WorldWideScience

Sample records for association recommended targets

  1. Economic evaluation of targeted cancer interventions: critical review and recommendations.

    Science.gov (United States)

    Elkin, Elena B; Marshall, Deborah A; Kulin, Nathalie A; Ferrusi, Ilia L; Hassett, Michael J; Ladabaum, Uri; Phillips, Kathryn A

    2011-10-01

    Scientific advances have improved our ability to target cancer interventions to individuals who will benefit most and spare the risks and costs to those who will derive little benefit or even be harmed. Several approaches are currently used for targeting interventions for cancer risk reduction, screening, and treatment, including risk prediction algorithms for identifying high-risk subgroups and diagnostic tests for tumor markers and germline genetic mutations. Economic evaluation can inform decisions about the use of targeted interventions, which may be more costly than traditional strategies. However, assessing the impact of a targeted intervention on costs and health outcomes requires explicit consideration of the method of targeting. In this study, we describe the importance of this principle by reviewing published cost-effectiveness analyses of targeted interventions in breast cancer. Few studies we identified explicitly evaluated the relationships among the method of targeting, the accuracy of the targeting test, and outcomes of the targeted intervention. Those that did found that characteristics of targeting tests had a substantial impact on outcomes. We posit that the method of targeting and the outcomes of a targeted intervention are inextricably linked and recommend that cost-effectiveness analyses of targeted interventions explicitly consider costs and outcomes of the method of targeting.

  2. Drug Target Interference in Immunogenicity Assays: Recommendations and Mitigation Strategies.

    Science.gov (United States)

    Zhong, Zhandong Don; Clements-Egan, Adrienne; Gorovits, Boris; Maia, Mauricio; Sumner, Giane; Theobald, Valerie; Wu, Yuling; Rajadhyaksha, Manoj

    2017-11-01

    Sensitive and specific methodology is required for the detection and characterization of anti-drug antibodies (ADAs). High-quality ADA data enables the evaluation of potential impact of ADAs on the drug pharmacokinetic profile, patient safety, and efficacious response to the drug. Immunogenicity assessments are typically initiated at early stages in preclinical studies and continue throughout the drug development program. One of the potential bioanalytical challenges encountered with ADA testing is the need to identify and mitigate the interference mediated by the presence of soluble drug target. A drug target, when present at sufficiently high circulating concentrations, can potentially interfere with the performance of ADA and neutralizing antibody (NAb) assays, leading to either false-positive or, in some cases, false-negative ADA and NAb assay results. This publication describes various mechanisms of assay interference by soluble drug target, as well as strategies to recognize and mitigate such target interference. Pertinent examples are presented to illustrate the impact of target interference on ADA and NAb assays as well as several mitigation strategies, including the use of anti-target antibodies, soluble versions of the receptors, target-binding proteins, lectins, and solid-phase removal of targets. Furthermore, recommendations for detection and mitigation of such interference in different formats of ADA and NAb assays are provided.

  3. 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/.

  4. Long-rod projectiles against oblique targets: analysis and design recommendations

    International Nuclear Information System (INIS)

    Norris, D.M.; McMaster, W.H.; Wilkins, M.L.

    1976-01-01

    Computer calculations provide an understanding of impact phenomena associated with long rod penetrators striking targets at oblique angles. The rod and target material behaviors are described by elastic-plastic work-hardening constitutive models. Ductile fracture is simulated by setting all tensile and shear stresses to zero when the calculated plastic deformation reaches a critical value. The important penetration material properties to defeat a given target are identified. There is no single material property of overriding importance; a combination of properties is required for an efficient penetrator. Experimental results are presented to demonstrate the effects of ductility and toughness on penetration performance. Recommendations for possible improvement are suggested

  5. 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.

  6. Treating juvenile idiopathic arthritis to target: recommendations of an international task force.

    Science.gov (United States)

    Ravelli, Angelo; Consolaro, Alessandro; Horneff, Gerd; Laxer, Ronald M; Lovell, Daniel J; Wulffraat, Nico M; Akikusa, Jonathan D; Al-Mayouf, Sulaiman M; Antón, Jordi; Avcin, Tadej; Berard, Roberta A; Beresford, Michael W; Burgos-Vargas, Ruben; Cimaz, Rolando; De Benedetti, Fabrizio; Demirkaya, Erkan; Foell, Dirk; Itoh, Yasuhiko; Lahdenne, Pekka; Morgan, Esi M; Quartier, Pierre; Ruperto, Nicolino; Russo, Ricardo; Saad-Magalhães, Claudia; Sawhney, Sujata; Scott, Christiaan; Shenoi, Susan; Swart, Joost F; Uziel, Yosef; Vastert, Sebastiaan J; Smolen, Josef S

    2018-06-01

    Recent therapeutic advances in juvenile idiopathic arthritis (JIA) have made remission an achievable goal for most patients. Reaching this target leads to improved outcomes. The objective was to develop recommendations for treating JIA to target. A Steering Committee formulated a set of recommendations based on evidence derived from a systematic literature review. These were subsequently discussed, amended and voted on by an international Task Force of 30 paediatric rheumatologists in a consensus-based, Delphi-like procedure. Although the literature review did not reveal trials that compared a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated development of recommendations. The group agreed on six overarching principles and eight recommendations. The main treatment target, which should be based on a shared decision with parents/patients, was defined as remission, with the alternative target of low disease activity. The frequency and timeline of follow-up evaluations to ensure achievement and maintenance of the target depend on JIA category and level of disease activity. Additional recommendations emphasise the importance of ensuring adequate growth and development and avoiding long-term systemic glucocorticoid administration to maintain the target. All items were agreed on by more than 80% of the members of the Task Force. A research agenda was formulated. The Task Force developed recommendations for treating JIA to target, being aware that the evidence is not strong and needs to be expanded by future research. These recommendations can inform various stakeholders about strategies to reach optimal outcomes for JIA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Ventilator-associated pneumonia: current status and future recommendations.

    Science.gov (United States)

    Efrati, Shai; Deutsch, Israel; Antonelli, Massimo; Hockey, Peter M; Rozenblum, Ronen; Gurman, Gabriel M

    2010-04-01

    Ventilator-associated pneumonia (VAP) is a common hazardous complication in ICU patients. The aim of the current review is to give an update on the current status and future recommendations for VAP prevention. This article gives an updated review of the current literature on VAP. The first part briefly reviews pathogenesis and epidemiology while the second includes an in-depth review of evidence-based practice guidelines (EBPG) and new technologies developed for prevention of VAP. VAP remains a frequent and costly complication of critical illness with a pooled relative risk of 9-27% and mortality of 25-50%. Strikingly, VAP adds an estimated cost of more than $40,000 to a typical hospital admission. An important aetiological mechanism of VAP is gross or micro-aspiration of oropharyngeal organisms around the cuff of the endotracheal tube (ETT) into the distal bronchi. Prevention of VAP is preferable. Preventative measures can be divided into two main groups: the implemen- tation of EBPGs and use of device-based technologies. EBPGs have been authored jointly by the American Thoracic Society and the Infectious Diseases Society of America. The Canadian Critical Care Trials group also published VAP Guidelines in 2008. Their recommendations are detailed in this review. The current device-based technologies include drainage of subglottic secretions, silver coated ETTs aiming to influence the internal bio-layer of the ETT, better sealing of the lower airways with ultrathin cuffs and loops for optimal cuff pressure control. EBPG consensus includes: elevation of the head of the bed, use of daily "sedation vacations" and decontamination of the oropharynx. Technological solutions should aim to use the most comprehensive combination of subglottic suction of secretions, optimization of ETT cuff pressure and ultrathin cuffs. VAP is a type of hospital-acquired pneumonia that develops more than 48 h after endotracheal intubation. Its incidence is estimated to be 9-27%, with a

  8. [Immunisation schedule of the Spanish Association of Paediatrics: 2018 recommendations].

    Science.gov (United States)

    Moreno-Pérez, David; Álvarez García, Francisco José; Álvarez Aldeán, Javier; Cilleruelo Ortega, María José; Garcés Sánchez, María; García Sánchez, Nuria; Hernández Merino, Ángel; Méndez Hernández, María; Merino Moína, Manuel; Montesdeoca Melián, Abián; Ruiz-Contreras, Jesús

    2018-01-01

    The Advisory Committee on Vaccines of the Spanish Association of Paediatrics annually publishes the immunisation schedule considered optimal for children resident in Spain, according to available evidence on current vaccines. Regarding funded immunisations, 2+1 strategy (2, 4, 11-12 months) with hexavalent (DTPa-IPV-Hib-HB) and 13-valent pneumococcal vaccines are recommended. Administration of the 6-year booster dose with DTPa is recommended, and a poliomyelitis dose for children who had received the 2+1 scheme, as well as Tdap vaccine for adolescents and pregnant women in every pregnancy 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). MMRV vaccine could be applied as the second dose if available. Coverage of human papillomavirus vaccination in girls aged 12 with a two dose scheme (0, 6 months) should be improved. Information and recommendation for male adolescents about potential beneficial effects of this immunisation should be provided as well. The new 9 genotypes vaccine is now available, expanding the coverage for both gender. Regarding non-funded immunisations, Committee on Vaccines of the Spanish Association of Paediatrics recommends meningococcal B vaccination, with a 3+1 schedule, and requests to be included in the National Immunisation Program. Tetravalent meningococcal vaccine (MenACWY) is recommended to adolescents (14-18 years) who are going to live in countries with systematic vaccination against ACWY serogroups, and people >6 weeks of age with risk factors or travellers to countries with very high incidence. Vaccination against rotavirus is recommended in all infants. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Factors associated With Medicaid providers' recommendation of the HPV vaccine to low-income adolescent girls.

    Science.gov (United States)

    Bynum, Shalanda A; Staras, Stephanie A S; Malo, Teri L; Giuliano, Anna R; Shenkman, Elizabeth; Vadaparampil, Susan T

    2014-02-01

    Human papillomavirus (HPV) vaccination in the United States remains a public health challenge with vaccine rates of 50%. Although health care providers can facilitate HPV vaccination, several factors may impede their ability to universally recommend the vaccine. To maximize the potential of HPV vaccines, it is important to understand challenges providers face in the clinical environment. The study sought to identify factors associated with recommendation of the HPV vaccine for low-income adolescents in the early (9-10), target (11-12), early adolescent catch-up (13-14), and late adolescent catch-up (15-17) vaccination groups. Surveys were mailed between October 2009 and April 2010 to a random sample of Florida-based physicians serving Medicaid-enrolled adolescents. Data were analyzed in 2013. Among early adolescents, discomfort discussing sexually transmitted infections (STIs) with teens (odds ratio [OR] = 1.75), difficulty ensuring vaccine completion (OR = .73), and discomfort discussing STIs with parents (OR = .44) were associated with recommendation. For target adolescents, discomfort discussing STIs with teens (OR = 2.45), time constraints (OR = .70), vaccine efficacy concerns (OR = .65), discomfort discussing STIs with parents (OR = .33), obstetrics/gynecology (OR = .25) and family medicine (OR = .24) specialty, and non-Hispanic black patient (OR = .15) were associated with recommendation. In early catch-up adolescents, concerns that teens will practice riskier behaviors (OR = .57), discomfort discussing STIs with parents (OR = .47), and family medicine specialty (OR = .20) were associated with recommendation. For late catch-up adolescents, family medicine specialty (OR = .13) was associated with recommendation. Modifiable factors that impede or influence provider recommendations of HPV vaccines can be addressed through intervention. Overall, findings suggest that efforts should focus on sexuality communication and family medicine specialty

  10. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force

    Science.gov (United States)

    Smolen, Josef S; Breedveld, Ferdinand C; Burmester, Gerd R; Bykerk, Vivian; Dougados, Maxime; Emery, Paul; Kvien, Tore K; Navarro-Compán, M Victoria; Oliver, Susan; Schoels, Monika; Scholte-Voshaar, Marieke; Stamm, Tanja; Stoffer, Michaela; Takeuchi, Tsutomu; Aletaha, Daniel; Andreu, Jose Louis; Aringer, Martin; Bergman, Martin; Betteridge, Neil; Bijlsma, Hans; Burkhardt, Harald; Combe, Bernard; Durez, Patrick; Fonseca, Joao Eurico; Gibofsky, Alan; Gomez-Reino, Juan J; Graninger, Winfried; Hannonen, Pekka; Haraoui, Boulos; Kouloumas, Marios; Landewe, Robert; Martin-Mola, Emilio; Nash, Peter; Ostergaard, Mikkel; Östör, Andrew; Richards, Pam; Sokka-Isler, Tuulikki; Thorne, Carter; Tzioufas, Athanasios G; van Vollenhoven, Ronald; de Wit, Martinus

    2016-01-01

    Background Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. Objective To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. Methods A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. Results The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the

  11. 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.

  12. Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

    Science.gov (United States)

    Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

    Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

  13. Recommendation Techniques for Drug-Target Interaction Prediction and Drug Repositioning.

    Science.gov (United States)

    Alaimo, Salvatore; Giugno, Rosalba; Pulvirenti, Alfredo

    2016-01-01

    The usage of computational methods in drug discovery is a common practice. More recently, by exploiting the wealth of biological knowledge bases, a novel approach called drug repositioning has raised. Several computational methods are available, and these try to make a high-level integration of all the knowledge in order to discover unknown mechanisms. In this chapter, we review drug-target interaction prediction methods based on a recommendation system. We also give some extensions which go beyond the bipartite network case.

  14. 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.

  15. 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....

  16. 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

  17. Shilling Attacks Detection in Recommender Systems Based on Target Item Analysis.

    Science.gov (United States)

    Zhou, Wei; Wen, Junhao; Koh, Yun Sing; Xiong, Qingyu; Gao, Min; Dobbie, Gillian; Alam, Shafiq

    2015-01-01

    Recommender systems are highly vulnerable to shilling attacks, both by individuals and groups. Attackers who introduce biased ratings in order to affect recommendations, have been shown to negatively affect collaborative filtering (CF) algorithms. Previous research focuses only on the differences between genuine profiles and attack profiles, ignoring the group characteristics in attack profiles. In this paper, we study the use of statistical metrics to detect rating patterns of attackers and group characteristics in attack profiles. Another question is that most existing detecting methods are model specific. Two metrics, Rating Deviation from Mean Agreement (RDMA) and Degree of Similarity with Top Neighbors (DegSim), are used for analyzing rating patterns between malicious profiles and genuine profiles in attack models. Building upon this, we also propose and evaluate a detection structure called RD-TIA for detecting shilling attacks in recommender systems using a statistical approach. In order to detect more complicated attack models, we propose a novel metric called DegSim' based on DegSim. The experimental results show that our detection model based on target item analysis is an effective approach for detecting shilling attacks.

  18. Shilling Attacks Detection in Recommender Systems Based on Target Item Analysis

    Science.gov (United States)

    Zhou, Wei; Wen, Junhao; Koh, Yun Sing; Xiong, Qingyu; Gao, Min; Dobbie, Gillian; Alam, Shafiq

    2015-01-01

    Recommender systems are highly vulnerable to shilling attacks, both by individuals and groups. Attackers who introduce biased ratings in order to affect recommendations, have been shown to negatively affect collaborative filtering (CF) algorithms. Previous research focuses only on the differences between genuine profiles and attack profiles, ignoring the group characteristics in attack profiles. In this paper, we study the use of statistical metrics to detect rating patterns of attackers and group characteristics in attack profiles. Another question is that most existing detecting methods are model specific. Two metrics, Rating Deviation from Mean Agreement (RDMA) and Degree of Similarity with Top Neighbors (DegSim), are used for analyzing rating patterns between malicious profiles and genuine profiles in attack models. Building upon this, we also propose and evaluate a detection structure called RD-TIA for detecting shilling attacks in recommender systems using a statistical approach. In order to detect more complicated attack models, we propose a novel metric called DegSim’ based on DegSim. The experimental results show that our detection model based on target item analysis is an effective approach for detecting shilling attacks. PMID:26222882

  19. Strength of recommendations in WHO guidelines using GRADE was associated with uptake in national policy.

    Science.gov (United States)

    Nasser, Syed Muhammad Umar; Cooke, Graham; Kranzer, Katharina; Norris, Susan L; Olliaro, Piero; Ford, Nathan

    2015-06-01

    This study assesses the extent to which the strength of a recommendation in a World Health Organization (WHO) guideline affects uptake of the recommendation in national guidelines. The uptake of recommendations included in HIV and TB guidelines issued by WHO from 2009 to 2013 was assessed across guidelines from 20 low- and middle-income countries in Africa and Southeast Asia. Associations between characteristics of recommendations (strength, quality of the evidence, type) and uptake were assessed using logistic regression. Eight WHO guidelines consisting of 109 strong recommendations and 49 conditional recommendations were included, and uptake assessed across 44 national guidelines (1,255 recommendations) from 20 countries. Uptake of WHO recommendations in national guidelines was 82% for strong recommendations and 61% for conditional recommendations. The odds of uptake comparing strong recommendations and conditional recommendations was 1.9 (95% confidence interval: 1.4, 2.7), after adjustment for quality of evidence. Higher levels of evidence quality were associated with greater uptake, independent of recommendation strength. Guideline developers should be confident that conditional recommendations are frequently adopted. The fact that strong recommendations are more frequently adopted than conditional recommendations underscores the importance of ensuring that such recommendations are justified. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. 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.…

  1. The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients with the recommended dosing regimens.

    Science.gov (United States)

    Haeseker, Michiel; Stolk, Leo; Nieman, Fred; Hoebe, Christian; Neef, Cees; Bruggeman, Cathrien; Verbon, Annelies

    2013-01-01

    The aim of this study was to determine the ciprofloxacin serum concentrations in hospitalized patients and to determine which percentage reached the efficacy target of AUC : MIC > 125. Additionally, the influence of demographic anthropomorphic and clinical parameters on the pharmacokinetics and pharmacodynamics of ciprofloxacin were investigated. In serum of 80 hospitalized patients ciprofloxacin concentrations were measured with reverse phase high performance liquid chromatography with fluorescence detection. The ciprofloxacin dose was 400-1200 mg day(-1) i.v. in two or three doses depending on renal function and causative bacteria. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\\PHARM 3.60). A two compartment open model was used. Mean (± SD) age was 66 (± 17) years, the mean clearance corrected for bodyweight was 0.24 l h(-1) kg(-1) and the mean AUC was 49 mg l(-1) h. Ciprofloxacin clearance and thus AUC were associated with both age and serum creatinine. Of all patients, 21% and 75% of the patients, did not reach the proposed ciprofloxacin AUC : MIC > 125 target with MICs of 0.25 and 0.5 mg l(-1), respectively. A computer simulated increase in the daily dose from 800 mg to 1200 mg, decreased these percentages to 1% and 37%, respectively. A substantial proportion of the hospitalized patients did not reach the target ciprofloxacin AUC : MIC and are suboptimally dosed with recommended doses. Taking into account the increasing resistance to ciprofloxacin worldwide, a ciprofloxacin dose of 1200 mg i.v. daily in patients with normal renal function is necessary to reach the targeted AUC : MIC > 125. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  2. ASSOCIATION RULE ANALYSIS FOR TOUR ROUTE RECOMMENDATION AND APPLICATION TO WCTSNOP

    Directory of Open Access Journals (Sweden)

    H. Fang

    2017-09-01

    Full Text Available 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.

  3. 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.

  4. Are Adults Diagnosed with Diabetes achieving the American Diabetes Association Clinical Practice Recommendations?

    Science.gov (United States)

    Pérez, Cynthia M.; Febo-Vázquez, Isaedmarie; Guzmán, Manuel; Ortiz, Ana Patricia; Suárez, Erick

    2012-01-01

    Objective This study assessed the proportion of adults with previously diagnosed diabetes mellitus (DM) who met selected preventive practices and treatment goals according to the American Diabetes Association (ADA) standards of medical care. Methods A secondary analysis of data collected for a previous epidemiologic study that used a probability cluster design to select 859 persons aged 21–79 years in the San Juan metropolitan area was undertaken. This study focused on 136 (15.8%) adults who self-reported DM. The Standards of Medical Care in Diabetes published by the ADA in 2011 were used to determine the proportion of adults achieving selected clinical practice recommendations. Results Less than half of adults achieved recommended treatment goals for LDL-cholesterol (47.8%), HDL-cholesterol (44.1%), blood pressure (41.2%) and HbA1c (28.7%). The percentage of adults achieving recommended levels of HbA1c, blood pressure and LDL-cholesterol simultaneously was 6.6%; the percentage achieving HbA1c, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides and albumin-to-creatinine ratio target levels was only 2.2%. More than half (60.2%) reported daily self-monitoring of foot ulcers and HbA1c testing at least twice over the past year (52.3%). However, less than half reported annual dilated eye examination (49.2%), annual comprehensive foot examination (43.8%), daily self-monitoring blood glucose (37.5%), moderate or vigorous physical activity (33.8%), and self-management DM education (28.9%). Conclusion This study showed that a substantial proportion of adults with DM did not achieve ADA recommendations on selected preventive practices and treatment goals. Strategies to improve DM medical care and surveillance of preventive-care practices and treatment goals among affected individuals are essential for planning further initiatives that contribute to reduce the burden of DM complications. PMID:22432404

  5. 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

    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

  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 < .001) and in physical education (PE) classes 5 days a week (p < .001) were strongly associated with meeting recommended 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. [RECOMMENDATION FOR EVALUATION AND TREATMENT OF CHRONIC URTICARIA - THE ISRAELI ASSOCIATION FOR ALLERGY AND CLINICAL IMMUNOLOGY].

    Science.gov (United States)

    Levin Agmon, Nancy; Kessel, Aharon; Maoz Segal, Ramit; Rottem, Menachem; Tal, Yuval; Confino-Cohen, Ronit; Tobi, Elias

    2017-06-01

    Chronic urticaria is a disease manifested by a pruritic rash lasting longer than 6 weeks that may severely affect quality of life and daily function. Chronic urticaria can be further divided into chronic spontaneous urticaria which appears without a trigger and chronic inducible urticaria which evolves following distinct physical triggers. These two clinical manifestations could coexist in the same patient. The pathogenesis of chronic urticaria is not fully elucidated, although it is considered an autoimmune disease in at least 50% patients that produce auto- IgG antibodies targeted against the high affinity Fc receptor and to a lesser extent against IgE itself. Auto-antibodies associated with different autoimmune diseases can be detected such as those directed at thyroid proteins. Urticaria tends to spontaneously resolve in 50% of patients within the first year while others will suffer from it for a much longer period of time. The treatment of chronic urticaria has dramatically progressed in the last decade, enabling reduction of systemic corticosteroid use which has been the cornerstone of treatment in the past. The recommended treatment for chronic urticaria is currently based on a stepwise approach that enables achieving disease control with a reasonably good quality of life. The first step of the treatment ladder consists of selective, new generation, anti-H1 histamine blockers, which do not cross the blood brain barrier, starting from the recommended dose (first line) and increasing up to four-fold (second line). The third line of treatment is the addition of immune modulators such as leukotriene receptor blockers (Singulair), anti-IgE biological therapy (Xolair), or cyclosporine. In this review we present the updates and considerations arising during evaluation and treatment of chronic urticaria. The need for specific tests, immunologist/allergologist evaluation, as well as treatment modalities taking into consideration the large body of evidence that has

  8. A Stock Trading Recommender System Based on Temporal Association Rule Mining

    Directory of Open Access Journals (Sweden)

    Binoy B. Nair

    2015-04-01

    Full Text Available Recommender systems capable of discovering patterns in stock price movements and generating stock recommendations based on the patterns thus discovered can significantly supplement the decision-making process of a stock trader. Such recommender systems are of great significance to a layperson who wishes to profit by stock trading even while not possessing the skill or expertise of a seasoned trader. A genetic algorithm optimized Symbolic Aggregate approXimation (SAX–Apriori based stock trading recommender system, which can mine temporal association rules from the stock price data set to generate stock trading recommendations, is presented in this article. The proposed system is validated on 12 different data sets. The results indicate that the proposed system significantly outperforms the passive buy-and-hold strategy, offering scope for a layperson to successfully invest in capital markets.

  9. 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.

  10. Recommendations for the classification of HIV associated neuromanifestations in the German DRG system.

    Science.gov (United States)

    Evers, Stefan; Fiori, W; Brockmeyer, N; Arendt, G; Husstedt, I-W

    2005-09-12

    HIV associated neuromanifestations are of growing importance in the in-patient treatment of HIV infected patients. In Germany, all in-patients have to be coded according to the ICD-10 classification and the German DRG-system. We present recommendations how to code the different primary and secondary neuromanifestations of HIV infection. These recommendations are based on the commentary of the German DRG procedures and are aimed to establish uniform coding of neuromanifestations.

  11. 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.

  12. Recommendations of the Brazilian Society of Rheumatology for the induction therapy of ANCA-associated vasculitis

    Directory of Open Access Journals (Sweden)

    Alexandre Wagner Silva de Souza

    Full Text Available Abstract The purpose of these recommendations is to guide the appropriate induction treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV patients with active disease. The recommendations proposed by the Vasculopathies Committee of the Brazilian Society Rheumatology for induction therapy of AAV, including granulomatosis with polyangiitis, microscopic polyangiitis and renal-limited vasculitis, were based on systematic literature review and expert opinion. Literature review was performed using Medline (PubMed, EMBASE and Cochrane database to retrieve articles until October 2016. PRISMA guidelines were used for the systematic review and articles were assessed according to the Oxford levels of evidence. Sixteen recommendations were made regarding different aspects of induction therapy for AAV. The purpose of these recommendations is to serve as a guide for therapeutic decisions by health care professionals in the management of AAV patients presenting active disease.

  13. Compliance with recommended care at trauma centers: association with patient outcomes.

    Science.gov (United States)

    Shafi, Shahid; Barnes, Sunni A; Rayan, Nadine; Kudyakov, Rustam; Foreman, Michael; Cryer, H Gil; Alam, Hasan B; Hoff, William; Holcomb, John

    2014-08-01

    State health departments and the American College of Surgeons focus on the availability of optimal resources to designate hospitals as trauma centers, with little emphasis on actual delivery of care. There is no systematic information on clinical practices at designated trauma centers. The objective of this study was to measure compliance with 22 commonly recommended clinical practices at trauma centers and its association with in-hospital mortality. This retrospective observational study was conducted at 5 Level I trauma centers across the country. Participants were adult patients with moderate to severe injuries (n = 3,867). The association between compliance with 22 commonly recommended clinical practices and in-hospital mortality was measured after adjusting for patient demographics and injuries and their severity. Compliance with individual clinical practices ranged from as low as 12% to as high as 94%. After adjusting for patient demographics and injury severity, each 10% increase in compliance with recommended care was associated with a 14% reduction in the risk of death. Patients who received all recommended care were 58% less likely to die (odds ratio = 0.42; 95% CI, 0.28-0.62) compared with those who did not. Compliance with commonly recommended clinical practices remains suboptimal at designated trauma centers. Improved adoption of these practices can reduce mortality. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  14. 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.

  15. Association of American Universities Policy Recommendations for President-Elect Obama

    Science.gov (United States)

    Association of American Universities, 2008

    2008-01-01

    In this document, the Association of American Universities offers a series of research and technology policy recommendations that would help our nation to continue its global pre-eminence in science and high technology, improve the quality of life and national security of our citizens, and speed our nation's economic recovery. After policy…

  16. Recommendations of the International Medical Informatics Association (IMIA) on Education in Health and Medical Informatics

    Czech Academy of Sciences Publication Activity Database

    Arokiasamy, J.; Ball, M.; Barnett, D.; Bearman, M.; Bemmel van, J.; Douglas, J.; Fisher, P.; Garrie, R.; Gatewood, L.; Goossen, W.; Grant, A.; Hales, J.; Hasman, A.; Haux, R.; Hovenga, E.; Johns, M.; Knaup, P.; Leven, F. J.; Lorenzi, N.; Murray, P.; Neame, R.; Protti, D.; Power, M.; Richard, J.; Schuster, E.; Swinkels, W.; Yang, J.; Zelmer, L.; Zvárová, Jana

    2001-01-01

    Roč. 40, č. 5 (2001), s. 267-277 ISSN 0026-1270 Institutional research plan: AV0Z1030915 Keywords : health informatics * medical informatics * education * recommendations * International Medical Informatics Association * IMIA Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.254, year: 2001

  17. Glossary of terms recommended for use in radiation control legislation and associated codes of practice

    International Nuclear Information System (INIS)

    Swindon, T.; Kennedy, K.N.; Elliott, G.

    1983-06-01

    A glossary of terms associated with radiological health is presented. It includes basic physics terms, quantities and units, radiological physics terms and radiation protection terms. The National Health and Medical Research Council has recommended that the glossary be used by organizations producing official documents and by appropriate regulatory authorities

  18. Targeting outpatient drug safety: recommendations of the Dutch HARM-Wrestling Task Force.

    NARCIS (Netherlands)

    Warle-van Herwaarden, M.F.; Kramers, C.; Sturkenboom, M.C.; Bemt, P.M. van den; Smet, P.A.G.M. de

    2012-01-01

    BACKGROUND: Two Dutch observational studies (HARM [Hospital Admissions Related to Medication] and IPCI [Integrated Primary Care Information]) have shown that approximately 5% of all unplanned hospital admissions are associated with adverse drug events (ADEs), of which 40-46% are potentially

  19. Smaller Fixation Target Size Is Associated with More Stable Fixation and Less Variance in Threshold Sensitivity.

    Directory of Open Access Journals (Sweden)

    Kazunori Hirasawa

    Full Text Available The aims of this randomized observational case control study were to quantify fixation behavior during standard automated perimetry (SAP with different fixation targets and to evaluate the relationship between fixation behavior and threshold variability at each test point in healthy young participants experienced with perimetry. SAP was performed on the right eyes of 29 participants using the Octopus 900 perimeter, program 32, dynamic strategy. The fixation targets of Point, Cross, and Ring were used for SAP. Fixation behavior was recorded using a wearable eye-tracking glass. All participants underwent SAP twice with each fixation target in a random fashion. Fixation behavior was quantified by calculating the bivariate contour ellipse area (BCEA and the frequency of deviation from the fixation target. The BCEAs (deg2 of Point, Cross, and Ring targets were 1.11, 1.46, and 2.02, respectively. In all cases, BCEA increased significantly with increasing fixation target size (p < 0.05. The logarithmic value of BCEA demonstrated the same tendency (p < 0.05. A positive correlation was identified between fixation behavior and threshold variability for the Point and Cross targets (ρ = 0.413-0.534, p < 0.05. Fixation behavior increased with increasing fixation target size. Moreover, a larger fixation behavior tended to be associated with a higher threshold variability. A small fixation target is recommended during the visual field test.

  20. 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.

  1. Adherence to physical activity recommendations and its associated factors: an interregional population-based study

    Directory of Open Access Journals (Sweden)

    Ala'a Alkerwi

    2015-03-01

    Full Text Available Background. Though the influence of physical activity in preventing cardiovascular diseases is well documented, only a few comparative studies have determined the degree of adherence to physical activity recommendations among populations and identified the demographic, socioeconomic, behavioural and health-related factors associated with good compliance. Design and methods. Cross-sectional interregional NESCaV survey of 3133 subjects compared three populations, Luxembourg, Lorraine (France and Wallonia (Belgium, by using the International Physical Activity Questionnaire. Age and gender prevalence rates of physical activity were standardized to the European population. Results. The likelihood to meet the recommendations was higher in Luxembourg, after adjustment for age, gender, education, employment, weight status, morbidity score, health perception and level of importance attributed to the practice of physical activity (P<0.0001. The odds for meeting the recommendations were significantly higher among those with secondary than tertiary education. Compared to good self-health perception, subjects with poor or fair self-perceived health were less likely to meet the recommendations; this also applied to those attributing little or enough importance to physical activity compared with great importance. Conclusions. Region, education, self-perceived health and perception of importance of physical activity were emerged as independent determinants of meeting the recommendations. Awareness of the positive health effects of physical activity might thus be crucial for motivating the people to become more active. Further research is needed to explore potential region-specific factors which might explain the difference in population behaviours with respect to physical activity.

  2. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee.

    Science.gov (United States)

    Lichtenstein, Alice H; Appel, Lawrence J; Brands, Michael; Carnethon, Mercedes; Daniels, Stephen; Franch, Harold A; Franklin, Barry; Kris-Etherton, Penny; Harris, William S; Howard, Barbara; Karanja, Njeri; Lefevre, Michael; Rudel, Lawrence; Sacks, Frank; Van Horn, Linda; Winston, Mary; Wylie-Rosett, Judith

    2006-07-04

    Improving diet and lifestyle is a critical component of the American Heart Association's strategy for cardiovascular disease risk reduction in the general population. This document presents recommendations designed to meet this objective. Specific goals are to consume an overall healthy diet; aim for a healthy body weight; aim for recommended levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides; aim for normal blood pressure; aim for a normal blood glucose level; be physically active; and avoid use of and exposure to tobacco products. The recommendations are to balance caloric intake and physical activity to achieve and maintain a healthy body weight; consume a diet rich in vegetables and fruits; choose whole-grain, high-fiber foods; consume fish, especially oily fish, at least twice a week; limit intake of saturated fat to foods with added sugars; choose and prepare foods with little or no salt; if you consume alcohol, do so in moderation; and when you eat food prepared outside of the home, follow these Diet and Lifestyle Recommendations. By adhering to these diet and lifestyle recommendations, Americans can substantially reduce their risk of developing cardiovascular disease, which remains the leading cause of morbidity and mortality in the United States.

  3. Evidence-based guidelines for treating bipolar disorder: revised third edition Recommendations from the British Association for Psychopharmacology

    Science.gov (United States)

    Goodwin, G.M.; Haddad, P. M.; Ferrier, I.N.; Aronson, J.K.; Barnes, T.R.H.; Cipriani, A.; Coghill, D.R.; Fazel, S.; Geddes, J.R.; Grunze, H.; Holmes, E.A.; Howes, O.; Hudson, S.; Hunt, N.; Jones, I.; Macmillan, I.C.; McAllister-Williams, H.; Miklowitz, D.M.; Morriss, R.; Munafò, M.; Paton, C.; Saharkian, B.J.; Saunders, K.E.A.; Sinclair, J.M.A.; Taylor, D.; Vieta, E.; Young, A.H.

    2016-01-01

    The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines: in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change. PMID:26979387

  4. Association between patients' recommendation of their GP and their evaluation of the GP.

    Science.gov (United States)

    Vedsted, Peter; Heje, Hanne N

    2008-01-01

    Patient priorities and patient evaluations indicate that accessibility should receive more attention to increase quality in general practice. The definition of family medicine emphasizes the patient-centred approach, communication skills, continuity, and clinical skills. We aimed to explore the associations between the 23 items in the Europep questionnaire measuring patient evaluation of general practice and the patients' recommendation of their general practitioner (GP) to friends and to study the relationship of these items with the core competences of family medicine. Cross-sectional study where patients aged 18 years and over attending the practice were included. Patients completed the Danish version of the 23 item Europep questionnaire and an additional item about the degree to which they could recommend their GP to friends. Danish general practice (the DanPEP study). A total of 50 191 patients and 690 GPs were included in the analyses. For each item, associations were calculated between a positive answer and the degree to which the patient could recommend the GP. Analyses were made at patient and GP levels. We found 12 items that covered the 10 most strongly associated items from both analyses: four of six items from the "doctor-patient relationship", two of five items from "medical care", and all items from "information and support" and "organization of services". No items from "accessibility" were among the 12 items. Recommending the GP to others was most strongly associated with the "emphatic", "patient-oriented", "informative and coordinating", and "competent/skilled" GP and to a lesser degree with accessibility to general practice.

  5. Backrest position in prevention of pressure ulcers and ventilator-associated pneumonia: Conflicting recommendations

    OpenAIRE

    Burk, Ruth Srednicki; Jo Grap, Mary

    2012-01-01

    Pressure ulcers and ventilator-associated pneumonia (VAP) are both common in acute and critical care settings and are considerable sources of morbidity, mortality, and health care costs. To prevent pressure ulcers, guidelines limit bed backrest elevation to less than 30 degrees, whereas recommendations to reduce VAP include use of backrest elevations of 30 degrees or more. Although a variety of risk factors beyond patient position have been identified for both pressure ulcers and VAP, this ar...

  6. SGLT2 Inhibitor-associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis.

    Science.gov (United States)

    Goldenberg, Ronald M; Berard, Lori D; Cheng, Alice Y Y; Gilbert, Jeremy D; Verma, Subodh; Woo, Vincent C; Yale, Jean-François

    2016-12-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of antihyperglycemic agents available on the market. Regulator warnings and concerns regarding the risk of developing diabetic ketoacidosis (DKA), however, have dampened enthusiasm for the class despite the combined glycemic, blood pressure, and occasional weight benefits of SGLT2 inhibitors. With the goal of improving patient safety, a cross-Canada expert panel and writing group were convened to review the evidence to-date on reported SGLT2 inhibitor-related DKA incidents and to offer recommendations for preventing and recognizing patients with SGLT2 inhibitor-associated DKA. Reports covering DKA events in subjects taking SGLT2 inhibitors that were published in PubMed, presented at professional conferences, or in the public domain from January 2013 to mid-August 2016 were reviewed by the group independently and collectively. Practical recommendations for diagnosis and prevention were established by the panel. DKA is rarely associated with SGLT2 inhibitor therapy. Patients with SGLT2 inhibitor-associated DKA may be euglycemic (plasma glucose level SGLT2 inhibitor-associated DKA may be prevented by withholding SGLT2 inhibitors when precipitants develop, avoiding insulin omission or inappropriate insulin dose reduction, and by following sick day protocols as recommended. Preventive strategies should help avoid SGLT2 inhibitor-associated DKA. All SGLT2 inhibitor-treated patients presenting with signs or symptoms of DKA should be suspected to have DKA and be investigated for DKA, especially euglycemic patients. If DKA is diagnosed, SGLT2 inhibitor treatment should be stopped, and the DKA should be treated with a traditional treatment protocol. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  7. Nuclear Security Recommendations on Radioactive Material and Associated Facilities: Recommendations (Spanish Edition); Recomendaciones de Seguridad Fisica Nuclear sobre Materiales Radiactivos e Instalaciones Conexas: Recomendaciones

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-06-15

    The purpose of this publication is to provide guidance to States and competent authorities on how to develop or enhance, implement and maintain a nuclear security regime for facilities dealing with radioactive material and associated activities. This is to be achieved through the establishment or improvement of their capabilities to implement a legislative and regulatory framework to address the security of radioactive material, associated facilities and associated activities in order to reduce the likelihood of malicious acts involving those materials. These recommendations reflect a broad consensus among States on the requirements which should be met for the security of radioactive material, associated facilities and activities.

  8. Toward the Target Model 2.0. Policy Recommendations for a Sustainable EU Power Market Design. Executive summary

    International Nuclear Information System (INIS)

    Roques, Fabien; Perekhodtsev, Dmitri; Verhaeghe, Charles

    2015-06-01

    One of the 10 key priorities of the new European Commission President Jean-Claude Juncker consists of 'reform(ing) and reorganis(ing) Europe's energy policy into a new European Energy Union'. The Energy Union work programme released on 25 February 2015 suggests that a new electricity market design is needed in order to tackle Europe's chosen policy objectives of de-carbonisation whilst maintaining security of supply. The current regulatory and market framework does not provide a sound basis for the investments needed to maintain security of supply and de-carbonise the power sector at an affordable cost. As policy priorities in favour of de-carbonisation and maintaining security of supply have taken centre stage on the policy agenda in the past decade, the design of liberalised electricity markets has failed to evolve and be reconciled with these new priorities. In addition, the issues of competitiveness and affordability of electricity in Europe remain central in the discussions about the market framework. The objective of this study is to assess the deficiencies and gaps in the current European Target Model and the wider regulatory framework for power generation and to propose a number of policy recommendations for improvement. Recognising the need for 'fresh thinking' on the issue, this study looks outside Europe to learn the lessons from experiences with a range of alternative market designs that exist around the globe. The study provides a comprehensive assessment of the issues with current European electricity markets. The study investigates the lessons from market reforms in North America and in Latin America in the past decade to identify 'out of the box' thinking to fill the gaps in the current European Target model. This report presents some of the research findings and concludes with a set of alternative potential directions for reform of European power markets models in the long term, as well as a number of

  9. 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. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

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

    Science.gov (United States)

    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

    Endurance exercise is associated with adverse outcomes in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Exercise recommendations for family members remain undetermined. The purposes of this study were to determine if (1) endurance exercise (Bethesda class C) and exercise intensity (metabolic equivalent hours per year [MET-Hr/year]) increase the likelihood of fulfilling 2010 Task Force Criteria and ventricular arrhythmias/implantable cardioverter-defibrillator shock (ventricular tachycardia/ventricular fibrillation [VT/VF]), and (2) exercise restriction to the American Heart Association (AHA)-recommended minimum for healthy adults is associated with favorable outcomes of at-risk family members. Twenty-eight family members of 10 probands inheriting a PKP2 mutation were interviewed about exercise from age 10. Exercise threshold to maintain overall health was based on the 2007 AHA guidelines of a minimum 390 to 650 MET-Hr/year. After adjustment for age, sex, and family membership, both participation in endurance athletics (odds ratio [OR] 7.4, P = .03) and higher-intensity exercise (OR = 4.2, P = .004) were associated with diagnosis (n = 13). Endurance athletes were also significantly more likely to develop VT/VF (n = 6, P = .02). Family members who restricted exercise at or below the upper bound of the AHA goal (≤650 MET-Hr/year) were significantly less likely to be diagnosed (OR = 0.07, P = .002) and had no VT/VF. At diagnosis and first VT/VF, family members had accumulated 2.8-fold (P = .002) and 3.5-fold (P = .03), respectively, greater MET-Hr exercise than the AHA-recommended minimum. Those who developed VT/VF had performed particularly high-intensity exercise in adolescence compared to unaffected family members (age 10-14: P = .04; age 14-19: P = .02). The results of this study suggest restricting unaffected desmosomal mutation carriers from endurance and high-intensity athletics but potentially not from AHA-recommended

  11. Meeting UK dietary recommendations is associated with higher estimated consumer food costs: an analysis using the National Diet and Nutrition Survey and consumer expenditure data, 2008-2012.

    Science.gov (United States)

    Jones, Nicholas Rv; Tong, Tammy Yn; Monsivais, Pablo

    2018-04-01

    To test whether diets achieving recommendations from the UK's Scientific Advisory Committee on Nutrition (SACN) were associated with higher monetary costs in a nationally representative sample of UK adults. A cross-sectional study linking 4 d diet diaries in the National Diet and Nutrition Survey (NDNS) to contemporaneous food price data from a market research firm. The monetary cost of diets was assessed in relation to whether or not they met eight food- and nutrient-based recommendations from SACN. Regression models adjusted for potential confounding factors. The primary outcome measure was individual dietary cost per day and per 2000 kcal (8368 kJ). UK. Adults (n 2045) sampled between 2008 and 2012 in the NDNS. On an isoenergetic basis, diets that met the recommendations for fruit and vegetables, oily fish, non-milk extrinsic sugars, fat, saturated fat and salt were estimated to be between 3 and 17 % more expensive. Diets meeting the recommendation for red and processed meats were 4 % less expensive, while meeting the recommendation for fibre was cost-neutral. Meeting multiple targets was also associated with higher costs; on average, diets meeting six or more SACN recommendations were estimated to be 29 % more costly than isoenergetic diets that met no recommendations. Food costs may be a population-level barrier limiting the adoption of dietary recommendations in the UK. Future research should focus on identifying systems- and individual-level strategies to enable consumers achieve dietary recommendations without increasing food costs. Such strategies may improve the uptake of healthy eating in the population.

  12. Association of provider recommendation and offer and influenza vaccination among adults aged ≥18 years - United States.

    Science.gov (United States)

    Lu, Peng-Jun; Srivastav, Anup; Amaya, Ashley; Dever, Jill A; Roycroft, Jessica; Kurtz, Marshica Stanley; O'Halloran, Alissa; Williams, Walter W

    2018-02-01

    Influenza vaccination has been recommended for all persons aged ≥6 months since 2010. Data from the 2016 National Internet Flu Survey were analyzed to assess provider vaccination recommendations and early influenza vaccination during the 2016-17 season among adults aged ≥18 years. Predictive marginals from a multivariable logistic regression model were used to identify factors independently associated with early vaccine uptake by provider vaccination recommendation status. Overall, 24.0% visited a provider who both recommended and offered influenza vaccination, 9.0% visited a provider who only recommended but did not offer, 25.1% visited a provider who neither recommended nor offered, and 41.9% did not visit a doctor from July 1 through date of interview. Adults who reported that a provider both recommended and offered vaccine had significantly higher vaccination coverage (66.6%) compared with those who reported that a provider only recommended but did not offer (48.4%), those who neither received recommendation nor offer (32.0%), and those who did not visit a doctor during the vaccination period (28.8%). Results of multivariable logistic regression indicated that having received a provider recommendation, with or without an offer for vaccination, was significantly associated with higher vaccination coverage after controlling for demographic and access-to-care factors. Provider recommendation was significantly associated with influenza vaccination. However, overall, 67.0% of adults did not visit a doctor during the vaccination period or did visit a doctor but did not receive a provider recommendation. Evidence-based strategies such as client reminder/recall, standing orders, provider reminders, or health systems interventions in combination should be undertaken to improve provider recommendation and influenza vaccination coverage. Other factors significantly associated with a higher level of influenza vaccination included age ≥50 years, being Hispanic

  13. Whom to treat? Factors associated with chemotherapy recommendations and outcomes among patients with NHL at the Uganda Cancer Institute.

    Directory of Open Access Journals (Sweden)

    Manoj Menon

    Full Text Available Cancer treatment options in sub-Saharan Africa are scarce despite an increasing burden of disease. Identification of those cancer patients who would benefit most from the limited resources available would allow broader and more effective therapy.We conducted a retrospective analysis of patients over the age of 18 at the time of a pathologic diagnosis of NHL between 2003 and 2010 who were residents of Kyandondo County (Uganda and presented to the Uganda Cancer Institute for care.A total of 128 patients were included in this analysis. Chemotherapy was recommended to 117 (91.4% of the patients; the odds of recommending chemotherapy decreased for each additional month of reported symptoms prior to diagnosis. Of the 117 patients to whom chemotherapy was recommended, 111 (86.7% patients received at least 1 cycle of chemotherapy; HIV infected patients, as well as those with a lower hemoglobin and advanced disease at the time of diagnosis were significantly less likely to complete therapy. Among the patients who initiated chemotherapy, twenty patients died prior to treatment completion (including nine who died within 30 days. Hemoglobin level at the time of presentation was the only variable associated with early mortality in the adjusted model.In resource-poor areas, it is essential to align health care expenditures with interventions likely to provide benefit to affected populations. Targeting cancer therapy to those with a favorable chance of responding will not only save limited resources, but will also prevent harm in those patients unlikely to realize an effect of cancer-directed therapy.

  14. Hyperglycemia Associated With Targeted Oncologic Treatment: Mechanisms and Management.

    Science.gov (United States)

    Goldman, Jonathan W; Mendenhall, Melody A; Rettinger, Sarah R

    2016-07-29

    : Molecularly targeted cancer therapy has rapidly changed the landscape of oncologic care, often improving patients' prognosis without causing as substantial a quality-of-life decrement as cytotoxic chemotherapy does. Nevertheless, targeted agents can cause side effects that may be less familiar to medical oncologists and that require the attention and expertise of subspecialists. In this review, we focus on hyperglycemia, which can occur with use of new anticancer agents that interact with cell proliferation pathways. Key mediators of these pathways include the tyrosine kinase receptors insulin growth factor receptor 1 (IGF-1R) and epidermal growth factor receptor (EGFR), as well as intracellular signaling molecules phosphatidylinositol 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). We summarize available information on hyperglycemia associated with agents that inhibit these molecules within the larger context of adverse event profiles. The highest incidence of hyperglycemia is observed with inhibition of IGF-1R or mTOR, and although the incidence is lower with PI3K, AKT, and EGFR inhibitors, hyperglycemia is still a common adverse event. Given the interrelationships between the IGF-1R and cell proliferation pathways, it is important for oncologists to understand the etiology of hyperglycemia caused by anticancer agents that target those pathways. We also discuss monitoring and management approaches for treatment-related hyperglycemia for some of these agents, with a focus on our experience during the clinical development of the EGFR inhibitor rociletinib. Treatment-related hyperglycemia is associated with several anticancer agents. Many cancer patients may also have preexisting or undiagnosed diabetes or glucose intolerance. Screening can identify patients at risk for hyperglycemia before treatment with these agents. Proper monitoring and management of symptoms, including lifestyle changes and pharmacologic intervention, may allow patients to

  15. Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target

    International Nuclear Information System (INIS)

    Togo, Shinsaku; Polanska, Urszula M.; Horimoto, Yoshiya; Orimo, Akira

    2013-01-01

    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

  16. Semantics based approach for analyzing disease-target associations.

    Science.gov (United States)

    Kaalia, Rama; Ghosh, Indira

    2016-08-01

    A complex disease is caused by heterogeneous biological interactions between genes and their products along with the influence of environmental factors. There have been many attempts for understanding the cause of these diseases using experimental, statistical and computational methods. In the present work the objective is to address the challenge of representation and integration of information from heterogeneous biomedical aspects of a complex disease using semantics based approach. Semantic web technology is used to design Disease Association Ontology (DAO-db) for representation and integration of disease associated information with diabetes as the case study. The functional associations of disease genes are integrated using RDF graphs of DAO-db. Three semantic web based scoring algorithms (PageRank, HITS (Hyperlink Induced Topic Search) and HITS with semantic weights) are used to score the gene nodes on the basis of their functional interactions in the graph. Disease Association Ontology for Diabetes (DAO-db) provides a standard ontology-driven platform for describing genes, proteins, pathways involved in diabetes and for integrating functional associations from various interaction levels (gene-disease, gene-pathway, gene-function, gene-cellular component and protein-protein interactions). An automatic instance loader module is also developed in present work that helps in adding instances to DAO-db on a large scale. Our ontology provides a framework for querying and analyzing the disease associated information in the form of RDF graphs. The above developed methodology is used to predict novel potential targets involved in diabetes disease from the long list of loose (statistically associated) gene-disease associations. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. The Policy Recommendations of the Association of American Geographers as Reflected In the Ventura County Community College.

    Science.gov (United States)

    McDannold, Thomas A.

    A survey was conducted to identify the degree to which the Association of American Geographers (AAG) 1970 recommendations on geography programs in two-year colleges were reflected in geography programs offered in the Ventura County Community College District (California). Results indicated that the recommendations were followed to a great extent,…

  18. Compliance of patients concerning recommended radiotherapy in breast cancer. Association with recurrence, age, and hormonal therapy

    International Nuclear Information System (INIS)

    Winzer, K.J.; Gruber, C.; Badakhshi, H.; Charite Universitaetsmedizin Berlin; Hinkelbein, M.; Denkert, C.

    2012-01-01

    Background and purpose: In this study, we investigated how often guidelines for radiation therapy in patients with breast cancer are not complied with, which patient group is mostly affected, and how this influences local recurrence. Patients and methods: All patients (n = 1,903) diagnosed between November 2003 and December 2008 with primary invasive or intraductal breast cancer in the interdisciplinary breast center of the Charite Hospital Berlin were included and followed for a median 2.18 years. Results: Patients who, in contrast to the recommendation of the interdisciplinary tumor board, did not undergo postoperative radiation experienced a fivefold higher local recurrence rate (p < 0.0005), corresponding to a 5-year locoregional recurrence-free survival of 74.5% in this group. The 5-year locoregional recurrence-free survival of patients following the recommendations was 93.3%. Guideline compliance was dependent on age of patients, acceptance of adjuvant hormonal treatment or chemotherapy, and increased diameter of the primary tumor. Multiple logistic regression analysis showed an association between compliance and age or hormonal therapy. Conclusion: In order to avoid local recurrence patients should be motivated to comply with guideline driven therapy. Since a higher number of local recurrences is observed in health services research compared to clinical research, studies on the value of adjuvant treatment following local recurrence should be performed. (orig.)

  19. Backrest position in prevention of pressure ulcers and ventilator-associated pneumonia: conflicting recommendations.

    Science.gov (United States)

    Burk, Ruth Srednicki; Grap, Mary Jo

    2012-01-01

    Pressure ulcers and ventilator-associated pneumonia (VAP) are both common in acute and critical care settings and are considerable sources of morbidity, mortality, and health care costs. To prevent pressure ulcers, guidelines limit bed backrest elevation to less than 30 degrees, whereas recommendations to reduce VAP include use of backrest elevations of 30 degrees or more. Although a variety of risk factors beyond patient position have been identified for both pressure ulcers and VAP, this article will focus on summarizing the major evidence for each of these apparently conflicting positioning strategies and discuss implications for practice in managing mechanically ventilated patients with risk factors for both pressure ulcers and VAP. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Personal health record use and association with immunizations and well-child care visits recommendations.

    Science.gov (United States)

    Tom, Jeffrey O; Chen, Chuhe; Zhou, Yi Yvonne

    2014-01-01

    To determine the association of parental use of integrated personal health records (PHRs) with children's adherence to immunization and well-child care (WCC) visit recommendations. For the immunization and WCC visit measures, we retrospectively analyzed, respectively, 766 and 639 matched pairs at Kaiser Permanente (KP) Hawaii and 2795 and 2448 pairs at KP Northwest who were ≤ 31 days old at enrollment and continuously enrolled for 2 years between January 2007 and July 2011. The independent variable (≥ 1 PHR feature used vs none) was matched using propensity scores on parental and children characteristics. The dependent variables were 2 measures from the 2010 Healthcare Effectiveness Data and Information Set: combination 2 immunization (all immunizations vs immunizations only at KP Northwest (KP Hawaii: OR 1.1, 95% CI 0.8-1.4, P > .05; KP Northwest OR 1.2, 95% CI 1.0-1.3, P immunizations in only 1 region. Copyright © 2014 Mosby, Inc. All rights reserved.

  1. Recommendations of the International Medical Informatics Association (IMIA) on Education in Biomedical and Health Informatics. First Revision

    NARCIS (Netherlands)

    Mantas, John; Ammenwerth, Elske; Demiris, George; Hasman, Arie; Haux, Reinhold; Hersh, William; Hovenga, Evelyn; Lun, K. C.; Marin, Heimar; Martin-Sanchez, Fernando; Wright, Graham

    2010-01-01

    Objective: The International Medical Informatics Association (IMIA) agreed on revising the existing international recommendations in health informatics/medical informatics education. These should help to establish courses, course tracks or even complete programs in this field, to further develop

  2. Mining association rule based on the diseases population for recommendation of medicine need

    Science.gov (United States)

    Harahap, M.; Husein, A. M.; Aisyah, S.; Lubis, F. R.; Wijaya, B. A.

    2018-04-01

    Selection of medicines that is inappropriate will lead to an empty result at medicines, this has an impact on medical services and economic value in hospital. The importance of an appropriate medicine selection process requires an automated way to select need based on the development of the patient's illness. In this study, we analyzed patient prescriptions to identify the relationship between the disease and the medicine used by the physician in treating the patient's illness. The analytical framework includes: (1) patient prescription data collection, (2) applying k-means clustering to classify the top 10 diseases, (3) applying Apriori algorithm to find association rules based on support, confidence and lift value. The results of the tests of patient prescription datasets in 2015-2016, the application of the k-means algorithm for the clustering of 10 dominant diseases significantly affects the value of trust and support of all association rules on the Apriori algorithm making it more consistent with finding association rules of disease and related medicine. The value of support, confidence and the lift value of disease and related medicine can be used as recommendations for appropriate medicine selection. Based on the conditions of disease progressions of the hospital, there is so more optimal medicine procurement.

  3. Policy recommendations for addressing privacy challenges associated with cell-based research and interventions.

    Science.gov (United States)

    Ogbogu, Ubaka; Burningham, Sarah; Ollenberger, Adam; Calder, Kathryn; Du, Li; El Emam, Khaled; Hyde-Lay, Robyn; Isasi, Rosario; Joly, Yann; Kerr, Ian; Malin, Bradley; McDonald, Michael; Penney, Steven; Piat, Gayle; Roy, Denis-Claude; Sugarman, Jeremy; Vercauteren, Suzanne; Verhenneman, Griet; West, Lori; Caulfield, Timothy

    2014-02-03

    The increased use of human biological material for cell-based research and clinical interventions poses risks to the privacy of patients and donors, including the possibility of re-identification of individuals from anonymized cell lines and associated genetic data. These risks will increase as technologies and databases used for re-identification become affordable and more sophisticated. Policies that require ongoing linkage of cell lines to donors' clinical information for research and regulatory purposes, and existing practices that limit research participants' ability to control what is done with their genetic data, amplify the privacy concerns. To date, the privacy issues associated with cell-based research and interventions have not received much attention in the academic and policymaking contexts. This paper, arising out of a multi-disciplinary workshop, aims to rectify this by outlining the issues, proposing novel governance strategies and policy recommendations, and identifying areas where further evidence is required to make sound policy decisions. The authors of this paper take the position that existing rules and norms can be reasonably extended to address privacy risks in this context without compromising emerging developments in the research environment, and that exceptions from such rules should be justified using a case-by-case approach. In developing new policies, the broader framework of regulations governing cell-based research and related areas must be taken into account, as well as the views of impacted groups, including scientists, research participants and the general public. This paper outlines deliberations at a policy development workshop focusing on privacy challenges associated with cell-based research and interventions. The paper provides an overview of these challenges, followed by a discussion of key themes and recommendations that emerged from discussions at the workshop. The paper concludes that privacy risks associated with cell

  4. 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.

  5. 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.

  6. Consensus recommendations for preventing and managing bleeding complications associated with novel oral anticoagulants in singapore.

    Science.gov (United States)

    Ng, Heng Joo; Chee, Yen Lin; Ponnudurai, Kuperan; Lim, Lay Cheng; Tan, Daryl; Tay, Jam Chin; Handa, Pankaj Kumar; Akbar Ali, Mufeedha; Lee, Lai Heng

    2013-11-01

    Novel oral anticoagulants (NOACs) have at least equivalent efficacy compared to standard anticoagulants with similar bleeding risk. Optimal management strategies for bleeding complications associated with NOACs are currently unestablished. A working group comprising haematologists and vascular medicine specialists representing the major institutions in Singapore was convened to produce this consensus recommendation. A Medline and EMBASE search was conducted for articles related to the 3 available NOACs (dabigatran, rivaroxaban, apixaban), bleeding and its management. Additional information was obtained from the product monographs and bibliographic search of articles identified. The NOACs still has substantial interactions with a number of drugs for which concomitant administration should best be avoided. As they are renally excreted, albeit to different degrees, NOACs should not be prescribed to patients with creatinine clearance of factor VIIa and prothrombin complex may be considered although their effectiveness is currently unsupported by firm clinical evidence. The NOACs have varying effect on the prothrombin time and activated partial thromboplastin time which has to be interpreted with caution. Routine monitoring of drug level is not usually required. NOACs are an important advancement in antithrombotic management and careful patient selection and monitoring will permit optimisation of their potential and limit bleeding events.

  7. Action to Support Practices Implement Research Evidence (ASPIRE): protocol for a cluster-randomised evaluation of adaptable implementation packages targeting 'high impact' clinical practice recommendations in general practice.

    Science.gov (United States)

    Willis, Thomas A; Hartley, Suzanne; Glidewell, Liz; Farrin, Amanda J; Lawton, Rebecca; McEachan, Rosemary R C; Ingleson, Emma; Heudtlass, Peter; Collinson, Michelle; Clamp, Susan; Hunter, Cheryl; Ward, Vicky; Hulme, Claire; Meads, David; Bregantini, Daniele; Carder, Paul; Foy, Robbie

    2016-02-29

    There are recognised gaps between evidence and practice in general practice, a setting which provides particular challenges for implementation. We earlier screened clinical guideline recommendations to derive a set of 'high impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. We aim to evaluate the effectiveness and cost-effectiveness of a multifaceted, adaptable intervention package to implement four targeted, high impact recommendations in general practice. The research programme Action to Support Practice Implement Research Evidence (ASPIRE) includes a pair of pragmatic cluster-randomised trials which use a balanced incomplete block design. Clusters are general practices in West Yorkshire, United Kingdom (UK), recruited using an 'opt-out' recruitment process. The intervention package adapted to each recommendation includes combinations of audit and feedback, educational outreach visits and computerised prompts with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. In trial 1, practices are randomised to adapted interventions targeting either diabetes control or risky prescribing and those in trial 2 to adapted interventions targeting either blood pressure control in patients at risk of cardiovascular events or anticoagulation in atrial fibrillation. The respective primary endpoints comprise achievement of all recommended target levels of haemoglobin A1c (HbA1c), blood pressure and cholesterol in patients with type 2 diabetes, a composite indicator of risky prescribing, achievement of recommended blood pressure targets for specific patient groups and anticoagulation prescribing in patients with atrial fibrillation. We are also randomising practices to a fifth, non-intervention control group to further assess Hawthorne effects. Outcomes will be assessed using routinely collected data

  8. 28 CFR 0.165 - Recommendations to the Deputy Attorney General or Associate Attorney General, as appropriate...

    Science.gov (United States)

    2010-07-01

    ... General or Associate Attorney General, as appropriate, that certain claims be closed. 0.165 Section 0.165... Recommendations to the Deputy Attorney General or Associate Attorney General, as appropriate, that certain claims... the authority delegated by §§ 0.160(a) and 0.164, the Assistant Attorney General concerned shall, when...

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

    DEFF Research Database (Denmark)

    Miskowiak, K W; Burdick, K E; Martinez-Aran, A

    2017-01-01

    OBJECTIVES: 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. METHODS...... 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...... of treatments to illness stage and using a multimodal approach. CONCLUSIONS: 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...

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

    DEFF Research Database (Denmark)

    Miskowiak, K W; Burdick, K E; Martinez-Aran, A

    2017-01-01

    OBJECTIVES: 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. METHODS...... of treatments to illness stage and using a multimodal approach. CONCLUSIONS: 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...

  11. 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

  12. Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative.

    Science.gov (United States)

    Constantin, Tamas; Foeldvari, Ivan; Anton, Jordi; de Boer, Joke; Czitrom-Guillaume, Severine; Edelsten, Clive; Gepstein, Raz; Heiligenhaus, Arnd; Pilkington, Clarissa A; Simonini, Gabriele; Uziel, Yosef; Vastert, Sebastian J; Wulffraat, Nico M; Haasnoot, Anne-Mieke; Walscheid, Karoline; Pálinkás, Annamária; Pattani, Reshma; Györgyi, Zoltán; Kozma, Richárd; Boom, Victor; Ponyi, Andrea; Ravelli, Angelo; Ramanan, Athimalaipet V

    2018-03-28

    In 2012, a European initiative called S ingle Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is possibly its most devastating extra-articular manifestation. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. Consequently, treatment practices differ widely, within and between nations. To provide recommendations for the diagnosis and treatment of JIA-associated uveitis. Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of nine experienced paediatric rheumatologists and three experts in ophthalmology from Europe. Recommendations derived from a validated systematic literature review were evaluated by an Expert Committee and subsequently discussed at two consensus meetings using nominal group techniques. Recommendations were accepted if >80% agreement was reached (including all three ophthalmologists). In total, 22 recommendations were accepted (with >80% agreement among experts): 3 on diagnosis, 5 on disease activity measurements, 12 on treatment and 2 on future recommendations. The SHARE initiative aims to identify best practices for treatment of patients suffering from JIA-associated uveitis. Within this remit, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated by an evidence-informed consensus process to suggest a standard of care for JIA-associated uveitis patients throughout Europe. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. Research on intelligent recommendation algorithm of e-commerce based on association rules

    Science.gov (United States)

    Shen, Jiajie; Cheng, Xianyi

    2017-09-01

    As the commodities of e-commerce are more and more rich, more and more consumers are willing to choose online shopping, because of these rich varieties of commodity information, customers will often appear aesthetic fatigue. Therefore, we need a recommendation algorithm according to the recent behavior of customers including browsing and consuming to predicate and intelligently recommend goods which the customers need, thus to improve the satisfaction of customers and to increase the profit of e-commerce. This paper first discusses recommendation algorithm, then improves Apriori. Finally, using R language realizes a recommendation algorithm of commodities. The result shows that this algorithm provides a certain decision-making role for customers to buy commodities.

  14. 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,

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

    OpenAIRE

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

    2015-01-01

    International audience; IntroductionIn 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 years 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. Patients and methodsA survey was proposed to 706 general...

  16. 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.

  17. 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

  18. Proceedings of the 15th nuclear safety research association symposium ICRP's 2005 Recommendations on radiological protection

    International Nuclear Information System (INIS)

    2003-02-01

    This is the document of the Symposium in the title, held in Tokyo, 2003. The document contains the greeting by chairperson (Toshiso Kosako, International Commission of Radiological Protection (ICRP) member, Tokyo University): lecture 1; for the title subject presented as ''ICRP's 2005 Recommendations on Radiological Protection'' with its slides entitled ''The Evolution of the System of Radiological Protection-The Justification for ICRP's 2005 Recommendations'' by L.-E. Holm (ICRP Vice-Chairman, Swedish Radiation Protection Authority): lecture 2; ''Protection of the Environment: from Ethics to Genetics''' with slides, ''Ionising Radiation and the Environment'', by R. J. Pentreath (ICRP member, The University of Reading, the United Kingdom (UK)): respectively followed by discussion with 3 Japanese panelists for each lecture: and chairperson's summary. The chair's greeting is about the rise of interest in environmental radiation protection, its background, and related trends in The Organization for Economic Co-operation and Development (OECD)/Nuclear Energy Agency (NEA) Committee on Radiation Protection and Public Health (CRPPH). L-EH's presentation involves sections of the background of the recommendations and protection of the environment, mentioning some of the proposed changes in the Commission's recommendations for its 2005 Recommendations. RJP's presentation involves sections of a philosophical platform, environmental management, relevance to radiation and its effects, points of reference and discussion where the impact of radionuclides and radiation in environment on various biological systems is mentioned in view for future. (R.T.)

  19. 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

  20. How Picture Books on the National Science Teacher's Association Recommend List Portray Scientists

    Science.gov (United States)

    Farland-Smith, Donna; Finson, Kevin D.; Arquette, Cecile M.

    2017-01-01

    This study utilized the Draw-A-Scientist Test Checklist (DAST-C) to assess the illustrations of scientists in the most recent three years of NSTA Recommends book lists. A total of 15,778 images were contained in the 148 books from those lists, of which 1,676 were of scientists. ANOVA procedures revealed no significant differences in stereotypical…

  1. CanVasc recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides - Executive summary.

    Science.gov (United States)

    McGeoch, Lucy; Twilt, Marinka; Famorca, Leilani; Bakowsky, Volodko; Barra, Lillian; Benseler, Susan; Cabral, David A; Carette, Simon; Cox, Gerald P; Dhindsa, Navjot; Dipchand, Christine; Fifi-Mah, Aurore; Goulet, Michele; Khalidi, Nader; Khraishi, Majed M; Liang, Patrick; Milman, Nataliya; Pineau, Christian A; Reich, Heather; Samadi, Nooshin; Shojania, Kam; Taylor-Gjevre, Regina; Towheed, Tanveer E; Trudeau, Judith; Walsh, Michael; Yacyshyn, Elaine; Pagnoux, Christian

    2015-01-01

    The Canadian Vasculitis research network (CanVasc) is composed of physicians from different medical specialties, including rheumatology and nephrology and researchers with expertise in vasculitis. One of its aims was to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides in Canada. This executive summary features the 19 recommendations and 17 statements addressing general AAV diagnosis and management, developed by CanVasc group based on a synthesis of existing international guidelines, other published supporting evidence and expert consensus considering the Canadian healthcare context.

  2. CanVasc Recommendations for the Management of Antineutrophil Cytoplasm Antibody (ANCA-Associated Vasculitides – Executive Summary

    Directory of Open Access Journals (Sweden)

    Lucy McGeoch

    2015-11-01

    Full Text Available The Canadian Vasculitis research network (CanVasc is composed of physicians from different medical specialties, including rheumatology and nephrology and researchers with expertise in vasculitis. One of its aims was to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA-associated vasculitides in Canada. This executive summary features the 19 recommendations and 17 statements addressing general AAV diagnosis and management, developed by CanVasc group based on a synthesis of existing international guidelines, other published supporting evidence and expert consensus considering the Canadian healthcare context.

  3. Mobile Phone Use and its Association With Sitting Time and Meeting Physical Activity Recommendations in a Mexican American Cohort.

    Science.gov (United States)

    Chrisman, Matthew; Chow, Wong-Ho; Daniel, Carrie R; Wu, Xifeng; Zhao, Hua

    2016-06-16

    The benefits of physical activity (PA) are well-documented. Mobile phones influence PA by promoting screen-based sedentary time, providing prompts or reminders to be active, aiding in tracking and monitoring PA, or providing entertainment during PA. It is not known how mobile phone use is associated with PA and sitting time in Mexican Americans, and how mobile phone users may differ from nonusers. To determine the associations between mobile phone use, PA, and sitting time and how these behaviors differ from mobile phone nonusers in a sample of 2982 Mexican-American adults from the Mano a Mano cohort. Differences in meeting PA recommendations and sitting time between mobile phone users and nonusers were examined using chi-square and analysis of variance tests. Logistic regression was used to examine associations between mobile phone use, PA, and sitting. Mobile phone users were more likely to be obese by body mass index criteria (≥30 kg/m(2)), younger, born in the United States and lived there longer, more educated, and sit more hours per day but more likely to meet PA recommendations than nonusers. Males (odds ratio [OR] 1.42, 95% CI 1.16-1.74), use of text messaging (OR 1.26, 95% CI 1.03-1.56), and having a higher acculturation score (OR 1.27, 95% CI 1.07-1.52) were associated with higher odds of meeting PA recommendations. Sitting more hours per day was associated with being male, obese, born in the United States, a former alcohol drinker, and having at least a high school education. Among nonusers, being born in the United States was associated with higher odds of more sitting time, and being married was associated with higher odds of meeting PA recommendations. Mobile phone interventions using text messages could be tailored to promote PA in less acculturated and female Mexican American mobile phone users.

  4. Adherence to Dietary Recommendations Is Associated with Acculturation among Latino Farm Workers12

    OpenAIRE

    Matias, Susana L.; Stoecklin-Marois, Maria T.; Tancredi, Daniel J.; Schenker, Marc B.

    2013-01-01

    We examined adherence to dietary recommendations on fruit/vegetable and fat intake and identified correlates with acculturation indicators as well as with family, lifestyle, and occupational factors in a farm worker cohort in central California. Interviewer-administered questionnaires for this cross-sectional study were completed from January 2006 to April 2007. Participants were 18- to 55-y-old Latinos living in Mendota in a farm worker household. We assessed fruit/vegetable consumption and ...

  5. European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor-Targeted Therapy

    NARCIS (Netherlands)

    Powles, Thomas; Staehler, Michael; Ljungberg, Börje; Bensalah, Karim; Canfield, Steven E; Dabestani, Saeed; Giles, Rachel H; Hofmann, Fabian; Hora, Milan; Kuczyk, Markus A; Lam, Thomas; Marconi, Lorenzo; Merseburger, Axel S; Volpe, Alessandro; Bex, Axel

    2016-01-01

    The European Association of Urology renal cancer guidelines panel recommends nivolumab and cabozantinib over the previous standard of care in patients who have failed one or more lines of vascular endothelial growth factor-targeted therapy. New data have recently become available showing a survival

  6. 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.

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

    Science.gov (United States)

    Sebastian, Rhonda S; Wilkinson Enns, Cecilia; Goldman, Joseph D

    2009-02-01

    To determine whether fast-food consumption is associated with adolescents' food group intakes and likelihood of meeting recommendations outlined in the MyPyramid Food Guidance System. Data from two 24-hour recalls collected in What We Eat in America, National Health and Nutrition Examination Survey 2003-2004 were analyzed. Fast-food consumers were divided into tertiles based on the proportion of 2-day energy intake derived from fast food. Adolescent boys and nonpregnant girls aged 12 to 19 years (n=1,956). All statistical analyses included sample weights to account for the survey design. Regression analyses were used to detect associations between fast-food consumption and both food group intakes and percentages of individuals meeting MyPyramid recommendations, and to predict odds of meeting recommendations by fast-food consumption level. Fast-food consumption was associated negatively with MyPyramid fruit and milk group intakes (boys and girls) and positively with discretionary energy and solid fats (girls only). Negative associations were also found between fast-food consumption and percentages of adolescents meeting recommendations for milk (boys), fruits (girls), and vegetables and discretionary energy (boys and girls). Compared with those consuming no fast food, adolescents in the highest tertile of energy from fast food were less likely to meet recommendations for vegetables (odds ratio [OR]=0.16, 95% confidence interval [CI]: 0.05 to 0.52 for boys; OR=0.18, 95% CI: 0.04 to 0.79 for girls) and discretionary energy (OR=0.41, 95% CI: 0.22 to 0.77 for boys; OR=0.04, 95% CI: 0.01 to 0.24 for girls). No relationships were found between fast-food consumption and grains, meat/beans, and oils. Adolescents' intakes, whether containing fast food or not, need improvement. Fast food is one factor that impacts adolescents' intake of MyPyramid groups and their likelihood of meeting recommendations. Awareness of fast-food's role in discrepancies between adolescent intakes

  8. Translation and implementation of added sugars consumption recommendations: a conference report from the American Heart Association Added Sugars Conference 2010.

    Science.gov (United States)

    Van Horn, Linda; Johnson, Rachel K; Flickinger, Brent D; Vafiadis, Dorothea K; Yin-Piazza, Shirley

    2010-12-07

    A 2-day forum was convened to (1) discuss ways to translate the 2009 American Heart Association added sugars recommendations into actions in areas such as regulation, food labeling, nutrient content claims, and practical application in the American diet; (2) review surveillance methodology and metrics for tracking and understanding the impact of reducing added sugars in the diet; and (3) initiate the development of a framework for future collaboration to help Americans implement science-based guidance relative to added sugars. More than 100 multinational participants representing scientists from academia and government and stakeholders engaged in food production, development, and processing, food manufacturing and servicing, food and nutrition policy, and nutrition recommendations for the public attended the conference. Presentations included definitions and examples of added sugars, current US and international added sugars perspectives, added sugars in diets of individuals and in the food supply, food technology behind added sugars, added sugars and health, food manufacturer perspectives, added sugars food-labeling considerations, and examples of positive approaches to improve eating behaviors and the food environment. Facilitated breakout sessions were conducted after the plenary sessions to allow participants to contribute their expertise and thoughts. The American Heart Association Added Sugars Conference is the first step in an important process that facilitates collaboration across science, public health, and industry to foster innovation, partnerships, policy, and implementation of new products and services for the benefit of the health and well-being of the American public. Science has advanced in the area of added sugars and health, creating mounting pressure to use better methods for translation and dissemination of the science for consumer education and for food companies to respond by producing foods and beverages with fewer added sugars. The new

  9. 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

    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...... 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...

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

    Directory of Open Access Journals (Sweden)

    Xiao-Hong Wang

    2015-01-01

    Full Text Available 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 internus (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.

  11. 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. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Recommendations for managing patients with diabetes mellitus in cardiopulmonary rehabilitation: an American Association of Cardiovascular and Pulmonary Rehabilitation statement.

    Science.gov (United States)

    Lopez-Jimenez, Francisco; Kramer, Valerie Carroll; Masters, Barbara; Stuart, Patricia Mickey W; Mullooly, Cathy; Hinshaw, Ling; Haas, Linda; Warwick, Kathy

    2012-01-01

    Diabetes mellitus is a highly prevalent condition in patients participating in cardiopulmonary rehabilitation. However, research and subsequent guidelines specifically applicable to patients with diabetes, participating in cardiopulmonary rehabilitation, are limited. Recognizing this limitation, the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) initiated this statement, with the goal of developing a template that incorporated recommendations provided in the AACVPR Core Components and the American Association of Diabetes Educators 7 Self-Care Behaviors. This statement describes key processes regarding evaluation, interventions, and expected outcomes in each of the core components for the management of patients with diabetes in a cardiopulmonary rehabilitation program.

  13. SRMDAP: SimRank and Density-Based Clustering Recommender Model for miRNA-Disease Association Prediction

    Directory of Open Access Journals (Sweden)

    Xiaoying Li

    2018-01-01

    Full Text Available Aberrant expression of microRNAs (miRNAs can be applied for the diagnosis, prognosis, and treatment of human diseases. Identifying the relationship between miRNA and human disease is important to further investigate the pathogenesis of human diseases. However, experimental identification of the associations between diseases and miRNAs is time-consuming and expensive. Computational methods are efficient approaches to determine the potential associations between diseases and miRNAs. This paper presents a new computational method based on the SimRank and density-based clustering recommender model for miRNA-disease associations prediction (SRMDAP. The AUC of 0.8838 based on leave-one-out cross-validation and case studies suggested the excellent performance of the SRMDAP in predicting miRNA-disease associations. SRMDAP could also predict diseases without any related miRNAs and miRNAs without any related diseases.

  14. 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

  15. 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.

  16. 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. Copyright © 2011 Mosby, Inc. All rights reserved.

  17. Rho-associated kinase is a therapeutic target in neuroblastoma.

    Science.gov (United States)

    Dyberg, Cecilia; Fransson, Susanne; Andonova, Teodora; Sveinbjörnsson, Baldur; Lännerholm-Palm, Jessika; Olsen, Thale K; Forsberg, David; Herlenius, Eric; Martinsson, Tommy; Brodin, Bertha; Kogner, Per; Johnsen, John Inge; Wickström, Malin

    2017-08-08

    Neuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. Here we show that neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma patients, and elevated expression of Rho-associated kinase (ROCK)2 is associated with poor patient survival. Pharmacological or genetic inhibition of ROCK1 and 2, key molecules in Rho signaling, resulted in neuroblastoma cell differentiation and inhibition of neuroblastoma cell growth, migration, and invasion. Molecularly, ROCK inhibition induced glycogen synthase kinase 3β-dependent phosphorylation and degradation of MYCN protein. Small-molecule inhibition of ROCK suppressed MYCN -driven neuroblastoma growth in TH- MYCN homozygous transgenic mice and MYCN gene-amplified neuroblastoma xenograft growth in nude mice. Interference with Rho/Rac signaling might offer therapeutic perspectives for high-risk neuroblastoma.

  18. 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. Crown Copyright © 2016. Published by Elsevier Inc. All rights

  19. Adoption of American Heart Association 2020 ideal healthy diet recommendations prevents weight gain in young adults.

    Science.gov (United States)

    Forget, Geneviève; Doyon, Myriam; Lacerte, Guillaume; Labonté, Mélissa; Brown, Christine; Carpentier, André C; Langlois, Marie-France; Hivert, Marie-France

    2013-11-01

    In 2010, the American Heart Association established the concept of ideal cardiovascular health. Nationally representative data estimated that Healthy Diet Score. In a cohort of young adults (N=196), we aimed to investigate the prevalence of ideal cardiovascular health and ideal Healthy Diet Score and its association to weight gain over a 4-year follow-up period. Anthropometric measures, blood pressure, and blood samples were taken according to standardized procedures. Dietary intake was measured by a 3-day food diary and verified by a registered dietitian. We observed that only 0.5% of our sample met the criteria for ideal cardiovascular health and only 4.1% met the criteria for an ideal Healthy Diet Score. The components of the Healthy Diet Score with the lowest observance were consumption of fruits and vegetables (9.7%) and whole grains (14.8%). Meeting zero or one out of five of the Healthy Diet Score components was associated with increased risk of weight gain over 4 years compared with meeting at least two components (P=0.03). With the exception of dietary criteria, prevalence was high for achieving ideal levels of the remaining six cardiovascular health metrics. In conclusion, in this sample of young adults, a very low prevalence of ideal overall cardiovascular health was observed, mainly driven by poor dietary habits, and a poor Healthy Diet Score was associated with increased weight gain. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  20. Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome

    OpenAIRE

    Burkhart, Keith K.; Abernethy, Darrell; Jackson, David

    2015-01-01

    Drug features that are associated with Stevens-Johnson syndrome (SJS) have not been fully characterized. A molecular target analysis of the drugs associated with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to mechanistic insights into SJS pathophysiology. The publicly available version of FAERS was analyzed to identify disproportionality among the molecular targets, metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS in-house version was al...

  1. 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. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  2. The association between compliance with recommended follow-up and glaucomatous disease severity in a county hospital population.

    Science.gov (United States)

    Ung, Cindy; Murakami, Yohko; Zhang, Elisa; Alfaro, Tatyana; Zhang, Monica; Seider, Michael I; Singh, Kuldev; Lin, Shan C

    2013-08-01

    To assess the association between insufficient follow-up and clinical parameters such as disease severity and medication use among glaucoma patients at a metropolitan county hospital. Cross-sectional study. Two-hundred and six patients with established glaucoma were recruited from San Francisco General Hospital. Subjects were classified based on compliance with recommended follow-up examination intervals over the year preceding commencement of the study, as determined by patient medical records. Glaucoma severity was determined based on the American Academy of Ophthalmology Preferred Practice Patterns guidelines. Multivariate logistic regression analysis was used to assess the relationship between adherence with follow-up visits and disease severity. After adjustment for the impact of potential confounding variables, subjects with severe glaucomatous disease were found to have been less adherent to their recommended follow-up than those patients with mild or moderate glaucomatous disease (adjusted OR 1.89, 95% CI 1.21-2.94; P = .01). Subjects who were on glaucoma medications were found to be less adherent to follow-up recommendations (adjusted OR 3.29, 95% CI 1.41-7.65, P = .01). Subjects with poor follow-up adherence were significantly more likely to have severe glaucomatous disease, suggesting that poor follow-up may contribute to disease worsening or, alternatively, those with more severe disease are less inclined to follow up at appropriate intervals. Published by Elsevier Inc.

  3. [Detailed methodological recommendations for the treatment of Clostridium difficile-associated diarrhea with faecal transplantation].

    Science.gov (United States)

    Nagy, Gergely György; Várvölgyi, Csaba; Balogh, Zoltán; Orosi, Piroska; Paragh, György

    2013-01-06

    The incidence of Clostridium difficile associated enteral disease shows dramatic increase worldwide, with appallingly high treatment costs, mortality figures, recurrence rates and treatment refractoriness. It is not surprising, that there is significant interest in the development and introduction of alternative therapeutic strategies. Among these only stool transplantation (or faecal bacteriotherapy) is gaining international acceptance due to its excellent cure rate (≈92%), low recurrence rate (≈6%), safety and cost-effectiveness. Unfortunately faecal transplantation is not available for most patients, although based on promising international results, its introduction into the routine clinical practice is well justified and widely expected. The authors would like to facilitate this process, by presenting a detailed faecal transplantation protocol prepared in their Institution based on the available literature and clinical rationality. Officially accepted national methodological guidelines will need to be issued in the future, founded on the expert opinion of relevant professional societies and upcoming advances in this field.

  4. Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome.

    Science.gov (United States)

    Burkhart, Keith K; Abernethy, Darrell; Jackson, David

    2015-06-01

    Drug features that are associated with Stevens-Johnson syndrome (SJS) have not been fully characterized. A molecular target analysis of the drugs associated with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to mechanistic insights into SJS pathophysiology. The publicly available version of FAERS was analyzed to identify disproportionality among the molecular targets, metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS in-house version was also analyzed for an internal comparison of the drugs most highly associated with SJS. Cyclooxygenases 1 and 2, carbonic anhydrase 2, and sodium channel 2 alpha were identified as disproportionately associated with SJS. Cytochrome P450 (CYPs) 3A4 and 2C9 are disproportionately represented as metabolizing enzymes of the drugs associated with SJS adverse event reports. Multidrug resistance protein 1 (MRP-1), organic anion transporter 1 (OAT1), and PEPT2 were also identified and are highly associated with the transport of these drugs. A detailed review of the molecular targets identifies important roles for these targets in immune response. The association with CYP metabolizing enzymes suggests that reactive metabolites and oxidative stress may have a contributory role. Drug transporters may enhance intracellular tissue concentrations and also have vital physiologic roles that impact keratinocyte proliferation and survival. Data mining FAERS may be used to hypothesize mechanisms for adverse drug events by identifying molecular targets that are highly associated with drug-induced adverse events. The information gained may contribute to systems biology disease models.

  5. 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

  6. In silico prediction of novel therapeutic targets using gene-disease association data.

    Science.gov (United States)

    Ferrero, Enrico; Dunham, Ian; Sanseau, Philippe

    2017-08-29

    Target identification and validation is a pressing challenge in the pharmaceutical industry, with many of the programmes that fail for efficacy reasons showing poor association between the drug target and the disease. Computational prediction of successful targets could have a considerable impact on attrition rates in the drug discovery pipeline by significantly reducing the initial search space. Here, we explore whether gene-disease association data from the Open Targets platform is sufficient to predict therapeutic targets that are actively being pursued by pharmaceutical companies or are already on the market. To test our hypothesis, we train four different classifiers (a random forest, a support vector machine, a neural network and a gradient boosting machine) on partially labelled data and evaluate their performance using nested cross-validation and testing on an independent set. We then select the best performing model and use it to make predictions on more than 15,000 genes. Finally, we validate our predictions by mining the scientific literature for proposed therapeutic targets. We observe that the data types with the best predictive power are animal models showing a disease-relevant phenotype, differential expression in diseased tissue and genetic association with the disease under investigation. On a test set, the neural network classifier achieves over 71% accuracy with an AUC of 0.76 when predicting therapeutic targets in a semi-supervised learning setting. We use this model to gain insights into current and failed programmes and to predict 1431 novel targets, of which a highly significant proportion has been independently proposed in the literature. Our in silico approach shows that data linking genes and diseases is sufficient to predict novel therapeutic targets effectively and confirms that this type of evidence is essential for formulating or strengthening hypotheses in the target discovery process. Ultimately, more rapid and automated target

  7. Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors

    Science.gov (United States)

    2016-10-01

    development of the principal discipline(s) of the project? • We have learned that the drug PEGPH20, which degrades a component of connective tissue called...AWARD NUMBER: W81XWH-15-1-0114 TITLE: Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors PRINCIPAL INVESTIGATOR...14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER NF140089 Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors 5b

  8. PROJECT: RECOMMENDATIONS ON TREATMENT OF RHEUMATOID ARTHRITIS DEVELOPED BY ALL-RUSSIAN PUBLIC ORGANIZATION «ASSOCIATION OF RHEUMATOLOGISTS OF RUSSIA» – 2014 (PART 1

    Directory of Open Access Journals (Sweden)

    E. L. Nasonov

    2015-01-01

    Full Text Available Authors report new recommendations of All-Russian Public Organization «Association of Rheumatologists of Russia» (ARR on treatment of rheumatoid arthritis (RA, which adapts contemporary concept accepted in the respective field of pharmacotherapy known as «Treat to Target». According to it, the main objective of RA pharmacotherapy is a remission (or low disease activity. To achieve it, disease modifying anti-rheumatic drugs (DMARD should be administered to all RA patients as early as possible, with efficacy monitoring and therapy correction according to the disease activity. Special attention has been paid to the use of methotrexate (MTX as «the gold standard» of RA pharmacotherapy and the key component of «Treat to Target» strategy. Early MTX administration (including subcutaneous injections should become an obligatory component of RA treatment at all stages of the disease. If MTX is not efficient or not well tolerated (including subcutaneous form of the drug as monotherapy or combined with conventional DMARD, biological agents should be used. Those include TNFα inhibitors, antagonist of interleukin-6 receptor (Tocilizumab, anti-B-cell drugs (Rituximab and agents blocking T-cell activation (Abatacept. Tofacitinib therapy (JAK inhibitor is indicated in patients who are resistant to conventional DMARDs and biologics. All biologics and Tofacitinib are more effective in combination with MTX (or other DMARD. 

  9. PROJECT: RECOMMENDATIONS ON TREATMENT OF RHEUMATOID ARTHRITIS DEVELOPED BY ALL-RUSSIAN PUBLIC ORGANIZATION «ASSOCIATION OF RHEUMATOLOGISTS OF RUSSIA» – 2014 (PART 1

    Directory of Open Access Journals (Sweden)

    E. L. Nasonov

    2016-01-01

    Full Text Available Authors report new recommendations of All-Russian Public Organization «Association of Rheumatologists of Russia» (ARR on treatment of rheumatoid arthritis (RA, which adapts contemporary concept accepted in the respective field of pharmacotherapy known as «Treat to Target». According to it, the main objective of RA pharmacotherapyis a remission (or low disease activity. To achieve it, disease modifying anti-rheumatic drugs (DMARD should be administered to all RA patients as early as possible, with efficacy monitoring and therapy correction according to the disease activity. Special attention has been paid to the use of methotrexate (MTX as «the gold standard» of RA pharmacotherapy and the key component of «Treat to Target» strategy. Early MTX administration (including subcutaneous injections should become an obligatory component of RA treatment at all stages of the disease. If MTX is not efficient or not well tolerated (including subcutaneous form of the drug as monotherapy or combined with conventional DMARD, biological agents should be used. Those include TNFα inhibitors, antagonist of interleukin-6 receptor (Tocilizumab, anti-B-cell drugs  Rituximab and agents blocking T-cell activation (Abatacept. Tofacitinib therapy (JAK inhibitor is indicated in patients who are resistant to conventional DMARDs and biologics. All biologics and Tofacitinib are more effective in combination with MTX (or other DMARD.

  10. Adherence to Voice Therapy Recommendations Is Associated With Preserved Employment Fitness Among Teachers With Work-Related Dysphonia.

    Science.gov (United States)

    Rinsky-Halivni, Lilah; Klebanov, Miriam; Lerman, Yehuda; Paltiel, Ora

    2017-05-01

    Referral to voice therapy and recommendations for voice rest and microphone use are common interventions in occupational medicine aimed at preserving the working capability of teachers with occupation-related voice problems. Research on the impact of such interventions in terms of employment is lacking. This study examined changes in fitness (ie, ability) to work of dysphonic teachers referred to an occupational clinic and evaluated employment outcomes following voice therapy, voice rest, and microphone use. A historical prospective study was carried out. Of 365 classroom teachers who were first referred to a regional occupational medicine clinic due to dysphonia between January 2007 and December 2012, 156 were sampled and 153 were followed-up for an average of 5 years (range 2-8). Data were collected from medical records and from interviews conducted in 2014 aimed at assessing employment status. Logistic regression models were used to assess associations between interventions and employment outcomes. Survival analyses were performed to evaluate the association between participating in voice therapy and length of retained employment fitness. Thirty-four (22.2%) teachers suffered declines in working capabilities due to dysphonia. Voice therapy was demonstrated as being a protective factor against such declines (odds ratio = 0.05 [0.01-0.27]). Adherence to recommendation of voice therapy was teachers occurred within 20 months after referral. Unlike voice therapy, voice rest and microphone use were not associated with retention of working capabilities. Voice therapy, especially when instituted early, is a strong predictor for retaining fitness for employment among dysphonic teachers. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  11. Prediction of microbe-disease association from the integration of neighbor and graph with collaborative recommendation model.

    Science.gov (United States)

    Huang, Yu-An; You, Zhu-Hong; Chen, Xing; Huang, Zhi-An; Zhang, Shanwen; Yan, Gui-Ying

    2017-10-16

    Accumulating clinical researches have shown that specific microbes with abnormal levels are closely associated with the development of various human diseases. Knowledge of microbe-disease associations can provide valuable insights for complex disease mechanism understanding as well as the prevention, diagnosis and treatment of various diseases. However, little effort has been made to predict microbial candidates for human complex diseases on a large scale. In this work, we developed a new computational model for predicting microbe-disease associations by combining two single recommendation methods. Based on the assumption that functionally similar microbes tend to get involved in the mechanism of similar disease, we adopted neighbor-based collaborative filtering and a graph-based scoring method to compute association possibility of microbe-disease pairs. The promising prediction performance could be attributed to the use of hybrid approach based on two single recommendation methods as well as the introduction of Gaussian kernel-based similarity and symptom-based disease similarity. To evaluate the performance of the proposed model, we implemented leave-one-out and fivefold cross validations on the HMDAD database, which is recently built as the first database collecting experimentally-confirmed microbe-disease associations. As a result, NGRHMDA achieved reliable results with AUCs of 0.9023 ± 0.0031 and 0.9111 in the validation frameworks of fivefold CV and LOOCV. In addition, 78.2% microbe samples and 66.7% disease samples are found to be consistent with the basic assumption of our work that microbes tend to get involved in the similar disease clusters, and vice versa. Compared with other methods, the prediction results yielded by NGRHMDA demonstrate its effective prediction performance for microbe-disease associations. It is anticipated that NGRHMDA can be used as a useful tool to search the most potential microbial candidates for various diseases, and therefore

  12. Recommended Dietary Pattern to Achieve Adherence to the American Heart Association/American College of Cardiology (AHA/ACC) Guidelines: A Scientific Statement From the American Heart Association.

    Science.gov (United States)

    Van Horn, Linda; Carson, Jo Ann S; Appel, Lawrence J; Burke, Lora E; Economos, Christina; Karmally, Wahida; Lancaster, Kristie; Lichtenstein, Alice H; Johnson, Rachel K; Thomas, Randal J; Vos, Miriam; Wylie-Rosett, Judith; Kris-Etherton, Penny

    2016-11-29

    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 American Heart Association's 2020 Strategic Impact Goals for cardiovascular health promotion and disease reduction by providing more specific details for adopting evidence-based diet and lifestyle behaviors to achieve those goals. In addition, the 2015-2020 Dietary Guidelines for Americans issued updated evidence relevant to reducing cardiovascular risk and provided additional recommendations for adopting healthy diet and lifestyle approaches. This scientific statement, intended for healthcare providers, summarizes relevant scientific and translational evidence and offers practical tips, tools, and dietary approaches to help patients/clients adapt these guidelines according to their sociocultural, economic, and taste preferences. © 2016 American Heart Association, Inc.

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

    International Nuclear Information System (INIS)

    Muhogora, Wilbroad; Padovani, Renato; Bonutti, Faustino; Msaki, Peter; Kazema, R.

    2011-01-01

    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. (author)

  14. 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.

  15. Getting a Handle on Neuropharmacology by Targeting Receptor-Associated Proteins.

    Science.gov (United States)

    Maher, Michael P; Matta, Jose A; Gu, Shenyan; Seierstad, Mark; Bredt, David S

    2017-12-06

    Targeted therapy for neuropsychiatric disorders requires selective modulation of dysfunctional neuronal pathways. Receptors relevant to CNS disorders typically have associated proteins discretely expressed in specific neuronal pathways; these accessory proteins provide a new dimension for drug discovery. Recent studies show that targeting a TARP auxiliary subunit of AMPA receptors selectively modulates neuronal excitability in specific forebrain pathways relevant to epilepsy. Other medicinally important ion channels, gated by glutamate, γ-aminobutyric acid (GABA), and acetylcholine, also have associated proteins, which may be druggable. This emerging pharmacology of receptor-associated proteins provides a new approach for improving drug efficacy while mitigating side effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. 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.

