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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Veda N. Giri; Karen E. Knudsen; William Kevin Kelly; Wassim Abida; +66 Authors

    Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA—a clinically heterogeneous disease.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ NARCIS; Journal of C...arrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Other literature type . 2017
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Journal of Clinical Oncology
    Article . 2018
    Data sources: NARCIS
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    European Urology
    Article . 2018
    License: Elsevier TDM
    Data sources: Crossref
    Journal of Clinical Oncology
    Article . 2018
    Data sources: Crossref
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ NARCIS; Journal of C...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Europe PubMed Central
      Other literature type . 2017
      Data sources: PubMed Central
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Journal of Clinical Oncology
      Article . 2018
      Data sources: NARCIS
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      European Urology
      Article . 2018
      License: Elsevier TDM
      Data sources: Crossref
      Journal of Clinical Oncology
      Article . 2018
      Data sources: Crossref
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Vijaya M, Musini; Kendra Ak, Lawrence; Patricia M, Fortin; Ken, Bassett; +1 Authors

    Background Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. Renin is the enzyme responsible for converting angiotensinogen to angiotensin I, which is then converted to angiotensin II. Renin inhibitors are a new class of drugs that decrease blood pressure (BP) by preventing the formation of both angiotensin I and angiotensin II. Objectives To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension. To determine the change in BP variability, pulse pressure, and heart rate and to evaluate adverse events (mortality, non-fatal serious adverse events, total adverse events, withdrawal due to adverse effects and specific adverse events such as dry cough, diarrhoea and angioedema). Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to February 2017: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. There was no restriction by language or publication status. We also searched the European Medicines Agency (EMA) for clinical study reports, the Novartis Clinical Study Results Database, bibliographic citations from retrieved references, and contacted authors of relevant papers regarding further published and unpublished work. Selection criteria We included randomized, double-blinded, placebo-controlled studies evaluating BP lowering efficacy of fixed-dose monotherapy with renin inhibitor compared with placebo for a minimum duration of three to 12 weeks in adult patients with primary hypertension. Data collection and analysis This systematic review is a comprehensive update which includes four additional studies and extensive detail from nine clinical study reports (CSRs) of previously included studies obtained from EMA. The remaining three CSRs are not available. Two review authors independently assessed study eligibility and extracted data. In all cases where there was a difference between the CSR and the published report, data from the CSR was used. Dichotomous outcomes were reported as risk ratio (RR) with 95% confidence intervals (CIs) and continuous outcomes as mean difference (MD) with 95% CIs. Main results 12 studies (mean duration of eight weeks) in 7439 mostly Caucasian patients (mean age 54 years) with mild-to-moderate uncomplicated hypertension were eligible for inclusion in the review. Aliskiren was the only renin inhibitor evaluated. All included studies were assessed to have high likelihood of attrition, reporting and funding bias. Aliskiren has a dose-related systolic/diastolic blood pressure (SBP/DBP) lowering effect as compared with placebo MD with 95% CI: aliskiren 75 mg (MD -2.97, 95% CI -4.76 to -1.18)/(MD -2.05, 95% CI -3.13 to -0.96) mm Hg (moderate-quality evidence), aliskiren 150 mg (MD -5.95, 95% CI -6.85 to -5.06)/ (MD -3.16, 95% CI -3.74 to -2.58) mm Hg (moderate-quality evidence), aliskiren 300 mg (MD -7.88, 95% CI -8.94 to -6.82)/ (MD -4.49, 95% CI -5.17 to -3.82) mm Hg (moderate-quality evidence), aliskiren 600 mg (MD -11.35, 95% CI -14.43 to -8.27)/ (MD -5.86, 95% CI -7.73 to -3.99) mm Hg (low-quality evidence). There was a dose-dependent decrease in blood pressure for aliskiren 75 mg, 150 mg and 300 mg. The blood pressure lowering effect of aliskiren 600 mg was not different from 300 mg (MD -0.61, 95% CI -2.78 to 1.56)/(MD -0.68, 95% CI -2.03 to 0.67). Aliskiren had no effect on blood pressure variability. Due to very limited information available regarding change in heart rate and pulse pressure, it was not possible to meta-analyze these outcomes. Mortality and non-fatal serious adverse events were not increased. This review found that in studies of eight week duration aliskiren may not increase withdrawal due to adverse events (low-quality evidence). Diarrhoea was increased in a dose-dependent manner (RR 7.00, 95% CI 2.48 to 19.72) with aliskiren 600 mg (low-quality evidence). The most frequent adverse events reported were headache, nasopharyngitis, diarrhoea, dizziness and fatigue. Authors' conclusions Compared to placebo, aliskiren lowered BP and this effect is dose-dependent. This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). There is no difference in mortality, nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy. Diarrhoea was considerably increased with aliskiren 600 mg.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Cochrane Database of...arrow_drop_down
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Other literature type . 2017
    Data sources: PubMed Central
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Cochrane Database of...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Europe PubMed Central
      Other literature type . 2017
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    Authors: Eric B. Laber; Fan Wu; Catherine Munera; Ilya Lipkovich; +2 Authors

    There is growing interest and investment in precision medicine as a means to provide the best possible health care. A treatment regime formalizes precision medicine as a sequence of decision rules, one per clinical intervention period, that specify if, when and how current treatment should be adjusted in response to a patient's evolving health status. It is standard to define a regime as optimal if, when applied to a population of interest, it maximizes the mean of some desirable clinical outcome, such as efficacy. However, in many clinical settings, a high‐quality treatment regime must balance multiple competing outcomes; eg, when a high dose is associated with substantial symptom reduction but a greater risk of an adverse event. We consider the problem of estimating the most efficacious treatment regime subject to constraints on the risk of adverse events. We combine nonparametric Q‐learning with policy‐search to estimate a high‐quality yet parsimonious treatment regime. This estimator applies to both observational and randomized data, as well as settings with variable, outcome‐dependent follow‐up, mixed treatment types, and multiple time points. This work is motivated by and framed in the context of dosing for chronic pain; however, the proposed framework can be applied generally to estimate a treatment regime which maximizes the mean of one primary outcome subject to constraints on one or more secondary outcomes. We illustrate the proposed method using data pooled from 5 open‐label flexible dosing clinical trials for chronic pain.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Statistics in Medici...arrow_drop_down
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    Statistics in Medicine
    Article . 2018
    License: CC BY NC ND
    Data sources: Crossref
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Other literature type . 2018
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Statistics in Medicine
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Statistics in Medici...arrow_drop_down
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      Statistics in Medicine
      Article . 2018
      License: CC BY NC ND
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      Europe PubMed Central
      Other literature type . 2018
      Data sources: PubMed Central
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      Statistics in Medicine
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    Authors: Anna-Maria, Carvalho; Vincent, Poirier;

    As emergency physicians with a subspecialty in aviation medicine, we agree with Dr. Rieb’s response[1][1] to an analysis article by Kodama and colleagues[2][2] that having naloxone on board is a necessary tool to treat the increasingly common medical emergency of opioid intoxication. Some airlines

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Other literature type . 2018
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    Article . 2018
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Europe PubMed Central
      Other literature type . 2018
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      Article . 2018
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    Authors: Yoshida, Sachiyo; Wazny, Kerri; Cousens, Simon; Chan, Kit Yee;

    Setting health research priorities is a complex and value–driven process. The introduction of the Child Health and Nutrition Research Initiative (CHNRI) method has made the process of setting research priorities more transparent and inclusive, but much of the process remains in the hands of funders and researchers, as described in the previous two papers in this series [1,2]. However, the value systems of numerous other important stakeholders, particularly those on the receiving end of health research products, are very rarely addressed in any process of priority setting. Inclusion of a larger and more diverse group of stakeholders in the process would result in a better reflection of the system of values of the broader community, resulting in recommendations that are more legitimate and acceptable. The CHNRI method, as originally proposed, took into account the importance of stakeholders and made provisions for their participation in the process. Although the involvement of a large and diverse group of stakeholders is desirable, they were not expected to propose research ideas, or score them against the set of pre–defined criteria. Because of this, the original CHNRI method proposed that stakeholders should be allowed to “weigh” pre–defined criteria and set “thresholds” for a minimum acceptable score against each criterion that would be required for a research idea to be considered a “research priority”. In choosing the stakeholders, the context of each exercise will be very important and the goals of the specific exercise should be defined before choosing an appropriate “stakeholder group”. Among stakeholders, we would expect to see those affected by the disease of interest and their family members, their carers and health workers, members of general public, media representatives interested in the topic, community leaders, representatives of the consumer groups and industry, but also potentially researchers and funders themselves. Although the latter two groups – researchers and funders – already have a different role assigned in the CHNRI process, this does not exclude them from also being stakeholders in the process [1,2]. In this paper, we aim to review and analyse the experiences in stakeholder involvement across the 50 CHNRI exercises published in the 10–year period between 2007 and 2016, the proposed approaches to involving stakeholders and their effects on the outcome of the prioritization process. One paper in the original CHNRI method series focused on involving stakeholders [3]. That paper presented practical experiences from three separate attempts to involve stakeholders that took place in 2006. The three groups approached were: (i) members of the global research priority setting network; (ii) a diverse group of national–level stakeholders from South Africa; and (iii) participants at a conference related to international child health held in Washington, DC, USA. Each group was asked to complete a short questionnaire to assess the relative importance of the five original CHNRI criteria. Different versions of the questionnaire were used with each group [3]. The results of this exercise indicated that groups of stakeholders vary in the weights they assigned to the 5 criteria, reflecting divergence in the “value” placed on each criterion by each stakeholder group. The diverse group of respondents within the priority–setting network placed the greatest weight on the criterion of “maximum potential for disease burden reduction” and the most stringent threshold on “answerability in an ethical way”. Among the attendees at the international conference on child health, the criterion of “deliverability, answerability and sustainability” was identified as the most important. Finally, in South Africa, where inequity has been a national problem historically, the greatest weight was placed on the “predicted impact on equity” criterion. This comparative analysis by Kapiriri et al. [3] effectively demonstrated that involving a wide range of stakeholders is an important goal for any research priority setting exercise. The criteria that may be of importance to funders, scientists and other technical experts involved in the process of planning and conducting the exercise may not be well aligned with the values of those who should eventually benefit from health research, or with the sentiments of wider society as a whole [3]. This is an important observation, because if the CHNRI process is conducted without regard for the broader social value or research, then it is unrealistic to expect it to fulfil its purpose of being accepted as a fair, transparent and legitimate process for setting investment priorities for health research.

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    Europe PubMed Central
    Article . 2016
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    Authors: R. Thomas Lumbers; Sonia Shah; Honghuang Lin; Tomasz Czuba; +164 Authors

    Abstract: Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome‐wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow‐up following heart failure diagnosis ranged from 2 to 116 months. Forty‐nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low‐frequency variants (allele frequency 0.01–0.05) at P < 5 × 10−8 under an additive genetic model. Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction. Funder: Department of Medicine, Boston University School of Medicine; Id: http://dx.doi.org/10.13039/100008748 Funder: National Heart, Lung, and Blood Institute; Id: http://dx.doi.org/10.13039/100000050 Funder: Knut and Alice Wallenberg Foundation; Id: http://dx.doi.org/10.13039/501100004063 Funder: NIHR UCLH Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100012317 Funder: Skåne University Hospital; Id: http://dx.doi.org/10.13039/501100011077 Funder: Evans Medical Foundation; Id: http://dx.doi.org/10.13039/100015927 Funder: Crafoord Foundation; Id: http://dx.doi.org/10.13039/501100003173 Funder: British Heart Foundation Cardiovascular Biomedicine Funder: Swedish National Health Service

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    ESC Heart Failure
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      Europe PubMed Central
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      ESC Heart Failure
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      ESC Heart Failure
      Article . 2021
      Data sources: NARCIS
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      ESC Heart Failure
      Article . 2022
      Data sources: VIRTA
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      Apollo
      Other literature type . 2021
      Data sources: Apollo
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      NARCIS
      Article . 2021
      Data sources: NARCIS
      Apollo
      Article . 2021
      Data sources: Datacite
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    Authors: Magdalena Rychlowska; Yuri Miyamoto; David Matsumoto; Ursula Hess; +5 Authors

    A small number of facial expressions may be universal in that they are produced by the same basic affective states and recognized as such throughout the world. However, other aspects of emotionally expressive behavior vary widely across culture. Just why do they vary? We propose that some cultural differences in expressive behavior are determined by historical heterogeneity, or the extent to which a country’s present-day population descended from migration from numerous vs. few source countries over a period of 500 y. Our reanalysis of data on cultural rules for displaying emotion from 32 countries [n = 5,340; Matsumoto D, Yoo S, Fontaine J (2008) J Cross Cult Psychol 39(1):55–74] reveals that historical heterogeneity explains substantial, unique variance in the degree to which individuals believe that emotions should be openly expressed. We also report an original study of the underlying states that people believe are signified by a smile. Cluster analysis applied to data from nine countries (n = 726), including Canada, France, Germany, India, Indonesia, Israel, Japan, New Zealand, and the United States, reveals that countries group into “cultures of smiling” determined by historical heterogeneity. Factor analysis shows that smiles sort into three social-functional subtypes: pleasure, affiliative, and dominance. The relative importance of these smile subtypes varies as a function of historical heterogeneity. These findings thus highlight the power of social-historical factors to explain cross-cultural variation in emotional expression and smile behavior.

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    Europe PubMed Central
    Other literature type . 2015
    Data sources: PubMed Central
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Europe PubMed Central
      Other literature type . 2015
      Data sources: PubMed Central
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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    Authors: Nagel, Rebecca; Kirschbaum, Frank; Engelmann, Jacob; Hofmann, Volker; +2 Authors

    Effective communication among sympatric species is often instrumental for behavioural isolation, where the failure to successfully discriminate between potential mates could lead to less fit hybrid offspring. Discrimination between con- and heterospecifics tends to occur more often in the sex that invests more in offspring production, i.e. females, but males may also mediate reproductive isolation. In this study, we show that among two Campylomormyrus Africanweakly electric fish species, males preferentially associate with conspecific females during choice tests using live fish as stimuli, i.e. when all sensory modalities potentially used for communication were present. We then conducted playback experiments to determine whether the species-specific electric organ discharge (EOD) used for electrocommunication serves as the cue for this conspecific association preference. Interestingly, only C. compressirostris males associated significantly more with the conspecific EOD waveform when playback stimuli were provided, while no such association preference was observed in C. tamandua males. Given our results, the EOD appears to serve, in part, as a male-mediated pre-zygotic isolation mechanism among sympatric species. However, the failure of C. tamandua males to discriminate between con- and heterospecific playback discharges suggests that multiple modalities may be necessary for species recognition in some African weakly electric fish species. Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe, 645

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    Europe PubMed Central
    Article . 2018
    Data sources: PubMed Central
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    Royal Society Open Science
    Article
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    Royal Society Open Science
    Article . 2018
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    DOAJ
    Article . 2018
    Data sources: DOAJ
    https://doi.org/10.25932/publi...
    Other literature type . 2019
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      Europe PubMed Central
      Article . 2018
      Data sources: PubMed Central
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Royal Society Open Science
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      Royal Society Open Science
      Article . 2018
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      DOAJ
      Article . 2018
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      https://doi.org/10.25932/publi...
      Other literature type . 2019
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    Authors: Peige Song; Manli Wang; Xinlei Chang; Jiawen Wang; +2 Authors

    ABSTRACTAimTo assess the prevalence of impaired renal function and its associated factors in Chinese children.MethodsChildren aged 7–18 years in China Health and Nutrition Survey (CHNS) 2009 were included as participants, and their anthropometric measurements, blood pressure (BP) and biochemical parameters were taken for analysis. The estimated glomerular filtration rate (eGFR) was calculated by using the Schwartz ‘original’ formula.ResultsThe prevalence of estimated glomerular filtration rate (eGFR) < 90 mL/min per 1.73 m2 and <75 mL/min per 1.73 m2 was 10.09% (95% CI: 8.03–12.11) and 1.01% (95% CI: 0.38–1.77), respectively. The prevalence of impaired renal function (eGFR <60 mL/min per 1.73 m2) was 0.25%. Age was detected as a negative associated factor whereas hyperuricemia and elevated total cholesterol (TC) were positively associated factors for subjects with eGFR <90 mL/min per 1.73 m2. In the group of eGFR <75 mL/min per 1.73 m2, only elevated TC was related to the increased odds of decreased eGFR.ConclusionOur findings underscore the need for large‐scale programs to detect and treat the early‐stage impaired renal function in the paediatric population in China.

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    Europe PubMed Central
    Other literature type . 2019
    Data sources: PubMed Central
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    Nephrology
    Article
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Nephrology
    Article . 2019
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      Europe PubMed Central
      Other literature type . 2019
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      Nephrology
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Nephrology
      Article . 2019
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    Authors: Naida L. Graham; Carol Leonard; David F. Tang-Wai; Sandra Black; +5 Authors

    <b><i>Background/Aims:</i></b> Frank agrammatism, defined as the omission and/or substitution of grammatical morphemes with associated grammatical errors, is variably reported in patients with nonfluent variant primary progressive aphasia (nfPPA). This study addressed whether frank agrammatism is typical in agrammatic nfPPA patients when this feature is not required for diagnosis. <b><i>Method:</i></b> We assessed grammatical production in 9 patients who satisfied current diagnostic criteria. Although the focus was agrammatism, motor speech skills were also evaluated to determine whether dysfluency arose primarily from apraxia of speech (AOS), instead of, or in addition to, agrammatism. Volumetric MRI analyses provided impartial imaging-supported diagnosis. <b><i>Results:</i></b> The majority of cases exhibited neither frank agrammatism nor AOS. <b><i>Conclusion:</i></b> There are nfPPA patients with imaging-supported diagnosis and preserved motor speech skills who do not exhibit frank agrammatism, and this may persist beyond the earliest stages of the illness. Because absence of frank agrammatism is a subsidiary diagnostic feature in the logopenic variant of PPA, this result has implications for differentiation of the nonfluent and logopenic variants, and indicates that PPA patients with nonfluent speech in the absence of frank agrammatism or AOS do not necessarily have the logopenic variant.

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    Europe PubMed Central
    Article . 2016
    Data sources: PubMed Central
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    Dementia and Geriatric Cognitive Disorders Extra
    Article . 2016
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    Dementia and Geriatric Cognitive Disorders Extra
    Article
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    DOAJ
    Article . 2016
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      Dementia and Geriatric Cognitive Disorders Extra
      Article . 2016
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      Dementia and Geriatric Cognitive Disorders Extra
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Veda N. Giri; Karen E. Knudsen; William Kevin Kelly; Wassim Abida; +66 Authors

    Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA—a clinically heterogeneous disease.

