A systematic review of economic evaluations of whole genome sequencing for the surveillance of bacterial pathogens

Whole-genome sequencing (WGS) has unparalleled ability to distinguish between bacteria, with many public health applications. The generation and analysis of WGS data require significant financial investment. We describe a systematic review summarizing economic analyses of genomic surveillance of bacterial pathogens, reviewing the evidence for economic viability. The protocol was registered on PROSPERO (CRD42021289030). Six databases were searched on 8 November 2021 using terms related to ‘WGS’, ‘population surveillance’ and ‘economic analysis’. Quality was assessed with the Drummond–Jefferson checklist. Following data extraction, a narrative synthesis approach was taken. Six hundred and eighty-one articles were identified, of which 49 proceeded to full-text screening, with 9 selected for inclusion. All had been published since 2019. Heterogeneity was high. Five studies assessed WGS for hospital surveillance and four analysed foodborne pathogens. Four were cost–benefit analyses, one was a cost–utility analysis, one was a cost-effectiveness analysis, one was a combined cost-effectiveness and cost–utility analysis, one combined cost-effectiveness and cost–benefit analyses and one was a partial analysis. All studies supported the use of WGS as a surveillance tool on economic grounds. The available evidence supports the use of WGS for pathogen surveillance but is limited by marked heterogeneity. Further work should include analysis relevant to low- and middle-income countries and should use real-world effectiveness data

Measuring our universe from galaxy redshift surveys

Galaxy redshift surveys have achieved significant progress over the last couple of decades. Those surveys tell us in the most straightforward way what our local universe looks like. While the galaxy distribution traces the bright side of the universe, detailed quantitative analyses of the data have even revealed the dark side of the universe dominated by non-baryonic dark matter as well as more mysterious dark energy (or Einstein's cosmological constant). We describe several methodologies of using galaxy redshift surveys as cosmological probes, and then summarize the recent results from the existing surveys. Finally we present our views on the future of redshift surveys in the era of Precision Cosmology.Comment: 82 pages, 31 figures, invited review article published in Living Reviews in Relativity, http://www.livingreviews.org/lrr-2004-

Toward High-Precision Measures of Large-Scale Structure

I review some results of estimation of the power spectrum of density fluctuations from galaxy redshift surveys and discuss advances that may be possible with the Sloan Digital Sky Survey. I then examine the realities of power spectrum estimation in the presence of Galactic extinction, photometric errors, galaxy evolution, clustering evolution, and uncertainty about the background cosmology.Comment: 24 pages, including 11 postscript figures. Uses crckapb.sty (included in submission). To appear in ``Ringberg Workshop on Large-Scale Structure,'' ed D. Hamilton (Kluwer, Amsterdam), p. 39

ENGINES: exploring single nucleotide variation in entire human genomes

<p>Abstract</p> <p>Background</p> <p>Next generation ultra-sequencing technologies are starting to produce extensive quantities of data from entire human genome or exome sequences, and therefore new software is needed to present and analyse this vast amount of information. The 1000 Genomes project has recently released raw data for 629 complete genomes representing several human populations through their Phase I interim analysis and, although there are certain public tools available that allow exploration of these genomes, to date there is no tool that permits comprehensive population analysis of the variation catalogued by such data.</p> <p>Description</p> <p>We have developed a genetic variant site explorer able to retrieve data for Single Nucleotide Variation (SNVs), population by population, from entire genomes without compromising future scalability and agility. ENGINES (ENtire Genome INterface for Exploring SNVs) uses data from the 1000 Genomes Phase I to demonstrate its capacity to handle large amounts of genetic variation (>7.3 billion genotypes and 28 million SNVs), as well as deriving summary statistics of interest for medical and population genetics applications. The whole dataset is pre-processed and summarized into a data mart accessible through a web interface. The query system allows the combination and comparison of each available population sample, while searching by rs-number list, chromosome region, or genes of interest. Frequency and F_STfilters are available to further refine queries, while results can be visually compared with other large-scale Single Nucleotide Polymorphism (SNP) repositories such as HapMap or Perlegen.</p> <p>Conclusions</p> <p>ENGINES is capable of accessing large-scale variation data repositories in a fast and comprehensive manner. It allows quick browsing of whole genome variation, while providing statistical information for each variant site such as allele frequency, heterozygosity or F_STvalues for genetic differentiation. Access to the data mart generating scripts and to the web interface is granted from <url>http://spsmart.cesga.es/engines.php</url></p

Quality research in healthcare: are researchers getting enough statistical support?

