Investigating the characteristics of expressed preferences for reducing the impacts of air pollution: A contingent valuation experiment

This paper presents the findings of research intended to investigate the nature of expressed preferences for reducing air pollution impacts. Specifically a contingent valuation (CV) experiment is designed to elicit individuals' values for reducing these impacts and examine how these may change when multiple schemes for reducing differing impacts are valued. Results indicate substantial substitution effects between a scheme delivering improvements to human health and one to reduce impacts upon plant life such that the value of a combined programme, delivering both types of benefit, is substantially less than the sum of values for the two separate schemes implemented in isolation of each other. A practical consequence of these findings is that estimates of the value of combined programmes may not readily be obtained by summing the values of their constituent parts

ENV-608: A FEASIBILITY STUDY ON SULFOLANE DEGRADATION IN GROUNDWATER USING NEUTRAL FENTON CATALYSTS

In this paper, degradation of sufolane in an acidic or near neutral pH using Fenton or modified Fenton catalysts was investigated. The catalysts included nitrilotriacetic acid (NTA) iron complex and several commercially available products marketed as neutral pH catalysts. The experiments were conducted both in lab synthetic water and sulfolane contaminated groundwater. Our results showed that more than 99% of sulfolane can be removed by the classic Fenton-like reagent in acidic condition. At near neutral pH, 60% of sulfolane reduction in groundwater was achieved by adding NTA/Fe(III)/H2O2. Among the four commercially available products investigated, ethylenediaminetetraacetic acid (EDTA) chelated iron showed the most positive result in sulfolane degradation in the groundwater. Fifty percent of sulfolane in groundwater degraded when EDTA chelated iron was used with hydrogen peroxide. The decomplexation of chelated iron during reaction caused iron to precipitate and led to the cessation of the reaction

Quantum teleportation on a photonic chip

Quantum teleportation is a fundamental concept in quantum physics which now finds important applications at the heart of quantum technology including quantum relays, quantum repeaters and linear optics quantum computing (LOQC). Photonic implementations have largely focussed on achieving long distance teleportation due to its suitability for decoherence-free communication. Teleportation also plays a vital role in the scalability of photonic quantum computing, for which large linear optical networks will likely require an integrated architecture. Here we report the first demonstration of quantum teleportation in which all key parts - entanglement preparation, Bell-state analysis and quantum state tomography - are performed on a reconfigurable integrated photonic chip. We also show that a novel element-wise characterisation method is critical to mitigate component errors, a key technique which will become increasingly important as integrated circuits reach higher complexities necessary for quantum enhanced operation.Comment: Originally submitted version - refer to online journal for accepted manuscript; Nature Photonics (2014

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

Patient engagement in designing, conducting, and disseminating clinical pain research : IMMPACT recommended considerations

The consensus recommendations are based on the views of IMMPACT meeting participants and do not necessarily represent the views of the organizations with which the authors are affiliated. The following individuals made important contributions to the IMMPACT meeting but were not able to participate in the preparation of this article: David Atkins, MD (Department of Veterans Affairs), Rebecca Baker, PhD (National Institutes of Health), Allan Basbaum, PhD (University of California San Francisco), Robyn Bent, RN, MS (Food and Drug Administration), Nathalie Bere, MPH (European Medicines Agency), Alysha Croker, PhD (Health Canada), Stephen Bruehl, PhD (Vanderbilt University), Michael Cobas Meyer, MD, MBS (Eli Lilly), Scott Evans, PhD (George Washington University), Gail Graham (University of Maryland), Jennifer Haythornthwaite, PhD (Johns Hopkins University), Sharon Hertz, MD (Hertz and Fields Consulting), Jonathan Jackson, PhD (Harvard Medical School), Mark Jensen, PhD (University of Washington), Francis Keefe, PhD (Duke University), Karim Khan, MD, PhD, MBA (Canadian Institutes of Health Research), Lynn Laidlaw (University of Aberdeen), Steven Lane (Patient-Centered Outcomes Research Institute), Karen Morales, BS (University of Maryland), David Leventhal, MBA (Pfizer), Jeremy Taylor, OBE (National Institute for Health Research), and Lena Sun, MD (Columbia University). The manuscript has not been submitted, presented, or published elsewhere. Parts of the manuscript have been presented in a topical workshop at IASP World Congress on Pain in Toronto, in 2022.Peer reviewedPublisher PD

Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants

Many Labs 5:Testing pre-data collection peer review as an intervention to increase replicability

Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3?9; median total sample = 1,279.5, range = 276?3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (?r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00?.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19?.50)

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease