Multifactorial approach and superior treatment efficacy in renal patients with the aid of nurse practitioners. Design of The MASTERPLAN Study [ISRCTN73187232]

BACKGROUND: Patients with chronic kidney disease (CKD) are at a greatly increased risk of developing cardiovascular disease. Recently developed guidelines address multiple risk factors and life-style interventions. However, in current practice few patients reach their targets. A multifactorial approach with the aid of nurse practitioners was effective in achieving treatment goals and reducing vascular events in patients with diabetes mellitus and in patients with heart failure. We propose that this also holds for the CKD population. DESIGN: MASTERPLAN is a multicenter randomized controlled clinical trial designed to evaluate whether a multifactorial approach with the aid of nurse-practicioners reduces cardiovascular risk in patients with CKD. Approximately 800 patients with a creatinine clearance (estimated by Cockcroft-Gault) between 20 to 70 ml/min, will be included. To all patients the same set of guidelines will be applied and specific cardioprotective medication will be prescribed. In the intervention group the nurse practitioner will provide lifestyle advice and actively address treatment goals. Follow-up will be five years. Primary endpoint is the composite of myocardial infarction, stroke and cardiovascular mortality. Secondary endpoints are cardiovascular morbidity, overall mortality, decline of renal function, change in markers of vascular damage and change in quality of life. Enrollment has started in April 2004 and the study is on track with 700 patients included on October 15th, 2005. This article describes the design of the MASTERPLAN study

Effectiveness of the universal prevention program 'Healthy School and Drugs': Study protocol of a randomized clustered trial

Contains fulltext : 90260.pdf (publisher's version ) (Open Access)Background: Substance use is highly prevalent among Dutch adolescents. The Healthy School and Drugs program is a nationally implemented school-based prevention program aimed at reducing early and excessive substance use among adolescents. Although the program's effectiveness was tested in a quasi-experimental design before, many program changes were made afterwards. The present study, therefore, aims to test the effects of this widely used, renewed universal prevention program. Methods/Design: A randomized clustered trial will be conducted among 3,784 adolescents of 23 secondary schools in The Netherlands. The trial has three conditions; two intervention conditions (i.e., e-learning and integral) and a control condition. The e-learning condition consists of three digital learning modules (i.e., about alcohol, tobacco, and marijuana) that are sequentially offered over the course of three school years (i.e., grade 1, grade 2, and grade 3). The integral condition consists of parental participation in a parental meeting on substance use, regulation of substance use, and monitoring and counseling of students' substance use at school, over and above the three digital modules. The control condition is characterized as business as usual. Participating schools were randomly assigned to either an intervention or control condition. Participants filled out a digital questionnaire at baseline and will fill out the same questionnaire three more times at follow-up measurements (8, 20, and 32 months after baseline). Outcome variables included in the questionnaire are the percentage of binge drinking (more than five drinks per occasion), the average weekly number of drinks, and the percentage of adolescents who ever drunk a glass of alcohol and the percentage of adolescents who ever smoked a cigarette or a joint respectively for tobacco and marijuana. Discussion: This study protocol describes the design of a randomized clustered trial that evaluates the effectiveness of a school-based prevention program. We expect that significantly fewer adolescents will engage in early or excessive substance use behaviors in the intervention conditions compared to the control condition as a direct result of the intervention. We expect that the integral condition will yield most positive results, compared with the e-learning condition and control condition.10 p

The desirability of transitions in demand: Incorporating behavioural and societal transformations into energy modelling

Quantitative systems modelling in support of climate policy has tended to focus more on the supply side in assessing interactions among technology, economy, environment, policy and society. By contrast, the demand side is usually underrepresented, often emphasising technological options for energy efficiency improvements. In this perspective, we argue that scientific support to climate action is not only about exploring capacity of "what", in terms of policy and outcome, but also about assessing feasibility and desirability, in terms of "when", "where" and especially for "whom". Without the necessary behavioural and societal transformations, the world faces an inadequate response to the climate crisis challenge. This could result from poor uptake of low-carbon technologies, continued high-carbon intensive lifestyles, or economy-wide rebound effects. For this reason, we propose a framing for a holistic and transdisciplinary perspective on the role of human choices and behaviours in influencing the low-carbon transition, starting from the desires of individuals and communities, and analysing how these interact with the energy and economic landscape, leading to systemic change at the macro-level. In making a case for a political ecology agenda, we expand our scope, from comprehending the role of societal acceptance and uptake of end-use technologies, to co-developing knowledge with citizens from non-mainstream and marginalised communities, and to defining the modelling requirements to assess the decarbonisation potential of shifting lifestyle patterns in climate change and action

Desmin Knock-Out Cardiomyopathy: A Heart on the Verge of Metabolic Crisis

Desmin mutations cause familial and sporadic cardiomyopathies. In addition to perturbing the contractile apparatus, both desmin deficiency and mutated desmin negatively impact mitochondria. Impaired myocardial metabolism secondary to mitochondrial defects could conceivably exacerbate cardiac contractile dysfunction. We performed metabolic myocardial phenotyping in left ventricular cardiac muscle tissue in desmin knock-out mice. Our analyses revealed decreased mitochondrial number, ultrastructural mitochondrial defects, and impaired mitochondria-related metabolic pathways including fatty acid transport, activation, and catabolism. Glucose transporter 1 and hexokinase-1 expression and hexokinase activity were increased. While mitochondrial creatine kinase expression was reduced, fetal creatine kinase expression was increased. Proteomic analysis revealed reduced expression of proteins involved in electron transport mainly of complexes I and II, oxidative phosphorylation, citrate cycle, beta-oxidation including auxiliary pathways, amino acid catabolism, and redox reactions and oxidative stress. Thus, desmin deficiency elicits a secondary cardiac mitochondriopathy with severely impaired oxidative phosphorylation and fatty and amino acid metabolism. Increased glucose utilization and fetal creatine kinase upregulation likely portray attempts to maintain myocardial energy supply. It may be prudent to avoid medications worsening mitochondrial function and other metabolic stressors. Therapeutic interventions for mitochondriopathies might also improve the metabolic condition in desmin deficient hearts

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

The handbook for standardized field and laboratory measurements in terrestrial climate change experiments and observational studies (ClimEx)

1. Climate change is a world‐wide threat to biodiversity and ecosystem structure, functioning and services. To understand the underlying drivers and mechanisms, and to predict the consequences for nature and people, we urgently need better understanding of the direction and magnitude of climate change impacts across the soil–plant–atmosphere continuum. An increasing number of climate change studies are creating new opportunities for meaningful and high‐quality generalizations and improved process understanding. However, significant challenges exist related to data availability and/or compatibility across studies, compromising opportunities for data re‐use, synthesis and upscaling. Many of these challenges relate to a lack of an established ‘best practice’ for measuring key impacts and responses. This restrains our current understanding of complex processes and mechanisms in terrestrial ecosystems related to climate change. 2. To overcome these challenges, we collected best‐practice methods emerging from major ecological research networks and experiments, as synthesized by 115 experts from across a wide range of scientific disciplines. Our handbook contains guidance on the selection of response variables for different purposes, protocols for standardized measurements of 66 such response variables and advice on data management. Specifically, we recommend a minimum subset of variables that should be collected in all climate change studies to allow data re‐use and synthesis, and give guidance on additional variables critical for different types of synthesis and upscaling. The goal of this community effort is to facilitate awareness of the importance and broader application of standardized methods to promote data re‐use, availability, compatibility and transparency. We envision improved research practices that will increase returns on investments in individual research projects, facilitate second‐order research outputs and create opportunities for collaboration across scientific communities. Ultimately, this should significantly improve the quality and impact of the science, which is required to fulfil society's needs in a changing world

The future in the stars European policy-making and the exploration of the future : the Turkey - EU accession dossier

Ven, Karin H. J. Van Der (Dogus Author)The role of future exploration as a type of expertise in the policy-making process has increased in the past decades. Research about the relationship between future exploration and policy-making is largely limited to national policy-making processes, and there has not been much research of the European Union in this context. The aim of this empirical study is to provide insights about future exploration and policy-making in the European Union structures. Its main focus is on the Turkey-EU accession dossier; a topical issue on the European agenda today, as well as one with certain presumed orientation towards the future, namely Turkish membership. On the basis of the Turkey-EU dossier, closely related to EU enlargement policy at large, the ambition of this study is to derive meaningful conclusions for the wider realm of European policy-making. The study focuses both on the formal (institutionalized) methods of future exploration, as well as the informal ways in which the future plays a role in European policy making. Qualitative methods are employed to detect and analyse relevant policy-documents from the European Parliament, European Commission, and Council, as well as those from their subunits dedicated to enlargement policy. In addition, an inquiry of external future explorative bodies in the field of Turkey-EU relations is made to contribute to a comprehensive view of the existence of future explorations, as well as their role in policy-making. Interviews with three officials, active in the EU-Turkey policy-making process in different ways, serve to complement the analysis. Theoretical insights in relation to expertise and policy-making, as well as the more specific field future exploration and policy-making are employed to position the findings within their proper field. The realization that future exploration plays a very limited role in policy making regarding the Turkey-EU accession dossier is among the most important fınding of this study in relation to the formal role of future explorations in the EU. Furthermore, the practice of future exploration seems to be closely intertwined with the actual policy-making process, and the involvement of external agencies is marginal. About the more in formal relationship between future exploration and policy-making, it can be said in this dossier, the EU seeks to plan its future rather than explore it, primarily by establishing objectives and creating policy for the long-term.PREFACE, I -- EXECUTIVE SUMMARY, II -- LIST OF FIGURES, VII -- INTRODUCTION, 1 -- 1. EXPERTISE AND POLICY-MAKING, 5 -- 2. FUTURE EXPLORATION AND POLICY-MAKING, 12 -- 2.1. What is future exploration?, 12 -- 2.2. The (potential) role of future exploration in policy-making, 15 -- 2.3. Challenges of future exploration in policy-making, 16 -- 2.4. Who explores the future?, 19 -- 2.5. Prior insights, 20 -- 2.6. Conclusion, 22 -- 3. EU ENLARGEMENT, 23 -- 3.1. A special kind of policy, 23 -- 3.2. Why enlarge?, 24 -- 3.3. Process and players, 25 -- 3.4. Challenges of enlargement, 32 -- 3.5. Conclusion, 33 -- 4. THE TURKISH ACCESSION DOSSIER, 35 -- 4.1. Chronology and important documents, 35 -- 4.2. The ' promise' of membership, 43 -- 4.3. The future, 44 -- 4.4. Challenges and key issues, 45 -- 4.5. Attitudes, 53 -- 4.6. Conclusion, 54 -- 5. METHODOLOGY, 56 -- 5.1. Research questions, 56 -- 5.2. Link to existing theory, 56 -- 5.3. The case study, 57 -- 5.4. Definitions, 59 -- 5.5. Research methodology, 59 -- 5.5. l. Research step 1, 60 -- 5.5.2. Research step 2, 71 -- 5.5.3. Research step 3: Interviews, 74 -- 6. FINDINGS-P ART 1, 78 -- 6.1. Findings according to institution, 78 -- 6.1. l. European Commission, 78 -- 6.1.2. European Council, 79 -- 6.1.3. European Parliament, 80 -- 6.2. Category A, 81 -- 6.3. Commonalities in categories B and C, 82 -- 6.4. Category B, 85 -- 6.4. l. Focal points, 85 -- 6.4.2. Anticipation and planning, 89 -- 6.5. Category C, 102 -- 6.6. Thinking about the future, 111 -- 6.7. The role of previous enlargements, 113 -- 6.8. Thinking about Turkey when thinking about the future, 114 -- 6.9. Political vs. economic criteria, 115 -- 6.10. Conclusions, 116 -- 7. FINDINGS-PART 2, 118 -- 7. l. Meeting documents, 118 -- 7.2. Awareness, 120 -- 7.3. EU Internal advisory bodies, 122 -- 7.3.1. Economic and Social Committee, 122 -- 7.3.2. The Committee ofthe Regions, 123 -- 7.3.3. The Forward Studies Unit and the Bureau of European Policy Advisers, 124 -- 7.4. External agencies, 128 -- 7.4. l. Independent Commission on Turkey, 128 -- 7.4.2. Center for European Policy Studies, 129 -- 7.4.3. Centre for European Reform, 133 -- 7.4.4. The Centre, 133 -- 7.4.5. The European Policy Centre, 134 -- 7.4.6. The Bertelsmann Foundation, 134 -- 7.5. Conclusions, 135 -- 8. CONCLUSIONS AND DISCUSSION, 137 -- 8.1. Summary of most relevant findings, 137 -- 8.2. The research objectives and additional questions, 138 -- 8.3. Possible reasons for limited use of future exploration, 144 -- 8.4. Potential, 149 -- 8.5. Methodological reflection, 151 -- 8.6. Final remarks, 152 -- BIBLIOGRAPHY, 153 -- ANNEX-LIST OF DOCUMENTS ANALYZED, 16

Behavioral, Neural, and Cognitive Characteristics of Mathematical Skills in the Developing and Adult brain

Interactions from brain to behavior are still unclear in the field of numerical cognition, especially over various developmental stages. The aim is to provide a comprehensive framework between neural characteristics (resting-state), cognition (e.g., working memory and number sense) and behavior that could contribute to an increased understanding of mathematical skills during development. The present study is a developmental comparison between children and adults which could contribute to more detailed knowledge relating mathematical skills that could translate to educational settings

Immunological effects of shift work in healthcare workers

The immune system potentially plays an important mechanistic role in the relation between shift work and adverse health effects. To better understand the immunological effects of shift work, we compared numbers and functionality of immune cells between night-shift and non-shift workers. Blood samples were collected from 254 night-shift and 57 non-shift workers employed in hospitals. Absolute numbers of monocytes, granulocytes, lymphocytes, and T cell subsets were assessed. As read out of immune function, monocyte cytokine production and proliferative capacity of CD4 and CD8 T cells in response to various stimuli were analysed. The mean number of monocytes was 1.15 (95%-CI = 1.05–1.26) times higher in night-shift than in non-shift workers. Furthermore, night-shift workers who worked night shifts in the past three days had a higher mean number of lymphocytes (B = 1.12 (95%-CI = 1.01–1.26)), T cells (B = 1.16 (95%-CI = 1.03–1.31)), and CD8 T cells (B = 1.23 (95%-CI = 1.05–1.45)) compared to non-shift workers. No differences in functional parameters of monocytes and lymphocytes were observed. The differences in numbers of monocytes and T cells suggest that chronic exposure to night-shift work as well as recent night-shift work may influence the immune status of healthcare workers. This knowledge could be relevant for preventive initiatives in night-shift workers, such as timing of vaccination