BACKGROUND: Reviews of peer-reviewed health studies have highlighted problems with their methodological quality. As published health studies form the basis of many clinical decisions including evaluation and provisions of health services, this has scientific and ethical implications. The lack of involvement of methodologists (defined as statisticians or quantitative epidemiologists) has been suggested as one key reason for this problem and this has been linked to the lack of access to methodologists. This issue was highlighted several years ago and it was suggested that more investments were needed from health care organisations and Universities to alleviate this problem. METHODS: To assess the current level of methodological support available for health researchers in England, we surveyed the 25 National Health Services Trusts in England, that are the major recipients of the Department of Health's research and development (R&D) support funding. RESULTS AND DISCUSSION: The survey shows that the earmarking of resources to provide appropriate methodological support to health researchers in these organisations is not widespread. Neither the level of R&D support funding received nor the volume of research undertaken by these organisations showed any association with the amount they spent in providing a central resource for methodological support for their researchers. CONCLUSION: The promotion and delivery of high quality health research requires that organisations hosting health research and their academic partners put in place funding and systems to provide appropriate methodological support to ensure valid research findings. If resources are limited, health researchers may have to rely on short courses and/or a limited number of advisory sessions which may not always produce satisfactory results

Large Scale Structure of the Universe

Galaxies are not uniformly distributed in space. On large scales the Universe displays coherent structure, with galaxies residing in groups and clusters on scales of ~1-3 Mpc/h, which lie at the intersections of long filaments of galaxies that are >10 Mpc/h in length. Vast regions of relatively empty space, known as voids, contain very few galaxies and span the volume in between these structures. This observed large scale structure depends both on cosmological parameters and on the formation and evolution of galaxies. Using the two-point correlation function, one can trace the dependence of large scale structure on galaxy properties such as luminosity, color, stellar mass, and track its evolution with redshift. Comparison of the observed galaxy clustering signatures with dark matter simulations allows one to model and understand the clustering of galaxies and their formation and evolution within their parent dark matter halos. Clustering measurements can determine the parent dark matter halo mass of a given galaxy population, connect observed galaxy populations at different epochs, and constrain cosmological parameters and galaxy evolution models. This chapter describes the methods used to measure the two-point correlation function in both redshift and real space, presents the current results of how the clustering amplitude depends on various galaxy properties, and discusses quantitative measurements of the structures of voids and filaments. The interpretation of these results with current theoretical models is also presented.Comment: Invited contribution to be published in Vol. 8 of book "Planets, Stars, and Stellar Systems", Springer, series editor T. D. Oswalt, volume editor W. C. Keel, v2 includes additional references, updated to match published versio

No evidence for association between SLC11A1 and visceral leishmaniasis in India.

BACKGROUND: SLC11A1 has pleiotropic effects on macrophage function and remains a strong candidate for infectious disease susceptibility. 5' and/or 3' polymorphisms have been associated with tuberculosis, leprosy, and visceral leishmaniasis (VL). Most studies undertaken to date were under-powered, and none has been replicated within a population. Association with tuberculosis has replicated variably across populations. Here we investigate SLC11A1 and VL in India. METHODS: Nine polymorphisms (rs34448891, rs7573065, rs2276631, rs3731865, rs17221959, rs2279015, rs17235409, rs17235416, rs17229009) that tag linkage disequilibrium blocks across SLC11A1 were genotyped in primary family-based (313 cases; 176 families) and replication (941 cases; 992 controls) samples. Family- and population-based analyses were performed to look for association between SLC11A1 variants and VL. Quantitative RT/PCR was used to compare SLC11A1 expression in mRNA from paired splenic aspirates taken before and after treatment from 24 VL patients carrying different genotypes at the functional promoter GTn polymorphism (rs34448891). RESULTS: No associations were observed between VL and polymorphisms at SLC11A1 that were either robust to correction for multiple testing or replicated across primary and replication samples. No differences in expression of SLC11A1 were observed when comparing pre- and post-treatment samples, or between individuals carrying different genotypes at the GTn repeat. CONCLUSIONS: This is the first well-powered study of SLC11A1 as a candidate for VL, which we conclude does not have a major role in regulating VL susceptibility in India.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

What is a hospital bed day worth? A contingent valuation study of hospital Chief Executive Officers

BACKGROUND: Decreasing hospital length of stay, and so freeing up hospital beds, represents an important cost saving which is often used in economic evaluations. The savings need to be accurately quantified in order to make optimal health care resource allocation decisions. Traditionally the accounting cost of a bed is used. We argue instead that the economic cost of a bed day is the better value for making resource decisions, and we describe our valuation method and estimations for costing this important resource. METHODS: We performed a contingent valuation using 37 Australian Chief Executive Officers’ (CEOs) willingness to pay (WTP) to release bed days in their hospitals, both generally and using specific cases. We provide a succinct thematic analysis from qualitative interviews post survey completion, which provide insight into the decision making process. RESULTS: On average CEOs are willing to pay a marginal rate of $216 for a ward bed day and$436 for an Intensive Care Unit (ICU) bed day, with estimates of uncertainty being greater for ICU beds. These estimates are significantly lower (four times for ward beds and seven times for ICU beds) than the traditional accounting costs often used. Key themes to emerge from the interviews include the importance of national funding and targets, and their associated incentive structures, as well as the aversion to discuss bed days as an economic resource. CONCLUSIONS: This study highlights the importance for valuing bed days as an economic resource to inform cost effectiveness models and thus improve hospital decision making and resource allocation. Significantly under or over valuing the resource is very likely to result in sub-optimal decision making. We discuss the importance of recognising the opportunity costs of this resource and highlight areas for future research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12913-017-2079-5) contains supplementary material, which is available to authorized users

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P &lt; 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk