Refinement and preliminary evaluation of two tablet-based tests of real-world visual function

PURPOSE: To describe, refine, evaluate, and provide normative control data for two freely available tablet-based tests of real-world visual function, using a cohort of young, normally-sighted adults. METHODS: Fifty young (18-40 years), normally-sighted adults completed tablet-based assessments of (1) face discrimination and (2) visual search. Each test was performed twice, to assess test-retest repeatability. Post-hoc analyses were performed to determine the number of trials required to obtain stable estimates of performance. Distributions were fitted to the normative data to determine the 99% population-boundary for normally sighted observers. Participants were also asked to rate their comprehension of each test. RESULTS: Both tests provided stable estimates in around 20 trials (~1-4 min), with only a further reduction of 14%-17% in the 95% Coefficient of Repeatability (CoR95 ) when an additional 40 trials were included. When using only ~20 trials: median durations for the first run of each test were 191 s (Faces) and 51 s (Search); test-retest CoR95 were 0.27 d (Faces) and 0.84 s (Search); and normative 99% population-limits were 3.50 d (Faces) and 3.1 s (Search). No participants exhibited any difficulties completing either test (100% completion rate), and ratings of task-understanding were high (Faces: 9.6 out of 10; Search: 9.7 out of 10). CONCLUSIONS: This preliminary assessment indicated that both tablet-based tests are able to provide simple, quick, and easy-to-administer measures of real-world visual function in normally-sighted young adults. Further work is required to assess their accuracy and utility in older people and individuals with visual impairment. Potential applications are discussed, including their use in clinic waiting rooms, and as an objective complement to Patient Reported Outcome Measures (PROMs)

Refinement and preliminary evaluation of two tablet-based tests of real-world visual function

PURPOSE To describe, refine, evaluate, and provide normative control data for two freely available tablet‐based tests of real‐world visual function, using a cohort of young, normally‐sighted adults. METHODS Fifty young (18–40 years), normally‐sighted adults completed tablet‐based assessments of (1) face discrimination and (2) visual search. Each test was performed twice, to assess test‐retest repeatability. Post‐hoc analyses were performed to determine the number of trials required to obtain stable estimates of performance. Distributions were fitted to the normative data to determine the 99% population‐boundary for normally sighted observers. Participants were also asked to rate their comprehension of each test. RESULTS Both tests provided stable estimates in around 20 trials (~1–4 min), with only a further reduction of 14%–17% in the 95% Coefficient of Repeatability (CoR95) when an additional 40 trials were included. When using only ~20 trials: median durations for the first run of each test were 191 s (Faces) and 51 s (Search); test‐retest CoR95 were 0.27 d (Faces) and 0.84 s (Search); and normative 99% population‐limits were 3.50 d (Faces) and 3.1 s (Search). No participants exhibited any difficulties completing either test (100% completion rate), and ratings of task‐understanding were high (Faces: 9.6 out of 10; Search: 9.7 out of 10). CONCLUSIONS This preliminary assessment indicated that both tablet‐based tests are able to provide simple, quick, and easy‐to‐administer measures of real‐world visual function in normally‐sighted young adults. Further work is required to assess their accuracy and utility in older people and individuals with visual impairment. Potential applications are discussed, including their use in clinic waiting rooms, and as an objective complement to Patient Reported Outcome Measures (PROMs)

Back to reality: How domestic energy efficiency policies in four European countries can be improved by using empirical data instead of normative calculation.

It is now well established that there is a serious gap between normative Energy Performance Certificate (EPC) calculations and measured energy consumption in the domestic sector. The fact that there are similarities in this gap between different European countries with varied housing stocks, different normative (EPC) dwelling consumption calculation methods and different cultural norms is surprising. This gap affects the analysis of current energy consumption and the estimation of future energy saving and its cost-effectiveness. This paper presents the results of comparing the differences between measured consumption and normative estimations of residential energy consumptions using national standard (EPC) calculations in four European countries (United Kingdom, France, The Netherlands and Germany). The potential causes of this gap are discussed in terms of behavioural change, technological performance and the application of normative models. Normative calculations are currently used to help develop both European and national energy efficiency policies. In the recast of the EPBD directive for example, cost-optimality calculations for major renovations and Nearly-Zero-Energy Buildings are based on normative standards. The paper provides examples of the potential impact that using normative as opposed to calculations grounded in empirical data may have on policy decisions