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    Europe PubMed Central
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    Journal of Clinical Oncology
    Article . 2018
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    European Urology
    Article . 2018
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    Journal of Clinical Oncology
    Article . 2018
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      Journal of Clinical Oncology
      Article . 2018
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      European Urology
      Article . 2018
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      Article . 2018
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    Authors: Vijaya M, Musini; Kendra Ak, Lawrence; Patricia M, Fortin; Ken, Bassett; +1 Authors

    Background Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. Renin is the enzyme responsible for converting angiotensinogen to angiotensin I, which is then converted to angiotensin II. Renin inhibitors are a new class of drugs that decrease blood pressure (BP) by preventing the formation of both angiotensin I and angiotensin II. Objectives To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension. To determine the change in BP variability, pulse pressure, and heart rate and to evaluate adverse events (mortality, non-fatal serious adverse events, total adverse events, withdrawal due to adverse effects and specific adverse events such as dry cough, diarrhoea and angioedema). Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to February 2017: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. There was no restriction by language or publication status. We also searched the European Medicines Agency (EMA) for clinical study reports, the Novartis Clinical Study Results Database, bibliographic citations from retrieved references, and contacted authors of relevant papers regarding further published and unpublished work. Selection criteria We included randomized, double-blinded, placebo-controlled studies evaluating BP lowering efficacy of fixed-dose monotherapy with renin inhibitor compared with placebo for a minimum duration of three to 12 weeks in adult patients with primary hypertension. Data collection and analysis This systematic review is a comprehensive update which includes four additional studies and extensive detail from nine clinical study reports (CSRs) of previously included studies obtained from EMA. The remaining three CSRs are not available. Two review authors independently assessed study eligibility and extracted data. In all cases where there was a difference between the CSR and the published report, data from the CSR was used. Dichotomous outcomes were reported as risk ratio (RR) with 95% confidence intervals (CIs) and continuous outcomes as mean difference (MD) with 95% CIs. Main results 12 studies (mean duration of eight weeks) in 7439 mostly Caucasian patients (mean age 54 years) with mild-to-moderate uncomplicated hypertension were eligible for inclusion in the review. Aliskiren was the only renin inhibitor evaluated. All included studies were assessed to have high likelihood of attrition, reporting and funding bias. Aliskiren has a dose-related systolic/diastolic blood pressure (SBP/DBP) lowering effect as compared with placebo MD with 95% CI: aliskiren 75 mg (MD -2.97, 95% CI -4.76 to -1.18)/(MD -2.05, 95% CI -3.13 to -0.96) mm Hg (moderate-quality evidence), aliskiren 150 mg (MD -5.95, 95% CI -6.85 to -5.06)/ (MD -3.16, 95% CI -3.74 to -2.58) mm Hg (moderate-quality evidence), aliskiren 300 mg (MD -7.88, 95% CI -8.94 to -6.82)/ (MD -4.49, 95% CI -5.17 to -3.82) mm Hg (moderate-quality evidence), aliskiren 600 mg (MD -11.35, 95% CI -14.43 to -8.27)/ (MD -5.86, 95% CI -7.73 to -3.99) mm Hg (low-quality evidence). There was a dose-dependent decrease in blood pressure for aliskiren 75 mg, 150 mg and 300 mg. The blood pressure lowering effect of aliskiren 600 mg was not different from 300 mg (MD -0.61, 95% CI -2.78 to 1.56)/(MD -0.68, 95% CI -2.03 to 0.67). Aliskiren had no effect on blood pressure variability. Due to very limited information available regarding change in heart rate and pulse pressure, it was not possible to meta-analyze these outcomes. Mortality and non-fatal serious adverse events were not increased. This review found that in studies of eight week duration aliskiren may not increase withdrawal due to adverse events (low-quality evidence). Diarrhoea was increased in a dose-dependent manner (RR 7.00, 95% CI 2.48 to 19.72) with aliskiren 600 mg (low-quality evidence). The most frequent adverse events reported were headache, nasopharyngitis, diarrhoea, dizziness and fatigue. Authors' conclusions Compared to placebo, aliskiren lowered BP and this effect is dose-dependent. This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). There is no difference in mortality, nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy. Diarrhoea was considerably increased with aliskiren 600 mg.

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    Europe PubMed Central
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    Authors: Eric B. Laber; Fan Wu; Catherine Munera; Ilya Lipkovich; +2 Authors

    There is growing interest and investment in precision medicine as a means to provide the best possible health care. A treatment regime formalizes precision medicine as a sequence of decision rules, one per clinical intervention period, that specify if, when and how current treatment should be adjusted in response to a patient's evolving health status. It is standard to define a regime as optimal if, when applied to a population of interest, it maximizes the mean of some desirable clinical outcome, such as efficacy. However, in many clinical settings, a high‐quality treatment regime must balance multiple competing outcomes; eg, when a high dose is associated with substantial symptom reduction but a greater risk of an adverse event. We consider the problem of estimating the most efficacious treatment regime subject to constraints on the risk of adverse events. We combine nonparametric Q‐learning with policy‐search to estimate a high‐quality yet parsimonious treatment regime. This estimator applies to both observational and randomized data, as well as settings with variable, outcome‐dependent follow‐up, mixed treatment types, and multiple time points. This work is motivated by and framed in the context of dosing for chronic pain; however, the proposed framework can be applied generally to estimate a treatment regime which maximizes the mean of one primary outcome subject to constraints on one or more secondary outcomes. We illustrate the proposed method using data pooled from 5 open‐label flexible dosing clinical trials for chronic pain.

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    Statistics in Medicine
    Article . 2018
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    Statistics in Medicine
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    Authors: Anna-Maria, Carvalho; Vincent, Poirier;

    As emergency physicians with a subspecialty in aviation medicine, we agree with Dr. Rieb’s response[1][1] to an analysis article by Kodama and colleagues[2][2] that having naloxone on board is a necessary tool to treat the increasingly common medical emergency of opioid intoxication. Some airlines

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    Article . 2018
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    Authors: Yoshida, Sachiyo; Wazny, Kerri; Cousens, Simon; Chan, Kit Yee;

    Setting health research priorities is a complex and value–driven process. The introduction of the Child Health and Nutrition Research Initiative (CHNRI) method has made the process of setting research priorities more transparent and inclusive, but much of the process remains in the hands of funders and researchers, as described in the previous two papers in this series [1,2]. However, the value systems of numerous other important stakeholders, particularly those on the receiving end of health research products, are very rarely addressed in any process of priority setting. Inclusion of a larger and more diverse group of stakeholders in the process would result in a better reflection of the system of values of the broader community, resulting in recommendations that are more legitimate and acceptable. The CHNRI method, as originally proposed, took into account the importance of stakeholders and made provisions for their participation in the process. Although the involvement of a large and diverse group of stakeholders is desirable, they were not expected to propose research ideas, or score them against the set of pre–defined criteria. Because of this, the original CHNRI method proposed that stakeholders should be allowed to “weigh” pre–defined criteria and set “thresholds” for a minimum acceptable score against each criterion that would be required for a research idea to be considered a “research priority”. In choosing the stakeholders, the context of each exercise will be very important and the goals of the specific exercise should be defined before choosing an appropriate “stakeholder group”. Among stakeholders, we would expect to see those affected by the disease of interest and their family members, their carers and health workers, members of general public, media representatives interested in the topic, community leaders, representatives of the consumer groups and industry, but also potentially researchers and funders themselves. Although the latter two groups – researchers and funders – already have a different role assigned in the CHNRI process, this does not exclude them from also being stakeholders in the process [1,2]. In this paper, we aim to review and analyse the experiences in stakeholder involvement across the 50 CHNRI exercises published in the 10–year period between 2007 and 2016, the proposed approaches to involving stakeholders and their effects on the outcome of the prioritization process. One paper in the original CHNRI method series focused on involving stakeholders [3]. That paper presented practical experiences from three separate attempts to involve stakeholders that took place in 2006. The three groups approached were: (i) members of the global research priority setting network; (ii) a diverse group of national–level stakeholders from South Africa; and (iii) participants at a conference related to international child health held in Washington, DC, USA. Each group was asked to complete a short questionnaire to assess the relative importance of the five original CHNRI criteria. Different versions of the questionnaire were used with each group [3]. The results of this exercise indicated that groups of stakeholders vary in the weights they assigned to the 5 criteria, reflecting divergence in the “value” placed on each criterion by each stakeholder group. The diverse group of respondents within the priority–setting network placed the greatest weight on the criterion of “maximum potential for disease burden reduction” and the most stringent threshold on “answerability in an ethical way”. Among the attendees at the international conference on child health, the criterion of “deliverability, answerability and sustainability” was identified as the most important. Finally, in South Africa, where inequity has been a national problem historically, the greatest weight was placed on the “predicted impact on equity” criterion. This comparative analysis by Kapiriri et al. [3] effectively demonstrated that involving a wide range of stakeholders is an important goal for any research priority setting exercise. The criteria that may be of importance to funders, scientists and other technical experts involved in the process of planning and conducting the exercise may not be well aligned with the values of those who should eventually benefit from health research, or with the sentiments of wider society as a whole [3]. This is an important observation, because if the CHNRI process is conducted without regard for the broader social value or research, then it is unrealistic to expect it to fulfil its purpose of being accepted as a fair, transparent and legitimate process for setting investment priorities for health research.

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    Europe PubMed Central
    Article . 2016
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    Journal of Global Health
    Article . 2016
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    Journal of Global Health
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      Europe PubMed Central
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      Journal of Global Health
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    Authors: R. Thomas Lumbers; Sonia Shah; Honghuang Lin; Tomasz Czuba; +164 Authors

    Abstract: Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome‐wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow‐up following heart failure diagnosis ranged from 2 to 116 months. Forty‐nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low‐frequency variants (allele frequency 0.01–0.05) at P < 5 × 10−8 under an additive genetic model. Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction. Funder: Department of Medicine, Boston University School of Medicine; Id: http://dx.doi.org/10.13039/100008748 Funder: National Heart, Lung, and Blood Institute; Id: http://dx.doi.org/10.13039/100000050 Funder: Knut and Alice Wallenberg Foundation; Id: http://dx.doi.org/10.13039/501100004063 Funder: NIHR UCLH Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100012317 Funder: Skåne University Hospital; Id: http://dx.doi.org/10.13039/501100011077 Funder: Evans Medical Foundation; Id: http://dx.doi.org/10.13039/100015927 Funder: Crafoord Foundation; Id: http://dx.doi.org/10.13039/501100003173 Funder: British Heart Foundation Cardiovascular Biomedicine Funder: Swedish National Health Service

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    Europe PubMed Central
    Article . 2021
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    ESC Heart Failure
    Other literature type . Article . 2021
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    Apollo
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    ESC Heart Failure
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    ESC Heart Failure
    Article . 2021
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    ESC Heart Failure
    Article . 2022
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      Europe PubMed Central
      Article . 2021
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      ESC Heart Failure
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      Apollo
      Article . 2021
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      ESC Heart Failure
      Article
      License: CC BY NC
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      ESC Heart Failure
      Article . 2021
      Data sources: NARCIS
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      ESC Heart Failure
      Article . 2022
      Data sources: VIRTA
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      Apollo
      Other literature type . 2021
      Data sources: Apollo
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      NARCIS
      Article . 2021
      Data sources: NARCIS
      Apollo
      Article . 2021
      Data sources: Datacite
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    Authors: Magdalena Rychlowska; Yuri Miyamoto; David Matsumoto; Ursula Hess; +5 Authors

    A small number of facial expressions may be universal in that they are produced by the same basic affective states and recognized as such throughout the world. However, other aspects of emotionally expressive behavior vary widely across culture. Just why do they vary? We propose that some cultural differences in expressive behavior are determined by historical heterogeneity, or the extent to which a country’s present-day population descended from migration from numerous vs. few source countries over a period of 500 y. Our reanalysis of data on cultural rules for displaying emotion from 32 countries [n = 5,340; Matsumoto D, Yoo S, Fontaine J (2008) J Cross Cult Psychol 39(1):55–74] reveals that historical heterogeneity explains substantial, unique variance in the degree to which individuals believe that emotions should be openly expressed. We also report an original study of the underlying states that people believe are signified by a smile. Cluster analysis applied to data from nine countries (n = 726), including Canada, France, Germany, India, Indonesia, Israel, Japan, New Zealand, and the United States, reveals that countries group into “cultures of smiling” determined by historical heterogeneity. Factor analysis shows that smiles sort into three social-functional subtypes: pleasure, affiliative, and dominance. The relative importance of these smile subtypes varies as a function of historical heterogeneity. These findings thus highlight the power of social-historical factors to explain cross-cultural variation in emotional expression and smile behavior.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Other literature type . 2015
    Data sources: PubMed Central
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Europe PubMed Central
      Other literature type . 2015
      Data sources: PubMed Central
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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    Authors: Nagel, Rebecca; Kirschbaum, Frank; Engelmann, Jacob; Hofmann, Volker; +2 Authors

    Effective communication among sympatric species is often instrumental for behavioural isolation, where the failure to successfully discriminate between potential mates could lead to less fit hybrid offspring. Discrimination between con- and heterospecifics tends to occur more often in the sex that invests more in offspring production, i.e. females, but males may also mediate reproductive isolation. In this study, we show that among two Campylomormyrus Africanweakly electric fish species, males preferentially associate with conspecific females during choice tests using live fish as stimuli, i.e. when all sensory modalities potentially used for communication were present. We then conducted playback experiments to determine whether the species-specific electric organ discharge (EOD) used for electrocommunication serves as the cue for this conspecific association preference. Interestingly, only C. compressirostris males associated significantly more with the conspecific EOD waveform when playback stimuli were provided, while no such association preference was observed in C. tamandua males. Given our results, the EOD appears to serve, in part, as a male-mediated pre-zygotic isolation mechanism among sympatric species. However, the failure of C. tamandua males to discriminate between con- and heterospecific playback discharges suggests that multiple modalities may be necessary for species recognition in some African weakly electric fish species. Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe, 645

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2018
    Data sources: PubMed Central
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    Royal Society Open Science
    Article
    License: CC BY
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    Royal Society Open Science
    Article . 2018
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    DOAJ
    Article . 2018
    Data sources: DOAJ
    https://doi.org/10.25932/publi...
    Other literature type . 2019
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      Europe PubMed Central
      Article . 2018
      Data sources: PubMed Central
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Royal Society Open Science
      Article
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      Royal Society Open Science
      Article . 2018
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      DOAJ
      Article . 2018
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      https://doi.org/10.25932/publi...
      Other literature type . 2019
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    Authors: Peige Song; Manli Wang; Xinlei Chang; Jiawen Wang; +2 Authors

    ABSTRACTAimTo assess the prevalence of impaired renal function and its associated factors in Chinese children.MethodsChildren aged 7–18 years in China Health and Nutrition Survey (CHNS) 2009 were included as participants, and their anthropometric measurements, blood pressure (BP) and biochemical parameters were taken for analysis. The estimated glomerular filtration rate (eGFR) was calculated by using the Schwartz ‘original’ formula.ResultsThe prevalence of estimated glomerular filtration rate (eGFR) < 90 mL/min per 1.73 m2 and <75 mL/min per 1.73 m2 was 10.09% (95% CI: 8.03–12.11) and 1.01% (95% CI: 0.38–1.77), respectively. The prevalence of impaired renal function (eGFR <60 mL/min per 1.73 m2) was 0.25%. Age was detected as a negative associated factor whereas hyperuricemia and elevated total cholesterol (TC) were positively associated factors for subjects with eGFR <90 mL/min per 1.73 m2. In the group of eGFR <75 mL/min per 1.73 m2, only elevated TC was related to the increased odds of decreased eGFR.ConclusionOur findings underscore the need for large‐scale programs to detect and treat the early‐stage impaired renal function in the paediatric population in China.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Other literature type . 2019
    Data sources: PubMed Central
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    Nephrology
    Article
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Nephrology
    Article . 2019
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      Europe PubMed Central
      Other literature type . 2019
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      Nephrology
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Nephrology
      Article . 2019
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    Authors: Naida L. Graham; Carol Leonard; David F. Tang-Wai; Sandra Black; +5 Authors

    <b><i>Background/Aims:</i></b> Frank agrammatism, defined as the omission and/or substitution of grammatical morphemes with associated grammatical errors, is variably reported in patients with nonfluent variant primary progressive aphasia (nfPPA). This study addressed whether frank agrammatism is typical in agrammatic nfPPA patients when this feature is not required for diagnosis. <b><i>Method:</i></b> We assessed grammatical production in 9 patients who satisfied current diagnostic criteria. Although the focus was agrammatism, motor speech skills were also evaluated to determine whether dysfluency arose primarily from apraxia of speech (AOS), instead of, or in addition to, agrammatism. Volumetric MRI analyses provided impartial imaging-supported diagnosis. <b><i>Results:</i></b> The majority of cases exhibited neither frank agrammatism nor AOS. <b><i>Conclusion:</i></b> There are nfPPA patients with imaging-supported diagnosis and preserved motor speech skills who do not exhibit frank agrammatism, and this may persist beyond the earliest stages of the illness. Because absence of frank agrammatism is a subsidiary diagnostic feature in the logopenic variant of PPA, this result has implications for differentiation of the nonfluent and logopenic variants, and indicates that PPA patients with nonfluent speech in the absence of frank agrammatism or AOS do not necessarily have the logopenic variant.

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    Europe PubMed Central
    Article . 2016
    Data sources: PubMed Central
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    Dementia and Geriatric Cognitive Disorders Extra
    Article . 2016
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    Dementia and Geriatric Cognitive Disorders Extra
    Article
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    DOAJ
    Article . 2016
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Europe PubMed Central
      Article . 2016
      Data sources: PubMed Central
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Dementia and Geriatric Cognitive Disorders Extra
      Article . 2016
      License: CC BY NC ND
      Data sources: Crossref
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Dementia and Geriatric Cognitive Disorders Extra
      Article
      License: CC BY NC ND
      Data sources: UnpayWall
      DOAJ
      Article . 2016
      Data sources: DOAJ
      addClaim

      This Research product is the result of merged Research products in OpenAIRE.

      You have already added works in your ORCID record related to the merged Research product.