; Nakamura, Takashi; Kubo, Akiko; Minamishima, Shizuka; Yamaguchi, Kyoji; Hishiki, Takako; Morisaki, Hiroshi; Suematsu, Makoto; Minamishima, Yoji Andrew

    2017-08-15

    Metformin is one of the most widely used therapeutics for type 2 diabetes mellitus and also has anticancer and antiaging properties. However, it is known to induce metformin-associated lactic acidosis (MALA), a severe medical condition with poor prognosis, especially in individuals with renal dysfunction. Inhibition of prolyl hydroxylase (PHD) is known to activate the transcription factor hypoxia-inducible factor (HIF) that increases lactate efflux as a result of enhanced glycolysis, but it also enhances gluconeogenesis from lactate in the liver that contributes to reducing circulating lactate levels. Here, we investigated the outcome of pharmaceutical inhibition of PHD in mice with MALA induced through the administration of metformin per os and an intraperitoneal injection of lactic acid. We found that the PHD inhibitors significantly increased the expression levels of genes involved in gluconeogenesis in the liver and the kidney and significantly improved the survival of mice with MALA. Furthermore, the PHD inhibitor also improved the rate of survival of MALA induced in mice with chronic kidney disease (CKD). Thus, PHD represents a new therapeutic target for MALA, which is a critical complication of metformin therapy. Copyright © 2017 American Society for Microbiology.

  7. Leukemia associated antigens: their dual role as biomarkers and immunotherapeutic targets for acute myeloid leukemia.

    Science.gov (United States)

    Guinn, Barbara-Ann; Mohamedali, Azim; Mills, Ken I; Czepulkowski, Barbara; Schmitt, Michael; Greiner, Jochen

    2007-02-14

    Leukemia associated antigens (LAAs) are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL) cloning, serological analysis of recombinant cDNA expression libraries (SEREX) and mass spectrometry (MS). In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs), serial analysis of gene expression (SAGE) and 2-dimensional gel electrophoresis (2-DE) have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML). It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel) and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.

  8. MHC class-I associated phosphopeptides are the targets of memory-like immunity in leukemia

    Science.gov (United States)

    Cobbold, Mark; De La Peña, Hugo; Norris, Andrew; Polefrone, Joy; Qian, Jie; English, A. Michelle; Cummings, Kara; Penny, Sarah; Turner, James E.; Cottine, Jennifer; Abelin, Jennifer G; Malaker, Stacy A; Zarling, Angela L; Huang, Hsing-Wen; Goodyear, Oliver; Freeman, Sylvie; Shabanowitz, Jeffrey; Pratt, Guy; Craddock, Charles; Williams, Michael E; Hunt, Donald F; Engelhard, Victor H

    2014-01-01

    Deregulation of signaling pathways involving phosphorylation is a hallmark of malignant transformation. Degradation of phosphoproteins generates cancer-specific phosphopeptides that are associated with MHC-I and II molecules and recognized by T-cells. We identified 95 phosphopeptides presented on the surface of primary hematological tumors and normal tissues, including 61 that were tumor-specific. Phosphopeptides were more prevalent on more aggressive and malignant samples. CD8 T-cell lines specific for these phosphopeptides recognized and killed both leukemia cell lines and HLA-matched primary leukemia cells ex vivo. Healthy individuals showed surprisingly high levels of CD8 T-cell responses against many of these phosphopeptides within the circulating memory compartment. This immunity was significantly reduced or absent in some leukemia patients, which correlated with clinical outcome, and was restored following allogeneic stem cell transplantation. These results suggest that phosphopeptides may be targets of cancer immune surveillance in humans, and point to their importance for development of vaccine-based and T-cell adoptive transfer immunotherapies.. PMID:24048523

  9. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

    DEFF Research Database (Denmark)

    Ehret, Georg B; Ferreira, Teresa; Chasman, Daniel I;

    2016-01-01

    To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66...... across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings...

  10. Dietary Recommendations for Healthy Children

    Science.gov (United States)

    ... Restaurant Deciphering the Menu Ordering Your Meal Eating Fast Food Dining Out Tips by Cuisine Physical Activity Fitness ... Food and Beverage Toolkit Dietary Recommendations for Healthy Children Updated:Jul 22,2016 The American Heart Association ...

  11. Infectious prosthetic hip joint loosening: bacterial species involved in its aetiology and their antibiotic resistance profiles against antibiotics recommended for the therapy of implant-associated infections.

    Science.gov (United States)

    Bogut, Agnieszka; Niedźwiadek, Justyna; Strzelec-Nowak, Dagmara; Blacha, Jan; Mazurkiewicz, Tomasz; Marczyński, Wojciech; Kozioł-Montewka, Maria

    2014-04-01

    Reliable microbiological diagnosis along with surgery and prolonged antibiotic therapy are key elements in the management of prosthetic-joint infections (PJIs). The purpose of this study was to characterize antibiotic resistance profiles of bacteria involved in the aetiology of PJIs. A total of 33 bacterial isolates cultured from 31 patients undergoing exchange of total hip prostheses were analyzed. The diagnostic approach toward isolation of prosthesis- associated microorganisms included sonication of retrieved implants and conventional cultures of periprosthetic tissues and synovial fluid. The in vitro resistance profiles of bacterial isolates were determined in relation to antibiotics recommended for the therapy of PJIs using the disc diffusion method, E-tests(®) and broth microdilution system. Coagulase-negative staphylococci (CNS) were predominant microorganisms followed by Staphylococcus aureus, Enterobacter cloacae, Streptococcus mitis, and Propionibacterium acnes. Twenty out of 30 and 12 out of 30 staphylococcal isolates were methicillin- and multi-drug resistant, respectively. Only two isolates were rifampicinresistant. All staphylococci were susceptible to glycopeptides and linezolid. This paper stresses the pathogenic role of staphylococci in patients suffering from implant loosening and reports high methicillin- and multidrug-resistance rates in these bacteria. Hence, antimicrobial susceptibility tests of individual bacterial isolates must always be performed to guide selection of the optimal therapeutic option.

  12. Association Study between Cervical Lesions and Single or Multiple Vaccine-Target and Non-Vaccine Target Human Papillomavirus (HPV Types in Women from Northeastern Brazil.

    Directory of Open Access Journals (Sweden)

    Bárbara Simas Chagas

    Full Text Available We performed an association between high-grade squamous intraepithelial lesions (HSIL, low-grade squamous intraepithelial lesions (LSIL and single or multiple vaccine-target as well as non-vaccine target Human papillomavirus (HPV types. Using bead-based HPV genotyping, 594 gynecological samples were genotyped. An association between squamous intraepithelial lesion (SIL and presence of HPV16, 18, 31, 58 and 56 types were calculated. The risk was estimated by using odds ratio (OR and 95% of confidence intervals (CI. A total of 370 (62.3% women were HPV positive. Among these, 157 (42.7% presented a single HPV infection, and 212 (57.3% were infected by more than one HPV type. HPV31 was the most prevalent genotype, regardless single and multiple HPV infections. Single infection with HPV31 was associated with LSIL (OR=2.32; 95%CI: 1.01 to 5.32; p=0.04; HPV31 was also associated with LSIL (OR=3.28; 95%CI: 1.74 to 6.19; p= 0.0002 and HSIL (OR=3.82; 95%CI: 2.10 to 6.97; p<0.001 in multiple HPV infections. Risk to harbor cervical lesions was observed in multiple HPV infections with regard to the HPV56 (OR=5.39; 95%CI: 2.44 to 11.90; p<0.001for LSIL; OR=5.37; 95%CI: 2.71 to 10.69; p<0.001 and HPV58 (OR=3.29; 95%CI: 1.34 to 8.09; p=0.0091 for LSIL; OR=3.55; 95%CI: 1.56 to 8.11; p=0.0026 genotypes. In addition, women coinfected with HPV16/31/56 types had 6 and 5-fold increased risk of HSIL (OR=6.46; 95%CI: 1.89 to 22.09; p=0.002 and LSIL (OR=5.22; 95%CI: 1.10 to 24.70; p=0.03, respectively. Multiple HPV infections without HPV16/18 has 2-fold increased risk of HSIL (OR=2.57; 95%CI: 1.41 to 4.70; p=0.002 and LSIL OR=2.03; 95%CI: 1.08 to 3.79; p=0.02. The results of this study suggest that single and multiple vaccine target as well as non-vaccine target HPV types are associated with LSIL and HSIL. These finding should be taken into consideration in the design of HPV vaccination strategies.

  13. TiPs: a database of therapeutic targets in pathogens and associated tools.

    KAUST Repository

    Lepore, Rosalba

    2013-05-21

    MOTIVATION: The need for new drugs and new targets is particularly compelling in an era that is witnessing an alarming increase of drug resistance in human pathogens. The identification of new targets of known drugs is a promising approach, which has proven successful in several cases. Here, we describe a database that includes information on 5153 putative drug-target pairs for 150 human pathogens derived from available drug-target crystallographic complexes. AVAILABILITY AND IMPLEMENTATION: The TiPs database is freely available at http://biocomputing.it/tips. CONTACT: anna.tramontano@uniroma1.it or allegra.via@uniroma1.it.

  14. The SWEET SPOTS study: a real-world interpretation of the 2012 American Diabetes Association Position Statement regarding individualized A1C targets

    Directory of Open Access Journals (Sweden)

    Bieszk N

    2016-11-01

    Full Text Available Nella Bieszk,1 Michael Grabner,2 Wenhui Wei,1 Nicole G Bonine,2 Judith J Stephenson,2 1Sanofi US, Inc., Bridgewater, NJ, 2HealthCore, Inc., Wilmington, DE, USA Objective: To evaluate awareness of the 2012 American Diabetes Association (ADA Position Statement among physicians and assess its effects on patient-centered glycated hemoglobin (A1C goals in the management of type 2 diabetes (T2D. Research design and methods: The Summarizing Real-World Individualized TrEatmEnT GoalS and Potential SuppOrT Systems in Type 2 Diabetes (SWEET SPOTS study used the HealthCore claims database to identify T2D patients, stratified by risk, and their treating physicians to assess primary care physician and endocrinologist awareness of the 2012 ADA Position Statement. Physicians completed online surveys on A1C targets before and after receiving an educational intervention to review the position statement. Results: Of 125 responding physicians (mean age 50.3 years, 12.8% endocrinologists who were linked to 125 patient profiles (mean age 56.9 years, 42% female, mean A1C 7.2%, 92% were at least somewhat aware of the position statement prior to the intervention and 59% believed that the statement would impact how they set A1C targets. The educational intervention resulted in mostly less stringent goal setting for both lower and higher risk patients, but changes were not significant. The proportion of physician-assigned A1C targets within ADA-recommended ranges increased from 56% to 66% post-intervention (P<0.0001. Conclusion: Physicians treating T2D are aware of the 2012 ADA Position Statement and believe that it may influence treatment goals. While patient-specific A1C targets were not significantly impacted, physicians indicated that they would make targets more or less stringent for lower and higher risk patients, respectively, across their practice. Further research into optimizing physician education regarding individualized A1C targets is warranted. Keywords

  15. The Universal Recommender

    CERN Document Server

    Kunegis, Jérôme; Umbrath, Winfried

    2009-01-01

    We describe the Universal Recommender, a recommender system for semantic datasets that generalizes domain-specific recommenders such a content-based, collaborative, social, bibliographic, lexicographic, hybrid and other recommenders. In contrast to existing recommender systems, the Universal Recommender applies to any dataset that allows a semantic representation. We describe the scalable three-stage architecture of the Universal Recommender and its application to Internet Protocol Television (IPTV). To achieve good recommendation accuracy, several novel machine learning and optimization problems are identified. We finally give a brief argument supporting the need for machine learning recommenders.

  16. Measurement of azimuthal asymmetries associated with deeply virtual Compton scattering on a longitudinally polarized deuterium target

    Energy Technology Data Exchange (ETDEWEB)

    Airapetian, A. [Giessen Univ. (Germany). Physikalisches Inst.; Michigan Univ., Ann Arbor, MI (United States). Randall Laboratory of Physics; Akopov, N. [Yerevan Physical Institute, Yerevan (Armenia); Akopov, Z. [DESY Hamburg (DE)] (and others)

    2010-08-15

    Azimuthal asymmetries in exclusive electroproduction of a real photon from a longitudinally polarized deuterium target are measured with respect to target polarization alone and with respect to target polarization combined with beam helicity and/or beam charge. The asymmetries appear in the distribution of the real photons in the azimuthal angle {phi} around the virtual photon direction, relative to the lepton scattering plane. The asymmetries arise from the deeply virtual Compton scattering process and its interference with the Bethe-Heitler process. The results for the beam-charge and beam-helicity asymmetries from a tensor polarized deuterium target with vanishing vector polarization are shown to be compatible with those from an unpolarized deuterium target, which is expected for incoherent scattering dominant at larger momentum transfer. Furthermore, the results for the single target-spin asymmetry and for the double-spin asymmetry are found to be compatible with the corresponding asymmetries previously measured on a hydrogen target. For coherent scattering on the deuteron at small momentum transfer to the target, these findings imply that the tensor contribution to the cross section is small. Furthermore, the tensor asymmetry is found to be compatible with zero. (orig.)

  17. BRCA1-Associated Protein BRCC36: A Novel Target for Breast Cancer Therapy

    Science.gov (United States)

    2008-10-01

    plasma membranes of target cells (“smart drug”); and (iv) the siRNAs can be efficiently delivered into the target cells through endocytosis. BODY...BRCA2: 1994 and beyond. Nat Rev Cancer 4(9):665-76. Peer D, Zhu P, Carman CV, Lieberman J, Shimaoka M. 2007. Selective gene silencing in activated

  18. Identification of potential target genes associated with the pathogenesis of osteoarthritis using microarray based analysis.

    Science.gov (United States)

    Li, Meng; Zhi, Liqiang; Zhang, Zhi; Bian, Weiguo; Qiu, Yusheng

    2017-09-01

    The aim of the present study was to investigate the molecular circuitry of osteoarthritis (OA) and identify more potential target genes for OA treatment. Microarray data of GSE32317 was downloaded from the National Center for Biotechnology Information Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in samples of synovial membrane from patients with early stage of knee OA (OA_Early) and late stage of knee OA (OA_End) that were compared with healthy specimens. Bioinformatics analysis was applied to analyze the significant functions and pathways that were enriched by the common DEGs identified in OA_Early and OA_End samples. Furthermore, a protein‑protein interaction (PPI) network was constructed and significant modules were extracted. Transcription factors (TFs) that could regulate genes in the significant modules were identified. A total of 1,207 and 1,575 DEGs were identified in OA_Early and OA_End samples compared with healthy samples, respectively. A total of 740 genes were upregulated and 308 genes were downregulated across the OA_Early and OA_End samples. These common DEGs were enriched in different gene ontology terms and pathways, such as immune response. Angiotensinogen (AGT) and C‑X‑C motif chemokine ligand 12 (CXCL12) were identified to be hub proteins in the PPI network or in the selected module 1. In addition, the DEG lysine demethylase 2B (KDM2B) was identified as a TF that can regulate genes in the significant modules 2 and 3. In conclusion, the present study has identified AGT, CXCL12 and KDM2B as potentially essential genes associated with the pathogenesis of knee OA.

  19. MicroRNAs and liver cancer associated with iron overload: therapeutic targets unravelled.

    Science.gov (United States)

    Greene, Catherine M; Varley, Robert B; Lawless, Matthew W

    2013-08-28

    Primary liver cancer is a global disease that is on the increase. Hepatocellular carcinoma (HCC) accounts for most primary liver cancers and has a notably low survival rate, largely attributable to late diagnosis, resistance to treatment, tumour recurrence and metastasis. MicroRNAs (miRNAs/miRs) are regulatory RNAs that modulate protein synthesis. miRNAs are involved in several biological and pathological processes including the development and progression of HCC. Given the poor outcomes with current HCC treatments, miRNAs represent an important new target for therapeutic intervention. Several studies have demonstrated their role in HCC development and progression. While many risk factors underlie the development of HCC, one process commonly altered is iron homeostasis. Iron overload occurs in several liver diseases associated with the development of HCC including Hepatitis C infection and the importance of miRNAs in iron homeostasis and hepatic iron overload is well characterised. Aberrant miRNA expression in hepatic fibrosis and injury response have been reported, as have dysregulated miRNA expression patterns affecting cell cycle progression, evasion of apoptosis, invasion and metastasis. In 2009, miR-26a delivery was shown to prevent HCC progression, highlighting its therapeutic potential. Several studies have since investigated the clinical potential of other miRNAs with one drug, Miravirsen, currently in phase II clinical trials. miRNAs also have potential as biomarkers for the diagnosis of HCC and to evaluate treatment efficacy. Ongoing studies and clinical trials suggest miRNA-based treatments and diagnostic methods will have novel clinical applications for HCC in the coming years, yielding improved HCC survival rates and patient outcomes.

  20. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

    Science.gov (United States)

    Ward, Michael M; Deodhar, Atul; Akl, Elie A; Lui, Andrew; Ermann, Joerg; Gensler, Lianne S; Smith, Judith A; Borenstein, David; Hiratzka, Jayme; Weiss, Pamela F; Inman, Robert D; Majithia, Vikas; Haroon, Nigil; Maksymowych, Walter P; Joyce, Janet; Clark, Bruce M; Colbert, Robert A; Figgie, Mark P; Hallegua, David S; Prete, Pamela E; Rosenbaum, James T; Stebulis, Judith A; van den Bosch, Filip; Yu, David T Y; Miller, Amy S; Reveille, John D; Caplan, Liron

    2016-02-01

    To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas. © 2015, American College of Rheumatology.

  1. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis

    Science.gov (United States)

    Ward, Michael M.; Deodhar, Atul; Akl, Elie A.; Lui, Andrew; Ermann, Joerg; Gensler, Lianne S.; Smith, Judith A.; Borenstein, David; Hiratzka, Jayme; Weiss, Pamela F.; Inman, Robert D.; Majithia, Vikas; Haroon, Nigil; Maksymowych, Walter P.; Joyce, Janet; Clark, Bruce M.; Colbert, Robert A.; Figgie, Mark P.; Hallegua, David S.; Prete, Pamela E.; Rosenbaum, James T.; Stebulis, Judith A.; van den Bosch, Filip; Yu, David T. Y.; Miller, Amy S.; Reveille, John D.; Caplan, Liron

    2016-01-01

    Objective To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). Methods A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946–2014), PubMed (1966–2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. Results In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. Conclusion These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas. PMID:26401991

  2. Congenital segmental lymphedema in tuberous sclerosis complex with associated subependymal giant cell astrocytomas treated with Mammalian target of rapamycin inhibitors.

    Science.gov (United States)

    Prato, Giulia; Mancardi, Maria Margherita; Baglietto, Maria Giuseppina; Janis, Sara; Vercellino, Nadia; Rossi, Andrea; Consales, Alessandro; Raso, Alessandro; Garrè, Maria Luisa

    2014-09-01

    Tuberous sclerosis complex is a genetic, multisystemic disorder characterized by circumscribed benign lesions (hamartomas) in several organs, including brain. This is the result of defects in the TSC1 and/or TSC2 tumor suppressor genes, encoding the hamartin-tuberin complex that inhibits the mammalian target of rapamycin pathway. Specific inhibitors of this pathway have been shown to reduce the volume of subependymal giant cell astrocytomas associated with tuberous sclerosis. Congenital lymphedema is rarely seen in association with tuberous sclerosis, with only a few reported cases. Although this association can be coincidental, the dysgenetic lymphatic system can represent a hamartia as a consequence of gene mutation. We describe a child with congenital lymphedema in tuberous sclerosis and associated subependymal giant cell astrocytoma who experienced lymphangitis under treatment with mammalian target of rapamycin inhibitors. Because our patient did not show worsening of lymphedema, congenital lymphedema does not seem to be a contraindication for this therapy.

  3. Targeted Genome Editing by Recombinant Adeno-Associated Virus (rAAV) Vectors for Generating Genetically Modified Pigs

    Institute of Scientific and Technical Information of China (English)

    Yonglun Luo; Emil Kofod-Olsen; Rikke Christensen; Charlotte Brandt S(φ)rensen; Lars Bolund

    2012-01-01

    Recombinant adeno-associated virus (rAAV) vectors have been extensively used for experimental gene therapy of inherited human diseases.Several advantages,such as simple vector construction,high targeting frequency by homologous recombination,and applicability to many cell types,make rAAV an attractive approach for targeted genome editing.Combined with cloning by somatic cell nuclear transfer (SCNT),this technology has recently been successfully adapted to generate gene-targeted pigs as models for cystic fibrosis,hereditary tyrosinemia type 1,and breast cancer.This review summarizes the development of rAAV for targeted genome editing in mammalian cells and provides strategies for enhancing the rAAV-mediated targeting frequency by homologous recombination.We discuss current development and application of the rAAV vectors for targeted genome editing in porcine primary fibroblasts,which are subsequently used as donor cells for SCNT to generate cloned genetically designed pigs and provide positive perspectives for the generation of gene-targeted pigs with rAAV in the future.

  4. Genome-Wide Association Study with Targeted and Non-targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality.

    Directory of Open Access Journals (Sweden)

    Johannes Raffler

    2015-09-01

    Full Text Available Genome-wide association studies with metabolic traits (mGWAS uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to specific diseases. While metabolic homeostasis in blood is a well investigated topic in large mGWAS with over 150 known loci, metabolic detoxification through urinary excretion has only been addressed by few small mGWAS with only 11 associated loci so far. Here we report the largest mGWAS to date, combining targeted and non-targeted 1H NMR analysis of urine samples from 3,861 participants of the SHIP-0 cohort and 1,691 subjects of the KORA F4 cohort. We identified and replicated 22 loci with significant associations with urinary traits, 15 of which are new (HIBCH, CPS1, AGXT, XYLB, TKT, ETNPPL, SLC6A19, DMGDH, SLC36A2, GLDC, SLC6A13, ACSM3, SLC5A11, PNMT, SLC13A3. Two-thirds of the urinary loci also have a metabolite association in blood. For all but one of the 6 loci where significant associations target the same metabolite in blood and urine, the genetic effects have the same direction in both fluids. In contrast, for the SLC5A11 locus, we found increased levels of myo-inositol in urine whereas mGWAS in blood reported decreased levels for the same genetic variant. This might indicate less effective re-absorption of myo-inositol in the kidneys of carriers. In summary, our study more than doubles the number of known loci that influence urinary phenotypes. It thus allows novel insights into the relationship between blood homeostasis and its regulation through excretion. The newly discovered loci also include variants previously linked to chronic kidney disease (CPS1, SLC6A13, pulmonary hypertension (CPS1, and ischemic stroke (XYLB. By establishing connections from gene to disease via metabolic traits our results provide novel hypotheses about molecular

  5. Associating Drugs, Targets and Clinical Outcomes into an Integrated Network Affords a New Platform for Computer-Aided Drug Repurposing

    DEFF Research Database (Denmark)

    Oprea, Tudor; Nielsen, Sonny Kim; Ursu, Oleg

    2011-01-01

    benefit from an integrated, semantic-web compliant computer-aided drug repurposing (CADR) effort, one that would enable deep data mining of associations between approved drugs (D), targets (T), clinical outcomes (CO) and SE. We report preliminary results from text mining and multivariate statistics, based...

  6. An application of improved association rules of an association graph in a recommendation system%基于关联图的改进关联规则在推荐系统中的应用

    Institute of Scientific and Technical Information of China (English)

    王林林; 石冰; 胡元; 邢海华

    2011-01-01

    提出了推荐模型中的关联规则挖掘方法的改进,给出了自定义的页面权值的定义,并改进了基于关联图的关联规则挖掘算法,将页面权值应用于关联规则的挖掘中。此算法是利用Web日志中经过预处理后得到的数据进行规则挖掘,将处理后的数据应用正态分布函数来得到页面权值。用页面权值重新计算支持度,最后将得到的支持度应用于改进的规则挖掘算法中,形成一种基于权值的关联图的关联规则算法。%This paper presents an improved association rule mining algorithm for the recommended system, and our definition for the page weights. We improve the association graph based association rules mining algorithm, and apply the page weights to the mining of association rules. This algorithm employs the data acquired after pretreatment to web log to mine the association rules. Page weights are obtained through the processing of such data with a normal distribution function. The algorithm then uses the page weights to recalculate the page support, which is applied to the improved rule mining algorithm. We can therefore acquire page weights based association rule algorithm of an association graph.

  7. Practical recommendations for the management of cardiovascular risk associated with atherogenic dyslipidemia, with special attention to residual risk. Spanish adaptation of a European Consensus of Experts.

    Science.gov (United States)

    This document has discussed clinical approaches to managing cardiovascular risk in clinical practice, with special focus on residual cardiovascular risk associated with lipid abnormalities, especially atherogenic dyslipidaemia (AD). A simplified definition of AD was proposed to enhance understanding of this condition, its prevalence and its impact on cardiovascular risk. AD can be defined by high fasting triglyceride levels (≥2.3mmol/L / ≥200mg/dL) and low high-density lipoprotein cholesterol (HDL-c) levels (≤1,0 / 40 and ≤1,3mmol/L / 50mg/dL in men and women, respectively) in statin-treated patients at high cardiovascular risk. The use of a single marker for the diagnosis and treatment of AD, such as non-HDL-c, was advocated. Interventions including lifestyle optimization and low density lipoprotein (LDL) lowering therapy with statins (±ezetimibe) are recommended by experts. Treatment of residual AD can be performed with the addition of fenofibrate, since it can improve the complete lipoprotein profile and reduce the risk of cardiovascular events in patients with AD. Others clinical condictions in which fenofibrate may be prescribed include patients with very high TGs (≥5.6mmol/L / 500mg/dL), patients who are intolerant or resistant to statins, and patients with AD and at high cardiovascular risk. The fenofibrate-statin combination was considered by the experts to benefit from a favorable benefit-risk profile. In conclusion, cardiovascular experts adopt a multifaceted approach to the prevention of atherosclerotic cardiovascular disease, with lifestyle optimization, LDL-lowering therapy and treatment of AD with fenofibrate routinely used to help reduce a patient's overall cardiovascular risk. Copyright © 2016. Publicado por Elsevier España, S.L.U.

  8. Adherence to recommended lifestyle modifications and factors associated for hypertensive patients attending chronic follow-up units of selected public hospitals in Addis Ababa, Ethiopia

    Science.gov (United States)

    Tibebu, Abel; Mengistu, Daniel; Negesa, Lemma

    2017-01-01

    Introduction One of the most prevalent noncommunicable diseases is hypertension (HTN). The availability of effective antihypertensive medications does not result in the expected outcomes in terms of controlling blood pressure. The rationale for these and other findings of uncontrolled HTN points toward poor adherence. The most neglected causes of uncontrolled HTN are unhealthy lifestyles. Few studies have been conducted to show the gap and magnitude of self-management adherence. Objective This study aimed to assess adherence to recommended lifestyle modifications of hypertensive patients undergoing follow-up at chronic follow-up units of public health hospitals in Addis Ababa, Ethiopia, 2016. Methods Institutional-based cross-sectional study was conducted in four public health hospitals which were selected by drawing lots. Systematic random sampling was used to select study subjects. The results of the descriptive statistics were expressed as percentages and frequencies. Associations between lifestyle modification and independent variables were ana-lyzed using bivariate and multivariate logistic regression analysis. The study was conducted from February 15, 2016 to April 15, 2016. Results The study included 404 respondents with a 97% response rate; 210 (52%) were male and the mean age was 54.00±10.77 years. The respondents’ adherence to lifestyle modifications was 23%. The lifestyle adherence was found to be better in females, patients who had comorbidities, and had been knowledgeable about the disease and was poor among young adult respondents. Conclusion The rates of adherence to lifestyle changes were generally found to be low. Educational sessions that especially focus on lifestyle modifications and ongoing support for patients should be designed and studies which assess all the components of self-management should be conducted for comparison among different subgroups. PMID:28280305

  9. From micronutrient recommendations to policy

    DEFF Research Database (Denmark)

    Timotijevic, Lada; Raats, Monique M.; Barnett, Julie

    2010-01-01

    Background/Objectives: To achieve the nutritional goals stipulated by micronutrient recommendations, greater attention must be paid to the behavioural routes to such nutritional outcomes. Coopting stakeholders and consumers into decisions regarding micronutrient recommendations is an important step...... towards achieving a greater link between micronutrient recommendations and behaviour. This study aims to examine the rationale and processes associated with consumer and stakeholder involvement in setting micronutrient recommendations across Europe. Subjects/Methods: Using the contacts established through...... the Eurreca network of excellence (commissioned by the European Commission), the research involved in-depth desk research of key documents and communication channels linked to the process of setting micronutrient recommendations across seven countries: the United Kingdom, Norway, Denmark, Germany, Spain...

  10. Clinical Recommendation: Vulvovaginitis.

    Science.gov (United States)

    Zuckerman, Andrea; Romano, Mary

    2016-12-01

    Vulvovaginitis is a commonly encountered condition among prepubertal and adolescent females. The objective of this report is to provide the latest evidence regarding the diagnosis and management of vulvovaginitis in prepubertal and adolescent females. In this systematic review we used the Grading of Recommendations Assessment, Development and Evaluation evidence system. Vulvovaginal complaints are common in the pediatric and adolescent age group. The patient's age in conjunction with history and associated complaints will guide evaluation, diagnosis, and treatment. Treatment should include counseling on hygiene and voiding techniques as well as therapy for any specific pathogens identified.

  11. Improving door-to-needle times in acute ischemic stroke: the design and rationale for the American Heart Association/American Stroke Association's Target: Stroke initiative.

    Science.gov (United States)

    Fonarow, Gregg C; Smith, Eric E; Saver, Jeffrey L; Reeves, Mathew J; Hernandez, Adrian F; Peterson, Eric D; Sacco, Ralph L; Schwamm, Lee H

    2011-10-01

    The benefits of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke are time-dependent, and guidelines recommend a door-to-needle time of ≤60 minutes. However, fewer than one third of acute ischemic stroke patients who receive tPA are treated within guideline-recommended door-to-needle times. This article describes the design and rationale of Stroke, a national initiative organized by the American Heart Association/American Stroke Association in partnership with other organizations to assist hospitals in increasing the proportion of tPA-treated patients who achieve guideline-recommended door-to-needle times. The initial program goal is to achieve a door-to-needle time≤60 minutes for at least 50% of acute ischemic stroke patients. Key best practice strategies previously associated with achieving faster door-to-needle times in acute ischemic stroke were identified. The 10 key strategies chosen by Stroke include emergency medical service prenotification, activating the stroke team with a single call, rapid acquisition and interpretation of brain imaging, use of specific protocols and tools, premixing tPA, a team-based approach, and rapid data feedback. The program includes many approaches intended to promote hospital participation, implement effective strategies, share best practices, foster collaboration, and achieve stated goals. A detailed program evaluation is also included. In the first year, Stroke has enrolled over 1200 United States hospitals. Stroke, a multidimensional initiative to improve the timeliness of tPA administration, aims to elevate clinical performance in the care of acute ischemic stroke, facilitate the more rapid integration of evidence into clinical practice, and improve outcomes.

  12. Associative plasticity in the human motor cortex is enhanced by concurrently targeting separate muscle representations with excitatory and inhibitory protocols.

    Science.gov (United States)

    Kamke, Marc R; Nydam, Abbey S; Sale, Martin V; Mattingley, Jason B

    2016-04-01

    Paired associative stimulation (PAS) induces changes in the excitability of human sensorimotor cortex that outlast the procedure. PAS typically involves repeatedly pairing stimulation of a peripheral nerve that innervates an intrinsic hand muscle with transcranial magnetic stimulation over the representation of that muscle in the primary motor cortex. Depending on the timing of the stimuli (interstimulus interval of 25 or 10 ms), PAS leads to either an increase (PAS25) or a decrease (PAS10) in excitability. Both protocols, however, have been associated with an increase in excitability of nearby muscle representations not specifically targeted by PAS. Based on these spillover effects, we hypothesized that an additive, excitability-enhancing effect of PAS25 applied to one muscle representation may be produced by simultaneously applying PAS25 or PAS10 to a nearby representation. In different experiments prototypical PAS25 targeting the left thumb representation [abductor pollicis brevis (APB)] was combined with either PAS25 or PAS10 applied to the left little finger representation [abductor digiti minimi (ADM)] or, in a control experiment, with PAS10 also targeting the APB. In an additional control experiment PAS10 targeted both representations. The plasticity effects were quantified by measuring the amplitude of motor evoked potentials (MEPs) recorded before and after PAS. As expected, prototypical PAS25 was associated with an increase in MEP amplitude in the APB muscle. This effect was enhanced when PAS also targeted the ADM representation but only when a different interstimulus timing (PAS10) was used. These results suggest that PAS-induced plasticity is modified by concurrently targeting separate motor cortical representations with excitatory and inhibitory protocols.

  13. Real-time detection of implant-associated neutrophil responses using a formyl peptide receptor-targeting NIR nanoprobe

    Science.gov (United States)

    Zhou, Jun; Tsai, Yi-Ting; Weng, Hong; Tang, Ewin N; Nair, Ashwin; Davé, Digant P; Tang, Liping

    2012-01-01

    Neutrophils play an important role in implant-mediated inflammation and infection. Unfortunately, current methods which monitor neutrophil activity, including enzyme measurements and histological evaluation, require many animals and cannot be used to accurately depict the dynamic cellular responses. To understand the neutrophil interactions around implant-mediated inflammation and infection it is critical to develop methods which can monitor in vivo cellular activity in real time. In this study, formyl peptide receptor (FPR)-targeting near-infrared nanoprobes were fabricated. This was accomplished by conjugating near-infrared dye with specific peptides having a high affinity to the FPRs present on activated neutrophils. The ability of FPR-targeting nanoprobes to detect and quantify activated neutrophils was assessed both in vitro and in vivo. As expected, FPR-targeting nanoprobes preferentially accumulated on activated neutrophils in vitro. Following transplantation, FPR-targeting nanoprobes preferentially accumulated at the biomaterial implantation site. Equally important, a strong relationship was observed between the extent of fluorescence intensity in vivo and the number of recruited neutrophils at the implantation site. Furthermore, FPR-targeting nanoprobes may be used to detect and quantify the number of neutrophils responding to a catheter-associated infection. The results show that FPR-targeting nanoprobes may serve as a powerful tool to monitor and measure the extent of neutrophil responses to biomaterial implants in vivo. PMID:22619542

  14. Towards Information Enrichment through Recommendation Sharing

    Science.gov (United States)

    Weng, Li-Tung; Xu, Yue; Li, Yuefeng; Nayak, Richi

    Nowadays most existing recommender systems operate in a single organisational basis, i.e. a recommender system recommends items to customers of one organisation based on the organisation's datasets only. Very often the datasets of a single organisation do not have sufficient resources to be used to generate quality recommendations. Therefore, it would be beneficial if recommender systems of different organisations with similar nature can cooperate together to share their resources and recommendations. In this chapter, we present an Ecommerce-oriented Distributed Recommender System (EDRS) that consists of multiple recommender systems from different organisations. By sharing resources and recommendations with each other, these recommenders in the distributed recommendation system can provide better recommendation service to their users. As for most of the distributed systems, peer selection is often an important aspect. This chapter also presents a recommender selection technique for the proposed EDRS, and it selects and profiles recommenders based on their stability, average performance and selection frequency. Based on our experiments, it is shown that recommenders' recommendation quality can be effectively improved by adopting the proposed EDRS and the associated peer selection technique.

  15. Reporter Gene Silencing in Targeted Mouse Mutants Is Associated with Promoter CpG Island Methylation.

    Science.gov (United States)

    Kirov, Julia V; Adkisson, Michael; Nava, A J; Cipollone, Andreana; Willis, Brandon; Engelhard, Eric K; Lloyd, K C Kent; de Jong, Pieter; West, David B

    2015-01-01

    Targeted mutations in mouse disrupt local chromatin structure and may lead to unanticipated local effects. We evaluated targeted gene promoter silencing in a group of six mutants carrying the tm1a Knockout Mouse Project allele containing both a LacZ reporter gene driven by the native promoter and a neo selection cassette. Messenger RNA levels of the reporter gene and targeted gene were assessed by qRT-PCR, and methylation of the promoter CpG islands and LacZ coding sequence were evaluated by sequencing of bisulfite-treated DNA. Mutants were stratified by LacZ staining into presumed Silenced and Expressed reporter genes. Silenced mutants had reduced relative quantities LacZ mRNA and greater CpG Island methylation compared with the Expressed mutant group. Within the silenced group, LacZ coding sequence methylation was significantly and positively correlated with CpG Island methylation, while promoter CpG methylation was only weakly correlated with LacZ gene mRNA. The results support the conclusion that there is promoter silencing in a subset of mutants carrying the tm1a allele. The features of targeted genes which promote local silencing when targeted remain unknown.

  16. Implementation of the updated 2015 Commission for Hospital Hygiene and Infection Prevention (KRINKO recommendations “Prevention and control of catheter-associated urinary tract infections” in the hospitals in Frankfurt/Main, Germany

    Directory of Open Access Journals (Sweden)

    Heudorf, Ursel

    2016-06-01

    Full Text Available Aim: The Commission for Hospital Hygiene and Infection Prevention (KRINKO updated the recommendations for the prevention of catheter-associated urinary tract infections in 2015. This article will describe the implementation of these recommendations in Frankfurt’s hospitals in autumn, 2015.Material and methods: In two non-ICU wards of each of Frankfurt’s , inspections were performed using a checklist based on the new KRINKO recommendations. In one large hospital, a total of were inspected. The inspections covered the structure and process quality (operating instructions, training, indication, the placement and maintenance of catheters and the demonstration of the preparation for insertion of a catheter using an empty bed and an imaginary patient, or insertion in a model.Results: Operating instructions were available in all hospital wards; approximately half of the wards regularly performed training sessions. The indications were largely in line with the recommendations of the KRINKO. Alternatives to urinary tract catheters were available and were used more often than the urinary tract catheters themselves (15.9% vs. 13.5%. In accordance with the recommendations, catheters were placed without antibiotic prophylaxis or the instillation of antiseptic or antimicrobial substances or catheter flushing solutions. The demonstration of catheter placement was conscientiously performed. Need for improvement was seen in the daily documentation and the regular verification of continuing indication for a urinary catheter, as well as the omission of regular catheter change.Conclusion: Overall, the recommendations of the KRINKO on the prevention of catheter-associated urinary tract infections were adequately implemented. However, it cannot be ruled out that in situations with time pressure and staff shortage, the handling of urinary tract catheters may be of lower quality than that observed during the inspections, when catheter insertion was done by two

  17. Targeting of MAPK-associated molecules identifies SON as a prime target to attenuate the proliferation and tumorigenicity of pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Furukawa Toru

    2012-12-01

    Full Text Available Abstract Background Pancreatic cancer is characterized by constitutive activation of mitogen-activated protein kinase (MAPK. Activation of MAPK is associated with the upregulation of genes implicated in the proliferation and survival of pancreatic cancer cells. We hypothesized that knockdown of these MAPK-associated molecules could produce notable anticancer phenotypes. Methods A RNA interference-mediated knockdown screening of 78 MAPK-associated molecules previously identified was performed to find molecules specifically associated with proliferation of pancreatic cancer cells in vitro. Expression of an identified molecule in pancreatic cancer tissues was examined by immunohistochemistry. In vivo tumorigenicity of cancer cells with stable knockdown of the molecule was assayed by using xenograft models. Flow cytometry and live cell imaging were employed to assess an association of the molecule with cell cycle. Results The knockdown screening revealed that knockdown of SON, the gene encoding SON, which is a large serine/arginine-rich protein involved in RNA processing, substantially suppressed pancreatic cancer cell proliferation and survival in vitro and tumorigenicity in vivo. SON expression was higher in ductal adenocarcinomas than in cells of normal ducts and precursor lesions in pancreatic cancer tissues. Knockdown of SON induced G2/M arrest and apoptosis in cultured cancer cells. The suppressive effect of SON knockdown on proliferation was less pronounced in cultured normal duct epithelial cells. SON formed nuclear speckles in the interphase of the cell cycle and dispersed in the cytoplasm during mitosis. Live cell imaging showed that SON diffusely dispersed in the early mitotic phase, accumulated in some foci in the cytoplasm in the late mitotic phase, and gradually reassembled into speckles after mitosis. Conclusion These results indicate that SON plays a critical role in the proliferation, survival, and tumorigenicity of pancreatic

  18. The readiness of German GPs to recommend and conduct cancer screening is associated with patient-physician gender concordance. Results of a survey.

    Science.gov (United States)

    Engler, Jennifer; Dahlhaus, Anne; Güthlin, Corina

    2017-12-01

    Cancer screening participation rates in Germany differ depending on patients' gender. International studies have found that patient-physician gender concordance fosters recommendation and conducting of cancer screening, and especially cancer screening for women. We aimed to ascertain whether gender concordance influences general practitioners' (GPs') rating of the usefulness of cancer screening, as well as their recommendations and readiness to conduct cancer screening in general practice in Germany. For an exploratory cross-sectional survey, 500 randomly selected GPs from all over Germany were asked to fill in a questionnaire on cancer screening in general practice between March and June 2015. We asked them to rate the usefulness of each cancer screening examination, how frequently they recommended and conducted them and whether they viewed GPs or specialists as responsible for carrying them out. We used multiple logistic regression to analyse gender effect size by calculating odds ratios. Our study sample consisted of 139 GPs of which 65% were male. Male and female GPs did not differ significantly in their rating of the general usefulness of any of the specified cancer screening examinations. Male GPs were 2.9 to 6.8 times as likely to consider GPs responsible for recommending and conducting PSA testing and digital rectal examinations and were 3.7 to 7.9 times as likely to recommend and conduct these examinations on a regular basis. Patient-physician gender concordance made it more likely that male-specific cancer screenings would be recommended and conducted, but not female-specific screenings. [Box: see text].

  19. Association of target organ damage with 24-hour systolic and diastolic blood pressure levels and hypertension subtypes in untreated Chinese.

    Science.gov (United States)

    Wei, Fang-Fei; Li, Yan; Zhang, Lu; Xu, Ting-Yan; Ding, Feng-Hua; Staessen, Jan A; Wang, Ji-Guang

    2014-02-01

    The association of target organ damage with 24-hour systolic and diastolic blood pressure levels and ambulatory hypertension subtypes has not yet been examined in untreated Chinese patients. We measured left ventricular mass index by echocardiography (n=619), the urinary albumin:creatinine ratio (n=1047), and aortic pulse wave velocity by tonometry (n=1013) in 1047 untreated subjects (mean age, 50.6 years; 48.9% women). Normotension was a 24-hour systolic/diastolic blood pressure Hypertension subtypes were isolated diastolic hypertension and mixed systolic plus diastolic hypertension. We assessed associations of interest by multivariable-adjusted linear models. Using normotension as reference, mixed hypertension was associated with higher (P≤0.003) left ventricular mass index (+4.31 g/m(2)), urinary albumin:creatinine ratio (+1.63 mg/mmol), and pulse wave velocity (+0.76 m/s); and isolated diastolic hypertension was associated with similar left ventricular mass index and pulse wave velocity (P≥0.39), but higher urinary albumin:creatinine ratio (+1.24 mg/mmol; P=0.002). In younger participants (hypertension are major determinants of target organ damage irrespective of age and target organ, whereas 24-hour diastolic blood pressure and isolated diastolic hypertension only relate to the urinary albumin:creatinine ratio below middle age.

  20. Targeted therapies and radiotherapy in lung cancer; Les therapeutiques ciblees en association avec la radiotherapie dans le cancer bronchique

    Energy Technology Data Exchange (ETDEWEB)

    Hennequin, C. [Hopital Saint-Louis (APHP), Serv. de Cancerologie-radiotherapie, 75 - Paris (France); Institut Curie-Orsay, Unite Inserm 612, Centre Universitaire, 91 - Orsay (France)

    2007-01-15

    Targeted therapies are now more often used in lung cancer. Inhibitors of EGFR and of angiogenesis have demonstrated a certain activity in this disease. Some experimental in vitro or in vivo studies are in favour of combined targeted therapies and radiation. For example, additive or supra-additive effects have been shown when inhibitors of the EGFR tyrosine kinase were given with radiation. In advanced lung cancer, the combination of bevacizumab with chemotherapy was demonstrated to produce better survival outcomes. But a high rate of fatal hemoptysis was reported with this drug, particularly for central and squamous tumors. This could be a limitation for its use in combination with radiation. Drugs with multiple targets are becoming available; their association with radiation seems to be promising. (author)

  1. Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families.

    Science.gov (United States)

    Woodbury-Smith, M; Bilder, D A; Morgan, J; Jerominski, L; Darlington, T; Dyer, T; Paterson, A D; Coon, H

    2017-01-01

    It has long been recognized that there is an association between enlarged head circumference (HC) and autism spectrum disorder (ASD), but the genetics of HC in ASD is not well understood. In order to investigate the genetic underpinning of HC in ASD, we undertook a genome-wide linkage study of HC followed by linkage signal targeted association among a sample of 67 extended pedigrees with ASD. HC measurements on members of 67 multiplex ASD extended pedigrees were used as a quantitative trait in a genome-wide linkage analysis. The Illumina 6K SNP linkage panel was used, and analyses were carried out using the SOLAR implemented variance components model. Loci identified in this way formed the target for subsequent association analysis using the Illumina OmniExpress chip and imputed genotypes. A modification of the qTDT was used as implemented in SOLAR. We identified a linkage signal spanning 6p21.31 to 6p22.2 (maximum LOD = 3.4). Although targeted association did not find evidence of association with any SNP overall, in one family with the strongest evidence of linkage, there was evidence for association (rs17586672, p = 1.72E-07). Although this region does not overlap with ASD linkage signals in these same samples, it has been associated with other psychiatric risk, including ADHD, developmental dyslexia, schizophrenia, specific language impairment, and juvenile bipolar disorder. The genome-wide significant linkage signal represents the first reported observation of a potential quantitative trait locus for HC in ASD and may be relevant in the context of complex multivariate risk likely leading to ASD.

  2. HER2-targeted liposomal doxorubicin displays enhanced anti-tumorigenic effects without associated cardiotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, Joseph G.; Geretti, Elena; Hendriks, Bart S.; Lee, Helen; Leonard, Shannon C.; Klinz, Stephan G.; Noble, Charles O. [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States); Lücker, Petra B.; Zandstra, Peter W. [University of Toronto, 160 College Street, Office 1116, Toronto, Ontario M5S 3E1 (Canada); Drummond, Daryl C.; Olivier, Kenneth J.; Nielsen, Ulrik B.; Niyikiza, Clet; Agresta, Samuel V. [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States); Wickham, Thomas J., E-mail: twickham@merrimackpharma.com [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States)

    2012-07-01

    Anthracycline-based regimens are a mainstay of early breast cancer therapy, however their use is limited by cardiac toxicity. The potential for cardiotoxicity is a major consideration in the design and development of combinatorial therapies incorporating anthracyclines and agents that target the HER2-mediated signaling pathway, such as trastuzumab. In this regard, HER2-targeted liposomal doxorubicin was developed to provide clinical benefit by both reducing the cardiotoxicity observed with anthracyclines and enhancing the therapeutic potential of HER2-based therapies that are currently available for HER2-overexpressing cancers. While documenting the enhanced therapeutic potential of HER2-targeted liposomal doxorubicin can be done with existing models, there has been no validated human cardiac cell-based assay system to rigorously assess the cardiotoxicity of anthracyclines. To understand if HER2-targeting of liposomal doxorubicin is possible with a favorable cardiac safety profile, we applied a human stem cell-derived cardiomyocyte platform to evaluate the doxorubicin exposure of human cardiac cells to HER2-targeted liposomal doxorubicin. To the best of our knowledge, this is the first known application of a stem cell-derived system for evaluating preclinical cardiotoxicity of an investigational agent. We demonstrate that HER2-targeted liposomal doxorubicin has little or no uptake into human cardiomyocytes, does not inhibit HER2-mediated signaling, results in little or no evidence of cardiomyocyte cell death or dysfunction, and retains the low penetration into heart tissue of liposomal doxorubicin. Taken together, this data ultimately led to the clinical decision to advance this drug to Phase I clinical testing, which is now ongoing as a single agent in HER2-expressing cancers. -- Highlights: ► Novel approach using stem cell-derived cardiomyocytes to assess preclinical safety. ► HER2-targeted liposomal doxorubicin has improved safety profile vs free doxorubicin

  3. Cancer-associated fibroblast-targeted strategy enhances antitumor immune responses in dendritic cell-based vaccine

    Science.gov (United States)

    Ohshio, Yasuhiko; Teramoto, Koji; Hanaoka, Jun; Tezuka, Noriaki; Itoh, Yasushi; Asai, Tohru; Daigo, Yataro; Ogasawara, Kazumasa

    2015-01-01

    Given the close interaction between tumor cells and stromal cells in the tumor microenvironment (TME), TME-targeted strategies would be promising for developing integrated cancer immunotherapy. Cancer-associated fibroblasts (CAFs) are the dominant stromal component, playing critical roles in generation of the pro-tumorigenic TME. We focused on the immunosuppressive trait of CAFs, and systematically explored the alteration of tumor-associated immune responses by CAF-targeted therapy. C57BL/6 mice s.c. bearing syngeneic E.G7 lymphoma, LLC1 Lewis lung cancer, or B16F1 melanoma were treated with an anti-fibrotic agent, tranilast, to inhibit CAF function. The infiltration of immune suppressor cell types, including regulatory T cells and myeloid-derived suppressor cells, in the TME was effectively decreased through reduction of stromal cell-derived factor-1, prostaglandin E2, and transforming growth factor-β. In tumor-draining lymph nodes, these immune suppressor cell types were significantly decreased, leading to activation of tumor-associated antigen-specific CD8+ T cells. In addition, CAF-targeted therapy synergistically enhanced multiple types of systemic antitumor immune responses such as the cytotoxic CD8+ T cell response, natural killer activity, and antitumor humoral immunity in combination with dendritic cell-based vaccines; however, the suppressive effect on tumor growth was not observed in tumor-bearing SCID mice. These data indicate that systemic antitumor immune responses by various immunologic cell types are required to bring out the efficacy of CAF-targeted therapy, and these effects are enhanced when combined with effector-stimulatory immunotherapy such as dendritic cell-based vaccines. Our mouse model provides a novel rationale with TME-targeted strategy for the development of cell-based cancer immunotherapy. PMID:25483888

  4. Efficacy and safety of biological and targeted-synthetic DMARDs: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis

    Science.gov (United States)

    Regel, Andrea; van der Heijde, Désirée; Braun, Jürgen; Baraliakos, Xenofon; Landewé, Robert; Van den Bosch, Filip; Falzon, Louise; Ramiro, Sofia

    2017-01-01

    Objectives To update the evidence for the efficacy and safety of (b)biological and (ts)targeted-synthetic disease-modifying anti-rheumatic drugs (DMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2016 update of the Assessment of SpondyloArthritis international Society/European League Against Rheumatism (ASAS/EULAR) recommendations for the management of axSpA. Methods Systematic literature review (2009–2016) for randomised controlled trials (RCT), including long-term extensions, strategy trials and observational studies (the latter was only for safety assessment and a comparator was required). Interventions were any bDMARD or tsDMARD. All relevant efficacy and safety outcomes were included. Results 76 papers and 24 abstracts fulfilled the inclusion criteria. Large treatment effects were found both in radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) for all tumour necrosis factor inhibitors (TNFi) (NNT to achieve ASAS40 response ranged between 2.6–5.2 for r-axSpA and 2.3–5.4 for nr-axSpA). For nr-axSpA, efficacy was superior for those who had objective signs of inflammation (positive C reactive protein or inflammation on MRI-SI). Secukinumab 150 mg has shown efficacy in two phase 3 RCTs (NNT to achieve ASAS40 response: 3.4 and 4.0). Ustekinumab and tofacitinib have shown positive results in phase 2/proof-of-concept trials; trials with apremilast, rituximab, interleukin (IL)-6 antagonists and abatacept have failed their primary end points. New (unknown) safety signals were not found in the trials but long-term observational safety data for TNFi are still scarce. Conclusions New evidence supports the efficacy and safety of TNFi both in r-axSpA and nr-axSpA. Secukinumab is the first drug targeting the IL-17 pathway in r-axSpA that has shown efficacy. PMID:28176964

  5. Personalized Social Recommendations - Accurate or Private?

    CERN Document Server

    Machanavajjhala, Ashwin; Sarma, Atish Das

    2011-01-01

    With the recent surge of social networks like Facebook, new forms of recommendations have become possible - personalized recommendations of ads, content, and even new friend and product connections based on one's social interactions. Since recommendations may use sensitive social information, it is speculated that these recommendations are associated with privacy risks. The main contribution of this work is in formalizing these expected trade-offs between the accuracy and privacy of personalized social recommendations. In this paper, we study whether "social recommendations", or recommendations that are solely based on a user's social network, can be made without disclosing sensitive links in the social graph. More precisely, we quantify the loss in utility when existing recommendation algorithms are modified to satisfy a strong notion of privacy, called differential privacy. We prove lower bounds on the minimum loss in utility for any recommendation algorithm that is differentially private. We adapt two priv...

  6. Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma

    Science.gov (United States)

    Posey, Avery D.; Schwab, Robert D.; Boesteanu, Alina C.; Steentoft, Catharina; Mandel, Ulla; Engels, Boris; Stone, Jennifer D.; Madsen, Thomas D.; Schreiber, Karin; Haines, Kathleen M.; Cogdill, Alexandria P.; Chen, Taylor J.; Song, Decheng; Scholler, John; Kranz, David M.; Feldman, Michael D.; Young, Regina; Keith, Brian; Schreiber, Hans; Clausen, Henrik; Johnson, Laura A.; June, Carl H.

    2017-01-01

    SUMMARY Genetically modified T cells expressing chimeric antigen receptors (CARs) demonstrate robust responses against lineage restricted, non-essential targets in hematologic cancers. However, in solid tumors, the full potential of CAR T cell therapy is limited by the availability of cell surface antigens with sufficient cancer-specific expression. The majority of CAR targets have been normal self-antigens on dispensable hematopoietic tissues or overexpressed shared antigens. Here, we established that abnormal self-antigens can serve as targets for tumor rejection. We developed a CAR that recognized cancer-associated Tn glycoform of MUC1, a neoantigen expressed in a variety of cancers. Anti-Tn-MUC1 CAR T cells demonstrated target-specific cytotoxicity and successfully controlled tumor growth in xenograft models of T cell leukemia and pancreatic cancer. These findings demonstrate the therapeutic efficacy of CAR T cells directed against Tn-MUC1 and present aberrantly glycosylated antigens as a novel class of targets for tumor therapy with engineered T cells. PMID:27332733

  7. BTK gene targeting by homologous recombination using a helper-dependent adenovirus/adeno-associated virus hybrid vector.

    Science.gov (United States)

    Yamamoto, H; Ishimura, M; Ochiai, M; Takada, H; Kusuhara, K; Nakatsu, Y; Tsuzuki, T; Mitani, K; Hara, T

    2016-02-01

    X-linked agammaglobulinemia (XLA) is one of the most common humoral immunodeficiencies, which is caused by mutations in Bruton's tyrosine kinase (BTK) gene. To examine the possibility of using gene therapy for XLA, we constructed a helper-dependent adenovirus/adeno-associated virus BTK targeting vector (HD-Ad.AAV BTK vector) composed of a genomic sequence containing BTK exons 6-19 and a green fluorescence protein-hygromycin cassette driven by a cytomegalovirus promoter. We first used NALM-6, a human male pre-B acute lymphoblastic leukemia cell line, as a recipient to measure the efficiency of gene targeting by homologous recombination. We identified 10 clones with the homologous recombination of the BTK gene among 107 hygromycin-resistant stable clones isolated from two independent experiments. We next used cord blood CD34⁺ cells as the recipient cells for the gene targeting. We isolated colonies grown in medium containing cytokines and hygromycin. We found that the targeting of the BTK gene occurred in four of the 755 hygromycin-resistant colonies. Importantly, the gene targeting was also observed in CD19⁺ lymphoid progenitor cells that were differentiated from the homologous recombinant CD34⁺ cells during growth in selection media. Our study shows the potential for the BTK gene therapy using the HD-Ad.AAV BTK vector via homologous recombination in hematopoietic stem cells.

  8. Treatment practice for IBD-associated anaemia remains out of tune with recommendations - A two year follow-up survey in five European countries

    DEFF Research Database (Denmark)

    Stein, Jürgen; Bager, Palle; Befrits, Ragnar

    in correcting anaemia, and worse baseline Hb and iron status compared to a prior survey. The on-going lack in awareness of evidence-based recommendations on iron supplementation emphasises the need for new educational strategies to improve implementation of current and upcoming guidelines....

  9. Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas

    DEFF Research Database (Denmark)

    Albert, Nathalie L.; Weller, Michael; Suchorska, Bogdana

    2016-01-01

    This guideline provides recommendations for the use of PET imaging in gliomas. The review examines established clinical benefit in glioma patients of PET using glucose (18F-FDG) and amino acid tracers (11C-MET, 18F-FET, and 18F-FDOPA). An increasing number of studies have been published on PET im...

  10. SPATA18, a Spermatogenesis-Associated Gene, Is a Novel Transcriptional Target of p53 and p63▿

    OpenAIRE

    Bornstein, Chamutal; Brosh, Ran; Molchadsky, Alina; Madar, Shalom; Kogan-Sakin, Ira; Goldstein, Ido; Chakravarti, Deepavali; Flores, Elsa R.; Goldfinger, Naomi; Sarig, Rachel; Rotter, Varda

    2011-01-01

    The transcription factor p53 functions not only to suppress tumorigenesis but also to maintain normal development and homeostasis. Although p53 was implicated in different aspects of fertility, including spermatogenesis and implantation, the mechanism underlying p53 involvement in spermatogenesis is poorly resolved. In this study we describe the identification of a spermatogenesis-associated gene, SPATA18, as a novel p53 transcriptional target and show that SPATA18 transcription is induced by...

  11. AP-2-Associated Protein Kinase 1 and Cyclin G-Associated Kinase Regulate Hepatitis C Virus Entry and Are Potential Drug Targets

    OpenAIRE

    Neveu, Gregory; Ziv-Av, Amotz; Barouch-Bentov, Rina; Berkerman, Elena; Mulholland, Jon; Einav, Shirit

    2015-01-01

    Hepatitis C virus (HCV) enters its target cell via clathrin-mediated endocytosis. AP-2-associated protein kinase 1 (AAK1) and cyclin G-associated kinase (GAK) are host kinases that regulate clathrin adaptor protein (AP)-mediated trafficking in the endocytic and secretory pathways. We previously reported that AAK1 and GAK regulate HCV assembly by stimulating binding of the μ subunit of AP-2, AP2M1, to HCV core protein. We also discovered that AAK1 and GAK inhibitors, including the approved ant...

  12. Identification of Soldier Behaviors Associated with Search and Target Acquisition (STA)

    Science.gov (United States)

    2010-05-01

    3 UNCLASSIFIED different gaps. Each of these FACTs focused on several critical research areas ( CRAs ). The Fiscal Year (FY) 08 Soldier FACT Call...for Proposals identified the following CRA : Soldier Search and Target Acquisition (STA): Determine validity of current Soldier STA processes for...place him in a position where he can engage any threats (i.e., can see where to aim and shoot ). The order of behaviors for “audio cues” and

  13. Rheumatoid arthritis pathophysiology: update on emerging cytokine and cytokine-associated cell targets.

    Science.gov (United States)

    Furst, Daniel E; Emery, Paul

    2014-09-01

    Biologic therapies that target pathogenic cytokines such as TNF, IL-1β or IL-6 have greatly improved the treatment of RA. Unfortunately, not all RA patients respond to current biologic therapies and responses are not always maintained, suggesting that there are alternative drivers of RA pathogenesis that might serve as promising therapeutic targets. Discovery of the new Th17 subset of Th cells, and their role in autoimmune disease development, has implicated the proinflammatory IL-12 and IL-17 families of cytokines in RA disease pathogenesis. Members of these cytokine families are elevated in the blood and joints of RA patients and have been shown to remain elevated in patients who do not respond to current biologics. In addition, these cytokines have been shown to play roles in joint destruction and erosion. A new subclass of biologics that target the IL-12 and/or IL-17 signalling pathways are under development. Here we review evidence for a role of Th17 cells as well as IL-12 and IL-17 cytokines in RA pathogenesis as the rationale for a subsequent discussion of the ongoing and completed clinical trials of newly emerging biologic therapies directed at IL-12 or IL-17 pathway inhibition.

  14. Fetal Alcohol Spectrum Disorder (FASD Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    James A. Marrs

    2013-06-01

    Full Text Available Fetal alcohol spectrum disorder (FASD, caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.

  15. Uterine sarcoma part III—Targeted therapy: The Taiwan Association of Gynecology (TAG systematic review

    Directory of Open Access Journals (Sweden)

    Ming-Shyen Yen

    2016-10-01

    Full Text Available Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy, many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

  16. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

    Science.gov (United States)

    Ehret, Georg B; Ferreira, Teresa; Chasman, Daniel I; Jackson, Anne U; Schmidt, Ellen M; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'an; Donnelly, Lousie A; Kanoni, Stavroula; Petersen, Ann-Kristin; Pihur, Vasyl; Strawbridge, Rona J; Shungin, Dmitry; Hughes, Maria F; Meirelles, Osorio; Kaakinen, Marika; Bouatia-Naji, Nabila; Kristiansson, Kati; Shah, Sonia; Kleber, Marcus E; Guo, Xiuqing; Lyytikäinen, Leo-Pekka; Fava, Cristiano; Eriksson, Niclas; Nolte, Ilja M; Magnusson, Patrik K; Salfati, Elias L; Rallidis, Loukianos S; Theusch, Elizabeth; Smith, Andrew J P; Folkersen, Lasse; Witkowska, Kate; Pers, Tune H; Joehanes, Roby; Kim, Stuart K; Lataniotis, Lazaros; Jansen, Rick; Johnson, Andrew D; Warren, Helen; Kim, Young Jin; Zhao, Wei; Wu, Ying; Tayo, Bamidele O; Bochud, Murielle; Absher, Devin; Adair, Linda S; Amin, Najaf; Arking, Dan E; Axelsson, Tomas; Baldassarre, Damiano; Balkau, Beverley; Bandinelli, Stefania; Barnes, Michael R; Barroso, Inês; Bevan, Stephen; Bis, Joshua C; Bjornsdottir, Gyda; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L; Boomsma, Dorret I; Bornstein, Stefan R; Brown, Morris J; Burnier, Michel; Cabrera, Claudia P; Chambers, John C; Chang, I-Shou; Cheng, Ching-Yu; Chines, Peter S; Chung, Ren-Hua; Collins, Francis S; Connell, John M; Döring, Angela; Dallongeville, Jean; Danesh, John; de Faire, Ulf; Delgado, Graciela; Dominiczak, Anna F; Doney, Alex S F; Drenos, Fotios; Edkins, Sarah; Eicher, John D; Elosua, Roberto; Enroth, Stefan; Erdmann, Jeanette; Eriksson, Per; Esko, Tonu; Evangelou, Evangelos; Evans, Alun; Fall, Tove; Farrall, Martin; Felix, Janine F; Ferrières, Jean; Ferrucci, Luigi; Fornage, Myriam; Forrester, Terrence; Franceschini, Nora; Duran, Oscar H Franco; Franco-Cereceda, Anders; Fraser, Ross M; Ganesh, Santhi K; Gao, He; Gertow, Karl; Gianfagna, Francesco; Gigante, Bruna; Giulianini, Franco; Goel, Anuj; Goodall, Alison H; Goodarzi, Mark O; Gorski, Mathias; Gräßler, Jürgen; Groves, Christopher; Gudnason, Vilmundur; Gyllensten, Ulf; Hallmans, Göran; Hartikainen, Anna-Liisa; Hassinen, Maija; Havulinna, Aki S; Hayward, Caroline; Hercberg, Serge; Herzig, Karl-Heinz; Hicks, Andrew A; Hingorani, Aroon D; Hirschhorn, Joel N; Hofman, Albert; Holmen, Jostein; Holmen, Oddgeir Lingaas; Hottenga, Jouke-Jan; Howard, Phil; Hsiung, Chao A; Hunt, Steven C; Ikram, M Arfan; Illig, Thomas; Iribarren, Carlos; Jensen, Richard A; Kähönen, Mika; Kang, Hyun; Kathiresan, Sekar; Keating, Brendan J; Khaw, Kay-Tee; Kim, Yun Kyoung; Kim, Eric; Kivimaki, Mika; Klopp, Norman; Kolovou, Genovefa; Komulainen, Pirjo; Kooner, Jaspal S; Kosova, Gulum; Krauss, Ronald M; Kuh, Diana; Kutalik, Zoltan; Kuusisto, Johanna; Kvaløy, Kirsti; Lakka, Timo A; Lee, Nanette R; Lee, I-Te; Lee, Wen-Jane; Levy, Daniel; Li, Xiaohui; Liang, Kae-Woei; Lin, Honghuang; Lin, Li; Lindström, Jaana; Lobbens, Stéphane; Männistö, Satu; Müller, Gabriele; Müller-Nurasyid, Martina; Mach, François; Markus, Hugh S; Marouli, Eirini; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Menni, Cristina; Metspalu, Andres; Mijatovic, Vladan; Moilanen, Leena; Montasser, May E; Morris, Andrew D; Morrison, Alanna C; Mulas, Antonella; Nagaraja, Ramaiah; Narisu, Narisu; Nikus, Kjell; O'Donnell, Christopher J; O'Reilly, Paul F; Ong, Ken K; Paccaud, Fred; Palmer, Cameron D; Parsa, Afshin; Pedersen, Nancy L; Penninx, Brenda W; Perola, Markus; Peters, Annette; Poulter, Neil; Pramstaller, Peter P; Psaty, Bruce M; Quertermous, Thomas; Rao, Dabeeru C; Rasheed, Asif; Rayner, N William N W R; Renström, Frida; Rettig, Rainer; Rice, Kenneth M; Roberts, Robert; Rose, Lynda M; Rossouw, Jacques; Samani, Nilesh J; Sanna, Serena; Saramies, Jouko; Schunkert, Heribert; Sebert, Sylvain; Sheu, Wayne H-H; Shin, Young-Ah; Sim, Xueling; Smit, Johannes H; Smith, Albert V; Sosa, Maria X; Spector, Tim D; Stančáková, Alena; Stanton, Alice; Stirrups, Kathleen E; Stringham, Heather M; Sundstrom, Johan; Swift, Amy J; Syvänen, Ann-Christine; Tai, E-Shyong; Tanaka, Toshiko; Tarasov, Kirill V; Teumer, Alexander; Thorsteinsdottir, Unnur; Tobin, Martin D; Tremoli, Elena; Uitterlinden, Andre G; Uusitupa, Matti; Vaez, Ahmad; Vaidya, Dhananjay; van Duijn, Cornelia M; van Iperen, Erik P A; Vasan, Ramachandran S; Verwoert, Germaine C; Virtamo, Jarmo; Vitart, Veronique; Voight, Benjamin F; Vollenweider, Peter; Wagner, Aline; Wain, Louise V; Wareham, Nicholas J; Watkins, Hugh; Weder, Alan B; Westra, Harm-Jan; Wilks, Rainford; Wilsgaard, Tom; Wilson, James F; Wong, Tien Y; Yang, Tsun-Po; Yao, Jie; Yengo, Loic; Zhang, Weihua; Zhao, Jing Hua; Zhu, Xiaofeng; Bovet, Pascal; Cooper, Richard S; Mohlke, Karen L; Saleheen, Danish; Lee, Jong-Young; Elliott, Paul; Gierman, Hinco J; Willer, Cristen J; Franke, Lude; Hovingh, G Kees; Taylor, Kent D; Dedoussis, George; Sever, Peter; Wong, Andrew; Lind, Lars; Assimes, Themistocles L; Njølstad, Inger; Schwarz, Peter Eh; Langenberg, Claudia; Snieder, Harold; Caulfield, Mark J; Melander, Olle; Laakso, Markku; Saltevo, Juha; Rauramaa, Rainer; Tuomilehto, Jaakko; Ingelsson, Erik; Lehtimäki, Terho; Hveem, Kristian; Palmas, Walter; März, Winfried; Kumari, Meena; Salomaa, Veikko; Chen, Yii-Der I; Rotter, Jerome I; Froguel, Philippe; Jarvelin, Marjo-Riitta; Lakatta, Edward G; Kuulasmaa, Kari; Franks, Paul W; Hamsten, Anders; Wichmann, H-Erich; Palmer, Colin N A; Stefansson, Kari; Ridker, Paul M; Loos, Ruth J F; Chakravarti, Aravinda; Deloukas, Panos; Morris, Andrew P; Newton-Cheh, Christopher; Munroe, Patricia B

    2016-10-01

    To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

  17. Peptide Targeted by Human Antibodies Associated with HIV Vaccine-Associated Protection Assumes a Dynamic α-Helical Structure

    Science.gov (United States)

    Dominguez, Lorenzo; Goger, Michael; Battacharya, Shibani; deCamp, Allan C.; Gilbert, Peter B.; Berman, Phillip W.; Cardozo, Timothy

    2017-01-01

    The only evidence of vaccine-induced protection from HIV acquisition in humans was obtained in the RV144 HIV vaccine clinical trial. One immune correlate of risk in RV144 was observed to be higher titers of vaccine-induced antibodies (Abs) reacting with a 23-mer non-glycosylated peptide with the same amino acid sequence as a segment in the second variable (V2) loop of the MN strain of HIV. We used NMR to analyze the dynamic 3D structure of this peptide. Distance restraints between spatially proximate inter-residue protons were calculated from NOE cross peak intensities and used to constrain a thorough search of all possible conformations of the peptide. α–helical folding was strongly preferred by part of the peptide. A high-throughput structure prediction of this segment in all circulating HIV strains demonstrated that α–helical conformations are preferred by this segment almost universally across all subtypes. Notably, α–helical conformations of this segment of the V2 loop cluster cross-subtype-conserved amino acids on one face of the helix and the variable amino acid positions on the other in a semblance of an amphipathic α–helix. Accordingly, some Abs that protected against HIV in RV144 may have targeted a specific, conserved α–helical peptide epitope in the V2 loop of HIV’s surface envelope glycoprotein. PMID:28107435

  18. Vesicle-associated membrane protein 7 (VAMP-7) is essential for target cell killing in a natural killer cell line.

    Science.gov (United States)

    Marcet-Palacios, Marcelo; Odemuyiwa, Solomon O; Coughlin, Jason J; Garofoli, Daniella; Ewen, Catherine; Davidson, Courtney E; Ghaffari, Mazyar; Kane, Kevin P; Lacy, Paige; Logan, Michael R; Befus, A Dean; Bleackley, R Chris; Moqbel, Redwan

    2008-02-15

    Natural killer cells recognize and induce apoptosis in foreign, transformed or virus-infected cells through the release of perforin and granzymes from secretory lysosomes. Clinically, NK-cell mediated killing is a major limitation to successful allo- and xenotransplantation. The molecular mechanisms that regulate the fusion of granzyme B-containing secretory lysosomes to the plasma membrane in activated NK cells, prior to target cell killing, are not fully understood. Using the NK cell line YT-Indy as a model, we have investigated the expression of SNAP REceptors (SNAREs), both target (t-) and vesicular (v-) SNAREs, and their function in granzyme B-mediated target cell killing. Our data showed that YT-Indy cells express VAMP-7 and SNAP-23, but not VAMP-2. VAMP-7 was associated with granzyme B-containing lysosomal granules. Using VAMP-7 small interfering RNA (siRNA), we successfully knocked down the expression of VAMP-7 protein in YT-Indy to less than 10% of untreated cells in 24h. VAMP7-deficient YT-Indy cells activated via co-culture with Jurkat cells released <1ng/mL of granzyme B, compared to 1.5-2.5 microg/mL from controls. Using Jurkat cells as targets, we showed a 7-fold reduction in NK cell-mediated killing by VAMP-7 deficient YT-Indy cells. Our results show that VAMP-7 is a crucial component of granzyme B release and target cell killing in the NK cell line YT-Indy. Thus, targeting VAMP-7 expression specifically with siRNA, following transplantation, may be a viable strategy for preventing NK cell-mediated transplant rejection, in vivo.

  19. Real-time detection of implant-associated neutrophil responses using a formyl peptide receptor-targeting NIR nanoprobe

    Directory of Open Access Journals (Sweden)

    Zhou J

    2012-05-01

    Full Text Available Jun Zhou*, Yi-Ting Tsai*, Hong Weng, Ewin N Tang, Ashwin Nair, Digant P Davé, Liping Tang, Department of Bioengineering, University of Texas at Arlington, Arlington, TX *Both authors contributed equally to this workAbstract: Neutrophils play an important role in implant-mediated inflammation and infection. Unfortunately, current methods which monitor neutrophil activity, including enzyme measurements and histological evaluation, require many animals and cannot be used to accurately depict the dynamic cellular responses. To understand the neutrophil interactions around implant-mediated inflammation and infection it is critical to develop methods which can monitor in vivo cellular activity in real time. In this study, formyl peptide receptor (FPR-targeting near-infrared nanoprobes were fabricated. This was accomplished by conjugating near-infrared dye with specific peptides having a high affinity to the FPRs present on activated neutrophils. The ability of FPR-targeting nanoprobes to detect and quantify activated neutrophils was assessed both in vitro and in vivo. As expected, FPR-targeting nanoprobes preferentially accumulated on activated neutrophils in vitro. Following transplantation, FPR-targeting nanoprobes preferentially accumulated at the biomaterial implantation site. Equally important, a strong relationship was observed between the extent of fluorescence intensity in vivo and the number of recruited neutrophils at the implantation site. Furthermore, FPR-targeting nanoprobes may be used to detect and quantify the number of neutrophils responding to a catheter-associated infection. The results show that FPR-targeting nanoprobes may serve as a powerful tool to monitor and measure the extent of neutrophil responses to biomaterial implants in vivo.Keywords: in vivo imaging, nanoprobe, neutrophils, inflammation, biocompatibility

  20. Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas.

    Science.gov (United States)

    Albert, Nathalie L; Weller, Michael; Suchorska, Bogdana; Galldiks, Norbert; Soffietti, Riccardo; Kim, Michelle M; la Fougère, Christian; Pope, Whitney; Law, Ian; Arbizu, Javier; Chamberlain, Marc C; Vogelbaum, Michael; Ellingson, Ben M; Tonn, Joerg C

    2016-09-01

    This guideline provides recommendations for the use of PET imaging in gliomas. The review examines established clinical benefit in glioma patients of PET using glucose ((18)F-FDG) and amino acid tracers ((11)C-MET, (18)F-FET, and (18)F-FDOPA). An increasing number of studies have been published on PET imaging in the setting of diagnosis, biopsy, and resection as well radiotherapy planning, treatment monitoring, and response assessment. Recommendations are based on evidence generated from studies which validated PET findings by histology or clinical course. This guideline emphasizes the clinical value of PET imaging with superiority of amino acid PET over glucose PET and provides a framework for the use of PET to assist in the management of patients with gliomas.

  1. The future of surgical training in the context of the 'Shape of Training' Review: Consensus recommendations by the Association of Surgeons in Training.

    Science.gov (United States)

    Harries, Rhiannon L; Williams, Adam P; Ferguson, Henry J M; Mohan, Helen M; Beamish, Andrew J; Gokani, Vimal J

    2016-11-01

    ASiT has long maintained that in order to provide the best quality care to patients in the UK and Republic of Ireland, it is critical that surgeons are trained to the highest standards. In addition, it is imperative that surgery remains an attractive career choice, with opportunities for career progression and job satisfaction to attract and retain the best candidates. In 2013, the Shape of Training review report set out recommendations for the structure and delivery of postgraduate training in light of an ever increasingly poly-morbid and ageing population. This consensus statement outlines ASIT's position regarding recommendations for improving surgical training and aims to help guide discussions with regard to future proposed changes to surgical training.

  2. FATS is a transcriptional target of p53 and associated with antitumor activity

    OpenAIRE

    2010-01-01

    Abstract Frequent mutations of p53 in human cancers exemplify its crucial role as a tumor suppressor transcription factor, and p21, a transcriptional target of p53, plays a central role in surveillance of cell-cycle checkpoints. Our previous study has shown that FATS stabilize p21 to preserve genome integrity. In this study we identified a novel transcript variant of FATS (GenBank: GQ499374) through screening a cDNA library from mouse testis, which uncovered the promoter region of mouse FATS....

  3. A Search for Brief Optical Flashes Associated with the SETI Target KIC 8462852

    Science.gov (United States)

    Abeysekara, A. U.; Archambault, S.; Archer, A.; Benbow, W.; Bird, R.; Buchovecky, M.; Buckley, J. H.; Byrum, K.; Cardenzana, J. V.; Cerruti, M.; Chen, X.; Christiansen, J. L.; Ciupik, L.; Cui, W.; Dickinson, H. J.; Eisch, J. D.; Errando, M.; Falcone, A.; Fegan, D. J.; Feng, Q.; Finley, J. P.; Fleischhack, H.; Fortin, P.; Fortson, L.; Furniss, A.; Gillanders, G. H.; Griffin, S.; Grube, J.; Gyuk, G.; Hütten, M.; Håkansson, N.; Hanna, D.; Holder, J.; Humensky, T. B.; Johnson, C. A.; Kaaret, P.; Kar, P.; Kelley-Hoskins, N.; Kertzman, M.; Kieda, D.; Krause, M.; Krennrich, F.; Kumar, S.; Lang, M. J.; Lin, T. T. Y.; Maier, G.; McArthur, S.; McCann, A.; Meagher, K.; Moriarty, P.; Mukherjee, R.; Nieto, D.; O'Brien, S.; O'Faoláin de Bhróithe, A.; Ong, R. A.; Otte, A. N.; Park, N.; Perkins, J. S.; Petrashyk, A.; Pohl, M.; Popkow, A.; Pueschel, E.; Quinn, J.; Ragan, K.; Ratliff, G.; Reynolds, P. T.; Richards, G. T.; Roache, E.; Santander, M.; Sembroski, G. H.; Shahinyan, K.; Staszak, D.; Telezhinsky, I.; Tucci, J. V.; Tyler, J.; Vincent, S.; Wakely, S. P.; Weiner, O. M.; Weinstein, A.; Williams, D. A.; Zitzer, B.

    2016-02-01

    The F-type star KIC 8462852 has recently been identified as an exceptional target for search for extraterrestrial intelligence (SETI) observations. We describe an analysis methodology for optical SETI, which we have used to analyze nine hours of serendipitous archival observations of KIC 8462852 made with the VERITAS gamma-ray observatory between 2009 and 2015. No evidence of pulsed optical beacons, above a pulse intensity at the Earth of approximately 1 {photon} {{{m}}}-2, is found. We also discuss the potential use of imaging atmospheric Cherenkov telescope arrays in searching for extremely short duration optical transients in general.

  4. A Search for Brief Optical Flashes Associated with the SETI Target KIC 8462852

    CERN Document Server

    Abeysekara, A U; Archer, A; Benbow, W; Bird, R; Buchovecky, M; Buckley, J H; Byrum, K; Cardenzana, J V; Cerruti, M; Chen, X; Christiansen, J L; Ciupik, L; Cui, W; Dickinson, H J; Eisch, J D; Errando, M; Falcone, A; Fegan, D J; Feng, Q; Finley, J P; Fleischhack, H; Fortin, P; Fortson, L; Furniss, A; Gillanders, G H; Griffin, S; Grube, J; Gyuk, G; Huetten, M; Hakansson, N; Hanna, D; Holder, J; Humensky, T B; Johnson, C A; Kaaret, P; Kar, P; Kelley-Hoskins, N; Kertzman, M; Kieda, D; Krause, M; Krennrich, F; Kumar, S; Lang, M J; Lin, T T Y; Maier, G; McArthur, S; McCann, A; Meagher, K; Moriarty, P; Mukherjee, R; Nieto, D; O'Brien, S; de Bhroithe, A O'Faolain; Ong, R A; Otte, A N; Park, N; Perkins, J S; Petrashyk, A; Pohl, M; Popkow, A; Pueschel, E; Quinn, J; Ragan, K; Ratliff, G; Reynolds, P T; Richards, G T; Roache, E; Santander, M; Sembroski, G H; Shahinyan, K; Staszak, D; Telezhinsky, I; Tucci, J V; Tyler, J; Vincent, S; Wakely, S P; Weiner, O M; Weinstein, A; Williams, D A; Zitzer, B

    2016-01-01

    The F-type star KIC 8462852 has recently been identified as an exceptional target for SETI (search for extraterrestrial intelligence) observations. We describe an analysis methodology for optical SETI, which we have used to analyse nine hours of serendipitous archival observations of KIC 8462852 made with the VERITAS gamma-ray observatory between 2009 and 2015. No evidence of pulsed optical beacons, above a pulse intensity at the Earth of approximately 1 photon per m^2, is found. We also discuss the potential use of imaging atmospheric Cherenkov telescope arrays in searching for extremely short duration optical transients in general.

  5. Mining drug-disease relationships as a complement to medical genetics-based drug repositioning: Where a recommendation system meets genome-wide association studies.

    Science.gov (United States)

    Wang, H; Gu, Q; Wei, J; Cao, Z; Liu, Q

    2015-05-01

    A novel recommendation-based drug repositioning strategy is presented to simultaneously determine novel drug indications and side effects in one integrated framework. This strategy provides a complementary method to medical genetics-based drug repositioning, which reduces the occurrence of false positives in medical genetics-based drug repositioning, resulting in a ranked list of new candidate indications and/or side effects with different confidence levels. Several new drug indications and side effects are reported with high prediction confidences.

  6. Characterization of leukemia-associated minor histocompatibility antigens as targets in anti-leukemic immunotherapy

    NARCIS (Netherlands)

    Rijke, Björn de

    2007-01-01

    This thesis describes the characterization and identification of CTL-defined leukemia-associated minor histocompatibility antigens (mHAg) for the development of novel cellular immunotherapeutic approaches to successfully treat patients with relapsed hematopoietic malignancies after allogeneic stem c

  7. The association between fruit and vegetable intake, knowledge of the recommendations, and health information seeking within adults in the U.S. mainland and in Puerto Rico.

    Science.gov (United States)

    Colón-Ramos, Uriyoán; Finney Rutten, Lila J; Moser, Richard P; Colón-Lopez, Vivian; Ortiz, Ana P; Yaroch, Amy Lazarus

    2015-01-01

    Health information correlates of fruit and vegetable intake and of knowledge of the fruit and vegetable recommendations were examined using bivariate and multivariate regressions with data from the 2007-2008 U.S. National Cancer Institute's Health Information National Trends Survey in the United States and in Puerto Rico. Residents from Puerto Rico had the lowest reported fruit and vegetable intake and the lowest knowledge of the recommended servings of fruits and vegetables to maintain good health, compared with U.S. Hispanics, non-Hispanic Whites, and Blacks. Sixty-seven percent of Puerto Rican residents and 62% of U.S. Hispanics reported never seeking information on health or medical topics. In multivariate analysis, those who never sought information on health or medical topics reported significantly lower fruit and vegetable intake (coefficient = -0.24; 95% CI [-0.38, -0.09]), and were less likely to know the fruit and vegetable recommendations (OR = 0.32; 95% CI [0.20, 0.52]), compared with those who obtained information from their health care providers. Health promotion initiatives in the United States and Puerto Rico have invested in mass media campaigns to increase consumption of and knowledge about fruit and vegetables, but populations with the lowest intake are less likely to seek information. Strategies must be multipronged to address institutional, economic, and behavioral constraints of populations who do not seek out health information from any sources.

  8. Associates of an Elevated Natriuretic Peptide Level in Stable Heart Failure Patients: Implications for Targeted Management

    Directory of Open Access Journals (Sweden)

    Aftab Jan

    2013-01-01

    Full Text Available Background. Persistently elevated natriuretic peptide (NP levels in heart failure (HF patients are associated with impaired prognosis. Recent work suggests that NP-guided therapy can improve outcome, but the mechanisms behind an elevated BNP remain unclear. Among the potential stimuli for NP in clinically stable patients are persistent occult fluid overload, wall stress, inflammation, fibrosis, and ischemia. The purpose of this study was to identify associates of B-type natriuretic peptide (BNP in a stable HF population. Methods. In a prospective observational study of 179 stable HF patients, the association between BNP and markers of collagen metabolism, inflammation, and Doppler-echocardiographic parameters including left ventricular ejection fraction (LVEF, left atrial volume index (LAVI, and E/e prime (E/e′ was measured. Results. Univariable associates of elevated BNP were age, LVEF, LAVI, E/e′, creatinine, and markers of collagen turnover. In a multiple linear regression model, age, creatinine, and LVEF remained significant associates of BNP. E/e′ and markers of collagen turnover had a persistent impact on BNP independent of these covariates. Conclusion. Multiple variables are associated with persistently elevated BNP levels in stable HF patients. Clarification of the relative importance of NP stimuli may help refine NP-guided therapy, potentially improving outcome for this at-risk population.

  9. Cross species association examination of UCN3 and CRHR2 as potential pharmacological targets for antiobesity drugs.

    Directory of Open Access Journals (Sweden)

    Zhihua Jiang

    Full Text Available BACKGROUND: Obesity now constitutes a leading global public health problem. Studies have shown that insulin resistance affiliated with obesity is associated with intramyocellular lipid (IMCL accumulation. Therefore, identification of genes associated with the phenotype would provide a clear target for pharmaceutical intervention and care for the condition. We hypothesized that urocortin 3 (UCN3 and corticotropin-releasing hormone receptor 2 (CRHR2 are associated with IMCL and subcutaneous fat depth (SFD, because the corticotropin-releasing hormone family of peptides are capable of strong anorectic and thermogenic effects. METHODOLOGY/PRINCIPAL FINDINGS: We annotated both bovine UCN3 and CRHR2 genes and identified 12 genetic mutations in the former gene and 5 genetic markers in the promoter region of the latter gene. Genotyping of these 17 markers on Wagyu times Limousin F(2 progeny revealed significant associations between promoter polymorphisms and SFD (P = 0.0203-0.0685 and between missense mutations of exon 2 and IMCL (P = 0.0055-0.0369 in the bovine UCN3 gene. The SFD associated promoter SNPs caused a gain/loss of 12 potential transcription regulatory binding sites, while the IMCL associated coding SNPs affected the secondary structure of UCN3 mRNA. However, none of five polymorphisms in CRHR2 gene clearly co-segregated with either trait in the population (P>0.6000. CONCLUSIONS/SIGNIFICANCE: Because UCN3 is located on human chromosome 10p15.1 where quantitative trait loci for obesity have been reported, our cross species study provides further evidence that it could be proposed as a potential target for developing antiobesity drugs. None of the markers in CRHR2 was associated with obesity-type traits in cattle, which is consistent with findings in human. Therefore, CRHR2 does not lend itself to the development of antiobesity drugs.

  10. Parental Factors Associated with Child Post-traumatic Stress Following Injury: A Consideration of Intervention Targets

    Directory of Open Access Journals (Sweden)

    Anna E. Wise

    2017-08-01

    Full Text Available Post-traumatic stress disorder (PTSD symptoms are relatively common following pediatric traumatic injury and are related to poor long-term child outcomes. However, due to concerns regarding the efficacy of early child preventive interventions, and difficulty intervening with injured and medicated children soon after the event, it is not feasible to provide early psychological interventions to children exposed to traumatic injury. Parental PTSD symptoms and reactions to the child’s traumatic injury impact child outcomes and provide potential targets for early intervention to reduce child symptom development without involving the child. The authors conducted a review of the literature using Psycinfo and Pubmed research databases (publication years = 1990–2017 and identified 65 published studies relevant to the topic of the review. The present review considers parent factors [parenting styles, parental post-traumatic pathology (PTS, adaptive and maladaptive coping strategies, and communication regarding the traumatic injury] and their impact on child PTS. We focus specifically on factors amenable to intervention. We further review moderators of these relationships (e.g., child age and gender, parent gender and conclude that it is unlikely that a one-size-fits-all approach to treatment will be successful. Rather, it is necessary to consider the age and gender of parent child dyads in designing and providing targeted interventions to families following the traumatic injury of a child.

  11. Targeting of cancer‑associated fibroblasts enhances the efficacy of cancer chemotherapy by regulating the tumor microenvironment.

    Science.gov (United States)

    Li, Minmin; Li, Mei; Yin, Tao; Shi, Huashan; Wen, Yuan; Zhang, Binglan; Chen, Meihua; Xu, Guangchao; Ren, Kexin; Wei, Yuquan

    2016-03-01

    Cancer‑associated fibroblasts (CAFs), key components of the tumor stroma, can regulate tumorigenesis by altering the tumor microenvironment in variety of ways to promote angiogenesis, recruit inflammatory immune cells and remodel the extracellular matrix. Using a murine xenograft model of colon carcinoma, the present study observed that oxaliplatin increased the accumulation of CAFs and stimulated the production of cytokines associated with CAFs. When oxaliplatin was combined with the small‑molecule dipeptidyl peptidase inhibitor PT‑100, which inhibits CAFs by targeting fibroblast activation protein (FAP), the accumulation of CAFs was markedly reduced, xenograft tumor growth was significantly suppressed and the survival of the mice increased, compared to those of mice treated with oxaliplatin or PT‑100 alone. Furthermore, the xenograft tumor tissues of mice treated with oxaliplatin and PT‑100 contained lower numbers of tumor‑associated macrophages and dendritic cells, expressed lower levels of cytokines associated with CAFs and had a lower density of CD31+ endothelial cells. The present study demonstrated that pharmacological inhibition of CAFs improved the response to chemotherapy, reduced the recruitment of immune tumor‑promoting cells and inhibited angiogenesis. Combining chemotherapy with agents which target CAFs may represent a novel strategy for improving the efficacy of chemotherapy and reducing chemoresistance.

  12. A combination algorithm of Chaos optimization and genetic algorithm and its application in maneuvering multiple targets data association

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The most important problem in targets tracking is data association which may be represented as a sort of constraint combinational optimization problem. Chaos optimization and adaptive genetic algorithm were used to deal with the problem of multi-targets data association separately. Based on the analysis of the limitation of chaos optimization and genetic algorithm, a new chaos genetic optimization combination algorithm was presented. This new algorithm first applied the "rough" search of chaos optimization to initialize the population of GA, then optimized the population by real-coded adaptive GA. In this way, GA can not only jump out of the "trap" of local optimal results easily but also increase the rate of convergence. And the new method can also avoid the complexity and time-consumed limitation of conventional way. The simulation results show that the combination algorithm can obtain higher correct association percent and the effect of association is obviously superior to chaos optimization or genetic algorithm separately. This method has better convergence property as well as time property than the conventional ones.

  13. Targeting of pseudorabies virus structural proteins to axons requires association of the viral Us9 protein with lipid rafts.

    Directory of Open Access Journals (Sweden)

    Mathew G Lyman

    2008-05-01

    Full Text Available The pseudorabies virus (PRV Us9 protein plays a central role in targeting viral capsids and glycoproteins to axons of dissociated sympathetic neurons. As a result, Us9 null mutants are defective in anterograde transmission of infection in vivo. However, it is unclear how Us9 promotes axonal sorting of so many viral proteins. It is known that the glycoproteins gB, gC, gD and gE are associated with lipid raft microdomains on the surface of infected swine kidney cells and monocytes, and are directed into the axon in a Us9-dependent manner. In this report, we determined that Us9 is associated with lipid rafts, and that this association is critical to Us9-mediated sorting of viral structural proteins. We used infected non-polarized and polarized PC12 cells, a rat pheochromocytoma cell line that acquires many of the characteristics of sympathetic neurons in the presence of nerve growth factor (NGF. In these cells, Us9 is highly enriched in detergent-resistant membranes (DRMs. Moreover, reducing the affinity of Us9 for lipid rafts inhibited anterograde transmission of infection from sympathetic neurons to epithelial cells in vitro. We conclude that association of Us9 with lipid rafts is key for efficient targeting of structural proteins to axons and, as a consequence, for directional spread of PRV from pre-synaptic to post-synaptic neurons and cells of the mammalian nervous system.

  14. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

    Science.gov (United States)

    Chasman, Daniel I.; Jackson, Anne U.; Schmidt, Ellen M.; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'an; Donnelly, Lousie A.; Kanoni, Stavroula; Petersen, Ann-Kristin; Pihur, Vasyl; Strawbridge, Rona J.; Shungin, Dmitry; Hughes, Maria F.; Meirelles, Osorio; Kaakinen, Marika; Bouatia-Naji, Nabila; Kristiansson, Kati; Shah, Sonia; Kleber, Marcus E.; Guo, Xiuqing; Lyytikäinen, Leo-Pekka; Fava, Cristiano; Eriksson, Niclas; Nolte, Ilja M.; Magnusson, Patrik K.; Salfati, Elias L.; Rallidis, Loukianos S.; Theusch, Elizabeth; Smith, Andrew J.P.; Folkersen, Lasse; Witkowska, Kate; Pers, Tune H.; Joehanes, Roby; Kim, Stuart K.; Lataniotis, Lazaros; Jansen, Rick; Johnson, Andrew D.; Warren, Helen; Kim, Young Jin; Zhao, Wei; Wu, Ying; Tayo, Bamidele O.; Bochud, Murielle; Absher, Devin; Adair, Linda S.; Amin, Najaf; Arking, Dan E.; Axelsson, Tomas; Baldassarre, Damiano; Balkau, Beverley; Bandinelli, Stefania; Barnes, Michael R.; Barroso, Inês; Bevan, Stephen; Bis, Joshua C.; Bjornsdottir, Gyda; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Bornstein, Stefan R.; Brown, Morris J.; Burnier, Michel; Cabrera, Claudia P.; Chambers, John C.; Chang, I-Shou; Cheng, Ching-Yu; Chines, Peter S.; Chung, Ren-Hua; Collins, Francis S.; Connell, John M.; Döring, Angela; Dallongeville, Jean; Danesh, John; de Faire, Ulf; Delgado, Graciela; Dominiczak, Anna F.; Doney, Alex S.F.; Drenos, Fotios; Edkins, Sarah; Eicher, John D.; Elosua, Roberto; Enroth, Stefan; Erdmann, Jeanette; Eriksson, Per; Esko, Tonu; Evangelou, Evangelos; Evans, Alun; Fall, Tove; Farrall, Martin; Felix, Janine F.; Ferrières, Jean; Ferrucci, Luigi; Fornage, Myriam; Forrester, Terrence; Franceschini, Nora; Duran, Oscar H. Franco; Franco-Cereceda, Anders; Fraser, Ross M.; Ganesh, Santhi K.; Gao, He; Gertow, Karl; Gianfagna, Francesco; Gigante, Bruna; Giulianini, Franco; Goel, Anuj; Goodall, Alison H.; Goodarzi, Mark O.; Gorski, Mathias; Gräßler, Jürgen; Groves, Christopher; Gudnason, Vilmundur; Gyllensten, Ulf; Hallmans, Göran; Hartikainen, Anna-Liisa; Hassinen, Maija; Havulinna, Aki S.; Hayward, Caroline; Hercberg, Serge; Herzig, Karl-Heinz; Hicks, Andrew A.; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofman, Albert; Holmen, Jostein; Holmen, Oddgeir Lingaas; Hottenga, Jouke-Jan; Howard, Phil; Hsiung, Chao A.; Hunt, Steven C.; Ikram, M. Arfan; Illig, Thomas; Iribarren, Carlos; Jensen, Richard A.; Kähönen, Mika; Kang, Hyun; Kathiresan, Sekar; Keating, Brendan J.; Khaw, Kay-Tee; Kim, Yun Kyoung; Kim, Eric; Kivimaki, Mika; Klopp, Norman; Kolovou, Genovefa; Komulainen, Pirjo; Kooner, Jaspal S.; Kosova, Gulum; Krauss, Ronald M.; Kuh, Diana; Kutalik, Zoltan; Kuusisto, Johanna; Kvaløy, Kirsti; Lakka, Timo A; Lee, Nanette R.; Lee, I-Te; Lee, Wen-Jane; Levy, Daniel; Li, Xiaohui; Liang, Kae-Woei; Lin, Honghuang; Lin, Li; Lindström, Jaana; Lobbens, Stéphane; Männistö, Satu; Müller, Gabriele; Müller-Nurasyid, Martina; Mach, François; Markus, Hugh S.; Marouli, Eirini; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Menni, Cristina; Metspalu, Andres; Mijatovic, Vladan; Moilanen, Leena; Montasser, May E.; Morris, Andrew D.; Morrison, Alanna C.; Mulas, Antonella; Nagaraja, Ramaiah; Narisu, Narisu; Nikus, Kjell; O'Donnell, Christopher J.; O'Reilly, Paul F.; Ong, Ken K.; Paccaud, Fred; Palmer, Cameron D.; Parsa, Afshin; Pedersen, Nancy L.; Penninx, Brenda W.; Perola, Markus; Peters, Annette; Poulter, Neil; Pramstaller, Peter P.; Psaty, Bruce M.; Quertermous, Thomas; Rao, Dabeeru C.; Rasheed, Asif; Rayner, N William N.W.R.; Renström, Frida; Rettig, Rainer; Rice, Kenneth M.; Roberts, Robert; Rose, Lynda M.; Rossouw, Jacques; Samani, Nilesh J.; Sanna, Serena; Saramies, Jouko; Schunkert, Heribert; Sebert, Sylvain; Sheu, Wayne H.-H.; Shin, Young-Ah; Sim, Xueling; Smit, Johannes H.; Smith, Albert V.; Sosa, Maria X.; Spector, Tim D.; Stančáková, Alena; Stanton, Alice; Stirrups, Kathleen E.; Stringham, Heather M.; Sundstrom, Johan; Swift, Amy J.; Syvänen, Ann-Christine; Tai, E-Shyong; Tanaka, Toshiko; Tarasov, Kirill V.; Teumer, Alexander; Thorsteinsdottir, Unnur; Tobin, Martin D.; Tremoli, Elena; Uitterlinden, Andre G.; Uusitupa, Matti; Vaez, Ahmad; Vaidya, Dhananjay; van Duijn, Cornelia M.; van Iperen, Erik P.A.; Vasan, Ramachandran S.; Verwoert, Germaine C.; Virtamo, Jarmo; Vitart, Veronique; Voight, Benjamin F.; Vollenweider, Peter; Wagner, Aline; Wain, Louise V.; Wareham, Nicholas J.; Watkins, Hugh; Weder, Alan B.; Westra, Harm-Jan; Wilks, Rainford; Wilsgaard, Tom; Wilson, James F.; Wong, Tien Y.; Yang, Tsun-Po; Yao, Jie; Yengo, Loic; Zhang, Weihua; Zhao, Jing Hua; Zhu, Xiaofeng; Bovet, Pascal; Cooper, Richard S.; Mohlke, Karen L.; Saleheen, Danish; Lee, Jong-Young; Elliott, Paul; Gierman, Hinco J.; Willer, Cristen J.; Franke, Lude; Hovingh, G Kees; Taylor, Kent D.; Dedoussis, George; Sever, Peter; Wong, Andrew; Lind, Lars; Assimes, Themistocles L.; Njølstad, Inger; Schwarz, Peter EH.; Langenberg, Claudia; Snieder, Harold; Caulfield, Mark J.; Melander, Olle; Laakso, Markku; Saltevo, Juha; Rauramaa, Rainer; Tuomilehto, Jaakko; Ingelsson, Erik; Lehtimäki, Terho; Hveem, Kristian; Palmas, Walter; März, Winfried; Kumari, Meena; Salomaa, Veikko; Chen, Yii-Der I.; Rotter, Jerome I.; Froguel, Philippe; Jarvelin, Marjo-Riitta; Lakatta, Edward G.; Kuulasmaa, Kari; Franks, Paul W.; Hamsten, Anders; Wichmann, H.-Erich; Palmer, Colin N.A.; Stefansson, Kari; Ridker, Paul M; Loos, Ruth J.F.; Chakravarti, Aravinda; Deloukas, Panos; Morris, Andrew P.; Newton-Cheh, Christopher; Munroe, Patricia B.

    2016-01-01

    To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation. PMID:27618452

  15. Systematic genetic analysis identifies Cis-eQTL target genes associated with glioblastoma patient survival.

    Directory of Open Access Journals (Sweden)

    Qing-Rong Chen

    Full Text Available Prior expression quantitative trait locus (eQTL studies have demonstrated heritable variation determining differences in gene expression. The majority of eQTL studies were based on cell lines and normal tissues. We performed cis-eQTL analysis using glioblastoma multiforme (GBM data sets obtained from The Cancer Genome Atlas (TCGA to systematically investigate germline variation's contribution to tumor gene expression levels. We identified 985 significant cis-eQTL associations (FDR<0.05 mapped to 978 SNP loci and 159 unique genes. Approximately 57% of these eQTLs have been previously linked to the gene expression in cell lines and normal tissues; 43% of these share cis associations known to be associated with functional annotations. About 25% of these cis-eQTL associations are also common to those identified in Breast Cancer from a recent study. Further investigation of the relationship between gene expression and patient clinical information identified 13 eQTL genes whose expression level significantly correlates with GBM patient survival (p<0.05. Most of these genes are also differentially expressed in tumor samples and organ-specific controls (p<0.05. Our results demonstrated a significant relationship of germline variation with gene expression levels in GBM. The identification of eQTLs-based expression associated survival might be important to the understanding of genetic contribution to GBM cancer prognosis.

  16. Development of oligoclonal nanobodies for targeting the tumor-associated glycoprotein 72 antigen

    DEFF Research Database (Denmark)

    Sharifzadeh, Zahra; Rahbarizadeh, Fatemeh; Shokrgozar, Mohammad Ali;

    2013-01-01

    The tumor-associated glycoprotein 72 (TAG-72) is a membrane mucin whose over-expression is correlated with advanced tumor stage and increased invasion and metastasis. In this study, we identified a panel of four nanobodies, single variable domains of dromedary heavy-chain antibodies that specific......The tumor-associated glycoprotein 72 (TAG-72) is a membrane mucin whose over-expression is correlated with advanced tumor stage and increased invasion and metastasis. In this study, we identified a panel of four nanobodies, single variable domains of dromedary heavy-chain antibodies...

  17. Profound parental bias associated with chromosome 14 acquired uniparental disomy indicates targeting of an imprinted locus.

    Science.gov (United States)

    Chase, A; Leung, W; Tapper, W; Jones, A V; Knoops, L; Rasi, C; Forsberg, L A; Guglielmelli, P; Zoi, K; Hall, V; Chiecchio, L; Eder-Azanza, L; Bryant, C; Lannfelt, L; Docherty, L; White, H E; Score, J; Mackay, D J G; Vannucchi, A M; Dumanski, J P; Cross, N C P

    2015-10-01

    Acquired uniparental disomy (aUPD) is a common finding in myeloid malignancies and typically acts to convert a somatically acquired heterozygous mutation to homozygosity. We sought to identify the target of chromosome 14 aUPD (aUPD14), a recurrent abnormality in myeloid neoplasms and population cohorts of elderly individuals. We identified 29 cases with aUPD14q that defined a minimal affected region (MAR) of 11.2 Mb running from 14q32.12 to the telomere. Exome sequencing (n=7) did not identify recurrently mutated genes, but methylation-specific PCR at the imprinted MEG3-DLK1 locus located within the MAR demonstrated loss of maternal chromosome 14 and gain of paternal chromosome 14 (P<0.0001), with the degree of methylation imbalance correlating with the level of aUPD (r=0.76; P=0.0001). The absence of driver gene mutations in the exomes of three individuals with aUPD14q but no known haematological disorder suggests that aUPD14q may be sufficient to drive clonal haemopoiesis. Analysis of cases with both aUPD14q and JAK2 V617F (n=11) indicated that aUPD14q may be an early event in some cases but a late event in others. We conclude that aUPD14q is a recurrent abnormality that targets an imprinted locus and may promote clonal haemopoiesis either as an initiating event or as a secondary change.

  18. Arabidopsis chromatin-associated HMGA and HMGB use different nuclear targeting signals and display highly dynamic localization within the nucleus

    DEFF Research Database (Denmark)

    Launholt, Dorte; Merkle, Thomas; Houben, Andreas;

    2006-01-01

    HMGproteins appear to be involved in the regulation of transcription and other DNA-dependent processes. We have examined the subcellular localization of Arabidopsis thaliana HMGA, HMGB1, and HMGB5, revealing that they localize to the cell nucleus. They display a speckled distribution pattern throughout the chromatin...... of interphase nuclei, whereas none of the proteins associate with condensed mitotic chromosomes. HMGA is targeted to the nucleus by a monopartite nuclear localization signal, while efficient nuclear accumulation of HMGB1/5 requires large portions of the basic N-terminal part of the proteins. The acidic C......-terminal domain interferes with nucleolar targeting of HMGB1. Fluorescence recovery after photobleaching experiments revealed that HMGA and HMGB proteins are extremely dynamic in the nucleus, indicating that they bind chromatin only transiently before moving on to the next site, thereby continuously scanning...

  19. Molecular biology of cancer-associated fibroblasts: can these cells be targeted in anti-cancer therapy?

    Science.gov (United States)

    Gonda, Tamas A; Varro, Andrea; Wang, Timothy C; Tycko, Benjamin

    2010-02-01

    It is increasingly recognized that the non-neoplastic stromal compartment in most solid cancers plays an active role in tumor proliferation, invasion and metastasis. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types in the tumor stroma, and these cells are pro-tumorigenic. Evidence that CAFs are epigenetically and possibly also genetically distinct from normal fibroblasts is beginning to define these cells as potential targets of anti-cancer therapy. Here, we review the cell-of-origin and molecular biology of CAFs, arguing that such knowledge provides a rational basis for designing therapeutic strategies to coordinately and synergistically target both the stromal and malignant epithelial component of human cancers.

  20. Palmitoylated TMX and calnexin target to the mitochondria-associated membrane

    DEFF Research Database (Denmark)

    Lynes, Emily M.; Bui, Michael; Yap, Megan C.;

    2012-01-01

    The mitochondria-associated membrane (MAM) is a domain of the endoplasmic reticulum (ER) that mediates the exchange of ions, lipids and metabolites between the ER and mitochondria. ER chaperones and oxidoreductases are critical components of the MAM. However, the localization motifs and mechanism...

  1. Formulaic Sequences and L2 Oral Proficiency: Does the Type of Target Language Influence the Association?

    Science.gov (United States)

    Stengers, Helene; Boers, Frank; Housen, Alex; Eyckmans, June

    2011-01-01

    This paper investigates the extent to which productive use of formulaic sequences by intermediate students of two typologically different languages, i.e., English and Spanish, is associated with their oral proficiency in these languages. Previous research (e.g., Boers et al., "Language Teaching Research" 10: 245-261, 2006) has shown that…

  2. Prevention and control of catheter-associated urinary tract infections – implementation of the recommendations of the Commission for Hospital Hygiene and Infection Prevention (KRINKO) in nursing homes for the elderly in Frankfurt am Main, Germany

    OpenAIRE

    Heudorf, U; Gasteyer, S.; Müller, M.; Samoiski, Y; Serra, N.; Westphal, T

    2016-01-01

    Introduction: Urinary tract infections range among the most frequent infections not only in hospital patients but also in residents of long-term care facilities for the elderly. Urinary catheters are the greatest risk factor for urinary tract infections. In the guidance paper on the "prevention of infections in nursing homes" (2005) as well as in the updated recommendations for the "prevention and control of catheter-associated urinary tract infections" (2015), the Commission for Hospital Hy...

  3. Education and WHO recommendations for fruit and vegetable intake are associated with better cognitive function in a disadvantaged Brazilian elderly population: a population-based cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Maria Pastor-Valero

    Full Text Available Brazil has one of the fastest aging populations in the world and the incidence of cognitive impairment in the elderly is expected to increase exponentially. We examined the association between cognitive impairment and fruit and vegetable intake and associated factors in a low-income elderly population. A cross-sectional population-based study was carried out with 1849 individuals aged 65 or over living in São Paulo, Brazil. Cognitive function was assessed using the Community Screening Instrument for Dementia (CSI-D. Fruit and vegetable intake was assessed with a Food Frequency Questionnaire (FFQ and categorized into quartiles of intake and into total daily fruit and vegetable intake using the cut-off points for the WHO recommendations (<400 grams/day or ≥ 400 grams/day. The association between cognitive impairment and each quartile of intake, and WHO recommendation levels, was evaluated in two separate multivariate logistic models. The WHO recommendations for daily intakes ≥ 400 grams/day were significantly associated with 47% decreased prevalence of cognitive impairment. An effect modification was found in both models between cognitive impairment and "years of education and physical activity" and "years of education and blood levels of HDL" So that, having 1 or more years of education and being physically active or having 1 or more years of education and levels higher than 50 mg/dl of HDL-cholesterol strongly decreased the prevalence of cognitive impairment. In this socially deprived population with very low levels of education and physical activity and fruit and vegetable intake, those who attained WHO recommendations, had 1 year or more of education and were physically active had a significantly lower prevalence of cognitive impairment. A more comprehensive understanding of the social determinants of mental health is needed to develop effective public policies in developing countries.

  4. An Automated Recommender System for Course Selection

    Directory of Open Access Journals (Sweden)

    Amer Al-Badarenah

    2016-03-01

    Full Text Available Most of electronic commerce and knowledge management` systems use recommender systems as the underling tools for identifying a set of items that will be of interest to a certain user. Collaborative recommender systems recommend items based on similarities and dissimilarities among users’ preferences. This paper presents a collaborative recommender system that recommends university elective courses to students by exploiting courses that other similar students had taken. The proposed system employs an association rules mining algorithm as an underlying technique to discover patterns between courses. Experiments were conducted with real datasets to assess the overall performance of the proposed approach.

  5. Association of impulsivity and polymorphic microRNA-641 target sites in the SNAP-25 gene.

    Directory of Open Access Journals (Sweden)

    Nóra Németh

    Full Text Available Impulsivity is a personality trait of high impact and is connected with several types of maladaptive behavior and psychiatric diseases, such as attention deficit hyperactivity disorder, alcohol and drug abuse, as well as pathological gambling and mood disorders. Polymorphic variants of the SNAP-25 gene emerged as putative genetic components of impulsivity, as SNAP-25 protein plays an important role in the central nervous system, and its SNPs are associated with several psychiatric disorders. In this study we aimed to investigate if polymorphisms in the regulatory regions of the SNAP-25 gene are in association with normal variability of impulsivity. Genotypes and haplotypes of two polymorphisms in the promoter (rs6077690 and rs6039769 and two SNPs in the 3' UTR (rs3746544 and rs1051312 of the SNAP-25 gene were determined in a healthy Hungarian population (N = 901 using PCR-RFLP or real-time PCR in combination with sequence specific probes. Significant association was found between the T-T 3' UTR haplotype and impulsivity, whereas no association could be detected with genotypes or haplotypes of the promoter loci. According to sequence alignment, the polymorphisms in the 3' UTR of the gene alter the binding site of microRNA-641, which was analyzed by luciferase reporter system. It was observed that haplotypes altering one or two nucleotides in the binding site of the seed region of microRNA-641 significantly increased the amount of generated protein in vitro. These findings support the role of polymorphic SNAP-25 variants both at psychogenetic and molecular biological levels.

  6. [Identification of mutations associated with coronary artery lesion susceptibility in Kawasaki disease by targeted enrichment of genomic region sequencing technique].

    Science.gov (United States)

    Zhu, D Y; Song, S R; Xie, L J; Qiu, F; Yang, J; Xiao, T T; Huang, M

    2017-07-02

    Objective: To screen and identify the mutations in Kawasaki disease by targeted enrichment of genomic region sequencing technique and investigate susceptibility genes associated with coronary artery lesion. Method: This was a case-control study.A total of 114 patients diagnosed as Kawasaki disease treated in Shanghai Children's Hospital between December 2015 and November 2016 were studied and another 45 healthy children who were physically examined in outpatient department were enrolled as control group. Patients were divided into two groups based on the results of echocardiogram. Peripheral venous blood was obtained from patients and controls. Genomic DNA was extracted. SeqCap EZ Choice libraries were prepared by targeted enrichment of genomic region technology. Then the libraries were sequenced to identify susceptibility genes associated with coronary artery lesion in patients diagnosed as Kawasaki disease.Susceptible genes were identified by Burden test, Pearson chi-square test or Fisher's exact probability test. Result: There was statistically significant difference in TNFRSF11B(rs2073618)G>C(p.N3K)mutation and GG/GC/CC genotype between Kawasaki disease group and control group(χ(2)=15.52, P=0.00). There was statistically significant difference in TNFRSF13B(rs34562254)C>T(p.P251L)mutation(χ(2)=10.40, P=0.01)and LEFTY1(rs360057)T>G(p.D322A)mutation(χ(2)=8.505, P=0.01)between patients with coronary artery lesions and those without. Conclusion: Targeted enrichment of genomic region sequencing technology can be used to do primary screening for the susceptible genes associated with coronary artery lesions in Chinese Kawasaki patients and may provide theoretical basis for larger sample investigation of risk prediction score standard in Kawasaki disease.

  7. Lipoprotein cholesterol and triglyceride concentrations associated with dog body condition score; effect of recommended fasting duration on sample concentrations in Japanese private clinics.

    Science.gov (United States)

    Usui, Shiho; Yasuda, Hidemi; Koketsu, Yuzo

    2015-09-01

    The objectives of this study were to survey clinics' guidance about recommended fasting duration (FD) prior to lipoprotein analysis, and to characterize lipoprotein cholesterol and triglyceride concentrations in obese and overweight dogs categorized on the basis of the 5-point body condition score (BCS) scale. A dataset was created from lipoprotein analysis medical records of 1,538 dogs from 75 breeds in 354 clinics from 2012 to 2013. A phone survey was conducted to obtain the clinics' FD. Two-level linear mixed-effects models were applied to the data. Over 50% of the clinics said they recommended fasting for 12 hr or more. Dogs in clinics with FD 12 hr or more had lower chylomicron triglyceride concentrations than those in clinics with FD less than 8 hr (P=0.05). Mean (± SEM) BCS at sampling was 3.7 ± 0.02. Obese and overweight dogs had higher very low density lipoprotein (VLDL) and high density lipoprotein (HDL) cholesterol and triglyceride concentrations than ideal dogs (Plipoprotein cholesterol and triglyceride concentrations (P≥0.07). Across all BCS, as dog age rose from 0 to 8 years old, HDL cholesterol concentrations decreased by 13.5 mg/dl, whereas VLDL triglyceride concentrations increased by 81.7 mg/dl (Plipoprotein lipid concentrations. Obese and overweight dogs were characterized as having high VLDL and HDL cholesterol and triglyceride concentrations.

  8. Recommendations for the use of PET imaging biomarkers in the diagnosis of neurodegenerative conditions associated with dementia: SEMNIM and SEN consensus.

    Science.gov (United States)

    Arbizu, Javier; García-Ribas, Guillermo; Carrió, Ignasi; Garrastachu, Puy; Martínez-Lage, Pablo; Molinuevo, José Luis

    2015-01-01

    The new diagnostic criteria for Alzheimer's disease (AD) acknowledges the interest given to biomarkers to improve the specificity in subjects with dementia and to facilitate an early diagnosis of the pathophysiological process of AD in the prodromal or pre-dementia stage. The current availability of PET imaging biomarkers of synaptic dysfunction (PET-FDG) and beta amyloid deposition using amyloid-PET provides clinicians with the opportunity to apply the new criteria and improve diagnostic accuracy in their clinical practice. Therefore, it seems essential for the scientific societies involved to use the new clinical diagnostic support tools to establish clear, evidence-based and agreed set of recommendations for their appropriate use. The present work includes a systematic review of the literature on the utility of FDG-PET and amyloid-PET for the diagnosis of AD and related neurodegenerative diseases that occur with dementia. Thus, we propose a series of recommendations agreed on by the Spanish Society of Nuclear Medicine and Spanish Society of Neurology as a consensus statement on the appropriate use of PET imaging biomarkers. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  9. Thermodynamic instability of viral proteins is a pathogen-associated molecular pattern targeted by human defensins.

    Science.gov (United States)

    Kudryashova, Elena; Koneru, Pratibha C; Kvaratskhelia, Mamuka; Strömstedt, Adam A; Lu, Wuyuan; Kudryashov, Dmitri S

    2016-09-01

    Human defensins are innate immune defense peptides with a remarkably broad repertoire of anti-pathogen activities. In addition to modulating immune response, inflammation, and angiogenesis, disintegrating bacterial membranes, and inactivating bacterial toxins, defensins are known to intercept various viruses at different stages of their life cycles, while remaining relatively benign towards human cells and proteins. Recently we have found that human defensins inactivate proteinaceous bacterial toxins by taking advantage of their low thermodynamic stability and acting as natural "anti-chaperones", i.e. destabilizing the native conformation of the toxins. In the present study we tested various proteins produced by several viruses (HIV-1, PFV, and TEV) and found them to be susceptible to destabilizing effects of human α-defensins HNP-1 and HD-5 and the synthetic θ-defensin RC-101, but not β-defensins hBD-1 and hBD-2 or structurally related plant-derived peptides. Defensin-induced unfolding promoted exposure of hydrophobic groups otherwise confined to the core of the viral proteins. This resulted in precipitation, an enhanced susceptibility to proteolytic cleavage, and a loss of viral protein activities. We propose, that defensins recognize and target a common and essential physico-chemical property shared by many bacterial toxins and viral proteins - the intrinsically low thermodynamic protein stability.

  10. Neuropeptides as therapeutic targets to combat stress-associated behavioral and neuroendocrinological effects.

    Science.gov (United States)

    Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

    2014-03-01

    Stress has become an integral part of human life and organisms are being constantly subjected to stress and the ability to cope with such stress is a crucial determinant of health and disease. Neuropeptides (bioactive peptides) play a crucial role in mediating different effects of acute and chronic stress. Some of these neuropeptides including oxytocin, urocortins, neuropeptide Y (NPY), neuropeptide S, cocaine and amphetamine regulated transcript, endorphins, enkephalins, ghrelin and thyrotropin-releasing hormone primarily attenuate stress and act as anxiolytic. On the other hand, neuropeptides including corticotropin releasing hormone, vasopressin, dynorphin, angiotensin, nesfatin-1, orexin and cholecystokinin primarily tend to promote stress related anxiety behavior. However, these neuropeptide tend to produce different actions depending on the type of receptors, the nature and intensity of the stressor. For example, NPY may exhibit anxiolytic effects by activating NPY1 and Y5 receptors, while pro-depressive effects are produced through NPY2 and Y4 receptors. Galanin may produce 'prodepressive' effects by activating its Gal 1 receptors and exert 'antidepressant' effects through Gal 2 receptors. The present review describes different neuropeptides as therapeutic targets to attenuate stress-induced behavioral and neuroendocrinological effects.

  11. Novel Drug Targets Based on Association between Inflammation and Pancreatic Ductal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Muhammad Wasif Saif

    2010-07-01

    Full Text Available Dear Sir We read with great interest the editorial published by Uomo et al. in the 2010 May issue of JOP. J Pancreas (Online titled: “Inflammation and Pancreatic Ductal Adenocarcinoma: A Potential Scenario for Novel Drug Targets” [1]. There is a growing amount of evidence that inflammation plays a contributory role in the pathogenesis of cancer, including pancreatic carcinogenesis. Inflammatory states are characterized by the formation of reactive oxygen species and the induction of cell cycling for tissue growth and repair [1, 2, 3]. The initiation, promotion and expansion of tumors may be influenced by numerous components that also function in the inflammatory response. Recognized risk factors for pancreatic cancer include cigarette smoking, chronic/hereditary pancreatitis, obesity and type II diabetes. Each risk factor is linked by the fact that the inflammatory state significantly drives its pathology. We agree with the authors that multiple links between inflammation and pancreatic adenocarcinoma has led to development of novel targeted therapy which is under evaluation both in vivo and in vitro studies to fight against pancreatic adenocarcinoma. Pancreatic cancer is one of the leading causes of cancer mortality in the United States. Current therapy for pancreatic cancer involves surgery, chemotherapy, and radiation therapy; however, the 5-year survival rate remains less than 5%. Therefore, developments of novel agents, in particular based on the pathogenesis of pancreatic adenocarcinoma are urgently indicated.

  12. Overview and Management of Dermatologic Events Associated with Targeted Therapies for Medullary Thyroid Cancer

    Science.gov (United States)

    Ciccolini, Kathryn; Kloos, Richard T.; Agulnik, Mark

    2014-01-01

    Background: Treatment options for patients with advanced or metastatic medullary thyroid cancer (MTC) have, in recent years, expanded with the approval of two tyrosine kinase inhibitors (TKIs): vandetanib and cabozantinib. Other agents, including TKIs, are under clinical investigation for MTC. Although patients treated with TKIs are at risk of developing dermatologic adverse events (AE), these untoward events may be mitigated through AE-driven algorithms. Summary: AE-driven algorithms combine effective nonpharmaceutical and pharmaceutical treatment modalities implemented by a multidisciplinary effort that incorporates nursing interventions, patient education, and referrals to pain-management specialists, podiatrists, and dermatologists, as appropriate. Effective AE prevention and management reduce the need for dose interruptions and modifications, allowing patients the opportunity to derive the maximal benefit from TKI therapy, while maintaining quality of life. Conclusions: Optimal use of targeted therapies in the treatment of MTC depends on careful patient selection, interdisciplinary communication, and patient education and encouragement to enhance compliance and safety, optimize consistent dosing, and maximize the use of effective therapies. PMID:24902006

  13. Photodynamic Therapy with Hypericin Improved by Targeting HSP90 Associated Proteins

    Directory of Open Access Journals (Sweden)

    Peter Ferenc

    2011-11-01

    Full Text Available In this study we have focused on the response of SKBR-3 cells to both single 17-DMAG treatment as well as its combination with photodynamic therapy with hypericin. Low concentrations of 17-DMAG without any effect on survival of SKBR-3 cells significantly reduced metabolic activity, viability and cell number when combined with photodynamic therapy with hypericin. Moreover, IC10 concentation of 17-DMAG resulted in significant increase of SKBR-3 cells in G1 phase of the cell cycle, followed by an increase of cells in G2 phase when combined with photodynamic therapy. Furthermore, 17-DMAG already decreased HER2, Akt, P-Erk1/2 and survivin protein levels in SKBR-3 cells a short time after its application. In this regard, 17-DMAG protected also SKBR-3 cells against both P-Erk1/2 as well as survivin upregulations induced by photodynamic therapy with hypericin. Interestingly, IC10 concentration of 17-DMAG led to total depletion of Akt, P-Erk1/2 proteins and to decrease of survivin level at 48 h. On the other hand, 17-DMAG did not change HER2 relative expression in SKBR-3 cells, but caused a significant decrease of HER2 mRNA in MCF-7 cells characterized by low HER2 expression. These results show that targeting HSP90 client proteins increases the efficiency of antineoplastic effect of photodynamic therapy in vitro.

  14. FATS is a transcriptional target of p53 and associated with antitumor activity

    Directory of Open Access Journals (Sweden)

    Zhang Xifeng

    2010-09-01

    Full Text Available Abstract Frequent mutations of p53 in human cancers exemplify its crucial role as a tumor suppressor transcription factor, and p21, a transcriptional target of p53, plays a central role in surveillance of cell-cycle checkpoints. Our previous study has shown that FATS stabilize p21 to preserve genome integrity. In this study we identified a novel transcript variant of FATS (GenBank: GQ499374 through screening a cDNA library from mouse testis, which uncovered the promoter region of mouse FATS. Mouse FATS was highly expressed in testis. The p53-responsive elements existed in proximal region of both mouse and human FATS promoters. Functional study indicated that the transcription of FATS gene was activated by p53, whereas such effect was abolished by site-directed mutagenesis in the p53-RE of FATS promoter. Furthermore, the expression of FATS increased upon DNA damage in a p53-dependent manner. FATS expression was silent or downregulated in human cancers, and overexpression of FATS suppressed tumorigenicity in vivo independently of p53. Our results reveal FATS as a p53-regulated gene to monitor genomic stability.

  15. Prevention of colitis-associated cancer by selective targeting of immunoproteasome subunit LMP7

    DEFF Research Database (Denmark)

    Vachharajani, Niyati; Joeris, Thorsten; Luu, Maik;

    2017-01-01

    Chronic inflammation is a well-known risk factor in development of intestinal tumorigenesis, although the exact mechanisms underlying development of colitis-associated cancer (CAC) still remain obscure. The activity and function of immunoproteasome has been extensively analyzed in the context...... of inflammation and infectious diseases. Here, we show that the proteasomal immunosubunit LMP7 plays an essential role in development of CAC. Mice devoid of LMP7 were resistant to chronic inflammation and formation of neoplasia, and developed virtually no tumors after AOM/DSS treatment. Our data reveal that LMP7...

  16. Rising Prices of Targeted Oral Anticancer Medications and Associated Financial Burden on Medicare Beneficiaries.

    Science.gov (United States)

    Shih, Ya-Chen Tina; Xu, Ying; Liu, Lei; Smieliauskas, Fabrice

    2017-08-01

    Purpose The high cost of oncology drugs threatens the affordability of cancer care. Previous research identified drivers of price growth of targeted oral anticancer medications (TOAMs) in private insurance plans and projected the impact of closing the coverage gap in Medicare Part D in 2020. This study examined trends in TOAM prices and patient out-of-pocket (OOP) payments in Medicare Part D and estimated the actual effects on patient OOP payments of partial filling of the coverage gap by 2012. Methods Using SEER linked to Medicare Part D, 2007 to 2012, we identified patients who take TOAMs via National Drug Codes in Part D claims. We calculated total drug costs (prices) and OOP payments per patient per month and compared their rates of inflation with general health care prices. Results The study cohort included 42,111 patients who received TOAMs between 2007 and 2012. Although the general prescription drug consumer price index grew at 3% per year over 2007 to 2012, mean TOAM prices increased by nearly 12% per year, reaching $7,719 per patient per month in 2012. Prices increased over time for newly and previously launched TOAMs. Mean patient OOP payments dropped by 4% per year over the study period, with a 40% drop among patients with a high financial burden in 2011, when the coverage gap began to close. Conclusion Rising TOAM prices threaten the financial relief patients have begun to experience under closure of the coverage gap in Medicare Part D. Policymakers should explore methods of harnessing the surge of novel TOAMs to increase price competition for Medicare beneficiaries.

  17. Cancer-associated mutations in the protrusion-targeting region of p190RhoGAP impact tumor cell migration.

    Science.gov (United States)

    Binamé, Fabien; Bidaud-Meynard, Aurélien; Magnan, Laure; Piquet, Léo; Montibus, Bertille; Chabadel, Anne; Saltel, Frédéric; Lagrée, Valérie; Moreau, Violaine

    2016-09-26

    Spatiotemporal regulation of RhoGTPases such as RhoA is required at the cell leading edge to achieve cell migration. p190RhoGAP (p190A) is the main negative regulator of RhoA and localizes to membrane protrusions, where its GTPase-activating protein (GAP) activity is required for directional migration. In this study, we investigated the molecular processes responsible for p190A targeting to actin protrusions. By analyzing the subcellular localization of truncated versions of p190A in hepatocellular carcinoma cells, we identified a novel functional p190A domain: the protrusion localization sequence (PLS) necessary and sufficient for p190A targeting to leading edges. Interestingly, the PLS is also required for the negative regulation of p190A RhoGAP activity. Further, we show that the F-actin binding protein cortactin binds the PLS and is required for p190A targeting to protrusions. Lastly, we demonstrate that cancer-associated mutations in PLS affect p190A localization and function, as well as tumor cell migration. Altogether, our data unveil a new mechanism of regulation of p190A in migrating tumor cells.

  18. Insulin-Associated Neuroinflammatory Pathways as Therapeutic Targets for Traumatic Brain Injury

    Science.gov (United States)

    Cerecedo-López, Christian D.; Kim-Lee, Jennifer H.; Hernandez, Diana; Acosta, Sandra A.; Borlongan, Cesar V.

    2014-01-01

    Traumatic brain injury (TBI) is characterized by an abrupt blow or exchange of force against the head and can be categorized as mild, moderate, and severe. The secondary cell death after TBI displays ischemic-like patterns including neuroinflammation. The scavenger receptor cluster of differentiation (CD) 36 is a lipid-associated protein capable of transducing intracellular signals to promote inflammatory mechanisms within different cell types. Expression and activation of CD36 is closely related to dyslipidemia secondary to diabetes. Diabetes mellitus (DM) has been documented as a co-morbidity factor in TBI, in that patients with a history of diabetes present with more severe brain damage and slower recovery from TBI than non-diabetic patients. Indeed, a strict regulation of blood serum glucose by the use of insulin promotes a better outcome for TBI patients. Based on these recent findings, we now advance the hypothesis that CD36 via DM insulin-associated pathways is closely involved in TBI chronic pathology. PMID:24332562

  19. Effects of ongoing task context and target typicality on prospective memory performance: the importance of associative cueing

    Science.gov (United States)

    Nowinski, Jessica Lang; Dismukes, Key R.

    2005-01-01

    Two experiments examined whether prospective memory performance is influenced by contextual cues. In our automatic activation model, any information available at encoding and retrieval should aid recall of the prospective task. The first experiment demonstrated an effect of the ongoing task context; performance was better when information about the ongoing task present at retrieval was available at encoding. Performance was also improved by a strong association between the prospective memory target as it was presented at retrieval and the intention as it was encoded. Experiment 2 demonstrated boundary conditions of the ongoing task context effect, which implicate the association between the ongoing and prospective tasks formed at encoding as the source of the context effect. The results of this study are consistent with predictions based on automatic activation of intentions.

  20. Juvenile Spondyloarthritis Treatment Recommendations

    OpenAIRE

    Tse, Shirley; Burgos-Vargas, Ruben; Colbert, Robert A

    2012-01-01

    No specific recommendations for the treatment of juvenile spondyloarthritis have been established. Important differences exist in how spondyloarthritis begins and progresses in children and adults, supporting the need for pediatric-specific recommendations. Recently published recommendations for the treatment of juvenile arthritis consider children with sacroiliitis in a separate group, and allow for more accelerated institution of a TNF inhibitor depending on disease activity and prognostic ...

  1. Mammalian target of rapamycin is activated in association with myometrial proliferation during pregnancy.

    Science.gov (United States)

    Jaffer, Shabana; Shynlova, Oksana; Lye, Stephen

    2009-10-01

    The adaptive growth of the uterus during gestation involves gradual changes in cellular phenotypes from the early proliferative to the intermediate synthetic phase of cellular hypertrophy, ending in the final contractile/labour phenotype. The mammalian target of rapamycin (mTOR) signaling pathway regulates cell growth and proliferation in many tissues. We hypothesized that mTOR was a mediator of hormone-initiated myometrial hyperplasia during gestation. The protein expression and phosphorylation levels of mTOR, its upstream regulators [insulin receptor substrate-1, phosphoinositide-3-kinase (PI3K), Akt], and downstream effectors [S6-kinase-1 (S6K1) and eI4FE-binding protein 1 (4EBP1)] were analyzed throughout normal pregnancy in rats. In addition, we used an ovariectomized (OVX) rat model to analyze the modulation of the mTOR pathway and proliferative activity of the uterine myocytes by estradiol alone and in combination with the mTOR-specific inhibitor rapamycin. Our results demonstrate that insulin receptor substrate-1 protein levels and the phosphorylated (activated) forms of PI3K, mTOR, and S6K1 were significantly up-regulated in the rat myometrium during the proliferative phase of pregnancy. Treatment of the OVX rats with estradiol caused a transient increase in IGF-I followed by an up-regulation of the PI3K/mTOR pathway, which became apparent by a cascade of phosphorylation reactions (P-P85, P-Akt, P-mTOR, P-S6K1, and P-4EBP1). Rapamycin blocked activation of P-mTOR, P-S6K1, and P-4EBP1 proteins and significantly reduced the number of proliferating cells in the myometrium of OVX rats. Our in vivo data demonstrate that estradiol was able to activate the PI3K/mTOR signaling pathway in uterine myocytes and suggest that this activation is responsible for the induction of myometrial hyperplasia during early gestation.

  2. "Targeting" triple-negative breast cancer: the lessons learned from BRCA1-associated breast cancers.

    Science.gov (United States)

    Nanda, Rita

    2011-04-01

    Breast cancer has long been recognized as a heterogeneous entity, with distinct subsets characterized by differences in tumor biology and response to therapy. With the advent of molecular profiling, we have gained a further appreciation of the heterogeneity of this complex disease. While the last decade has seen advances in the treatment of hormone receptor (HR) and human epidermal growth factor receptor 2/erb-B2 (HER2)-positive breast cancers, outcomes for women with estrogen receptor (ER)-, progesterone receptor (PR)-, and HER2-negative-or "triple-negative"-breast cancer (TNBC) remain poor. A better understanding of the shared biology of BRCA1-associated breast cancer and sporadic TNBC holds much promise for changing the outlook for women with this aggressive disease. This review focuses on our current understanding of the clinicopathological features of TNBC, therapeutic options and ongoing research efforts.

  3. Quality improvement projects targeting health care-associated infections: comparing Virtual Collaborative and Toolkit approaches.

    Science.gov (United States)

    Speroff, Theodore; Ely, E Wes; Greevy, Robert; Weinger, Matthew B; Talbot, Thomas R; Wall, Richard J; Deshpande, Jayant K; France, Daniel J; Nwosu, Sam; Burgess, Hayley; Englebright, Jane; Williams, Mark V; Dittus, Robert S

    2011-05-01

    Collaborative and toolkit approaches have gained traction for improving quality in health care. To determine if a quality improvement virtual collaborative intervention would perform better than a toolkit-only approach at preventing central line-associated bloodstream infections (CLABSIs) and ventilator-associated pneumonias (VAPs). Cluster randomized trial with the Intensive Care Units (ICUs) of 60 hospitals assigned to the Toolkit (n=29) or Virtual Collaborative (n=31) group from January 2006 through September 2007. CLABSI and VAP rates. Follow-up survey on improvement interventions, toolkit utilization, and strategies for implementing improvement. A total of 83% of the Collaborative ICUs implemented all CLABSI interventions compared to 64% of those in the Toolkit group (P = 0.13), implemented daily catheter reviews more often (P = 0.04), and began this intervention sooner (P < 0.01). Eighty-six percent of the Collaborative group implemented the VAP bundle compared to 64% of the Toolkit group (P = 0.06). The CLABSI rate was 2.42 infections per 1000 catheter days at baseline and 2.73 at 18 months (P = 0.59). The VAP rate was 3.97 per 1000 ventilator days at baseline and 4.61 at 18 months (P = 0.50). Neither group improved outcomes over time; there was no differential performance between the 2 groups for either CLABSI rates (P = 0.71) or VAP rates (P = 0.80). The intensive collaborative approach outpaced the simpler toolkit approach in changing processes of care, but neither approach improved outcomes. Incorporating quality improvement methods, such as ICU checklists, into routine care processes is complex, highly context-dependent, and may take longer than 18 months to achieve. Copyright © 2011 Society of Hospital Medicine.

  4. A Splice-Isoform of Vesicle-associated Membrane Protein-1 (VAMP-1) Contains a Mitochondrial Targeting Signal

    Science.gov (United States)

    Isenmann, Sandra; Khew-Goodall, Yeesim; Gamble, Jennifer; Vadas, Mathew; Wattenberg, Binks W.

    1998-01-01

    Screening of a library derived from primary human endothelial cells revealed a novel human isoform of vesicle-associated membrane protein-1 (VAMP-1), a protein involved in the targeting and/or fusion of transport vesicles to their target membrane. We have termed this novel isoform VAMP-1B and designated the previously described isoform VAMP-1A. VAMP-1B appears to be an alternatively spliced form of VAMP-1. A similar rat splice variant of VAMP-1 (also termed VAMP-1B) has recently been reported. Five different cultured cell lines, from different lineages, all contained VAMP-1B but little or no detectable VAMP-1A mRNA, as assessed by PCR. In contrast, brain mRNA contained VAMP-1A but no VAMP-1B. The VAMP-1B sequence encodes a protein identical to VAMP-1A except for the carboxy-terminal five amino acids. VAMP-1 is anchored in the vesicle membrane by a carboxy-terminal hydrophobic sequence. In VAMP-1A the hydrophobic anchor is followed by a single threonine, which is the carboxy-terminal amino acid. In VAMP-1B the predicted hydrophobic membrane anchor is shortened by four amino acids, and the hydrophobic sequence is immediately followed by three charged amino acids, arginine-arginine-aspartic acid. Transfection of human endothelial cells with epitope-tagged VAMP-1B demonstrated that VAMP-1B was targeted to mitochondria whereas VAMP-1A was localized to the plasma membrane and endosome-like structures. Analysis of C-terminal mutations of VAMP-1B demonstrated that mitochondrial targeting depends both on the addition of positive charge at the C terminus and a shortened hydrophobic membrane anchor. These data suggest that mitochondria may be integrated, at least at a mechanistic level, to the vesicular trafficking pathways that govern protein movement between other organelles of the cell. PMID:9658161

  5. Leukemic progenitor cells are susceptible to targeting by stimulated cytotoxic T cells against immunogenic leukemia-associated antigens.

    Science.gov (United States)

    Schneider, Vanessa; Zhang, Lu; Rojewski, Markus; Fekete, Natalie; Schrezenmeier, Hubert; Erle, Alexander; Bullinger, Lars; Hofmann, Susanne; Götz, Marlies; Döhner, Konstanze; Ihme, Susann; Döhner, Hartmut; Buske, Christian; Feuring-Buske, Michaela; Greiner, Jochen

    2015-11-01

    Leukemic stem cells (LSC) might be the source for leukemic disease self-renewal and account for disease relapse after treatment, which makes them a critical target for further therapeutic options. We investigated the role of cytotoxic T-lymphocytes (CTL) counteracting and recognizing LSC. Leukemia-associated antigens (LAA) represent immunogenic structures to target LSC. We enriched the LSC-containing fraction of 20 AML patients and hematopoietic stem cells (HSC) of healthy volunteers. Using microarray analysis and qRT-PCR we detected high expression of several LAA in AML cells but also in LSC. PRAME (p = 0.0085), RHAMM (p = 0.03), WT1 (p = 0.04) and Proteinase 3 (p = 0.04) showed significant differential expression in LSC compared with HSC. PRAME, RHAMM and WT1 are furthermore also lower expressed on leukemic bulk. In contrast, Proteinase 3 indicates a higher expression on leukemic bulk than on LSC. In colony forming unit (CFU) immunoassays, T cells stimulated against various LAA indicated a significant inhibition of CFUs in AML patient samples. The LAA PRAME, RHAMM and WT1 showed highest immunogenic responses with a range up to 58-83%. In a proof of principle xenotransplant mouse model, PRAME-stimulated CTL targeted AML stem cells, reflected by a delayed engraftment of leukemia (p = 0.0159). Taken together, we demonstrated the expression of several LAA in LSC. LAA-specific T cells are able to hamper LSC in immunoassays and in a mouse model, which suggests that immunotherapeutic approaches have the potential to target malignant stem cells. © 2015 UICC.

  6. Exogenous antigen targeted to FcgammaRI on myeloid cells is presented in association with MHC class I.

    Science.gov (United States)

    Wallace, P K; Tsang, K Y; Goldstein, J; Correale, P; Jarry, T M; Schlom, J; Guyre, P M; Ernstoff, M S; Fanger, M W

    2001-02-01

    Vaccine therapy is attractive for prostate cancer patients because the tumor is slow growing (allowing time to augment host responses) and occurs in an older population less likely to tolerate more toxic treatments. We have constructed an expression vector based on a monoclonal antibody (mAb) that targets the high affinity receptor for IgG (FcgammaRI, CD64) which is exclusively expressed on myeloid cells including dendritic cells (DC). The heavy chain of mAb H22 CH2 and CH3 domains were removed and replaced with the gene for prostate specific antigen (PSA). Using that vector, we have constructed and purified FPH22.PSA, a fusion protein that targets PSA to FcgammaRI on antigen presenting cells (APC). This fusion protein has an apparent molecular mass of 80-83 kDa, binds to FcgammaRI with high affinity and expresses PSA. We demonstrate that FPH22.PSA targeted PSA was internalized and processed by the human myeloid THP-1 cell line resulting in presentation of MHC class I-associated PSA peptides and lysis of THP-1 by PSA-specific human CTL. Moreover, pretreatment of THP-1 cells with antibodies to block either FcgammaRI or MHC class I, blocked lysis indicating that targeting to FcgammaRI results in presentation of exogenous antigen on MHC class I molecules. These data demonstrate that FPH22.PSA was processed in such a manner by the myeloid cell line to allow for presentation of immunodominant peptides in MHC class I molecules and suggests that uptake of antigen via FcgammaRI results in cross-priming.

  7. Associating Drugs, Targets and Clinical Outcomes into an Integrated Network Affords a New Platform for Computer-Aided Drug Repurposing.

    Science.gov (United States)

    Oprea, Tudor I; Nielsen, Sonny Kim; Ursu, Oleg; Yang, Jeremy J; Taboureau, Olivier; Mathias, Stephen L; Kouskoumvekaki, Lrene; Sklar, Larry A; Bologa, Cristian G

    2011-03-14

    Finding new uses for old drugs is a strategy embraced by the pharmaceutical industry, with increasing participation from the academic sector. Drug repurposing efforts focus on identifying novel modes of action, but not in a systematic manner. With intensive data mining and curation, we aim to apply bio- and cheminformatics tools using the DRUGS database, containing 3,837 unique small molecules annotated on 1,750 proteins. These are likely to serve as drug targets and antitargets (i.e., associated with side effects, SE). The academic community, the pharmaceutical sector and clinicians alike could benefit from an integrated, semantic-web compliant computer-aided drug repurposing (CADR) effort, one that would enable deep data mining of associations between approved drugs (D), targets (T), clinical outcomes (CO) and SE. We report preliminary results from text mining and multivariate statistics, based on 7,684 approved drug labels, ADL (Dailymed) via text mining. From the ADL corresponding to 988 unique drugs, the "adverse reactions" section was mapped onto 174 SE, then clustered via principal component analysis into a 5x5 self-organizing map that was integrated into a Cytoscape network of SE-D-T-CO. This type of data can be used to streamline drug repurposing and may result in novel insights that can lead to the identification of novel drug actions.

  8. SPATA18, a Spermatogenesis-Associated Gene, Is a Novel Transcriptional Target of p53 and p63▿

    Science.gov (United States)

    Bornstein, Chamutal; Brosh, Ran; Molchadsky, Alina; Madar, Shalom; Kogan-Sakin, Ira; Goldstein, Ido; Chakravarti, Deepavali; Flores, Elsa R.; Goldfinger, Naomi; Sarig, Rachel; Rotter, Varda

    2011-01-01

    The transcription factor p53 functions not only to suppress tumorigenesis but also to maintain normal development and homeostasis. Although p53 was implicated in different aspects of fertility, including spermatogenesis and implantation, the mechanism underlying p53 involvement in spermatogenesis is poorly resolved. In this study we describe the identification of a spermatogenesis-associated gene, SPATA18, as a novel p53 transcriptional target and show that SPATA18 transcription is induced by p53 in a variety of cell types of both human and mouse origin. p53 binds a consensus DNA motif that resides within the first intron of SPATA18. We describe the spatiotemporal expression patterns of SPATA18 in mouse seminiferous tubules and suggest that SPATA18 transcription is regulated in vivo by p53. We also demonstrate the induction of SPATA18 by p63 and suggest that p63 can compensate for the loss of p53 activity in vivo. Our data not only enrich the known collection of p53 targets but may also provide insights on spermatogenesis defects that are associated with p53 deficiency. PMID:21300779

  9. Risk assessment of Bt crops on the non-target plant-associated insects and soil organisms.

    Science.gov (United States)

    Yaqoob, Amina; Shahid, Ahmad Ali; Samiullah, Tahir Rehman; Rao, Abdul Qayyum; Khan, Muhammad Azmat Ullah; Tahir, Sana; Mirza, Safdar Ali; Husnain, Tayyab

    2016-06-01

    Transgenic plants containing Bacillus thuringiensis (Bt) genes are being cultivated worldwide to express toxic insecticidal proteins. However, the commercial utilisation of Bt crops greatly highlights biosafety issues worldwide. Therefore, assessing the risks caused by genetically modified crops prior to their commercial cultivation is a critical issue to be addressed. In agricultural biotechnology, the goal of safety assessment is not just to identify the safety of a genetically modified (GM) plant, rather to demonstrate its impact on the ecosystem. Various experimental studies have been made worldwide during the last 20 years to investigate the risks and fears associated with non-target organisms (NTOs). The NTOs include beneficial insects, natural pest controllers, rhizobacteria, growth promoting microbes, pollinators, soil dwellers, aquatic and terrestrial vertebrates, mammals and humans. To highlight all the possible risks associated with different GM events, information has been gathered from a total of 76 articles, regarding non-target plant and soil inhabiting organisms, and summarised in the form of the current review article. No significant harmful impact has been reported in any case study related to approved GM events, although critical risk assessments are still needed before commercialisation of these crops. © 2016 Society of Chemical Industry.

  10. New Mechanisms of Tumor-Associated Macrophages on Promoting Tumor Progression: Recent Research Advances and Potential Targets for Tumor Immunotherapy

    Directory of Open Access Journals (Sweden)

    Qiujun Guo

    2016-01-01

    Full Text Available The majority of basic and clinical studies have shown a protumor function of tumor-associated macrophages (TAMs, which represent a large proportion of matrix cells. TAMs promote tumorigenesis, and their number is related to the malignancy degree and poor prognosis of many kinds of tumors. Macrophage plasticity makes it possible to change the tumor microenvironment and remodel antitumor immunity during cancer immunotherapy. Increasing numbers of studies have revealed the effects of TAMs on the tumor microenvironment, for example, via promotion of tumor growth and tumorigenesis and through an increase in the number of cancer stem cells or via facilitation of angiogenesis, lymphangiogenesis, and metastasis. Investigators also proposed tumor-immunological treatments targeting TAMs by inhibiting TAM recruitment and differentiation, by regulating TAM polarization, and by blocking factors and pathways associated with the protumor function of TAMs. This comprehensive review presents recent research on TAMs in relation to prediction of poor outcomes, remodeling of the tumor immune microenvironment, and immunological targeted therapies.

  11. QTL replication and targeted association highlight the nerve growth factor gene for nonverbal communication deficits in autism spectrum disorders.

    Science.gov (United States)

    Lu, A T-H; Yoon, J; Geschwind, D H; Cantor, R M

    2013-02-01

    Autism Spectrum Disorder (ASD) has a heterogeneous etiology that is genetically complex. It is defined by deficits in communication and social skills and the presence of restricted and repetitive behaviors. Genetic analyses of heritable quantitative traits that correlate with ASD may reduce heterogeneity. With this in mind, deficits in nonverbal communication (NVC) were quantified based on items from the Autism Diagnostic Interview Revised. Our previous analysis of 228 families from the Autism Genetics Research Exchange (AGRE) repository reported 5 potential quantitative trait loci (QTL). Here we report an NVC QTL replication study in an independent sample of 213 AGRE families. One QTL was replicated (PNVC with a P-value of 0.001. Three associated haplotype blocks were intronic to the Nerve Growth Factor (NGF) gene (P=0.001, 0.001, 0.002), and one was intronic to KCND3 (P=0.001). Individual haplotypes within the associated blocks drove the associations (0.003, 0.0004 and 0.0002) for NGF and 0.0001 for KCND3. Using the same methods, these genes were tested for association with NVC in an independent sample of 1517 families from an Autism Genome Project (AGP). NVC was associated with a haplotype in an adjacent NGF block (P=0.0005) and one 46 kb away from the associated block in KCND3 (0.008). These analyses illustrate the value of QTL and targeted association studies for genetically complex disorders such as ASD. NGF is a promising risk gene for NVC deficits.

  12. Ocular toxicity of targeted therapies.

    Science.gov (United States)

    Renouf, Daniel J; Velazquez-Martin, Juan P; Simpson, Rand; Siu, Lillian L; Bedard, Philippe L

    2012-09-10

    Molecularly targeted agents are commonly used in oncology practice, and many new targeted agents are currently being tested in clinical trials. Although these agents are thought to be more specific and less toxic then traditional cytotoxic chemotherapy, they are associated with a variety of toxicities, including ocular toxicity. Many of the molecules targeted by anticancer agents are also expressed in ocular tissues. We reviewed the literature for described ocular toxicities associated with both approved and investigational molecularly targeted agents. Ocular toxicity has been described with numerous approved targeted agents and also seems to be associated with several classes of agents currently being tested in early-phase clinical trials. We discuss the proposed pathogenesis, monitoring guidelines, and management recommendations. It is important for oncologists to be aware of the potential for ocular toxicity, with prompt recognition of symptoms that require referral to an ophthalmologist. Ongoing collaboration between oncologists and ocular disease specialists is critical as the use of molecularly targeted agents continues to expand and novel targeted drug combinations are developed.

  13. Prostate cancer characteristics associated with response to pre-receptor targeting of the androgen axis.

    Directory of Open Access Journals (Sweden)

    Elahe A Mostaghel

    Full Text Available Factors influencing differential responses of prostate tumors to androgen receptor (AR axis-directed therapeutics are poorly understood, and predictors of treatment efficacy are needed. We hypothesized that the efficacy of inhibiting DHT ligand synthesis would associate with intra-tumoral androgen ratios indicative of relative dependence on DHT-mediated growth.We characterized two androgen-sensitive prostate cancer xenograft models after androgen suppression by castration in combination with the SRD5A inhibitor, dutasteride, as well as a panel of castration resistant metastases obtained via rapid autopsy.In LuCaP35 tumors (intra-tumoral T:DHT ratio 2:1 dutasteride suppressed DHT to 0.02 ng/gm and prolonged survival vs. castration alone (337 vs.152 days, HR 2.8, p = 0.0015. In LuCaP96 tumors (T:DHT 10:1, survival was not improved despite similar DHT reduction (0.02 ng/gm. LuCaP35 demonstrated higher expression of steroid biosynthetic enzymes maintaining DHT levels (5-fold higher SRD5A1, 41 fold higher, 99-fold higher RL-HSD, p<0.0001 for both, reconstitution of intra-tumoral DHT (to ∼30% of untreated tumors, and ∼2 fold increased expression of full length AR. In contrast, LuCaP96 demonstrated higher levels of steroid catabolizing enzymes (6.9-fold higher AKR1C2, 3000-fold higher UGT2B15, p = 0.002 and p<0.0001 respectively, persistent suppression of intra-tumoral DHT, and 6-8 fold induction of full length AR and the ligand independent V7 AR splice variant. Human metastases demonstrated bio-active androgen levels and AR full length and AR splice-variant expression consistent with the range observed in xenografts.Intrinsic differences in basal steroidogenesis, as well as variable expression of full length and splice-variant AR, associate with response and resistance to pre-receptor AR ligand suppression. Expression of steroidogenic enzymes and AR isoforms may serve as potential biomarkers of sensitivity to potent AR-axis inhibition and

  14. Using the Targeted Solutions Tool® to Improve Hand Hygiene Compliance Is Associated with Decreased Health Care-Associated Infections.

    Science.gov (United States)

    Shabot, M Michael; Chassin, Mark R; France, Anne-Claire; Inurria, Juan; Kendrick, Jan; Schmaltz, Stephen P

    2016-01-01

    In 2010 Memorial Hermann Health System (MHHS) implemented the Joint Commission Center for Transforming Healthcare's (the Center's) Web-based Targeted Solutions Tool ®(TST ®) for improving hand hygiene through-out its 12 hospitals after participating in the Center's first project on hand hygiene, pilot testing the TST, and achieving significant improvement for each pilot unit. Because hand hygiene is a key contributing factor in health care-associated infections (HAIs), this project was an important part of MHHS's strategy to eliminate HAIs. MHHS implemented the TST for hand hygiene in 150 inpatient units in 12 hospitals and conducted a system wide process improvement project from October 2010 through December 2014. The TST enabled MHHS to measure compliance rates, identify reasons for noncompliance, implement tested interventions provided by the TST, and sustain the improvements. Data on rates of ICU central line- associated bloodstream infections (CLABSIs) and ventilator- associated pneumonia (VAP) were also collected and analyzed. Based on 31,600 observations (October 2010- May 2011), MHHS's system wide hand hygiene compliance baseline rate averaged 58.1%. Compliance averaged 84.4% during the "improve" phase (June 2011-November 2012), 94.7% in the first 13 months of the "control phase" (December 2012-December 2014) and 95.6% in the final 12 months (p hand hygiene compliance in its hospitals and sustained high levels of compliance for 25 months following implementation. Adult ICU CLABSI and VAP rates decreased in association with the hand hygiene compliance improvements.

  15. Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets.

    Directory of Open Access Journals (Sweden)

    Sonia Paco

    Full Text Available Ullrich congenital muscular dystrophy (UCMD, caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of UCMD muscle and compare it to healthy muscle and other muscular dystrophies. We identified 389 genes which are differentially regulated in UCMD relative to controls. In addition, there were 718 genes differentially expressed between UCMD and dystrophin deficient muscle. In contrast, only 29 genes were altered relative to other congenital muscular dystrophies. Changes in gene expression were confirmed by real-time PCR. The set of regulated genes was analysed by Gene Ontology, KEGG pathways and Ingenuity Pathway analysis to reveal the molecular functions and gene networks associated with collagen VI defects. The most significantly regulated pathways were those involved in muscle regeneration, extracellular matrix remodelling and inflammation. We characterised the immune response in UCMD biopsies as being mainly mediated via M2 macrophages and the complement pathway indicating that anti-inflammatory treatment may be beneficial to UCMD as for other dystrophies. We studied the immunolocalisation of ECM components and found that biglycan, a collagen VI interacting proteoglycan, was reduced in the basal lamina of UCMD patients. We propose that biglycan reduction is secondary to collagen VI loss and that it may be contributing towards UCMD pathophysiology. Consequently, strategies aimed at over-expressing biglycan and restore the link between the muscle cell surface and the extracellular matrix should be considered.

  16. Gene Expression Profiling Identifies Molecular Pathways Associated with Collagen VI Deficiency and Provides Novel Therapeutic Targets

    Science.gov (United States)

    Paco, Sonia; Kalko, Susana G.; Jou, Cristina; Rodríguez, María A.; Corbera, Joan; Muntoni, Francesco; Feng, Lucy; Rivas, Eloy; Torner, Ferran; Gualandi, Francesca; Gomez-Foix, Anna M.; Ferrer, Anna; Ortez, Carlos; Nascimento, Andrés; Colomer, Jaume; Jimenez-Mallebrera, Cecilia

    2013-01-01

    Ullrich congenital muscular dystrophy (UCMD), caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of UCMD muscle and compare it to healthy muscle and other muscular dystrophies. We identified 389 genes which are differentially regulated in UCMD relative to controls. In addition, there were 718 genes differentially expressed between UCMD and dystrophin deficient muscle. In contrast, only 29 genes were altered relative to other congenital muscular dystrophies. Changes in gene expression were confirmed by real-time PCR. The set of regulated genes was analysed by Gene Ontology, KEGG pathways and Ingenuity Pathway analysis to reveal the molecular functions and gene networks associated with collagen VI defects. The most significantly regulated pathways were those involved in muscle regeneration, extracellular matrix remodelling and inflammation. We characterised the immune response in UCMD biopsies as being mainly mediated via M2 macrophages and the complement pathway indicating that anti-inflammatory treatment may be beneficial to UCMD as for other dystrophies. We studied the immunolocalisation of ECM components and found that biglycan, a collagen VI interacting proteoglycan, was reduced in the basal lamina of UCMD patients. We propose that biglycan reduction is secondary to collagen VI loss and that it may be contributing towards UCMD pathophysiology. Consequently, strategies aimed at over-expressing biglycan and restore the link between the muscle cell surface and the extracellular matrix should be considered. PMID:24223098

  17. A novel photodynamic therapy targeting cancer cells and tumor-associated macrophages.

    Science.gov (United States)

    Hayashi, Noriyuki; Kataoka, Hiromi; Yano, Shigenobu; Tanaka, Mamoru; Moriwaki, Kazuhiro; Akashi, Haruo; Suzuki, Shugo; Mori, Yoshinori; Kubota, Eiji; Tanida, Satoshi; Takahashi, Satoru; Joh, Takashi

    2015-02-01

    Tumor-associated macrophages (TAM) in cancer stroma play important roles for cancer cell growth, invasion, angiogenesis, and metastases. We synthesized a novel photosensitizer, mannose-conjugated chlorin (M-chlorin), designed to bind mannose receptors highly expressed on TAMs. We evaluated the newly available photodynamic therapy (PDT) with M-chlorin against gastric and colon cancer. We evaluated PDT with M-chlorin for in vitro cytotoxicity and apoptosis induction in cancer cells compared with chlorin alone and glucose-conjugated chlorin (G-chlorin). The subcellular localization of M-chlorin was observed by confocal microscopy, and the M-chlorin PDT effects against TAMs including THP-1-induced M2-polarized macrophages were evaluated. Anticancer effects were also investigated in an allograft model where cytotoxic effects against TAMs in the cancer cell stroma were analyzed by immunohistochemistry. M-chlorin PDT strongly induced cell death in cancer cells to almost the same extent as G-chlorin PDT by inducing apoptosis. M-chlorin was incorporated into cancer cells where it localized mainly in lysosomes and endoplasmic reticula. M-chlorin PDT revealed strong cytotoxicity for M2 macrophages induced from THP-1 cell lines, and it induced stronger cytotoxicity than G-chlorin PDT in the allograft model through killing both cancer cells and TAMs in the cancer stroma. The M-chlorin PDT produced strong cytotoxicity against cancer tissue by inducing apoptosis of both cancer cells and TAMs in the cancer stroma. This novel PDT thus stands as a new candidate for very effective, next-generation PDT.

  18. Discovery of novel targets for multi-epitope vaccines: Screening of HIV-1 genomes using association rule mining

    Directory of Open Access Journals (Sweden)

    Piontkivska Helen

    2009-07-01

    Full Text Available Abstract Background Studies have shown that in the genome of human immunodeficiency virus (HIV-1 regions responsible for interactions with the host's immune system, namely, cytotoxic T-lymphocyte (CTL epitopes tend to cluster together in relatively conserved regions. On the other hand, "epitope-less" regions or regions with relatively low density of epitopes tend to be more variable. However, very little is known about relationships among epitopes from different genes, in other words, whether particular epitopes from different genes would occur together in the same viral genome. To identify CTL epitopes in different genes that co-occur in HIV genomes, association rule mining was used. Results Using a set of 189 best-defined HIV-1 CTL/CD8+ epitopes from 9 different protein-coding genes, as described by Frahm, Linde & Brander (2007, we examined the complete genomic sequences of 62 reference HIV sequences (including 13 subtypes and sub-subtypes with approximately 4 representative sequences for each subtype or sub-subtype, and 18 circulating recombinant forms. The results showed that despite inclusion of recombinant sequences that would be expected to break-up associations of epitopes in different genes when two different genomes are recombined, there exist particular combinations of epitopes (epitope associations that occur repeatedly across the world-wide population of HIV-1. For example, Pol epitope LFLDGIDKA is found to be significantly associated with epitopes GHQAAMQML and FLKEKGGL from Gag and Nef, respectively, and this association rule is observed even among circulating recombinant forms. Conclusion We have identified CTL epitope combinations co-occurring in HIV-1 genomes including different subtypes and recombinant forms. Such co-occurrence has important implications for design of complex vaccines (multi-epitope vaccines and/or drugs that would target multiple HIV-1 regions at once and, thus, may be expected to overcome challenges

  19. Efficiently Computing Private Recommendations

    NARCIS (Netherlands)

    Erkin, Z.; Beye, M.; Veugen, P.J.M.; Lagendijk, R.L.

    2011-01-01

    Online recommender systems enable personalized service to users. The underlying collaborative filtering techniques operate on privacy sensitive user data, which could be misused by the service provider. To protect user privacy, we propose to encrypt the data and generate recommendations by processin

  20. Efficiently computing private recommendations

    NARCIS (Netherlands)

    Erkin, Z.; Beye, M.; Veugen, T.; Lagendijk, R.L.

    2011-01-01

    Online recommender systems enable personalized service to users. The underlying collaborative filtering techniques operate on privacy sensitive user data, which could be misused by the service provider. To protect user privacy, we propose to encrypt the data and generate recommendations by processin

  1. Search and Recommendation

    DEFF Research Database (Denmark)

    Bogers, Toine

    2014-01-01

    -scale application by companies like Amazon, Facebook, and Netflix. But are search and recommendation really two different fields of research that address different problems with different sets of algorithms in papers published at distinct conferences? In my talk, I want to argue that search and recommendation...

  2. APLAR rheumatoid arthritis treatment recommendations.

    Science.gov (United States)

    Lau, Chak Sing; Chia, Faith; Harrison, Andrew; Hsieh, Tsu-Yi; Jain, Rahul; Jung, Seung Min; Kishimoto, Mitsumasa; Kumar, Ashok; Leong, Khai Pang; Li, Zhanguo; Lichauco, Juan Javier; Louthrenoo, Worawit; Luo, Shue-Fen; Nash, Peter; Ng, Chin Teck; Park, Sung-Hwan; Suryana, Bagus Putu Putra; Suwannalai, Parawee; Wijaya, Linda Kurniaty; Yamamoto, Kazuhiko; Yang, Yue; Yeap, Swan Sim

    2015-09-01

    Rheumatoid arthritis is a chronic inflammatory condition that affects approximately 1% of the world's population. There are a wide number of guidelines and recommendations available to support the treatment of rheumatoid arthritis; however, the evidence used for these guidelines is predominantly based on studies in Caucasian subjects and may not be relevant for rheumatoid arthritis patients in the Asia-Pacific region. Therefore, the Asia Pacific League of Associations for Rheumatology established a Steering Committee in 2013 to address this issue. The AGREE II instrument and the ADAPTE Collaboration framework were applied to systematically identify, appraise, synthesize, and adapt international rheumatoid arthritis guidelines for use in the Asia-Pacific region. Forty rheumatoid arthritis treatment recommendations, based on evidence and expert opinion, were drafted and are presented in this report. The Asia Pacific of Associations for Rheumatology rheumatoid arthritis treatment recommendations are intended to serve as a reference for best practice management of rheumatoid arthritis in Asia-Pacific, focusing on local issues to ensure the delivery of basic care for these patients, and to improve their outcomes. In addition, the document will serve as a reference for national rheumatology associations in Asia-Pacific for developing guidelines in their respective countries. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  3. Genome-wide identification of polycomb target genes reveals a functional association of Pho with Scm in Bombyx mori.

    Science.gov (United States)

    Li, Zhiqing; Cheng, Daojun; Mon, Hiroaki; Tatsuke, Tsuneyuki; Zhu, Li; Xu, Jian; Lee, Jae Man; Xia, Qingyou; Kusakabe, Takahiro

    2012-01-01

    Polycomb group (PcG) proteins are evolutionarily conserved chromatin modifiers and act together in three multimeric complexes, Polycomb repressive complex 1 (PRC1), Polycomb repressive complex 2 (PRC2), and Pleiohomeotic repressive complex (PhoRC), to repress transcription of the target genes. Here, we identified Polycomb target genes in Bombyx mori with holocentric centromere using genome-wide expression screening based on the knockdown of BmSCE, BmESC, BmPHO, or BmSCM gene, which represent the distinct complexes. As a result, the expressions of 29 genes were up-regulated after knocking down 4 PcG genes. Particularly, there is a significant overlap between targets of BmPho (331 out of 524) and BmScm (331 out of 532), and among these, 190 genes function as regulator factors playing important roles in development. We also found that BmPho, as well as BmScm, can interact with other Polycomb components examined in this study. Further detailed analysis revealed that the C-terminus of BmPho containing zinc finger domain is involved in the interaction between BmPho and BmScm. Moreover, the zinc finger domain in BmPho contributes to its inhibitory function and ectopic overexpression of BmScm is able to promote transcriptional repression by Gal4-Pho fusions including BmScm-interacting domain. Loss of BmPho expression causes relocalization of BmScm into the cytoplasm. Collectively, we provide evidence of a functional link between BmPho and BmScm, and propose two Polycomb-related repression mechanisms requiring only BmPho associated with BmScm or a whole set of PcG complexes.

  4. Elongation factor 1 alpha1 and genes associated with Usher syndromes are downstream targets of GBX2.

    Directory of Open Access Journals (Sweden)

    David A Roeseler

    Full Text Available Gbx2 encodes a DNA-binding transcription factor that plays pivotal roles during embryogenesis. Gain-and loss-of-function studies in several vertebrate species have demonstrated a requirement for Gbx2 in development of the anterior hindbrain, spinal cord, inner ear, heart, and neural crest cells. However, the target genes through which GBX2 exerts its effects remain obscure. Using chromatin immunoprecipitation coupled with direct sequencing (ChIP-Seq analysis in a human prostate cancer cell line, we identified cis-regulatory elements bound by GBX2 to provide insight into its direct downstream targets. The analysis revealed more than 286 highly significant candidate target genes, falling into various functional groups, of which 51% are expressed in the nervous system. Several of the top candidate genes include EEF1A1, ROBO1, PLXNA4, SLIT3, NRP1, and NOTCH2, as well as genes associated with the Usher syndrome, PCDH15 and USH2A, and are plausible candidates contributing to the developmental defects in Gbx2(-/- mice. We show through gel shift analyses that sequences within the promoter or introns of EEF1A1, ROBO1, PCDH15, USH2A and NOTCH2, are directly bound by GBX2. Consistent with these in vitro results, analyses of Gbx2(-/- embryos indicate that Gbx2 function is required for migration of Robo1-expressing neural crest cells out of the hindbrain. Furthermore, we show that GBX2 activates transcriptional activity through the promoter of EEF1A1, suggesting that GBX2 could also regulate gene expression indirectly via EEF1A. Taken together, our studies show that GBX2 plays a dynamic role in development and diseases.

  5. Associative learning changes the organization of functional excitatory circuits targeting the supragranular layers of mouse barrel cortex

    Directory of Open Access Journals (Sweden)

    Céline eRosselet

    2011-01-01

    Full Text Available In primary sensory cortices, neuronal circuits change throughout life as a function of learning. During associative learning a neutral sensory stimulus acquires the emotional valence of an aversive event or a reward after repetitive contingent pairing. One important consequence is the enlargement of the representational area of the conditioned stimulus in the cortical map of its sensory modality. The details of this phenomenon at the circuit level are still largely unknown.Here, mice were trained in a differential conditioning paradigm where the deflections of one whisker row were paired with tail shocks and the deflections of two others were not. Changes occurring in excitatory circuits of barrel cortex were then examined in brain slices with laser scanning photostimulation mapping. We found that learning affected the projections targeting the supragranular layers in the columns of unpaired whiskers: Pyramidal cells located in layer (L 3 received enhanced inputs from L5A cells located in their home column and new inputs from L2/3 and L4 cells located in the neighboring column of the paired whisker. In contrast, the excitatory projections impinging onto L2/3 cells in the column of the paired whisker were not altered. Together, these data reveal that associative learning alters the canonical columnar organization of functional ascending L4 projections and strengthens transcolumnar excitatory projections in barrel cortex. These phenomena could participate to the transformation of the whisker somatotopic map induced by associative learning.

  6. Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegypti by deep targeted sequencing.

    Science.gov (United States)

    Faucon, Frederic; Dusfour, Isabelle; Gaude, Thierry; Navratil, Vincent; Boyer, Frederic; Chandre, Fabrice; Sirisopa, Patcharawan; Thanispong, Kanutcharee; Juntarajumnong, Waraporn; Poupardin, Rodolphe; Chareonviriyaphap, Theeraphap; Girod, Romain; Corbel, Vincent; Reynaud, Stephane; David, Jean-Philippe

    2015-09-01

    The capacity of mosquitoes to resist insecticides threatens the control of diseases such as dengue and malaria. Until alternative control tools are implemented, characterizing resistance mechanisms is crucial for managing resistance in natural populations. Insecticide biodegradation by detoxification enzymes is a common resistance mechanism; however, the genomic changes underlying this mechanism have rarely been identified, precluding individual resistance genotyping. In particular, the role of copy number variations (CNVs) and polymorphisms of detoxification enzymes have never been investigated at the genome level, although they can represent robust markers of metabolic resistance. In this context, we combined target enrichment with high-throughput sequencing for conducting the first comprehensive screening of gene amplifications and polymorphisms associated with insecticide resistance in mosquitoes. More than 760 candidate genes were captured and deep sequenced in several populations of the dengue mosquito Ae. aegypti displaying distinct genetic backgrounds and contrasted resistance levels to the insecticide deltamethrin. CNV analysis identified 41 gene amplifications associated with resistance, most affecting cytochrome P450s overtranscribed in resistant populations. Polymorphism analysis detected more than 30,000 variants and strong selection footprints in specific genomic regions. Combining Bayesian and allele frequency filtering approaches identified 55 nonsynonymous variants strongly associated with resistance. Both CNVs and polymorphisms were conserved within regions but differed across continents, confirming that genomic changes underlying metabolic resistance to insecticides are not universal. By identifying novel DNA markers of insecticide resistance, this study opens the way for tracking down metabolic changes developed by mosquitoes to resist insecticides within and among populations.

  7. Targeting anandamide metabolism rescues core and associated autistic-like symptoms in rats prenatally exposed to valproic acid

    Science.gov (United States)

    Servadio, M; Melancia, F; Manduca, A; di Masi, A; Schiavi, S; Cartocci, V; Pallottini, V; Campolongo, P; Ascenzi, P; Trezza, V

    2016-01-01

    Autism spectrum disorders (ASD) are characterized by altered sociability, compromised communication and stereotyped/repetitive behaviors, for which no specific treatments are currently available. Prenatal exposure to valproic acid (VPA) is a known, although still underestimated, environmental risk factor for ASD. Altered endocannabinoid activity has been observed in autistic patients, and endocannabinoids are known to modulate behavioral traits that are typically affected in ASD. On this basis, we tested the hypothesis that changes in the endocannabinoid tone contribute to the altered phenotype induced by prenatal VPA exposure in rats, with focus on behavioral features that resemble the core and associated symptoms of ASD. In the course of development, VPA-exposed rats showed early deficits in social communication and discrimination, compromised sociability and social play behavior, stereotypies and increased anxiety, thus providing preclinical proof of the long-lasting deleterious effects induced by prenatal VPA exposure. At the neurochemical level, VPA-exposed rats displayed altered phosphorylation of CB1 cannabinoid receptors in different brain areas, associated with changes in anandamide metabolism from infancy to adulthood. Interestingly, enhancing anandamide signaling through inhibition of its degradation rescued the behavioral deficits displayed by VPA-exposed rats at infancy, adolescence and adulthood. This study therefore shows that abnormalities in anandamide activity may underlie the deleterious impact of environmental risk factors on ASD-relevant behaviors and that the endocannabinoid system may represent a therapeutic target for the core and associated symptoms displayed by autistic patients. PMID:27676443

  8. Network modelling reveals the mechanism underlying colitis-associated colon cancer and identifies novel combinatorial anti-cancer targets.

    Science.gov (United States)

    Lu, Junyan; Zeng, Hanlin; Liang, Zhongjie; Chen, Limin; Zhang, Liyi; Zhang, Hao; Liu, Hong; Jiang, Hualiang; Shen, Bairong; Huang, Ming; Geng, Meiyu; Spiegel, Sarah; Luo, Cheng

    2015-10-08

    The connection between inflammation and tumourigenesis has been well established. However, the detailed molecular mechanism underlying inflammation-associated tumourigenesis remains unknown because this process involves a complex interplay between immune microenvironments and epithelial cells. To obtain a more systematic understanding of inflammation-associated tumourigenesis as well as to identify novel therapeutic approaches, we constructed a knowledge-based network describing the development of colitis-associated colon cancer (CAC) by integrating the extracellular microenvironment and intracellular signalling pathways. Dynamic simulations of the CAC network revealed a core network module, including P53, MDM2, and AKT, that may govern the malignant transformation of colon epithelial cells in a pro-tumor inflammatory microenvironment. Furthermore, in silico mutation studies and experimental validations led to a novel finding that concurrently targeting ceramide and PI3K/AKT pathway by chemical probes or marketed drugs achieves synergistic anti-cancer effects. Overall, our network model can guide further mechanistic studies on CAC and provide new insights into the design of combinatorial cancer therapies in a rational manner.

  9. Identifying genomic changes associated with insecticide resistance in the dengue mosquito Aedes aegypti by deep targeted sequencing

    Science.gov (United States)

    Faucon, Frederic; Dusfour, Isabelle; Gaude, Thierry; Navratil, Vincent; Boyer, Frederic; Chandre, Fabrice; Sirisopa, Patcharawan; Thanispong, Kanutcharee; Juntarajumnong, Waraporn; Poupardin, Rodolphe; Chareonviriyaphap, Theeraphap; Girod, Romain; Corbel, Vincent; Reynaud, Stephane; David, Jean-Philippe

    2015-01-01

    The capacity of mosquitoes to resist insecticides threatens the control of diseases such as dengue and malaria. Until alternative control tools are implemented, characterizing resistance mechanisms is crucial for managing resistance in natural populations. Insecticide biodegradation by detoxification enzymes is a common resistance mechanism; however, the genomic changes underlying this mechanism have rarely been identified, precluding individual resistance genotyping. In particular, the role of copy number variations (CNVs) and polymorphisms of detoxification enzymes have never been investigated at the genome level, although they can represent robust markers of metabolic resistance. In this context, we combined target enrichment with high-throughput sequencing for conducting the first comprehensive screening of gene amplifications and polymorphisms associated with insecticide resistance in mosquitoes. More than 760 candidate genes were captured and deep sequenced in several populations of the dengue mosquito Ae. aegypti displaying distinct genetic backgrounds and contrasted resistance levels to the insecticide deltamethrin. CNV analysis identified 41 gene amplifications associated with resistance, most affecting cytochrome P450s overtranscribed in resistant populations. Polymorphism analysis detected more than 30,000 variants and strong selection footprints in specific genomic regions. Combining Bayesian and allele frequency filtering approaches identified 55 nonsynonymous variants strongly associated with resistance. Both CNVs and polymorphisms were conserved within regions but differed across continents, confirming that genomic changes underlying metabolic resistance to insecticides are not universal. By identifying novel DNA markers of insecticide resistance, this study opens the way for tracking down metabolic changes developed by mosquitoes to resist insecticides within and among populations. PMID:26206155

  10. Targeted delivery of let-7b to reprogramme tumor-associated macrophages and tumor infiltrating dendritic cells for tumor rejection.

    Science.gov (United States)

    Huang, Zhen; Gan, Jingjing; Long, Ziyan; Guo, Guangxing; Shi, Xiafei; Wang, Chunming; Zang, Yuhui; Ding, Zhi; Chen, Jiangning; Zhang, Junfeng; Dong, Lei

    2016-06-01

    Both tumor associated macrophages (TAMs) and tumor infiltrating dendritic cells (TIDCs) are important components in the tumor microenvironment that mediate tumor immunosuppression and promote cancer progression. Targeting these cells and altering their phenotypes may become a new strategy to recover their anti-tumor activities and thereby restore the local immune surveillance against tumor. In this study, we constructed a nucleic acid delivery system for the delivery of let-7b, a synthetic microRNA mimic. Our carrier has an affinity for the mannose receptors on TAMs/TIDCs and is responsive to the low-pH tumor microenvironment. The delivery of let-7b could reactivate TAMs/TIDCs by acting as a TLR-7 agonist and suppressing IL-10 production in vitro. In a breast cancer mouse model, let-7b delivered by this system efficiently reprogrammed the functions of TAMs/TIDCs, reversed the suppressive tumor microenvironment, and inhibited tumor growth. Taken together, this strategy, designed based upon TAMs/TIDCs-targeting delivery and the dual biological functions of let-7b (TLR-7 ligand and IL-10 inhibitor), may provide a new approach for cancer immunotherapy.

  11. Proteomic screening of human targets of viral microRNAs reveals functions associated with immune evasion and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Amelia M Gallaher

    Full Text Available Kaposi's sarcoma (KS is caused by infection with Kaposi's sarcoma-associated herpesvirus (KSHV. The virus expresses unique microRNAs (miRNAs, but the targets and functions of these miRNAs are not completely understood. In order to identify human targets of viral miRNAs, we measured protein expression changes caused by multiple KSHV miRNAs using pulsed stable labeling with amino acids in cell culture (pSILAC in primary endothelial cells. This led to the identification of multiple human genes that are repressed at the protein level, but not at the miRNA level. Further analysis also identified that KSHV miRNAs can modulate activity or expression of upstream regulatory factors, resulting in suppressed activation of a protein involved in leukocyte recruitment (ICAM1 following lysophosphatidic acid treatment, as well as up-regulation of a pro-angiogenic protein (HIF1α, and up-regulation of a protein involved in stimulating angiogenesis (HMOX1. This study aids in our understanding of miRNA mechanisms of repression and miRNA contributions to viral pathogenesis.

  12. MicroRNA-186 targets Yes-associated protein 1 to inhibit Hippo signaling and tumorigenesis in hepatocellular carcinoma.

