Challenges of DNA-based mark-recapture studies of American black bears

USGS Publications Warehouse

Settlage, K.E.; Van Manen, F.T.; Clark, J.D.; King, T.L.

2008-01-01

We explored whether genetic sampling would be feasible to provide a region-wide population estimate for American black bears (Ursus americanus) in the southern Appalachians, USA. Specifically, we determined whether adequate capture probabilities (p >0.20) and population estimates with a low coefficient of variation (CV <20%) could be achieved given typical agency budget and personnel constraints. We extracted DNA from hair collected from baited barbed-wire enclosures sampled over a 10-week period on 2 study areas: a high-density black bear population in a portion of Great Smoky Mountains National Park and a lower density population on National Forest lands in North Carolina, South Carolina, and Georgia. We identified individual bears by their unique genotypes obtained from 9 microsatellite loci. We sampled 129 and 60 different bears in the National Park and National Forest study areas, respectively, and applied closed mark–recapture models to estimate population abundance. Capture probabilities and precision of the population estimates were acceptable only for sampling scenarios for which we pooled weekly sampling periods. We detected capture heterogeneity biases, probably because of inadequate spatial coverage by the hair-trapping grid. The logistical challenges of establishing and checking a sufficiently high density of hair traps make DNA-based estimates of black bears impractical for the southern Appalachian region. Alternatives are to estimate population size for smaller areas, estimate population growth rates or survival using mark–recapture methods, or use independent marking and recapturing techniques to reduce capture heterogeneity.

Direct comparisons of Illumina vs. Roche 454 sequencing technologies on the same microbial community DNA sample.

PubMed

Luo, Chengwei; Tsementzi, Despina; Kyrpides, Nikos; Read, Timothy; Konstantinidis, Konstantinos T

2012-01-01

Next-generation sequencing (NGS) is commonly used in metagenomic studies of complex microbial communities but whether or not different NGS platforms recover the same diversity from a sample and their assembled sequences are of comparable quality remain unclear. We compared the two most frequently used platforms, the Roche 454 FLX Titanium and the Illumina Genome Analyzer (GA) II, on the same DNA sample obtained from a complex freshwater planktonic community. Despite the substantial differences in read length and sequencing protocols, the platforms provided a comparable view of the community sampled. For instance, derived assemblies overlapped in ~90% of their total sequences and in situ abundances of genes and genotypes (estimated based on sequence coverage) correlated highly between the two platforms (R(2)>0.9). Evaluation of base-call error, frameshift frequency, and contig length suggested that Illumina offered equivalent, if not better, assemblies than Roche 454. The results from metagenomic samples were further validated against DNA samples of eighteen isolate genomes, which showed a range of genome sizes and G+C% content. We also provide quantitative estimates of the errors in gene and contig sequences assembled from datasets characterized by different levels of complexity and G+C% content. For instance, we noted that homopolymer-associated, single-base errors affected ~1% of the protein sequences recovered in Illumina contigs of 10× coverage and 50% G+C; this frequency increased to ~3% when non-homopolymer errors were also considered. Collectively, our results should serve as a useful practical guide for choosing proper sampling strategies and data possessing protocols for future metagenomic studies.

AD-LIBS: inferring ancestry across hybrid genomes using low-coverage sequence data.

PubMed

Schaefer, Nathan K; Shapiro, Beth; Green, Richard E

2017-04-04

Inferring the ancestry of each region of admixed individuals' genomes is useful in studies ranging from disease gene mapping to speciation genetics. Current methods require high-coverage genotype data and phased reference panels, and are therefore inappropriate for many data sets. We present a software application, AD-LIBS, that uses a hidden Markov model to infer ancestry across hybrid genomes without requiring variant calling or phasing. This approach is useful for non-model organisms and in cases of low-coverage data, such as ancient DNA. We demonstrate the utility of AD-LIBS with synthetic data. We then use AD-LIBS to infer ancestry in two published data sets: European human genomes with Neanderthal ancestry and brown bear genomes with polar bear ancestry. AD-LIBS correctly infers 87-91% of ancestry in simulations and produces ancestry maps that agree with published results and global ancestry estimates in humans. In brown bears, we find more polar bear ancestry than has been published previously, using both AD-LIBS and an existing software application for local ancestry inference, HAPMIX. We validate AD-LIBS polar bear ancestry maps by recovering a geographic signal within bears that mirrors what is seen in SNP data. Finally, we demonstrate that AD-LIBS is more effective than HAPMIX at inferring ancestry when preexisting phased reference data are unavailable and genomes are sequenced to low coverage. AD-LIBS is an effective tool for ancestry inference that can be used even when few individuals are available for comparison or when genomes are sequenced to low coverage. AD-LIBS is therefore likely to be useful in studies of non-model or ancient organisms that lack large amounts of genomic DNA. AD-LIBS can therefore expand the range of studies in which admixture mapping is a viable tool.

Estimating genotype error rates from high-coverage next-generation sequence data.

PubMed

Wall, Jeffrey D; Tang, Ling Fung; Zerbe, Brandon; Kvale, Mark N; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil

2014-11-01

Exome and whole-genome sequencing studies are becoming increasingly common, but little is known about the accuracy of the genotype calls made by the commonly used platforms. Here we use replicate high-coverage sequencing of blood and saliva DNA samples from four European-American individuals to estimate lower bounds on the error rates of Complete Genomics and Illumina HiSeq whole-genome and whole-exome sequencing. Error rates for nonreference genotype calls range from 0.1% to 0.6%, depending on the platform and the depth of coverage. Additionally, we found (1) no difference in the error profiles or rates between blood and saliva samples; (2) Complete Genomics sequences had substantially higher error rates than Illumina sequences had; (3) error rates were higher (up to 6%) for rare or unique variants; (4) error rates generally declined with genotype quality (GQ) score, but in a nonlinear fashion for the Illumina data, likely due to loss of specificity of GQ scores greater than 60; and (5) error rates increased with increasing depth of coverage for the Illumina data. These findings, especially (3)-(5), suggest that caution should be taken in interpreting the results of next-generation sequencing-based association studies, and even more so in clinical application of this technology in the absence of validation by other more robust sequencing or genotyping methods. © 2014 Wall et al.; Published by Cold Spring Harbor Laboratory Press.

Determining the specific microbial populations and their spatial distribution within the stromatolite ecosystem of Shark Bay.

PubMed

Goh, Falicia; Allen, Michelle A; Leuko, Stefan; Kawaguchi, Tomohiro; Decho, Alan W; Burns, Brendan P; Neilan, Brett A

2009-04-01

The stromatolites at Shark Bay, Western Australia, are analogues of some of the oldest evidence of life on Earth. The aim of this study was to identify and spatially characterize the specific microbial communities associated with Shark Bay intertidal columnar stromatolites. Conventional culturing methods and construction of 16S rDNA clone libraries from community genomic DNA with both universal and specific PCR primers were employed. The estimated coverage, richness and diversity of stromatolite microbial populations were compared with earlier studies on these ecosystems. The estimated coverage for all clone libraries indicated that population coverage was comprehensive. Phylogenetic analyses of stromatolite and surrounding seawater sequences were performed in ARB with the Greengenes database of full-length non-chimaeric 16S rRNA genes. The communities identified exhibited extensive diversity. The most abundant sequences from the stromatolites were alpha- and gamma-proteobacteria (58%), whereas the cyanobacterial community was characterized by sequences related to the genera Euhalothece, Gloeocapsa, Gloeothece, Chroococcidiopsis, Dermocarpella, Acaryochloris, Geitlerinema and Schizothrix. All clones from the archaeal-specific clone libraries were related to the halophilic archaea; however, no archaeal sequence was identified from the surrounding seawater. Fluorescence in situ hybridization also revealed stromatolite surfaces to be dominated by unicellular cyanobacteria, in contrast to the sub-surface archaea and sulphate-reducing bacteria. This study is the first to compare the microbial composition of morphologically similar stromatolites over time and examine the spatial distribution of specific microorganismic groups in these intertidal structures and the surrounding seawater at Shark Bay. The results provide a platform for identifying the key microbial physiology groups and their potential roles in modern stromatolite morphogenesis and ecology.

Revisiting the ichthyodiversity of Java and Bali through DNA barcodes: taxonomic coverage, identification accuracy, cryptic diversity and identification of exotic species.

PubMed

Dahruddin, Hadi; Hutama, Aditya; Busson, Frédéric; Sauri, Sopian; Hanner, Robert; Keith, Philippe; Hadiaty, Renny; Hubert, Nicolas

2017-03-01

Among the 899 species of freshwater fishes reported from Sundaland biodiversity hotspot, nearly 50% are endemics. The functional integrity of aquatic ecosystems is currently jeopardized by human activities, and landscape conversion led to the decline of fish populations in several part of Sundaland, particularly in Java. The inventory of the Javanese ichthyofauna has been discontinuous, and the taxonomic knowledge is scattered in the literature. This study provides a DNA barcode reference library for the inland fishes of Java and Bali with the aim to streamline the inventory of fishes in this part of Sundaland. Owing to the lack of available checklist for estimating the taxonomic coverage of this study, a checklist was compiled based on online catalogues. A total of 95 sites were visited, and a library including 1046 DNA barcodes for 159 species was assembled. Nearest neighbour distance was 28-fold higher than maximum intraspecific distance on average, and a DNA barcoding gap was observed. The list of species with DNA barcodes displayed large discrepancies with the checklist compiled here as only 36% (i.e. 77 species) and 60% (i.e. 24 species) of the known species were sampled in Java and Bali, respectively. This result was contrasted by a high number of new occurrences and the ceiling of the accumulation curves for both species and genera. These results highlight the poor taxonomic knowledge of this ichthyofauna, and the apparent discrepancy between present and historical occurrence data is to be attributed to species extirpations, synonymy and misidentifications in previous studies. © 2016 John Wiley & Sons Ltd.

Improved Analysis of Nanopore Sequence Data and Scanning Nanopore Techniques

NASA Astrophysics Data System (ADS)

Szalay, Tamas

The field of nanopore research has been driven by the need to inexpensively and rapidly sequence DNA. In order to help realize this goal, this thesis describes the PoreSeq algorithm that identifies and corrects errors in real-world nanopore sequencing data and improves the accuracy of de novo genome assembly with increasing coverage depth. The approach relies on modeling the possible sources of uncertainty that occur as DNA advances through the nanopore and then using this model to find the sequence that best explains multiple reads of the same region of DNA. PoreSeq increases nanopore sequencing read accuracy of M13 bacteriophage DNA from 85% to 99% at 100X coverage. We also use the algorithm to assemble E. coli with 30X coverage and the lambda genome at a range of coverages from 3X to 50X. Additionally, we classify sequence variants at an order of magnitude lower coverage than is possible with existing methods. This thesis also reports preliminary progress towards controlling the motion of DNA using two nanopores instead of one. The speed at which the DNA travels through the nanopore needs to be carefully controlled to facilitate the detection of individual bases. A second nanopore in close proximity to the first could be used to slow or stop the motion of the DNA in order to enable a more accurate readout. The fabrication process for a new pyramidal nanopore geometry was developed in order to facilitate the positioning of the nanopores. This thesis demonstrates that two of them can be placed close enough to interact with a single molecule of DNA, which is a prerequisite for being able to use the driving force of the pores to exert fine control over the motion of the DNA. Another strategy for reading the DNA is to trap it completely with one pore and to move the second nanopore instead. To that end, this thesis also shows that a single strand of immobilized DNA can be captured in a scanning nanopore and examined for a full hour, with data from many scans at many different voltages obtained in order to detect a bound protein placed partway along the molecule.

Making medical decisions in dependence of genetic background: estimation of the utility of DNA testing in clinical, pharmaco-epidemiological or genetic studies.

PubMed

Nguyen, Thuy Trang; Schäfer, Helmut; Timmesfeld, Nina

2013-05-01

An index measuring the utility of testing a DNA marker before deciding between two alternative treatments is proposed which can be estimated from pharmaco-epidemiological case-control or cohort studies. In the case-control design, external estimates of the prevalence of the disease and of the frequency of the genetic risk variant are required for estimating the utility index. Formulas for point and interval estimates are derived. Empirical coverage probabilities of the confidence intervals were estimated under different scenarios of disease prevalence, prevalence of drug use, and population frequency of the genetic variant. To illustrate our method, we re-analyse pharmaco-epidemiological case-control data on oral contraceptive intake and venous thrombosis in carriers and non-carriers of the factor V Leiden mutation. We also re-analyse cross-sectional data from the Framingham study on a gene-diet interaction between an APOA2 polymorphism and high saturated fat intake on obesity. We conclude that the utility index may be helpful to evaluate and appraise the potential clinical and public health relevance of gene-environment interaction effects detected in genomic and candidate gene association studies and may be a valuable decision support for designing prospective studies on the clinical utility. © 2013 Wiley Periodicals, Inc.

Health and economic impact of HPV 16 and 18 vaccination and cervical cancer screening in India

PubMed Central

Diaz, M; Kim, J J; Albero, G; de Sanjosé, S; Clifford, G; Bosch, F X; Goldie, S J

2008-01-01

Cervical cancer is a leading cause of cancer death among women in low-income countries, with ∼25% of cases worldwide occurring in India. We estimated the potential health and economic impact of different cervical cancer prevention strategies. After empirically calibrating a cervical cancer model to country-specific epidemiologic data, we projected cancer incidence, life expectancy, and lifetime costs (I$2005), and calculated incremental cost-effectiveness ratios (I$/YLS) for the following strategies: pre-adolescent vaccination of girls before age 12, screening of women over age 30, and combined vaccination and screening. Screening differed by test (cytology, visual inspection, HPV DNA testing), number of clinical visits (1, 2 or 3), frequency (1 × , 2 × , 3 × per lifetime), and age range (35–45). Vaccine efficacy, coverage, and costs were varied in sensitivity analyses. Assuming 70% coverage, mean reduction in lifetime cancer risk was 44% (range, 28–57%) with HPV 16,18 vaccination alone, and 21–33% with screening three times per lifetime. Combining vaccination and screening three times per lifetime provided a mean reduction of 56% (vaccination plus 3-visit conventional cytology) to 63% (vaccination plus 2-visit HPV DNA testing). At a cost per vaccinated girl of I$10 (per dose cost of $2), pre-adolescent vaccination followed by screening three times per lifetime using either VIA or HPV DNA testing, would be considered cost-effective using the country's per capita gross domestic product (I$3452) as a threshold. In India, if high coverage of pre-adolescent girls with a low-cost HPV vaccine that provides long-term protection is achievable, vaccination followed by screening three times per lifetime is expected to reduce cancer deaths by half, and be cost-effective. PMID:18612311

Estimating the coverage of mental health programmes: a systematic review.

PubMed

De Silva, Mary J; Lee, Lucy; Fuhr, Daniela C; Rathod, Sujit; Chisholm, Dan; Schellenberg, Joanna; Patel, Vikram

2014-04-01

The large treatment gap for people suffering from mental disorders has led to initiatives to scale up mental health services. In order to track progress, estimates of programme coverage, and changes in coverage over time, are needed. Systematic review of mental health programme evaluations that assess coverage, measured either as the proportion of the target population in contact with services (contact coverage) or as the proportion of the target population who receive appropriate and effective care (effective coverage). We performed a search of electronic databases and grey literature up to March 2013 and contacted experts in the field. Methods to estimate the numerator (service utilization) and the denominator (target population) were reviewed to explore methods which could be used in programme evaluations. We identified 15 735 unique records of which only seven met the inclusion criteria. All studies reported contact coverage. No study explicitly measured effective coverage, but it was possible to estimate this for one study. In six studies the numerator of coverage, service utilization, was estimated using routine clinical information, whereas one study used a national community survey. The methods for estimating the denominator, the population in need of services, were more varied and included national prevalence surveys case registers, and estimates from the literature. Very few coverage estimates are available. Coverage could be estimated at low cost by combining routine programme data with population prevalence estimates from national surveys.

Improved multiple displacement amplification (iMDA) and ultraclean reagents.

PubMed

Motley, S Timothy; Picuri, John M; Crowder, Chris D; Minich, Jeremiah J; Hofstadler, Steven A; Eshoo, Mark W

2014-06-06

Next-generation sequencing sample preparation requires nanogram to microgram quantities of DNA; however, many relevant samples are comprised of only a few cells. Genomic analysis of these samples requires a whole genome amplification method that is unbiased and free of exogenous DNA contamination. To address these challenges we have developed protocols for the production of DNA-free consumables including reagents and have improved upon multiple displacement amplification (iMDA). A specialized ethylene oxide treatment was developed that renders free DNA and DNA present within Gram positive bacterial cells undetectable by qPCR. To reduce DNA contamination in amplification reagents, a combination of ion exchange chromatography, filtration, and lot testing protocols were developed. Our multiple displacement amplification protocol employs a second strand-displacing DNA polymerase, improved buffers, improved reaction conditions and DNA free reagents. The iMDA protocol, when used in combination with DNA-free laboratory consumables and reagents, significantly improved efficiency and accuracy of amplification and sequencing of specimens with moderate to low levels of DNA. The sensitivity and specificity of sequencing of amplified DNA prepared using iMDA was compared to that of DNA obtained with two commercial whole genome amplification kits using 10 fg (~1-2 bacterial cells worth) of bacterial genomic DNA as a template. Analysis showed >99% of the iMDA reads mapped to the template organism whereas only 0.02% of the reads from the commercial kits mapped to the template. To assess the ability of iMDA to achieve balanced genomic coverage, a non-stochastic amount of bacterial genomic DNA (1 pg) was amplified and sequenced, and data obtained were compared to sequencing data obtained directly from genomic DNA. The iMDA DNA and genomic DNA sequencing had comparable coverage 99.98% of the reference genome at ≥1X coverage and 99.9% at ≥5X coverage while maintaining both balance and representation of the genome. The iMDA protocol in combination with DNA-free laboratory consumables, significantly improved the ability to sequence specimens with low levels of DNA. iMDA has broad utility in metagenomics, diagnostics, ancient DNA analysis, pre-implantation embryo screening, single-cell genomics, whole genome sequencing of unculturable organisms, and forensic applications for both human and microbial targets.

Quantification of differential gene expression by multiplexed targeted resequencing of cDNA

PubMed Central

Arts, Peer; van der Raadt, Jori; van Gestel, Sebastianus H.C.; Steehouwer, Marloes; Shendure, Jay; Hoischen, Alexander; Albers, Cornelis A.

2017-01-01

Whole-transcriptome or RNA sequencing (RNA-Seq) is a powerful and versatile tool for functional analysis of different types of RNA molecules, but sample reagent and sequencing cost can be prohibitive for hypothesis-driven studies where the aim is to quantify differential expression of a limited number of genes. Here we present an approach for quantification of differential mRNA expression by targeted resequencing of complementary DNA using single-molecule molecular inversion probes (cDNA-smMIPs) that enable highly multiplexed resequencing of cDNA target regions of ∼100 nucleotides and counting of individual molecules. We show that accurate estimates of differential expression can be obtained from molecule counts for hundreds of smMIPs per reaction and that smMIPs are also suitable for quantification of relative gene expression and allele-specific expression. Compared with low-coverage RNA-Seq and a hybridization-based targeted RNA-Seq method, cDNA-smMIPs are a cost-effective high-throughput tool for hypothesis-driven expression analysis in large numbers of genes (10 to 500) and samples (hundreds to thousands). PMID:28474677

Cervical Cancer Screening in Low-Resource Settings: A Cost-Effectiveness Framework for Valuing Tradeoffs between Test Performance and Program Coverage

PubMed Central

Campos, Nicole G.; Castle, Philip E.; Wright, Thomas C.; Kim, Jane J.

2016-01-01

As cervical cancer screening programs are implemented in low-resource settings, protocols are needed to maximize health benefits under operational constraints. Our objective was to develop a framework for examining health and economic tradeoffs between screening test sensitivity, population coverage, and follow-up of screen-positive women, to help decision makers identify where program investments yield the greatest value. As an illustrative example, we used an individual-based Monte Carlo simulation model of the natural history of human papillomavirus (HPV) and cervical cancer calibrated to epidemiologic data from Uganda. We assumed once in a lifetime screening at age 35 with two-visit HPV DNA testing or one-visit visual inspection with acetic acid (VIA). We assessed the health and economic tradeoffs that arise between 1) test sensitivity and screening coverage; 2) test sensitivity and loss to follow-up (LTFU) of screen-positive women; and 3) test sensitivity, screening coverage, and LTFU simultaneously. The decline in health benefits associated with sacrificing HPV DNA test sensitivity by 20% (e.g., shifting from provider- to self-collection of specimens) could be offset by gains in coverage if coverage increased by at least 20%. When LTFU was 10%, two-visit HPV DNA testing with 80-90% sensitivity was more effective and more cost-effective than one-visit VIA with 40% sensitivity, and yielded greater health benefits than VIA even as VIA sensitivity increased to 60% and HPV test sensitivity declined to 70%. As LTFU increased, two-visit HPV DNA testing became more costly and less effective than one-visit VIA. Setting-specific data on achievable test sensitivity, coverage, follow-up rates, and programmatic costs are needed to guide programmatic decision making for cervical cancer screening. PMID:25943074

Estimating the coverage of mental health programmes: a systematic review

PubMed Central

De Silva, Mary J; Lee, Lucy; Fuhr, Daniela C; Rathod, Sujit; Chisholm, Dan; Schellenberg, Joanna; Patel, Vikram

2014-01-01

Background The large treatment gap for people suffering from mental disorders has led to initiatives to scale up mental health services. In order to track progress, estimates of programme coverage, and changes in coverage over time, are needed. Methods Systematic review of mental health programme evaluations that assess coverage, measured either as the proportion of the target population in contact with services (contact coverage) or as the proportion of the target population who receive appropriate and effective care (effective coverage). We performed a search of electronic databases and grey literature up to March 2013 and contacted experts in the field. Methods to estimate the numerator (service utilization) and the denominator (target population) were reviewed to explore methods which could be used in programme evaluations. Results We identified 15 735 unique records of which only seven met the inclusion criteria. All studies reported contact coverage. No study explicitly measured effective coverage, but it was possible to estimate this for one study. In six studies the numerator of coverage, service utilization, was estimated using routine clinical information, whereas one study used a national community survey. The methods for estimating the denominator, the population in need of services, were more varied and included national prevalence surveys case registers, and estimates from the literature. Conclusions Very few coverage estimates are available. Coverage could be estimated at low cost by combining routine programme data with population prevalence estimates from national surveys. PMID:24760874

Cost-effectiveness of an HPV self-collection campaign in Uganda: comparing models for delivery of cervical cancer screening in a low-income setting

PubMed Central

Campos, Nicole G; Tsu, Vivien; Jeronimo, Jose; Njama-Meya, Denise; Mvundura, Mercy; Kim, Jane J

2017-01-01

Abstract With the availability of a low-cost HPV DNA test that can be administered by either a healthcare provider or a woman herself, programme planners require information on the costs and cost-effectiveness of implementing cervical cancer screening programmes in low-resource settings under different models of healthcare delivery. Using data from the START-UP demonstration project and a micro-costing approach, we estimated the health and economic impact of once-in-a-lifetime HPV self-collection campaign relative to clinic-based provider-collection of HPV specimens in Uganda. We used an individual-based Monte Carlo simulation model of the natural history of HPV and cervical cancer to estimate lifetime health and economic outcomes associated with screening with HPV DNA testing once in a lifetime (clinic-based provider-collection vs a self-collection campaign). Test performance and cost data were obtained from the START-UP demonstration project using a micro-costing approach. Model outcomes included lifetime risk of cervical cancer, total lifetime costs (in 2011 international dollars [I$]), and life expectancy. Cost-effectiveness ratios were expressed using incremental cost-effectiveness ratios (ICERs). When both strategies achieved 75% population coverage, ICERs were below Uganda’s per capita GDP (self-collection: I$80 per year of life saved [YLS]; provider-collection: I$120 per YLS). When the self-collection campaign achieved coverage gains of 15–20%, it was more effective than provider-collection, and had a lower ICER unless coverage with both strategies was 50% or less. Findings were sensitive to cryotherapy compliance among screen-positive women and relative HPV test performance. The primary limitation of this analysis is that self-collection costs are based on a hypothetical campaign but are based on unit costs from Uganda. Once-in-a-lifetime screening with HPV self-collection may be very cost-effective and reduce cervical cancer risk by > 20% if coverage is high. Demonstration projects will be needed to confirm the validity of our logistical, costing and compliance assumptions. PMID:28369405

Cost-effectiveness of an HPV self-collection campaign in Uganda: comparing models for delivery of cervical cancer screening in a low-income setting.

PubMed

Campos, Nicole G; Tsu, Vivien; Jeronimo, Jose; Njama-Meya, Denise; Mvundura, Mercy; Kim, Jane J

2017-09-01

With the availability of a low-cost HPV DNA test that can be administered by either a healthcare provider or a woman herself, programme planners require information on the costs and cost-effectiveness of implementing cervical cancer screening programmes in low-resource settings under different models of healthcare delivery. Using data from the START-UP demonstration project and a micro-costing approach, we estimated the health and economic impact of once-in-a-lifetime HPV self-collection campaign relative to clinic-based provider-collection of HPV specimens in Uganda. We used an individual-based Monte Carlo simulation model of the natural history of HPV and cervical cancer to estimate lifetime health and economic outcomes associated with screening with HPV DNA testing once in a lifetime (clinic-based provider-collection vs a self-collection campaign). Test performance and cost data were obtained from the START-UP demonstration project using a micro-costing approach. Model outcomes included lifetime risk of cervical cancer, total lifetime costs (in 2011 international dollars [I$]), and life expectancy. Cost-effectiveness ratios were expressed using incremental cost-effectiveness ratios (ICERs). When both strategies achieved 75% population coverage, ICERs were below Uganda's per capita GDP (self-collection: I$80 per year of life saved [YLS]; provider-collection: I$120 per YLS). When the self-collection campaign achieved coverage gains of 15-20%, it was more effective than provider-collection, and had a lower ICER unless coverage with both strategies was 50% or less. Findings were sensitive to cryotherapy compliance among screen-positive women and relative HPV test performance. The primary limitation of this analysis is that self-collection costs are based on a hypothetical campaign but are based on unit costs from Uganda. Once-in-a-lifetime screening with HPV self-collection may be very cost-effective and reduce cervical cancer risk by > 20% if coverage is high. Demonstration projects will be needed to confirm the validity of our logistical, costing and compliance assumptions. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Estimating P-coverage of biosynthetic pathways in DNA libraries and screening by genetic selection: biotin biosynthesis in the marine microorganism Chromohalobacter.

PubMed

Kim, Eun Jin; Angell, Scott; Janes, Jeff; Watanabe, Coran M H

2008-06-01

Traditional approaches to natural product discovery involve cell-based screening of natural product extracts followed by compound isolation and characterization. Their importance notwithstanding, continued mining leads to depletion of natural resources and the reisolation of previously identified metabolites. Metagenomic strategies aimed at localizing the biosynthetic cluster genes and expressing them in surrogate hosts offers one possible alternative. A fundamental question that naturally arises when pursuing such a strategy is, how large must the genomic library be to effectively represent the genome of an organism(s) and the biosynthetic gene clusters they harbor? Such an issue is certainly augmented in the absence of expensive robotics to expedite colony picking and/or screening of clones. We have developed an algorism, named BPC (biosynthetic pathway coverage), supported by molecular simulations to deduce the number of BAC clones required to achieve proper coverage of the genome and their respective biosynthetic pathways. The strategy has been applied to the construction of a large-insert BAC library from a marine microorganism, Hon6 (isolated from Honokohau, Maui) thought to represent a new species. The genomic library is constructed with a BAC yeast shuttle vector pClasper lacZ paving the way for the culturing of libraries in both prokaryotic and eukaryotic hosts. Flow cytometric methods are utilized to estimate the genome size of the organism and BPC implemented to assess P-coverage or percent coverage. A genetic selection strategy is illustrated, applications of which could expedite screening efforts in the identification and localization of biosynthetic pathways from marine microbial consortia, offering a powerful complement to genome sequencing and degenerate probe strategies. Implementing this approach, we report on the biotin biosynthetic pathway from the marine microorganism Hon6.

Cost-effectiveness of increasing cervical cancer screening coverage in the Middle East: An example from Lebanon.

PubMed

Sharma, Monisha; Seoud, Muhieddine; Kim, Jane J

2017-01-23

Most cervical cancer (CC) cases in Lebanon are detected at later stages and associated with high mortality. There is no national organized CC screening program so screening is opportunistic and limited to women who can pay out-of-pocket. Therefore, a small percentage of women receive repeated screenings while most are under-or never screened. We evaluated the cost-effectiveness of increasing screening coverage and extending intervals. We used an individual-based Monte Carlo model simulating HPV and CC natural history and screening. We calibrated the model to epidemiological data from Lebanon, including CC incidence and HPV type distribution. We evaluated cytology and HPV DNA screening for women aged 25-65years, varying coverage from 20 to 70% and frequency from 1 to 5years. At 20% coverage, annual cytologic screening reduced lifetime CC risk by 14% and had an incremental cost-effectiveness ratio of I$80,670/year of life saved (YLS), far exceeding Lebanon's gross domestic product (GDP) per capita (I$17,460), a commonly cited cost-effectiveness threshold. By comparison, increasing cytologic screening coverage to 50% and extending screening intervals to 3 and 5years provided greater CC reduction (26.1% and 21.4, respectively) at lower costs compared to 20% coverage with annual screening. Screening every 5years with HPV DNA testing at 50% coverage provided greater CC reductions than cytology at the same frequency (23.4%) and was cost-effective assuming a cost of I$18 per HPV test administered (I$12,210/YLS); HPV DNA testing every 4years at 50% coverage was also cost-effective at the same cost per test (I$16,340). Increasing coverage of annual cytology was not found to be cost-effective. Current practice of repeated cytology in a small percentage of women is inefficient. Increasing coverage to 50% with extended screening intervals provides greater health benefits at a reasonable cost and can more equitably distribute health gains. Novel HPV DNA strategies offer greater CC reductions and may be more cost-effective than cytology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modeling genome coverage in single-cell sequencing

PubMed Central

Daley, Timothy; Smith, Andrew D.

2014-01-01

Motivation: Single-cell DNA sequencing is necessary for examining genetic variation at the cellular level, which remains hidden in bulk sequencing experiments. But because they begin with such small amounts of starting material, the amount of information that is obtained from single-cell sequencing experiment is highly sensitive to the choice of protocol employed and variability in library preparation. In particular, the fraction of the genome represented in single-cell sequencing libraries exhibits extreme variability due to quantitative biases in amplification and loss of genetic material. Results: We propose a method to predict the genome coverage of a deep sequencing experiment using information from an initial shallow sequencing experiment mapped to a reference genome. The observed coverage statistics are used in a non-parametric empirical Bayes Poisson model to estimate the gain in coverage from deeper sequencing. This approach allows researchers to know statistical features of deep sequencing experiments without actually sequencing deeply, providing a basis for optimizing and comparing single-cell sequencing protocols or screening libraries. Availability and implementation: The method is available as part of the preseq software package. Source code is available at http://smithlabresearch.org/preseq. Contact: andrewds@usc.edu Supplementary information: Supplementary material is available at Bioinformatics online. PMID:25107873

Evaluating Childhood Vaccination Coverage of NIP Vaccines: Coverage Survey versus Zhejiang Provincial Immunization Information System.

PubMed

Hu, Yu; Chen, Yaping

2017-07-11

Vaccination coverage in Zhejiang province, east China, is evaluated through repeated coverage surveys. The Zhejiang provincial immunization information system (ZJIIS) was established in 2004 with links to all immunization clinics. ZJIIS has become an alternative to quickly assess the vaccination coverage. To assess the current completeness and accuracy on the vaccination coverage derived from ZJIIS, we compared the estimates from ZJIIS with the estimates from the most recent provincial coverage survey in 2014, which combined interview data with verified data from ZJIIS. Of the enrolled 2772 children in the 2014 provincial survey, the proportions of children with vaccination cards and registered in ZJIIS were 94.0% and 87.4%, respectively. Coverage estimates from ZJIIS were systematically higher than the corresponding estimates obtained through the survey, with a mean difference of 4.5%. Of the vaccination doses registered in ZJIIS, 16.7% differed from the date recorded in the corresponding vaccination cards. Under-registration in ZJIIS significantly influenced the coverage estimates derived from ZJIIS. Therefore, periodic coverage surveys currently provide more complete and reliable results than the estimates based on ZJIIS alone. However, further improvement of completeness and accuracy of ZJIIS will likely allow more reliable and timely estimates in future.

Calibrating genomic and allelic coverage bias in single-cell sequencing.

PubMed

Zhang, Cheng-Zhong; Adalsteinsson, Viktor A; Francis, Joshua; Cornils, Hauke; Jung, Joonil; Maire, Cecile; Ligon, Keith L; Meyerson, Matthew; Love, J Christopher

2015-04-16

Artifacts introduced in whole-genome amplification (WGA) make it difficult to derive accurate genomic information from single-cell genomes and require different analytical strategies from bulk genome analysis. Here, we describe statistical methods to quantitatively assess the amplification bias resulting from whole-genome amplification of single-cell genomic DNA. Analysis of single-cell DNA libraries generated by different technologies revealed universal features of the genome coverage bias predominantly generated at the amplicon level (1-10 kb). The magnitude of coverage bias can be accurately calibrated from low-pass sequencing (∼0.1 × ) to predict the depth-of-coverage yield of single-cell DNA libraries sequenced at arbitrary depths. We further provide a benchmark comparison of single-cell libraries generated by multi-strand displacement amplification (MDA) and multiple annealing and looping-based amplification cycles (MALBAC). Finally, we develop statistical models to calibrate allelic bias in single-cell whole-genome amplification and demonstrate a census-based strategy for efficient and accurate variant detection from low-input biopsy samples.

Calibrating genomic and allelic coverage bias in single-cell sequencing

PubMed Central

Francis, Joshua; Cornils, Hauke; Jung, Joonil; Maire, Cecile; Ligon, Keith L.; Meyerson, Matthew; Love, J. Christopher

2016-01-01

Artifacts introduced in whole-genome amplification (WGA) make it difficult to derive accurate genomic information from single-cell genomes and require different analytical strategies from bulk genome analysis. Here, we describe statistical methods to quantitatively assess the amplification bias resulting from whole-genome amplification of single-cell genomic DNA. Analysis of single-cell DNA libraries generated by different technologies revealed universal features of the genome coverage bias predominantly generated at the amplicon level (1–10 kb). The magnitude of coverage bias can be accurately calibrated from low-pass sequencing (~0.1 ×) to predict the depth-of-coverage yield of single-cell DNA libraries sequenced at arbitrary depths. We further provide a benchmark comparison of single-cell libraries generated by multi-strand displacement amplification (MDA) and multiple annealing and looping-based amplification cycles (MALBAC). Finally, we develop statistical models to calibrate allelic bias in single-cell whole-genome amplification and demonstrate a census-based strategy for efficient and accurate variant detection from low-input biopsy samples. PMID:25879913

Exploring mechanisms of transport and persistence of environmental DNA (eDNA)

NASA Astrophysics Data System (ADS)

Shogren, A.; Tank, J. L.; Riis, T.; Rosi, E. J.; Bolster, D.

2017-12-01

Sampling for eDNA is a non-intrusive method to detect species presence without direct observation, which allows for earlier detection and more rapid response than conventional sampling methods. However, our current understanding of how eDNA is transported and persists in flowing waters (e.g., streams and rivers) remains imprecise; in flowing waters, the target organism may be some distance away from where the eDNA in water is collected. It is uncertain how the unique transport properties of suspended eDNA or the inherent heterogeneity of natural flowing systems may impact the probability of downstream eDNA detection. To improve understanding of eDNA fate, we first conducted experimental releases and modeled the impact of benthic substrate heterogeneity and size on eDNA transport and retention in streams. We also used recirculating artificial streams to constrain estimates of eDNA degradation in systems with varying flow and microbial biofilm coverage. We found that eDNA retention in streams is substrate-specific, and that streambed hydraulics have significant influence on how far eDNA is transported downstream. Through the degradation experiments, we found that eDNA degradation is strongly context dependent, but even in systems with low velocity, eDNA can remain detectable in the water column >24hrs after introduction. This differential persistence of eDNA particles confirms that eDNA dynamics in flowing waters are not constant along a spatial continuum, which complicates interpretation of a positive detection in flowing waters, which presents a scaling problem for future modeling efforts to support transport predictions. To test our experimental results in a natural system, we compared our previous estimates for eDNA transport, retention, and degradation to field data collected during a longitudinal field survey for zebra mussel eDNA on the Gudena River in Silkeborg, Denmark. We found that though heterogeneity indeed complicates scaling efforts to extrapolate results from small experimental streams to larger natural systems, we can use the small-scale experiments to improve how we interpret spatial variation in eDNA signal in larger scale flowing systems.

Comparison of inflation of third dose diphtheria tetanus pertussis (DTP3) administrative coverage to other vaccine antigens.

PubMed

Dolan, Samantha B; MacNeil, Adam

2017-06-14

Third dose diphtheria tetanus pertussis (DTP3) administrative coverage is a commonly used indicator for immunization program performance, although studies have demonstrated data quality issues with administrative DTP3 coverage. It is possible that administrative coverage for DTP3 may be inflated more than for other antigens. To examine this, theory, we compiled immunization coverage estimates from recent country surveys (n=71) and paired these with corresponding administrative coverage estimates, by country and cohort year, for DTP3 and 4 other antigens. Median administrative coverage was higher than survey estimates of coverage for all antigens (median differences from 26 to 30%), however this difference was similar for DTP3 as for all other antigens. These findings were consistent when countries were stratified by income level and eligibility for Gavi funding. Our findings demonstrate that while country administrative coverage estimates tend to be higher than survey estimates, DTP3 administrative coverage is not inflated more than other antigens. Published by Elsevier Ltd.

Evaluating Childhood Vaccination Coverage of NIP Vaccines: Coverage Survey versus Zhejiang Provincial Immunization Information System

PubMed Central

Hu, Yu; Chen, Yaping

2017-01-01

Vaccination coverage in Zhejiang province, east China, is evaluated through repeated coverage surveys. The Zhejiang provincial immunization information system (ZJIIS) was established in 2004 with links to all immunization clinics. ZJIIS has become an alternative to quickly assess the vaccination coverage. To assess the current completeness and accuracy on the vaccination coverage derived from ZJIIS, we compared the estimates from ZJIIS with the estimates from the most recent provincial coverage survey in 2014, which combined interview data with verified data from ZJIIS. Of the enrolled 2772 children in the 2014 provincial survey, the proportions of children with vaccination cards and registered in ZJIIS were 94.0% and 87.4%, respectively. Coverage estimates from ZJIIS were systematically higher than the corresponding estimates obtained through the survey, with a mean difference of 4.5%. Of the vaccination doses registered in ZJIIS, 16.7% differed from the date recorded in the corresponding vaccination cards. Under-registration in ZJIIS significantly influenced the coverage estimates derived from ZJIIS. Therefore, periodic coverage surveys currently provide more complete and reliable results than the estimates based on ZJIIS alone. However, further improvement of completeness and accuracy of ZJIIS will likely allow more reliable and timely estimates in future. PMID:28696387

Two Birds With One Stone: Estimating Population Vaccination Coverage From a Test-negative Vaccine Effectiveness Case-control Study.

PubMed

Doll, Margaret K; Morrison, Kathryn T; Buckeridge, David L; Quach, Caroline

2016-10-15

Vaccination program evaluation includes assessment of vaccine uptake and direct vaccine effectiveness (VE). Often examined separately, we propose a design to estimate rotavirus vaccination coverage using controls from a rotavirus VE test-negative case-control study and to examine coverage following implementation of the Quebec, Canada, rotavirus vaccination program. We present our assumptions for using these data as a proxy for coverage in the general population, explore effects of diagnostic accuracy on coverage estimates via simulations, and validate estimates with an external source. We found 79.0% (95% confidence interval, 74.3%, 83.0%) ≥2-dose rotavirus coverage among participants eligible for publicly funded vaccination. No differences were detected between study and external coverage estimates. Simulations revealed minimal bias in estimates with high diagnostic sensitivity and specificity. We conclude that controls from a VE case-control study may be a valuable resource of coverage information when reasonable assumptions can be made for estimate generalizability; high rotavirus coverage demonstrates success of the Quebec program. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Deep sampling of the Palomero maize transcriptome by a high throughput strategy of pyrosequencing.

PubMed

Vega-Arreguín, Julio C; Ibarra-Laclette, Enrique; Jiménez-Moraila, Beatriz; Martínez, Octavio; Vielle-Calzada, Jean Philippe; Herrera-Estrella, Luis; Herrera-Estrella, Alfredo

2009-07-06

In-depth sequencing analysis has not been able to determine the overall complexity of transcriptional activity of a plant organ or tissue sample. In some cases, deep parallel sequencing of Expressed Sequence Tags (ESTs), although not yet optimized for the sequencing of cDNAs, has represented an efficient procedure for validating gene prediction and estimating overall gene coverage. This approach could be very valuable for complex plant genomes. In addition, little emphasis has been given to efforts aiming at an estimation of the overall transcriptional universe found in a multicellular organism at a specific developmental stage. To explore, in depth, the transcriptional diversity in an ancient maize landrace, we developed a protocol to optimize the sequencing of cDNAs and performed 4 consecutive GS20-454 pyrosequencing runs of a cDNA library obtained from 2 week-old Palomero Toluqueño maize plants. The protocol reported here allowed obtaining over 90% of informative sequences. These GS20-454 runs generated over 1.5 Million reads, representing the largest amount of sequences reported from a single plant cDNA library. A collection of 367,391 quality-filtered reads (30.09 Mb) from a single run was sufficient to identify transcripts corresponding to 34% of public maize ESTs databases; total sequences generated after 4 filtered runs increased this coverage to 50%. Comparisons of all 1.5 Million reads to the Maize Assembled Genomic Islands (MAGIs) provided evidence for the transcriptional activity of 11% of MAGIs. We estimate that 5.67% (86,069 sequences) do not align with public ESTs or annotated genes, potentially representing new maize transcripts. Following the assembly of 74.4% of the reads in 65,493 contigs, real-time PCR of selected genes confirmed a predicted correlation between the abundance of GS20-454 sequences and corresponding levels of gene expression. A protocol was developed that significantly increases the number, length and quality of cDNA reads using massive 454 parallel sequencing. We show that recurrent 454 pyrosequencing of a single cDNA sample is necessary to attain a thorough representation of the transcriptional universe present in maize, that can also be used to estimate transcript abundance of specific genes. This data suggests that the molecular and functional diversity contained in the vast native landraces remains to be explored, and that large-scale transcriptional sequencing of a presumed ancestor of the modern maize varieties represents a valuable approach to characterize the functional diversity of maize for future agricultural and evolutionary studies.

Development and application of a 6.5 million feature Affymetrix Genechip® for massively parallel discovery of single position polymorphisms in lettuce (Lactuca spp.)

PubMed Central

2012-01-01

Background High-resolution genetic maps are needed in many crops to help characterize the genetic diversity that determines agriculturally important traits. Hybridization to microarrays to detect single feature polymorphisms is a powerful technique for marker discovery and genotyping because of its highly parallel nature. However, microarrays designed for gene expression analysis rarely provide sufficient gene coverage for optimal detection of nucleotide polymorphisms, which limits utility in species with low rates of polymorphism such as lettuce (Lactuca sativa). Results We developed a 6.5 million feature Affymetrix GeneChip® for efficient polymorphism discovery and genotyping, as well as for analysis of gene expression in lettuce. Probes on the microarray were designed from 26,809 unigenes from cultivated lettuce and an additional 8,819 unigenes from four related species (L. serriola, L. saligna, L. virosa and L. perennis). Where possible, probes were tiled with a 2 bp stagger, alternating on each DNA strand; providing an average of 187 probes covering approximately 600 bp for each of over 35,000 unigenes; resulting in up to 13 fold redundancy in coverage per nucleotide. We developed protocols for hybridization of genomic DNA to the GeneChip® and refined custom algorithms that utilized coverage from multiple, high quality probes to detect single position polymorphisms in 2 bp sliding windows across each unigene. This allowed us to detect greater than 18,000 polymorphisms between the parental lines of our core mapping population, as well as numerous polymorphisms between cultivated lettuce and wild species in the lettuce genepool. Using marker data from our diversity panel comprised of 52 accessions from the five species listed above, we were able to separate accessions by species using both phylogenetic and principal component analyses. Additionally, we estimated the diversity between different types of cultivated lettuce and distinguished morphological types. Conclusion By hybridizing genomic DNA to a custom oligonucleotide array designed for maximum gene coverage, we were able to identify polymorphisms using two approaches for pair-wise comparisons, as well as a highly parallel method that compared all 52 genotypes simultaneously. PMID:22583801

Development and application of a 6.5 million feature Affymetrix Genechip® for massively parallel discovery of single position polymorphisms in lettuce (Lactuca spp.).

PubMed

Stoffel, Kevin; van Leeuwen, Hans; Kozik, Alexander; Caldwell, David; Ashrafi, Hamid; Cui, Xinping; Tan, Xiaoping; Hill, Theresa; Reyes-Chin-Wo, Sebastian; Truco, Maria-Jose; Michelmore, Richard W; Van Deynze, Allen

2012-05-14

High-resolution genetic maps are needed in many crops to help characterize the genetic diversity that determines agriculturally important traits. Hybridization to microarrays to detect single feature polymorphisms is a powerful technique for marker discovery and genotyping because of its highly parallel nature. However, microarrays designed for gene expression analysis rarely provide sufficient gene coverage for optimal detection of nucleotide polymorphisms, which limits utility in species with low rates of polymorphism such as lettuce (Lactuca sativa). We developed a 6.5 million feature Affymetrix GeneChip® for efficient polymorphism discovery and genotyping, as well as for analysis of gene expression in lettuce. Probes on the microarray were designed from 26,809 unigenes from cultivated lettuce and an additional 8,819 unigenes from four related species (L. serriola, L. saligna, L. virosa and L. perennis). Where possible, probes were tiled with a 2 bp stagger, alternating on each DNA strand; providing an average of 187 probes covering approximately 600 bp for each of over 35,000 unigenes; resulting in up to 13 fold redundancy in coverage per nucleotide. We developed protocols for hybridization of genomic DNA to the GeneChip® and refined custom algorithms that utilized coverage from multiple, high quality probes to detect single position polymorphisms in 2 bp sliding windows across each unigene. This allowed us to detect greater than 18,000 polymorphisms between the parental lines of our core mapping population, as well as numerous polymorphisms between cultivated lettuce and wild species in the lettuce genepool. Using marker data from our diversity panel comprised of 52 accessions from the five species listed above, we were able to separate accessions by species using both phylogenetic and principal component analyses. Additionally, we estimated the diversity between different types of cultivated lettuce and distinguished morphological types. By hybridizing genomic DNA to a custom oligonucleotide array designed for maximum gene coverage, we were able to identify polymorphisms using two approaches for pair-wise comparisons, as well as a highly parallel method that compared all 52 genotypes simultaneously.

Methods used for immunization coverage assessment in Canada, a Canadian Immunization Research Network (CIRN) study.

PubMed

Wilson, Sarah E; Quach, Susan; MacDonald, Shannon E; Naus, Monika; Deeks, Shelley L; Crowcroft, Natasha S; Mahmud, Salaheddin M; Tran, Dat; Kwong, Jeff; Tu, Karen; Gilbert, Nicolas L; Johnson, Caitlin; Desai, Shalini

2017-08-03

Accurate and complete immunization data are necessary to assess vaccine coverage, safety and effectiveness. Across Canada, different methods and data sources are used to assess vaccine coverage, but these have not been systematically described. Our primary objective was to examine and describe the methods used to determine immunization coverage in Canada. The secondary objective was to compare routine infant and childhood coverage estimates derived from the Canadian 2013 Childhood National Immunization Coverage Survey (cNICS) with estimates collected from provinces and territories (P/Ts). We collected information from key informants regarding their provincial, territorial or federal methods for assessing immunization coverage. We also collected P/T coverage estimates for select antigens and birth cohorts to determine absolute differences between these and estimates from cNICS. Twenty-six individuals across 16 public health organizations participated between April and August 2015. Coverage surveys are conducted regularly for toddlers in Quebec and in one health authority in British Columbia. Across P/Ts, different methodologies for measuring coverage are used (e.g., valid doses, grace periods). Most P/Ts, except Ontario, measure up-to-date (UTD) coverage and 4 P/Ts also assess on-time coverage. The degree of concordance between P/T and cNICS coverage estimates varied by jurisdiction, antigen and age group. In addition to differences in the data sources and processes used for coverage assessment, there are also differences between Canadian P/Ts in the methods used for calculating immunization coverage. Comparisons between P/T and cNICS estimates leave remaining questions about the proportion of children fully vaccinated in Canada.

Methods used for immunization coverage assessment in Canada, a Canadian Immunization Research Network (CIRN) study

PubMed Central

Quach, Susan; MacDonald, Shannon E.; Naus, Monika; Deeks, Shelley L.; Crowcroft, Natasha S.; Mahmud, Salaheddin M.; Tran, Dat; Kwong, Jeff; Tu, Karen; Johnson, Caitlin; Desai, Shalini

2017-01-01

ABSTRACT Accurate and complete immunization data are necessary to assess vaccine coverage, safety and effectiveness. Across Canada, different methods and data sources are used to assess vaccine coverage, but these have not been systematically described. Our primary objective was to examine and describe the methods used to determine immunization coverage in Canada. The secondary objective was to compare routine infant and childhood coverage estimates derived from the Canadian 2013 Childhood National Immunization Coverage Survey (cNICS) with estimates collected from provinces and territories (P/Ts). We collected information from key informants regarding their provincial, territorial or federal methods for assessing immunization coverage. We also collected P/T coverage estimates for select antigens and birth cohorts to determine absolute differences between these and estimates from cNICS. Twenty-six individuals across 16 public health organizations participated between April and August 2015. Coverage surveys are conducted regularly for toddlers in Quebec and in one health authority in British Columbia. Across P/Ts, different methodologies for measuring coverage are used (e.g., valid doses, grace periods). Most P/Ts, except Ontario, measure up-to-date (UTD) coverage and 4 P/Ts also assess on-time coverage. The degree of concordance between P/T and cNICS coverage estimates varied by jurisdiction, antigen and age group. In addition to differences in the data sources and processes used for coverage assessment, there are also differences between Canadian P/Ts in the methods used for calculating immunization coverage. Comparisons between P/T and cNICS estimates leave remaining questions about the proportion of children fully vaccinated in Canada. PMID:28708945

Human papillomavirus (HPV) vaccination coverage in young Australian women is higher than previously estimated: independent estimates from a nationally representative mobile phone survey.

PubMed

Brotherton, Julia M L; Liu, Bette; Donovan, Basil; Kaldor, John M; Saville, Marion

2014-01-23

Accurate estimates of coverage are essential for estimating the population effectiveness of human papillomavirus (HPV) vaccination. Australia has a purpose built National HPV Vaccination Program Register for monitoring coverage, however notification of doses administered to young women in the community during the national catch-up program (2007-2009) was not compulsory. In 2011, we undertook a population-based mobile phone survey of young women to independently estimate HPV vaccination coverage. Randomly generated mobile phone numbers were dialed to recruit women aged 22-30 (age eligible for HPV vaccination) to complete a computer assisted telephone interview. Consent was sought to validate self reported HPV vaccination status against the national register. Coverage rates were calculated based on self report and weighted to the age and state of residence structure of the Australian female population. These were compared with coverage estimates from the register using Australian Bureau of Statistics estimated resident populations as the denominator. Among the 1379 participants, the national estimate for self reported HPV vaccination coverage for doses 1/2/3, respectively, weighted for age and state of residence, was 64/59/53%. This compares with coverage of 55/45/32% and 49/40/28% based on register records, using 2007 and 2011 population data as the denominators respectively. Some significant differences in coverage between the states were identified. 20% (223) of women returned a consent form allowing validation of doses against the register and provider records: among these women 85.6% (538) of self reported doses were confirmed. We confirmed that coverage rates for young women vaccinated in the community (at age 18-26 years) are underestimated by the national register and that under-notification is greater for second and third doses. Using 2011 population estimates, rather than estimates contemporaneous with the program rollout, reduces register-based coverage estimates further because of large population increases due to immigration since the program. Copyright © 2013 Elsevier Ltd. All rights reserved.

Guidelines for whole genome bisulphite sequencing of intact and FFPET DNA on the Illumina HiSeq X Ten.

PubMed

Nair, Shalima S; Luu, Phuc-Loi; Qu, Wenjia; Maddugoda, Madhavi; Huschtscha, Lily; Reddel, Roger; Chenevix-Trench, Georgia; Toso, Martina; Kench, James G; Horvath, Lisa G; Hayes, Vanessa M; Stricker, Phillip D; Hughes, Timothy P; White, Deborah L; Rasko, John E J; Wong, Justin J-L; Clark, Susan J

2018-05-28

Comprehensive genome-wide DNA methylation profiling is critical to gain insights into epigenetic reprogramming during development and disease processes. Among the different genome-wide DNA methylation technologies, whole genome bisulphite sequencing (WGBS) is considered the gold standard for assaying genome-wide DNA methylation at single base resolution. However, the high sequencing cost to achieve the optimal depth of coverage limits its application in both basic and clinical research. To achieve 15× coverage of the human methylome, using WGBS, requires approximately three lanes of 100-bp-paired-end Illumina HiSeq 2500 sequencing. It is important, therefore, for advances in sequencing technologies to be developed to enable cost-effective high-coverage sequencing. In this study, we provide an optimised WGBS methodology, from library preparation to sequencing and data processing, to enable 16-20× genome-wide coverage per single lane of HiSeq X Ten, HCS 3.3.76. To process and analyse the data, we developed a WGBS pipeline (METH10X) that is fast and can call SNPs. We performed WGBS on both high-quality intact DNA and degraded DNA from formalin-fixed paraffin-embedded tissue. First, we compared different library preparation methods on the HiSeq 2500 platform to identify the best method for sequencing on the HiSeq X Ten. Second, we optimised the PhiX and genome spike-ins to achieve higher quality and coverage of WGBS data on the HiSeq X Ten. Third, we performed integrated whole genome sequencing (WGS) and WGBS of the same DNA sample in a single lane of HiSeq X Ten to improve data output. Finally, we compared methylation data from the HiSeq 2500 and HiSeq X Ten and found high concordance (Pearson r > 0.9×). Together we provide a systematic, efficient and complete approach to perform and analyse WGBS on the HiSeq X Ten. Our protocol allows for large-scale WGBS studies at reasonable processing time and cost on the HiSeq X Ten platform.

Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors.

PubMed

Adalsteinsson, Viktor A; Ha, Gavin; Freeman, Samuel S; Choudhury, Atish D; Stover, Daniel G; Parsons, Heather A; Gydush, Gregory; Reed, Sarah C; Rotem, Denisse; Rhoades, Justin; Loginov, Denis; Livitz, Dimitri; Rosebrock, Daniel; Leshchiner, Ignaty; Kim, Jaegil; Stewart, Chip; Rosenberg, Mara; Francis, Joshua M; Zhang, Cheng-Zhong; Cohen, Ofir; Oh, Coyin; Ding, Huiming; Polak, Paz; Lloyd, Max; Mahmud, Sairah; Helvie, Karla; Merrill, Margaret S; Santiago, Rebecca A; O'Connor, Edward P; Jeong, Seong H; Leeson, Rachel; Barry, Rachel M; Kramkowski, Joseph F; Zhang, Zhenwei; Polacek, Laura; Lohr, Jens G; Schleicher, Molly; Lipscomb, Emily; Saltzman, Andrea; Oliver, Nelly M; Marini, Lori; Waks, Adrienne G; Harshman, Lauren C; Tolaney, Sara M; Van Allen, Eliezer M; Winer, Eric P; Lin, Nancy U; Nakabayashi, Mari; Taplin, Mary-Ellen; Johannessen, Cory M; Garraway, Levi A; Golub, Todd R; Boehm, Jesse S; Wagle, Nikhil; Getz, Gad; Love, J Christopher; Meyerson, Matthew

2017-11-06

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing.

Reproducibility and Consistency of In Vitro Nucleosome Reconstitutions Demonstrated by Invitrosome Isolation and Sequencing

PubMed Central

Kempton, Colton E.; Heninger, Justin R.; Johnson, Steven M.

2014-01-01

Nucleosomes and their positions in the eukaryotic genome play an important role in regulating gene expression by influencing accessibility to DNA. Many factors influence a nucleosome's final position in the chromatin landscape including the underlying genomic sequence. One of the primary reasons for performing in vitro nucleosome reconstitution experiments is to identify how the underlying DNA sequence will influence a nucleosome's position in the absence of other compounding cellular factors. However, concerns have been raised about the reproducibility of data generated from these kinds of experiments. Here we present data for in vitro nucleosome reconstitution experiments performed on linear plasmid DNA that demonstrate that, when coverage is deep enough, these reconstitution experiments are exquisitely reproducible and highly consistent. Our data also suggests that a coverage depth of 35X be maintained for maximal confidence when assaying nucleosome positions, but lower coverage levels may be generally sufficient. These coverage depth recommendations are sufficient in the experimental system and conditions used in this study, but may vary depending on the exact parameters used in other systems. PMID:25093869

First Nuclear DNA C-values for 18 Eudicot Families

PubMed Central

HANSON, LYNDA; BOYD, AMY; JOHNSON, MARGARET A. T.; BENNETT, MICHAEL D.

2005-01-01

• Background and Aims A key target set at the second Plant Genome Size Workshop, held at the Royal Botanic Gardens, Kew in 2003, was to produce first DNA C-value data for an additional 1 % of angiosperm species, and, within this, to achieve 75 % familial coverage overall (up from approx. 50 %) by 2009. The present study targeted eudicot families for which representation in 2003 (42·5 %) was much lower than monocot (72·8 %) and basal angiosperm (69·0 %) families. • Methods Flow cytometry or Feulgen microdensitometry were used to estimate nuclear DNA C-values, and chromosome counts were obtained where possible. • Key Results First nuclear DNA C-values are reported for 20 angiosperm families, including 18 eudicots. This substantially increases familial representation to 55·2 % for angiosperms and 48·5 % for eudicots. • Conclusions The importance of targeting specific plant families to improve familial nuclear DNA C-value representation is reconfirmed. International collaboration will be increasingly essential to locate and obtain material of unsampled plant families, if the target set by the second Plant Genome Size Workshop is to be met. PMID:16239248

In-solution hybridization for mammalian mitogenome enrichment: pros, cons and challenges associated with multiplexing degraded DNA.

PubMed

Hawkins, Melissa T R; Hofman, Courtney A; Callicrate, Taylor; McDonough, Molly M; Tsuchiya, Mirian T N; Gutiérrez, Eliécer E; Helgen, Kristofer M; Maldonado, Jesus E

2016-09-01

Here, we present a set of RNA-based probes for whole mitochondrial genome in-solution enrichment, targeting a diversity of mammalian mitogenomes. This probes set was designed from seven mammalian orders and tested to determine the utility for enriching degraded DNA. We generated 63 mitogenomes representing five orders and 22 genera of mammals that yielded varying coverage ranging from 0 to >5400X. Based on a threshold of 70% mitogenome recovery and at least 10× average coverage, 32 individuals or 51% of samples were considered successful. The estimated sequence divergence of samples from the probe sequences used to construct the array ranged up to nearly 20%. Sample type was more predictive of mitogenome recovery than sample age. The proportion of reads from each individual in multiplexed enrichments was highly skewed, with each pool having one sample that yielded a majority of the reads. Recovery across each mitochondrial gene varied with most samples exhibiting regions with gaps or ambiguous sites. We estimated the ability of the probes to capture mitogenomes from a diversity of mammalian taxa not included here by performing a clustering analysis of published sequences for 100 taxa representing most mammalian orders. Our study demonstrates that a general array can be cost and time effective when there is a need to screen a modest number of individuals from a variety of taxa. We also address the practical concerns for using such a tool, with regard to pooling samples, generating high quality mitogenomes and detail a pipeline to remove chimeric molecules. © 2015 John Wiley & Sons Ltd.

Novel Degenerate PCR Method for Whole-Genome Amplification Applied to Peru Margin (ODP Leg 201) Subsurface Samples

PubMed Central

Martino, Amanda J.; Rhodes, Matthew E.; Biddle, Jennifer F.; Brandt, Leah D.; Tomsho, Lynn P.; House, Christopher H.

2011-01-01

A degenerate polymerase chain reaction (PCR)-based method of whole-genome amplification, designed to work fluidly with 454 sequencing technology, was developed and tested for use on deep marine subsurface DNA samples. While optimized here for use with Roche 454 technology, the general framework presented may be applicable to other next generation sequencing systems as well (e.g., Illumina, Ion Torrent). The method, which we have called random amplification metagenomic PCR (RAMP), involves the use of specific primers from Roche 454 amplicon sequencing, modified by the addition of a degenerate region at the 3′ end. It utilizes a PCR reaction, which resulted in no amplification from blanks, even after 50 cycles of PCR. After efforts to optimize experimental conditions, the method was tested with DNA extracted from cultured E. coli cells, and genome coverage was estimated after sequencing on three different occasions. Coverage did not vary greatly with the different experimental conditions tested, and was around 62% with a sequencing effort equivalent to a theoretical genome coverage of 14.10×. The GC content of the sequenced amplification product was within 2% of the predicted values for this strain of E. coli. The method was also applied to DNA extracted from marine subsurface samples from ODP Leg 201 site 1229 (Peru Margin), and results of a taxonomic analysis revealed microbial communities dominated by Proteobacteria, Chloroflexi, Firmicutes, Euryarchaeota, and Crenarchaeota, among others. These results were similar to those obtained previously for those samples; however, variations in the proportions of taxa identified illustrates well the generally accepted view that community analysis is sensitive to both the amplification technique used and the method of assigning sequences to taxonomic groups. Overall, we find that RAMP represents a valid methodology for amplifying metagenomes from low-biomass samples. PMID:22319519

Sequential strand displacement beacon for detection of DNA coverage on functionalized gold nanoparticles.

PubMed

Paliwoda, Rebecca E; Li, Feng; Reid, Michael S; Lin, Yanwen; Le, X Chris

2014-06-17

Functionalizing nanomaterials for diverse analytical, biomedical, and therapeutic applications requires determination of surface coverage (or density) of DNA on nanomaterials. We describe a sequential strand displacement beacon assay that is able to quantify specific DNA sequences conjugated or coconjugated onto gold nanoparticles (AuNPs). Unlike the conventional fluorescence assay that requires the target DNA to be fluorescently labeled, the sequential strand displacement beacon method is able to quantify multiple unlabeled DNA oligonucleotides using a single (universal) strand displacement beacon. This unique feature is achieved by introducing two short unlabeled DNA probes for each specific DNA sequence and by performing sequential DNA strand displacement reactions. Varying the relative amounts of the specific DNA sequences and spacing DNA sequences during their coconjugation onto AuNPs results in different densities of the specific DNA on AuNP, ranging from 90 to 230 DNA molecules per AuNP. Results obtained from our sequential strand displacement beacon assay are consistent with those obtained from the conventional fluorescence assays. However, labeling of DNA with some fluorescent dyes, e.g., tetramethylrhodamine, alters DNA density on AuNP. The strand displacement strategy overcomes this problem by obviating direct labeling of the target DNA. This method has broad potential to facilitate more efficient design and characterization of novel multifunctional materials for diverse applications.

Structural properties of oligonucleotide monolayers on gold surfaces probed by fluorescence investigations.

PubMed

Rant, Ulrich; Arinaga, Kenji; Fujita, Shozo; Yokoyama, Naoki; Abstreiter, Gerhard; Tornow, Marc

2004-11-09

We present optical investigations on the conformation of oligonucleotide layers on Au surfaces. Our studies concentrate on the effect of varying surface coverage densities on the structural properties of layers of 12- and 24mer single-stranded DNA, tethered to the Au surface at one end while being labeled with a fluorescent marker at the opposing end. The distance-dependent energy transfer from the marker dye to the metal surface, which causes quenching of the observed fluorescence, is used to provide information on the orientation of the DNA strands relative to the surface. Variations in the oligonucleotide coverage density, as determined from electrochemical quantification, over 2 orders of magnitude are achieved by employing different preparation conditions. The observed enhancement in fluorescence intensity with increasing DNA coverage can be related to a model involving mutual steric interactions of oligonucleotides on the surface, as well as fluorescence quenching theory. Finally, the applicability of the presented concepts for investigations of heterogeneous monolayers is demonstrated by means of studying the coadsorption of mercaptohexanol onto DNA-modified Au surfaces.

Enhanced sequencing coverage with digital droplet multiple displacement amplification

PubMed Central

Sidore, Angus M.; Lan, Freeman; Lim, Shaun W.; Abate, Adam R.

2016-01-01

Sequencing small quantities of DNA is important for applications ranging from the assembly of uncultivable microbial genomes to the identification of cancer-associated mutations. To obtain sufficient quantities of DNA for sequencing, the small amount of starting material must be amplified significantly. However, existing methods often yield errors or non-uniform coverage, reducing sequencing data quality. Here, we describe digital droplet multiple displacement amplification, a method that enables massive amplification of low-input material while maintaining sequence accuracy and uniformity. The low-input material is compartmentalized as single molecules in millions of picoliter droplets. Because the molecules are isolated in compartments, they amplify to saturation without competing for resources; this yields uniform representation of all sequences in the final product and, in turn, enhances the quality of the sequence data. We demonstrate the ability to uniformly amplify the genomes of single Escherichia coli cells, comprising just 4.7 fg of starting DNA, and obtain sequencing coverage distributions that rival that of unamplified material. Digital droplet multiple displacement amplification provides a simple and effective method for amplifying minute amounts of DNA for accurate and uniform sequencing. PMID:26704978

Measuring and Specifying Combinatorial Coverage of Test Input Configurations

PubMed Central

Kuhn, D. Richard; Kacker, Raghu N.; Lei, Yu

2015-01-01

A key issue in testing is how many tests are needed for a required level of coverage or fault detection. Estimates are often based on error rates in initial testing, or on code coverage. For example, tests may be run until a desired level of statement or branch coverage is achieved. Combinatorial methods present an opportunity for a different approach to estimating required test set size, using characteristics of the test set. This paper describes methods for estimating the coverage of, and ability to detect, t-way interaction faults of a test set based on a covering array. We also develop a connection between (static) combinatorial coverage and (dynamic) code coverage, such that if a specific condition is satisfied, 100% branch coverage is assured. Using these results, we propose practical recommendations for using combinatorial coverage in specifying test requirements. PMID:28133442

Cluster-sample surveys and lot quality assurance sampling to evaluate yellow fever immunisation coverage following a national campaign, Bolivia, 2007.

PubMed

Pezzoli, Lorenzo; Pineda, Silvia; Halkyer, Percy; Crespo, Gladys; Andrews, Nick; Ronveaux, Olivier

2009-03-01

To estimate the yellow fever (YF) vaccine coverage for the endemic and non-endemic areas of Bolivia and to determine whether selected districts had acceptable levels of coverage (>70%). We conducted two surveys of 600 individuals (25 x 12 clusters) to estimate coverage in the endemic and non-endemic areas. We assessed 11 districts using lot quality assurance sampling (LQAS). The lot (district) sample was 35 individuals with six as decision value (alpha error 6% if true coverage 70%; beta error 6% if true coverage 90%). To increase feasibility, we divided the lots into five clusters of seven individuals; to investigate the effect of clustering, we calculated alpha and beta by conducting simulations where each cluster's true coverage was sampled from a normal distribution with a mean of 70% or 90% and standard deviations of 5% or 10%. Estimated coverage was 84.3% (95% CI: 78.9-89.7) in endemic areas, 86.8% (82.5-91.0) in non-endemic and 86.0% (82.8-89.1) nationally. LQAS showed that four lots had unacceptable coverage levels. In six lots, results were inconsistent with the estimated administrative coverage. The simulations suggested that the effect of clustering the lots is unlikely to have significantly increased the risk of making incorrect accept/reject decisions. Estimated YF coverage was high. Discrepancies between administrative coverage and LQAS results may be due to incorrect population data. Even allowing for clustering in LQAS, the statistical errors would remain low. Catch-up campaigns are recommended in districts with unacceptable coverage.

Accelerating plant DNA barcode reference library construction using herbarium specimens: improved experimental techniques.

PubMed

Xu, Chao; Dong, Wenpan; Shi, Shuo; Cheng, Tao; Li, Changhao; Liu, Yanlei; Wu, Ping; Wu, Hongkun; Gao, Peng; Zhou, Shiliang

2015-11-01

A well-covered reference library is crucial for successful identification of species by DNA barcoding. The biggest difficulty in building such a reference library is the lack of materials of organisms. Herbarium collections are potentially an enormous resource of materials. In this study, we demonstrate that it is likely to build such reference libraries using the reconstructed (self-primed PCR amplified) DNA from the herbarium specimens. We used 179 rosaceous specimens to test the effects of DNA reconstruction, 420 randomly sampled specimens to estimate the usable percentage and another 223 specimens of true cherries (Cerasus, Rosaceae) to test the coverage of usable specimens to the species. The barcode rbcLb (the central four-sevenths of rbcL gene) and matK was each amplified in two halves and sequenced on Roche GS 454 FLX+. DNA from the herbarium specimens was typically shorter than 300 bp. DNA reconstruction enabled amplification fragments of 400-500 bp without bringing or inducing any sequence errors. About one-third of specimens in the national herbarium of China (PE) were proven usable after DNA reconstruction. The specimens in PE cover all Chinese true cherry species and 91.5% of vascular species listed in Flora of China. It is very possible to build well-covered reference libraries for DNA barcoding of vascular species in China. As exemplified in this study, DNA reconstruction and DNA-labelled next-generation sequencing can accelerate the construction of local reference libraries. By putting the local reference libraries together, a global library for DNA barcoding becomes closer to reality. © 2015 John Wiley & Sons Ltd.

Highly multiplexed targeted DNA sequencing from single nuclei.

PubMed

Leung, Marco L; Wang, Yong; Kim, Charissa; Gao, Ruli; Jiang, Jerry; Sei, Emi; Navin, Nicholas E

2016-02-01

Single-cell DNA sequencing methods are challenged by poor physical coverage, high technical error rates and low throughput. To address these issues, we developed a single-cell DNA sequencing protocol that combines flow-sorting of single nuclei, time-limited multiple-displacement amplification (MDA), low-input library preparation, DNA barcoding, targeted capture and next-generation sequencing (NGS). This approach represents a major improvement over our previous single nucleus sequencing (SNS) Nature Protocols paper in terms of generating higher-coverage data (>90%), thereby enabling the detection of genome-wide variants in single mammalian cells at base-pair resolution. Furthermore, by pooling 48-96 single-cell libraries together for targeted capture, this approach can be used to sequence many single-cell libraries in parallel in a single reaction. This protocol greatly reduces the cost of single-cell DNA sequencing, and it can be completed in 5-6 d by advanced users. This single-cell DNA sequencing protocol has broad applications for studying rare cells and complex populations in diverse fields of biological research and medicine.

Assessing vaccination coverage in infants, survey studies versus the Flemish immunisation register: achieving the best of both worlds.

PubMed

Braeckman, Tessa; Lernout, Tinne; Top, Geert; Paeps, Annick; Roelants, Mathieu; Hoppenbrouwers, Karel; Van Damme, Pierre; Theeten, Heidi

2014-01-09

Infant immunisation coverage in Flanders, Belgium, is monitored through repeated coverage surveys. With the increased use of Vaccinnet, the web-based ordering system for vaccines in Flanders set up in 2004 and linked to an immunisation register, this database could become an alternative to quickly estimate vaccination coverage. To evaluate its current accuracy, coverage estimates generated from Vaccinnet alone were compared with estimates from the most recent survey (2012) that combined interview data with data from Vaccinnet and medical files. Coverage rates from registrations in Vaccinnet were systematically lower than the corresponding estimates obtained through the survey (mean difference 7.7%). This difference increased by dose number for vaccines that require multiple doses. Differences in administration date between the two sources were observed for 3.8-8.2% of registered doses. Underparticipation in Vaccinnet thus significantly impacts on the register-based immunisation coverage estimates, amplified by underregistration of administered doses among vaccinators using Vaccinnet. Therefore, survey studies, despite being labour-intensive and expensive, currently provide more complete and reliable results than register-based estimates alone in Flanders. However, further improvement of Vaccinnet's completeness will likely allow more accurate estimates in the nearby future. Copyright © 2013 Elsevier Ltd. All rights reserved.

Microbial diversity of an anoxic zone of a hydroelectric power station reservoir in Brazilian Amazonia.

PubMed

Graças, Diego A; Miranda, Paulo R; Baraúna, Rafael A; McCulloch, John A; Ghilardi, Rubens; Schneider, Maria Paula C; Silva, Artur

2011-11-01

Microbial diversity was evaluated in an anoxic zone of Tucuruí Hydroelectric Power Station reservoir in Brazilian Amazonia using a culture-independent approach by amplifying and sequencing fragments of the 16S rRNA gene using metagenomic DNA as a template. Samples obtained from the photic, aphotic (40 m) and sediment (60 m) layers were used to construct six 16S rDNA libraries containing a total of 1,152 clones. The sediment, aphotic and photic layers presented 64, 33 and 35 unique archaeal operational taxonomic units (OTUs). The estimated richness of these layers was evaluated to be 153, 106 and 79 archaeal OTUs, respectively, using the abundance-based coverage estimator (ACE) and 114, 83 and 77 OTUs using the Chao1 estimator. For bacterial sequences, 114, 69 and 57 OTUs were found in the sediment, aphotic and photic layers, which presented estimated richnesses of 1,414, 522 and 197 OTUs (ACE) and 1,059, 1,014 and 148 OTUs (Chao1), respectively. Phylogenetic analyses of the sequences obtained revealed a high richness of microorganisms which participate in the carbon cycle, namely, methanogenic archaea and methanotrophic proteobacteria. Most sequences obtained belong to non-culturable prokaryotes. The present study offers the first glimpse of the huge microbial diversity of an anoxic area of a man-made lacustrine environment in the tropics.

A MBD-seq protocol for large-scale methylome-wide studies with (very) low amounts of DNA.

PubMed

Aberg, Karolina A; Chan, Robin F; Shabalin, Andrey A; Zhao, Min; Turecki, Gustavo; Staunstrup, Nicklas Heine; Starnawska, Anna; Mors, Ole; Xie, Lin Y; van den Oord, Edwin Jcg

2017-09-01

We recently showed that, after optimization, our methyl-CpG binding domain sequencing (MBD-seq) application approximates the methylome-wide coverage obtained with whole-genome bisulfite sequencing (WGB-seq), but at a cost that enables adequately powered large-scale association studies. A prior drawback of MBD-seq is the relatively large amount of genomic DNA (ideally >1 µg) required to obtain high-quality data. Biomaterials are typically expensive to collect, provide a finite amount of DNA, and may simply not yield sufficient starting material. The ability to use low amounts of DNA will increase the breadth and number of studies that can be conducted. Therefore, we further optimized the enrichment step. With this low starting material protocol, MBD-seq performed equally well, or better, than the protocol requiring ample starting material (>1 µg). Using only 15 ng of DNA as input, there is minimal loss in data quality, achieving 93% of the coverage of WGB-seq (with standard amounts of input DNA) at similar false/positive rates. Furthermore, across a large number of genomic features, the MBD-seq methylation profiles closely tracked those observed for WGB-seq with even slightly larger effect sizes. This suggests that MBD-seq provides similar information about the methylome and classifies methylation status somewhat more accurately. Performance decreases with <15 ng DNA as starting material but, even with as little as 5 ng, MBD-seq still achieves 90% of the coverage of WGB-seq with comparable genome-wide methylation profiles. Thus, the proposed protocol is an attractive option for adequately powered and cost-effective methylome-wide investigations using (very) low amounts of DNA.

Human papillomavirus (HPV) vaccine coverage achievements in low and middle-income countries 2007-2016.

PubMed

Gallagher, Katherine E; Howard, Natasha; Kabakama, Severin; Mounier-Jack, Sandra; Burchett, Helen E D; LaMontagne, D Scott; Watson-Jones, Deborah

2017-12-01

Since 2007, HPV vaccine has been available to low and middle income countries (LAMIC) for small-scale 'demonstration projects', or national programmes. We analysed coverage achieved in HPV vaccine demonstration projects and national programmes that had completed at least 6 months of implementation between January 2007-2016. A mapping exercise identified 45 LAMICs with HPV vaccine delivery experience. Estimates of coverage and factors influencing coverage were obtained from 56 key informant interviews, a systematic published literature search of 5 databases that identified 61 relevant full texts and 188 solicited unpublished documents, including coverage surveys. Coverage achievements were analysed descriptively against country or project/programme characteristics. Heterogeneity in data, funder requirements, and project/programme design precluded multivariate analysis. Estimates of uptake, schedule completion rates and/or final dose coverage were available from 41 of 45 LAMICs included in the study. Only 17 estimates from 13 countries were from coverage surveys, most were administrative data. Final dose coverage estimates were all over 50% with most between 70% and 90%, and showed no trend over time. The majority of delivery strategies included schools as a vaccination venue. In countries with school enrolment rates below 90%, inclusion of strategies to reach out-of-school girls contributed to obtaining high coverage compared to school-only strategies. There was no correlation between final dose coverage and estimated recurrent financial costs of delivery from cost analyses. Coverage achieved during joint delivery of HPV vaccine combined with another intervention was variable with little/no evaluation of the correlates of success. This is the most comprehensive descriptive analysis of HPV vaccine coverage in LAMICs to date. It is possible to deliver HPV vaccine with excellent coverage in LAMICs. Further good quality data are needed from health facility based delivery strategies and national programmes to aid policymakers to effectively and sustainably scale-up HPV vaccination. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Comparison of administrative and survey data for estimating vitamin A supplementation and deworming coverage of children under five years of age in Sub-Saharan Africa.

PubMed

Janmohamed, Amynah; Doledec, David

2017-07-01

To compare administrative coverage data with results from household coverage surveys for vitamin A supplementation (VAS) and deworming campaigns conducted during 2010-2015 in 12 African countries. Paired t-tests examined differences between administrative and survey coverage for 52 VAS and 34 deworming dyads. Independent t-tests measured VAS and deworming coverage differences between data sources for door-to-door and fixed-site delivery strategies and VAS coverage differences between 6- to 11-month and 12- to 59-month age group. For VAS, administrative coverage was higher than survey estimates in 47 of 52 (90%) campaign rounds, with a mean difference of 16.1% (95% CI: 9.5-22.7; P < 0.001). For deworming, administrative coverage exceeded survey estimates in 31 of 34 (91%) comparisons, with a mean difference of 29.8% (95% CI: 16.9-42.6; P < 0.001). Mean ± SD differences in coverage between administrative and survey data were 12.2% ± 22.5% for the door-to-door delivery strategy and 25.9% ± 24.7% for the fixed-site model (P = 0.06). For deworming, mean ± SD differences in coverage between data sources were 28.1% ± 43.5% and 33.1% ± 17.9% for door-to-door and fixed-site distribution, respectively (P = 0.64). VAS administrative coverage was higher than survey estimates in 37 of 49 (76%) comparisons for the 6- to 11-month age group and 45 of 48 (94%) comparisons for the 12- to 59-month age group. Reliance on health facility data alone for calculating VAS and deworming coverage may mask low coverage and prevent measures to improve programmes. Countries should periodically validate administrative coverage estimates with population-based methods. © 2017 John Wiley & Sons Ltd.

Measuring coverage in MNCH: total survey error and the interpretation of intervention coverage estimates from household surveys.

PubMed

Eisele, Thomas P; Rhoda, Dale A; Cutts, Felicity T; Keating, Joseph; Ren, Ruilin; Barros, Aluisio J D; Arnold, Fred

2013-01-01

Nationally representative household surveys are increasingly relied upon to measure maternal, newborn, and child health (MNCH) intervention coverage at the population level in low- and middle-income countries. Surveys are the best tool we have for this purpose and are central to national and global decision making. However, all survey point estimates have a certain level of error (total survey error) comprising sampling and non-sampling error, both of which must be considered when interpreting survey results for decision making. In this review, we discuss the importance of considering these errors when interpreting MNCH intervention coverage estimates derived from household surveys, using relevant examples from national surveys to provide context. Sampling error is usually thought of as the precision of a point estimate and is represented by 95% confidence intervals, which are measurable. Confidence intervals can inform judgments about whether estimated parameters are likely to be different from the real value of a parameter. We recommend, therefore, that confidence intervals for key coverage indicators should always be provided in survey reports. By contrast, the direction and magnitude of non-sampling error is almost always unmeasurable, and therefore unknown. Information error and bias are the most common sources of non-sampling error in household survey estimates and we recommend that they should always be carefully considered when interpreting MNCH intervention coverage based on survey data. Overall, we recommend that future research on measuring MNCH intervention coverage should focus on refining and improving survey-based coverage estimates to develop a better understanding of how results should be interpreted and used.

Measuring Coverage in MNCH: Total Survey Error and the Interpretation of Intervention Coverage Estimates from Household Surveys

PubMed Central

Eisele, Thomas P.; Rhoda, Dale A.; Cutts, Felicity T.; Keating, Joseph; Ren, Ruilin; Barros, Aluisio J. D.; Arnold, Fred

2013-01-01

Nationally representative household surveys are increasingly relied upon to measure maternal, newborn, and child health (MNCH) intervention coverage at the population level in low- and middle-income countries. Surveys are the best tool we have for this purpose and are central to national and global decision making. However, all survey point estimates have a certain level of error (total survey error) comprising sampling and non-sampling error, both of which must be considered when interpreting survey results for decision making. In this review, we discuss the importance of considering these errors when interpreting MNCH intervention coverage estimates derived from household surveys, using relevant examples from national surveys to provide context. Sampling error is usually thought of as the precision of a point estimate and is represented by 95% confidence intervals, which are measurable. Confidence intervals can inform judgments about whether estimated parameters are likely to be different from the real value of a parameter. We recommend, therefore, that confidence intervals for key coverage indicators should always be provided in survey reports. By contrast, the direction and magnitude of non-sampling error is almost always unmeasurable, and therefore unknown. Information error and bias are the most common sources of non-sampling error in household survey estimates and we recommend that they should always be carefully considered when interpreting MNCH intervention coverage based on survey data. Overall, we recommend that future research on measuring MNCH intervention coverage should focus on refining and improving survey-based coverage estimates to develop a better understanding of how results should be interpreted and used. PMID:23667331

An Annotated Draft Genome for Radix auricularia (Gastropoda, Mollusca)

PubMed Central

Feldmeyer, Barbara; Schmidt, Hanno; Greshake, Bastian; Tills, Oliver; Truebano, Manuela; Rundle, Simon D.; Paule, Juraj; Ebersberger, Ingo; Pfenninger, Markus

2017-01-01

Molluscs are the second most species-rich phylum in the animal kingdom, yet only 11 genomes of this group have been published so far. Here, we present the draft genome sequence of the pulmonate freshwater snail Radix auricularia. Six whole genome shotgun libraries with different layouts were sequenced. The resulting assembly comprises 4,823 scaffolds with a cumulative length of 910 Mb and an overall read coverage of 72×. The assembly contains 94.6% of a metazoan core gene collection, indicating an almost complete coverage of the coding fraction. The discrepancy of ∼690 Mb compared with the estimated genome size of R. auricularia (1.6 Gb) results from a high repeat content of 70% mainly comprising DNA transposons. The annotation of 17,338 protein coding genes was supported by the use of publicly available transcriptome data. This draft will serve as starting point for further genomic and population genetic research in this scientifically important phylum. PMID:28204581

Comparison of NIS and NHIS/NIPRCS vaccination coverage estimates. National Immunization Survey. National Health Interview Survey/National Immunization Provider Record Check Study.

PubMed

Bartlett, D L; Ezzati-Rice, T M; Stokley, S; Zhao, Z

2001-05-01

The National Immunization Survey (NIS) and the National Health Interview Survey (NHIS) produce national coverage estimates for children aged 19 months to 35 months. The NIS is a cost-effective, random-digit-dialing telephone survey that produces national and state-level vaccination coverage estimates. The National Immunization Provider Record Check Study (NIPRCS) is conducted in conjunction with the annual NHIS, which is a face-to-face household survey. As the NIS is a telephone survey, potential coverage bias exists as the survey excludes children living in nontelephone households. To assess the validity of estimates of vaccine coverage from the NIS, we compared 1995 and 1996 NIS national estimates with results from the NHIS/NIPRCS for the same years. Both the NIS and the NHIS/NIPRCS produce similar results. The NHIS/NIPRCS supports the findings of the NIS.

Characterization and electrochemical response of DNA functionalized 2nm gold nanoparticles confined in a nanochannel array.

PubMed

Peinetti, Ana S; Ceretti, Helena; Mizrahi, Martín; González, Graciela A; Ramírez, Silvana A; Requejo, Félix G; Montserrat, Javier M; Battaglini, Fernando

2018-06-01

Polyvalent gold nanoparticle oligonucleotide conjugates are subject of intense research. Even though 2nm diameter AuNPs have been previously modified with DNA, little is known about their structure and electrochemical behavior. In this work, we examine the influence of different surface modification strategies on the interplay between the meso-organization and the molecular recognition properties of a 27-mer DNA strand. This DNA strand is functionalized with different sulfur-containing moieties and immobilized on 2nm gold nanoparticles confined on a nanoporous alumina, working the whole system as an electrode array. Surface coverages were determined by EXAFS and the performance as recognition elements for impedance-based sensors is evaluated. Our results prove that low DNA coverages on the confined nanoparticles prompt to a more sensitive response, showing the relevance in avoiding the DNA strand overcrowding. The system was able to determine a concentration as low as 100pM of the complementary strand, thus introducing the foundations for the construction of label-free genosensors at the nanometer scale. Copyright © 2018 Elsevier B.V. All rights reserved.

A Case Study into Microbial Genome Assembly Gap Sequences and Finishing Strategies.

PubMed

Utturkar, Sagar M; Klingeman, Dawn M; Hurt, Richard A; Brown, Steven D

2017-01-01

This study characterized regions of DNA which remained unassembled by either PacBio and Illumina sequencing technologies for seven bacterial genomes. Two genomes were manually finished using bioinformatics and PCR/Sanger sequencing approaches and regions not assembled by automated software were analyzed. Gaps present within Illumina assemblies mostly correspond to repetitive DNA regions such as multiple rRNA operon sequences. PacBio gap sequences were evaluated for several properties such as GC content, read coverage, gap length, ability to form strong secondary structures, and corresponding annotations. Our hypothesis that strong secondary DNA structures blocked DNA polymerases and contributed to gap sequences was not accepted. PacBio assemblies had few limitations overall and gaps were explained as cumulative effect of lower than average sequence coverage and repetitive sequences at contig termini. An important aspect of the present study is the compilation of biological features that interfered with assembly and included active transposons, multiple plasmid sequences, phage DNA integration, and large sequence duplication. Our targeted genome finishing approach and systematic evaluation of the unassembled DNA will be useful for others looking to close, finish, and polish microbial genome sequences.

Is a 'convenience' sample useful for estimating immunization coverage in a small population?

PubMed

Weir, Jean E; Jones, Carrie

2008-01-01

Rapid survey methodologies are widely used for assessing immunization coverage in developing countries, approximating true stratified random sampling. Non-random ('convenience') sampling is not considered appropriate for estimating immunization coverage rates but has the advantages of low cost and expediency. We assessed the validity of a convenience sample of children presenting to a travelling clinic by comparing the coverage rate in the convenience sample to the true coverage established by surveying each child in three villages in rural Papua New Guinea. The rate of DTF immunization coverage as estimated by the convenience sample was within 10% of the true coverage when the proportion of children in the sample was two-thirds or when only children over the age of one year were counted, but differed by 11% when the sample included only 53% of the children and when all eligible children were included. The convenience sample may be sufficiently accurate for reporting purposes and is useful for identifying areas of low coverage.

Estimation after classification using lot quality assurance sampling: corrections for curtailed sampling with application to evaluating polio vaccination campaigns.

PubMed

Olives, Casey; Valadez, Joseph J; Pagano, Marcello

2014-03-01

To assess the bias incurred when curtailment of Lot Quality Assurance Sampling (LQAS) is ignored, to present unbiased estimators, to consider the impact of cluster sampling by simulation and to apply our method to published polio immunization data from Nigeria. We present estimators of coverage when using two kinds of curtailed LQAS strategies: semicurtailed and curtailed. We study the proposed estimators with independent and clustered data using three field-tested LQAS designs for assessing polio vaccination coverage, with samples of size 60 and decision rules of 9, 21 and 33, and compare them to biased maximum likelihood estimators. Lastly, we present estimates of polio vaccination coverage from previously published data in 20 local government authorities (LGAs) from five Nigerian states. Simulations illustrate substantial bias if one ignores the curtailed sampling design. Proposed estimators show no bias. Clustering does not affect the bias of these estimators. Across simulations, standard errors show signs of inflation as clustering increases. Neither sampling strategy nor LQAS design influences estimates of polio vaccination coverage in 20 Nigerian LGAs. When coverage is low, semicurtailed LQAS strategies considerably reduces the sample size required to make a decision. Curtailed LQAS designs further reduce the sample size when coverage is high. Results presented dispel the misconception that curtailed LQAS data are unsuitable for estimation. These findings augment the utility of LQAS as a tool for monitoring vaccination efforts by demonstrating that unbiased estimation using curtailed designs is not only possible but these designs also reduce the sample size. © 2014 John Wiley & Sons Ltd.

A novel quantitative electrochemical method to monitor DNA double-strand breaks caused by a DNA cleavage agent at a DNA sensor.

PubMed

Banasiak, Anna; Cassidy, John; Colleran, John

2018-06-01

To date, DNA cleavage, caused by cleavage agents, has been monitored mainly by gel and capillary electrophoresis. However, these techniques are time-consuming, non-quantitative and require gel stains. In this work, a novel, simple and, importantly, a quantitative method for monitoring the DNA nuclease activity of potential anti-cancer drugs, at a DNA electrochemical sensor, is presented. The DNA sensors were prepared using thiol-modified oligonucleotides that self-assembled to create a DNA monolayer at gold electrode surfaces. The quantification of DNA double-strand breaks is based on calculating the DNA surface coverage, before and after exposure to a DNA cleavage agent. The nuclease properties of a model DNA cleavage agent, copper bis-phenanthroline ([Cu II (phen) 2 ] 2+ ), that can cleave DNA in a Fenton-type reaction, were quantified electrochemically. The DNA surface coverage decreased on average by 21% after subjecting the DNA sensor to a nuclease assay containing [Cu II (phen) 2 ] 2+ , a reductant and an oxidant. This percentage indicates that 6 base pairs were cleaved in the nuclease assay from the immobilised 30 base pair strands. The DNA cleavage can be also induced electrochemically in the absence of a chemical reductant. [Cu II (phen) 2 ] 2+ intercalates between DNA base pairs and, on application of a suitable potential, can be reduced to [Cu I (phen) 2 ] + , with dissolved oxygen acting as the required oxidant. This reduction process is facilitated through DNA strands via long-range electron transfer, resulting in DNA cleavage of 23%. The control measurements for both chemically and electrochemically induced cleavage revealed that DNA strand breaks did not occur under experimental conditions in the absence of [Cu II (phen) 2 ] 2+ . Copyright © 2018 Elsevier B.V. All rights reserved.

Efficient Genome-Wide Sequencing and Low-Coverage Pedigree Analysis from Noninvasively Collected Samples

PubMed Central

Snyder-Mackler, Noah; Majoros, William H.; Yuan, Michael L.; Shaver, Amanda O.; Gordon, Jacob B.; Kopp, Gisela H.; Schlebusch, Stephen A.; Wall, Jeffrey D.; Alberts, Susan C.; Mukherjee, Sayan; Zhou, Xiang; Tung, Jenny

2016-01-01

Research on the genetics of natural populations was revolutionized in the 1990s by methods for genotyping noninvasively collected samples. However, these methods have remained largely unchanged for the past 20 years and lag far behind the genomics era. To close this gap, here we report an optimized laboratory protocol for genome-wide capture of endogenous DNA from noninvasively collected samples, coupled with a novel computational approach to reconstruct pedigree links from the resulting low-coverage data. We validated both methods using fecal samples from 62 wild baboons, including 48 from an independently constructed extended pedigree. We enriched fecal-derived DNA samples up to 40-fold for endogenous baboon DNA and reconstructed near-perfect pedigree relationships even with extremely low-coverage sequencing. We anticipate that these methods will be broadly applicable to the many research systems for which only noninvasive samples are available. The lab protocol and software (“WHODAD”) are freely available at www.tung-lab.org/protocols-and-software.html and www.xzlab.org/software.html, respectively. PMID:27098910

Cost-effectiveness of human papillomavirus vaccination and cervical cancer screening in Thailand.

PubMed

Sharma, M; Ortendahl, J; van der Ham, E; Sy, S; Kim, J J

2012-01-01

To assess the health and economic outcomes of various screening and vaccination strategies for cervical cancer prevention. Cost-effectiveness analysis from a societal perspective. Thailand. Females aged 9 years and older. Using a mathematical model of human papillomavirus (HPV) infection and cervical cancer, calibrated to epidemiological data from Thailand, we estimated the cost-effectiveness of pre-adolescent HPV vaccination, screening [visual inspection with acetic acid (VIA), HPV DNA testing, and cytology] between one and five times per lifetime in adulthood, and combined pre-adolescent vaccination and screening. Vaccine efficacy, coverage, cost, and screening frequency were varied in sensitivity analyses. Incremental cost-effectiveness ratios, expressed as cost per year of life saved (YLS). Assuming lifelong efficacy and 80% coverage, pre-adolescent HPV vaccination alone was projected to reduce the lifetime risk of cervical cancer by 55%, which was greater than any strategy of screening alone. When cost per vaccinated girl was I$10 (approximately $2 per dose) or less, HPV vaccination alone was cost saving. Pre-adolescent vaccination and HPV DNA testing five times per lifetime, starting at age 35 years, reduced the lifetime cervical cancer risk by 70%, and had a cost-effectiveness ratio less than Thailand's GDP per capita (I$8100), provided the cost per vaccinated girl was I$200 or less. Low cost pre-adolescent HPV vaccination followed by HPV screening five times per lifetime is an efficient strategy for Thailand. Costs may need to be lower, however, for this strategy to be affordable. If vaccination is not feasible, HPV DNA testing five times per lifetime is efficient. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

A long way to go - Estimates of combined water, sanitation and hygiene coverage for 25 sub-Saharan African countries.

PubMed

Roche, Rachel; Bain, Robert; Cumming, Oliver

2017-01-01

Water, sanitation and hygiene (WASH) are essential for a healthy and dignified life. International targets to reduce inadequate WASH coverage were set under the Millennium Development Goals (MDGs, 1990-2015) and now the Sustainable Development Goals (SDGs, 2016-2030). The MDGs called for halving the proportion of the population without access to adequate water and sanitation, whereas the SDGs call for universal access, require the progressive reduction of inequalities, and include hygiene in addition to water and sanitation. Estimating access to complete WASH coverage provides a baseline for monitoring during the SDG period. Sub-Saharan Africa (SSA) has among the lowest rates of WASH coverage globally. The most recent available Demographic Household Survey (DHS) or Multiple Indicator Cluster Survey (MICS) data for 25 countries in SSA were analysed to estimate national and regional coverage for combined water and sanitation (a combined MDG indicator for 'improved' access) and combined water with collection time within 30 minutes plus sanitation and hygiene (a combined SDG indicator for 'basic' access). Coverage rates were estimated separately for urban and rural populations and for wealth quintiles. Frequency ratios and percentage point differences for urban and rural coverage were calculated to give both relative and absolute measures of urban-rural inequality. Wealth inequalities were assessed by visual examination of coverage across wealth quintiles in urban and rural populations and by calculating concentration indices as standard measures of relative wealth related inequality that give an indication of how unevenly a health indicator is distributed across the wealth distribution. Combined MDG coverage in SSA was 20%, and combined basic SDG coverage was 4%; an estimated 921 million people lacked basic SDG coverage. Relative measures of inequality were higher for combined basic SDG coverage than combined MDG coverage, but absolute inequality was lower. Rural combined basic SDG coverage was close to zero in many countries. Our estimates help to quantify the scale of progress required to achieve universal WASH access in low-income countries, as envisaged under the water and sanitation SDG. Monitoring and reporting changes in the proportion of the national population with access to water, sanitation and hygiene may be useful in focusing WASH policy and investments towards the areas of greatest need.

A long way to go – Estimates of combined water, sanitation and hygiene coverage for 25 sub-Saharan African countries

PubMed Central

Bain, Robert; Cumming, Oliver

2017-01-01

Background Water, sanitation and hygiene (WASH) are essential for a healthy and dignified life. International targets to reduce inadequate WASH coverage were set under the Millennium Development Goals (MDGs, 1990–2015) and now the Sustainable Development Goals (SDGs, 2016–2030). The MDGs called for halving the proportion of the population without access to adequate water and sanitation, whereas the SDGs call for universal access, require the progressive reduction of inequalities, and include hygiene in addition to water and sanitation. Estimating access to complete WASH coverage provides a baseline for monitoring during the SDG period. Sub-Saharan Africa (SSA) has among the lowest rates of WASH coverage globally. Methods The most recent available Demographic Household Survey (DHS) or Multiple Indicator Cluster Survey (MICS) data for 25 countries in SSA were analysed to estimate national and regional coverage for combined water and sanitation (a combined MDG indicator for ‘improved’ access) and combined water with collection time within 30 minutes plus sanitation and hygiene (a combined SDG indicator for ‘basic’ access). Coverage rates were estimated separately for urban and rural populations and for wealth quintiles. Frequency ratios and percentage point differences for urban and rural coverage were calculated to give both relative and absolute measures of urban-rural inequality. Wealth inequalities were assessed by visual examination of coverage across wealth quintiles in urban and rural populations and by calculating concentration indices as standard measures of relative wealth related inequality that give an indication of how unevenly a health indicator is distributed across the wealth distribution. Results Combined MDG coverage in SSA was 20%, and combined basic SDG coverage was 4%; an estimated 921 million people lacked basic SDG coverage. Relative measures of inequality were higher for combined basic SDG coverage than combined MDG coverage, but absolute inequality was lower. Rural combined basic SDG coverage was close to zero in many countries. Conclusions Our estimates help to quantify the scale of progress required to achieve universal WASH access in low-income countries, as envisaged under the water and sanitation SDG. Monitoring and reporting changes in the proportion of the national population with access to water, sanitation and hygiene may be useful in focusing WASH policy and investments towards the areas of greatest need. PMID:28182796

Digital droplet multiple displacement amplification (ddMDA) for whole genome sequencing of limited DNA samples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rhee, Minsoung; Light, Yooli K.; Meagher, Robert J.

Here, multiple displacement amplification (MDA) is a widely used technique for amplification of DNA from samples containing limited amounts of DNA (e.g., uncultivable microbes or clinical samples) before whole genome sequencing. Despite its advantages of high yield and fidelity, it suffers from high amplification bias and non-specific amplification when amplifying sub-nanogram of template DNA. Here, we present a microfluidic digital droplet MDA (ddMDA) technique where partitioning of the template DNA into thousands of sub-nanoliter droplets, each containing a small number of DNA fragments, greatly reduces the competition among DNA fragments for primers and polymerase thereby greatly reducing amplification bias. Consequently,more » the ddMDA approach enabled a more uniform coverage of amplification over the entire length of the genome, with significantly lower bias and non-specific amplification than conventional MDA. For a sample containing 0.1 pg/μL of E. coli DNA (equivalent of ~3/1000 of an E. coli genome per droplet), ddMDA achieves a 65-fold increase in coverage in de novo assembly, and more than 20-fold increase in specificity (percentage of reads mapping to E. coli) compared to the conventional tube MDA. ddMDA offers a powerful method useful for many applications including medical diagnostics, forensics, and environmental microbiology.« less

Digital droplet multiple displacement amplification (ddMDA) for whole genome sequencing of limited DNA samples

DOE PAGES

Rhee, Minsoung; Light, Yooli K.; Meagher, Robert J.; ...

2016-05-04

Here, multiple displacement amplification (MDA) is a widely used technique for amplification of DNA from samples containing limited amounts of DNA (e.g., uncultivable microbes or clinical samples) before whole genome sequencing. Despite its advantages of high yield and fidelity, it suffers from high amplification bias and non-specific amplification when amplifying sub-nanogram of template DNA. Here, we present a microfluidic digital droplet MDA (ddMDA) technique where partitioning of the template DNA into thousands of sub-nanoliter droplets, each containing a small number of DNA fragments, greatly reduces the competition among DNA fragments for primers and polymerase thereby greatly reducing amplification bias. Consequently,more » the ddMDA approach enabled a more uniform coverage of amplification over the entire length of the genome, with significantly lower bias and non-specific amplification than conventional MDA. For a sample containing 0.1 pg/μL of E. coli DNA (equivalent of ~3/1000 of an E. coli genome per droplet), ddMDA achieves a 65-fold increase in coverage in de novo assembly, and more than 20-fold increase in specificity (percentage of reads mapping to E. coli) compared to the conventional tube MDA. ddMDA offers a powerful method useful for many applications including medical diagnostics, forensics, and environmental microbiology.« less

Estimation of child vaccination coverage at state and national levels in India

PubMed Central

Gupta, Satish; Kumar, Rakesh; Haldar, Pradeep; Sethi, Raman; Bahl, Sunil

2016-01-01

Abstract Objective To review the data, for 1999–2013, on state-level child vaccination coverage in India and provide estimates of coverage at state and national levels. Methods We collated data from administrative reports, population-based surveys and other sources and used them to produce annual estimates of vaccination coverage. We investigated bacille Calmette–Guérin vaccine, the first and third doses of vaccine against diphtheria, tetanus and pertussis, the third dose of oral polio vaccine and the first dose of vaccine against measles. We obtained relevant data covering the period 1999–2013 for each of 16 states and territories and the period 2001–2013 for the state of Jharkhand – which was only created in 2000. We aggregated the resultant state-level estimates, using a population-weighted approach, to give national values. Findings For each of the vaccinations we investigated, about half of the 253 estimates of annual coverage at state level that we produced were based on survey results. The rest were based on interpolation between – or extrapolation from – so-called anchor points or, more rarely, on administrative data. Our national estimates indicated that, for each of the vaccines we investigated, coverage gradually increased between 1999 and 2010 but then levelled off. Conclusion The delivery of routine vaccination services to Indian children appears to have improved between 1999 and 2013. There remains considerable scope to improve the recording and reporting of childhood vaccination coverage in India and regular systematic reviews of the coverage data are recommended. PMID:27843162

Analysis of quality raw data of second generation sequencers with Quality Assessment Software.

PubMed

Ramos, Rommel Tj; Carneiro, Adriana R; Baumbach, Jan; Azevedo, Vasco; Schneider, Maria Pc; Silva, Artur

2011-04-18

Second generation technologies have advantages over Sanger; however, they have resulted in new challenges for the genome construction process, especially because of the small size of the reads, despite the high degree of coverage. Independent of the program chosen for the construction process, DNA sequences are superimposed, based on identity, to extend the reads, generating contigs; mismatches indicate a lack of homology and are not included. This process improves our confidence in the sequences that are generated. We developed Quality Assessment Software, with which one can review graphs showing the distribution of quality values from the sequencing reads. This software allow us to adopt more stringent quality standards for sequence data, based on quality-graph analysis and estimated coverage after applying the quality filter, providing acceptable sequence coverage for genome construction from short reads. Quality filtering is a fundamental step in the process of constructing genomes, as it reduces the frequency of incorrect alignments that are caused by measuring errors, which can occur during the construction process due to the size of the reads, provoking misassemblies. Application of quality filters to sequence data, using the software Quality Assessment, along with graphing analyses, provided greater precision in the definition of cutoff parameters, which increased the accuracy of genome construction.

MicroCantilever (MC) based nanomechanical sensor for detection of molecular interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, Kyung

Specific aims of this study are to investigate the mechanism governing surface stress generation associated with chemical or molecular binding on functionalized microcantilevers. Formation of affinity complexes on cantilever surfaces leads to charge redistribution, configurational change and steric hindrance between neighboring molecules resulting in surface stress change and measureable cantilever deformation. A novel interferometry technique employing two adjacent micromachined cantilevers (a sensing/reference pair) was utilized to measure the cantilever deformation. The sensing principle is that binding/reaction of specific chemical or biological species on the sensing cantilever transduces to mechanical deformation. The differential bending of the sensing cantilever respect to themore » reference cantilever ensures that measured response is insensitive to environmental disturbances. As a proof of principle for the measurement technique, surface stress changes associated with: self-assembly of alkanethiol, hybridization of ssDNA, and the formation of cocaine-aptamer complexes were measured. Dissociation constant (K d) for each molecular reaction was utilized to estimate the surface coverage of affinity complexes. In the cases of DNA hybridization and cocaine-aptamer binding, measured surface stress was found to be dependent on the surface coverage of the affinity complexes. In order to achieve a better sensitivity for DNA hybridization, immobilization of receptor molecules was modified to enhance the deformation of underlying surface. Single-stranded DNA (ssDNA) strands with thiol-modification on both 3-foot and 5-foot ends were immobilized on the gold surface such that both ends are attached to the gold surface. Immobilization condition was controlled to obtain similar receptor density as single-thiolated DNA strands. Hybridization of double-thiolated DNA strands leads to an almost two orders of magnitude increase in cantilever deformation. In both DNA hybridization and the conventional mode for cocaine detection, the lowest detectable concentration was determined by binding activity between the ligand and receptor molecules. In order to overcome this limitation for cocaine detection, a novel competition sensing mode that relies on rate of aptamers unbinding from the cantilever due to either diffusion or reaction with cocaine as target ligands in solution was investigated. The rate of unbinding is found to be dependent on the concentration of cocaine molecules. A model based on diffusion-reaction equation was developed to explain the experimental observation. Experimental results indicate that the competition mode reduces the lowest detectable threshold to 200 nM which is comparable to that achieved analytical techniques such as mass spectrometry.« less

Evaluation of Two Highly-Multiplexed Custom Panels for Massively Parallel Semiconductor Sequencing on Paraffin DNA

PubMed Central

Kotoula, Vassiliki; Lyberopoulou, Aggeliki; Papadopoulou, Kyriaki; Charalambous, Elpida; Alexopoulou, Zoi; Gakou, Chryssa; Lakis, Sotiris; Tsolaki, Eleftheria; Lilakos, Konstantinos; Fountzilas, George

2015-01-01

Background—Aim Massively parallel sequencing (MPS) holds promise for expanding cancer translational research and diagnostics. As yet, it has been applied on paraffin DNA (FFPE) with commercially available highly multiplexed gene panels (100s of DNA targets), while custom panels of low multiplexing are used for re-sequencing. Here, we evaluated the performance of two highly multiplexed custom panels on FFPE DNA. Methods Two custom multiplex amplification panels (B, 373 amplicons; T, 286 amplicons) were coupled with semiconductor sequencing on DNA samples from FFPE breast tumors and matched peripheral blood samples (n samples: 316; n libraries: 332). The two panels shared 37% DNA targets (common or shifted amplicons). Panel performance was evaluated in paired sample groups and quartets of libraries, where possible. Results Amplicon read ratios yielded similar patterns per gene with the same panel in FFPE and blood samples; however, performance of common amplicons differed between panels (p<0.001). FFPE genotypes were compared for 1267 coding and non-coding variant replicates, 999 out of which (78.8%) were concordant in different paired sample combinations. Variant frequency was highly reproducible (Spearman’s rho 0.959). Repeatedly discordant variants were of high coverage / low frequency (p<0.001). Genotype concordance was (a) high, for intra-run duplicates with the same panel (mean±SD: 97.2±4.7, 95%CI: 94.8–99.7, p<0.001); (b) modest, when the same DNA was analyzed with different panels (mean±SD: 81.1±20.3, 95%CI: 66.1–95.1, p = 0.004); and (c) low, when different DNA samples from the same tumor were compared with the same panel (mean±SD: 59.9±24.0; 95%CI: 43.3–76.5; p = 0.282). Low coverage / low frequency variants were validated with Sanger sequencing even in samples with unfavourable DNA quality. Conclusions Custom MPS may yield novel information on genomic alterations, provided that data evaluation is adjusted to tumor tissue FFPE DNA. To this scope, eligibility of all amplicons along with variant coverage and frequency need to be assessed. PMID:26039550

A Case Study into Microbial Genome Assembly Gap Sequences and Finishing Strategies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Utturkar, Sagar M.; Klingeman, Dawn M.; Hurt, Jr., Richard A.

This study characterized regions of DNA which remained unassembled by either PacBio and Illumina sequencing technologies for seven bacterial genomes. Two genomes were manually finished using bioinformatics and PCR/Sanger sequencing approaches and regions not assembled by automated software were analyzed. Gaps present within Illumina assemblies mostly correspond to repetitive DNA regions such as multiple rRNA operon sequences. PacBio gap sequences were evaluated for several properties such as GC content, read coverage, gap length, ability to form strong secondary structures, and corresponding annotations. Our hypothesis that strong secondary DNA structures blocked DNA polymerases and contributed to gap sequences was not accepted.more » PacBio assemblies had few limitations overall and gaps were explained as cumulative effect of lower than average sequence coverage and repetitive sequences at contig termini. An important aspect of the present study is the compilation of biological features that interfered with assembly and included active transposons, multiple plasmid sequences, phage DNA integration, and large sequence duplication. Furthermore, our targeted genome finishing approach and systematic evaluation of the unassembled DNA will be useful for others looking to close, finish, and polish microbial genome sequences.« less

A Case Study into Microbial Genome Assembly Gap Sequences and Finishing Strategies

DOE PAGES

Utturkar, Sagar M.; Klingeman, Dawn M.; Hurt, Jr., Richard A.; ...

2017-07-18

This study characterized regions of DNA which remained unassembled by either PacBio and Illumina sequencing technologies for seven bacterial genomes. Two genomes were manually finished using bioinformatics and PCR/Sanger sequencing approaches and regions not assembled by automated software were analyzed. Gaps present within Illumina assemblies mostly correspond to repetitive DNA regions such as multiple rRNA operon sequences. PacBio gap sequences were evaluated for several properties such as GC content, read coverage, gap length, ability to form strong secondary structures, and corresponding annotations. Our hypothesis that strong secondary DNA structures blocked DNA polymerases and contributed to gap sequences was not accepted.more » PacBio assemblies had few limitations overall and gaps were explained as cumulative effect of lower than average sequence coverage and repetitive sequences at contig termini. An important aspect of the present study is the compilation of biological features that interfered with assembly and included active transposons, multiple plasmid sequences, phage DNA integration, and large sequence duplication. Furthermore, our targeted genome finishing approach and systematic evaluation of the unassembled DNA will be useful for others looking to close, finish, and polish microbial genome sequences.« less

A Case Study into Microbial Genome Assembly Gap Sequences and Finishing Strategies

PubMed Central

Utturkar, Sagar M.; Klingeman, Dawn M.; Hurt, Richard A.; Brown, Steven D.

2017-01-01

This study characterized regions of DNA which remained unassembled by either PacBio and Illumina sequencing technologies for seven bacterial genomes. Two genomes were manually finished using bioinformatics and PCR/Sanger sequencing approaches and regions not assembled by automated software were analyzed. Gaps present within Illumina assemblies mostly correspond to repetitive DNA regions such as multiple rRNA operon sequences. PacBio gap sequences were evaluated for several properties such as GC content, read coverage, gap length, ability to form strong secondary structures, and corresponding annotations. Our hypothesis that strong secondary DNA structures blocked DNA polymerases and contributed to gap sequences was not accepted. PacBio assemblies had few limitations overall and gaps were explained as cumulative effect of lower than average sequence coverage and repetitive sequences at contig termini. An important aspect of the present study is the compilation of biological features that interfered with assembly and included active transposons, multiple plasmid sequences, phage DNA integration, and large sequence duplication. Our targeted genome finishing approach and systematic evaluation of the unassembled DNA will be useful for others looking to close, finish, and polish microbial genome sequences. PMID:28769883

Changes in Cirrus Cloudiness and their Relationship to Contrails

NASA Technical Reports Server (NTRS)

Minnis, Patrick; Ayers, J. Kirk; Palikonda, Rabindra; Doelling, David R.; Schumann, Ulrich; Gierens, Klaus

2001-01-01

Condensation trails, or contrails, formed in the wake of high-altitude aircraft have long been suspected of causing the formation of additional cirrus cloud cover. More cirrus is possible because 10 - 20% of the atmosphere at typical commercial flight altitudes is clear but ice-saturated. Since they can affect the radiation budget like natural cirrus clouds of equivalent optical depth and microphysical properties, contrail -generated cirrus clouds are another potential source of anthropogenic influence on climate. Initial estimates of contrail radiative forcing (CRF) were based on linear contrail coverage and optical depths derived from a limited number of satellite observations. Assuming that such estimates are accurate, they can be considered as the minimum possible CRF because contrails often develop into cirrus clouds unrecognizable as contrails. These anthropogenic cirrus are not likely to be identified as contrails from satellites and would, therefore, not contribute to estimates of contrail coverage. The mean lifetime and coverage of spreading contrails relative to linear contrails are needed to fully assess the climatic effect of contrails, but are difficult to measure directly. However, the maximum possible impact can be estimated using the relative trends in cirrus coverage over regions with and without air traffic. In this paper, the upper bound of CRF is derived by first computing the change in cirrus coverage over areas with heavy air traffic relative to that over the remainder of the globe assuming that the difference between the two trends is due solely to contrails. This difference is normalized to the corresponding linear contrail coverage for the same regions to obtain an average spreading factor. The maximum contrail-cirrus coverage, estimated as the product of the spreading factor and the linear contrail coverage, is then used in the radiative model to estimate the maximum potential CRF for current air traffic.

Screening, prevention and treatment of cervical cancer -- a global and regional generalized cost-effectiveness analysis.

PubMed

Ginsberg, Gary Michael; Edejer, Tessa Tan-Torres; Lauer, Jeremy A; Sepulveda, Cecilia

2009-10-09

The paper calculates regional generalized cost-effectiveness estimates of screening, prevention, treatment and combined interventions for cervical cancer. Using standardised WHO-CHOICE methodology, a cervical cancer model was employed to provide estimates of screening, vaccination and treatment effectiveness. Intervention effectiveness was determined via a population state-transition model (PopMod) that simulates the evolution of a sub-regional population accounting for births, deaths and disease epidemiology. Economic costs of procedures and treatment were estimated, including programme overhead and training costs. In regions characterized by high income, low mortality and high existing treatment coverage, the addition of any screening programme to the current high treatment levels is very cost-effective. However, based on projections of the future price per dose (representing the economic costs of the vaccination excluding monopolistic rents and vaccine development cost) vaccination is the most cost-effective intervention. In regions characterized by low income, low mortality and existing treatment coverage around 50%, expanding treatment with or without combining it with screening appears to be cost-effective or very cost-effective. Abandoning treatment in favour of screening in a no-treatment scenario would not be cost-effective. Vaccination is usually the most cost-effective intervention. Penta or tri-annual PAP smears appear to be cost-effective, though when combined with HPV-DNA testing they are not cost-effective. In regions characterized by low income, high mortality and low treatment levels, expanding treatment with or without adding screening would be very cost-effective. A one off vaccination plus expanding treatment was usually very cost-effective. One-off PAP or VIA screening at age 40 are more cost-effective than other interventions though less effective overall. From a cost-effectiveness perspective, consideration should be given to implementing vaccination (depending on cost per dose and longevity of efficacy) and screening programmes on a worldwide basis to reduce the burden of disease from cervical cancer. Treatment should also be increased where coverage is low.

Reduction in HPV 16/18 prevalence in sexually active young women following the introduction of HPV immunisation in England.

PubMed

Mesher, D; Soldan, K; Howell-Jones, R; Panwar, K; Manyenga, P; Jit, M; Beddows, S; Gill, O N

2013-12-17

Reduction in the prevalence of vaccine type HPV infection in young women is an early indication of the impact of the HPV immunisation programme and a necessary outcome if the subsequent impact on cervical cancer is to be realised. Residual vulva-vaginal swab (VVS) specimens from young women aged 16-24 years undergoing chlamydia screening in community sexual health services (formerly known as family planning clinics), general practice (GP), and youth clinics in 2010-2012 were submitted from 10 laboratories in seven regions around England. These specimens were linked to demographic and sexual behaviour data reported with the chlamydia test, anonymised, and tested for type-specific HPV DNA using a multiplex PCR and Luminex-based genotyping test. Estimated immunisation coverage was calculated and findings were compared to a baseline survey conducted prior to the introduction of HPV immunisation in 2008. A total of 4664 eligible specimens were collected and 4178 had a valid test result. The post-immunisation prevalence of HPV 16/18 infection was lowest in this youngest age group (16-18 years) and increased with age. This increase with age was a reversal of the pattern seen prior to immunisation and was inversely associated with estimates of age-specific immunisation coverage (65% for 16-18 year olds). The prevalence of HPV 16/18 infection in the post-immunisation survey was 6.5% amongst 16-18 year olds, compared to 19.1% in the similar survey conducted prior to the introduction of HPV immunisation. These findings are the first indication that the national HPV immunisation programme is successfully preventing HPV 16/18 infection in sexually active young women in England. The reductions seen suggest, for the estimated coverage, high vaccine effectiveness and some herd-protection benefits. Continued surveillance is needed to determine the effects of immunisation on non-vaccine HPV types. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Use of Lot Quality Assurance Sampling (LQAS) to estimate vaccination coverage helps guide future vaccination efforts.

PubMed

Alberti, K P; Guthmann, J P; Fermon, F; Nargaye, K D; Grais, R F

2008-03-01

Inadequate evaluation of vaccine coverage after mass vaccination campaigns, such as used in national measles control programmes, can lead to inappropriate public health responses. Overestimation of vaccination coverage may leave populations at risk, whilst underestimation can lead to unnecessary catch-up campaigns. The problem is more complex in large urban areas where vaccination coverage may be heterogeneous and the programme may have to be fine-tuned at the level of geographic subunits. Lack of accurate population figures in many contexts further complicates accurate vaccination coverage estimates. During the evaluation of a mass vaccination campaign carried out in N'Djamena, the capital of Chad, Lot Quality Assurance Sampling was used to estimate vaccination coverage. Using this method, vaccination coverage could be evaluated within smaller geographic areas of the city as well as for the entire city. Despite the lack of accurate population data by neighbourhood, the results of the survey showed heterogeneity of vaccination coverage within the city. These differences would not have been identified using a more traditional method. The results can be used to target areas of low vaccination coverage during follow-up vaccination activities.

Measuring HPV vaccination coverage in Australia: comparing two alternative population-based denominators.

PubMed

Barbaro, Bianca; Brotherton, Julia M L

2015-08-01

To compare the use of two alternative population-based denominators in calculating HPV vaccine coverage in Australia by age groups, jurisdiction and remoteness areas. Data from the National HPV Vaccination Program Register (NHVPR) were analysed at Local Government Area (LGA) level, by state/territory and by the Australian Standard Geographical Classification Remoteness Structure. The proportion of females vaccinated was calculated using both the ABS ERP and Medicare enrolments as the denominator. HPV vaccine coverage estimates were slightly higher using Medicare enrolments than using the ABS estimated resident population nationally (70.8% compared with 70.4% for 12 to 17-year-old females, and 33.3% compared with 31.9% for 18 to 26-year-old females, respectively.) The greatest differences in coverage were found in the remote areas of Australia. There is minimal difference between coverage estimates made using the two denominators except in Remote and Very Remote areas where small residential populations make interpretation more difficult. Adoption of Medicare enrolments for the denominator in the ongoing program would make minimal, if any, difference to routine coverage estimates. © 2015 Public Health Association of Australia.

Measurement of inelastic cross sections for low-energy electron scattering from DNA bases.

PubMed

Michaud, Marc; Bazin, Marc; Sanche, Léon

2012-01-01

To determine experimentally the absolute cross sections (CS) to deposit various amount of energies into DNA bases by low-energy electron (LEE) impact. Electron energy loss (EEL) spectra of DNA bases were recorded for different LEE impact energies on the molecules deposited at very low coverage on an inert argon (Ar) substrate. Following their normalisation to the effective incident electron current and molecular surface number density, the EEL spectra were then fitted with multiple Gaussian functions in order to delimit the various excitation energy regions. The CS to excite a molecule into its various excitation modes were finally obtained from computing the area under the corresponding Gaussians. The EEL spectra and absolute CS for the electronic excitations of pyrimidine and the DNA bases thymine, adenine, and cytosine by electron impacts below 18 eV were reported for the molecules deposited at about monolayer coverage on a solid Ar substrate. The CS for electronic excitations of DNA bases by LEE impact were found to lie within the 10(216) to 10(218) cm(2) range. The large value of the total ionisation CS indicated that ionisation of DNA bases by LEE is an important dissipative process via which ionising radiation degrades and is absorbed in DNA.

Measurement of inelastic cross sections for low-energy electron scattering from DNA bases

PubMed Central

Michaud, Marc; Bazin, Marc.; Sanche, Léon

2013-01-01

Purpose Determine experimentally the absolute cross sections (CS) to deposit various amount of energies into DNA bases by low-energy electron (LEE) impact. Materials and methods Electron energy loss (EEL) spectra of DNA bases are recorded for different LEE impact energies on the molecules deposited at very low coverage on an inert argon (Ar) substrate. Following their normalisation to the effective incident electron current and molecular surface number density, the EEL spectra are then fitted with multiple Gaussian functions in order to delimit the various excitation energy regions. The CS to excite a molecule into its various excitation modes are finally obtained from computing the area under the corresponding Gaussians. Results The EEL spectra and absolute CS for the electronic excitations of pyrimidine and the DNA bases thymine, adenine, and cytosine by electron impacts below 18 eV are reported for the molecules deposited at about monolayer coverage on a solid Ar substrate. Conclusions The CS for electronic excitations of DNA bases by LEE impact are found to lie within the 10−16 – 10−18 cm2 range. The large value of the total ionisation CS indicates that ionisation of DNA bases by LEE is an important dissipative process via which ionising radiation degrades and is absorbed in DNA. PMID:21615242

Measuring coverage in MNCH: design, implementation, and interpretation challenges associated with tracking vaccination coverage using household surveys.

PubMed

Cutts, Felicity T; Izurieta, Hector S; Rhoda, Dale A

2013-01-01

Vaccination coverage is an important public health indicator that is measured using administrative reports and/or surveys. The measurement of vaccination coverage in low- and middle-income countries using surveys is susceptible to numerous challenges. These challenges include selection bias and information bias, which cannot be solved by increasing the sample size, and the precision of the coverage estimate, which is determined by the survey sample size and sampling method. Selection bias can result from an inaccurate sampling frame or inappropriate field procedures and, since populations likely to be missed in a vaccination coverage survey are also likely to be missed by vaccination teams, most often inflates coverage estimates. Importantly, the large multi-purpose household surveys that are often used to measure vaccination coverage have invested substantial effort to reduce selection bias. Information bias occurs when a child's vaccination status is misclassified due to mistakes on his or her vaccination record, in data transcription, in the way survey questions are presented, or in the guardian's recall of vaccination for children without a written record. There has been substantial reliance on the guardian's recall in recent surveys, and, worryingly, information bias may become more likely in the future as immunization schedules become more complex and variable. Finally, some surveys assess immunity directly using serological assays. Sero-surveys are important for assessing public health risk, but currently are unable to validate coverage estimates directly. To improve vaccination coverage estimates based on surveys, we recommend that recording tools and practices should be improved and that surveys should incorporate best practices for design, implementation, and analysis.

Mapping and analysis of Caenorhabditis elegans transcription factor sequence specificities

PubMed Central

Narasimhan, Kamesh; Lambert, Samuel A; Yang, Ally WH; Riddell, Jeremy; Mnaimneh, Sanie; Zheng, Hong; Albu, Mihai; Najafabadi, Hamed S; Reece-Hoyes, John S; Fuxman Bass, Juan I; Walhout, Albertha JM; Weirauch, Matthew T; Hughes, Timothy R

2015-01-01

Caenorhabditis elegans is a powerful model for studying gene regulation, as it has a compact genome and a wealth of genomic tools. However, identification of regulatory elements has been limited, as DNA-binding motifs are known for only 71 of the estimated 763 sequence-specific transcription factors (TFs). To address this problem, we performed protein binding microarray experiments on representatives of canonical TF families in C. elegans, obtaining motifs for 129 TFs. Additionally, we predict motifs for many TFs that have DNA-binding domains similar to those already characterized, increasing coverage of binding specificities to 292 C. elegans TFs (∼40%). These data highlight the diversification of binding motifs for the nuclear hormone receptor and C2H2 zinc finger families and reveal unexpected diversity of motifs for T-box and DM families. Motif enrichment in promoters of functionally related genes is consistent with known biology and also identifies putative regulatory roles for unstudied TFs. DOI: http://dx.doi.org/10.7554/eLife.06967.001 PMID:25905672

[Real-time monitoring of anti-influenza vaccination in the 65 and over population in France based on vaccine sales].

PubMed

Pivette, M; Auvigne, V; Guérin, P; Mueller, J E

2017-04-01

The aim of this study was to describe a tool based on vaccine sales to estimate vaccination coverage against seasonal influenza in near real-time in the French population aged 65 and over. Vaccine sales data available on sale-day +1 came from a stratified sample of 3004 pharmacies in metropolitan France. Vaccination coverage rates were estimated between 2009 and 2014 and compared with those obtained based on vaccination refund data from the general health insurance scheme. The seasonal vaccination coverage estimates were highly correlated with those obtained from refund data. They were also slightly higher, which can be explained by the inclusion of non-reimbursed vaccines and the consideration of all individuals aged 65 and over. We have developed an online tool that provides estimates of daily vaccination coverage during each vaccination campaign. The developed tool provides a reliable and near real-time estimation of vaccination coverage among people aged 65 and over. It can be used to evaluate and adjust public health messages. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Comparing viral metagenomics methods using a highly multiplexed human viral pathogens reagent

PubMed Central

Li, Linlin; Deng, Xutao; Mee, Edward T.; Collot-Teixeira, Sophie; Anderson, Rob; Schepelmann, Silke; Minor, Philip D.; Delwart, Eric

2014-01-01

Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes including drug susceptibility or neutralization serotypes. In this study, different variables of the laboratory methods often used to generate viral metagenomics libraries on the efficiency of viral detection and virus genome coverage were compared. A biological reagent consisting of 25 different human RNA and DNA viral pathogens was used to estimate the effect of filtration and nuclease digestion, DNA/RNA extraction methods, pre-amplification and the use of different library preparation kits on the detection of viral nucleic acids. Filtration and nuclease treatment led to slight decreases in the percentage of viral sequence reads and number of viruses detected. For nucleic acid extractions silica spin columns improved viral sequence recovery relative to magnetic beads and Trizol extraction. Pre-amplification using random RT-PCR while generating more viral sequence reads resulted in detection of fewer viruses, more overlapping sequences, and lower genome coverage. The ScriptSeq library preparation method retrieved more viruses and a greater fraction of their genomes than the TruSeq and Nextera methods. Viral metagenomics sequencing was able to simultaneously detect up to 22 different viruses in the biological reagent analyzed including all those detected by qPCR. Further optimization will be required for the detection of viruses in biologically more complex samples such as tissues, blood, or feces. PMID:25497414

A Comparison of Various Estimators for Updating Forest Area Coverage Using AVHRR and Forest Inventory Data

Treesearch

Francis A. Roesch; Paul C. van Deusen; Zhiliang Zhu

1995-01-01

Various methods of adjusting low-cost and possibly biased estimates of percent forest coverage from AVHRR data with a subsample of higher-cost estimates from the USDA Forest Service's Forest Inventory and Analysis plots were investigated. Two ratio and two regression estimators were evaluated. Previous work (Zhu and Teuber, 1991) finding that the estimates from...

Uterotonic use immediately following birth: using a novel methodology to estimate population coverage in four countries.

PubMed

Ricca, Jim; Dwivedi, Vikas; Varallo, John; Singh, Gajendra; Pallipamula, Suranjeen Prasad; Amade, Nazir; de Luz Vaz, Maria; Bishanga, Dustan; Plotkin, Marya; Al-Makaleh, Bushra; Suhowatsky, Stephanie; Smith, Jeffrey Michael

2015-01-22

Postpartum hemorrhage (PPH) is the leading cause of maternal mortality in developing countries. While incidence of PPH can be dramatically reduced by uterotonic use immediately following birth (UUIFB) in both community and facility settings, national coverage estimates are rare. Most national health systems have no indicator to track this, and community-based measurements are even more scarce. To fill this information gap, a methodology for estimating national coverage for UUIFB was developed and piloted in four settings. The rapid estimation methodology consisted of convening a group of national technical experts and using the Delphi method to come to consensus on key data elements that were applied to a simple algorithm, generating a non-precise national estimate of coverage of UUIFB. Data elements needed for the calculation were the distribution of births by location and estimates of UUIFB in each of those settings, adjusted to take account of stockout rates and potency of uterotonics. This exercise was conducted in 2013 in Mozambique, Tanzania, the state of Jharkhand in India, and Yemen. Available data showed that deliveries in public health facilities account for approximately half of births in Mozambique and Tanzania, 16% in Jharkhand and 24% of births in Yemen. Significant proportions of births occur in private facilities in Jharkhand and faith-based facilities in Tanzania. Estimated uterotonic use for facility births ranged from 70 to 100%. Uterotonics are not used routinely for PPH prevention at home births in any of the settings. National UUIFB coverage estimates of all births were 43% in Mozambique, 40% in Tanzania, 44% in Jharkhand, and 14% in Yemen. This methodology for estimating coverage of UUIFB was found to be feasible and acceptable. While the exercise produces imprecise estimates whose validity cannot be assessed objectively in the absence of a gold standard estimate, stakeholders felt they were accurate enough to be actionable. The exercise highlighted information and practice gaps and promoted discussion on ways to improve UUIFB measurement and coverage, particularly of home births. Further follow up is needed to verify actions taken. The methodology produces useful data to help accelerate efforts to reduce maternal mortality.

Effects of ACA Medicaid Expansions on Health Insurance Coverage and Labor Supply.

PubMed

Kaestner, Robert; Garrett, Bowen; Chen, Jiajia; Gangopadhyaya, Anuj; Fleming, Caitlyn

We examined the effect of the expansion of Medicaid eligibility under the Affordable Care Act on health insurance coverage and labor supply of low-educated and low-income adults. We found that the Medicaid expansions were associated with large increases in Medicaid coverage, for example, 50 percent among childless adults, and corresponding decreases in the proportion uninsured. There was relatively little change in private insurance coverage, although the expansions tended to decrease such coverage slightly. In terms of labor supply, estimates indicated that the Medicaid expansions had little effect on work effort despite the substantial changes in health insurance coverage. Most estimates suggested that the expansions increased work effort, although not significantly.

Comparing Methods of Assessing Dog Rabies Vaccination Coverage in Rural and Urban Communities in Tanzania

PubMed Central

Sambo, Maganga; Johnson, Paul C. D.; Hotopp, Karen; Changalucha, Joel; Cleaveland, Sarah; Kazwala, Rudovick; Lembo, Tiziana; Lugelo, Ahmed; Lushasi, Kennedy; Maziku, Mathew; Mbunda, Eberhard; Mtema, Zacharia; Sikana, Lwitiko; Townsend, Sunny E.; Hampson, Katie

2017-01-01

Rabies can be eliminated by achieving comprehensive coverage of 70% of domestic dogs during annual mass vaccination campaigns. Estimates of vaccination coverage are, therefore, required to evaluate and manage mass dog vaccination programs; however, there is no specific guidance for the most accurate and efficient methods for estimating coverage in different settings. Here, we compare post-vaccination transects, school-based surveys, and household surveys across 28 districts in southeast Tanzania and Pemba island covering rural, urban, coastal and inland settings, and a range of different livelihoods and religious backgrounds. These approaches were explored in detail in a single district in northwest Tanzania (Serengeti), where their performance was compared with a complete dog population census that also recorded dog vaccination status. Post-vaccination transects involved counting marked (vaccinated) and unmarked (unvaccinated) dogs immediately after campaigns in 2,155 villages (24,721 dogs counted). School-based surveys were administered to 8,587 primary school pupils each representing a unique household, in 119 randomly selected schools approximately 2 months after campaigns. Household surveys were conducted in 160 randomly selected villages (4,488 households) in July/August 2011. Costs to implement these coverage assessments were $12.01, $66.12, and $155.70 per village for post-vaccination transects, school-based, and household surveys, respectively. Simulations were performed to assess the effect of sampling on the precision of coverage estimation. The sampling effort required to obtain reasonably precise estimates of coverage from household surveys is generally very high and probably prohibitively expensive for routine monitoring across large areas, particularly in communities with high human to dog ratios. School-based surveys partially overcame sampling constraints, however, were also costly to obtain reasonably precise estimates of coverage. Post-vaccination transects provided precise and timely estimates of community-level coverage that could be used to troubleshoot the performance of campaigns across large areas. However, transects typically overestimated coverage by around 10%, which therefore needs consideration when evaluating the impacts of campaigns. We discuss the advantages and disadvantages of these different methods and make recommendations for how vaccination campaigns can be better monitored and managed at different stages of rabies control and elimination programs. PMID:28352630

[Estimated mammogram coverage in Goiás State, Brazil].

PubMed

Corrêa, Rosangela da Silveira; Freitas-Júnior, Ruffo; Peixoto, João Emílio; Rodrigues, Danielle Cristina Netto; Lemos, Maria Eugênia da Fonseca; Marins, Lucy Aparecida Parreira; Silveira, Erika Aparecida da

2011-09-01

This cross-sectional study aimed to estimate mammogram coverage in the State of Goiás, Brazil, describing the supply, demand, and variations in different age groups, evaluating 98 mammography services as observational units. We estimated the mammogram rates by age group and type of health service, as well as the number of tests required to cover 70% and 100% of the target population. We assessed the association between mammograms, geographical distribution of mammography machines, type of service, and age group. Full coverage estimates, considering 100% of women in the 40-69 and 50-69-year age brackets, were 61% and 66%, of which the Brazilian Unified National Health System provided 13% and 14%, respectively. To achieve 70% coverage, 43,424 additional mammograms would be needed. All the associations showed statistically significant differences (p < 0.001). We conclude that mammogram coverage is unevenly distributed in the State of Goiás and that fewer tests are performed than required.

Measuring Coverage in MNCH: Design, Implementation, and Interpretation Challenges Associated with Tracking Vaccination Coverage Using Household Surveys

PubMed Central

Cutts, Felicity T.; Izurieta, Hector S.; Rhoda, Dale A.

2013-01-01

Vaccination coverage is an important public health indicator that is measured using administrative reports and/or surveys. The measurement of vaccination coverage in low- and middle-income countries using surveys is susceptible to numerous challenges. These challenges include selection bias and information bias, which cannot be solved by increasing the sample size, and the precision of the coverage estimate, which is determined by the survey sample size and sampling method. Selection bias can result from an inaccurate sampling frame or inappropriate field procedures and, since populations likely to be missed in a vaccination coverage survey are also likely to be missed by vaccination teams, most often inflates coverage estimates. Importantly, the large multi-purpose household surveys that are often used to measure vaccination coverage have invested substantial effort to reduce selection bias. Information bias occurs when a child's vaccination status is misclassified due to mistakes on his or her vaccination record, in data transcription, in the way survey questions are presented, or in the guardian's recall of vaccination for children without a written record. There has been substantial reliance on the guardian's recall in recent surveys, and, worryingly, information bias may become more likely in the future as immunization schedules become more complex and variable. Finally, some surveys assess immunity directly using serological assays. Sero-surveys are important for assessing public health risk, but currently are unable to validate coverage estimates directly. To improve vaccination coverage estimates based on surveys, we recommend that recording tools and practices should be improved and that surveys should incorporate best practices for design, implementation, and analysis. PMID:23667334

CancerLocator: non-invasive cancer diagnosis and tissue-of-origin prediction using methylation profiles of cell-free DNA.

PubMed

Kang, Shuli; Li, Qingjiao; Chen, Quan; Zhou, Yonggang; Park, Stacy; Lee, Gina; Grimes, Brandon; Krysan, Kostyantyn; Yu, Min; Wang, Wei; Alber, Frank; Sun, Fengzhu; Dubinett, Steven M; Li, Wenyuan; Zhou, Xianghong Jasmine

2017-03-24

We propose a probabilistic method, CancerLocator, which exploits the diagnostic potential of cell-free DNA by determining not only the presence but also the location of tumors. CancerLocator simultaneously infers the proportions and the tissue-of-origin of tumor-derived cell-free DNA in a blood sample using genome-wide DNA methylation data. CancerLocator outperforms two established multi-class classification methods on simulations and real data, even with the low proportion of tumor-derived DNA in the cell-free DNA scenarios. CancerLocator also achieves promising results on patient plasma samples with low DNA methylation sequencing coverage.

Monitoring the scale-up of antiretroviral therapy programmes: methods to estimate coverage.

PubMed Central

Boerma, J. Ties; Stanecki, Karen A.; Newell, Marie-Louise; Luo, Chewe; Beusenberg, Michel; Garnett, Geoff P.; Little, Kirsty; Calleja, Jesus Garcia; Crowley, Siobhan; Kim, Jim Yong; Zaniewski, Elizabeth; Walker, Neff; Stover, John; Ghys, Peter D.

2006-01-01

This paper reviews the data sources and methods used to estimate the number of people on, and coverage of, antiretroviral therapy (ART) programmes in low- and middle-income countries and to monitor the progress towards the "3 by 5" target set by WHO and UNAIDS. We include a review of the data sources used to estimate the coverage of ART programmes as well as the efforts made to avoid double counting and over-reporting. The methods used to estimate the number of people in need of ART are described and expanded with estimates of treatment needs for children, both for ART and for cotrimoxazole prophylaxis. An estimated 6.5 million people were in need of treatment in low- and middle-income countries by the end of 2004, including 660,000 children under age 15 years. The mid-2005 estimate of 970,000 people receiving ART in low- and middle-income countries (with an uncertainty range 840,000-1,100,000) corresponds to a coverage of 15% of people in need of treatment. PMID:16501733

Selective DNA-Mediated Assembly of Gold Nanoparticles on Electroded Substrates

DTIC Science & Technology

2008-06-01

might use the Watson - Crick base-pairing of DNA as a means for ultrahigh-precision engineering is well- known.5,6 The idea is to use the highly specific...Selective DNA -Mediated Assembly of Gold Nanoparticles on Electroded Substrates K. E. Sapsford,†,‡,∇ D. Park,§ E. R. Goldman,‡ E. E. Foos,| S. A...electrodes via DNA hybridization. Protocols are demonstrated for maximizing selectivity and coverage using 15mers as the active binding agents. Detailed

J-Adaptive estimation with estimated noise statistics. [for orbit determination

NASA Technical Reports Server (NTRS)

Jazwinski, A. H.; Hipkins, C.

1975-01-01

The J-Adaptive estimator described by Jazwinski and Hipkins (1972) is extended to include the simultaneous estimation of the statistics of the unmodeled system accelerations. With the aid of simulations it is demonstrated that the J-Adaptive estimator with estimated noise statistics can automatically estimate satellite orbits to an accuracy comparable with the data noise levels, when excellent, continuous tracking coverage is available. Such tracking coverage will be available from satellite-to-satellite tracking.

Exploring Pandora's Box: Potential and Pitfalls of Low Coverage Genome Surveys for Evolutionary Biology

PubMed Central

Leese, Florian; Mayer, Christoph; Agrawal, Shobhit; Dambach, Johannes; Dietz, Lars; Doemel, Jana S.; Goodall-Copstake, William P.; Held, Christoph; Jackson, Jennifer A.; Lampert, Kathrin P.; Linse, Katrin; Macher, Jan N.; Nolzen, Jennifer; Raupach, Michael J.; Rivera, Nicole T.; Schubart, Christoph D.; Striewski, Sebastian; Tollrian, Ralph; Sands, Chester J.

2012-01-01

High throughput sequencing technologies are revolutionizing genetic research. With this “rise of the machines”, genomic sequences can be obtained even for unknown genomes within a short time and for reasonable costs. This has enabled evolutionary biologists studying genetically unexplored species to identify molecular markers or genomic regions of interest (e.g. micro- and minisatellites, mitochondrial and nuclear genes) by sequencing only a fraction of the genome. However, when using such datasets from non-model species, it is possible that DNA from non-target contaminant species such as bacteria, viruses, fungi, or other eukaryotic organisms may complicate the interpretation of the results. In this study we analysed 14 genomic pyrosequencing libraries of aquatic non-model taxa from four major evolutionary lineages. We quantified the amount of suitable micro- and minisatellites, mitochondrial genomes, known nuclear genes and transposable elements and searched for contamination from various sources using bioinformatic approaches. Our results show that in all sequence libraries with estimated coverage of about 0.02–25%, many appropriate micro- and minisatellites, mitochondrial gene sequences and nuclear genes from different KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways could be identified and characterized. These can serve as markers for phylogenetic and population genetic analyses. A central finding of our study is that several genomic libraries suffered from different biases owing to non-target DNA or mobile elements. In particular, viruses, bacteria or eukaryote endosymbionts contributed significantly (up to 10%) to some of the libraries analysed. If not identified as such, genetic markers developed from high-throughput sequencing data for non-model organisms may bias evolutionary studies or fail completely in experimental tests. In conclusion, our study demonstrates the enormous potential of low-coverage genome survey sequences and suggests bioinformatic analysis workflows. The results also advise a more sophisticated filtering for problematic sequences and non-target genome sequences prior to developing markers. PMID:23185309

Trends in Childhood Influenza Vaccination Coverage—U.S., 2004–2012

PubMed Central

Lu, Peng-Jun; O'Halloran, Alissa; Meghani, Ankita; Grabowsky, Mark; Singleton, James A.

2014-01-01

Objective We compared estimates of childhood influenza vaccination coverage by health status, age, and racial/ethnic group across eight consecutive influenza seasons (2004 through 2012) based on two survey systems to assess trends in childhood influenza vaccination coverage in the U.S. Methods We used National Health Interview Survey (NHIS) and National Immunization Survey-Flu (NIS-Flu) data to estimate receipt of at least one dose of influenza vaccination among children aged 6 months to 17 years based on parental report. We computed estimates using Kaplan-Meier survival analysis methods. Results Based on the NHIS, overall influenza vaccination coverage with at least one dose of influenza vaccine among children increased from 16.2% during the 2004–2005 influenza season to 47.1% during the 2011–2012 influenza season. Children with health conditions that put them at high risk for complications from influenza had higher influenza vaccination coverage than children without these health conditions for all the seasons studied. In seven of the eight seasons studied, there were no significant differences in influenza vaccination coverage between non-Hispanic black and non-Hispanic white children. Influenza vaccination coverage estimates for children were slightly higher based on NIS-Flu data compared with NHIS data for the 2010–2011 and 2011–2012 influenza seasons (4.1 and 4.4 percentage points higher, respectively); both NIS-Flu and NHIS estimates had similar patterns of decreasing vaccination coverage with increasing age. Conclusions Although influenza vaccination coverage among children continued to increase, by the 2011–2012 influenza season, only slightly less than half of U.S. children were vaccinated against influenza. Much improvement is needed to ensure all children aged ≥6 months are vaccinated annually against influenza. PMID:25177053

NSW annual immunisation coverage report, 2011.

PubMed

Hull, Brynley; Dey, Aditi; Campbell-Lloyd, Sue; Menzies, Robert I; McIntyre, Peter B

2012-12-01

This annual report, the third in the series, documents trends in immunisation coverage in NSW for children, adolescents and the elderly, to the end of 2011. Data from the Australian Childhood Immunisation Register, the NSW School Immunisation Program and the NSW Population Health Survey were used to calculate various measures of population coverage. During 2011, greater than 90% coverage was maintained for children at 12 and 24 months of age. For children at 5 years of age the improvement seen in 2010 was sustained, with coverage at or near 90%. For adolescents, there was improved coverage for all doses of human papillomavirus vaccine, both doses of hepatitis B vaccine, varicella vaccine and the dose of diphtheria, tetanus and acellular pertussis given to school attendees in Years 7 and 10. Pneumococcal vaccination coverage in the elderly has been steadily rising, although it has remained lower than the influenza coverage estimates. This report provides trends in immunisation coverage in NSW across the age spectrum. The inclusion of coverage estimates for the pneumococcal conjugate, varicella and meningococcal C vaccines in the official coverage assessments for 'fully immunised' in 2013 is a welcome initiative.

Establishing a community-wide DNA barcode library as a new tool for arctic research.

PubMed

Wirta, H; Várkonyi, G; Rasmussen, C; Kaartinen, R; Schmidt, N M; Hebert, P D N; Barták, M; Blagoev, G; Disney, H; Ertl, S; Gjelstrup, P; Gwiazdowicz, D J; Huldén, L; Ilmonen, J; Jakovlev, J; Jaschhof, M; Kahanpää, J; Kankaanpää, T; Krogh, P H; Labbee, R; Lettner, C; Michelsen, V; Nielsen, S A; Nielsen, T R; Paasivirta, L; Pedersen, S; Pohjoismäki, J; Salmela, J; Vilkamaa, P; Väre, H; von Tschirnhaus, M; Roslin, T

2016-05-01

DNA sequences offer powerful tools for describing the members and interactions of natural communities. In this study, we establish the to-date most comprehensive library of DNA barcodes for a terrestrial site, including all known macroscopic animals and vascular plants of an intensively studied area of the High Arctic, the Zackenberg Valley in Northeast Greenland. To demonstrate its utility, we apply the library to identify nearly 20 000 arthropod individuals from two Malaise traps, each operated for two summers. Drawing on this material, we estimate the coverage of previous morphology-based species inventories, derive a snapshot of faunal turnover in space and time and describe the abundance and phenology of species in the rapidly changing arctic environment. Overall, 403 terrestrial animal and 160 vascular plant species were recorded by morphology-based techniques. DNA barcodes (CO1) offered high resolution in discriminating among the local animal taxa, with 92% of morphologically distinguishable taxa assigned to unique Barcode Index Numbers (BINs) and 93% to monophyletic clusters. For vascular plants, resolution was lower, with 54% of species forming monophyletic clusters based on barcode regions rbcLa and ITS2. Malaise catches revealed 122 BINs not detected by previous sampling and DNA barcoding. The insect community was dominated by a few highly abundant taxa. Even closely related taxa differed in phenology, emphasizing the need for species-level resolution when describing ongoing shifts in arctic communities and ecosystems. The DNA barcode library now established for Zackenberg offers new scope for such explorations, and for the detailed dissection of interspecific interactions throughout the community. © 2015 John Wiley & Sons Ltd.

Coprolites as a source of information on the genome and diet of the cave hyena

PubMed Central

Bon, Céline; Berthonaud, Véronique; Maksud, Frédéric; Labadie, Karine; Poulain, Julie; Artiguenave, François; Wincker, Patrick; Aury, Jean-Marc; Elalouf, Jean-Marc

2012-01-01

We performed high-throughput sequencing of DNA from fossilized faeces to evaluate this material as a source of information on the genome and diet of Pleistocene carnivores. We analysed coprolites derived from the extinct cave hyena (Crocuta crocuta spelaea), and sequenced 90 million DNA fragments from two specimens. The DNA reads enabled a reconstruction of the cave hyena mitochondrial genome with up to a 158-fold coverage. This genome, and those sequenced from extant spotted (Crocuta crocuta) and striped (Hyaena hyaena) hyena specimens, allows for the establishment of a robust phylogeny that supports a close relationship between the cave and the spotted hyena. We also demonstrate that high-throughput sequencing yields data for cave hyena multi-copy and single-copy nuclear genes, and that about 50 per cent of the coprolite DNA can be ascribed to this species. Analysing the data for additional species to indicate the cave hyena diet, we retrieved abundant sequences for the red deer (Cervus elaphus), and characterized its mitochondrial genome with up to a 3.8-fold coverage. In conclusion, we have demonstrated the presence of abundant ancient DNA in the coprolites surveyed. Shotgun sequencing of this material yielded a wealth of DNA sequences for a Pleistocene carnivore and allowed unbiased identification of diet. PMID:22456883

Functionalization of quantum rods with oligonucleotides for programmable assembly with DNA origami

NASA Astrophysics Data System (ADS)

Doane, Tennyson L.; Alam, Rabeka; Maye, Mathew M.

2015-02-01

The DNA-mediated self-assembly of CdSe/CdS quantum rods (QRs) onto DNA origami is described. Two QR types with unique optical emission and high polarization were synthesized, and then functionalized with oligonucleotides (ssDNA) using a novel protection-deprotection approach, which harnessed ssDNA's tailorable rigidity and denaturation temperature to increase DNA coverage by reducing non-specific coordination and wrapping. The QR assembly was programmable, and occurred at two different assembly zones that had capture strands in parallel alignment. QRs with different optical properties were assembled, opening up future studies on orientation dependent QR FRET. The QR-origami conjugates could be purified via gel electrophoresis and sucrose gradient ultracentrifugation. Assembly yields, QR stoichiometry and orientation, as well as energy transfer implications were studied in light of QR distances, origami flexibility, and conditions.The DNA-mediated self-assembly of CdSe/CdS quantum rods (QRs) onto DNA origami is described. Two QR types with unique optical emission and high polarization were synthesized, and then functionalized with oligonucleotides (ssDNA) using a novel protection-deprotection approach, which harnessed ssDNA's tailorable rigidity and denaturation temperature to increase DNA coverage by reducing non-specific coordination and wrapping. The QR assembly was programmable, and occurred at two different assembly zones that had capture strands in parallel alignment. QRs with different optical properties were assembled, opening up future studies on orientation dependent QR FRET. The QR-origami conjugates could be purified via gel electrophoresis and sucrose gradient ultracentrifugation. Assembly yields, QR stoichiometry and orientation, as well as energy transfer implications were studied in light of QR distances, origami flexibility, and conditions. Electronic supplementary information (ESI) available: Experimental conditions, DNA origami blueprint and sequences, FRET calculations. Additional Fig. S1-S13. See DOI: 10.1039/c4nr07662a

High-coverage methylation data of a gene model before and after DNA damage and homologous repair.

PubMed

Pezone, Antonio; Russo, Giusi; Tramontano, Alfonso; Florio, Ermanno; Scala, Giovanni; Landi, Rosaria; Zuchegna, Candida; Romano, Antonella; Chiariotti, Lorenzo; Muller, Mark T; Gottesman, Max E; Porcellini, Antonio; Avvedimento, Enrico V

2017-04-11

Genome-wide methylation analysis is limited by its low coverage and the inability to detect single variants below 10%. Quantitative analysis provides accurate information on the extent of methylation of single CpG dinucleotide, but it does not measure the actual polymorphism of the methylation profiles of single molecules. To understand the polymorphism of DNA methylation and to decode the methylation signatures before and after DNA damage and repair, we have deep sequenced in bisulfite-treated DNA a reporter gene undergoing site-specific DNA damage and homologous repair. In this paper, we provide information on the data generation, the rationale for the experiments and the type of assays used, such as cytofluorimetry and immunoblot data derived during a previous work published in Scientific Reports, describing the methylation and expression changes of a model gene (GFP) before and after formation of a double-strand break and repair by homologous-recombination or non-homologous-end-joining. These data provide: 1) a reference for the analysis of methylation polymorphism at selected loci in complex cell populations; 2) a platform and the tools to compare transcription and methylation profiles.

High-coverage methylation data of a gene model before and after DNA damage and homologous repair

PubMed Central

Pezone, Antonio; Russo, Giusi; Tramontano, Alfonso; Florio, Ermanno; Scala, Giovanni; Landi, Rosaria; Zuchegna, Candida; Romano, Antonella; Chiariotti, Lorenzo; Muller, Mark T.; Gottesman, Max E.; Porcellini, Antonio; Avvedimento, Enrico V.

2017-01-01

Genome-wide methylation analysis is limited by its low coverage and the inability to detect single variants below 10%. Quantitative analysis provides accurate information on the extent of methylation of single CpG dinucleotide, but it does not measure the actual polymorphism of the methylation profiles of single molecules. To understand the polymorphism of DNA methylation and to decode the methylation signatures before and after DNA damage and repair, we have deep sequenced in bisulfite-treated DNA a reporter gene undergoing site-specific DNA damage and homologous repair. In this paper, we provide information on the data generation, the rationale for the experiments and the type of assays used, such as cytofluorimetry and immunoblot data derived during a previous work published in Scientific Reports, describing the methylation and expression changes of a model gene (GFP) before and after formation of a double-strand break and repair by homologous-recombination or non-homologous-end-joining. These data provide: 1) a reference for the analysis of methylation polymorphism at selected loci in complex cell populations; 2) a platform and the tools to compare transcription and methylation profiles. PMID:28398335

Assessing DNA Barcodes for Species Identification in North American Reptiles and Amphibians in Natural History Collections.

PubMed

Chambers, E Anne; Hebert, Paul D N

2016-01-01

High rates of species discovery and loss have led to the urgent need for more rapid assessment of species diversity in the herpetofauna. DNA barcoding allows for the preliminary identification of species based on sequence divergence. Prior DNA barcoding work on reptiles and amphibians has revealed higher biodiversity counts than previously estimated due to cases of cryptic and undiscovered species. Past studies have provided DNA barcodes for just 14% of the North American herpetofauna, revealing the need for expanded coverage. This study extends the DNA barcode reference library for North American herpetofauna, assesses the utility of this approach in aiding species delimitation, and examines the correspondence between current species boundaries and sequence clusters designated by the BIN system. Sequences were obtained from 730 specimens, representing 274 species (43%) from the North American herpetofauna. Mean intraspecific divergences were 1% and 3%, while average congeneric sequence divergences were 16% and 14% in amphibians and reptiles, respectively. BIN assignments corresponded with current species boundaries in 79% of amphibians, 100% of turtles, and 60% of squamates. Deep divergences (>2%) were noted in 35% of squamate and 16% of amphibian species, and low divergences (<2%) occurred in 12% of reptiles and 23% of amphibians, patterns reflected in BIN assignments. Sequence recovery declined with specimen age, and variation in recovery success was noted among collections. Within collections, barcodes effectively flagged seven mislabeled tissues, and barcode fragments were recovered from five formalin-fixed specimens. This study demonstrates that DNA barcodes can effectively flag errors in museum collections, while BIN splits and merges reveal taxa belonging to deeply diverged or hybridizing lineages. This study is the first effort to compile a reference library of DNA barcodes for herpetofauna on a continental scale.

Assessing DNA Barcodes for Species Identification in North American Reptiles and Amphibians in Natural History Collections

PubMed Central

Chambers, E. Anne; Hebert, Paul D. N.

2016-01-01

Background High rates of species discovery and loss have led to the urgent need for more rapid assessment of species diversity in the herpetofauna. DNA barcoding allows for the preliminary identification of species based on sequence divergence. Prior DNA barcoding work on reptiles and amphibians has revealed higher biodiversity counts than previously estimated due to cases of cryptic and undiscovered species. Past studies have provided DNA barcodes for just 14% of the North American herpetofauna, revealing the need for expanded coverage. Methodology/Principal Findings This study extends the DNA barcode reference library for North American herpetofauna, assesses the utility of this approach in aiding species delimitation, and examines the correspondence between current species boundaries and sequence clusters designated by the BIN system. Sequences were obtained from 730 specimens, representing 274 species (43%) from the North American herpetofauna. Mean intraspecific divergences were 1% and 3%, while average congeneric sequence divergences were 16% and 14% in amphibians and reptiles, respectively. BIN assignments corresponded with current species boundaries in 79% of amphibians, 100% of turtles, and 60% of squamates. Deep divergences (>2%) were noted in 35% of squamate and 16% of amphibian species, and low divergences (<2%) occurred in 12% of reptiles and 23% of amphibians, patterns reflected in BIN assignments. Sequence recovery declined with specimen age, and variation in recovery success was noted among collections. Within collections, barcodes effectively flagged seven mislabeled tissues, and barcode fragments were recovered from five formalin-fixed specimens. Conclusions/Significance This study demonstrates that DNA barcodes can effectively flag errors in museum collections, while BIN splits and merges reveal taxa belonging to deeply diverged or hybridizing lineages. This study is the first effort to compile a reference library of DNA barcodes for herpetofauna on a continental scale. PMID:27116180

State of equity: childhood immunization in the World Health Organization African Region.

PubMed

Casey, Rebecca Mary; Hampton, Lee McCalla; Anya, Blanche-Philomene Melanga; Gacic-Dobo, Marta; Diallo, Mamadou Saliou; Wallace, Aaron Stuart

2017-01-01

In 2010, the Global Vaccine Action Plan called on all countries to reach and sustain 90% national coverage and 80% coverage in all districts for the third dose of diphtheria-tetanus-pertussis vaccine (DTP3) by 2015 and for all vaccines in national immunization schedules by 2020. The aims of this study are to analyze recent trends in national vaccination coverage in the World Health Organization African Region andto assess how these trends differ by country income category. We compared national vaccination coverage estimates for DTP3 and the first dose of measles-containing vaccine (MCV) obtained from the World Health Organization (WHO)/United Nations Children's Fund (UNICEF) joint estimates of national immunization coverage for all African Region countries. Using United Nations (UN) population estimates of surviving infants and country income category for the corresponding year, we calculated population-weighted average vaccination coverage by country income category (i.e., low, lower middle, and upper middle-income) for the years 2000, 2005, 2010 and 2015. DTP3 coverage in the African Region increased from 52% in 2000 to 76% in 2015,and MCV1 coverage increased from 53% to 74% during the same period, but with considerable differences among countries. Thirty-six African Region countries were low income in 2000 with an average DTP3 coverage of 50% while 26 were low income in 2015 with an average coverage of 80%. Five countries were lower middle-income in 2000 with an average DTP3 coverage of 84% while 12 were lower middle-income in 2015 with an average coverage of 69%. Five countries were upper middle-income in 2000 with an average DTP3 coverage of 73% and eight were upper middle-income in 2015 with an average coverage of 76%. Disparities in vaccination coverage by country persist in the African Region, with countries that were lower middle-income having the lowest coverage on average in 2015. Monitoring and addressing these disparities is essential for meeting global immunization targets.

Measuring populations to improve vaccination coverage

NASA Astrophysics Data System (ADS)

Bharti, Nita; Djibo, Ali; Tatem, Andrew J.; Grenfell, Bryan T.; Ferrari, Matthew J.

2016-10-01

In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes.

Measuring populations to improve vaccination coverage

PubMed Central

Bharti, Nita; Djibo, Ali; Tatem, Andrew J.; Grenfell, Bryan T.; Ferrari, Matthew J.

2016-01-01

In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes. PMID:27703191

Surface Coverage and Structure of Mixed DNA/Alkylthiol Monolayers on Gold: Characterization by XPS, NEXAFS, and Fluorescence Intensity Measurements

PubMed Central

Lee, Chi-Ying; Gong, Ping; Harbers, Gregory M.; Grainger, David W.; Castner, David G.; Gamble, Lara J.

2006-01-01

Self-assembly of thiol-terminated single-stranded DNA (HS-ssDNA) on gold has served as an important model system for DNA immobilization at surfaces. Here, we report a detailed study of the surface composition and structure of mixed self-assembled DNA monolayers containing a short alkylthiol surface diluent [11-mercapto-1-undecanol (MCU)] on gold supports. These mixed DNA monolayers were studied with X-ray photoelectron spectroscopy (XPS), near-edge X-ray absorption fine structure spectroscopy (NEXAFS), and fluorescence intensity measurements. XPS results on sequentially adsorbed DNA/MCU monolayers on gold indicated that adsorbed MCU molecules first incorporate into the HS-ssDNA monolayer and, upon longer MCU exposures, displace adsorbed HS-ssDNA molecules from the surface. Thus, HS-ssDNA surface coverage steadily decreased with MCU exposure time. Polarization-dependent NEXAFS and fluorescence results both show changes in signals consistent with changes in DNA orientation after only 30 min of MCU exposure. NEXAFS polarization dependence (followed by monitoring the N 1s → π* transition) of the mixed DNA monolayers indicated that the DNA nucleotide base ring structures are oriented more parallel to the gold surface compared to DNA bases in pure HS-ssDNA monolayers. This indicates that HS-ssDNA oligomers reorient toward a more-upright position upon MCU incorporation. Fluorescence intensity results using end-labeled DNA probes on gold show little observable fluorescence on pure HS-ssDNA monolayers, likely due to substrate quenching effects between the fluorophore and the gold. MCU diluent incorporation into HS-ssDNA monolayers initially increases DNA fluorescence signal by densifying the chemisorbed monolayer, prompting an upright orientation of the DNA, and moving the terminal fluorophore away from the substrate. Immobilized DNA probe density and DNA target hybridization in these mixed DNA monolayers, as well as effects of MCU diluent on DNA hybridization in complex milieu (i.e., serum) were characterized by surface plasmon resonance (SPR) and 32P-radiometric assays and reported in a related study PMID:16689533

Estimation of Nationwide Vaccination Coverage and Comparison of Interview and Telephone Survey Methodology for Estimating Vaccination Status

PubMed Central

Park, Boyoung; Lee, Yeon-Kyeng; Cho, Lisa Y.; Go, Un Yeong; Yang, Jae Jeong; Ma, Seung Hyun; Choi, Bo-Youl; Lee, Moo-Sik; Lee, Jin-Seok; Choi, Eun Hwa; Lee, Hoan Jong

2011-01-01

This study compared interview and telephone surveys to select the better method for regularly estimating nationwide vaccination coverage rates in Korea. Interview surveys using multi-stage cluster sampling and telephone surveys using stratified random sampling were conducted. Nationwide coverage rates were estimated in subjects with vaccination cards in the interview survey. The interview survey relative to the telephone survey showed a higher response rate, lower missing rate, higher validity and a less difference in vaccination coverage rates between card owners and non-owners. Primary vaccination coverage rate was greater than 90% except for the fourth dose of DTaP (diphtheria/tetanus/pertussis), the third dose of polio, and the third dose of Japanese B encephalitis (JBE). The DTaP4: Polio3: MMR1 fully vaccination rate was 62.0% and BCG1:HepB3:DTaP4:Polio3:MMR1 was 59.5%. For age-appropriate vaccination, the coverage rate was 50%-80%. We concluded that the interview survey was better than the telephone survey. These results can be applied to countries with incomplete registry and decreasing rates of landline telephone coverage due to increased cell phone usage and countries. Among mandatory vaccines, efforts to increase vaccination rate for the fourth dose of DTaP, the third dose of polio, JBE and regular vaccinations at recommended periods should be conducted in Korea. PMID:21655054

Epidemiologic and Molecular Relationship Between Vaccine Manufacture and Autism Spectrum Disorder Prevalence.

PubMed

Deisher, Theresa A; Doan, Ngoc V; Koyama, Kumiko; Bwabye, Sarah

2015-01-01

To assess the public health consequences of fetal cell line manufactured vaccines that contain residual human fetal DNA fragments utilizing laboratory and ecological approaches including statistics, molecular biology and genomics. MMR coverage and autism disorder or autism spectrum disorder prevalence data for Norway, Sweden and the UK were obtained from public and government websites as well as peer reviewed published articles. Biologically, the size and quantity of the contaminating fetal DNA in Meruvax II and Havrix as well as the propensity of various cell lines for cellular and nuclear uptake of primitive human DNA fragments were measured and quantified using gel electrophoresis, fluorescence microscopy and fluorometry. Lastly, genomic analysis identified the specific sites where fetal DNA fragment integration into a child's genome is most likely to occur. The average MMR coverage for the three countries fell below 90% after Dr. Wakefield's infamous 1998 publication but started to recover slowly after 2001 until reaching over 90% coverage again by 2004. During the same time period, the average autism spectrum disorder prevalence in the United Kingdom, Norway and Sweden dropped substantially after birth year 1998 and gradually increased again after birth year 2000. Average single stranded DNA and double stranded DNA in Meruvax II were 142.05 ng/vial and 35.00 ng/vial, respectively, and 276.00 ng/vial and 35.74 ng/vial in Havrix respectively. The size of the fetal DNA fragments in Meruvax II was approximately 215 base pairs. There was spontaneous cellular and nuclear DNA uptake in HFF1 and NCCIT cells. Genes that have been linked to autism (autism associated genes; AAGs) have a more concentrated susceptibility for insults to genomic stability in comparison to the group of all genes contained within the human genome. Of the X chromosome AAGs, 15 of 19 have double strand break motifs less than 100 kilobases away from the center of a meiotic recombination hotspot located within an exon. Vaccines manufactured in human fetal cell lines contain unacceptably high levels of fetal DNA fragment contaminants. The human genome naturally contains regions that are susceptible to double strand break formation and DNA insertional mutagenesis. The "Wakefield Scare" created a natural experiment that may demonstrate a causal relationship between fetal cell-line manufactured vaccines and ASD prevalence.

Young Adults' Selection and Use of Dependent Coverage under the Affordable Care Act.

PubMed

Chen, Weiwei

2018-01-01

The dependent coverage expansion under the Affordable Care Act (ACA) required health insurance policies that cover dependents to offer coverage for policyholder' children up to age 26. It has been well documented that the provision successfully reduced the uninsured rate among the young adults. However, less is known about whether dependent coverage crowded out other insurance types and whether young adults used dependent coverage as a fill-in-the-gap short-term option. Using data from the Survey of Income and Program Participation 2008 Panel, the paper assesses dependent coverage uptake and duration before and after the ACA provision among young adults aged 19-26 versus those aged 27-30. Regressions for additional coverage outcomes were also performed to estimate the crowd-out rate. It was found that the ACA provision had a significant positive impact on dependent coverage uptake and duration. The estimated crowd-out rate ranges from 27 to 42%, depending on the definition. Most dependent coverage enrollees used the coverage for 1 or 2 years. Differences in dependent coverage uptake and duration remained among racial groups. Less healthy individuals were also less likely to make use of dependent coverage.

Young Adults’ Selection and Use of Dependent Coverage under the Affordable Care Act

PubMed Central

Chen, Weiwei

2018-01-01

The dependent coverage expansion under the Affordable Care Act (ACA) required health insurance policies that cover dependents to offer coverage for policyholder’ children up to age 26. It has been well documented that the provision successfully reduced the uninsured rate among the young adults. However, less is known about whether dependent coverage crowded out other insurance types and whether young adults used dependent coverage as a fill-in-the-gap short-term option. Using data from the Survey of Income and Program Participation 2008 Panel, the paper assesses dependent coverage uptake and duration before and after the ACA provision among young adults aged 19–26 versus those aged 27–30. Regressions for additional coverage outcomes were also performed to estimate the crowd-out rate. It was found that the ACA provision had a significant positive impact on dependent coverage uptake and duration. The estimated crowd-out rate ranges from 27 to 42%, depending on the definition. Most dependent coverage enrollees used the coverage for 1 or 2 years. Differences in dependent coverage uptake and duration remained among racial groups. Less healthy individuals were also less likely to make use of dependent coverage. PMID:29445721

Whom and where are we not vaccinating? Coverage after the introduction of a new conjugate vaccine against group A meningococcus in Niger in 2010.

PubMed

Kim, Sung Hye; Pezzoli, Lorenzo; Yacouba, Harouna; Coulibaly, Tiekoura; Djingarey, Mamoudou H; Perea, William A; Wierzba, Thomas F

2012-01-01

MenAfriVac is a new conjugate vaccine against Neisseria meningitidis serogroup A developed for the African "meningitis belt". In Niger, the first two phases of the MenAfriVac introduction campaign were conducted targeting 3,135,942 individuals aged 1 to 29 years in the regions of Tillabéri, Niamey, and Dosso, in September and December 2010. We evaluated the campaign and determined which sub-populations or areas had low levels of vaccination coverage in the regions of Tillabéri and Niamey. After Phase I, conducted in the Filingué district, we estimated coverage using a 30×15 cluster-sampling survey and nested lot quality assurance (LQA) analysis in the clustered samples to identify which subpopulations (defined by age 1-14/15-29 and sex) had unacceptable vaccination coverage (<70%). After Phase II, we used Clustered Lot Quality Assurance Sampling (CLQAS) to assess if any of eight districts in Niamey and Tillabéri had unacceptable vaccination coverage (<75%) and estimated overall coverage. Estimated vaccination coverage was 77.4% (95%CI: 84.6-70.2) as documented by vaccination cards and 85.5% (95% CI: 79.7-91.2) considering verbal history of vaccination for Phase I; 81.5% (95%CI: 86.1-77.0) by card and 93.4% (95% CI: 91.0-95.9) by verbal history for Phase II. Based on vaccination cards, in Filingué, we identified both the male and female adult (age 15-29) subpopulations as not reaching 70% coverage; and we identified three (one in Tillabéri and two in Niamey) out of eight districts as not reaching 75% coverage confirmed by card. Combined use of LQA and cluster sampling was useful to estimate vaccination coverage and to identify pockets with unacceptable levels of coverage (adult population and three districts). Although overall vaccination coverage was satisfactory, we recommend continuing vaccination in the areas or sub-populations with low coverage and reinforcing the social mobilization of the adult population.

Biosensing via light scattering from plasmonic core-shell nanospheres coated with DNA molecules

NASA Astrophysics Data System (ADS)

Xie, Huai-Yi; Chen, Minfeng; Chang, Yia-Chung; Moirangthem, Rakesh Singh

2017-05-01

We present both experimental and theoretical studies for investigating DNA molecules attached on metallic nanospheres. We have developed an efficient and accurate numerical method to investigate light scattering from plasmonic nanospheres on a substrate covered by a shell, based on the Green's function approach with suitable spherical harmonic basis. Next, we use this method to study optical scattering from DNA molecules attached to metallic nanoparticles placed on a substrate and compare with experimental results. We obtain fairly good agreement between theoretical predictions and the measured ellipsometric spectra. The metallic nanoparticles were used to detect the binding with DNA molecules in a microfluidic setup via spectroscopic ellipsometry (SE), and a detectable change in ellipsometric spectra was found when DNA molecules are captured on Au nanoparticles. Our theoretical simulation indicates that the coverage of Au nanosphere by a submonolayer of DNA molecules, which is modeled by a thin layer of dielectric material (which may absorb light), can lead to a small but detectable spectroscopic shift in both the Ψ and Δ spectra with more significant change in Δ spectra in agreement with experimental results. Our studies demonstrated the ultrasensitive capability of SE for sensing submonolayer coverage of DNA molecules on Au nanospheres. Hence the spectroscopic ellipsometric measurements coupled with theoretical analysis via an efficient computation method can be an effective tool for detecting DNA molecules attached on Au nanoparticles, thus achieving label-free, non-destructive, and high-sensitivity biosensing with nanoscale resolution.

Complete Mitochondrial DNA Analysis of Eastern Eurasian Haplogroups Rarely Found in Populations of Northern Asia and Eastern Europe

PubMed Central

Derenko, Miroslava; Malyarchuk, Boris; Denisova, Galina; Perkova, Maria; Rogalla, Urszula; Grzybowski, Tomasz; Khusnutdinova, Elza; Dambueva, Irina; Zakharov, Ilia

2012-01-01

With the aim of uncovering all of the most basal variation in the northern Asian mitochondrial DNA (mtDNA) haplogroups, we have analyzed mtDNA control region and coding region sequence variation in 98 Altaian Kazakhs from southern Siberia and 149 Barghuts from Inner Mongolia, China. Both populations exhibit the prevalence of eastern Eurasian lineages accounting for 91.9% in Barghuts and 60.2% in Altaian Kazakhs. The strong affinity of Altaian Kazakhs and populations of northern and central Asia has been revealed, reflecting both influences of central Asian inhabitants and essential genetic interaction with the Altai region indigenous populations. Statistical analyses data demonstrate a close positioning of all Mongolic-speaking populations (Mongolians, Buryats, Khamnigans, Kalmyks as well as Barghuts studied here) and Turkic-speaking Sojots, thus suggesting their origin from a common maternal ancestral gene pool. In order to achieve a thorough coverage of DNA lineages revealed in the northern Asian matrilineal gene pool, we have completely sequenced the mtDNA of 55 samples representing haplogroups R11b, B4, B5, F2, M9, M10, M11, M13, N9a and R9c1, which were pinpointed from a massive collection (over 5000 individuals) of northern and eastern Asian, as well as European control region mtDNA sequences. Applying the newly updated mtDNA tree to the previously reported northern Asian and eastern Asian mtDNA data sets has resolved the status of the poorly classified mtDNA types and allowed us to obtain the coalescence age estimates of the nodes of interest using different calibrated rates. Our findings confirm our previous conclusion that northern Asian maternal gene pool consists of predominantly post-LGM components of eastern Asian ancestry, though some genetic lineages may have a pre-LGM/LGM origin. PMID:22363811

The study of human Y chromosome variation through ancient DNA.

PubMed

Kivisild, Toomas

2017-05-01

High throughput sequencing methods have completely transformed the study of human Y chromosome variation by offering a genome-scale view on genetic variation retrieved from ancient human remains in context of a growing number of high coverage whole Y chromosome sequence data from living populations from across the world. The ancient Y chromosome sequences are providing us the first exciting glimpses into the past variation of male-specific compartment of the genome and the opportunity to evaluate models based on previously made inferences from patterns of genetic variation in living populations. Analyses of the ancient Y chromosome sequences are challenging not only because of issues generally related to ancient DNA work, such as DNA damage-induced mutations and low content of endogenous DNA in most human remains, but also because of specific properties of the Y chromosome, such as its highly repetitive nature and high homology with the X chromosome. Shotgun sequencing of uniquely mapping regions of the Y chromosomes to sufficiently high coverage is still challenging and costly in poorly preserved samples. To increase the coverage of specific target SNPs capture-based methods have been developed and used in recent years to generate Y chromosome sequence data from hundreds of prehistoric skeletal remains. Besides the prospects of testing directly as how much genetic change in a given time period has accompanied changes in material culture the sequencing of ancient Y chromosomes allows us also to better understand the rate at which mutations accumulate and get fixed over time. This review considers genome-scale evidence on ancient Y chromosome diversity that has recently started to accumulate in geographic areas favourable to DNA preservation. More specifically the review focuses on examples of regional continuity and change of the Y chromosome haplogroups in North Eurasia and in the New World.

Improving estimates of insecticide-treated mosquito net coverage from household surveys: using geographic coordinates to account for endemicity

PubMed Central

2014-01-01

Background Coverage estimates of insecticide-treated nets (ITNs) are often calculated at the national level, but are intended to be a proxy for coverage among the population at risk of malaria. The analysis uses data for surveyed households, linking survey enumeration areas (clusters) with levels of malaria endemicity and adjusting coverage estimates based on the population at risk. This analysis proposes an approach that is not dependent on being able to identify malaria risk in a location during the survey design (since survey samples are typically selected on the basis of census sampling frames that do not include information on malaria zones), but rather being able to assign risk zones after a survey has already been completed. Methods The analysis uses data from 20 recent nationally representative Demographic and Health Survey (DHS), Malaria Indicator Surveys (MIS), an AIDS Indicator Survey (AIS), and an Anemia and Malaria Prevalence Survey (AMP). The malaria endemicity classification was assigned from the Malaria Atlas Project (MAP) 2010 interpolated data layers, using the Geographic Positioning System (GPS) location of the survey clusters. National ITN coverage estimates were compared with coverage estimates in intermediate/high endemicity zones (i.e., the population at risk of malaria) to determine whether the difference between estimates was statistically different from zero (p-value <0.5). Results Endemicity varies substantially in eight of the 20 studied countries. In these countries with heterogeneous transmission of malaria, stratification of households by endemicity zones shows that ITN coverage in intermediate/high endemicity zones is significantly higher than ITN coverage at the national level (Burundi, Kenya, Namibia, Rwanda, Tanzania, Senegal, Zambia, and Zimbabwe.). For example in Zimbabwe, the national ownership of ITNs is 28%, but ownership in the intermediate/high endemicity zone is 46%. Conclusion Incorporating this study’s basic and easily reproducible approach into estimates of ITN coverage is applicable and even preferable in countries with areas at no/low risk of malaria and will help ensure that the highest-quality data are available to inform programmatic decisions in countries affected by malaria. The extension of this type of analysis to other malaria interventions can provide further valuable information to support evidence-based decision-making. PMID:24993082

Role of Mitochondrial Inheritance on Prostate Cancer Outcome in African American Men. Addendum

DTIC Science & Technology

2016-11-01

DNA sequencing technique developed by our collaborator using single amplicon long-range PCR that permits deep coverage (10,000-20,000X on average) of...the mitochondrial genome. We have sequenced 652 samples derived from frozen fully using this technology. The additional DNA samples derived from...paraffin embedded (FFPE) tissue were more challenging, but have now been sequenced . Mapping of DNA variants in our sequenced genomes to mitochondrial

Measles vaccination coverage estimates from surveys, clinic records, and immune markers in oral fluid and blood: a population-based cross-sectional study.

PubMed

Hayford, Kyla T; Shomik, Mohammed S; Al-Emran, Hassan M; Moss, William J; Bishai, David; Levine, Orin S

2013-12-20

Recent outbreaks of measles and polio in low-income countries illustrate that conventional methods for estimating vaccination coverage do not adequately identify susceptible children. Immune markers of protection against vaccine-preventable diseases in oral fluid (OF) or blood may generate more accurate measures of effective vaccination history, but questions remain about whether antibody surveys are feasible and informative tools for monitoring immunization program performance compared to conventional vaccination coverage indicators. This study compares six indicators of measles vaccination status, including immune markers in oral fluid and blood, from children in rural Bangladesh and evaluates the implications of using each indicator to estimate measles vaccination coverage. A cross-sectional population-based study of children ages 12-16 months in Mirzapur, Bangladesh, ascertained measles vaccination (MCV1) history from conventional indicators: maternal report, vaccination card records, 'card+history' and EPI clinic records. Oral fluid from all participants (n=1226) and blood from a subset (n=342) were tested for measles IgG antibodies as indicators of MCV1 history and compared to conventional MCV1 coverage indicators. Maternal report yielded the highest MCV1 coverage estimates (90.8%), followed by EPI records (88.6%), and card+history (84.2%). Seroprotection against measles by OF (57.3%) was significantly lower than other indicators, even after adjusting for incomplete seroconversion and assay performance (71.5%). Among children with blood results, 88.6% were seroprotected, which was significantly higher than coverage by card+history and OF serostatus but consistent with coverage by maternal report and EPI records. Children with vaccination cards or EPI records were more likely to have a history of receiving MCV1 than those without cards or records. Despite similar MCV1 coverage estimates across most indicators, within-child agreement was poor for all indicators. Measles IgG antibodies in OF was not a suitable immune marker for monitoring measles vaccination coverage in this setting. Because agreement between conventional MCV1 indicators was mediocre, immune marker surveillance with blood samples could be used to validate conventional MCV1 indicators and generate adjusted results that can be compared across indicators.

Sub-national variation in measles vaccine coverage and outbreak risk: a case study from a 2010 outbreak in Malawi.

PubMed

Kundrick, Avery; Huang, Zhuojie; Carran, Spencer; Kagoli, Matthew; Grais, Rebecca Freeman; Hurtado, Northan; Ferrari, Matthew

2018-06-15

Despite progress towards increasing global vaccination coverage, measles continues to be one of the leading, preventable causes of death among children worldwide. Whether and how to target sub-national areas for vaccination campaigns continues to remain a question. We analyzed three metrics for prioritizing target areas: vaccination coverage, susceptible birth cohort, and the effective reproductive ratio (R E ) in the context of the 2010 measles epidemic in Malawi. Using case-based surveillance data from the 2010 measles outbreak in Malawi, we estimated vaccination coverage from the proportion of cases reporting with a history of prior vaccination at the district and health facility catchment scale. Health facility catchments were defined as the set of locations closer to a given health facility than to any other. We combined these estimates with regional birth rates to estimate the size of the annual susceptible birth cohort. We also estimated the effective reproductive ratio, R E , at the health facility polygon scale based on the observed rate of exponential increase of the epidemic. We combined these estimates to identify spatial regions that would be of high priority for supplemental vaccination activities. The estimated vaccination coverage across all districts was 84%, but ranged from 61 to 99%. We found that 8 districts and 354 health facility catchments had estimated vaccination coverage below 80%. Areas that had highest birth cohort size were frequently large urban centers that had high vaccination coverage. The estimated R E ranged between 1 and 2.56. The ranking of districts and health facility catchments as priority areas varied depending on the measure used. Each metric for prioritization may result in discrete target areas for vaccination campaigns; thus, there are tradeoffs to choosing one metric over another. However, in some cases, certain areas may be prioritized by all three metrics. These areas should be treated with particular concern. Furthermore, the spatial scale at which each metric is calculated impacts the resulting prioritization and should also be considered when prioritizing areas for vaccination campaigns. These methods may be used to allocate effort for prophylactic campaigns or to prioritize response for outbreak response vaccination.

A genome-wide 20 K citrus microarray for gene expression analysis

PubMed Central

Martinez-Godoy, M Angeles; Mauri, Nuria; Juarez, Jose; Marques, M Carmen; Santiago, Julia; Forment, Javier; Gadea, Jose

2008-01-01

Background Understanding of genetic elements that contribute to key aspects of citrus biology will impact future improvements in this economically important crop. Global gene expression analysis demands microarray platforms with a high genome coverage. In the last years, genome-wide EST collections have been generated in citrus, opening the possibility to create new tools for functional genomics in this crop plant. Results We have designed and constructed a publicly available genome-wide cDNA microarray that include 21,081 putative unigenes of citrus. As a functional companion to the microarray, a web-browsable database [1] was created and populated with information about the unigenes represented in the microarray, including cDNA libraries, isolated clones, raw and processed nucleotide and protein sequences, and results of all the structural and functional annotation of the unigenes, like general description, BLAST hits, putative Arabidopsis orthologs, microsatellites, putative SNPs, GO classification and PFAM domains. We have performed a Gene Ontology comparison with the full set of Arabidopsis proteins to estimate the genome coverage of the microarray. We have also performed microarray hybridizations to check its usability. Conclusion This new cDNA microarray replaces the first 7K microarray generated two years ago and allows gene expression analysis at a more global scale. We have followed a rational design to minimize cross-hybridization while maintaining its utility for different citrus species. Furthermore, we also provide access to a website with full structural and functional annotation of the unigenes represented in the microarray, along with the ability to use this site to directly perform gene expression analysis using standard tools at different publicly available servers. Furthermore, we show how this microarray offers a good representation of the citrus genome and present the usefulness of this genomic tool for global studies in citrus by using it to catalogue genes expressed in citrus globular embryos. PMID:18598343

Estimation of measles vaccination coverage using the Lot Quality Assurance Sampling (LQAS) method--Tamilnadu, India, 2002-2003.

PubMed

Sivasankaran, Saravanan; Manickam, P; Ramakrishnan, R; Hutin, Y; Gupte, M D

2006-04-28

As part of the global strategic plan to reduce the number of measles deaths in India, the state of Tamilnadu aims at > or =95% measles vaccination coverage. A study was conducted to measure overall coverage levels for the Poondi Primary Health Center (PPHC), a rural health-care facility in Tiruvallur District, and to determine whether any of the PPHC's six health subcenters had coverage levels <95%. The Lot Quality Assurance Sampling (LQAS) method was used to identify health subcenters in the PPHC area with measles vaccination coverage levels <95% among children aged 12-23 months. Lemeshow and Taber sampling plans were used to determine that the measles vaccination status of 73 children aged 12--23 months had to be assessed in each health subcenter coverage area, with a 5% level of significance and a decision value of two. If more than two children were unvaccinated, the null hypothesis (i.e., that coverage in the health subcenter was low [<95%]) was not rejected. If the number of unvaccinated children was two or fewer, the null hypothesis was rejected, and coverage in the subcenter was considered to be good (i.e., > or =95%). All data were pooled in a stratified sample to estimate overall total coverage in the PPHC area. For two (33.3%) of the six health subcenters, more than two children were unvaccinated (i.e., coverage was <95%). Combining results from all six health subcenters generated a coverage estimate of 97.7% (95% confidence interval = 95.7-98.8) on the basis of 428 (97.7%) of 438 children identified as vaccinated. LQAS techniques proved useful in identifying small health areas with lower vaccination coverage, which helps to target interventions. Monthly review of vaccination coverage by subcenter and village is recommended to identify pockets of unvaccinated children and to maintain uniform high coverage in the PPHC area.

Second generation noninvasive fetal genome analysis reveals de novo mutations, single-base parental inheritance, and preferred DNA ends

PubMed Central

Chan, K. C. Allen; Jiang, Peiyong; Sun, Kun; Cheng, Yvonne K. Y.; Tong, Yu K.; Cheng, Suk Hang; Wong, Ada I. C.; Hudecova, Irena; Leung, Tak Y.; Chiu, Rossa W. K.; Lo, Yuk Ming Dennis

2016-01-01

Plasma DNA obtained from a pregnant woman was sequenced to a depth of 270× haploid genome coverage. Comparing the maternal plasma DNA sequencing data with the parental genomic DNA data and using a series of bioinformatics filters, fetal de novo mutations were detected at a sensitivity of 85% and a positive predictive value of 74%. These results represent a 169-fold improvement in the positive predictive value over previous attempts. Improvements in the interpretation of the sequence information of every base position in the genome allowed us to interrogate the maternal inheritance of the fetus for 618,271 of 656,676 (94.2%) heterozygous SNPs within the maternal genome. The fetal genotype at each of these sites was deduced individually, unlike previously, where the inheritance was determined for a collection of sites within a haplotype. These results represent a 90-fold enhancement in the resolution in determining the fetus’s maternal inheritance. Selected genomic locations were more likely to be found at the ends of plasma DNA molecules. We found that a subset of such preferred ends exhibited selectivity for fetal- or maternal-derived DNA in maternal plasma. The ratio of the number of maternal plasma DNA molecules with fetal preferred ends to those with maternal preferred ends showed a correlation with the fetal DNA fraction. Finally, this second generation approach for noninvasive fetal whole-genome analysis was validated in a pregnancy diagnosed with cardiofaciocutaneous syndrome with maternal plasma DNA sequenced to 195× coverage. The causative de novo BRAF mutation was successfully detected through the maternal plasma DNA analysis. PMID:27799561

Comparing errors in Medicaid reporting across surveys: evidence to date.

PubMed

Call, Kathleen T; Davern, Michael E; Klerman, Jacob A; Lynch, Victoria

2013-04-01

To synthesize evidence on the accuracy of Medicaid reporting across state and federal surveys. All available validation studies. Compare results from existing research to understand variation in reporting across surveys. Synthesize all available studies validating survey reports of Medicaid coverage. Across all surveys, reporting some type of insurance coverage is better than reporting Medicaid specifically. Therefore, estimates of uninsurance are less biased than estimates of specific sources of coverage. The CPS stands out as being particularly inaccurate. Measuring health insurance coverage is prone to some level of error, yet survey overstatements of uninsurance are modest in most surveys. Accounting for all forms of bias is complex. Researchers should consider adjusting estimates of Medicaid and uninsurance in surveys prone to high levels of misreporting. © Health Research and Educational Trust.

Variation in rotavirus vaccine coverage by sub-counties in Kenya.

PubMed

Wandera, Ernest Apondi; Mohammad, Shah; Ouko, John Odhiambo; Yatitch, James; Taniguchi, Koki; Ichinose, Yoshio

2017-01-01

Rotavirus gastroenteritis is an important cause of childhood morbidity and mortality in Kenya. In July 2014, Kenya introduced the rotavirus vaccine into her national immunization program. Although immunization coverage is crucial in assessing the real-world impact of this vaccine, variability in the vaccine coverage across the country is likely to occur. In view of this, we estimated the extent of coverage for the rotavirus vaccine at two socio-economically different sub-counties using the administrative data. The findings indicate disparities in vaccine coverage and access between the sub-counties and, thus, underscore the need to strengthen immunization systems to facilitate timely, accessible, and equitable vaccine delivery across the country. Both sub-counties recorded high vaccine dropout, suggestive of poor utilization of the vaccine. In this regard, increased social mobilization is needed to encourage vaccine compliance and to enhance tracking of vaccine defaulters. While efforts to improve the accuracy of the administrative coverage estimates are crucial, vaccination coverage surveys will be needed to verify the administrative coverage data and help identify specific factors relating to rotavirus vaccine coverage in the country.

DNA adsorption characteristics of hollow spherule allophane nano-particles.

PubMed

Matsuura, Yoko; Iyoda, Fumitoshi; Arakawa, Shuichi; John, Baiju; Okamoto, Masami; Hayashi, Hidetomo

2013-12-01

To understand the propensity of natural allophane to adsorb the DNA molecules, the adsorption characteristics were assessed against natural allophane (AK70), using single-stranded DNA (ss-DNA) and adenosine 5'-monophosphate (5'-AMP) as a reference molecule. The adsorption capacity of ss-DNA on AK70 exhibited one order of magnitude lower value as compared with that of 5'-AMP. The adsorption capacity of ss-DNA decreased with increasing pH due to the interaction generated between phosphate groups of ss-DNA and functional Al-OH groups on the wall perforations through deprotonating, associated with higher energy barrier for the adsorption of ss-DNA. The adsorption morphologies consisting of the individual ss-DNA with mono-layer coverage of the clustered allophane particle were observed successfully through transmission electron microscopy analysis. © 2013.

Population-based rare variant detection via pooled exome or custom hybridization capture with or without individual indexing.

PubMed

Ramos, Enrique; Levinson, Benjamin T; Chasnoff, Sara; Hughes, Andrew; Young, Andrew L; Thornton, Katherine; Li, Allie; Vallania, Francesco L M; Province, Michael; Druley, Todd E

2012-12-06

Rare genetic variation in the human population is a major source of pathophysiological variability and has been implicated in a host of complex phenotypes and diseases. Finding disease-related genes harboring disparate functional rare variants requires sequencing of many individuals across many genomic regions and comparing against unaffected cohorts. However, despite persistent declines in sequencing costs, population-based rare variant detection across large genomic target regions remains cost prohibitive for most investigators. In addition, DNA samples are often precious and hybridization methods typically require large amounts of input DNA. Pooled sample DNA sequencing is a cost and time-efficient strategy for surveying populations of individuals for rare variants. We set out to 1) create a scalable, multiplexing method for custom capture with or without individual DNA indexing that was amenable to low amounts of input DNA and 2) expand the functionality of the SPLINTER algorithm for calling substitutions, insertions and deletions across either candidate genes or the entire exome by integrating the variant calling algorithm with the dynamic programming aligner, Novoalign. We report methodology for pooled hybridization capture with pre-enrichment, indexed multiplexing of up to 48 individuals or non-indexed pooled sequencing of up to 92 individuals with as little as 70 ng of DNA per person. Modified solid phase reversible immobilization bead purification strategies enable no sample transfers from sonication in 96-well plates through adapter ligation, resulting in 50% less library preparation reagent consumption. Custom Y-shaped adapters containing novel 7 base pair index sequences with a Hamming distance of ≥2 were directly ligated onto fragmented source DNA eliminating the need for PCR to incorporate indexes, and was followed by a custom blocking strategy using a single oligonucleotide regardless of index sequence. These results were obtained aligning raw reads against the entire genome using Novoalign followed by variant calling of non-indexed pools using SPLINTER or SAMtools for indexed samples. With these pipelines, we find sensitivity and specificity of 99.4% and 99.7% for pooled exome sequencing. Sensitivity, and to a lesser degree specificity, proved to be a function of coverage. For rare variants (≤2% minor allele frequency), we achieved sensitivity and specificity of ≥94.9% and ≥99.99% for custom capture of 2.5 Mb in multiplexed libraries of 22-48 individuals with only ≥5-fold coverage/chromosome, but these parameters improved to ≥98.7 and 100% with 20-fold coverage/chromosome. This highly scalable methodology enables accurate rare variant detection, with or without individual DNA sample indexing, while reducing the amount of required source DNA and total costs through less hybridization reagent consumption, multi-sample sonication in a standard PCR plate, multiplexed pre-enrichment pooling with a single hybridization and lesser sequencing coverage required to obtain high sensitivity.

State of equity: childhood immunization in the World Health Organization African Region

PubMed Central

Casey, Rebecca Mary; Hampton, Lee McCalla; Anya, Blanche-philomene Melanga; Gacic-Dobo, Marta; Diallo, Mamadou Saliou; Wallace, Aaron Stuart

2017-01-01

Introduction In 2010, the Global Vaccine Action Plan called on all countries to reach and sustain 90% national coverage and 80% coverage in all districts for the third dose of diphtheria-tetanus-pertussis vaccine (DTP3) by 2015 and for all vaccines in national immunization schedules by 2020. The aims of this study are to analyze recent trends in national vaccination coverage in the World Health Organization African Region andto assess how these trends differ by country income category. Methods We compared national vaccination coverage estimates for DTP3 and the first dose of measles-containing vaccine (MCV) obtained from the World Health Organization (WHO)/United Nations Children’s Fund (UNICEF) joint estimates of national immunization coverage for all African Region countries. Using United Nations (UN) population estimates of surviving infants and country income category for the corresponding year, we calculated population-weighted average vaccination coverage by country income category (i.e., low, lower middle, and upper middle-income) for the years 2000, 2005, 2010 and 2015. Results DTP3 coverage in the African Region increased from 52% in 2000 to 76% in 2015,and MCV1 coverage increased from 53% to 74% during the same period, but with considerable differences among countries. Thirty-six African Region countries were low income in 2000 with an average DTP3 coverage of 50% while 26 were low income in 2015 with an average coverage of 80%. Five countries were lower middle-income in 2000 with an average DTP3 coverage of 84% while 12 were lower middle-income in 2015 with an average coverage of 69%. Five countries were upper middle-income in 2000 with an average DTP3 coverage of 73% and eight were upper middle-income in 2015 with an average coverage of 76%. Conclusion Disparities in vaccination coverage by country persist in the African Region, with countries that were lower middle-income having the lowest coverage on average in 2015. Monitoring and addressing these disparities is essential for meeting global immunization targets. PMID:29296140

Genetic Perturbation of the Maize Methylome[W

PubMed Central

Li, Qing; Hermanson, Peter J.; Zaunbrecher, Virginia M.; Song, Jawon; Wendt, Jennifer; Rosenbaum, Heidi; Madzima, Thelma F.; Sloan, Amy E.; Huang, Ji; Burgess, Daniel L.; Richmond, Todd A.; McGinnis, Karen M.; Meeley, Robert B.; Danilevskaya, Olga N.; Vaughn, Matthew W.; Kaeppler, Shawn M.; Jeddeloh, Jeffrey A.

2014-01-01

DNA methylation can play important roles in the regulation of transposable elements and genes. A collection of mutant alleles for 11 maize (Zea mays) genes predicted to play roles in controlling DNA methylation were isolated through forward- or reverse-genetic approaches. Low-coverage whole-genome bisulfite sequencing and high-coverage sequence-capture bisulfite sequencing were applied to mutant lines to determine context- and locus-specific effects of these mutations on DNA methylation profiles. Plants containing mutant alleles for components of the RNA-directed DNA methylation pathway exhibit loss of CHH methylation at many loci as well as CG and CHG methylation at a small number of loci. Plants containing loss-of-function alleles for chromomethylase (CMT) genes exhibit strong genome-wide reductions in CHG methylation and some locus-specific loss of CHH methylation. In an attempt to identify stocks with stronger reductions in DNA methylation levels than provided by single gene mutations, we performed crosses to create double mutants for the maize CMT3 orthologs, Zmet2 and Zmet5, and for the maize DDM1 orthologs, Chr101 and Chr106. While loss-of-function alleles are viable as single gene mutants, the double mutants were not recovered, suggesting that severe perturbations of the maize methylome may have stronger deleterious phenotypic effects than in Arabidopsis thaliana. PMID:25527708

Replication-guided nucleosome packing and nucleosome breathing expedite the formation of dense arrays

PubMed Central

Osberg, Brendan; Nuebler, Johannes; Korber, Philipp; Gerland, Ulrich

2014-01-01

The first level of genome packaging in eukaryotic cells involves the formation of dense nucleosome arrays, with DNA coverage near 90% in yeasts. How cells achieve such high coverage within a short time, e.g. after DNA replication, remains poorly understood. It is known that random sequential adsorption of impenetrable particles on a line reaches high density extremely slowly, due to a jamming phenomenon. The nucleosome-shifting action of remodeling enzymes has been proposed as a mechanism to resolve such jams. Here, we suggest two biophysical mechanisms which assist rapid filling of DNA with nucleosomes, and we quantitatively characterize these mechanisms within mathematical models. First, we show that the ‘softness’ of nucleosomes, due to nucleosome breathing and stepwise nucleosome assembly, significantly alters the filling behavior, speeding up the process relative to ‘hard’ particles with fixed, mutually exclusive DNA footprints. Second, we explore model scenarios in which the progression of the replication fork could eliminate nucleosome jamming, either by rapid filling in its wake or via memory of the parental nucleosome positions. Taken together, our results suggest that biophysical effects promote rapid nucleosome filling, making the reassembly of densely packed nucleosomes after DNA replication a simpler task for cells than was previously thought. PMID:25428353

Origins of domestic dog in southern East Asia is supported by analysis of Y-chromosome DNA.

PubMed

Ding, Z-L; Oskarsson, M; Ardalan, A; Angleby, H; Dahlgren, L-G; Tepeli, C; Kirkness, E; Savolainen, P; Zhang, Y-P

2012-05-01

Global mitochondrial DNA (mtDNA) data indicates that the dog originates from domestication of wolf in Asia South of Yangtze River (ASY), with minor genetic contributions from dog-wolf hybridisation elsewhere. Archaeological data and autosomal single nucleotide polymorphism data have instead suggested that dogs originate from Europe and/or South West Asia but, because these datasets lack data from ASY, evidence pointing to ASY may have been overlooked. Analyses of additional markers for global datasets, including ASY, are therefore necessary to test if mtDNA phylogeography reflects the actual dog history and not merely stochastic events or selection. Here, we analyse 14,437 bp of Y-chromosome DNA sequence in 151 dogs sampled worldwide. We found 28 haplotypes distributed in five haplogroups. Two haplogroups were universally shared and included three haplotypes carried by 46% of all dogs, but two other haplogroups were primarily restricted to East Asia. Highest genetic diversity and virtually complete phylogenetic coverage was found within ASY. The 151 dogs were estimated to originate from 13-24 wolf founders, but there was no indication of post-domestication dog-wolf hybridisations. Thus, Y-chromosome and mtDNA data give strikingly similar pictures of dog phylogeography, most importantly that roughly 50% of the gene pools are shared universally but only ASY has nearly the full range of genetic diversity, such that the gene pools in all other regions may derive from ASY. This corroborates that ASY was the principal, and possibly sole region of wolf domestication, that a large number of wolves were domesticated, and that subsequent dog-wolf hybridisation contributed modestly to the dog gene pool.

Origins of domestic dog in Southern East Asia is supported by analysis of Y-chromosome DNA

PubMed Central

Ding, Z-L; Oskarsson, M; Ardalan, A; Angleby, H; Dahlgren, L-G; Tepeli, C; Kirkness, E; Savolainen, P; Zhang, Y-P

2012-01-01

Global mitochondrial DNA (mtDNA) data indicates that the dog originates from domestication of wolf in Asia South of Yangtze River (ASY), with minor genetic contributions from dog–wolf hybridisation elsewhere. Archaeological data and autosomal single nucleotide polymorphism data have instead suggested that dogs originate from Europe and/or South West Asia but, because these datasets lack data from ASY, evidence pointing to ASY may have been overlooked. Analyses of additional markers for global datasets, including ASY, are therefore necessary to test if mtDNA phylogeography reflects the actual dog history and not merely stochastic events or selection. Here, we analyse 14 437 bp of Y-chromosome DNA sequence in 151 dogs sampled worldwide. We found 28 haplotypes distributed in five haplogroups. Two haplogroups were universally shared and included three haplotypes carried by 46% of all dogs, but two other haplogroups were primarily restricted to East Asia. Highest genetic diversity and virtually complete phylogenetic coverage was found within ASY. The 151 dogs were estimated to originate from 13–24 wolf founders, but there was no indication of post-domestication dog–wolf hybridisations. Thus, Y-chromosome and mtDNA data give strikingly similar pictures of dog phylogeography, most importantly that roughly 50% of the gene pools are shared universally but only ASY has nearly the full range of genetic diversity, such that the gene pools in all other regions may derive from ASY. This corroborates that ASY was the principal, and possibly sole region of wolf domestication, that a large number of wolves were domesticated, and that subsequent dog–wolf hybridisation contributed modestly to the dog gene pool. PMID:22108628

Routine immunization in Pakistan: comparison of multiple data sources and identification of factors associated with vaccination.

PubMed

Imran, Hafsa; Raja, Dania; Grassly, Nicholas C; Wadood, M Zubair; Safdar, Rana M; O'Reilly, Kathleen M

2018-03-01

Within Pakistan, estimates of vaccination coverage with the pentavalent vaccine, oral polio vaccine (OPV) and measles vaccine (MV) in 2011 were reported to be 74%, 75% and 53%, respectively. These national estimates may mask regional variation. The reasons for this variation have not been explored. Data from the Multiple Indicator Cluster Surveys (MICS) for Balochistan and Punjab (2010-2011) are analysed to examine factors associated with receiving three or more doses of the pentavalent vaccine and one or more MVs using regression modelling. Pentavalent and OPV estimates from the MICS were compared to vaccine dose histories from surveillance for acute flaccid paralysis (AFP; poliomyelitis) to ascertain agreement. Adjusted coverage of children 12-23 months of age were estimated to be 16.0%, 75.5% and 34.2% in Balochistan and 58.0%, 87.7% and 72.6% in Punjab for the pentavalent vaccine, OPV and MV, respectively. Maternal education, healthcare utilization and wealth were associated with receiving the pentavalent vaccine and the MV. There was a strong correlation of district estimates of vaccination coverage between AFP and MICS data, but AFP estimates of pentavalent coverage in Punjab were biased toward higher values. National estimates mask variation and estimates from individual surveys should be considered alongside other estimates. The development of strategies targeted towards poorly educated parents within low-wealth quintiles that may not typically access healthcare could improve vaccination rates.

Estimated cost of universal public coverage of prescription drugs in Canada

PubMed Central

Morgan, Steven G.; Law, Michael; Daw, Jamie R.; Abraham, Liza; Martin, Danielle

2015-01-01

Background: With the exception of Canada, all countries with universal health insurance systems provide universal coverage of prescription drugs. Progress toward universal public drug coverage in Canada has been slow, in part because of concerns about the potential costs. We sought to estimate the cost of implementing universal public coverage of prescription drugs in Canada. Methods: We used published data on prescribing patterns and costs by drug type, as well as source of funding (i.e., private drug plans, public drug plans and out-of-pocket expenses), in each province to estimate the cost of universal public coverage of prescription drugs from the perspectives of government, private payers and society as a whole. We estimated the cost of universal public drug coverage based on its anticipated effects on the volume of prescriptions filled, products selected and prices paid. We selected these parameters based on current policies and practices seen either in a Canadian province or in an international comparator. Results: Universal public drug coverage would reduce total spending on prescription drugs in Canada by $7.3 billion (worst-case scenario $4.2 billion, best-case scenario $9.4 billion). The private sector would save $8.2 billion (worst-case scenario $6.6 billion, best-case scenario $9.6 billion), whereas costs to government would increase by about $1.0 billion (worst-case scenario $5.4 billion net increase, best-case scenario $2.9 billion net savings). Most of the projected increase in government costs would arise from a small number of drug classes. Interpretation: The long-term barrier to the implementation of universal pharmacare owing to its perceived costs appears to be unjustified. Universal public drug coverage would likely yield substantial savings to the private sector with comparatively little increase in costs to government. PMID:25780047

High-Resolution Spatial Distribution and Estimation of Access to Improved Sanitation in Kenya.

PubMed

Jia, Peng; Anderson, John D; Leitner, Michael; Rheingans, Richard

2016-01-01

Access to sanitation facilities is imperative in reducing the risk of multiple adverse health outcomes. A distinct disparity in sanitation exists among different wealth levels in many low-income countries, which may hinder the progress across each of the Millennium Development Goals. The surveyed households in 397 clusters from 2008-2009 Kenya Demographic and Health Surveys were divided into five wealth quintiles based on their national asset scores. A series of spatial analysis methods including excess risk, local spatial autocorrelation, and spatial interpolation were applied to observe disparities in coverage of improved sanitation among different wealth categories. The total number of the population with improved sanitation was estimated by interpolating, time-adjusting, and multiplying the surveyed coverage rates by high-resolution population grids. A comparison was then made with the annual estimates from United Nations Population Division and World Health Organization /United Nations Children's Fund Joint Monitoring Program for Water Supply and Sanitation. The Empirical Bayesian Kriging interpolation produced minimal root mean squared error for all clusters and five quintiles while predicting the raw and spatial coverage rates of improved sanitation. The coverage in southern regions was generally higher than in the north and east, and the coverage in the south decreased from Nairobi in all directions, while Nyanza and North Eastern Province had relatively poor coverage. The general clustering trend of high and low sanitation improvement among surveyed clusters was confirmed after spatial smoothing. There exists an apparent disparity in sanitation among different wealth categories across Kenya and spatially smoothed coverage rates resulted in a closer estimation of the available statistics than raw coverage rates. Future intervention activities need to be tailored for both different wealth categories and nationally where there are areas of greater needs when resources are limited.

Estimated cost of universal public coverage of prescription drugs in Canada.

PubMed

Morgan, Steven G; Law, Michael; Daw, Jamie R; Abraham, Liza; Martin, Danielle

2015-04-21

With the exception of Canada, all countries with universal health insurance systems provide universal coverage of prescription drugs. Progress toward universal public drug coverage in Canada has been slow, in part because of concerns about the potential costs. We sought to estimate the cost of implementing universal public coverage of prescription drugs in Canada. We used published data on prescribing patterns and costs by drug type, as well as source of funding (i.e., private drug plans, public drug plans and out-of-pocket expenses), in each province to estimate the cost of universal public coverage of prescription drugs from the perspectives of government, private payers and society as a whole. We estimated the cost of universal public drug coverage based on its anticipated effects on the volume of prescriptions filled, products selected and prices paid. We selected these parameters based on current policies and practices seen either in a Canadian province or in an international comparator. Universal public drug coverage would reduce total spending on prescription drugs in Canada by $7.3 billion (worst-case scenario $4.2 billion, best-case scenario $9.4 billion). The private sector would save $8.2 billion (worst-case scenario $6.6 billion, best-case scenario $9.6 billion), whereas costs to government would increase by about $1.0 billion (worst-case scenario $5.4 billion net increase, best-case scenario $2.9 billion net savings). Most of the projected increase in government costs would arise from a small number of drug classes. The long-term barrier to the implementation of universal pharmacare owing to its perceived costs appears to be unjustified. Universal public drug coverage would likely yield substantial savings to the private sector with comparatively little increase in costs to government. © 2015 Canadian Medical Association or its licensors.

Methods for estimating population coverage of mass distribution programmes: a review of practices in relation to trachoma control.

PubMed

Cromwell, Elizabeth A; Ngondi, Jeremiah; McFarland, Deborah; King, Jonathan D; Emerson, Paul M

2012-10-01

In the context of trachoma control, population coverage with mass drug administration (MDA) using antibiotics is measured using routine data. Due to the limitations of administrative records as well as the potential for bias from incomplete or incorrect records, a literature review of coverage survey methods applied in neglected tropical disease control programmes and immunisation outreach was conducted to inform the design of coverage surveys for trachoma control. Several methods were identified, including the '30 × 7' survey method for the Expanded Programme on Immunization (EPI 30×7), other cluster random sampling (CRS) methods, lot quality assurance sampling (LQAS), purposive sampling and routine data. When compared against one another, the EPI and other CRS methods produced similar population coverage estimates, whilst LQAS, purposive sampling and use of administrative data did not generate estimates consistent with CRS. In conclusion, CRS methods present a consistent approach for MDA coverage surveys despite different methods of household selection. They merit use until standard guidelines are available. CRS methods should be used to verify population coverage derived from LQAS, purposive sampling methods and administrative reports. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

[Estimation of desert vegetation coverage based on multi-source remote sensing data].

PubMed

Wan, Hong-Mei; Li, Xia; Dong, Dao-Rui

2012-12-01

Taking the lower reaches of Tarim River in Xinjiang of Northwest China as study areaAbstract: Taking the lower reaches of Tarim River in Xinjiang of Northwest China as study area and based on the ground investigation and the multi-source remote sensing data of different resolutions, the estimation models for desert vegetation coverage were built, with the precisions of different estimation methods and models compared. The results showed that with the increasing spatial resolution of remote sensing data, the precisions of the estimation models increased. The estimation precision of the models based on the high, middle-high, and middle-low resolution remote sensing data was 89.5%, 87.0%, and 84.56%, respectively, and the precisions of the remote sensing models were higher than that of vegetation index method. This study revealed the change patterns of the estimation precision of desert vegetation coverage based on different spatial resolution remote sensing data, and realized the quantitative conversion of the parameters and scales among the high, middle, and low spatial resolution remote sensing data of desert vegetation coverage, which would provide direct evidence for establishing and implementing comprehensive remote sensing monitoring scheme for the ecological restoration in the study area.

A fast Monte Carlo EM algorithm for estimation in latent class model analysis with an application to assess diagnostic accuracy for cervical neoplasia in women with AGC

PubMed Central

Kang, Le; Carter, Randy; Darcy, Kathleen; Kauderer, James; Liao, Shu-Yuan

2013-01-01

In this article we use a latent class model (LCM) with prevalence modeled as a function of covariates to assess diagnostic test accuracy in situations where the true disease status is not observed, but observations on three or more conditionally independent diagnostic tests are available. A fast Monte Carlo EM (MCEM) algorithm with binary (disease) diagnostic data is implemented to estimate parameters of interest; namely, sensitivity, specificity, and prevalence of the disease as a function of covariates. To obtain standard errors for confidence interval construction of estimated parameters, the missing information principle is applied to adjust information matrix estimates. We compare the adjusted information matrix based standard error estimates with the bootstrap standard error estimates both obtained using the fast MCEM algorithm through an extensive Monte Carlo study. Simulation demonstrates that the adjusted information matrix approach estimates the standard error similarly with the bootstrap methods under certain scenarios. The bootstrap percentile intervals have satisfactory coverage probabilities. We then apply the LCM analysis to a real data set of 122 subjects from a Gynecologic Oncology Group (GOG) study of significant cervical lesion (S-CL) diagnosis in women with atypical glandular cells of undetermined significance (AGC) to compare the diagnostic accuracy of a histology-based evaluation, a CA-IX biomarker-based test and a human papillomavirus (HPV) DNA test. PMID:24163493

Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans.

PubMed

Pyle, Angela; Hudson, Gavin; Wilson, Ian J; Coxhead, Jonathan; Smertenko, Tania; Herbert, Mary; Santibanez-Koref, Mauro; Chinnery, Patrick F

2015-05-01

Recent reports have questioned the accepted dogma that mammalian mitochondrial DNA (mtDNA) is strictly maternally inherited. In humans, the argument hinges on detecting a signature of inter-molecular recombination in mtDNA sequences sampled at the population level, inferring a paternal source for the mixed haplotypes. However, interpreting these data is fraught with difficulty, and direct experimental evidence is lacking. Using extreme-high depth mtDNA re-sequencing up to ~1.2 million-fold coverage, we find no evidence that paternal mtDNA haplotypes are transmitted to offspring in humans, thus excluding a simple dilution mechanism for uniparental transmission of mtDNA present in all healthy individuals. Our findings indicate that an active mechanism eliminates paternal mtDNA which likely acts at the molecular level.

Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans

PubMed Central

Pyle, Angela; Hudson, Gavin; Wilson, Ian J.; Coxhead, Jonathan; Smertenko, Tania; Herbert, Mary; Santibanez-Koref, Mauro; Chinnery, Patrick F.

2015-01-01

Recent reports have questioned the accepted dogma that mammalian mitochondrial DNA (mtDNA) is strictly maternally inherited. In humans, the argument hinges on detecting a signature of inter-molecular recombination in mtDNA sequences sampled at the population level, inferring a paternal source for the mixed haplotypes. However, interpreting these data is fraught with difficulty, and direct experimental evidence is lacking. Using extreme-high depth mtDNA re-sequencing up to ~1.2 million-fold coverage, we find no evidence that paternal mtDNA haplotypes are transmitted to offspring in humans, thus excluding a simple dilution mechanism for uniparental transmission of mtDNA present in all healthy individuals. Our findings indicate that an active mechanism eliminates paternal mtDNA which likely acts at the molecular level. PMID:25973765

Low-Cost, High-Throughput Sequencing of DNA Assemblies Using a Highly Multiplexed Nextera Process.

PubMed

Shapland, Elaine B; Holmes, Victor; Reeves, Christopher D; Sorokin, Elena; Durot, Maxime; Platt, Darren; Allen, Christopher; Dean, Jed; Serber, Zach; Newman, Jack; Chandran, Sunil

2015-07-17

In recent years, next-generation sequencing (NGS) technology has greatly reduced the cost of sequencing whole genomes, whereas the cost of sequence verification of plasmids via Sanger sequencing has remained high. Consequently, industrial-scale strain engineers either limit the number of designs or take short cuts in quality control. Here, we show that over 4000 plasmids can be completely sequenced in one Illumina MiSeq run for less than $3 each (15× coverage), which is a 20-fold reduction over using Sanger sequencing (2× coverage). We reduced the volume of the Nextera tagmentation reaction by 100-fold and developed an automated workflow to prepare thousands of samples for sequencing. We also developed software to track the samples and associated sequence data and to rapidly identify correctly assembled constructs having the fewest defects. As DNA synthesis and assembly become a centralized commodity, this NGS quality control (QC) process will be essential to groups operating high-throughput pipelines for DNA construction.

Multilocus Bayesian Estimates of Intra-Oceanic Genetic Differentiation, Connectivity, and Admixture in Atlantic Swordfish (Xiphias gladius L.)

PubMed Central

Smith, Brad L.; Lu, Ching-Ping; García-Cortés, Blanca; Viñas, Jordi; Yeh, Shean-Ya; Alvarado Bremer, Jaime R.

2015-01-01

Previous genetic studies of Atlantic swordfish (Xiphias gladius L.) revealed significant differentiation among Mediterranean, North Atlantic and South Atlantic populations using both mitochondrial and nuclear DNA data. However, limitations in geographic sampling coverage, and the use of single loci, precluded an accurate placement of boundaries and of estimates of admixture. In this study, we present multilocus analyses of 26 single nucleotide polymorphisms (SNPs) within 10 nuclear genes to estimate population differentiation and admixture based on the characterization of 774 individuals representing North Atlantic, South Atlantic, and Mediterranean swordfish populations. Pairwise F ST values, AMOVA, PCoA, and Bayesian individual assignments support the differentiation of swordfish inhabiting these three basins, but not the current placement of the boundaries that separate them. Specifically, the range of the South Atlantic population extends beyond 5°N management boundary to 20°N-25°N from 45°W. Likewise the Mediterranean population extends beyond the current management boundary at the Strait of Gibraltar to approximately 10°W. Further, admixture zones, characterized by asymmetric contributions of adjacent populations within samples, are confined to the Northeast Atlantic. While South Atlantic and Mediterranean migrants were identified within these Northeast Atlantic admixture zones no North Atlantic migrants were identified respectively in these two neighboring basins. Owing to both, the characterization of larger number of loci and a more ample spatial sampling coverage, it was possible to provide a finer resolution of the boundaries separating Atlantic swordfish populations than previous studies. Finally, the patterns of population structure and admixture are discussed in the light of the reproductive biology, the known patterns of dispersal, and oceanographic features that may act as barriers to gene flow to Atlantic swordfish. PMID:26057382

Building a model: developing genomic resources for common milkweed (Asclepias syriaca) with low coverage genome sequencing

PubMed Central

2011-01-01

Background Milkweeds (Asclepias L.) have been extensively investigated in diverse areas of evolutionary biology and ecology; however, there are few genetic resources available to facilitate and compliment these studies. This study explored how low coverage genome sequencing of the common milkweed (Asclepias syriaca L.) could be useful in characterizing the genome of a plant without prior genomic information and for development of genomic resources as a step toward further developing A. syriaca as a model in ecology and evolution. Results A 0.5× genome of A. syriaca was produced using Illumina sequencing. A virtually complete chloroplast genome of 158,598 bp was assembled, revealing few repeats and loss of three genes: accD, clpP, and ycf1. A nearly complete rDNA cistron (18S-5.8S-26S; 7,541 bp) and 5S rDNA (120 bp) sequence were obtained. Assessment of polymorphism revealed that the rDNA cistron and 5S rDNA had 0.3% and 26.7% polymorphic sites, respectively. A partial mitochondrial genome sequence (130,764 bp), with identical gene content to tobacco, was also assembled. An initial characterization of repeat content indicated that Ty1/copia-like retroelements are the most common repeat type in the milkweed genome. At least one A. syriaca microread hit 88% of Catharanthus roseus (Apocynaceae) unigenes (median coverage of 0.29×) and 66% of single copy orthologs (COSII) in asterids (median coverage of 0.14×). From this partial characterization of the A. syriaca genome, markers for population genetics (microsatellites) and phylogenetics (low-copy nuclear genes) studies were developed. Conclusions The results highlight the promise of next generation sequencing for development of genomic resources for any organism. Low coverage genome sequencing allows characterization of the high copy fraction of the genome and exploration of the low copy fraction of the genome, which facilitate the development of molecular tools for further study of a target species and its relatives. This study represents a first step in the development of a community resource for further study of plant-insect co-evolution, anti-herbivore defense, floral developmental genetics, reproductive biology, chemical evolution, population genetics, and comparative genomics using milkweeds, and A. syriaca in particular, as ecological and evolutionary models. PMID:21542930

Building a model: developing genomic resources for common milkweed (Asclepias syriaca) with low coverage genome sequencing.

PubMed

Straub, Shannon C K; Fishbein, Mark; Livshultz, Tatyana; Foster, Zachary; Parks, Matthew; Weitemier, Kevin; Cronn, Richard C; Liston, Aaron

2011-05-04

Milkweeds (Asclepias L.) have been extensively investigated in diverse areas of evolutionary biology and ecology; however, there are few genetic resources available to facilitate and compliment these studies. This study explored how low coverage genome sequencing of the common milkweed (Asclepias syriaca L.) could be useful in characterizing the genome of a plant without prior genomic information and for development of genomic resources as a step toward further developing A. syriaca as a model in ecology and evolution. A 0.5× genome of A. syriaca was produced using Illumina sequencing. A virtually complete chloroplast genome of 158,598 bp was assembled, revealing few repeats and loss of three genes: accD, clpP, and ycf1. A nearly complete rDNA cistron (18S-5.8S-26S; 7,541 bp) and 5S rDNA (120 bp) sequence were obtained. Assessment of polymorphism revealed that the rDNA cistron and 5S rDNA had 0.3% and 26.7% polymorphic sites, respectively. A partial mitochondrial genome sequence (130,764 bp), with identical gene content to tobacco, was also assembled. An initial characterization of repeat content indicated that Ty1/copia-like retroelements are the most common repeat type in the milkweed genome. At least one A. syriaca microread hit 88% of Catharanthus roseus (Apocynaceae) unigenes (median coverage of 0.29×) and 66% of single copy orthologs (COSII) in asterids (median coverage of 0.14×). From this partial characterization of the A. syriaca genome, markers for population genetics (microsatellites) and phylogenetics (low-copy nuclear genes) studies were developed. The results highlight the promise of next generation sequencing for development of genomic resources for any organism. Low coverage genome sequencing allows characterization of the high copy fraction of the genome and exploration of the low copy fraction of the genome, which facilitate the development of molecular tools for further study of a target species and its relatives. This study represents a first step in the development of a community resource for further study of plant-insect co-evolution, anti-herbivore defense, floral developmental genetics, reproductive biology, chemical evolution, population genetics, and comparative genomics using milkweeds, and A. syriaca in particular, as ecological and evolutionary models.

Comparing Errors in Medicaid Reporting across Surveys: Evidence to Date

PubMed Central

Call, Kathleen T; Davern, Michael E; Klerman, Jacob A; Lynch, Victoria

2013-01-01

Objective To synthesize evidence on the accuracy of Medicaid reporting across state and federal surveys. Data Sources All available validation studies. Study Design Compare results from existing research to understand variation in reporting across surveys. Data Collection Methods Synthesize all available studies validating survey reports of Medicaid coverage. Principal Findings Across all surveys, reporting some type of insurance coverage is better than reporting Medicaid specifically. Therefore, estimates of uninsurance are less biased than estimates of specific sources of coverage. The CPS stands out as being particularly inaccurate. Conclusions Measuring health insurance coverage is prone to some level of error, yet survey overstatements of uninsurance are modest in most surveys. Accounting for all forms of bias is complex. Researchers should consider adjusting estimates of Medicaid and uninsurance in surveys prone to high levels of misreporting. PMID:22816493

Genotyping of 25 leukemia-associated genes in a single work flow by next-generation sequencing technology with low amounts of input template DNA.

PubMed

Rinke, Jenny; Schäfer, Vivien; Schmidt, Mathias; Ziermann, Janine; Kohlmann, Alexander; Hochhaus, Andreas; Ernst, Thomas

2013-08-01

We sought to establish a convenient, sensitive next-generation sequencing (NGS) method for genotyping the 26 most commonly mutated leukemia-associated genes in a single work flow and to optimize this method for low amounts of input template DNA. We designed 184 PCR amplicons that cover all of the candidate genes. NGS was performed with genomic DNA (gDNA) from a cohort of 10 individuals with chronic myelomonocytic leukemia. The results were compared with NGS data obtained from sequencing of DNA generated by whole-genome amplification (WGA) of 20 ng template gDNA. Differences between gDNA and WGA samples in variant frequencies were determined for 2 different WGA kits. For gDNA samples, 25 of 26 genes were successfully sequenced with a sensitivity of 5%, which was achieved by a median coverage of 492 reads (range, 308-636 reads) per amplicon. We identified 24 distinct mutations in 11 genes. With WGA samples, we reliably detected all mutations above 5% sensitivity with a median coverage of 506 reads (range, 256-653 reads) per amplicon. With all variants included in the analysis, WGA amplification by the 2 kits tested yielded differences in variant frequencies that ranged from -28.19% to +9.94% [mean (SD) difference, -0.2% (4.08%)] and from -35.03% to +18.67% [mean difference, -0.75% (5.12%)]. Our method permits simultaneous analysis of a wide range of leukemia-associated target genes in a single sequencing run. NGS can be performed after WGA of template DNA for reliable detection of variants without introducing appreciable bias.

Assessing Measurement Error in Medicare Coverage From the National Health Interview Survey

PubMed Central

Gindi, Renee; Cohen, Robin A.

2012-01-01

Objectives Using linked administrative data, to validate Medicare coverage estimates among adults aged 65 or older from the National Health Interview Survey (NHIS), and to assess the impact of a recently added Medicare probe question on the validity of these estimates. Data sources Linked 2005 NHIS and Master Beneficiary Record and Payment History Update System files from the Social Security Administration (SSA). Study design We compared Medicare coverage reported on NHIS with “benchmark” benefit records from SSA. Principal findings With the addition of the probe question, more reports of coverage were captured, and the agreement between the NHIS-reported coverage and SSA records increased from 88% to 95%. Few additional overreports were observed. Conclusions Increased accuracy of the Medicare coverage status of NHIS participants was achieved with the Medicare probe question. Though some misclassification remains, data users interested in Medicare coverage as an outcome or correlate can use this survey measure with confidence. PMID:24800138

LiST modelling with monitoring data to estimate impact on child mortality of an ORS and zinc programme with public sector providers in Bihar, India.

PubMed

Ayyanat, Jayachandran A; Harbour, Catherine; Kumar, Sanjeev; Singh, Manjula

2018-01-05

Many interventions have attempted to increase vulnerable and remote populations' access to ORS and zinc to reduce child mortality from diarrhoea. However, the impact of these interventions is difficult to measure. From 2010 to 15, Micronutrient Initiative (MI), worked with the public sector in Bihar, India to enable community health workers to treat and report uncomplicated child diarrhoea with ORS and zinc. We describe how we estimated programme's impact on child mortality with Lives Saved Tool (LiST) modelling and data from MI's management information system (MIS). This study demonstrates that using LiST modelling and MIS data are viable options for evaluating programmes to reduce child mortality. We used MI's programme monitoring data to estimate coverage rates and LiST modelling software to estimate programme impact on child mortality. Four scenarios estimated the effects of different rates of programme scale-up and programme coverage on estimated child mortality by measuring children's lives saved. The programme saved an estimated 806-975 children under-5 who had diarrhoea during five-year project phase. Increasing ORS and zinc coverage rates to 19.8% & 18.3% respectively under public sector coverage with effective treatment would have increased the programme's impact on child mortality and could have achieved the project goal of saving 4200 children's lives during the five-year programme. Programme monitoring data can be used with LiST modelling software to estimate coverage rates and programme impact on child mortality. This modelling approach may cost less and yield estimates sooner than directly measuring programme impact with population-based surveys. However, users must be cautious about relying on modelled estimates of impact and ensure that the programme monitoring data used is complete and precise about the programme aspects that are modelled. Otherwise, LiST may mis-estimate impact on child mortality. Further, LiST software may require modifications to its built-in assumptions to capture programmatic inputs. LiST assumes that mortality rates and cause of death structure change only in response to changes in programme coverage. In Bihar, overall child mortality has decreased and diarrhoea seems to be less lethal than previously, but at present LiST does not adjust its estimates for these sorts of changes.

Without the individual mandate, the Affordable Care Act would still cover 23 million; premiums would rise less than predicted.

PubMed

Sheils, John F; Haught, Randall

2011-11-01

Many policy analysts fear that eliminating the individual health insurance mandate and penalty from the Affordable Care Act of 2010 would lead to a "premium spiral," in which healthy people would drop coverage, premiums would soar, and the number of people with coverage would plummet. However, there are other provisions of the law that would greatly mitigate this effect. For example, the subsidies provided in the law to help people purchase coverage through health insurance exchanges would restrain a premium spiral by absorbing much of the impact of premium increases. We estimate that if the mandate were lifted, premiums in the individual market would increase by 12.6 percent-somewhat less than other estimates-with 7.8 million people losing coverage, versus other estimates for coverage loss of 16-24 million people. In sum, the Affordable Care Act would still cover 23 million people who would have been uninsured without the law. Our study suggests that although the mandate would have important effects on premiums and coverage, it might not be essential to the act's successful implementation.

Visualization of nanoconstructions with DNA-Aptamers for targeted molecules binding on the surface of screen-printed electrodes

NASA Astrophysics Data System (ADS)

Lapin, Ivan N.; Shabalina, Anastasiia V.; Svetlichyi, Valery A.; Kolovskaya, Olga S.

2018-04-01

Nanoconstructions of gold nanoparticles (NPs) obtained via pulsed laser ablation in liquid with DNA-aptamer specific to protein tumor marker were visualized on the surface of screen-printed electrode using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). AuNPs/aptamer nanoconstuctions distribution on the solid surface was studied. More uniform coverage of the carbon electrode surface with the nanoconstuctions was showed in comparison with DNA-aptamer alone on the golden electrode surface. Targeted binding of the tumor marker molecules with the AuNPs/DNA-aptamer nanoconstuctions was approved.

Systematic review of the incremental costs of interventions that increase immunization coverage.

PubMed

Ozawa, Sachiko; Yemeke, Tatenda T; Thompson, Kimberly M

2018-05-10

Achieving and maintaining high vaccination coverage requires investments, but the costs and effectiveness of interventions to increase coverage remain poorly characterized. We conducted a systematic review of the literature to identify peer-reviewed studies published in English that reported interventions aimed at increasing immunization coverage and the associated costs and effectiveness of the interventions. We found limited information in the literature, with many studies reporting effectiveness estimates, but not providing cost information. Using the available data, we developed a cost function to support future programmatic decisions about investments in interventions to increase immunization coverage for relatively low and high-income countries. The cost function estimates the non-vaccine cost per dose of interventions to increase absolute immunization coverage by one percent, through either campaigns or routine immunization. The cost per dose per percent increase in absolute coverage increased with higher baseline coverage, demonstrating increasing incremental costs required to reach higher coverage levels. Future studies should evaluate the performance of the cost function and add to the database of available evidence to better characterize heterogeneity in costs and generalizability of the cost function. Copyright © 2018. Published by Elsevier Ltd.

Discordance between genomic divergence and phenotypic variation in a rapidly evolving avian genus (Motacilla).

PubMed

Harris, Rebecca B; Alström, Per; Ödeen, Anders; Leaché, Adam D

2018-03-01

Generally, genotypes and phenotypes are expected to be spatially congruent; however, in widespread species complexes with few barriers to dispersal, multiple contact zones, and limited reproductive isolation, discordance between phenotypes and phylogeographic groups is more probable. Wagtails (Motacilla) are a genus of birds with striking plumage pattern variation across the Old World. Up to 13 subspecies are recognized within a single species, yet previous studies using mitochondrial DNA have supported polyphyletic phylogeographic groups that are inconsistent with subspecies plumage characteristics. In this study, we investigate the link between phenotypes and genotype by taking a phylogenetic approach. We use genome-wide SNPs, nuclear introns, and mitochondrial DNA to estimate population structure, isolation by distance, and species relationships. Together, our genetic sampling includes complete species-level sampling and comprehensive coverage of the three most phenotypically diverse Palearctic species. Our study provides strong evidence for species-level patterns of differentiation, however population-level differentiation is less pronounced. SNPs provide a robust estimate of species-level relationships, which are mostly corroborated by a combined analysis of mtDNA and nuclear introns (the first time-calibrated species tree for the genus). However, the mtDNA tree is strongly incongruent and is considered to misrepresent the species phylogeny. The extant wagtail lineages originated during the Pliocene and the Eurasian lineage underwent rapid diversification during the Pleistocene. Three of four widespread Eurasian species exhibit an east-west divide that contradicts both subspecies taxonomy and phenotypic variation. Indeed, SNPs fail to distinguish between phenotypically distinct subspecies within the M. alba and M. flava complexes, and instead support geographical regions, each of which is home to two or more different looking subspecies. This is a major step towards our understanding of wagtail phylogeny compared to previous analyses of fewer species and considerably less sequence data. Copyright © 2017 Elsevier Inc. All rights reserved.

Lessons for livestock genomics from genome and transcriptome sequencing in cattle and other mammals.

PubMed

Taylor, Jeremy F; Whitacre, Lynsey K; Hoff, Jesse L; Tizioto, Polyana C; Kim, JaeWoo; Decker, Jared E; Schnabel, Robert D

2016-08-17

Decreasing sequencing costs and development of new protocols for characterizing global methylation, gene expression patterns and regulatory regions have stimulated the generation of large livestock datasets. Here, we discuss experiences in the analysis of whole-genome and transcriptome sequence data. We analyzed whole-genome sequence (WGS) data from 132 individuals from five canid species (Canis familiaris, C. latrans, C. dingo, C. aureus and C. lupus) and 61 breeds, three bison (Bison bison), 64 water buffalo (Bubalus bubalis) and 297 bovines from 17 breeds. By individual, data vary in extent of reference genome depth of coverage from 4.9X to 64.0X. We have also analyzed RNA-seq data for 580 samples representing 159 Bos taurus and Rattus norvegicus animals and 98 tissues. By aligning reads to a reference assembly and calling variants, we assessed effects of average depth of coverage on the actual coverage and on the number of called variants. We examined the identity of unmapped reads by assembling them and querying produced contigs against the non-redundant nucleic acids database. By imputing high-density single nucleotide polymorphism data on 4010 US registered Angus animals to WGS using Run4 of the 1000 Bull Genomes Project and assessing the accuracy of imputation, we identified misassembled reference sequence regions. We estimate that a 24X depth of coverage is required to achieve 99.5 % coverage of the reference assembly and identify 95 % of the variants within an individual's genome. Genomes sequenced to low average coverage (e.g., <10X) may fail to cover 10 % of the reference genome and identify <75 % of variants. About 10 % of genomic DNA or transcriptome sequence reads fail to align to the reference assembly. These reads include loci missing from the reference assembly and misassembled genes and interesting symbionts, commensal and pathogenic organisms. Assembly errors and a lack of annotation of functional elements significantly limit the utility of the current draft livestock reference assemblies. The Functional Annotation of Animal Genomes initiative seeks to annotate functional elements, while a 70X Pac-Bio assembly for cow is underway and may result in a significantly improved reference assembly.

Estimation of fish biomass using environmental DNA.

PubMed

Takahara, Teruhiko; Minamoto, Toshifumi; Yamanaka, Hiroki; Doi, Hideyuki; Kawabata, Zen'ichiro

2012-01-01

Environmental DNA (eDNA) from aquatic vertebrates has recently been used to estimate the presence of a species. We hypothesized that fish release DNA into the water at a rate commensurate with their biomass. Thus, the concentration of eDNA of a target species may be used to estimate the species biomass. We developed an eDNA method to estimate the biomass of common carp (Cyprinus carpio L.) using laboratory and field experiments. In the aquarium, the concentration of eDNA changed initially, but reached an equilibrium after 6 days. Temperature had no effect on eDNA concentrations in aquaria. The concentration of eDNA was positively correlated with carp biomass in both aquaria and experimental ponds. We used this method to estimate the biomass and distribution of carp in a natural freshwater lagoon. We demonstrated that the distribution of carp eDNA concentration was explained by water temperature. Our results suggest that biomass data estimated from eDNA concentration reflects the potential distribution of common carp in the natural environment. Measuring eDNA concentration offers a non-invasive, simple, and rapid method for estimating biomass. This method could inform management plans for the conservation of ecosystems.

Estimation of Fish Biomass Using Environmental DNA

PubMed Central

Takahara, Teruhiko; Minamoto, Toshifumi; Yamanaka, Hiroki; Doi, Hideyuki; Kawabata, Zen'ichiro

2012-01-01

Environmental DNA (eDNA) from aquatic vertebrates has recently been used to estimate the presence of a species. We hypothesized that fish release DNA into the water at a rate commensurate with their biomass. Thus, the concentration of eDNA of a target species may be used to estimate the species biomass. We developed an eDNA method to estimate the biomass of common carp (Cyprinus carpio L.) using laboratory and field experiments. In the aquarium, the concentration of eDNA changed initially, but reached an equilibrium after 6 days. Temperature had no effect on eDNA concentrations in aquaria. The concentration of eDNA was positively correlated with carp biomass in both aquaria and experimental ponds. We used this method to estimate the biomass and distribution of carp in a natural freshwater lagoon. We demonstrated that the distribution of carp eDNA concentration was explained by water temperature. Our results suggest that biomass data estimated from eDNA concentration reflects the potential distribution of common carp in the natural environment. Measuring eDNA concentration offers a non-invasive, simple, and rapid method for estimating biomass. This method could inform management plans for the conservation of ecosystems. PMID:22563411

Blood from a turnip: tissue origin of low-coverage shotgun sequencing libraries affects recovery of mitogenome sequences

USGS Publications Warehouse

Barker, F. Keith; Oyler-McCance, Sara; Tomback, Diana F.

2015-01-01

Next generation sequencing methods allow rapid, economical accumulation of data that have many applications, even at relatively low levels of genome coverage. However, the utility of shotgun sequencing data sets for specific goals may vary depending on the biological nature of the samples sequenced. We show that the ability to assemble mitogenomes from three avian samples of two different tissue types varies widely. In particular, data with coverage typical of microsatellite development efforts (∼1×) from DNA extracted from avian blood failed to cover even 50% of the mitogenome, relative to at least 500-fold coverage from muscle-derived data. Researchers should consider possible applications of their data and select the tissue source for their work accordingly. Practitioners analyzing low-coverage shotgun sequencing data (including for microsatellite locus development) should consider the potential benefits of mitogenome assembly, including internal barcode verification of species identity, mitochondrial primer development, and phylogenetics.

A sequence of 'factishes': the media-metaphorical knowledge dynamics structuring the German press coverage of the human genome.

PubMed

Doring, Martin

2005-12-01

This article deals with the cultural framing of the near sequencing of the human genome and its impact on the media coverage in Germany. It investigates in particular the way in which the weekly journal Die Zeit and the daily newspaper Frankfurter Rundschau reported this media event and its aftermath between June 2000 and June 2001. Both newspapers are quality papers that played an essential role in framing the human genome debate--alongside the Frankfurter Allgemeine Zeitung--which became the most prominent genomic forum. The decoding of the human genome prompted a huge controversy concerning the ethics of human engineering, research on stem cells and Preimplantation Genetic Diagnosis. The main aim of this article is to show how this controversy was structured by metaphor. The media coverage of the genome generated DNA-factishes--a neologism designating the ambivalence of something as fact (fait) and as a fetish (fetiche)--that mostly propagated images of a new DNA-scienticism or biological determinism. Mediated by cultural experiences, the human genome became a highly artificial and social construct of a 'NatureCulture'.

Kinetic control of the coverage of oil droplets by DNA-functionalized colloids

PubMed Central

Joshi, Darshana; Bargteil, Dylan; Caciagli, Alessio; Burelbach, Jerome; Xing, Zhongyang; Nunes, André S.; Pinto, Diogo E. P.; Araújo, Nuno A. M.; Brujic, Jasna; Eiser, Erika

2016-01-01

We report a study of reversible adsorption of DNA-coated colloids on complementary functionalized oil droplets. We show that it is possible to control the surface coverage of oil droplets using colloidal particles by exploiting the fact that, during slow adsorption, compositional arrest takes place well before structural arrest occurs. As a consequence, we can prepare colloid-coated oil droplets with a “frozen” degree of loading but with fully ergodic colloidal dynamics on the droplets. We illustrate the equilibrium nature of the adsorbed colloidal phase by exploring the quasi–two-dimensional phase behavior of the adsorbed colloids under the influence of depletion interactions and present simulations of a simple model that illustrates the nature of the compositional arrest and the structural ergodicity. PMID:27532053

Routine immunization in Pakistan: comparison of multiple data sources and identification of factors associated with vaccination

PubMed Central

Imran, Hafsa; Raja, Dania; Grassly, Nicholas C; Wadood, M Zubair; Safdar, Rana M; O’Reilly, Kathleen M

2018-01-01

Abstract Background Within Pakistan, estimates of vaccination coverage with the pentavalent vaccine, oral polio vaccine (OPV) and measles vaccine (MV) in 2011 were reported to be 74%, 75% and 53%, respectively. These national estimates may mask regional variation. The reasons for this variation have not been explored. Methods Data from the Multiple Indicator Cluster Surveys (MICS) for Balochistan and Punjab (2010–2011) are analysed to examine factors associated with receiving three or more doses of the pentavalent vaccine and one or more MVs using regression modelling. Pentavalent and OPV estimates from the MICS were compared to vaccine dose histories from surveillance for acute flaccid paralysis (AFP; poliomyelitis) to ascertain agreement. Results Adjusted coverage of children 12–23 months of age were estimated to be 16.0%, 75.5% and 34.2% in Balochistan and 58.0%, 87.7% and 72.6% in Punjab for the pentavalent vaccine, OPV and MV, respectively. Maternal education, healthcare utilization and wealth were associated with receiving the pentavalent vaccine and the MV. There was a strong correlation of district estimates of vaccination coverage between AFP and MICS data, but AFP estimates of pentavalent coverage in Punjab were biased toward higher values. Conclusions National estimates mask variation and estimates from individual surveys should be considered alongside other estimates. The development of strategies targeted towards poorly educated parents within low-wealth quintiles that may not typically access healthcare could improve vaccination rates. PMID:29432552

Modelling preventive effectiveness to estimate the equity tipping point: at what coverage can individual preventive interventions reduce socioeconomic disparities in diabetes risk?

PubMed

Manuel, D G; Ho, T H; Harper, S; Anderson, G M; Lynch, J; Rosella, L C

2014-07-01

Most individual preventive therapies potentially narrow or widen health disparities depending on the difference in community effectiveness across socioeconomic position (SEP). The equity tipping point (defined as the point at which health disparities become larger) can be calculated by varying components of community effectiveness such as baseline risk of disease, intervention coverage and/or intervention efficacy across SEP. We used a simple modelling approach to estimate the community effectiveness of diabetes prevention across SEP in Canada under different scenarios of intervention coverage. Five-year baseline diabetes risk differed between the lowest and highest income groups by 1.76%. Assuming complete coverage across all income groups, the difference was reduced to 0.90% (144 000 cases prevented) with lifestyle interventions and 1.24% (88 100 cases prevented) with pharmacotherapy. The equity tipping point was estimated to be a coverage difference of 30% for preventive interventions (100% and 70% coverage among the highest and lowest income earners, respectively). Disparities in diabetes risk could be measurably reduced if existing interventions were equally adopted across SEP. However, disparities in coverage could lead to increased inequity in risk. Simple modelling approaches can be used to examine the community effectiveness of individual preventive interventions and their potential to reduce (or increase) disparities. The equity tipping point can be used as a critical threshold for disparities analyses.

Combined Targeted DNA Sequencing in Non-Small Cell Lung Cancer (NSCLC) Using UNCseq and NGScopy, and RNA Sequencing Using UNCqeR for the Detection of Genetic Aberrations in NSCLC

PubMed Central

Walter, Vonn; Patel, Nirali M.; Eberhard, David A.; Hayward, Michele C.; Salazar, Ashley H.; Jo, Heejoon; Soloway, Matthew G.; Wilkerson, Matthew D.; Parker, Joel S.; Yin, Xiaoying; Zhang, Guosheng; Siegel, Marni B.; Rosson, Gary B.; Earp, H. Shelton; Sharpless, Norman E.; Gulley, Margaret L.; Weck, Karen E.

2015-01-01

The recent FDA approval of the MiSeqDx platform provides a unique opportunity to develop targeted next generation sequencing (NGS) panels for human disease, including cancer. We have developed a scalable, targeted panel-based assay termed UNCseq, which involves a NGS panel of over 200 cancer-associated genes and a standardized downstream bioinformatics pipeline for detection of single nucleotide variations (SNV) as well as small insertions and deletions (indel). In addition, we developed a novel algorithm, NGScopy, designed for samples with sparse sequencing coverage to detect large-scale copy number variations (CNV), similar to human SNP Array 6.0 as well as small-scale intragenic CNV. Overall, we applied this assay to 100 snap-frozen lung cancer specimens lacking same-patient germline DNA (07–0120 tissue cohort) and validated our results against Sanger sequencing, SNP Array, and our recently published integrated DNA-seq/RNA-seq assay, UNCqeR, where RNA-seq of same-patient tumor specimens confirmed SNV detected by DNA-seq, if RNA-seq coverage depth was adequate. In addition, we applied the UNCseq assay on an independent lung cancer tumor tissue collection with available same-patient germline DNA (11–1115 tissue cohort) and confirmed mutations using assays performed in a CLIA-certified laboratory. We conclude that UNCseq can identify SNV, indel, and CNV in tumor specimens lacking germline DNA in a cost-efficient fashion. PMID:26076459

Infant immunization coverage in Italy: estimates by simultaneous EPI cluster surveys of regions. ICONA Study Group.

PubMed Central

Salmaso, S.; Rota, M. C.; Ciofi Degli Atti, M. L.; Tozzi, A. E.; Kreidl, P.

1999-01-01

In 1998, a series of regional cluster surveys (the ICONA Study) was conducted simultaneously in 19 out of the 20 regions in Italy to estimate the mandatory immunization coverage of children aged 12-24 months with oral poliovirus (OPV), diphtheria-tetanus (DT) and viral hepatitis B (HBV) vaccines, as well as optional immunization coverage with pertussis, measles and Haemophilus influenzae b (Hib) vaccines. The study children were born in 1996 and selected from birth registries using the Expanded Programme of Immunization (EPI) cluster sampling technique. Interviews with parents were conducted to determine each child's immunization status and the reasons for any missed or delayed vaccinations. The study population comprised 4310 children aged 12-24 months. Coverage for both mandatory and optional vaccinations differed by region. The overall coverage for mandatory vaccines (OPV, DT and HBV) exceeded 94%, but only 79% had been vaccinated in accord with the recommended schedule (i.e. during the first year of life). Immunization coverage for pertussis increased from 40% (1993 survey) to 88%, but measles coverage (56%) remained inadequate for controlling the disease; Hib coverage was 20%. These results confirm that in Italy the coverage of only mandatory immunizations is satisfactory. Pertussis immunization coverage has improved dramatically since the introduction of acellular vaccines. A greater effort to educate parents and physicians is still needed to improve the coverage of optional vaccinations in all regions. PMID:10593033

Infant immunization coverage in Italy: estimates by simultaneous EPI cluster surveys of regions. ICONA Study Group.

PubMed

Salmaso, S; Rota, M C; Ciofi Degli Atti, M L; Tozzi, A E; Kreidl, P

1999-01-01

In 1998, a series of regional cluster surveys (the ICONA Study) was conducted simultaneously in 19 out of the 20 regions in Italy to estimate the mandatory immunization coverage of children aged 12-24 months with oral poliovirus (OPV), diphtheria-tetanus (DT) and viral hepatitis B (HBV) vaccines, as well as optional immunization coverage with pertussis, measles and Haemophilus influenzae b (Hib) vaccines. The study children were born in 1996 and selected from birth registries using the Expanded Programme of Immunization (EPI) cluster sampling technique. Interviews with parents were conducted to determine each child's immunization status and the reasons for any missed or delayed vaccinations. The study population comprised 4310 children aged 12-24 months. Coverage for both mandatory and optional vaccinations differed by region. The overall coverage for mandatory vaccines (OPV, DT and HBV) exceeded 94%, but only 79% had been vaccinated in accord with the recommended schedule (i.e. during the first year of life). Immunization coverage for pertussis increased from 40% (1993 survey) to 88%, but measles coverage (56%) remained inadequate for controlling the disease; Hib coverage was 20%. These results confirm that in Italy the coverage of only mandatory immunizations is satisfactory. Pertussis immunization coverage has improved dramatically since the introduction of acellular vaccines. A greater effort to educate parents and physicians is still needed to improve the coverage of optional vaccinations in all regions.

Impact of Adverse Events Following Immunization in Viet Nam in 2013 on chronic hepatitis B infection.

PubMed

Li, Xi; Wiesen, Eric; Diorditsa, Sergey; Toda, Kohei; Duong, Thi Hong; Nguyen, Lien Huong; Nguyen, Van Cuong; Nguyen, Tran Hien

2016-02-03

Adverse Events Following Immunization in Viet Nam in 2013 led to substantial reductions in hepatitis B vaccination coverage (both the birth dose and the three-dose series). In order to estimate the impact of the reduction in vaccination coverage on hepatitis B transmission and future mortality, a widely-used mathematical model was applied to the data from Viet Nam. Using the model, we estimated the number of chronic infections and deaths that are expected to occur in the birth cohort in 2013 and the number of excessive infections and deaths attributable to the drop in immunization coverage in 2013. An excess of 90,137 chronic infections and 17,456 future deaths were estimated to occur in the 2013 birth cohort due to the drop in vaccination coverage. This analysis highlights the importance of maintaining high vaccination coverage and swiftly responding to reported Adverse Events Following Immunization in order to regain consumer confidence in the hepatitis B vaccine. Copyright © 2015 World Health Organization; licensee Elsevier. Published by Elsevier Ltd.. All rights reserved.

Use of geographic information systems in rabies vaccination campaigns.

PubMed

Grisi-Filho, José Henrique de Hildebrand e; Amaku, Marcos; Dias, Ricardo Augusto; Montenegro Netto, Hildebrando; Paranhos, Noemia Tucunduva; Mendes, Maria Cristina Novo Campos; Ferreira Neto, José Soares; Ferreira, Fernando

2008-12-01

To develop a method to assist in the design and assessment of animal rabies control campaigns. A methodology was developed based on geographic information systems to estimate the animal (canine and feline) population and density per census tract and per subregion (known as "Subprefeituras") in the city of São Paulo (Southeastern Brazil) in 2002. The number of vaccination units in a given region was estimated to achieve a certain proportion of vaccination coverage. Census database was used for the human population, as well as estimates ratios of dog:inhabitant and cat:inhabitant. Estimated figures were 1,490,500 dogs and 226,954 cats in the city, i.e. an animal population density of 1138.14 owned animals per km(2). In the 2002 campaign, 926,462 were vaccinated, resulting in a vaccination coverage of 54%. The estimated number of vaccination units to be able to reach a 70%-vaccination coverage, by vaccinating 700 animals per unit on average, was 1,729. These estimates are presented as maps of animal density according to census tracts and "Subprefeituras". The methodology used in the study may be applied in a systematic way to the design and evaluation of rabies vaccination campaigns, enabling the identification of areas of critical vaccination coverage.

Can We Spin Straw Into Gold? An Evaluation of Immigrant Legal Status Imputation Approaches

PubMed Central

Van Hook, Jennifer; Bachmeier, James D.; Coffman, Donna; Harel, Ofer

2014-01-01

Researchers have developed logical, demographic, and statistical strategies for imputing immigrants’ legal status, but these methods have never been empirically assessed. We used Monte Carlo simulations to test whether, and under what conditions, legal status imputation approaches yield unbiased estimates of the association of unauthorized status with health insurance coverage. We tested five methods under a range of missing data scenarios. Logical and demographic imputation methods yielded biased estimates across all missing data scenarios. Statistical imputation approaches yielded unbiased estimates only when unauthorized status was jointly observed with insurance coverage; when this condition was not met, these methods overestimated insurance coverage for unauthorized relative to legal immigrants. We next showed how bias can be reduced by incorporating prior information about unauthorized immigrants. Finally, we demonstrated the utility of the best-performing statistical method for increasing power. We used it to produce state/regional estimates of insurance coverage among unauthorized immigrants in the Current Population Survey, a data source that contains no direct measures of immigrants’ legal status. We conclude that commonly employed legal status imputation approaches are likely to produce biased estimates, but data and statistical methods exist that could substantially reduce these biases. PMID:25511332

Monitoring maternal, newborn, and child health interventions using lot quality assurance sampling in Sokoto State of northern Nigeria.

PubMed

Abegunde, Dele; Orobaton, Nosa; Shoretire, Kamil; Ibrahim, Mohammed; Mohammed, Zainab; Abdulazeez, Jumare; Gwamzhi, Ringpon; Ganiyu, Akeem

2015-01-01

Maternal mortality ratio and infant mortality rate are as high as 1,576 per 100,000 live births and 78 per 1,000 live births, respectively, in Nigeria's northwestern region, where Sokoto State is located. Using applicable monitoring indicators for tracking progress in the UN/WHO framework on continuum of maternal, newborn, and child health care, this study evaluated the progress of Sokoto toward achieving the Millennium Development Goals (MDGs) 4 and 5 by December 2015. The changes in outcomes in 2012-2013 associated with maternal and child health interventions were assessed. We used baseline and follow-up lot quality assurance sampling (LQAS) data obtained in 2012 and 2013, respectively. In each of the surveys, data were obtained from 437 households sampled from 19 LQAS locations in each of the 23 local government areas (LGAs). The composite state-level coverage estimates of the respective indicators were aggregated from estimated LGA coverage estimates. None of the nine indicators associated with the continuum of maternal, neonatal, and child care satisfied the recommended 90% coverage target for achieving MDGs 4 and 5. Similarly, the average state coverage estimates were lower than national coverage estimates. Marginal improvements in coverage were obtained in the demand for family planning satisfied, antenatal care visits, postnatal care for mothers, and exclusive breast-feeding. Antibiotic treatment for acute pneumonia increased significantly by 12.8 percentage points. The majority of the LGAs were classifiable as low-performing, high-priority areas for intensified program intervention. Despite the limited time left in the countdown to December 2015, Sokoto State, Nigeria, is not on track to achieving the MDG 90% coverage of indicators tied to the continuum of maternal and child care, to reduce maternal and childhood mortality by a third by 2015. Targeted health system investments at the primary care level remain a priority, for intensive program scale-up to accelerate impact.

Monitoring maternal, newborn, and child health interventions using lot quality assurance sampling in Sokoto State of northern Nigeria

PubMed Central

Abegunde, Dele; Orobaton, Nosa; Shoretire, Kamil; Ibrahim, Mohammed; Mohammed, Zainab; Abdulazeez, Jumare; Gwamzhi, Ringpon; Ganiyu, Akeem

2015-01-01

Background Maternal mortality ratio and infant mortality rate are as high as 1,576 per 100,000 live births and 78 per 1,000 live births, respectively, in Nigeria's northwestern region, where Sokoto State is located. Using applicable monitoring indicators for tracking progress in the UN/WHO framework on continuum of maternal, newborn, and child health care, this study evaluated the progress of Sokoto toward achieving the Millennium Development Goals (MDGs) 4 and 5 by December 2015. The changes in outcomes in 2012–2013 associated with maternal and child health interventions were assessed. Design We used baseline and follow-up lot quality assurance sampling (LQAS) data obtained in 2012 and 2013, respectively. In each of the surveys, data were obtained from 437 households sampled from 19 LQAS locations in each of the 23 local government areas (LGAs). The composite state-level coverage estimates of the respective indicators were aggregated from estimated LGA coverage estimates. Results None of the nine indicators associated with the continuum of maternal, neonatal, and child care satisfied the recommended 90% coverage target for achieving MDGs 4 and 5. Similarly, the average state coverage estimates were lower than national coverage estimates. Marginal improvements in coverage were obtained in the demand for family planning satisfied, antenatal care visits, postnatal care for mothers, and exclusive breast-feeding. Antibiotic treatment for acute pneumonia increased significantly by 12.8 percentage points. The majority of the LGAs were classifiable as low-performing, high-priority areas for intensified program intervention. Conclusions Despite the limited time left in the countdown to December 2015, Sokoto State, Nigeria, is not on track to achieving the MDG 90% coverage of indicators tied to the continuum of maternal and child care, to reduce maternal and childhood mortality by a third by 2015. Targeted health system investments at the primary care level remain a priority, for intensive program scale-up to accelerate impact. PMID:26455491

Estimated effects of adding universal public coverage of an essential medicines list to existing public drug plans in Canada.

PubMed

Morgan, Steven G; Li, Winny; Yau, Brandon; Persaud, Nav

2017-02-27

Canada's universal health care system does not include universal coverage of prescription drugs. We sought to estimate the effects of adding universal public coverage of an essential medicines list to existing public drug plans in Canada. We used administrative and market research data to estimate the 2015 shares of the volume and cost of prescriptions filled in the community setting that were for 117 drugs on a model list of essential medicines for Canada. We compared prices of these essential medicines in Canada with prices in the United States, Sweden and New Zealand. We estimated the cost of adding universal public drug coverage of these essential medicines based on anticipated effects on medication use and pricing. The 117 essential medicines on the model list accounted for 44% of all prescriptions and 30% of total prescription drug expenditures in 2015. Average prices of generic essential medicines were 47% lower in the US, 60% lower in Sweden and 84% lower in New Zealand; brand-name drugs were priced 43% lower in the US. Estimated savings from universal public coverage of these essential medicines was $4.27 billion per year (range $2.72 billion to $5.83 billion; 28% reduction) for patients and private drug plan sponsors, at an incremental government cost of $1.23 billion per year (range $373 million to $1.98 billion; 11% reduction). Our analysis showed that adding universal public coverage of essential medicines to the existing public drug plans in Canada could address most of Canadians' pharmaceutical needs and save billions of dollars annually. Doing so may be a pragmatic step forward while more comprehensive pharmacare reforms are planned. © 2017 Canadian Medical Association or its licensors.

Does extending health insurance coverage to the uninsured improve population health outcomes?

PubMed

Thornton, James A; Rice, Jennifer L

2008-01-01

An ongoing debate exists about whether the US should adopt a universal health insurance programme. Much of the debate has focused on programme implementation and cost, with relatively little attention to benefits for social welfare. To estimate the effect on US population health outcomes, measured by mortality, of extending private health insurance to the uninsured, and to obtain a rough estimate of the aggregate economic benefits of extending insurance coverage to the uninsured. We use state-level panel data for all 50 states for the period 1990-2000 to estimate a health insurance augmented, aggregate health production function for the US. An instrumental variables fixed-effects estimator is used to account for confounding variables and reverse causation from health status to insurance coverage. Several observed factors, such as income, education, unemployment, cigarette and alcohol consumption and population demographic characteristics are included to control for potential confounding variables that vary across both states and time. The results indicate a negative relationship between private insurance and mortality, thus suggesting that extending insurance to the uninsured population would result in an improvement in population health outcomes. The estimate of the marginal effect of insurance coverage indicates that a 10% increase in the population-insured rate of a state reduces mortality by 1.69-1.92%. Using data for the year 2003, we calculate that extending private insurance coverage to the entire uninsured population in the US would save over 75 000 lives annually and may yield annual net benefits to the nation in excess of $US400 billion. This analysis suggests that extending health insurance coverage through the private market to the 46 million Americans without health insurance may well produce large social economic benefits for the nation as a whole.

[Effective coverage to manage domestic violence against women in Mexican municipalities: limits of metrics].

PubMed

Viviescas-Vargas, Diana P; Idrovo, Alvaro Javier; López-López, Erika; Uicab-Pool, Gloria; Herrera-Trujillo, Mónica; Balam-Gómez, Maricela; Hidalgo-Solórzano, Elisa

2013-08-01

The study estimated the effective coverage of health services in primary care for the management of domestic violence against women in three municipalities in Mexico. We estimated the prevalence and severity of violence using a validated scale, and the effective coverage proposed by Shengelia and partners with any modifications. Quality care was considered when there was a suggestion to report it to authorities. The use and quality of care was low in the three municipalities analyzed, used most frequently when there was sexual or physical violence. Effective coverage was 29.41%, 16.67% and zero in Guachochi, Jojutla and Tizimín, respectively. The effective coverage indicator had difficulties in measuring events and responses that were not based on biomedical models. Findings suggest that the indicator can be improved by incorporating other dimensions of quality.

Low coverage of central point vaccination against dog rabies in Bamako, Mali.

PubMed

Muthiani, Yvonne; Traoré, Abdallah; Mauti, Stephanie; Zinsstag, Jakob; Hattendorf, Jan

2015-06-15

Canine rabies remains an important public-health problem in Africa. Dog mass vaccination is the recommended method for rabies control and elimination. We report on the first small-scale mass dog vaccination campaign trial in Bamako, Mali. Our objective was to estimate coverage of the vaccination campaign and to quantify determinants of intervention effectiveness. In September 2013, a central point vaccination campaign--free of cost for dog owners--was carried out in 17 posts on three consecutive days within Bamako's Commune 1. Vaccination coverage and the proportion of ownerless dogs were estimated by combining mark-recapture household and transect surveys using Bayesian modeling. The estimated vaccination coverage was 17.6% (95% Credibility Interval, CI: 14.4-22.1%) which is far below the World Health Organization (WHO) recommended vaccination coverage of 70%. The Bayesian estimate for the owned dog population of Commune 1 was 3459 dogs (95% CI: 2786-4131) and the proportion of ownerless dogs was about 8%. The low coverage observed is primarily attributed to low participation by dog owners. Dog owners reported several reasons for not bringing their dogs to the vaccination posts. The most frequently reported reasons for non-attendance were lack of information (25%) and the inability to handle the dog (16%). For 37% of respondents, no clear reason was given for non-vaccination. Despite low coverage, the vaccination campaign in Bamako was relatively easy to implement, both in terms of logistics and organization. Almost half of the participating dog owners brought their pets on the first day of the campaign. Participatory stakeholder processes involving communities and local authorities are needed to identify effective communication channels and locally adapted vaccination strategies, which could include both central-point and door-to-door vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

Incentives Increase Participation in Mass Dog Rabies Vaccination Clinics and Methods of Coverage Estimation Are Assessed to Be Accurate

PubMed Central

Steinmetz, Melissa; Czupryna, Anna; Bigambo, Machunde; Mzimbiri, Imam; Powell, George; Gwakisa, Paul

2015-01-01

In this study we show that incentives (dog collars and owner wristbands) are effective at increasing owner participation in mass dog rabies vaccination clinics and we conclude that household questionnaire surveys and the mark-re-sight (transect survey) method for estimating post-vaccination coverage are accurate when all dogs, including puppies, are included. Incentives were distributed during central-point rabies vaccination clinics in northern Tanzania to quantify their effect on owner participation. In villages where incentives were handed out participation increased, with an average of 34 more dogs being vaccinated. Through economies of scale, this represents a reduction in the cost-per-dog of $0.47. This represents the price-threshold under which the cost of the incentive used must fall to be economically viable. Additionally, vaccination coverage levels were determined in ten villages through the gold-standard village-wide census technique, as well as through two cheaper and quicker methods (randomized household questionnaire and the transect survey). Cost data were also collected. Both non-gold standard methods were found to be accurate when puppies were included in the calculations, although the transect survey and the household questionnaire survey over- and under-estimated the coverage respectively. Given that additional demographic data can be collected through the household questionnaire survey, and that its estimate of coverage is more conservative, we recommend this method. Despite the use of incentives the average vaccination coverage was below the 70% threshold for eliminating rabies. We discuss the reasons and suggest solutions to improve coverage. Given recent international targets to eliminate rabies, this study provides valuable and timely data to help improve mass dog vaccination programs in Africa and elsewhere. PMID:26633821

Development of genomic tools in a widespread tropical tree, Symphonia globulifera L.f.: a new low-coverage draft genome, SNP and SSR markers.

PubMed

Olsson, Sanna; Seoane-Zonjic, Pedro; Bautista, Rocío; Claros, M Gonzalo; González-Martínez, Santiago C; Scotti, Ivan; Scotti-Saintagne, Caroline; Hardy, Olivier J; Heuertz, Myriam

2017-07-01

Population genetic studies in tropical plants are often challenging because of limited information on taxonomy, phylogenetic relationships and distribution ranges, scarce genomic information and logistic challenges in sampling. We describe a strategy to develop robust and widely applicable genetic markers based on a modest development of genomic resources in the ancient tropical tree species Symphonia globulifera L.f. (Clusiaceae), a keystone species in African and Neotropical rainforests. We provide the first low-coverage (11X) fragmented draft genome sequenced on an individual from Cameroon, covering 1.027 Gbp or 67.5% of the estimated genome size. Annotation of 565 scaffolds (7.57 Mbp) resulted in the prediction of 1046 putative genes (231 of them containing a complete open reading frame) and 1523 exact simple sequence repeats (SSRs, microsatellites). Aligning a published transcriptome of a French Guiana population against this draft genome produced 923 high-quality single nucleotide polymorphisms. We also preselected genic SSRs in silico that were conserved and polymorphic across a wide geographical range, thus reducing marker development tests on rare DNA samples. Of 23 SSRs tested, 19 amplified and 18 were successfully genotyped in four S. globulifera populations from South America (Brazil and French Guiana) and Africa (Cameroon and São Tomé island, F ST  = 0.34). Most loci showed only population-specific deviations from Hardy-Weinberg proportions, pointing to local population effects (e.g. null alleles). The described genomic resources are valuable for evolutionary studies in Symphonia and for comparative studies in plants. The methods are especially interesting for widespread tropical or endangered taxa with limited DNA availability. © 2016 John Wiley & Sons Ltd.

Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage whole-genome sequencing of maternal plasma DNA: review of 1982 consecutive cases in a single center.

PubMed

Lau, T K; Cheung, S W; Lo, P S S; Pursley, A N; Chan, M K; Jiang, F; Zhang, H; Wang, W; Jong, L F J; Yuen, O K C; Chan, H Y C; Chan, W S K; Choy, K W

2014-03-01

To review the performance of non-invasive prenatal testing (NIPT) by low-coverage whole-genome sequencing of maternal plasma DNA at a single center. The NIPT result and pregnancy outcome of 1982 consecutive cases were reviewed. NIPT was based on low coverage (0.1×) whole-genome sequencing of maternal plasma DNA. All subjects were contacted for pregnancy and fetal outcome. Of the 1982 NIPT tests, a repeat blood sample was required in 23 (1.16%). In one case, a conclusive report could not be issued, probably because of an abnormal vanished twin fetus. NIPT was positive for common trisomies in 29 cases (23 were trisomy 21, four were trisomy 18 and two were trisomy 13); all were confirmed by prenatal karyotyping (specificity=100%). In addition, 11 cases were positive for sex-chromosomal abnormalities (SCA), and nine cases were positive for other aneuploidies or deletion/duplication. Fourteen of these 20 subjects agreed to undergo further investigations, and the abnormality was found to be of fetal origin in seven, confined placental mosaicism (CPM) in four, of maternal origin in two and not confirmed in one. Overall, 85.7% of the NIPT-suspected SCA were of fetal origin, and 66.7% of the other abnormalities were caused by CPM. Two of the six cases suspected or confirmed to have CPM were complicated by early-onset growth restriction requiring delivery before 34 weeks. Fetal outcome of the NIPT-negative cases was ascertained in 1645 (85.15%). Three chromosomal abnormalities were not detected by NIPT, including one case each of a balanced translocation, unbalanced translocation and triploidy. There were no known false negatives involving the common trisomies (sensitivity=100%). Low-coverage whole-genome sequencing of maternal plasma DNA was highly accurate in detecting common trisomies. It also enabled the detection of other aneuploidies and structural chromosomal abnormalities with high positive predictive value. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

What Fraction of Medicaid Enrollees Have Private Insurance Coverage at the Time of Enrollment? Estimates from Administrative Data

PubMed Central

DeLeire, Thomas; Friedsam, Donna; Leininger, Lindsey; Meier, Sarah; Voskuil, Kristen

2014-01-01

We use administrative data from Wisconsin to determine the fraction of new Medicaid enrollees who have private health insurance at the time of enrollment in the program. Through the linkage of several administrative data sources not previously used for research, we are able to observe coverage status directly for a large fraction of enrollees and indirectly for the remainder. We provide strict bounds for the percentages in each status and find that the percentage of new enrollees with private insurance coverage at the time of enrollment lies between 16 percent and 29 percent, and the percentage that dropped private coverage in favor of public insurance lies between 4 percent and 18 percent. Our point estimates indicate that, among all new enrollees, 21 percent had private health insurance at the time of enrollment and that 10 percent dropped this coverage. Our results show substantially lower rates than previous studies of crowd-out following public health insurance expansions and significant rates of dual coverage, whereby new enrollees into public insurance retain their previously held private insurance coverage. PMID:25316718

Response Error in Reporting Dental Coverage by Older Americans in the Health and Retirement Study

PubMed Central

Manski, Richard J.; Mathiowetz, Nancy A.; Campbell, Nancy; Pepper, John V.

2014-01-01

The aim of this research was to analyze the inconsistency in responses to survey questions within the Health and Retirement Study (HRS) regarding insurance coverage of dental services. Self-reports of dental coverage in the dental services section were compared with those in the insurance section of the 2002 HRS to identify inconsistent responses. Logistic regression identified characteristics of persons reporting discrepancies and assessed the effect of measurement error on dental coverage coefficient estimates in dental utilization models. In 18% of cases, data reported in the insurance section contradicted data reported in the dental use section of the HRS by those who said insurance at least partially covered (or would have covered) their (hypothetical) dental use. Additional findings included distinct characteristics of persons with potential reporting errors and a downward bias to the regression coefficient for coverage in a dental use model without controls for inconsistent self-reports of coverage. This study offers evidence for the need to validate self-reports of dental insurance coverage among a survey population of older Americans to obtain more accurate estimates of coverage and its impact on dental utilization. PMID:25428430

A systematic evaluation of different methods for calculating adolescent vaccination levels using immunization information system data.

PubMed

Gowda, Charitha; Dong, Shiming; Potter, Rachel C; Dombkowski, Kevin J; Stokley, Shannon; Dempsey, Amanda F

2013-01-01

Immunization information systems (IISs) are valuable surveillance tools; however, population relocation may introduce bias when determining immunization coverage. We explored alternative methods for estimating the vaccine-eligible population when calculating adolescent immunization levels using a statewide IIS. We performed a retrospective analysis of the Michigan State Care Improvement Registry (MCIR) for all adolescents aged 11-18 years registered in the MCIR as of October 2010. We explored four methods for determining denominators: (1) including all adolescents with MCIR records, (2) excluding adolescents with out-of-state residence, (3) further excluding those without MCIR activity ≥ 10 years prior to the evaluation date, and (4) using a denominator based on U.S. Census data. We estimated state- and county-specific coverage levels for four adolescent vaccines. We found a 20% difference in estimated vaccination coverage between the most inclusive and restrictive denominator populations. Although there was some variability among the four methods in vaccination at the state level (2%-11%), greater variation occurred at the county level (up to 21%). This variation was substantial enough to potentially impact public health assessments of immunization programs. Generally, vaccines with higher coverage levels had greater absolute variation, as did counties with smaller populations. At the county level, using the four denominator calculation methods resulted in substantial differences in estimated adolescent immunization rates that were less apparent when aggregated at the state level. Further research is needed to ascertain the most appropriate method for estimating vaccine coverage levels using IIS data.

Timeliness and completeness of measles vaccination among children in rural areas of Guangxi, China: A stratified three-stage cluster survey.

PubMed

Tang, Xianyan; Geater, Alan; McNeil, Edward; Zhou, Hongxia; Deng, Qiuyun; Dong, Aihu

2017-07-01

Large-scale outbreaks of measles occurred in 2013 and 2014 in rural Guangxi, a region in Southwest China with high coverage for measles-containing vaccine (MCV). This study aimed to estimate the timely vaccination coverage, the timely-and-complete vaccination coverage, and the median delay period for MCV among children aged 18-54 months in rural Guangxi. Based on quartiles of measles incidence during 2011-2013, a stratified three-stage cluster survey was conducted from June through August 2015. Using weighted estimation and finite population correction, vaccination coverage and 95% confidence intervals (CIs) were calculated. Weighted Kaplan-Meier analyses were used to estimate the median delay periods for the first (MCV1) and second (MCV2) doses of the vaccine. A total of 1216 children were surveyed. The timely vaccination coverage rate was 58.4% (95% CI, 54.9%-62.0%) for MCV1, and 76.9% (95% CI, 73.6%-80.0%) for MCV2. The timely-and-complete vaccination coverage rate was 47.4% (95% CI, 44.0%-51.0%). The median delay period was 32 (95% CI, 27-38) days for MCV1, and 159 (95% CI, 118-195) days for MCV2. The timeliness and completeness of measles vaccination was low, and the median delay period was long among children in rural Guangxi. Incorporating the timeliness and completeness into official routine vaccination coverage statistics may help appraise the coverage of vaccination in China. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Evaluation of the Environmental DNA Method for Estimating Distribution and Biomass of Submerged Aquatic Plants

PubMed Central

Matsuhashi, Saeko; Doi, Hideyuki; Fujiwara, Ayaka; Watanabe, Sonoko; Minamoto, Toshifumi

2016-01-01

The environmental DNA (eDNA) method has increasingly been recognized as a powerful tool for monitoring aquatic animal species; however, its application for monitoring aquatic plants is limited. To evaluate eDNA analysis for estimating the distribution of aquatic plants, we compared its estimated distributions with eDNA analysis, visual observation, and past distribution records for the submerged species Hydrilla verticillata. Moreover, we conducted aquarium experiments using H. verticillata and Egeria densa and analyzed the relationships between eDNA concentrations and plant biomass to investigate the potential for biomass estimation. The occurrences estimated by eDNA analysis closely corresponded to past distribution records, and eDNA detections were more frequent than visual observations, indicating that the method is potentially more sensitive. The results of the aquarium experiments showed a positive relationship between plant biomass and eDNA concentration; however, the relationship was not always significant. The eDNA concentration peaked within three days of the start of the experiment in most cases, suggesting that plants do not release constant amounts of DNA. These results showed that eDNA analysis can be used for distribution surveys, and has the potential to estimate the biomass of aquatic plants. PMID:27304876

Evaluation of the Environmental DNA Method for Estimating Distribution and Biomass of Submerged Aquatic Plants.

PubMed

Matsuhashi, Saeko; Doi, Hideyuki; Fujiwara, Ayaka; Watanabe, Sonoko; Minamoto, Toshifumi

2016-01-01

The environmental DNA (eDNA) method has increasingly been recognized as a powerful tool for monitoring aquatic animal species; however, its application for monitoring aquatic plants is limited. To evaluate eDNA analysis for estimating the distribution of aquatic plants, we compared its estimated distributions with eDNA analysis, visual observation, and past distribution records for the submerged species Hydrilla verticillata. Moreover, we conducted aquarium experiments using H. verticillata and Egeria densa and analyzed the relationships between eDNA concentrations and plant biomass to investigate the potential for biomass estimation. The occurrences estimated by eDNA analysis closely corresponded to past distribution records, and eDNA detections were more frequent than visual observations, indicating that the method is potentially more sensitive. The results of the aquarium experiments showed a positive relationship between plant biomass and eDNA concentration; however, the relationship was not always significant. The eDNA concentration peaked within three days of the start of the experiment in most cases, suggesting that plants do not release constant amounts of DNA. These results showed that eDNA analysis can be used for distribution surveys, and has the potential to estimate the biomass of aquatic plants.

Surveillance of influenza vaccination coverage--United States, 2007-08 through 2011-12 influenza seasons.

PubMed

Lu, Peng-jun; Santibanez, Tammy A; Williams, Walter W; Zhang, Jun; Ding, Helen; Bryan, Leah; O'Halloran, Alissa; Greby, Stacie M; Bridges, Carolyn B; Graitcer, Samuel B; Kennedy, Erin D; Lindley, Megan C; Ahluwalia, Indu B; LaVail, Katherine; Pabst, Laura J; Harris, LaTreace; Vogt, Tara; Town, Machell; Singleton, James A

2013-10-25

Substantial improvement in annual influenza vaccination of recommended groups is needed to reduce the health effects of influenza and reach Healthy People 2020 targets. No single data source provides season-specific estimates of influenza vaccination coverage and related information on place of influenza vaccination and concerns related to influenza and influenza vaccination. 2007-08 through 2011-12 influenza seasons. CDC uses multiple data sources to obtain estimates of vaccination coverage and related data that can guide program and policy decisions to improve coverage. These data sources include the National Health Interview Survey (NHIS), the Behavioral Risk Factor Surveillance System (BRFSS), the National Flu Survey (NFS), the National Immunization Survey (NIS), the Immunization Information Systems (IIS) eight sentinel sites, Internet panel surveys of health-care personnel and pregnant women, and the Pregnancy Risk Assessment and Monitoring System (PRAMS). National influenza vaccination coverage among children aged 6 months-17 years increased from 31.1% during 2007-08 to 56.7% during the 2011-12 influenza season as measured by NHIS. Vaccination coverage among children aged 6 months-17 years varied by state as measured by NIS. Changes from season to season differed as measured by NIS and NHIS. According to IIS sentinel site data, full vaccination (having either one or two seasonal influenza vaccinations, as recommended by the Advisory Committee on Immunization Practices for each influenza season, based on the child's influenza vaccination history) with up to two recommended doses for the 2011-12 season was 27.1% among children aged 6 months-8 years and was 44.3% for the youngest children (aged 6-23 months). Influenza vaccination coverage among adults aged ≥18 years increased from 33.0% during 2007-08 to 38.3% during the 2011-12 influenza season as measured by NHIS. Vaccination coverage by age group for the 2011-12 season as measured by BRFSS was <5 percentage points different from NHIS estimates, whereas NFS estimates were 6-8 percentage points higher than BRFSS estimates. Vaccination coverage among persons aged ≥18 years varied by state as measured by BRFSS. For adults aged ≥18 years, a doctor's office was the most common place for receipt of influenza vaccination (38.4%, BRFSS; 32.5%, NFS) followed by a pharmacy (20.1%, BRFSS; 19.7%, NFS). Overall, 66.9% of health-care personnel (HCP) reported having been vaccinated during the 2011-12 season, as measured by an Internet panel survey of HCP, compared with 62.4%, as estimated through NHIS. Vaccination coverage among pregnant women was 47.0%, as measured by an Internet panel survey of women pregnant during the influenza season, and 43.0%, as measured by BRFSS during the 2011-12 influenza season. Overall, as measured by NFS, 86.8% of adults aged ≥18 years rated the influenza vaccine as very or somewhat effective, and 46.5% of adults aged ≥18 years believed their risk for getting sick with influenza if unvaccinated was high or somewhat high. During the 2011-12 season, influenza vaccination coverage varied by state, age group, and selected populations (e.g., HCP and pregnant women), with coverage estimates well below the Healthy People 2020 goal of 70% for children aged 6 months-17 years, 70% for adults aged ≥18 years, and 90% for HCP. Continued efforts are needed to encourage health-care providers to offer influenza vaccination and to promote public health education efforts among various populations to improve vaccination coverage. Ongoing surveillance to obtain coverage estimates and information regarding other issues related to influenza vaccination (e.g., knowledge, attitudes, and beliefs) is needed to guide program and policy improvements to reduce morbidity and mortality associated with influenza by increasing vaccination rates. Ongoing comparisons of telephone and Internet panel surveys with in-person surveys such as NHIS are needed for appropriate interpretation of data and resulting public health actions. Examination of results from all data sources is necessary to fully assess the various components of influenza vaccination coverage among different populations in the United States.

Comparative scaffolding and gap filling of ancient bacterial genomes applied to two ancient Yersinia pestis genomes

PubMed Central

Doerr, Daniel; Chauve, Cedric

2017-01-01

Yersinia pestis is the causative agent of the bubonic plague, a disease responsible for several dramatic historical pandemics. Progress in ancient DNA (aDNA) sequencing rendered possible the sequencing of whole genomes of important human pathogens, including the ancient Y. pestis strains responsible for outbreaks of the bubonic plague in London in the 14th century and in Marseille in the 18th century, among others. However, aDNA sequencing data are still characterized by short reads and non-uniform coverage, so assembling ancient pathogen genomes remains challenging and often prevents a detailed study of genome rearrangements. It has recently been shown that comparative scaffolding approaches can improve the assembly of ancient Y. pestis genomes at a chromosome level. In the present work, we address the last step of genome assembly, the gap-filling stage. We describe an optimization-based method AGapEs (ancestral gap estimation) to fill in inter-contig gaps using a combination of a template obtained from related extant genomes and aDNA reads. We show how this approach can be used to refine comparative scaffolding by selecting contig adjacencies supported by a mix of unassembled aDNA reads and comparative signal. We applied our method to two Y. pestis data sets from the London and Marseilles outbreaks, for which we obtained highly improved genome assemblies for both genomes, comprised of, respectively, five and six scaffolds with 95 % of the assemblies supported by ancient reads. We analysed the genome evolution between both ancient genomes in terms of genome rearrangements, and observed a high level of synteny conservation between these strains. PMID:29114402

Comprehensive definition of genome features in Spirodela polyrhiza by high-depth physical mapping and short-read DNA sequencing strategies.

PubMed

Michael, Todd P; Bryant, Douglas; Gutierrez, Ryan; Borisjuk, Nikolai; Chu, Philomena; Zhang, Hanzhong; Xia, Jing; Zhou, Junfei; Peng, Hai; El Baidouri, Moaine; Ten Hallers, Boudewijn; Hastie, Alex R; Liang, Tiffany; Acosta, Kenneth; Gilbert, Sarah; McEntee, Connor; Jackson, Scott A; Mockler, Todd C; Zhang, Weixiong; Lam, Eric

2017-02-01

Spirodela polyrhiza is a fast-growing aquatic monocot with highly reduced morphology, genome size and number of protein-coding genes. Considering these biological features of Spirodela and its basal position in the monocot lineage, understanding its genome architecture could shed light on plant adaptation and genome evolution. Like many draft genomes, however, the 158-Mb Spirodela genome sequence has not been resolved to chromosomes, and important genome characteristics have not been defined. Here we deployed rapid genome-wide physical maps combined with high-coverage short-read sequencing to resolve the 20 chromosomes of Spirodela and to empirically delineate its genome features. Our data revealed a dramatic reduction in the number of the rDNA repeat units in Spirodela to fewer than 100, which is even fewer than that reported for yeast. Consistent with its unique phylogenetic position, small RNA sequencing revealed 29 Spirodela-specific microRNA, with only two being shared with Elaeis guineensis (oil palm) and Musa balbisiana (banana). Combining DNA methylation data and small RNA sequencing enabled the accurate prediction of 20.5% long terminal repeats (LTRs) that doubled the previous estimate, and revealed a high Solo:Intact LTR ratio of 8.2. Interestingly, we found that Spirodela has the lowest global DNA methylation levels (9%) of any plant species tested. Taken together our results reveal a genome that has undergone reduction, likely through eliminating non-essential protein coding genes, rDNA and LTRs. In addition to delineating the genome features of this unique plant, the methodologies described and large-scale genome resources from this work will enable future evolutionary and functional studies of this basal monocot family. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Sequencing of the large dsDNA genome of Oryctes rhinoceros nudivirus using multiple displacement amplification of nanogram amounts of virus DNA.

PubMed

Wang, Yongjie; Kleespies, Regina G; Ramle, Moslim B; Jehle, Johannes A

2008-09-01

The genomic sequence analysis of many large dsDNA viruses is hampered by the lack of enough sample materials. Here, we report a whole genome amplification of the Oryctes rhinoceros nudivirus (OrNV) isolate Ma07 starting from as few as about 10 ng of purified viral DNA by application of phi29 DNA polymerase- and exonuclease-resistant random hexamer-based multiple displacement amplification (MDA) method. About 60 microg of high molecular weight DNA with fragment sizes of up to 25 kbp was amplified. A genomic DNA clone library was generated using the product DNA. After 8-fold sequencing coverage, the 127,615 bp of OrNV whole genome was sequenced successfully. The results demonstrate that the MDA-based whole genome amplification enables rapid access to genomic information from exiguous virus samples.

The future of forensic DNA analysis

PubMed Central

Butler, John M.

2015-01-01

The author's thoughts and opinions on where the field of forensic DNA testing is headed for the next decade are provided in the context of where the field has come over the past 30 years. Similar to the Olympic motto of ‘faster, higher, stronger’, forensic DNA protocols can be expected to become more rapid and sensitive and provide stronger investigative potential. New short tandem repeat (STR) loci have expanded the core set of genetic markers used for human identification in Europe and the USA. Rapid DNA testing is on the verge of enabling new applications. Next-generation sequencing has the potential to provide greater depth of coverage for information on STR alleles. Familial DNA searching has expanded capabilities of DNA databases in parts of the world where it is allowed. Challenges and opportunities that will impact the future of forensic DNA are explored including the need for education and training to improve interpretation of complex DNA profiles. PMID:26101278

National, State, and Selected Local Area Vaccination Coverage Among Children Aged 19-35 Months - United States, 2014.

PubMed

Hill, Holly A; Elam-Evans, Laurie D; Yankey, David; Singleton, James A; Kolasa, Maureen

2015-08-28

The reduction in morbidity and mortality associated with vaccine-preventable diseases in the United States has been described as one of the 10 greatest public health achievements of the first decade of the 21st century. A recent analysis concluded that routine childhood vaccination will prevent 322 million cases of disease and about 732,000 early deaths among children born during 1994-2013, for a net societal cost savings of $1.38 trillion. The National Immunization Survey (NIS) has monitored vaccination coverage among U.S. children aged 19-35 months since 1994. This report presents national, regional, state, and selected local area vaccination coverage estimates for children born from January 2011 through May 2013, based on data from the 2014 NIS. For most vaccinations, there was no significant change in coverage between 2013 and 2014. The exception was hepatitis A vaccine (HepA), for which increases were observed in coverage with both ≥1 and ≥2 doses. As in previous years, <1% of children received no vaccinations. National coverage estimates indicate that the Healthy People 2020 target* of 90% was met for ≥3 doses of poliovirus vaccine (93.3%), ≥1 dose of measles, mumps, and rubella vaccine (MMR) (91.5%), ≥3 doses of hepatitis B vaccine (HepB) (91.6%), and ≥1 dose of varicella vaccine (91.0%). Coverage was below target for ≥4 doses of diphtheria, tetanus, and acellular pertussis vaccine (DTaP), the full series of Haemophilus influenzae type b (Hib) vaccine, hepatitis B (HepB) birth dose,† ≥4 doses pneumococcal conjugate vaccine (PCV), ≥2 doses of HepA, the full series of rotavirus vaccine, and the combined vaccine series.§ Examination of coverage by child's race/ethnicity revealed lower estimated coverage among non-Hispanic black children compared with non-Hispanic white children for several vaccinations, including DTaP, the full series of Hib, PCV, rotavirus vaccine, and the combined series. Children from households classified as below the federal poverty level had lower estimated coverage for almost all of the vaccinations assessed, compared with children living at or above the poverty level. Significant variation in coverage by state¶ was observed for several vaccinations, including HepB birth dose, HepA, and rotavirus. High vaccination coverage must be maintained across geographic and sociodemographic groups if progress in reducing the impact of vaccine-preventable diseases is to be sustained.

Coverage of neonatal screening: failure of coverage or failure of information system

PubMed Central

Ades, A; Walker, J; Jones, R; Smith, I

2001-01-01

OBJECTIVES—To evaluate neonatal screening coverage using data routinely collected on the laboratory computer.
SUBJECTS—90 850 births in 14 North East Thames community provider districts over a 21 month period.
METHODS—Births notified to local child health computers are electronically copied to the neonatal laboratory computer system, and incoming Guthrie cards are matched against these birth records before testing. The computer records for the study period were processed to estimate the coverage of the screening programme.
RESULTS—Out of an estimated 90 850 births notified to child health computers, all but 746 (0.82%) appeared to have been screened or could be otherwise accounted for (0.14% in non-metropolitan districts, 0.39% in suburban districts, and 1.68% in inner city districts). A further 893 resident infants had been tested, but could not be matched to the list of notified resident births. The calculated programme coverage already exceeds the 99.5% National Audit Programme standard in 7/14 districts. Elsewhere it is not clear whether it is coverage or recording of coverage that is low.
CONCLUSION—Previous reports of low coverage may have been exaggerated. High coverage can be shown using routine information systems. Design of information systems that deliver accurate measures of coverage would be more useful than comparison of inadequately measured coverage with a national standard. The new NHS number project will create an opportunity to achieve this.
 PMID:11369561

Evaluation of different strategies for magnetic particle functionalization with DNA aptamers.

PubMed

Pérez-Ruiz, Elena; Lammertyn, Jeroen; Spasic, Dragana

2016-12-25

The optimal bio-functionalization of magnetic particles is essential for developing magnetic particle-based bioassays. Whereas functionalization with antibodies is generally well established, immobilization of DNA probes, such as aptamers, is not yet fully explored. In this work, four different types of commercially available magnetic particles, coated with streptavidin, maleimide or carboxyl groups, were evaluated for their surface coverage with aptamer bioreceptors, efficiency in capturing target protein and non-specific protein adsorption on their surface. A recently developed aptamer against the peanut allergen, Ara h 1 protein, was used as a model system. Conjugation of biotinylated Ara h 1 aptamer to the streptavidin particles led to the highest surface coverage, whereas the coverage of maleimide particles was 25% lower. Carboxylated particles appeared to be inadequate for DNA functionalization. Streptavidin particles also showed the greatest target capturing efficiency, comparable to the one of particles functionalized with anti-Ara h 1 antibody. The performance of streptavidin particles was additionally tested in a sandwich assay with the aptamer as a capture receptor on the particle surface. While the limit of detection obtained was comparable to the same assay system with antibody as capture receptor, it was superior to previously reported values using the same aptamer in similar assay schemes with different detection platforms. These results point to the promising application of the Ara h 1 aptamer-functionalized particles in bioassay development. Copyright © 2016 Elsevier B.V. All rights reserved.

[Coverage of cervical cancer screening in Catalonia, Spain (2008-2011)].

PubMed

Rodríguez-Salés, Vanesa; Roura, Esther; Ibáñez, Raquel; Peris, Mercè; Bosch, F Xavier; Coma E, Ermengol; Silvia de Sanjosé

2014-01-01

To estimate cervical cytology coverage for the period 2008-2011 by age groups and health regions from data recorded in the medical records of women attending centers within the Catalan national health system. The data used to estimate coverage were obtained from the primary care information system. This information was anonymous and included age, center, date, and the results of cytological smears for a total of 2,292,564 women aged 15 years or more. A total of 758,690 smears were performed in 595,868 women. Among women aged 25-65 years, the estimated coverage was 32.4% of the assigned population and was 40.8% in the population attended. Geographical variation was observed, with higher coverage among health regions closer to Barcelona. Abnormal Pap smears increased slightly from 2008 to 2011 (from 3% to 3.5%, respectively, p <0.001). In women with a negative first smear, the mean interval until the second smear was 2.4 years, but only 50% of women with a negative first smear in 2008 attended a second round during the study period. Cervical screening coverage in the National Health Service of Catalonia includes one in three women. Second round participation was poor. Existing computer systems in primary care centers can ensure monitoring of population-based screening programs for cervical cancer. These systems could be used to plan an organized screening program to ensure wider coverage and better follow-up. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Annual Cycles of Multiyear Sea Ice Coverage of the Arctic Ocean: 1999-2003

NASA Technical Reports Server (NTRS)

Kwok, R.

2004-01-01

For the years 1999-2003, we estimate the time-varying perennial ice zone (PIZ) coverage and construct the annual cycles of multiyear (MY, including second year) ice coverage of the Arctic Ocean using QuikSCAT backscatter, MY fractions from RADARSAT, and the record of ice export from satellite passive microwave observations. An area balance approach extends the winter MY coverage from QuikSCAT to the remainder of the year. From these estimates, the coverage of MY ice at the beginning of each year is 3774 x 10(exp 3) sq km (2000), 3896 x 10(exp 3) sq km (2001), 4475 x 10(exp 3) sq km (2002), and 4122 x 10(exp 3) sq km (2003). Uncertainties in coverage are approx.150 x 10(exp 3) sq km. In the mean, on 1 January, MY ice covers approx.60% of the Arctic Ocean. Ice export reduces this coverage to approx.55% by 1 May. From the multiple annual cycles, the area of first-year (FY) ice that survives the intervening summers are 1192 x 10(exp 3) sq km (2000), 1509 x 10(exp 3) sq km (2001), and 582 x 10(exp 3) sq km (2002). In order for the MY coverage to remain constant from year to year, these replenishment areas must balance the overall area export and melt during the summer. The effect of the record minimum in Arctic sea ice area during the summer of 2002 is seen in the lowest area of surviving FY ice of the three summers. In addition to the spatial coverage, the location of the PIZ is important. One consequence of the unusual location of the PIZ at the end of the summer of 2002 is the preconditioning for enhanced export of MY ice into the Barents and Kara seas. Differences between the minimums in summer sea ice coverage from our estimates and passive microwave observations are discussed.

DNA barcoding the native flowering plants and conifers of Wales.

PubMed

de Vere, Natasha; Rich, Tim C G; Ford, Col R; Trinder, Sarah A; Long, Charlotte; Moore, Chris W; Satterthwaite, Danielle; Davies, Helena; Allainguillaume, Joel; Ronca, Sandra; Tatarinova, Tatiana; Garbett, Hannah; Walker, Kevin; Wilkinson, Mike J

2012-01-01

We present the first national DNA barcode resource that covers the native flowering plants and conifers for the nation of Wales (1143 species). Using the plant DNA barcode markers rbcL and matK, we have assembled 97.7% coverage for rbcL, 90.2% for matK, and a dual-locus barcode for 89.7% of the native Welsh flora. We have sampled multiple individuals for each species, resulting in 3304 rbcL and 2419 matK sequences. The majority of our samples (85%) are from DNA extracted from herbarium specimens. Recoverability of DNA barcodes is lower using herbarium specimens, compared to freshly collected material, mostly due to lower amplification success, but this is balanced by the increased efficiency of sampling species that have already been collected, identified, and verified by taxonomic experts. The effectiveness of the DNA barcodes for identification (level of discrimination) is assessed using four approaches: the presence of a barcode gap (using pairwise and multiple alignments), formation of monophyletic groups using Neighbour-Joining trees, and sequence similarity in BLASTn searches. These approaches yield similar results, providing relative discrimination levels of 69.4 to 74.9% of all species and 98.6 to 99.8% of genera using both markers. Species discrimination can be further improved using spatially explicit sampling. Mean species discrimination using barcode gap analysis (with a multiple alignment) is 81.6% within 10×10 km squares and 93.3% for 2×2 km squares. Our database of DNA barcodes for Welsh native flowering plants and conifers represents the most complete coverage of any national flora, and offers a valuable platform for a wide range of applications that require accurate species identification.

DNA Barcoding the Native Flowering Plants and Conifers of Wales

PubMed Central

de Vere, Natasha; Rich, Tim C. G.; Ford, Col R.; Trinder, Sarah A.; Long, Charlotte; Moore, Chris W.; Satterthwaite, Danielle; Davies, Helena; Allainguillaume, Joel; Ronca, Sandra; Tatarinova, Tatiana; Garbett, Hannah; Walker, Kevin; Wilkinson, Mike J.

2012-01-01

We present the first national DNA barcode resource that covers the native flowering plants and conifers for the nation of Wales (1143 species). Using the plant DNA barcode markers rbcL and matK, we have assembled 97.7% coverage for rbcL, 90.2% for matK, and a dual-locus barcode for 89.7% of the native Welsh flora. We have sampled multiple individuals for each species, resulting in 3304 rbcL and 2419 matK sequences. The majority of our samples (85%) are from DNA extracted from herbarium specimens. Recoverability of DNA barcodes is lower using herbarium specimens, compared to freshly collected material, mostly due to lower amplification success, but this is balanced by the increased efficiency of sampling species that have already been collected, identified, and verified by taxonomic experts. The effectiveness of the DNA barcodes for identification (level of discrimination) is assessed using four approaches: the presence of a barcode gap (using pairwise and multiple alignments), formation of monophyletic groups using Neighbour-Joining trees, and sequence similarity in BLASTn searches. These approaches yield similar results, providing relative discrimination levels of 69.4 to 74.9% of all species and 98.6 to 99.8% of genera using both markers. Species discrimination can be further improved using spatially explicit sampling. Mean species discrimination using barcode gap analysis (with a multiple alignment) is 81.6% within 10×10 km squares and 93.3% for 2×2 km squares. Our database of DNA barcodes for Welsh native flowering plants and conifers represents the most complete coverage of any national flora, and offers a valuable platform for a wide range of applications that require accurate species identification. PMID:22701588

Cost-effectiveness of community-based practitioner programmes in Ethiopia, Indonesia and Kenya.

PubMed

McPake, Barbara; Edoka, Ijeoma; Witter, Sophie; Kielmann, Karina; Taegtmeyer, Miriam; Dieleman, Marjolein; Vaughan, Kelsey; Gama, Elvis; Kok, Maryse; Datiko, Daniel; Otiso, Lillian; Ahmed, Rukhsana; Squires, Neil; Suraratdecha, Chutima; Cometto, Giorgio

2015-09-01

To assess the cost-effectiveness of community-based practitioner programmes in Ethiopia, Indonesia and Kenya. Incremental cost-effectiveness ratios for the three programmes were estimated from a government perspective. Cost data were collected for 2012. Life years gained were estimated based on coverage of reproductive, maternal, neonatal and child health services. For Ethiopia and Kenya, estimates of coverage before and after the implementation of the programme were obtained from empirical studies. For Indonesia, coverage of health service interventions was estimated from routine data. We used the Lives Saved Tool to estimate the number of lives saved from changes in reproductive, maternal, neonatal and child health-service coverage. Gross domestic product per capita was used as the reference willingness-to-pay threshold value. The estimated incremental cost per life year gained was 82 international dollars ($)in Kenya, $999 in Ethiopia and $3396 in Indonesia. The results were most sensitive to uncertainty in the estimates of life-years gained. Based on the results of probabilistic sensitivity analysis, there was greater than 80% certainty that each programme was cost-effective. Community-based approaches are likely to be cost-effective for delivery of some essential health interventions where community-based practitioners operate within an integrated team supported by the health system. Community-based practitioners may be most appropriate in rural poor communities that have limited access to more qualified health professionals. Further research is required to understand which programmatic design features are critical to effectiveness.

Estimating the Counterfactual

PubMed Central

Blumberg, Linda J.; Garrett, Bowen; Holahan, John

2016-01-01

Time lags in receiving data from long-standing, large federal surveys complicate real-time estimation of the coverage effects of full Affordable Care Act (ACA) implementation. Fast-turnaround household surveys fill some of the void in data on recent changes to insurance coverage, but they lack the historical data that allow analysts to account for trends that predate the ACA, economic fluctuations, and earlier public program expansions when predicting how many people would be uninsured without comprehensive health care reform. Using data from the Current Population Survey (CPS) from 2000 to 2012 and the Health Reform Monitoring Survey (HRMS) data for 2013 and 2015, this article develops an approach to estimate the number of people who would be uninsured in the absence of the ACA and isolates the change in coverage as of March 2015 that can be attributed to the ACA. We produce counterfactual forecasts of the number of uninsured absent the ACA for 9 age-income groups and compare these estimates with 2015 estimates based on HRMS relative coverage changes applied to CPS-based population estimates. As of March 2015, we find the ACA has reduced the number of uninsured adults by 18.1 million compared with the number who would have been uninsured at that time had the law not been implemented. That decline represents a 46% reduction in the number of nonelderly adults without insurance. The approach developed here can be applied to other federal data and timely surveys to provide a range of estimates of the overall effects of reform. PMID:27076474

A particle filter for ammonia coverage ratio and input simultaneous estimations in Diesel-engine SCR system.

PubMed

Sun, Kangfeng; Ji, Fenzhu; Yan, Xiaoyu; Jiang, Kai; Yang, Shichun

2018-01-01

As NOx emissions legislation for Diesel-engines is becoming more stringent than ever before, an aftertreatment system has been widely used in many countries. Specifically, to reduce the NOx emissions, a selective catalytic reduction(SCR) system has become one of the most promising techniques for Diesel-engine vehicle applications. In the SCR system, input ammonia concentration and ammonia coverage ratio are regarded as essential states in the control-oriental model. Currently, an ammonia sensor placed before the SCR Can is a good strategy for the input ammonia concentration value. However, physical sensor would increase the SCR system cost and the ammonia coverage ratio information cannot be directly measured by physical sensor. Aiming to tackle this problem, an observer based on particle filter(PF) is investigated to estimate the input ammonia concentration and ammonia coverage ratio. Simulation results through the experimentally-validated full vehicle simulator cX-Emission show that the performance of observer based on PF is outstanding, and the estimation error is very small.

A particle filter for ammonia coverage ratio and input simultaneous estimations in Diesel-engine SCR system

PubMed Central

Ji, Fenzhu; Yan, Xiaoyu; Jiang, Kai

2018-01-01

As NOx emissions legislation for Diesel-engines is becoming more stringent than ever before, an aftertreatment system has been widely used in many countries. Specifically, to reduce the NOx emissions, a selective catalytic reduction(SCR) system has become one of the most promising techniques for Diesel-engine vehicle applications. In the SCR system, input ammonia concentration and ammonia coverage ratio are regarded as essential states in the control-oriental model. Currently, an ammonia sensor placed before the SCR Can is a good strategy for the input ammonia concentration value. However, physical sensor would increase the SCR system cost and the ammonia coverage ratio information cannot be directly measured by physical sensor. Aiming to tackle this problem, an observer based on particle filter(PF) is investigated to estimate the input ammonia concentration and ammonia coverage ratio. Simulation results through the experimentally-validated full vehicle simulator cX-Emission show that the performance of observer based on PF is outstanding, and the estimation error is very small. PMID:29408924

Serologic and molecular characteristics of hepatitis B virus among school children in East Java, Indonesia.

PubMed

Utsumi, Takako; Yano, Yoshihiko; Lusida, Maria Inge; Amin, Mochamad; Soetjipto; Hotta, Hak; Hayashi, Yoshitake

2010-07-01

Universal childhood hepatitis B vaccination was introduced in Indonesia in 1997; by 2008, coverage was estimated to be 78%. This study aimed to investigate the serologic status and virologic characteristics of hepatitis B virus (HBV) among the children in East Java. A total of 229 healthy children born during 1994-1999 were enrolled in this study. Overall, 3.1% were positive for hepatitis B surface antigen (HBsAg) and 23.6% were positive for antibody to HBsAg (anti-HBs). HBV DNA was detected in 5 of 222 HBsAg-negative carriers, which were suggested to be cases of occult HBV infection. A single amino substitution (T126I) in the S region was frequently found. HBV infection remains endemic, and the prevalence of anti-HBs remains insufficient among children in East Java, Indonesia.

Surface-Enhanced Raman Scattering Based Nonfluorescent Probe for Multiplex DNA Detection

PubMed Central

Sun, Lan; Yu, Chenxu; Irudayaraj, Joseph

2008-01-01

To provide rapid and accurate detection of DNA markers in a straightforward, inexpensive and multiplex format, an alternative surface enhanced Raman scattering (SERS) based probe was designed and fabricated to covalently attach both DNA probing sequence and non-fluorescent Raman tags to the surface of gold nanoparticles (DNA-AuP-RTag). The intensity of Raman signal of the probes could be controlled through the surface coverage of the non-fluorescent Raman tags (RTags). Detection sensitivity of these probes could be optimized by fine-tuning the amount of DNA molecules and RTags on the probes. Long-term stability of the DNA-AuP-RTag probes was found to be good (over 3 months). Excellent multiplexing capability of the DNA-AuP-RTag scheme was demonstrated by simultaneous identification of up to eight probes in a mixture. Detection of hybridization of single-stranded DNA (ssDNA) to its complementary targets was successfully accomplished with a long-term goal to use non-fluorescent RTags in a Raman-based DNA microarray platform. PMID:17465531

Quantum Point Contact Single-Nucleotide Conductance for DNA and RNA Sequence Identification.

PubMed

Afsari, Sepideh; Korshoj, Lee E; Abel, Gary R; Khan, Sajida; Chatterjee, Anushree; Nagpal, Prashant

2017-11-28

Several nanoscale electronic methods have been proposed for high-throughput single-molecule nucleic acid sequence identification. While many studies display a large ensemble of measurements as "electronic fingerprints" with some promise for distinguishing the DNA and RNA nucleobases (adenine, guanine, cytosine, thymine, and uracil), important metrics such as accuracy and confidence of base calling fall well below the current genomic methods. Issues such as unreliable metal-molecule junction formation, variation of nucleotide conformations, insufficient differences between the molecular orbitals responsible for single-nucleotide conduction, and lack of rigorous base calling algorithms lead to overlapping nanoelectronic measurements and poor nucleotide discrimination, especially at low coverage on single molecules. Here, we demonstrate a technique for reproducible conductance measurements on conformation-constrained single nucleotides and an advanced algorithmic approach for distinguishing the nucleobases. Our quantum point contact single-nucleotide conductance sequencing (QPICS) method uses combed and electrostatically bound single DNA and RNA nucleotides on a self-assembled monolayer of cysteamine molecules. We demonstrate that by varying the applied bias and pH conditions, molecular conductance can be switched ON and OFF, leading to reversible nucleotide perturbation for electronic recognition (NPER). We utilize NPER as a method to achieve >99.7% accuracy for DNA and RNA base calling at low molecular coverage (∼12×) using unbiased single measurements on DNA/RNA nucleotides, which represents a significant advance compared to existing sequencing methods. These results demonstrate the potential for utilizing simple surface modifications and existing biochemical moieties in individual nucleobases for a reliable, direct, single-molecule, nanoelectronic DNA and RNA nucleotide identification method for sequencing.

The estimated impact of human papillomavirus vaccine coverage on the lifetime cervical cancer burden among girls currently aged 12 years and younger in the United States.

PubMed

Chesson, Harrell W; Ekwueme, Donatus U; Saraiya, Mona; Dunne, Eileen F; Markowitz, Lauri E

2014-11-01

Using a previously published dynamic model, we illustrate the potential benefits of human papillomavirus vaccination among girls currently 12 years or younger in the United States. Increasing vaccine coverage of young girls to 80% would avert 53,300 lifetime cervical cancer cases versus 30% coverage and 28,800 cases versus 50% coverage.

A Systematic Evaluation of Different Methods for Calculating Adolescent Vaccination Levels Using Immunization Information System Data

PubMed Central

Gowda, Charitha; Dong, Shiming; Potter, Rachel C.; Dombkowski, Kevin J.; Stokley, Shannon

2013-01-01

Objective Immunization information systems (IISs) are valuable surveillance tools; however, population relocation may introduce bias when determining immunization coverage. We explored alternative methods for estimating the vaccine-eligible population when calculating adolescent immunization levels using a statewide IIS. Methods We performed a retrospective analysis of the Michigan State Care Improvement Registry (MCIR) for all adolescents aged 11–18 years registered in the MCIR as of October 2010. We explored four methods for determining denominators: (1) including all adolescents with MCIR records, (2) excluding adolescents with out-of-state residence, (3) further excluding those without MCIR activity ≥10 years prior to the evaluation date, and (4) using a denominator based on U.S. Census data. We estimated state- and county-specific coverage levels for four adolescent vaccines. Results We found a 20% difference in estimated vaccination coverage between the most inclusive and restrictive denominator populations. Although there was some variability among the four methods in vaccination at the state level (2%–11%), greater variation occurred at the county level (up to 21%). This variation was substantial enough to potentially impact public health assessments of immunization programs. Generally, vaccines with higher coverage levels had greater absolute variation, as did counties with smaller populations. Conclusion At the county level, using the four denominator calculation methods resulted in substantial differences in estimated adolescent immunization rates that were less apparent when aggregated at the state level. Further research is needed to ascertain the most appropriate method for estimating vaccine coverage levels using IIS data. PMID:24179260

Cancer Internet search activity on a major search engine, United States 2001-2003.

PubMed

Cooper, Crystale Purvis; Mallon, Kenneth P; Leadbetter, Steven; Pollack, Lori A; Peipins, Lucy A

2005-07-01

To locate online health information, Internet users typically use a search engine, such as Yahoo! or Google. We studied Yahoo! search activity related to the 23 most common cancers in the United States. The objective was to test three potential correlates of Yahoo! cancer search activity--estimated cancer incidence, estimated cancer mortality, and the volume of cancer news coverage--and to study the periodicity of and peaks in Yahoo! cancer search activity. Yahoo! cancer search activity was obtained from a proprietary database called the Yahoo! Buzz Index. The American Cancer Society's estimates of cancer incidence and mortality were used. News reports associated with specific cancer types were identified using the LexisNexis "US News" database, which includes more than 400 national and regional newspapers and a variety of newswire services. The Yahoo! search activity associated with specific cancers correlated with their estimated incidence (Spearman rank correlation, rho = 0.50, P = .015), estimated mortality (rho = 0.66, P = .001), and volume of related news coverage (rho = 0.88, P < .001). Yahoo! cancer search activity tended to be higher on weekdays and during national cancer awareness months but lower during summer months; cancer news coverage also tended to follow these trends. Sharp increases in Yahoo! search activity scores from one day to the next appeared to be associated with increases in relevant news coverage. Media coverage appears to play a powerful role in prompting online searches for cancer information. Internet search activity offers an innovative tool for passive surveillance of health information-seeking behavior.

Molecular tracing of confiscated pangolin scales for conservation and illegal trade monitoring in Southeast Asia

USGS Publications Warehouse

Zhang, Huarong; Miller, Mark P.; Yang, Feng; Chan, Hon Ki; Gaubert, Philippe; Ades, Gary; Fischer, Gunter A

2015-01-01

Despite being protected by both international and national regulations, pangolins are threatened by illegal trade. Here we report mitochondrial DNA identification and haplotype richness estimation, using 239 pangolin scale samples from two confiscations in Hong Kong. We found a total of 13 genetically distinct cytochrome c oxidase I (COI) haplotypes in two confiscations (13 and ten haplotypes respectively, with ten shared haplotypes between confiscations). These haplotypes clustered in two distinct clades with one clade representing the Sunda pangolin (Manisjavanica). The other clade did not match with any known Asian pangolin sequences, and likely represented a cryptic pangolin lineage in Asia. By fitting sample coverage and rarefaction/regression models to our sample data, we predicted that the total number of COI haplotypes in two confiscations were 14.86 and 11.06 respectively, suggesting that our sampling caught the majority of haplotypes and that we had adequately characterized each confiscation. We detected substantial sequence divergence among the seized scales, likely evidencing that the Sunda pangolins were harvested over wide geographical areas across Southeast Asia. Our study illustrates the value of applying DNA forensics for illegal wildlife trade monitoring.

Coverage of Nutrition Interventions Intended for Infants and Young Children Varies Greatly across Programs: Results from Coverage Surveys in 5 Countries.

PubMed

Leyvraz, Magali; Aaron, Grant J; Poonawala, Alia; van Liere, Marti J; Schofield, Dominic; Myatt, Mark; Neufeld, Lynnette M

2017-05-01

Background: The efficacy of a number of interventions that include fortified complementary foods (FCFs) or other products to improve infant and young child feeding (IYCF) is well established. Programs that provide such products free or at a subsidized price are implemented in many countries around the world. Demonstrating the impact at scale of these programs has been challenging, and rigorous information on coverage and utilization is lacking. Objective: The objective of this article is to review key findings from 11 coverage surveys of IYCF programs distributing or selling FCFs or micronutrient powders in 5 countries. Methods: Programs were implemented in Ghana, Cote d'Ivoire, India, Bangladesh, and Vietnam. Surveys were implemented at different stages of program implementation between 2013 and 2015. The Fortification Assessment Coverage Toolkit (FACT) was developed to assess 3 levels of coverage (message: awareness of the product; contact: use of the product ≥1 time; and effective: regular use aligned with program-specific goals), as well as barriers and factors that facilitate coverage. Analyses included the coverage estimates, as well as an assessment of equity of coverage between the poor and nonpoor, and between those with poor and adequate child feeding practices. Results: Coverage varied greatly between countries and program models. Message coverage ranged from 29.0% to 99.7%, contact coverage from 22.6% to 94.4%, and effective coverage from 0.8% to 88.3%. Beyond creating awareness, programs that achieved high coverage were those with effective mechanisms in place to overcome barriers for both supply and demand. Conclusions: Variability in coverage was likely due to the program design, delivery model, quality of implementation, and product type. Measuring program coverage and understanding its determinants is essential for program improvement and to estimate the potential for impact of programs at scale. Use of the FACT can help overcome this evidence gap.

Coverage of Nutrition Interventions Intended for Infants and Young Children Varies Greatly across Programs: Results from Coverage Surveys in 5 Countries123

PubMed Central

Aaron, Grant J; Poonawala, Alia; van Liere, Marti J; Schofield, Dominic; Myatt, Mark

2017-01-01

Background: The efficacy of a number of interventions that include fortified complementary foods (FCFs) or other products to improve infant and young child feeding (IYCF) is well established. Programs that provide such products free or at a subsidized price are implemented in many countries around the world. Demonstrating the impact at scale of these programs has been challenging, and rigorous information on coverage and utilization is lacking. Objective: The objective of this article is to review key findings from 11 coverage surveys of IYCF programs distributing or selling FCFs or micronutrient powders in 5 countries. Methods: Programs were implemented in Ghana, Cote d’Ivoire, India, Bangladesh, and Vietnam. Surveys were implemented at different stages of program implementation between 2013 and 2015. The Fortification Assessment Coverage Toolkit (FACT) was developed to assess 3 levels of coverage (message: awareness of the product; contact: use of the product ≥1 time; and effective: regular use aligned with program-specific goals), as well as barriers and factors that facilitate coverage. Analyses included the coverage estimates, as well as an assessment of equity of coverage between the poor and nonpoor, and between those with poor and adequate child feeding practices. Results: Coverage varied greatly between countries and program models. Message coverage ranged from 29.0% to 99.7%, contact coverage from 22.6% to 94.4%, and effective coverage from 0.8% to 88.3%. Beyond creating awareness, programs that achieved high coverage were those with effective mechanisms in place to overcome barriers for both supply and demand. Conclusions: Variability in coverage was likely due to the program design, delivery model, quality of implementation, and product type. Measuring program coverage and understanding its determinants is essential for program improvement and to estimate the potential for impact of programs at scale. Use of the FACT can help overcome this evidence gap. PMID:28404839

Routine Vaccination Coverage in Northern Nigeria: Results from 40 District-Level Cluster Surveys, 2014-2015

PubMed Central

Ogbuanu, Ikechukwu U.; Adegoke, Oluwasegun J.; Scobie, Heather M.; Uba, Belinda V.; Wannemuehler, Kathleen A.; Ruiz, Alicia; Elmousaad, Hashim; Ohuabunwo, Chima J.; Mustafa, Mahmud; Nguku, Patrick; Waziri, Ndadilnasiya Endie; Vertefeuille, John F.

2016-01-01

Background Despite recent success towards controlling poliovirus transmission, Nigeria has struggled to achieve uniformly high routine vaccination coverage. A lack of reliable vaccination coverage data at the operational level makes it challenging to target program improvement. To reliably estimate vaccination coverage, we conducted district-level vaccine coverage surveys using a pre-existing infrastructure of polio technical staff in northern Nigeria. Methods Household-level cluster surveys were conducted in 40 polio high risk districts of Nigeria during 2014–2015. Global positioning system technology and intensive supervision by a pool of qualified technical staff were used to ensure high survey quality. Vaccination status of children aged 12–23 months was documented based on vaccination card or caretaker’s recall. District-level coverage estimates were calculated using survey methods. Results Data from 7,815 children across 40 districts were analyzed. District-level coverage with the third dose of diphtheria-pertussis-tetanus vaccine (DPT3) ranged widely from 1–63%, with all districts having DPT3 coverage below the target of 80%. Median coverage across all districts for each of eight vaccine doses (1 Bacille Calmette-Guérin dose, 3 DPT doses, 3 oral poliovirus vaccine doses, and 1 measles vaccine dose) was <50%. DPT3 coverage by survey was substantially lower (range: 28%–139%) than the 2013 administrative coverage reported among children aged <12 months. Common reported reasons for non-vaccination included lack of knowledge about vaccines and vaccination services (50%) and factors related to access to routine immunization services (15%). Conclusions Survey results highlighted vaccine coverage gaps that were systematically underestimated by administrative reporting across 40 polio high risk districts in northern Nigeria. Given the limitations of administrative coverage data, our approach to conducting quality district-level coverage surveys and providing data to assess and remediate issues contributing to poor vaccination coverage could serve as an example in countries with sub-optimal vaccination coverage, similar to Nigeria. PMID:27936077

Routine Vaccination Coverage in Northern Nigeria: Results from 40 District-Level Cluster Surveys, 2014-2015.

PubMed

Gunnala, Rajni; Ogbuanu, Ikechukwu U; Adegoke, Oluwasegun J; Scobie, Heather M; Uba, Belinda V; Wannemuehler, Kathleen A; Ruiz, Alicia; Elmousaad, Hashim; Ohuabunwo, Chima J; Mustafa, Mahmud; Nguku, Patrick; Waziri, Ndadilnasiya Endie; Vertefeuille, John F

2016-01-01

Despite recent success towards controlling poliovirus transmission, Nigeria has struggled to achieve uniformly high routine vaccination coverage. A lack of reliable vaccination coverage data at the operational level makes it challenging to target program improvement. To reliably estimate vaccination coverage, we conducted district-level vaccine coverage surveys using a pre-existing infrastructure of polio technical staff in northern Nigeria. Household-level cluster surveys were conducted in 40 polio high risk districts of Nigeria during 2014-2015. Global positioning system technology and intensive supervision by a pool of qualified technical staff were used to ensure high survey quality. Vaccination status of children aged 12-23 months was documented based on vaccination card or caretaker's recall. District-level coverage estimates were calculated using survey methods. Data from 7,815 children across 40 districts were analyzed. District-level coverage with the third dose of diphtheria-pertussis-tetanus vaccine (DPT3) ranged widely from 1-63%, with all districts having DPT3 coverage below the target of 80%. Median coverage across all districts for each of eight vaccine doses (1 Bacille Calmette-Guérin dose, 3 DPT doses, 3 oral poliovirus vaccine doses, and 1 measles vaccine dose) was <50%. DPT3 coverage by survey was substantially lower (range: 28%-139%) than the 2013 administrative coverage reported among children aged <12 months. Common reported reasons for non-vaccination included lack of knowledge about vaccines and vaccination services (50%) and factors related to access to routine immunization services (15%). Survey results highlighted vaccine coverage gaps that were systematically underestimated by administrative reporting across 40 polio high risk districts in northern Nigeria. Given the limitations of administrative coverage data, our approach to conducting quality district-level coverage surveys and providing data to assess and remediate issues contributing to poor vaccination coverage could serve as an example in countries with sub-optimal vaccination coverage, similar to Nigeria.

Sensitivity of postplanning target and OAR coverage estimates to dosimetric margin distribution sampling parameters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu Huijun; Gordon, J. James; Siebers, Jeffrey V.

2011-02-15

Purpose: A dosimetric margin (DM) is the margin in a specified direction between a structure and a specified isodose surface, corresponding to a prescription or tolerance dose. The dosimetric margin distribution (DMD) is the distribution of DMs over all directions. Given a geometric uncertainty model, representing inter- or intrafraction setup uncertainties or internal organ motion, the DMD can be used to calculate coverage Q, which is the probability that a realized target or organ-at-risk (OAR) dose metric D{sub v} exceeds the corresponding prescription or tolerance dose. Postplanning coverage evaluation quantifies the percentage of uncertainties for which target and OAR structuresmore » meet their intended dose constraints. The goal of the present work is to evaluate coverage probabilities for 28 prostate treatment plans to determine DMD sampling parameters that ensure adequate accuracy for postplanning coverage estimates. Methods: Normally distributed interfraction setup uncertainties were applied to 28 plans for localized prostate cancer, with prescribed dose of 79.2 Gy and 10 mm clinical target volume to planning target volume (CTV-to-PTV) margins. Using angular or isotropic sampling techniques, dosimetric margins were determined for the CTV, bladder and rectum, assuming shift invariance of the dose distribution. For angular sampling, DMDs were sampled at fixed angular intervals {omega} (e.g., {omega}=1 deg., 2 deg., 5 deg., 10 deg., 20 deg.). Isotropic samples were uniformly distributed on the unit sphere resulting in variable angular increments, but were calculated for the same number of sampling directions as angular DMDs, and accordingly characterized by the effective angular increment {omega}{sub eff}. In each direction, the DM was calculated by moving the structure in radial steps of size {delta}(=0.1,0.2,0.5,1 mm) until the specified isodose was crossed. Coverage estimation accuracy {Delta}Q was quantified as a function of the sampling parameters {omega} or {omega}{sub eff} and {delta}. Results: The accuracy of coverage estimates depends on angular and radial DMD sampling parameters {omega} or {omega}{sub eff} and {delta}, as well as the employed sampling technique. Target |{Delta}Q|<1% and OAR |{Delta}Q|<3% can be achieved with sampling parameters {omega} or {omega}{sub eff}=20 deg., {delta}=1 mm. Better accuracy (target |{Delta}Q|<0.5% and OAR |{Delta}Q|<{approx}1%) can be achieved with {omega} or {omega}{sub eff}=10 deg., {delta}=0.5 mm. As the number of sampling points decreases, the isotropic sampling method maintains better accuracy than fixed angular sampling. Conclusions: Coverage estimates for post-planning evaluation are essential since coverage values of targets and OARs often differ from the values implied by the static margin-based plans. Finer sampling of the DMD enables more accurate assessment of the effect of geometric uncertainties on coverage estimates prior to treatment. DMD sampling with {omega} or {omega}{sub eff}=10 deg. and {delta}=0.5 mm should be adequate for planning purposes.« less

Sensitivity of postplanning target and OAR coverage estimates to dosimetric margin distribution sampling parameters.

PubMed

Xu, Huijun; Gordon, J James; Siebers, Jeffrey V

2011-02-01

A dosimetric margin (DM) is the margin in a specified direction between a structure and a specified isodose surface, corresponding to a prescription or tolerance dose. The dosimetric margin distribution (DMD) is the distribution of DMs over all directions. Given a geometric uncertainty model, representing inter- or intrafraction setup uncertainties or internal organ motion, the DMD can be used to calculate coverage Q, which is the probability that a realized target or organ-at-risk (OAR) dose metric D, exceeds the corresponding prescription or tolerance dose. Postplanning coverage evaluation quantifies the percentage of uncertainties for which target and OAR structures meet their intended dose constraints. The goal of the present work is to evaluate coverage probabilities for 28 prostate treatment plans to determine DMD sampling parameters that ensure adequate accuracy for postplanning coverage estimates. Normally distributed interfraction setup uncertainties were applied to 28 plans for localized prostate cancer, with prescribed dose of 79.2 Gy and 10 mm clinical target volume to planning target volume (CTV-to-PTV) margins. Using angular or isotropic sampling techniques, dosimetric margins were determined for the CTV, bladder and rectum, assuming shift invariance of the dose distribution. For angular sampling, DMDs were sampled at fixed angular intervals w (e.g., w = 1 degree, 2 degrees, 5 degrees, 10 degrees, 20 degrees). Isotropic samples were uniformly distributed on the unit sphere resulting in variable angular increments, but were calculated for the same number of sampling directions as angular DMDs, and accordingly characterized by the effective angular increment omega eff. In each direction, the DM was calculated by moving the structure in radial steps of size delta (=0.1, 0.2, 0.5, 1 mm) until the specified isodose was crossed. Coverage estimation accuracy deltaQ was quantified as a function of the sampling parameters omega or omega eff and delta. The accuracy of coverage estimates depends on angular and radial DMD sampling parameters omega or omega eff and delta, as well as the employed sampling technique. Target deltaQ/ < l% and OAR /deltaQ/ < 3% can be achieved with sampling parameters omega or omega eef = 20 degrees, delta =1 mm. Better accuracy (target /deltaQ < 0.5% and OAR /deltaQ < approximately 1%) can be achieved with omega or omega eff = 10 degrees, delta = 0.5 mm. As the number of sampling points decreases, the isotropic sampling method maintains better accuracy than fixed angular sampling. Coverage estimates for post-planning evaluation are essential since coverage values of targets and OARs often differ from the values implied by the static margin-based plans. Finer sampling of the DMD enables more accurate assessment of the effect of geometric uncertainties on coverage estimates prior to treatment. DMD sampling with omega or omega eff = 10 degrees and delta = 0.5 mm should be adequate for planning purposes.

Cost of lifetime immunosuppression coverage for kidney transplant recipients.

PubMed

Page, Timothy F; Woodward, Robert S

2008-01-01

On January 1, 2000, Medicare extended the coverage of immunosuppression medications from 3 years to life for elderly and disabled kidney transplant recipients. This research estimates the impact of extending this lifetime coverage to all kidney transplant recipients on Medicare's cash flows. The study finds that extending coverage to all kidney transplant recipients would have increased Medicare's net cash outflows if the coverage were extended for patients of all income levels. There is evidence that extending coverage to only patients in the lowest income quartile could have resulted in a net cost savings to Medicare.

Joint coverage probability in a simulation study on Continuous-Time Markov Chain parameter estimation.

PubMed

Benoit, Julia S; Chan, Wenyaw; Doody, Rachelle S

2015-01-01

Parameter dependency within data sets in simulation studies is common, especially in models such as Continuous-Time Markov Chains (CTMC). Additionally, the literature lacks a comprehensive examination of estimation performance for the likelihood-based general multi-state CTMC. Among studies attempting to assess the estimation, none have accounted for dependency among parameter estimates. The purpose of this research is twofold: 1) to develop a multivariate approach for assessing accuracy and precision for simulation studies 2) to add to the literature a comprehensive examination of the estimation of a general 3-state CTMC model. Simulation studies are conducted to analyze longitudinal data with a trinomial outcome using a CTMC with and without covariates. Measures of performance including bias, component-wise coverage probabilities, and joint coverage probabilities are calculated. An application is presented using Alzheimer's disease caregiver stress levels. Comparisons of joint and component-wise parameter estimates yield conflicting inferential results in simulations from models with and without covariates. In conclusion, caution should be taken when conducting simulation studies aiming to assess performance and choice of inference should properly reflect the purpose of the simulation.

Label-free DNA biosensor based on resistance change of platinum nanoparticles assemblies.

PubMed

Skotadis, Evangelos; Voutyras, Konstantinos; Chatzipetrou, Marianneza; Tsekenis, Georgios; Patsiouras, Lampros; Madianos, Leonidas; Chatzandroulis, Stavros; Zergioti, Ioanna; Tsoukalas, Dimitris

2016-07-15

A novel nanoparticle based biosensor for the fast and simple detection of DNA hybridization events is presented. The sensor utilizes hybridized DNA's charge transport properties, combining them with metallic nanoparticle networks that act as nano-gapped electrodes. The DNA hybridization events can be detected by a significant reduction in the sensor's resistance due to the conductive bridging offered by hybridized DNA. By modifying the nanoparticle surface coverage, which can be controlled experimentally being a function of deposition time, and the structural properties of the electrodes, an optimized biosensor for the in situ detection of DNA hybridization events is ultimately fabricated. The fabricated biosensor exhibits a wide response range, covering four orders of magnitude, a limit of detection of 1nM and can detect a single base pair mismatch between probe and complementary DNA. Copyright © 2016 Elsevier B.V. All rights reserved.

Conformational Smear Characterization and Binning of Single-Molecule Conductance Measurements for Enhanced Molecular Recognition.

PubMed

Korshoj, Lee E; Afsari, Sepideh; Chatterjee, Anushree; Nagpal, Prashant

2017-11-01

Electronic conduction or charge transport through single molecules depends primarily on molecular structure and anchoring groups and forms the basis for a wide range of studies from molecular electronics to DNA sequencing. Several high-throughput nanoelectronic methods such as mechanical break junctions, nanopores, conductive atomic force microscopy, scanning tunneling break junctions, and static nanoscale electrodes are often used for measuring single-molecule conductance. In these measurements, "smearing" due to conformational changes and other entropic factors leads to large variances in the observed molecular conductance, especially in individual measurements. Here, we show a method for characterizing smear in single-molecule conductance measurements and demonstrate how binning measurements according to smear can significantly enhance the use of individual conductance measurements for molecular recognition. Using quantum point contact measurements on single nucleotides within DNA macromolecules, we demonstrate that the distance over which molecular junctions are maintained is a measure of smear, and the resulting variance in unbiased single measurements depends on this smear parameter. Our ability to identify individual DNA nucleotides at 20× coverage increases from 81.3% accuracy without smear analysis to 93.9% with smear characterization and binning (SCRIB). Furthermore, merely 7 conductance measurements (7× coverage) are needed to achieve 97.8% accuracy for DNA nucleotide recognition when only low molecular smear measurements are used, which represents a significant improvement over contemporary sequencing methods. These results have important implications in a broad range of molecular electronics applications from designing robust molecular switches to nanoelectronic DNA sequencing.

Illuminating choices for library prep: a comparison of library preparation methods for whole genome sequencing of Cryptococcus neoformans using Illumina HiSeq.

PubMed

Rhodes, Johanna; Beale, Mathew A; Fisher, Matthew C

2014-01-01

The industry of next-generation sequencing is constantly evolving, with novel library preparation methods and new sequencing machines being released by the major sequencing technology companies annually. The Illumina TruSeq v2 library preparation method was the most widely used kit and the market leader; however, it has now been discontinued, and in 2013 was replaced by the TruSeq Nano and TruSeq PCR-free methods, leaving a gap in knowledge regarding which is the most appropriate library preparation method to use. Here, we used isolates from the pathogenic fungi Cryptococcus neoformans var. grubii and sequenced them using the existing TruSeq DNA v2 kit (Illumina), along with two new kits: the TruSeq Nano DNA kit (Illumina) and the NEBNext Ultra DNA kit (New England Biolabs) to provide a comparison. Compared to the original TruSeq DNA v2 kit, both newer kits gave equivalent or better sequencing data, with increased coverage. When comparing the two newer kits, we found little difference in cost and workflow, with the NEBNext Ultra both slightly cheaper and faster than the TruSeq Nano. However, the quality of data generated using the TruSeq Nano DNA kit was superior due to higher coverage at regions of low GC content, and more SNPs identified. Researchers should therefore evaluate their resources and the type of application (and hence data quality) being considered when ultimately deciding on which library prep method to use.

Effective coverage of essential inpatient care for small and sick newborns in a high mortality urban setting: a cross-sectional study in Nairobi City County, Kenya.

PubMed

Murphy, Georgina A V; Gathara, David; Mwachiro, Jacintah; Abuya, Nancy; Aluvaala, Jalemba; English, Mike

2018-05-22

Effective coverage requires that those in need can access skilled care supported by adequate resources. There are, however, few studies of effective coverage of facility-based neonatal care in low-income settings, despite the recognition that improving newborn survival is a global priority. We used a detailed retrospective review of medical records for neonatal admissions to public, private not-for-profit (mission) and private-for-profit (private) sector facilities providing 24×7 inpatient neonatal care in Nairobi City County to estimate the proportion of small and sick newborns receiving nationally recommended care across six process domains. We used our findings to explore the relationship between facility measures of structure and process and estimate effective coverage. Of 33 eligible facilities, 28 (four public, six mission and 18 private), providing an estimated 98.7% of inpatient neonatal care in the county, agreed to partake. Data from 1184 admission episodes were collected. Overall performance was lowest (weighted mean score 0.35 [95% confidence interval or CI: 0.22-0.48] out of 1) for correct prescription of fluid and feed volumes and best (0.86 [95% CI: 0.80-0.93]) for documentation of demographic characteristics. Doses of gentamicin, when prescribed, were at least 20% higher than recommended in 11.7% cases. Larger (often public) facilities tended to have higher process and structural quality scores compared with smaller, predominantly private, facilities. We estimate effective coverage to be 25% (estimate range: 21-31%). These newborns received high-quality inpatient care, while almost half (44.5%) of newborns needed care but did not receive it and a further 30.4% of newborns received an inadequate service. Failure to receive services and gaps in quality of care both contribute to a shortfall in effective coverage in Nairobi City County. Three-quarters of small and sick newborns do not have access to high-quality facility-based care. Substantial improvements in effective coverage will be required to tackle high neonatal mortality in this urban setting with high levels of poverty.

Learning Time-Varying Coverage Functions

PubMed Central

Du, Nan; Liang, Yingyu; Balcan, Maria-Florina; Song, Le

2015-01-01

Coverage functions are an important class of discrete functions that capture the law of diminishing returns arising naturally from applications in social network analysis, machine learning, and algorithmic game theory. In this paper, we propose a new problem of learning time-varying coverage functions, and develop a novel parametrization of these functions using random features. Based on the connection between time-varying coverage functions and counting processes, we also propose an efficient parameter learning algorithm based on likelihood maximization, and provide a sample complexity analysis. We applied our algorithm to the influence function estimation problem in information diffusion in social networks, and show that with few assumptions about the diffusion processes, our algorithm is able to estimate influence significantly more accurately than existing approaches on both synthetic and real world data. PMID:25960624

Learning Time-Varying Coverage Functions.

PubMed

Du, Nan; Liang, Yingyu; Balcan, Maria-Florina; Song, Le

2014-12-08

Coverage functions are an important class of discrete functions that capture the law of diminishing returns arising naturally from applications in social network analysis, machine learning, and algorithmic game theory. In this paper, we propose a new problem of learning time-varying coverage functions, and develop a novel parametrization of these functions using random features. Based on the connection between time-varying coverage functions and counting processes, we also propose an efficient parameter learning algorithm based on likelihood maximization, and provide a sample complexity analysis. We applied our algorithm to the influence function estimation problem in information diffusion in social networks, and show that with few assumptions about the diffusion processes, our algorithm is able to estimate influence significantly more accurately than existing approaches on both synthetic and real world data.

Trends in, and projections of, indicators of universal health coverage in Bangladesh, 1995-2030: a Bayesian analysis of population-based household data.

PubMed

Rahman, Md Shafiur; Rahman, Md Mizanur; Gilmour, Stuart; Swe, Khin Thet; Krull Abe, Sarah; Shibuya, Kenji

2018-01-01

Many countries are implementing health system reforms to achieve universal health coverage (UHC) by 2030. To understand the progress towards UHC in Bangladesh, we estimated trends in indicators of the health service and of financial risk protection. We also estimated the probability of Bangladesh's achieving of UHC targets of 80% essential health-service coverage and 100% financial risk protection by 2030. We estimated the coverage of UHC indicators-13 prevention indicators and four treatment indicators-from 19 nationally representative population-based household surveys done in Bangladesh from Jan 1, 1991, to Dec 31, 2014. We used a Bayesian regression model to estimate the trend and to predict the coverage of UHC indicators along with the probabilities of achieving UHC targets of 80% coverage of health services and 100% coverage of financial risk protection from catastrophic and impoverishing health payments by 2030. We used the concentration index and relative index of inequality to assess wealth-based inequality in UHC indicators. If the current trends remain unchanged, we estimated that coverage of childhood vaccinations, improved water, oral rehydration treatment, satisfaction with family planning, and non-use of tobacco will achieve the 80% target by 2030. However, coverage of four antenatal care visits, facility-based delivery, skilled birth attendance, postnatal checkups, care seeking for pneumonia, exclusive breastfeeding, non-overweight, and adequate sanitation were not projected to achieve the target. Quintile-specific projections showed wide wealth-based inequality in access to antenatal care, postnatal care, delivery care, adequate sanitation, and care seeking for pneumonia, and this inequality was projected to continue for all indicators. The incidence of catastrophic health expenditure and impoverishment were projected to increase from 17% and 4%, respectively, in 2015, to 20% and 9%, respectively, by 2030. Inequality analysis suggested that wealthiest households would disproportionately face more financial catastrophe than the most disadvantaged households. Despite progress, Bangladesh will not achieve the 2030 UHC targets unless the country scales up interventions related to maternal and child health services, and reforms health financing systems to avoid high dependency on out-of-pocket payments. The introduction of a national health insurance system, increased public funding for health care, and expansion of community-based clinics in rural areas could help to move the country towards UHC. Japan Ministry of Health, Labour, and Welfare. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Misconceptions on Missing Data in RAD-seq Phylogenetics with a Deep-scale Example from Flowering Plants.

PubMed

Eaton, Deren A R; Spriggs, Elizabeth L; Park, Brian; Donoghue, Michael J

2017-05-01

Restriction-site associated DNA (RAD) sequencing and related methods rely on the conservation of enzyme recognition sites to isolate homologous DNA fragments for sequencing, with the consequence that mutations disrupting these sites lead to missing information. There is thus a clear expectation for how missing data should be distributed, with fewer loci recovered between more distantly related samples. This observation has led to a related expectation: that RAD-seq data are insufficiently informative for resolving deeper scale phylogenetic relationships. Here we investigate the relationship between missing information among samples at the tips of a tree and information at edges within it. We re-analyze and review the distribution of missing data across ten RAD-seq data sets and carry out simulations to determine expected patterns of missing information. We also present new empirical results for the angiosperm clade Viburnum (Adoxaceae, with a crown age >50 Ma) for which we examine phylogenetic information at different depths in the tree and with varied sequencing effort. The total number of loci, the proportion that are shared, and phylogenetic informativeness varied dramatically across the examined RAD-seq data sets. Insufficient or uneven sequencing coverage accounted for similar proportions of missing data as dropout from mutation-disruption. Simulations reveal that mutation-disruption, which results in phylogenetically distributed missing data, can be distinguished from the more stochastic patterns of missing data caused by low sequencing coverage. In Viburnum, doubling sequencing coverage nearly doubled the number of parsimony informative sites, and increased by >10X the number of loci with data shared across >40 taxa. Our analysis leads to a set of practical recommendations for maximizing phylogenetic information in RAD-seq studies. [hierarchical redundancy; phylogenetic informativeness; quartet informativeness; Restriction-site associated DNA (RAD) sequencing; sequencing coverage; Viburnum.]. © The authors 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Surface-enhanced Raman scattering based nonfluorescent probe for multiplex DNA detection.

PubMed

Sun, Lan; Yu, Chenxu; Irudayaraj, Joseph

2007-06-01

To provide rapid and accurate detection of DNA markers in a straightforward, inexpensive, and multiplex format, an alternative surface-enhanced Raman scattering based probe was designed and fabricated to covalently attach both DNA probing sequence and nonfluorescent Raman tags to the surface of gold nanoparticles (DNA-AuP-RTag). The intensity of Raman signal of the probes could be controlled through the surface coverage of the nonfluorescent Raman tags (RTags). Detection sensitivity of these probes could be optimized by fine-tuning the amount of DNA molecules and RTags on the probes. Long-term stability of the DNA-AuP-RTag probes was found to be good (over 3 months). Excellent multiplexing capability of the DNA-AuP-RTag scheme was demonstrated by simultaneous identification of up to eight probes in a mixture. Detection of hybridization of single-stranded DNA to its complementary targets was successfully accomplished with a long-term goal to use nonfluorescent RTags in a Raman-based DNA microarray platform.

Distribution of alcohol consumption and expenditures and the impact of improved measurement on coverage of alcohol sales in the 2000 National Alcohol Survey.

PubMed

Kerr, William C; Greenfield, Thomas K

2007-10-01

To validate improved survey estimates of alcohol volume and new expenditures questions, these measures were aggregated and evaluated through comparison to sales data. Using the new measures, we examined their distributions by estimating the proportion of mean intake, heavy drinking days, and alcohol expenditures among drinkers grouped by volume. The 2000 National Alcohol Survey is a random digit dialed telephone survey of the United States with 7,612 respondents including 323 who were recontacted for drink ethanol measurement. Among drinkers, we utilized improved drink ethanol content estimates and beverage-specific graduated frequency measures to assess alcohol consumption and past month beverage-specific spending reports to estimate expenditures. Coverage of alcohol sales by the new measures was estimated to be 52.3% for consumption and 59.3% for expenditures. Coverage was best for wine at 92.1% of sales, but improved most for spirits from 37.2% to 55.2%, when empirical drink ethanol content was applied. Distribution estimates showed that the top 10% of drinkers drank 55.3% of the total alcohol consumed, accounted for 61.6% of all 5+ and nearly 80% of all 12+ drinking days. Spirits consumption was the most concentrated with the top decile consuming 62.9% of the total for this beverage. This decile accounted for 33% of total expenditures, even though its mean expenditure per drink was considerably lower ($0.79) than the bottom 50% of drinkers ($4.75). The distributions of mean alcohol intake and heavy drinking days are highly concentrated in the U.S. population. Lower expenditures per drink by the heaviest drinkers suggest substantial downward quality substitution, drinking in cheaper contexts or other bargain pricing strategies. Empirical drink ethanol estimates improved survey coverage of sales particularly for spirits, but significant under-coverage remains, highlighting need for further self-report measurement improvement.

Free-Roaming Dog Population Estimation and Status of the Dog Population Management and Rabies Control Program in Dhaka City, Bangladesh

PubMed Central

Tenzin, Tenzin; Ahmed, Rubaiya; Debnath, Nitish C.; Ahmed, Garba; Yamage, Mat

2015-01-01

Beginning January 2012, a humane method of dog population management using a Catch-Neuter-Vaccinate-Release (CNVR) program was implemented in Dhaka City, Bangladesh as part of the national rabies control program. To enable this program, the size and distribution of the free-roaming dog population needed to be estimated. We present the results of a dog population survey and a pilot assessment of the CNVR program coverage in Dhaka City. Free-roaming dog population surveys were undertaken in 18 wards of Dhaka City on consecutive days using mark-resight methods. Data was analyzed using Lincoln-Petersen index-Chapman correction methods. The CNVR program was assessed over the two years (2012–2013) whilst the coverage of the CNVR program was assessed by estimating the proportion of dogs that were ear-notched (processed dogs) via dog population surveys. The free-roaming dog population was estimated to be 1,242 (95 % CI: 1205–1278) in the 18 sampled wards and 18,585 dogs in Dhaka City (52 dogs/km2) with an estimated human-to-free-roaming dog ratio of 828:1. During the two year CNVR program, a total of 6,665 dogs (3,357 male and 3,308 female) were neutered and vaccinated against rabies in 29 of the 92 city wards. A pilot population survey indicated a mean CNVR coverage of 60.6% (range 19.2–79.3%) with only eight wards achieving > 70% coverage. Given that the coverage in many neighborhoods was below the WHO-recommended threshold level of 70% for rabies eradications and since the CNVR program takes considerable time to implement throughout the entire Dhaka City area, a mass dog vaccination program in the non-CNVR coverage area is recommended to create herd immunity. The findings from this study are expected to guide dog population management and the rabies control program in Dhaka City and elsewhere in Bangladesh. PMID:25978406

Free-roaming dog population estimation and status of the dog population management and rabies control program in Dhaka City, Bangladesh.

PubMed

Tenzin, Tenzin; Ahmed, Rubaiya; Debnath, Nitish C; Ahmed, Garba; Yamage, Mat

2015-05-01

Beginning January 2012, a humane method of dog population management using a Catch-Neuter-Vaccinate-Release (CNVR) program was implemented in Dhaka City, Bangladesh as part of the national rabies control program. To enable this program, the size and distribution of the free-roaming dog population needed to be estimated. We present the results of a dog population survey and a pilot assessment of the CNVR program coverage in Dhaka City. Free-roaming dog population surveys were undertaken in 18 wards of Dhaka City on consecutive days using mark-resight methods. Data was analyzed using Lincoln-Petersen index-Chapman correction methods. The CNVR program was assessed over the two years (2012-2013) whilst the coverage of the CNVR program was assessed by estimating the proportion of dogs that were ear-notched (processed dogs) via dog population surveys. The free-roaming dog population was estimated to be 1,242 (95 % CI: 1205-1278) in the 18 sampled wards and 18,585 dogs in Dhaka City (52 dogs/km2) with an estimated human-to-free-roaming dog ratio of 828:1. During the two year CNVR program, a total of 6,665 dogs (3,357 male and 3,308 female) were neutered and vaccinated against rabies in 29 of the 92 city wards. A pilot population survey indicated a mean CNVR coverage of 60.6% (range 19.2-79.3%) with only eight wards achieving > 70% coverage. Given that the coverage in many neighborhoods was below the WHO-recommended threshold level of 70% for rabies eradications and since the CNVR program takes considerable time to implement throughout the entire Dhaka City area, a mass dog vaccination program in the non-CNVR coverage area is recommended to create herd immunity. The findings from this study are expected to guide dog population management and the rabies control program in Dhaka City and elsewhere in Bangladesh.

Vegetation Coverage Mapping and Soil Effect Correction in Estimating Vegetation Water Content and Dry Biomass from Satellites

NASA Astrophysics Data System (ADS)

Huang, J.; Chen, D.

2005-12-01

Vegetation water content (VWC) attracts great research interests in hydrology research in recent years. As an important parameter describing the horizontal expansion of vegetation, vegetation coverage is essential to implement soil effect correction for partially vegetated fields to estimate VWC accurately. Ground measurements of corn and soybeans in SMEX02 resulted in an identical expolinear relationship between vegetation coverage and leaf area index (LAI), which is used for vegetation coverage mapping. Results illustrated two parts of LAI growth quantitatively: the horizontal expansion of leaf coverage and the vertical accumulation of leaf layers. It is believed that the former part contributes significantly to LAI growth at initial vegetation growth stage and the latter is more dominant after vegetation coverage reaches a certain level. The Normalized Difference Water Index (NDWI) using short-wave infrared bands is convinced for its late saturation at high LAI values, in contrast to the Normalized Difference Vegetation Index (NDVI). NDWI is then utilized to estimate LAI, via another expolinear relationship, which is evidenced having vegetation species independency in study of corn and soybeans in SMEX02 sites. It is believed that the surface reflectance measured at satellites spectral bands are the mixed results of signals reflected from vegetation and bare soil, especially at partially vegetated fields. A simple linear mixture model utilizing vegetation coverage information is proposed to correct soil effect in such cases. Surface reflectance fractions for -rpure- vegetation are derived from the model. Comparing with ground measurements, empirical models using soil effect corrected vegetation indices to estimate VWC and dry biomass (DB) are generated. The study enhanced the in-depth understanding of the mechanisms how vegetation growth takes effect on satellites spectral reflectance with and without soil effect, which are particularly useful for modeling in hydrology, agriculture, forestry and meteorology etc.

The cost-effectiveness of male HPV vaccination in the United States.

PubMed

Chesson, Harrell W; Ekwueme, Donatus U; Saraiya, Mona; Dunne, Eileen F; Markowitz, Lauri E

2011-10-26

The objective of this study was to estimate the cost-effectiveness of adding human papillomavirus (HPV) vaccination of 12-year-old males to a female-only vaccination program for ages 12-26 years in the United States. We used a simplified model of HPV transmission to estimate the reduction in the health and economic burden of HPV-associated diseases in males and females as a result of HPV vaccination. Estimates of the incidence, cost-per-case, and quality-of-life impact of HPV-associated health outcomes were based on the literature. The HPV-associated outcomes included were: cervical intraepithelial neoplasia (CIN); genital warts; juvenile-onset recurrent respiratory papillomatosis (RRP); and cervical, vaginal, vulvar, anal, oropharyngeal, and penile cancers. The cost-effectiveness of male vaccination depended on vaccine coverage of females. When including all HPV-associated outcomes in the analysis, the incremental cost per quality-adjusted life year (QALY) gained by adding male vaccination to a female-only vaccination program was $23,600 in the lower female coverage scenario (20% coverage at age 12 years) and $184,300 in the higher female coverage scenario (75% coverage at age 12 years). The cost-effectiveness of male vaccination appeared less favorable when compared to a strategy of increased female vaccination coverage. For example, we found that increasing coverage of 12-year-old girls would be more cost-effective than adding male vaccination even if the increased female vaccination strategy incurred program costs of $350 per additional girl vaccinated. HPV vaccination of 12-year-old males might potentially be cost-effective, particularly if female HPV vaccination coverage is low and if all potential health benefits of HPV vaccination are included in the analysis. However, increasing female coverage could be a more efficient strategy than male vaccination for reducing the overall health burden of HPV in the population. Published by Elsevier Ltd.

Directional, seamless, and restriction enzyme-free construction of random-primed complementary DNA libraries using phosphorothioate-modified primers.

PubMed

Howland, Shanshan W; Poh, Chek-Meng; Rénia, Laurent

2011-09-01

Directional cloning of complementary DNA (cDNA) primed by oligo(dT) is commonly achieved by appending a restriction site to the primer, whereas the second strand is synthesized through the combined action of RNase H and Escherichia coli DNA polymerase I (PolI). Although random primers provide more uniform and complete coverage, directional cloning with the same strategy is highly inefficient. We report that phosphorothioate linkages protect the tail sequence appended to random primers from the 5'→3' exonuclease activity of PolI. We present a simple strategy for constructing a random-primed cDNA library using the efficient, size-independent, and seamless In-Fusion cloning method instead of restriction enzymes. Copyright © 2011 Elsevier Inc. All rights reserved.

New options for national population surveys: The implications of internet and smartphone coverage.

PubMed

Couper, Mick P; Gremel, Garret; Axinn, William; Guyer, Heidi; Wagner, James; West, Brady T

2018-07-01

Challenges to survey data collection have increased the costs of social research via face-to-face surveys so much that it may become extremely difficult for social scientists to continue using these methods. A key drawback to less expensive Internet-based alternatives is the threat of biased results from coverage errors in survey data. The rise of Internet-enabled smartphones presents an opportunity to re-examine the issue of Internet coverage for surveys and its implications for coverage bias. Two questions (on Internet access and smartphone ownership) were added to the National Survey of Family Growth (NSFG), a U.S. national probability survey of women and men age 15-44, using a continuous sample design. We examine 16 quarters (4 years) of data, from September 2012 to August 2016. Overall, we estimate that 82.9% of the target NSFG population has Internet access, and 81.6% has a smartphone. Combined, this means that about 90.7% of U.S. residents age 15-44 have Internet access, via either traditional devices or a smartphone. We find some evidence of compensatory coverage when looking at key race/ethnicity and age subgroups. For instance, while Black teens (15-18) have the lowest estimated rate of Internet access (81.9%) and the lowest rate of smartphone usage (72.6%), an estimated 88.0% of this subgroup has some form of Internet access. We also examine the socio-demographic correlates of Internet and smartphone coverage, separately and combined, as indicators of technology access in this population. In addition, we look at the effect of differential coverage on key estimates produced by the NSFG, related to fertility, family formation, and sexual activity. While this does not address nonresponse or measurement biases that may differ for alternative modes, our paper has implications for possible coverage biases that may arise when switching to a Web-based mode of data collection, either for follow-up surveys or to replace the main face-to-face data collection. Copyright © 2018. Published by Elsevier Inc.

Estimating the Counterfactual: How Many Uninsured Adults Would There Be Today Without the ACA?

PubMed

Blumberg, Linda J; Garrett, Bowen; Holahan, John

2016-01-01

Time lags in receiving data from long-standing, large federal surveys complicate real-time estimation of the coverage effects of full Affordable Care Act (ACA) implementation. Fast-turnaround household surveys fill some of the void in data on recent changes to insurance coverage, but they lack the historical data that allow analysts to account for trends that predate the ACA, economic fluctuations, and earlier public program expansions when predicting how many people would be uninsured without comprehensive health care reform. Using data from the Current Population Survey (CPS) from 2000 to 2012 and the Health Reform Monitoring Survey (HRMS) data for 2013 and 2015, this article develops an approach to estimate the number of people who would be uninsured in the absence of the ACA and isolates the change in coverage as of March 2015 that can be attributed to the ACA. We produce counterfactual forecasts of the number of uninsured absent the ACA for 9 age-income groups and compare these estimates with 2015 estimates based on HRMS relative coverage changes applied to CPS-based population estimates. As of March 2015, we find the ACA has reduced the number of uninsured adults by 18.1 million compared with the number who would have been uninsured at that time had the law not been implemented. That decline represents a 46% reduction in the number of nonelderly adults without insurance. The approach developed here can be applied to other federal data and timely surveys to provide a range of estimates of the overall effects of reform. © The Author(s) 2016.

Analysis of three strategies to increase screening coverage for cervical cancer in the general population of women aged 60 to 70 years: the CRICERVA study

PubMed Central

2014-01-01

Background Cervical cancer is a frequently diagnosed cancer in women worldwide. Despite having easy preventive and therapeutic approaches, it is an important cause of mortality among women. Methods The CRICERVA study is a cluster clinical trial which assigned one of three interventions to the target population registered in Cerdanyola, Barcelona. Among the 5,707 resident women aged 60 to 70 years in the study area, women with no record of cervical cytology over the last three years were selected. The study included four arms: three interventions all including a pre-assigned date for screening visit and i) personalized invitation letter; ii) adding to i) an informative leaflet; and, iii) in addition to ii) a personalized appointment reminder phone call, and iv) no specific action taken (control group). Participants were offered a personal interview about social-demographic characteristics and about screening attitudes. Cervical cytology and HPV DNA test (HC2) were offered as screening tests. In the case of screening positive in any of these tests, the women were followed up until a full diagnosis could be obtained. The effect size of each study arm was estimated as the absolute gain in coverage between the original coverage and the final coverage. Results From the intervention groups (4,775 women), we identified 3,616 who were not appropriately screened, of which 2,560 women answered the trial call and 1,376 were amenable to screening. HPV was tested in 920 women and cervical cytology in all 1,376. Overall, there was an absolute gain in coverage of 28.8% in the intervention groups compared to 6% in the control group. Coverage increased from 51.2% to 76.0% in strategy i); from 47.4% to 79.0% in strategy ii) and from 44.5% to 74.6% in strategy iii). Lack of information about the relevance of screening was the most important factor for not attending the screening program. Conclusions The study confirms that actively contacting women and including a date for a screening visit, notably increased participation in the screening program. Efforts to improve health education in preventative activities are warranted. Trial registration Clinical Trials.gov Identifier NCT01373723. Registered 14 June 2011. PMID:25026889

Survey results show that adults are willing to pay higher insurance premiums for generous coverage of specialty drugs.

PubMed

Romley, John A; Sanchez, Yuri; Penrod, John R; Goldman, Dana P

2012-04-01

Generous coverage of specialty drugs for cancer and other diseases may be valuable not only for sick patients currently using these drugs, but also for healthy people who recognize the potential need for them in the future. This study estimated how healthy people value insurance coverage of specialty drugs, defined as high-cost drugs that treat cancer and other serious health conditions like multiple sclerosis, by quantifying willingness to pay via a survey. US adults were estimated to be willing to pay an extra $12.94 on average in insurance premiums per month for generous specialty-drug coverage--in effect, $2.58 for every dollar in out-of-pocket costs that they would expect to pay with a less generous insurance plan. Given the value that people assign to generous coverage of specialty drugs, having high cost sharing on these drugs seemingly runs contrary to what people value in their health insurance.

Sequencing degraded DNA from non-destructively sampled museum specimens for RAD-tagging and low-coverage shotgun phylogenetics.

PubMed

Tin, Mandy Man-Ying; Economo, Evan Philip; Mikheyev, Alexander Sergeyevich

2014-01-01

Ancient and archival DNA samples are valuable resources for the study of diverse historical processes. In particular, museum specimens provide access to biotas distant in time and space, and can provide insights into ecological and evolutionary changes over time. However, archival specimens are difficult to handle; they are often fragile and irreplaceable, and typically contain only short segments of denatured DNA. Here we present a set of tools for processing such samples for state-of-the-art genetic analysis. First, we report a protocol for minimally destructive DNA extraction of insect museum specimens, which produced sequenceable DNA from all of the samples assayed. The 11 specimens analyzed had fragmented DNA, rarely exceeding 100 bp in length, and could not be amplified by conventional PCR targeting the mitochondrial cytochrome oxidase I gene. Our approach made these samples amenable to analysis with commonly used next-generation sequencing-based molecular analytic tools, including RAD-tagging and shotgun genome re-sequencing. First, we used museum ant specimens from three species, each with its own reference genome, for RAD-tag mapping. Were able to use the degraded DNA sequences, which were sequenced in full, to identify duplicate reads and filter them prior to base calling. Second, we re-sequenced six Hawaiian Drosophila species, with millions of years of divergence, but with only a single available reference genome. Despite a shallow coverage of 0.37 ± 0.42 per base, we could recover a sufficient number of overlapping SNPs to fully resolve the species tree, which was consistent with earlier karyotypic studies, and previous molecular studies, at least in the regions of the tree that these studies could resolve. Although developed for use with degraded DNA, all of these techniques are readily applicable to more recent tissue, and are suitable for liquid handling automation.

Herpes zoster vaccine (HZV): utilization and coverage 2009 - 2013, Alberta, Canada.

PubMed

Liu, Xianfang C; Simmonds, Kimberley A; Russell, Margaret L; Svenson, Lawrence W

2014-10-23

Herpes zoster vaccine (HZV) is not publicly funded in the province of Alberta, Canada. We estimated vaccine coverage among those aged 60 years or older for 2013, as well as vaccine utilization rates per hundred thousand population over the period 2009 - 2013. We explored for factors associated with HZV dispensing rates. We used administrative data from the Alberta Pharmaceutical Information Network (PIN) database to identify unique persons for whom HZV had been dispensed from community pharmacies over 2009 - 2013. PIN data were also used to estimate the pharmacy/population ratios for rural and urban Alberta over the period. Denominators for rates were estimated using mid-year population estimates from the Alberta Health Care Insurance Plan Registry. Income quintile data were estimated from the 2006 Census of Canada. Crude, age, sex, geographic (rural vs. urban), income-quintile and year specific rates of HZV vaccine dispensing were estimated per 100,000 population. Rates were adjusted for pharmacy/population ratio. Vaccine coverage for persons aged 60 years or older was estimated using counts of all unique persons for whom the vaccine was dispensed over the period in the numerator and a 2013 mid- year population denominator. HZV dispensing rates rose annually from 2009 - 2013. Vaccine coverage was estimated to be 8.4% among persons aged 60 years or older. Rates of dispensing were highest for persons aged 60-69 years and were higher for females than males and for persons from higher compared to lower income quintiles. Dispensing rates were lower for rural than for urban residents. About 2% of vaccine was dispensed for persons aged less than 50 years. Rates of HZV dispensing are increasing rapidly in Alberta despite a lack of public funding. A small proportion of the vaccine may be dispensed off-label.

Taking up or turning down: new estimates of household demand for employer-sponsored health insurance.

PubMed

Abraham, Jean Marie; Feldman, Roger

2010-01-01

This study provides new estimates of demand for employer-sponsored health insurance, using the 1997-2001 linked Household Component-Insurance Component of the Medical Expenditure Panel Survey (MEPS). Our focus is on households' decisions to take up coverage through a worker's employer. We found a significant inverse relationship between the out-of-pocket premium and the probability of taking up coverage, with the price effect considerably larger when we used instrumental variables methods to account for endogenous out-of-pocket premiums. Additionally, workers in families with more children eligible for Medicaid were less likely to take up coverage.

Massively parallel sequencing of forensic STRs and SNPs using the Illumina® ForenSeq™ DNA Signature Prep Kit on the MiSeq FGx™ Forensic Genomics System.

PubMed

Guo, Fei; Yu, Jiao; Zhang, Lu; Li, Jun

2017-11-01

The ForenSeq™ DNA Signature Prep Kit (ForenSeq Kit) is designed to detect more than 200 forensically relevant markers in a single reaction on the MiSeq FGx™ Forensic Genomics System (MiSeq FGx System), including Amelogenin, 27 autosomal short tandem repeats (A-STRs), 7 X chromosomal STRs (X-STRs), 24 Y chromosomal STRs (Y-STRs) and 94 identity-informative single nucleotide polymorphisms (iSNPs) with the option to contain 22 phenotypic-informative SNPs (pSNPs) and 56 ancestry-informative SNPs (aSNPs). In this study, we evaluated the MiSeq FGx System on three major parts: methodological optimization (DNA extraction, sample quantification, library normalization, diluted libraries concentration, and sample-to-cell arrangement), massively parallel sequencing (MPS) performance (depth of coverage, sequence coverage ratio, and allele coverage ratio), and ForenSeq Kit characteristics (repeatability and concordance, sensitivity, mixture, stability and case-type samples). Results showed that quantitative polymerase chain reaction (qPCR)-based sample quantification and library normalization and the appropriate number of pooled libraries and concentration of diluted libraries provided a greater level of MPS performance and repeatability. Repeatable and concordant genotypes were obtained by the ForenSeq Kit. Full profiles were obtained from ≥100pg input DNA for STRs and ≥200pg for SNPs. A sample with ≥5% minor contributors was considered as a mixture by imbalanced allele coverage ratio distribution, and full profiles from minor contributors were easily detected between 9:1 and 1:9 mixtures with known reference profiles. The ForenSeq Kit tolerated considerable concentrations of inhibitors like ≤200μM hematin and ≤50μg/ml humic acid, and >56% STR profiles and >88% SNP profiles were obtained from ≥200-bp degraded samples. Also, it was adapted to case-type samples. As a whole, the ForenSeq Kit is a well-performed, robust, reliable, reproducible and highly informative assay, and it can fully meet requirements for human identification. Further, sensitive QC indicator and automated sample comparison function in the ForenSeq™ Universal Analysis Software are quite helpful, so that we can concentrate on questionable genotypes and avoid tedious and time-consuming labor to maximum the time spent in data analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Small-area estimation of health insurance coverage for California legislative districts.

PubMed

Yu, Hongjian; Meng, Ying-Ying; Mendez-Luck, Carolyn A; Jhawar, Mona; Wallace, Steven P

2007-04-01

To aid state and local policymakers, program planners, and community advocates, we created estimates of the percentage of the population lacking health insurance in small geographic areas of California. Finally, calibration ensured the consistency and stability of the estimates when they were aggregated. Health insurance coverage among nonelderly persons varied widely across assembly districts, from 10% to 44%. The utility of local-level estimates was most apparent when the variations in subcounty uninsured rates in Los Angeles County (19%-44%) were examined. Stable and useful estimates of health insurance rates for small areas such as legislative districts can be created through use of multiple sources of publicly available data.

Vegetation Coverage and Impervious Surface Area Estimated Based on the Estarfm Model and Remote Sensing Monitoring

NASA Astrophysics Data System (ADS)

Hu, Rongming; Wang, Shu; Guo, Jiao; Guo, Liankun

2018-04-01

Impervious surface area and vegetation coverage are important biophysical indicators of urban surface features which can be derived from medium-resolution images. However, remote sensing data obtained by a single sensor are easily affected by many factors such as weather conditions, and the spatial and temporal resolution can not meet the needs for soil erosion estimation. Therefore, the integrated multi-source remote sensing data are needed to carry out high spatio-temporal resolution vegetation coverage estimation. Two spatial and temporal vegetation coverage data and impervious data were obtained from MODIS and Landsat 8 remote sensing images. Based on the Enhanced Spatial and Temporal Adaptive Reflectance Fusion Model (ESTARFM), the vegetation coverage data of two scales were fused and the data of vegetation coverage fusion (ESTARFM FVC) and impervious layer with high spatiotemporal resolution (30 m, 8 day) were obtained. On this basis, the spatial variability of the seepage-free surface and the vegetation cover landscape in the study area was measured by means of statistics and spatial autocorrelation analysis. The results showed that: 1) ESTARFM FVC and impermeable surface have higher accuracy and can characterize the characteristics of the biophysical components covered by the earth's surface; 2) The average impervious surface proportion and the spatial configuration of each area are different, which are affected by natural conditions and urbanization. In the urban area of Xi'an, which has typical characteristics of spontaneous urbanization, landscapes are fragmented and have less spatial dependence.

The future of forensic DNA analysis.

PubMed

Butler, John M

2015-08-05

The author's thoughts and opinions on where the field of forensic DNA testing is headed for the next decade are provided in the context of where the field has come over the past 30 years. Similar to the Olympic motto of 'faster, higher, stronger', forensic DNA protocols can be expected to become more rapid and sensitive and provide stronger investigative potential. New short tandem repeat (STR) loci have expanded the core set of genetic markers used for human identification in Europe and the USA. Rapid DNA testing is on the verge of enabling new applications. Next-generation sequencing has the potential to provide greater depth of coverage for information on STR alleles. Familial DNA searching has expanded capabilities of DNA databases in parts of the world where it is allowed. Challenges and opportunities that will impact the future of forensic DNA are explored including the need for education and training to improve interpretation of complex DNA profiles. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Multi-Ligand-Binding Flavoprotein Dodecin as a Key Element for Reversible Surface Modification in Nano-biotechnology.

PubMed

Gutiérrez Sánchez, Cristina; Su, Qiang; Schönherr, Holger; Grininger, Martin; Nöll, Gilbert

2015-01-01

In this paper the multiple (re)programming of protein-DNA nanostructures comprising generation, deletion, and reprogramming on the same flavin-DNA-modified surface is introduced. This work is based on a systematic study of the binding affinity of the multi-ligand-binding flavoprotein dodecin on flavin-terminated DNA monolayers by surface plasmon resonance and quartz crystal microbalance with dissipation (QCM-D) measurements, surface plasmon fluorescence spectroscopy (SPFS), and dynamic AFM force spectroscopy. Depending on the flavin surface coverage, a single apododecin is captured by one or more surface-immobilized flavins. The corresponding complex binding and unbinding rate constants kon(QCM) = 7.7 × 10(3) M(-1)·s(-1) and koff(QCM) = 4.5 × 10(-3) s(-1) (Kd(QCM) = 580 nM) were determined by QCM and were found to be in agreement with values for koff determined by SPFS and force spectroscopy. Even though a single apododecin-flavin bond is relatively weak, stable dodecin monolayers were formed on flavin-DNA-modified surfaces at high flavin surface coverage due to multivalent interactions between apododecin bearing six binding pockets and the surface-bound flavin-DNA ligands. If bi- or multivalent flavin ligands are adsorbed on dodecin monolayers, stable sandwich-type surface-DNA-flavin-apododecin-flavin ligand arrays are obtained. Nevertheless, the apododecin flavin complex is easily and quantitatively disassembled by flavin reduction. Binding and release of apododecin are reversible processes, which can be carried out alternatingly several times to release one type of ligand by an external redox trigger and subsequently replace it with a different ligand. Hence the versatile concept of reprogrammable functional biointerfaces with the multi-ligand-binding flavoprotein dodecin is demonstrated.

Prescription drug coverage and effects on drug expenditures among elderly Medicare beneficiaries.

PubMed

Huh, Soonim; Rice, Thomas; Ettner, Susan L

2008-06-01

To identify determinants of drug coverage among elderly Medicare beneficiaries and to investigate the impact of drug coverage on drug expenditures with and without taking selection bias into account. The primary data were from the 2000 Medicare Current Beneficiary Survey (MCBS) Cost and Use file, linked to other data sources at the county or state-level that provided instrumental variables. Community-dwelling elderly Medicare beneficiaries who completed the survey were included in the study (N=7,525). A probit regression to predict the probability of having drug coverage and the effects of drug coverage on drug expenditures was estimated by a two-part model, assuming no correlation across equations. In addition, the discrete factor model estimated choice of drug coverage and expenditures for prescription drugs simultaneously to control for self-selection into drug coverage, allowing for correlation of error terms across equations. Findings indicated that unobservable characteristics leading elderly Medicare beneficiaries to purchase drug coverage also lead them to have higher drug expenditures on conditional use (i.e., adverse selection), while the same unobservable factors do not influence their decisions whether to use any drugs. After controlling for potential selection bias, the probability of any drug use among persons with drug coverage use was 4.5 percent higher than among those without, and drug coverage led to an increase in drug expenditures of $308 among those who used prescription drugs. Given significant adverse selection into drug coverage before the implementation of the Medicare Prescription Drug Improvement and Modernization Act, it is essential that selection effects be monitored as beneficiaries choose whether or not to enroll in this voluntary program.

Effect of the Global Alliance for Vaccines and Immunisation on diphtheria, tetanus, and pertussis vaccine coverage: an independent assessment.

PubMed

Lu, Chunling; Michaud, Catherine M; Gakidou, Emmanuela; Khan, Kashif; Murray, Christopher J L

2006-09-23

The Global Alliance for Vaccines and Immunisation (GAVI) was created in 1999 to enable even the poorest countries to provide vaccines to all children. We aimed to assess the effect of GAVI on combined diphtheria, tetanus, and pertussis vaccine (DTP3) coverage. We examined the relation between DTP3 coverage for GAVI recipient countries from 1995 to 2004 and immunisation services support (ISS) and non-ISS expenditure per surviving child, controlling for income per head and local political governance variables. We analysed DTP3 coverage reported by governments and estimated by WHO/UNICEF. We also investigated the effect of GAVI on country reporting behaviour. In countries with DTP3 coverage of 65% or less at baseline, ISS spending per surviving child had a significant positive effect on DTP3 coverage (p=0.0005). This effect was not present in countries with DTP3 coverage of 65-80% or 80% or more at baseline. If ISS expenditure only is assessed, the estimated cost per additional child immunised in countries with baseline coverage of 65% or less is US$14 and if ISS and non-ISS expenditures are included the cost per child is almost $20. The success of ISS funding in countries with baseline DTP3 coverage of 65% or less provides evidence that a public-private partnership can work to reverse a negative trend in global health and that performance-related disbursement can work in some settings. Because ISS funding seems to have no effect in countries with baseline coverage greater than 65%, GAVI should consider redistributing its resources to countries with the lowest coverage.

A magnetic nanobead-based bioassay provides sensitive detection of single- and biplex bacterial DNA using a portable AC susceptometer

PubMed Central

Strömberg, Mattias; Zardán Gómez de la Torre, Teresa; Nilsson, Mats; Svedlindh, Peter; Strømme, Maria

2014-01-01

Bioassays relying on magnetic read-out using probe-tagged magnetic nanobeads are potential platforms for low-cost biodiagnostic devices for pathogen detection. For optimal assay performance it is crucial to apply an easy, efficient and robust bead-probe conjugation protocol. In this paper, sensitive (1.5 pM) singleplex detection of bacterial DNA sequences is demonstrated in a portable AC susceptometer by a magnetic nanobead-based bioassay principle; the volume-amplified magnetic nanobead detection assay (VAM-NDA). Two bead sizes, 100 and 250 nm, are investigated along with a highly efficient, rapid, robust, and stable conjugation chemistry relying on the avidin–biotin interaction for bead-probe attachment. Avidin-biotin conjugation gives easy control of the number of detection probes per bead; thus allowing for systematic investigation of the impact of varying the detection probe surface coverage upon bead immobilization in rolling circle amplified DNA-coils. The existence of an optimal surface coverage is discussed. Biplex VAM-NDA detection is for the first time demonstrated in the susceptometer: Semi-quantitative results are obtained and it is concluded that the concentration of DNA-coils in the incubation volume is of crucial importance for target quantification. The present findings bring the development of commercial biodiagnostic devices relying on the VAM–NDA further towards implementation in point-of-care and outpatient settings. PMID:24174315

Early impact of the Affordable Care Act on health insurance coverage of young adults.

PubMed

Cantor, Joel C; Monheit, Alan C; DeLia, Derek; Lloyd, Kristen

2012-10-01

To evaluate one of the first implemented provisions of the Patient Protection and Affordable Care Act (ACA), which permits young adults up to age 26 to enroll as dependents on a parent's private health plan. Nearly one-in-three young adults lacked coverage before the ACA. STUDY DESIGN, METHODS, AND DATA: Data from the Current Population Survey 2005-2011 are used to estimate linear probability models within a difference-in-differences framework to estimate how the ACA affected coverage of eligible young adults compared to slightly older adults. Multivariate models control for individual characteristics, economic trends, and prior state-dependent coverage laws. This ACA provision led to a rapid and substantial increase in the share of young adults with dependent coverage and a reduction in their uninsured rate in the early months of implementation. Models accounting for prior state dependent expansions suggest greater policy impact in 2010 among young adults who were also eligible under a state law. ACA-dependent coverage expansion represents a rare public policy success in the effort to cover the uninsured. Still, this policy may have later unintended consequences for premiums for alternative forms of coverage and employer-offered rates for young adult workers. © Health Research and Educational Trust.

Proper joint analysis of summary association statistics requires the adjustment of heterogeneity in SNP coverage pattern.

PubMed

Zhang, Han; Wheeler, William; Song, Lei; Yu, Kai

2017-07-07

As meta-analysis results published by consortia of genome-wide association studies (GWASs) become increasingly available, many association summary statistics-based multi-locus tests have been developed to jointly evaluate multiple single-nucleotide polymorphisms (SNPs) to reveal novel genetic architectures of various complex traits. The validity of these approaches relies on the accurate estimate of z-score correlations at considered SNPs, which in turn requires knowledge on the set of SNPs assessed by each study participating in the meta-analysis. However, this exact SNP coverage information is usually unavailable from the meta-analysis results published by GWAS consortia. In the absence of the coverage information, researchers typically estimate the z-score correlations by making oversimplified coverage assumptions. We show through real studies that such a practice can generate highly inflated type I errors, and we demonstrate the proper way to incorporate correct coverage information into multi-locus analyses. We advocate that consortia should make SNP coverage information available when posting their meta-analysis results, and that investigators who develop analytic tools for joint analyses based on summary data should pay attention to the variation in SNP coverage and adjust for it appropriately. Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.

Early Impact of the Affordable Care Act on Health Insurance Coverage of Young Adults

PubMed Central

Cantor, Joel C; Monheit, Alan C; DeLia, Derek; Lloyd, Kristen

2012-01-01

Research Objective To evaluate one of the first implemented provisions of the Patient Protection and Affordable Care Act (ACA), which permits young adults up to age 26 to enroll as dependents on a parent's private health plan. Nearly one-in-three young adults lacked coverage before the ACA. Study Design, Methods, and Data Data from the Current Population Survey 2005–2011 are used to estimate linear probability models within a difference-in-differences framework to estimate how the ACA affected coverage of eligible young adults compared to slightly older adults. Multivariate models control for individual characteristics, economic trends, and prior state-dependent coverage laws. Principal Findings This ACA provision led to a rapid and substantial increase in the share of young adults with dependent coverage and a reduction in their uninsured rate in the early months of implementation. Models accounting for prior state dependent expansions suggest greater policy impact in 2010 among young adults who were also eligible under a state law. Conclusions and Implications ACA-dependent coverage expansion represents a rare public policy success in the effort to cover the uninsured. Still, this policy may have later unintended consequences for premiums for alternative forms of coverage and employer-offered rates for young adult workers. PMID:22924684

A flexible microneedle array as low-voltage electroporation electrodes for in vivo DNA and siRNA delivery.

PubMed

Wei, Zewen; Zheng, Shuquan; Wang, Renxin; Bu, Xiangli; Ma, Huailei; Wu, Yidi; Zhu, Ling; Hu, Zhiyuan; Liang, Zicai; Li, Zhihong

2014-10-21

In vivo electroporation is an appealing method to deliver nucleic acid into living tissues, but the clinical application of such a method was limited due to severe tissue damage and poor coverage of the tissue surface. Here we present the validation of a novel flexible microneedle array electrode (MNAE) chip, in which the microneedle array and the flexible substrate are integrated together to simultaneously facilitate low-voltage electroporation and accomplish good coverage of the tissue surface. The efficient delivery of both DNA and siRNA was demonstrated on mice. Upon penetrating the high-resistance stratum corneum, the electroporation voltage was reduced to about 35 V, which was generally recognized safe for humans. Also, a pathological analysis of the microneedle-electroporated tissues was carried out to thoroughly assess the skin damage, which is an important consideration in pre-clinical studies of electroporation devices. This MNAE constitutes a novel way of in vivo delivery of siRNA and DNA to certain tissues or organs with satisfactory efficiency and good adaptation to the tissue surface profile as well as minimum tissue damage, thus avoiding the disadvantages of existing electroporation methods.

Whole-genome multiple displacement amplification from single cells.

PubMed

Spits, Claudia; Le Caignec, Cédric; De Rycke, Martine; Van Haute, Lindsey; Van Steirteghem, André; Liebaers, Inge; Sermon, Karen

2006-01-01

Multiple displacement amplification (MDA) is a recently described method of whole-genome amplification (WGA) that has proven efficient in the amplification of small amounts of DNA, including DNA from single cells. Compared with PCR-based WGA methods, MDA generates DNA with a higher molecular weight and shows better genome coverage. This protocol was developed for preimplantation genetic diagnosis, and details a method for performing single-cell MDA using the phi29 DNA polymerase. It can also be useful for the amplification of other minute quantities of DNA, such as from forensic material or microdissected tissue. The protocol includes the collection and lysis of single cells, and all materials and steps involved in the MDA reaction. The whole procedure takes 3 h and generates 1-2 microg of DNA from a single cell, which is suitable for multiple downstream applications, such as sequencing, short tandem repeat analysis or array comparative genomic hybridization.

Random access in large-scale DNA data storage.

PubMed

Organick, Lee; Ang, Siena Dumas; Chen, Yuan-Jyue; Lopez, Randolph; Yekhanin, Sergey; Makarychev, Konstantin; Racz, Miklos Z; Kamath, Govinda; Gopalan, Parikshit; Nguyen, Bichlien; Takahashi, Christopher N; Newman, Sharon; Parker, Hsing-Yeh; Rashtchian, Cyrus; Stewart, Kendall; Gupta, Gagan; Carlson, Robert; Mulligan, John; Carmean, Douglas; Seelig, Georg; Ceze, Luis; Strauss, Karin

2018-03-01

Synthetic DNA is durable and can encode digital data with high density, making it an attractive medium for data storage. However, recovering stored data on a large-scale currently requires all the DNA in a pool to be sequenced, even if only a subset of the information needs to be extracted. Here, we encode and store 35 distinct files (over 200 MB of data), in more than 13 million DNA oligonucleotides, and show that we can recover each file individually and with no errors, using a random access approach. We design and validate a large library of primers that enable individual recovery of all files stored within the DNA. We also develop an algorithm that greatly reduces the sequencing read coverage required for error-free decoding by maximizing information from all sequence reads. These advances demonstrate a viable, large-scale system for DNA data storage and retrieval.

Meeting the Need for State-Level Estimates of Health Insurance Coverage: Use of State and Federal Survey Data

PubMed Central

Blewett, Lynn A; Davern, Michael

2006-01-01

Objective Critically review estimates of health insurance coverage available from different sources, including the federal government, state survey initiatives, and foundation-sponsored surveys for use in state policy research. Study Setting and Design We review the surveys in an attempt to flesh out the current weaknesses of survey data for state policy uses. The main data sources assessed in this analysis are federal government surveys (such as the Current Population Survey's Annual Social and Economic Supplement, and the National Health Interview Survey), foundation-supported surveys (National Survey of America's Families, and the Community Tracking Survey), and state-sponsored surveys. Principal Findings Despite information on estimates of health insurance coverage from six federal surveys, states find the data lacking for state policy purposes. We document the need for state representative data on the uninsured and the recent history of state data collection efforts spurred in part by the Health Resources Services Administration State Planning Grant program. We assess the state estimates of uninsurance from the Current Population Survey and make recommendations for a new consolidated federal survey with better state representative data. Conclusions We think there are several options to consider for coordinating a federal and state data collection strategy to inform state and national policy on coverage and access. PMID:16704521

Maiden immunization coverage survey in the republic of South Sudan: a cross-sectional study providing baselines for future performance measurement.

PubMed

Mbabazi, William; Lako, Anthony K; Ngemera, Daniel; Laku, Richard; Yehia, Mostafah; Nshakira, Nathan

2013-01-01

Since the comprehensive peace agreement was signed in 2005, institutionalization of immunization services in South Sudan remained a priority. Routine administrative reporting systems were established and showed that national coverage rates for DTP-3 rose from 20% in 2002 to 80% in 2011. This survey was conducted as part of an overall review of progress in implementation of the first EPI Multi-Year Plan for South Sudan 2007-2011. This report provides maiden community coverage estimates for immunization. A cross sectional community survey was conducted between January and May 2012. Ten cluster surveys were conducted to generate state-specific coverage estimates. The WHO 30x7 cluster sampling method was employed. Data was collected using pre-tested, interviewer guided, structured questionnaires through house to house visits. The fully immunized children were 7.3%. Coverage for specific antigens were; BCG (28.3%), DTP-1(25.9%), DTP-3 (22.0%), Measles (16.8%). The drop-out rate between the first and third doses of DTP was 21.3%. Immunization coverage estimates based on card and history were higher, at 45.7% for DTP-3, 45.8% for MCV and 32.2% for full immunization. Majority of immunizations (80.8%) were received at health facilities compared to community service points (19.2%). The major reason for missed immunizations was inadequate information (41.1%). The proportion of card-verified, fully vaccinated among children aged 12-23 months is very low at 7.3%. Future efforts to improve vaccination quality and coverage should prioritize training of vaccinators and program communication to levels equivalent or higher than investments in EPI cold chain systems since 2007.

Maiden immunization coverage survey in the republic of South Sudan: a cross-sectional study providing baselines for future performance measurement

PubMed Central

Mbabazi, William; Lako, Anthony K; Ngemera, Daniel; Laku, Richard; Yehia, Mostafah; Nshakira, Nathan

2013-01-01

Introduction Since the comprehensive peace agreement was signed in 2005, institutionalization of immunization services in South Sudan remained a priority. Routine administrative reporting systems were established and showed that national coverage rates for DTP-3 rose from 20% in 2002 to 80% in 2011. This survey was conducted as part of an overall review of progress in implementation of the first EPI Multi-Year Plan for South Sudan 2007-2011. This report provides maiden community coverage estimates for immunization. Methods A cross sectional community survey was conducted between January and May 2012. Ten cluster surveys were conducted to generate state-specific coverage estimates. The WHO 30x7 cluster sampling method was employed. Data was collected using pre-tested, interviewer guided, structured questionnaires through house to house visits. Results The fully immunized children were 7.3%. Coverage for specific antigens were; BCG (28.3%), DTP-1(25.9%), DTP-3 (22.0%), Measles (16.8%). The drop-out rate between the first and third doses of DTP was 21.3%. Immunization coverage estimates based on card and history were higher, at 45.7% for DTP-3, 45.8% for MCV and 32.2% for full immunization. Majority of immunizations (80.8%) were received at health facilities compared to community service points (19.2%). The major reason for missed immunizations was inadequate information (41.1%). Conclusion The proportion of card-verified, fully vaccinated among children aged 12-23 months is very low at 7.3%. Future efforts to improve vaccination quality and coverage should prioritize training of vaccinators and program communication to levels equivalent or higher than investments in EPI cold chain systems since 2007. PMID:24876899

Vaccination coverage against pertussis in pregnant women of Catalonia in the first year of implementation of the immunisation program.

PubMed

Fernández-Cano, María Isabel; Espada-Trespalacios, Xavier; Reyes-Lacalle, Azahara; Manresa Domínguez, Josep Maria; Armadans-Gil, Lluís; Campins-Martí, Magda; Falguera-Puig, Gemma; Toran Monserrat, Pere

2017-11-01

The re-emergence of pertussis and the severity of its complications in infants younger than 3 months, were determining factors for starting a vaccination program for pregnant women in the third trimester of gestation in Catalonia in February 2014. This was the first autonomous community to introduce it in Spain. The aim of the study was to estimate the coverage of the program in its first year of implementation. A retrospective analysis was performed on the data from the Primary Care Centre computerised medical records of pregnant women attending Sexual and Reproductive Health Care centres of the Metropolitan Nord area of the province of Barcelona, part of the Catalan Institute of Health. The overall coverage was estimated, as well as the sociodemographic variables of Tdap vaccination of women who had registered a delivery of a live birth between August 2014 and August 2015. A total of 6,697 deliveries of live births were recorded, and 1,713 pregnant women were vaccinated, which represented an overall coverage of 25.6% (95% CI; 24.1-26.1). Vaccination coverage was higher in pregnant women under 18 years and Spanish women (P=.018 and P=.036, respectively). The estimation of vaccine coverage against pertussis in pregnant women in the third trimester of pregnancy, after the first year of implementation of the program in a health area of Catalonia was lower than the objective set. Strategies need to be designed in order to improve program coverage. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

The Effect of the Affordable Care Act's Young Adult Insurance Expansions on Hospital-Based Behavioral Health Care

PubMed Central

Golberstein, Ezra; Busch, Susan H.; Zaha, Rebecca; Greenfield, Shelly F.; Beardslee, William R.; Meara, Ellen

2014-01-01

Objective Insurance coverage for young adults has increased since 2010, when the Affordable Care Act (ACA) required insurers to permit children on parental policies until age 26 as dependents. This study estimated changes in young adults’ use of hospital-based services with diagnosis codes for mental illness and substance abuse associated with the dependent coverage provision. Method Quasi-experimental comparison of national sample of non-birth hospital inpatient admissions to general hospitals (n=2,670,463 total, n=430,583 with primary behavioral health diagnosis) and California emergency department (ED) visits with behavioral health diagnoses (n=11,139,689). Data spanned 2005 to 2011. Estimates compared young adults who were and were not targeted by the ACA dependent coverage provision (19 to 25 versus 26 to 29 year olds), estimating changes in utilization before and after 2010. Primary outcomes included: quarterly inpatient admissions for primary diagnosis of any behavioral health disorder per 1000 population; ED visits with any behavioral health diagnosis per 1000 population; and payer source. Results Dependent coverage expansion was associated with 0.14 per 1000 more (p<0.001) inpatient admissions for behavioral health for 19-25 (ACA covered) versus 26-29 (then ACA uncovered) year olds. The coverage expansion was associated with 0.45 fewer behavioral health ED visits per 1000 (p=0.001) in California. The probability that inpatient admissions nationally, and ED visits in California were uninsured, decreased significantly (p<0.001). Conclusions ACA dependent coverage provisions produced modest increases in general hospital psychiatric inpatient admissions and higher rates of insurance coverage for young adult children nationally. Lower ED visit rates were observed in California. PMID:25263817

Uptake of oral rotavirus vaccine and timeliness of routine immunization in Brazil’s National Immunization Program

PubMed Central

Flannery, Brendan; Samad, Samia; de Moraes, José Cássio; Tate, Jacqueline E.; Danovaro-Holliday, M. Carolina; de Oliveira, Lúcia Helena; Rainey, Jeanette J.

2015-01-01

Introduction In March, 2006, oral rotavirus vaccine was added to Brazil’s infant immunization schedule with recommended upper age limits for initiating (by age 14 weeks) and completing (by age 24 weeks) the two-dose series to minimize age-specific risk of intussusception following rotavirus vaccination. Several years after introduction, estimated coverage with rotavirus vaccine (83%) was lower compared to coverage for other recommended childhood immunizations (≥94%). Methods We analyzed data from Brazil’s national immunization program on uptake of oral rotavirus vaccine by geographic region and compared administrative coverage estimates for first and second doses of oral rotavirus vaccine (Rota1 and Rota2) with first and second doses of diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP-Hib1 and DTP-Hib2). For 27 Brazilian cities, we compared differences between estimated rotavirus and DTP-Hib coverage in 2010 with delayed receipt of DTP-Hib vaccine among a cohort of children surveyed before rotavirus introduction. Results In 2010, infant vaccination coverage was 99.0% for DTP-Hib1 versus 95.2% for Rota1 (3.8% difference), and 98.4% for DTP-Hib2 versus 83.0% for Rota2 (15.4% difference), with substantial regional variation. Differences between DTP-Hib and rotavirus vaccination coverage in Brazilian cities correlated with delay in DTP-Hib vaccination among children surveyed. Age restrictions for initiating and completing the rotavirus vaccination series likely contributed to lower coverage with rotavirus vaccine in Brazil. Conclusion To maximize benefits of rotavirus vaccination, strategies are needed to improve timeliness of routine immunizations; monitoring rotavirus vaccine uptake and intussusception risk is needed to guide further recommendations for rotavirus vaccination. PMID:23313652

Coverage of pilot parenteral vaccination campaign against canine rabies in N'Djaména, Chad.

PubMed Central

Kayali, U.; Mindekem, R.; Yémadji, N.; Vounatsou, P.; Kaninga, Y.; Ndoutamia, A. G.; Zinsstag, J.

2003-01-01

Canine rabies, and thus human exposure to rabies, can be controlled through mass vaccination of the animal reservoir if dog owners are willing to cooperate. Inaccessible, ownerless dogs, however, reduce the vaccination coverage achieved in parenteral campaigns. This study aimed to estimate the vaccination coverage in dogs in three study zones of N'Djaména, Chad, after a pilot free parenteral mass vaccination campaign against rabies. We used a capture-mark-recapture approach for population estimates, with a Bayesian, Markov chain, Monte Carlo method to estimate the total number of owned dogs, and the ratio of ownerless to owned dogs to calculate vaccination coverage. When we took into account ownerless dogs, the vaccination coverage in the dog populations was 87% (95% confidence interval (CI), 84-89%) in study zone I, 71% (95% CI, 64-76%) in zone II, and 64% (95% CI, 58-71%) in zone III. The proportions of ownerless dogs to owned dogs were 1.1% (95% CI, 0-3.1%), 7.6% (95% CI, 0.7-16.5%), and 10.6% (95% CI, 1.6-19.1%) in the three study zones, respectively. Vaccination coverage in the three populations of owned dogs was 88% (95% CI, 84-92%) in zone I, 76% (95% CI, 71-81%) in zone II, and 70% (95% CI, 66-76%) in zone III. Participation of dog owners in the free campaign was high, and the number of inaccessible ownerless dogs was low. High levels of vaccination coverage could be achieved with parenteral mass vaccination. Regular parenteral vaccination campaigns to cover all of N'Djaména should be considered as an ethical way of preventing human rabies when post-exposure treatment is of limited availability and high in cost. PMID:14758434

Challenges in Estimating Vaccine Coverage in Refugee and Displaced Populations: Results From Household Surveys in Jordan and Lebanon

PubMed Central

Roberton, Timothy; Weiss, William; Doocy, Shannon

2017-01-01

Ensuring the sustained immunization of displaced persons is a key objective in humanitarian emergencies. Typically, humanitarian actors measure coverage of single vaccines following an immunization campaign; few measure routine coverage of all vaccines. We undertook household surveys of Syrian refugees in Jordan and Lebanon, outside of camps, using a mix of random and respondent-driven sampling, to measure coverage of all vaccinations included in the host country’s vaccine schedule. We analyzed the results with a critical eye to data limitations and implications for similar studies. Among households with a child aged 12–23 months, 55.1% of respondents in Jordan and 46.6% in Lebanon were able to produce the child’s EPI card. Only 24.5% of Syrian refugee children in Jordan and 12.5% in Lebanon were fully immunized through routine vaccination services (having received from non-campaign sources: measles, polio 1–3, and DPT 1–3 in Jordan and Lebanon, and BCG in Jordan). Respondents in Jordan (33.5%) and Lebanon (40.1%) reported difficulties obtaining child vaccinations. Our estimated immunization rates were lower than expected and raise serious concerns about gaps in vaccine coverage among Syrian refugees. Although our estimates likely under-represent true coverage, given the additional benefit of campaigns (not captured in our surveys), there is a clear need to increase awareness, accessibility, and uptake of immunization services. Current methods to measure vaccine coverage in refugee and displaced populations have limitations. To better understand health needs in such groups, we need research on: validity of recall methods, links between campaigns and routine immunization programs, and improved sampling of hard-to-reach populations. PMID:28805672

Serologic and Molecular Characteristics of Hepatitis B Virus among School Children in East Java, Indonesia

PubMed Central

Utsumi, Takako; Yano, Yoshihiko; Lusida, Maria Inge; Amin, Mochamad; Soetjipto; Hotta, Hak; Hayashi, Yoshitake

2010-01-01

Universal childhood hepatitis B vaccination was introduced in Indonesia in 1997; by 2008, coverage was estimated to be 78%. This study aimed to investigate the serologic status and virologic characteristics of hepatitis B virus (HBV) among the children in East Java. A total of 229 healthy children born during 1994–1999 were enrolled in this study. Overall, 3.1% were positive for hepatitis B surface antigen (HBsAg) and 23.6% were positive for antibody to HBsAg (anti-HBs). HBV DNA was detected in 5 of 222 HBsAg-negative carriers, which were suggested to be cases of occult HBV infection. A single amino substitution (T126I) in the S region was frequently found. HBV infection remains endemic, and the prevalence of anti-HBs remains insufficient among children in East Java, Indonesia. PMID:20595500

Evaluation of the measles, mumps and rubella vaccination catch-up campaign in England in 2013.

PubMed

Simone, Benedetto; Balasegaram, Sooria; Gobin, Maya; Anderson, Charlotte; Charlett, André; Coole, Louise; Maguire, Helen; Nichols, Tom; Rawlings, Chas; Ramsay, Mary; Oliver, Isabel

2014-08-06

In January-March 2013 in England, confirmed measles cases increased in children aged 10-16 years. In April-September 2013, the National Health System and Public Health England launched a national measles-mumps-rubella (MMR) campaign based on data from Child Health Information Systems (CHIS) estimating that approximately 8% in this age group were unvaccinated. We estimated coverage at baseline, and, of those unvaccinated (target), the proportion vaccinated up to 20/08/2013 (mid-point) to inform further public health action. We selected a sample of 6644 children aged 10-16 years using multistage sampling from those reported unvaccinated in CHIS at baseline and validated their records against GP records. We adjusted the CHIS MMR vaccine coverage estimates correcting by the proportion of vaccinated children obtained through sample validation. We validated 5179/6644 (78%) of the sample records. Coverage at baseline was estimated as 94.7% (95% confidence intervals, CI: 93.5-96.0%), lower in London (86.9%, 95%CI: 83.0-90.9%) than outside (96.1%, 95%CI 95.5-96.8%). The campaign reached 10.8% (95%CI: 7.0-14.6%) of the target population, lower in London (7.1%, 95%CI: 4.9-9.3) than in the rest of England (11.4%, 95%CI: 7.0-15.9%). Coverage increased by 0.5% up to 95.3% (95% CI: 94.1-96.4%) but an estimated 210,000 10-16 year old children remained unvaccinated nationally. Baseline MMR coverage was higher than previously reported and was estimated to have reached the 95% campaign objective at midpoint. Eleven per cent of the target population were vaccinated during the campaign, and may be underestimated, especially in London. No further national campaigns are needed but targeted local vaccination activities should be considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

Patient Experience Of Provider Refusal Of Medicaid Coverage And Its Implications.

PubMed

Bhandari, Neeraj; Shi, Yunfeng; Jung, Kyoungrae

2016-01-01

Previous studies show that many physicians do not accept new patients with Medicaid coverage, but no study has examined Medicaid enrollees' actual experience of provider refusal of their coverage and its implications. Using the 2012 National Health Interview Survey, we estimate provider refusal of health insurance coverage reported by 23,992 adults with continuous coverage for the past 12 months. We find that among Medicaid enrollees, 6.73% reported their coverage being refused by a provider in 2012, a rate higher than that in Medicare and private insurance by 4.07 (p<.01) and 3.68 (p<.001) percentage points, respectively. Refusal of Medicaid coverage is associated with delaying needed care, using emergency room (ER) as a usual source of care, and perceiving current coverage as worse than last year. In view of the Affordable Care Act's (ACA) Medicaid expansion, future studies should continue monitoring enrollees' experience of coverage refusal.

The mitochondrial genome of Malus domestica and the import-driven hypothesis of mitochondrial genome expansion in seed plants.

PubMed

Goremykin, Vadim V; Lockhart, Peter J; Viola, Roberto; Velasco, Riccardo

2012-08-01

Mitochondrial genomes of spermatophytes are the largest of all organellar genomes. Their large size has been attributed to various factors; however, the relative contribution of these factors to mitochondrial DNA (mtDNA) expansion remains undetermined. We estimated their relative contribution in Malus domestica (apple). The mitochondrial genome of apple has a size of 396 947 bp and a one to nine ratio of coding to non-coding DNA, close to the corresponding average values for angiosperms. We determined that 71.5% of the apple mtDNA sequence was highly similar to sequences of its nuclear DNA. Using nuclear gene exons, nuclear transposable elements and chloroplast DNA as markers of promiscuous DNA content in mtDNA, we estimated that approximately 20% of the apple mtDNA consisted of DNA sequences imported from other cell compartments, mostly from the nucleus. Similar marker-based estimates of promiscuous DNA content in the mitochondrial genomes of other species ranged between 21.2 and 25.3% of the total mtDNA length for grape, between 23.1 and 38.6% for rice, and between 47.1 and 78.4% for maize. All these estimates are conservative, because they underestimate the import of non-functional DNA. We propose that the import of promiscuous DNA is a core mechanism for mtDNA size expansion in seed plants. In apple, maize and grape this mechanism contributed far more to genome expansion than did homologous recombination. In rice the estimated contribution of both mechanisms was found to be similar. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

Two New Species of Homalometron (Digenea: Apocreadiidae) from Nearctic Freshwater Fundulids, Elucidation of the Life Cycle of H. cupuloris, and Molecular Phylogenetic Analysis of Some Congeners.

PubMed

Fayton, Thomas J; Curran, Stephen S; Andres, Michael J; Overstreet, Robin M; McAllister, Chris T

2016-02-01

Two species of digeneans belonging in Homalometron are described from Nearctic freshwater fundulid fishes: Homalometron robisoni n. sp. is described from the Blackstripe Topminnow, Fundulus notatus, from Oklahoma and Homalometron frocioneae n. sp. is described from the Banded Killifish, Fundulus diaphanus, from New York. Homalometron robisoni n. sp. differs from all congeners by having vitelline follicles that extend into the forebody, a feature that necessitates altering the generic diagnosis for the genus. Homalometron frocioneae n. sp. may be distinguished from North and Middle American congeners by the position of the intestinal bifurcation (relatively more posterior in the forebody than in other species) and tegumental spine coverage on the body (spines are absent from the posterior body extremity and on most of the dorsal surface). Comparison of ribosomal DNA (ITS 1 and 2 regions, 5.8S gene, and partial fragment of 28S gene) from the 2 new species and some congeners from the Western Hemisphere provided evidence for the validity of the 2 new species and affirmed a close relationship between H. robisoni n. sp. and Homalometron pallidum. Comparison of ribosomal DNA from newly collected Homalometron spp. and larval stages of an apocreadiid from brackish water hydrobiid snails (cercariae in rediae in Littoridinops palustris and metacercariae in L. palustris and Amnicola limosa ) from a tidal river in Mississippi revealed that larval stages represented Homalometron cupuloris. A phylogeny based on Bayesian inference analysis using partial 28S rDNA gene fragments from 14 species of Homalometron (all from the Western Hemisphere) and 1 megaperine and rooted by a second megaperine was conducted and produced a strongly supported phylogram that estimates the interrelationships among species. The estimated phylogeny suggests that ecological factors such as salinity and food web interactions between species of Homalometron, intermediate hosts, and fishes drive coevolutionary forces influencing speciation within Homalometron.

A superstructure-based electrochemical assay for signal-amplified detection of DNA methyltransferase activity.

PubMed

Zhang, Hui; Yang, Yin; Dong, Huilei; Cai, Chenxin

2016-12-15

DNA methyltransferase (MTase) activity is highly correlated with the occurrence and development of cancer. This work reports a superstructure-based electrochemical assay for signal-amplified detection of DNA MTase activity using M.SssI as an example. First, low-density coverage of DNA duplexes on the surface of the gold electrode was achieved by immobilized mercaptohexanol, followed by immobilization of DNA duplexes. The duplex can be cleaved by BstUI endonuclease in the absence of DNA superstructures. However, the cleavage is blocked after the DNA is methylated by M.SssI. The DNA superstructures are formed with the addition of helper DNA. By using an electroactive complex, RuHex, which can bind to DNA double strands, the activity of M.SssI can be quantitatively detected by differential pulse voltammetry. Due to the high site-specific cleavage by BstUI and signal amplification by the DNA superstructure, the biosensor can achieve ultrasensitive detection of DNA MTase activity down to 0.025U/mL. The method can be used for evaluation and screening of the inhibitors of MTase, and thus has potential in the discovery of methylation-related anticancer drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Parental employment, family structure, and child's health insurance.

PubMed

Rolett, A; Parker, J D; Heck, K E; Makuc, D M

2001-01-01

To examine the impact of family structure on the relationship between parental employment characteristics and employer-sponsored health insurance coverage among children with employed parents in the United States. National Health Interview Survey data for 1993-1995 was used to estimate proportions of children without employer-sponsored health insurance, by family structure, separately according to maternal and paternal employment characteristics. In addition, relative odds of being without employer-sponsored insurance were estimated, controlling for family structure and child's age, race, and poverty status. Children with 2 employed parents were more likely to have employer-sponsored health insurance coverage than children with 1 employed parent, even among children in 2-parent families. However, among children with employed parents, the percentage with employer-sponsored health insurance coverage varied widely, depending on the hours worked, employment sector, occupation, industry, and firm size. Employer-sponsored health insurance coverage for children is extremely variable, depending on employment characteristics and marital status of the parents.

Interactive computation of coverage regions for indoor wireless communication

NASA Astrophysics Data System (ADS)

Abbott, A. Lynn; Bhat, Nitin; Rappaport, Theodore S.

1995-12-01

This paper describes a system which assists in the strategic placement of rf base stations within buildings. Known as the site modeling tool (SMT), this system allows the user to display graphical floor plans and to select base station transceiver parameters, including location and orientation, interactively. The system then computes and highlights estimated coverage regions for each transceiver, enabling the user to assess the total coverage within the building. For single-floor operation, the user can choose between distance-dependent and partition- dependent path-loss models. Similar path-loss models are also available for the case of multiple floors. This paper describes the method used by the system to estimate coverage for both directional and omnidirectional antennas. The site modeling tool is intended to be simple to use by individuals who are not experts at wireless communication system design, and is expected to be very useful in the specification of indoor wireless systems.

Population-based coverage survey results following the mass drug administration of azithromycin for the treatment of trachoma in Amhara, Ethiopia.

PubMed

Astale, Tigist; Sata, Eshetu; Zerihun, Mulat; Nute, Andrew W; Stewart, Aisha E P; Gessese, Demelash; Ayenew, Gedefaw; Melak, Berhanu; Chanyalew, Melsew; Tadesse, Zerihun; Callahan, E Kelly; Nash, Scott D

2018-02-01

Trachoma is the leading infectious cause of blindness worldwide. In communities where the district level prevalence of trachomatous inflammation-follicular among children ages 1-9 years is ≥5%, WHO recommends annual mass drug administration (MDA) of antibiotics with the aim of at least 80% coverage. Population-based post-MDA coverage surveys are essential to understand the effectiveness of MDA programs, yet published reports from trachoma programs are rare. In the Amhara region of Ethiopia, a population-based MDA coverage survey was conducted 3 weeks following the 2016 MDA to estimate the zonal prevalence of self-reported drug coverage in all 10 administrative zones. Survey households were selected using a multi-stage cluster random sampling design and all individuals in selected households were presented with a drug sample and asked about taking the drug during the campaign. Zonal estimates were weighted and confidence intervals were calculated using survey procedures. Self-reported drug coverage was then compared with regional reported administrative coverage. Region-wide, 24,248 individuals were enumerated, of which, 20,942 (86.4%) individuals were present. The regional self-reported antibiotic coverage was 76.8% (95%Confidence Interval (CI):69.3-82.9%) in the population overall and 77.4% (95%CI = 65.7-85.9%) among children ages 1-9 years old. Zonal coverage ranged from 67.8% to 90.2%. Five out of 10 zones achieved a coverage >80%. In all zones, the reported administrative coverage was greater than 90% and was considerably higher than self-reported MDA coverage. Main reasons reported for MDA campaign non-attendance included being physically unable to get to MDA site (22.5%), traveling (20.6%), and not knowing about the campaign (21.0%). MDA refusal was low (2.8%) in this population. Although self-reported MDA coverage in Amhara was greater than 80% in some zones, programmatic improvements are warranted throughout Amhara to achieve higher coverage. These results will be used to enhance community mobilization and improve training for MDA distributors and supervisors to improve coverage in future MDAs.

Estimation of the herd protection of Haemophilus influenzae type b conjugate vaccine against radiologically confirmed pneumonia in children under 2 years old in Dhaka, Bangladesh.

PubMed

Chen, Wei-Ju; Moulton, Lawrence H; Saha, Samir K; Mahmud, Abdullah Al; Arifeen, Shams El; Baqui, Abdullah H

2014-02-12

Herd protection of Haemophilus influenzae type b (Hib) conjugate vaccine has been associated with excessive decrease of invasive Hib diseases, i.e., pneumonia and meningitis, with increased national or regional Hib vaccine coverage. Only a few studies have examined herd protection at the individual level and even less evidence is available from Asia. We examined Hib vaccine herd protection against radiologically confirmed pneumonia among children less than 2 years old. We incorporated data from a matched case-control study and a vaccine coverage survey in Dhaka, Bangladesh. Pneumonia cases (n=343) were confirmed by radiology. For each case, two controls with conditions other than pneumonia or meningitis were selected from the same hospital. Hib vaccine coverage was calculated as percentages of children who received at least 2 doses of Hib vaccine from a survey in the neighborhood centered on each case and control. Conditional logistic regression was fit to examine the association between vaccine coverage and risk of radiologically confirmed pneumonia. Neighborhood Hib vaccine coverage varied from 0% to 63.5% for cases and from 8.7% to 61.5% for controls, respectively. Cases were less likely to have neighborhood coverage higher than 20% (OR=0.49, 0.52, 0.55, and 0.69 for coverage 20-29%, 30-39%, 40-49%, and ≥50%, respectively) than coverage <20%, compared to controls, although the estimates for coverage 40-49% and ≥50% were not statistically significant. The study indicates that Hib vaccine may provide herd protection, even when the coverage is as low as 20-39%, in a low-income country. Asian countries should consider herd protection in implementing effective vaccine policy with limited resources. Copyright © 2014 Elsevier Ltd. All rights reserved.

Implications of employer coverage of contraception: Cost-effectiveness analysis of contraception coverage under an employer mandate.

PubMed

Canestaro, W; Vodicka, E; Downing, D; Trussell, J

2017-01-01

Mandatory employer-based insurance coverage of contraception in the US has been a controversial component of the Affordable Care Act (ACA). Prior research has examined the cost-effectiveness of contraception in general; however, no studies have developed a formal decision model in the context of the new ACA provisions. As such, this study aims to estimate the relative cost-effectiveness of insurance coverage of contraception under employer-sponsored insurance coverage taking into consideration newer regulations allowing for religious exemptions. A decision model was developed from the employer perspective to simulate pregnancy costs and outcomes associated with insurance coverage. Method-specific estimates of contraception failure rates, outcomes and costs were derived from the literature. Uptake by marital status and age was drawn from a nationally representative database. Providing no contraception coverage resulted in 33 more unintended pregnancies per 1000 women (95% confidence range: 22.4; 44.0). This subsequently significantly increased the number of unintended births and terminations. Total costs were higher among uninsured women owing to higher costs of pregnancy outcomes. The effect of no insurance was greatest on unmarried women 20-29 years old. Denying female employees' full coverage of contraceptives increases total costs from the employer perspective, as well as the total number of terminations. Insurance coverage was found to be significantly associated with women's choice of contraceptive method in a large nationally representative sample. Using a decision model to extrapolate to pregnancy outcomes, we found a large and statistically significant difference in unintended pregnancy and terminations. Denying women contraception coverage may have significant consequences for pregnancy outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Vaccination Coverage Disparities Between Foreign-Born and U.S.-Born Children Aged 19-35 Months, United States, 2010-2012.

PubMed

Varan, Aiden K; Rodriguez-Lainz, Alfonso; Hill, Holly A; Elam-Evans, Laurie D; Yankey, David; Li, Qian

2017-08-01

Healthy People 2020 targets high vaccination coverage among children. Although reductions in coverage disparities by race/ethnicity have been described, data by nativity are limited. The National Immunization Survey is a random-digit-dialed telephone survey that estimates vaccination coverage among U.S. children aged 19-35 months. We assessed coverage among 52,441 children from pooled 2010-2012 data for individual vaccines and the combined 4:3:1:3*:3:1:4 series (which includes ≥4 doses of diphtheria, tetanus, and acellular pertussis vaccine/diphtheria and tetanus toxoids vaccine/diphtheria, tetanus toxoids, and pertussis vaccine, ≥3 doses of poliovirus vaccine, ≥1 dose of measles-containing vaccine, ≥3 or ≥4 doses of Haemophilus influenzae type b vaccine (depending on product type of vaccine; denoted as 3* in the series name), ≥3 doses of hepatitis B vaccine, ≥1 dose of varicella vaccine, and ≥4 doses of pneumococcal conjugate vaccine). Coverage estimates controlling for sociodemographic factors and multivariable logistic regression modeling for 4:3:1:3*:3:1:4 series completion are presented. Significantly lower coverage among foreign-born children was detected for DTaP, hepatitis A, hepatitis B, Hib, pneumococcal conjugate, and rotavirus vaccines, and for the combined series. Series completion disparities persisted after control for demographic, access-to-care, poverty, and language effects. Substantial and potentially widening disparities in vaccination coverage exist among foreign-born children. Improved immunization strategies targeting this population and continued vaccination coverage monitoring by nativity are needed.

Transport networks and inequities in vaccination: remoteness shapes measles vaccine coverage and prospects for elimination across Africa.

PubMed

Metcalf, C J E; Tatem, A; Bjornstad, O N; Lessler, J; O'Reilly, K; Takahashi, S; Cutts, F; Grenfell, B T

2015-05-01

Measles vaccination is estimated to have averted 13·8 million deaths between 2000 and 2012. Persisting heterogeneity in coverage is a major contributor to continued measles mortality, and a barrier to measles elimination and introduction of rubella-containing vaccine. Our objective is to identify determinants of inequities in coverage, and how vaccine delivery must change to achieve elimination goals, which is a focus of the WHO Decade of Vaccines. We combined estimates of travel time to the nearest urban centre (⩾50 000 people) with vaccination data from Demographic Health Surveys to assess how remoteness affects coverage in 26 African countries. Building on a statistical mapping of coverage against age and geographical isolation, we quantified how modifying the rate and age range of vaccine delivery affects national coverage. Our scenario analysis considers increasing the rate of delivery of routine vaccination, increasing the target age range of routine vaccination, and enhanced delivery to remote areas. Geographical isolation plays a key role in defining vaccine inequity, with greater inequity in countries with lower measles vaccine coverage. Eliminating geographical inequities alone will not achieve thresholds for herd immunity, indicating that changes in delivery rate or age range of routine vaccination will be required. Measles vaccine coverage remains far below targets for herd immunity in many countries on the African continent and is likely to be inadequate for achieving rubella elimination. The impact of strategies such as increasing the upper age range eligible for routine vaccination should be considered.

Modelling the implications of moving towards universal coverage in Tanzania.

PubMed

Borghi, Josephine; Mtei, Gemini; Ally, Mariam

2012-03-01

A model was developed to assess the impact of possible moves towards universal coverage in Tanzania over a 15-year time frame. Three scenarios were considered: maintaining the current situation ('the status quo'); expanded health insurance coverage (the estimated maximum achievable coverage in the absence of premium subsidies, coverage restricted to those who can pay); universal coverage to all (government revenues used to pay the premiums for the poor). The model estimated the costs of delivering public health services and all health services to the population as a proportion of Gross Domestic Product (GDP), and forecast revenue from user fees and insurance premiums. Under the status quo, financial protection is provided to 10% of the population through health insurance schemes, with the remaining population benefiting from subsidized user charges in public facilities. Seventy-six per cent of the population would benefit from financial protection through health insurance under the expanded coverage scenario, and 100% of the population would receive such protection through a mix of insurance cover and government funding under the universal coverage scenario. The expanded and universal coverage scenarios have a significant effect on utilization levels, especially for public outpatient care. Universal coverage would require an initial doubling in the proportion of GDP going to the public health system. Government health expenditure would increase to 18% of total government expenditure. The results are sensitive to the cost of health system strengthening, the level of real GDP growth, provider reimbursement rates and administrative costs. Promoting greater cross-subsidization between insurance schemes would provide sufficient resources to finance universal coverage. Alternately, greater tax funding for health could be generated through an increase in the rate of Value-Added Tax (VAT) or expanding the income tax base. The feasibility and sustainability of efforts to promote universal coverage will depend on the ability of the system to contain costs.

Estimating Premium and Out-of-Pocket Outlays Under All Child Dental Coverage Options in the Federally Facilitated Marketplace.

PubMed

Vujicic, Marko; Yarbrough, Cassandra

2017-03-01

To estimate premium and out-of-pocket costs for child dental care services under various dental coverage options offered within the federally facilitated marketplace. We estimated premium and out-of-pocket costs for child dental care services for 12 patient profiles, which vary by dental care use and spending. We did this for 1039 medical plans that include child dental coverage, 2703 medical plans that do not include child dental coverage, and 583 stand-alone dental plans for the 2015 plan year. Our analysis is based on plan data from the Center for Consumer Information and Insurance Oversight and Data.HealthCare.Gov. On average, expected total financial outlays for child dental care services were lower when dental coverage was embedded within a medical plan compared with the alternative of a stand-alone dental plan. The difference, however, in average expected out-of-pocket spending varied significantly for our 12 patient profiles. Older children who are very high users of dental care, for example, have lower expected out-of-pocket costs under a stand-alone dental plan. For the vast majority of other age groups and dental care use profiles, the reverse holds. Our results show that embedding dental coverage within medical plans, on average, results in lower total financial outlays for child beneficiaries. Although our results are specific to the federally facilitated marketplace, they hold lessons for both state-based marketplaces and the general private health insurance and dental benefits market, as well. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Undernutrition, poor feeding practices, and low coverage of key nutrition interventions.

PubMed

Lutter, Chessa K; Daelmans, Bernadette M E G; de Onis, Mercedes; Kothari, Monica T; Ruel, Marie T; Arimond, Mary; Deitchler, Megan; Dewey, Kathryn G; Blössner, Monika; Borghi, Elaine

2011-12-01

To estimate the global burden of malnutrition and highlight data on child feeding practices and coverage of key nutrition interventions. Linear mixed-effects modeling was used to estimate prevalence rates and numbers of underweight and stunted children according to United Nations region from 1990 to 2010 by using surveys from 147 countries. Indicators of infant and young child feeding practices and intervention coverage were calculated from Demographic and Health Survey data from 46 developing countries between 2002 and 2008. In 2010, globally, an estimated 27% (171 million) of children younger than 5 years were stunted and 16% (104 million) were underweight. Africa and Asia have more severe burdens of undernutrition, but the problem persists in some Latin American countries. Few children in the developing world benefit from optimal breastfeeding and complementary feeding practices. Fewer than half of infants were put to the breast within 1 hour of birth, and 36% of infants younger than 6 months were exclusively breastfed. Fewer than one-third of 6- to 23-month-old children met the minimum criteria for dietary diversity, and only ∼50% received the minimum number of meals. Although effective health-sector-based interventions for tackling childhood undernutrition are known, intervention-coverage data are available for only a small proportion of them and reveal mostly low coverage. Undernutrition continues to be high and progress toward reaching Millennium Development Goal 1 has been slow. Previously unrecognized extremely poor breastfeeding and complementary feeding practices and lack of comprehensive data on intervention coverage require urgent action to improve child nutrition.

Measuring Coverage in MNCH: Tracking Progress in Health for Women and Children Using DHS and MICS Household Surveys

PubMed Central

Hancioglu, Attila; Arnold, Fred

2013-01-01

Household surveys are the primary data source of coverage indicators for children and women for most developing countries. Most of this information is generated by two global household survey programmes—the USAID-supported Demographic and Health Surveys (DHS) and the UNICEF-supported Multiple Indicator Cluster Surveys (MICS). In this review, we provide an overview of these two programmes, which cover a wide range of child and maternal health topics and provide estimates of many Millennium Development Goal indicators, as well as estimates of the indicators for the Countdown to 2015 initiative and the Commission on Information and Accountability for Women's and Children's Health. MICS and DHS collaborate closely and work through interagency processes to ensure that survey tools are harmonized and comparable as far as possible, but we highlight differences between DHS and MICS in the population covered and the reference periods used to measure coverage. These differences need to be considered when comparing estimates of reproductive, maternal, newborn, and child health indicators across countries and over time and we discuss the implications of these differences for coverage measurement. Finally, we discuss the need for survey planners and consumers of survey results to understand the strengths, limitations, and constraints of coverage measurements generated through household surveys, and address some technical issues surrounding sampling and quality control. We conclude that, although much effort has been made to improve coverage measurement in household surveys, continuing efforts are needed, including further research to improve and refine survey methods and analytical techniques. PMID:23667333

Subsidies and the Demand for Individual Health Insurance in California

PubMed Central

Susan Marquis, M; Buntin, Melinda Beeuwkes; Escarce, José J; Kapur, Kanika; Yegian, Jill M

2004-01-01

Objective To estimate the effect of changes in premiums for individual insurance on decisions to purchase individual insurance and how this price response varies among subgroups of the population. Data Source Survey responses from the Current Population Survey (), the Survey of Income and Program Participation (), the National Health Interview Survey (), and data about premiums and plans offered in the individual insurance market in California, 1996–2001. Study Design A logit model was used to estimate the decisions to purchase individual insurance by families without access to group insurance. This was modeled as a function of premiums, controlling for family characteristics and other characteristics of the market. A multinomial model was used to estimate the choice between group coverage, individual coverage, and remaining uninsured for workers offered group coverage as a function of premiums for individual insurance and out-of-pocket costs of group coverage. Principal Findings The elasticity of demand for individual insurance by those without access to group insurance is about −.2 to −.4, as has been found in earlier studies. However, there are substantial differences in price responses among subgroups with low-income, young, and self-employed families showing the greatest response. Among workers offered group insurance, a decrease in individual premiums has very small effects on the choice to purchase individual coverage versus group coverage. Conclusions Subsidy programs may make insurance more affordable for some families, but even sizeable subsidies are unlikely to solve the problem of the uninsured. We do not find evidence that subsidies to individual insurance will produce an unraveling of the employer-based health insurance system. PMID:15333122

Dental Care Coverage and Use: Modeling Limitations and Opportunities

PubMed Central

Moeller, John F.; Chen, Haiyan

2014-01-01

Objectives. We examined why older US adults without dental care coverage and use would have lower use rates if offered coverage than do those who currently have coverage. Methods. We used data from the 2008 Health and Retirement Study to estimate a multinomial logistic model to analyze the influence of personal characteristics in the grouping of older US adults into those with and those without dental care coverage and dental care use. Results. Compared with persons with no coverage and no dental care use, users of dental care with coverage were more likely to be younger, female, wealthier, college graduates, married, in excellent or very good health, and not missing all their permanent teeth. Conclusions. Providing dental care coverage to uninsured older US adults without use will not necessarily result in use rates similar to those with prior coverage and use. We have offered a model using modifiable factors that may help policy planners facilitate programs to increase dental care coverage uptake and use. PMID:24328635

Dental Care Coverage and Use: Modeling Limitations and Opportunities

PubMed Central

Moeller, John F.; Chen, Haiyan

2014-01-01

Objectives. We examined why older US adults without dental care coverage and use would have lower use rates if offered coverage than do those who currently have coverage. Methods. We used data from the 2008 Health and Retirement Study to estimate a multinomial logistic model to analyze the influence of personal characteristics in the grouping of older US adults into those with and those without dental care coverage and dental care use. Results. Compared with persons with no coverage and no dental care use, users of dental care with coverage were more likely to be younger, female, wealthier, college graduates, married, in excellent or very good health, and not missing all their permanent teeth. Conclusions. Providing dental care coverage to uninsured older US adults without use will not necessarily result in use rates similar to those with prior coverage and use. We have offered a model using modifiable factors that may help policy planners facilitate programs to increase dental care coverage uptake and use. PMID:25343171

Global yellow fever vaccination coverage from 1970 to 2016: an adjusted retrospective analysis.

PubMed

Shearer, Freya M; Moyes, Catherine L; Pigott, David M; Brady, Oliver J; Marinho, Fatima; Deshpande, Aniruddha; Longbottom, Joshua; Browne, Annie J; Kraemer, Moritz U G; O'Reilly, Kathleen M; Hombach, Joachim; Yactayo, Sergio; de Araújo, Valdelaine E M; da Nóbrega, Aglaêr A; Mosser, Jonathan F; Stanaway, Jeffrey D; Lim, Stephen S; Hay, Simon I; Golding, Nick; Reiner, Robert C

2017-11-01

Substantial outbreaks of yellow fever in Angola and Brazil in the past 2 years, combined with global shortages in vaccine stockpiles, highlight a pressing need to assess present control strategies. The aims of this study were to estimate global yellow fever vaccination coverage from 1970 through to 2016 at high spatial resolution and to calculate the number of individuals still requiring vaccination to reach population coverage thresholds for outbreak prevention. For this adjusted retrospective analysis, we compiled data from a range of sources (eg, WHO reports and health-service-provider registeries) reporting on yellow fever vaccination activities between May 1, 1939, and Oct 29, 2016. To account for uncertainty in how vaccine campaigns were targeted, we calculated three population coverage values to encompass alternative scenarios. We combined these data with demographic information and tracked vaccination coverage through time to estimate the proportion of the population who had ever received a yellow fever vaccine for each second level administrative division across countries at risk of yellow fever virus transmission from 1970 to 2016. Overall, substantial increases in vaccine coverage have occurred since 1970, but notable gaps still exist in contemporary coverage within yellow fever risk zones. We estimate that between 393·7 million and 472·9 million people still require vaccination in areas at risk of yellow fever virus transmission to achieve the 80% population coverage threshold recommended by WHO; this represents between 43% and 52% of the population within yellow fever risk zones, compared with between 66% and 76% of the population who would have required vaccination in 1970. Our results highlight important gaps in yellow fever vaccination coverage, can contribute to improved quantification of outbreak risk, and help to guide planning of future vaccination efforts and emergency stockpiling. The Rhodes Trust, Bill & Melinda Gates Foundation, the Wellcome Trust, the National Library of Medicine of the National Institutes of Health, the European Union's Horizon 2020 research and innovation programme. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

The accuracy of mother's reports about their children's vaccination status.

PubMed

Gareaballah, E T; Loevinsohn, B P

1989-01-01

Estimates of measles vaccination coverage in the Sudan vary on average by 23 percentage points, depending on whether or not information supplied by mothers who have lost their children's vaccination cards is included. To determine the accuracy of mother's reports, we collected data during four large coverage surveys in which illiterate mothers with vaccination cards were asked about their children's vaccination status and their answers were compared with the information given on the cards. Mothers' replies were very accurate. For example, for measles vaccination, the data supplied were both sensitive (87%) and specific (79%) compared with those on the vaccination cards. For both DPT and measles vaccination, accurate estimates of the true coverage rates could therefore be obtained by relying solely on mothers' reports. Within +/- 1 month, 78% of the women knew the age at which their children had received their first dose of poliovaccine. Ignoring mothers' reports of their children's vaccination status could therefore result in serious underestimates of the true vaccination coverage. A simple method of dealing with the problem posed by lost vaccination cards during coverage surveys is also suggested.

PWHATSHAP: efficient haplotyping for future generation sequencing.

PubMed

Bracciali, Andrea; Aldinucci, Marco; Patterson, Murray; Marschall, Tobias; Pisanti, Nadia; Merelli, Ivan; Torquati, Massimo

2016-09-22

Haplotype phasing is an important problem in the analysis of genomics information. Given a set of DNA fragments of an individual, it consists of determining which one of the possible alleles (alternative forms of a gene) each fragment comes from. Haplotype information is relevant to gene regulation, epigenetics, genome-wide association studies, evolutionary and population studies, and the study of mutations. Haplotyping is currently addressed as an optimisation problem aiming at solutions that minimise, for instance, error correction costs, where costs are a measure of the confidence in the accuracy of the information acquired from DNA sequencing. Solutions have typically an exponential computational complexity. WHATSHAP is a recent optimal approach which moves computational complexity from DNA fragment length to fragment overlap, i.e., coverage, and is hence of particular interest when considering sequencing technology's current trends that are producing longer fragments. Given the potential relevance of efficient haplotyping in several analysis pipelines, we have designed and engineered PWHATSHAP, a parallel, high-performance version of WHATSHAP. PWHATSHAP is embedded in a toolkit developed in Python and supports genomics datasets in standard file formats. Building on WHATSHAP, PWHATSHAP exhibits the same complexity exploring a number of possible solutions which is exponential in the coverage of the dataset. The parallel implementation on multi-core architectures allows for a relevant reduction of the execution time for haplotyping, while the provided results enjoy the same high accuracy as that provided by WHATSHAP, which increases with coverage. Due to its structure and management of the large datasets, the parallelisation of WHATSHAP posed demanding technical challenges, which have been addressed exploiting a high-level parallel programming framework. The result, PWHATSHAP, is a freely available toolkit that improves the efficiency of the analysis of genomics information.

Environmental DNA (eDNA): A tool for quantifying the abundant but elusive round goby (Neogobius melanostomus)

USGS Publications Warehouse

Nevers, Meredith; Byappanahalli, Muruleedhara; Morris, Charles C.; Shively, Dawn; Przybyla-Kelly, Katarzyna; Spoljaric, Ashley M.; Dickey, Joshua; Roseman, Edward

2018-01-01

Environmental DNA (eDNA) is revolutionizing biodiversity monitoring, occupancy estimates, and real-time detections of invasive species. In the Great Lakes, the round goby (Neogobius melanostomus), an invasive benthic fish from the Black Sea, has spread to encompass all five lakes and many tributaries, outcompeting or consuming native species; however, estimates of round goby abundance are confounded by behavior and habitat preference, which impact reliable methods for estimating their population. By integrating eDNA into round goby monitoring, improved estimates of biomass may be obtainable. We conducted mesocosm experiments to estimate rates of goby DNA shedding and decay. Further, we compared eDNA with several methods of traditional field sampling to compare its use as an alternative/complementary monitoring method. Environmental DNA decay was comparable to other fish species, and first-order decay was lower at 12°C (k = 0.043) than at 19°C (k = 0.058). Round goby eDNA was routinely detected in known invaded sites of Lake Michigan and its tributaries (range log10 4.8–6.2 CN/L), but not upstream of an artificial fish barrier. Traditional techniques (mark-recapture, seining, trapping) in Lakes Michigan and Huron resulted in fewer, more variable detections than eDNA, but trapping and eDNA were correlated (Pearson R = 0.87). Additional field testing will help correlate round goby abundance with eDNA, providing insight on its role as a prey fish and its impact on food webs.

Environmental DNA (eDNA): A tool for quantifying the abundant but elusive round goby (Neogobius melanostomus)

PubMed Central

Byappanahalli, Murulee N.; Morris, Charles C.; Shively, Dawn; Przybyla-Kelly, Kasia; Spoljaric, Ashley M.; Dickey, Joshua; Roseman, Edward F.

2018-01-01

Environmental DNA (eDNA) is revolutionizing biodiversity monitoring, occupancy estimates, and real-time detections of invasive species. In the Great Lakes, the round goby (Neogobius melanostomus), an invasive benthic fish from the Black Sea, has spread to encompass all five lakes and many tributaries, outcompeting or consuming native species; however, estimates of round goby abundance are confounded by behavior and habitat preference, which impact reliable methods for estimating their population. By integrating eDNA into round goby monitoring, improved estimates of biomass may be obtainable. We conducted mesocosm experiments to estimate rates of goby DNA shedding and decay. Further, we compared eDNA with several methods of traditional field sampling to compare its use as an alternative/complementary monitoring method. Environmental DNA decay was comparable to other fish species, and first-order decay was lower at 12°C (k = 0.043) than at 19°C (k = 0.058). Round goby eDNA was routinely detected in known invaded sites of Lake Michigan and its tributaries (range log10 4.8–6.2 CN/L), but not upstream of an artificial fish barrier. Traditional techniques (mark-recapture, seining, trapping) in Lakes Michigan and Huron resulted in fewer, more variable detections than eDNA, but trapping and eDNA were correlated (Pearson R = 0.87). Additional field testing will help correlate round goby abundance with eDNA, providing insight on its role as a prey fish and its impact on food webs. PMID:29357382

Environmental DNA (eDNA): A tool for quantifying the abundant but elusive round goby (Neogobius melanostomus).

PubMed

Nevers, Meredith B; Byappanahalli, Murulee N; Morris, Charles C; Shively, Dawn; Przybyla-Kelly, Kasia; Spoljaric, Ashley M; Dickey, Joshua; Roseman, Edward F

2018-01-01

Environmental DNA (eDNA) is revolutionizing biodiversity monitoring, occupancy estimates, and real-time detections of invasive species. In the Great Lakes, the round goby (Neogobius melanostomus), an invasive benthic fish from the Black Sea, has spread to encompass all five lakes and many tributaries, outcompeting or consuming native species; however, estimates of round goby abundance are confounded by behavior and habitat preference, which impact reliable methods for estimating their population. By integrating eDNA into round goby monitoring, improved estimates of biomass may be obtainable. We conducted mesocosm experiments to estimate rates of goby DNA shedding and decay. Further, we compared eDNA with several methods of traditional field sampling to compare its use as an alternative/complementary monitoring method. Environmental DNA decay was comparable to other fish species, and first-order decay was lower at 12°C (k = 0.043) than at 19°C (k = 0.058). Round goby eDNA was routinely detected in known invaded sites of Lake Michigan and its tributaries (range log10 4.8-6.2 CN/L), but not upstream of an artificial fish barrier. Traditional techniques (mark-recapture, seining, trapping) in Lakes Michigan and Huron resulted in fewer, more variable detections than eDNA, but trapping and eDNA were correlated (Pearson R = 0.87). Additional field testing will help correlate round goby abundance with eDNA, providing insight on its role as a prey fish and its impact on food webs.

Exploring the relationship between population density and maternal health coverage.

PubMed

Hanlon, Michael; Burstein, Roy; Masters, Samuel H; Zhang, Raymond

2012-11-21

Delivering health services to dense populations is more practical than to dispersed populations, other factors constant. This engenders the hypothesis that population density positively affects coverage rates of health services. This hypothesis has been tested indirectly for some services at a local level, but not at a national level. We use cross-sectional data to conduct cross-country, OLS regressions at the national level to estimate the relationship between population density and maternal health coverage. We separately estimate the effect of two measures of density on three population-level coverage rates (6 tests in total). Our coverage indicators are the fraction of the maternal population completing four antenatal care visits and the utilization rates of both skilled birth attendants and in-facility delivery. The first density metric we use is the percentage of a population living in an urban area. The second metric, which we denote as a density score, is a relative ranking of countries by population density. The score's calculation discounts a nation's uninhabited territory under the assumption those areas are irrelevant to service delivery. We find significantly positive relationships between our maternal health indicators and density measures. On average, a one-unit increase in our density score is equivalent to a 0.2% increase in coverage rates. Countries with dispersed populations face higher burdens to achieve multinational coverage targets such as the United Nations' Millennial Development Goals.

Using known populations of pronghorn to evaluate sampling plans and estimators

USGS Publications Warehouse

Kraft, K.M.; Johnson, D.H.; Samuelson, J.M.; Allen, S.H.

1995-01-01

Although sampling plans and estimators of abundance have good theoretical properties, their performance in real situations is rarely assessed because true population sizes are unknown. We evaluated widely used sampling plans and estimators of population size on 3 known clustered distributions of pronghorn (Antilocapra americana). Our criteria were accuracy of the estimate, coverage of 95% confidence intervals, and cost. Sampling plans were combinations of sampling intensities (16, 33, and 50%), sample selection (simple random sampling without replacement, systematic sampling, and probability proportional to size sampling with replacement), and stratification. We paired sampling plans with suitable estimators (simple, ratio, and probability proportional to size). We used area of the sampling unit as the auxiliary variable for the ratio and probability proportional to size estimators. All estimators were nearly unbiased, but precision was generally low (overall mean coefficient of variation [CV] = 29). Coverage of 95% confidence intervals was only 89% because of the highly skewed distribution of the pronghorn counts and small sample sizes, especially with stratification. Stratification combined with accurate estimates of optimal stratum sample sizes increased precision, reducing the mean CV from 33 without stratification to 25 with stratification; costs increased 23%. Precise results (mean CV = 13) but poor confidence interval coverage (83%) were obtained with simple and ratio estimators when the allocation scheme included all sampling units in the stratum containing most pronghorn. Although areas of the sampling units varied, ratio estimators and probability proportional to size sampling did not increase precision, possibly because of the clumped distribution of pronghorn. Managers should be cautious in using sampling plans and estimators to estimate abundance of aggregated populations.

Environmental DNA as a ‘Snapshot’ of Fish Distribution: A Case Study of Japanese Jack Mackerel in Maizuru Bay, Sea of Japan

PubMed Central

Takahashi, Kohji; Sawada, Hideki; Murakami, Hiroaki; Tsuji, Satsuki; Hashizume, Hiroki; Kubonaga, Shou; Horiuchi, Tomoya; Hongo, Masamichi; Nishida, Jo; Okugawa, Yuta; Fujiwara, Ayaka; Fukuda, Miho; Hidaka, Shunsuke; Suzuki, Keita W.; Miya, Masaki; Araki, Hitoshi; Yamanaka, Hiroki; Maruyama, Atsushi; Miyashita, Kazushi; Masuda, Reiji; Minamoto, Toshifumi; Kondoh, Michio

2016-01-01

Recent studies in streams and ponds have demonstrated that the distribution and biomass of aquatic organisms can be estimated by detection and quantification of environmental DNA (eDNA). In more open systems such as seas, it is not evident whether eDNA can represent the distribution and biomass of aquatic organisms because various environmental factors (e.g., water flow) are expected to affect eDNA distribution and concentration. To test the relationships between the distribution of fish and eDNA, we conducted a grid survey in Maizuru Bay, Sea of Japan, and sampled surface and bottom waters while monitoring biomass of the Japanese jack mackerel (Trachurus japonicus) using echo sounder technology. A linear model showed a high R2 value (0.665) without outlier data points, and the association between estimated eDNA concentrations from the surface water samples and echo intensity was significantly positive, suggesting that the estimated spatial variation in eDNA concentration can reflect the local biomass of the jack mackerel. We also found that a best-fit model included echo intensity obtained within 10–150 m from water sampling sites, indicating that the estimated eDNA concentration most likely reflects fish biomass within 150 m in the bay. Although eDNA from a wholesale fish market partially affected eDNA concentration, we conclude that eDNA generally provides a ‘snapshot’ of fish distribution and biomass in a large area. Further studies in which dynamics of eDNA under field conditions (e.g., patterns of release, degradation, and diffusion of eDNA) are taken into account will provide a better estimate of fish distribution and biomass based on eDNA. PMID:26933889

Estimates of the timing of reductions in genital warts and high grade cervical intraepithelial neoplasia after onset of human papillomavirus (HPV) vaccination in the United States.

PubMed

Chesson, Harrell W; Ekwueme, Donatus U; Saraiya, Mona; Dunne, Eileen F; Markowitz, Lauri E

2013-08-20

The objective of this study was to estimate the number of years after onset of a quadrivalent HPV vaccination program before notable reductions in genital warts and cervical intraepithelial neoplasia (CIN) will occur in teenagers and young adults in the United States. We applied a previously published model of HPV vaccination in the United States and focused on the timing of reductions in genital warts among both sexes and reductions in CIN 2/3 among females. Using different coverage scenarios, the lowest being consistent with current 3-dose coverage in the United States, we estimated the number of years before reductions of 10%, 25%, and 50% would be observed after onset of an HPV vaccination program for ages 12-26 years. The model suggested female-only HPV vaccination in the intermediate coverage scenario will result in a 10% reduction in genital warts within 2-4 years for females aged 15-19 years and a 10% reduction in CIN 2/3 among females aged 20-29 years within 7-11 years. Coverage had a major impact on when reductions would be observed. For example, in the higher coverage scenario a 25% reduction in CIN2/3 would be observed with 8 years compared with 15 years in the lower coverage scenario. Our model provides estimates of the potential timing and magnitude of the impact of HPV vaccination on genital warts and CIN 2/3 at the population level in the United States. Notable, population-level impacts of HPV vaccination on genital warts and CIN 2/3 can occur within a few years after onset of vaccination, particularly among younger age groups. Our results are generally consistent with early reports of declines in genital warts among youth. Published by Elsevier Ltd.

Determination of a Screening Metric for High Diversity DNA Libraries.

PubMed

Guido, Nicholas J; Handerson, Steven; Joseph, Elaine M; Leake, Devin; Kung, Li A

2016-01-01

The fields of antibody engineering, enzyme optimization and pathway construction rely increasingly on screening complex variant DNA libraries. These highly diverse libraries allow researchers to sample a maximized sequence space; and therefore, more rapidly identify proteins with significantly improved activity. The current state of the art in synthetic biology allows for libraries with billions of variants, pushing the limits of researchers' ability to qualify libraries for screening by measuring the traditional quality metrics of fidelity and diversity of variants. Instead, when screening variant libraries, researchers typically use a generic, and often insufficient, oversampling rate based on a common rule-of-thumb. We have developed methods to calculate a library-specific oversampling metric, based on fidelity, diversity, and representation of variants, which informs researchers, prior to screening the library, of the amount of oversampling required to ensure that the desired fraction of variant molecules will be sampled. To derive this oversampling metric, we developed a novel alignment tool to efficiently measure frequency counts of individual nucleotide variant positions using next-generation sequencing data. Next, we apply a method based on the "coupon collector" probability theory to construct a curve of upper bound estimates of the sampling size required for any desired variant coverage. The calculated oversampling metric will guide researchers to maximize their efficiency in using highly variant libraries.

Status and prospects of DNA barcoding in medically important parasites and vectors.

PubMed

Ondrejicka, Danielle A; Locke, Sean A; Morey, Kevin; Borisenko, Alex V; Hanner, Robert H

2014-12-01

For over 10 years, DNA barcoding has been used to identify specimens and discern species. Its potential benefits in parasitology were recognized early, but its utility and uptake remain unclear. Here we review studies using DNA barcoding in parasites and vectors affecting humans and find that the technique is accurate (accords with author identifications based on morphology or other markers) in 94-95% of cases, although aspects of DNA barcoding (vouchering, marker implicated) have often been misunderstood. In a newly compiled checklist of parasites, vectors, and hazards, barcodes are available for 43% of all 1403 species and for more than half of 429 species of greater medical importance. This is encouraging coverage that would improve with an active campaign targeting parasites and vectors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Vaccination and All-Cause Child Mortality From 1985 to 2011: Global Evidence From the Demographic and Health Surveys

PubMed Central

McGovern, Mark E.; Canning, David

2015-01-01

Based on models with calibrated parameters for infection, case fatality rates, and vaccine efficacy, basic childhood vaccinations have been estimated to be highly cost effective. We estimated the association of vaccination with mortality directly from survey data. Using 149 cross-sectional Demographic and Health Surveys, we determined the relationship between vaccination coverage and the probability of dying between birth and 5 years of age at the survey cluster level. Our data included approximately 1 million children in 68,490 clusters from 62 countries. We considered the childhood measles, bacillus Calmette-Guérin, diphtheria-pertussis-tetanus, polio, and maternal tetanus vaccinations. Using modified Poisson regression to estimate the relative risk of child mortality in each cluster, we also adjusted for selection bias that resulted from the vaccination status of dead children not being reported. Childhood vaccination, and in particular measles and tetanus vaccination, is associated with substantial reductions in childhood mortality. We estimated that children in clusters with complete vaccination coverage have a relative risk of mortality that is 0.73 (95% confidence interval: 0.68, 0.77) times that of children in a cluster with no vaccinations. Although widely used, basic vaccines still have coverage rates well below 100% in many countries, and our results emphasize the effectiveness of increasing coverage rates in order to reduce child mortality. PMID:26453618

Sequence analysis of the genome of carnation (Dianthus caryophyllus L.).

PubMed

Yagi, Masafumi; Kosugi, Shunichi; Hirakawa, Hideki; Ohmiya, Akemi; Tanase, Koji; Harada, Taro; Kishimoto, Kyutaro; Nakayama, Masayoshi; Ichimura, Kazuo; Onozaki, Takashi; Yamaguchi, Hiroyasu; Sasaki, Nobuhiro; Miyahara, Taira; Nishizaki, Yuzo; Ozeki, Yoshihiro; Nakamura, Noriko; Suzuki, Takamasa; Tanaka, Yoshikazu; Sato, Shusei; Shirasawa, Kenta; Isobe, Sachiko; Miyamura, Yoshinori; Watanabe, Akiko; Nakayama, Shinobu; Kishida, Yoshie; Kohara, Mitsuyo; Tabata, Satoshi

2014-06-01

The whole-genome sequence of carnation (Dianthus caryophyllus L.) cv. 'Francesco' was determined using a combination of different new-generation multiplex sequencing platforms. The total length of the non-redundant sequences was 568,887,315 bp, consisting of 45,088 scaffolds, which covered 91% of the 622 Mb carnation genome estimated by k-mer analysis. The N50 values of contigs and scaffolds were 16,644 bp and 60,737 bp, respectively, and the longest scaffold was 1,287,144 bp. The average GC content of the contig sequences was 36%. A total of 1050, 13, 92 and 143 genes for tRNAs, rRNAs, snoRNA and miRNA, respectively, were identified in the assembled genomic sequences. For protein-encoding genes, 43 266 complete and partial gene structures excluding those in transposable elements were deduced. Gene coverage was ∼ 98%, as deduced from the coverage of the core eukaryotic genes. Intensive characterization of the assigned carnation genes and comparison with those of other plant species revealed characteristic features of the carnation genome. The results of this study will serve as a valuable resource for fundamental and applied research of carnation, especially for breeding new carnation varieties. Further information on the genomic sequences is available at http://carnation.kazusa.or.jp. © The Author 2013. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Report on noninvasive prenatal testing: classical and alternative approaches.

PubMed

Pantiukh, Kateryna S; Chekanov, Nikolay N; Zaigrin, Igor V; Zotov, Alexei M; Mazur, Alexander M; Prokhortchouk, Egor B

2016-01-01

Concerns of traditional prenatal aneuploidy testing methods, such as low accuracy of noninvasive and health risks associated with invasive procedures, were overcome with the introduction of novel noninvasive methods based on genetics (NIPT). These were rapidly adopted into clinical practice in many countries after a series of successful trials of various independent submethods. Here we present results of own NIPT trial carried out in Moscow, Russia. 1012 samples were subjected to the method aimed at measuring chromosome coverage by massive parallel sequencing. Two alternative approaches are ascertained: one based on maternal/fetal differential methylation and another based on allelic difference. While the former failed to provide stable results, the latter was found to be promising and worthy of conducting a large-scale trial. One critical point in any NIPT approach is the determination of fetal cell-free DNA fraction, which dictates the reliability of obtained results for a given sample. We show that two different chromosome Y representation measures-by real-time PCR and by whole-genome massive parallel sequencing-are practically interchangeable (r=0.94). We also propose a novel method based on maternal/fetal allelic difference which is applicable in pregnancies with fetuses of either sex. Even in its pilot form it correlates well with chromosome Y coverage estimates (r=0.74) and can be further improved by increasing the number of polymorphisms.

Effectiveness of VIA, Pap, and HPV DNA Testing in a Cervical Cancer Screening Program in a Peri-Urban Community in Andhra Pradesh, India

PubMed Central

Gravitt, Patti E.; Paul, Proma; Katki, Hormuzd A.; Vendantham, Haripriya; Ramakrishna, Gayatri; Sudula, Mrudula; Kalpana, Basany; Ronnett, Brigitte M.; Vijayaraghavan, K.; Shah, Keerti V.

2010-01-01

Background While many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness. Methods and Findings A population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity  =  78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures. Conclusions We conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality. PMID:21060889

Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast cancer.

PubMed

Hartmaier, R J; Trabucco, S E; Priedigkeit, N; Chung, J H; Parachoniak, C A; Vanden Borre, P; Morley, S; Rosenzweig, M; Gay, L M; Goldberg, M E; Suh, J; Ali, S M; Ross, J; Leyland-Jones, B; Young, B; Williams, C; Park, B; Tsai, M; Haley, B; Peguero, J; Callahan, R D; Sachelarie, I; Cho, J; Atkinson, J M; Bahreini, A; Nagle, A M; Puhalla, S L; Watters, R J; Erdogan-Yildirim, Z; Cao, L; Oesterreich, S; Mathew, A; Lucas, P C; Davidson, N E; Brufsky, A M; Frampton, G M; Stephens, P J; Chmielecki, J; Lee, A V

2018-04-01

Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287-395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3' partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Collectively, these data indicate that N-terminal ESR1 fusions involving exons 6-7 are a recurrent driver of endocrine therapy resistance and are impervious to ER-targeted therapies.

Comparison and quantitative verification of mapping algorithms for whole genome bisulfite sequencing

USDA-ARS?s Scientific Manuscript database

Coupling bisulfite conversion with next-generation sequencing (Bisulfite-seq) enables genome-wide measurement of DNA methylation, but poses unique challenges for mapping. However, despite a proliferation of Bisulfite-seq mapping tools, no systematic comparison of their genomic coverage and quantitat...

DNA barcodes for two scale insect families, mealybugs (Hemiptera: Pseudococcidae) and armored scales (Hemiptera: Diaspididae).

PubMed

Park, D-S; Suh, S-J; Hebert, P D N; Oh, H-W; Hong, K-J

2011-08-01

Although DNA barcode coverage has grown rapidly for many insect orders, there are some groups, such as scale insects, where sequence recovery has been difficult. However, using a recently developed primer set, we recovered barcode records from 373 specimens, providing coverage for 75 species from 31 genera in two families. Overall success was >90% for mealybugs and >80% for armored scale species. The G·C content was very low in most species, averaging just 16.3%. Sequence divergences (K2P) between congeneric species averaged 10.7%, while intra-specific divergences averaged 0.97%. However, the latter value was inflated by high intra-specific divergence in nine taxa, cases that may indicate species overlooked by current taxonomic treatments. Our study establishes the feasibility of developing a comprehensive barcode library for scale insects and indicates that its construction will both create an effective system for identifying scale insects and reveal taxonomic situations worthy of deeper analysis.

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications

PubMed Central

Harris, R. Alan; Wang, Ting; Coarfa, Cristian; Nagarajan, Raman P.; Hong, Chibo; Downey, Sara L.; Johnson, Brett E.; Fouse, Shaun D.; Delaney, Allen; Zhao, Yongjun; Olshen, Adam; Ballinger, Tracy; Zhou, Xin; Forsberg, Kevin J.; Gu, Junchen; Echipare, Lorigail; O’Geen, Henriette; Lister, Ryan; Pelizzola, Mattia; Xi, Yuanxin; Epstein, Charles B.; Bernstein, Bradley E.; Hawkins, R. David; Ren, Bing; Chung, Wen-Yu; Gu, Hongcang; Bock, Christoph; Gnirke, Andreas; Zhang, Michael Q.; Haussler, David; Ecker, Joseph; Li, Wei; Farnham, Peggy J.; Waterland, Robert A.; Meissner, Alexander; Marra, Marco A.; Hirst, Martin; Milosavljevic, Aleksandar; Costello, Joseph F.

2010-01-01

Sequencing-based DNA methylation profiling methods are comprehensive and, as accuracy and affordability improve, will increasingly supplant microarrays for genome-scale analyses. Here, four sequencing-based methodologies were applied to biological replicates of human embryonic stem cells to compare their CpG coverage genome-wide and in transposons, resolution, cost, concordance and its relationship with CpG density and genomic context. The two bisulfite methods reached concordance of 82% for CpG methylation levels and 99% for non-CpG cytosine methylation levels. Using binary methylation calls, two enrichment methods were 99% concordant, while regions assessed by all four methods were 97% concordant. To achieve comprehensive methylome coverage while reducing cost, an approach integrating two complementary methods was examined. The integrative methylome profile along with histone methylation, RNA, and SNP profiles derived from the sequence reads allowed genome-wide assessment of allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression. PMID:20852635

Developmental validation of a custom panel including 273 SNPs for forensic application using Ion Torrent PGM.

PubMed

Zhang, Suhua; Bian, Yingnan; Chen, Anqi; Zheng, Hancheng; Gao, Yuzhen; Hou, Yiping; Li, Chengtao

2017-03-01

Utilizing massively parallel sequencing (MPS) technology for SNP testing in forensic genetics is becoming attractive because of the shortcomings of STR markers, such as their high mutation rates and disadvantages associated with the current PCR-CE method as well as its limitations regarding multiplex capabilities. MPS offers the potential to genotype hundreds to thousands of SNPs from multiple samples in a single experimental run. In this study, we designed a customized SNP panel that includes 273 forensically relevant identity SNPs chosen from SNPforID, IISNP, and the HapMap database as well as previously related studies and evaluated the levels of genotyping precision, sequence coverage, sensitivity and SNP performance using the Ion Torrent PGM. In a concordant study of the custom MPS-SNP panel, only four MPS callings were missing due to coverage reads that were too low (<20), whereas the others were fully concordant with Sanger's sequencing results across the two control samples, that is, 9947A and 9948. The analyses indicated a balanced coverage among the included loci, with the exception of the 16 SNPs that were used to detect an inconsistent allele balance and/or lower coverage reads among 50 tested individuals from the Chinese HAN population and the above controls. With the exception of the 16 poorly performing SNPs, the sequence coverage obtained was extensive for the bulk of the SNPs, and only three Y-SNPs (rs16980601, rs11096432, rs3900) showed a mean coverage below 1000. Analyses of the dilution series of control DNA 9948 yielded reproducible results down to 1ng of DNA input. In addition, we provide an analysis tool for automated data quality control and genotyping checks, and we conclude that the SNP targets are polymorphic and independent in the Chinese HAN population. In summary, the evaluation of the sensitivity, accuracy and genotyping performance provides strong support for the application of MPS technology in forensic SNP analysis, and the assay offers a straightforward sample-to-genotype workflow that could be beneficial in forensic casework with respect to both individual identification and complex kinship issues. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Health Insurance Exchanges: Health Insurance Navigators and In-Person Assistance

DTIC Science & Technology

2013-09-25

apply for coverage through the exchanges may be eligible for small business tax credits.5 Consumers may apply for coverage over the phone, online , via...more recent CMS announcements reference 20-30 hours of training. 47 The Medicare Learning Network online navigator training is estimated to take 20...about scam artists seeking to obtain personal information under the guise of verifying information regarding ACA coverage.114

Vaccine coverage estimation using a computerized vaccination registry with potential underreporting and a seroprevalence study.

PubMed

Breva, Lina Pérez; Domingo, Javier Díez; Martínez Beneito, Miguel Ángel; Barberà, Joan Puig

2015-04-27

To develop a method to estimate vaccination coverage using both a computerized vaccine registry with an unknown underreporting rate and a seroprevalence study. A real example of a meningococcal C conjugate vaccine (MCCV) coverage estimation is studied to illustrate the proposed methodology. We reviewed the Vaccine Information System of Valencia (Sistema de Información Vacunal, SIV) for the MCCV status of 1430 subjects aged 3-29 years as part of a seroprevalence study. When MCCV was not registered in SIV, subjects were classified into three groups (MCCV non-registered, no vaccination records and missing information) depending on the registry of other vaccines. A Bayesian model was developed to ascertain the percentage of MCCV-vaccinated subjects based on the meningococcal C seroprotection levels from the seroprevalence study. The seroprotection levels in subjects with no MCCV registered in SIV (358) were similar to those in subjects with MCCV registered (1072). This indicated a large proportion of vaccinated subjects with no MCCV registered. The estimated vaccine coverage was over 80% in all age groups, except >22 years, where it was 67.6% (95% CI: [54.0-80.4]), which corresponded to those aged over 13 years at the time of the catch-up campaign. An underreporting rate of 23.5-73.4%, depending on the age group, was estimated in those vaccinated in the 2002 catch-up campaign. The Bayesian model allowed for a more realistic estimation of MCCV uptake. In this example, we quantified the underreporting of a vaccine registry, especially occurring during a catch-up campaign that occurred at the establishment of the registry. Copyright © 2015. Published by Elsevier Ltd.

Challenges of Estimating the Annual Caseload of Severe Acute Malnutrition: The Case of Niger

PubMed Central

Hallarou, Mahaman; Gérard, Jean-Christophe; Donnen, Philippe; Macq, Jean

2016-01-01

Introduction Reliable prospective estimates of annual severe acute malnutrition (SAM) caseloads for treatment are needed for policy decisions and planning of quality services in the context of competing public health priorities and limited resources. This paper compares the reliability of SAM caseloads of children 6–59 months of age in Niger estimated from prevalence at the start of the year and counted from incidence at the end of the year. Methods Secondary data from two health districts for 2012 and the country overall for 2013 were used to calculate annual caseload of SAM. Prevalence and coverage were extracted from survey reports, and incidence from weekly surveillance systems. Results The prospective caseload estimate derived from prevalence and duration of illness underestimated the true burden. Similar incidence was derived from two weekly surveillance systems, but differed from that obtained from the monthly system. Incidence conversion factors were two to five times higher than recommended. Discussion Obtaining reliable prospective caseloads was challenging because prevalence is unsuitable for estimating incidence of SAM. Different SAM indicators identified different SAM populations, and duration of illness, expected contact coverage and population figures were inaccurate. The quality of primary data measurement, recording and reporting affected incidence numbers from surveillance. Coverage estimated in population surveys was rarely available, and coverage obtained by comparing admissions with prospective caseload estimates was unrealistic or impractical. Conclusions Caseload estimates derived from prevalence are unreliable and should be used with caution. Policy and service decisions that depend on these numbers may weaken performance of service delivery. Niger may improve SAM surveillance by simplifying and improving primary data collection and methods using innovative information technologies for single data entry at the first contact with the health system. Lessons may be relevant for countries with a high burden of SAM, including for targeted emergency responses. PMID:27606677

Tunable Signal-Off and Signal-On Electrochemical Cisplatin Sensor.

PubMed

Wu, Yao; Lai, Rebecca Y

2017-09-19

We report the first electrochemical cisplatin sensor fabricated with a thiolated and methylene blue (MB)-modified oligo-adenine (A)-guanine (G) DNA probe. Depending on the probe coverage, the sensor can behave as a signal-off or signal-on sensor. For the high-coverage sensor, formation of intrastrand Pt(II)-AG adducts rigidifies the oligo-AG probe, resulting in a concentration-dependent decrease in the MB signal. For the low-coverage sensor, the increase in probe-to-probe spacing enables binding of cisplatin via the intrastrand GNG motif (N = A), generating a bend in the probe which results in an increase in the MB current. Although both high-coverage signal-off and low-coverage signal-on sensors are capable of detecting cisplatin, the signal-on sensing mechanism is better suited for real time analysis of cisplatin. The low-coverage sensor has a lower limit of detection, wider optimal AC frequency range, and faster response time. It has high specificity for cisplatin and potentially other Pt(II) drugs and does not cross-react with satraplatin, a Pt(IV) prodrug. It is also selective enough to be employed directly in 50% saliva and 50% urine. This detection strategy may offer a new approach for sensitive and real time analysis of cisplatin in clinical samples.

How might immunization rates change if cost sharing is eliminated?

PubMed

Shen, Angela K; O'Grady, Michael J; McDevitt, Roland D; Pickreign, Jeremy D; Laudenberger, Laura K; Esber, Allahna; Shortridge, Emily F

2014-01-01

There is a debate regarding the effect of cost sharing on immunization, particularly as the Affordable Care Act will eliminate cost sharing for recommended vaccines. This study estimates changes in immunization rates and spending associated with extending first-dollar coverage to privately insured children for four childhood vaccines. We used the 2008 National Immunization Survey and peer-reviewed literature to generate estimates of immunization status for each vaccine by age group and insurance type. We used the Truven Health Analytics 2006 MarketScan Commercial Claims and Encounters Database of line-item medical claims to estimate changes in immunization rates that would result from eliminating cost sharing, and we used the Kaiser Family Foundation/Health Research and Educational Trust Employer Health Benefits Survey to determine the prevalence of coverage for patients with first-dollar coverage, patients who face office visit cost sharing, and patients who face cost sharing for all vaccine cost components. We assumed that once cost sharing is removed, coverage rates in plans that impose cost sharing will rise to the level of plans that do not. We estimate that immunization rates would increase modestly and result in additional direct spending of $26.0 million to insurers/employers. Further, these payers would have an additional $11.0 million in spending associated with eliminating cost sharing for children already receiving immunizations. The effects of eliminating cost sharing for vaccines vary by vaccine. Overall, immunization rates will rise modestly given high insurance coverage for vaccinations, and these increases would be more substantial for those currently facing cost sharing. However, in addition to the removal of cost sharing for immunizations, these findings suggest other strategies to consider to further increase immunization rates.

Reduction in child mortality in Ethiopia: analysis of data from demographic and health surveys.

PubMed

Doherty, Tanya; Rohde, Sarah; Besada, Donela; Kerber, Kate; Manda, Samuel; Loveday, Marian; Nsibande, Duduzile; Daviaud, Emmanuelle; Kinney, Mary; Zembe, Wanga; Leon, Natalie; Rudan, Igor; Degefie, Tedbabe; Sanders, David

2016-12-01

To examine changes in under-5 mortality, coverage of child survival interventions and nutritional status of children in Ethiopia between 2000 and 2011. Using the Lives Saved Tool, the impact of changes in coverage of child survival interventions on under-5 lives saved was estimated. Estimates of child mortality were generated using three Ethiopia Demographic and Health Surveys undertaken between 2000 and 2011. Coverage indicators for high impact child health interventions were calculated and the Lives Saved Tool (LiST) was used to estimate child lives saved in 2011. The mortality rate in children younger than 5 years decreased rapidly from 218 child deaths per 1000 live births (95% confidence interval 183 to 252) in the period 1987-1991 to 88 child deaths per 1000 live births in the period 2007-2011 (78 to 98). The prevalence of moderate or severe stunting in children aged 6-35 months also declined significantly. Improvements in the coverage of interventions relevant to child survival in rural areas of Ethiopia between 2000 and 2011 were found for tetanus toxoid, DPT3 and measles vaccination, oral rehydration solution (ORS) and care-seeking for suspected pneumonia. The LiST analysis estimates that there were 60 700 child deaths averted in 2011, primarily attributable to decreases in wasting rates (18%), stunting rates (13%) and water, sanitation and hygiene (WASH) interventions (13%). Improvements in the nutritional status of children and increases in coverage of high impact interventions most notably WASH and ORS have contributed to the decline in under-5 mortality in Ethiopia. These proximal determinants however do not fully explain the mortality reduction which is plausibly also due to the synergistic effect of major child health and nutrition policies and delivery strategies.

Medicaid Coverage Expansions and Cigarette Smoking Cessation Among Low-income Adults.

PubMed

Koma, Jonathan W; Donohue, Julie M; Barry, Colleen L; Huskamp, Haiden A; Jarlenski, Marian

2017-12-01

Expanding Medicaid coverage to low-income adults may have increased smoking cessation through improved access to evidence-based treatments. Our study sought to determine if states' decisions to expand Medicaid increased recent smoking cessation. Using pooled cross-sectional data from the Behavioral Risk Factor Surveillance Survey for the years 2011-2015, we examined the association between state Medicaid coverage and the probability of recent smoking cessation among low-income adults without dependent children who were current or former smokers (n=36,083). We used difference-in-differences estimation to examine the effects of Medicaid coverage on smoking cessation, comparing low-income adult smokers in states with Medicaid coverage to comparable adults in states without Medicaid coverage, with ages 18-64 years to those ages 65 years and above. Analyses were conducted for the full sample and stratified by sex. Residence in a state with Medicaid coverage among low-income adult smokers ages 18-64 years was associated with an increase in recent smoking cessation of 2.1 percentage points (95% confidence interval, 0.25-3.9). In the comparison group of individuals ages 65 years and above, residence in a state with Medicaid coverage expansion was not associated with a change in recent smoking cessation (-0.1 percentage point, 95% confidence interval, -2.1 to 1.8). Similar increases in smoking cessation among those ages 18-64 years were estimated for females and males (1.9 and 2.2 percentage point, respectively). Findings are consistent with the hypothesis that Medicaid coverage expansions may have increased smoking cessation among low-income adults without dependent children via greater access to preventive health care services, including evidence-based smoking cessation services.

Massively parallel pyrosequencing of the mitochondrial genome with the 454 methodology in forensic genetics.

PubMed

Mikkelsen, Martin; Frank-Hansen, Rune; Hansen, Anders J; Morling, Niels

2014-09-01

of sequencing of whole mitochondrial genome, HV1 and HV2 DNA with the second generation system (SGS) Roche 454 GS Junior were compared with results of Sanger sequencing and SNP typing with SNaPshot single base extension detected with MALDI-TOF and capillary electrophoresis. We investigated the performance of the software analysis of the data, reproducibility, ability to sequence homopolymeric regions, detection of mixtures and heteroplasmy as well as the implications of the depth of coverage. We found full reproducibility between samples sequenced twice with SGS. We found close to full concordance between the mtDNA sequences of 26 samples obtained with (1) the 454 SGS method using a depth of coverage above 100 and (2) Sanger sequencing and SNP typing. The discrepancies were primarily observed in homopolymeric regions. The 454 SGS method was able to sequence 95% of the reads correctly in homopolymers up to 4 bases, and up to 6 bases could be sequenced with similar success if the results were carefully, visually inspected. The 454 technology was able to detect mixtures or heteroplasmy of approximately 10%. We detected previously unreported heteroplasmy in the GM9947A component of the NIST human mitochondrial DNA SRM-2392 standard reference material. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Annual immunisation coverage report, 2010.

PubMed

Hull, Brynley; Dey, Aditi; Menzies, Rob; McIntyre, Peter

2013-03-31

This, the fourth annual immunisation coverage report, documents trends during 2010 for a range of standard measures derived from Australian Childhood Immunisation Register (ACIR) data. These include coverage at standard age milestones and for individual vaccines included on the National Immunisation Program (NIP). For the first time, coverage from other sources for adolescents and the elderly are included. The proportion of children 'fully vaccinated' at 12, 24 and 60 months of age was 91.6%, 92.1% and 89.1% respectively. For vaccines available on the NIP but not currently assessed for 'fully immunised' status or for eligibility for incentive payments (rotavirus and pneumococcal at 12 months and meningococcal C and varicella at 24 months) coverage varied. Although pneumococcal vaccine had similar coverage at 12 months to other vaccines, coverage was lower for rotavirus at 12 months (84.7%) and varicella at 24 months (83.0%). Overall coverage at 24 months of age exceeded that at 12 months of age nationally and for most jurisdictions, but as receipt of varicella vaccine at 18 months is excluded from calculations, this represents delayed immunisation, with some contribution from immunisation incentives. The 'fully immunised' coverage estimates for immunisations due by 60 months increased substantially in 2009, reaching almost 90% in 2010, probably related to completed immunisation by 60 months of age being introduced in 2009 as a requirement for GP incentive payments. As previously documented, vaccines recommended for Indigenous children only (hepatitis A and pneumococcal polysaccharide vaccine) had suboptimal coverage at around 57%. Delayed receipt of vaccines by Indigenous children at the 60-month milestone age improved from 56% to 62% but the disparity in on-time vaccination between Indigenous and non-Indigenous children at earlier age milestones did not improve. Coverage data for human papillomavirus (HPV)from the national HPV register are consistent with high coverage in the school-based program (73%) but were lower for the catch-up program for women outside school (30-38%). Coverage estimates for vaccines on the NIP from 65 years of age were comparable with other developed countries.

Single-molecule optical genome mapping of a human HapMap and a colorectal cancer cell line.

PubMed

Teo, Audrey S M; Verzotto, Davide; Yao, Fei; Nagarajan, Niranjan; Hillmer, Axel M

2015-01-01

Next-generation sequencing (NGS) technologies have changed our understanding of the variability of the human genome. However, the identification of genome structural variations based on NGS approaches with read lengths of 35-300 bases remains a challenge. Single-molecule optical mapping technologies allow the analysis of DNA molecules of up to 2 Mb and as such are suitable for the identification of large-scale genome structural variations, and for de novo genome assemblies when combined with short-read NGS data. Here we present optical mapping data for two human genomes: the HapMap cell line GM12878 and the colorectal cancer cell line HCT116. High molecular weight DNA was obtained by embedding GM12878 and HCT116 cells, respectively, in agarose plugs, followed by DNA extraction under mild conditions. Genomic DNA was digested with KpnI and 310,000 and 296,000 DNA molecules (≥ 150 kb and 10 restriction fragments), respectively, were analyzed per cell line using the Argus optical mapping system. Maps were aligned to the human reference by OPTIMA, a new glocal alignment method. Genome coverage of 6.8× and 5.7× was obtained, respectively; 2.9× and 1.7× more than the coverage obtained with previously available software. Optical mapping allows the resolution of large-scale structural variations of the genome, and the scaffold extension of NGS-based de novo assemblies. OPTIMA is an efficient new alignment method; our optical mapping data provide a resource for genome structure analyses of the human HapMap reference cell line GM12878, and the colorectal cancer cell line HCT116.

Studies on visual detection and surface modification testing of glass microfiber filter paper based biosensor.

PubMed

Adiguzel, Yekbun; Kulah, Haluk

2014-04-15

Glass microfibers are commonly used as biomolecule adsorption media, as structural or disposable components of the optical biosensors. While any improvement in these components are appreciated, utilizing basic tools of traditional approaches may lead to original sensor opportunities as simple, functional designs that can be easily disseminated. Following this pursuit, surface modification of glass microfiber paper surface was performed by 3-aminopropyltriethoxysilane (APTES) and resulting improvement in the cell entrapment capacity could be observed visually, only after Gram staining. Gram staining offered rapid validation of enhanced binding on the glass surface. The same APTES-modified samples were also tested for binding of complementary DNA sequences and the results were less straightforward due to the necessity of DNA visualization by using a fluorescent stain, YOYO-1. Accordingly, when there were no surface modification, DNA and YOYO-1 adsorbed readily on the glass microfiber filter paper, and prolonged the interaction between DNA and YOYO-1. YOYO-1 adsorption on glass could be recognized from the color profile of YOYO-1 emission. This phenomenon can be used to examine suitability of APTES coverage on glass surfaces since YOYO-1 emission can be distinguished by its glass adsorbed versus DNA-bound forms. Aptness of surface coverage is vital to biosensor studies in the sense that it is preceding the forthcoming surface modifications and its precision is imperative for attaining the anticipated interaction kinetics of the surface-immobilized species. The proposed testing scheme offered in this study secures the work, which is aimed to be carried out utilizing such sensing systems and device components. © 2013 Published by Elsevier B.V.

Cancer Internet Search Activity on a Major Search Engine, United States 2001-2003

PubMed Central

Cooper, Crystale Purvis; Mallon, Kenneth P; Leadbetter, Steven; Peipins, Lucy A

2005-01-01

Background To locate online health information, Internet users typically use a search engine, such as Yahoo! or Google. We studied Yahoo! search activity related to the 23 most common cancers in the United States. Objective The objective was to test three potential correlates of Yahoo! cancer search activity—estimated cancer incidence, estimated cancer mortality, and the volume of cancer news coverage—and to study the periodicity of and peaks in Yahoo! cancer search activity. Methods Yahoo! cancer search activity was obtained from a proprietary database called the Yahoo! Buzz Index. The American Cancer Society's estimates of cancer incidence and mortality were used. News reports associated with specific cancer types were identified using the LexisNexis “US News” database, which includes more than 400 national and regional newspapers and a variety of newswire services. Results The Yahoo! search activity associated with specific cancers correlated with their estimated incidence (Spearman rank correlation, ρ = 0.50, P = .015), estimated mortality (ρ = 0.66, P = .001), and volume of related news coverage (ρ = 0.88, P < .001). Yahoo! cancer search activity tended to be higher on weekdays and during national cancer awareness months but lower during summer months; cancer news coverage also tended to follow these trends. Sharp increases in Yahoo! search activity scores from one day to the next appeared to be associated with increases in relevant news coverage. Conclusions Media coverage appears to play a powerful role in prompting online searches for cancer information. Internet search activity offers an innovative tool for passive surveillance of health information–seeking behavior. PMID:15998627

The detection of HBV DNA with gold-coated iron oxide nanoparticle gene probes

NASA Astrophysics Data System (ADS)

Xi, Dong; Luo, XiaoPing; Lu, QiangHua; Yao, KaiLun; Liu, ZuLi; Ning, Qin

2008-03-01

Gold-coated iron oxide nanoparticle Hepatitis B virus (HBV) DNA probes were prepared, and their application for HBV DNA measurement was studied. Gold-coated iron oxide nanoparticles were prepared by the citrate reduction of tetra-chloroauric acid in the presence of iron oxide nanoparticles which were added as seeds. With a fluorescence-based method, the maximal surface coverage of hexaethiol 30-mer oligonucleotides and the maximal percentage of hybridization strands on gold-coated iron oxide nanoparticles were (120 ± 8) oligonucleotides per nanoparticle, and (14 ± 2%), respectively, which were comparable with those of (132 ± 10) and (22 ± 3%) in Au nanoparticle groups. Large network aggregates were formed when gold-coated iron oxide nanoparticle HBV DNA gene probe was applied to detect HBV DNA molecules as evidenced by transmission electron microscopy and the high specificity was verified by blot hybridization. Our results further suggested that detecting DNA with iron oxide nanoparticles and magnetic separator was feasible and might be an alternative effective method.

Global estimates of human papillomavirus vaccination coverage by region and income level: a pooled analysis.

PubMed

Bruni, Laia; Diaz, Mireia; Barrionuevo-Rosas, Leslie; Herrero, Rolando; Bray, Freddie; Bosch, F Xavier; de Sanjosé, Silvia; Castellsagué, Xavier

2016-07-01

Since 2006, many countries have implemented publicly funded human papillomavirus (HPV) immunisation programmes. However, global estimates of the extent and impact of vaccine coverage are still unavailable. We aimed to quantify worldwide cumulative coverage of publicly funded HPV immunisation programmes up to 2014, and the potential impact on future cervical cancer cases and deaths. Between Nov 1 and Dec 22, 2014, we systematically reviewed PubMed, Scopus, and official websites to identify HPV immunisation programmes worldwide, and retrieved age-specific HPV vaccination coverage rates up to October, 2014. To estimate the coverage and number of vaccinated women, retrieved coverage rates were converted into birth-cohort-specific rates, with an imputation algorithm to impute missing data, and applied to global population estimates and cervical cancer projections by country and income level. From June, 2006, to October, 2014, 64 countries nationally, four countries subnationally, and 12 overseas territories had implemented HPV immunisation programmes. An estimated 118 million women had been targeted through these programmes, but only 1% were from low-income or lower-middle-income countries. 47 million women (95% CI 39-55 million) received the full course of vaccine, representing a total population coverage of 1·4% (95% CI 1·1-1·6), and 59 million women (48-71 million) had received at least one dose, representing a total population coverage of 1·7% (1·4-2·1). In more developed regions, 33·6% (95% CI 25·9-41·7) of females aged 10-20 years received the full course of vaccine, compared with only 2·7% (1·8-3·6) of females in less developed regions. The impact of the vaccine will be higher in upper-middle-income countries (178 192 averted cases by age 75 years) than in high-income countries (165 033 averted cases), despite the lower number of vaccinated women (13·3 million vs 32·2 million). Many women from high-income and upper-middle-income countries have been vaccinated against HPV. However, populations with the highest incidence and mortality of disease remain largely unprotected. Rapid roll-out of the vaccine in low-income and middle-income countries might be the only feasible way to narrow present inequalities in cervical cancer burden and prevention. PATH, Instituto de Salud Carlos III, and Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR). Copyright © 2016 Bruni et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Genome Wide Characterization of Simple Sequence Repeats in Cucumber

USDA-ARS?s Scientific Manuscript database

The whole genome sequence of the cucumber cultivar Gy14 was recently sequenced at 15× coverage with the Roche 454 Titanium technology. The microsatellite DNA sequences (simple sequence repeats, SSRs) in the assembled scaffolds were computationally explored and characterized. A total of 112,073 SSRs ...

A Method of the UMTS-FDD Network Design Based on Universal Load Characteristics

NASA Astrophysics Data System (ADS)

Gajewski, Slawomir

In the paper an original method of the UMTS radio network design was presented. The method is based on simple way of capacity-coverage trade-off estimation for WCDMA/FDD radio interface. This trade-off is estimated by using universal load characteristics and normalized coverage characteristics. The characteristics are useful for any propagation environment as well as for any service performance requirements. The practical applications of these characteristics on radio network planning and maintenance were described.

Expansion of Coverage under the Patient Protection and Affordable Care Act and Primary Care Utilization

PubMed Central

Hofer, Adam N; Abraham, Jean Marie; Moscovice, Ira

2011-01-01

Context: Provisions of the Patient Protection and Affordable Care Act of 2010 (PPACA) expand Medicaid to all individuals in families earning less than 133 percent of the federal poverty level (FPL) and make available subsidies to uninsured lower-income Americans (133 to 400 percent of FPL) without access to employer-based coverage to purchase insurance in new exchanges. Since primary care physicians typically serve as the point of entry into the health care delivery system, an adequate supply of them is critical to meeting the anticipated increase in demand for medical care resulting from the expansion of coverage. This article provides state-level estimates of the anticipated increases in primary care utilization given the PPACA's provisions for expanded coverage. Methods: Using the Medical Expenditure Panel Survey, this article estimates a multivariate regression model of annual primary care utilization. Using the model estimates and state-level information regarding the number of uninsured, it predicts, by state, the change in primary care visits expected from the expanded coverage. Finally, the article predicts the number of primary care physicians needed to accommodate this change in utilization. Findings: This expanded coverage is predicted to increase by 2019 the number of annual primary care visits between 15.07 million and 24.26 million. Assuming stable levels of physicians’ productivity, between 4,307 and 6,940 additional primary care physicians would be needed to accommodate this increase. Conclusions: The PPACA's health insurance expansion parameters are expected to significantly increase the use of primary care. Two strategies that policymakers may consider are creating stronger financial incentives to attract medical school students to primary care and changing the delivery of care in ways that lead to operational improvements, higher throughput, and better quality of care. PMID:21418313

RNA-seq: technical variability and sampling

PubMed Central

2011-01-01

Background RNA-seq is revolutionizing the way we study transcriptomes. mRNA can be surveyed without prior knowledge of gene transcripts. Alternative splicing of transcript isoforms and the identification of previously unknown exons are being reported. Initial reports of differences in exon usage, and splicing between samples as well as quantitative differences among samples are beginning to surface. Biological variation has been reported to be larger than technical variation. In addition, technical variation has been reported to be in line with expectations due to random sampling. However, strategies for dealing with technical variation will differ depending on the magnitude. The size of technical variance, and the role of sampling are examined in this manuscript. Results In this study three independent Solexa/Illumina experiments containing technical replicates are analyzed. When coverage is low, large disagreements between technical replicates are apparent. Exon detection between technical replicates is highly variable when the coverage is less than 5 reads per nucleotide and estimates of gene expression are more likely to disagree when coverage is low. Although large disagreements in the estimates of expression are observed at all levels of coverage. Conclusions Technical variability is too high to ignore. Technical variability results in inconsistent detection of exons at low levels of coverage. Further, the estimate of the relative abundance of a transcript can substantially disagree, even when coverage levels are high. This may be due to the low sampling fraction and if so, it will persist as an issue needing to be addressed in experimental design even as the next wave of technology produces larger numbers of reads. We provide practical recommendations for dealing with the technical variability, without dramatic cost increases. PMID:21645359

Subsidies and the demand for individual health insurance in California.

PubMed

Marquis, M Susan; Buntin, Melinda Beeuwkes; Escarce, José J; Kapur, Kanika; Yegian, Jill M

2004-10-01

To estimate the effect of changes in premiums for individual insurance on decisions to purchase individual insurance and how this price response varies among subgroups of the population. Survey responses from the Current Population Survey (http://www.bls.census.gov/cps/cpsmain.htm), the Survey of Income and Program Participation (http://www.sipp.census.gov/sipp), the National Health Interview Survey (http://www.cdc.gov/nchs/nhis.htm), and data about premiums and plans offered in the individual insurance market in California, 1996-2001. A logit model was used to estimate the decisions to purchase individual insurance by families without access to group insurance. This was modeled as a function of premiums, controlling for family characteristics and other characteristics of the market. A multinomial model was used to estimate the choice between group coverage, individual coverage, and remaining uninsured for workers offered group coverage as a function of premiums for individual insurance and out-of-pocket costs of group coverage. The elasticity of demand for individual insurance by those without access to group insurance is about -.2 to -.4, as has been found in earlier studies. However, there are substantial differences in price responses among subgroups with low-income, young, and self-employed families showing the greatest response. Among workers offered group insurance, a decrease in individual premiums has very small effects on the choice to purchase individual coverage versus group coverage. Subsidy programs may make insurance more affordable for some families, but even sizeable subsidies are unlikely to solve the problem of the uninsured. We do not find evidence that subsidies to individual insurance will produce an unraveling of the employer-based health insurance system.

Current Term Enrollment Estimates: Spring 2014

ERIC Educational Resources Information Center

National Student Clearinghouse, 2014

2014-01-01

Current Term Enrollment Estimates, published every December and May by the National Student Clearinghouse Research Center, include national enrollment estimates by institutional sector, state, enrollment intensity, age group, and gender. Enrollment estimates are adjusted for Clearinghouse data coverage rates by institutional sector, state, and…

Current Term Enrollment Estimates: Fall 2014

ERIC Educational Resources Information Center

National Student Clearinghouse, 2014

2014-01-01

Current Term Enrollment Estimates, published every December and May by the National Student Clearinghouse Research Center (NSCRC), include national enrollment estimates by institutional sector, state, enrollment intensity, age group, and gender. Enrollment estimates are adjusted for Clearinghouse data coverage rates by institutional sector, state,…

Estimation of the cost-effectiveness of HIV prevention portfolios for people who inject drugs in the United States: A model-based analysis

PubMed Central

Owens, Douglas K.; Goldhaber-Fiebert, Jeremy D.; Brandeau, Margaret L.

2017-01-01

Background The risks of HIV transmission associated with the opioid epidemic make cost-effective programs for people who inject drugs (PWID) a public health priority. Some of these programs have benefits beyond prevention of HIV—a critical consideration given that injection drug use is increasing across most United States demographic groups. To identify high-value HIV prevention program portfolios for US PWID, we consider combinations of four interventions with demonstrated efficacy: opioid agonist therapy (OAT), needle and syringe programs (NSPs), HIV testing and treatment (Test & Treat), and oral HIV pre-exposure prophylaxis (PrEP). Methods and findings We adapted an empirically calibrated dynamic compartmental model and used it to assess the discounted costs (in 2015 US dollars), health outcomes (HIV infections averted, change in HIV prevalence, and discounted quality-adjusted life years [QALYs]), and incremental cost-effectiveness ratios (ICERs) of the four prevention programs, considered singly and in combination over a 20-y time horizon. We obtained epidemiologic, economic, and health utility parameter estimates from the literature, previously published models, and expert opinion. We estimate that expansions of OAT, NSPs, and Test & Treat implemented singly up to 50% coverage levels can be cost-effective relative to the next highest coverage level (low, medium, and high at 40%, 45%, and 50%, respectively) and that OAT, which we assume to have immediate and direct health benefits for the individual, has the potential to be the highest value investment, even under scenarios where it prevents fewer infections than other programs. Although a model-based analysis can provide only estimates of health outcomes, we project that, over 20 y, 50% coverage with OAT could avert up to 22,000 (95% CI: 5,200, 46,000) infections and cost US$18,000 (95% CI: US$14,000, US$24,000) per QALY gained, 50% NSP coverage could avert up to 35,000 (95% CI: 8,900, 43,000) infections and cost US$25,000 (95% CI: US$7,000, US$76,000) per QALY gained, 50% Test & Treat coverage could avert up to 6,700 (95% CI: 1,200, 16,000) infections and cost US$27,000 (95% CI: US$15,000, US$48,000) per QALY gained, and 50% PrEP coverage could avert up to 37,000 (22,000, 58,000) infections and cost US$300,000 (95% CI: US$162,000, US$667,000) per QALY gained. When coverage expansions are allowed to include combined investment with other programs and are compared to the next best intervention, the model projects that scaling OAT coverage up to 50%, then scaling NSP coverage to 50%, then scaling Test & Treat coverage to 50% can be cost-effective, with each coverage expansion having the potential to cost less than US$50,000 per QALY gained relative to the next best portfolio. In probabilistic sensitivity analyses, 59% of portfolios prioritized the addition of OAT and 41% prioritized the addition of NSPs, while PrEP was not likely to be a priority nor a cost-effective addition. Our findings are intended to be illustrative, as data on achievable coverage are limited and, in practice, the expansion scenarios considered may exceed feasible levels. We assumed independence of interventions and constant returns to scale. Extensive sensitivity analyses allowed us to assess parameter sensitivity, but the use of a dynamic compartmental model limited the exploration of structural sensitivities. Conclusions We estimate that OAT, NSPs, and Test & Treat, implemented singly or in combination, have the potential to effectively and cost-effectively prevent HIV in US PWID. PrEP is not likely to be cost-effective in this population, based on the scenarios we evaluated. While local budgets or policy may constrain feasible coverage levels for the various interventions, our findings suggest that investments in combined prevention programs can substantially reduce HIV transmission and improve health outcomes among PWID. PMID:28542184

Estimation of the cost-effectiveness of HIV prevention portfolios for people who inject drugs in the United States: A model-based analysis.

PubMed

Bernard, Cora L; Owens, Douglas K; Goldhaber-Fiebert, Jeremy D; Brandeau, Margaret L

2017-05-01

The risks of HIV transmission associated with the opioid epidemic make cost-effective programs for people who inject drugs (PWID) a public health priority. Some of these programs have benefits beyond prevention of HIV-a critical consideration given that injection drug use is increasing across most United States demographic groups. To identify high-value HIV prevention program portfolios for US PWID, we consider combinations of four interventions with demonstrated efficacy: opioid agonist therapy (OAT), needle and syringe programs (NSPs), HIV testing and treatment (Test & Treat), and oral HIV pre-exposure prophylaxis (PrEP). We adapted an empirically calibrated dynamic compartmental model and used it to assess the discounted costs (in 2015 US dollars), health outcomes (HIV infections averted, change in HIV prevalence, and discounted quality-adjusted life years [QALYs]), and incremental cost-effectiveness ratios (ICERs) of the four prevention programs, considered singly and in combination over a 20-y time horizon. We obtained epidemiologic, economic, and health utility parameter estimates from the literature, previously published models, and expert opinion. We estimate that expansions of OAT, NSPs, and Test & Treat implemented singly up to 50% coverage levels can be cost-effective relative to the next highest coverage level (low, medium, and high at 40%, 45%, and 50%, respectively) and that OAT, which we assume to have immediate and direct health benefits for the individual, has the potential to be the highest value investment, even under scenarios where it prevents fewer infections than other programs. Although a model-based analysis can provide only estimates of health outcomes, we project that, over 20 y, 50% coverage with OAT could avert up to 22,000 (95% CI: 5,200, 46,000) infections and cost US$18,000 (95% CI: US$14,000, US$24,000) per QALY gained, 50% NSP coverage could avert up to 35,000 (95% CI: 8,900, 43,000) infections and cost US$25,000 (95% CI: US$7,000, US$76,000) per QALY gained, 50% Test & Treat coverage could avert up to 6,700 (95% CI: 1,200, 16,000) infections and cost US$27,000 (95% CI: US$15,000, US$48,000) per QALY gained, and 50% PrEP coverage could avert up to 37,000 (22,000, 58,000) infections and cost US$300,000 (95% CI: US$162,000, US$667,000) per QALY gained. When coverage expansions are allowed to include combined investment with other programs and are compared to the next best intervention, the model projects that scaling OAT coverage up to 50%, then scaling NSP coverage to 50%, then scaling Test & Treat coverage to 50% can be cost-effective, with each coverage expansion having the potential to cost less than US$50,000 per QALY gained relative to the next best portfolio. In probabilistic sensitivity analyses, 59% of portfolios prioritized the addition of OAT and 41% prioritized the addition of NSPs, while PrEP was not likely to be a priority nor a cost-effective addition. Our findings are intended to be illustrative, as data on achievable coverage are limited and, in practice, the expansion scenarios considered may exceed feasible levels. We assumed independence of interventions and constant returns to scale. Extensive sensitivity analyses allowed us to assess parameter sensitivity, but the use of a dynamic compartmental model limited the exploration of structural sensitivities. We estimate that OAT, NSPs, and Test & Treat, implemented singly or in combination, have the potential to effectively and cost-effectively prevent HIV in US PWID. PrEP is not likely to be cost-effective in this population, based on the scenarios we evaluated. While local budgets or policy may constrain feasible coverage levels for the various interventions, our findings suggest that investments in combined prevention programs can substantially reduce HIV transmission and improve health outcomes among PWID.

Properties of model-averaged BMDLs: a study of model averaging in dichotomous response risk estimation.

PubMed

Wheeler, Matthew W; Bailer, A John

2007-06-01

Model averaging (MA) has been proposed as a method of accounting for model uncertainty in benchmark dose (BMD) estimation. The technique has been used to average BMD dose estimates derived from dichotomous dose-response experiments, microbial dose-response experiments, as well as observational epidemiological studies. While MA is a promising tool for the risk assessor, a previous study suggested that the simple strategy of averaging individual models' BMD lower limits did not yield interval estimators that met nominal coverage levels in certain situations, and this performance was very sensitive to the underlying model space chosen. We present a different, more computationally intensive, approach in which the BMD is estimated using the average dose-response model and the corresponding benchmark dose lower bound (BMDL) is computed by bootstrapping. This method is illustrated with TiO(2) dose-response rat lung cancer data, and then systematically studied through an extensive Monte Carlo simulation. The results of this study suggest that the MA-BMD, estimated using this technique, performs better, in terms of bias and coverage, than the previous MA methodology. Further, the MA-BMDL achieves nominal coverage in most cases, and is superior to picking the "best fitting model" when estimating the benchmark dose. Although these results show utility of MA for benchmark dose risk estimation, they continue to highlight the importance of choosing an adequate model space as well as proper model fit diagnostics.

Exploring the effect of asymmetric mitochondrial DNA introgression on estimating niche divergence in morphologically cryptic species.

PubMed

Wielstra, Ben; Arntzen, Jan W

2014-01-01

If potential morphologically cryptic species, identified based on differentiated mitochondrial DNA, express ecological divergence, this increases support for their treatment as distinct species. However, mitochondrial DNA introgression hampers the correct estimation of ecological divergence. We test the hypothesis that estimated niche divergence differs when considering nuclear DNA composition or mitochondrial DNA type as representing the true species range. We use empirical data of two crested newt species (Amphibia: Triturus) which possess introgressed mitochondrial DNA from a third species in part of their ranges. We analyze the data in environmental space by determining Fisher distances in a principal component analysis and in geographical space by determining geographical overlap of species distribution models. We find that under mtDNA guidance in one of the two study cases niche divergence is overestimated, whereas in the other it is underestimated. In the light of our results we discuss the role of estimated niche divergence in species delineation.

Quantitative Viral Community DNA Analysis Reveals the Dominance of Single-Stranded DNA Viruses in Offshore Upper Bathyal Sediment from Tohoku, Japan

PubMed Central

Yoshida, Mitsuhiro; Mochizuki, Tomohiro; Urayama, Syun-Ichi; Yoshida-Takashima, Yukari; Nishi, Shinro; Hirai, Miho; Nomaki, Hidetaka; Takaki, Yoshihiro; Nunoura, Takuro; Takai, Ken

2018-01-01

Previous studies on marine environmental virology have primarily focused on double-stranded DNA (dsDNA) viruses; however, it has recently been suggested that single-stranded DNA (ssDNA) viruses are more abundant in marine ecosystems. In this study, we performed a quantitative viral community DNA analysis to estimate the relative abundance and composition of both ssDNA and dsDNA viruses in offshore upper bathyal sediment from Tohoku, Japan (water depth = 500 m). The estimated dsDNA viral abundance ranged from 3 × 106 to 5 × 106 genome copies per cm3 sediment, showing values similar to the range of fluorescence-based direct virus counts. In contrast, the estimated ssDNA viral abundance ranged from 1 × 108 to 3 × 109 genome copies per cm3 sediment, thus providing an estimation that the ssDNA viral populations represent 96.3–99.8% of the benthic total DNA viral assemblages. In the ssDNA viral metagenome, most of the identified viral sequences were associated with ssDNA viral families such as Circoviridae and Microviridae. The principle components analysis of the ssDNA viral sequence components from the sedimentary ssDNA viral metagenomic libraries found that the different depth viral communities at the study site all exhibited similar profiles compared with deep-sea sediment ones at other reference sites. Our results suggested that deep-sea benthic ssDNA viruses have been significantly underestimated by conventional direct virus counts and that their contributions to deep-sea benthic microbial mortality and geochemical cycles should be further addressed by such a new quantitative approach. PMID:29467725

Comparing interval estimates for small sample ordinal CFA models

PubMed Central

Natesan, Prathiba

2015-01-01

Robust maximum likelihood (RML) and asymptotically generalized least squares (AGLS) methods have been recommended for fitting ordinal structural equation models. Studies show that some of these methods underestimate standard errors. However, these studies have not investigated the coverage and bias of interval estimates. An estimate with a reasonable standard error could still be severely biased. This can only be known by systematically investigating the interval estimates. The present study compares Bayesian, RML, and AGLS interval estimates of factor correlations in ordinal confirmatory factor analysis models (CFA) for small sample data. Six sample sizes, 3 factor correlations, and 2 factor score distributions (multivariate normal and multivariate mildly skewed) were studied. Two Bayesian prior specifications, informative and relatively less informative were studied. Undercoverage of confidence intervals and underestimation of standard errors was common in non-Bayesian methods. Underestimated standard errors may lead to inflated Type-I error rates. Non-Bayesian intervals were more positive biased than negatively biased, that is, most intervals that did not contain the true value were greater than the true value. Some non-Bayesian methods had non-converging and inadmissible solutions for small samples and non-normal data. Bayesian empirical standard error estimates for informative and relatively less informative priors were closer to the average standard errors of the estimates. The coverage of Bayesian credibility intervals was closer to what was expected with overcoverage in a few cases. Although some Bayesian credibility intervals were wider, they reflected the nature of statistical uncertainty that comes with the data (e.g., small sample). Bayesian point estimates were also more accurate than non-Bayesian estimates. The results illustrate the importance of analyzing coverage and bias of interval estimates, and how ignoring interval estimates can be misleading. Therefore, editors and policymakers should continue to emphasize the inclusion of interval estimates in research. PMID:26579002

Comparing interval estimates for small sample ordinal CFA models.

PubMed

Natesan, Prathiba

2015-01-01

Robust maximum likelihood (RML) and asymptotically generalized least squares (AGLS) methods have been recommended for fitting ordinal structural equation models. Studies show that some of these methods underestimate standard errors. However, these studies have not investigated the coverage and bias of interval estimates. An estimate with a reasonable standard error could still be severely biased. This can only be known by systematically investigating the interval estimates. The present study compares Bayesian, RML, and AGLS interval estimates of factor correlations in ordinal confirmatory factor analysis models (CFA) for small sample data. Six sample sizes, 3 factor correlations, and 2 factor score distributions (multivariate normal and multivariate mildly skewed) were studied. Two Bayesian prior specifications, informative and relatively less informative were studied. Undercoverage of confidence intervals and underestimation of standard errors was common in non-Bayesian methods. Underestimated standard errors may lead to inflated Type-I error rates. Non-Bayesian intervals were more positive biased than negatively biased, that is, most intervals that did not contain the true value were greater than the true value. Some non-Bayesian methods had non-converging and inadmissible solutions for small samples and non-normal data. Bayesian empirical standard error estimates for informative and relatively less informative priors were closer to the average standard errors of the estimates. The coverage of Bayesian credibility intervals was closer to what was expected with overcoverage in a few cases. Although some Bayesian credibility intervals were wider, they reflected the nature of statistical uncertainty that comes with the data (e.g., small sample). Bayesian point estimates were also more accurate than non-Bayesian estimates. The results illustrate the importance of analyzing coverage and bias of interval estimates, and how ignoring interval estimates can be misleading. Therefore, editors and policymakers should continue to emphasize the inclusion of interval estimates in research.

Estimating occupancy and abundance of stream amphibians using environmental DNA from filtered water samples

USGS Publications Warehouse

Pilliod, David S.; Goldberg, Caren S.; Arkle, Robert S.; Waits, Lisette P.

2013-01-01

Environmental DNA (eDNA) methods for detecting aquatic species are advancing rapidly, but with little evaluation of field protocols or precision of resulting estimates. We compared sampling results from traditional field methods with eDNA methods for two amphibians in 13 streams in central Idaho, USA. We also evaluated three water collection protocols and the influence of sampling location, time of day, and distance from animals on eDNA concentration in the water. We found no difference in detection or amount of eDNA among water collection protocols. eDNA methods had slightly higher detection rates than traditional field methods, particularly when species occurred at low densities. eDNA concentration was positively related to field-measured density, biomass, and proportion of transects occupied. Precision of eDNA-based abundance estimates increased with the amount of eDNA in the water and the number of replicate subsamples collected. eDNA concentration did not vary significantly with sample location in the stream, time of day, or distance downstream from animals. Our results further advance the implementation of eDNA methods for monitoring aquatic vertebrates in stream habitats.

Nuclear dna amounts in angiosperms.

PubMed

Bennett, M D; Smith, J B

1976-05-27

The number of angiosperm species for which nuclear DNA amount estimates have been made has nearly trebled since the last collected lists of such values were published, and therefore, publication of a more comprehensive list is over due. This paper lists absolute nuclear DNA amounts for 753 angiosperm species. The dats were assembled primarily for reference purposes, and so the species are listed in alphabetical order, as this was felt to be more helpful to cyto- and biochemists whom, it is anticipated, will be among its major users. The paper also reviews aspects of the history, nomenclature, methods, accuracy and problems of nuclear DNA estimation in angiosperms. No attempt is made to reconsider those aspects of nuclear DNA estimation which have been fully revised previously, although the bibliography of such aspects is given. Instead, the paper is intended as a source of basic information regarding the terminology, practice and limitations of nuclear DNA estimation, especially by Feulgen microdensitometry, as currently practiced.

[Coverage by the Family Health Strategy and diagnosis of syphilis in pregnancy and congenital syphilis].

PubMed

Saraceni, Valéria; Miranda, Angélica Espinosa

2012-03-01

This paper aimed to correlate syphilis in pregnancy and congenital syphilis with coverage of the Family Health Strategy (FHS), based on available data in the national health information systems. The syphilis notification estimates were calculated according to the Sentinel Childbirth Study for 2004 under the Ministry of Health and the data were obtained from the websites of the Health Surveillance Secretariat and Healthcare Secretariat, for the year 2008. The ratios between observed and estimated gestational syphilis and congenital syphilis were not statistically correlated with population coverage by the FHS (r = -0.28 and r = -0.40, respectively). The FHS is a privileged area for prenatal care and logically a source of compulsory notification of syphilis in pregnancy. By combining diagnosis with adequate treatment of syphilis in pregnant women and their partners, the FHS becomes a prime instrument for eliminating congenital syphilis in Brazil. Expanding the FHS coverage and quality of care are essential for achieving this goal.

Take-up of public insurance and crowd-out of private insurance under recent CHIP expansions to higher income children.

PubMed

Gresenz, Carole Roan; Edgington, Sarah E; Laugesen, Miriam; Escarce, José J

2012-10-01

To analyze the effects of states' expansions of Children's Health Insurance Program (CHIP) eligibility to children in higher income families on health insurance coverage outcomes. 2002-2009 Current Population Survey linked to multiple secondary data sources. Instrumental variables estimation of linear probability models. Outcomes are whether the child had any public insurance, any private insurance, or no insurance coverage during the year. Among children in families with incomes between two and four times the federal poverty line (FPL), four enrolled in CHIP for every 100 who became eligible. Roughly half of the newly eligible children who took up public insurance were previously uninsured. The upper bound "crowd-out" rate was estimated to be 46 percent. The CHIP expansions to children in higher income families were associated with limited uptake of public coverage. Our results additionally suggest that there was crowd-out of private insurance coverage. © Health Research and Educational Trust.

Measuring effective coverage of curative child health services in rural Burkina Faso: a cross-sectional study

PubMed Central

Koulidiati, Jean-Louis; Nesbitt, Robin C; Ouedraogo, Nobila; Hien, Hervé; Robyn, Paul Jacob; Compaoré, Philippe; Souares, Aurélia; Brenner, Stephan

2018-01-01

Objective To estimate both crude and effective curative health services coverage provided by rural health facilities to under 5-year-old (U5YO) children in Burkina Faso. Methods We surveyed 1298 child health providers and 1681 clinical cases across 494 primary-level health facilities, as well as 12 497 U5YO children across 7347households in the facilities’ catchment areas. Facilities were scored based on a set of indicators along three quality-of-care dimensions: management of common childhood diseases, management of severe childhood diseases and general service readiness. Linking service quality to service utilisation, we estimated both crude and effective coverage of U5YO children by these selected curative services. Results Measured performance quality among facilities was generally low with only 12.7% of facilities surveyed reaching our definition of high and 57.1% our definition of intermediate quality of care. The crude coverage was 69.5% while the effective coverages indicated that 5.3% and 44.6% of children reporting an illness episode received services of only high or high and intermediate quality, respectively. Conclusion Our study showed that the quality of U5YO child health services provided by primary-level health facilities in Burkina Faso was low, resulting in relatively ineffective population coverage. Poor adherence to clinical treatment guidelines combined with the lack of equipment and qualified clinical staff that performed U5YO consultations seemed to be contributors to the gap between crude and effective coverage. PMID:29858415

Understanding consumer preferences in the context of managed competition: evidence from a choice experiment in Colombia.

PubMed

Trujillo, Antonio J; Ruiz, Fernando; Bridges, John F P; Amaya, Jeannette L; Buttorff, Christine; Quiroga, Angélica M

2012-03-01

In many countries, health insurance coverage is the primary way for individuals to access care. Governments can support access through social insurance programmes; however, after a certain period, governments struggle to achieve universal coverage. Evidence suggests that complex individual behaviour may play a role. Using a choice experiment, this research explored consumer preferences for health insurance in Colombia. We also evaluated whether preferences differed across consumers with differing demographic and health status factors. A household field experiment was conducted in Bogotá in 2010. The sample consisted of 109 uninsured and 133 low-income insured individuals. Each individual evaluated 12 pair-wise comparisons of hypothetical health plans. We focused on six characteristics of health insurance: premium, out-of-pocket expenditure, chronic condition coverage, quality of care, family coverage and sick leave. A main effects orthogonal design was used to derive the 72 scenarios used in the choice experiment. Parameters were estimated using conditional logit models. Since price data were included, we estimated respondents' willingness to pay for characteristics. Consumers valued health benefits and family coverage more than other attributes. Additionally, differences in preferences can be exploited to increase coverage. The willingness to pay for benefits may partially cover the average cost of providing them. Policy makers might be able to encourage those insured via the subsidized system to enrol in the next level of the social health insurance scheme through expanding benefits to family members and expanding the level of chronic condition coverage.

Exploring the relationship between population density and maternal health coverage

PubMed Central

2012-01-01

Background Delivering health services to dense populations is more practical than to dispersed populations, other factors constant. This engenders the hypothesis that population density positively affects coverage rates of health services. This hypothesis has been tested indirectly for some services at a local level, but not at a national level. Methods We use cross-sectional data to conduct cross-country, OLS regressions at the national level to estimate the relationship between population density and maternal health coverage. We separately estimate the effect of two measures of density on three population-level coverage rates (6 tests in total). Our coverage indicators are the fraction of the maternal population completing four antenatal care visits and the utilization rates of both skilled birth attendants and in-facility delivery. The first density metric we use is the percentage of a population living in an urban area. The second metric, which we denote as a density score, is a relative ranking of countries by population density. The score’s calculation discounts a nation’s uninhabited territory under the assumption those areas are irrelevant to service delivery. Results We find significantly positive relationships between our maternal health indicators and density measures. On average, a one-unit increase in our density score is equivalent to a 0.2% increase in coverage rates. Conclusions Countries with dispersed populations face higher burdens to achieve multinational coverage targets such as the United Nations’ Millennial Development Goals. PMID:23170895

Methods for estimating the labour force insured by the Ontario Workplace Safety and Insurance Board: 1990-2000.

PubMed

Smith, Peter M; Mustard, Cameron A; Payne, Jennifer I

2004-01-01

This paper presents a methodology for estimating the size and composition of the Ontario labour force eligible for coverage under the Ontario Workplace Safety & Insurance Act (WSIA). Using customized tabulations from Statistics Canada's Labour Force Survey (LFS), we made adjustments for self-employment, unemployment, part-time employment and employment in specific industrial sectors excluded from insurance coverage under the WSIA. Each adjustment to the LFS reduced the estimates of the insured labour force relative to the total Ontario labour force. These estimates were then developed for major occupational and industrial groups stratified by gender. Additional estimates created to test assumptions used in the methodology produced similar results. The methods described in this paper advance those previously used to estimate the insured labour force, providing researchers with a useful tool to describe trends in the rate of injury across differing occupational, industrial and gender groups in Ontario.

Drug Coverage Surveys for Neglected Tropical Diseases: 10 Years of Field Experience

PubMed Central

Worrell, Caitlin; Mathieu, Els

2012-01-01

Mass drug administration is one of the public health strategies recommended by the World Health Organization for the control and elimination of seven neglected tropical diseases (NTDs). Because adequate coverage is vital to achieve program goals, periodically conducting surveys to validate reported coverage to guide NTD programs is recommended. Over the past decade, the Centers for Disease Control and Prevention (CDC) and collaborators conducted more than 30 two-stage cluster household surveys across three continents. The questionnaires gathered coverage data and information relevant to improving NTD programs including NTD-related attitudes and practices. From the 37 coverage survey estimates obtained in those surveys, 73.3% indicated an over reporting of coverage, including all three that assessed school-based distributions. It took an average of 1 week to conduct a survey. Our experiences led us to conclude that coverage surveys are useful and feasible tools to ensure NTD elimination and control goals are reached. PMID:22855750

Influenza vaccination coverage estimates in the fee-for service Medicare beneficiary population 2006 - 2016: Using population-based administrative data to support a geographic based near real-time tool.

PubMed

Shen, Angela K; Warnock, Rob; Brereton, Stephaeno; McKean, Stephen; Wernecke, Michael; Chu, Steve; Kelman, Jeffrey A

2018-04-11

Older adults are at great risk of developing serious complications from seasonal influenza. We explore vaccination coverage estimates in the Medicare population through the use of administrative claims data and describe a tool designed to help shape outreach efforts and inform strategies to help raise influenza vaccination rates. This interactive mapping tool uses claims data to compare vaccination levels between geographic (i.e., state, county, zip code) and demographic (i.e., race, age) groups at different points in a season. Trends can also be compared across seasons. Utilization of this tool can assist key actors interested in prevention - medical groups, health plans, hospitals, and state and local public health authorities - in supporting strategies for reaching pools of unvaccinated beneficiaries where general national population estimates of coverage are less informative. Implementing evidence-based tools can be used to address persistent racial and ethnic disparities and prevent a substantial number of influenza cases and hospitalizations.

Health insurance tax credits, the earned income tax credit, and health insurance coverage of single mothers.

PubMed

Cebi, Merve; Woodbury, Stephen A

2014-05-01

The Omnibus Budget Reconciliation Act of 1990 enacted a refundable tax credit for low-income working families who purchased health insurance coverage for their children. This health insurance tax credit (HITC) existed during tax years 1991, 1992, and 1993, and was then rescinded. A difference-in-differences estimator applied to Current Population Survey data suggests that adoption of the HITC, along with accompanying increases in the Earned Income Tax Credit (EITC), was associated with a relative increase of about 4.7 percentage points in the private health insurance coverage of working single mothers with high school or less education. Also, a difference-in-difference-in-differences estimator, which attempts to net out the possible influence of the EITC increases but which requires strong assumptions, suggests that the HITC was responsible for about three-quarters (3.6 percentage points) of the total increase. The latter estimate implies a price elasticity of health insurance take-up of -0.42. Copyright © 2013 John Wiley & Sons, Ltd.

Profiling DNA methylome landscapes of mammalian cells with single-cell reduced-representation bisulfite sequencing.

PubMed

Guo, Hongshan; Zhu, Ping; Guo, Fan; Li, Xianlong; Wu, Xinglong; Fan, Xiaoying; Wen, Lu; Tang, Fuchou

2015-05-01

The heterogeneity of DNA methylation within a population of cells necessitates DNA methylome profiling at single-cell resolution. Recently, we developed a single-cell reduced-representation bisulfite sequencing (scRRBS) technique in which we modified the original RRBS method by integrating all the experimental steps before PCR amplification into a single-tube reaction. These modifications enable scRRBS to provide digitized methylation information on ∼1 million CpG sites within an individual diploid mouse or human cell at single-base resolution. Compared with the single-cell bisulfite sequencing (scBS) technique, scRRBS covers fewer CpG sites, but it provides better coverage for CpG islands (CGIs), which are likely to be the most informative elements for DNA methylation. The entire procedure takes ∼3 weeks, and it requires strong molecular biology skills.

Quantitative imaging biomarkers: Effect of sample size and bias on confidence interval coverage.

PubMed

Obuchowski, Nancy A; Bullen, Jennifer

2017-01-01

Introduction Quantitative imaging biomarkers (QIBs) are being increasingly used in medical practice and clinical trials. An essential first step in the adoption of a quantitative imaging biomarker is the characterization of its technical performance, i.e. precision and bias, through one or more performance studies. Then, given the technical performance, a confidence interval for a new patient's true biomarker value can be constructed. Estimating bias and precision can be problematic because rarely are both estimated in the same study, precision studies are usually quite small, and bias cannot be measured when there is no reference standard. Methods A Monte Carlo simulation study was conducted to assess factors affecting nominal coverage of confidence intervals for a new patient's quantitative imaging biomarker measurement and for change in the quantitative imaging biomarker over time. Factors considered include sample size for estimating bias and precision, effect of fixed and non-proportional bias, clustered data, and absence of a reference standard. Results Technical performance studies of a quantitative imaging biomarker should include at least 35 test-retest subjects to estimate precision and 65 cases to estimate bias. Confidence intervals for a new patient's quantitative imaging biomarker measurement constructed under the no-bias assumption provide nominal coverage as long as the fixed bias is <12%. For confidence intervals of the true change over time, linearity must hold and the slope of the regression of the measurements vs. true values should be between 0.95 and 1.05. The regression slope can be assessed adequately as long as fixed multiples of the measurand can be generated. Even small non-proportional bias greatly reduces confidence interval coverage. Multiple lesions in the same subject can be treated as independent when estimating precision. Conclusion Technical performance studies of quantitative imaging biomarkers require moderate sample sizes in order to provide robust estimates of bias and precision for constructing confidence intervals for new patients. Assumptions of linearity and non-proportional bias should be assessed thoroughly.

One-step large-scale deposition of salt-free DNA origami nanostructures

PubMed Central

Linko, Veikko; Shen, Boxuan; Tapio, Kosti; Toppari, J. Jussi; Kostiainen, Mauri A.; Tuukkanen, Sampo

2015-01-01

DNA origami nanostructures have tremendous potential to serve as versatile platforms in self-assembly -based nanofabrication and in highly parallel nanoscale patterning. However, uniform deposition and reliable anchoring of DNA nanostructures often requires specific conditions, such as pre-treatment of the chosen substrate or a fine-tuned salt concentration for the deposition buffer. In addition, currently available deposition techniques are suitable merely for small scales. In this article, we exploit a spray-coating technique in order to resolve the aforementioned issues in the deposition of different 2D and 3D DNA origami nanostructures. We show that purified DNA origamis can be controllably deposited on silicon and glass substrates by the proposed method. The results are verified using either atomic force microscopy or fluorescence microscopy depending on the shape of the DNA origami. DNA origamis are successfully deposited onto untreated substrates with surface coverage of about 4 objects/mm2. Further, the DNA nanostructures maintain their shape even if the salt residues are removed from the DNA origami fabrication buffer after the folding procedure. We believe that the presented one-step spray-coating method will find use in various fields of material sciences, especially in the development of DNA biochips and in the fabrication of metamaterials and plasmonic devices through DNA metallisation. PMID:26492833

Cost-Effectiveness of Providing Full Drug Coverage to Increase Medication Adherence in Post–Myocardial Infarction Medicare Beneficiaries

PubMed Central

Choudhry, Niteesh K.; Patrick, Amanda R.; Antman, Elliott M.; Avorn, Jerry; Shrank, William H.

2009-01-01

Background Effective therapies for the secondary prevention of coronary heart disease–related events are significantly underused, and attempts to improve adherence have often yielded disappointing results. Elimination of patient out-of-pocket costs may be an effective strategy to enhance medication use. We sought to estimate the incremental cost-effectiveness of providing full coverage for aspirin, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins (combination pharmacotherapy) to individuals enrolled in the Medicare drug benefit program after acute myocardial infarction. Methods and Results We created a Markov cost-effectiveness model to estimate the incremental cost-effectiveness of providing Medicare beneficiaries with full coverage for combination pharmacotherapy compared with current coverage under the Medicare Part D program. Our analysis was conducted from the societal perspective and considered a lifetime time horizon. In a sensitivity analysis, we repeated our analysis from the perspective of Medicare. In the model, post–myocardial infarction Medicare beneficiaries who received usual prescription drug coverage under the Part D program lived an average of 8.21 quality-adjusted life-years after their initial event, incurring coronary heart disease–related medical costs of $114 000. Those who received prescription drug coverage without deductibles or copayments lived an average of 8.56 quality-adjusted life-years and incurred $111 600 in coronary heart disease–related costs. Compared with current prescription drug coverage, full coverage for post–myocardial infarction secondary prevention therapies would result in greater functional life expectancy (0.35 quality-adjusted life-year) and less resource use ($2500). From the perspective of Medicare, full drug coverage was highly cost-effective ($7182/quality-adjusted life-year) but not cost saving. Conclusions Our analysis suggests that providing full coverage for combination therapy to post–myocardial infarction Medicare beneficiaries would save both lives and money from the societal perspective. PMID:18285564

Estimating Premium Sensitivity for Children's Public Health Insurance Coverage: Selection but No Death Spiral

PubMed Central

Marton, James; Ketsche, Patricia G; Snyder, Angela; Adams, E Kathleen; Zhou, Mei

2015-01-01

Objective To estimate the effect of premium increases on the probability that near-poor and moderate-income children disenroll from public coverage. Data Sources Enrollment, eligibility, and claims data for Georgia's PeachCare for Kids™ (CHIP) program for multiple years. Study Design We exploited policy-induced variation in premiums generated by cross-sectional differences and changes over time in enrollee age, family size, and income to estimate the duration of enrollment as a function of the effective (per child) premium. We classify children as being of low, medium, or high illness severity. Principal Findings A dollar increase in the per-child premium is associated with a slight increase in a typical child's monthly probability of exiting coverage from 7.70 to 7.83 percent. Children with low illness severity have a significantly higher monthly baseline probability of exiting than children with medium or high illness severity, but the enrollment response to premium increases is similar across all three groups. Conclusions Success in achieving coverage gains through public programs is tempered by persistent problems in maintaining enrollment, which is modestly affected by premium increases. Retention is subject to adverse selection problems, but premium increases do not appear to significantly magnify the selection problem in this case. PMID:25130764

Global Estimates of Syphilis in Pregnancy and Associated Adverse Outcomes: Analysis of Multinational Antenatal Surveillance Data

PubMed Central

Newman, Lori; Kamb, Mary; Hawkes, Sarah; Gomez, Gabriela; Say, Lale; Seuc, Armando; Broutet, Nathalie

2013-01-01

Background The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥90% of pregnant women to be tested for syphilis and ≥90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. Methods and Findings Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was “probable active,” and for testing and treatment coverage. Conclusions Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment. In this analysis, most adverse outcomes occurred among women who attended ANC but were not tested or treated for syphilis, highlighting the need to improve the quality of ANC as well as ANC coverage. In addition, improved ANC data on syphilis testing coverage, positivity, and treatment are needed. Please see later in the article for the Editors' Summary PMID:23468598

Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data.

PubMed

Newman, Lori; Kamb, Mary; Hawkes, Sarah; Gomez, Gabriela; Say, Lale; Seuc, Armando; Broutet, Nathalie

2013-01-01

The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥ 90% of pregnant women to be tested for syphilis and ≥ 90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was "probable active," and for testing and treatment coverage. Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment. In this analysis, most adverse outcomes occurred among women who attended ANC but were not tested or treated for syphilis, highlighting the need to improve the quality of ANC as well as ANC coverage. In addition, improved ANC data on syphilis testing coverage, positivity, and treatment are needed. Please see later in the article for the Editors' Summary.

Multiscale site-response mapping: A case study of Parkfield, California

USGS Publications Warehouse

Thompson, E.M.; Baise, L.G.; Kayen, R.E.; Morgan, E.C.; Kaklamanos, J.

2011-01-01

The scale of previously proposed methods for mapping site-response ranges from global coverage down to individual urban regions. Typically, spatial coverage and accuracy are inversely related.We use the densely spaced strong-motion stations in Parkfield, California, to estimate the accuracy of different site-response mapping methods and demonstrate a method for integrating multiple site-response estimates from the site to the global scale. This method is simply a weighted mean of a suite of different estimates, where the weights are the inverse of the variance of the individual estimates. Thus, the dominant site-response model varies in space as a function of the accuracy of the different models. For mapping applications, site-response models should be judged in terms of both spatial coverage and the degree of correlation with observed amplifications. Performance varies with period, but in general the Parkfield data show that: (1) where a velocity profile is available, the square-rootof- impedance (SRI) method outperforms the measured VS30 (30 m divided by the S-wave travel time to 30 m depth) and (2) where velocity profiles are unavailable, the topographic slope method outperforms surficial geology for short periods, but geology outperforms slope at longer periods. We develop new equations to estimate site response from topographic slope, derived from the Next Generation Attenuation (NGA) database.

Liposomal lipid and plasmid DNA delivery to B16/BL6 tumors after intraperitoneal administration of cationic liposome DNA aggregates.

PubMed

Reimer, D L; Kong, S; Monck, M; Wyles, J; Tam, P; Wasan, E K; Bally, M B

1999-05-01

The transfer of plasmid expression vectors to cells is essential for transfection after administration of lipid-based DNA formulations (lipoplexes). A murine i.p. B16/BL6 tumor model was used to characterize DNA delivery, liposomal lipid delivery, and gene transfer after regional (i.p.) administration of free plasmid DNA and DNA lipoplexes. DNA lipoplexes were prepared using cationic dioleoyldimethylammonium chloride/dioleoylphosphatidylethanolamine (50:50 mol ratio) liposomes mixed with plasmid DNA (1 microgram DNA/10 nmol lipid). The plasmid used contained the chloramphenicol acetyltransferase gene and chloramphenicol acetyltransferase expression (mU/g tumor) was measured to estimate transfection efficiency. Tumor-associated DNA and liposomal lipid levels were measured to estimate the efficiency of lipid-mediated DNA delivery to tumors. Plasmid DNA delivery was estimated using [3H]-labeled plasmid as a tracer, dot blot analysis, and/or Southern analysis. Liposomal lipid delivery was estimated using [14C]-dioleoylphosphatidylethanolamine as a liposomal lipid marker. Gene expression in the B16/BL6 tumors was highly variable, with values ranging from greater than 2,000 mU/g tumor to less than 100 mU/g tumor. There was a tendency to observe enhanced transfection in small (<250 mg) tumors. Approximately 18% of the injected dose of DNA was associated with these small tumors 2 h after i.p. administration. Southern analysis of extracted tumor DNA indicated that plasmid DNA associated with tumors was intact 24 h after administration. DNA and associated liposomal lipid are efficiently bound to tumors after regional administration; however, it is unclear whether delivery is sufficient to abet internalization and appropriate subcellular localization of the expression vector.

Impact of the CDC's Section 317 Immunization Grants Program funding on childhood vaccination coverage.

PubMed

Rein, David B; Honeycutt, Amanda A; Rojas-Smith, Lucia; Hersey, James C

2006-09-01

The Centers for Disease Control and Prevention's Section 317 Grants Program is the main source of funding for state and jurisdictional immunization programs, yet no study has evaluated its direct impact on vaccination coverage rates. Therefore, we used a fixed-effects model and data collected from 56 US jurisdictions to estimate the impact of Section 317 financial assistance immunization grants on childhood vaccination coverage rates from 1997 to 2003. Our results showed that increases in Section 317 funding were significantly and meaningfully associated with higher rates of vaccination coverage; a 10 dollars increase in per capita funding corresponded with a 1.6-percentage-point increase in vaccination coverage. Policymakers charged with funding public health programs should consider this study's findings, which indicate that money allocated to vaccine activities translates directly into higher vaccine coverage rates.

Performance evaluation of a mitogenome capture and Illumina sequencing protocol using non-probative, case-type skeletal samples: Implications for the use of a positive control in a next-generation sequencing procedure.

PubMed

Marshall, Charla; Sturk-Andreaggi, Kimberly; Daniels-Higginbotham, Jennifer; Oliver, Robert Sean; Barritt-Ross, Suzanne; McMahon, Timothy P

2017-11-01

Next-generation ancient DNA technologies have the potential to assist in the analysis of degraded DNA extracted from forensic specimens. Mitochondrial genome (mitogenome) sequencing, specifically, may be of benefit to samples that fail to yield forensically relevant genetic information using conventional PCR-based techniques. This report summarizes the Armed Forces Medical Examiner System's Armed Forces DNA Identification Laboratory's (AFMES-AFDIL) performance evaluation of a Next-Generation Sequencing protocol for degraded and chemically treated past accounting samples. The procedure involves hybridization capture for targeted enrichment of mitochondrial DNA, massively parallel sequencing using Illumina chemistry, and an automated bioinformatic pipeline for forensic mtDNA profile generation. A total of 22 non-probative samples and associated controls were processed in the present study, spanning a range of DNA quantity and quality. Data were generated from over 100 DNA libraries by ten DNA analysts over the course of five months. The results show that the mitogenome sequencing procedure is reliable and robust, sensitive to low template (one ng control DNA) as well as degraded DNA, and specific to the analysis of the human mitogenome. Haplotypes were overall concordant between NGS replicates and with previously generated Sanger control region data. Due to the inherent risk for contamination when working with low-template, degraded DNA, a contamination assessment was performed. The consumables were shown to be void of human DNA contaminants and suitable for forensic use. Reagent blanks and negative controls were analyzed to determine the background signal of the procedure. This background signal was then used to set analytical and reporting thresholds, which were designated at 4.0X (limit of detection) and 10.0X (limit of quantiation) average coverage across the mitogenome, respectively. Nearly all human samples exceeded the reporting threshold, although coverage was reduced in chemically treated samples resulting in a ∼58% passing rate for these poor-quality samples. A concordance assessment demonstrated the reliability of the NGS data when compared to known Sanger profiles. One case sample was shown to be mixed with a co-processed sample and two reagent blanks indicated the presence of DNA above the analytical threshold. This contamination was attributed to sequencing crosstalk from simultaneously sequenced high-quality samples to include the positive control. Overall this study demonstrated that hybridization capture and Illumina sequencing provide a viable method for mitogenome sequencing of degraded and chemically treated skeletal DNA samples, yet may require alternative measures of quality control. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Insurance premiums and insurance coverage of near-poor children.

PubMed

Hadley, Jack; Reschovsky, James D; Cunningham, Peter; Kenney, Genevieve; Dubay, Lisa

States increasingly are using premiums for near-poor children in their public insurance programs (Medicaid/SCHIP) to limit private insurance crowd-out and constrain program costs. Using national data from four rounds of the Community Tracking Study Household Surveys spanning the seven years from 1996 to 2003, this study estimates a multinomial logistic regression model examining how public and private insurance premiums affect insurance coverage outcomes (Medicaid/SCHIP coverage, private coverage, and no coverage). Higher public premiums are significantly associated with a lower probability of public coverage and higher probabilities of private coverage and uninsurance; higher private premiums are significantly related to a lower probability of private coverage and higher probabilities of public coverage and uninsurance. The results imply that uninsurance rates will rise if both public and private premiums increase, and suggest that states that impose or increase public insurance premiums for near-poor children will succeed in discouraging crowd-out of private insurance, but at the expense of higher rates of uninsurance. Sustained increases in private insurance premiums will continue to create enrollment pressures on state insurance programs for children.

The demand for health insurance coverage by low-income workers: can reduced premiums achieve full coverage?

PubMed

Chernew, M; Frick, K; McLaughlin, C G

1997-10-01

To assess the degree to which premium reductions will increase the participation in employer-sponsored health plans by low-income workers who are employed in small businesses. Sample of workers in small business (25 or fewer employees) in seven metropolitan areas. The data were gathered as part of the Small Business Benefits Survey, a telephone survey of small business conducted between October 1992 and February 1993. Probit regressions were used to estimate the demand for health insurance coverage by low-income workers. Predictions based on these findings were made to assess the extent to which premium reductions might increase coverage rates. Workers included in the sample were selected, at random, from a randomly generated set of firms drawn from Dun and Bradstreet's DMI (Dun's Market Inclusion). The response rate was 81 percent. Participation in employer-sponsored plans is high when coverage is offered. However, even when coverage is offered to employees who have no other source of insurance, participation is not universal. Although premium reductions will increase participation in employer-sponsored plans, even large subsidies will not induce all workers to participate in employer-sponsored plans. For workers eligible to participate, subsidies as high as 75 percent of premiums are estimated to increase participation rates from 89.0 percent to 92.6 percent. For workers in firms that do not sponsor plans, similar subsidies are projected to achieve only modest increases in coverage above that which would be observed if the workers had access to plans at unsubsidized, group market rates. Policies that rely on voluntary purchase of coverage to reduce the number of uninsured will have only modest success.

Health insurance for all long-term care workers: estimated costs and coverage impacts in Minnesota and recommendations for States.

PubMed

Wright, Bernadette; Gruman, Cindy; Alecxih, Lisa; Knatterud, Larhae

2012-01-01

A major barrier to building a strong workforce to meet the growing need for long-care is lack of affordable health benefits. This study projects impacts of funding health coverage for all long-term care workers in Minnesota. Under the most cost effective model plan design, enrollment in employer-sponsored coverage would increase 73% to 100% for individual coverage and 26% to 42% for family coverage. Total monthly costs would be $698/worker in the commercial market or $634/worker through a new dedicated risk pool. Based on our findings and past research, the authors present recommendations for structuring and implementing a long-term care worker health insurance initiative.

Low-coverage MiSeq next generation sequencing reveals the mitochondrial genome of the Eastern Rock Lobster, Sagmariasus verreauxi.

PubMed

Doyle, Stephen R; Griffith, Ian S; Murphy, Nick P; Strugnell, Jan M

2015-01-01

The complete mitochondrial genome of the Eastern Rock lobster, Sagmariasus verreauxi, is reported for the first time. Using low-coverage, long read MiSeq next generation sequencing, we constructed and determined the mtDNA genome organization of the 15,470 bp sequence from two isolates from Eastern Tasmania, Australia and Northern New Zealand, and identified 46 polymorphic nucleotides between the two sequences. This genome sequence and its genetic polymorphisms will likely be useful in understanding the distribution and population connectivity of the Eastern Rock Lobster, and in the fisheries management of this commercially important species.

Influenza vaccination coverage among US children from 2004/2005 to 2015/2016.

PubMed

Tian, Changwei; Wang, Hua; Wang, Wenming; Luo, Xiaoming

2018-05-15

Quantify the influenza vaccine coverage is essential to identify emerging concerns and to immunization programs for targeting interventions. Data from National Health Interview Survey were used to estimate receipt of at least one dose of influenza vaccination among children 6 months to 17 years of age. Influenza vaccination coverage increased from 16.70% during 2004/2005 to 49.43% during 2015/2016 (3.18% per year, P < 0.001); however, the coverage increased slightly after 2010/2011. Children at high risk of influenza complications had higher influenza vaccination coverage than non at-risk children. Boys and girls had similar coverage each year. While the coverage increased from 2004/2005 to 2015/2016 for all age groups, the coverage decreased with age each year (-0.64 to -1.58% per age group). There was a higher and rapid increase of coverage in Northeast than Midwest, South and West. American Indian or Alaskan Native and Asian showed higher coverage than other race groups (White, Black/African American, Multiple race). Multivariable analysis showed that high-risk status and region had the greatest associations with levels of vaccine coverage. Although the influenza vaccination coverage among children had increased remarkably since 2004/2005, establishing more effective immunization programs are warranted to achieve the Healthy People 2020 target.

Programmable and Multifunctional DNA-Based Materials for Biomedical Applications.

PubMed

Zhang, Yuezhou; Tu, Jing; Wang, Dongqing; Zhu, Haitao; Maity, Sajal Kumar; Qu, Xiangmeng; Bogaert, Bram; Pei, Hao; Zhang, Hongbo

2018-06-01

DNA encodes the genetic information; recently, it has also become a key player in material science. Given the specific Watson-Crick base-pairing interactions between only four types of nucleotides, well-designed DNA self-assembly can be programmable and predictable. Stem-loops, sticky ends, Holliday junctions, DNA tiles, and lattices are typical motifs for forming DNA-based structures. The oligonucleotides experience thermal annealing in a near-neutral buffer containing a divalent cation (usually Mg 2+ ) to produce a variety of DNA nanostructures. These structures not only show beautiful landscape, but can also be endowed with multifaceted functionalities. This Review begins with the fundamental characterization and evolutionary trajectory of DNA-based artificial structures, but concentrates on their biomedical applications. The coverage spans from controlled drug delivery to high therapeutic profile and accurate diagnosis. A variety of DNA-based materials, including aptamers, hydrogels, origamis, and tetrahedrons, are widely utilized in different biomedical fields. In addition, to achieve better performance and functionality, material hybridization is widely witnessed, and DNA nanostructure modification is also discussed. Although there are impressive advances and high expectations, the development of DNA-based structures/technologies is still hindered by several commonly recognized challenges, such as nuclease instability, lack of pharmacokinetics data, and relatively high synthesis cost. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preferential access to genetic information from endogenous hominin ancient DNA and accurate quantitative SNP-typing via SPEX

PubMed Central

Brotherton, Paul; Sanchez, Juan J.; Cooper, Alan; Endicott, Phillip

2010-01-01

The analysis of targeted genetic loci from ancient, forensic and clinical samples is usually built upon polymerase chain reaction (PCR)-generated sequence data. However, many studies have shown that PCR amplification from poor-quality DNA templates can create sequence artefacts at significant levels. With hominin (human and other hominid) samples, the pervasive presence of highly PCR-amplifiable human DNA contaminants in the vast majority of samples can lead to the creation of recombinant hybrids and other non-authentic artefacts. The resulting PCR-generated sequences can then be difficult, if not impossible, to authenticate. In contrast, single primer extension (SPEX)-based approaches can genotype single nucleotide polymorphisms from ancient fragments of DNA as accurately as modern DNA. A single SPEX-type assay can amplify just one of the duplex DNA strands at target loci and generate a multi-fold depth-of-coverage, with non-authentic recombinant hybrids reduced to undetectable levels. Crucially, SPEX-type approaches can preferentially access genetic information from damaged and degraded endogenous ancient DNA templates over modern human DNA contaminants. The development of SPEX-type assays offers the potential for highly accurate, quantitative genotyping from ancient hominin samples. PMID:19864251

Environmental DNA (eDNA) Sampling Improves Occurrence and Detection Estimates of Invasive Burmese Pythons

PubMed Central

Hunter, Margaret E.; Oyler-McCance, Sara J.; Dorazio, Robert M.; Fike, Jennifer A.; Smith, Brian J.; Hunter, Charles T.; Reed, Robert N.; Hart, Kristen M.

2015-01-01

Environmental DNA (eDNA) methods are used to detect DNA that is shed into the aquatic environment by cryptic or low density species. Applied in eDNA studies, occupancy models can be used to estimate occurrence and detection probabilities and thereby account for imperfect detection. However, occupancy terminology has been applied inconsistently in eDNA studies, and many have calculated occurrence probabilities while not considering the effects of imperfect detection. Low detection of invasive giant constrictors using visual surveys and traps has hampered the estimation of occupancy and detection estimates needed for population management in southern Florida, USA. Giant constrictor snakes pose a threat to native species and the ecological restoration of the Florida Everglades. To assist with detection, we developed species-specific eDNA assays using quantitative PCR (qPCR) for the Burmese python (Python molurus bivittatus), Northern African python (P. sebae), boa constrictor (Boa constrictor), and the green (Eunectes murinus) and yellow anaconda (E. notaeus). Burmese pythons, Northern African pythons, and boa constrictors are established and reproducing, while the green and yellow anaconda have the potential to become established. We validated the python and boa constrictor assays using laboratory trials and tested all species in 21 field locations distributed in eight southern Florida regions. Burmese python eDNA was detected in 37 of 63 field sampling events; however, the other species were not detected. Although eDNA was heterogeneously distributed in the environment, occupancy models were able to provide the first estimates of detection probabilities, which were greater than 91%. Burmese python eDNA was detected along the leading northern edge of the known population boundary. The development of informative detection tools and eDNA occupancy models can improve conservation efforts in southern Florida and support more extensive studies of invasive constrictors. Generic sampling design and terminology are proposed to standardize and clarify interpretations of eDNA-based occupancy models. PMID:25874630

Environmental DNA (eDNA) sampling improves occurrence and detection estimates of invasive Burmese pythons

USGS Publications Warehouse

Hunter, Margaret E.; Oyler-McCance, Sara J.; Dorazio, Robert M.; Fike, Jennifer A.; Smith, Brian J.; Hunter, Charles T.; Reed, Robert N.; Hart, Kristen M.

2015-01-01

Environmental DNA (eDNA) methods are used to detect DNA that is shed into the aquatic environment by cryptic or low density species. Applied in eDNA studies, occupancy models can be used to estimate occurrence and detection probabilities and thereby account for imperfect detection. However, occupancy terminology has been applied inconsistently in eDNA studies, and many have calculated occurrence probabilities while not considering the effects of imperfect detection. Low detection of invasive giant constrictors using visual surveys and traps has hampered the estimation of occupancy and detection estimates needed for population management in southern Florida, USA. Giant constrictor snakes pose a threat to native species and the ecological restoration of the Florida Everglades. To assist with detection, we developed species-specific eDNA assays using quantitative PCR (qPCR) for the Burmese python (Python molurus bivittatus), Northern African python (P. sebae), boa constrictor (Boa constrictor), and the green (Eunectes murinus) and yellow anaconda (E. notaeus). Burmese pythons, Northern African pythons, and boa constrictors are established and reproducing, while the green and yellow anaconda have the potential to become established. We validated the python and boa constrictor assays using laboratory trials and tested all species in 21 field locations distributed in eight southern Florida regions. Burmese python eDNA was detected in 37 of 63 field sampling events; however, the other species were not detected. Although eDNA was heterogeneously distributed in the environment, occupancy models were able to provide the first estimates of detection probabilities, which were greater than 91%. Burmese python eDNA was detected along the leading northern edge of the known population boundary. The development of informative detection tools and eDNA occupancy models can improve conservation efforts in southern Florida and support more extensive studies of invasive constrictors. Generic sampling design and terminology are proposed to standardize and clarify interpretations of eDNA-based occupancy models.

Environmental DNA (eDNA) sampling improves occurrence and detection estimates of invasive burmese pythons.

PubMed

Hunter, Margaret E; Oyler-McCance, Sara J; Dorazio, Robert M; Fike, Jennifer A; Smith, Brian J; Hunter, Charles T; Reed, Robert N; Hart, Kristen M

2015-01-01

Environmental DNA (eDNA) methods are used to detect DNA that is shed into the aquatic environment by cryptic or low density species. Applied in eDNA studies, occupancy models can be used to estimate occurrence and detection probabilities and thereby account for imperfect detection. However, occupancy terminology has been applied inconsistently in eDNA studies, and many have calculated occurrence probabilities while not considering the effects of imperfect detection. Low detection of invasive giant constrictors using visual surveys and traps has hampered the estimation of occupancy and detection estimates needed for population management in southern Florida, USA. Giant constrictor snakes pose a threat to native species and the ecological restoration of the Florida Everglades. To assist with detection, we developed species-specific eDNA assays using quantitative PCR (qPCR) for the Burmese python (Python molurus bivittatus), Northern African python (P. sebae), boa constrictor (Boa constrictor), and the green (Eunectes murinus) and yellow anaconda (E. notaeus). Burmese pythons, Northern African pythons, and boa constrictors are established and reproducing, while the green and yellow anaconda have the potential to become established. We validated the python and boa constrictor assays using laboratory trials and tested all species in 21 field locations distributed in eight southern Florida regions. Burmese python eDNA was detected in 37 of 63 field sampling events; however, the other species were not detected. Although eDNA was heterogeneously distributed in the environment, occupancy models were able to provide the first estimates of detection probabilities, which were greater than 91%. Burmese python eDNA was detected along the leading northern edge of the known population boundary. The development of informative detection tools and eDNA occupancy models can improve conservation efforts in southern Florida and support more extensive studies of invasive constrictors. Generic sampling design and terminology are proposed to standardize and clarify interpretations of eDNA-based occupancy models.

Vaccination coverage among foreign-born and U.S.-born adolescents in the United States: Successes and gaps - National Immunization Survey-Teen, 2012-2014.

PubMed

Healy, Jessica; Rodriguez-Lainz, Alfonso; Elam-Evans, Laurie D; Hill, Holly A; Reagan-Steiner, Sarah; Yankey, David

2018-03-20

An overall increase has been reported in vaccination rates among adolescents during the past decade. Studies of vaccination coverage have shown disparities when comparing foreign-born and U.S.-born populations among children and adults; however, limited information is available concerning potential disparities in adolescents. The National Immunization Survey-Teen is a random-digit-dialed telephone survey of caregivers of adolescents aged 13-17 years, followed by a mail survey to vaccination providers that is used to estimate vaccination coverage among the U.S. population of adolescents. Using the National Immunization Survey-Teen data, we assessed vaccination coverage during 2012-2014 among adolescents for routinely recommended vaccines for this age group (≥1 dose tetanus and diphtheria toxoids and acellular pertussis [Tdap] vaccine, ≥1 dose quadrivalent meningococcal conjugate [MenACWY] vaccine, ≥3 doses human papillomavirus [HPV] vaccine) and for routine childhood vaccination catch-up doses (≥2 doses measles, mumps, and rubella [MMR] vaccine, ≥2 doses varicella vaccine, and ≥3 doses hepatitis B [HepB] vaccine). Vaccination coverage prevalence and vaccination prevalence ratios were estimated. Of the 58,090 respondents included, 3.3% were foreign-born adolescents. Significant differences were observed between foreign-born and U.S.-born adolescents for insurance status, income-to-poverty ratio, education, interview language, and household size. Foreign-born adolescents had significantly lower unadjusted vaccination coverage for HepB (89% vs. 93%), and higher coverage for the recommended ≥3 doses of HPV vaccine among males, compared with U.S.-born adolescents (22% vs. 14%). Adjustment for demographic and socioeconomic factors accounted for the disparity in HPV but not HepB vaccination coverage. We report comparable unadjusted vaccination coverage among foreign-born and U.S.-born adolescents for Tdap, MenACWY, MMR, ≥2 varicella. Although coverage was high for HepB vaccine, it was significantly lower among foreign-born adolescents, compared with U.S.-born adolescents. HPV and ≥2-dose varicella vaccination coverage were low among both groups. Published by Elsevier Ltd.

Income Eligibility Thresholds, Premium Contributions, and Children's Coverage Outcomes: A Study of CHIP Expansions

PubMed Central

Gresenz, Carole Roan; Edgington, Sarah E; Laugesen, Miriam J; Escarce, José J

2013-01-01

Objective To understand the effects of Children's Health Insurance Program (CHIP) income eligibility thresholds and premium contribution requirements on health insurance coverage outcomes among children. Data Sources 2002–2009 Annual Social and Economic Supplements of the Current Population Survey linked to data from multiple secondary data sources. Study Design We use a selection correction model to simultaneously estimate program eligibility and coverage outcomes conditional upon eligibility. We simulate the effects of three premium schedules representing a range of generosity levels and the effects of income eligibility thresholds ranging from 200 to 400 percent of the federal poverty line. Principal Findings Premium contribution requirements decrease enrollment in public coverage and increase enrollment in private coverage, with larger effects for greater contribution levels. Our simulation results suggest minimal changes in coverage outcomes from eligibility expansions to higher income families under premium schedules that require more than a modest contribution (medium or high schedules). Conclusions Our simulation results are useful counterpoints to previous research that has estimated the average effect of program expansions as they were implemented without disentangling the effects of premiums or other program features. The sensitivity to premiums observed suggests that although contribution requirements may be effective in reducing crowd-out, they also have the potential, depending on the level of contribution required, to nullify the effects of CHIP expansions entirely. The persistence of uninsurance among children under the range of simulated scenarios points to the importance of Affordable Care Act provisions designed to make the process of obtaining coverage transparent and navigable. PMID:23398477

Using health-facility data to assess subnational coverage of maternal and child health indicators, Kenya.

PubMed

Maina, Isabella; Wanjala, Pepela; Soti, David; Kipruto, Hillary; Droti, Benson; Boerma, Ties

2017-10-01

To develop a systematic approach to obtain the best possible national and subnational statistics for maternal and child health coverage indicators from routine health-facility data. Our approach aimed to obtain improved numerators and denominators for calculating coverage at the subnational level from health-facility data. This involved assessing data quality and determining adjustment factors for incomplete reporting by facilities, then estimating local target populations based on interventions with near-universal coverage (first antenatal visit and first dose of pentavalent vaccine). We applied the method to Kenya at the county level, where routine electronic reporting by facilities is in place via the district health information software system. Reporting completeness for facility data were well above 80% in all 47 counties and the consistency of data over time was good. Coverage of the first dose of pentavalent vaccine, adjusted for facility reporting completeness, was used to obtain estimates of the county target populations for maternal and child health indicators. The country and national statistics for the four-year period 2012/13 to 2015/16 showed good consistency with results of the 2014 Kenya demographic and health survey. Our results indicated a stagnation of immunization coverage in almost all counties, a rapid increase of facility-based deliveries and caesarean sections and limited progress in antenatal care coverage. While surveys will continue to be necessary to provide population-based data, web-based information systems for health facility reporting provide an opportunity for more frequent, local monitoring of progress, in maternal and child health.

Income eligibility thresholds, premium contributions, and children's coverage outcomes: a study of CHIP expansions.

PubMed

Gresenz, Carole Roan; Edgington, Sarah E; Laugesen, Miriam J; Escarce, José J

2013-04-01

To understand the effects of Children's Health Insurance Program (CHIP) income eligibility thresholds and premium contribution requirements on health insurance coverage outcomes among children. 2002-2009 Annual Social and Economic Supplements of the Current Population Survey linked to data from multiple secondary data sources. We use a selection correction model to simultaneously estimate program eligibility and coverage outcomes conditional upon eligibility. We simulate the effects of three premium schedules representing a range of generosity levels and the effects of income eligibility thresholds ranging from 200 to 400 percent of the federal poverty line. Premium contribution requirements decrease enrollment in public coverage and increase enrollment in private coverage, with larger effects for greater contribution levels. Our simulation results suggest minimal changes in coverage outcomes from eligibility expansions to higher income families under premium schedules that require more than a modest contribution (medium or high schedules). Our simulation results are useful counterpoints to previous research that has estimated the average effect of program expansions as they were implemented without disentangling the effects of premiums or other program features. The sensitivity to premiums observed suggests that although contribution requirements may be effective in reducing crowd-out, they also have the potential, depending on the level of contribution required, to nullify the effects of CHIP expansions entirely. The persistence of uninsurance among children under the range of simulated scenarios points to the importance of Affordable Care Act provisions designed to make the process of obtaining coverage transparent and navigable. © Health Research and Educational Trust.

Correlates of syringe coverage for heroin injection in 35 large metropolitan areas in the US in which heroin is the dominant injected drug

PubMed Central

Tempalski, Barbara; Cooper, Hannah L.; Friedman, Samuel R.; Des Jarlais, Don C.; Brady, Joanne; Gostnell, Karla

2009-01-01

Background Scientific consensus holds that if, at the outset of the HIV/AIDS epidemic, injection drug users (IDUs) had had better access to sterile syringes, much of the epidemic among IDUs in the U.S. could have been prevented. In the context of preventing infectious diseases, 100% syringe coverage—that is, one sterile syringe per injector for each injection—is a public health goal. Notably, we know little about variations in syringe coverage within the U.S. and elsewhere, or about the social and political factors that might determine this coverage. Methods Using data from Holmberg (AJPH, 1996), the 1990 United States Census, the 2000 Beth Israel National Syringe Exchange Survey (n=72), and estimates of IDUs in metropolitan areas (MSAs); (Friedman et al., 2004), we explore the impact of (1) political factors (ACT UP, outreach, early syringe exchange programme (SEP) presence, men who have sex with men (MSM) per capita, drug arrests, and police per capita); (2) local resources for SEPs; and (3) indicators of socioeconomic inequality on SEP coverage. We define “syringe coverage” as the ratio of syringes distributed at SEPs to the number of syringes heroin injectors need in a year. We calculated the number of syringes heroin injectors need in a year by multiplying an estimate of the number of IDUs in each MSA by an estimate of the average number of times heroin injectors inject heroin per year (2.8 times per day times 365 days). In this analysis, the sample was limited to 35 MSAs in which the primary drug of choice among injectors was heroin. Results SEP coverage varies greatly across MSAs, with an average of 3 syringes distributed per 100 injection events (std dev = 0.045; range: 2 syringes per 10 injection events, to 3 syringes per 10,000 injection events). In bivariate regression analyses, a 1 unit difference in the proportion of the population that was MSM per 1,000 was associated with a difference of 0.002 in SEP coverage (p=0.052); early SEP presence was associated with a difference of 0.038 in coverage (p=0.012); and having government funding was associated with a 0.040 difference in SEP coverage (p=0.021). Conclusions This analysis suggests that longer duration of SEP presence may increase syringe distribution and enhance successful programme utilization. Furthermore, MSAs with greater proportions of MSM tend to have better SEP coverage, perhaps providing further evidence that grassroots activism plays an important role in programme implementation and successful SEP coverage. This research provides evidence that government funding for SEPs contributes to better syringe coverage. PMID:18295468

DNA Methyltransferase Activity Assays: Advances and Challenges

PubMed Central

Poh, Wan Jun; Wee, Cayden Pang Pee; Gao, Zhiqiang

2016-01-01

DNA methyltransferases (MTases), a family of enzymes that catalyse the methylation of DNA, have a profound effect on gene regulation. A large body of evidence has indicated that DNA MTase is potentially a predictive biomarker closely associated with genetic disorders and genetic diseases like cancer. Given the attention bestowed onto DNA MTases in molecular biology and medicine, highly sensitive detection of DNA MTase activity is essential in determining gene regulation, epigenetic modification, clinical diagnosis and therapeutics. Conventional techniques such as isotope labelling are effective, but they often require laborious sample preparation, isotope labelling, sophisticated equipment and large amounts of DNA, rendering them unsuitable for uses at point-of-care. Simple, portable, highly sensitive and low-cost assays are urgently needed for DNA MTase activity screening. In most recent technological advances, many alternative DNA MTase activity assays such as fluorescent, electrochemical, colorimetric and chemiluminescent assays have been proposed. In addition, many of them are coupled with nanomaterials and/or enzymes to significantly enhance their sensitivity. Herein we review the progress in the development of DNA MTase activity assays with an emphasis on assay mechanism and performance with some discussion on challenges and perspectives. It is hoped that this article will provide a broad coverage of DNA MTase activity assays and their latest developments and open new perspectives toward the development of DNA MTase activity assays with much improved performance for uses in molecular biology and clinical practice. PMID:26909112

Effects of 16S rDNA sampling on estimates of the number of endosymbiont lineages in sucking lice

PubMed Central

Burleigh, J. Gordon; Light, Jessica E.; Reed, David L.

2016-01-01

Phylogenetic trees can reveal the origins of endosymbiotic lineages of bacteria and detect patterns of co-evolution with their hosts. Although taxon sampling can greatly affect phylogenetic and co-evolutionary inference, most hypotheses of endosymbiont relationships are based on few available bacterial sequences. Here we examined how different sampling strategies of Gammaproteobacteria sequences affect estimates of the number of endosymbiont lineages in parasitic sucking lice (Insecta: Phthirapatera: Anoplura). We estimated the number of louse endosymbiont lineages using both newly obtained and previously sequenced 16S rDNA bacterial sequences and more than 42,000 16S rDNA sequences from other Gammaproteobacteria. We also performed parametric and nonparametric bootstrapping experiments to examine the effects of phylogenetic error and uncertainty on these estimates. Sampling of 16S rDNA sequences affects the estimates of endosymbiont diversity in sucking lice until we reach a threshold of genetic diversity, the size of which depends on the sampling strategy. Sampling by maximizing the diversity of 16S rDNA sequences is more efficient than randomly sampling available 16S rDNA sequences. Although simulation results validate estimates of multiple endosymbiont lineages in sucking lice, the bootstrap results suggest that the precise number of endosymbiont origins is still uncertain. PMID:27547523

Measuring Aptamer Equilbria Using Gradient Micro Free Flow Electrophoresis

PubMed Central

Turgeon, Ryan T.; Fonslow, Bryan R.; Jing, Meng; Bowser, Michael T.

2010-01-01

Gradient micro free flow electrophoresis (μFFE) was used to observe the equilibria of DNA aptamers with their targets (IgE or HIVRT) across a range of ligand concentrations. A continuous stream of aptamer was mixed online with an increasing concentration of target and introduced into the μFFE device, which separated ligand-aptamer complexes from the unbound aptamer. The continuous nature of μFFE allowed the equilibrium distribution of aptamer and complex to be measured at 300 discrete target concentrations within 5 minutes. This is a significant improvement in speed and precision over affinity capillary electrophoresis (ACE) assays. The dissociation constant of the aptamer-IgE complex was estimated to be 48± 3 nM. The high coverage across the range of ligand concentrations allowed complex stoichiometries of the aptamer-HIVRT complexes to be observed. Nearly continuous observation of the equilibrium distribution from 0 to 500 nM HIVRT revealed the presence of complexes with 3:1 (aptamer:HIVRT), 2:1 and 1:1 stoichiometries. PMID:20373790

Optimal Redundancy Management in Reconfigurable Control Systems Based on Normalized Nonspecificity

NASA Technical Reports Server (NTRS)

Wu, N.Eva; Klir, George J.

1998-01-01

In this paper the notion of normalized nonspecificity is introduced. The nonspecifity measures the uncertainty of the estimated parameters that reflect impairment in a controlled system. Based on this notion, a quantity called a reconfiguration coverage is calculated. It represents the likelihood of success of a control reconfiguration action. This coverage links the overall system reliability to the achievable and required control, as well as diagnostic performance. The coverage, when calculated on-line, is used for managing the redundancy in the system.

Clinical trials finance and operations.

PubMed

O'Brien, Jennifer A

2007-01-01

The National Coverage Decision of 2000 was designed to enhance the participation in clinical trials for both patients and physicians by mandating the governmental coverage for services in a clinical trial that are considered "routine" regardless of the trial. Participation in clinical trials can be a practice builder as well as a contribution to the betterment of medical science. Without proper coverage analysis, study budgeting, accurate time estimates, and effective negotiation prior to signing the contract, participation in clinical trials can cost a practice rather than benefit it.

Effects of public premiums on children's health insurance coverage: evidence from 1999 to 2003.

PubMed

Kenney, Genevieve; Hadley, Jack; Blavin, Fredric

This study uses 2000 to 2004 Current Population Survey data to examine the effects of public premiums on the insurance coverage of children whose family incomes are between 100% and 300% of the federal poverty level. The analysis employs multinomial logistic models that control for factors other than premium costs. While the magnitude of the estimated effects varies across models, the results consistently indicate that raising public premiums reduces enrollment in public programs, with some children who forgo public coverage having private coverage instead and others being uninsured. The results indicate that public premiums have larger effects when applied to lower-income families.

Reversible Regulation of Catalytic Activity of Gold Nanoparticles with DNA Nanomachines

NASA Astrophysics Data System (ADS)

Zhou, Peipei; Jia, Sisi; Pan, Dun; Wang, Lihua; Gao, Jimin; Lu, Jianxin; Shi, Jiye; Tang, Zisheng; Liu, Huajie

2015-09-01

Reversible catalysis regulation has gained much attention and traditional strategies utilized reversible ligand coordination for switching catalyst’s conformations. However, it remains challenging to regulate the catalytic activity of metal nanoparticle-based catalysts. Herein, we report a new DNA nanomachine-driven reversible nano-shield strategy for circumventing this problem. The basic idea is based on the fact that the conformational change of surface-attached DNA nanomachines will cause the variation of the exposed surface active area on metal nanoparticles. As a proof-of-concept study, we immobilized G-rich DNA strands on gold nanoparticles (AuNPs) which have glucose oxidase (GOx) like activity. Through the reversible conformational change of the G-rich DNA between a flexible single-stranded form and a compact G-quadruplex form, the catalytic activity of AuNPs has been regulated reversibly for several cycles. This strategy is reliable and robust, which demonstrated the possibility of reversibly adjusting catalytic activity with external surface coverage switching, rather than coordination interactions.

No Genetic Influence for Childhood Behavior Problems From DNA Analysis

PubMed Central

Trzaskowski, Maciej; Dale, Philip S.; Plomin, Robert

2013-01-01

Objective Twin studies of behavior problems in childhood point to substantial genetic influence. It is now possible to estimate genetic influence using DNA alone in samples of unrelated individuals, not relying on family-based designs such as twins. A linear mixed model, which incorporates DNA microarray data, has confirmed twin results by showing substantial genetic influence for diverse traits in adults. Here we present direct comparisons between twin and DNA heritability estimates for childhood behavior problems as rated by parents, teachers, and children themselves. Method Behavior problem data from 2,500 UK-representative 12-year-old twin pairs were used in twin analyses; DNA analyses were based on 1 member of the twin pair with genotype data for 1.7 million DNA markers. Diverse behavior problems were assessed, including autistic, depressive, and hyperactive symptoms. Genetic influence from DNA was estimated using genome-wide complex trait analysis (GCTA), and the twin estimates of heritability were based on standard twin model fitting. Results Behavior problems in childhood—whether rated by parents, teachers, or children themselves—show no significant genetic influence using GCTA, even though twin study estimates of heritability are substantial in the same sample, and even though both GCTA and twin study estimates of genetic influence are substantial for cognitive and anthropometric traits. Conclusions We suggest that this new type of “missing heritability,” that is, the gap between GCTA and twin study estimates for behavior problems in childhood, is due to nonadditive genetic influence, which will make it more difficult to identify genes responsible for heritability. PMID:24074471

Disk-based compression of data from genome sequencing.

PubMed

Grabowski, Szymon; Deorowicz, Sebastian; Roguski, Łukasz

2015-05-01

High-coverage sequencing data have significant, yet hard to exploit, redundancy. Most FASTQ compressors cannot efficiently compress the DNA stream of large datasets, since the redundancy between overlapping reads cannot be easily captured in the (relatively small) main memory. More interesting solutions for this problem are disk based, where the better of these two, from Cox et al. (2012), is based on the Burrows-Wheeler transform (BWT) and achieves 0.518 bits per base for a 134.0 Gbp human genome sequencing collection with almost 45-fold coverage. We propose overlapping reads compression with minimizers, a compression algorithm dedicated to sequencing reads (DNA only). Our method makes use of a conceptually simple and easily parallelizable idea of minimizers, to obtain 0.317 bits per base as the compression ratio, allowing to fit the 134.0 Gbp dataset into only 5.31 GB of space. http://sun.aei.polsl.pl/orcom under a free license. sebastian.deorowicz@polsl.pl Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Dfam: a database of repetitive DNA based on profile hidden Markov models.

PubMed

Wheeler, Travis J; Clements, Jody; Eddy, Sean R; Hubley, Robert; Jones, Thomas A; Jurka, Jerzy; Smit, Arian F A; Finn, Robert D

2013-01-01

We present a database of repetitive DNA elements, called Dfam (http://dfam.janelia.org). Many genomes contain a large fraction of repetitive DNA, much of which is made up of remnants of transposable elements (TEs). Accurate annotation of TEs enables research into their biology and can shed light on the evolutionary processes that shape genomes. Identification and masking of TEs can also greatly simplify many downstream genome annotation and sequence analysis tasks. The commonly used TE annotation tools RepeatMasker and Censor depend on sequence homology search tools such as cross_match and BLAST variants, as well as Repbase, a collection of known TE families each represented by a single consensus sequence. Dfam contains entries corresponding to all Repbase TE entries for which instances have been found in the human genome. Each Dfam entry is represented by a profile hidden Markov model, built from alignments generated using RepeatMasker and Repbase. When used in conjunction with the hidden Markov model search tool nhmmer, Dfam produces a 2.9% increase in coverage over consensus sequence search methods on a large human benchmark, while maintaining low false discovery rates, and coverage of the full human genome is 54.5%. The website provides a collection of tools and data views to support improved TE curation and annotation efforts. Dfam is also available for download in flat file format or in the form of MySQL table dumps.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruggles, Kelly V.; Tang, Zuojian; Wang, Xuya

Improvements in mass spectrometry (MS)-based peptide sequencing provide a new opportunity to determine whether polymorphisms, mutations and splice variants identified in cancer cells are translated. Herein we therefore describe a proteogenomic data integration tool (QUILTS) and illustrate its application to whole genome, transcriptome and global MS peptide sequence datasets generated from a pair of luminal and basal-like breast cancer patient derived xenografts (PDX). The sensitivity of proteogenomic analysis for singe nucleotide variant (SNV) expression and novel splice junction (NSJ) detection was probed using multiple MS/MS process replicates. Despite over thirty sample replicates, only about 10% of all SNV (somatic andmore » germline) were detected by both DNA and RNA sequencing were observed as peptides. An even smaller proportion of peptides corresponding to NSJ observed by RNA sequencing were detected (<0.1%). Peptides mapping to DNA-detected SNV without a detectable mRNA transcript were also observed demonstrating the transcriptome coverage was also incomplete (~80%). In contrast to germ-line variants, somatic variants were less likely to be detected at the peptide level in the basal-like tumor than the luminal tumor raising the possibility of differential translation or protein degradation effects. In conclusion, the QUILTS program integrates DNA, RNA and peptide sequencing to assess the degree to which somatic mutations are translated and therefore biologically active. By identifying gaps in sequence coverage QUILTS benchmarks current technology and assesses progress towards whole cancer proteome and transcriptome analysis.« less

Care 3 phase 2 report, maintenance manual

NASA Technical Reports Server (NTRS)

Bryant, L. A.; Stiffler, J. J.

1982-01-01

CARE 3 (Computer-Aided Reliability Estimation, version three) is a computer program designed to help estimate the reliability of complex, redundant systems. Although the program can model a wide variety of redundant structures, it was developed specifically for fault-tolerant avionics systems--systems distinguished by the need for extremely reliable performance since a system failure could well result in the loss of human life. It substantially generalizes the class of redundant configurations that could be accommodated, and includes a coverage model to determine the various coverage probabilities as a function of the applicable fault recovery mechanisms (detection delay, diagnostic scheduling interval, isolation and recovery delay, etc.). CARE 3 further generalizes the class of system structures that can be modeled and greatly expands the coverage model to take into account such effects as intermittent and transient faults, latent faults, error propagation, etc.

At the forefront: evidence of the applicability of using environmental DNA to quantify the abundance of fish populations in natural lentic waters with additional sampling considerations

USGS Publications Warehouse

Klobucar, Stephen L.; Rodgers, Torrey W.; Budy, Phaedra

2017-01-01

Environmental DNA (eDNA) sampling has proven to be a valuable tool for detecting species in aquatic ecosystems. Within this rapidly evolving field, a promising application is the ability to obtain quantitative estimates of relative species abundance based on eDNA concentration rather than traditionally labor-intensive methods. We investigated the relationship between eDNA concentration and Arctic char (Salvelinus alpinus) abundance in five well-studied natural lakes; additionally, we examined the effects of different temporal (e.g., season) and spatial (e.g., depth) scales on eDNA concentration. Concentrations of eDNA were linearly correlated with char population estimates ( = 0.78) and exponentially correlated with char densities ( = 0.96 by area; 0.82 by volume). Across lakes, eDNA concentrations were greater and more homogeneous in the water column during mixis; however, when stratified, eDNA concentrations were greater in the hypolimnion. Overall, our findings demonstrate that eDNA techniques can produce effective estimates of relative fish abundance in natural lakes. These findings can guide future studies to improve and expand eDNA methods while informing research and management using rapid and minimally invasive sampling.

Pipeline for large-scale microdroplet bisulfite PCR-based sequencing allows the tracking of hepitype evolution in tumors.

PubMed

Herrmann, Alexander; Haake, Andrea; Ammerpohl, Ole; Martin-Guerrero, Idoia; Szafranski, Karol; Stemshorn, Kathryn; Nothnagel, Michael; Kotsopoulos, Steve K; Richter, Julia; Warner, Jason; Olson, Jeff; Link, Darren R; Schreiber, Stefan; Krawczak, Michael; Platzer, Matthias; Nürnberg, Peter; Siebert, Reiner; Hampe, Jochen

2011-01-01

Cytosine methylation provides an epigenetic level of cellular plasticity that is important for development, differentiation and cancerogenesis. We adopted microdroplet PCR to bisulfite treated target DNA in combination with second generation sequencing to simultaneously assess DNA sequence and methylation. We show measurement of methylation status in a wide range of target sequences (total 34 kb) with an average coverage of 95% (median 100%) and good correlation to the opposite strand (rho = 0.96) and to pyrosequencing (rho = 0.87). Data from lymphoma and colorectal cancer samples for SNRPN (imprinted gene), FGF6 (demethylated in the cancer samples) and HS3ST2 (methylated in the cancer samples) serve as a proof of principle showing the integration of SNP data and phased DNA-methylation information into "hepitypes" and thus the analysis of DNA methylation phylogeny in the somatic evolution of cancer.

Pooled-DNA Sequencing for Elucidating New Genomic Risk Factors, Rare Variants Underlying Alzheimer's Disease.

PubMed

Jin, Sheng Chih; Benitez, Bruno A; Deming, Yuetiva; Cruchaga, Carlos

2016-01-01

Analyses of genome-wide association studies (GWAS) for complex disorders usually identify common variants with a relatively small effect size that only explain a small proportion of phenotypic heritability. Several studies have suggested that a significant fraction of heritability may be explained by low-frequency (minor allele frequency (MAF) of 1-5 %) and rare-variants that are not contained in the commercial GWAS genotyping arrays (Schork et al., Curr Opin Genet Dev 19:212, 2009). Rare variants can also have relatively large effects on risk for developing human diseases or disease phenotype (Cruchaga et al., PLoS One 7:e31039, 2012). However, it is necessary to perform next-generation sequencing (NGS) studies in a large population (>4,000 samples) to detect a significant rare-variant association. Several NGS methods, such as custom capture sequencing and amplicon-based sequencing, are designed to screen a small proportion of the genome, but most of these methods are limited in the number of samples that can be multiplexed (i.e. most sequencing kits only provide 96 distinct index). Additionally, the sequencing library preparation for 4,000 samples remains expensive and thus conducting NGS studies with the aforementioned methods are not feasible for most research laboratories.The need for low-cost large scale rare-variant detection makes pooled-DNA sequencing an ideally efficient and cost-effective technique to identify rare variants in target regions by sequencing hundreds to thousands of samples. Our recent work has demonstrated that pooled-DNA sequencing can accurately detect rare variants in targeted regions in multiple DNA samples with high sensitivity and specificity (Jin et al., Alzheimers Res Ther 4:34, 2012). In these studies we used a well-established pooled-DNA sequencing approach and a computational package, SPLINTER (short indel prediction by large deviation inference and nonlinear true frequency estimation by recursion) (Vallania et al., Genome Res 20:1711, 2010), for accurate identification of rare variants in large DNA pools. Given an average sequencing coverage of 30× per haploid genome, SPLINTER can detect rare variants and short indels up to 4 base pairs (bp) with high sensitivity and specificity (up to 1 haploid allele in a pool as large as 500 individuals). Step-by-step instructions on how to conduct pooled-DNA sequencing experiments and data analyses are described in this chapter.

Comparative Estimates of Crude and Effective Coverage of Measles Immunization in Low-Resource Settings: Findings from Salud Mesoamérica 2015.

PubMed

Colson, K Ellicott; Zúñiga-Brenes, Paola; Ríos-Zertuche, Diego; Conde-Glez, Carlos J; Gagnier, Marielle C; Palmisano, Erin; Ranganathan, Dharani; Usmanova, Gulnoza; Salvatierra, Benito; Nazar, Austreberta; Tristao, Ignez; Sanchez Monin, Emmanuelle; Anderson, Brent W; Haakenstad, Annie; Murphy, Tasha; Lim, Stephen; Hernandez, Bernardo; Lozano, Rafael; Iriarte, Emma; Mokdad, Ali H

2015-01-01

Timely and accurate measurement of population protection against measles is critical for decision-making and prevention of outbreaks. However, little is known about how survey-based estimates of immunization (crude coverage) compare to the seroprevalence of antibodies (effective coverage), particularly in low-resource settings. In poor areas of Mexico and Nicaragua, we used household surveys to gather information on measles immunization from child health cards and caregiver recall. We also collected dried blood spots (DBS) from children aged 12 to 23 months to compare crude and effective coverage of measles immunization. We used survey-weighted logistic regression to identify individual, maternal, household, community, and health facility characteristics that predict gaps between crude coverage and effective coverage. We found that crude coverage was significantly higher than effective coverage (83% versus 68% in Mexico; 85% versus 50% in Nicaragua). A large proportion of children (19% in Mexico; 43% in Nicaragua) had health card documentation of measles immunization but lacked antibodies. These discrepancies varied from 0% to 100% across municipalities in each country. In multivariate analyses, card-positive children in Mexico were more likely to lack antibodies if they resided in urban areas or the jurisdiction of De Los Llanos. In contrast, card-positive children in Nicaragua were more likely to lack antibodies if they resided in rural areas or the North Atlantic region, had low weight-for-age, or attended health facilities with a greater number of refrigerators. Findings highlight that reliance on child health cards to measure population protection against measles is unwise. We call for the evaluation of immunization programs using serological methods, especially in poor areas where the cold chain is likely to be compromised. Identification of within-country variation in effective coverage of measles immunization will allow researchers and public health professionals to address challenges in current immunization programs.

Comparative Estimates of Crude and Effective Coverage of Measles Immunization in Low-Resource Settings: Findings from Salud Mesoamérica 2015

PubMed Central

Colson, K. Ellicott; Zúñiga-Brenes, Paola; Ríos-Zertuche, Diego; Conde-Glez, Carlos J.; Gagnier, Marielle C.; Palmisano, Erin; Ranganathan, Dharani; Usmanova, Gulnoza; Salvatierra, Benito; Nazar, Austreberta; Tristao, Ignez; Sanchez Monin, Emmanuelle; Anderson, Brent W.; Haakenstad, Annie; Murphy, Tasha; Lim, Stephen; Hernandez, Bernardo; Lozano, Rafael

2015-01-01

Timely and accurate measurement of population protection against measles is critical for decision-making and prevention of outbreaks. However, little is known about how survey-based estimates of immunization (crude coverage) compare to the seroprevalence of antibodies (effective coverage), particularly in low-resource settings. In poor areas of Mexico and Nicaragua, we used household surveys to gather information on measles immunization from child health cards and caregiver recall. We also collected dried blood spots (DBS) from children aged 12 to 23 months to compare crude and effective coverage of measles immunization. We used survey-weighted logistic regression to identify individual, maternal, household, community, and health facility characteristics that predict gaps between crude coverage and effective coverage. We found that crude coverage was significantly higher than effective coverage (83% versus 68% in Mexico; 85% versus 50% in Nicaragua). A large proportion of children (19% in Mexico; 43% in Nicaragua) had health card documentation of measles immunization but lacked antibodies. These discrepancies varied from 0% to 100% across municipalities in each country. In multivariate analyses, card-positive children in Mexico were more likely to lack antibodies if they resided in urban areas or the jurisdiction of De Los Llanos. In contrast, card-positive children in Nicaragua were more likely to lack antibodies if they resided in rural areas or the North Atlantic region, had low weight-for-age, or attended health facilities with a greater number of refrigerators. Findings highlight that reliance on child health cards to measure population protection against measles is unwise. We call for the evaluation of immunization programs using serological methods, especially in poor areas where the cold chain is likely to be compromised. Identification of within-country variation in effective coverage of measles immunization will allow researchers and public health professionals to address challenges in current immunization programs. PMID:26136239

Immunisation coverage in rural–urban migrant children in low and middle-income countries (LMICs): a systematic review and meta-analysis

PubMed Central

Awoh, Abiyemi Benita; Plugge, Emma

2016-01-01

Background The majority of children who die from vaccine-preventable diseases (VPDs) live in low-income and-middle-income countries (LMICs). With the rapid urbanisation and rural–urban migration ongoing in LMICs, available research suggests that migration status might be a determinant of immunisation coverage in LMICs, with rural–urban migrant (RUM) children being less likely to be immunised. Objectives To examine and synthesise the data on immunisation coverage in RUM children in LMICs and to compare coverage in these children with non-migrant children. Methods A multiple database search of published and unpublished literature on immunisation coverage for the routine Expanded Programme on Immunisation (EPI) vaccines in RUM children aged 5 years and below was conducted. Following a staged exclusion process, studies that met the inclusion criteria were assessed for quality and data extracted for meta-analysis. Results Eleven studies from three countries (China, India and Nigeria) were included in the review. There was substantial statistical heterogeneity between the studies, thus no summary estimate was reported for the meta-analysis. Data synthesis from the studies showed that the proportion of fully immunised RUM children was lower than the WHO bench-mark of 90% at the national level. RUMs were also less likely to be fully immunised than the urban-non-migrants and general population. For the individual EPI vaccines, all but two studies showed lower immunisation coverage in RUMs compared with the general population using national coverage estimates. Conclusions This review indicates that there is an association between rural–urban migration and immunisation coverage in LMICs with RUMs being less likely to be fully immunised than the urban non-migrants and the general population. Specific efforts to improve immunisation coverage in this subpopulation of urban residents will not only reduce morbidity and mortality from VPDs in migrants but will also reduce health inequity and the risk of infectious disease outbreaks in wider society. PMID:26347277

Intervene before leaving: clustered lot quality assurance sampling to monitor vaccination coverage at health district level before the end of a yellow fever and measles vaccination campaign in Sierra Leone in 2009.

PubMed

Pezzoli, Lorenzo; Conteh, Ishata; Kamara, Wogba; Gacic-Dobo, Marta; Ronveaux, Olivier; Perea, William A; Lewis, Rosamund F

2012-06-07

In November 2009, Sierra Leone conducted a preventive yellow fever (YF) vaccination campaign targeting individuals aged nine months and older in six health districts. The campaign was integrated with a measles follow-up campaign throughout the country targeting children aged 9-59 months. For both campaigns, the operational objective was to reach 95% of the target population. During the campaign, we used clustered lot quality assurance sampling (C-LQAS) to identify areas of low coverage to recommend timely mop-up actions. We divided the country in 20 non-overlapping lots. Twelve lots were targeted by both vaccinations, while eight only by measles. In each lot, five clusters of ten eligible individuals were selected for each vaccine. The upper threshold (UT) was set at 90% and the lower threshold (LT) at 75%. A lot was rejected for low vaccination coverage if more than 7 unvaccinated individuals (not presenting vaccination card) were found. After the campaign, we plotted the C-LQAS results against the post-campaign coverage estimations to assess if early interventions were successful enough to increase coverage in the lots that were at the level of rejection before the end of the campaign. During the last two days of campaign, based on card-confirmed vaccination status, five lots out of 20 (25.0%) failed for having low measles vaccination coverage and three lots out of 12 (25.0%) for low YF coverage. In one district, estimated post-campaign vaccination coverage for both vaccines was still not significantly above the minimum acceptable level (LT = 75%) even after vaccination mop-up activities. C-LQAS during the vaccination campaign was informative to identify areas requiring mop-up activities to reach the coverage target prior to leaving the region. The only district where mop-up activities seemed to be unsuccessful might have had logistical difficulties that should be further investigated and resolved.

Comparison of self-report influenza vaccination coverage with data from a population based computerized vaccination registry and factors associated with discordance.

PubMed

Jiménez-García, Rodrigo; Hernandez-Barrera, Valentín; Rodríguez-Rieiro, Cristina; Carrasco Garrido, Pilar; López de Andres, Ana; Jimenez-Trujillo, Isabel; Esteban-Vasallo, María D; Domínguez-Berjón, Maria Felicitas; de Miguel-Diez, Javier; Astray-Mochales, Jenaro

2014-07-31

We aim to compare influenza vaccination coverages obtained using two different methods; a population based computerized vaccination registry and self-reported influenza vaccination status as captured by a population survey. The study was conducted in the Autonomous Community of Madrid (ACM), Spain, and refers to the 2011/12 influenza vaccination campaign. Information on influenza vaccination status according to a computerized registry was extracted from the SISPAL database and crossed with the electronic clinical records in primary care (ECRPC). Self-reported vaccine uptake was obtained from subjects living in the ACM included in the 2011-12 Spanish National Health Survey (SNHS). Independent study variables included: age, sex, immigrant status and the presence of high risk chronic conditions. Vaccination coverages were calculated according to study variables. Crude and adjusted prevalence ratios were computed to assess concordance. The study population included 5,245,238 adults living in the ACM in year 2011 with an individual ECRPC and 1449 adult living the ACM and interviewed in the SNHS from October 2011 to June 2012. The weighted vaccination coverage for the study population according to self-reported data was 19.77% and 15.04% from computerized registries resulting in a crude prevalence ratio (cPR) of 1.31 (95% CI 1.20-1.44) so self-reported data significantly overestimated 31% the registry coverage. Self-reported coverages are always higher than registry based coverages when the study population is stratified by the study variables. Self-reported overestimation was higher among men than women, younger age groups, immigrants and those without chronic conditions. Both methods provide the most concordant estimations for the target population of the influenza vaccine. Self-report influenza vaccination uptake overestimates vaccination registries coverages. The validity of self-report seems to be negatively affected by socio-demographic variables and the absence of chronic conditions. Possible strategies must be considered and implemented to improve both coverage estimation methods. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impact of the CDC’s Section 317 Immunization Grants Program Funding on Childhood Vaccination Coverage

PubMed Central

Rein, David B.; Honeycutt, Amanda A.; Rojas-Smith, Lucia; Hersey, James C.

