Haplotype Reconstruction Error as a Classical Misclassification Problem: Introducing Sensitivity and Specificity as Error Measures

BACKGROUND: Statistically reconstructing haplotypes from single nucleotide polymorphism (SNP) genotypes, can lead to falsely classified haplotypes. This can be an issue when interpreting haplotype association results or when selecting subjects with certain haplotypes for subsequent functional studies. It was our aim to quantify haplotype reconstruction error and to provide tools for it. METHODS AND RESULTS: By numerous simulation scenarios, we systematically investigated several error measures, including discrepancy, error rate, and R(2), and introduced the sensitivity and specificity to this context. We exemplified several measures in the KORA study, a large population-based study from Southern Germany. We find that the specificity is slightly reduced only for common haplotypes, while the sensitivity was decreased for some, but not all rare haplotypes. The overall error rate was generally increasing with increasing number of loci, increasing minor allele frequency of SNPs, decreasing correlation between the alleles and increasing ambiguity. CONCLUSIONS: We conclude that, with the analytical approach presented here, haplotype-specific error measures can be computed to gain insight into the haplotype uncertainty. This method provides the information, if a specific risk haplotype can be expected to be reconstructed with rather no or high misclassification and thus on the magnitude of expected bias in association estimates. We also illustrate that sensitivity and specificity separate two dimensions of the haplotype reconstruction error, which completely describe the misclassification matrix and thus provide the prerequisite for methods accounting for misclassification

Efficacy and Safety of Lacosamide in Painful Diabetic Neuropathy

OBJECTIVE: To evaluate efficacy and safety of lacosamide compared with placebo in painful diabetic polyneuropathy. RESEARCH DESIGN AND METHODS: Diabetic patients with at least moderate neuropathic pain were randomized to placebo or lacosamide 400 (in a slow or standard titration) or 600 mg/day over 6-week titration and 12-week maintenance periods. Primary efficacy criterion was intra-individual change in average daily Numeric Pain Rating Scale score from baseline to the last 4 weeks. RESULTS: For the primary end point, pain reduction was numerically but not statistically greater with lacosamide compared with placebo (400 mg/day, P = 0.12; 600 mg/day, P = 0.18). Both doses were significantly more effective compared with placebo over the titration (P = 0.03, P = 0.006), maintenance (P = 0.01, P = 0.005), and entire treatment periods (P = 0.03, P = 0.02). Safety profiles between titration schemes were similar. CONCLUSIONS: Lacosamide reduced neuropathic pain and was well tolerated in diabetic patients, but the primary efficacy criterion was not met, possibly due to an increased placebo response over the last 4 weeks.status: publishe

Intra- and Inter-Individual Differences in Adolescent Depressive Mood: the Role of Relationships with Parents and Friends

Abstract: Utilizing four waves of data from 1126 secondary school Dutch adolescents (Mage = 13.95 at the first wave; 53% boys), the current study examined the interplay between parent-adolescent and friend-adolescent relationship quality (satisfaction and conflict) in relation to adolescents’ depressive mood. Using multilevel analyses, the interacting effects of parent/friend relationship quality on depressive mood were tested at both the intra- and inter-individual level. Analyses at the intra-individual level investigated whether individual depressive mood fluctuated along with changes in their social relationships regardless of one’s general level of depressive mood; and analyses at the inter-individual level examined whether the average differences in depressive mood between adolescents were associated with different qualities of social relationships. We interpreted the patterns of interactions between parent and friend relationships using four theoretical models: the reinforcement, toxic friends, compensation, and additive model. The results demonstrate the covariation of parent- and friend- relationship quality with adolescents’ depressive mood, and highlight that parent and peer effects are not independent from each other—affirming the compensation and additive models at the intra-individual and the reinforcement and additive models at the inter-individual level. The findings highlight the robustness of the protective effects of parent and peer support and the deleterious effects of conflictual relationships for adolescent mental health. The results have implications for both the theoretical and practical design of (preventive) interventions aimed at decreasing adolescents’ depressive mood

Connecting the sustainable development goals by their energy inter-linkages

The United Nations' Sustainable Development Goals (SDGs) provide guide-posts to society as it attempts to respond to an array of pressing challenges. One of these challenges is energy; thus, the SDGs have become paramount for energy policy-making. Yet, while governments throughout the world have already declared the SDGs to be 'integrated and indivisible', there are still knowledge gaps surrounding how the interactions between the energy SDG targets and those of the non-energy-focused SDGs might play out in different contexts. In this review, we report on a large-scale assessment of the relevant energy literature, which we conducted to better our understanding of key energy-related interactions between SDGs, as well as their context-dependencies (relating to time, geography, governance, technology, and directionality). By (i) evaluating the nature and strength of the interactions identified, (ii) indicating the robustness of the evidence base, the agreement of that evidence, and our confidence in it, and (iii) highlighting critical areas where better understanding is needed or context dependencies should be considered, our review points to potential ways forward for both the policy making and scientific communities. First, we find that positive interactions between the SDGs outweigh the negative ones, both in number and magnitude. Second, of relevance for the scientific community, in order to fill knowledge gaps in critical areas, there is an urgent need for interdisciplinary research geared toward developing new data, scientific tools, and fresh perspectives. Third, of relevance for policy-making, wider efforts to promote policy coherence and integrated assessments are required to address potential policy spillovers across sectors, sustainability domains, and geographic and temporal boundaries. The task of conducting comprehensive science-to-policy assessments covering all SDGs, such as for the UN's Global Sustainable Development Report, remains manageable pending the availability of systematic reviews focusing on a limited number of SDG dimensions in each case

Nuclide inventories in Hg-targets

EURISOL DS/Task5/TN-06-0

The radiotoxic and conventional toxic relevance of Hg-target inventories

EURISOL DS/Task5/TN-06-1