    Science.gov (United States)

    Ruan, Tingyan; He, Xiaoting; Yu, Jun; Hang, Zhiqiang

    2016-04-01

    Liver cancer, particularly hepatocellular carcinoma (HCC), is one of leading causes of cancer-related mortality worldwide. Upregulation of the evolutionary conserved Hippo signaling pathway has been observed in HCC patients, and Yes-associated protein 1 (YAP1) has been reported to play a key role in HCC tumorigenesis. microRNAs (miRNAs) are a family of small non-coding RNAs, usually 21-25 nucleotides in length, and are essential in the regulation of gene expression. Abnormal miRNA expression has been implicated in the initiation and progression of numerous forms of cancers, including liver cancer. Here, we report the identification of a novel miRNA, miR-186, and its functions as an HCC tumor suppressor. We observed that miR-186 was downregulated in several HCC cell lines, and that it directly targets YAP1 mRNA. Overexpression of miR-186 in HCC cells significantly downregulates YAP1 mRNA and protein levels, leading to downregulation of the Hippo signaling pathway, which in turn severely inhibits HCC cell migration, invasion and proliferation. Our study is the first to report the direct involvement of miR-186 in downregulating YAP1 and, more significantly, inhibiting HCC tumorigenesis, and supports the role miR-186 as a potential therapeutic target in treating liver cancer.

  13. Prophylactic antibiotics are associated with a lower incidence of pneumonia in cardiac arrest survivors treated with targeted temperature management

    DEFF Research Database (Denmark)

    Gagnon, David J; Nielsen, Niklas; Fraser, Gilles L

    2015-01-01

    INTRODUCTION: Prophylactic antibiotics (PRO) reduce the incidence of early-onset pneumonia in comatose patients with structural brain injury, but have not been examined in cardiac arrest survivors undergoing targeted temperature management (TTM). We investigated the effect of PRO on the development......-34 °C were enrolled in the registry. Differences were analyzed in univariate analyses and with logistic regression models to evaluate independent associations of clinical factors with incidence of pneumonia and good functional outcome. RESULTS: 416 of 1240 patients (33.5%) received PRO. Groups were...... similar in age, gender, arrest location, initial rhythm, and time from collapse to return of spontaneous circulation. PRO patients had less pneumonia (12.6% vs. 54.9%, p incidence...

  14. [Three Patients with Acute Myocardial Infarction Associated with Targeted Therapy of Sorafenib for Metastatic Renal Cell Carcinoma : Case Report].

    Science.gov (United States)

    Takagi, Kimiaki; Takai, Manabu; Kawata, Kei; Horie, Kengo; Kikuchi, Mina; Kato, Taku; Mizutani, Kosuke; Seike, Kensaku; Tsuchiya, Tomohiro; Yasuda, Mitsuru; Yokoi, Shigeaki; Nakano, Masahiro; Ushikoshi, Hiroaki; Miyazaki, Tatsuhiko; Deguchi, Takashi

    2015-09-01

    Sorafenib is a tyrosine kinase inhibitor (TKI) of the vascular endothelial growth factor receptor (VEGFR) used for advanced renal cell carcinoma. Treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal cell carcinoma. However, in spite of its therapeutic efficacy, sorafenib causes a wide range of adverse events. Cardiovascular adverse events have been observed when sorafenib was used with targeted agents. Although these adverse events like hypertension, reduced left ventricular ejection fraction, cardiac ischemia or infarction were manageable with standard medical therapies in most cases, some had a poor clinical outcome. We report three cases of acute myocardial infarction associated with sorafenib in patients with metastatic renal cell carcinoma.

  15. Targeted biological therapies for Graves' disease and thyroid-associated ophthalmopathy. Focus on B-cell depletion with Rituximab

    DEFF Research Database (Denmark)

    Hegedüs, Laszlo; Douglas, Raymond S; Nielsen, Claus H

    2011-01-01

    Based on experience from the treatment of other autoimmune diseases and because of the limitations imposed by existing therapeutic options for Graves' disease (GD) and thyroid-associated ophthalmopathy (TAO), rituximab (RTX) was recently proposed as a novel therapy option. Here, we summarize...... the rationale for using RTX; give an overview of the possible mechanisms of action; and give an account of its effects and side-effects when used in GD and TAO. Scant evidence, originating from only a few methodologically inhomogeneous studies, suggests that RTX may prolong remission for hyperthyroidism over...... favourably to conventional therapy. It is the first in what is likely to be a series of new and emerging treatments specifically targeting relevant components of the immune system. Further studies will hopefully lead to improved and better tailored, individualized therapy for GD and especially TAO....

  16. Targeted deletion of Kif18a protects from colitis-associated colorectal (CAC) tumors in mice through impairing Akt phosphorylation.

    Science.gov (United States)

    Zhu, Houbao; Xu, Wangyang; Zhang, Hongxin; Liu, Jianbing; Xu, Haimin; Lu, Shunyuan; Dang, Suying; Kuang, Ying; Jin, Xiaolong; Wang, Zhugang

    2013-08-16

    Kinesins are a superfamily of molecular motors involved in cell division or intracellular transport. They are becoming important targets for chemotherapeutic intervention of cancer due to their crucial role in mitosis. Here, we demonstrate that the kinesin-8 Kif18a is overexpressed in murine CAC and is a crucial promoter during early CAC carcinogenesis. Kif18a-deficient mice are evidently protected from AOM-DSS-induced colon carcinogenesis. Kif18A is responsible for proliferation of colonic tumor cells, while Kif18a ablation in mice promotes cell apoptosis. Mechanistically, Kif18a is responsible for induction of Akt phosphorylation, which is known to be associated with cell survival regulation. In conclusion, Kif18a is critical for colorectal carcinogenesis in the setting of inflammation by mechanisms of increased PI3K-AKT signaling. Inhibition of Kif18A activity may be useful in the prevention or chemotherapeutic intervention of CAC.

  17. Model cortical association fields account for the time course and dependence on target complexity of human contour perception.

    Directory of Open Access Journals (Sweden)

    Vadas Gintautas

    2011-10-01

    Full Text Available Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas distributed among groups of randomly rotated fragments (clutter. The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms, followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least [Formula: see text] ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas.

  18. Overexpression of miR-664 is associated with enhanced osteosarcoma cell migration and invasion ability via targeting SOX7.

    Science.gov (United States)

    Bao, Yongzheng; Chen, Bin; Wu, Qiang; Hu, Konghe; Xi, Xinhua; Zhu, Wengang; Zhong, Xueren; Chen, Jianting

    2017-02-01

    Osteosarcoma (OS) is one of the most common types of primary sarcoma of bone in children and young adults, and the long-term prognosis for OS patients still remains dismal due to the lack of effective early diagnostic biomarkers. Identifying sensitive and specific biomarkers in carcinogenesis may improve diagnostic and therapeutic strategies for this malignancy. The expression of miR-664 in osteosarcoma cell lines and osteosarcoma tissues was examined using real-time PCR. The effects of miR-664 on osteosarcoma cell migration and invasion were evaluated by cell invasion assays, migration assays, and three-dimension spheroid invasion assay. The effect of miR-664 on SOX7 was determined by luciferase assays and Western blot assay. The clinical association between miR-664 and SOX7 was analyzed by real-time PCR and Western blot assay. Expression of miR-664 was found to be upregulated in OS cell lines and tissues. Overexpression of miR-664 was associated with increased migration and invasive abilities of OS cells in vitro, whereas downregulation of miR-664 appeared to inhibit their migration and invasive potential. Furthermore, using biological approaches, we showed that miR-664 directly targeted and suppressed expression of the tumor suppressor SOX7. Additionally, the expression of miR-664 was negatively correlated with SOX7 expression in OS clinical tissues. Our findings suggest that miR-664 functions as an oncogene miRNA and has an important role in promoting human OS cell invasion and migration by suppressing SOX7 expression. Consequently, miR-664 may have potential as a novel diagnostic and therapeutic target of osteosarcoma.

  19. Targeted deletion of the metastasis-associated phosphatase Ptp4a3 (PRL-3) suppresses murine colon cancer.

    Science.gov (United States)

    Zimmerman, Mark W; Homanics, Gregg E; Lazo, John S

    2013-01-01

    Ptp4a3 (commonly known as PRL-3) is an enigmatic member of the Ptp4a family of prenylated protein tyrosine phosphatases that are highly expressed in many human cancers. Despite strong correlations with tumor metastasis and poor patient prognosis, there is very limited understanding of this gene family's role in malignancy. Therefore, we created a gene-targeted murine knockout model for Ptp4a3, the most widely studied Ptp4a family member. Mice deficient for Ptp4a3 were grossly normal. Fewer homozygous-null males were observed at weaning, however, and they maintained a decreased body mass. Although Ptp4a3 is normally associated with late-stage cancer and metastasis, we observed increased Ptp4a3 expression in the colon of wildtype mice immediately following treatment with the carcinogen azoxymethane. To investigate the role of Ptp4a3 in malignancy, we used the most commonly studied murine colitis-associated colon cancer model. Wildtype mice treated with azoxymethane and dextran sodium sulfate developed approximately 7-10 tumors per mouse in the distal colon. The resulting tumor tissue had 4-fold more Ptp4a3 mRNA relative to normal colon epithelium and increased PTP4A3 protein. Ptp4a3-null mice developed 50% fewer colon tumors than wildtype mice after exposure to azoxymethane and dextran sodium sulfate. Tumors from the Ptp4a3-null mice had elevated levels of both IGF1Rβ and c-MYC compared to tumors replete with Ptp4a3, suggesting an enhanced cell signaling pathway engagement in the absence of the phosphatase. These results provide the first definitive evidence implicating Ptp4a3 in colon tumorigenesis and highlight the potential value of the phosphatase as a therapeutic target for early stage malignant disease.

  20. Recommender Systems for Learning

    CERN Document Server

    Manouselis, Nikos; Verbert, Katrien; Duval, Erik

    2013-01-01

    Technology enhanced learning (TEL) aims to design, develop and test sociotechnical innovations that will support and enhance learning practices of both individuals and organisations. It is therefore an application domain that generally covers technologies that support all forms of teaching and learning activities. Since information retrieval (in terms of searching for relevant learning resources to support teachers or learners) is a pivotal activity in TEL, the deployment of recommender systems has attracted increased interest. This brief attempts to provide an introduction to recommender systems for TEL settings, as well as to highlight their particularities compared to recommender systems for other application domains.

  1. Achievement of Target Blood Pressure Levels among Japanese Workers with Hypertension and Healthy Lifestyle Characteristics Associated with Therapeutic Failure.

    Directory of Open Access Journals (Sweden)

    Nagako Kudo

    Full Text Available Few studies have examined Japanese with regard to the achievement rates for target blood pressure levels, or the relationship between these rates and healthy lifestyle characteristics in patients with hypertension as defined by the newly established hypertension management guidelines (JSH2014. The aim of this study was to elucidate achievement rates and examine healthy lifestyle characteristics associated with achievement status among Japanese.This cross-sectional study, conducted in January-December 2012, examined blood pressure control and healthy lifestyle characteristics in 8,001 Japanese workers with hypertension (mean age, 57.0 years; 78.8% were men who participated in a workplace health checkup. Data were collected from workplace medical checkup records and participants' self-administered questionnaires. We divided into 5 groups [G1; young, middle-aged, and early-phase elderly patients (65-74 years old without diabetes mellitus or chronic kidney disease (CKD (<140/90 mmHg, G2; late-phase elderly patients (≥75 years old without diabetes mellitus or CKD (<150/90 mmHg, G3; diabetic patients (<130/80 mmHg, G4; patients with CKD (<130/80 mmHg, and G5; patients with cerebrovascular and/or coronary artery diseases (<140/90 mmHg] according to JSH2014. And then, achievement rates were calculated in each group. Multivariate analysis identified healthy lifestyle characteristics associated with "therapeutic failure" of target blood pressure.Target blood pressures were achieved by 60.2% of young, middle-aged, and early-phase elderly patients (G1, 71.4% of late-phase elderly patients (G2, 30.5% of diabetic patients (G3, 33.4% of those with chronic kidney disease (G4, and 66.0% of those with cerebrovascular and/or coronary artery diseases (G5. A body mass index of 18.5-24.9 and non-daily alcohol consumption were protective factors, and adequate sleep was found to contribute to therapeutic success.We found low achievement rates for treatment goals

  2. Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol.

    Science.gov (United States)

    Patel, Reesha R; Barbosa, Cindy; Brustovetsky, Tatiana; Brustovetsky, Nickolay; Cummins, Theodore R

    2016-08-01

    Mutations in brain isoforms of voltage-gated sodium channels have been identified in patients with distinct epileptic phenotypes. Clinically, these patients often do not respond well to classic anti-epileptics and many remain refractory to treatment. Exogenous as well as endogenous cannabinoids have been shown to target voltage-gated sodium channels and cannabidiol has recently received attention for its potential efficacy in the treatment of childhood epilepsies. In this study, we further investigated the ability of cannabinoids to modulate sodium currents from wild-type and epilepsy-associated mutant voltage-gated sodium channels. We first determined the biophysical consequences of epilepsy-associated missense mutations in both Nav1.1 (arginine 1648 to histidine and asparagine 1788 to lysine) and Nav1.6 (asparagine 1768 to aspartic acid and leucine 1331 to valine) by obtaining whole-cell patch clamp recordings in human embryonic kidney 293T cells with 200 μM Navβ4 peptide in the pipette solution to induce resurgent sodium currents. Resurgent sodium current is an atypical near threshold current predicted to increase neuronal excitability and has been implicated in multiple disorders of excitability. We found that both mutations in Nav1.6 dramatically increased resurgent currents while mutations in Nav1.1 did not. We then examined the effects of anandamide and cannabidiol on peak transient and resurgent currents from wild-type and mutant channels. Interestingly, we found that cannabidiol can preferentially target resurgent sodium currents over peak transient currents generated by wild-type Nav1.6 as well as the aberrant resurgent and persistent current generated by Nav1.6 mutant channels. To further validate our findings, we examined the effects of cannabidiol on endogenous sodium currents from striatal neurons, and similarly we found an inhibition of resurgent and persistent current by cannabidiol. Moreover, current clamp recordings show that cannabidiol reduces

  3. Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder.

    Science.gov (United States)

    Sarachana, Tewarit; Hu, Valerie W

    2013-05-22

    We have recently identified the nuclear hormone receptor RORA (retinoic acid-related orphan receptor-alpha) as a novel candidate gene for autism spectrum disorder (ASD). Our independent cohort studies have consistently demonstrated the reduction of RORA transcript and/or protein levels in blood-derived lymphoblasts as well as in the postmortem prefrontal cortex and cerebellum of individuals with ASD. Moreover, we have also shown that RORA has the potential to be under negative and positive regulation by androgen and estrogen, respectively, suggesting the possibility that RORA may contribute to the male bias of ASD. However, little is known about transcriptional targets of this nuclear receptor, particularly in humans. Here we identify transcriptional targets of RORA in human neuronal cells on a genome-wide level using chromatin immunoprecipitation (ChIP) with an anti-RORA antibody followed by whole-genome promoter array (chip) analysis. Selected potential targets of RORA were then validated by an independent ChIP followed by quantitative PCR analysis. To further demonstrate that reduced RORA expression results in reduced transcription of RORA targets, we determined the expression levels of the selected transcriptional targets in RORA-deficient human neuronal cells, as well as in postmortem brain tissues from individuals with ASD who exhibit reduced RORA expression. The ChIP-on-chip analysis reveals that RORA1, a major isoform of RORA protein in human brain, can be recruited to as many as 2,764 genomic locations corresponding to promoter regions of 2,544 genes across the human genome. Gene ontology analysis of this dataset of genes that are potentially directly regulated by RORA1 reveals statistically significant enrichment in biological functions negatively impacted in individuals with ASD, including neuronal differentiation, adhesion and survival, synaptogenesis, synaptic transmission and plasticity, and axonogenesis, as well as higher level functions such as

  4. MCMC Particle Filter Using New Data Association Technique with Viterbi Filtered Gate Method for Multi-Target Tracking in Heavy Clutter

    Directory of Open Access Journals (Sweden)

    E. M.Saad

    2011-08-01

    Full Text Available Improving data association technique in dense clutter environment for multi-target tracking used in Markov chain Monte Carlo based particle filter (MCMC-PF are discussed in this paper. A new method named Viterbi filtered gate Markov chain Monte Carlo VFG-MCMC is introduced to avoid track swap and to overcome the issue of loosing track to highly maneuvering targets in the presence of more background clutter and false signals. An adaptive search based on Viterbi algorithm is then used to detect the valid filtered data point in each target gate. The detected valid point for each target is applied to the estimation algorithm of MCMC-PF during calculating the sampling weights. This proposed method makes the MCMC interacts only with the valid target that is candidate from the filtered gate and no more calculations are considered for invalid targets. Simulation results demonstrate the effectiveness and better performance when compared to conventional algorithm MCMC-PF.

  5. Management recommendations: Tewaukon Complex

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This document is a review of land management practices at the Tewaukon Complex, by a land use specialist. Recommendations, time frame and additional comments are...

  6. Recommended Textbooks (Booksearch).

    Science.gov (United States)

    English Journal, 1988

    1988-01-01

    Evaluates four textbooks recommended by junior high and high school teachers for teaching writing and literature: "Enjoying Literature" (published by Macmillan, 1985); "Exposition: Critical Writing and Thinking" (Robert J. Gula); "Situational Writing" (Gene Krupa); and "Double Exposure: Composing through Writing…

  7. Management recommendations: Kirwin Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This document is a review of land management practices at the Kirwin National Wildlife Refuge, by a land use specialist. Recommendations, time frame and additional...

  8. Probabilistic approaches to recommendations

    CERN Document Server

    Barbieri, Nicola; Ritacco, Ettore

    2014-01-01

    The importance of accurate recommender systems has been widely recognized by academia and industry, and recommendation is rapidly becoming one of the most successful applications of data mining and machine learning. Understanding and predicting the choices and preferences of users is a challenging task: real-world scenarios involve users behaving in complex situations, where prior beliefs, specific tendencies, and reciprocal influences jointly contribute to determining the preferences of users toward huge amounts of information, services, and products. Probabilistic modeling represents a robus

  9. Recommendations for the interpretation of "black carbon" measurements

    Directory of Open Access Journals (Sweden)

    A. Petzold

    2013-04-01

    Full Text Available Although black carbon (BC is one of the key atmospheric particulate components driving climate change and air quality, there is no agreement on the terminology that considers all aspects of specific properties, definitions, measurement methods, and related uncertainties. As a result, there is much ambiguity in the scientific literature of measurements and numerical models that refer to BC with different names and based on different properties of the particles, with no clear definition of the terms. The authors present here a recommended terminology to clarify the terms used for BC in atmospheric research, with the goal of establishing unambiguous links between terms, targeted material properties and associated measurement techniques.

  10. New Insulin Delivery Recommendations.

    Science.gov (United States)

    Frid, Anders H; Kreugel, Gillian; Grassi, Giorgio; Halimi, Serge; Hicks, Debbie; Hirsch, Laurence J; Smith, Mike J; Wellhoener, Regine; Bode, Bruce W; Hirsch, Irl B; Kalra, Sanjay; Ji, Linong; Strauss, Kenneth W

    2016-09-01

    Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes.

  11. Association Between Loyalty to Community Pharmacy and Medication Persistence and Compliance, and the Use of Guidelines-Recommended Drugs in Type 2 Diabetes: A Cohort Study.

    Science.gov (United States)

    Dossa, Anara Richi; Grégoire, Jean-Pierre; Lauzier, Sophie; Guénette, Line; Sirois, Caroline; Moisan, Jocelyne

    2015-07-01

    Pharmacists record data on all drugs claimed and may build a personal relationship with their clients. We hypothesized that loyalty to a single pharmacy could be associated with a better quality of drug use.To assess the association between pharmacy loyalty and quality of drug use among individuals treated with oral antidiabetes drugs (OADs).This is a cohort study using Quebec Health Insurance Board data. Associations were assessed using multivariable logistic regression.New OAD users, aged ≥18 years.Individuals who filled all their prescription drugs in the same pharmacy during the first year of treatment were considered loyal. During year 2 of treatment we assessed 4 quality indicators of drug use: persistence with antidiabetes treatment, compliance with antidiabetes treatment among those considered persistent, use of an angiotensin-converting enzyme inhibitor or of an angiotensin II receptor blocker (ACEi/ARB), and use of a lipid-lowering drug.Of 124,009 individuals, 59.75% were identified as loyal. Nonloyal individuals were less likely to persist with their antidiabetes treatment (adjusted odds ratio = 0.89; 95% CI: 0.86-0.91), to comply with their antidiabetes treatment (0.82; 0.79-0.84), to use an ACEi/ARB (0.85; 0.83-0.88) and to use a lipid-lowering drug (0.83; 0.80-0.85). Quality of drug use decreased as the number of different pharmacies increased (linear contrast tests loyalty are specifically due to pharmacists.

  12. Association Between Loyalty to Community Pharmacy and Medication Persistence and Compliance, and the Use of Guidelines-Recommended Drugs in Type 2 Diabetes

    Science.gov (United States)

    Dossa, Anara Richi; Grégoire, Jean-Pierre; Lauzier, Sophie; Guénette, Line; Sirois, Caroline; Moisan, Jocelyne

    2015-01-01

    Abstract Pharmacists record data on all drugs claimed and may build a personal relationship with their clients. We hypothesized that loyalty to a single pharmacy could be associated with a better quality of drug use. To assess the association between pharmacy loyalty and quality of drug use among individuals treated with oral antidiabetes drugs (OADs). This is a cohort study using Quebec Health Insurance Board data. Associations were assessed using multivariable logistic regression. New OAD users, aged ≥18 years. Individuals who filled all their prescription drugs in the same pharmacy during the first year of treatment were considered loyal. During year 2 of treatment we assessed 4 quality indicators of drug use: persistence with antidiabetes treatment, compliance with antidiabetes treatment among those considered persistent, use of an angiotensin-converting enzyme inhibitor or of an angiotensin II receptor blocker (ACEi/ARB), and use of a lipid-lowering drug. Of 124,009 individuals, 59.75% were identified as loyal. Nonloyal individuals were less likely to persist with their antidiabetes treatment (adjusted odds ratio = 0.89; 95% CI: 0.86–0.91), to comply with their antidiabetes treatment (0.82; 0.79–0.84), to use an ACEi/ARB (0.85; 0.83–0.88) and to use a lipid-lowering drug (0.83; 0.80–0.85). Quality of drug use decreased as the number of different pharmacies increased (linear contrast tests loyalty are specifically due to pharmacists. PMID:26166087

  13. [Antiseptics and disinfectants: aiming at rational use. Recommendations of the Advisory Committee on Healthcare Associated Infections. Sociedad Chilena de Infectología].

    Science.gov (United States)

    Diomedi, Alexis; Chacón, Eiiana; Delpiano, Luis; Hervé, Beatrice; Jemenao, M Irene; Medel, Myriam; Quintanilla, Marcela; Riedel, Gisela; Tinoco, Javier; Cifuentes, Marcela

    2017-04-01

    Proper use of antiseptics and disinfectants, is an essential tool to prevent the spread of infectious agents and to control of healthcare-associated infections (HAI). Given the increasing importance of environmental aspects, as well as several advances and updates in the field of its proper use at local and intemational level, the SOCHINF HAI Advisory Committee considers that it is necessary to develop a guide for the rational use of antiseptics and disinfectants, which it will provide consistent scientific basis with that purpose.

  14. Mathematical models of tissue stem and transit target cell divisions and the risk of radiation- or smoking-associated cancer.

    Science.gov (United States)

    Little, Mark P; Hendry, Jolyon H

    2017-02-01

    There is compelling biological data to suggest that cancer arises from a series of mutations in single target cells, resulting in defects in cell renewal and differentiation processes which lead to malignancy. Because much mutagenic damage is expressed following cell division, more-rapidly renewing tissues could be at higher risk because of the larger number of cell replications. Cairns suggested that renewing tissues may reduce cancer risk by partitioning the dividing cell populations into lineages comprising infrequently-dividing long-lived stem cells and frequently-dividing short-lived daughter transit cells. We develop generalizations of three recent cancer-induction models that account for the joint maintenance and renewal of stem and transit cells, also competing processes of partially transformed cell proliferation and differentiation/apoptosis. We are particularly interested in using these models to separately assess the probabilities of mutation and development of cancer associated with "spontaneous" processes and with those linked to a specific environmental mutagen, specifically ionizing radiation or cigarette smoking. All three models demonstrate substantial variation in cancer risks, by at least 20 orders of magnitude, depending on the assumed number of critical mutations required for cancer, and the stem-cell and transition-cell mutation rates. However, in most cases the conditional probabilities of cancer being mutagen-induced range between 7-96%. The relative risks associated with mutagen exposure compared to background rates are also stable, ranging from 1.0-16.0. Very few cancers, generally Little difference is made to relative risks if competing processes of proliferation and differentiation in the partially transformed stem and transit cell population are allowed for, nor is any difference made if one assumes that transit cells require an extra mutation to confer malignancy from the number required by stem cells. The probability of a cancer

  15. Plausible Drug Targets in the Streptococcus mutans Quorum Sensing Pathways to Combat Dental Biofilms and Associated Risks.

    Science.gov (United States)

    Kaur, Gurmeet; Rajesh, Shrinidhi; Princy, S Adline

    2015-12-01

    Streptococcus mutans, a Gram positive facultative anaerobe, is one among the approximately seven hundred bacterial species to exist in human buccal cavity and cause dental caries. Quorum sensing (QS) is a cell-density dependent communication process that respond to the inter/intra-species signals and elicit responses to show behavioral changes in the bacteria to an aggressive forms. In accordance to this phenomenon, the S. mutans also harbors a Competing Stimulating Peptide (CSP)-mediated quorum sensing, ComCDE (Two-component regulatory system) to regulate several virulence-associated traits that includes the formation of the oral biofilm (dental plaque), genetic competence and acidogenicity. The QS-mediated response of S. mutans adherence on tooth surface (dental plaque) imparts antibiotic resistance to the bacterium and further progresses to lead a chronic state, known as periodontitis. In recent years, the oral streptococci, S. mutans are not only recognized for its cariogenic potential but also well known to worsen the infective endocarditis due to its inherent ability to colonize and form biofilm on heart valves. The review significantly appreciate the increasing complexity of the CSP-mediated quorum-sensing pathway with a special emphasis to identify the plausible drug targets within the system for the development of anti-quorum drugs to control biofilm formation and associated risks.

  16. “Inflammaging” as a Druggable Target: A Senescence-Associated Secretory Phenotype—Centered View of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Francesco Prattichizzo

    2016-01-01

    Full Text Available Aging is a complex phenomenon driven by a variety of molecular alterations. A relevant feature of aging is chronic low-grade inflammation, termed “inflammaging.” In type 2 diabetes mellitus (T2DM, many elements of aging appear earlier or are overrepresented, including consistent inflammaging. T2DM patients have an increased death rate, associated with an incremented inflammatory score. The source of this inflammation is debated. Recently, the senescence-associated secretory phenotype (SASP has been proposed as the main origin of inflammaging in both aging and T2DM. Different pathogenic mechanisms linked to T2DM progression and complications development have been linked to senescence and SASP, that is, oxidative stress and endoplasmic reticulum (ER stress. Here we review the latest data connecting oxidative and ER stress with the SASP in the context of aging and T2DM, with emphasis on endothelial cells (ECs and endothelial dysfunction. Moreover, since current medical practice is insufficient to completely suppress the increased death rate of diabetic patients, we propose a SASP-centered view of T2DM as a futuristic therapeutic option, possibly opening new prospects by moving the attention from one-organ studies of diabetes complications to a wider targeting of the aging process.

  17. Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft.

    Science.gov (United States)

    Gazzaniga, Silvina; Bravo, Alicia I; Guglielmotti, Angelo; van Rooijen, Nico; Maschi, Fabricio; Vecchi, Annunciata; Mantovani, Alberto; Mordoh, José; Wainstok, Rosa

    2007-08-01

    Chemokines such as monocyte chemoattractant protein (MCP)-1 are key agonists that attract macrophages to tumors. In melanoma, it has been previously shown that variable levels of MCP-1/CCL2 appear to correlate with infiltrating macrophages and tumor fate, with low to intermediate levels of the chemokine contributing to melanoma development. To work under such conditions, a poorly tumorigenic human melanoma cell line was transfected with an expression vector encoding MCP-1. We found that M2 macrophages are associated to MCP-1+ tumors, triggering a profuse vascular network. To target the protumoral macrophages recruitment and reverting tumor growth promotion, clodronate-laden liposomes (Clod-Lip) or bindarit were administered to melanoma-bearing mice. Macrophage depletion after Clod-Lip treatment induced development of smaller tumors than in untreated mice. Immunohistochemical analysis with an anti-CD31 antibody revealed scarce vascular structures mainly characterized by narrow vascular lights. Pharmacological inhibition of MCP-1 with bindarit also reduced tumor growth and macrophage recruitment, rendering necrotic tumor masses. We suggest that bindarit or Clod-Lip abrogates protumoral-associated macrophages in human melanoma xenografts and could be considered as complementary approaches to antiangiogenic therapy.

  18. Recommendation-Aware Smartphone Sensing System

    Directory of Open Access Journals (Sweden)

    Mu-Yen Chen

    2014-12-01

    Full Text Available The context-aware concept is to reduce the gap between users and information systems so that the information systems actively get to understand users’ context and demand and in return provide users with better experience. This study integrates the concept of context-aware with association algorithms to establish the context-aware recommendation systems (CARS. The CARS contains three modules and provides the product recommendations for users with their smartphone. First, the simple RSSI Indoor localization module (SRILM locates the user position and detects the context information surrounding around users. Second, the Apriori recommendation module (ARM provides effective recommended product information for users through association rules mining. The appropriate product information can be received effectiveness and greatly enhanced the recommendation service.

  19. Evaluation of military field-water quality: Volume 6, Infectious organisms of military concern associated with nonconsumptive exposure: Assessment of health risks and recommendations for establishing related standards

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, R.C.; Olivieri, A.W.; Danielson, R.E.; Badger, P.G.

    1986-02-01

    This study is an assessment of the risk of illness due to exposure to water-related (i.e., water-based, water-washed) infectious organisms. The organisms under consideration are Aeromonas spp., Leptospira spp., Pseudomonas spp., Staphylococcus spp., non-cholerae Vibrio spp., Acanthamoeba spp., Balantidium coli, Naegleria spp., Ascaris lumbricoides, Dracunculus medinesis, Schistosoma spp., and the agents responsible for cercarial dermatitis (i.e., Trichobilharzia, Gigantobilharzia, and Austrobilharzia). Evaluation of the risk to disease associated with the above pathogens requires information in specific areas such as dose response, concentration of agents in the environment, and environmental persistence. The existing body of knowledge concerning these agents ranges from speculation to established fact. Unfortunately, areas of information critical to risk assessment are frequently unavailable. Because of this lack of data, the risk assessment presented is semiquantitative and limited to the presentation of an environmental classification scheme. 14 refs., 2 figs., 57 tabs.

  20. Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

    Science.gov (United States)

    Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

    2017-02-01

    To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA1c) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA1c of reached the target HbA1c. The higher the HbA1c quartile, the greater was the decrease in HbA1c, but also the smaller the percentage of patients achieving the target HbA1c. HbA1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA1c quartiles with either insulin treatment. Patients not achieving the target HbA1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA1c, suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Targeting nuclear receptors in cancer-associated fibroblasts as concurrent therapy to inhibit development of chemoresistant tumors.

    Science.gov (United States)

    Chan, J S K; Sng, M K; Teo, Z Q; Chong, H C; Twang, J S; Tan, N S

    2017-09-11

    Most anticancer therapies to date focus on druggable features of tumor epithelia. Despite the increasing repertoire of treatment options, patient responses remain varied. Moreover, tumor resistance and relapse remain persistent clinical challenges. These observations imply an incomplete understanding of tumor heterogeneity. The tumor microenvironment is a major determinant of disease progression and therapy outcome. Cancer-associated fibroblasts (CAFs) are the dominant cell type within the reactive stroma of tumors. They orchestrate paracrine pro-tumorigenic signaling with adjacent tumor cells, thus exacerbating the hallmarks of cancer and accelerating tumor malignancy. Although CAF-derived soluble factors have been investigated for tumor stroma-directed therapy, the underlying transcriptional programs that enable the oncogenic functions of CAFs remain poorly understood. Nuclear receptors (NRs), a large family of ligand-responsive transcription factors, are pharmacologically viable targets for the suppression of CAF-facilitated oncogenesis. In this study, we defined the expression profiles of NRs in CAFs from clinical cutaneous squamous cell carcinoma (SCC) biopsies. We further identified a cluster of driver NRs in CAFs as important modifiers of CAF function with profound influence on cancer cell invasiveness, proliferation, drug resistance, energy metabolism and oxidative stress status. Importantly, guided by the NR profile of CAFs, retinoic acid receptor β and androgen receptor antagonists were identified for concurrent therapy with cisplatin, resulting in the inhibition of chemoresistance in recurred SCC:CAF xenografts. Our work demonstrates that treatments targeting both the tumor epithelia and the surrounding CAFs can extend the efficacy of conventional chemotherapy.Oncogene advance online publication, 11 September 2017; doi:10.1038/onc.2017.319.

  2. Expression of the p53 target Wig-1 is associated with HPV status and patient survival in cervical carcinoma.

    Directory of Open Access Journals (Sweden)

    Li-Di Xu

    Full Text Available The p53 target gene WIG-1 (ZMAT3 is located in chromosomal region 3q26, that is frequently amplified in human tumors, including cervical cancer. We have examined the status of WIG-1 and the encoded Wig-1 protein in cervical carcinoma cell lines and tumor tissue samples. Our analysis of eight cervical cancer lines (Ca Ski, ME-180, MS751, SiHa, SW756, C-4I, C-33A, and HT-3 by spectral karyotype, comparative genomic hybridization and Southern blotting revealed WIG-1 is not the primary target for chromosome 3 gains. However, WIG-1/Wig-1 were readily expressed and WIG-1 mRNA expression was higher in the two HPV-negative cervical cell lines (C33-A, HT-3 than in HPV-positive lines. We then assessed Wig-1 expression by immunohistochemistry in 38 cervical tumor samples. We found higher nuclear Wig-1 expression levels in HPV-negative compared to HPV positive cases (p = 0.002 and in adenocarcinomas as compared to squamous cell lesions (p<0.0001. Cases with moderate nuclear Wig-1 staining and positive cytoplasmic Wig-1 staining showed longer survival than patients with strong nuclear and negative cytoplasmic staining (p = 0.042. Nuclear Wig-1 expression levels were positively associated with age at diagnosis (p = 0.023 and histologic grade (p = 0.034. These results are consistent with a growth-promoting and/or anti-cell death function of nuclear Wig-1 and suggest that Wig-1 expression can serve as a prognostic marker in cervical carcinoma.

  3. miR-138 suppresses the proliferation of oral squamous cell carcinoma cells by targeting Yes-associated protein 1.

    Science.gov (United States)

    Xu, Ran; Zeng, Guang; Gao, Jing; Ren, Yue; Zhang, Zhe; Zhang, Qingna; Zhao, Jinxiu; Tao, Hong; Li, Daxu

    2015-10-01

    Aberrant microRNA expression has been suggested to be an important event in the pathologies of various types of cancer. MicroRNA-138 (miR-138) has been reported to be frequently downregulated in various types of human cancer, including oral squamous cell carcinoma (OSCC). However, the precise molecular mechanism of miR-138 underlying OSCC remains largely unknown. The aim of the present study was to investigate the expression of miR-138 in OSCC tumor tissues and several OSCC cell lines and validated its interaction with the 3'-untranslated region (3'-UTR) of Yes-associated protein 1 (YAP1). The results showed that, miR-138 was significantly downregulated in OSCC tumor tissues and cell lines. Overexpression of miR-138 inhibited cell proliferation of OSCC cells whereas the downregulation of miR-138 promoted cell proliferation. A direct interaction between miR-138 and 3'-UTR of YAP1 was validated by dual-luciferase reporter assay. Moreover, overexpression of miR-138 in OSCC cells significantly decreased the expression of YAP1 and downregulation of miR-138 inhibited the expression of YAP1. Specifically, the inhibitory effect of miR-138 on the proliferation of OSCC cells was eliminated by transfection with YAP1 overexpression vectors that did not harbor any specific miR-138 binding specific sequences in 3'-UTR. In addition, the miR-138‑overexpressing OSCC cells exhibited a low growth rate in the xenograft tumor assay with a decreased expression of YAP1 in tumor tissues. The results suggest that miR-138 is a tumor suppressor miRNA in OSCC through targeting YAP1, which serves as a promising therapeutic target for the treatment of OSCC.

  4. Assuring the Proper Analytical Performance of Measurement Procedures for Immunosuppressive Drug Concentrations in Clinical Practice: Recommendations of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology Immunosuppressive Drug Scientific Committee.

    Science.gov (United States)

    Seger, Christoph; Shipkova, Maria; Christians, Uwe; Billaud, Elaine M; Wang, Ping; Holt, David W; Brunet, Mercè; Kunicki, Paweł K; Pawiński, Thomasz; Langman, Loralie J; Marquet, Pierre; Oellerich, Michael; Wieland, Eberhard; Wallemacq, Pierre

    2016-04-01

    Monitoring immunosuppressive drugs (ISDs) in blood or plasma is still a key therapeutic drug monitoring (TDM) application in clinical settings. Narrow target ranges and severe side effects at drug underexposure or overexposure make accurate and precise measurements a must. This overview prepared by the Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology is intended to serve as a summary and guidance document describing the current state-of-the-art in the TDM of ISDs.

  5. Distributed Deliberative Recommender Systems

    Science.gov (United States)

    Recio-García, Juan A.; Díaz-Agudo, Belén; González-Sanz, Sergio; Sanchez, Lara Quijano

    Case-Based Reasoning (CBR) is one of most successful applied AI technologies of recent years. Although many CBR systems reason locally on a previous experience base to solve new problems, in this paper we focus on distributed retrieval processes working on a network of collaborating CBR systems. In such systems, each node in a network of CBR agents collaborates, arguments and counterarguments its local results with other nodes to improve the performance of the system's global response. We describe D2ISCO: a framework to design and implement deliberative and collaborative CBR systems that is integrated as a part of jcolibritwo an established framework in the CBR community. We apply D2ISCO to one particular simplified type of CBR systems: recommender systems. We perform a first case study for a collaborative music recommender system and present the results of an experiment of the accuracy of the system results using a fuzzy version of the argumentation system AMAL and a network topology based on a social network. Besides individual recommendation we also discuss how D2ISCO can be used to improve recommendations to groups and we present a second case of study based on the movie recommendation domain with heterogeneous groups according to the group personality composition and a group topology based on a social network.

  6. Scientific and educational recommender systems

    Science.gov (United States)

    Guseva, A. I.; Kireev, V. S.; Bochkarev, P. V.; Kuznetsov, I. A.; Philippov, S. A.

    2017-01-01

    This article discusses the questions associated with the use of reference systems in the preparation of graduates in physical function. The objective of this research is creation of model of recommender system user from the sphere of science and education. The detailed review of current scientific and social network for scientists and the problem of constructing recommender systems in this area. The result of this study is to research user information model systems. The model is presented in two versions: the full one - in the form of a semantic network, and short - in a relational form. The relational model is the projection in the form of semantic network, taking into account the restrictions on the amount of bonds that characterize the number of information items (research results), which interact with the system user.

  7. Order Theoretical Semantic Recommendation

    Energy Technology Data Exchange (ETDEWEB)

    Joslyn, Cliff A.; Hogan, Emilie A.; Paulson, Patrick R.; Peterson, Elena S.; Stephan, Eric G.; Thomas, Dennis G.

    2013-07-23

    Mathematical concepts of order and ordering relations play multiple roles in semantic technologies. Discrete totally ordered data characterize both input streams and top-k rank-ordered recommendations and query output, while temporal attributes establish numerical total orders, either over time points or in the more complex case of startend temporal intervals. But also of note are the fully partially ordered data, including both lattices and non-lattices, which actually dominate the semantic strcuture of ontological systems. Scalar semantic similarities over partially-ordered semantic data are traditionally used to return rank-ordered recommendations, but these require complementation with true metrics available over partially ordered sets. In this paper we report on our work in the foundations of partial order measurement in ontologies, with application to top-k semantic recommendation in workflows.

  8. [2013 Ambulatory blood pressure monitoring recommendations for the diagnosis of adult hypertension, assessment of cardiovascular and other hypertension-associated risk, and attainment of therapeutic goals (summary). Joint recommendations from the International Society for Chronobiology (ISC), American Association of Medical Chronobiology and Chronotherapeutics (AAMCC), Spanish Society of Applied Chronobiology, Chronotherapy, and Vascular Risk (SECAC), Spanish Society of Atherosclerosis (SEA), and Romanian Society of Internal Medicine (RSIM)].

    Science.gov (United States)

    Hermida, Ramón C; Smolensky, Michael H; Ayala, Diana E; Portaluppi, Francesco; Crespo, Juan J; Fabbian, Fabio; Haus, Erhard; Manfredini, Roberto; Mojón, Artemio; Moyá, Ana; Piñeiro, Luis; Ríos, María T; Otero, Alfonso; Balan, Horia; Fernández, José R

    2013-01-01

    Correlation between systolic (SBP) and diastolic (DBP) blood pressure (BP) level and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is much greater for ambulatory BP monitoring (ABPM) than daytime office measurements. The 2013 ABPM guidelines specified herein are based on ABPM patient outcomes studies and constitute a substantial revision of current knowledge. The asleep SBP mean and sleep-time relative SBP decline are the most significant predictors of CVD events, both individually as well as jointly when combined with other ABPM-derived prognostic markers. Thus, they should be preferably used to diagnose hypertension and assess CVD and other associated risks. Progressive decrease by therapeutic intervention in the asleep BP mean is the most significant predictor of CVD event-free interval. The 24 h BP mean is not recommended to diagnose hypertension because it disregards the more valuable clinical information pertaining to the features of the 24 h BP pattern. Persons with the same 24 h BP mean may display radically different 24 h BP patterns, ranging from extreme-dipper to riser types, representative of markedly different risk states. Classification of individuals by comparing office with either the 24 h or awake BP mean as "masked normotensives" (elevated clinic BP but normal ABPM), which should replace the terms of "isolated office" or "white-coat hypertension", and "masked hypertensives" (normal clinic BP but elevated ABPM) is misleading and should be avoided because it disregards the clinical significance of the asleep BP mean. Outcome-based ABPM reference thresholds for men, which in the absence of compelling clinical conditions are 135/85 mmHg for the awake and 120/70 mmHg for the asleep SBP/DBP means, are lower by 10/5 mmHg for SBP/DBP in uncomplicated, low-CVD risk, women and lower by 15/10 mmHg for SBP/DBP in male and female high-risk patients, e.g., with diabetes, chronic kidney disease (CKD), and/or past CVD events. In

  9. Targeted interventions of the Avahan program and their association with intermediate outcomes among female sex workers in Maharashtra, India

    Directory of Open Access Journals (Sweden)

    Mainkar Mandar M

    2011-12-01

    Full Text Available Abstract Background Avahan, the India AIDS Initiative has been a partner supporting targeted interventions of high risk populations under India’s National AIDS Control Organisation (NACO since 2004 in the state of Maharashtra. This paper presents an assessment of the Avahan program among female sex workers (FSWs in Maharashtra, its coverage, outcomes achieved and their association with Avahan program. Methods An analytical framework based on the Avahan evaluation design was used, addressing assessment questions on program implementation, intermediate outcomes and association of outcomes with Avahan. Data from routine program monitoring, two rounds of cross-sectional Integrated Behavioural and Biological Assessments (IBBAs conducted in 2006 (Round 1- R1 and 2009 (Round 2 – R2 and quality assessments of program clinics were used. Bi-variate and multivariate analysis were conducted using the complex samples module in SPSS 15® (IBM, Somers NY. Results The Avahan program achieved coverage of over 66% of FSWs within four years of implementation. The IBBA data showed increased contact by peers in R2 compared to R1 (AOR:2.34; p=0.001. Reported condom use with clients increased in R2 and number of FSWs reporting zero unprotected sex acts increased from 76.2% (R1 to 94.6% (R2 [AOR: 5.1, p=0.001]. Significant declines were observed in prevalence of syphilis (RPR (15.8% to 10.8%; AOR:0.54; p=0.001, chlamydia (8% to 6.2%; AOR:.0.65; p=0.010 and gonorrohoea (7.4% to 3.9; AOR:.0.60; p=0.026 between R1 and R2. HIV prevalence increased (25.8% to 27.5%; AOR:1.29; p=0.04. District-wise analysis showed decline in three districts and increase in Mumbai and Thane districts. FSWs exposed to Avahan had higher consistent condom use with occasional (94.3% vs. 90.6%; AOR: 1.55; p=0.04 and regular clients (92.5% vs. 86.0%; AOR: 1.95, p=0.001 compared to FSWs unexposed to Avahan. Decline in high titre syphilis was associated with Avahan exposure. Conclusion The Avahan

  10. Archetypal Game Recommender Systems

    DEFF Research Database (Denmark)

    Sifa, Rafet; Bauckhage, C.; Drachen, Anders

    2014-01-01

    feedback are presented: factor- and neighborhood-oriented models. These form the rst application of rec- ommender systems to digital games. Both models are tested on a dataset of 500,000 users of the game distribution platform Steam, covering game ownership and playtime data across more than 3000 games....... Compared to four other recommender models (nearest neighbor, two popularity mod- els, random baseline), the archetype based models provide the highest recall rates showing that Archetypal Analysis can be successfully applied for Top-L recommendation purposes...

  11. ISFG: Recommendations on biostatistics in paternity testing.

    Science.gov (United States)

    Gjertson, David W; Brenner, Charles H; Baur, Max P; Carracedo, Angel; Guidet, Francois; Luque, Juan A; Lessig, Rüdiger; Mayr, Wolfgang R; Pascali, Vince L; Prinz, Mechthild; Schneider, Peter M; Morling, Niels

    2007-12-01

    The Paternity Testing Commission (PTC) of the International Society for Forensic Genetics has taken up the task of establishing the biostatistical recommendations in accordance with the ISO 17025 standards and a previous set of ISFG recommendations specific to the genetic investigations in paternity cases. In the initial set, the PTC recommended that biostatistical evaluations of paternity are based on a likelihood ratio principle - yielding the paternity index, PI. Here, we have made five supplementary biostatistical recommendations. The first recommendation clarifies and defines basic concepts of genetic hypotheses and calculation concerns needed to produce valid PIs. The second and third recommendations address issues associated with population genetics (allele probabilities, Y-chromosome markers, mtDNA, and population substructuring) and special circumstances (deficiency/reconstruction and immigration cases), respectively. The fourth recommendation considers strategies regarding genetic evidence against paternity. The fifth recommendation covers necessary documentation, reporting details and assumptions underlying calculations. The PTC strongly suggests that these recommendations should be adopted by all laboratories involved in paternity testing as the basis for their biostatistical analysis.

  12. Recommendations for the target volume definition on dosimetry scanning in the oropharynx cancers; Recommandations pour la definition d'un volume cible sur scanographie dosimetrique dans les cancers de l'oropharynx

    Energy Technology Data Exchange (ETDEWEB)

    Maingon, P. [Centre Georges-Francois-Leclerc, Dept. de Radiotherapie, 21 - Dijon (France); Gregoire, V. [Hopital Universitaire Saint Luc, Dept. d' Oncologie Radiotherapie et Lab. de Radiologie, Brussels (Belgium)

    2004-11-01

    The oropharynx includes the base of tongue, tonsil pillars, soft palate, lateral and posterior wall of the hypopharynx. Tumors involving each part of these areas are often treated by external beam radiation therapy. The development of conformal approaches and the implementation of intensity modulated radiation therapy, combined with accurate definition of target volumes, endorsed by the international community, allows to propose guidelines for definition of target volumes. First of all imaging acquisition for dosimetry is reminded. For tumors involving the base of tongue and vallecula, early superficial tumors should be distinguished from tumors involving the muscles, indicating an increased margin defining the clinical target volume around the tumor to 1.5 cm. Tumors developed in the posterior wall of the hypopharynx should include constrictor muscles of the pharynx inside of the CTV. Tonsil carcinomas should be treated with a 1.5 cm margin around the tumor in the three dimensions. In spite of modern imaging, external beam treatment of tumors developed in the soft palate and in palatine arch remains difficult. The high rate of nodal involvement of these tumors and significant rates of bilateral extension have to be taken into consideration. Accurate criteria have been available to integrate a probability of bilateral extension in oropharynx 1 tumors. It should be analyzed according to the size of the tumor and the rate of extension in the base of the tongue and in the palatine arch. (authors)

  13. Functional TRAIL receptors in monocytes and tumor-associated macrophages: A possible targeting pathway in the tumor microenvironment

    Science.gov (United States)

    Liguori, Manuela; Buracchi, Chiara; Pasqualini, Fabio; Bergomas, Francesca; Pesce, Samantha; Sironi, Marina; Grizzi, Fabio; Mantovani, Alberto

    2016-01-01

    Despite the accepted dogma that TRAIL kills only tumor cells and spares normal ones, we show in this study that mononuclear phagocytes are susceptible to recombinant TRAIL via caspase-dependent apoptosis. Human resting monocytes and in vitro-differentiated macrophages expressed substantial levels of the functional TRAIL receptors (TRAIL-R1 and TRAIL-R2), while neutrophils and lymphocytes mostly expressed the non-signaling decoy receptor (TRAIL-R3). Accordingly, exclusively monocytes and macrophages activated caspase-8 and underwent apoptosis upon recombinant TRAIL treatment. TRAIL-Rs were up-regulated by anti-inflammatory agents (IL-10, glucocorticoids) and by natural compounds (Apigenin, Quercetin, Palmitate) and their treatment resulted in increased TRAIL-induced apoptosis. In mice, the only signaling TRAIL-R (DR5) was preferentially expressed by blood monocytes rather than neutrophils or lymphocytes. In both mice and humans, Tumor-Associated Macrophages (TAM) expressed functional TRAIL-R, while resident macrophages in normal tissues did not. As a proof of principle, we treated mice bearing a murine TRAIL-resistant fibrosarcoma with recombinant TRAIL. We observed significant decrease of circulating monocytes and infiltrating TAM, as well as reduced tumor growth and lower metastasis formation. Overall, these findings demonstrate that human and murine monocytes/macrophages are, among leukocytes, uniquely susceptible to TRAIL-mediated killing. This differential susceptibility to TRAIL could be exploited to selectively target macrophages in tumors. PMID:27191500

  14. Targeted deletion of Kif18a protects from colitis-associated colorectal (CAC) tumors in mice through impairing Akt phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Houbao [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Xu, Wangyang [Department of Clinical Laboratories, Ninth People’s Hospital, SJTUSM, Shanghai 200011 (China); Zhang, Hongxin [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Liu, Jianbing [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Shanghai Research Center for Model Organisms, Shanghai 201203 (China); Xu, Haimin [Department of Pathology, Rui-Jin Hospital, SJTUSM, Shanghai 200025 (China); Lu, Shunyuan; Dang, Suying [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Kuang, Ying [Shanghai Research Center for Model Organisms, Shanghai 201203 (China); Jin, Xiaolong [Department of Pathology, Rui-Jin Hospital, SJTUSM, Shanghai 200025 (China); Wang, Zhugang, E-mail: zhugangw@shsmu.edu.cn [State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital and Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025 (China); Shanghai Research Center for Model Organisms, Shanghai 201203 (China)

    2013-08-16

    Highlights: •Kif18A is up-regulated in CAC of mouse model. •Kif18a{sup −/−} mice are protected from CAC. •Tumor cells from Kif18a{sup −/−} mice undergo more apoptosis. •Kif18A deficiency induces poor Atk phosphorylation. -- Abstract: Kinesins are a superfamily of molecular motors involved in cell division or intracellular transport. They are becoming important targets for chemotherapeutic intervention of cancer due to their crucial role in mitosis. Here, we demonstrate that the kinesin-8 Kif18a is overexpressed in murine CAC and is a crucial promoter during early CAC carcinogenesis. Kif18a-deficient mice are evidently protected from AOM–DSS-induced colon carcinogenesis. Kif18A is responsible for proliferation of colonic tumor cells, while Kif18a ablation in mice promotes cell apoptosis. Mechanistically, Kif18a is responsible for induction of Akt phosphorylation, which is known to be associated with cell survival regulation. In conclusion, Kif18a is critical for colorectal carcinogenesis in the setting of inflammation by mechanisms of increased PI3K-AKT signaling. Inhibition of Kif18A activity may be useful in the prevention or chemotherapeutic intervention of CAC.

  15. Identification of bacteria associated with underground parts of Crocus sativus by 16S rRNA gene targeted metagenomic approach.

    Science.gov (United States)

    Ambardar, Sheetal; Sangwan, Naseer; Manjula, A; Rajendhran, J; Gunasekaran, P; Lal, Rup; Vakhlu, Jyoti

    2014-10-01

    Saffron (Crocus sativus L), an autumn-flowering perennial sterile plant, reproduces vegetatively by underground corms. Saffron has biannual corm-root cycle that makes it an interesting candidate to study microbial dynamics in its rhizosphere and cormosphere (area under influence of corm). Culture independent 16S rRNA gene metagenomic study of rhizosphere and cormosphere of Saffron during flowering stage revealed presence of 22 genera but none of the genus was common in all the three samples. Bulk soil bacterial community was represented by 13 genera with Acidobacteria being dominant. In rhizosphere, out of eight different genera identified, Pseudomonas was the most dominant genus. Cormosphere bacteria comprised of six different genera, dominated by the genus Pantoea. This study revealed that the bacterial composition of all the three samples is significantly different (P < 0.05) from each other. This is the first report on the identification of bacteria associated with rhizosphere, cormosphere and bulk soil of Saffron, using cultivation independent 16S rRNA gene targeted metagenomic approach.

  16. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs.

    Science.gov (United States)

    Saccone, Scott F; Hinrichs, Anthony L; Saccone, Nancy L; Chase, Gary A; Konvicka, Karel; Madden, Pamela A F; Breslau, Naomi; Johnson, Eric O; Hatsukami, Dorothy; Pomerleau, Ovide; Swan, Gary E; Goate, Alison M; Rutter, Joni; Bertelsen, Sarah; Fox, Louis; Fugman, Douglas; Martin, Nicholas G; Montgomery, Grant W; Wang, Jen C; Ballinger, Dennis G; Rice, John P; Bierut, Laura Jean

    2007-01-01

    Nicotine dependence is one of the world's leading causes of preventable death. To discover genetic variants that influence risk for nicotine dependence, we targeted over 300 candidate genes and analyzed 3713 single nucleotide polymorphisms (SNPs) in 1050 cases and 879 controls. The Fagerström test for nicotine dependence (FTND) was used to assess dependence, in which cases were required to have an FTND of 4 or more. The control criterion was strict: control subjects must have smoked at least 100 cigarettes in their lifetimes and had an FTND of 0 during the heaviest period of smoking. After correcting for multiple testing by controlling the false discovery rate, several cholinergic nicotinic receptor genes dominated the top signals. The strongest association was from an SNP representing CHRNB3, the beta3 nicotinic receptor subunit gene (P = 9.4 x 10(-5)). Biologically, the most compelling evidence for a risk variant came from a non-synonymous SNP in the alpha5 nicotinic receptor subunit gene CHRNA5 (P = 6.4 x 10(-4)). This SNP exhibited evidence of a recessive mode of inheritance, resulting in individuals having a 2-fold increase in risk of developing nicotine dependence once exposed to cigarette smoking. Other genes among the top signals were KCNJ6 and GABRA4. This study represents one of the most powerful and extensive studies of nicotine dependence to date and has found novel risk loci that require confirmation by replication studies.

  17. MicroRNA-155 Regulates Inflammatory Cytokine Production in Tumor-associated Macrophages via Targeting C/EBPβ

    Institute of Scientific and Technical Information of China (English)

    Min He; Zhenqun Xu; Tong Ding; Dong-Ming Kuang; Limin Zheng

    2009-01-01

    Macrophages (Mψ) are prominent components of solid tumors and exhibit distinct phenotypes in different microenvironments. We have recently found that tumors can alter the normal developmental process of Mψ to trigger transient activation of monocytes, but the underlying regulatory mechanisms are incompletely understood. Here, we showed that the protein expression of transcription factor C/EBPβ was markedly elevated in tumor-associated Mψ both in vitro and human tumors in situ. The expression of C/EBPβ protein correlated with cytokine production in tumor-activated monocytes. Moreover, we found that C/EBPβ expression was regulated at the post-transcriptional level and correlated with sustained reduction of microRNA-155 (miR-155) in tumor-activated monocytes. Bioinformatic analysis revealed that C/EBPβ is a potential target of miR-155 and luciferase assay confirmed that C/EBPβ translation is suppressed by miR-155 through interaction with the 3'UTR of C/EBPβ mRNA. Further analysis showed that induction of miR-155 suppressed C/EBPβ protein expression as well as cytokine production in tumor-activated monocytes, an effect which could be mimicked by silencing of C/EBPβ. These results indicate that tumor environment causes a sustained reduction of miR-155 in monocytes/Mψ, which in turn regulates the functional activities of monocytes/Mψ by releasing the translational inhibition of transcription factor C/EBPβ. Cellular & Molecular Immunology. 2009;6(5):343-352.

  18. TRANSCULTURALIZATION RECOMMENDATIONS FOR DEVELOPING LATIN AMERICAN CLINICAL PRACTICE ALGORITHMS IN ENDOCRINOLOGY--PROCEEDINGS OF THE 2015 PAN-AMERICAN WORKSHOP BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY.

    Science.gov (United States)

    Mechanick, Jeffrey I; Harrell, R Mack; Allende-Vigo, Myriam Z; Alvayero, Carlos; Arita-Melzer, Onix; Aschner, Pablo; Camacho, Pauline M; Castillo, Rogelio Zacarias; Cerdas, Sonia; Coutinho, Walmir F; Davidson, Jaime A; Garber, Jeffrey R; Garvey, W Timothy; González, Fernando Javier Lavalle; Granados, Denis O; Hamdy, Osama; Handelsman, Yehuda; Jiménez-Navarrete, Manuel Francisco; Lupo, Mark A; Mendoza, Enrique J; Jiménez-Montero, José G; Zangeneh, Farhad

    2016-04-01

    The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) convened their first Workshop for recommendations to optimize Clinical Practice Algorithm (CPA) development for Latin America (LA) in diabetes (focusing on glycemic control), obesity (focusing on weight loss), thyroid (focusing on thyroid nodule diagnostics), and bone (focusing on postmenopausal osteoporosis) on February 28, 2015, in San Jose, Costa Rica. A standardized methodology is presented incorporating various transculturalization factors: resource availability (including imaging equipment and approved pharmaceuticals), health care professional and patient preferences, lifestyle variables, socio-economic parameters, web-based global accessibility, electronic implementation, and need for validation protocols. A standardized CPA template with node-specific recommendations to assist the local transculturalization process is provided. Participants unanimously agreed on the following five overarching principles for LA: (1) there is only one level of optimal endocrine care, (2) hemoglobin A1C should be utilized at every level of diabetes care, (3) nutrition education and increased pharmaceutical options are necessary to optimize the obesity care model, (4) quality neck ultrasound must be part of an optimal thyroid nodule care model, and (5) more scientific evidence is needed on osteoporosis prevalence and cost to justify intervention by governmental health care authorities. This 2015 AACE/ACE Workshop marks the beginning of a structured activity that assists local experts in creating culturally sensitive, evidence-based, and easy-to-implement tools for optimizing endocrine care on a global scale.

  19. Towards Geosocial Recommender Systems

    NARCIS (Netherlands)

    Graaff, de Victor; Keulen, van Maurice; By, de Rolf A.

    2012-01-01

    The usage of social networks sites (SNSs), such as Facebook, and geosocial networks (GSNs), such as Foursquare, has increased tremendously over the past years. The willingness of users to share their current locations and experiences facilitate the creation of geographical recommender systems based

  20. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    Emery, C. A.; Roos, Ewa M.; Verhagen, E.;

    2015-01-01

    The risk of post-traumatic osteoarthritis (PTOA) substantially increases following joint injury. Research efforts should focus on investigating the efficacy of preventative strategies in high quality randomized controlled trials (RCT). The objective of these OARSI RCT recommendations is to inform...

  1. ICRS Recommendation Document

    DEFF Research Database (Denmark)

    Roos, Ewa M.; Engelhart, Luella; Ranstam, Jonas

    2011-01-01

    Abstract Objective: The purpose of this article is to describe and recommend patient-reported outcome instruments for use in patients with articular cartilage lesions undergoing cartilage repair interventions. Methods: Nonsystematic literature search identifying measures addressing pain and funct......Abstract Objective: The purpose of this article is to describe and recommend patient-reported outcome instruments for use in patients with articular cartilage lesions undergoing cartilage repair interventions. Methods: Nonsystematic literature search identifying measures addressing pain...... constructs at all levels according to the International Classification of Functioning. Conclusions: Because there is no obvious superiority of either instrument at this time, both outcome measures are recommended for use in cartilage repair. Rescaling of the Lysholm Scoring Scale has been suggested......, and confirmatory longitudinal studies are needed prior to recommending this scale for use in cartilage repair. Inclusion of a generic measure is feasible in cartilage repair studies and allows analysis of health-related quality of life and health economic outcomes. The Marx or Tegner Activity Rating Scales...

  2. Privacy in recommender systems

    NARCIS (Netherlands)

    Jeckmans, Arjan; Beye, Michael; Erkin, Zekeriya; Hartel, Pieter; Lagendijk, Reginald; Tang, Qiang; Ramzan, Naeem; Zwol, van Roelof; Lee, Jong-Seok; Clüver, Kai; Hua, Xian-Sheng

    2013-01-01

    In many online applications, the range of content that is offered to users is so wide that a need for automated recommender systems arises. Such systems can provide a personalized selection of relevant items to users. In practice, this can help people find entertaining movies, boost sales through ta

  3. The ICRP 2007 recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Streffer, C. [Chairman of ICRP Committee 2, Institute of Science and Ethics, University Duisburg-Essen, 45117 Essen (Germany)

    2007-07-01

    The last comprehensive International Commission on Radiological Protection (ICRP) recommendations have been published in 1991(1). Since that time new data in physics and biology that are relevant for radiological protection have appeared in the scientific literature. Also, the general thinking about safety standards at the workplace as well as for the protection of the public has developed. Thus, a review of the recommendations is needed. However, as the present standards have worked well, these new recommendations should build on the present ones. Only a process of further development should take place allowing for the following key points: - new biological and physical information and trends in the setting of safety standards; - improvement in the presentation of the recommendations; as much stability in the recommendations as is consistent with the new information and environmental aspects will be included. The fundamental principles of radiological protection will remain the same as they have been described in ICRP publication 60(1): Justification: Actions involving new exposures or changes in exposures of individuals have to be justified in advance. A positive net benefit must result. Optimisation: Exposures should be as low as reasonably achievable and should be optimised in relation to with dose constraints. Dose limits: The values will not to be changed from Publication 60. Dose constraints: Development of the concept proposed in Publication 60 will be explained. The ICRP Committees have prepared foundation documents in the fields for which they are responsible and their members have the corresponding expertise. These foundation documents will support the decisions and explain the various statements of the Main Commission in a broader sense. Some of them will be published as Annexes to the recommendations (Annex A: Biological and Epidemiological Information on Health Risks Attributable to Ionising Radiation; Annex B: Quantities used in Radiological

  4. Prevention and control of catheter-associated urinary tract infections – implementation of the recommendations of the Commission for Hospital Hygiene and Infection Prevention (KRINKO in nursing homes for the elderly in Frankfurt am Main, Germany

    Directory of Open Access Journals (Sweden)

    Heudorf, Ursel

    2016-06-01

    Full Text Available Introduction: Urinary tract infections range among the most frequent infections not only in hospital patients but also in residents of long-term care facilities for the elderly. Urinary catheters are the greatest risk factor for urinary tract infections. In the guidance paper on the “prevention of infections in nursing homes” (2005 as well as in the updated recommendations for the “prevention and control of catheter-associated urinary tract infections” (2015, the Commission for Hospital Hygiene and Infection Prevention (KRINKO has recommended adequate preventive measures. In 2015, the implementation of these KRINKO recommendations was investigated.Method: All of Frankfurt’s 40 nursing homes were evaluated using a checklist based on the KRINKO recommendations. The evaluation included assessing the availability of operating instructions, appropriate indications for the placement of catheters etc. Age, sex and duration of catheterization, as well as current and previous infections within the past 6 months were documented for every resident with a catheter.Results: In 35 (87.5% of the nursing homes, operating instructions for the handling of urinary tract catheters were available. The decision as to whether a catheter is indicated is made by physicians, while its placement is often delegated to the nursing service. Typically, silicon catheters are used. In three-quarters of the nursing homes, regular intervals of 4–6 weeks for changing catheters were reported. On the respective survey day, 7.3% of the residents were catheterized. On the survey day, 3.6% (4.2% and in the previous 6 months a total of 28% (28.9% of the residents had a urinary tract infection (prevalence of antibiotic therapy in parentheses. Ciprofloxacin was used most often followed by cefuroxime and cotrimoxazole.Discussion: In the current evaluation, fewer nursing home residents were catheterized than in previous years and the rate of urinary tract infections was low

  5. E-book recommender system design and implementation based on data mining

    Science.gov (United States)

    Wang, Zongjiang

    2011-12-01

    In the knowledge explosion, rapid development of information age, how quickly the user or users interested in useful information for feedback to the user problem to be solved in this article. This paper based on data mining, association rules to the model and classification model a combination of electronic books on the recommendation of the user's neighboring users interested in e-books to target users. Introduced the e-book recommendation and the key technologies, system implementation algorithms, and implementation process, was proved through experiments that this system can help users quickly find the required e-books.

  6. Dietetic recommendations in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    María Rosa Alhambra-Expósito

    2013-12-01

    Full Text Available Rheumatoid arthritis (RA is a chronic autoimmune disease that has a significant effect on patients’ physical, emotional, and social functioning. For decades, patients have used different diets to try to improve the symptoms of RA. The possible benefits of dietary therapy for rheumatoid arthritis are reviewed in this article. Nutritional objectives for RA, are to halt the loss of bone mass, promote healing of bone fractures and improving bone-associated inflammatory disorders and joints. In general, diets low in saturated fat, rich in polyunsaturated fats: omega 3 and omega 6, rich in complex carbohydrates and fiber are recommended.

  7. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

    NARCIS (Netherlands)

    G.B. Ehret (Georg); T. Ferreira (Teresa); D.I. Chasman (Daniel); A.U. Jackson (Anne); E.M. Schmidt (Ellen); T. Johnson (Toby); G. Thorleifsson (Gudmar); J. Luan (Jian'An); L.A. Donnelly (Louise); S. Kanoni (Stavroula); A.K. Petersen; V. Pihur (Vasyl); R.J. Strawbridge (Rona); D. Shungin (Dmitry); Hughes, M.F. (Maria F.); O. Meirelles; M. Kaakinen (Marika); N. Bouatia-Naji (Nabila); K. Kristiansson (Kati); S. Shah (Sonia); M.E. Kleber (Marcus); X. Guo (Xiuqing); L.-P. Lyytikäinen (Leo-Pekka); C. Fava (Cristiano); N. Eriksson (Niclas); I.M. Nolte (Ilja); P.K. Magnusson (Patrik); E. Salfati (Elias); L.S. Rallidis (Loukianos); Theusch, E. (Elizabeth); A.J.P. Smith; L. Folkersen (Lasse); H.E. Witkowska (Ewa); T.H. Pers (Tune); R. Joehanes (Roby); Kim, S.K. (Stuart K.); L. Lataniotis (Lazaros); R. Jansen; A.D. Johnson (Andrew); H. Warren (Helen); Y.J. Kim; Zhao, W. (Wei); Y. Wu (Ying); B. Tayo (Bamidele); M. Bochud (Murielle); D. Absher (Devin); L.S. Adair (Linda); N. Amin (Najaf); D.E. Arking (Dan); T. Axelsson (Tomas); D. Baldassarre (Damiano); B. Balkau (Beverley); S. Bandinelli (Stefania); M. Barnes (Michael); I. Barroso (Inês); Bevan, S. (Stephen); J.C. Bis (Joshua); Bjornsdottir, G. (Gyda); M. Boehnke (Michael); E.A. Boerwinkle (Eric); L.L. Bonnycastle (Lori); D.I. Boomsma (Dorret); S.R. Bornstein (Stefan); M.J. Brown (Morris); M. Burnier (Michel); Cabrera, C.P. (Claudia P.); J.C. Chambers (John); Chang, I.-S. (I-Shou); Cheng, C.-Y. (Ching-Yu); P.S. Chines (Peter); Chung, R.-H. (Ren-Hua); F.S. Collins (Francis); Connell, J.M. (John M.); A. Döring (Angela); J. Dallongeville; J. Danesh (John); U. de Faire (Ulf); G. Delgado; A. Dominiczak (Anna); A.S.F. Doney (Alex); F. Drenos (Fotios); T. Edkins (Ted); Eicher, J.D. (John D.); R. Elosua (Roberto); S. Enroth (Stefan); J. Erdmann (Jeanette); P. Eriksson (Per); T. Esko (Tõnu); E. Evangelou (Evangelos); A. Evans (Alun); M. Fall (Magnus); M. Farrall (Martin); J.F. Felix (Janine); J. Ferrieres (Jean); L. Ferrucci (Luigi); M. Fornage (Myriam); T. Forrester (Terrence); N. Franceschini (Nora); O.H. Franco (Oscar); A. Franco-Cereceda (Anders); R.M. Fraser (Ross); S.K. Ganesh (Santhi); Gao, H. (He); K. Gertow (Karl); F. Gianfagna (Francesco); B. Gigante (Bruna); F. Giulianini (Franco); A. Goel (Anuj); A.H. Goodall (Alison); M. Goodarzi (Mark); M. Gorski (Mathias); J. Gräßler (Jürgen); C.J. Groves (Christopher); V. Gudnason (Vilmundur); U. Gyllensten (Ulf); G. Hallmans (Göran); A.L. Hartikainen; Hassinen, M. (Maija); A.S. Havulinna (Aki); C. Hayward (Caroline); S. Hercberg (Serge); K.H. Herzig; A.A. Hicks (Andrew); A. Hingorani (Aroon); J.N. Hirschhorn (Joel); Hofman, A. (Albert); Holmen, J. (Jostein); O.L. Holmen (Oddgeir); J.J. Hottenga (Jouke Jan); P. Howard (Philip); Hsiung, C.A. (Chao A.); S.C. Hunt (Steven); M.K. Ikram (Kamran); T. Illig (Thomas); C. Iribarren (Carlos); Jensen, R.A. (Richard A.); M. Kähönen (Mika); H.M. Kang (Hyun Min); S. Kathiresan (Sekar); J. Keating (John); K.T. Khaw; Y.K. Kim (Yun Kyoung); E. Kim (Eric); M. Kivimaki (Mika); N. Klopp (Norman); Kolovou, G. (Genovefa); P. Komulainen (Pirjo); J.S. Kooner (Jaspal S.); Kosova, G. (Gulum); R.M. Krauss (Ronald); D. Kuh (Diana); Z. Kutalik (Zoltán); J. Kuusisto (Johanna); K. Kvaløy (Kirsti); T.A. Lakka (Timo); N.R. Lee (Nanette); I.T. Lee; W.-J. Lee (Wen-Jane); D. Levy (Daniel); X. Li (Xiaohui); Liang, K.-W. (Kae-Woei); Lin, H. (Honghuang); Lin, L. (Li); J. Lindström (Jaana); S. Lobbens (Stéphane); S. Männistö (Satu); G. Müller (Gabriele); M. Müller-Nurasyid (Martina); F. MacH (François); H.S. Markus (Hugh); E. Marouli (Eirini); M.I. McCarthy (Mark); C.A. McKenzie (Colin); P. Meneton (Pierre); C. Menni (Cristina); A. Metspalu (Andres); Mijatovic, V. (Vladan); L. Moilanen (Leena); M.E. Montasser (May E.); A.D. Morris (Andrew); A.C. Morrison (Alanna); Mulas, A. (Antonella); R. Nagaraja (Ramaiah); N. Narisu (Narisu); K. Nikus (Kjell); C.J. O'Donnell (Christopher); P.F. O'Reilly (Paul); K.K. Ong (Ken); Paccaud, F. (Fred); C. Palmer (Cameron); A. Parsa (Afshin); N.L. Pedersen (Nancy); B.W.J.H. Penninx (Brenda); M. Perola (Markus); A. Peters (Annette); N.R. Poulter (Neil); P.P. Pramstaller (Peter Paul); B.M. Psaty (Bruce); T. Quertermous (Thomas); D.C. Rao (Dabeeru C.); A. Rasheed (Asif); N.W. Rayner (Nigel William); F. Renström (Frida); R. Rettig (Rainer); K.M. Rice (Kenneth); R. Roberts (Robert); L.M. Rose (Lynda); Rossouw, J. (Jacques); N.J. Samani (Nilesh); S. Sanna (Serena); J. Saramies (Jouko); H. Schunkert (Heribert); S. Sebert (Sylvain); Sheu, W.H.-H. (Wayne H.-H.); Shin, Y.-A. (Young-Ah); X. Sim (Xueling); G.D. Smith; A.V. Smith (Albert Vernon); M.X. Sosa (Maria X.); T.D. Spector (Timothy); A. Stancáková (Alena); A. Stanton (Alice); K. Stirrups (Kathy); H.M. Stringham (Heather); Sundstrom, J. (Johan); A.J. Swift (Amy); A.C. Syvänen; Tai, E.-S. (E-Shyong); T. Tanaka (Toshiko); K.V. Tarasov (Kirill); A. Teumer (Alexander); U. Thorsteinsdottir (Unnur); M.D. Tobin (Martin); E. Tremoli (Elena); Uitterlinden, A.G. (Andre G.); M. Uusitupa (Matti); A. Vaez (Ahmad); D. Vaidya (Dhananjay); Van Duijn, C.M. (Cornelia M.); E.P.A. van Iperen (Erik); Vasan, R.S. (Ramachandran S.); G.C. Verwoert (Germaine); J. Virtamo (Jarmo); Vitart, V. (Veronique); B.F. Voight (Benjamin); P. Vollenweider (Peter); Wagner, A. (Aline); Wain, L.V. (Louise V.); N.J. Wareham (Nick); H. Watkins (Hugh); A.B. Weder (Alan); H.J. Westra (Harm-Jan); Wilks, R. (Rainford); T. Wilsgaard (Tom); J.F. Wilson (James F.); Wong, T.Y. (Tien Y.); T.-P. Yang (Tsun-Po); J. Yao (Jiefen); L. Yengo (Loic); W. Zhang (Weihua); J.H. Zhao; X. Zhu (Xiaofeng); P. Bovet (Pascal); Cooper, R.S. (Richard S.); K.L. Mohlke (Karen); Saleheen, D. (Danish); J.-Y. Lee (Jong-Young); P. Elliott (Paul); L.M. Gierman (Lobke); C.J. Willer (Cristen); L. Franke (Lude); G. Kees Hovingh; K.D. Taylor (Kent); G.V. Dedoussis (George); P. Sever (Peter); A. Wong (Andrew); W.H.L. Kao (Wen); T.L. Assimes (Themistocles); I. Njølstad (Inger); P.E.H. Schwarz (Peter); C. Langenberg (Claudia); H. Snieder (Harold); M. Caulfield (Mark); O. Melander (Olle); M. Laakso (Markku); J. Saltevo (Juha); R. Rauramaa (Rainer); J. Tuomilehto (Jaakko); Ingelsson, E. (Erik); T. Lehtimäki (Terho); K. Hveem (Kristian); W. Palmas (Walter); W. März (Winfried); M. Kumari (Meena); V. Salomaa (Veikko); Y.D. Chen (Y.); Rotter, J.I. (Jerome I.); P. Froguel (Philippe); M.-R. Jarvelin (Marjo-Riitta); E. Lakatta (Edward); K. Kuulasmaa (Kari); P.W. Franks (Paul); A. Hamsten (Anders); H.E. Wichmann (Heinz Erich); C.N.A. Palmer (Colin); Stefansson, K. (Kari); P.M. Ridker (Paul); R.J.F. Loos (Ruth); A. Chakravarti (Aravinda); P. Deloukas (Panagiotis); A.P. Morris (Andrew); C. Newton-Cheh (C.); P. Munroe (Patricia)

    2016-01-01

    textabstractTo dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We

  8. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

    NARCIS (Netherlands)

    Ehret, Georg B.; Ferreira, Teresa; Chasman, Daniel I.; Jackson, Anne U.; Schmidt, Ellen M.; Johnson, Toby; Thorleifsson, Gudmar; Luan, Jian'an; Donnelly, Louise A.; Kanoni, Stavroula; Petersen, Ann -Kristin; Pihurl, Vasyl; Strawbridge, Rona J.; Shungin, Dmitry; Hughes, Maria F.; Meirelles, Osorio; Kaakinen, Marika; Bouatia-Naji, Nabila; Kristiansson, Kati; Shah, Sonia; Kleber, Marcus E.; Guo, Xiuqing; Lyytikainen, Leo-Pekka; Fava, Cristiano; Eriksson, Nidas; Nolte, Ilja M.; Magnusson, Patrik K.; Salfati, Elias L.; Rallidis, Loukianos S.; Theusch, Elizabeth; Smith, Andrew J. P.; Folkersen, Lasse; Witkowska, Kate; Pers, Tune H.; Joehanes, Roby; Kim, Stuart K.; Lataniotis, Lazaros; Jansen, Rick; Johnson, Andrew D.; Warren, Helen; Kim, Young Jin; Zhao, Wei; Wu, Ying; Tayo, Bamidele O.; Bochud, Murielle; Absher, Devin; Adair, Linda S.; Amin, Najaf; Arkingl, Dan E.; Axelsson, Tomas; Baldassarre, Damian; Balkau, Beverley; Bandinelli, Stefania; Barnes, Michael R.; Barroso, Ines; Bevan, Stephen; Bis, Joshua C.; Bjornsdottir, Gyda; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Bornstein, Stefan R.; Brown, Morris J.; Burnier, Michel; Cabrera, Claudia P.; Chambers, John C.; Chang, I-Shou; Cheng, Ching-Yu; Chines, Peter S.; Chung, Ren-Hua; Collins, Francis S.; Connell, John M.; Doring, Angela; Dallongeville, Jean; Danesh, John; de Faire, Ulf; Delgado, Graciela; Dominiczak, Anna F.; Doney, Alex S. F.; Drenos, Fotios; Edkins, Sarah; Eicher, John D.; Elosua, Roberto; Enroth, Stefan; Erdmann, Jeanette; Eriksson, Per; Esko, Tonu; Evangelou, Evangelos; Evans, Alun; Fai, Tove; Farra, Martin; Felixl, Janine F.; Ferrieres, Jean; Ferrucci, Luigi; Fornage, Myriam; Forrester, Terrence; Franceschinil, Nora; Franco, Oscar H.; Franco-Cereceda, Anders; Fraser, Ross M.; Ganesh, Santhi K.; Gao, He; Gertow, Karl; Gianfagna, Francesco; Gigante, Bruna; Giulianini, Franco; Goe, Anuj; Goodall, Alison H.; Goodarzi, Mark; Gorski, Mathias; Grassler, Jurgen; Groves, Christopher J.; Gudnason, Vilmundur; Gyllensten, Ulf; Hallmans, Goran; Hartikainen, Anna-Liisa; Hassinen, Maija; Havulinna, Aki S.; Hayward, Caroline; Hercberg, Serge; Herzig, Karl-Heinz; Hicks, Andrew A.; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofmanl, Albert; Holmen, Jostein; Holmen, Oddgeir Lingaas; Hottenga, Jouke-Jan; Howard, Phil; Hsiung, Chao A.; Hunt, Steven C.; Ikram, M. Arfan; Illig, Thomas; Iribarren, Carlos; Jensen, Richard A.; Kahonen, Mika; Kang, Hyun Min; Kathiresan, Sekar; Keating, Brendan J.; Khaw, Kay-Tee; Kim, Yun Kyoung; Kim, Eric; Kivimaki, Mika; Klopp, Norman; Kolovou, Genovefa; Komulainen, Pirjo; Kooner, Jaspal S.; Kosova, Gulum; Krauss, Ronald M.; Kuh, Diana; Kutalik, Zoltan; Kuusisto, Johanna; Kvaloy, Kirsti; Lakka, Timo A.; Lee, Nanette R.; Lee, I-Te; Lee, Wen-Jane; Levy, Daniel; Li, Xiaohui; Liang, Kae-Woei; Lin, Honghuang; Lin, Li; Lindstrom, Jaana; Lobbens, Stephane; Mannisto, Satu; Muller, Gabriele; Muller-Nurasyid, Martina; Mach, Francois; Markus, Hugh S.; Marouli, Eirini; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Menni, Cristina; Metspalu, Andres; Mijatovic, Vladan; Moilanen, Leena; Montasser, May E.; Morris, Andrew D.; Morrison, Alanna C.; Mulas, Antonella; Nagaraja, Ramaiah; Narisu, Narisu; Nikus, Kjell; O'Donnell, Christopher J.; O'Reilly, Paul F.; Ong, Ken K.; Paccaud, Fred; Palmer, Cameron D.; Parsa, Afshin; Pedersen, Nancy L.; Penninx, Brenda W.; Perola, Markus; Peters, Annette; Poulter, Neil; Pramstaller, Peter P.; Psaty, Bruce M.; Quertermous, Thomas; Rao, Dabeeru C.; Rasheed, Asif; Rayner, N. William; Renstrom, Frida; Rettig, Rainer; Rice, Kenneth M.; Roberts, Robert; Rose, Lynda M.; Rossouw, Jacques; Samani, Nilesh J.; Sanna, Serena; Saramies, Jouko; Schunkert, Heribert; Sebert, Sylvain; Sheu, Wayne H-H; Shin, Young-Ah; Sim, Xueling; Smit, Johannes H.; Smith, Albert V.; Sosa, Maria X.; Spector, Tim D.; Stancakova, Alena; Stanton, Alice V.; Stirrups, Kathleen E.; Stringham, Heather M.; Sundstrom, Johan; Swift, Amy J.; Syvanen, Ann-Christine; Tai, E-Shyong; Tanaka, Toshiko; Tarasov, Kirill V.; Teumer, Alexander; Thorsteinsdottir, Unnur; Tobin, Martin D.; Tremoli, Elena; Uitterlinden, Andre G.; Uusitupa, Matti; Vaez, Ahmad; Vaidya, Dhananjay; van Duijn, Cornelia M.; van Iperen, Erik P. A.; Vasan, Ramachandran S.; Verwoert, Germaine C.; Virtamo, Jarmo; Vitart, Veronique; Voight, Benjamin F.; Vollenweider, Peter; Wagner, Aline; Wain, Louise V.; Wareham, Nicholas J.; Watldns, Hugh; Weder, Alan B.; Westra, Harm Jan; Wilks, Rainford; Wilsgaard, Tom; Wilson, James F.; Wong, Tien Y.; Yang, Tsun-Po; Yao, Jie; Yengo, Loic; Zhang, Weihua; Zhao, Jing Hua; Zhu, Xiaofeng; Bovet, Pascal; Cooper, Richard S.; Mohlke, Karen L.; Saleheen, Danish; Lee, Jong-Young; Elliott, Paul; Gierman, Hinco J.; Willer, Cristen J.; Franke, Lude; Hovingh, G. Kees; Taylor, Kent D.; Dedoussis, George; Sever, Peter; Wong, Andrew; Lind, Lars; Assimes, Themistocles L.; Njolstad, Inger; Schwarz, Peter E. H.; Langenberg, Claudia; Snieder, Harold; Caulfield, Mark J.; Melander, E.; Laakso, Markku; Saltevo, Juha; Rauramaa, Rainer; Tuomilehto, Jaakko; Ingelsson, Erik; Lehtimaki, Terho; Hveem, Kristian; Palmas, Walter; Marz, Winfried; Kumar, Meena; Salomaa, Veikko; Chen, Yii-Der I.; Rotter, Jerome I.; Froguel, Philippe; Jarvelin, Marjo-Riitta; Lakatta, Edward G.; Kuulasmaa, Kari; Franks, Paul W.; Hamsten, Anders; Wichmann, H-Erich; Palmer, Colin N. A.; Stefansson, Kari; Ridker, Paul M.; Loos, Ruth J. F.; Chalcravarti, Aravinda; Deloukas, Panos; Morris, Andrew P.; Newton-Cheh, Christopher; Munroe, Patricia B.

    2016-01-01

    To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66

  9. Dietary patterns are associated with dietary recommendations but have limited relationship to BMI in the Communities Advancing the Studies of Tribal Nations Across the Lifespan (CoASTAL) cohort.

    Science.gov (United States)

    Fialkowski, Marie K; McCrory, Megan A; Roberts, Sparkle M; Tracy, J Kathleen; Grattan, Lynn M; Boushey, Carol J

    2012-10-01

    Traditional food systems in indigenous groups have historically had health-promoting benefits. The objectives of the present study were to determine if a traditional dietary pattern of Pacific Northwest Tribal Nations (PNwT) could be derived using reduced rank regression and if the pattern would be associated with lower BMI and current Dietary Reference Intakes. The baseline data from the Communities Advancing the Studies of Tribal Nations Across the Lifespan (CoASTAL) cohort were used to derive dietary patterns for the total sample and those with plausibly reported energy intakes. Pacific Northwest Coast of Washington State, USA. Adult PNwT members of the CoASTAL cohort with laboratory-measured weight and height and up to 4 d of dietary records (n 418). A traditional dietary pattern did not evolve from the analysis. Moderate consumption of a sweet drinks dietary pattern was associated with lower BMI while higher consumption of a vegetarian-based dietary pattern was associated with higher BMI. The highest consumers of the vegetarian-based dietary pattern were almost six times more likely to meet the recommendations for dietary fibre. Distinct dietary patterns were found. Further exploration is needed to confirm whether the lack of finding a traditional pattern is due to methodology or the loss of a traditional dietary pattern among this population. Longitudinal assessment of the CoASTAL cohort's dietary patterns needs to continue.

  10. Nuclear matrix associated protein PML: an arsenic trioxide apoptosis therapeutic target protein in HepG2 cells

    Institute of Scientific and Technical Information of China (English)

    于鼎; 王子慧; 朱立元; 邱殷庆

    2003-01-01

    Objective To investigate arsenic trioxide (As2O3)-induced apoptosis and the effects on cell nuclear matrix related protein promyelocytic leukaemia (PML). Methods HepG2 cells were cultured in MEM medium and treated with 0.5, 2, 5 and 10 μmol/L As2O3 for either 24 h or 96 h at each concentration. In situ terminal deoxynucleotidyl transferase (TdT) labeling (TUNEL) and DNA ladders were used to detect apoptosis. Confocal microscopy and Western blotting were used to observe the expression of PML. Results The growth rates of HepG2 cells were slower in the As2O3 treated than the untreated control group. DNA ladder and TUNEL positive apoptotic cells could be detected in As2O3 treated groups. The expression of PML decreased in HepG2 cells with 2 μmol/L As2O3 treatment. Confocal images demonstrated that the expression of PML protein in HepG2 cell nuclei decreased after treatment with 2 μmol/L As2O3, and micropunctates characteristic of PML protein in HepG2 cell nuclei disappeared after treatment with 5 μmol/L As2O3.Conclusions Our results show that arsenic trioxide can significantly inhibit the growth of HepG2 cells in vitro. As2O3 induces apoptosis in HepG2 tumor cells in a time and concentration dependent manner. As2O3 may degrade the PML protein in HepG2 cell nuclei. The decreased expression of PML in As2O3 treated tumor cells is most likely to be caused by apoptosis. Nuclear matrix associated protein PML could be the target of As2O3 therapy.

  11. The enteropathogenic E. coli (EPEC Tir effector inhibits NF-κB activity by targeting TNFα receptor-associated factors.

    Directory of Open Access Journals (Sweden)

    Marie-Hélène Ruchaud-Sparagano

    2011-12-01

    Full Text Available Enteropathogenic Escherichia coli (EPEC disease depends on the transfer of effector proteins into epithelia lining the human small intestine. EPEC E2348/69 has at least 20 effector genes of which six are located with the effector-delivery system genes on the Locus of Enterocyte Effacement (LEE Pathogenicity Island. Our previous work implied that non-LEE-encoded (Nle effectors possess functions that inhibit epithelial anti-microbial and inflammation-inducing responses by blocking NF-κB transcription factor activity. Indeed, screens by us and others have identified novel inhibitory mechanisms for NleC and NleH, with key co-operative functions for NleB1 and NleE1. Here, we demonstrate that the LEE-encoded Translocated-intimin receptor (Tir effector has a potent and specific ability to inhibit NF-κB activation. Indeed, biochemical, imaging and immunoprecipitation studies reveal a novel inhibitory mechanism whereby Tir interaction with cytoplasm-located TNFα receptor-associated factor (TRAF adaptor proteins induces their proteasomal-independent degradation. Infection studies support this Tir-TRAF relationship but reveal that Tir, like NleC and NleH, has a non-essential contribution in EPEC's NF-κB inhibitory capacity linked to Tir's activity being suppressed by undefined EPEC factors. Infections in a disease-relevant intestinal model confirm key NF-κB inhibitory roles for the NleB1/NleE1 effectors, with other studies providing insights on host targets. The work not only reveals a second Intimin-independent property for Tir and a novel EPEC effector-mediated NF-κB inhibitory mechanism but also lends itself to speculations on the evolution of EPEC's capacity to inhibit NF-κB function.

  12. Modulation of excitability in human primary somatosensory and motor cortex by paired associative stimulation targeting the primary somatosensory cortex.

    Science.gov (United States)

    Kriváneková, Lucia; Lu, Ming-Kuei; Bliem, Barbara; Ziemann, Ulf

    2011-10-01

    Input from primary somatosensory cortex (S1) to primary motor cortex (M1) is important for high-level motor performance, motor skill learning and motor recovery after brain lesion. This study tested the effects of manipulating S1 excitability with paired associative transcranial stimulation (S1-PAS) on M1 excitability. Given the important role of S1 in sensorimotor integration, we hypothesized that changes in S1 excitability would be directly paralleled by changes in M1 excitability. We applied two established protocols (S1-PAS(LTP) and S1-PAS(LTD) ) to the left S1 to induce long-term potentiation (LTP)-like or long-term depression (LTD)-like plasticity. S1 excitability was assessed by the early cortical components (N20-P25) of the median nerve somatosensory-evoked potential. M1 excitability was assessed by motor-evoked potential amplitude and short-interval intracortical inhibition. Effects of S1-PAS(LTP) were compared with those of a PAS(LTP) protocol targeting the left M1 (M1-PAS(LTP) ). S1-PAS(LTP) and S1-PAS(LTD) did not result in significant modifications of S1 or M1 excitability at the group level due to substantial interindividual variability. The individual S1-PAS-induced changes in S1 and M1 excitability showed no correlation. Furthermore, the individual changes in S1 and M1 excitability induced by S1-PAS(LTP) did not correlate with changes in M1 excitability induced by M1-PAS(LTP) . This demonstrates that the effects of S1-PAS in S1 are variable across individuals and, within a given individual, unrelated to those induced by S1-PAS or M1-PAS in M1. Potentially, this extends the opportunities of therapeutic PAS applications because M1-PAS 'non-responders' may well respond to S1-PAS.

  13. Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system.

    Science.gov (United States)

    Toh, Sengwee; Reichman, Marsha E; Houstoun, Monika; Ross Southworth, Mary; Ding, Xiao; Hernandez, Adrian F; Levenson, Mark; Li, Lingling; McCloskey, Carolyn; Shoaibi, Azadeh; Wu, Eileen; Zornberg, Gwen; Hennessy, Sean

    2012-11-12

    Although certain drugs that target the renin- angiotensin-aldosterone system are linked to an increased risk for angioedema, data on their absolute and comparative risks are limited. We assessed the risk for angioedema associated with the use of angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and the direct renin inhibitor aliskiren. We conducted a retrospective, observational, inception cohort study of patients 18 years or older from 17 health plans participating in the Mini-Sentinel program who had initiated the use of an ACEI (n = 1 845 138), an ARB (n = 467 313), aliskiren (n = 4867), or a β-blocker (n = 1 592 278) between January 1, 2001, and December 31, 2010. We calculated the cumulative incidence and incidence rate of angioedema during a maximal 365-day follow-up period. Using β-blockers as a reference and a propensity score approach, we estimated the hazard ratios of angioedema separately for ACEIs, ARBs, and aliskiren, adjusting for age, sex, history of allergic reactions, diabetes mellitus, heart failure, or ischemic heart disease, and the use of prescription nonsteroidal anti-inflammatory drugs. A total of 4511 angioedema events (3301 for ACEIs, 288 for ARBs, 7 for aliskiren, and 915 for β-blockers) were observed during the follow-up period. The cumulative incidences per 1000 persons were 1.79 (95% CI, 1.73-1.85) cases for ACEIs, 0.62 (95% CI, 0.55-0.69) cases for ARBs, 1.44 (95% CI, 0.58-2.96) cases for aliskiren, and 0.58 (95% CI, 0.54-0.61) cases for β-blockers. The incidence rates per 1000 person-years were 4.38 (95% CI, 4.24-4.54) cases for ACEIs, 1.66 (95% CI, 1.47-1.86) cases for ARBs, 4.67 (95% CI, 1.88-9.63) cases for aliskiren, and 1.67 (95% CI, 1.56-1.78) cases for β-blockers. Compared with the use of β-blockers, the adjusted hazard ratios were 3.04 (95% CI, 2.81-3.27) for ACEIs, 1.16 (95% CI, 1.00-1.34) for ARBs, and 2.85 (95% CI, 1.34-6.04) for aliskiren. Compared with β-blockers, ACEIs or

  14. Rheumatologic rehabilitation: towards recommendations

    Directory of Open Access Journals (Sweden)

    S. Maddali Bongi

    2014-11-01

    Full Text Available Rheumatic patients are highly complex and often affected by chronic diseases. Rehabilitation is generally needed for proper management of the underlying disease. This article describes the characteristics of an effective rheumatologic rehabilitation, takes into account data published in international literature, suggests recommendations based on scientific evidence to develop a correct rehabilitation plan for rheumatic patients and proposes the basis to draw up guidelines in the field of rheumatologic rehabilitation.

  15. Recommending Given Names

    CERN Document Server

    Mitzlaff, Folke

    2013-01-01

    All over the world, future parents are facing the task of finding a suitable given name for their child. This choice is influenced by different factors, such as the social context, language, cultural background and especially personal taste. Although this task is omnipresent, little research has been conducted on the analysis and application of interrelations among given names from a data mining perspective. The present work tackles the problem of recommending given names, by firstly mining for inter-name relatedness in data from the Social Web. Based on these results, the name search engine "Nameling" was built, which attracted more than 35,000 users within less than six months, underpinning the relevance of the underlying recommendation task. The accruing usage data is then used for evaluating different state-of-the-art recommendation systems, as well our new \\NR algorithm which we adopted from our previous work on folksonomies and which yields the best results, considering the trade-off between prediction ...

  16. Algorithms for Academic Search and Recommendation Systems

    DEFF Research Database (Denmark)

    Amolochitis, Emmanouil

    2014-01-01

    In this work we present novel algorithms for academic search, recommendation and association rules mining. In the first part of the work we introduce a novel hierarchical heuristic scheme for re-ranking academic publications. The scheme is based on the hierarchical combination of a custom...... are part of a developed Movie Recommendation system, the first such system to be commercially deployed in Greece by a major Triple Play services provider. In the third part of the work we present the design of a quantitative association rule mining algorithm. The introduced mining algorithm processes...... a specific number of user histories in order to generate a set of association rules with a minimally required support and confidence value. We have introduced a post processor that uses the generated association rules and improves the quality (in terms of recall) of the original recommendation functionality....

  17. Concept-based Recommendations for Internet Advertisement

    CERN Document Server

    Ignatov, Dmitry I

    2009-01-01

    The problem of detecting terms that can be interesting to the advertiser is considered. If a company has already bought some advertising terms which describe certain services, it is reasonable to find out the terms bought by competing companies. A part of them can be recommended as future advertising terms to the company. The goal of this work is to propose better interpretable recommendations based on FCA and association rules.

  18. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: Executive Summary of recommendations

    DEFF Research Database (Denmark)

    Gharib, H; Papini, E; Paschke, R;

    2010-01-01

    American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules are systematically developed statements to assist health care professionals in medical...... decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes...

  19. Systematic literature analysis and review of targeted preventive measures to limit healthcare-associated infections by meticillin-resistant staphylococcus aureus

    NARCIS (Netherlands)

    Köck, R.; Becker, K.; Cookson, B.; Gemert-Pijnen, van J.E.; Harbath, S.; Kluytmans, J.; Mielke, M.; Peters, G.; Skov, R.L.; Struelens, M.J.; Tacconelli, E.; Witte, W.; Friedrich, A.W.

    2014-01-01

    Meticillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated infections in Europe. Many examples have demonstrated that the spread of MRSA within healthcare settings can be reduced by targeted infection control measures. The aim of this systematic literature analysis a

  20. Identification of a novel FGFRL1 MicroRNA target site polymorphism for bone mineral density in meta-analyses of genome-wide association studies

    NARCIS (Netherlands)

    T. Niu (Tianhua); N. Liu (Ning); M. Zhao (Ming); G. Xie (Guie); L. Zhang (Lei); J. Li (Jian); Y.-F. Pei (Yu-Fang); H. Shen (Hui); X. Fu (Xiaoying); H. He (Hao); S. Lu (Shan); X. Chen (Xiangding); L. Tan (Lijun); T.-L. Yang (Tie-Lin); Y. Guo (Yan); P.J. Leo (Paul); E.L. Duncan (Emma); J. Shen (Jie); Y.-F. Guo (Yan-fang); G.C. Nicholson (Geoffrey); R.L. Prince (Richard L.); J.A. Eisman (John); G. Jones (Graeme); P.N. Sambrook (Philip); X. Hu (Xiang); P.M. Das (Partha M.); Q. Tian (Qing); X.-Z. Zhu (Xue-Zhen); C.J. Papasian (Christopher J.); M.A. Brown (Matthew); A.G. Uitterlinden (André G.); Y.-P. Wang (Yu-Ping); S. Xiang (Shuanglin); H.-W. Deng

    2015-01-01

    textabstractMicroRNAs (miRNAs) are critical post-transcriptional regulators. Based on a previous genome-wide association (GWA) scan, we conducted a polymorphism in microRNAs' Target Sites (poly-miRTS)-centric multistage meta-analysis for lumbar spine (LS)-, total hip (HIP)-, and femoral neck (FN)-bo

  1. Association studies in Populus tomentosa reveal the genetic interactions of Pto-MIR156c and its targets in wood formation

    Directory of Open Access Journals (Sweden)

    Mingyang Quan

    2016-08-01

    Full Text Available MicroRNAs (miRNAs regulate gene expression in many biological processes, but the significance of the interaction between a miRNA and its targets in perennial trees remains largely unknown. Here, we employed transcript profiling and association studies in Populus tomentosa (Pto to decipher the effect of genetic variation and interactions between Pto-miR156c and its potential targets (Pto-SPL15, Pto-SPL20, and Pto-SPL25 in 435 unrelated individuals from a natural population of P. tomentosa. Single-SNP (single-nucleotide polymorphism based association studies with analysis of the underlying additive and dominant effects identified 69 significant associations (P 0.05 from Pto-MIR156c and its three potential targets, with six wood and growth traits, revealing their common roles in wood formation. Epistasis analysis uncovered 129 significant SNP-SNP associations with ten traits, indicating the potential genetic interactions of Pto-MIR156c and its three putative targets. Interestingly, expression analysis in stem (phloem, cambium, and xylem revealed that Pto-miR156c expression showed strong negative correlations with Pto-SPL20 (r = -0.90, P < 0.01 and Pto-SPL25 (r = -0.65, P < 0.01, and a positive correlation with Pto-SPL15 (r = 0.40, P < 0.01, which also indicated the putative interactions of Pto-miR156c and its potential targets and their common roles in wood formation. Thus, our study provided an alternative approach to decipher the interaction between miRNAs and their targets and to dissect the genetic architecture of complex traits in trees.

  2. No association between the use of Bti for mosquito control and the dynamics of non-target aquatic invertebrates in French coastal and continental wetlands

    Energy Technology Data Exchange (ETDEWEB)

    Lagadic, Laurent, E-mail: Laurent.Lagadic@rennes.inra.fr [INRA, UMR985 Écologie et Santé des Écosystèmes, Agrocampus Ouest, 65 rue de Saint Brieuc, F-35042 Rennes (France); Schäfer, Ralf B. [Quantitative Landscape Ecology, Institute for Environmental Sciences, University of Koblenz-Landau, Fortstraße 7, D-76829 Landau (Germany); Roucaute, Marc [INRA, UMR985 Écologie et Santé des Écosystèmes, Agrocampus Ouest, 65 rue de Saint Brieuc, F-35042 Rennes (France); Szöcs, Eduard [Quantitative Landscape Ecology, Institute for Environmental Sciences, University of Koblenz-Landau, Fortstraße 7, D-76829 Landau (Germany); Chouin, Sébastien; Maupeou, Jérôme de [Etablissement Interdépartemental pour la Démoustication du Littoral Atlantique, 1 rue Toufaire, F-17300 Rochefort-sur-Mer (France); Duchet, Claire [Entente Interdépartementale pour la Démoustication du Littoral Méditerranéen, 165 avenue Paul-Rimbaud, F-34184 Montpellier (France); and others

    2016-05-15

    The environmental safety of Bacillus thuringiensis subsp. israelensis (Bti) is still controversial, mainly because most of the previous field studies on its undesired effects were spatially limited and did not address the relationship between community similarity and application time and frequency. No general statement can therefore be drawn on the usage conditions of Bti that insure protection of non-target organisms. The present study was conducted in eight sites distributed over the main geographical sectors where mosquito control is implemented in mainland France and Corsica. Changes in non-target aquatic invertebrates were followed at elapsed time after repeated applications of two Bti formulations (VectoBac® WDG or 12AS) up to four consecutive years. We examined the influence of both larvicide treatments and environmental variables on community dynamics and dissimilarity between treated and control areas. As it can be argued that chironomids are the most vulnerable group of non-target invertebrates, we scrutinised potential Bti-related effects on the dynamics of their community. The use of VectoBac® WDG and 12AS in coastal and continental wetlands had no immediate or long-term detectable effect on the taxonomic structure and taxa abundance of non-target aquatic invertebrate communities, including chironomids. This applied to the main habitats where mosquito larvae occur, regardless of their geographic location. Flooding, whose frequency and duration depend on local meteorological and hydrological conditions, was identified as the main environmental driver of invertebrate community dynamics. Our findings add support to the environmental safety of currently available Bti formulations when following recommended application rates and best mosquito control practices. - Highlights: • Bti is used in a variety of continental and coastal wetlands against mosquito larvae. • Bti dosages recommended for mosquito control do not affect non-target invertebrates.

  3. Measurements of double-spin asymmetries associated with deeply virtual Compton scattering on a transversely polarized hydrogen target

    CERN Document Server

    Airapetian, A; Akopov, Z; Aschenauer, E C; Augustyniak, W; Avakian, R; Avetissian, A; Avetisyan, E; Belostotski, S; Bianchi, N; Blok, H P; Borissov, A; Bowles, J; Brodski, I; Bryzgalov, V; Burns, J; Capiluppi, M; Capitani, G P; Cisbani, E; Ciullo, G; Contalbrigo, M; Dalpiaz, P F; Deconinck, W; De Leo, R; De Nardo, L; De Sanctis, E; Di Nezza, P; Dueren, M; Ehrenfried, M; Elbakian, G; Ellinghaus, F; Fabbri, R; Fantoni, A; Felawka, L; Frullani, S; Gabbert, D; Gapienko, G; Gapienko, V; Garibaldi, F; Gavrilov, G; Gharibyan, V; Giordano, F; Gliske, S; Golembiovskaya, M; Hartig, M; Hasch, D; Hoek, M; Holler, Y; Hristova, I; Imazu, Y; Ivanilov, A; Jackson, H E; Jo, H S; Joosten, S; Kaiser, R; Karyan, G; Keri, T; Kinney, E; Kisselev, A; Korotkov, V; Kozlov, V; Kravchenko, P; Krivokhijine, V G; Lagamba, L; Lamb, R; Lapikas, L; Lehmann, I; Lenisa, P; Ruiz, A Lopez; Lorenzon, W; Lu, X -G; Lu, X -R; Ma, B -Q; Mahon, D; Makins, N C R; Manaenkov, S I; Manfre, L; Mao, Y; de la Ossa, B Marianski A Martinez; Marukyan, H; Miller, C A; Miyachi, Y; Movsisyan, A; Murray, M; Mussgiller, A; Nappi, E; Naryshkin, Y; Nass, A; Negodaev, M; Nowak, W -D; Pappalardo, L L; Perez-Benito, R; Raithel, M; Reimer, P E; Reolon, A R; Riedl, C; Rith, K; Rosner, G; Rostomyan, A; Rubin, J; Ryckbosch, D; Salomatin, Y; Schaefer, A; Schnell, G; Schueler, K P; Seitz, B; Shibata, T -A; Shutov, V; Stancari, M; Statera, M; Steffens, E; Steijger, J J M; Stinzing, F; Taroian, S; Terkulov, A; Trzcinski, A; Tytgat, M; Van Haarlem, Y; Van Hulse, C; Veretennikov, D; Vikhrov, V; Vilardi, I; Wang, S; Yaschenko, S; Ye, Z; Yen, S; Zagrebelnyy, V; Zeiler, D; Zihlmann, B; Zupranski, P

    2011-01-01

    Double-spin asymmetries in exclusive electroproduction of real photons from a transversely polarized hydrogen target are measured with respect to the product of target polarization with beam helicity and beam charge, and with respect to the product of target polarization with beam helicity alone. The asymmetries arise from the deeply virtual Compton scattering process and its interference with the Bethe--Heitler process. They are related to the real part of the same combination of Compton form factors as that determining the transverse target single-spin asymmetries through the imaginary part. The results for the double-spin asymmetries are found to be compatible with zero within the uncertainties of the measurement, and are not incompatible with the predictions of the only available GPD-based calculation.

  4. Impact of general practitioners' sex and age on systematic recommendation for cancer screening.

    Science.gov (United States)

    Eisinger, François; Pivot, Xavier; Coscas, Yvan; Viguier, Jérôme; Calazel-Benque, Anne; Blay, Jean-Yves; Roussel, Claire; Morère, Jean-François

    2011-01-01

    associated with systematic recommendation for screening are both a matter of concern and a target for action, to improve adherence of individuals through GP commitment.

  5. Glycation of nail proteins: from basic biochemical findings to a representative marker for diabetic glycation-associated target organ damage.

    Directory of Open Access Journals (Sweden)

    Antoine Sadiki Kishabongo

    Full Text Available Although assessment of glycated nail proteins may be a useful marker for monitoring of diabetes, their nature and formation are still poorly understood. Besides a