Abfallwirtschaft und Stoffstrommanagement: Ökonomische Instrumente in der Bundesrepublik Deutschland und in der EU ; Tagungsband

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Meta-analyses of randomized controlled trials show suboptimal validity of surrogate outcomes for overall survival in advanced colorectal cancer

Comparative StudyMeta-AnalysisReviewValidation StudiesThis is the final version of the article. Available from Elsevier via the DOI in this record.OBJECTIVES: To quantify and compare the treatment effects on three surrogate end points, progression-free survival (PFS), time to progression (TTP), and tumor response rate (TR) vs. overall survival (OS) based on a meta-analysis of randomized controlled trials (RCTs) of drug interventions in advanced colorectal cancer (aCRC). STUDY DESIGN AND SETTING: We systematically searched for RCTs of pharmacologic therapies in aCRC between 2003 and 2013. Trial characteristics, risk of bias, and outcomes were recorded based on a predefined form. Univariate and multivariate random-effects meta-analyses were used to estimate pooled summary treatment effects. The ratio of hazard ratios (HRs)/odds ratios (ORs) and difference in medians were used to quantify the degree of difference in treatment effects on the surrogate end points and OS. Spearman ρ, surrogate threshold effect (STE), and R(2) were also estimated across predefined trial-level covariates. RESULTS: We included 101 RCTs. In univariate and multivariate meta-analyses, we found larger treatment effects for the surrogates than for OS. Compared with OS, treatment effects were on average 13% higher when HRs were measured and 3% to 45% higher when ORs were considered; differences in median PFS/TTP were higher than on OS by an average of 0.5 month. Spearman ρ ranged from 0.39 to 0.80, mean R(2) from 0.06 to 0.65, and STE was 0.8 for HRPFS, 0.64 for HRTTP, or 0.28 for ORTR. The stratified analyses revealed high variability across all strata. CONCLUSION: None of the end points in this study were found to achieve the level of evidence (ie, mean R(2)trial > 0.60) that has been set to select high or excellent correlation levels by common surrogate evaluation tools. Previous surrogacy relationships observed between PFS and TTP vs. OS in selected settings may not apply across other classes or lines of therapy

Self-determination theory in HCI: shaping a research agenda

Self-determination theory (SDT) has become one of the most frequently used and well-validated theories used in HCI research, modelling the relation of basic psychological needs, intrinsic motivation, positive experience and wellbeing. This makes it a prime candidate for a ‘motor theme’ driving more integrated, systematic, theory-guided research. However, its use in HCI has remained superficial and disjointed across various application domains like games, health and wellbeing, or learning. This workshop therefore convenes researchers across HCI to co-create a research agenda on how SDT-informed HCI research can maximise its progress in the coming years

Essays on river mechanics

CER92-93-PYJ-5.Presented by the Graduate Students in CE 717 - River Mechanics (Spring 1993).Includes bibliographical references.April 1993

Traffic, Susceptibility, and Childhood Asthma

Results from studies of traffic and childhood asthma have been inconsistent, but there has been little systematic evaluation of susceptible subgroups. In this study, we examined the relationship of local traffic-related exposure and asthma and wheeze in southern California school children (5–7 years of age). Lifetime history of doctor-diagnosed asthma and prevalent asthma and wheeze were evaluated by questionnaire. Parental history of asthma and child’s history of allergic symptoms, sex, and early-life exposure (residence at the same home since 2 years of age) were examined as susceptibility factors. Residential exposure was assessed by proximity to a major road and by modeling exposure to local traffic-related pollutants. Residence within 75 m of a major road was associated with an increased risk of lifetime asthma [odds ratio (OR) = 1.29; 95% confidence interval (CI), 1.01–1.86], prevalent asthma (OR = 1.50; 95% CI, 1.16–1.95), and wheeze (OR = 1.40; 95% CI, 1.09–1.78). Susceptibility increased in long-term residents with no parental history of asthma for lifetime asthma (OR = 1.85; 95% CI, 1.11–3.09), prevalent asthma (OR = 2.46; 95% CI, 0.48–4.09), and recent wheeze (OR = 2.74; 95% CI, 1.71–4.39). The higher risk of asthma near a major road decreased to background rates at 150–200 m from the road. In children with a parental history of asthma and in children moving to the residence after 2 years of age, there was no increased risk associated with exposure. Effect of residential proximity to roadways was also larger in girls. A similar pattern of effects was observed with traffic-modeled exposure. These results indicate that residence near a major road is associated with asthma. The reason for larger effects in those with no parental history of asthma merits further investigation

Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation.

BackgroundMucopolysaccharidosis I (MPS IH) is a lysosomal storage disease treated with hematopoietic cell transplantation (HCT) because it stabilizes cognitive deterioration, but is insufficient to alleviate all somatic manifestations. Intravenous laronidase improves somatic burden in attenuated MPS I. It is unknown whether laronidase can improve somatic disease following HCT in MPS IH. The objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT.MethodsThis 2-year open-label pilot study of laronidase included ten patients (age 5-13 years) who were at least 2 years post-HCT and donor engrafted. Outcomes were assessed semi-annually and compared to historic controls.ResultsThe two youngest participants had a statistically significant improvement in growth compared to controls. Development of persistent high-titer anti-drug antibodies (ADA) was associated with poorer 6-min walk test (6MWT) performance; when patients with high ADA titers were excluded, there was a significant improvement in the 6MWT in the remaining seven patients.ConclusionsLaronidase seemed to improve growth in participants <8 years old, and 6MWT performance in participants without ADA. Given the small number of patients treated in this pilot study, additional study is needed before definitive conclusions can be made

Survey of the quality of experimental design, statistical analysis and reporting of research using animals

For scientific, ethical and economic reasons, experiments involving animals should be appropriately designed, correctly analysed and transparently reported. This increases the scientific validity of the results, and maximises the knowledge gained from each experiment. A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be reviewed, analysed and repeated. Omitting essential information can raise scientific and ethical concerns. We report the findings of a systematic survey of reporting, experimental design and statistical analysis in published biomedical research using laboratory animals. Medline and EMBASE were searched for studies reporting research on live rats, mice and non-human primates carried out in UK and US publicly funded research establishments. Detailed information was collected from 271 publications, about the objective or hypothesis of the study, the number, sex, age and/or weight of animals used, and experimental and statistical methods. Only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used. Appropriate and efficient experimental design is a critical component of high-quality science. Most of the papers surveyed did not use randomisation (87%) or blinding (86%), to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods described their methods and presented the results with a measure of error or variability. This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals. Scientific publication is a powerful and important source of information; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively, accurately and transparently, and peer reviewers and journal editors share the responsibility to ensure that published studies fulfil these criteria

Emergent complex neural dynamics

A large repertoire of spatiotemporal activity patterns in the brain is the basis for adaptive behaviour. Understanding the mechanism by which the brain's hundred billion neurons and hundred trillion synapses manage to produce such a range of cortical configurations in a flexible manner remains a fundamental problem in neuroscience. One plausible solution is the involvement of universal mechanisms of emergent complex phenomena evident in dynamical systems poised near a critical point of a second-order phase transition. We review recent theoretical and empirical results supporting the notion that the brain is naturally poised near criticality, as well as its implications for better understanding of the brain