  17. Slow, target associated particles produced in ultrarelativistic heavy-ion interactions

    Energy Technology Data Exchange (ETDEWEB)

    Adamovich, M I; Aggarwal, M M; Alexandrov, Y A; Andreeva, N P; Anson, Z V; Arora, R; Avetyan, F A; Badyal, S K; Basova, E; Bhalla, K B; Bhasin, A; Bhatia, V S; Bogdanov, V G; Bubnov, V I; Burnett, T H; Cai, X; Chasnikov, I Y; Chernova, L P; Chernyavsky, M M; Dressel, B; Eligbaeva, G Z; Eremenko, L E; Friedlander, E M; Gaitinov, A S; Ganssauge, E R; Garpman, S; Gerassimov, S G; Grote, J; Gulamov, K G; Gupta, S K; Gupta, V; Heckman, H H; Huang, H; Jakobsson, B; Judek, B; Kachroo, S; Kadyrov, F G; Kalyachkina, G S; Kanygina, E K; Karabova, M; Kaul, G L; Kaur, M; Kharlamov, S P; Koss, Y; Krasnov,; Kumar,; Lal, P; Larionova,; Lepetan,; Lindstrom,; Liu,; Lokanathan, S; Lord, J; Lukicheva, N S; Luo, S B; Mangotra, L K; Marutyan,; Maslennikova, N V; Mittra, I S; Mookerjee, S; Mueller, C; Nasrulaeva, H; Nasyrov, S H; Navotny, V S; Orlova, G I; Otterlund, I; Palsania, H S; Peresadko, N G; Petrov, N V; Plyushchev, V A; Qian, W Y; Raniwala,; EMU01 Collaboration

    1991-06-20

    The slow, target associated particles produced in ultrarelativistic heavy-ion interactions are a quantitative probe of the cascading processes in the spectator parts of the target nucleus. These processes are directly influenced by the proper timescale for the formation of hadronic matter. In this letter we show experimental data on singly and multiply charged particles, with velocities smaller than 0.7c, produced in ultrarelativistic heavy-ion interactions in nuclear emulsion. (orig.).

  18. 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

  19. 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 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.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.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.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 and randomized clinical trials are

  20. Treatment Patterns Associated with ACR-Recommended Medications in the Management of Fibromyalgia in the United States.

    Science.gov (United States)

    Liu, Yifei; Qian, Chunlin; Yang, Mei

    2016-03-01

    Fibromyalgia (FM) affects up to 6% of U.S. adults, resulting in a significant burden on the health care system and poor quality of life for patients. Duloxetine, pregabalin, and milnacipran are approved for management of FM; however, consensus is lacking regarding optimal therapy. Patients with FM taking approved medications often do not experience meaningful symptom relief, and many experience intolerable adverse events. To assess treatment patterns associated with available and commonly used medications for the management of FM using U.S. health insurance claims. This retrospective analysis used the MarketScan claims database to identify adults with a first diagnosis of FM (ICD-9-CM code 729.1) between 2009 and 2011 with continuous health plan enrollment for 12 months pre- and post-index. Medications of interest were pregabalin, gabapentin, duloxetine, milnacipran, cyclobenzaprine, and tramadol. These are 6 of the 8 medications recommended by the American College of Rheumatology (ACR) for treating FM; the other 2 (amitriptyline and venlafaxine) were only included in some initial assessments. The Charlson Comorbidity Index (CCI) was used to assess overall comorbidity burden. Endpoints included proportion of patients treated within 1 year after first diagnosis; initial treatment pattern; adherence over the first-year follow-up period for the medications of interest; and discontinuation, switching, and combination therapy patterns among pain medications of interest at different time points. Proportion of days covered (PDC; defined as number of days in the period when the patient had drug supply divided by the number of days in the period) was used to define adherence, which was categorized as low (PDC time to discontinuation (defined as the first drug supply gap ≥ 90 days) was estimated using Kaplan-Meier analysis. Overall, 240,144 patients met the inclusion criteria. Patients were predominantly women (68%), had preferred provider organization insurance coverage

  1. Associative Interference in Pavlovian Conditioning: A Function of Similarity Between the Interfering and Target Associative Structures

    OpenAIRE

    Amundson, Jeffrey C.; Miller, Ralph R.

    2008-01-01

    Three lever-press suppression studies were conducted with water-deprived rats to investigate the role of similarity in proactive interference within first-order Pavlovian conditioning. Experiments 1a and 1b assessed the influence of stimulus complexity in proactive interference. Both experiments found greater interference when the interfering cue and target cue were composed of the same number of elements. Experiment 2 assessed the influence of context similarity in proactive interference and...

  2. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Evaluation of an inpatient psychiatric hospital physician education program and adherence to American Diabetes Association practice recommendations.

    Science.gov (United States)

    Koffarnus, Robin L; Mican, Lisa M; Lopez, Debra A; Barner, Jamie C

    2016-03-01

    This study evaluated adherence to American Diabetes Association (ADA) recommendations for diabetes monitoring following an educational intervention for physicians in an inpatient psychiatric hospital. This retrospective chart review was conducted in an inpatient psychiatric institution from July 1, 2010-January 15, 2011. A total of 120 subjects (60 subjects each in the pre- and post-intervention groups) meeting the inclusion criteria served as the study sample. Included subjects were admitted and discharged from an inpatient psychiatric institution within 90 days prior to (pre-intervention) and following (post-intervention) the physician education program. The medical staff was presented an educational program intervention, consisting of a 30 minute overview of the ADA 2010 Standards of Care recommendations and distribution of laminated treatment reminders. Electronic grouped order sets for patients with diabetes were also created and implemented. The primary outcome was change (pre-intervention to post-intervention) in frequency of hemoglobin A1c documentation on admission following the intervention. Secondary outcomes included the change in frequency of documentation of fasting plasma glucose, serum creatinine, urine creatinine/microalbumin ratio (UMA), fasting lipid profile (FLP), and change in days on sliding scale insulin. Regarding change in frequency of documentation of A1c values on admission, chi-square analysis revealed a significant increase from pre-intervention to post-intervention period of 30% (n = 18) to 61.7% (n = 37), respectively (p = 0.0005). Documentation of FLP also significantly increased [73.3% vs. 91.7% (p = 0.0082)]. There were no significant differences in the documentation of fasting plasma glucose, serum creatinine, and UMA or days treated with sliding scale insulin. The physician education program was successful in increasing the assessment of A1c values and lipid profiles for patients with diabetes mellitus in a psychiatric

  4. Clustering of unhealthy lifestyle behaviors is associated with nonadherence to clinical preventive recommendations among adults with diabetes.

    Science.gov (United States)

    Jiménez-García, Rodrigo; Esteban-Hernández, Jesus; Hernández-Barrera, Valentín; Jimenez-Trujillo, Isabel; López-de-Andrés, Ana; Carrasco Garrido, Pilar

    2011-01-01

    Analyze clustering of unhealthy lifestyle behavior and its relationship with nonadherence to clinical preventive care services among Spanish diabetic adults. Cross-sectional study including 2156 diabetic adults from the 2006 Spanish National Health Survey. Subjects were asked about their uptake of BP measurement, lipid profile, influenza vaccination, and dental examination. Lifestyle behaviors included smoking status, physical activity, alcohol consumption, and dieting. Binary logistic regression models were built to assess the association between clustering of unhealthy lifestyle and the uptake of each preventive activity. Almost 16% and 36% of the subjects had not undergone blood pressure (BP) and blood lipids measurements, respectively. Forty percent had not been vaccinated and 72% had not received dental examination. Fourteen percent of the subjects had three to four unhealthy behaviors and this increased the probability of not having BP check-up (OR 2.32, 95% CI 1.38-3.91), blood lipids testing (OR 1.63, 95% CI 1.14-2.33), and not being vaccinated (OR 1.99, 95% CI 1.37-2.89). Number of unhealthy lifestyle behaviors is linearly associated with number of preventive measures unfulfilled. Adherence to recommended clinical preventive services is under desirable levels among Spanish diabetes sufferers. These preventive services are provided neither equitably nor efficiently, since subjects with unhealthier lifestyles are less likely to receive them. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Impact of a medication therapy management intervention targeting medications associated with falling: Results of a pilot study.

    Science.gov (United States)

    Mott, David A; Martin, Beth; Breslow, Robert; Michaels, Barb; Kirchner, Jeff; Mahoney, Jane; Margolis, Amanda

    2016-01-01

    The use of fall risk-increasing drugs (FRIDs) by older adults is one factor associated with falling, and FRID use is common among older adults. A targeted medication therapy management intervention focused on FRID use that included prescription and over-the-counter (OTC) medications, along with follow-up telephone calls was designed. The purpose of this pilot study was to examine preliminary effects of a medication therapy management (MTM) intervention focused on FRIDs provided by a community pharmacist to older adults. Randomized, controlled trial. One community pharmacy. Eighty older adults who completed a fall prevention workshop. The main outcome measures were the rate of discontinuing FRIDs, the proportion of older adults falling, and the number of falls. A secondary outcome was the acceptance rate of medication recommendations by patients and prescribers. Thirty-eight older adults received the targeted MTM intervention. Of the 31 older adults using a FRID, a larger proportion in the intervention group had FRID use modified relative to controls (77% and 28%, respectively; P FRID use among older adults was effective in modifying FRID use. This result supports the preliminary conclusion that community pharmacists can play an important role in modifying FRID use among older adults. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  6. Deep mining heterogeneous networks of biomedical linked data to predict novel drug-target associations.

    Science.gov (United States)

    Zong, Nansu; Kim, Hyeoneui; Ngo, Victoria; Harismendy, Olivier

    2017-08-01

    A heterogeneous network topology possessing abundant interactions between biomedical entities has yet to be utilized in similarity-based methods for predicting drug-target associations based on the array of varying features of drugs and their targets. Deep learning reveals features of vertices of a large network that can be adapted in accommodating the similarity-based solutions to provide a flexible method of drug-target prediction. We propose a similarity-based drug-target prediction method that enhances existing association discovery methods by using a topology-based similarity measure. DeepWalk, a deep learning method, is adopted in this study to calculate the similarities within Linked Tripartite Network (LTN), a heterogeneous network generated from biomedical linked datasets. This proposed method shows promising results for drug-target association prediction: 98.96% AUC ROC score with a 10-fold cross-validation and 99.25% AUC ROC score with a Monte Carlo cross-validation with LTN. By utilizing DeepWalk, we demonstrate that: (i) this method outperforms other existing topology-based similarity computation methods, (ii) the performance is better for tripartite than with bipartite networks and (iii) the measure of similarity using network topology outperforms the ones derived from chemical structure (drugs) or genomic sequence (targets). Our proposed methodology proves to be capable of providing a promising solution for drug-target prediction based on topological similarity with a heterogeneous network, and may be readily re-purposed and adapted in the existing of similarity-based methodologies. The proposed method has been developed in JAVA and it is available, along with the data at the following URL: https://github.com/zongnansu1982/drug-target-prediction . nazong@ucsd.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  7. 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

    2018-02-01

    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.

  8. 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

    Directory of Open Access Journals (Sweden)

    Linei Augusta Brolini Dellê Urban

    Full Text Available Abstract 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.

  9. 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...

  10. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. 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 <3 recommendations. 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.

  12. Learning the association between a context and a target location in infancy.

    Science.gov (United States)

    Bertels, Julie; San Anton, Estibaliz; Gebuis, Titia; Destrebecqz, Arnaud

    2017-07-01

    Extracting the statistical regularities present in the environment is a central learning mechanism in infancy. For instance, infants are able to learn the associations between simultaneously or successively presented visual objects (Fiser & Aslin, ; Kirkham, Slemmer & Johnson, ). The present study extends these results by investigating whether infants can learn the association between a target location and the context in which it is presented. With this aim, we used a visual associative learning procedure inspired by the contextual cuing paradigm, with infants from 8 to 12 months of age. In two experiments, in which we varied the complexity of the stimuli, we first habituated infants to several scenes where the location of a target (a cartoon character) was consistently associated with a context, namely a specific configuration of geometrical shapes. Second, we examined whether infants learned the covariation between the target location and the context by measuring looking times at scenes that either respected or violated the association. In both experiments, results showed that infants learned the target-context associations, as they looked longer at the familiar scenes than at the novel ones. In particular, infants selected clusters of co-occurring contextual shapes and learned the covariation between the target location and this subset. These results support the existence of a powerful and versatile statistical learning mechanism that may influence the orientation of infants' visual attention toward areas of interest in their environment during early developmental stages. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=9Hm1unyLBn0. © 2016 John Wiley & Sons Ltd.

  13. Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

    Science.gov (United States)

    2016-09-01

    analysis of tumor necrosis factor - alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype...AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor - Associated...Cancer and Impairs Tumor -Associated Angiogenesis 5b. GRANT NUMBER W81XWH-15-1-0296 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

  14. 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. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Induction of associative olfactory memory by targeted activation of single olfactory neurons in Drosophila larvae.

    Science.gov (United States)

    Honda, Takato; Lee, Chi-Yu; Yoshida-Kasikawa, Maki; Honjo, Ken; Furukubo-Tokunaga, Katsuo

    2014-04-25

    It has been postulated that associative memory is formed by at least two sets of external stimuli, CS and US, that are transmitted to the memory centers by distinctive conversing pathways. However, whether associative memory can be induced by the activation of only the olfactory CS and a biogenic amine-mediated US pathways remains to be elucidated. In this study, we substituted the reward signals with dTrpA1-mediated thermogenetic activation of octopaminergic neurons and the odor signals by ChR2-mediated optical activation of a specific class of olfactory neurons. We show that targeted activation of the olfactory receptor and the octopaminergic neurons is indeed sufficient for the formation of associative olfactory memory in the larval brain. We also show that targeted stimulation of only a single type of olfactory receptor neurons is sufficient to induce olfactory memory that is indistinguishable from natural memory induced by the activation of multiple olfactory receptor neurons.

  16. Disease-Associated Particulates and Joint Inflammation; Mechanistic Insights and Potential Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Olwyn R. Mahon

    2018-05-01

    Full Text Available It is now well established that intra-articular deposition of endogenous particulates, such as osteoarthritis-associated basic calcium phosphate crystals, gout-associated monosodium urate crystals, and calcium deposition disease-associated calcium pyrophosphate crystals, contributes to joint destruction through the production of cartilage-degrading enzymes and pro-inflammatory cytokines. Furthermore, exogenous wear-debris particles, generated from prosthetic implants, drive periprosthetic osteolysis which impacts on the longevity of total joint replacements. Over the last few years, significant insight has been gained into the mechanisms through which these particulates exert their effects. Not only has this increased our understanding of the pathological processes associated with crystal deposition but it has also led to the identification of a number of therapeutic targets to treat particulate-associated disease. In this review, we discuss recent developments regarding the cellular events triggered by joint-associated particulates, as well as future directions in therapy for particulate-related arthropathies.

  17. Updated recommendations for managing the care of patients receiving oral bisphosphonate therapy: an advisory statement from the American Dental Association Council on Scientific Affairs.

    Science.gov (United States)

    Edwards, Beatrice J; Hellstein, John W; Jacobsen, Peter L; Kaltman, Steven; Mariotti, Angelo; Migliorati, Cesar A

    2008-12-01

    and Overview. In 2005, the American Dental Association (ADA) Council on Scientific Affairs convened an expert panel to develop clinical recommendations for dentists treating patients who are receiving oral bisphosphonate therapy. The Journal of the American Dental Association published the resulting report in 2006. This 2008 advisory statement is the first of projected periodic updates of the 2006 clinical recommendations. This 2008 advisory statement concludes, on the basis of a review of the current literature, that for patients receiving bisphosphonate therapy, the risk of developing bisphosphonate-associated osteonecrosis (BON) of the jaw apparently remains low. It also newly concludes that current screening and diagnostic tests are unreliable for predicting a patient's risk of developing the condition. This statement updates the 2006 recommendations regarding general dentistry, management of periodontal diseases, implant placement and maintenance, oral and maxillofacial surgery, endodontics, restorative dentistry and prosthodontics, and orthodontics.

  18. 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

  19. [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.

  20. 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

  1. A drug development perspective on targeting tumor-associated myeloid cells.

    Science.gov (United States)

    Majety, Meher; Runza, Valeria; Lehmann, Christian; Hoves, Sabine; Ries, Carola H

    2018-02-01

    Despite decades of research, cancer remains a devastating disease and new treatment options are needed. Today cancer is acknowledged as a multifactorial disease not only comprising of aberrant tumor cells but also the associated stroma including tumor vasculature, fibrotic plaques, and immune cells that interact in a complex heterotypic interplay. Myeloid cells represent one of the most abundant immune cell population within the tumor stroma and are equipped with a broad functional repertoire that promotes tumor growth by suppressing cytotoxic T cell activity, stimulating neoangiogenesis and tissue remodeling. Therefore, myeloid cells have become an attractive target for pharmacological intervention. In this review, we summarize the pharmacological approaches to therapeutically target tumor-associated myeloid cells with a focus on advanced programs that are clinically evaluated. In addition, for each therapeutic strategy, the preclinical rationale as well as advantages and challenges from a drug development perspective are discussed. © 2017 Federation of European Biochemical Societies.

  2. Associations among Life Events, Empathic Concern, and Adolescents' Prosocial and Aggressive Behaviors Toward Specific Targets.

    Science.gov (United States)

    Davis, Alexandra N; Luce, Haley; Davalos, Natasha

    2018-05-25

    The goal of the present study was to examine the links between life events and adolescents' social behaviors (prosocial and aggressive behaviors) toward specific targets and to examine how empathic concern may play a role in these associations. The study examined two hypotheses: both the mediating role of empathic concern and the moderating role of empathic concern. The sample included 311 high school students from the Midwest (M age = 16.10 years; age range = 14-19 years; 58.7% girls; 82.7% White, 13.6% Latino). The results demonstrated support for the moderation model as well as complex links between life events and prosocial and aggressive behaviors toward specific targets. The discussion focuses on the role of empathic concern in understanding how life events are ultimately associated with adolescents' social development.

  3. Data association approaches in bearings-only multi-target tracking

    Science.gov (United States)

    Xu, Benlian; Wang, Zhiquan

    2008-03-01

    According to requirements of time computation complexity and correctness of data association of the multi-target tracking, two algorithms are suggested in this paper. The proposed Algorithm 1 is developed from the modified version of dual Simplex method, and it has the advantage of direct and explicit form of the optimal solution. The Algorithm 2 is based on the idea of Algorithm 1 and rotational sort method, it combines not only advantages of Algorithm 1, but also reduces the computational burden, whose complexity is only 1/ N times that of Algorithm 1. Finally, numerical analyses are carried out to evaluate the performance of the two data association algorithms.

  4. Engagement and role of surgical trainees in global surgery: Consensus statement and recommendations from the Association of Surgeons in Training.

    Science.gov (United States)

    Mohan, Helen M; Fitzgerald, Edward; Gokani, Vimal; Sutton, Paul; Harries, Rhiannon; Bethune, Robert; McDermott, Frank D

    2018-04-01

    There is a wide chasm in access to essential and emergency surgery between high and low/middle income countries (LMICs). Surgeons worldwide are integral to solutions needed to address this imbalance. Involving surgical trainees, who represent the future of surgery, is vital to this endeavour. The Association of Surgeons in Training (ASiT) is an independent charity that support surgical trainees of all ten surgical specialties in the UK and Ireland. ASiT convened a consensus meeting at the ASiT conference in Liverpool 2016 to discuss trainee engagement with global surgery, including potential barriers and solutions. A face-to-face consensus meeting reviewed the engagement of, and roles for, surgical trainees in global surgery at the ASiT Conference (Liverpool, England), March 2016. Participants self-identified based on experience and interest in the field, and included trainees (residents and students) and consultants (attending grade). Following expert review, seven pre-determined core areas were presented for review and debate. Extensive discussion was facilitated by a consultant and a senior surgical trainee, with expertise in global surgery. The draft derived from these initial discussions was circulated to all those who had participated, and an iterative process of revision was undertaken until a final consensus and recommendations were reached. There is increasing interest from trainee surgeons to work in LMICs. There are however, ethical considerations, and it is important that trainees working in LMICs undertake work appropriate to their training stage and competencies. Visiting surgeons must consider the requirements of the hosting centres rather than just their own objectives. If appropriately organised, both short and long-term visits, can enable development of transferable clinical, organisational, research and education skills. A central repository of information on global surgery would be useful to trainees, to complement existing resources. Challenges

  5. Recommender systems

    OpenAIRE

    Lu L.; Medo M.; Yeung C.H.; Zhang Y.-C.; Zhang Z.-K.; Zhou T.

    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...

  6. Functional profiling of microtumors to identify cancer associated fibroblast-derived drug targets.

    Science.gov (United States)

    Horman, Shane R; To, Jeremy; Lamb, John; Zoll, Jocelyn H; Leonetti, Nicole; Tu, Buu; Moran, Rita; Newlin, Robbin; Walker, John R; Orth, Anthony P

    2017-11-21

    Recent advances in chemotherapeutics highlight the importance of molecularly-targeted perturbagens. Although these therapies typically address dysregulated cancer cell proteins, there are increasing therapeutic modalities that take into consideration cancer cell-extrinsic factors. Targeting components of tumor stroma such as vascular or immune cells has been shown to represent an efficacious approach in cancer treatment. Cancer-associated fibroblasts (CAFs) exemplify an important stromal component that can be exploited in targeted therapeutics, though their employment in drug discovery campaigns has been relatively minimal due to technical logistics in assaying for CAF-tumor interactions. Here we report a 3-dimensional multi-culture tumor:CAF spheroid phenotypic screening platform that can be applied to high-content drug discovery initiatives. Using a functional genomics approach we systematically profiled 1,024 candidate genes for CAF-intrinsic anti-spheroid activity; identifying several CAF genes important for development and maintenance of tumor:CAF co-culture spheroids. Along with previously reported genes such as WNT, we identify CAF-derived targets such as ARAF and COL3A1 upon which the tumor compartment depends for spheroid development. Specifically, we highlight the G-protein-coupled receptor OGR1 as a unique CAF-specific protein that may represent an attractive drug target for treating colorectal cancer. In vivo , murine colon tumor implants in OGR1 knockout mice displayed delayed tumor growth compared to tumors implanted in wild type littermate controls. These findings demonstrate a robust microphysiological screening approach for identifying new CAF targets that may be applied to drug discovery efforts.

  7. Compliance with different physical activity recommendations and its association with socio-demographic characteristics using an objective measure.

    Science.gov (United States)

    Scheers, Tineke; Philippaerts, Renaat; Lefevre, Johan

    2013-02-14

    In the past decades, several public health guidelines concerning physical activity have been published. This study evaluated compliance with various physical activity guidelines and examined the associations between meeting the guidelines and socio-demographic characteristics. Data were obtained from 357 Flemish men and women (41.9 ± 9.6 years). Physical activity was assessed for seven consecutive days using the SenseWear Armband. The prevalence of sufficient physical activity was calculated according to various public health guidelines. Logistic regressions examined the associations between socio-demographic characteristics and the odds of meeting the different guidelines. 87.2% of men and 68.1% of women achieved ≥150 min/week of moderate-to-vigorous physical activity (MVPA), but only 57.6% and 37.3% accumulated this amount as ≥30 min/day on ≥5 days/week. With regard to vigorous physical activity, 27.9% of men and 15.7% of women achieved ≥75 min/week and 12.8% and 7.0% achieved ≥20 min/day on ≥3 days/week. In addition, 34.9% of men and 21.6% of women attained an average physical activity level (PAL) of 1.75 MET and thus met the criteria for weight maintenance. Only 16.3% of men and 14.1% of women took 10000 steps/day on 7 days/week. Women had a lower probability of achieving 30 min/day MVPA on 5 days/week (OR: 0.40), or a weekly total of 150 min or 500 MET.min MVPA or 75 min of vigorous activity compared to men (OR: 0.27-0.46). In addition, they were 50% less likely to meet the guidelines for weight maintenance. The odds of engaging in 150 min/week MVPA or attaining a PAL of 1.75 was lower with higher age. Educational level was positively related with accumulating 75 min/week of vigorous activity, but negatively with taking 10000 steps/day. Smokers were 60% less likely to participate weekly in 150 min of MVPA compared to non-smokers. The prevalence of sufficient physical activity differed greatly depending on the definition used. Women and subjects

  8. 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

  9. Sleep- and circadian rhythm-associated pathways as therapeutic targets in bipolar disorder.

    Science.gov (United States)

    Bellivier, Frank; Geoffroy, Pierre-Alexis; Etain, Bruno; Scott, Jan

    2015-06-01

    Disruptions in sleep and circadian rhythms are observed in individuals with bipolar disorders (BD), both during acute mood episodes and remission. Such abnormalities may relate to dysfunction of the molecular circadian clock and could offer a target for new drugs. This review focuses on clinical, actigraphic, biochemical and genetic biomarkers of BDs, as well as animal and cellular models, and highlights that sleep and circadian rhythm disturbances are closely linked to the susceptibility to BDs and vulnerability to mood relapses. As lithium is likely to act as a synchronizer and stabilizer of circadian rhythms, we will review pharmacogenetic studies testing circadian gene polymorphisms and prophylactic response to lithium. Interventions such as sleep deprivation, light therapy and psychological therapies may also target sleep and circadian disruptions in BDs efficiently for treatment and prevention of bipolar depression. We suggest that future research should clarify the associations between sleep and circadian rhythm disturbances and alterations of the molecular clock in order to identify critical targets within the circadian pathway. The investigation of such targets using human cellular models or animal models combined with 'omics' approaches are crucial steps for new drug development.

  10. Targeting tumor-associated macrophages by anti-tumor Chinese materia medica.

    Science.gov (United States)

    Pu, Wei-Ling; Sun, Li-Kang; Gao, Xiu-Mei; Rüegg, Curzio; Cuendet, Muriel; Hottiger, Micheal O; Zhou, Kun; Miao, Lin; Zhang, Yun-Sha; Gebauer, Margaret

    2017-10-01

    Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy.

  11. Targeted Assessment for Prevention of Healthcare-Associated Infections: A New Prioritization Metric.

    Science.gov (United States)

    Soe, Minn M; Gould, Carolyn V; Pollock, Daniel; Edwards, Jonathan

    2015-12-01

    To develop a method for calculating the number of healthcare-associated infections (HAIs) that must be prevented to reach a HAI reduction goal and identifying and prioritizing healthcare facilities where the largest reductions can be achieved. Acute care hospitals that report HAI data to the Centers for Disease Control and Prevention's National Healthcare Safety Network. METHODS :The cumulative attributable difference (CAD) is calculated by subtracting a numerical prevention target from an observed number of HAIs. The prevention target is the product of the predicted number of HAIs and a standardized infection ratio goal, which represents a HAI reduction goal. The CAD is a numeric value that if positive is the number of infections to prevent to reach the HAI reduction goal. We calculated the CAD for catheter-associated urinary tract infections for each of the 3,639 hospitals that reported such data to National Healthcare Safety Network in 2013 and ranked the hospitals by their CAD values in descending order. Of 1,578 hospitals with positive CAD values, preventing 10,040 catheter-associated urinary tract infections at 293 hospitals (19%) with the highest CAD would enable achievement of the national 25% catheter-associated urinary tract infection reduction goal. The CAD is a new metric that facilitates ranking of facilities, and locations within facilities, to prioritize HAI prevention efforts where the greatest impact can be achieved toward a HAI reduction goal.

  12. Slower resting alpha frequency is associated with superior localisation of moving targets.

    Science.gov (United States)

    Howard, Christina J; Arnold, Craig P A; Belmonte, Matthew K

    2017-10-01

    We examined the neurophysiological underpinnings of individual differences in the ability to maintain up-to-date representations of the positions of moving objects. In two experiments similar to the multiple object tracking (MOT) task, we asked observers to monitor continuously one or several targets as they moved unpredictably for a semi-random period. After all objects disappeared, observers were immediately prompted to report the perceived final position of one queried target. Precision of these position reports declined with attentional load, and reports tended to best resemble positions occupied by the queried target between 0 and 30ms in the past. Measurement of event-related potentials showed a contralateral delay activity over occipital scalp, maximal in the right hemisphere. The peak power-spectral frequency of observers' eyes-closed resting occipital alpha oscillations reliably predicted performance, such that lower-frequency alpha was associated with superior spatial localisation. Slower resting alpha might be associated with a cognitive style that depends less on memory-related processing and instead emphasises attention to changing stimuli. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  13. Enhancing prescribing of guideline-recommended medications for ischaemic heart diseases: a systematic review and meta-analysis of interventions targeted at healthcare professionals

    NARCIS (Netherlands)

    Nguyen, Thang; Nguyen, Hoa Q; Widyakusuma, Niken N; Nguyen, Thao H; Pham, Tam T; Taxis, Katja

    Objectives Ischaemic heart diseases (IHDs) are a leading cause of death worldwide. Although prescribing according to guidelines improves health outcomes, it remains suboptimal. We determined whether interventions targeted at healthcare professionals are effective to enhance prescribing and health

  14. Cancer-associated fibroblasts as target and tool in cancer therapeutics and diagnostics.

    Science.gov (United States)

    De Vlieghere, Elly; Verset, Laurine; Demetter, Pieter; Bracke, Marc; De Wever, Olivier

    2015-10-01

    Cancer-associated fibroblasts (CAFs) are drivers of tumour progression and are considered as a target and a tool in cancer diagnostic and therapeutic applications. An increased abundance of CAFs or CAF signatures are recognized as a bad prognostic marker in several cancer types. Tumour-environment biomimetics strongly improve our understanding of the communication between CAFs, cancer cells and other host cells. Several experimental drugs targeting CAFs are in clinical trials for multiple tumour entities; alternatively, CAFs can be exploited as a tool to characterize the functionality of circulating tumour cells or to capture them as a tool to prevent metastasis. The continuous interaction between tissue engineers, biomaterial experts and cancer researchers creates the possibility to biomimic the tumour-environment and provides new opportunities in cancer diagnostics and management.

  15. 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.

  16. Increased Heat Generation in Postcardiac Arrest Patients During Targeted Temperature Management Is Associated With Better Outcomes.

    Science.gov (United States)

    Uber, Amy J; Perman, Sarah M; Cocchi, Michael N; Patel, Parth V; Ganley, Sarah E; Portmann, Jocelyn M; Donnino, Michael W; Grossestreuer, Anne V

    2018-04-03

    Assess if amount of heat generated by postcardiac arrest patients to reach target temperature (Ttarget) during targeted temperature management is associated with outcomes by serving as a proxy for thermoregulatory ability, and whether it modifies the relationship between time to Ttarget and outcomes. Retrospective cohort study. Urban tertiary-care hospital. Successfully resuscitated targeted temperature management-treated adult postarrest patients between 2008 and 2015 with serial temperature data and Ttarget less than or equal to 34°C. None. Time to Ttarget was defined as time from targeted temperature management initiation to first recorded patient temperature less than or equal to 34°C. Patient heat generation ("heat units") was calculated as inverse of average water temperature × hours between initiation and Ttarget × 100. Primary outcome was neurologic status measured by Cerebral Performance Category score; secondary outcome was survival, both at hospital discharge. Univariate analyses were performed using Wilcoxon rank-sum tests; multivariate analyses used logistic regression. Of 203 patients included, those with Cerebral Performance Category score 3-5 generated less heat before reaching Ttarget (median, 8.1 heat units [interquartile range, 3.6-21.6 heat units] vs median, 20.0 heat units [interquartile range, 9.0-33.5 heat units]; p = 0.001) and reached Ttarget quicker (median, 2.3 hr [interquartile range, 1.5-4.0 hr] vs median, 3.6 hr [interquartile range, 2.0-5.0 hr]; p = 0.01) than patients with Cerebral Performance Category score 1-2. Nonsurvivors generated less heat than survivors (median, 8.1 heat units [interquartile range, 3.6-20.8 heat units] vs median, 19.0 heat units [interquartile range, 6.5-33.5 heat units]; p = 0.001) and reached Ttarget quicker (median, 2.2 hr [interquartile range, 1.5-3.8 hr] vs median, 3.6 hr [interquartile range, 2.0-5.0 hr]; p = 0.01). Controlling for average water temperature between initiation and Ttarget, the

  17. 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

  18. Targeted association mapping demonstrating the complex molecular genetics of fatty acid formation in soybean.

    Science.gov (United States)

    Li, Ying-hui; Reif, Jochen C; Ma, Yan-song; Hong, Hui-long; Liu, Zhang-xiong; Chang, Ru-zhen; Qiu, Li-juan

    2015-10-23

    The relative abundance of five dominant fatty acids (FAs) (palmitic, stearic, oleic, linoleic and linolenic acids) is a major factor determining seed quality in soybean. To clarify the currently poorly understood genetic architecture of FAs in soybean, targeted association analysis was conducted in 421 diverse accessions phenotyped in three environments and genotyped using 1536 pre-selected SNPs. The population of 421 soybean accessions displayed significant genetic variation for each FA. Analysis of the molecular data revealed three subpopulations, which reflected a trend depending on latitude of cultivation. A total of 37 significant (p seed quality of soybean with benefits for human health and for food processing.

  19. Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

    Science.gov (United States)

    Baay, Marc; Brouwer, Anja; Pauwels, Patrick; Peeters, Marc; Lardon, Filip

    2011-01-01

    Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention. PMID:22162712

  20. Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

    Directory of Open Access Journals (Sweden)

    Marc Baay

    2011-01-01

    Full Text Available Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs, which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention.

  1. 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...... 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......% for subthreshold PAbi-PAS. PAS using a biphasic pulse form at subthreshold intensities induces similar effects to conventional PAS....

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

    Directory of Open Access Journals (Sweden)

    Priscila Daniele Ramos Cirilo

    Full Text Available 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 have copy number alterations (CNAs. Gene expression microarrays studies have demonstrated that cell proliferation genes act in response to growth factors and steroids. However, only a few genes mapping to CNAs regions were found to be associated with ULs.We applied an integrative analysis using genomic and transcriptomic data to identify the pathways and molecular markers associated with ULs. Fifty-one fresh frozen specimens were evaluated by array CGH (JISTIC and gene expression microarrays (SAM. The CONEXIC algorithm was applied to integrate the data.The integrated analysis identified the top 30 significant genes (P<0.01, which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (P = 0.006 and P<0.01, respectively and IGFBP5 (P = 0.0002 and P = 0.006, respectively were up-regulated in the tumours when compared with the adjacent normal myometrium.The integrative genomic 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.

  3. Factors associated with mothers' knowledge on infant and young child feeding recommendation in slum areas of Bahir Dar City, Ethiopia: cross sectional study.

    Science.gov (United States)

    Demilew, Yeshalem Mulugeta

    2017-06-05

    Malnutrition is a public health concern in Ethiopia. This might be correlated with inappropriate infant and young child feeding practice. This in turn is affected by Mothers' knowledge on feeding practice. However, information on mothers' knowledge on infant and young child feeding recommendation was scarce in Ethiopia. Therefore, this study was designed to assess mothers' knowledge on infant and young child feeding recommendation and associated factors in slum areas of Bahir Dar City, Ethiopia. A community based cross-sectional study was conducted from May 1-26/2015. Systematic sampling technique was used to select respondents. Data were collected by pretested, structured, interviewer administered questionnaire. Data were entered and analyzed by SPSS version 20 software. Knowledge score was computed. Binary and multivariable logistic regression analysis were used to identify factors associated with maternal knowledge. Only 28.7% of mothers had sufficient knowledge on infant and young child feeding recommendation. Factors associated with mothers, knowledge were above primary education [AOR 2.5, 95% CI (1.5, 3.9)], possession of radio [AOR 1.7, 95% CI (1.1, 2.7)], attending antenatal care [AOR 2.4, 95% CI (1.5, 4.0)], and having employed husband [AOR 2.3, 95% CI (1.2, 4.4)]. Mothers' knowledge on infant and young child feeding recommendation was very low. Hence, education on infant and young child feeding recommendation should be strengthened during antenatal care visit and using mass media especially for mothers with lower educational status to fill up of this gap.

  4. 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.

  5. Temperament Is Associated With Outdoor Free Play in Young Children: A TARGet Kids! Study.

    Science.gov (United States)

    Sharp, Julia R; Maguire, Jonathon L; Carsley, Sarah; Abdullah, Kawsari; Chen, Yang; Perrin, Eliana M; Parkin, Patricia C; Birken, Catherine S

    Outdoor free play is important for preschoolers' physical activity, health, and development. Certain temperamental characteristics are associated with obesity, nutrition, and sedentary behaviors in preschoolers, but the relationship between temperament and outdoor play has not been examined. This study examined whether there is an association between temperament and outdoor play in young children. Healthy children aged 1 to 5 years recruited to The Applied Research Group for Kids (TARGet Kids!), a community-based primary care research network, from July 2008 to September 2013 were included. Parent-reported child temperament was assessed using the Childhood Behavior Questionnaire. Outdoor free play and other potential confounding variables were assessed through validated questionnaires. Multivariable linear regression was used to determine the association between temperament and outdoor play, adjusted for potential confounders. There were 3393 children with data on outdoor play. The association between negative affectivity and outdoor play was moderated by sex; in boys, for every 1-point increase in negative affectivity score, mean outdoor play decreased by 4.7 minutes per day. There was no significant association in girls. Surgency was associated with outdoor play; for every 1-point increase in surgency/extraversion, outdoor play increased by 4.6 minutes per day. Young children's temperamental characteristics were associated with their participation in outdoor free play. Consideration of temperament could enhance interventions and strategies to increase outdoor play in young children. Longitudinal studies are needed to elucidate the relationship between children's early temperament and physical activity. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  6. [Prevalence of target organ damage and factors associated with cardiovascular events in subjects with refractory hypertension].

    Science.gov (United States)

    Armario, Pedro; Oliveras, Anna; Hernández Del Rey, Raquel; Poch, Esteban; Larrouse, María; Roca-Cusachs, Alex; de la Sierra, Alejandro

    2009-06-27

    To asses the prevalence of target organ damage (TOD) and factors associated with cardiovascular events in subjects with refractory hypertension. Cross-sectional study of 146 patients with clinical diagnosis of refractory hypertension. TOD was defined as the presence of microalbuminuria (MA), renal failure (RF), left ventricular hypertrophy (LVH) or left atrial enlargement (LAE). Cardiovascular events were defined as the antecedent of stroke, coronary heart disease, heart failure or peripheral arterial disease. 24-h ambulatory blood pressure monitoring was (ABPM) performed with a validated Spacelabs 90207. The prevalence of LVH was 62.3%, and LAE was observed in 27.7% of the subjects. The prevalence of RF was 28.1% and MA was found in 41,4%. An association between MA and LVH was observed. After adjusting by age, the urinary albumin excretion (UAE) correlated with clinical blood pressure (BP) and BP during 24-h ABPM, whereas LVMI correlated with ambulatory BP but not with clinical BP. The prevalence of previous cardiovascular events was 22% and in the multivariate regression analysis, UAE was the only independent factor associated with the antecedent of cardiovascular events. In subjects with refractory hypertension, the prevalence of TOD was high, and an association between heart and renal organ damage was observed. UAE was independently associated with the antecedent of cardiovascular disease.

  7. STOPGAP: a database for systematic target opportunity assessment by genetic association predictions.

    Science.gov (United States)

    Shen, Judong; Song, Kijoung; Slater, Andrew J; Ferrero, Enrico; Nelson, Matthew R

    2017-09-01

    We developed the STOPGAP (Systematic Target OPportunity assessment by Genetic Association Predictions) database, an extensive catalog of human genetic associations mapped to effector gene candidates. STOPGAP draws on a variety of publicly available GWAS associations, linkage disequilibrium (LD) measures, functional genomic and variant annotation sources. Algorithms were developed to merge the association data, partition associations into non-overlapping LD clusters, map variants to genes and produce a variant-to-gene score used to rank the relative confidence among potential effector genes. This database can be used for a multitude of investigations into the genes and genetic mechanisms underlying inter-individual variation in human traits, as well as supporting drug discovery applications. Shell, R, Perl and Python scripts and STOPGAP R data files (version 2.5.1 at publication) are available at https://github.com/StatGenPRD/STOPGAP . Some of the most useful STOPGAP fields can be queried through an R Shiny web application at http://stopgapwebapp.com . matthew.r.nelson@gsk.com. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  8. Factors associated with high probability of target blood pressure non-achievement in hypertensive patients

    Directory of Open Access Journals (Sweden)

    S. P. Zhemanyuk

    2017-12-01

    periods DBP (HS = 36,6; the average pulse blood pressure (OR = 65.9, the rate of morning rise of SBP (OR = 3.6, and the maximum aggregation time of 5-minute ADP-induced platelet aggregation (OR = 3.5. Independent factors influencing the target blood pressure level pure reaching are the average diurnal DBP (OR = 47.8; variability of diurnal SBP (HS = 4.6; the maximum aggregation time of ADP-induced platelet aggregation (OR = 3.4. Female sex is associated with the best prognosis for the target level of BP reaching (OR = 0.4; 95% CI = 0.2‒0.8; p = 0.012. Conclusions. The independent factors influencing the target blood pressure level poor reaching in patients with EH are two ABPM parameters (the average diurnal diastolic blood pressure of more than 76 mm Hg and the variability of SBP diurnal more than 17 mm Hg; and one ADP-induced platelet aggregation parameter (the maximum aggregation time more than 143 seconds. The female sex is associated with better prediction of achieving the target level of blood pressure.

  9. Melanin targets LC3-associated phagocytosis (LAP): A novel pathogenetic mechanism in fungal disease.

    Science.gov (United States)

    Chamilos, Georgios; Akoumianaki, Tonia; Kyrmizi, Irene; Brakhage, Axel; Beauvais, Anne; Latge, Jean-Paul

    2016-05-03

    Intracellular swelling of conidia of the major human airborne fungal pathogen Aspergillus fumigatus results in surface exposure of immunostimulatory pathogen-associated molecular patterns (PAMPs) and triggers activation of a specialized autophagy pathway called LC3-associated phagocytosis (LAP) to promote fungal killing. We have recently discovered that, apart from PAMPs exposure, cell wall melanin removal during germination of A. fumigatus is a prerequisite for activation of LAP. Importantly, melanin promotes fungal pathogenicity via targeting LAP, as a melanin-deficient A. fumigatus mutant restores its virulence upon conditional inactivation of Atg5 in hematopoietic cells of mice. Mechanistically, fungal cell wall melanin selectively excludes the CYBA/p22phox subunit of NADPH oxidase from the phagosome to inhibit LAP, without interfering with signaling regulating cytokine responses. Notably, inhibition of LAP is a general property of melanin pigments, a finding with broad physiological implications.

  10. Factors associated with adherence to diabetes care recommendations among children and adolescents with type 1 diabetes: a facility-based study in two urban diabetes clinics in Uganda

    Directory of Open Access Journals (Sweden)

    Kyokunzire C

    2018-03-01

    Full Text Available Catherine Kyokunzire,1 Nicholas Matovu2,3 1Department of Community Health and Behavioural Sciences, School of Public Health, College of Health Sciences, Makerere University, Kampala, Uganda; 2Department of Community Health, Division of Noncommunicable Diseases, Ministry of Health – Uganda, Kampala, Uganda; 3Global Health Corps Fellowship Program 2017/2018, New York, NY, USA Purpose: The purpose of this study was to determine the level of adherence and the factors associated with adherence to diabetes care recommendations among type 1 diabetic children and adolescents at two urban diabetes clinics in Kampala, Uganda.Research design and methods: A facility-based cross-sectional study was carried out among 200 children and adolescents with type 1 diabetes at two major diabetes clinics in Kampala. Caretakers of the children and adolescents were interviewed using pretested questionnaires to provide information on sociodemographic characteristics, diabetes care, knowledge, attitudes, and adherence to diabetes care recommendations in type 1 diabetes. Prevalence rate ratios (PRRs at the 95% confidence interval (CI were used to establish the factors associated with adherence using modified Poisson regression, with robust standard errors. The data were analyzed by using STATA Version 13.0.Results: The overall prevalence of adherence to diabetes care recommendations was at 37%. However, evaluating adherence to specific treatment parameters showed that 52%, 76.5%, and 29.5% of the children and adolescents adhered to insulin, blood glucose monitoring, and dietary recommendations, respectively. In the final adjusted model, active diet monitoring (adjusted PRR [APRR]: 1.95; 95% CI: 1.01, 3.78, being under care of a sibling (APRR: 1.66; 95% CI: 1.61, 1.71, being under care of a married caretaker (APRR: 1.10; 95% CI: 1.05, 1.14 and a separated or divorced caretaker (APRR: 1.60; 95% CI: 1.12, 2.27, taking three or less tests of blood glucose per day (APRR: 0

  11. Multifaceted Sexual Desire and Hormonal Associations: Accounting for Social Location, Relationship Status, and Desire Target.

    Science.gov (United States)

    Chadwick, Sara B; Burke, Shannon M; Goldey, Katherine L; van Anders, Sari M

    2017-11-01

    Sexual desire is typically measured as a unitary erotic phenomenon and is often assumed by biological and biomedical researchers, as well as the lay public, to be directly connected to physiological parameters like testosterone (T). In the present study, we empirically examined how conceptualizing sexual desire as multifaceted might clarify associations with T and contextual variables. To do so, we used the Sexual Desire Questionnaire (DESQ), which assesses multifaceted dyadic sexual desire, to explore how contextual variables such as social location, relationship status, and desire target (e.g., partner vs. stranger) might be meaningful for reports of sexual desire and associated hormonal correlations. We focused on women (N = 198), because sexual desire and testosterone are generally unlinked in healthy men. Participants imagined a partner or stranger while answering the 65 DESQ items and provided a saliva sample for hormone assay. Analyses showed that the DESQ factored differently for the current sample than in previous research, highlighting how sexual desire can be constructed differently across different populations. We also found that, for the Intimacy, Eroticism, and Partner Focus factors, mean scores were higher when the desire target was a partner relative to a stranger for participants in a relationship, but equally high between partner versus stranger target for single participants. DESQ items resolved into meaningful hormonal desire components, such that high endorsement of Fantasy Experience was linked to higher T, and higher cortisol was linked with lower endorsement of the Intimacy factor. We argue that conceptualizing desire as multifaceted and contextualized when assessing hormonal links-or questions in general about desire-can clarify some of its complexities and lead to new research avenues.

  12. Experimental Assessment of Flow Fields Associated with Heart Valve Prostheses Using Particle Image Velocimetry (PIV): Recommendations for Best Practices.

    Science.gov (United States)

    Raghav, Vrishank; Sastry, Sudeep; Saikrishnan, Neelakantan

    2018-03-12

    Experimental flow field characterization is a critical component of the assessment of the hemolytic and thrombogenic potential of heart valve substitutes, thus it is important to identify best practices for these experimental techniques. This paper presents a brief review of commonly used flow assessment techniques such as Particle image velocimetry (PIV), Laser doppler velocimetry, and Phase contrast magnetic resonance imaging and a comparison of these methodologies. In particular, recommendations for setting up planar PIV experiments such as recommended imaging instrumentation, acquisition and data processing are discussed in the context of heart valve flows. Multiple metrics such as residence time, local velocity and shear stress that have been identified in the literature as being relevant to hemolysis and thrombosis in heart valves are discussed. Additionally, a framework for uncertainty analysis and data reporting for PIV studies of heart valves is presented in this paper. It is anticipated that this paper will provide useful information for heart valve device manufacturers and researchers to assess heart valve flow fields for the potential for hemolysis and thrombosis.

  13. No time for the gym? Housework and other non-labor market time use patterns are associated with meeting physical activity recommendations among adults in full-time, sedentary jobs.

    Science.gov (United States)

    Smith, Lindsey P; Ng, Shu Wen; Popkin, Barry M

    2014-11-01

    Physical activity and inactivity have distinct cardio-metabolic consequences, suggesting that combinations of activities can impact health above and beyond the effects of a single activity. However, little work has examined patterns of non-labor market time activity in the US population, particularly among full-time employees in sedentary occupations, who are at increased risk of adverse health consequences associated with a sedentary lifestyle. Identification of these patterns, and how they are related to total physical activity levels, is important for developing effective, attainable physical activity recommendations among sedentary employees, who typically have less time available for exercise. This is especially the case for low-income employees who face the highest time and financial barriers to achieving physical activity goals. This study uses cluster analysis to examine patterns of non-labor market time use among full-time (≥40 h/week) employed adults in sedentary occupations (working days in the American Time Use Study. We then examine whether these patterns are associated with higher likelihood of meeting physical activity recommendations and higher overall physical activity (MET-h). We find that non-labor market time use patterns include those characterized by screen activities, housework, caregiving, sedentary leisure, and exercise. For both genders, the screen pattern was the most common and increased from 2003 to 2012, while the exercise pattern was infrequent and consistent across time. Screen, sedentary leisure, and community patterns were associated with lower likelihoods of meeting physical activity recommendations, suggesting that interventions targeting screen time may miss opportunities to improve physical activity among similarly sedentary groups. Alternately, non-labor market time use patterns characterized by housework and caregiving represented feasible avenues for increasing overall physical activity levels, especially for those with

  14. 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.

  15. ceRNAs in plants: computational approaches and associated challenges for target mimic research.

    Science.gov (United States)

    Paschoal, Alexandre Rossi; Lozada-Chávez, Irma; Domingues, Douglas Silva; Stadler, Peter F

    2017-05-30

    The competing endogenous RNA hypothesis has gained increasing attention as a potential global regulatory mechanism of microRNAs (miRNAs), and as a powerful tool to predict the function of many noncoding RNAs, including miRNAs themselves. Most studies have been focused on animals, although target mimic (TMs) discovery as well as important computational and experimental advances has been developed in plants over the past decade. Thus, our contribution summarizes recent progresses in computational approaches for research of miRNA:TM interactions. We divided this article in three main contributions. First, a general overview of research on TMs in plants is presented with practical descriptions of the available literature, tools, data, databases and computational reports. Second, we describe a common protocol for the computational and experimental analyses of TM. Third, we provide a bioinformatics approach for the prediction of TM motifs potentially cross-targeting both members within the same or from different miRNA families, based on the identification of consensus miRNA-binding sites from known TMs across sequenced genomes, transcriptomes and known miRNAs. This computational approach is promising because, in contrast to animals, miRNA families in plants are large with identical or similar members, several of which are also highly conserved. From the three consensus TM motifs found with our approach: MIM166, MIM171 and MIM159/319, the last one has found strong support on the recent experimental work by Reichel and Millar [Specificity of plant microRNA TMs: cross-targeting of mir159 and mir319. J Plant Physiol 2015;180:45-8]. Finally, we stress the discussion on the major computational and associated experimental challenges that have to be faced in future ceRNA studies. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Targeted decorin gene therapy delivered with adeno-associated virus effectively retards corneal neovascularization in vivo.

    Directory of Open Access Journals (Sweden)

    Rajiv R Mohan

    Full Text Available Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5 impedes corneal neovascularization (CNV in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 µl; 5×10(12 vg/ml application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and CD31 immunoblotting. Real-time PCR quantified mRNA expression of pro- and anti-angiogenic genes. Corneal health in live animals was monitored with clinical, slit-lamp and optical coherence tomography biomicroscopic examinations. Selective decorin delivery into stroma showed significant 52% (p<0.05, 66% (p<0.001, and 63% (p<0.01 reduction at early (day 5, mid (day 10, and late (day 14 stages of CNV in decorin-delivered rabbit corneas compared to control (no decorin delivered corneas in morphometric analysis. The H&E staining, lectin, collagen type IV, CD31 immunostaining (57-65, p<0.5, and CD31 immunoblotting (62-67%, p<0.05 supported morphometric findings. Quantitative PCR studies demonstrated decorin gene therapy down-regulated expression of VEGF, MCP1 and angiopoietin (pro-angiogenic and up-regulated PEDF (anti-angiogenic genes. The clinical, biomicroscopy and transmission electron microscopy studies revealed that AAV5-mediated decorin gene therapy is safe for the cornea. Tissue-targeted AAV5-mediated decorin gene therapy decreases CNV with no major side effects, and could potentially be used for treating patients.

  17. Breeding for cuticle-associated traits in crop species: traits, targets, and strategies.

    Science.gov (United States)

    Petit, Johann; Bres, Cécile; Mauxion, Jean-Philippe; Bakan, Bénédicte; Rothan, Christophe

    2017-11-09

    Improving crop productivity and quality while promoting sustainable agriculture have become major goals in plant breeding. The cuticle is a natural film covering the aerial organs of plants and consists of lipid polyesters covered and embedded with wax. The cuticle protects plants against water loss and pathogens and affects traits with strong impacts on crop quality such as, for horticultural crops, fruit brightness, cracking, russeting, netting, and shelf life. Here we provide an overview of the most important cuticle-associated traits that can be targeted for crop improvement. To date, most studies on cuticle-associated traits aimed at crop breeding have been done on fleshy fruits. Less information is available for staple crops such as rice, wheat or maize. Here we present new insights into cuticle formation and properties resulting from the study of genetic resources available for the various crop species. Our review also covers the current strategies and tools aimed at exploiting available natural and artificially induced genetic diversity and the technologies used to transfer the beneficial alleles affecting cuticle-associated traits to commercial varieties. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Water disinfection in the mountains - state of the art recommendation paper of the Union Internationale des Associations d'Alpinisme Medical Commission.

    Science.gov (United States)

    Küpper, Thomas E A H; Schöffl, Volker; Milledge, Jim S

    2009-01-01

    This paper provides the official recommendation of the Union Internationale des Associations d'Alpinisme (UIAA) Medical Commission to manage the problem of safe drinking water. The recommendation was accepted and authorized for publication by the Medical Commission during their annual meeting at Treplice, Tzechia, 2008. Safe water is essential for mountaineers worldwide in order to balance challenges associated with high altitude dehydration. The paper summarizes the advantages and disadvantages of several procedures used to procure safe drinking water in the mountains or at high altitude. Limitations or critical details, which may cause failure of the methods are mentioned systematically. We differentiate between "conventional" methods, which should be preferred because they produce safe water and "improvisation". The latter does not produce safe water but may be used if conventional methods are not available for any reason. They decrease the concentration of pathogenic microorganisms and by this they reduce the risk of enteral infection. Water filtration using a ceramic filter system or chemical disinfection is recommended as a standard method. Boiling water should be avoided because it is too fuel consuming and has the potential to increase deforestation. Generally, with regard to infections by water or food, all mountaineers should be vaccinated against hepatitis A and poliomyelitis in regions where they may be at-risk.

  19. Plasma Membrane Targeting of Protocadherin 15 Is Regulated by the Golgi-Associated Chaperone Protein PIST

    Directory of Open Access Journals (Sweden)

    Hongyun Nie

    2016-01-01

    Full Text Available Protocadherin 15 (PCDH15 is a core component of hair cell tip-links and crucial for proper function of inner ear hair cells. Mutations of PCDH15 gene cause syndromic and nonsyndromic hearing loss. At present, the regulatory mechanisms responsible for the intracellular transportation of PCDH15 largely remain unknown. Here we show that PIST, a Golgi-associated, PDZ domain-containing protein, interacts with PCDH15. The interaction is mediated by the PDZ domain of PIST and the C-terminal PDZ domain-binding interface (PBI of PCDH15. Through this interaction, PIST retains PCDH15 in the trans-Golgi network (TGN and reduces the membrane expression of PCDH15. We have previously showed that PIST regulates the membrane expression of another tip-link component, cadherin 23 (CDH23. Taken together, our finding suggests that PIST regulates the intracellular trafficking and membrane targeting of the tip-link proteins CDH23 and PCDH15.

  20. Not Just "A Walking the Dog": Dog Walking and Pet Play and Their Association With Recommended Physical Activity Among Adolescents.

    Science.gov (United States)

    Martin, Karen E; Wood, Lisa; Christian, Hayley; Trapp, Georgina S A

    2015-01-01

    To examine the role of pet play and dog walking in children's and adolescents' leisure time, and the relationship between these activities and physical activity. The study design was observational. The study setting was metropolitan Perth and nonmetropolitan regions in Western Australia. The study included 1097 primary school (mean age, 10.1 years; SD, 1.6 years) and 657 secondary school (mean age, 14.0 years; SD, 1.3 years) students. Validated measures of total physical activity, dog walking, and pet play activity (prevalence and time) were calculated. Generalized linear models tested for differences between proportions, while adjusting for socioeconomic status, age, and school-level clustering. Approximately one third of primary school and one quarter of secondary school students reported that they walked the dog at least once in the last week. Pet play was the most common play activity for primary and secondary school girls, and the second and third most popular play activity for secondary and primary school boys, respectively. Secondary school students who walked the dog or played with pets spent an average of 1 hour per week on each activity, and they were significantly more likely (p physical activity recommendations than secondary school students not reporting these activities. Given the significant proportion of young people who frequently engage in dog walking and pet play, and the high level of pet ownership in many Western countries, promotion of these activities to support young people's health is warranted.

  1. Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach.

    Science.gov (United States)

    Floegel, Anna; Stefan, Norbert; Yu, Zhonghao; Mühlenbruch, Kristin; Drogan, Dagmar; Joost, Hans-Georg; Fritsche, Andreas; Häring, Hans-Ulrich; Hrabě de Angelis, Martin; Peters, Annette; Roden, Michael; Prehn, Cornelia; Wang-Sattler, Rui; Illig, Thomas; Schulze, Matthias B; Adamski, Jerzy; Boeing, Heiner; Pischon, Tobias

    2013-02-01

    Metabolomic discovery of biomarkers of type 2 diabetes (T2D) risk may reveal etiological pathways and help to identify individuals at risk for disease. We prospectively investigated the association between serum metabolites measured by targeted metabolomics and risk of T2D in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam (27,548 adults) among all incident cases of T2D (n = 800, mean follow-up 7 years) and a randomly drawn subcohort (n = 2,282). Flow injection analysis tandem mass spectrometry was used to quantify 163 metabolites, including acylcarnitines, amino acids, hexose, and phospholipids, in baseline serum samples. Serum hexose; phenylalanine; and diacyl-phosphatidylcholines C32:1, C36:1, C38:3, and C40:5 were independently associated with increased risk of T2D and serum glycine; sphingomyelin C16:1; acyl-alkyl-phosphatidylcholines C34:3, C40:6, C42:5, C44:4, and C44:5; and lysophosphatidylcholine C18:2 with decreased risk. Variance of the metabolites was largely explained by two metabolite factors with opposing risk associations (factor 1 relative risk in extreme quintiles 0.31 [95% CI 0.21-0.44], factor 2 3.82 [2.64-5.52]). The metabolites significantly improved T2D prediction compared with established risk factors. They were further linked to insulin sensitivity and secretion in the Tübingen Family study and were partly replicated in the independent KORA (Cooperative Health Research in the Region of Augsburg) cohort. The data indicate that metabolic alterations, including sugar metabolites, amino acids, and choline-containing phospholipids, are associated early on with a higher risk of T2D.

  2. 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...

  3. Molecular-Targeted Immunotherapeutic Strategy for Melanoma via Dual-Targeting Nanoparticles Delivering Small Interfering RNA to Tumor-Associated Macrophages.

    Science.gov (United States)

    Qian, Yuan; Qiao, Sha; Dai, Yanfeng; Xu, Guoqiang; Dai, Bolei; Lu, Lisen; Yu, Xiang; Luo, Qingming; Zhang, Zhihong

    2017-09-26

    Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancer immunotherapy. Targeted delivery of therapeutic drugs to the tumor-promoting M2-like TAMs is challenging. Here, we developed M2-like TAM dual-targeting nanoparticles (M2NPs), whose structure and function were controlled by α-peptide (a scavenger receptor B type 1 (SR-B1) targeting peptide) linked with M2pep (an M2 macrophage binding peptide). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, we developed a molecular-targeted immunotherapeutic approach to specifically block the survival signal of M2-like TAMs and deplete them from melanoma tumors. We confirmed the validity of SR-B1 for M2-like TAM targeting and demonstrated the synergistic effect of the two targeting units (α-peptide and M2pep) in the fusion peptide (α-M2pep). After being administered to tumor-bearing mice, M2NPs had higher affinity to M2-like TAMs than to tissue-resident macrophages in liver, spleen, and lung. Compared with control treatment groups, M2NP-based siRNA delivery resulted in a dramatic elimination of M2-like TAMs (52%), decreased tumor size (87%), and prolonged survival. Additionally, this molecular-targeted strategy inhibited immunosuppressive IL-10 and TGF-β production and increased immunostimulatory cytokines (IL-12 and IFN-γ) expression and CD8 + T cell infiltration (2.9-fold) in the tumor microenvironment. Moreover, the siRNA-carrying M2NPs down-regulated expression of the exhaustion markers (PD-1 and Tim-3) on the infiltrating CD8 + T cells and stimulated their IFN-γ secretion (6.2-fold), indicating the restoration of T cell immune function. Thus, the dual-targeting property of M2NPs combined with RNA interference provides a potential strategy of molecular-targeted cancer immunotherapy for clinical application.

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

    Science.gov (United States)

    Bieszk, Nella; Grabner, Michael; Wei, Wenhui; Bonine, Nicole G; Stephenson, Judith J

    2016-01-01

    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). 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. 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 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.

  5. Uvrag targeting by Mir125a and Mir351 modulates autophagy associated with Ewsr1 deficiency.

    Science.gov (United States)

    Kim, Yunha; Kang, Young-Sook; Lee, Na-Young; Kim, Ki Yoon; Hwang, Yu Jin; Kim, Hyun-Wook; Rhyu, Im Joo; Her, Song; Jung, Min-Kyung; Kim, Sun; Lee, Chai-Jin; Ko, Seyoon; Kowall, Neil W; Lee, Sean Bong; Lee, Junghee; Ryu, Hoon

    2015-01-01

    The EWSR1 (EWS RNA-binding protein 1/Ewing Sarcoma Break Point Region 1) gene encodes a RNA/DNA binding protein that is ubiquitously expressed and involved in various cellular processes. EWSR1 deficiency leads to impairment of development and accelerated senescence but the mechanism is not known. Herein, we found that EWSR1 modulates the Uvrag (UV radiation resistance associated) gene at the post-transcription level. Interestingly, EWSR1 deficiency led to the activation of the DROSHA-mediated microprocessor complex and increased the level of Mir125a and Mir351, which directly target Uvrag. Moreover, the Mir125a- and Mir351-mediated reduction of Uvrag was associated with the inhibition of autophagy that was confirmed in ewsr1 knockout (KO) MEFs and ewsr1 KO mice. Taken together, our data indicate that EWSR1 is involved in the post-transcriptional regulation of Uvrag via a miRNA-dependent pathway, resulting in the deregulation of autophagy inhibition. The mechanism of Uvrag and autophagy regulation by EWSR1 provides new insights into the role of EWSR1 deficiency-related cellular dysfunction.

  6. Dnmts and Tet target memory-associated genes after appetitive olfactory training in honey bees.

    Science.gov (United States)

    Biergans, Stephanie D; Giovanni Galizia, C; Reinhard, Judith; Claudianos, Charles

    2015-11-04

    DNA methylation and demethylation are epigenetic mechanisms involved in memory formation. In honey bees DNA methyltransferase (Dnmt) function is necessary for long-term memory to be stimulus specific (i.e. to reduce generalization). So far, however, it remains elusive which genes are targeted and what the time-course of DNA methylation is during memory formation. Here, we analyse how DNA methylation affects memory retention, gene expression, and differential methylation in stimulus-specific olfactory long-term memory formation. Out of 30 memory-associated genes investigated here, 9 were upregulated following Dnmt inhibition in trained bees. These included Dnmt3 suggesting a negative feedback loop for DNA methylation. Within these genes also the DNA methylation pattern changed during the first 24 hours after training. Interestingly, this was accompanied by sequential activation of the DNA methylation machinery (i.e. Dnmts and Tet). In sum, memory formation involves a temporally complex epigenetic regulation of memory-associated genes that facilitates stimulus specific long-term memory in the honey bee.

  7. Targeted disruption of the blood-brain barrier with focused ultrasound: association with cavitation activity

    International Nuclear Information System (INIS)

    McDannold, N; Vykhodtseva, N; Hynynen, K

    2006-01-01

    Acoustic emission was monitored during focused ultrasound exposures in conjunction with an ultrasound contrast agent (Optison (registered) ) in order to determine if cavitation activity is associated with the induction of blood-brain barrier disruption (BBBD). Thirty-four locations were sonicated (frequency: 260 kHz) at targets 10 mm deep in rabbit brain (N = 9). The sonications were applied at peak pressure amplitudes ranging from 0.11 to 0.57 MPa (burst length: 10 ms; repetition frequency of 1 Hz; duration: 20 s). Acoustic emission was recorded with a focused passive cavitation detector. This emission was recorded at each location during sonications with and without Optison (registered) . Detectable wideband acoustic emission was observed only at 0.40 and 0.57 MPa. BBBD was observed in contrast MRI after sonication at 0.29-0.57 MPa. The appearance of small regions of extravasated erythrocytes appeared to be associated with this wideband emission signal. The results thus suggest that BBBD resulting from focused ultrasound pulses in the presence of Optison (registered) can occur without indicators for inertial cavitation in vivo, wideband emission and extravasation. If inertial cavitation is not responsible for the BBBD, other ultrasound/microbubble interactions are likely the source. A significant increase in the emission signal due to Optison (registered) at the second and third harmonics of the ultrasound driving frequency was found to correlate with BBBD and might be useful as an online method to indicate when the disruption occurs

  8. Knowledge of physical activity recommendations in adults employed in England: associations with individual and workplace-related predictors.

    Science.gov (United States)

    Knox, Emily C L; Musson, Hayley; Adams, Emma J

    2015-05-23

    Physical activity guidelines state that adults should engage in at least 150 min of moderate to vigorous physical activity (MVPA) per week to benefit health. A high proportion of adults in England fail to reach this target. Accurate knowledge of MVPA guidelines could influence the amount and quality of MVPA engaged in by adults. This study aimed to determine knowledge of the MVPA guideline within a large sample of working adults in England and identify individual and workplace-related predictors of knowledge. 10,992 adults completed an online survey which included questions on demographics, knowledge of the MVPA guideline and workplace predictors for physical activity. Multinomial logistic regression identified predictors of underestimating, overestimating or not knowing the MVPA guideline relative to accurately reporting the guideline for males and females separately. Respondents were 37% male, 95% White, 63% with a degree or higher, and had a mean age of 38.9 ± 11 years. The MVPA guideline was accurately reported by 15% of adults while 13.8% overestimated, 8.9% underestimated and 62.3% failed to provide any estimate of the guideline. Low education predicted underestimation (females: OR = 0.36, 95% CI 0.17, 0.80) and not knowing (males: OR = 0.37, 95% CI 0.14, 0.96; females: OR = 0.36, 95% CI 0.19, 0.69). Ethnicity was a significant predictor for females only (OR 3.55, 95% CI 1.46, 8.63; OR 4.03, 95% CI 1.58, 10.27; OR 3.73, 95% CI 1.67, 8.33). Employer support for physical activity was a significant predictor of accurate knowledge of the MVPA guideline for both males (underestimation: OR = 0.63, 95% CI 0.40, 1.00; 'don't know': OR = 0.71, 95% CI 0.51, 1.00) and females (overestimation: OR = 0.72, 95% CI 0.53, 0.97; underestimation: OR = 0.66, 95% CI 0.47, 0.92; 'don't know': OR = 0.60, 95% CI 0.47, 0.76). Knowledge of the MVPA guideline within working adults in England is low. Employers should play a role in using targeted

  9. International recommendations

    International Nuclear Information System (INIS)

    Lindell, Bo

    1986-01-01

    Full text: This short presentation will indicate the general radiation protection background to protective measures against foodstuffs contaminated with radioactive substances. A number of international organizations are involved in various aspects of radiation protection, for example, the International Atomic Energy Agency (IAEA), the United Nations Food and Agriculture Organization (FAO), the United Nations Environment Programme (UNEP), and the World Health Organization (WHO). Two international organizations, however, provide the basic background. These are the International Commission on Radiological Protection (ICRP) and the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). UNSCEAR provides the scientific information on radiation levels and effects. It consists of 21 member countries, with truly international coverage. It issues reports to the UN General Assembly, including comprehensive scientific annexes. Its latest comprehensive report was issued in 1982, the next is expected to be published in 1988. That report will include an assessment of the radiological consequences of the Chernobyl accident. The ICRP is a non-governmental organization. It has issued recommendations on radiation protection since 1928. The postulated biological basis for radiation protection recommendations involves two types of biological effects. The so-called non-stochastic effects, mainly due to cell death, appear only when the radiation doses exceed a certain threshold value. These effects, therefore, can only appear after high accidental exposures. After the Chernobyl accident, they only affected about 200 individuals involved in fire extinction and rescue work at the damaged nuclear power plant. Stochastic effects, with some simplification, may be seen as the result of initial changes in the genetic code of some surviving cells. If these cells are germ cells, this may lead to hereditary harm. If they are somatic cells, the result could be cancer

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

    KAUST Repository

    Lepore, Rosalba; Tramontano, Anna; Via, Allegra

    2013-01-01

    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

  11. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association.

    Science.gov (United States)

    Lichtman, Judith H; Froelicher, Erika S; Blumenthal, James A; Carney, Robert M; Doering, Lynn V; Frasure-Smith, Nancy; Freedland, Kenneth E; Jaffe, Allan S; Leifheit-Limson, Erica C; Sheps, David S; Vaccarino, Viola; Wulsin, Lawson

    2014-03-25

    Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations. The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome. Writing group members were approved by the American Heart Association's Scientific Statement and Manuscript Oversight Committees. A systematic literature review on depression and adverse medical outcomes after acute coronary syndrome was conducted that included all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events. The review assessed the strength, consistency, independence, and generalizability of the published studies. A total of 53 individual studies (32 reported on associations with all-cause mortality, 12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met inclusion criteria. There was heterogeneity across studies in terms of the demographic composition of study samples, definition and measurement of depression, length of follow-up, and covariates included in the multivariable models. Despite limitations in some individual studies, our review identified generally consistent associations between depression and adverse outcomes. Despite the heterogeneity of published studies included in this review, the preponderance of evidence supports the recommendation that the American Heart Association should elevate depression to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome.

  12. Limonene inhibits streptococcal biofilm formation by targeting surface-associated virulence factors.

    Science.gov (United States)

    Subramenium, Ganapathy Ashwinkumar; Vijayakumar, Karuppiah; Pandian, Shunmugiah Karutha

    2015-08-01

    The present study explores the efficacy of limonene, a cyclic terpene found in the rind of citrus fruits, for antibiofilm potential against species of the genus Streptococcus, which have been deeply studied worldwide owing to their multiple pathogenic efficacy. Limonene showed a concentration-dependent reduction in the biofilm formation of Streptococcus pyogenes (SF370), with minimal biofilm inhibitory concentration (MBIC) of 400 μg ml - 1. Limonene was found to possess about 75-95 % antibiofilm activity against all the pathogens tested, viz. Streptococcus pyogenes (SF370 and 5 clinical isolates), Streptococcus mutans (UA159) and Streptococcus mitis (ATCC 6249) at 400 μg ml - 1 concentration. Microscopic analysis of biofilm architecture revealed a quantitative breach in biofilm formation. Results of a surface-coating assay suggested that the possible mode of action of limonene could be by inhibiting bacterial adhesion to surfaces, thereby preventing the biofilm formation cascade. Susceptibility of limonene-treated Streptococcus pyogenes to healthy human blood goes in unison with gene expression studies in which the mga gene was found to be downregulated. Anti-cariogenic efficacy of limonene against Streptococcus mutans was confirmed, with inhibition of acid production and downregulation of the vicR gene. Downregulation of the covR, mga and vicR genes, which play a critical role in regulating surface-associated proteins in Streptococcus pyogenes and Streptococcus mutans, respectively, is yet further evidence to show that limonene targets surface-associated proteins. The results of physiological assays and gene expression studies clearly show that the surface-associated antagonistic mechanism of limonene also reduces surface-mediated virulence factors.

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

    International Nuclear Information System (INIS)

    Chantarawong, Wipa; Takeda, Kazuhisa; Sangartit, Weerapon; Yoshizawa, Miki; Pradermwong, Kantimanee; Shibahara, Shigeki

    2014-01-01

    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

  14. 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.

  15. American Association for Emergency Psychiatry Task Force on Medical Clearance of Adult Psychiatric Patients. Part II: Controversies over Medical Assessment, and Consensus Recommendations

    Directory of Open Access Journals (Sweden)

    Michael P. Wilson

    2017-05-01

    Full Text Available Introduction: The emergency medical evaluation of psychiatric patients presenting to United States emergency departments (ED, usually termed “medical clearance,” often varies between EDs. A task force of the American Association for Emergency Psychiatry (AAEP, consisting of physicians from emergency medicine, physicians from psychiatry and a psychologist, was convened to form consensus recommendations for the medical evaluation of psychiatric patients presenting to U.S.EDs. Methods: The task force reviewed existing literature on the topic of medical evaluation of psychiatric patients in the ED and then combined this with expert consensus. Consensus was achieved by group discussion as well as iterative revisions of the written document. The document was reviewed and approved by the AAEP Board of Directors. Results: Eight recommendations were formulated. These recommendations cover various topics in emergency medical examination of psychiatric patients, including goals of medical screening in the ED, the identification of patients at low risk for co-existing medical disease, key elements in the ED evaluation of psychiatric patients including those with cognitive disorders, specific language replacing the term “medical clearance,” and the need for better science in this area. Conclusion: The evidence indicates that a thorough history and physical examination, including vital signs and mental status examination, are the minimum necessary elements in the evaluation of psychiatric patients. With respect to laboratory testing, the picture is less clear and much more controversial.

  16. Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for the Post-Bariatric Surgery Medical Management

    Directory of Open Access Journals (Sweden)

    Luca Busetto

    2017-12-01

    Full Text Available Bariatric surgery is today the most effective long-term therapy for the management of patients with severe obesity, and its use is recommended by the relevant guidelines of the management of obesity in adults. Bariatric surgery is in general safe and effective, but it can cause new clinical problems and is associated with specific diagnostic, preventive and therapeutic needs. For clinicians, the acquisition of special knowledge and skills is required in order to deliver appropriate and effective care to the post-bariatric patient. In the present recommendations, the basic notions needed to provide first-level adequate medical care to post-bariatric patients are summarised. Basic information about nutrition, management of co-morbidities, pregnancy, psychological issues as well as weight regain prevention and management is derived from current evidences and existing guidelines. A short list of clinical practical recommendations is included for each item. It remains clear that referral to a bariatric multidisciplinary centre, preferably the one performing the original procedure, should be considered in case of more complex clinical situations.

  17. Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for the Post-Bariatric Surgery Medical Management

    Science.gov (United States)

    Busetto, Luca; Dicker, Dror; Azran, Carmil; Batterham, Rachel L.; Farpour-Lambert, Nathalie; Fried, Martin; Hjelmesæth, Jøran; Kinzl, Johann; Leitner, Deborah R.; Makaronidis, Janine M.; Schindler, Karin; Toplak, Hermann; Yumuk, Volkan

    2018-01-01

    Bariatric surgery is today the most effective long-term therapy for the management of patients with severe obesity, and its use is recommended by the relevant guidelines of the management of obesity in adults. Bariatric surgery is in general safe and effective, but it can cause new clinical problems and is associated with specific diagnostic, preventive and therapeutic needs. For clinicians, the acquisition of special knowledge and skills is required in order to deliver appropriate and effective care to the post-bariatric patient. In the present recommendations, the basic notions needed to provide first-level adequate medical care to post-bariatric patients are summarised. Basic information about nutrition, management of co-morbidities, pregnancy, psychological issues as well as weight regain prevention and management is derived from current evidences and existing guidelines. A short list of clinical practical recommendations is included for each item. It remains clear that referral to a bariatric multidisciplinary centre, preferably the one performing the original procedure, should be considered in case of more complex clinical situations. PMID:29207379

  18. Perceived success/failure and attributions associated with self-regulatory efficacy to meet physical activity recommendations for women with arthritis.

    Science.gov (United States)

    Spink, Kevin S; Brawley, Lawrence R; Gyurcsik, Nancy C

    2016-10-01

    The relationship between attributional dimensions women assign to the cause of their perceived success or failure at meeting the recommended physical activity dose and self-regulatory efficacy for future physical activity was examined among women with arthritis. Women (N = 117) aged 18-84 years, with self-reported medically-diagnosed arthritis, completed on-line questions in the fall of 2013 assessing endurance physical activity, perceived outcome for meeting the recommended levels of endurance activity, attributions for one's success or failure in meeting the recommendations, and self-regulatory efficacy to schedule/plan endurance activity over the next month. The main theoretically-driven finding revealed that the interaction of the stability dimension with perceived success/failure was significantly related to self-regulatory efficacy for scheduling and planning future physical activity (β = 0.35, p = .002). Outcomes attributed to more versus less stable factors accentuated differences in self-regulatory efficacy beliefs following perceived success and failure at being active. It appears that attributional dimensions were associated with self-regulatory efficacy in women with arthritis. This suggests that rather than objectively observed past mastery experience, women's subjective perceptions and explanations of their past experiences were related to efficacy beliefs, especially following a failure experience.

  19. American Association for Emergency Psychiatry Task Force on Medical Clearance of Adult Psychiatric Patients. Part II: Controversies over Medical Assessment, and Consensus Recommendations.

    Science.gov (United States)

    Wilson, Michael P; Nordstrom, Kimberly; Anderson, Eric L; Ng, Anthony T; Zun, Leslie S; Peltzer-Jones, Jennifer M; Allen, Michael H

    2017-06-01

    The emergency medical evaluation of psychiatric patients presenting to United States emergency departments (ED), usually termed "medical clearance," often varies between EDs. A task force of the American Association for Emergency Psychiatry (AAEP), consisting of physicians from emergency medicine, physicians from psychiatry and a psychologist, was convened to form consensus recommendations for the medical evaluation of psychiatric patients presenting to U.S.EDs. The task force reviewed existing literature on the topic of medical evaluation of psychiatric patients in the ED and then combined this with expert consensus. Consensus was achieved by group discussion as well as iterative revisions of the written document. The document was reviewed and approved by the AAEP Board of Directors. Eight recommendations were formulated. These recommendations cover various topics in emergency medical examination of psychiatric patients, including goals of medical screening in the ED, the identification of patients at low risk for co-existing medical disease, key elements in the ED evaluation of psychiatric patients including those with cognitive disorders, specific language replacing the term "medical clearance," and the need for better science in this area. The evidence indicates that a thorough history and physical examination, including vital signs and mental status examination, are the minimum necessary elements in the evaluation of psychiatric patients. With respect to laboratory testing, the picture is less clear and much more controversial.

  20. Prevalence of and factors associated with antenatal care seeking and adherence to recommended iron-folic acid supplementation among pregnant women in Zinder, Niger.

    Science.gov (United States)

    Begum, Khadija; Ouédraogo, Césaire T; Wessells, K Ryan; Young, Rebecca R; Faye, M Thierno; Wuehler, Sara E; Hess, Sonja Y

    2018-02-01

    The World Health Organization recommends iron and folic acid (IFA) supplementation for pregnant women. The high prevalence of anaemia among pregnant women in Niger warrants better understanding of the utilization of antenatal care (ANC) and IFA. We aimed to assess the prevalence of and factors associated with ANC coverage and adherence to IFA recommendation among pregnant women. Pregnant women (n = 923) from 64 randomly selected villages within the catchment area of 12 health centres were interviewed during a baseline household survey in Zinder, Niger. ANC and IFA coverage were 60.1% and 43.6%, respectively. Only 71.7% of women who attended ANC received IFA. Of the 401 women who reportedly received any IFA supplements, 99.3% had attended any ANC during their current pregnancy and 68.6% reported adherence to recommended IFA supplementation (i.e., consumed IFA every day in the previous week). Women with gestational age ≥27 weeks were more likely to have attended ANC than women with gestational age ANC were more likely to attend ANC (OR: 1.48, 95% CI [1.03, 2.11]) and adhere to IFA recommendations (OR: 1.80, 95% CI [1.04, 3.13]) compared to those who did not receive any advice. ANC attendance is crucial to ensure distribution of IFA supplementation among pregnant women in Zinder. Interventions to improve ANC and IFA adherence will require promotion of early ANC, ensure availability of IFA at ANC, and involve husbands in ANC. © 2018 John Wiley & Sons Ltd.

  1. Large-scale automatic extraction of side effects associated with targeted anticancer drugs from full-text oncological articles.

    Science.gov (United States)

    Xu, Rong; Wang, QuanQiu

    2015-06-01

    Targeted anticancer drugs such as imatinib, trastuzumab and erlotinib dramatically improved treatment outcomes in cancer patients, however, these innovative agents are often associated with unexpected side effects. The pathophysiological mechanisms underlying these side effects are not well understood. The availability of a comprehensive knowledge base of side effects associated with targeted anticancer drugs has the potential to illuminate complex pathways underlying toxicities induced by these innovative drugs. While side effect association knowledge for targeted drugs exists in multiple heterogeneous data sources, published full-text oncological articles represent an important source of pivotal, investigational, and even failed trials in a variety of patient populations. In this study, we present an automatic process to extract targeted anticancer drug-associated side effects (drug-SE pairs) from a large number of high profile full-text oncological articles. We downloaded 13,855 full-text articles from the Journal of Oncology (JCO) published between 1983 and 2013. We developed text classification, relationship extraction, signaling filtering, and signal prioritization algorithms to extract drug-SE pairs from downloaded articles. We extracted a total of 26,264 drug-SE pairs with an average precision of 0.405, a recall of 0.899, and an F1 score of 0.465. We show that side effect knowledge from JCO articles is largely complementary to that from the US Food and Drug Administration (FDA) drug labels. Through integrative correlation analysis, we show that targeted drug-associated side effects positively correlate with their gene targets and disease indications. In conclusion, this unique database that we built from a large number of high-profile oncological articles could facilitate the development of computational models to understand toxic effects associated with targeted anticancer drugs. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Clinical factors associated with rape victims' ability to testify in court: a records-based study of final psychiatric recommendation to court.

    Science.gov (United States)

    Phaswana, T D; Van der Westhuizen, D; Krüger, C

    2013-09-01

    A rape victim may encounter professionals in both the health and the legal systems. Unanswered questions remain about clinical factors associated with a rape victim's ability to testify in court, and the quality of care offered to rape victims. The objectives of this study were thus to determine the clinical factors that are associated with a rape victim's ability to testify in court, as well as to undertake a preliminary exploration of the referral system between the court and the mental health services. A retrospective study was conducted of rape victims referred by the court (n=70) to be assessed psycho-legally by psychiatrists. Rape victims who were recommended as able and those recommended as unable to testify in court were compared with regard to their clinical characteristics. Thirty-seven (53.6%) victims were recommended as able to testify and 32 (46.4%) victims as unable to testify in court. Victims from rural areas and victims with severe mental retardation were statistically significantly more often found to be unable to testify in court. Almost half (49.2%) of the victims were referred by court for first assessment within six months of being raped. Most (63.5%) victims were assessed for the first time within one month of being referred. The decision about a victim's ability to testify should not be based solely on the two statistically significant variables but, rather, individualised. Optimal mental health and legal services should be offered to rape victims. Further studies are required in assessing the collaboration between the health and legal systems.

  3. Broad target cell selectivity of Kaposi's sarcoma-associated herpesvirus glycoprotein-mediated cell fusion and virion entry

    International Nuclear Information System (INIS)

    Kaleeba, Johnan A.R.; Berger, Edward A.

    2006-01-01

    The molecular mechanism of Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) entry is poorly understood. We tested a broad variety of cell types of diverse species and tissue origin for their ability to function as targets in a quantitative reporter gene assay for KSHV-glycoprotein-mediated cell fusion. Several human, non-human primate, and rabbit cell lines were efficient targets, whereas rodent and all human lymphoblastoid cell lines were weak targets. Parallel findings were obtained with a virion entry assay using a recombinant KSHV encoding a reporter gene. No correlation was observed between target cell activity and surface expression of α3β1 integrin, a proposed KSHV receptor. We hypothesize that target cell permissiveness in both the cell fusion and virion entry assays reflects the presence of a putative KSHV fusion-entry receptor

  4. 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

  5. Hope for children and families: targeting abusive parenting and the associated impairment of children.

    Science.gov (United States)

    Bentovim, Arnon; Elliott, Ian

    2014-01-01

    The purpose of this study is to distill the "effective practice elements" from randomised controlled interventions (RCTs) to prevent the recurrence of abusive and neglectful parenting and the associated health and developmental impairment of children. The resulting elements would be used then to develop a step-by-step modular-systemic approach to intervention that is suitable to the needs of a variety of frontline practitioners in social care, health, and education. A series of 22 randomised RCTs were analysed using the distillation and matching approach to establish the presence of effective practice elements. The focus was physical and sexual abuse, victims and children, and young people as perpetrators; neglect including failure to thrive, emotional abuse (exposure to violence and mental health issues). The studies were analysed for effective practice elements, across different approaches matched to interventions focused on parenting, on children and young people, and on family/professional relationships. The proportion of practice elements utilised in each form of maltreatment was defined. The distillation process resulted in a total of 47 practice elements present across all forms of maltreatment studied. An experienced group of practitioners from statutory and voluntary agencies ordered and integrated the most frequently utilised emerging elements into a series of step-by-step modules, which could fit the complex needs of families when maltreatment had occurred. The resulting manual, Hope for Children and Families, provides a "menu" of evidence-based, step-by-step modular interventions targeting the profile of abusive and neglectful parenting and associated impairments of children. To be effective for frontline practitioners, the manual will need to be delivered in a user-friendly format, training developed, and supervision and support provided.

  6. Ultrasound Targeted Microbubble Destruction Stimulates Cellular Endocytosis in Facilitation of Adeno-Associated Virus Delivery

    Directory of Open Access Journals (Sweden)

    Lian-Fang Du

    2013-05-01

    Full Text Available The generally accepted mechanism for ultrasound targeted microbubble destruction (UTMD to enhance drug and gene delivery is through sonoporation. However, passive uptake of adeno-associated virus (AAV into cells following sonoporation does not adequately explain observations of enhanced transduction by UTMD. This study investigated alternative mechanisms of UTMD enhancement in AAV delivery. UTMD significantly enhanced transduction efficiency of AAV in a dose-dependent manner. UTMD stimulated a persistent uptake of AAV into the cytoplasm and nucleus. This phenomenon occurred over several hours, suggesting that some viral particles are endocytosed by cells rather than exclusively passing through pores created by sonoporation. Additionally, UTMD enhanced clathrin expression and accumulation at the plasma membrane suggesting greater clathrin-mediated endocytosis following UTMD. Transmission electron microscopy (TEM revealed that UTMD stimulated formation of clathrin-coated pits (CPs and uncoated pits (nCPs. Furthermore, inhibition of clathrin-mediated endocytosis partially blocked the enhancement of AAV uptake following UTMD. The results of this study implicate endocytosis as a mechanism that contributes to UTMD-enhanced AAV delivery.

  7. Examining the bleeding incidences associated with targeted therapies used in metastatic renal cell carcinoma.

    Science.gov (United States)

    Crist, MacKenzie; Hansen, Elizabeth; Chablani, Lipika; Guancial, Elizabeth

    2017-12-01

    A systematic review was conducted to illustrate the bleeding risks associated with targeted therapies used in the treatment of metastatic renal cell carcinoma (mRCC). Eligible studies included phase II, III, or IV clinical trials using pazopanib, sunitinib, cabozantinib, lenvatinib, everolimus, temsirolimus, bevacizumab, axitinib, and/or sorafenib in the setting of mRCC. Types of bleeding event(s), bleeding event frequency, and incidence of thrombocytopenia were collected from the relevant articles. ClinicalTrials.gov was also searched for incidence of "Serious bleeding adverse effects" reported in these trials. The incidences of bleeding events ranged from 1 to 36%, and incidences of thrombocytopenia ranged from 2 to 78%. Available serious bleeding adverse events ranged from 1 to 7%. The highest percentage of bleeding incidences were seen with bevacizumab, while the lowest percentage of bleeding incidences were seen with axitinib. All of the included trials were of high quality per Jadad scoring. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Paired Associative Stimulation Targeting the Tibialis Anterior Muscle using either Mono or Biphasic Transcranial Magnetic Stimulation

    Directory of Open Access Journals (Sweden)

    Natalie Mrachacz-Kersting

    2017-04-01

    Full Text Available 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 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 pulse form at 120% resting motor threshold (RMT; (3 subthreshold PAbi-PAS (n = 10 where PAS was applied as for (1 at 95% active motor threshold (AMT. The peak-to-peak motor evoked potentials (MEPs were quantified prior to, immediately following, and 30 min after the cessation of the intervention. TA MEP size increased significantly for all interventions immediately post (61% for suprathreshold PAbi-PAS, 83% for suprathreshold PAmono-PAS, 55% for subthreshold PAbi-PAS and 30 min after the cessation of the intervention (123% for suprathreshold PAbi-PAS, 105% for suprathreshold PAmono-PAS, 80% for subthreshold PAbi-PAS. PAS using a biphasic pulse form at subthreshold intensities induces similar effects to conventional PAS.

  9. Small Molecule Targeting of a MicroRNA Associated with Hepatocellular Carcinoma.

    Science.gov (United States)

    Childs-Disney, Jessica L; Disney, Matthew D

    2016-02-19

    Development of precision therapeutics is of immense interest, particularly as applied to the treatment of cancer. By analyzing the preferred cellular RNA targets of small molecules, we discovered that 5"-azido neomycin B binds the Drosha processing site in the microRNA (miR)-525 precursor. MiR-525 confers invasive properties to hepatocellular carcinoma (HCC) cells. Although HCC is one of the most common cancers, treatment options are limited, making the disease often fatal. Herein, we find that addition of 5"-azido neomycin B and its FDA-approved precursor, neomycin B, to an HCC cell line selectively inhibits production of the mature miRNA, boosts a downstream protein, and inhibits invasion. Interestingly, neomycin B is a second-line agent for hepatic encephalopathy (HE) and bacterial infections due to cirrhosis. Our results provocatively suggest that neomycin B, or second-generation derivatives, may be dual functioning molecules to treat both HE and HCC. Collectively, these studies show that rational design approaches can be tailored to disease-associated RNAs to afford potential lead therapeutics.

  10. 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.

  11. [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.

  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. Adeno-associated virus Rep-mediated targeting of integrase-defective retroviral vector DNA circles into human chromosome 19

    International Nuclear Information System (INIS)

    Huang, Shuohao; Kawabe, Yoshinori; Ito, Akira; Kamihira, Masamichi

    2012-01-01

    Highlights: ► Adeno-associated virus (AAV) is capable of targeted integration in human cells. ► Integrase-defective retroviral vector (IDRV) enables a circular DNA delivery. ► A targeted integration system of IDRV DNA using the AAV integration mechanism. ► Targeted IDRV integration ameliorates the safety concerns for retroviral vectors. -- Abstract: Retroviral vectors have been employed in clinical trials for gene therapy owing to their relative large packaging capacity, alterable cell tropism, and chromosomal integration for stable transgene expression. However, uncontrollable integrations of transgenes are likely to cause safety issues, such as insertional mutagenesis. A targeted transgene integration system for retroviral vectors, therefore, is a straightforward way to address the insertional mutagenesis issue. Adeno-associated virus (AAV) is the only known virus capable of targeted integration in human cells. In the presence of AAV Rep proteins, plasmids possessing the p5 integration efficiency element (p5IEE) can be integrated into the AAV integration site (AAVS1) in the human genome. In this report, we describe a system that can target the circular DNA derived from non-integrating retroviral vectors to the AAVS1 site by utilizing the Rep/p5IEE integration mechanism. Our results showed that after G418 selection 30% of collected clones had retroviral DNA targeted at the AAVS1 site.

  15. 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.

  16. 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.

  17. Recall of "The Real Cost" Anti-Smoking Campaign Is Specifically Associated With Endorsement of Campaign-Targeted Beliefs.

    Science.gov (United States)

    Kranzler, Elissa C; Gibson, Laura A; Hornik, Robert C

    2017-10-01

    Though previous research suggests the FDA's "The Real Cost" anti-smoking campaign has reduced smoking initiation, the theorized pathway of effects (through targeted beliefs) has not been evaluated. This study assesses the relationship between recall of campaign television advertisements and ad-specific anti-smoking beliefs. Respondents in a nationally representative survey of nonsmoking youths age 13-17 (n = 4,831) reported exposure to four The Real Cost advertisements and a fake ad, smoking-relevant beliefs, and nonsmoking intentions. Analyses separately predicted each targeted belief from specific ad recall, adjusting for potential confounders and survey weights. Parallel analyses with non-targeted beliefs showed smaller effects, strengthening claims of campaign effects. Recall of four campaign ads (but not the fake ad) significantly predicted endorsement of the ad-targeted belief (Mean β = .13). Two-sided sign tests indicated stronger ad recall associations with the targeted belief relative to the non-targeted belief (p < .05). Logistic regression analyses indicated that respondents who endorsed campaign-targeted beliefs were more likely to have no intention to smoke (p < .01). This study is the first to demonstrate a relationship between recall of ads from The Real Cost campaign and the theorized pathway of effects (through targeted beliefs). These analyses also provide a methodological template for showing campaign effects despite limitations of available data.

  18. 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.

  19. Light Video Game Play is Associated with Enhanced Visual Processing of Rapid Serial Visual Presentation Targets.

    Science.gov (United States)

    Howard, Christina J; Wilding, Robert; Guest, Duncan

    2017-02-01

    There is mixed evidence that video game players (VGPs) may demonstrate better performance in perceptual and attentional tasks than non-VGPs (NVGPs). The rapid serial visual presentation task is one such case, where observers respond to two successive targets embedded within a stream of serially presented items. We tested light VGPs (LVGPs) and NVGPs on this task. LVGPs were better at correct identification of second targets whether they were also attempting to respond to the first target. This performance benefit seen for LVGPs suggests enhanced visual processing for briefly presented stimuli even with only very moderate game play. Observers were less accurate at discriminating the orientation of a second target within the stream if it occurred shortly after presentation of the first target, that is to say, they were subject to the attentional blink (AB). We find no evidence for any reduction in AB in LVGPs compared with NVGPs.

  20. MicroRNAs and liver cancer associated with iron overload: Therapeutic targets unravelled

    Science.gov (United States)

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

    2013-01-01

    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. PMID:23983424

  1. 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

  2. Radiotherapy for non-small cell lung cancer: volume definition and patient selection. Annecy 1998 international Association for the study of lung cancer (IASLC) Workshop recommendations

    International Nuclear Information System (INIS)

    Mornex, F.; Loubeyre, P.; Van houtte, P.; Scalliet, P.

    1998-01-01

    Chemo-radiation is the standard treatment of unresectable, locally advanced non-small cell lung cancer, with a mean dose of 60-66 Gy, excluding escalation dose schemes. The standard treated volume includes primary tumor, ipsilateral hilar and mediastinal nodes, supraclavicular and contralateral nodes as well, regardless of the node status. This work tries to answer the question of the optimal volume to be treated. Drainage routes analysis is in favor of large volumes, while toxicity analysis favors small volumes. Combined modality treatment may increase the observed toxicity. The optimal volume definition is difficult, and requires available conformal therapy tools. Patients selection is another important issue. A volume definition is then attempted, based on the IASLC (International Association for the Study of Lung Cancer) Annecy workshop experience, highlighting the inter-observers discrepancies, and suggests basic recommendations to harmonize volume definition. (author)

  3. 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

  4. Determination of Eligibility in Related Pediatric Hematopoietic Cell Donors: Ethical and Clinical Considerations. Recommendations from a Working Group of the Worldwide Network for Blood and Marrow Transplantation Association.

    Science.gov (United States)

    Bitan, Menachem; van Walraven, Suzanna M; Worel, Nina; Ball, Lynne M; Styczynski, Jan; Torrabadella, Marta; Witt, Volker; Shaw, Bronwen E; Seber, Adriana; Yabe, Hiromasa; Greinix, Hildegard T; Peters, Christina; Gluckman, Eliane; Rocha, Vanderson; Halter, Joerg; Pulsipher, Michael A

    2016-01-01

    Related donors for hematopoietic cell (HC) transplantation are a growing population in recent years because of expanding indications for allogeneic transplantation. The safety and welfare of the donor are major concerns for the transplantation community, especially for related sibling donors of young recipients who are children and, thus, not able to fully consent. Because donation of HC does not improve the donor's own physical health and carries a risk of side effects, careful assessment of medical risks specific to the individual donor, as well as consideration of ethical and legal aspects associated with donation from a child, must be considered. In addition, donor centers must balance the needs of both the donor and the recipient, understanding the inherent conflict parents may have as they can be overly focused on the very sick child receiving a transplant, rather than on the relatively less significant health or emotional problems that a sibling donor may have, which could impact risk with donation. Likewise, consideration must be made regarding the nature of the relationship of the sibling donor to the recipient and also aspects of performing research on pediatric HC donors. In this article, as members of the Donor Issues Committee of the Worldwide Network for Blood and Marrow Transplantation, we review key ethical concerns associated with pediatric donation and then give recommendations for screening potential child donors with underlying health conditions. These recommendations are aimed at protecting the physical and emotional well-being of childhood donors and arise out of the Third International Conference on Health and Safety of Donors sponsored by the Worldwide Network for Blood and Marrow Transplantation. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  5. Recommendations for the management of cerebral and cerebellar infarction with swelling: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

    Science.gov (United States)

    Wijdicks, Eelco F M; Sheth, Kevin N; Carter, Bob S; Greer, David M; Kasner, Scott E; Kimberly, W Taylor; Schwab, Stefan; Smith, Eric E; Tamargo, Rafael J; Wintermark, Max

    2014-04-01

    There are uncertainties surrounding the optimal management of patients with brain swelling after an ischemic stroke. Guidelines are needed on how to manage this major complication, how to provide the best comprehensive neurological and medical care, and how to best inform families facing complex decisions on surgical intervention in deteriorating patients. This scientific statement addresses the early approach to the patient with a swollen ischemic stroke in a cerebral or cerebellar hemisphere. The writing group 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 to indicate gaps in current knowledge. The panel reviewed the most relevant articles on adults through computerized searches of the medical literature using MEDLINE, EMBASE, and Web of Science through March 2013. The evidence is organized within the context of the American Heart Association framework and is classified according to the joint American Heart Association/American College of Cardiology Foundation and supplementary American Heart Association Stroke Council methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive American Heart Association internal peer review. Clinical criteria are available for hemispheric (involving the entire middle cerebral artery territory or more) and cerebellar (involving the posterior inferior cerebellar artery or superior cerebellar artery) swelling caused by ischemic infarction. Clinical signs that signify deterioration in swollen supratentorial hemispheric ischemic stroke include new or further impairment of consciousness, cerebral ptosis, and changes in pupillary size. In swollen cerebellar infarction, a decrease in level of consciousness occurs as a result of brainstem compression and therefore may

  6. Strong shock wave and areal mass oscillations associated with impulsive loading of planar laser targets

    International Nuclear Information System (INIS)

    Velikovich, A.L.; Schmitt, A.J.; Metzler, N.; Gardner, J.H.

    2003-01-01

    When a rippled surface of a planar target is irradiated with a short (subnanosecond) laser pulse, the shock wave launched into the target and the mass distribution of the shocked plasma will oscillate. These oscillations are found to be surprisingly strong compared, for example, to the case when the laser radiation is not turned off but rather keeps pushing the shock wave into the target. Being stronger than the areal mass oscillations due to ablative Richtmyer-Meshkov instability and feedout in planar targets, which have recently been observed at the Naval Research Laboratory (NRL) [Aglitskiy et al., Phys. Plasmas 9, 2264 (2002)], these oscillations should therefore be directly observable with the same diagnostic technique. Irradiation of a target with a short laser pulse represents a particular case of an impulsive loading, a fast release of finite energy in a thin layer near the surface of a target. Renewed interest to the impulsive loading in the area of direct-drive laser fusion is due to the recent proposals of using a short pulse prior to the drive pulse to make the target more resistant to laser imprint and Rayleigh-Taylor growth. Impulsive loading produces a shock wave that propagates into the target and is immediately followed by an expansion wave, which gradually reduces the shock strength. If the irradiated surface is rippled, then, while the shock wave propagates through the target, its modulation amplitude grows, exceeding the initial ripple amplitude by a factor of 2 or more. The oscillating areal mass reaches the peak values that exceed the initial mass modulation amplitude (density times ripple height) by a factor of 5-7 or more, and reverses its phase several times after the laser pulse is over. The oscillatory growth is more pronounced in fluids with higher shock compressibility and is probably related to the Vishniac's instability of a blast wave. Frequency of the oscillations is determined by the speed of sound in the shocked material, and

  7. Additional recommendations to reduce sexual and drug abuse-related transmission of human T-lymphotropic virus type III/lymphadenopathy-associated virus.

    Science.gov (United States)

    1986-03-14

    Previous US Public Health Service recommendations pertaining to sexual, IV drug abuse, and perinatal transmission of human-T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) have been published. Reduction of sexual and IV transmission of HTLV-III/LAV should be enhanced by using available serologic tests to give asymptomatic, infected individuals in high-risk groups the opportunity to know their status so they can take appropriate steps to prevent the further transmission of this virus. Since the objective of these additional recommendations is to help interrupt transmission by encouraging testing and counseling among persons in high-risk groups, careful attention must be paid to maintaining confidentiality and to protecting records from any unauthorized disclosure. The ability of health departments to assure confidentiality, and the public confidence in that ability, are crucial to efforts to increase the number of persons requesting such testing and counseling. Persons at increased risk of HTLV-III/LAV infection include: homosexual and bisexual men; present or past IV drug abusers; persons with clinical or laboratory evidence of infection, such as those with signs or symptoms compatible with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC); persons born in countries where heterosexual transmission is thought to play a major role; male or female prostitutes and their sex partners; sex partners of infected persons or persons at increased risk; all persons with hemophilia who have received clotting-factor products; and newborn infants of high-risk or infected mothers. Recommendations include: community health education programs should be aimed at members of high-risk groups to increase knowledge of AIDS, to facilitate behavioral changes to reduce risks of HTLV-III/LAV infection, and encourage voluntary testing and counseling; counseling and voluntary serologic testing for HTLV-III/LAV should be routinely offered to

  8. 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.

  9. 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

    2017-01-01

    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 < 0.001), waist circumference (p = 0.001) and a positive relationship with fibre (p < 0.001). Model adjustments for diet and lifestyle factors resulted in a smaller difference in waist circumference (p = 0.006) and BMI (p = 0.006). Core grain serves was significantly associated with higher fibre, but marginally clinically significant for lower adiposity. PMID:28218715

  10. 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 < 0.001), waist circumference ( p = 0.001) and a positive relationship with fibre ( p < 0.001). Model adjustments for diet and lifestyle factors resulted in a smaller difference in waist circumference ( p = 0.006) and BMI ( p = 0.006). Core grain serves was significantly associated with higher fibre, but marginally clinically significant for lower adiposity.

  11. YCF45 protein, usually associated with plastids, is targeted into the mitochondrion of Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Týč, Jiří; Long, Shaojun; Jirků, Milan; Lukeš, Julius

    2010-01-01

    Roč. 173, č. 1 (2010), s. 43-47 ISSN 0166-6851 R&D Projects: GA ČR GA204/09/1667 Institutional research plan: CEZ:AV0Z60220518 Keywords : Trypanosoma * Plastid * Mitochondrion * Targeting * YCF45 * Horizontal gene transfer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.875, year: 2010

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

    International Nuclear Information System (INIS)

    Reynolds, Joseph G.; Geretti, Elena; Hendriks, Bart S.; Lee, Helen; Leonard, Shannon C.; Klinz, Stephan G.; Noble, Charles O.; Lücker, Petra B.; Zandstra, Peter W.; Drummond, Daryl C.; Olivier, Kenneth J.; Nielsen, Ulrik B.; Niyikiza, Clet; Agresta, Samuel V.; Wickham, Thomas J.

    2012-01-01

    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

  13. 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

  14. Signature of intermittent behavior in the emission spectra of target associated particles from 84Kr-AgBr interactions at 0.95 GeV/A

    International Nuclear Information System (INIS)

    Bhattacharjee, B.

    2005-01-01

    Intermittency and fractal behavior have been studied for emission spectra of target associated fast and slow particles from 84 Kr-AgBr interactions at 0.95 GeV/A. Intermittent behavior is observed for both knocked out and slow target fragments. In both the cases anomalous dimensions are seen to increase with the order of moments thereby indicating the association of multifractility with production mechanism of both fast and slow target associated particles

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

    Science.gov (United States)

    Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C; Marrs, James A

    2013-06-19

    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.

  16. 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.

  17. Identification of chromatin-associated regulators of MSL complex targeting in Drosophila dosage compensation.

    Directory of Open Access Journals (Sweden)

    Erica Larschan

    Full Text Available Sex chromosome dosage compensation in Drosophila provides a model for understanding how chromatin organization can modulate coordinate gene regulation. Male Drosophila increase the transcript levels of genes on the single male X approximately two-fold to equal the gene expression in females, which have two X-chromosomes. Dosage compensation is mediated by the Male-Specific Lethal (MSL histone acetyltransferase complex. Five core components of the MSL complex were identified by genetic screens for genes that are specifically required for male viability and are dispensable for females. However, because dosage compensation must interface with the general transcriptional machinery, it is likely that identifying additional regulators that are not strictly male-specific will be key to understanding the process at a mechanistic level. Such regulators would not have been recovered from previous male-specific lethal screening strategies. Therefore, we have performed a cell culture-based, genome-wide RNAi screen to search for factors required for MSL targeting or function. Here we focus on the discovery of proteins that function to promote MSL complex recruitment to "chromatin entry sites," which are proposed to be the initial sites of MSL targeting. We find that components of the NSL (Non-specific lethal complex, and a previously unstudied zinc-finger protein, facilitate MSL targeting and display a striking enrichment at MSL entry sites. Identification of these factors provides new insight into how MSL complex establishes the specialized hyperactive chromatin required for dosage compensation in Drosophila.

  18. 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.

  19. 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.

  20. The Indian National Association for Study of the Liver (INASL) Consensus on Prevention, Diagnosis and Management of Hepatocellular Carcinoma in India: The Puri Recommendations.

    Science.gov (United States)

    Kumar, Ashish; Acharya, Subrat K; Singh, Shivaram P; Saraswat, Vivek A; Arora, Anil; Duseja, Ajay; Goenka, Mahesh K; Jain, Deepali; Kar, Premashish; Kumar, Manoj; Kumaran, Vinay; Mohandas, Kunisshery M; Panda, Dipanjan; Paul, Shashi B; Ramachandran, Jeyamani; Ramesh, Hariharan; Rao, Padaki N; Shah, Samir R; Sharma, Hanish; Thandassery, Ragesh B

    2014-08-01

    Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality and healthcare expenditure in patients with chronic liver disease. There are no consensus guidelines on diagnosis and management of HCC in India. The Indian National Association for Study of the Liver (INASL) set up a Task-Force on HCC in 2011, with a mandate to develop consensus guidelines for diagnosis and management of HCC, relevant to disease patterns and clinical practices in India. The Task-Force first identified various contentious issues on various aspects of HCC and these issues were allotted to individual members of the Task-Force who reviewed them in detail. The Task-Force used the Oxford Center for Evidence Based Medicine-Levels of Evidence of 2009 for developing an evidence-based approach. A 2-day round table discussion was held on 9th and 10th February, 2013 at Puri, Odisha, to discuss, debate, and finalize the consensus statements. The members of the Task-Force reviewed and discussed the existing literature at this meeting and formulated the INASL consensus statements for each of the issues. We present here the INASL consensus guidelines (The Puri Recommendations) on prevention, diagnosis and management of HCC in India.

  1. 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. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: executive summary of recommendations from the American Dental Association Council on Scientific Affairs.

    Science.gov (United States)

    Hellstein, John W; Adler, Robert A; Edwards, Beatrice; Jacobsen, Peter L; Kalmar, John R; Koka, Sreenivas; Migliorati, Cesar A; Ristic, Helen

    2011-11-01

    This narrative review of osteonecrosis of the jaw in patients with low bone mass receiving treatment with antiresorptive agents is based on an appraisal of the literature by an advisory committee of the American Dental Association Council on Scientific Affairs. It updates the committee's 2008 advisory statement. The authors searched MEDLINE for literature published between May 2008 (the end date of the last search) and February 2011. This report contains recommendations based on the findings of the literature search and on expert opinion that relate to general dentistry; periodontal disease management; implant placement and maintenance; oral and maxillofacial surgery; endodontics; restorative dentistry and prosthodontics; orthodontics; and C-terminal telopeptide testing and drug holidays. The highest reliable estimate of antiresorptive agent-induced osteonecrosis of the jaw (ARONJ) prevalence is approximately 0.10 percent. Osteoporosis is responsible for considerable morbidity and mortality. Therefore, the benefit provided by antiresorptive therapy outweighs the low risk of developing osteonecrosis of the jaw. An oral health program consisting of sound hygiene practices and regular dental care may be the optimal approach for lowering ARONJ risk. No validated diagnostic technique exists to determine which patients are at increased risk of developing ARONJ. Discontinuing bisphosphonate therapy may not lower the risk but may have a negative effect on low-bone-mass-treatment outcomes.

  3. FATS is a transcriptional target of p53 and associated with antitumor activity

    OpenAIRE

    Zhang Xifeng; Zhang Qian; Zhang Jun; Qiu Li; Yan Shuang-shuang; Feng Juling; Sun Yan; Huang Xingxu; Lu Karen H; Li Zheng

    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....

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

    International Nuclear Information System (INIS)

    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

    2008-01-01

    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 24 h. VAMP7-deficient YT-Indy cells activated via co-culture with Jurkat cells released <1 ng/mL of granzyme B, compared to 1.5-2.5 μg/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

  5. Development of Y-shaped peptide for constructing nanoparticle systems targeting tumor-associated macrophages in vitro and in vivo

    International Nuclear Information System (INIS)

    Yan, Lu; Gao, Yunxiang; Pierce, Ryan; Dai, Liming; Kim, Julian; Zhang, Mei

    2014-01-01

    Tumor-associated macrophage (TAM) is increasingly being viewed as a target of great interest in tumor microenvironment due to its important role in the progression and metastasis of cancers. It has been shown that TAM indeed overexpresses unique surface marker legumain. In this study, we designed and synthesized a Y-shaped legumain-targeting peptide (Y-Leg) with functional groups allowing for further conjugation with imaging and therapeutic moieties (vide infra). The in vitro cell experiments using FITC-conjugated Y-Leg revealed its specific and selective interaction with M2-polarized macrophages (i.e., TAMs) with preference to M1 macrophages, and that the interaction was not interfered with by conjugating FITC to its functional group. Further, we constructed a nanotube system by grafting Y-Leg onto oxidized carbon nanotubes (OCNTs) loaded with paramagnetic Fe 3 O 4 nanoparticles. The intravenous injection of the resultant Y-Leg-OCNT/Fe 3 O 4 nanotubes to 4T1 mammary tumor-bearing mouse led to the magnetic resonance imaging (MRI) of TAM-infiltrated tumor microenvironment, revealing the targeting specificity of Y-Leg-conjugated nanotubes in vivo. The Y shape of peptide and its functional groups containing amines and imidazole can protonate at different pHs, contributing to the in vitro and in vivo targeting specificity. This study represents the first development of novel peptide and peptide-grafted nanotube system targeting M2-polarized TAMs in vivo. The methodology developed in this study is applicable to the construction of various multifunctional nanoparticle systems for selectively targeting, imaging and manipulating of TAMs for the diagnosis and treatment of cancers and inflammatory diseases identified with macrophage-infiltrated disease tissue. (papers)

  6. Learning the association between a context and a target location in infancy

    NARCIS (Netherlands)

    Bertels, Julie; San Anton, Estibaliz; Gebuis, Titia; Destrebecqz, Arnaud

    2017-01-01

    Extracting the statistical regularities present in the environment is a central learning mechanism in infancy. For instance, infants are able to learn the associations between simultaneously or successively presented visual objects (Fiser & Aslin,; Kirkham, Slemmer & Johnson,). The present study

  7. Gene-set analysis shows association between FMRP targets and autism spectrum disorder

    NARCIS (Netherlands)

    Jansen, Arija; Dieleman, Gwen C; Smit, August B; Verhage, Matthijs; Verhulst, Frank C; Polderman, Tinca J C; Posthuma, Danielle

    Autism spectrum disorder (ASD) is a heterogeneous group of disorders characterized by problems with social interaction, communication, and repetitive and restricted behavior. Despite its high heritability and the substantial progress made in elucidating genetic associations, the corresponding

  8. 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.

  9. Evaluation of bias associated with high-multiplex, target-specific pre-amplification

    Directory of Open Access Journals (Sweden)

    Steven T. Okino

    2016-01-01

    Full Text Available We developed a novel PCR-based pre-amplification (PreAmp technology that can increase the abundance of over 350 target genes one million-fold. To assess potential bias introduced by PreAmp we utilized ERCC RNA reference standards, a model system that quantifies measurement error in RNA analysis. We assessed three types of bias: amplification bias, dynamic range bias and fold-change bias. We show that our PreAmp workflow introduces only minimal amplification and fold-change bias under stringent conditions. We do detect dynamic range bias if a target gene is highly abundant and PreAmp occurred for 16 or more PCR cycles; however, this type of bias is easily correctable. To assess PreAmp bias in a gene expression profiling experiment, we analyzed a panel of genes that are regulated during differentiation using the NTera2 stem cell model system. We find that results generated using PreAmp are similar to results obtained using standard qPCR (without the pre-amplification step. Importantly, PreAmp maintains patterns of gene expression changes across samples; the same biological insights would be derived from a PreAmp experiment as with a standard gene expression profiling experiment. We conclude that our PreAmp technology can facilitate analysis of extremely limited samples in gene expression quantification experiments.

  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. 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.

  12. Target setting in intensive insulin management is associated with metabolic control

    DEFF Research Database (Denmark)

    Swift, P G F; Skinner, T C; de Beaufort, C E

    2010-01-01

    Objective: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. Methods: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c...... was measured centrally. Results: A total of 2062 adolescents completed questionnaires (age 14.4 +/- 2.3 yr; diabetes duration 6.1 +/- 3.5 yr). Mean HbA 1c = 8.2 +/- 1.4% with significant differences between centres (F = 12.3; p ... (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant...

  13. 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

  14. A Small Molecule that Targets r(CGG)exp and Improves Defects in Fragile X-Associated Tremor Ataxia Syndrome

    Science.gov (United States)

    Disney, Matthew D.; Liu, Biao; Yang, Wang-Yong; Sellier, Chantal; Tran, Tuan; Charlet-Berguerand, Nicolas; Childs-Disney, Jessica L.

    2012-01-01

    The development of small molecule chemical probes or therapeutics that target RNA remains a significant challenge despite the great interest in such compounds. The most significant barrier to compound development is a lack of knowledge of the chemical and RNA motif spaces that interact specifically. Herein, we describe a bioactive small molecule probe that targets expanded r(CGG) repeats, or r(CGG)exp , that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5’CGG/3’GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp -protein complex in vitro. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition to r(CGG)exp . Importantly, the compound is efficacious in FXTAS model cellular systems as evidenced by its ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the size and number of r(CGG)exp -protein aggregates. This approach may establish a general strategy to identify lead ligands that target RNA while also providing a chemical probe to dissect the varied mechanisms by which r(CGG)exp promotes toxicity. PMID:22948243

  15. Induction of Associative Olfactory Memory by Targeted Activation of Single Olfactory Neurons in Drosophila Larvae

    OpenAIRE

    Honda, Takato; Lee, Chi-Yu; Yoshida-Kasikawa, Maki; Honjo, Ken; Furukubo-Tokunaga, Katsuo

    2014-01-01

    It has been postulated that associative memory is formed by at least two sets of external stimuli, CS and US, that are transmitted to the memory centers by distinctive conversing pathways. However, whether associative memory can be induced by the activation of only the olfactory CS and a biogenic amine-mediated US pathways remains to be elucidated. In this study, we substituted the reward signals with dTrpA1-mediated thermogenetic activation of octopaminergic neurons and the odor signals by C...

  16. An evaluation of different target enrichment methods in pooled sequencing designs for complex disease association studies.

    Directory of Open Access Journals (Sweden)

    Aaron G Day-Williams

    Full Text Available Pooled sequencing can be a cost-effective approach to disease variant discovery, but its applicability in association studies remains unclear. We compare sequence enrichment methods coupled to next-generation sequencing in non-indexed pools of 1, 2, 10, 20 and 50 individuals and assess their ability to discover variants and to estimate their allele frequencies. We find that pooled resequencing is most usefully applied as a variant discovery tool due to limitations in estimating allele frequency with high enough accuracy for association studies, and that in-solution hybrid-capture performs best among the enrichment methods examined regardless of pool size.

  17. Endoplasmic Reticulum-Associated Degradation Factor ERLIN2: Oncogenic Roles and Molecular Targeting of Breast Cancer

    Science.gov (United States)

    2013-06-01

    Chemicals were purchased from Sigma unless indicated otherwise. Synthetic oligonucleotides were purchased from Integrated DNA Technologies. Human insulin was...otherwise. Synthetic oligonucleotides were purchased from Integrated DNA Technolo- gies, Inc. (Coralville, IA). Antibodies against XBP1, C/EBPα, and...component of marijuana , induces human glioma cancer cell death through stimulation of ER stress-associated autophagy [92]. δ- tetrahydrocannabinol can

  18. Targeted assessment of lower motor neuron burden is associated with survival in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Devine, Matthew S; Ballard, Emma; O'Rourke, Peter; Kiernan, Matthew C; Mccombe, Pamela A; Henderson, Robert D

    2016-01-01

    Estimating survival in amyotrophic lateral sclerosis (ALS) is challenging due to heterogeneity in clinical features of disease and a lack of suitable markers that predict survival. Our aim was to determine whether scoring of upper or lower motor neuron weakness is associated with survival. With this objective, 161 ALS subjects were recruited from two tertiary referral centres. Scoring of upper (UMN) and lower motor neuron (LMN) signs was performed, in addition to a brief questionnaire. Subjects were then followed until the censorship date. Univariate analysis was performed to identify variables associated with survival to either non-invasive ventilation (NIV) or death, which were then further characterized using Cox regression. Results showed that factors associated with reduced survival included older age, bulbar and respiratory involvement and shorter diagnostic delay (all p NIV or death (p ≤0.001) whereas UMN scores were poorly associated with survival. In conclusion, our results suggest that, early in disease assessment and in the context of other factors (age, bulbar, respiratory status), the burden of LMN weakness provides an accurate estimate of outcome. Such a scoring system could predict prognosis, and thereby aid in selection of patients for clinical trials.

  19. 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...

  20. 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

    In plants, the chromatin-associated high mobility group (HMG) proteins occur in twosubfamilies termedHMGAandHMGB.The HMGAproteins are characterized by the presence of four AT-hookDNAbinding motifs, and theHMGBproteins contain anHMG boxDNAbinding domain. As architectural factors, theHMGproteins ap......In plants, the chromatin-associated high mobility group (HMG) proteins occur in twosubfamilies termedHMGAandHMGB.The HMGAproteins are characterized by the presence of four AT-hookDNAbinding motifs, and theHMGBproteins contain anHMG boxDNAbinding domain. As architectural factors, the...... 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...

  1. Targeting Tumor-Associated Macrophages as a Potential Strategy to Enhance the Response to Immune Checkpoint Inhibitors.

    Science.gov (United States)

    Cassetta, Luca; Kitamura, Takanori

    2018-01-01

    Inhibition of immune checkpoint pathways in CD8 + T cell is a promising therapeutic strategy for the treatment of solid tumors that has shown significant anti-tumor effects and is now approved by the FDA to treat patients with melanoma and lung cancer. However the response to this therapy is limited to a certain fraction of patients and tumor types, for reasons still unknown. To ensure success of this treatment, CD8 + T cells, the main target of the checkpoint inhibitors, should exert full cytotoxicity against tumor cells. However recent studies show that tumor-associated macrophages (TAM) can impede this process by different mechanisms. In this mini-review we will summarize recent studies showing the effect of TAM targeting on immune checkpoint inhibitors efficacy. We will also discuss on the limitations of the current strategies as well on the future scientific challenges for the progress of the tumor immunology field.

  2. Guidelines for Improving Entry Into and Retention in Care and Antiretroviral Adherence for Persons With HIV: Evidence-Based Recommendations From an International Association of Physicians in AIDS Care Panel

    Science.gov (United States)

    Thompson, Melanie A.; Mugavero, Michael J.; Amico, K. Rivet; Cargill, Victoria A.; Chang, Larry W.; Gross, Robert; Orrell, Catherine; Altice, Frederick L.; Bangsberg, David R.; Bartlett, John G.; Beckwith, Curt G.; Dowshen, Nadia; Gordon, Christopher M.; Horn, Tim; Kumar, Princy; Scott, James D.; Stirratt, Michael J.; Remien, Robert H.; Simoni, Jane M.; Nachega, Jean B.

    2014-01-01

    Description After HIV diagnosis, timely entry into HIV medical care and retention in that care are essential to the provision of effective antiretroviral therapy (ART). ART adherence is among the key determinants of successful HIV treatment outcome and is essential to minimize the emergence of drug resistance. The International Association of Physicians in AIDS Care convened a panel to develop evidence-based recommendations to optimize entry into and retention in care and ART adherence for people with HIV. Methods A systematic literature search was conducted to produce an evidence base restricted to randomized, controlled trials and observational studies with comparators that had at least 1 measured biological or behavioral end point. A total of 325 studies met the criteria. Two reviewers independently extracted and coded data from each study using a standardized data extraction form. Panel members drafted recommendations based on the body of evidence for each method or intervention and then graded the overall quality of the body of evidence and the strength for each recommendation. Recommendations Recommendations are provided for monitoring of entry into and retention in care, interventions to improve entry and retention, and monitoring of and interventions to improve ART adherence. Recommendations cover ART strategies, adherence tools, education and counseling, and health system and service delivery interventions. In addition, they cover specific issues pertaining to pregnant women, incarcerated individuals, homeless and marginally housed individuals, and children and adolescents, as well as substance use and mental health disorders. Recommendations for future research in all areas are also provided. PMID:22393036

  3. Impact of age on the association between 24-h ambulatory blood pressure measurements and target organ damage.

    Science.gov (United States)

    Olesen, Thomas B; Pareek, Manan; Stidsen, Jacob V; Blicher, Marie K; Rasmussen, Susanne; Vishram-Nielsen, Julie K K; Kjaer-Hansen, Kathrine; Olsen, Michael H

    2018-05-17

    The aim of this study was to evaluate the impact of age on the associations between hemodynamic components derived from 24-h ambulatory blood pressure (24-h ABPM) and target organ damage, in apparently healthy, nonmedicated individuals. Twenty-four-hour ABPM and target organ damage (left ventricular mass index, pulse wave velocity, urine albumin : creatinine ratio and carotid atherosclerotic plaques) were evaluated in 1408 individuals. Associations were examined in regression models, stratified for age [middle-aged (41 or 51 years) or elderly (61 or 71 years)], and adjusted for sex, smoking status, and total-cholesterol. In middle-aged individuals, an increase of 10 mmHg in 24-h SBP was independently associated with an increase of 3.8 (2.7-4.8) g/m in LVMI. The effect was nearly doubled in the elderly subgroup, where the same increase resulted in an increase in LVMI of 6.3 (5.0-7.6) g/m (P for interaction h SBP was associated with a 6.7% increase in pulse wave velocity in middle-aged individuals and with an 9.1% increase in elderly individuals (P for interaction h ABPM and urine albumin : creatinine ratio was only observed in the elderly subgroup. Associations between the presence of atherosclerotic plaques and components from 24-h ABPM except 24-h DBP were not modified by age (all P for interaction >0.26). Age enhances the associations between hemodynamic components obtained from 24-h ABPM and measures of arterial stiffness, microvascular damage, and cardiac structure, but not atherosclerosis.

  4. Aberrant status and clinicopathologic characteristic associations of 11 target genes in 1,321 Chinese patients with lung adenocarcinoma.

    Science.gov (United States)

    Zhao, Mengnan; Zhan, Cheng; Li, Ming; Yang, Xiaodong; Yang, Xinyu; Zhang, Yong; Lin, Miao; Xia, Yifeng; Feng, Mingxiang; Wang, Qun

    2018-01-01

    The aberrant status of target genes and their associations with clinicopathologic characteristics are still unclear in primary lung adenocarcinoma. The common mutations and translocations of nine target genes were evaluated in 1,247 specimens of surgically-resected primary lung adenocarcinoma. Immunohistochemistry was used to analyze the expressions of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) in 731 specimens. The frequency of the aberrations and their associations with clinicopathologic characteristics were analyzed. Overall, 952 (76.3%) of 1,247 patients harbored at least one target mutation or translocation: epidermal growth factor receptor ( EGFR ) (729, 58.5%), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS ) (83, 6.7%), human epidermal growth factor receptor 2 ( HER2 ) (82, 6.6%), anaplastic lymphoma kinase ( ALK) (23, 1.8%), phosphoinositide-3-kinase catalytic alpha polypeptide ( PIK3CA ) (20, 1.6%), Ret proto-oncogene RET (15, 1.2%), ROS proto-oncogene 1 receptor tyrosine kinase ( ROS1 ) (12, 1.0%), B-raf proto-oncogene ( BRAF ) (9, 0.7%), neuroblastoma RAS viral (v-ras) oncogene homolog ( NRAS ) (3, 0.2%). Fourteen (1.9%) of 731 patients were PD-1 positive and 95 (13.0%) were PD-L1 positive in tumor cells. In men and smokers, there were more frequent KRAS mutations (both Ppatients, while HER2 (Ppatients with EGFR mutations (all Ppatients with primary lung adenocarcinoma harbored target gene aberrations. The frequency of each alteration differed in patients depending on clinicopathologic characteristics.

  5. Senescence-associated microRNAs target cell cycle regulatory genes in normal human lung fibroblasts.

    Science.gov (United States)

    Markopoulos, Georgios S; Roupakia, Eugenia; Tokamani, Maria; Vartholomatos, George; Tzavaras, Theodore; Hatziapostolou, Maria; Fackelmayer, Frank O; Sandaltzopoulos, Raphael; Polytarchou, Christos; Kolettas, Evangelos

    2017-10-01

    Senescence recapitulates the ageing process at the cell level. A senescent cell stops dividing and exits the cell cycle. MicroRNAs (miRNAs) acting as master regulators of transcription, have been implicated in senescence. In the current study we investigated and compared the expression of miRNAs in young versus senescent human fibroblasts (HDFs), and analysed the role of mRNAs expressed in replicative senescent HFL-1 HDFs. Cell cycle analysis confirmed that HDFs accumulated in G 1 /S cell cycle phase. Nanostring analysis of isolated miRNAs from young and senescent HFL-1 showed that a distinct set of 15 miRNAs were significantly up-regulated in senescent cells including hsa-let-7d-5p, hsa-let-7e-5p, hsa-miR-23a-3p, hsa-miR-34a-5p, hsa-miR-122-5p, hsa-miR-125a-3p, hsa-miR-125a-5p, hsa-miR-125b-5p, hsa-miR-181a-5p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-503-5p, hsa-miR-574-3p, hsa-miR-574-5p and hsa-miR-4454. Importantly, pathway analysis of miRNA target genes down-regulated during replicative senescence in a public RNA-seq data set revealed a significant high number of genes regulating cell cycle progression, both G 1 /S and G 2 /M cell cycle phase transitions and telomere maintenance. The reduced expression of selected miRNA targets, upon replicative and oxidative-stress induced senescence, such as the cell cycle effectors E2F1, CcnE, Cdc6, CcnB1 and Cdc25C was verified at the protein and/or RNA levels. Induction of G1/S cell cycle phase arrest and down-regulation of cell cycle effectors correlated with the up-regulation of miR-221 upon both replicative and oxidative stress-induced senescence. Transient expression of miR-221/222 in HDFs promoted the accumulation of HDFs in G1/S cell cycle phase. We propose that miRNAs up-regulated during replicative senescence may act in concert to induce cell cycle phase arrest and telomere erosion, establishing a senescent phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. HIV-1 Tat and AIDS-associated cancer: targeting the cellular anti-cancer barrier?

    Directory of Open Access Journals (Sweden)

    Daniel René

    2008-05-01

    Full Text Available Abstract The acquired immunodeficiency syndrome (AIDS is accompanied by a significant increase in the incidence of neoplasms. Several causative agents have been proposed for this phenomenon. These include immunodeficiency and oncogenic DNA viruses and the HIV-1 protein Tat. Cancer in general is closely linked to genomic instability and DNA repair mechanisms. The latter maintains genomic stability and serves as a cellular anti-cancer barrier. Defects in DNA repair pathway are associated with carcinogenesis. This review focuses on newly discovered connections of the HIV-1 protein Tat, as well as cellular co-factors of Tat, to double-strand break DNA repair. We propose that the Tat-induced DNA repair deficiencies may play a significant role in the development of AIDS-associated cancer.

  7. Limbic system associated membrane protein as a potential target for neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Eero eVasar

    2013-03-01

    Full Text Available The studies performed in laboratory animals and psychiatric patients suggest a possible role of limbic system associated membrane protein (LAMP in the mechanisms of psychiatric disorders. Stressful manipulations and genetic invalidation have revealed a role of the Lsamp gene in the regulation of anxiety in rodents. Besides that, Lsamp deficient mice display reduced aggressiveness and impaired adaptation in novel and stressful environments. The behavioural effects of amphetamine were blunted in genetically modified mice. Recent pharmacological and biochemical studies point towards altered function of GABA-, 5-hydroxytryptamine- and dopaminergic systems in Lsamp deficient mice. Moreover, we found an association between the gene polymorphisms of LSAMP and major depressive disorder. Patients suffering from major depressive disorder had significantly increased ratio between risk and protective haplotypes of the LSAMP gene compared to healthy volunteers. However, the impact of these haplotypes for the function of LAMP is not clear and remains to be elucidated in future studies.

  8. Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease.

    Science.gov (United States)

    Gong, C-X; Iqbal, K

    2008-01-01

    Alzheimer disease (AD) is the most common cause of dementia in adults. The current therapy for AD has only moderate efficacy in controlling symptoms, and it does not cure the disease. Recent studies have suggested that abnormal hyperphosphorylation of tau in the brain plays a vital role in the molecular pathogenesis of AD and in neurodegeneration. This article reviews the current advances in understanding of tau protein, regulation of tau phosphorylation, and the role of its abnormal hyperphosphorylation in neurofibrillary degeneration. Furthermore, several therapeutic strategies for treating AD on the basis of the important role of tau hyperphosphorylation in the pathogenesis of the disease are described. These strategies include (1) inhibition of glycogen synthase kinase-3beta (GSK-3beta), cyclin-dependent kinase 5 (cdk5), and other tau kinases; (2) restoration of PP2A activity; and (3) targeting tau O-GlcNAcylation. Development of drugs on the basis of these strategies is likely to lead to disease-modifying therapies for AD.

  9. 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.

  10. Targeting interleukin-1β in CAPS (cryopyrin-associated periodic) syndromes: what did we learn?

    Science.gov (United States)

    Koné-Paut, Isabelle; Piram, Maryam

    2012-11-01

    CAPS is the prototype of an IL-1β driven auto inflammatory disorder. Features of recurrent systemic inflammation compromises patient's quality of life, and may reduce life expectancy by inducing definite organ damage. Recent treatment targeting IL-1 have shown dramatic effect on patient's clinical symptoms and quality of life. Anakinra was first used successfully in treating small series of patients with all CAPS phenotypes. Two pivotal randomized placebo-controlled studies allowed licensing of rilonacept and canakinumab as orphan drugs for CAPS patients. The use of anti-IL-1 drugs in CAPS is still relatively new, and their effect on a long term is not well known. As we can suppress the clinical symptoms of patients with CAPS, important questions remain regarding the full effect of anti-IL-1 treatment on organ involvement and their potential ability to prevent them. As important variations of treatment doses and schedules appear in reaching effectiveness, pharmacologic studies are still warranted to determine a potential diffusion of anti-IL-1 drugs in the fluids and tissues. More studies evaluating the efficacy and safety of anti-IL-1 drugs given in patients before 2 years of age are warranted, since it is believed that the earliest treatment could avoid secondary CAPS complications to develop. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Adult hippocampal neurogenesis: an important target associated with antidepressant effects of exercise.

    Science.gov (United States)

    Sun, Lina; Sun, Qingshan; Qi, Jinshun

    2017-10-26

    Depression is a prevalent devastating mental disorder that affects the normal life of patients and brings a heavy burden to whole society. Although many efforts have been made to attenuate depressive/anxiety symptoms, the current clinic antidepressants have limited effects. Scientists have long been making attempts to find some new strategies that can be applied as the alternative antidepressant therapy. Exercise, a widely recognized healthy lifestyle, has been suggested as a therapy that can relieve psychiatric stress. However, how exercise improves the brain functions and reaches the antidepressant target needs systematic summarization due to the complexity and heterogeneous feature of depression. Brain plasticity, especially adult neurogenesis in the hippocampus, is an important neurophysiology to facilitate animals for neurogenesis can occur in not only humans. Many studies indicated that an appropriate level of exercise can promote neurogenesis in the adult brains. In this article, we provide information about the antidepressant effects of exercise and its implications in adult neurogenesis. From the neurogenesis perspective, we summarize evidence about the effects of exercise in enhancing neurogenesis in the hippocampus through regulating growth factors, neurotrophins, neurotransmitters and metabolism as well as inflammations. Taken together, a large number of published works indicate the multiple benefits of exercise in the brain functions of animals, particularly brain plasticity like neurogenesis and synaptogenesis. Therefore, a new treatment method for depression therapy can be developed by regulating the exercise activity.

  12. Differentiating Immune Cell Targets in Gut-Associated Lymphoid Tissue for HIV Cure.

    Science.gov (United States)

    Khan, Shahzada; Telwatte, Sushama; Trapecar, Martin; Yukl, Steven; Sanjabi, Shomyseh

    2017-11-01

    The single greatest challenge to an HIV cure is the persistence of latently infected cells containing inducible, replication-competent proviral genomes, which constitute only a small fraction of total or infected cells in the body. Although resting CD4 + T cells in the blood are a well-known source of viral rebound, more than 90% of the body's lymphocytes reside elsewhere. Many are in gut tissue, where HIV DNA levels per million CD4 + T cells are considerably higher than in the blood. Despite the significant contribution of gut tissue to viral replication and persistence, little is known about the cell types that support persistence of HIV in the gut; importantly, T cells in the gut have phenotypic, functional, and survival properties that are distinct from T cells in other tissues. The mechanisms by which latency is established and maintained will likely depend on the location and cytokine milieu surrounding the latently infected cells in each compartment. Therefore, successful HIV cure strategies require identification and characterization of the exact cell types that support viral persistence, particularly in the gut. In this review, we describe the seeding of the latent HIV reservoir in the gut mucosa; highlight the evidence for compartmentalization and depletion of T cells; summarize the immunologic consequences of HIV infection within the gut milieu; propose how the damaged gut environment may promote the latent HIV reservoir; and explore several immune cell targets in the gut and their place on the path toward HIV cure.

  13. 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.

  14. Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

    OpenAIRE

    Baay, Marc; Brouwer, Anja; Pauwels, Patrick; Peeters, Marc; Lardon, Filip

    2011-01-01

    Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages pro...

  15. 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 (Panalysis of 476 haplotype blocks with 708 AGRE families using the Family Based Association Test (FBAT). Blocks in two QTL genes were associated with NVC 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.

  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. 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

    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...... attractive candidate for further study concerns SNP rs6336 (q=0.12) that causes the substitution of an evolutionarily highly conserved amino acid residue in the kinase domain of the neurodevelopmentally important receptor TRKA. Thus, TRKA signaling may represent a novel susceptibility pathway...

  18. E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis.

    Science.gov (United States)

    Jung, Cho-Rok; Hwang, Kyung-Sun; Yoo, Jinsang; Cho, Won-Kyung; Kim, Jin-Man; Kim, Woo Ho; Im, Dong-Soo

    2006-07-01

    The von Hippel-Lindau tumor suppressor, pVHL, forms part of an E3 ubiquitin ligase complex that targets specific substrates for degradation, including hypoxia-inducible factor-1alpha (HIF-1alpha), which is involved in tumor progression and angiogenesis. It remains unclear, however, how pVHL is destabilized. Here we show that E2-EPF ubiquitin carrier protein (UCP) associates with and targets pVHL for ubiquitin-mediated proteolysis in cells, thereby stabilizing HIF-1alpha. UCP is detected coincidently with HIF-1alpha in human primary liver, colon and breast tumors, and metastatic cholangiocarcinoma and colon cancer cells. UCP level correlates inversely with pVHL level in most tumor cell lines. In vitro and in vivo, forced expression of UCP boosts tumor-cell proliferation, invasion and metastasis through effects on the pVHL-HIF pathway. Our results suggest that UCP helps stabilize HIF-1alpha and may be a new molecular target for therapeutic intervention in human cancers.

  19. 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. Copyright © 2016.

  20. 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.

  1. 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

  2. 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].

  3. The major targets of acute norovirus infection are immune cells in the gut-associated lymphoid tissue.

    Science.gov (United States)

    Grau, Katrina R; Roth, Alexa N; Zhu, Shu; Hernandez, Abel; Colliou, Natacha; DiVita, Bayli B; Philip, Drake T; Riffe, Cara; Giasson, Benoit; Wallet, Shannon M; Mohamadzadeh, Mansour; Karst, Stephanie M

    2017-12-01

    Noroviruses are the leading cause of food-borne gastroenteritis outbreaks and childhood diarrhoea globally, estimated to be responsible for 200,000 deaths in children each year 1-4 . Thus, reducing norovirus-associated disease is a critical priority. Development of vaccines and therapeutics has been hindered by the limited understanding of basic norovirus pathogenesis and cell tropism. While macrophages, dendritic cells, B cells and stem-cell-derived enteroids can all support infection of certain noroviruses in vitro 5-7 , efforts to define in vivo norovirus cell tropism have generated conflicting results. Some studies detected infected intestinal immune cells 8-12 , other studies detected epithelial cells 13 , and still others detected immune and epithelial cells 14-16 . Major limitations of these studies are that they were performed on tissue sections from immunocompromised or germ-free hosts, chronically infected hosts where the timing of infection was unknown, or following non-biologically relevant inoculation routes. Here, we report that the dominant cellular targets of a murine norovirus inoculated orally into immunocompetent mice are macrophages, dendritic cells, B cells and T cells in the gut-associated lymphoid tissue. Importantly, we also demonstrate that a norovirus can infect T cells, a previously unrecognized target, in vitro. These findings represent the most extensive analyses to date of in vivo norovirus cell tropism in orally inoculated, immunocompetent hosts at the peak of acute infection and thus they significantly advance our basic understanding of norovirus pathogenesis.

  4. Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors.

    Science.gov (United States)

    Orgeur, Mickael; Martens, Marvin; Leonte, Georgeta; Nassari, Sonya; Bonnin, Marie-Ange; Börno, Stefan T; Timmermann, Bernd; Hecht, Jochen; Duprez, Delphine; Stricker, Sigmar

    2018-03-29

    Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling of chick limb micromass cultures revealed a set of common genes regulated by all five transcription factors, which we describe as a connective tissue core expression set. This common core was enriched with genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created by the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development. © 2018. Published by The Company of Biologists Ltd.

  5. Racial bias in implicit danger associations generalizes to older male targets.

    Directory of Open Access Journals (Sweden)

    Gustav J W Lundberg

    Full Text Available Across two experiments, we examined whether implicit stereotypes linking younger (~28-year-old Black versus White men with violence and criminality extend to older (~68-year-old Black versus White men. In Experiment 1, participants completed a sequential priming task wherein they categorized objects as guns or tools after seeing briefly-presented facial images of men who varied in age (younger versus older and race (Black versus White. In Experiment 2, we used different face primes of younger and older Black and White men, and participants categorized words as 'threatening' or 'safe.' Results consistently revealed robust racial biases in object and word identification: Dangerous objects and words were identified more easily (faster response times, lower error rates, and non-dangerous objects and words were identified less easily, after seeing Black face primes than after seeing White face primes. Process dissociation procedure analyses, which aim to isolate the unique contributions of automatic and controlled processes to task performance, further indicated that these effects were driven entirely by racial biases in automatic processing. In neither experiment did prime age moderate racial bias, suggesting that the implicit danger associations commonly evoked by younger Black versus White men appear to generalize to older Black versus White men.

  6. An SIV/macaque model targeted to study HIV-associated neurocognitive disorders.

    Science.gov (United States)

    Beck, Sarah E; Queen, Suzanne E; Metcalf Pate, Kelly A; Mangus, Lisa M; Abreu, Celina M; Gama, Lucio; Witwer, Kenneth W; Adams, Robert J; Zink, M Christine; Clements, Janice E; Mankowski, Joseph L

    2018-04-01

    Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART. By developing quantitative viral outgrowth assays that measure both CD4+ T cells and macrophages harboring replication competent SIV as well as a highly sensitive mouse-based viral outgrowth assay, we have positioned the SIV/pigtailed macaque model to advance our understanding of latent cellular reservoirs, including potential CNS reservoirs, to promote HIV cure. In addition to contributing to our understanding of the pathogenesis of HAND, the SIV/pigtailed macaque model also provides an excellent opportunity to test innovative approaches to eliminate the latent HIV reservoir in the brain.

  7. Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus.

    Science.gov (United States)

    Flannery, J G; Zolotukhin, S; Vaquero, M I; LaVail, M M; Muzyczka, N; Hauswirth, W W

    1997-06-24

    We describe a general approach for achieving efficient and cell type-specific expression of exogenous genes in photoreceptor cells of the mammalian retina. Recombinant adeno-associated virus (rAAV) vectors were used to transfer the bacterial lacZ gene or a synthetic green fluorescent protein gene (gfp) to mouse or rat retinas after injection into the subretinal space. Using a proximal murine rod opsin promoter (+86 to -385) to drive expression, reporter gene product was found exclusively in photoreceptors, not in any other retinal cell type or in the adjacent retinal pigment epithelium. GFP-expressing photoreceptors typically encompassed 10-20% of the total retinal area after a single 2-microl injection. Photoreceptors were transduced with nearly 100% efficiency in the region directly surrounding the injection site. We estimate approximately 2.5 million photoreceptors were transduced as a result of the single subretinal inoculation. This level of gene transfer and expression suggests the feasibility of genetic therapy for retinal disease. The gfp-containing rAAV stock was substantially free of both adenovirus and wild-type AAV, as judged by plaque assay and infectious center assay, respectively. Thus, highly purified, helper virus-free rAAV vectors can achieve high-frequency tissue-specific transduction of terminally differentiated, postmitotic photoreceptor cells.

  8. Toward Privacy-Preserving Personalized Recommendation Services

    Directory of Open Access Journals (Sweden)

    Cong Wang

    2018-02-01

    Full Text Available Recommendation systems are crucially important for the delivery of personalized services to users. With personalized recommendation services, users can enjoy a variety of targeted recommendations such as movies, books, ads, restaurants, and more. In addition, personalized recommendation services have become extremely effective revenue drivers for online business. Despite the great benefits, deploying personalized recommendation services typically requires the collection of users’ personal data for processing and analytics, which undesirably makes users susceptible to serious privacy violation issues. Therefore, it is of paramount importance to develop practical privacy-preserving techniques to maintain the intelligence of personalized recommendation services while respecting user privacy. In this paper, we provide a comprehensive survey of the literature related to personalized recommendation services with privacy protection. We present the general architecture of personalized recommendation systems, the privacy issues therein, and existing works that focus on privacy-preserving personalized recommendation services. We classify the existing works according to their underlying techniques for personalized recommendation and privacy protection, and thoroughly discuss and compare their merits and demerits, especially in terms of privacy and recommendation accuracy. We also identity some future research directions. Keywords: Privacy protection, Personalized recommendation services, Targeted delivery, Collaborative filtering, Machine learning

  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

    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

  10. 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.

    Science.gov (United States)

    Heudorf, Ursel; Grünewald, Miriam; Otto, Ulla

    2016-01-01

    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. 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 wards 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. 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. 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 nurses. Against this background, a sufficient

  11. Liver carbohydrates metabolism: A new islet-neogenesis associated protein peptide (INGAP-PP) target.

    Science.gov (United States)

    Villagarcía, Hernán Gonzalo; Román, Carolina Lisi; Castro, María Cecilia; González, Luisa Arbeláez; Ronco, María Teresa; Francés, Daniel Eleazar; Massa, María Laura; Maiztegui, Bárbara; Flores, Luis Emilio; Gagliardino, Juan José; Francini, Flavio

    2018-03-01

    Islet-Neogenesis Associated Protein-Pentadecapeptide (INGAP-PP) increases β-cell mass and enhances glucose and amino acids-induced insulin secretion. Our aim was to demonstrate its effect on liver metabolism. For that purpose, adult male Wistar rats were injected twice-daily (10 days) with saline solution or INGAP-PP (250 μg). Thereafter, serum glucose, triglyceride and insulin levels were measured and homeostasis model assessment (HOMA-IR) and hepatic insulin sensitivity (HIS) were determined. Liver glucokinase and glucose-6-phosphatase (G-6-Pase) expression and activity, phosphoenolpyruvate carboxykinase (PEPCK) expression, phosphofructokinase-2 (PFK-2) protein content, P-Akt/Akt and glycogen synthase kinase-3β (P-GSK3/GSK3) protein ratios and glycogen deposit were also determined. Additionally, glucokinase activity and G-6-Pase and PEPCK gene expression were also determined in isolated hepatocytes from normal rats incubated with INGAP-PP (5 μg/ml). INGAP-PP administration did not modify any of the serum parameters tested but significantly increased activity of liver glucokinase and the protein level of its cytosolic activator, PFK-2. Conversely, INGAP-PP treated rats decreased gene expression and enzyme activity of gluconeogenic enzymes, G-6-Pase and PEPCK. They also showed a higher glycogen deposit and P-GSK3/GSK3 and P-Akt/Akt ratio. In isolated hepatocytes, INGAP-PP increased GK activity and decreased G-6-Pase and PEPCK expression. These results demonstrate a direct effect of INGAP-PP on the liver acting through P-Akt signaling pathway. INGAP-PP enhances liver glucose metabolism and deposit and reduces its production/output, thereby contributing to maintain normal glucose homeostasis. These results reinforce the concept that INGAP-PP might become a useful tool to treat people with impaired islet/liver glucose metabolism as it occurs in T2D. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. 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...

  13. Microsatellite instability in pediatric high grade glioma is associated with genomic profile and differential target gene inactivation.

    Directory of Open Access Journals (Sweden)

    Marta Viana-Pereira

    Full Text Available High grade gliomas (HGG are one of the leading causes of cancer-related deaths in children, and there is increasing evidence that pediatric HGG may harbor distinct molecular characteristics compared to adult tumors. We have sought to clarify the role of microsatellite instability (MSI in pediatric versus adult HGG. MSI status was determined in 144 patients (71 pediatric and 73 adults using a well established panel of five quasimonomorphic mononucleotide repeat markers. Expression of MLH1, MSH2, MSH6 and PMS2 was determined by immunohistochemistry, MLH1 was assessed for mutations by direct sequencing and promoter methylation using MS-PCR. DNA copy number profiles were derived using array CGH, and mutations in eighteen MSI target genes studied by multiplex PCR and genotyping. MSI was found in 14/71 (19.7% pediatric cases, significantly more than observed in adults (5/73, 6.8%; p = 0.02, Chi-square test. MLH1 expression was downregulated in 10/13 cases, however no mutations or promoter methylation were found. MSH6 was absent in one pediatric MSI-High tumor, consistent with an inherited mismatch repair deficiency associated with germline MSH6 mutation. MSI was classed as Type A, and associated with a remarkably stable genomic profile. Of the eighteen classic MSI target genes, we identified mutations only in MSH6 and DNAPKcs and described a polymorphism in MRE11 without apparent functional consequences in DNA double strand break detection and repair. This study thus provides evidence for a potential novel molecular pathway in a proportion of gliomas associated with the presence of MSI.

  14. 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

  15. 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.

  16. 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.

  17. Preparation and characterization of anti-HIV nanodrug targeted to microfold cell of gut-associated lymphoid tissue.

    Science.gov (United States)

    Roy, Upal; Ding, Hong; Pilakka-Kanthikeel, Sudheesh; Raymond, Andrea D; Atluri, Venkata; Yndart, Adriana; Kaftanovskaya, Elena M; Batrakova, Elena; Agudelo, Marisela; Nair, Madhavan

    2015-01-01

    The human immunodeficiency virus 1 (HIV-1) still remains one of the leading life-threatening diseases in the world. The introduction of highly active antiretroviral therapy has significantly reduced disease morbidity and mortality. However, most of the drugs have variable penetrance into viral reservoir sites, including gut-associated lymphoid tissue (GALT). Being the largest lymphoid organ, GALT plays a key role in early HIV infection and host-pathogen interaction. Many different treatment options have been proposed to eradicate the virus from GALT. However, it becomes difficult to deliver traditional drugs to the GALT because of its complex physiology. In this regard, we developed a polymer-based Pluronic nanocarrier containing anti-HIV drug called efavirenz (EFV) targeting Microfold cells (M-cells) in the GALT. M-cells are specialized epithelial cells that are predominantly present in the GALT. In this work, we have exploited this paracellular transport property of M-cells for targeted delivery of Pluronic nanocarrier tagged EFV, bioconjugated with anti-M-cell-specific antibodies to the GALT (nanodrug). Preliminary characterization showed that the nanodrug (EFV-F12-COOH) is of 140 nm size with 0.3 polydispersion index, and the zeta potential of the particles was -19.38±2.2 mV. Further, drug dissolution study has shown a significantly improved sustained release over free drugs. Binding potential of nanodrug with M-cell was also confirmed with fluorescence microscopy and in vitro uptake and release studies. The anti-HIV activity of the nanodrug was also significantly higher compared to that of free drug. This novel formulation was able to show sustained release of EFV and inhibit the HIV-1 infection in the GALT compared to the free drug. The present study has potential for our in vivo targeted nanodrug delivery system by combining traditional enteric-coated capsule technique via oral administration.

  18. 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.

  19. Genome-wide identification of polycomb target genes reveals a functional association of Pho with Scm in Bombyx mori.

    Directory of Open Access Journals (Sweden)

    Zhiqing Li

    Full Text Available 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.

  20. 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

  1. 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.

  2. A comparison of the treatment recommendations for neurogenic lower urinary tract dysfunction in the national institute for health and care excellence, European Association of Urology and international consultations on incontinence guidelines.

    Science.gov (United States)

    Jaggi, Ashley; Drake, Marcus; Siddiqui, Emad; Fatoye, Francis

    2018-04-17

    Healthcare guidelines are an important vehicle in establishing up-to-date evidence based medicine (EBM) in clinical practice. Due to varying development processes, clinical guidelines created by different institutions can often contain contrasting recommendations. This can have implications for optimal and standardized patient care across management settings. The similarities and differences of treatment recommendations made in the National Institute for Health and Care Excellence (NICE), The European Association of Urology (EAU), and the International Consultation on Continence (ICI) guidelines for neurogenic lower urinary tract dysfunction (NLUTD) were assessed. The guidelines generally agree on their approach to conservative management, including behavioral therapies, and catheterization techniques. There was discrepancy on the benefit of using an alpha blocker in NLUTD and bladder outlet obstruction (BOO) and administering Botulinum toxin A (Onabotulinum-A) in NLUTD. The highest degree of divergence was seen in recommendations for surgical treatments, where the EAU made gender-specific recommendations, and gave continent urinary diversion higher preference than given in the NICE and ICI guidelines. In the absence of high-quality clinical evidence, many of the recommendations made across all three guidelines are based on expert opinion. NICE, the EAU and ICI have similarities but they place differing emphasis on costs and expert opinion, which translated in notably different recommendations. It is evident that increased research efforts, possibly in the form of prospective registries, pragmatic trials, and resource utilization studies are necessary to improve the underlying evidence base for NLUTD, and subsequently the strength and concordance of recommendations across guidelines. © 2018 Wiley Periodicals, Inc.

  3. 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...... on 7684 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 5 x 5 self-organizing map that was integrated into a Cytoscape network of SE......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...

  4. 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...... of pneumonia in that population. METHODS: We conducted a retrospective cohort study comparing patients treated with PRO to those not receiving PRO (no-PRO) using Northern Hypothermia Network registry data. Cardiac arrest survivors ≥ 18 years of age with a GCS...-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...

  5. 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.

  6. The Unculturables: targeted isolation of bacterial species associated with canine periodontal health or disease from dental plaque.

    Science.gov (United States)

    Davis, Ian J; Bull, Christopher; Horsfall, Alexander; Morley, Ian; Harris, Stephen

    2014-08-01

    The current inability to culture the entirety of observed bacteria is well known and with the advent of ever more powerful molecular tools, that can survey bacterial communities at previously unattainable depth, the gap in our capacity to culture and define all of these species increases exponentially. This gap has essentially become the rate limiting step in determining how the knowledge of which species are present in a sample can be applied to understand the role of these species in an ecosystem or disease process. A case in point is periodontal disease, which is the most widespread oral disease in dogs. If untreated the disease results in significant pain, eventual loss of the dentition and potentially an increased risk of systemic diseases. Previous molecular based studies have identified the bacterial species associated with periodontal disease in dogs; however without cultured strains from many of these species it has not been possible to study whether they play a role in the disease process. Using a quantitative polymerase chain reaction (qPCR) directed approach a range of microbiological media were screened and optimized to enrich for previously uncultivated target species. A systematic screening methodology was then employed to isolate the species of interest. In cases where the target species were not cultivable in isolation, helper strains grown underneath a nitrocellulose membrane were used to provide the necessary growth factors. This guided media optimization approach enabled the purification of 14 species, 8 of which we had previously been unable to cultivate in isolation. It is also applicable to the targeted isolation of isolates from species that have previously been cultured (for example to study intra-species variation) as demonstrated by the successful isolation of 6 targeted isolates of already cultured species. To our knowledge this is the first time this combination of qPCR guided media optimization, strategic screening and helper strain

  7. Performance Characteristics of qPCR Assays Targeting Human- and Ruminant-Associated Bacteroidetes for Microbial Source Tracking across Sixteen Countries on Six Continents

    Science.gov (United States)

    2013-01-01

    Numerous quantitative PCR assays for microbial fecal source tracking (MST) have been developed and evaluated in recent years. Widespread application has been hindered by a lack of knowledge regarding the geographical stability and hence applicability of such methods beyond the regional level. This study assessed the performance of five previously reported quantitative PCR assays targeting human-, cattle-, or ruminant-associated Bacteroidetes populations on 280 human and animal fecal samples from 16 countries across six continents. The tested cattle-associated markers were shown to be ruminant-associated. The quantitative distributions of marker concentrations in target and nontarget samples proved to be essential for the assessment of assay performance and were used to establish a new metric for quantitative source-specificity. In general, this study demonstrates that stable target populations required for marker-based MST occur around the globe. Ruminant-associated marker concentrations were strongly correlated with total intestinal Bacteroidetes populations and with each other, indicating that the detected ruminant-associated populations seem to be part of the intestinal core microbiome of ruminants worldwide. Consequently tested ruminant-targeted assays appear to be suitable quantitative MST tools beyond the regional level while the targeted human-associated populations seem to be less prevalent and stable, suggesting potential for improvements in human-targeted methods. PMID:23755882

  8. 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

  9. From micronutrient recommendations to policy

    DEFF Research Database (Denmark)

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

    2010-01-01

    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......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...... countries and its effect on final decisions. Stakeholders were not involved at the outset of the process ('framing' of the problem) in any of the countries, and there was no evidence of consumer involvement and open public fora. Conclusions: Some of the key explanatory factors for diversity in the degree...

  10. Assessment and management of risks associated with exposures to Auger- and beta-emitting radionuclides. Recommendations and proposals for lines of research

    International Nuclear Information System (INIS)

    2010-01-01

    of these phenomena has led some scientists to call for a revision or even the abandonment of the current radiological protection system and the creation of new concepts that would take into account the specific characteristics mentioned above. Various other systems have been proposed, based on a dosimetry conducted at the cellular or even molecular level, whose purpose is to determine the energy depositions occurring near or within the DNA molecule. The progress made in the field of modelling now makes it possible to accurately calculate these energy depositions at virtually all scales, from the molecules to the tissues overall. However, the algorithms developed for dose calculations at the molecular level are not sufficient to claim a better assessment of the risks incurred. Favouring a microdosimetric approach for risk assessments would require comprehensive knowledge of the biological targets of radiation, the dose-response relationships at the various levels of organisation, and, above all, all of the mechanisms leading from a cellular energy deposition to the appearance of a health detriment. It has been established that the human body has developed many defence mechanisms, including the repair of damaged molecules, the replacement of killed cells, and the elimination of mutated cells. Detailed knowledge of these mechanisms for repair or, conversely, propagation and amplification of molecular damage is therefore an essential prerequisite for the use of any molecular or cellular dosimetric information for radiological protection purposes. The required knowledge is not available today. In fact, it is not yet possible to link a cellular energy deposition to a probability of occurrence of health effects. These deficiencies have led the ICRP to choose a protection system based on the macroscopic observation of health detriments, associated with an aggregate dose of radiation rather than a mechanistic analysis at the cellular level and an incorporation of the various

  11. Utilizing individual fish biomass and relative abundance models to map environmental niche associations of adult and juvenile targeted fishes.

    Science.gov (United States)

    Galaiduk, Ronen; Radford, Ben T; Harvey, Euan S

    2018-06-21

    Many fishes undergo ontogenetic habitat shifts to meet their energy and resource needs as they grow. Habitat resource partitioning and patterns of habitat connectivity between conspecific fishes at different life-history stages is a significant knowledge gap. Species distribution models were used to examine patterns in the relative abundance, individual biomass estimates and environmental niche associations of different life stages of three iconic West Australian fishes. Continuous predictive maps describing the spatial distribution of abundance and individual biomass of the study species were created as well predictive hotspot maps that identify possible areas for aggregation of individuals of similar life stages of multiple species (i.e. spawning grounds, fisheries refugia or nursery areas). The models and maps indicate that processes driving the abundance patterns could be different from the body size associated demographic processes throughout an individual's life cycle. Incorporating life-history in the spatially explicit management plans can ensure that critical habitat of the vulnerable stages (e.g. juvenile fish, spawning stock) is included within proposed protected areas and can enhance connectivity between various functional areas (e.g. nursery areas and adult populations) which, in turn, can improve the abundance of targeted species as well as other fish species relying on healthy ecosystem functioning.

  12. 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. © 2015 American Society for Clinical Pharmacology and Therapeutics.

  13. Characteristics of Adolescents Lacking Provider-Recommended Human Papillomavirus Vaccination.

    Science.gov (United States)

    Krakow, Melinda; Beavis, Anna; Cosides, Olivia; Rositch, Anne F

    2017-05-01

    To characterize subgroups of teens in the United States for whom provider recommendation is less likely to impact human papillomavirus (HPV) vaccine initiation. We analyzed provider-verified vaccination data from the Centers for Disease Control and Prevention's 2014 National Immunization Survey-Teen. Poisson regression models identified characteristics associated with the lack of HPV vaccine initiation among teens who received a provider recommendation (n = 12,742). Top qualitative reasons for nonvaccination among teens who received a provider recommendation were summarized (n = 1,688). Among teens with provider recommendations, males, younger teens, and white teens were less likely to initiate vaccination, compared to peers. Believing the vaccine was unnecessary, concerns about safety and lack of vaccine knowledge were common reasons parents did not initiate the vaccine, despite receiving provider recommendations. These key subgroups and barriers to HPV vaccination should be targeted with interventions that complement provider recommendation to achieve broad vaccine uptake in the United States. Published by Elsevier Inc.

  14. Semantically Enhanced Recommender Systems

    Science.gov (United States)

    Ruiz-Montiel, Manuela; Aldana-Montes, José F.

    Recommender Systems have become a significant area in the context of web personalization, given the large amount of available data. Ontologies can be widely taken advantage of in recommender systems, since they provide a means of classifying and discovering of new information about the items to recommend, about user profiles and even about their context. We have developed a semantically enhanced recommender system based on this kind of ontologies. In this paper we present a description of the proposed system.

  15. 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.

  16. Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis

    NARCIS (Netherlands)

    Chatzidionysiou, Katerina; Emamikia, Sharzad; Nam, Jackie; Ramiro, Sofia; Smolen, Josef; van der Heijde, Désirée; Dougados, Maxime; Bijlsma, Johannes; Burmester, Gerd; Scholte, Marieke; van Vollenhoven, Ronald; Landewé, Robert

    2017-01-01

    To perform a systematic literature review (SLR) informing the 2016 update of the recommendations for the management of rheumatoid arthritis (RA). An SLR for the period between 2013 and 2016 was undertaken to assess the efficacy of glucocorticoids (GCs), conventional synthetic disease-modifying

  17. MicroRNA-4443 Causes CD4+ T Cells Dysfunction by Targeting TNFR-Associated Factor 4 in Graves’ Disease

    Directory of Open Access Journals (Sweden)

    Yicheng Qi

    2017-11-01

    Full Text Available ContextAberrant CD4+ T cell function plays a critical role in the process of Graves’ disease (GD. MicroRNAs (miRNAs are important regulators of T cell activation, proliferation, and cytokine production. However, the contribution of miRNAs to CD4+ T cell dysfunction in GD remains unclear.ObjectiveTo investigate how certain miRNA causes aberrant CD4+ T cell function in GD patients.MethodsWe compared the expression pattern of miRNAs in CD4+ T cells from untreated GD (UGD patients with those from healthy controls. The most significantly dysregulated miRNAs were selected and their correlations with clinical parameters were analyzed. The effect of miR-4443 on CD4+ T cells cytokines production and proliferation was assessed. The potential gene target was identified and validated.ResultsGD patients had unique pattern of miRNA expression profile in CD4+ T cells comparing to healthy subjects. miR-10a, miR-125b, and miR-4443 were the three most significantly dysregulated miRNAs. The elevated miR-4443 levels were strongly correlated with clinical parameters in an independent dataset of UGD patients (N = 40, while miR-4443 was normally expressed in GD patients with euthyroidism and negative TRAb level. We found that miR-4443 directly inhibited TNFR-associated factor (TRAF 4 expression to increase CD4+ T cells cytokines secretion as well as proliferation through the NF-κB pathway. Furthermore, the TRAF4 levels in GD patients were inversely correlated with miR-4443, and knocking down TRAF4 had a similar effect with miR-4443 overexpression.ConclusionThe increased expression of miR-4443 induced CD4+ T cells dysfunction by targeting TRAF4, which may cause GD.

  18. A low-volume polyethylene glycol solution was associated with an increased suboptimal bowel preparation rate but had similar recommendations for an early repeat colonoscopy, procedure times, and adenoma detection rates.

    Directory of Open Access Journals (Sweden)

    Sam C Hankins

    Full Text Available Low-volume polyethylene glycol (PEG bowel preparations are better tolerated by patients than high-volume preparations and may achieve similar preparation quality. However, there is little data comparing their effects on a recommendation for an early repeat colonoscopy (because of a suboptimal preparation, procedure times, adenoma detection rate (ADR, and advanced adenoma detection rate (AADR.This is a retrospective cohort study of outpatient colonoscopies performed during a one-year period at a single academic medical center in which low-volume MoviPrep® (n = 1841 or high-volume Colyte® (n = 1337 was used. All preparations were split-dosed. Appropriate covariates were included in regression models assessing suboptimal preparation quality (fair, poor, or inadequate, procedure times, recommendation for an early repeat colonoscopy, ADR, and AADR.MoviPrep® was associated with an increase in having a suboptimal bowel preparation (OR 1.36; 95% CI: 1.06-1.76, but it was not associated with differences in insertion (p = 0.43, withdrawal (p = 0.22, or total procedure times (p = 0.10. The adjusted percentage with a suboptimal preparation was 11.7% for patients using MoviPrep® and 8.8% for patients using Colyte®. MoviPrep® was not associated with a significant difference in overall ADR (OR 0.93; 95% CI: 0.78-1.11, AADR (OR 1.18; 95% CI: 0.87-1.62, or recommendation for early repeat colonoscopy (OR 1.16; 95% CI: 0.72-1.88.MoviPrep® was associated with a small absolute increase in having a suboptimal preparation, but did not affect recommendations for an early repeat colonoscopy, procedure times, or adenoma detection rates. Mechanisms to reduce financial barriers limiting low-volume preparations should be considered because of their favorable tolerability profile.

  19. 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.

  20. Recommendations for treatment of hypothyroidism with levothyroxine and levotriiodothyronine: a 2016 position statement of the Italian Society of Endocrinology and the Italian Thyroid Association.

    Science.gov (United States)

    Biondi, B; Bartalena, L; Chiovato, L; Lenzi, A; Mariotti, S; Pacini, F; Pontecorvi, A; Vitti, P; Trimarchi, F

    2016-12-01

    Levothyroxine (L-T4) is recommended as lifelong replacement therapy for hypothyroidism. Recent clinical and experimental data support the addition of levotriiodothyronine (L-T3) treatment in some selected hypothyroid patients when their symptoms persist and their quality of life remains impaired despite adequate L-T4 monotherapy. An increase in L-T3 prescriptions has been recently observed in Italy due to availability of different L-T3 formulations, making it possible to clinicians to prescribe L-T3 alone or in combination with L-T4. The aim of the present position statement was to define the correct clinical indications, schedule, duration of treatment and contraindications of combined treatment with L-T4 and L-T3 in hypothyroid patients in an attempt to guide clinicians and to avoid potential adverse effects of overtreatment.

  1. 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

  2. A study of the dietary intake of Cypriot children and adolescents aged 6-18 years and the association of mother's educational status and children's weight status on adherence to nutritional recommendations.

    Science.gov (United States)

    Tornaritis, Michael J; Philippou, Elena; Hadjigeorgiou, Charalambos; Kourides, Yiannis A; Panayi, Adamos; Savva, Savvas C

    2014-01-08

    A balanced diet is fundamental for healthy growth and development of children. The aim of this study was to document and evaluate the dietary intake of Cypriot children aged 6-18 years (y) against recommendations, and to determine whether maternal education and children's weight status are associated with adherence to recommendations. The dietary intake of a random sample of 1414 Cypriot children was assessed using a 3-day food diary. Adherence to recommendations was estimated and the association of their mother's education and their own weight status on adherence were explored. A large percentage of children consumed less than the minimum of 45% energy (en) of carbohydrate (18.4%-66.5% in different age groups) and exceeded the recommended intakes of total fat (42.4%-83.8%), saturated fatty acids (90.4%-97.1%) and protein (65.2%-82.7%), while almost all (94.7%-100%) failed to meet the recommended fibre intake. Additionally, a large proportion of children (27.0%-59.0%) consumed >300 mg/day cholesterol and exceeded the upper limit of sodium (47.5%-78.5%). In children aged 9.0-13.9y, there was a high prevalence of inadequacy for magnesium (85.0%-89.9%), in girls aged 14.0-18.9y, of Vitamin A (25.3%), Vitamin B6 (21.0%) and iron (25.3%) and in boys of the same group, of Vitamin A (35.8%). Children whose mother was more educated were more likely to consume >15%en from protein, Odds Ratio (OR) 1.85 (95% CI:1.13-3.03) for mothers with tertiary education and exceed the consumption of 300 mg/day cholesterol (OR 2.13 (95% CI:1.29-3.50) and OR 1.84 (95% CI:1.09-3.09) for mothers with secondary and tertiary education respectively). Children whose mothers were more educated, were less likely to have Vitamin B1 (pchildren were more likely to consume >15%en protein (OR 1.85 (95% CI:1.26-2.71) and have a children consume a low quality diet. Maternal education and children's own weight status are associated with children's adherence to recommendations. Public health policies

  3. Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target

    Energy Technology Data Exchange (ETDEWEB)

    Farace, Paolo; Merigo, Flavia; Galie, Mirco; Sbarbati, Andrea; Marzola, Pasquina [University of Verona, Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, Verona (Italy); D' Ambrosio, Daniela; Nanni, Cristina; Spinelli, Antonello; Fanti, Stefano [Policlinico ' S. Orsola-Malpighi' , Department of Nuclear Medicine, Bologna (Italy); Degrassi, Anna [Nerviano Medical Sciences, Milan (Italy); Rubello, Domenico [' S. Maria della Misericordia' Hospital, PET Centre, Department of Nuclear Medicine, Rovigo (Italy)

    2009-04-15

    To analyse the influence of cancer-associated stroma on FDG-uptake in two carcinoma models characterized by different stromal degrees. Eight nude mice were subcutaneously injected with DU-145 prostate cancer cells or BXPC-3 pancreatic cancer cells, and underwent FDG-PET imaging about 2 weeks after implantation. After the mice were killed, histology, and CD31 and GLUT1 immunohistochemistry were performed. To further evaluate the highly stromalized carcinoma using perfusion-sensitive imaging, four BXPC-3 tumours underwent two successive albumin-binding (MS-325) MRI scans during tumour growth. FDG uptake was significantly higher in the DU-145 than in the BXPC-3 tumours, which were hardly distinguishable from adjacent normal tissue. In the BXPC-3 tumours, histology confirmed the widespread presence of aberrant infiltrated stroma, embedded with numerous vessels marked by CD31. In both tumour types, the stromal matrix was negative for GLUT1. In DU-145 tumour cells, GLUT1 immunostaining was greater than in BXPC-3 tumour cells, but not homogeneously, since it was less evident in the tumour cells which were nearer to vessels and stroma. Finally, MS-325 MRI always clearly showed areas of enhancement in the BXPC-3 tumours. Cancer-associated stroma has been reported to be capable of aerobic metabolism with low glucose consumption. Furthermore, it has been proposed that regions with high vascular perfusion exhibit a significantly lower FDG uptake, suggesting some vascular/metabolic reciprocity. Since our results are consistent with these recent findings, they signal a risk of tumour volume underestimation in radiotherapy if FDG uptake alone is used for target delineation of carcinomas, which suggests that additional evaluation should be performed using vasculature/perfusion-sensitive imaging. (orig.)

  4. Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target.

    Science.gov (United States)

    Farace, Paolo; D'Ambrosio, Daniela; Merigo, Flavia; Galiè, Mirco; Nanni, Cristina; Spinelli, Antonello; Fanti, Stefano; Degrassi, Anna; Sbarbati, Andrea; Rubello, Domenico; Marzola, Pasquina

    2009-04-01

    To analyse the influence of cancer-associated stroma on FDG-uptake in two carcinoma models characterized by different stromal degrees. Eight nude mice were subcutaneously injected with DU-145 prostate cancer cells or BXPC-3 pancreatic cancer cells, and underwent FDG-PET imaging about 2 weeks after implantation. After the mice were killed, histology, and CD31 and GLUT1 immunohistochemistry were performed. To further evaluate the highly stromalized carcinoma using perfusion-sensitive imaging, four BXPC-3 tumours underwent two successive albumin-binding (MS-325) MRI scans during tumour growth. FDG uptake was significantly higher in the DU-145 than in the BXPC-3 tumours, which were hardly distinguishable from adjacent normal tissue. In the BXPC-3 tumours, histology confirmed the widespread presence of aberrant infiltrated stroma, embedded with numerous vessels marked by CD31. In both tumour types, the stromal matrix was negative for GLUT1. In DU-145 tumour cells, GLUT1 immunostaining was greater than in BXPC-3 tumour cells, but not homogeneously, since it was less evident in the tumour cells which were nearer to vessels and stroma. Finally, MS-325 MRI always clearly showed areas of enhancement in the BXPC-3 tumours. Cancer-associated stroma has been reported to be capable of aerobic metabolism with low glucose consumption. Furthermore, it has been proposed that regions with high vascular perfusion exhibit a significantly lower FDG uptake, suggesting some vascular/metabolic reciprocity. Since our results are consistent with these recent findings, they signal a risk of tumour volume underestimation in radiotherapy if FDG uptake alone is used for target delineation of carcinomas, which suggests that additional evaluation should be performed using vasculature/perfusion-sensitive imaging.

  5. Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target

    International Nuclear Information System (INIS)

    Farace, Paolo; Merigo, Flavia; Galie, Mirco; Sbarbati, Andrea; Marzola, Pasquina; D'Ambrosio, Daniela; Nanni, Cristina; Spinelli, Antonello; Fanti, Stefano; Degrassi, Anna; Rubello, Domenico

    2009-01-01

    To analyse the influence of cancer-associated stroma on FDG-uptake in two carcinoma models characterized by different stromal degrees. Eight nude mice were subcutaneously injected with DU-145 prostate cancer cells or BXPC-3 pancreatic cancer cells, and underwent FDG-PET imaging about 2 weeks after implantation. After the mice were killed, histology, and CD31 and GLUT1 immunohistochemistry were performed. To further evaluate the highly stromalized carcinoma using perfusion-sensitive imaging, four BXPC-3 tumours underwent two successive albumin-binding (MS-325) MRI scans during tumour growth. FDG uptake was significantly higher in the DU-145 than in the BXPC-3 tumours, which were hardly distinguishable from adjacent normal tissue. In the BXPC-3 tumours, histology confirmed the widespread presence of aberrant infiltrated stroma, embedded with numerous vessels marked by CD31. In both tumour types, the stromal matrix was negative for GLUT1. In DU-145 tumour cells, GLUT1 immunostaining was greater than in BXPC-3 tumour cells, but not homogeneously, since it was less evident in the tumour cells which were nearer to vessels and stroma. Finally, MS-325 MRI always clearly showed areas of enhancement in the BXPC-3 tumours. Cancer-associated stroma has been reported to be capable of aerobic metabolism with low glucose consumption. Furthermore, it has been proposed that regions with high vascular perfusion exhibit a significantly lower FDG uptake, suggesting some vascular/metabolic reciprocity. Since our results are consistent with these recent findings, they signal a risk of tumour volume underestimation in radiotherapy if FDG uptake alone is used for target delineation of carcinomas, which suggests that additional evaluation should be performed using vasculature/perfusion-sensitive imaging. (orig.)

  6. Respiration and nitrogen assimilation: targeting mitochondria-associated metabolism as a means to enhance nitrogen use efficiency.

    Science.gov (United States)

    Foyer, Christine H; Noctor, Graham; Hodges, Michael

    2011-02-01

    Considerable advances in our understanding of the control of mitochondrial metabolism and its interactions with nitrogen metabolism and associated carbon/nitrogen interactions have occurred in recent years, particularly highlighting important roles in cellular redox homeostasis. The tricarboxylic acid (TCA) cycle is a central metabolic hub for the interacting pathways of respiration, nitrogen assimilation, and photorespiration, with components that show considerable flexibility in relation to adaptations to the different functions of mitochondria in photosynthetic and non-photosynthetic cells. By comparison, the operation of the oxidative pentose phosphate pathway appears to represent a significant limitation to nitrogen assimilation in non-photosynthetic tissues. Valuable new insights have been gained concerning the roles of the different enzymes involved in the production of 2-oxoglutarate (2-OG) for ammonia assimilation, yielding an improved understanding of the crucial role of cellular energy balance as a broker of co-ordinate regulation. Taken together with new information on the mechanisms that co-ordinate the expression of genes involved in organellar functions, including energy metabolism, and the potential for exploiting the existing flexibility for NAD(P)H utilization in the respiratory electron transport chain to drive nitrogen assimilation, the evidence that mitochondrial metabolism and machinery are potential novel targets for the enhancement of nitrogen use efficiency (NUE) is explored.

  7. Liver fatty acid binding protein is the mitosis-associated polypeptide target of a carcinogen in rat hepatocytes

    International Nuclear Information System (INIS)

    Bassuk, J.A.; Tsichlis, P.N.; Sorof, S.

    1987-01-01

    Hepatocytes in normal rat liver were found previously to contain a cytoplasmic 14,000-dalton polypeptide (p14) that is associated with mitosis and is the principal early covalent target of activated metabolites of the carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene). The level of immunohistochemically detected p14 was low when growth activity of hepatocytes was low, was markedly elevated during mitosis in normal and regenerating livers, but was very high throughout interphase during proliferation of hyperplastic and malignant hepatocytes induced in rat liver by a carcinogen (N-2-fluorenylacetamide or 3'-methyl-4-dimethylaminoazobenzene). The authors report here that p14 is the liver fatty acid binding protein. The nucleotide sequence of p14 cDNA clones, isolated by screening a rat liver cDNA library in bacteriophage λgt11 using p14 antiserum, was completely identical to part of the sequence reported for liver fatty acid binding protein. Furthermore, the two proteins shared the following properties: size of mRNA, amino acid composition, molecular size according to NaDodSO 4 gel electrophoresis, and electrophoretic mobilities in a Triton X-100/acetic acid/urea gel. The two polypeptides bound oleic acid similarly. Finally, identical elevations of cytoplasmic immunostain were detected specifically in mitotic hepatocytes with either antiserum. The collected findings are suggestive that liver fatty acid binding protein may carry ligands that promote hepatocyte division and may transport certain activated chemical carcinogens

  8. Differentially Expressed microRNAs and Target Genes Associated with Plastic Internode Elongation in Alternanthera philoxeroides in Contrasting Hydrological Habitats

    Directory of Open Access Journals (Sweden)

    Gengyun Li

    2017-12-01

    Full Text Available Phenotypic plasticity is crucial for plants to survive in changing environments. Discovering microRNAs, identifying their targets and further inferring microRNA functions in mediating plastic developmental responses to environmental changes have been a critical strategy for understanding the underlying molecular mechanisms of phenotypic plasticity. In this study, the dynamic expression patterns of microRNAs under contrasting hydrological habitats in the amphibious species Alternanthera philoxeroides were identified by time course expression profiling using high-throughput sequencing technology. A total of 128 known and 18 novel microRNAs were found to be differentially expressed under contrasting hydrological habitats. The microRNA:mRNA pairs potentially associated with plastic internode elongation were identified by integrative analysis of microRNA and mRNA expression profiles, and were validated by qRT-PCR and 5′ RLM-RACE. The results showed that both the universal microRNAs conserved across different plants and the unique microRNAs novelly identified in A. philoxeroides were involved in the responses to varied water regimes. The results also showed that most of the differentially expressed microRNAs were transiently up-/down-regulated at certain time points during the treatments. The fine-scale temporal changes in microRNA expression highlighted the importance of time-series sampling in identifying stress-responsive microRNAs and analyzing their role in stress response/tolerance.

  9. 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.

  10. Targeted deletion of Kif18a protects from colitis-associated colorectal (CAC) tumors in mice through impairing Akt phosphorylation

    International Nuclear Information System (INIS)

    Zhu, Houbao; Xu, Wangyang; Zhang, Hongxin; Liu, Jianbing; Xu, Haimin; Lu, Shunyuan; Dang, Suying; Kuang, Ying; Jin, Xiaolong; Wang, Zhugang

    2013-01-01

    Highlights: •Kif18A is up-regulated in CAC of mouse model. •Kif18a −/− mice are protected from CAC. •Tumor cells from Kif18a −/− 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

  11. Intracellular and extracellular microtubule associated protein tau as a therapeutic target in Alzheimer disease and other tauopathies.

    Science.gov (United States)

    Avila, Jesús; Pallas, Noemí; Bolós, Marta; Sayas, C Laura; Hernandez, Felix

    2016-06-01

    Microtubule associated protein tau, a protein mainly expressed in neurons, plays an important role in several diseases related to dementia, named tauopathies. Alzheimer disease is the most relevant tauopathy. The role of tau protein in dementia is now a topic under discussion, and is the focus of this review. We have covered two major areas: tau pathology and tau as a therapeutic target. Tau pathology is mainly related to a gain of toxic function due to an abnormal accumulation, aberrant modifications (such as hyperphosphorylation and truncation, among others) and self-aggregation of tau into oligomers or larger structures. Also, tau can be found extracellularly in a toxic form. Tau-based therapy is mainly centered on avoiding the gain of these toxic functions of tau. Tau therapies are focused on lowering tau levels, mainly of modified tau species that could be toxic for neurons (phosphorylated, truncated or aggregated tau), in intracellular or extracellular form. Decreasing the levels of those toxic species is a possible therapeutic strategy.

  12. Recommender system based on scarce information mining.

    Science.gov (United States)

    Lu, Wei; Chung, Fu-Lai; Lai, Kunfeng; Zhang, Liang

    2017-09-01

    Guessing what user may like is now a typical interface for video recommendation. Nowadays, the highly popular user generated content sites provide various sources of information such as tags for recommendation tasks. Motivated by a real world online video recommendation problem, this work targets at the long tail phenomena of user behavior and the sparsity of item features. A personalized compound recommendation framework for online video recommendation called Dirichlet mixture probit model for information scarcity (DPIS) is hence proposed. Assuming that each clicking sample is generated from a representation of user preferences, DPIS models the sample level topic proportions as a multinomial item vector, and utilizes topical clustering on the user part for recommendation through a probit classifier. As demonstrated by the real-world application, the proposed DPIS achieves better performance in accuracy, perplexity as well as diversity in coverage than traditional methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) and the Association of Crohn's Disease and Ulcerative Colitis Patients (ACCU) in the management of psychological problems in Inflammatory Bowel Disease patients.

    Science.gov (United States)

    Barreiro-de Acosta, Manuel; Marín-Jiménez, Ignacio; Panadero, Abel; Guardiola, Jordi; Cañas, Mercedes; Gobbo Montoya, Milena; Modino, Yolanda; Alcaín, Guillermo; Bosca-Watts, Marta Maia; Calvet, Xavier; Casellas, Francesc; Chaparro, María; Fernández Salazar, Luis; Ferreiro-Iglesias, Rocío; Ginard, Daniel; Iborra, Marisa; Manceñido, Noemí; Mañosa, Miriam; Merino, Olga; Rivero, Montserrat; Roncero, Oscar; Sempere, Laura; Vega, Pablo; Zabana, Yamile; Mínguez, Miguel; Nos, Pilar; Gisbert, Javier P

    2018-02-01

    To establish recommendations for the management of psychological problems affecting patients with inflammatory bowel disease (IBD). A meeting of a group of IBD experts made up of doctors, psychologists, nurses and patient representatives was held. The following were presented: 1) Results of a previous focal group, 2) Results of doctor and patient surveys, 3) Results of a systematic review of tools for detecting anxiety and depression. A guided discussion was then held about the most important psychological and emotional problems associated with IBD, appropriate referral criteria and situations to be avoided. The validated instrument most applicable to clinical practice was selected. A recommendations document and a Delphi survey were designed. The survey was sent to the group and to a scientific committee of the GETECCU group in order to establish the level of agreement with these recommendations. Fifteen recommendations were established linked to 3 key processes: 1) What steps should be taken to identify psychological problems at an IBD appointment; 2) What are the criteria for referring patients to a mental health specialist; 3) How to approach psychological problems. Resources should be made available to healthcare professionals so that they can treat these problems during consultations, identify the disorders which could affect the clinical course of the disease and determine their impact on the patient's life in order that these can be treated and followed up by the most suitable professional. These recommendations could serve as a basis for redesigning IBD services or processes and as justification for the training of healthcare personnel. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  14. Report of the American Animal Hospital Association (AAHA) Canine Vaccine Task Force: executive summary and 2003 canine vaccine guidelines and recommendations.

    Science.gov (United States)

    Paul, Michael A; Appel, Max; Barrett, Ralph; Carmichael, Leland E; Childers, Henry; Cotter, Susan; Davidson, Autumn; Ford, Richard; Keil, Dan; Lappin, Michael; Schultz, Ronald D; Thacker, Eileen; Trumpeter, Janice L; Welborn, Link

    2003-01-01

    The AAHA has undertaken the development of this document in an effort to inform veterinary practitioners, clarify misunderstandings held by veterinarians, and encourage practitioners to recognize that immunization of patients is a medical procedure. As such, it is bound by the same tenets that govern the recommendation of other medical procedures-principally, that it be tailored to the needs of the individual patient. Many diseases we immunize against are ubiquitous. Many are serious and some even life threatening. Some are of limited demographic concern given the exposure risk for each patient. These factors have all been considered in developing the AAHA Canine Vaccination Guidelines. In the end, each veterinarian must do what he or she determines to be in the best interest of the patient. Vaccination of individual animals produces not only individual immunity but also population or herd immunity. Since we have no readily available and reliable way to determine if each patient has developed an adequate immune response, we encourage the practice philosophy of vaccinating more patients while vaccinating each patient no more than needed.

  15. Recommendations for the reporting of surgically resected specimens of renal cell carcinoma: the Association of Directors of Anatomic and Surgical Pathology.

    Science.gov (United States)

    Higgins, John P; McKenney, Jesse K; Brooks, James D; Argani, Pedram; Epstein, Jonathan I

    2009-04-01

    A checklist based approach to reporting the relevant pathologic details of renal cell carcinoma resection specimens improves the completeness of the report. Karyotypic evaluation of renal neoplasms has refined but also complicated their classification. The number of diagnostic possibilities has increased and the importance of distinguishing different tumor types has been underscored by dramatic variation in prognosis and the development of targeted therapies for specific subtypes. The increasing number of recognized renal neoplasms has implications for handling renal resection specimens. Furthermore, the prognostic significance of other features of renal neoplasms related to grade and stage has been demonstrated. This guideline for the handling of renal resection specimens will focus on problem areas in the evolving practice of diagnosis, grading, and staging of renal neoplasms. The accompanying checklist will serve to ensure that all necessary details of the renal resection specimen are included in the surgical pathology report.

  16. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis/Outcome Measures in Rheumatology Consensus-Based Recommendations and Research Agenda for Use of Composite Measures and Treatment Targets in Psoriatic Arthritis

    DEFF Research Database (Denmark)

    Coates, Laura C; FitzGerald, Oliver; Merola, Joseph F

    2018-01-01

    OBJECTIVE: A meeting was convened by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) to further the development of consensus among physicians and patients regarding composite disease activity measures and targets i...

  17. 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

    NARCIS (Netherlands)

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

    2017-01-01

    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

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

    DEFF Research Database (Denmark)

    Posey, Avery D; Schwab, Robert D; Boesteanu, Alina C

    2016-01-01

    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...

  19. 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 ...

  20. 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; 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; Franco, Oscar H.; 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 J.; 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 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; 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; 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 V.; 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 E. H.; 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

  1. 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.J. Barnes (Michael); I.E. 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 (Jing Hua); 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

  2. The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

    NARCIS (Netherlands)

    McKhann, G.M.; Knopman, D.S.; Chertkow, H.; Hyman, B.T.; Jack, C.R.; Kawas, C.H.; Klunk, W.E.; Koroshetz, W.J.; Manly, J.J.; Mayeux, R.; Mohs, R.C.; Morris, J.C.; Rossor, M.N.; Scheltens, P.; Carrillo, M.C.; Thies, B.; Weintraub, S.; Phelps, C.H.

    2011-01-01

    The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers

  3. Stromal Activation Associated with Development of Prostate Cancer in Prostate-Targeted Fibroblast Growth Factor 8b Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Teresa D. Elo

    2010-11-01

    Full Text Available Expression of fibroblast growth factor 8 (FGF-8 is commonly increased in prostate cancer. Experimental studies have provided evidence that it plays a role in prostate tumorigenesis and tumor progression. To study how increased FGF-8 affects the prostate, we generated and analyzed transgenic (TG mice expressing FGF-8b under the probasin promoter that targets expression to prostate epithelium. Prostates of the TG mice showed an increased size and changes in stromal and epithelialmorphology progressing fromatypia and prostatic intraepithelial neoplasia (mouse PIN, mPIN lesions to tumors with highly variable phenotype bearing features of adenocarcinoma, carcinosarcoma, and sarcoma. The development of mPIN lesions was preceded by formation of activated stroma containing increased proportion of fibroblastic cells, rich vasculature, and inflammation. The association between advancing stromal and epithelial alterations was statistically significant. Microarray analysis and validation with quantitative polymerase chain reaction revealed that expression of osteopontin and connective tissue growth factor was markedly upregulated in TG mouse prostates compared with wild type prostates. Androgen receptor staining was decreased in transformed epithelium and in hypercellular stroma but strongly increased in the sarcoma-like lesions. In conclusion, our data demonstrate that disruption of FGF signaling pathways by increased epithelial production of FGF-8b leads to strongly activated and atypical stroma, which precedes development of mPIN lesions and prostate cancer with mixed features of adenocarcinoma and sarcoma in the prostates of TG mice. The results suggest that increased FGF-8 in human prostate may also contribute to prostate tumorigenesis by stromal activation.

  4. 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 (HbA 1c ) 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 HbA 1c of <7.0% (<53mmol/mol) per baseline HbA 1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. Patients had comparable demographic characteristics and similar HbA 1c and FHG values at baseline in each HbA 1c quartile regardless of whether they reached the target HbA 1c . The higher the HbA 1c quartile, the greater was the decrease in HbA 1c , but also the smaller the percentage of patients achieving the target HbA 1c . HbA 1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA 1c quartiles with either insulin treatment. Patients not achieving the target HbA 1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA 1c , 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.

  5. 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

  6. 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.

  7. [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.

  8. Genome-Wide Identification of Polycomb Target Genes Reveals a Functional Association of Pho with Scm in Bombyx mori

    OpenAIRE

    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 ...

  9. Signature of intermittent behavior in the emission spectra of target associated particles from 84Kr-AgBr interactions at 0.95 GeV/A

    International Nuclear Information System (INIS)

    Bhattacharjee, B.; Sengupta, S.; Mukhopadhyay, A.; Singh, V.

    2004-01-01

    In this report an attempt has been made to study, by studying the fluctuation in spatial distribution in χ(cosθ) space, the intermittent behaviour and fractal properties of emission spectra of fast and slow target associated particles from 84 Kr-AgBr interactions at 0.95 GeV/A

  10. 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); 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

  11. Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Stott, Simon R W; Mattsson, Bengt

    2010-01-01

    Viral vector-mediated gene transfer has emerged as a powerful means to target transgene expression in the central nervous system. Here we characterized the efficacy of serotypes 1 and 5 recombinant adeno-associated virus (rAAV) vectors encoding green fluorescent protein (GFP) after stereotaxic...

  12. 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.

  13. 1990 recommendations of ICRP

    International Nuclear Information System (INIS)

    Clarke, R.H.

    1991-01-01

    The Main Commission of ICRP finalised its new recommendations during its November 1990 meeting. The recommendations will appear in the Annals of the ICRP in 1991 as Publication 60. This paper represents a personal summary of these recommendations. It covers the basic biological risk estimates and the conceptual framework of the system of radiological protection, the definition of radiation detriment and its use both in the definition of radiation quantities and in the establishment of the dose limits adopted by the Main Commissions. (author)

  14. High expression of Wee1 is associated with poor disease-free survival in malignant melanoma: potential for targeted therapy.

    Directory of Open Access Journals (Sweden)

    Gry Irene Magnussen

    Full Text Available Notoriously resistant malignant melanoma is one of the most increasing forms of cancer worldwide; there is thus a precarious need for new treatment options. The Wee1 kinase is a major regulator of the G(2/M checkpoint, and halts the cell cycle by adding a negative phosphorylation on CDK1 (Tyr15. Additionally, Wee1 has a function in safeguarding the genome integrity during DNA synthesis. To assess the role of Wee1 in development and progression of malignant melanoma we examined its expression in a panel of paraffin-embedded patient derived tissue of benign nevi and primary- and metastatic melanomas, as well as in agarose-embedded cultured melanocytes. We found that Wee1 expression increased in the direction of malignancy, and showed a strong, positive correlation with known biomarkers involved in cell cycle regulation: Cyclin A (p<0.0001, Ki67 (p<0.0001, Cyclin D3 (p = 0.001, p21(Cip1/WAF1 (p = 0.003, p53 (p = 0.025. Furthermore, high Wee1 expression was associated with thicker primary tumors (p = 0.001, ulceration (p = 0.005 and poor disease-free survival (p = 0.008. Transfections using siWee1 in metastatic melanoma cell lines; WM239(WTp53, WM45.1(MUTp53 and LOX(WTp53, further support our hypothesis of a tumor promoting role of Wee1 in melanomas. Whereas no effect was observed in LOX cells, transfection with siWee1 led to accumulation of cells in G(1/S and S phase of the cell cycle in WM239 and WM45.1 cells, respectively. Both latter cell lines displayed DNA damage and induction of apoptosis, in the absence of Wee1, indicating that the effect of silencing Wee1 may not be solely dependent of the p53 status of the cells. Together these results reveal the importance of Wee1 as a prognostic biomarker in melanomas, and indicate a potential role for targeted therapy, alone or in combination with other agents.

  15. 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.

  16. No association between the use of Bti for mosquito control and the dynamics of non-target aquatic invertebrates in French coastal and continental wetlands

    International Nuclear Information System (INIS)

    Lagadic, Laurent; Schäfer, Ralf B.; Roucaute, Marc; Szöcs, Eduard; Chouin, Sébastien; Maupeou, Jérôme de; Duchet, Claire

    2016-01-01

    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.

  17. 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.

  18. In Silico Identification of Proteins Associated with Drug-induced Liver Injury Based on the Prediction of Drug-target Interactions.

    Science.gov (United States)

    Ivanov, Sergey; Semin, Maxim; Lagunin, Alexey; Filimonov, Dmitry; Poroikov, Vladimir

    2017-07-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure as well as one of the major reasons for drug withdrawal from clinical trials and the market. Elucidation of molecular interactions associated with DILI may help to detect potentially hazardous pharmacological agents at the early stages of drug development. The purpose of our study is to investigate which interactions with specific human protein targets may cause DILI. Prediction of interactions with 1534 human proteins was performed for the dataset with information about 699 drugs, which were divided into three categories of DILI: severe (178 drugs), moderate (310 drugs) and without DILI (211 drugs). Based on the comparison of drug-target interactions predicted for different drugs' categories and interpretation of those results using clustering, Gene Ontology, pathway and gene expression analysis, we identified 61 protein targets associated with DILI. Most of the revealed proteins were linked with hepatocytes' death caused by disruption of vital cellular processes, as well as the emergence of inflammation in the liver. It was found that interaction of a drug with the identified targets is the essential molecular mechanism of the severe DILI for the most of the considered pharmaceuticals. Thus, pharmaceutical agents interacting with many of the identified targets may be considered as candidates for filtering out at the early stages of drug research. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. 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

  20. Deregulation of PPARβ/δ target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment

    Science.gov (United States)

    Finkernagel, Florian; Lieber, Sonja; Schnitzer, Evelyn; Legrand, Nathalie; Schober, Yvonne; Nockher, W. Andreas; Toth, Philipp M.; Diederich, Wibke E.; Nist, Andrea; Stiewe, Thorsten; Wagner, Uwe; Reinartz, Silke; Müller-Brüsselbach, Sabine; Müller, Rolf

    2015-01-01

    The nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a lipid ligand-inducible transcription factor associated with macrophage polarization. However, its function in tumor-associated macrophages (TAMs) has not been investigated to date. Here, we report the PPARβ/δ-regulated transcriptome and cistrome for TAMs from ovarian carcinoma patients. Comparison with monocyte-derived macrophages shows that the vast majority of direct PPARβ/δ target genes are upregulated in TAMs and largely refractory to synthetic agonists, but repressible by inverse agonists. Besides genes with metabolic functions, these include cell type-selective genes associated with immune regulation and tumor progression, e.g., LRP5, CD300A, MAP3K8 and ANGPTL4. This deregulation is not due to increased expression of PPARβ/δ or its enhanced recruitment to target genes. Instead, lipidomic analysis of malignancy-associated ascites revealed high concentrations of polyunsaturated fatty acids, in particular linoleic acid, acting as potent PPARβ/δ agonists in macrophages. These fatty acid ligands accumulate in lipid droplets in TAMs, thereby providing a reservoir of PPARβ/δ ligands. These observations suggest that the deregulation of PPARβ/δ target genes by ligands of the tumor microenvironment contributes to the pro-tumorigenic polarization of ovarian carcinoma TAMs. This conclusion is supported by the association of high ANGPTL4 expression with a shorter relapse-free survival in serous ovarian carcinoma. PMID:25968567

  1. Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association.

    Science.gov (United States)

    Lichtman, Judith H; Bigger, J Thomas; Blumenthal, James A; Frasure-Smith, Nancy; Kaufmann, Peter G; Lespérance, François; Mark, Daniel B; Sheps, David S; Taylor, C Barr; Froelicher, Erika Sivarajan

    2008-10-21

    Depression is commonly present in patients with coronary heart disease (CHD) and is independently associated with increased cardiovascular morbidity and mortality. Screening tests for depressive symptoms should be applied to identify patients who may require further assessment and treatment. This multispecialty consensus document reviews the evidence linking depression with CHD and provides recommendations for healthcare providers for the assessment, referral, and treatment of depression.

  2. Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting.

    Science.gov (United States)

    Walsh, Ryan R; Krismer, Florian; Galpern, Wendy R; Wenning, Gregor K; Low, Phillip A; Halliday, Glenda; Koroshetz, Walter J; Holton, Janice; Quinn, Niall P; Rascol, Olivier; Shaw, Leslie M; Eidelberg, David; Bower, Pam; Cummings, Jeffrey L; Abler, Victor; Biedenharn, Judy; Bitan, Gal; Brooks, David J; Brundin, Patrik; Fernandez, Hubert; Fortier, Philip; Freeman, Roy; Gasser, Thomas; Hewitt, Art; Höglinger, Günter U; Huentelman, Matt J; Jensen, Poul H; Jeromin, Andreas; Kang, Un Jung; Kaufmann, Horacio; Kellerman, Lawrence; Khurana, Vikram; Klockgether, Thomas; Kim, Woojin Scott; Langer, Carol; LeWitt, Peter; Masliah, Eliezer; Meissner, Wassilios; Melki, Ronald; Ostrowitzki, Susanne; Piantadosi, Steven; Poewe, Werner; Robertson, David; Roemer, Cyndi; Schenk, Dale; Schlossmacher, Michael; Schmahmann, Jeremy D; Seppi, Klaus; Shih, Lily; Siderowf, Andrew; Stebbins, Glenn T; Stefanova, Nadia; Tsuji, Shoji; Sutton, Sharon; Zhang, Jing

    2018-01-09

    Multiple system atrophy (MSA) is a rare neurodegenerative disorder with substantial knowledge gaps despite recent gains in basic and clinical research. In order to make further advances, concerted international collaboration is vital. In 2014, an international meeting involving leaders in the field and MSA advocacy groups was convened in Las Vegas, Nevada, to identify critical research areas where consensus and progress was needed to improve understanding, diagnosis, and treatment of the disease. Eight topic areas were defined: pathogenesis, preclinical modeling, target identification, endophenotyping, clinical measures, imaging biomarkers, nonimaging biomarkers, treatments/trial designs, and patient advocacy. For each topic area, an expert served as a working group chair and each working group developed priority-ranked research recommendations with associated timelines and pathways to reach the intended goals. In this report, each groups' recommendations are provided. Copyright © 2017 American Academy of Neurology.

  3. [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

  4. A Hybrid Recommender System Based on User-Recommender Interaction

    OpenAIRE

    Zhang, Heng-Ru; Min, Fan; He, Xu; Xu, Yuan-Yuan

    2015-01-01

    Recommender systems are used to make recommendations about products, information, or services for users. Most existing recommender systems implicitly assume one particular type of user behavior. However, they seldom consider user-recommender interactive scenarios in real-world environments. In this paper, we propose a hybrid recommender system based on user-recommender interaction and evaluate its performance with recall and diversity metrics. First, we define the user-recommender interaction...

  5. No association between the use of Bti for mosquito control and the dynamics of non-target aquatic invertebrates in French coastal and continental wetlands.

    Science.gov (United States)

    Lagadic, Laurent; Schäfer, Ralf B; Roucaute, Marc; Szöcs, Eduard; Chouin, Sébastien; de Maupeou, Jérôme; Duchet, Claire; Franquet, Evelyne; Le Hunsec, Benoit; Bertrand, Céline; Fayolle, Stéphanie; Francés, Benoît; Rozier, Yves; Foussadier, Rémi; Santoni, Jean-Baptiste; Lagneau, Christophe

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. ISFG: Recommendations on biostatistics in paternity testing

    DEFF Research Database (Denmark)

    Gjertson, David W; Brenner, Charles H; Baur, Max P

    2007-01-01

    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...

  7. Targeted delivery of antigens to the gut-associated lymphoid tissues: 2. Ex vivo evaluation of lectin-labelled albumin microspheres for targeted delivery of antigens to the M-cells of the Peyer's patches.

    Science.gov (United States)

    Akande, Janet; Yeboah, Kwame G; Addo, Richard T; Siddig, Aladin; Oettinger, Carl W; D'Souza, Martin J

    2010-01-01

    The purpose of this study was to evaluate the possibility of lectin-coupled microspheres to improve the targeted delivery of protein antigens to the lymphoid tissues of mucosal surfaces. Bovine serum albumin containing acid phosphatase model protein and polystyrene microspheres were coupled with mouse M-cell-specific Ulex europaeus lectin. The coupling efficiency, physical characteristics and the binding capabilities of the microspheres to the follicle associated epithelium of the Peyer's patches were evaluated in vitro and ex vivo in mice intestine. The results showed that coupling of lectin to albumin microspheres did not significantly affect the bioactivity of the encapsulated acid phosphatase model protein. It was also shown that there was preferential binding of the lectin-coupled microspheres to the follicle-associated epithelium. It was concluded from the results of the study that coupling of ligands such as lectin specific to cells of the follicle associated epithelium can increase the targeting of encapsulated candidate antigens for delivery to the Peyer's patches of the intestine for improved oral delivery.

  8. Summary (and) recommendations

    International Nuclear Information System (INIS)

    1992-01-01

    This report looks at the Health and Safety record at the Atomic Weapons Establishment at Aldermaston. The last outside report was by Pochin in 1978 which recommended that staffing for health physicists and maintenance staff should be increased and that some buildings where solid and liquid radioactive wastes were processed should be replaced. A new facility to process contaminated heavy equipment was also recommended. This report finds that none of the recommendations have been fully implemented. It also lists accidents, fires and worker contamination. It is concluded that some of the problems are that nuclear weapons production is inherently unsafe and cannot be made safe, that the secrecy surrounding the establishments' safety record is not good for improving it and finally the report calls for production at Aldermaston to be halted. (UK)

  9. Archetypal Game Recommender Systems

    DEFF Research Database (Denmark)

    Sifa, Rafet; Bauckhage, C.; Drachen, Anders

    2014-01-01

    Contemporary users (players, consumers) of digital games have thousands of products to choose from, which makes nding games that t their interests challenging. Towards addressing this challenge, in this paper two dierent formulations of Archetypal Analysis for Top-L recommender tasks using implicit...... 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...

  10. 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...... the design, conduct and analytical approaches to RCTs evaluating the preventative effect of joint injury prevention strategies. Recommendations regarding the design, conduct, and reporting of RCTs evaluating injury prevention interventions were established based on the consensus of nine researchers...... internationally with expertise in epidemiology, injury prevention and/or osteoarthritis (OA). Input and resultant consensus was established through teleconference, face to face and email correspondence over a 1 year period. Recommendations for injury prevention RCTs include context specific considerations...

  11. Recommending Multidimensional Queries

    Science.gov (United States)

    Giacometti, Arnaud; Marcel, Patrick; Negre, Elsa

    Interactive analysis of datacube, in which a user navigates a cube by launching a sequence of queries is often tedious since the user may have no idea of what the forthcoming query should be in his current analysis. To better support this process we propose in this paper to apply a Collaborative Work approach that leverages former explorations of the cube to recommend OLAP queries. The system that we have developed adapts Approximate String Matching, a technique popular in Information Retrieval, to match the current analysis with the former explorations and help suggesting a query to the user. Our approach has been implemented with the open source Mondrian OLAP server to recommend MDX queries and we have carried out some preliminary experiments that show its efficiency for generating effective query recommendations.

  12. 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.

  13. 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. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  14. Downregulation of the Sonic Hedgehog/Gli pathway transcriptional target Neogenin-1 is associated with basal cell carcinoma aggressiveness.

    Science.gov (United States)

    Casas, Bárbara S; Adolphe, Christelle; Lois, Pablo; Navarrete, Nelson; Solís, Natalia; Bustamante, Eva; Gac, Patricio; Cabané, Patricio; Gallegos, Ivan; Wainwright, Brandon J; Palma, Verónica

    2017-10-13

    Basal Cell Carcinoma (BCC) is one of the most diagnosed cancers worldwide. It develops due to an unrestrained Sonic Hedgehog (SHH) signaling activity in basal cells of the skin. Certain subtypes of BCC are more aggressive than others, although the molecular basis of this phenomenon remains unknown. We have previously reported that Neogenin-1 (NEO1) is a downstream target gene of the SHH/GLI pathway in neural tissue. Given that SHH participates in epidermal homeostasis, here we analyzed the epidermal expression of NEO1 in order to identify whether it plays a role in adult epidermis or BCC. We describe the mRNA and protein expression profile of NEO1 and its ligands (Netrin-1 and RGMA) in human and mouse control epidermis and in a broad range of human BCCs. We identify in human BCC a significant positive correlation in the levels of NEO1 receptor, NTN-1 and RGMA ligands with respect to GLI1 , the main target gene of the canonical SHH pathway. Moreover, we show via cyclopamine inhibition of the SHH/GLI pathway of ex vivo cultures that NEO1 likely functions as a downstream target of SHH/GLI signaling in the skin. We also show how Neo1 expression decreases throughout BCC progression in the K14-Cre:Ptch1 lox/lox mouse model and that aggressive subtypes of human BCC exhibit lower levels of NEO1 than non-aggressive BCC samples. Taken together, these data suggest that NEO1 is a SHH/GLI target in epidermis. We propose that NEO1 may be important in tumor onset and is then down-regulated in advanced BCC or aggressive subtypes.

  15. Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer?s-Associated A? Oligomers

    OpenAIRE

    Wilcox, Kyle C.; Marunde, Matthew R.; Das, Aditi; Velasco, Pauline T.; Kuhns, Benjamin D.; Marty, Michael T.; Jiang, Haoming; Luan, Chi-Hao; Sligar, Stephen G.; Klein, William L.

    2015-01-01

    Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein int...

  16. Review of ICRP recommendations

    International Nuclear Information System (INIS)

    Goldfinch, E.P.

    1987-01-01

    Events in both the scientific world and in the public domain have added pressure to review the recommendations of the ICRP on which radiation protection legislation in most countries is founded. A brief editorial pleads for clarity in ICRP recommendations, suggests the use solely of cumulative with age individual occupational dose limits, suggests that collective doses including both occupational and to the public should be kept as low as reasonably achievable, judged on quantitative economic grounds, and suggests the setting of a probability for serious accidents which may be disregarded in planning. (UK)

  17. Teacher Efficacy and Disproportional Special Education Recommendations

    Science.gov (United States)

    Branscombe, Peter

    2017-01-01

    According to literature, African American male students are disproportionately placed in special education programs throughout our national public school systems. Therefore, this study was intended to examine factors that may influence a teacher's decision to recommend students for special education services. The target population for this study…

  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. 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

  20. 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.

    Science.gov (United States)

    Heudorf, Ursel; Gasteyer, Stefanie; Müller, Maria; Samoiski, Yvonne; Serra, Nicole; Westphal, Tim

    2016-01-01

    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. 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. 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. In the current evaluation, fewer nursing home residents were catheterized than in previous years and the rate of urinary tract infections was low. This indicates an increasingly cautious and apparently appropriate

  1. Monocyte to macrophage differentiation-associated (MMD) targeted by miR-140-5p regulates tumor growth in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Li, Weina; He, Fei

    2014-01-01

    Highlights: • Expression of MMD is increased in lung cancer tissues. • Knockdown of MMD inhibits growth of A549 and LLC cells in vitro and in vivo. • MMD is a direct functional target of miR-140-5p. • MiR-140-5p/MMD axis regulates Erk1/2 signaling. - Abstract: Monocyte to macrophage differentiation-associated (MMD) is identified in macrophages as a gene associated with the differentiation from monocytes to macrophages. Recent microarray analysis for non-small cell lung cancer (NSCLC) suggests that MMD is an important signature associated with relapse and survival among patients with NSCLC. Therefore, we speculate that MMD likely plays a role in lung cancer. In this study, we found that the protein level of MMD was increased in lung cancer compared to benign lung tissues, and knockdown of MMD inhibited the growth of A549 and Lewis lung cancer cells (LLC) in vitro and in vivo. Integrated analysis demonstrated that MMD was a direct functional target of miR-140-5p. Furthermore, we found that miR-140-5p/MMD axis could affect the cell proliferation of lung cancer cells by regulating Erk signaling. Together, our results highlight the significance of miR-140-5p/MMD axis in lung cancer, and miR-140-5p/MMD axis could serve as new molecular targets for the therapy against lung cancer

  2. Privacy enhanced recommender system

    NARCIS (Netherlands)

    Erkin, Zekeriya; Erkin, Zekeriya; Beye, Michael; Veugen, Thijs; Lagendijk, Reginald L.

    2010-01-01

    Recommender systems are widely used in online applications since they enable personalized service to the users. The underlying collaborative filtering techniques work on user’s data which are mostly privacy sensitive and can be misused by the service provider. To protect the privacy of the users, we

  3. Recommendations for Alternative Credit.

    Science.gov (United States)

    Lenderman, Ed; And Others

    Following a review of the mathematics topics taught in accounting, electronics, auto, food and clothing, and metals courses at Linn-Benton Community College, Albany, Oregon, recommendations were made to grant one semester of mathematics credit for completing a two-year sequence of these courses. The other required semester of mathematics should be…

  4. Towards Geosocial Recommender Systems

    NARCIS (Netherlands)

    de Graaff, V.; van Keulen, Maurice; de By, R.A.; de By, 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

  5. Search and Recommendation

    DEFF Research Database (Denmark)

    Bogers, Toine

    2014-01-01

    In just a little over half a century, the field of information retrieval has experienced spectacular growth and success, with IR applications such as search engines becoming a billion-dollar industry in the past decades. Recommender systems have seen an even more meteoric rise to success with wide...

  6. Chapter 10: Management recommendations

    Science.gov (United States)

    Deborah M. Finch; Janie Agyagos; Tracy McCarthey; Robert M. Marshall; Scott H. Stoleson; Mary J. Whitfield

    2000-01-01

    This chapter was developed over a series of meetings using a group-consensus process. Our recommendations are based on published results, on information compiled in the previous chapters, on expert opinion, and on unpublished data of conservation team members. This chapter is available as temporary guidance until the Recovery Plan for the southwestern willow flycatcher...

  7. Privacy in Recommender Systems

    NARCIS (Netherlands)

    Jeckmans, Arjan; Beye, Michael; Erkin, Zekeriya; Erkin, Zekeriya; Hartel, Pieter H.; Lagendijk, Reginald; Tang, Qiang; Ramzan, Naeem; van Zwol, Roelof; Lee, Jong-Seok; Clüver, Kai; Hua, Xian-Sheng

    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

  8. The ICRP 2007 recommendations

    International Nuclear Information System (INIS)

    Streffer, C.

    2007-01-01

    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

  9. 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

  10. Temporary ovarian suppression during chemotherapy to preserve ovarian function and fertility in breast cancer patients: A GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

    Science.gov (United States)

    Lambertini, Matteo; Cinquini, Michela; Moschetti, Ivan; Peccatori, Fedro A; Anserini, Paola; Valenzano Menada, Mario; Tomirotti, Maurizio; Del Mastro, Lucia

    2017-01-01

    The development of premature ovarian failure and subsequent infertility are possible consequences of chemotherapy use in pre-menopausal women with early-stage breast cancer. Among the available strategies for fertility preservation, pharmacological protection of the ovaries using luteinising hormone-releasing hormone analogues (LHRHa) during chemotherapy has the potential to restore ovarian function and fertility after anticancer treatments; however, the possible efficacy and clinical application of this strategy has been highly debated in the last years. Following the availability of new data on this controversial topic, the Panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guideline on fertility preservation in cancer patients decided to apply the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology around the relevant and current question on the clinical utility of temporary ovarian suppression with LHRHa during chemotherapy as a strategy to preserve ovarian function and fertility in breast cancer patients. To answer this question, preservation of ovarian function and fertility were judged as critical outcomes for the decision-making. Three possible outcomes of harm were identified: LHRHa-associated toxicities, potential antagonism between concurrent LHRHa and chemotherapy, and lack of the prognostic impact of chemotherapy-induced premature ovarian failure. According to the GRADE evaluation conducted, the result was a strong positive recommendation in favour of using this option to preserve ovarian function and fertility in breast cancer patients. The present manuscript aims to update and summarise the evidence for the use of this strategy in light of the new data published up to January 2016, according to the GRADE process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Direct Targeting of Macrophages With Methylglyoxal-Bis-Guanylhydrazone Decreases SIV-Associated Cardiovascular Inflammation and Pathology.

    Science.gov (United States)

    Walker, Joshua A; Miller, Andrew D; Burdo, Tricia H; McGrath, Michael S; Williams, Kenneth C

    2017-04-15

    Despite effective combination antiretroviral therapy, HIV-infected individuals develop comorbidities, including cardiovascular disease, where activated macrophages play a key role. To date, few therapies target activated monocytes and macrophages. We evaluated a novel oral form of the polyamine biosynthesis inhibitor methylglyoxal-bis-guanylhydrazone (MGBG) on cardiovascular inflammation, carotid artery intima-media thickness (cIMT), and fibrosis in a simian immunodeficiency virus infection model of AIDS. Eleven simian immunodeficiency virus-infected animals received MGBG (30 mg/kg) once daily and 8 received a placebo control both beginning at 21 days postinfection (dpi). Animals were time sacrificed at 49 days post infection (dpi), when their matched placebo controls developed AIDS (63, 70, 77, 80), or at the study end-point (84 dpi). Aorta, carotid artery, and cardiac tissues were analyzed. Quantitative analyses of macrophage populations and T lymphocytes were done and correlated with cIMT and fibrosis. MGBG treatment resulted in 2.19-fold (CD163), 1.86-fold (CD68), 2.31-fold (CD206), and 2.12-fold (MAC387) decreases in macrophages in carotid arteries and significant 2.07-fold (CD163), 1.61-fold (CD68), 1.95-fold (MAC387), and 1.62-fold (CD206) decreases in macrophages in cardiac tissues. cIMT (1.49-fold) and fibrosis (2.05-fold) also were significantly decreased with MGBG treatment. Numbers of macrophage and the degree of fibrosis in treated animals were similar to uninfected animals. A positive correlation between decreased macrophage in the carotid artery and cIMT, and cardiac macrophages and fibrosis was found. These data demonstrate that directly targeting macrophages with MGBG can reduce cardiovascular inflammation, cIMT, and fibrosis. They suggest that therapies targeting macrophages with HIV could be used in conjunction with combination antiretroviral therapy.

  12. Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.

    Directory of Open Access Journals (Sweden)

    Sarah A Hamilton

    Full Text Available Current therapies for preterm labour (PTL focus on arresting myometrial contractions but are largely ineffective, thus alternative therapeutic targets need to be identified. Leukocytes infiltrate the uterus around the time of labour, and are in particularly abundant in decidua (maternal-fetal interface. Moreover, decidual inflammation precedes labour in rat pregnancies and thus may contribute to initiation of labour. We hypothesized that chemokines mediate decidual leukocyte trafficking during preterm labour (PTL and term labour (TL, thus representing potential targets for preventing PTL. Women were recruited into 4 groups: TL, term not in labour (TNL, idiopathic PTL and PTL with infection (PTLI. Choriodecidual RNA was subjected to a pathway-specific PCR array for chemokines. Differential expression of 12 candidate chemokines was validated by real time RT-PCR and Bioplex assay, with immunohistochemistry to confirm cellular origin. 25 chemokines were upregulated in choriodecidua from TL compared to TNL. A similar pattern was detected in PTL, however a distinct profile was observed in PTLI consistent with differences in leukocyte infiltration. Upregulation of CCL2, CCL4, CCL5, CXCL8 and CXCL10 mRNA and protein was confirmed in TL, with CCL8 upregulated in PTL. Significant correlations were detected between these chemokines and decidual leukocyte abundance previously assessed by immunohistochemical and image analysis. Chemokines were primarily expressed by decidual stromal cells. In addition, CXCL8 and CCL5 were significantly elevated in maternal plasma during labour, suggesting chemokines contribute to peripheral inflammatory events during labour. Differences in chemokine expression patterns between TL and idiopathic PTL may be attributable to suppression of chemokine expression by betamethasone administered to women in PTL; this was supported by in vitro evidence of chemokine downregulation by clinically relevant concentrations of the steroid

  13. Plasma membrane associated, virus-specific polypeptides required for the formation of target antigen complexes recognized by virus-specific cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Domber, E.A.

    1986-01-01

    These studies were undertaken to define some of the poxvirus-specific target antigens which are synthesized in infected cells and recognized by vaccinia virus-specific CTLs (VV-CTLs). Since vaccinia virus infected, unmanipulated target cells express numerous virus-specific antigens on the plasma membrane, attempts were made to manipulate expression of the poxvirus genome after infection so that one or a few defined virus-specified antigens were expressed on the surface of infected cells. In vitro [ 51 Cr]-release assays determined that viral DNA synthesis and expression of late viral proteins were not necessary to form a target cell which was fully competent for lysis by VV-CTLs. Under the conditions employed in these experiments, 90-120 minutes of viral protein synthesis were necessary to produce a competent cell for lysis by VV-CTLs. In order to further inhibit the expression of early viral proteins in infected cells, partially UV-inactivated vaccinia virus was employed to infect target cells. It was determined that L-cells infected with virus preparations which had been UV-irradiated for 90 seconds were fully competent for lysis by VV-CTLs. Cells infected with 90 second UV-irr virus expressed 3 predominant, plasma membrane associated antigens of 36-37K, 27-28K, and 19-17K. These 3 viral antigens represent the predominant membrane-associated viral antigens available for interaction with class I, major histocompatibility antigens and hence are potential target antigens for VV-CTLs

  14. Targets and tactics

    DEFF Research Database (Denmark)

    Woo, V; Shestakova, M V; Ørskov, C

    2008-01-01

    BACKGROUND: The incidence of type 2 diabetes is reaching pandemic proportions, impacting patients and healthcare systems across the globe. Evidence suggests that a majority of patients are not achieving recommended blood glucose targets resulting in an increased risk of micro- and macro-vascular ......BACKGROUND: The incidence of type 2 diabetes is reaching pandemic proportions, impacting patients and healthcare systems across the globe. Evidence suggests that a majority of patients are not achieving recommended blood glucose targets resulting in an increased risk of micro- and macro...... diabetes has never been more compelling; with a clear focus on strategies for glycaemic control, the impact of the diabetes pandemic can be limited....

  15. 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.

  16. Endosialin and Associated Protein Expression in Soft Tissue Sarcomas: A Potential Target for Anti-Endosialin Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Daniel J. O’Shannessy

    2016-01-01

    Full Text Available Endosialin (CD248, TEM-1 is expressed in pericytes, tumor vasculature, tumor fibroblasts, and some tumor cells, including sarcomas, with limited normal tissue expression, and appears to play a key role in tumor-stromal interactions, including angiogenesis. Monoclonal antibodies targeting endosialin have entered clinical trials, including soft tissue sarcomas. We evaluated a cohort of 94 soft tissue sarcoma samples to assess the correlation between gene expression and protein expression by immunohistochemistry for endosialin and PDGFR-β, a reported interacting protein, across available diagnoses. Correlations between the expression of endosialin and 13 other genes of interest were also examined. Within cohorts of soft tissue diagnoses assembled by tissue type (liposarcoma, leiomyosarcoma, undifferentiated sarcoma, and other, endosialin expression was significantly correlated with a better outcome. Endosialin expression was highest in liposarcomas and lowest in leiomyosarcomas. A robust correlation between protein and gene expression data for both endosialin and PDGFR-β was observed. Endosialin expression positively correlated with PDGFR-β and heparin sulphate proteoglycan 2 and negatively correlated with carbonic anhydrase IX. Endosialin likely interacts with a network of extracellular and hypoxia activated proteins in sarcomas and other tumor types. Since expression does vary across histologic groups, endosialin may represent a selective target in soft tissue sarcomas.

  17. Transcription factor HIF1A: downstream targets, associated pathways, polymorphic hypoxia response element (HRE) sites, and initiative for standardization of reporting in scientific literature.

    Science.gov (United States)

    Slemc, Lucija; Kunej, Tanja

    2016-11-01

    Hypoxia-inducible factor-1α (HIF-1α) has crucial role in adapting cells to hypoxia through expression regulation of many genes. Identification of HIF-1α target genes (HIF-1α-TGs) is important for understanding the adapting mechanism. The aim of the present study was to collect known HIF-1α-TGs and identify their associated pathways. Targets and associated genomics data were retrieved using PubMed, WoS ( http://apps.webofknowledge.com/ ), HGNC ( http://www.genenames.org/ ), NCBI ( http://www.ncbi.nlm.nih.gov/ ), Ensemblv.84 ( http://www.ensembl.org/index.html ), DAVID Bioinformatics Resources ( https://david.ncifcrf.gov /), and Disease Ontology database ( http://disease-ontology.org/ ). From 51 papers, we collected 98 HIF-1α TGs found to be associated with 20 pathways, including metabolism of carbohydrates and pathways in cancer. Reanalysis of genomic coordinates of published HREs (hypoxia response elements) revealed six polymorphisms within HRE sites (HRE-SNPs): ABCG2, ACE, CA9, and CP. Due to large heterogeneity of results presentation in scientific literature, we also propose a first step towards reporting standardization of HIF-1α-target interactions consisting of ten relevant data types. Suggested minimal checklist for reporting will enable faster development of a complete catalog of HIF-1α-TGs, data sharing, bioinformatics analyses, and setting novel more targeted hypotheses. The proposed format for data standardization is not yet complete but presents a baseline for further optimization of the protocol with additional details, for example, regarding the experimental validation.

  18. The Benefits of Targeted Memory Reactivation for Consolidation in Sleep are Contingent on Memory Accuracy and Direct Cue-Memory Associations.

    Science.gov (United States)

    Cairney, Scott A; Lindsay, Shane; Sobczak, Justyna M; Paller, Ken A; Gaskell, M Gareth

    2016-05-01

    To investigate how the effects of targeted memory reactivation (TMR) are influenced by memory accuracy prior to sleep and the presence or absence of direct cue-memory associations. 30 participants associated each of 50 pictures with an unrelated word and then with a screen location in two separate tasks. During picture-location training, each picture was also presented with a semantically related sound. The sounds were therefore directly associated with the picture locations but indirectly associated with the words. During a subsequent nap, half of the sounds were replayed in slow wave sleep (SWS). The effect of TMR on memory for the picture locations (direct cue-memory associations) and picture-word pairs (indirect cue-memory associations) was then examined. TMR reduced overall memory decay for recall of picture locations. Further analyses revealed a benefit of TMR for picture locations recalled with a low degree of accuracy prior to sleep, but not those recalled with a high degree of accuracy. The benefit of TMR for low accuracy memories was predicted by time spent in SWS. There was no benefit of TMR for memory of the picture-word pairs, irrespective of memory accuracy prior to sleep. TMR provides the greatest benefit to memories recalled with a low degree of accuracy prior to sleep. The memory benefits of TMR may also be contingent on direct cue-memory associations. © 2016 Associated Professional Sleep Societies, LLC.

  19. 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.

  20. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Aletaha, Daniel; Bijlsma, Johannes W J

    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: /st> To develop recommendations for achieving optimal therapeutic outcomes in RA. METHODS....... 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...

  1. Metabolomics reveals metabolic targets and biphasic responses in breast cancer cells treated by curcumin alone and in association with docetaxel.

    Directory of Open Access Journals (Sweden)

    Mathilde Bayet-Robert

    Full Text Available BACKGROUND: Curcumin (CUR has deserved extensive research due to its anti-inflammatory properties, of interest in human diseases including cancer. However, pleiotropic even paradoxical responses of tumor cells have been reported, and the mechanisms of action of CUR remain uncompletely elucidated. METHODOLOGY/PRINCIPAL FINDINGS: (1H-NMR spectroscopy-based metabolomics was applied to get novel insight into responses of MCF7 and MDA-MB-231 breast cancer cells to CUR alone, and MCF7 cells to CUR in cotreatment with docetaxel (DTX. In both cell types, a major target of CUR was glutathione metabolism. Total glutathione (GSx increased at low dose CUR (≤ 10 mg.l(-1-28 µM- (up to +121% in MCF7 cells, P<0.01, and +138% in MDA-MB-231 cells, P<0.01, but decreased at high dose (≥ 25 mg.l(-1 -70 µM- (-49%, in MCF7 cells, P<0.02, and -56% in MDA-MB-231 cells, P<0.025. At high dose, in both cell types, GSx-related metabolites decreased, including homocystein, creatine and taurine (-60 to -80%, all, P<0.05. Together with glutathione-S-transferase actvity, data established that GSx biosynthesis was upregulated at low dose, and GSx consumption activated at high dose. Another major target, in both cell types, was lipid metabolism involving, at high doses, accumulation of polyunsaturated and total free fatty acids (between ×4.5 and ×11, P<0.025, and decrease of glycerophospho-ethanolamine and -choline (about -60%, P<0.025. Multivariate statistical analyses showed a metabolic transition, even a biphasic behavior of some metabolites including GSx, between low and high doses. In addition, CUR at 10 mg.l(-1 in cotreatment with DTX induced modifications in glutathione metabolism, lipid metabolism, and glucose utilization. Some of these changes were biphasic depending on the duration of exposure to CUR. CONCLUSIONS/SIGNIFICANCE: Metabolomics reveals major metabolic targets of CUR in breast cancer cells, and biphasic responses that challenge the widely accepted

  2. The RDE-10/RDE-11 complex triggers RNAi-induced mRNA degradation by association with target mRNA in C. elegans.

    Science.gov (United States)

    Yang, Huan; Zhang, Ying; Vallandingham, Jim; Li, Hua; Li, Hau; Florens, Laurence; Mak, Ho Yi

    2012-04-15

    The molecular mechanisms for target mRNA degradation in Caenorhabditis elegans undergoing RNAi are not fully understood. Using a combination of genetic, proteomic, and biochemical approaches, we report a divergent RDE-10/RDE-11 complex that is required for RNAi in C. elegans. Genetic analysis indicates that the RDE-10/RDE-11 complex acts in parallel to nuclear RNAi. Association of the complex with target mRNA is dependent on RDE-1 but not RRF-1, suggesting that target mRNA recognition depends on primary but not secondary siRNA. Furthermore, RDE-11 is required for mRNA degradation subsequent to target engagement. Deep sequencing reveals a fivefold decrease in secondary siRNA abundance in rde-10 and rde-11 mutant animals, while primary siRNA and microRNA biogenesis is normal. Therefore, the RDE-10/RDE-11 complex is critical for amplifying the exogenous RNAi response. Our work uncovers an essential output of the RNAi pathway in C. elegans.

  3. ICRS Recommendation Document

    DEFF Research Database (Denmark)

    Roos, Ewa M.; Engelhart, Luella; Ranstam, Jonas

    2011-01-01

    and function evaluated for validity and psychometric properties in patients with articular cartilage lesions. Results: The knee-specific instruments, titled the International Knee Documentation Committee Subjective Knee Form and the Knee injury and Osteoarthritis and Outcome Score, both fulfill the basic......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...

  4. Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer's-Associated Aβ Oligomers.

    Directory of Open Access Journals (Sweden)

    Kyle C Wilcox

    Full Text Available Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs. AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AβOs to surface membranes. Here, we show that AβO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs. This method gives a soluble membrane protein library (SMPL--a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AβOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AβO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AβO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AβO binding will provide a useful experimental antagonist for future mechanistic studies of AβOs in Alzheimer's model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AβO binding antagonists, and illustrate in general how a SMPL Nanodisc system can

  5. Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer’s-Associated Aβ Oligomers

    Science.gov (United States)

    Wilcox, Kyle C.; Marunde, Matthew R.; Das, Aditi; Velasco, Pauline T.; Kuhns, Benjamin D.; Marty, Michael T.; Jiang, Haoming; Luan, Chi-Hao; Sligar, Stephen G.; Klein, William L.

    2015-01-01

    Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer’s dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AβOs to surface membranes. Here, we show that AβO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs). This method gives a soluble membrane protein library (SMPL)—a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AβOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AβO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AβO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AβO binding will provide a useful experimental antagonist for future mechanistic studies of AβOs in Alzheimer’s model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AβO binding antagonists, and illustrate in general how a SMPL Nanodisc system can facilitate drug

  6. Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer's-Associated Aβ Oligomers.

    Science.gov (United States)

    Wilcox, Kyle C; Marunde, Matthew R; Das, Aditi; Velasco, Pauline T; Kuhns, Benjamin D; Marty, Michael T; Jiang, Haoming; Luan, Chi-Hao; Sligar, Stephen G; Klein, William L

    2015-01-01

    Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AβOs to surface membranes. Here, we show that AβO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs). This method gives a soluble membrane protein library (SMPL)--a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AβOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AβO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AβO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AβO binding will provide a useful experimental antagonist for future mechanistic studies of AβOs in Alzheimer's model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AβO binding antagonists, and illustrate in general how a SMPL Nanodisc system can facilitate drug discovery

  7. Ubiquitome Analysis Reveals PCNA-Associated Factor 15 (PAF15) as a Specific Ubiquitination Target of UHRF1 in Embryonic Stem Cells.

    Science.gov (United States)

    Karg, Elisabeth; Smets, Martha; Ryan, Joel; Forné, Ignasi; Qin, Weihua; Mulholland, Christopher B; Kalideris, Georgia; Imhof, Axel; Bultmann, Sebastian; Leonhardt, Heinrich

    2017-12-08

    Ubiquitination is a multifunctional posttranslational modification controlling the activity, subcellular localization and stability of proteins. The E3 ubiquitin ligase ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1) is an essential epigenetic factor that recognizes repressive histone marks as well as hemi-methylated DNA and recruits DNA methyltransferase 1. To explore enzymatic functions of UHRF1 beyond epigenetic regulation, we conducted a comprehensive screen in mouse embryonic stem cells to identify novel ubiquitination targets of UHRF1 and its paralogue UHRF2. We found differentially ubiquitinated peptides associated with a variety of biological processes such as transcriptional regulation and DNA damage response. Most prominently, we identified PCNA-associated factor 15 (PAF15; also known as Pclaf, Ns5atp9, KIAA0101 and OEATC-1) as a specific ubiquitination target of UHRF1. Although the function of PAF15 ubiquitination in translesion DNA synthesis is well characterized, the respective E3 ligase had been unknown. We could show that UHRF1 ubiquitinates PAF15 at Lys 15 and Lys 24 and promotes its binding to PCNA during late S-phase. In summary, we identified novel ubiquitination targets that link UHRF1 to transcriptional regulation and DNA damage response. Copyright © 2017. Published by Elsevier Ltd.

  8. Badali recommends simplified bills

    International Nuclear Information System (INIS)

    Anon

    2003-01-01

    A report on the variety of retail electricity bills across the province, authored by Salvatore Badali of Deloitte Consulting, was recently released by the Ontario Government. The report was commissioned by the Government to examine the underlying reasons for the significant format differences and the wide variation of fixed and variable charges among the approximately 95 local electricity distribution companies across the province. Regarding the appropriateness of the charges the report recommends common definitions for local distribution company (LDC) fixed and variable costs, and consideration of options for reducing LDC charges, mainly by consolidating the sector and sharing such services as customer billing, accounting and out sourcing operations. Seven recommendations deal with bill simplification. These include bills that are clear and easy to read and provide sufficient information for consumers to verify charges; promote energy conservation, e.g. by including historical information; allow comparisons between retail suppliers and distributors; accommodate revenue collection, marketing needs and other billing services. The report also recommends clearly defined and consistently used terminology for standardized line items, suggests ways to provide consumer information in a form useful for making energy conservation decisions, development of an LDC scorecard to enable stake holders to compare their own LDCs with LDCs around the province, creation of a conservation and bill calculation website, consideration of further use of shared services, and solutions to address the removal of line losses from invoices

  9. Badali recommends simplified bills

    Energy Technology Data Exchange (ETDEWEB)

    Anon

    2003-04-01

    A report on the variety of retail electricity bills across the province, authored by Salvatore Badali of Deloitte Consulting, was recently released by the Ontario Government. The report was commissioned by the Government to examine the underlying reasons for the significant format differences and the wide variation of fixed and variable charges among the approximately 95 local electricity distribution companies across the province. Regarding the appropriateness of the charges the report recommends common definitions for local distribution company (LDC) fixed and variable costs, and consideration of options for reducing LDC charges, mainly by consolidating the sector and sharing such services as customer billing, accounting and out sourcing operations. Seven recommendations deal with bill simplification. These include bills that are clear and easy to read and provide sufficient information for consumers to verify charges; promote energy conservation, e.g. by including historical information; allow comparisons between retail suppliers and distributors; accommodate revenue collection, marketing needs and other billing services. The report also recommends clearly defined and consistently used terminology for standardized line items, suggests ways to provide consumer information in a form useful for making energy conservation decisions, development of an LDC scorecard to enable stake holders to compare their own LDCs with LDCs around the province, creation of a conservation and bill calculation website, consideration of further use of shared services, and solutions to address the removal of line losses from invoices.

  10. Kinase Associated-1 Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids

    Energy Technology Data Exchange (ETDEWEB)

    Moravcevic, Katarina; Mendrola, Jeannine M.; Schmitz, Karl R.; Wang, Yu-Hsiu; Slochower, David; Janmey, Paul A.; Lemmon, Mark A. (UPENN-MED)

    2011-09-28

    Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regulation of many protein kinases. Here, we identify the KA1 domain (kinase associated-1 domain), found at the C terminus of yeast septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases, as a membrane association domain that binds acidic phospholipids. Membrane localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray crystallography, we identified a structurally conserved binding site for anionic phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs membrane association of both KA1 domains and intact proteins and reveals the importance of phosphatidylserine for bud neck localization of yeast Kcc4p. Our data suggest that KA1 domains contribute to coincidence detection, allowing kinases to bind other regulators (such as septins) only at the membrane surface. These findings have important implications for understanding MARK/PAR1 kinases, which are implicated in Alzheimer's disease, cancer, and autism.

  11. The microtubule-associated protein 1A (MAP1A) is an early molecular target of soluble Aβ-peptide

    DEFF Research Database (Denmark)

    Clemmensen, C; Aznar, S; Knudsen, G M

    2012-01-01

    that microtubule rearrangements may be proximate to neuritic degeneration and deficits in episodic declarative memory. Here, we examined primary cortical neurons for changes in markers associated with synaptic function following exposure to sublethal concentrations of non-aggregated Aβ-peptide. This data show...

  12. Georgia Hospital Association leads long-term staff recruiting effort. Reaches wide target audience through innovative media use.

    Science.gov (United States)

    Botvin, Judith D

    2003-01-01

    The Georgia Hospital Association (GHA), faced with a critical healthcare workforce shortage, created a long-term response to the problem by creating a Workforce Shortage Media Campaign. Its single purpose was to encourage Georgians to pursue careers in healthcare. The four-week campaign took six months to develop and included print, radio and television.

  13. 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

    , and the infected red blood cell surface antigens were not. The combined ability of total IgG to inhibit parasite growth and mediate the release of reactive oxygen species from neutrophils was associated with a marked reduction in the odds of developing SM (OR = 0.07; 95% CI = 0.006 to 0.82;P= 0.03). Assays...

  14. European framework for tuberculosis control and elimination in countries with a low incidence. Recommendations of the World Health Organization (WHO), International Union Against Tuberculosis and Lung Disease (IUATLD) and Royal Netherlands Tuberculosis Association (KNCV) Working Group.

    Science.gov (United States)

    Broekmans, J F; Migliori, G B; Rieder, H L; Lees, J; Ruutu, P; Loddenkemper, R; Raviglione, M C

    2002-04-01

    As countries approach the elimination phase of tuberculosis, specific problems and challenges emerge, due to the steadily declining incidence in the native population, the gradually increasing importance of the importation of latent tuberculosis infection and tuberculosis from other countries and the emergence of groups at particularly high risk of tuberculosis. Therefore, a Working Group of the World Health Organization (WHO), the International Union Against Tuberculosis and Lung Disease (IUATLD) and the Royal Netherlands Tuberculosis Association (KNCV) have developed a new framework for low incidence countries based on concepts and definitions consistent with those of previous recommendations from WHO/IUATLD Working Groups. In low-incidence countries, a broader spectrum of interventions is available and feasible, including: 1) a general approach to tuberculosis which ensures rapid detection and treatment of all the cases and prevention of unnecessary deaths; 2) an overall control strategy aimed at reducing the incidence of tuberculosis infection (risk-group management and prevention of transmission of infection in institutional settings) and 3) a tuberculosis elimination strategy aimed at reducing the prevalence of tuberculosis infection (outbreak management and provision of preventive therapy for specified groups and individuals). Government and private sector commitment towards elimination, effective case detection among symptomatic individuals together with active case finding in special groups, standard treatment of disease and infection, access to tuberculosis diagnostic and treatment services, prevention (e.g. through screening and bacille Calmette-Guéria immunization in specified groups), surveillance and treatment outcome monitoring are prerequisites to implementing the policy package recommended in this new framework document.

  15. MicroRNAs responding to southern rice black-streaked dwarf virus infection and their target genes associated with symptom development in rice.

    Science.gov (United States)

    Xu, Donglin; Mou, Guiping; Wang, Kang; Zhou, Guohui

    2014-09-22

    Southern rice black-streaked dwarf virus (SRBSDV) is a recently emerged rice virus that has spread across Asia. This devastating virus causes rice plants to produce a variety of symptoms during different growth stages. MicroRNAs (miRNAs) comprise a large group of 21-24-nt RNA molecules that are important regulators of plant development processes and stress responses. In this study, we used microarray profiling to investigate rice miRNAs responding to SRBSDV infection at 3, 9, 15, and 20 days post-inoculation (dpi). Expression levels of 56 miRNAs were altered in SRBSDV-infected rice plants, with these changes classified into eight different regulation patterns according to their temporal expression dynamics. Fourteen miRNAs belonging to six families (miR164, R396, R530, R1846, R1858, and R2097) were significantly regulated at 20 dpi. We used RT-qPCR to search for expression level correlations between members of these families and their putative targets at 3, 9, and 15 dpi. Some members of the miR164, R396, R530, and R1846 families were found to be positively or negatively correlated with their respective targets during 3-15 days after SRBSDV infection, whereas in more cases the rice miRNAs were not in correlation with their targets along the post-inoculation period, suggesting that some additional factors may be involved in rice miRNA-target interactions. The reported functions of rice genes targeted by the miR164, R396, R530, R1846, and R1858 families indicated that these genes are associated with symptom development. These results provide insights into miRNA-mediated SRBSDV-rice interactions. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Characterization of microRNAs and their target genes associated with transcriptomic changes in gamma-irradiated Arabidopsis.

    Science.gov (United States)

    Kim, J H; Go, Y S; Kim, J K; Chung, B Y

    2016-07-29

    MicroRNAs (miRNAs) regulate gene expression in response to biotic and abiotic stress in plants. We investigated gamma-ray-responsive miRNAs in Arabidopsis wild-type and cmt3-11t mutant plants using miRNA microarray analysis. miRNA expression was differentiated between the wild-type and cmt3-11t mutants. miR164a, miR169d, miR169h, miR172b*, and miR403 were identified as repressible in the wild-type and/or cmt3-11t mutant in response to gamma irradiation, while miR827, miR840, and miR850 were strongly inducible. These eight miRNA genes contain UV-B-responsive cis-elements, including G-box, I-box core, ARE, and/or MBS in the putative promoter regions. Moreover, Box 4, MBS, TCA-element, and Unnamed_4, as well as CAAT- and TATA-box, were identified in these eight miRNA genes. However, a positive correlation between the transcriptions of miRNAs and their putative target genes was only observed between miR169d and At1g30560 in the wild-type, and between miR827 and At1g70700 in the cmt3-11t mutant. Quantitative RT-PCR analysis confirmed that the transcription of miR164a, miR169d, miR169h, miR172b*, miR403, and miR827 differed after gamma irradiation depending on the genotype (wild-type, cmt3-11t, drm2, drd1-6, and ddm1-2) and developmental stage (14 or 28 days after sowing). In contrast, high transcriptional induction of miR840 and miR850 was observed in these six genotypes regardless of the developmental stage. Although the actual target genes and functions of miR840 and miR850 remain to be determined, our results indicate that these two miRNAs may be strongly induced and reproducible genetic markers in Arabidopsis plants exposed to gamma rays.

  17. Association of the Purana basins and the middle Proterozoic mobile belts in peninsular India: implications on targeting uranium deposits

    International Nuclear Information System (INIS)

    Kale, V.S.

    1995-01-01

    The disparate Archaean Cratonic Nuclei of the Indian peninsular shield coalesced together through late Archaean - Palaeoproterozoic accretionary tectonic events. The subsequent Mesoproterozoic and Neoproterozoic sequences are preserved either in the Purana basins or in the middle Proterozoic mobile belts (MPMB). The latter contain deformed and metamorphosed supracrustal sequences; and can be ascribed to compressive tectonic regimes. The Purana basins on the other hand represent shallow marine, epicratonic, passive-margin sequences deposited in an extensional tectonic regime. Major deformational events and metamorphism of the MPMB are known to have taken place around 1600 ±200 Ma and 900 ± 100 Ma. These two periods coincide with the ages of initiation and major intrabasinal breaks in the growth of the Purana basins. The contemporary juxtapositioning of these two dissimilar tectonic regimes in peninsular India, is examined within the framework of the available data on them and the current models of Proterozoic tectonics. Its implications on uranium mineralization and possible regions for targeting exploration activities are discussed on this basis. (author). 112 refs., 4 figs

  18. Acute toxicity of chlorantraniliprole to non-target crayfish (Procambarus clarkii) associated with rice-crayfish cropping systems.

    Science.gov (United States)

    Barbee, Gary C; McClain, W Ray; Lanka, Srinivas K; Stout, Michael J

    2010-09-01

    Chlorantraniliprole, a novel anthranilic diamide insecticide, was recently introduced into the United States where rice-crayfish crop rotations are practiced to control rice water weevil (Lissorhoptrus oryzophilus Kuschel) infestations. Chlorantraniliprole has high margins of mammalian safety and excellent insecticidal efficacy, but its toxicity to non-target crayfish is uncertain. In this study, the acute toxicity of chlorantraniliprole to the red swamp crayfish Procambarus clarkii Girard was determined using aquatic and feeding assays. The aquatic 96 h median lethal toxicity (LC(50)) data indicate that technical-grade chlorantraniliprole is highly toxic (US EPA category) to crayfish with an LC(50) of 951 microg L(-1) (95% CL = 741-1118 microg L(-1)). A no observed effect concentration (NOEC) of 480 microg L(-1) was recorded. Neither the 36 day chronic feeding study, where crayfish fed on chlorantraniliprole-treated rice seed in aquaria, nor the 144 h acute feeding test, where crayfish fed on rice seeds treated with chlorantraniliprole, produced mortality or abnormal behavior. Chlorantraniliprole is three orders of magnitude less acutely toxic to P. clarkii than lambda-cyhalothrin and etofenprox, two pyrethroid insecticides also used in rice, and is less likely to cause acute crayfish toxicity in rice pond ecosystems. Based on acute toxicity data, the use of chlorantraniliprole should be more compatible with rice-crayfish crop rotations than pyrethroids. (c) 2010 Society of Chemical Industry.

  19. The Wnt-target gene Dlk-1 is regulated by the Prmt5-associated factor Copr5 during adipogenic conversion

    Directory of Open Access Journals (Sweden)

    Conception Paul

    2015-02-01

    Full Text Available Protein arginine methyl transferase 5 (Prmt5 regulates various differentiation processes, including adipogenesis. Here, we investigated adipogenic conversion in cells and mice in which Copr5, a Prmt5- and histone-binding protein, was genetically invalidated. Compared to control littermates, the retroperitoneal white adipose tissue (WAT of Copr5 KO mice was slightly but significantly reduced between 8 and 16 week/old and contained fewer and larger adipocytes. Moreover, the adipogenic conversion of Copr5 KO embryoid bodies (EB and of primary embryo fibroblasts (Mefs was markedly delayed. Differential transcriptomic analysis identified Copr5 as a negative regulator of the Dlk-1 gene, a Wnt target gene involved in the control of adipocyte progenitors cell fate. Dlk-1 expression was upregulated in Copr5 KO Mefs and the Vascular Stromal Fraction (VSF of Copr5 KO WAT. Chromatin immunoprecipitation (ChIP show that the ablation of Copr5 has impaired both the recruitment of Prmt5 and β-catenin at the Dlk-1 promoter. Overall, our data suggest that Copr5 is involved in the transcriptional control exerted by the Wnt pathway on early steps of adipogenesis.

  20. Tay–Sachs disease mutations in HEXA target the α chain of hexosaminidase A to endoplasmic reticulum–associated degradation

    Science.gov (United States)

    Dersh, Devin; Iwamoto, Yuichiro; Argon, Yair

    2016-01-01

    Loss of function of the enzyme β-hexosaminidase A (HexA) causes the lysosomal storage disorder Tay–Sachs disease (TSD). It has been proposed that mutations in the α chain of HexA can impair folding, enzyme assembly, and/or trafficking, yet there is surprisingly little known about the mechanisms of these potential routes of pathogenesis. We therefore investigated the biosynthesis and trafficking of TSD-associated HexA α mutants, seeking to identify relevant cellular quality control mechanisms. The α mutants E482K and G269S are defective in enzymatic activity, unprocessed by lysosomal proteases, and exhibit altered folding pathways compared with wild-type α. E482K is more severely misfolded than G269S, as observed by its aggregation and inability to associate with the HexA β chain. Importantly, both mutants are retrotranslocated from the endoplasmic reticulum (ER) to the cytosol and are degraded by the proteasome, indicating that they are cleared via ER-associated degradation (ERAD). Leveraging these discoveries, we observed that manipulating the cellular folding environment or ERAD pathways can alter the kinetics of mutant α degradation. Additionally, growth of patient fibroblasts at a permissive temperature or with chemical chaperones increases cellular Hex activity by improving mutant α folding. Therefore modulation of the ER quality control systems may be a potential therapeutic route for improving some forms of TSD. PMID:27682588

  1. Recommendation-Aware Smartphone Sensing System

    OpenAIRE

    Chen, Mu-Yen; Wu, Ming-Ni; Chen, Chia-Chen; Chen, Young-Long; Lin, Hsien-En

    2014-01-01

    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 Indoo...

  2. Mobile Application Recommender System

    OpenAIRE

    Davidsson, Christoffer

    2010-01-01

    With the amount of mobile applications available increasing rapidly, users have to put a lot of effort into finding applications of interest. The purpose of this thesis is to investigate how to aid users in the process of discovering new mobile applications by providing them with recommendations. A prototype system is then built as a proof-of-concept. The work of the thesis is divided into three phases where the aim of the first phase is to study related work and related systems to identify p...

  3. The new ICRP recommendations

    International Nuclear Information System (INIS)

    Schlesinger, T.

    1977-01-01

    The new ICRP recommendations are based on the concept of risk. The doses received by workers have to be justified and kept as low as practically achievable. The acceptable annual occupational risk is of the order of 10 -4 . This corresponds to an average annual dose equivalent of about 5 mSv(0.5 Rem). The annual dose equivalent limit for whole body irradiation will remain 50 mSv/year (5 Rem/year) provided that the average is about 1/10th of this value. The concept of the critical organ is abandoned and is replaced by the concept of equidetriment. (author)

  4. Personalized professional content recommendation

    Science.gov (United States)

    Xu, Songhua

    2015-10-27

    A personalized content recommendation system includes a client interface configured to automatically monitor a user's information data stream transmitted on the Internet. A hybrid contextual behavioral and collaborative personal interest inference engine resident to a non-transient media generates automatic predictions about the interests of individual users of the system. A database server retains the user's personal interest profile based on a plurality of monitored information. The system also includes a server programmed to filter items in an incoming information stream with the personal interest profile and is further programmed to identify only those items of the incoming information stream that substantially match the personal interest profile.

  5. miR-17-5p targets the p300/CBP-associated factor and modulates androgen receptor transcriptional activity in cultured prostate cancer cells

    International Nuclear Information System (INIS)

    Gong, Ai-Yu; Eischeid, Alex N; Xiao, Jing; Zhao, Jian; Chen, Dongqing; Wang, Zhao-Yi; Young, Charles YF; Chen, Xian-Ming

    2012-01-01

    Androgen receptor (AR) signalling is critical to the initiation and progression of prostate cancer (PCa). Transcriptional activity of AR involves chromatin recruitment of co-activators, including the p300/CBP-associated factor (PCAF). Distinct miRNA expression profiles have been identified in PCa cells during the development and progression of the disease. Whether miRNAs regulate PCAF expression in PCa cells to regulate AR transcriptional activity is still unclear. Expression of PCAF was investigated in several PCa cell lines by qRT-PCR, Western blot, and immunocytochemistry. The effects of PCAF expression on AR-regulated transcriptional activity and cell growth in PCa cells were determined by chromatin immunoprecipitation, reporter gene construct analysis, and MTS assay. Targeting of PCAF by miR-17-5p was evaluated using the luciferase reporter assay. PCAF was upregulated in several PCa cell lines. Upregulation of PCAF promoted AR transcriptional activation and cell growth in cultured PCa cells. Expression of PCAF in PCa cells was associated with the downregulation of miR-17-5p. Targeting of the 3’-untranslated region of PCAF mRNA by miR-17-5p caused translational suppression and RNA degradation, and, consequently, modulation of AR transcriptional activity in PCa cells. PCAF is upregulated in cultured PCa cells, and upregulation of PCAF is associated with the downregulation of miR-17-5p. Targeting of PCAF by miR-17-5p modulates AR transcriptional activity and cell growth in cultured PCa cells

  6. Evaluating the quality of outbreak reports on health care-associated infections in São Paulo, Brazil, during 2000-2010 using the ORION statement findings and recommendations.

    Science.gov (United States)

    Maciel, Amanda Luiz Pires; de Assis, Denise Brandão; Madalosso, Geraldine; Padoveze, Maria Clara

    2014-04-01

    The standard of outbreak reports must be improved to a level where they are robust enough to properly influence preventive strategies. We aimed to verify compliance with mandatory outbreak notification, describing epidemiologic characteristics and management, and evaluating the quality of outbreak reports on health care-associated infections in São Paulo State, Brazil. A systematic search was carried out on PubMed, the Latin American and Caribbean Health Sciences Literature database, Embase, Outbreak Database, the Annals of Brazilian Conferences on Healthcare-Associated Infection Prevention and Infectious Diseases, and reports from the São Paulo State Hospital Infection Division. The quality of reports was evaluated according to the Outbreak Reports and Intervention studies of Nosocomial Infection (ORION) statement guidelines. A total of 87 outbreak reports were identified; however, only 15 outbreaks (17.2%) were reported to the São Paulo State Hospital Infection Division. Bloodstream infection and neonatal intensive care units were mostly implicated (23% and 19.5%, respectively). Quality, evaluated according to ORION statement recommendations, was generally poor. The ORION categories of Background, Objectives, Participants, Setting, Infection-Related Outcomes, and Generality were properly described in 32.2%, 74.7%, 2.3%, 46%, 2.3%, and 12.6% of reports, respectively. Interventions and Culture-Typing were described with details in 51.9% and 55.2% of outbreak reports, respectively. Our findings pointed out the need for strategies to improve competence in outbreak reports, and the ORION statement guidelines may help in this matter. Efforts to promote confidence and consequent compliance with mandatory notification of outbreak reports are essential. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  7. Navy Advertising: Targeting Generation Z

    Science.gov (United States)

    2015-12-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA MBA PROFESSIONAL REPORT NAVY ADVERTISING : TARGETING GENERATION Z December......study recommends improvements for Navy advertising efficiency by examining characteristics of recruits defined as Generation Z. Data gathered from five

  8. Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau.

    Science.gov (United States)

    Starbuck, Kristen; Al-Alem, Linah; Eavarone, David A; Hernandez, Silvia Fatima; Bellio, Chiara; Prendergast, Jillian M; Stein, Jenna; Dransfield, Daniel T; Zarrella, Bianca; Growdon, Whitfield B; Behrens, Jeff; Foster, Rosemary; Rueda, Bo R

    2018-05-01

    Recurrent ovarian cancer (OvCa) is thought to result in part from the inability to eliminate rare quiescent cancer stem cells (CSCs) that survive cytotoxic chemotherapy and drive tumor resurgence. The Sialyl-Thomsen-nouveau antigen (STn) is a carbohydrate moiety present on protein markers of CSCs in pancreatic, colon, and gastric malignancies. We have demonstrated that human OvCa cell lines contain varying levels of cells that independently express either STn or the ovarian CSC marker CD133. Here we determine co-expression of STn and CD133 in a subset of human OvCa cell lines. Analyses of colony and sphere forming capacity and of response to standard-of-care cytotoxic therapy suggest a subset of OvCa STn + cells display some CSC features. The effect of the anti-STn antibody-drug conjugates (ADCs) S3F-CL-MMAE and 2G12-2B2-CL-MMAE on OvCa cell viability in vitro and in vivo was also assessed. Treatment with S3F-CL-MMAE reduced the viability of two of three OvCa cell lines in vitro and exposure to either S3F-CL-MMAE or 2G12-2B2-CL-MMAE reduced OVCAR3-derived xenograft volume in vivo , depleting STn + tumor cells. In summary, STn + cells demonstrate some stem-like properties and specific therapeutic targeting of STn in ovarian tumors may be an effective clinical strategy to eliminate both STn + CSC and STn + non-CSC populations.

  9. Monocarboxylate transporter 4, associated with the acidification of synovial fluid, is a novel therapeutic target for inflammatory arthritis.

    Science.gov (United States)

    Fujii, Wataru; Kawahito, Yutaka; Nagahara, Hidetake; Kukida, Yuji; Seno, Takahiro; Yamamoto, Aihiro; Kohno, Masataka; Oda, Ryo; Taniguchi, Daigo; Fujiwara, Hiroyoshi; Ejima, Akika; Kishida, Tsunao; Mazda, Osam; Ashihara, Eishi

    2015-11-01

    Synovial fluid pH is decreased in patients with rheumatoid arthritis (RA); however, the underlying mechanisms are unclear. We undertook this study to examine the mechanism by which synovial fluid pH is regulated and to explore the possibility of a therapeutic strategy by manipulating this mechanism. We determined the pH and lactate concentration in synovial fluid from 16 RA patients. Cultured synovial fibroblasts (SFs) from the inflamed joints of 9 RA patients (RASFs) were examined for the expression of ion transporters that regulate intracellular and extracellular pH. The ion transporter up-regulated in RASF lines was then suppressed in RASFs by small interfering RNA (siRNA), and the effect of transfection on viability and proliferation was investigated. Finally, we examined the therapeutic effect of electrotransfer of monocarboxylate transporter 4 (MCT4)-specific siRNA into the articular synovium of mice with collagen-induced arthritis (CIA). Synovial fluid pH correlated inversely with both the Disease Activity Score in 28 joints using the C-reactive protein level and the synovial fluid lactate levels. RASFs exhibited up-regulated transcription of MCT4 messenger RNA. MCT4 exported intracellular lactate into the extracellular space. RASFs had significantly higher MCT4 protein levels than did SFs from patients with osteoarthritis. Knockdown of MCT4 induced intrinsic apoptosis of RASFs, thereby inhibiting their proliferation. Moreover, electrotransfer of MCT4-specific siRNA into the articular synovium of mice with CIA significantly reduced the severity of arthritis. RA activity correlated with decreased synovial fluid pH. This may be due to increased MCT4 expression in RASFs. Silencing MCT4 induced apoptosis in RASFs and reduced the severity of CIA, suggesting that MCT4 is a potential therapeutic target for inflammatory arthritis. © 2015, American College of Rheumatology.

  10. Close to recommended caloric and protein intake by enteral nutrition is associated with better clinical outcome of critically ill septic patients: secondary analysis of a large international nutrition database.

    Science.gov (United States)

    Elke, Gunnar; Wang, Miao; Weiler, Norbert; Day, Andrew G; Heyland, Daren K

    2014-02-10

    Current international sepsis guidelines recommend low-dose enteral nutrition (EN) for the first week. This contradicts other nutrition guidelines for heterogenous groups of ICU patients. Data on the optimal dose of EN in septic patients are lacking. Our aim was to evaluate the effect of energy and protein amount given by EN on clinical outcomes in a large cohort of critically ill septic patients. We conducted a secondary analysis of pooled data collected prospectively from international nutrition studies. Eligible patients had a diagnosis of sepsis and/or pneumonia and were admitted to the ICU for ≥3 days, mechanically ventilated within 48 hours of ICU admission and only receiving EN. Patients receiving parenteral nutrition were excluded. Data were collected from ICU admission up to a maximum of 12 days. Regression models were used to examine the impact of calorie and protein intake on 60-day mortality and ventilator-free days. Of the 13,630 patients included in the dataset, 2,270 met the study inclusion criteria. Patients received a mean amount of 1,057 kcal/d (14.5 kcal/kg/day) and 49 g protein/day (0.7 g/kg/d) by EN alone. Patients were mechanically ventilated for a median of 8.4 days and 60-day mortality was 30.5%. An increase of 1,000 kcal was associated with reduced 60-day mortality (odds ratio (OR) 0.61; 95% confidence interval (CI) 0.48 to 0.77, P <0.001) and more ventilator-free days (2.81 days, 95% CI 0.53 to 5.08, P = 0.02) as was an increase of 30 g protein per day (OR 0.76; 95% CI 0.65 to 0.87, P <0.001 and 1.92 days, 95% CI 0.58 to 3.27, P = 0.005, respectively). In critically ill septic patients, a calorie and protein delivery closer to recommended amounts by EN in the early phase of ICU stay was associated with a more favorable outcome.

  11. Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection.

    Science.gov (United States)

    Byrareddy, Siddappa N; Kallam, Brianne; Arthos, James; Cicala, Claudia; Nawaz, Fatima; Hiatt, Joseph; Kersh, Ellen N; McNicholl, Janet M; Hanson, Debra; Reimann, Keith A; Brameier, Markus; Walter, Lutz; Rogers, Kenneth; Mayne, Ann E; Dunbar, Paul; Villinger, Tara; Little, Dawn; Parslow, Tristram G; Santangelo, Philip J; Villinger, Francois; Fauci, Anthony S; Ansari, Aftab A

    2014-12-01

    α4β7 integrin-expressing CD4(+) T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-α4β7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIVmac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4(+) T cell numbers were maintained in both the blood and the GALT. Thus, targeting α4β7 reduces mucosal transmission of SIV in macaques.

  12. Tay-Sachs disease mutations in HEXA target the α chain of hexosaminidase A to endoplasmic reticulum-associated degradation.

    Science.gov (United States)

    Dersh, Devin; Iwamoto, Yuichiro; Argon, Yair

    2016-12-01

    Loss of function of the enzyme β-hexosaminidase A (HexA) causes the lysosomal storage disorder Tay-Sachs disease (TSD). It has been proposed that mutations in the α chain of HexA can impair folding, enzyme assembly, and/or trafficking, yet there is surprisingly little known about the mechanisms of these potential routes of pathogenesis. We therefore investigated the biosynthesis and trafficking of TSD-associated HexA α mutants, seeking to identify relevant cellular quality control mechanisms. The α mutants E482K and G269S are defective in enzymatic activity, unprocessed by lysosomal proteases, and exhibit altered folding pathways compared with wild-type α. E482K is more severely misfolded than G269S, as observed by its aggregation and inability to associate with the HexA β chain. Importantly, both mutants are retrotranslocated from the endoplasmic reticulum (ER) to the cytosol and are degraded by the proteasome, indicating that they are cleared via ER-associated degradation (ERAD). Leveraging these discoveries, we observed that manipulating the cellular folding environment or ERAD pathways can alter the kinetics of mutant α degradation. Additionally, growth of patient fibroblasts at a permissive temperature or with chemical chaperones increases cellular Hex activity by improving mutant α folding. Therefore modulation of the ER quality control systems may be a potential therapeutic route for improving some forms of TSD. © 2016 Dersh et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  13. Recommender Systems in Commercial Use

    OpenAIRE

    Aldrich, Susan E.

    2011-01-01

    Commercial recommender systems are deployed by marketing teams to increase revenue and/or personalize user experience. Marketers evaluate recommender systems not on its algorithms but on how well the vendor‘s expertise and interfaces will support achieving business goals. Driven by a business model that pays based on recommendation success, vendors guide clients through continuous optimization of recommendations. While recommender technology is mature, the solutions and market are still young...

  14. Conclusions and recommendations

    International Nuclear Information System (INIS)

    Carrette, M.

    1997-01-01

    The paper presents conclusions and recommendations at the closing session of the NEA/OECD Workshop held at Fontenay-aux-Roses on 12-14 June 1995. The conclusions refer to issues like: public reaction to foodstuffs containing radioisotope concentrations under the danger standards, possible non-adherence of manufacturers, processors, distributors, et al, to the instructions and guidance from radiation protection specialists, integration of all the food chain factors in the elaboration of the emergency intervention programs, etc. Among the most significant recommendations the following may be mentioned: 1. Differences between different intervention levels and the maximum admissible levels agreed upon by national, regional or international nutrition authorities should be further studied; 2. Problems created by the Chernobyl accident (as for instance, the methods of treatment of food chain products containing unacceptable radioactivity concentrations) are still present and must be solved; 3. Further studies should be done on the socio-cultural aspects of the communication, particularly on the information in rural environment; 4. The preventive measures in agriculture should be implemented as rapidly as possible; 5. In elaborating programmes of agriculture countermeasures, the management of contaminated media, particularly, of forests and their effect on agriculture

  15. Ebola virus: recommendations

    CERN Multimedia

    CERN Medical Service

    2014-01-01

    The CERN Medical Service has been closely following, in particular via the WHO, the development of the Ebola virus outbreak currently affecting some African countries. This infectious disease may be passed on through direct contact with the bodily fluids of a sick person.   Based on the recommendations of the WHO and the two Host States, Switzerland and France, as updated on their respective websites, so far there has been no ban on travel to the countries concerned. However, unless it is absolutely essential, you are advised not to visit any of the countries affected by Ebola (Guinea, Republic of Sierra Leone, Liberia, Nigeria). The two Host States have established an alert system, and a check is carried out on departure from the airports of those countries. It is strongly recommended that you contact the Medical Service if you are travelling to those countries. We remind you to observe the basic rules of hygiene such as frequent hand washing, whatever your destination. The Medical Service is...

  16. The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets.

    Science.gov (United States)

    Mizejewski, G J

    2015-01-01

    Recent studies have demonstrated that the carboxyterminal third domain of alpha-fetoprotein (AFP-CD) binds with various ligands and receptors. Reports within the last decade have established that AFP-CD contains a large fragment of amino acids that interact with several different receptor types. Using computer software specifically designed to identify protein-to-protein interaction at amino acid sequence docking sites, the computer searches identified several types of scavenger-associated receptors and their amino acid sequence locations on the AFP-CD polypeptide chain. The scavenger receptors (SRs) identified were CD36, CD163, Stabilin, SSC5D, SRB1 and SREC; the SR-associated receptors included the mannose, low-density lipoprotein receptors, the asialoglycoprotein receptor, and the receptor for advanced glycation endproducts (RAGE). Interestingly, some SR interaction sites were localized on the AFP-derived Growth Inhibitory Peptide (GIP) segment at amino acids #480-500. Following the detection studies, a structural subdomain analysis of both the receptor and the AFP-CD revealed the presence of epidermal growth factor (EGF) repeats, extracellular matrix-like protein regions, amino acid-rich motifs and dimerization subdomains. For the first time, it was reported that EGF-like sequence repeats were identified on each of the three domains of AFP. Thereafter, the localization of receptors on specific cell types were reviewed and their functions were discussed.

  17. Oleosome-Associated Protein of the Oleaginous Diatom Fistulifera solaris Contains an Endoplasmic Reticulum-Targeting Signal Sequence

    Directory of Open Access Journals (Sweden)

    Yoshiaki Maeda

    2014-06-01

    Full Text Available Microalgae tend to accumulate lipids as an energy storage material in the specific organelle, oleosomes. Current studies have demonstrated that lipids derived from microalgal oleosomes are a promising source of biofuels, while the oleosome formation mechanism has not been fully elucidated. Oleosome-associated proteins have been identified from several microalgae to elucidate the fundamental mechanisms of oleosome formation, although understanding their functions is still in infancy. Recently, we discovered a diatom-oleosome-associated-protein 1 (DOAP1 from the oleaginous diatom, Fistulifera solaris JPCC DA0580. The DOAP1 sequence implied that this protein might be transported into the endoplasmic reticulum (ER due to the signal sequence. To ensure this, we fused the signal sequence to green fluorescence protein. The fusion protein distributed around the chloroplast as like a meshwork membrane structure, indicating the ER localization. This result suggests that DOAP1 could firstly localize at the ER, then move to the oleosomes. This study also demonstrated that the DOAP1 signal sequence allowed recombinant proteins to be specifically expressed in the ER of the oleaginous diatom. It would be a useful technique for engineering the lipid synthesis pathways existing in the ER, and finally controlling the biofuel quality.

  18. Targeted CNS delivery using human MiniPromoters and demonstrated compatibility with adeno-associated viral vectors

    Directory of Open Access Journals (Sweden)

    Charles N de Leeuw

    2014-01-01

    Full Text Available Critical for human gene therapy is the availability of small promoters tools to drive gene expression in a highly specific and reproducible manner. We tackled this challenge by developing human DNA MiniPromoters (MiniPs using computational biology and phylogenetic conservation. MiniPs were tested in mouse as single-copy knock-ins at the Hprt locus on the X chromosome and evaluated for lacZ reporter expression in central nervous system (CNS and non–CNS tissue. Eighteen novel MiniPs driving expression in mouse brain were identified, 2 MiniPs for driving pan-neuronal expression and 17 MiniPs for the mouse eye. Key areas of therapeutic interest were represented in this set: the cerebral cortex, embryonic hypothalamus, spinal cord, bipolar and ganglion cells of the retina, and skeletal muscle. We also demonstrated that three retinal ganglion cell MiniPs exhibit similar cell type specificity when delivered via adeno-associated virus vectors intravitreally. We conclude that our methodology and characterization has resulted in desirable expression characteristics that are intrinsic to the MiniPromoter, not dictated by copy-number effects or genomic location, and results in constructs predisposed to success in adeno-associated virus. These MiniPs are immediately applicable for preclinical studies toward gene therapy in humans and are publicly available to facilitate basic and clinical research, and human gene therapy.

  19. Critical evaluation of lowering the recommended dietary intake of folate.

    Science.gov (United States)

    Obeid, Rima; Koletzko, Berthold; Pietrzik, Klaus

    2014-04-01

    We evaluated the recommendation of the Austrian, German, and Swiss Societies for Nutrition of lowering dietary folate intake from 400 to 300 μg dietary folate equivalents/d. A dose-response relation exists between folate intake or plasma level and disease risk within the normal range. Improving folate status can prevent between 30% and 75% of neural tube defects. A prepregnancy plasma folate of >18.0 nmol/L (mean 26.1 nmol/L) is associated with low total homocysteine (tHcy) (folate intake cannot achieve maximal risk reduction. The Austrian, German, and Swiss Societies for Nutrition recommend that young women should additionally supplement with 400 μg folic acid at least 4 weeks before conception. This short time window is not sufficient to achieve optimal plasma folate and tHcy levels in the majority of women. Factors affecting the relation between folate intake and blood biomarkers are total folate intake, baseline plasma folate, time available for supplement use, dose and form (folic acid or methyl folate), genetic polymorphisms, physiological and lifestyle factors. Lowering the recommended dietary folate intake may have important public health consequences. Elderly people and young women are at risk for diseases related to folate shortage. Reducing birth defects through supplementation of folic acid remains a poor option, as folate intake is crucial for reaching the target protective plasma folate levels in the population. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  20. Mining and representing recommendations in actively evolving recommender systems

    DEFF Research Database (Denmark)

    Assent, Ira

    2010-01-01

    Recommender systems provide an automatic means of filtering out interesting items, usually based on past similarity of user ratings. In previous work, we have suggested a model that allows users to actively build a recommender network. Users express trust, obtain transparency, and grow (anonymous......) recommender connections. In this work, we propose mining such active systems to generate easily understandable representations of the recommender network. Users may review these representations to provide active feedback. This approach further enhances the quality of recommendations, especially as topics...... of interest change over time. Most notably, it extends the amount of control users have over the model that the recommender network builds of their interests....

  1. Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss

    Directory of Open Access Journals (Sweden)

    Selma Olsson Åkefeldt

    2013-01-01

    Full Text Available Rheumatoid arthritis (RA and Langerhans cell histiocytosis (LCH are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC, and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.

  2. Lipofection of purified adeno-associated virus Rep68 protein: toward a chromosome-targeting nonviral particle.

    Science.gov (United States)

    Lamartina, S; Roscilli, G; Rinaudo, D; Delmastro, P; Toniatti, C

    1998-09-01

    Adeno-associated virus (AAV) integrates very efficiently into a specific site (AAVS1) of human chromosome 19. Two elements of the AAV genome are sufficient: the inverted terminal repeats (ITRs) and the Rep78 or Rep68 protein. The incorporation of the AAV integration machinery in nonviral delivery systems is of great interest for gene therapy. We demonstrate that purified recombinant Rep68 protein is functionally active when directly delivered into human cells by using the polycationic liposome Lipofectamine, promoting the rescue-replication of a codelivered ITR-flanked cassette in adenovirus-infected cells and its site-specific integration in noninfected cells. The sequencing of cloned virus-host DNA junctions confirmed that lipofected Rep68 protein triggers site-specific integration at the same sites in chromosome 19 already characterized in cells latently infected with AAV.

  3. Identification of Novel Gene Targets and Putative Regulators of Arsenic-Associated DNA Methylation in Human Urothelial Cells and Bladder Cancer

    Science.gov (United States)

    Rager, Julia E.; Miller, Sloane; Tulenko, Samantha E.; Smeester, Lisa; Ray, Paul D.; Yosim, Andrew; Currier, Jenna M.; Ishida, María C.; González-Horta, Maria del Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Gutiérrez-Torres, Daniela S.; Drobná, Zuzana; Del Razo, Luz M.; García-Vargas, Gonzalo G.; Kim, William Y.; Zhou, Yi-Hui; Wright, Fred A.; Stýblo, Miroslav; Fry, Rebecca C.

    2016-01-01

    There is strong epidemiologic evidence linking chronic exposure to inorganic arsenic (iAs) to a myriad of adverse health effects, including cancer of the bladder. The present study set out to identify DNA methylation patterns associated with iAs and its metabolites in exfoliated urothelial cells (EUCs) that originate primarily from the urinary bladder, one of the targets of arsenic (As)-induced carcinogenesis. Genome-wide, gene-specific promoter DNA methylation levels were assessed in EUCs from 46 residents of Chihuahua, Mexico, and the relationship was examined between promoter methylation profiles and the intracellular concentrations of total As (tAs) and As species. A set of 49 differentially methylated genes was identified with increased promoter methylation associated with EUC tAs, iAs, and/or monomethylated As (MMAs) enriched for their roles in metabolic disease and cancer. Notably, no genes had differential methylation associated with EUC dimethylated As (DMAs), suggesting that DMAs may influence DNA methylation-mediated urothelial cell responses to a lesser extent than iAs or MMAs. Further analysis showed that 22 of the 49 As-associated genes (45%) are also differentially methylated in bladder cancer tissue identified using The Cancer Genome Atlas repository. Both the As- and cancer-associated genes are enriched for the binding sites of common transcription factors known to play roles in carcinogenesis, demonstrating a novel potential mechanistic link between iAs exposure and bladder cancer. PMID:26039340

  4. Target of rapamycin complex 1 and Tap42-associated phosphatases are required for sensing changes in nitrogen conditions in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Li, Jinmei; Yan, Gonghong; Liu, Sichi; Jiang, Tong; Zhong, Mingming; Yuan, Wenjie; Chen, Shaoxian; Zheng, Yin; Jiang, Yong; Jiang, Yu

    2017-12-01

    In yeast target of rapamycin complex 1 (TORC1) and Tap42-associated phosphatases regulate expression of genes involved in nitrogen limitation response and the nitrogen discrimination pathway. However, it remains unclear whether TORC1 and the phosphatases are required for sensing nitrogen conditions. Utilizing temperature sensitive mutants of tor2 and tap42, we examined the role of TORC1 and Tap42 in nuclear entry of Gln3, a key transcription factor in yeast nitrogen metabolism, in response to changes in nitrogen conditions. Our data show that TORC1 is essential for Gln3 nuclear entry upon nitrogen limitation and downshift in nitrogen quality. However, Tap42-associated phosphatases are required only under nitrogen limitation condition. In cells grown in poor nitrogen medium, the nitrogen permease reactivator kinase (Npr1) inhibits TORC1 activity and alters its association with Tap42, rendering Tap42-associated phosphatases unresponsive to nitrogen limitation. These findings demonstrate a direct role for TORC1 and Tap42-associated phosphatases in sensing nitrogen conditions and unveil an Npr1-dependent mechanism that controls TORC1 and the phosphatases in response to changes in nitrogen quality. © 2017 John Wiley & Sons Ltd.

  5. Minimum target prices for production of direct-acting antivirals and associated diagnostics to combat hepatitis C virus.

    Science.gov (United States)

    van de Ven, Nikolien; Fortunak, Joe; Simmons, Bryony; Ford, Nathan; Cooke, Graham S; Khoo, Saye; Hill, Andrew

    2015-04-01

    Combinations of direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-naïve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large-scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12-week courses of combination DAAs with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir; US$152 for sofosbuvir+ribavirin; US$192 for sofosbuvir+ledipasvir; and US$115 for MK-8742+MK-5172. Diagnostic testing costs were estimated at US$90 for genotyping US$34 for two HCV antigen tests and US$22 for two full blood count/clinical chemistry tests. Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US$171-360 per person without genotyping or US$261-450 per person with genotyping. These cost estimates assume that existing large-scale treatment programs can be established. © 2014 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

  6. Child-targeted on-pack communications in Belgian supermarkets: associations with nutritional value and type of brand.

    Science.gov (United States)

    Aerts, Goele; Smits, Tim

    2017-09-14

    Persuasive on-pack marketing strategies, such as colourful images and games, affect children's preferences and requests. The purpose of this study was to describe the prevalence of these child-directed (i.e. aimed at children) strategies on food packages at a Belgian retailer. Although previous research already demonstrated the frequency of most of these techniques directed at children, this paper extends to food pricing and facing strategies (i.e. the number of items from the same product aligned next to each other in the supermarket shelves) which were unstudied till now. Moreover, the association between the use of these strategies, the products' (un)healthiness and their type of brand (national vs. private) is investigated. The content analysis found that 372 food products contained one or more child-directed marketing strategies on-pack, all these communications were coded; the products could be classified in 15 food categories. On average, 3.9 (Min = 1; Max = 8) food promotion techniques were used per package. Unhealthiness of products was rated according to Food Standards Agency (FSA) Nutrient Profile UK. We found that 89.2% of all products with child-directed strategies were considered to be unhealthy. The presence of marketing strategies was associated with higher product unhealthiness, but did not differ much between types of brand. Overall, these findings suggest that (unhealthy) foods aimed at children typically feature many on-pack persuasive communications, which implies that policy makers should (continue to) monitor this. These findings highlight the need for further research to investigate the impact of on-pack communications on children's consumption. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Implementation of a secondary-ion tritium beam by means of the associated particle technique and its test on a gold target

    Energy Technology Data Exchange (ETDEWEB)

    Policroniades, R.; Fernández-Arnáiz, J.; Murillo, G.; Moreno, E.; Villaseñor, P.; Méndez, B. [Departamento de Aceleradores, Instituto Nacional de Investigaciones Nucleares, Carr. México-Toluca S/N, Ocoyoacac, Estado de México 52750 (Mexico); Chávez, E.; Ortíz-Salazar, M.E.; Huerta, A. [Instituto de Física, Universidad Nacional Autónoma de México, A.P. 20-364, México, D.F. 01000 (Mexico); Varela-González, A. [Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, A.P. 20-364, México, D.F. 01000 (Mexico)

    2014-05-21

    In this work we present the implementation and characterization of a (secondary ion) tritium beam generated through the D(d,t)p reaction, at deuteron energies of 2.0 and 1.88 MeV, tagging the tritium ions with the associated particle technique. In order to prove its utility as a projectile for scientific applications, this beam was made to impinge on a thin gold target to observe expected elastic scattering events. - Highlights: • A new secondary ion tritium beam obtained through the D(d,t)3He reaction. • Tritium beam tagging by the associated particle technique. • A low energy Tritium beam without radiation contamination of equipment. • Tritium elastic scattering on gold.

  8. Implementation of a secondary-ion tritium beam by means of the associated particle technique and its test on a gold target

    International Nuclear Information System (INIS)

    Policroniades, R.; Fernández-Arnáiz, J.; Murillo, G.; Moreno, E.; Villaseñor, P.; Méndez, B.; Chávez, E.; Ortíz-Salazar, M.E.; Huerta, A.; Varela-González, A.

    2014-01-01

    In this work we present the implementation and characterization of a (secondary ion) tritium beam generated through the D(d,t)p reaction, at deuteron energies of 2.0 and 1.88 MeV, tagging the tritium ions with the associated particle technique. In order to prove its utility as a projectile for scientific applications, this beam was made to impinge on a thin gold target to observe expected elastic scattering events. - Highlights: • A new secondary ion tritium beam obtained through the D(d,t)3He reaction. • Tritium beam tagging by the associated particle technique. • A low energy Tritium beam without radiation contamination of equipment. • Tritium elastic scattering on gold

  9. Deployment of Recommender Systems: Operational and Strategic Issues

    Science.gov (United States)

    Ghoshal, Abhijeet

    2011-01-01

    E-commerce firms are increasingly adopting recommendation systems to effectively target customers with products and services. The first essay examines the impact that improving a recommender system has on firms that deploy such systems. A market with customers heterogeneous in their search costs is considered. We find that in a monopoly, a firm…

  10. Odontogenic keratocysts in the Basal Cell Nevus (Gorlin-Goltz) Syndrome associated with paresthesia of the lower jaw: Case report, retrospective analysis of a representative Czech cohort and recommendations for the early diagnosis.

    Science.gov (United States)

    Hubacek, Milan; Kripnerova, Tereza; Nemcikova, Michaela; Krepelová, Anna; Puchmajerova, Alena; Malikova, Marcela; Havlovicová, Markéta; Cadova, Jana; Kodet, Roman; Macek, Milan; Dostalova, Tatjana

    2016-09-01

    Identification of early presenting signs of the Basal Cell Nevus (BCNS; synonyme Gorlin-Goltz) syndrome, which is associated with a principal triad of multiple basal cell nevi, jaw odontogenic keratocysts, and skeletal anomalies, in stomatological and neurological practices. Proposal of multidisciplinary diagnostic algorithm comprising other medical specialists, including pathology, imaging, laboratory and molecular analyses based on the study outcomes. Case report of a male patient reporting paresthesia of their lower jaw, with right facial asymmetry (maxilla and mandible) and radiological detection of large osteolytic lesions in both jaws, including a retrospective analysis of a representative Czech cohort with BCNS from within the last decade. Clinical, imaging and laboratory analyses were carried out at a national tertiary centre. A multidisciplinary clinical approach followed by surgical management lead to the identification of odontogenic cysts, which were substantiated by histological examination. DNA sequencing of the PTCH1 gene detected a c.2929dupT resulting in p. Tyr977Leufs*16 pathogenic variant. This finding confirmed the clinical and laboraoty diagnosis of BCNS. Parental DNA analysis showed that this causal genetic defect arose de novo. Surgical management and orthodontic therapy were successful. Analysis of the reported case and retrospective data analysis provided evidence that paresthesia of the lower jaw should be considered as one of the early presenting signs of this rare disorder in stomatological and neurological practice. Obtained results allowed us to formulate recommendations for diagnostic practice in stomatology and neurology.

  11. Combined genome-wide expression profiling and targeted RNA interference in primary mouse macrophages reveals perturbation of transcriptional networks associated with interferon signalling

    Directory of Open Access Journals (Sweden)

    Craigon Marie

    2009-08-01

    Full Text Available Abstract Background Interferons (IFNs are potent antiviral cytokines capable of reprogramming the macrophage phenotype through the induction of interferon-stimulated genes (ISGs. Here we have used targeted RNA interference to suppress the expression of a number of key genes associated with IFN signalling in murine macrophages prior to stimulation with interferon-gamma. Genome-wide changes in transcript abundance caused by siRNA activity were measured using exon-level microarrays in the presence or absence of IFNγ. Results Transfection of murine bone-marrow derived macrophages (BMDMs with a non-targeting (control siRNA and 11 sequence-specific siRNAs was performed using a cationic lipid transfection reagent (Lipofectamine2000 prior to stimulation with IFNγ. Total RNA was harvested from cells and gene expression measured on Affymetrix GeneChip Mouse Exon 1.0 ST Arrays. Network-based analysis of these data revealed six siRNAs to cause a marked shift in the macrophage transcriptome in the presence or absence IFNγ. These six siRNAs targeted the Ifnb1, Irf3, Irf5, Stat1, Stat2 and Nfkb2 transcripts. The perturbation of the transcriptome by the six siRNAs was highly similar in each case and affected the expression of over 600 downstream transcripts. Regulated transcripts were clustered based on co-expression into five major groups corresponding to transcriptional networks associated with the type I and II IFN response, cell cycle regulation, and NF-KB signalling. In addition we have observed a significant non-specific immune stimulation of cells transfected with siRNA using Lipofectamine2000, suggesting use of this reagent in BMDMs, even at low concentrations, is enough to induce a type I IFN response. Conclusion Our results provide evidence that the type I IFN response in murine BMDMs is dependent on Ifnb1, Irf3, Irf5, Stat1, Stat2 and Nfkb2, and that siRNAs targeted to these genes results in perturbation of key transcriptional networks associated

  12. Conclusions and recommendations

    International Nuclear Information System (INIS)

    1984-01-01

    The FAO/IAEA/GSF/SIDA Co-ordinated Research Programme on Cereal Grain Protein Improvement by Nuclear Techniques was a follow-up to the FAO/IAEA/GSF Co-ordinated Research Programme on the Use of Nuclear Techniques for Seed Protein Improvement. It was initiated in 1969 and ended in 1981. The objectives of the meeting were to review and evaluate the achievements of the current and previous programmes in order to draw conclusions on the possibility of genetic improvement of cereal grain protein using nuclear techniques, to identify unsolved problems and to discuss and propose possible approaches for their solution. Through reviews and discussions, conclusions and recommendations were made by the participants

  13. Recommendations for skin decontamination

    International Nuclear Information System (INIS)

    1989-01-01

    Further to the reecommendations for determining the surface contamination of the skin and estimating the radiation exposure of the skin after contamination (SAAS-Mitt--89-16), measures for skin decontamination are recommended. They are necessary if (1) after simple decontamination by means of water, soap and brush without damaging the skin the surface contamination limits are exceeded and the radiation exposure to be expected for the undamaged healthy skin is estimated as to high, and if (2) a wound is contaminated. To remove skin contaminations, in general universally applicable, non-aggressive decontamination means and methods are sufficient. In special cases, nuclide-specific decontamination is required taking into account the properties of the radioactive substance

  14. Impact of transgenic soybean expressing Cry1Ac and Cry1F proteins on the non-target arthropod community associated with soybean in Brazil.

    Science.gov (United States)

    Marques, Luiz H; Santos, Antonio C; Castro, Boris A; Storer, Nicholas P; Babcock, Jonathan M; Lepping, Miles D; Sa, Verissimo; Moscardini, Valéria F; Rule, Dwain M; Fernandes, Odair A

    2018-01-01

    Field-scale studies that examine the potential for adverse effects of Bt crop technology on non-target arthropods may supplement data from laboratory studies to support an environmental risk assessment. A three year field study was conducted in Brazil to evaluate potential for adverse effects of cultivating soybean event DAS-81419-2 that produces the Cry1Ac and Cry1F proteins. To do so, we examined the diversity and abundance of non-target arthropods (NTAs) in Bt soybean in comparison with its non-Bt near isoline, with and without conventional insecticide applications, in three Brazilian soybean producing regions. Non-target arthropod abundance was surveyed using Moericke traps (yellow pan) and pitfall trapping. Total abundance (N), richness (S), Shannon-Wiener (H'), Simpson's (D) and Pielou's evenness (J) values for arthropod samples were calculated for each treatment and sampling period (soybean growth stages). A faunistic analysis was used to select the most representative NTAs which were used to describe the NTA community structure associated with soybean, and to test for effects due to the treatments effects via application of the Principal Response Curve (PRC) method. Across all years and sites, a total of 254,054 individuals from 190 taxa were collected by Moericke traps, while 29,813 individuals from 100 taxa were collected using pitfall traps. Across sites and sampling dates, the abundance and diversity measurements of representative NTAs were not significantly affected by Bt soybean as compared with non-sprayed non-Bt soybean. Similarly, community analyses and repeated measures ANOVA, when applicable, indicated that neither Bt soybean nor insecticide sprays altered the structure of the NTA communities under study. These results support the conclusion that transgenic soybean event DAS-81419-2 producing Cry1Ac and Cry1F toxins does not adversely affect the NTA community associated with soybean.

  15. Determinants for membrane association and permeabilization of the coxsackievirus 2B protein and the identification of the Golgi complex as the target organelle.

    Science.gov (United States)

    de Jong, Arjan S; Wessels, Els; Dijkman, Henri B P M; Galama, Jochem M D; Melchers, Willem J G; Willems, Peter H G M; van Kuppeveld, Frank J M

    2003-01-10

    The 2B protein of enterovirus is responsible for the alterations in the permeability of secretory membranes and the plasma membrane in infected cells. The structural requirements for the membrane association and the subcellular localization of this essential virus protein, however, have not been defined. Here, we provide evidence that the 2B protein is an integral membrane protein in vivo that is predominantly localized at the Golgi complex upon individual expression. Addition of organelle-specific targeting signals to the 2B protein revealed that the Golgi localization is an absolute prerequisite for the ability of the protein to modify plasma membrane permeability. Expression of deletion mutants and heterologous proteins containing specific domains of the 2B protein demonstrated that each of the two hydrophobic regions could mediate membrane binding individually. However, the presence of both hydrophobic regions was required for the correct membrane association, efficient Golgi targeting, and the membrane-permeabilizing activity of the 2B protein, suggesting that the two hydrophobic regions are cooperatively involved in the formation of a membrane-integral complex. The formation of membrane-integral pores by the 2B protein in the Golgi complex and the possible mechanism by which a Golgi-localized virus protein modifies plasma membrane permeability are discussed.

  16. Urgent recommendation. Interim report

    International Nuclear Information System (INIS)

    Nakano, Masayuki

    2000-01-01

    The Investigation Committee for Critical Accident at Uranium Processing Plant was founded immediately after the accident to investigate the cause of the accident and to establish measures to prevent the similar accident. On September 30, 1999 around 10:35, the Japan's first criticality accident occurred at JCO Co. Ltd. Uranium processing plant (auxiliary conversion plant) located at Tokai-mura Ibaraki-ken. The criticality continued on and off for approximately 20 hours after the first instantaneous criticality. The accident led the recommendation of tentative evacuation and sheltering indoors for residents living in the neighborhood. The serious exposure to neutrons happened to three workers. The dominant effect is dose due to neutrons and gamma rays from the precipitation tank. When the accident took place, three workers dissolved sequentially about 2.4 kg uranium powder with 18.8 % enrichment in the 10-litter bucket with nitric acid. The procedure of homogenization of uranium nitrate was supposed to be controlled using the shape-limited narrow storage column. Actually, however, the thick and large precipitation tank was used. As a result, about 16.6 kg of uranium was fed into the tank, which presumably caused criticality. The first notification by JCO was delayed and the following communication was not smooth. This led to