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

Controlling bias and inflation in epigenome- and transcriptome-wide association studies using the empirical null distribution

We show that epigenome- and transcriptome-wide association studies (EWAS and TWAS) are prone to significant inflation and bias of test statistics, an unrecognized phenomenon introducing spurious findings if left unaddressed. Neither GWAS-based methodology nor state-of-the-art confounder adjustment methods completely remove bias and inflation. We propose a Bayesian method to control bias and inflation in EWAS and TWAS based on estimation of the empirical null distribution. Using simulations and real data, we demonstrate that our method maximizes power while properly controlling the false positive rate. We illustrate the utility of our method in large-scale EWAS and TWAS meta-analyses of age and smoking

Autosomal genetic variation is associated with DNA methylation in regions variably escaping X-chromosome inactivation

This is the final version of the article. Available from Springer Nature via the DOI in this record.Raw data were submitted to the European Genome-phenome Archive (EGA) under accession EGAS00001001077.X-chromosome inactivation (XCI), i.e., the inactivation of one of the female X chromosomes, restores equal expression of X-chromosomal genes between females and males. However, ~10% of genes show variable degrees of escape from XCI between females, although little is known about the causes of variable XCI. Using a discovery data-set of 1867 females and 1398 males and a replication sample of 3351 females, we show that genetic variation at three autosomal loci is associated with female-specific changes in X-chromosome methylation. Through cis-eQTL expression analysis, we map these loci to the genes SMCHD1/METTL4, TRIM6/HBG2, and ZSCAN9. Low-expression alleles of the loci are predominantly associated with mild hypomethylation of CpG islands near genes known to variably escape XCI, implicating the autosomal genes in variable XCI. Together, these results suggest a genetic basis for variable escape from XCI and highlight the potential of a population genomics approach to identify genes involved in XCI.This research was financially supported by several institutions: BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO, numbers 184.021.007 and 184.033.111); the UK Medical Research Council; Wellcome (www.wellcome.ac.uk; [grant number 102215/2/13/2 to ALSPAC]); the University of Bristol to ALSPAC; the UK Economic and Social Research Council (www.esrc.ac.uk; [ES/N000498/1] to CR); the UK Medical Research Council (www.mrc.ac.uk; grant numbers [MC_UU_12013/1, MC_UU_12013/2 to JLM, CR]); the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria; the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ; the Wellcome Trust, Medical Research Council, European Union (EU), and the National Institute for Health Research (NIHR)- funded BioResource, Clinical Research Facility, and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London

Microsatellite diversity of the Nordic type of goats in relation to breed conservation: how relevant is pure ancestry?

In the last decades, several endangered breeds of livestock species have been re-established effectively. However, the successful revival of the Dutch and Danish Landrace goats involved crossing with exotic breeds and the ancestry of the current populations is therefore not clear. We have generated genotypes for 27 FAO-recommended microsatellites of these landraces and three phenotypically similar Nordic-type landraces and compared these breeds with central European, Mediterranean and south-west Asian goats. We found decreasing levels of genetic diversity with increasing distance from the south-west Asian domestication site with a south-east-to-north-west cline that is clearly steeper than the Mediterranean east-to-west cline. In terms of genetic diversity, the Dutch Landrace comes next to the isolated Icelandic breed, which has an extremely low diversity. The Norwegian coastal goat and the Finnish and Icelandic landraces are clearly related. It appears that by a combination of mixed origin and a population bottleneck, the Dutch and Danish Land-races are separated from the other breeds. However, the current Dutch and Danish populations with the multicoloured and long-horned appearance effectively substitute for the original breed, illustrating that for conservation of cultural heritage, the phenotype of a breed is more relevant than pure ancestry and the genetic diversity of the original breed. More in general, we propose that for conservation, the retention of genetic diversity of an original breed and of the visual phenotype by which the breed is recognized and defined needs to be considered separately