The impact of intellectual disability and sport expertise on cognitive and executive functions.

Our aim was to identify the suitability of three assessment tools (i.e., Flanker test, Updating Word Span, and Color Trails Test) for future inclusion in the classification process of elite Paralympic athletes with intellectual disability and to assess the strength of the relation between Executive function (EF) and intelligence. Cognitive and EF assessments were performed on 59 participants, divided into four groups according to their cognitive level (with versus without intellectual disability) and sport expertise (athlete versus novice). Inhibition and working memory update skills were implicated in people with intellectual disability. For set-shifting, a more nuanced picture was observed. Strong associations between EF and intelligence was found in people with intellectual disability. Working memory updating and set-shifting are relevant EF skills to assess in the context of elite sport; however, culture-free alternatives for the Updating Word Span test are needed, and alternatives to the Color Trails Test, less reliant on literacy skills are required

Radiative decay lifetimes of CH^-₂

Recently the presence and radiative decay of vibrationally excited CH - 2, generated in a hot cathode discharge of methane, was established by measuring the time dependent photodetachment from excited states of CH - 2 as it radiatively relaxed in a high vacuum ion trap. The time dependence of the photodetachment was found to be consistent with an electron affinity of 5250 cm^−1 (0.65 eV) for ground state X-tilde 3B1 methylene. The radiative decay lifetimes of the first three excited bending vibrations of CH - 2 were also tentatively assigned. Here, we report a more refined analysis of the experimental data along with theoretical ab initio determinations of the radiative decay lifetimes of the first four excited bending vibrational levels of CH - 2. There is some discrepancy between the ab initio values (431, 207, 118, and 68 ms for the v2=1, 2, 3, and 4 levels respectively) and the experimental values (525, 70, and 14 ms for v2=1, 2, and 3 respectively) for v2=2 and 3. Possible reasons for this discrepancy are discussed but none of the alternatives are entirely satisfactory

Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B <em>Streptococcus</em>

ABSTRACT: Several bacterial pathogens decorate their surfaces with sialic acid (Sia) residues within cell wall components or capsular exopolysaccharides. Sialic acid expression can promote bacterial virulence by blocking complement activation or by engagement of inhibitory sialic acid-binding immunoglobulin-like lectins (Siglecs) on host leukocytes. Expressed at high levels on splenic and lymph node macrophages, sialoadhesin (Sn) is a unique Siglec with an elongated structure that lacks intracellular signaling motifs. Sialoadhesin allows macrophage to engage certain sialylated pathogens and stimulate inflammatory responses, but the in vivo significance of sialoadhesin in infection has not been shown. We demonstrate that macrophages phagocytose the sialylated pathogen group B Streptococcus (GBS) and increase bactericidal activity via sialoadhesin-sialic-acid-mediated recognition. Sialoadhesin expression on marginal zone metallophillic macrophages in the spleen trapped circulating GBS and restricted the spread of the GBS to distant organs, reducing mortality. Specific IgM antibody responses to GBS challenge were also impaired in sialoadhesin-deficient mice. Thus, sialoadhesin represents a key bridge to orchestrate innate and adaptive immune defenses against invasive sialylated bacterial pathogens. KEY MESSAGE: Sialoadhesin is critical for macrophages to phagocytose and clear GBS. Increased GBS organ dissemination in the sialoadhesin-deficient mice. Reduced anti-GBS IgM production in the sialoadhesin-deficient mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-014-1157-y) contains supplementary material, which is available to authorized users

Standardized Outcomes in Nephrology-Transplantation: A Global Initiative to Develop a Core Outcome Set for Trials in Kidney Transplantation.

BACKGROUND: Although advances in treatment have dramatically improved short-term graft survival and acute rejection in kidney transplant recipients, long-term graft outcomes have not substantially improved. Transplant recipients also have a considerably increased risk of cancer, cardiovascular disease, diabetes, and infection, which all contribute to appreciable morbidity and premature mortality. Many trials in kidney transplantation are short-term, frequently use unvalidated surrogate endpoints, outcomes of uncertain relevance to patients and clinicians, and do not consistently measure and report key outcomes like death, graft loss, graft function, and adverse effects of therapy. This diminishes the value of trials in supporting treatment decisions that require individual-level multiple tradeoffs between graft survival and the risk of side effects, adverse events, and mortality. The Standardized Outcomes in Nephrology-Transplantation initiative aims to develop a core outcome set for trials in kidney transplantation that is based on the shared priorities of all stakeholders. METHODS: This will include a systematic review to identify outcomes reported in randomized trials, a Delphi survey with an international multistakeholder panel (patients, caregivers, clinicians, researchers, policy makers, members from industry) to develop a consensus-based prioritized list of outcome domains and a consensus workshop to review and finalize the core outcome set for trials in kidney transplantation. CONCLUSIONS: Developing and implementing a core outcome set to be reported, at a minimum, in all kidney transplantation trials will improve the transparency, quality, and relevance of research; to enable kidney transplant recipients and their clinicians to make better-informed treatment decisions for improved patient outcomes

Clinicians' and researchers' perspectives on establishing and implementing core outcomes in haemodialysis: semistructured interview study

Objectives: To describe the perspectives of clinicians and researchers on identifying, establishing and implementing core outcomes in haemodialysis and their expected impact. / Design: Face-to-face, semistructured interviews; thematic analysis. / Stetting: Twenty-seven centres across nine countries. / Participants: Fifty-eight nephrologists (42 (72%) who were also triallists). / Results: We identified six themes: reflecting direct patient relevance and impact (survival as the primary goal of dialysis, enabling well-being and functioning, severe consequences of comorbidities and complications, indicators of treatment success, universal relevance, stakeholder consensus); amenable and responsive to interventions (realistic and possible to intervene on, differentiating between treatments); reflective of economic burden on healthcare; feasibility of implementation (clarity and consistency in definition, easily measurable, requiring minimal resources, creating a cultural shift, aversion to intensifying bureaucracy, allowing justifiable exceptions); authoritative inducement and directive (endorsement for legitimacy, necessity of buy-in from dialysis providers, incentivising uptake); instituting patient-centredness (explicitly addressing patient-important outcomes, reciprocating trial participation, improving comparability of interventions for decision-making, driving quality improvement and compelling a focus on quality of life). / Conclusions: Nephrologists emphasised that core outcomes should be relevant to patients, amenable to change, feasible to implement and supported by stakeholder organisations. They expected core outcomes would improve patient-centred care and outcomes

Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease:a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice

Recently, the European Medicines Agency approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adult patients with chronic kidney disease stages 1-3 at initiation of treatment with evidence of rapidly progressing disease. In this paper, on behalf of the ERA-EDTA Working Groups of Inherited Kidney Disorders and European Renal Best Practice, we aim to provide guidance for making the decision as to which ADPKD patients to treat with tolvaptan. The present position statement includes a series of recommendations resulting in a hierarchical decision algorithm that encompasses a sequence of risk-factor assessments in a descending order of reliability. By examining the best-validated markers first, we aim to identify ADPKD patients who have documented rapid disease progression or are likely to have rapid disease progression. We believe that this procedure offers the best opportunity to select patients who are most likely to benefit from tolvaptan, thus improving the benefit-to-risk ratio and cost-effectiveness of this treatment. It is important to emphasize that the decision to initiate treatment requires the consideration of many factors besides eligibility, such as contraindications, potential adverse events, as well as patient motivation and lifestyle factors, and requires shared decision-making with the patient.</p

Developing a Set of Core Outcomes for Trials in Haemodialysis: An International Delphi Survey

AIM: To generate a consensus-based, prioritized list of core outcomes for trials in haemodialysis. BACKGROUND: Survival and quality of life for patients on haemodialysis remain poor despite substantial research efforts. Existing trials often report surrogate outcomes that may not be relevant to patients and clinicians. A core outcome set that reflects stakeholder priorities would improve the relevance, efficiency, and comparability of haemodialysis trials. METHODS: In an online Delphi survey, participants rated the importance of outcomes using a 9-point Likert scale. In Round 2 and 3, participants reviewed the scores and comments of other respondents and re-rated the outcomes. For each outcome, we calculated the median, mean, and proportion rating 7-9 (“critically important”). RESULTS: 1,181 participants (202 [17%] patients/caregivers, 979 health professionals) from 73 countries completed Round 1 and 838 (150 [18%] patients/caregivers) completed Round 3 (71% response rate). Outcomes achieving consensus as high priorities across both groups were: vascular access complications, cardiovascular disease, mortality, dialysis adequacy and fatigue. Patients/caregivers rated four outcomes higher than health professionals: ability to travel (mean difference 0.9), dialysis-free time (0.5), dialysis adequacy (0.3), and washed out after dialysis (0.2). Health professionals rated 11 outcomes higher: mortality (1.0), hospitalization (1.0), drop in blood pressure (1.0), vascular access complications (0.9), depression (0.9), cardiovascular disease (0.8), target weight (0.7), infection (0.4), potassium (0.4), ability to work (0.3), and pain (0.3). CONCLUSIONS: The top stakeholder prioritized outcomes were vascular access problems, cardiovascular disease, mortality, dialysis adequacy and fatigue. Patients/caregivers gave higher priority to lifestyle-related outcomes than health professionals. This prioritized set of outcomes can inform the establishment of a core outcome set, to improve the value of trial evidence to support decision-making for people on haemodialysis

Comparison of markers of oxidative stress, inflammation and arterial stiffness between incident hemodialysis and peritoneal dialysis patients – an observational study

Background: Patients on peritoneal and hemodialysis have accelerated atherosclerosis associated with an increase in cardiovascular morbidity and mortality. The atherosclerosis is associated with increased arterial stiffness, endothelial dysfunction and elevated oxidative stress and inflammation. The aims of this study are to investigate the effects of peritoneal and hemodialysis on arterial stiffness, vascular function, myocardial structure and function, oxidative stress and inflammation in incident patients with end stage kidney disease