2006-01-01

The Centers for Disease Control and Prevention’s Section 317 Grants Program is the main source of funding for state and jurisdictional immunization programs, yet no study has evaluated its direct impact on vaccination coverage rates. Therefore, we used a fixed-effects model and data collected from 56 US jurisdictions to estimate the impact of Section 317 financial assistance immunization grants on childhood vaccination coverage rates from 1997 to 2003. Our results showed that increases in Section 317 funding were significantly and meaningfully associated with higher rates of vaccination coverage; a $10 increase in per capita funding corresponded with a 1.6-percentage-point increase in vaccination coverage. Policymakers charged with funding public health programs should consider this study’s findings, which indicate that money allocated to vaccine activities translates directly into higher vaccine coverage rates. PMID:16873738

Construction and Analysis of Siberian Tiger Bacterial Artificial Chromosome Library with Approximately 6.5-Fold Genome Equivalent Coverage

PubMed Central

Liu, Changqing; Bai, Chunyu; Guo, Yu; Liu, Dan; Lu, Taofeng; Li, Xiangchen; Ma, Jianzhang; Ma, Yuehui; Guan, Weijun

2014-01-01

Bacterial artificial chromosome (BAC) libraries are extremely valuable for the genome-wide genetic dissection of complex organisms. The Siberian tiger, one of the most well-known wild primitive carnivores in China, is an endangered animal. In order to promote research on its genome, a high-redundancy BAC library of the Siberian tiger was constructed and characterized. The library is divided into two sub-libraries prepared from blood cells and two sub-libraries prepared from fibroblasts. This BAC library contains 153,600 individually archived clones; for PCR-based screening of the library, BACs were placed into 40 superpools of 10 × 384-deep well microplates. The average insert size of BAC clones was estimated to be 116.5 kb, representing approximately 6.46 genome equivalents of the haploid genome and affording a 98.86% statistical probability of obtaining at least one clone containing a unique DNA sequence. Screening the library with 19 microsatellite markers and a SRY sequence revealed that each of these markers were present in the library; the average number of positive clones per marker was 6.74 (range 2 to 12), consistent with 6.46 coverage of the tiger genome. Additionally, we identified 72 microsatellite markers that could potentially be used as genetic markers. This BAC library will serve as a valuable resource for physical mapping, comparative genomic study and large-scale genome sequencing in the tiger. PMID:24608928

DNA methylome of the 20-gigabase Norway spruce genome

PubMed Central

Ausin, Israel; Feng, Suhua; Yu, Chaowei; Liu, Wanlu; Kuo, Hsuan Yu; Jacobsen, Elise L.; Zhai, Jixian; Gallego-Bartolome, Javier; Wang, Lin; Egertsdotter, Ulrika; Street, Nathaniel R.; Jacobsen, Steven E.; Wang, Haifeng

2016-01-01

DNA methylation plays important roles in many biological processes, such as silencing of transposable elements, imprinting, and regulating gene expression. Many studies of DNA methylation have shown its essential roles in angiosperms (flowering plants). However, few studies have examined the roles and patterns of DNA methylation in gymnosperms. Here, we present genome-wide high coverage single-base resolution methylation maps of Norway spruce (Picea abies) from both needles and somatic embryogenesis culture cells via whole genome bisulfite sequencing. On average, DNA methylation levels of CG and CHG of Norway spruce were higher than most other plants studied. CHH methylation was found at a relatively low level; however, at least one copy of most of the RNA-directed DNA methylation pathway genes was found in Norway spruce, and CHH methylation was correlated with levels of siRNAs. In comparison with needles, somatic embryogenesis culture cells that are used for clonally propagating spruce trees showed lower levels of CG and CHG methylation but higher level of CHH methylation, suggesting that like in other species, these culture cells show abnormal methylation patterns. PMID:27911846

Health coverage of low-income citizen and noncitizen wage earners: sources and disparities.

PubMed

Ponce, Ninez A; Cochran, Susan D; Mays, Vickie M; Chia, Jenny; Brown, E Richard

2008-04-01

The health coverage of low-income workers represents an area of continuing disparities in the United States system of health insurance. Using the 2001 California Health Interview Survey, we estimate the effect of low-income wage earners' citizenship and gender on the odds of obtaining primary employment-based health insurance (EBHI), dependent EBHI, public program coverage, and coverage from any source. We find that noncitizen men and women who comprise 40% of California's low-income workforce, share the disadvantage of much lower rates of insurance coverage, compared to naturalized and U.S.-born citizens. However, poor coverage rates of noncitizen men, regardless of permanent residency status, result from the cumulative disadvantage in obtaining dependent EBHI and public insurance. If public policies designed to provide a health care safety net fail to address the health care coverage needs of low-wage noncitizens, health disparities will continue to increase in this group that contributes essentially to the U.S. economy.

Premium subsidies, the mandate, and Medicaid expansion: Coverage effects of the Affordable Care Act.

PubMed

Frean, Molly; Gruber, Jonathan; Sommers, Benjamin D

2017-05-01

Using premium subsidies for private coverage, an individual mandate, and Medicaid expansion, the Affordable Care Act (ACA) has increased insurance coverage. We provide the first comprehensive assessment of these provisions' effects, using the 2012-2015 American Community Survey and a triple-difference estimation strategy that exploits variation by income, geography, and time. Overall, our model explains 60% of the coverage gains in 2014-2015. We find that coverage was moderately responsive to price subsidies, with larger gains in state-based insurance exchanges than the federal exchange. The individual mandate's exemptions and penalties had little impact on coverage rates. The law increased Medicaid among individuals gaining eligibility under the ACA and among previously-eligible populations ("woodwork effect") even in non-expansion states, with no resulting reductions in private insurance. Overall, exchange premium subsidies produced 40% of the coverage gains explained by our ACA policy measures, and Medicaid the other 60%, of which 1/2 occurred among previously-eligible individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

Insurance Coverage for Rehabilitation Therapies and Association with Social Participation Outcomes among Low-Income Children.

PubMed

Mirza, Mansha; Kim, Yoonsang

2016-01-01

(1) To profile children's health insurance coverage rates for specific rehabilitation therapies; (2) to determine whether coverage for rehabilitation therapies is associated with social participation outcomes after adjusting for child and household characteristics; (3) to assess whether rehabilitation insurance differentially affects social participation of children with and without disabilities. We conducted a cross-sectional analysis of secondary survey data on 756 children (ages 3-17) from 370 households living in low-income neighborhoods in a Midwestern U.S. city. Multivariate mixed effects logistic regression models were estimated. Significantly higher proportions of children with disabilities had coverage for physical therapy, occupational therapy, and speech and language pathology, yet gaps in coverage were noted. Multivariate analysis indicated that rehabilitation insurance coverage was significantly associated with social participation (OR = 1.67, 95% CI: 1.013-2.75). This trend was sustained in subgroup analysis. Findings support the need for comprehensive coverage of all essential services under children's health insurance programs.

A New Method for Estimating the Coverage of Mass Vaccination Campaigns Against Poliomyelitis From Surveillance Data

PubMed Central

O'Reilly, K. M.; Cori, A.; Durry, E.; Wadood, M. Z.; Bosan, A.; Aylward, R. B.; Grassly, N. C.

2015-01-01

Mass vaccination campaigns with the oral poliovirus vaccine targeting children aged <5 years are a critical component of the global poliomyelitis eradication effort. Monitoring the coverage of these campaigns is essential to allow corrective action, but current approaches are limited by their cross-sectional nature, nonrandom sampling, reporting biases, and accessibility issues. We describe a new Bayesian framework using data augmentation and Markov chain Monte Carlo methods to estimate variation in vaccination coverage from children's vaccination histories investigated during surveillance for acute flaccid paralysis. We tested the method using simulated data with at least 200 cases and were able to detect undervaccinated groups if they exceeded 10% of all children and temporal changes in coverage of ±10% with greater than 90% sensitivity. Application of the method to data from Pakistan for 2010–2011 identified undervaccinated groups within the Balochistan/Federally Administered Tribal Areas and Khyber Pakhtunkhwa regions, as well as temporal changes in coverage. The sizes of these groups are consistent with the multiple challenges faced by the program in these regions as a result of conflict and insecurity. Application of this new method to routinely collected data can be a useful tool for identifying poorly performing areas and assisting in eradication efforts. PMID:26568569

The repetitive landscape of the chicken genome.

PubMed

Wicker, Thomas; Robertson, Jon S; Schulze, Stefan R; Feltus, F Alex; Magrini, Vincent; Morrison, Jason A; Mardis, Elaine R; Wilson, Richard K; Peterson, Daniel G; Paterson, Andrew H; Ivarie, Robert

2005-01-01

Cot-based cloning and sequencing (CBCS) is a powerful tool for isolating and characterizing the various repetitive components of any genome, combining the established principles of DNA reassociation kinetics with high-throughput sequencing. CBCS was used to generate sequence libraries representing the high, middle, and low-copy fractions of the chicken genome. Sequencing high-copy DNA of chicken to about 2.7 x coverage of its estimated sequence complexity led to the initial identification of several new repeat families, which were then used for a survey of the newly released first draft of the complete chicken genome. The analysis provided insight into the diversity and biology of known repeat structures such as CR1 and CNM, for which only limited sequence data had previously been available. Cot sequence data also resulted in the identification of four novel repeats (Birddawg, Hitchcock, Kronos, and Soprano), two new subfamilies of CR1 repeats, and many elements absent from the chicken genome assembly. Multiple autonomous elements were found for a novel Mariner-like transposon, Galluhop, in addition to nonautonomous deletion derivatives. Phylogenetic analysis of the high-copy repeats CR1, Galluhop, and Birddawg provided insight into two distinct genome dispersion strategies. This study also exemplifies the power of the CBCS method to create representative databases for the repetitive fractions of genomes for which only limited sequence data is available.

The repetitive landscape of the chicken genome

PubMed Central

Wicker, Thomas; Robertson, Jon S.; Schulze, Stefan R.; Feltus, F. Alex; Magrini, Vincent; Morrison, Jason A.; Mardis, Elaine R.; Wilson, Richard K.; Peterson, Daniel G.; Paterson, Andrew H.; Ivarie, Robert

2005-01-01

Cot-based cloning and sequencing (CBCS) is a powerful tool for isolating and characterizing the various repetitive components of any genome, combining the established principles of DNA reassociation kinetics with high-throughput sequencing. CBCS was used to generate sequence libraries representing the high, middle, and low-copy fractions of the chicken genome. Sequencing high-copy DNA of chicken to about 2.7× coverage of its estimated sequence complexity led to the initial identification of several new repeat families, which were then used for a survey of the newly released first draft of the complete chicken genome. The analysis provided insight into the diversity and biology of known repeat structures such as CR1 and CNM, for which only limited sequence data had previously been available. Cot sequence data also resulted in the identification of four novel repeats (Birddawg, Hitchcock, Kronos, and Soprano), two new subfamilies of CR1 repeats, and many elements absent from the chicken genome assembly. Multiple autonomous elements were found for a novel Mariner-like transposon, Galluhop, in addition to nonautonomous deletion derivatives. Phylogenetic analysis of the high-copy repeats CR1, Galluhop, and Birddawg provided insight into two distinct genome dispersion strategies. This study also exemplifies the power of the CBCS method to create representative databases for the repetitive fractions of genomes for which only limited sequence data is available. PMID:15256510

The Genome Sequence of a Widespread Apex Predator, the Golden Eagle (Aquila chrysaetos)

PubMed Central

Doyle, Jacqueline M.; Katzner, Todd E.; Bloom, Peter H.; Ji, Yanzhu; Wijayawardena, Bhagya K.; DeWoody, J. Andrew

2014-01-01

Biologists routinely use molecular markers to identify conservation units, to quantify genetic connectivity, to estimate population sizes, and to identify targets of selection. Many imperiled eagle populations require such efforts and would benefit from enhanced genomic resources. We sequenced, assembled, and annotated the first eagle genome using DNA from a male golden eagle (Aquila chrysaetos) captured in western North America. We constructed genomic libraries that were sequenced using Illumina technology and assembled the high-quality data to a depth of ∼40x coverage. The genome assembly includes 2,552 scaffolds >10 Kb and 415 scaffolds >1.2 Mb. We annotated 16,571 genes that are involved in myriad biological processes, including such disparate traits as beak formation and color vision. We also identified repetitive regions spanning 92 Mb (∼6% of the assembly), including LINES, SINES, LTR-RTs and DNA transposons. The mitochondrial genome encompasses 17,332 bp and is ∼91% identical to the Mountain Hawk-Eagle (Nisaetus nipalensis). Finally, the data reveal that several anonymous microsatellites commonly used for population studies are embedded within protein-coding genes and thus may not have evolved in a neutral fashion. Because the genome sequence includes ∼800,000 novel polymorphisms, markers can now be chosen based on their proximity to functional genes involved in migration, carnivory, and other biological processes. PMID:24759626

"Stillbirth rates in 20 countries of Latin America: an ecological study".

PubMed

Pingray, Veronica; Althabe, Fernando; Vazquez, Paula; Correa, Malena; Pajuelo, Mónica; Belizán, José M

2018-05-23

To describe country-level stillbirth rates and their change over time in Latin America, and to measure the association of stillbirth rates with socioeconomic and health coverage indicators in the region. Ecological study. 20 countries of Latin America. Aggregated data from pregnant women with countries as units of analysis. We used stillbirth estimates, and socioeconomic and health care coverage indicators reported from 2006 to 2016 from UNICEF, United Nations Development Programme and World Bank datasets. We calculated Spearman's correlation coefficients between stillbirths rates and socioeconomic and health coverage indicators. National estimates of stillbirth rates in each country. The estimated stillbirth rate for Latin America for 2015 was 8.1 per 1000 births (range 3.1-24.9). Seven Latin America countries had rates higher than 10 stillbirths per 1000 births. The average annual reduction rate for the region was 2% (range 0.1-3.8%), with the majority of Latin America countries ranging between 1.5 and 2.5%. National stillbirth rates were correlated to: women's schooling (rS=-0.7910), gross domestic product per capita (rS=-0.8226), fertility rate (rS=0.6055), urban population (rS=-0.6316) and deliveries at health facilities (rS=-0.6454). Country-level estimated stillbirth rates in Latin America varied widely in 2015. The trend and magnitude of reduction in stillbirth rates between 2000 and 2015 was similar to the world average. Socioeconomic and health coverage indicators were correlated to stillbirth rates in Latin America. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Vaccination and all-cause child mortality from 1985 to 2011: global evidence from the Demographic and Health Surveys.

PubMed

McGovern, Mark E; Canning, David

2015-11-01

Based on models with calibrated parameters for infection, case fatality rates, and vaccine efficacy, basic childhood vaccinations have been estimated to be highly cost effective. We estimated the association of vaccination with mortality directly from survey data. Using 149 cross-sectional Demographic and Health Surveys, we determined the relationship between vaccination coverage and the probability of dying between birth and 5 years of age at the survey cluster level. Our data included approximately 1 million children in 68,490 clusters from 62 countries. We considered the childhood measles, bacillus Calmette-Guérin, diphtheria-pertussis-tetanus, polio, and maternal tetanus vaccinations. Using modified Poisson regression to estimate the relative risk of child mortality in each cluster, we also adjusted for selection bias that resulted from the vaccination status of dead children not being reported. Childhood vaccination, and in particular measles and tetanus vaccination, is associated with substantial reductions in childhood mortality. We estimated that children in clusters with complete vaccination coverage have a relative risk of mortality that is 0.73 (95% confidence interval: 0.68, 0.77) times that of children in a cluster with no vaccinations. Although widely used, basic vaccines still have coverage rates well below 100% in many countries, and our results emphasize the effectiveness of increasing coverage rates in order to reduce child mortality. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Comparison of DNA extraction methods for human gut microbial community profiling.

PubMed

Lim, Mi Young; Song, Eun-Ji; Kim, Sang Ho; Lee, Jangwon; Nam, Young-Do

2018-03-01

The human gut harbors a vast range of microbes that have significant impact on health and disease. Therefore, gut microbiome profiling holds promise for use in early diagnosis and precision medicine development. Accurate profiling of the highly complex gut microbiome requires DNA extraction methods that provide sufficient coverage of the original community as well as adequate quality and quantity. We tested nine different DNA extraction methods using three commercial kits (TianLong Stool DNA/RNA Extraction Kit (TS), QIAamp DNA Stool Mini Kit (QS), and QIAamp PowerFecal DNA Kit (QP)) with or without additional bead-beating step using manual or automated methods and compared them in terms of DNA extraction ability from human fecal sample. All methods produced DNA in sufficient concentration and quality for use in sequencing, and the samples were clustered according to the DNA extraction method. Inclusion of bead-beating step especially resulted in higher degrees of microbial diversity and had the greatest effect on gut microbiome composition. Among the samples subjected to bead-beating method, TS kit samples were more similar to QP kit samples than QS kit samples. Our results emphasize the importance of mechanical disruption step for a more comprehensive profiling of the human gut microbiome. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Identification of copy number variants in whole-genome data using Reference Coverage Profiles

PubMed Central

Glusman, Gustavo; Severson, Alissa; Dhankani, Varsha; Robinson, Max; Farrah, Terry; Mauldin, Denise E.; Stittrich, Anna B.; Ament, Seth A.; Roach, Jared C.; Brunkow, Mary E.; Bodian, Dale L.; Vockley, Joseph G.; Shmulevich, Ilya; Niederhuber, John E.; Hood, Leroy

2015-01-01

The identification of DNA copy numbers from short-read sequencing data remains a challenge for both technical and algorithmic reasons. The raw data for these analyses are measured in tens to hundreds of gigabytes per genome; transmitting, storing, and analyzing such large files is cumbersome, particularly for methods that analyze several samples simultaneously. We developed a very efficient representation of depth of coverage (150–1000× compression) that enables such analyses. Current methods for analyzing variants in whole-genome sequencing (WGS) data frequently miss copy number variants (CNVs), particularly hemizygous deletions in the 1–100 kb range. To fill this gap, we developed a method to identify CNVs in individual genomes, based on comparison to joint profiles pre-computed from a large set of genomes. We analyzed depth of coverage in over 6000 high quality (>40×) genomes. The depth of coverage has strong sequence-specific fluctuations only partially explained by global parameters like %GC. To account for these fluctuations, we constructed multi-genome profiles representing the observed or inferred diploid depth of coverage at each position along the genome. These Reference Coverage Profiles (RCPs) take into account the diverse technologies and pipeline versions used. Normalization of the scaled coverage to the RCP followed by hidden Markov model (HMM) segmentation enables efficient detection of CNVs and large deletions in individual genomes. Use of pre-computed multi-genome coverage profiles improves our ability to analyze each individual genome. We make available RCPs and tools for performing these analyses on personal genomes. We expect the increased sensitivity and specificity for individual genome analysis to be critical for achieving clinical-grade genome interpretation. PMID:25741365

Improved Yield of High Molecular Weight DNA Coincides with Increased Microbial Diversity Access from Iron Oxide Cemented Sub-Surface Clay Environments

PubMed Central

Hurt, Richard A.; Robeson, Michael S.; Shakya, Migun; Moberly, James G.; Vishnivetskaya, Tatiana A.; Gu, Baohua; Elias, Dwayne A.

2014-01-01

Despite over three decades of progress, extraction of high molecular weight (HMW) DNA from high clay soils or iron oxide cemented clay has remained challenging. HMW DNA is desirable for next generation sequencing as it yields the most comprehensive coverage. Several DNA extraction procedures were compared from samples that exhibit strong nucleic acid adsorption. pH manipulation or use of alternative ion solutions offered no improvement in nucleic acid recovery. Lysis by liquid N2 grinding in concentrated guanidine followed by concentrated sodium phosphate extraction supported HMW DNA recovery from clays high in iron oxides. DNA recovered using 1 M sodium phosphate buffer (PB) as a competitive desorptive wash was 15.22±2.33 µg DNA/g clay, with most DNA consisting of >20 Kb fragments, compared to 2.46±0.25 µg DNA/g clay with the Powerlyzer system (MoBio). Increasing PB concentration in the lysis reagent coincided with increasing DNA fragment length during initial extraction. Rarefaction plots of 16S rRNA (V1–V3 region) pyrosequencing from A-horizon and clay soils showed an ∼80% and ∼400% larger accessed diversity compared to the Powerlyzer soil DNA system, respectively. The observed diversity from the Firmicutes showed the strongest increase with >3-fold more operational taxonomic units (OTU) recovered. PMID:25033199

Understanding state variation in health insurance dynamics can help tailor enrollment strategies for ACA expansion.

PubMed

Graves, John A; Swartz, Katherine

2013-10-01

The number and types of people who become eligible for and enroll in the Affordable Care Act's (ACA's) health insurance expansions will depend in part on the factors that cause people to become uninsured for different lengths of time. We used a small-area estimation approach to estimate differences across states in percentages of adults losing health insurance and in lengths of their uninsured spells. We found that nearly 50 percent of the nonelderly adult population in Florida, Nevada, New Mexico, and Texas--but only 18 percent in Massachusetts and 22 percent in Vermont--experienced an uninsured spell between 2009 and 2012. Compared to people who lost private coverage, those with public insurance were more likely to experience an uninsured spell, but their spells of uninsurance were shorter. We categorized states based on estimated incidence of uninsured spells and the spells' duration. States should tailor their enrollment outreach and retention efforts for the ACA's coverage expansions to address their own mix of types of coverage lost and durations of uninsured spells.

A highly oriented hybrid microarray modified electrode fabricated by a template-free method for ultrasensitive electrochemical DNA recognition

NASA Astrophysics Data System (ADS)

Shi, Lei; Chu, Zhenyu; Dong, Xueliang; Jin, Wanqin; Dempsey, Eithne

2013-10-01

Highly oriented growth of a hybrid microarray was realized by a facile template-free method on gold substrates for the first time. The proposed formation mechanism involves an interfacial structure-directing force arising from self-assembled monolayers (SAMs) between gold substrates and hybrid crystals. Different SAMs and variable surface coverage of the assembled molecules play a critical role in the interfacial directing forces and influence the morphologies of hybrid films. A highly oriented hybrid microarray was formed on the highly aligned and vertical SAMs of 1,4-benzenedithiol molecules with rigid backbones, which afforded an intense structure-directing power for the oriented growth of hybrid crystals. Additionally, the density of the microarray could be adjusted by controlling the surface coverage of assembled molecules. Based on the hybrid microarray modified electrode with a large specific area (ca. 10 times its geometrical area), a label-free electrochemical DNA biosensor was constructed for the detection of an oligonucleotide fragment of the avian flu virus H5N1. The DNA biosensor displayed a significantly low detection limit of 5 pM (S/N = 3), a wide linear response from 10 pM to 10 nM, as well as excellent selectivity, good regeneration and high stability. We expect that the proposed template-free method can provide a new reference for the fabrication of a highly oriented hybrid array and the as-prepared microarray modified electrode will be a promising paradigm in constructing highly sensitive and selective biosensors.Highly oriented growth of a hybrid microarray was realized by a facile template-free method on gold substrates for the first time. The proposed formation mechanism involves an interfacial structure-directing force arising from self-assembled monolayers (SAMs) between gold substrates and hybrid crystals. Different SAMs and variable surface coverage of the assembled molecules play a critical role in the interfacial directing forces and influence the morphologies of hybrid films. A highly oriented hybrid microarray was formed on the highly aligned and vertical SAMs of 1,4-benzenedithiol molecules with rigid backbones, which afforded an intense structure-directing power for the oriented growth of hybrid crystals. Additionally, the density of the microarray could be adjusted by controlling the surface coverage of assembled molecules. Based on the hybrid microarray modified electrode with a large specific area (ca. 10 times its geometrical area), a label-free electrochemical DNA biosensor was constructed for the detection of an oligonucleotide fragment of the avian flu virus H5N1. The DNA biosensor displayed a significantly low detection limit of 5 pM (S/N = 3), a wide linear response from 10 pM to 10 nM, as well as excellent selectivity, good regeneration and high stability. We expect that the proposed template-free method can provide a new reference for the fabrication of a highly oriented hybrid array and the as-prepared microarray modified electrode will be a promising paradigm in constructing highly sensitive and selective biosensors. Electronic supplementary information (ESI) available: Four-probe method for determining the conductivity of the hybrid crystal (Fig. S1); stability comparisons of the hybrid films (Fig. S2); FESEM images of the hybrid microarray (Fig. S3); electrochemical characterizations of the hybrid films (Fig. S4); DFT simulations (Fig. S5); cross-sectional FESEM image of the hybrid microarray (Fig. S6); regeneration and stability tests of the DNA biosensor (Fig. S7). See DOI: 10.1039/c3nr03097k

Integration, Validation, and Application of a PV Snow Coverage Model in SAM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freeman, Janine M.; Ryberg, David Severin

2017-08-01

Due to the increasing deployment of PV systems in snowy climates, there is significant interest in a method capable of estimating PV losses resulting from snow coverage that has been verified for a variety of system designs and locations. Many independent snow coverage models have been developed over the last 15 years; however, there has been very little effort verifying these models beyond the system designs and locations on which they were based. Moreover, major PV modeling software products have not yet incorporated any of these models into their workflows. In response to this deficiency, we have integrated the methodologymore » of the snow model developed in the paper by Marion et al. (2013) into the National Renewable Energy Laboratory's (NREL) System Advisor Model (SAM). In this work, we describe how the snow model is implemented in SAM and we discuss our demonstration of the model's effectiveness at reducing error in annual estimations for three PV arrays. Next, we use this new functionality in conjunction with a long term historical data set to estimate average snow losses across the United States for two typical PV system designs. The open availability of the snow loss estimation capability in SAM to the PV modeling community, coupled with our results of the nationwide study, will better equip the industry to accurately estimate PV energy production in areas affected by snowfall.« less

Safe motherhood voucher programme coverage of health facility deliveries among poor women in South-western Uganda.

PubMed

Kanya, Lucy; Obare, Francis; Warren, Charlotte; Abuya, Timothy; Askew, Ian; Bellows, Ben

2014-07-01

There has been increased interest in and experimentation with demand-side mechanisms such as the use of vouchers that place purchasing power in the hands of targeted consumers to improve the uptake of healthcare services in low-income settings. A key measure of the success of such interventions is the extent to which the programmes have succeeded in reaching the target populations. This article estimates the coverage of facility deliveries by a maternal health voucher programme in South-western Uganda and examines whether such coverage is correlated with district-level characteristics such as poverty density and the number of contracted facilities. Analysis entails estimating the voucher coverage of health facility deliveries among the general population and poor population (PP) using programme data for 2010, which was the most complete calendar year of implementation of the Uganda safe motherhood (SM) voucher programme. The results show that: (1) the programme paid for 38% of estimated deliveries among the PP in the targeted districts, (2) there was a significant negative correlation between the poverty density in a district and proportions of births to poor women that were covered by the programme and (3) improving coverage of health facility deliveries for poor women is dependent upon increasing the sales and redemption rates. The findings suggest that to the extent that the programme stimulated demand for SM services by new users, it has the potential of increasing facility-based births among poor women in the region. In addition, the significant negative correlation between the poverty density and the proportions of facility-based births to poor women that are covered by the voucher programme suggests that there is need to increase both voucher sales and the rate of redemption to improve coverage in districts with high levels of poverty. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2013; all rights reserved.

Computerized method for automatic evaluation of lean body mass from PET/CT: comparison with predictive equations.

PubMed

Chan, Tao

2012-01-01

CT has become an established method for calculating body composition, but it requires data from the whole body, which are not typically obtained in routine PET/CT examinations. A computerized scheme that evaluates whole-body lean body mass (LBM) based on CT data from limited-whole-body coverage was developed. The LBM so obtained was compared with results from conventional predictive equations. LBM can be obtained automatically from limited-whole-body CT data by 3 means: quantification of body composition from CT images in the limited-whole-body scan, based on thresholding of CT attenuation; determination of the range of coverage based on a characteristic trend of changing composition across different levels and pattern recognition of specific features at strategic positions; and estimation of the LBM of the whole body on the basis of a predetermined relationship between proportion of fat mass and extent of coverage. This scheme was validated using 18 whole-body PET/CT examinations truncated at different lengths to emulate limited-whole-body data. LBM was also calculated using predictive equations that had been reported for use in SUV normalization. LBM derived from limited-whole-body data using the proposed method correlated strongly with LBM derived from whole-body CT data, with correlation coefficients ranging from 0.991 (shorter coverage) to 0.998 (longer coverage) and SEMs of LBM ranging from 0.14 to 0.33 kg. These were more accurate than results from different predictive equations, which ranged in correlation coefficient from 0.635 to 0.970 and in SEM from 0.64 to 2.40 kg. LBM of the whole body could be automatically estimated from CT data of limited-whole-body coverage typically acquired in PET/CT examinations. This estimation allows more accurate and consistent quantification of metabolic activity of tumors based on LBM-normalized standardized uptake value.

Assessment of immunization registry databases as supplemental sources of data to improve ascertainment of vaccination coverage estimates in the national immunization survey.

PubMed

Khare, Meena; Piccinino, Linda; Barker, Lawrence E; Linkins, Robert W

2006-08-01

To evaluate the use of immunization registry data to supplement missing or incomplete vaccination data reported by immunization providers (referred to as "providers" hereafter) in the National Immunization Survey. Cross-sectional, random-digit-dialing, telephone survey to measure vaccination coverage among children aged 19 to 35 months in the United States. Four sites with mature (with >67% of provider participation in the area) immunization registries. Of the 639 children with complete household interviews, interviewers had consent from the respondents for 569 (89.0%) children to contact their providers and for 556 (87.0%) children to contact both providers and registries. Percentages of children up-to-date for vaccines based on data from providers, registries, and both sources combined. According to provider-reported data, weighted estimates of coverage for the recommended childhood vaccine series 4:3:1:3 at the 4 sites were 65.6%, 78.8%, 81.6%, and 77.0%. According to registry data, these coverage rates were consistently lower: 31.7% (P<.05), 65.4%, 71.9%, and 61.8%, respectively. When all unique vaccine doses were combined from both sources, the pooled 4:3:1:3 coverage rates increased to 72.0%, 92.0%, 88.7%, and 80.2%, respectively. The quality and completeness of vaccination histories from the registries were inconsistent and varied by sites. Vaccination coverage estimates were the lowest when only registry-reported data were used and were the highest when provider- and registry-reported histories were combined. Although registries enrolled and matched more children, vaccination histories were missing, incomplete, and inconsistent. The quality and completeness of the registry data must be improved and must be comparable across all states before further consideration may be given to supplement or replace the provider-reported National Immunization Survey data.

Early changes in intervention coverage and mortality rates following the implementation of an integrated health system intervention in Madagascar.

PubMed

Garchitorena, Andres; Miller, Ann C; Cordier, Laura F; Rabeza, Victor R; Randriamanambintsoa, Marius; Razanadrakato, Hery-Tiana R; Hall, Lara; Gikic, Djordje; Haruna, Justin; McCarty, Meg; Randrianambinina, Andriamihaja; Thomson, Dana R; Atwood, Sidney; Rich, Michael L; Murray, Megan B; Ratsirarson, Josea; Ouenzar, Mohammed Ali; Bonds, Matthew H

2018-01-01

The Sustainable Development Goals framed an unprecedented commitment to achieve global convergence in child and maternal mortality rates through 2030. To meet those targets, essential health services must be scaled via integration with strengthened health systems. This is especially urgent in Madagascar, the country with the lowest level of financing for health in the world. Here, we present an interim evaluation of the first 2 years of a district-level health system strengthening (HSS) initiative in rural Madagascar, using estimates of intervention coverage and mortality rates from a district-wide longitudinal cohort. We carried out a district representative household survey at baseline of the HSS intervention in over 1500 households in Ifanadiana district. The first follow-up was after the first 2 years of the initiative. For each survey, we estimated maternal, newborn and child health (MNCH) coverage, healthcare inequalities and child mortality rates both in the initial intervention catchment area and in the rest of the district. We evaluated changes between the two areas through difference-in-differences analyses. We estimated annual changes in health centre per capita utilisation from 2013 to 2016. The intervention was associated with 19.1% and 36.4% decreases in under-five and neonatal mortality, respectively, although these were not statistically significant. The composite coverage index (a summary measure of MNCH coverage) increased by 30.1%, with a notable 63% increase in deliveries in health facilities. Improvements in coverage were substantially larger in the HSS catchment area and led to an overall reduction in healthcare inequalities. Health centre utilisation rates in the catchment tripled for most types of care during the study period. At the earliest stages of an HSS intervention, the rapid improvements observed for Ifanadiana add to preliminary evidence supporting the untapped and poorly understood potential of integrated HSS interventions on population health.

Modelling the cost-effectiveness of mass screening and treatment for reducing Plasmodium falciparum malaria burden.

PubMed

Crowell, Valerie; Briët, Olivier J T; Hardy, Diggory; Chitnis, Nakul; Maire, Nicolas; Di Pasquale, Aurelio; Smith, Thomas A

2013-01-03

Past experience and modelling suggest that, in most cases, mass treatment strategies are not likely to succeed in interrupting Plasmodium falciparum malaria transmission. However, this does not preclude their use to reduce disease burden. Mass screening and treatment (MSAT) is preferred to mass drug administration (MDA), as the latter involves massive over-use of drugs. This paper reports simulations of the incremental cost-effectiveness of well-conducted MSAT campaigns as a strategy for P. falciparum malaria disease-burden reduction in settings with varying receptivity (ability of the combined vector population in a setting to transmit disease) and access to case management. MSAT incremental cost-effectiveness ratios (ICERs) were estimated in different sub-Saharan African settings using simulation models of the dynamics of malaria and a literature-based MSAT cost estimate. Imported infections were simulated at a rate of two per 1,000 population per annum. These estimates were compared to the ICERs of scaling up case management or insecticide-treated net (ITN) coverage in each baseline health system, in the absence of MSAT. MSAT averted most episodes, and resulted in the lowest ICERs, in settings with a moderate level of disease burden. At a low pre-intervention entomological inoculation rate (EIR) of two infectious bites per adult per annum (IBPAPA) MSAT was never more cost-effective than scaling up ITNs or case management coverage. However, at pre-intervention entomological inoculation rates (EIRs) of 20 and 50 IBPAPA and ITN coverage levels of 40 or 60%, respectively, the ICER of MSAT was similar to that of scaling up ITN coverage further. In all the transmission settings considered, achieving a minimal level of ITN coverage is a "best buy". At low transmission, MSAT probably is not worth considering. Instead, MSAT may be suitable at medium to high levels of transmission and at moderate ITN coverage. If undertaken as a burden-reducing intervention, MSAT should be continued indefinitely and should complement, not replace, case management and vector control interventions.

Alternatives to the ACA's Affordability Firewall.

PubMed

Nowak, Sarah A; Saltzman, Evan; Cordova, Amado

2016-05-09

The Affordable Care Act (ACA) was designed to increase health insurance coverage while limiting the disruption to individuals with existing sources of insurance coverage, particularly those with employer-sponsored insurance (ESI). To limit disruption to those with coverage, the ACA implements the employer mandate, which requires firms with more than 50 employees to offer health insurance or face penalties, and the individual "affordability firewall," which limits subsidies to individuals lacking access to alternative sources of coverage that are "affordable." This article examines the policy impacts of the affordability firewall and investigates two potential modifications. Option 1, which is the "entire family" scenario, involves allowing an exception to the firewall for anyone in a family where the family ESI premium contribution exceeds 9.5 percent of the worker's household income. In Option 2, the "dependents only" scenario, only dependents (and not the worker) become eligible for Marketplace subsidies when the ESI premium contribution exceeds 9.5 percent of the worker's household income. Relative to the ACA, RAND researchers estimate that nongroup enrollment will increase by 4.1 million for Option 1 and by 1.4 million for Option 2. However, the number without insurance only declines by 1.5 million in Option 1 and 0.7 million in Option 2. The difference between the increase in nongroup enrollment and the decrease in uninsurance is primarily due to ESI crowd-out, which is more pronounced for Option 1. Researchers also estimated that about 1.3 million families who have ESI and unsubsidized nongroup coverage under current ACA policy would receive Marketplace subsidies under the alternative affordability firewall scenarios. For these families, health insurance coverage would become substantially more affordable; these families' risk of spending at least 20 percent of income on health care would drop by more than two thirds. We additionally estimated that federal spending will increase by $8.9 billion and $3.9 billion for Options 1 and 2, respectively, relative to the ACA.

Human papillomavirus vaccination coverage among females and males, National Health and Nutrition Examination Survey, United States, 2007-2016.

PubMed

Lewis, Rayleen M; Markowitz, Lauri E

2018-05-03

Human papillomavirus (HPV) vaccination has been routinely recommended at age 11-12 years in the United States for females since 2006 and males since 2011. Coverage can be estimated using self/parent-reported HPV vaccination collected in the National Health and Nutrition Examination Survey (NHANES) for a wider age range than other national surveys. We assessed vaccination coverage in 2015-2016, temporal trends by age, and the validity of self/parent-reported vaccination status. Participants aged 9-59 years completed an interview collecting demographic and vaccination information. Weighted coverage was estimated for two-year NHANES cycles by age group for 2007-2008 to 2015-2016 for females (N = 14318) and 2011-2012 to 2015-2016 for males (N = 7847). Temporal trends in coverage were assessed from 2007-2008 to 2011-2012 for females and from 2011-2012 to 2015-2016 for both sexes. Sensitivity and specificity of self/parent-reported vaccination were assessed using provider-verified vaccination records from a pilot study in 14-29 year-olds. In 2015-2016, ≥1 dose coverage among females was highest in 14-19 (54.7%) and 20-24 (56.0%) year-olds and lower in successively older age groups. Among males, ≥1 dose coverage was highest in 14-19 year-olds (39.5%) and lower at older ages. Coverage was similar in 9-13 year-old females and males. Between 2007-2008 and 2011-2012, there were increases among females younger than 30 years. Between 2011-2012 and 2015-2016, there were increases among female age groups including 20-39 year-olds; male coverage increased among ages 9-13, 14-19, and 20-24 years. Self/parent-reported receipt of ≥1 dose had a sensitivity and specificity of 87.0% and 83.3%. Performance was lower for 3 doses. While overall HPV vaccination coverage remains low, it is higher in females than males, except in 9-13 year-olds. There have been increases in coverage among many age groups, but coverage has stalled in younger females. Adequate validity was demonstrated for self/parent-reported vaccination of ≥1 dose, but not 3 doses, in a pilot study. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Novel Tool Improves Existing Estimates of Recent Tuberculosis Transmission in Settings of Sparse Data Collection.

PubMed

Kasaie, Parastu; Mathema, Barun; Kelton, W David; Azman, Andrew S; Pennington, Jeff; Dowdy, David W

2015-01-01

In any setting, a proportion of incident active tuberculosis (TB) reflects recent transmission ("recent transmission proportion"), whereas the remainder represents reactivation. Appropriately estimating the recent transmission proportion has important implications for local TB control, but existing approaches have known biases, especially where data are incomplete. We constructed a stochastic individual-based model of a TB epidemic and designed a set of simulations (derivation set) to develop two regression-based tools for estimating the recent transmission proportion from five inputs: underlying TB incidence, sampling coverage, study duration, clustered proportion of observed cases, and proportion of observed clusters in the sample. We tested these tools on a set of unrelated simulations (validation set), and compared their performance against that of the traditional 'n-1' approach. In the validation set, the regression tools reduced the absolute estimation bias (difference between estimated and true recent transmission proportion) in the 'n-1' technique by a median [interquartile range] of 60% [9%, 82%] and 69% [30%, 87%]. The bias in the 'n-1' model was highly sensitive to underlying levels of study coverage and duration, and substantially underestimated the recent transmission proportion in settings of incomplete data coverage. By contrast, the regression models' performance was more consistent across different epidemiological settings and study characteristics. We provide one of these regression models as a user-friendly, web-based tool. Novel tools can improve our ability to estimate the recent TB transmission proportion from data that are observable (or estimable) by public health practitioners with limited available molecular data.

A Novel Tool Improves Existing Estimates of Recent Tuberculosis Transmission in Settings of Sparse Data Collection

PubMed Central

Kasaie, Parastu; Mathema, Barun; Kelton, W. David; Azman, Andrew S.; Pennington, Jeff; Dowdy, David W.

2015-01-01

In any setting, a proportion of incident active tuberculosis (TB) reflects recent transmission (“recent transmission proportion”), whereas the remainder represents reactivation. Appropriately estimating the recent transmission proportion has important implications for local TB control, but existing approaches have known biases, especially where data are incomplete. We constructed a stochastic individual-based model of a TB epidemic and designed a set of simulations (derivation set) to develop two regression-based tools for estimating the recent transmission proportion from five inputs: underlying TB incidence, sampling coverage, study duration, clustered proportion of observed cases, and proportion of observed clusters in the sample. We tested these tools on a set of unrelated simulations (validation set), and compared their performance against that of the traditional ‘n-1’ approach. In the validation set, the regression tools reduced the absolute estimation bias (difference between estimated and true recent transmission proportion) in the ‘n-1’ technique by a median [interquartile range] of 60% [9%, 82%] and 69% [30%, 87%]. The bias in the ‘n-1’ model was highly sensitive to underlying levels of study coverage and duration, and substantially underestimated the recent transmission proportion in settings of incomplete data coverage. By contrast, the regression models’ performance was more consistent across different epidemiological settings and study characteristics. We provide one of these regression models as a user-friendly, web-based tool. Novel tools can improve our ability to estimate the recent TB transmission proportion from data that are observable (or estimable) by public health practitioners with limited available molecular data. PMID:26679499

A Transcontinental Challenge — A Test of DNA Barcode Performance for 1,541 Species of Canadian Noctuoidea (Lepidoptera)

PubMed Central

Zahiri, Reza; Lafontaine, J. Donald; Schmidt, B. Christian; deWaard, Jeremy R.; Zakharov, Evgeny V.; Hebert, Paul D. N.

2014-01-01

This study provides a first, comprehensive, diagnostic use of DNA barcodes for the Canadian fauna of noctuoids or “owlet” moths (Lepidoptera: Noctuoidea) based on vouchered records for 1,541 species (99.1% species coverage), and more than 30,000 sequences. When viewed from a Canada-wide perspective, DNA barcodes unambiguously discriminate 90% of the noctuoid species recognized through prior taxonomic study, and resolution reaches 95.6% when considered at a provincial scale. Barcode sharing is concentrated in certain lineages with 54% of the cases involving 1.8% of the genera. Deep intraspecific divergence exists in 7.7% of the species, but further studies are required to clarify whether these cases reflect an overlooked species complex or phylogeographic variation in a single species. Non-native species possess higher Nearest-Neighbour (NN) distances than native taxa, whereas generalist feeders have lower NN distances than those with more specialized feeding habits. We found high concordance between taxonomic names and sequence clusters delineated by the Barcode Index Number (BIN) system with 1,082 species (70%) assigned to a unique BIN. The cases of discordance involve both BIN mergers and BIN splits with 38 species falling into both categories, most likely reflecting bidirectional introgression. One fifth of the species are involved in a BIN merger reflecting the presence of 158 species sharing their barcode sequence with at least one other taxon, and 189 species with low, but diagnostic COI divergence. A very few cases (13) involved species whose members fell into both categories. Most of the remaining 140 species show a split into two or three BINs per species, while Virbia ferruginosa was divided into 16. The overall results confirm that DNA barcodes are effective for the identification of Canadian noctuoids. This study also affirms that BINs are a strong proxy for species, providing a pathway for a rapid, accurate estimation of animal diversity. PMID:24667847

Benchmarking health system performance across regions in Uganda: a systematic analysis of levels and trends in key maternal and child health interventions, 1990-2011.

PubMed

Roberts, D Allen; Ng, Marie; Ikilezi, Gloria; Gasasira, Anne; Dwyer-Lindgren, Laura; Fullman, Nancy; Nalugwa, Talemwa; Kamya, Moses; Gakidou, Emmanuela

2015-12-03

Globally, countries are increasingly prioritizing the reduction of health inequalities and provision of universal health coverage. While national benchmarking has become more common, such work at subnational levels is rare. The timely and rigorous measurement of local levels and trends in key health interventions and outcomes is vital to identifying areas of progress and detecting early signs of stalled or declining health system performance. Previous studies have yet to provide a comprehensive assessment of Uganda's maternal and child health (MCH) landscape at the subnational level. By triangulating a number of different data sources - population censuses, household surveys, and administrative data - we generated regional estimates of 27 key MCH outcomes, interventions, and socioeconomic indicators from 1990 to 2011. After calculating source-specific estimates of intervention coverage, we used a two-step statistical model involving a mixed-effects linear model as an input to Gaussian process regression to produce regional-level trends. We also generated national-level estimates and constructed an indicator of overall intervention coverage based on the average of 11 high-priority interventions. National estimates often veiled large differences in coverage levels and trends across Uganda's regions. Under-5 mortality declined dramatically, from 163 deaths per 1,000 live births in 1990 to 85 deaths per 1,000 live births in 2011, but a large gap between Kampala and the rest of the country persisted. Uganda rapidly scaled up a subset of interventions across regions, including household ownership of insecticide-treated nets, receipt of artemisinin-based combination therapies among children under 5, and pentavalent immunization. Conversely, most regions saw minimal increases, if not actual declines, in the coverage of indicators that required multiple contacts with the health system, such as four or more antenatal care visits, three doses of oral polio vaccine, and two doses of intermittent preventive therapy during pregnancy. Some of the regions with the lowest levels of overall intervention coverage in 1990, such as North and West Nile, saw marked progress by 2011; nonetheless, sizeable disparities remained between Kampala and the rest of the country. Countrywide, overall coverage increased from 40% in 1990 to 64% in 2011, but coverage in 2011 ranged from 57% to 70% across regions. The MCH landscape in Uganda has, for the most part, improved between 1990 and 2011. Subnational benchmarking quantified the persistence of geographic health inequalities and identified regions in need of additional health systems strengthening. The tracking and analysis of subnational health trends should be conducted regularly to better guide policy decisions and strengthen responsiveness to local health needs.

A draft genome of the brown alga, Cladosiphon okamuranus, S-strain: a platform for future studies of 'mozuku' biology.

PubMed

Nishitsuji, Koki; Arimoto, Asuka; Iwai, Kenji; Sudo, Yusuke; Hisata, Kanako; Fujie, Manabu; Arakaki, Nana; Kushiro, Tetsuo; Konishi, Teruko; Shinzato, Chuya; Satoh, Noriyuki; Shoguchi, Eiichi

2016-12-01

The brown alga, Cladosiphon okamuranus (Okinawa mozuku), is economically one of the most important edible seaweeds, and is cultivated for market primarily in Okinawa, Japan. C. okamuranus constitutes a significant source of fucoidan, which has various physiological and biological activities. To facilitate studies of seaweed biology, we decoded the draft genome of C. okamuranus S-strain. The genome size of C. okamuranus was estimated as ∼140 Mbp, smaller than genomes of two other brown algae, Ectocarpus siliculosus and Saccharina japonica Sequencing with ∼100× coverage yielded an assembly of 541 scaffolds with N50 = 416 kbp. Together with transcriptomic data, we estimated that the C. okamuranus genome contains 13,640 protein-coding genes, approximately 94% of which have been confirmed with corresponding mRNAs. Comparisons with the E. siliculosus genome identified a set of C. okamuranus genes that encode enzymes involved in biosynthetic pathways for sulfated fucans and alginate biosynthesis. In addition, we identified C. okamuranus genes for enzymes involved in phlorotannin biosynthesis. The present decoding of the Cladosiphon okamuranus genome provides a platform for future studies of mozuku biology. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

An AFLP genetic linkage map of pacific abalone ( Haliotis discus hannai)

NASA Astrophysics Data System (ADS)

Qi, Li; Yanhong, Xu; Ruihai, Yu; Akihiro, Kijima

2007-07-01

A genetic linkage map of Pacific abalone ( Haliotis discus hannai) was constructed using AFLP markers based on a two-way pseudo-testeross strategy in a full-sib family. With 33 primer combinations, a total of 455 markers (225 from the female parent and 230 from the male parent) segregated in a 1:1 ratio, corresponding to DNA polymorphism: heterozygous in one parent and null in the other. The female framework map consisted of 174 markers distributed in 18 linkage groups, equivalent to the H. discus hannai haploid chromosome number, and spanning a total length of 2031.4 cM, with an average interval of 13.0 cM between adjacent markers. The male framework map consisted of 195 markers mapped on 19 linkage groups, spanning a total length of 2273.4 cM, with an average spacing of 12.9 cM between adjacent markers. The estimated coverage for the framework linkage maps was 81.2% for the female and 82.1% for the male, on the basis of two estimates of genome length. Fifty-two markers (11.4%) remained unlinked. The level of segregation distortion observed in this cross was 20.4%. These linkage maps will serve as a starting point for linkage studies in the Pacific abalone with potential application for marker-assisted selection in breeding programs.

Introduction to Pharmaceutical Biotechnology, Volume 1; Basic techniques and concepts

NASA Astrophysics Data System (ADS)

Bhatia, Saurabh; Goli, Divakar

2018-05-01

Animal biotechnology is a broad field including polarities of fundamental and applied research, as well as DNA science, covering key topics of DNA studies and its recent applications. In Introduction to Pharmaceutical Biotechnology, DNA isolation procedures followed by molecular markers and screening methods of the genomic library are explained. Interesting areas like isolation, sequencing and synthesis of genes, with the broader coverage on synthesis of genes, are also described. The book begins with an introduction to biotechnology and its main branches, explaining both the basic science and the applications of biotechnology-derived pharmaceuticals, with special emphasis on their clinical use. It then moves on to historical development and scope of biotechnology with an overall review of early applications that scientists employed long before the field was defined.

Beat-to-beat heart rate estimation fusing multimodal video and sensor data

PubMed Central

Antink, Christoph Hoog; Gao, Hanno; Brüser, Christoph; Leonhardt, Steffen

2015-01-01

Coverage and accuracy of unobtrusively measured biosignals are generally relatively low compared to clinical modalities. This can be improved by exploiting redundancies in multiple channels with methods of sensor fusion. In this paper, we demonstrate that two modalities, skin color variation and head motion, can be extracted from the video stream recorded with a webcam. Using a Bayesian approach, these signals are fused with a ballistocardiographic signal obtained from the seat of a chair with a mean absolute beat-to-beat estimation error below 25 milliseconds and an average coverage above 90% compared to an ECG reference. PMID:26309754

Beat-to-beat heart rate estimation fusing multimodal video and sensor data.

PubMed

Antink, Christoph Hoog; Gao, Hanno; Brüser, Christoph; Leonhardt, Steffen

2015-08-01

Coverage and accuracy of unobtrusively measured biosignals are generally relatively low compared to clinical modalities. This can be improved by exploiting redundancies in multiple channels with methods of sensor fusion. In this paper, we demonstrate that two modalities, skin color variation and head motion, can be extracted from the video stream recorded with a webcam. Using a Bayesian approach, these signals are fused with a ballistocardiographic signal obtained from the seat of a chair with a mean absolute beat-to-beat estimation error below 25 milliseconds and an average coverage above 90% compared to an ECG reference.

A preliminary estimate of the EUVE cumulative distribution of exposure time on the unit sphere. [Extreme Ultra-Violet Explorer

NASA Technical Reports Server (NTRS)

Tang, C. C. H.

1984-01-01

A preliminary study of an all-sky coverage of the EUVE mission is given. Algorithms are provided to compute the exposure of the celestial sphere under the spinning telescopes, taking into account that during part of the exposure time the telescopes are blocked by the earth. The algorithms are used to give an estimate of exposure time at different ecliptic latitudes as a function of the angle of field of view of the telescope. Sample coverage patterns are also given for a 6-month mission.

Epidemiology of hepatitis D in patients infected with hepatitis B virus in bucharest: a cross-sectional study.

PubMed

Popescu, G A; Otelea, D; Gavriliu, L C; Neaga, E; Popescu, C; Paraschiv, S; Fratila, M

2013-05-01

Epidemiological analyses indicate a decreasing level of hepatitis D (HDV) infections in most developed countries during the last 15 years. Romania, however, is one of the European countries that still has high morbidity from HDV; this study was performed in order to estimate the HDV prevalence in the Bucharest area. Three thousand four hundred sixty-one hepatitis B (HBV) infected patients were invited to participate and 1,094 were recruited. Serum anti-HDV IgG was detected in 223 patients indicating a hepatitis D seroprevalence of 20.4% (95% CI = 18.1-22.9) in patients chronically infected with HBV, less than that seen in previous studies. Seroprevalence was not gender related, but patients over 40 years were more likely to have anti-HDV antibodies, RR = 1.9 (1.2; 3.0). Detectable hepatitis D viraemia was found in 67.7% of the patients who were positive for anti-HDV. The HDV genotype was characterized for 40 isolates; all were very similar and belonged to genotype 1. Serum HBV-DNA was detectable less frequently in patients positive for anti-HDV than in patients infected with HBV alone: 68.5% versus 89.3%, OR 3.9 (1.7; 10.0), but the extent of this HDV replicative dominance varies with the sensitivity of the HBV-DNA detection. 19.3% of the subjects who tested positive for anti-HDV IgG had a HBV-DNA level higher than four logs. This high prevalence prompts the need for better HBV vaccination coverage and measures to prevent super infection with HDV in patients infected with HBV. Copyright © 2013 Wiley Periodicals, Inc.

Recent proposals to limit Medigap coverage and modify Medicare cost sharing.

PubMed

Linehan, Kathryn

2012-02-24

As policymakers look for savings from the Medicare program, some have proposed eliminating or discouraging "first-dollar coverage" available through privately purchased Medigap policies. Medigap coverage, which beneficiaries obtain to protect themselves from Medicare's cost-sharing requirements and its lack of a cap on out-of-pocket spending, may discourage the judicious use of medical services by reducing or eliminating beneficiary cost sharing. It is estimated that eliminating such coverage, which has been shown to be associated with higher Medicare spending, and requiring some cost sharing would encourage beneficiaries to reduce their service use and thus reduce pro­gram spending. However, eliminating first-dollar coverage could cause some beneficiaries to incur higher spending or forego necessary services. Some policy proposals to eliminate first-dollar coverage would also modify Medicare's cost sharing and add an out-of-pocket spending cap for fee-for-service Medicare. This paper discusses Medicare's current cost-sharing requirements, Medigap insurance, and proposals to modify Medicare's cost sharing and eliminate first-dollar coverage in Medigap plans. It reviews the evidence on the effects of first-dollar coverage on spending, some objections to eliminating first-dollar coverage, and results of research that has modeled the impact of eliminating first-dollar coverage, modifying Medicare's cost-sharing requirements, and adding an out-of-pocket limit on beneficiaries' spending.

Impact of an Individual Mandate and Other Health Reforms on Dependent Coverage for Adolescents and Young Adults.

PubMed

Wisk, Lauren E; Finkelstein, Jonathan A; Toomey, Sara L; Sawicki, Gregory S; Schuster, Mark A; Galbraith, Alison A

2018-06-01

To determine the effect of state-level dependent coverage expansion (DCE) with and without other state health reforms on exit from dependent coverage for adolescents and young adults (AYA). Administrative longitudinal data for 131,542 privately insured AYA in Massachusetts (DCE with other reforms) versus Maine and New Hampshire (DCE without other reforms) across three periods: prereform (1/00-12/06), poststate reform (1/07-9/10), and postfederal reform (10/10-12/12). A difference-in-differences estimator was used to determine the rate of exit from dependent coverage, age at exit from dependent coverage, and re-uptake of dependent coverage among AYA in states with comprehensive reforms versus DCE only. Implementation of DCE with other reforms was significantly associated with a 23 percent reduction in exit from dependent coverage among AYA compared to the reduction observed for DCE alone. Additionally, comprehensive reforms were associated with over two additional years of dependent coverage for the average AYA and a 33 percent increase in the odds of regaining dependent coverage after a prior loss. Findings suggest that an individual mandate and other reforms may enhance the effect of DCE in preventing loss of coverage among AYA. © Health Research and Educational Trust.

Pew Memorial Trust policy synthesis: 5. State coverage for organ transplantation: a framework for decision making.

PubMed

Lindsey, P A; McGlynn, E A

1988-02-01

Transplantation of hearts and livers for both adults and children is increasingly viewed as therapeutic and lifesaving, but access to these procedures is impeded by their high cost as well as by a limited supply of organs. In the absence of comprehensive federal coverage, pressure is being brought to bear on states to provide broader access to these procedures. This synthesis provides a framework for the consideration of coverage decisions at the state level. While there are no "right" answers about whether a state should support such coverage, the analytic tools of cost analysis, demand estimation, and assessment of capacity described in this synthesis can better inform the decision-making process.

Environmental conditions in health care facilities in low- and middle-income countries: Coverage and inequalities.

PubMed

Cronk, Ryan; Bartram, Jamie

2018-04-01

Safe environmental conditions and the availability of standard precaution items are important to prevent and treat infection in health care facilities (HCFs) and to achieve Sustainable Development Goal (SDG) targets for health and water, sanitation, and hygiene. Baseline coverage estimates for HCFs have yet to be formed for the SDGs; and there is little evidence describing inequalities in coverage. To address this, we produced the first coverage estimates of environmental conditions and standard precaution items in HCFs in low- and middle-income countries (LMICs); and explored factors associated with low coverage. Data from monitoring reports and peer-reviewed literature were systematically compiled; and information on conditions, service levels, and inequalities tabulated. We used logistic regression to identify factors associated with low coverage. Data for 21 indicators of environmental conditions and standard precaution items were compiled from 78 LMICs which were representative of 129,557 HCFs. 50% of HCFs lack piped water, 33% lack improved sanitation, 39% lack handwashing soap, 39% lack adequate infectious waste disposal, 73% lack sterilization equipment, and 59% lack reliable energy services. Using nationally representative data from six countries, 2% of HCFs provide all four of water, sanitation, hygiene, and waste management services. Statistically significant inequalities in coverage exist between HCFs by: urban-rural setting, managing authority, facility type, and sub-national administrative unit. We identified important, previously undocumented inequalities and environmental health challenges faced by HCFs in LMICs. The information and analyses provide evidence for those engaged in improving HCF conditions to develop evidence-based policies and efficient programs, enhance service delivery systems, and make better use of available resources. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Tetanus toxoid coverage as an indicator of serological protection against neonatal tetanus.

PubMed Central

Deming, Michael S.; Roungou, Jean-Baptiste; Kristiansen, Max; Heron, Iver; Yango, Alphonse; Guenengafo, Alexis; Ndamobissi, Robert

2002-01-01

OBJECTIVE: A Multiple-Indicator Cluster Survey (MICS) was conducted at mid-decade in more than 60 developing countries to measure progress towards the year 2000 World Summit for Children goals. These goals included the protection of at least 90% of children against neonatal tetanus through the immunization of their mothers, as measured by tetanus toxoid (TT) coverage. In the Central African Republic (CAR), serological testing was added to the MICS to understand better the relationship between survey estimates of TT coverage and the prevalence of serological protection. METHODS: In the CAR MICS, mothers of children younger than one year of age gave verbal histories of the TT vaccinations they had received, using the MICS TT questionnaire. A subsample of mothers was tested for tetanus antitoxin, using a double-antigen enzyme-linked immunoadsorbent assay (ELISA). Seropositivity was defined as a titre of > or =0.01 IU/ml, and TT coverage was defined as the proportion of mothers protected at delivery, according to their history of TT vaccinations. FINDINGS: Among the 222 mothers in the subsample, weighted TT coverage was 74.4% (95% Confidence Interval (CI); 67.0% - 81.7%) and tetanus antitoxin seroprevalence was 88.7% (95% CI; 83.2% - 94.2%). The weighted median antitoxin titre was 0.35 IU/ml. CONCLUSIONS: Tetanus toxoid coverage in the CAR was lower than the prevalence of serological protection against neonatal tetanus. If this relationship holds for other countries, TT coverage estimates from the MICS may underestimate the extent to which the year 2000 goal for protecting children against neonatal tetanus was reached. We also showed that a high level of serological protection had been achieved in a country facing major public health challenges and resource constraints. PMID:12378286

Low vaccination coverage of Greek Roma children amid economic crisis: national survey using stratified cluster sampling

PubMed Central

Petraki, Ioanna; Arkoudis, Chrisoula; Terzidis, Agis; Smyrnakis, Emmanouil; Benos, Alexis; Panagiotopoulos, Takis

2017-01-01

Abstract Background: Research on Roma health is fragmentary as major methodological obstacles often exist. Reliable estimates on vaccination coverage of Roma children at a national level and identification of risk factors for low coverage could play an instrumental role in developing evidence-based policies to promote vaccination in this marginalized population group. Methods: We carried out a national vaccination coverage survey of Roma children. Thirty Roma settlements, stratified by geographical region and settlement type, were included; 7–10 children aged 24–77 months were selected from each settlement using systematic sampling. Information on children’s vaccination coverage was collected from multiple sources. In the analysis we applied weights for each stratum, identified through a consensus process. Results: A total of 251 Roma children participated in the study. A vaccination document was presented for the large majority (86%). We found very low vaccination coverage for all vaccines. In 35–39% of children ‘minimum vaccination’ (DTP3 and IPV2 and MMR1) was administered, while 34–38% had received HepB3 and 31–35% Hib3; no child was vaccinated against tuberculosis in the first year of life. Better living conditions and primary care services close to Roma settlements were associated with higher vaccination indices. Conclusions: Our study showed inadequate vaccination coverage of Roma children in Greece, much lower than that of the non-minority child population. This serious public health challenge should be systematically addressed, or, amid continuing economic recession, the gap may widen. Valid national estimates on important characteristics of the Roma population can contribute to planning inclusion policies. PMID:27694159

Low vaccination coverage of Greek Roma children amid economic crisis: national survey using stratified cluster sampling.

PubMed

Papamichail, Dimitris; Petraki, Ioanna; Arkoudis, Chrisoula; Terzidis, Agis; Smyrnakis, Emmanouil; Benos, Alexis; Panagiotopoulos, Takis

2017-04-01

Research on Roma health is fragmentary as major methodological obstacles often exist. Reliable estimates on vaccination coverage of Roma children at a national level and identification of risk factors for low coverage could play an instrumental role in developing evidence-based policies to promote vaccination in this marginalized population group. We carried out a national vaccination coverage survey of Roma children. Thirty Roma settlements, stratified by geographical region and settlement type, were included; 7-10 children aged 24-77 months were selected from each settlement using systematic sampling. Information on children's vaccination coverage was collected from multiple sources. In the analysis we applied weights for each stratum, identified through a consensus process. A total of 251 Roma children participated in the study. A vaccination document was presented for the large majority (86%). We found very low vaccination coverage for all vaccines. In 35-39% of children 'minimum vaccination' (DTP3 and IPV2 and MMR1) was administered, while 34-38% had received HepB3 and 31-35% Hib3; no child was vaccinated against tuberculosis in the first year of life. Better living conditions and primary care services close to Roma settlements were associated with higher vaccination indices. Our study showed inadequate vaccination coverage of Roma children in Greece, much lower than that of the non-minority child population. This serious public health challenge should be systematically addressed, or, amid continuing economic recession, the gap may widen. Valid national estimates on important characteristics of the Roma population can contribute to planning inclusion policies. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Antecedent causes of a measles resurgence in the Democratic Republic of the Congo

PubMed Central

Scobie, Heather Melissa; Ilunga, Benoît Kebela; Mulumba, Audry; Shidi, Calixte; Coulibaly, Tiekoura; Obama, Ricardo; Tamfum, Jean-Jacques Muyembe; Simbu, Elisabeth Pukuta; Smit, Sheilagh Brigitte; Masresha, Balcha; Perry, Robert Tyrrell; Alleman, Mary Margaret; Kretsinger, Katrina; Goodson, James

2015-01-01

Introduction Despite accelerated measles control efforts, a massive measles resurgence occurred in the Democratic Republic of the Congo (DRC) starting in mid-2010, prompting an investigation into likely causes. Methods We conducted a descriptive epidemiological analysis using measles immunization and surveillance data to understand the causes of the measles resurgence and to develop recommendations for elimination efforts in DRC. Results During 2004-2012, performance indicator targets for case-based surveillance and routine measles vaccination were not met. Estimated coverage with the routine first dose of measles-containing vaccine (MCV1) increased from 57% to 73%. Phased supplementary immunization activities (SIAs) were conducted starting in 2002, in some cases with sub-optimal coverage (≤95%). In 2010, SIAs in five of 11 provinces were not implemented as planned, resulting in a prolonged interval between SIAs, and a missed birth cohort in one province. During July 1, 2010-December 30, 2012, high measles attack rates (>100 cases per 100,000 population) occurred in provinces that had estimated MCV1 coverage lower than the national estimate and did not implement planned 2010 SIAs. The majority of confirmed case-patients were aged <10 years (87%) and unvaccinated or with unknown vaccination status (75%). Surveillance detected two genotype B3 and one genotype B2 measles virus strains that were previously identified in the region. Conclusion The resurgence was likely caused by an accumulation of unvaccinated, measles-susceptible children due to low MCV1 coverage and suboptimal SIA implementation. To achieve the regional goal of measles elimination by 2020, efforts are needed in DRC to improve case-based surveillance and increase two-dose measles vaccination coverage through routine services and SIAs. PMID:26401224

Patient-physician discussions about costs: definitions and impact on cost conversation incidence estimates.

PubMed

Hunter, Wynn G; Hesson, Ashley; Davis, J Kelly; Kirby, Christine; Williamson, Lillie D; Barnett, Jamison A; Ubel, Peter A

2016-03-31

Nearly one in three Americans are financially burdened by their medical expenses. To mitigate financial distress, experts recommend routine physician-patient cost conversations. However, the content and incidence of these conversations are unclear, and rigorous definitions are lacking. We sought to develop a novel set of cost conversation definitions, and determine the impact of definitional variation on cost conversation incidence in three clinical settings. Retrospective, mixed-methods analysis of transcribed dialogue from 1,755 outpatient encounters for routine clinical management of breast cancer, rheumatoid arthritis, and depression, occurring between 2010-2014. We developed cost conversation definitions using summative content analysis. Transcripts were evaluated independently by at least two members of our multi-disciplinary team to determine cost conversation incidence using each definition. Incidence estimates were compared using Pearson's Chi-Square Tests. Three cost conversation definitions emerged from our analysis: (a) Out-of-Pocket (OoP) Cost--discussion of the patient's OoP costs for a healthcare service; (b) Cost/Coverage--discussion of the patient's OoP costs or insurance coverage; (c) Cost of Illness- discussion of financial costs or insurance coverage related to health or healthcare. These definitions were hierarchical; OoP Cost was a subset of Cost/Coverage, which was a subset of Cost of Illness. In each clinical setting, we observed significant variation in the incidence of cost conversations when using different definitions; breast oncology: 16, 22, 24% of clinic visits contained cost conversation (OOP Cost, Cost/Coverage, Cost of Illness, respectively; P < 0.001); depression: 30, 38, 43%, (P < 0.001); and rheumatoid arthritis, 26, 33, 35%, (P < 0.001). The estimated incidence of physician-patient cost conversation varied significantly depending on the definition used. Our findings and proposed definitions may assist in retrospective interpretation and prospective design of investigations on this topic.

Assessing alternative industrial fortification portfolios: a Bangladesh case study.

PubMed

Fiedler, John L; Lividini, Keith; Guyondet, Christophe; Bermudez, Odilia I

2015-03-01

Approximately 1.2 million disability-adjusted life years (DALYs) are lost annually in Bangladesh due to deficiencies of vitamin A, iron, and zinc. To provide evidence on the coverage, costs, and cost-effectiveness of alternative fortification interventions to inform nutrition policy-making in Bangladesh. Combining the 2005 Bangladesh Household Income and Expenditure Survey with a Bangladesh food composition table, apparent intakes of energy, vitamin A, iron, and zinc, and the coverage and apparent consumption levels of fortifiable vegetable oil and wheat flour are estimated. Assuming that fortification levels are those established in official regulations, the costs and cost-effectiveness of the two vehicles are assessed independently and as a two-vehicle portfolio. Vegetable oil has a coverage rate of 76% and is estimated to reduce the prevalence of inadequate vitamin A intake from 83% to 64%. The coverage of wheat flour is high (65%), but the small quantities consumed result in small reductions in the prevalence of inadequate intakes: 1.5 percentage points for iron, less than 1 for zinc, and 2 for vitamin A, while reducing average Estimated Average Requirement (EAR) gaps by 8%, 9%, and 15%, respectively. The most cost-effective 10-micronutrient wheat flour formulation costs US $1.91 million annually, saving 129,212 DALYs at a unit cost of US $14.75. Fortifying vegetable oil would cost US $1.27 million annually, saving 406,877 DALYs at an average cost of US $3.25. Sensitivity analyses explore various permutations of the wheat flour formulation. Divisional variations in coverage, cost, and impact are examined. Vegetable oil fortification is the most cost-effective of the three portfolios analyzed, but all three are very cost-effective options for Bangladesh.

Progress in global measles control, 2000-2010.

PubMed

2012-02-03

In 1980, before widespread global use of measles vaccine, an estimated 2.6 million measles deaths occurred worldwide. In 2001, to accelerate the reduction in measles cases achieved by vaccination, the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) developed a strategy to deliver 2 doses of measles-containing vaccine (MCV) to all children through routine services and supplementary immunization activities (SIAs) and improved disease surveillance. After implementation of this strategy, the estimated number of annual measles deaths worldwide decreased from 733,000 in 2000 to 164,000 in 2008. In 2010, the World Health Assembly endorsed the following measles objectives for 2015: 1) raise routine coverage with the first dose of MCV (MCV1) for children aged 1 year to ≥90% nationally and ≥80% in every district or equivalent administrative unit, 2) reduce and maintain annual measles incidence at <5 cases per million, and 3) reduce measles mortality by ≥95% from the 2000 estimate. During 2000-2010, global MCV1 coverage increased from 72% to 85% with approximately 1 billion children vaccinated during measles SIAs. Reported measles cases decreased from 2000 to 2008, remained stable in 2009, and increased in 2010. By the end of 2010, 40% of countries still had not met the incidence target of <5 cases per million. Key challenges must be overcome to meet the 2015 objectives, including 1) declining political and financial commitments to measles control, 2) failure to reach uniform high coverage with 2 doses of MCV through routine services or SIAs, and 3) inadequate monitoring subnationally of coverage with the first and second dose of MCV to guide interventions to increase coverage.

Antecedent causes of a measles resurgence in the Democratic Republic of the Congo.

PubMed

Scobie, Heather Melissa; Ilunga, Benoît Kebela; Mulumba, Audry; Shidi, Calixte; Coulibaly, Tiekoura; Obama, Ricardo; Tamfum, Jean-Jacques Muyembe; Simbu, Elisabeth Pukuta; Smit, Sheilagh Brigitte; Masresha, Balcha; Perry, Robert Tyrrell; Alleman, Mary Margaret; Kretsinger, Katrina; Goodson, James

2015-01-01

Despite accelerated measles control efforts, a massive measles resurgence occurred in the Democratic Republic of the Congo (DRC) starting in mid-2010, prompting an investigation into likely causes. We conducted a descriptive epidemiological analysis using measles immunization and surveillance data to understand the causes of the measles resurgence and to develop recommendations for elimination efforts in DRC. During 2004-2012, performance indicator targets for case-based surveillance and routine measles vaccination were not met. Estimated coverage with the routine first dose of measles-containing vaccine (MCV1) increased from 57% to 73%. Phased supplementary immunization activities (SIAs) were conducted starting in 2002, in some cases with sub-optimal coverage (≤95%). In 2010, SIAs in five of 11 provinces were not implemented as planned, resulting in a prolonged interval between SIAs, and a missed birth cohort in one province. During July 1, 2010-December 30, 2012, high measles attack rates (>100 cases per 100,000 population) occurred in provinces that had estimated MCV1 coverage lower than the national estimate and did not implement planned 2010 SIAs. The majority of confirmed case-patients were aged <10 years (87%) and unvaccinated or with unknown vaccination status (75%). Surveillance detected two genotype B3 and one genotype B2 measles virus strains that were previously identified in the region. The resurgence was likely caused by an accumulation of unvaccinated, measles-susceptible children due to low MCV1 coverage and suboptimal SIA implementation. To achieve the regional goal of measles elimination by 2020, efforts are needed in DRC to improve case-based surveillance and increase two-dose measles vaccination coverage through routine services and SIAs.

Coverage and determinants of childhood immunization in Nigeria: A systematic review and meta-analysis.

PubMed

Adeloye, Davies; Jacobs, Wura; Amuta, Ann O; Ogundipe, Oluwatomisin; Mosaku, Oluwaseun; Gadanya, Muktar A; Oni, Gbolahan

2017-05-19

The proportion of fully immunized children in Nigeria is reportedly low. There are concerns over national immunization data quality, with this possibly limiting country-wide response. We reviewed publicly available evidence on routine immunization across Nigeria to estimate national and zonal coverage of childhood immunization and associated determinants. A systematic search of Medline, EMBASE, Global Health and African Journals Online (AJOL) was conducted. We included population-based studies on childhood immunization in Nigeria. A random effects meta-analysis was conducted on extracted crude rates to arrive at national and zonal pooled estimates for the country. Our search returned 646 hits. 21 studies covering 25 sites and 26,960 children were selected. The estimated proportion of fully immunized children in Nigeria was 34.4% (95% confidence interval [CI]: 27.0-41.9), with South-south zone having the highest at 51.5% (95% CI: 20.5-82.6), and North-west the lowest at 9.5% (95% CI: 4.6-14.4). Mother's social engagements (OR=4.0, 95% CI: 1.9-8.1) and vaccines unavailability (OR=3.9, 95% CI: 1.2-12.3) were mostly reported for low coverage. Other leading determinants were vaccine safety concerns (OR=3.0, 95% CI: 0.9-9.4), mother's low education (OR=2.5, 95% CI: 1.8-3.6) and poor information (OR=2.0, 95% CI: 0.8-4.7). Our study suggests a low coverage of childhood immunization in Nigeria. Due to the paucity of data in the Northern states, we are still uncertain of the quality of evidence presented. It is hoped that this study will prompt the needed research, public health and policy changes toward increased evenly-spread coverage of childhood immunization in the country. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Comparison of Grizzly Bear Demographic Parameters Estimated from Non-Spatial and Spatial Open Population Capture-Recapture Models.

PubMed

Whittington, Jesse; Sawaya, Michael A

2015-01-01

Capture-recapture studies are frequently used to monitor the status and trends of wildlife populations. Detection histories from individual animals are used to estimate probability of detection and abundance or density. The accuracy of abundance and density estimates depends on the ability to model factors affecting detection probability. Non-spatial capture-recapture models have recently evolved into spatial capture-recapture models that directly include the effect of distances between an animal's home range centre and trap locations on detection probability. Most studies comparing non-spatial and spatial capture-recapture biases focussed on single year models and no studies have compared the accuracy of demographic parameter estimates from open population models. We applied open population non-spatial and spatial capture-recapture models to three years of grizzly bear DNA-based data from Banff National Park and simulated data sets. The two models produced similar estimates of grizzly bear apparent survival, per capita recruitment, and population growth rates but the spatial capture-recapture models had better fit. Simulations showed that spatial capture-recapture models produced more accurate parameter estimates with better credible interval coverage than non-spatial capture-recapture models. Non-spatial capture-recapture models produced negatively biased estimates of apparent survival and positively biased estimates of per capita recruitment. The spatial capture-recapture grizzly bear population growth rates and 95% highest posterior density averaged across the three years were 0.925 (0.786-1.071) for females, 0.844 (0.703-0.975) for males, and 0.882 (0.779-0.981) for females and males combined. The non-spatial capture-recapture population growth rates were 0.894 (0.758-1.024) for females, 0.825 (0.700-0.948) for males, and 0.863 (0.771-0.957) for both sexes. The combination of low densities, low reproductive rates, and predominantly negative population growth rates suggest that Banff National Park's population of grizzly bears requires continued conservation-oriented management actions.

Coverage of Community-Based Management of Severe Acute Malnutrition Programmes in Twenty-One Countries, 2012-2013

PubMed Central

Rogers, Eleanor; Myatt, Mark; Woodhead, Sophie; Guerrero, Saul; Alvarez, Jose Luis

2015-01-01

Objective This paper reviews coverage data from programmes treating severe acute malnutrition (SAM) collected between July 2012 and June 2013. Design This is a descriptive study of coverage levels and barriers to coverage collected by coverage assessments of community-based SAM treatment programmes in 21 countries that were supported by the Coverage Monitoring Network. Data from 44 coverage assessments are reviewed. Setting These assessments analyse malnourished populations from 6 to 59 months old to understand the accessibility and coverage of services for treatment of acute malnutrition. The majority of assessments are from sub-Saharan Africa. Results Most of the programmes (33 of 44) failed to meet context-specific internationally agreed minimum standards for coverage. The mean level of estimated coverage achieved by the programmes in this analysis was 38.3%. The most frequently reported barriers to access were lack of awareness of malnutrition, lack of awareness of the programme, high opportunity costs, inter-programme interface problems, and previous rejection. Conclusions This study shows that coverage of CMAM is lower than previous analyses of early CTC programmes; therefore reducing programme impact. Barriers to access need to be addressed in order to start improving coverage by paying greater attention to certain activities such as community sensitisation. As barriers are interconnected focusing on specific activities, such as decentralising services to satellite sites, is likely to increase significantly utilisation of nutrition services. Programmes need to ensure that barriers are continuously monitored to ensure timely removal and increased coverage. PMID:26042827

Surveys of environmental DNA (eDNA): a new approach to estimate occurrence in Vulnerable manatee populations

USGS Publications Warehouse

Hunter, Margaret; Meigs-Friend, Gaia; Ferrante, Jason; Takoukam Kamla, Aristide; Dorazio, Robert; Keith Diagne, Lucy; Luna, Fabia; Lanyon, Janet M.; Reid, James P.

2018-01-01

Environmental DNA (eDNA) detection is a technique used to non-invasively detect cryptic, low density, or logistically difficult-to-study species, such as imperiled manatees. For eDNA measurement, genetic material shed into the environment is concentrated from water samples and analyzed for the presence of target species. Cytochrome bquantitative PCR and droplet digital PCR eDNA assays were developed for the 3 Vulnerable manatee species: African, Amazonian, and both subspecies of the West Indian (Florida and Antillean) manatee. Environmental DNA assays can help to delineate manatee habitat ranges, high use areas, and seasonal population changes. To validate the assay, water was analyzed from Florida’s east coast containing a high-density manatee population and produced 31564 DNA molecules l-1on average and high occurrence (ψ) and detection (p) estimates (ψ = 0.84 [0.40-0.99]; p = 0.99 [0.95-1.00]; limit of detection 3 copies µl-1). Similar occupancy estimates were produced in the Florida Panhandle (ψ = 0.79 [0.54-0.97]) and Cuba (ψ = 0.89 [0.54-1.00]), while occupancy estimates in Cameroon were lower (ψ = 0.49 [0.09-0.95]). The eDNA-derived detection estimates were higher than those generated using aerial survey data on the west coast of Florida and may be effective for population monitoring. Subsequent eDNA studies could be particularly useful in locations where manatees are (1) difficult to identify visually (e.g. the Amazon River and Africa), (2) are present in patchy distributions or are on the verge of extinction (e.g. Jamaica, Haiti), and (3) where repatriation efforts are proposed (e.g. Brazil, Guadeloupe). Extension of these eDNA techniques could be applied to other imperiled marine mammal populations such as African and Asian dugongs.

Determining accurate vaccination coverage rates for adolescents: the National Immunization Survey-Teen 2006.

PubMed

Jain, Nidhi; Singleton, James A; Montgomery, Margrethe; Skalland, Benjamin

2009-01-01

Since 1994, the Centers for Disease Control and Prevention has funded the National Immunization Survey (NIS), a large telephone survey used to estimate vaccination coverage of U.S. children aged 19-35 months. The NIS is a two-phase survey that obtains vaccination receipt information from a random-digit-dialed survey, designed to identify households with eligible children, followed by a provider record check, which obtains provider-reported vaccination histories for eligible children. In 2006, the survey was expanded for the first time to include a national sample of adolescents aged 13-17 years, called the NIS-Teen. This article summarizes the methodology used in the NIS-Teen. In 2008, the NIS-Teen was expanded to collect state-specific and national-level data to determine vaccination coverage estimates. This survey provides valuable information to guide immunization programs for adolescents.

Estimation of the fractional coverage of rainfall in climate models

NASA Technical Reports Server (NTRS)

Eltahir, E. A. B.; Bras, R. L.

1993-01-01

The fraction of the grid cell area covered by rainfall, mu, is an essential parameter in descriptions of land surface hydrology in climate models. A simple procedure is presented for estimating this fraction, based on extensive observations of storm areas and rainfall volumes. Storm area and rainfall volume are often linearly related; this relation can be used to compute the storm area from the volume of rainfall simulated by a climate model. A formula is developed for computing mu, which describes the dependence of the fractional coverage of rainfall on the season of the year, the geographical region, rainfall volume, and the spatial and temporal resolution of the model. The new formula is applied in computing mu over the Amazon region. Significant temporal variability in the fractional coverage of rainfall is demonstrated. The implications of this variability for the modeling of land surface hydrology in climate models are discussed.

Comparing estimates of child mortality reduction modelled in LiST with pregnancy history survey data for a community-based NGO project in Mozambique

PubMed Central

2011-01-01

Background There is a growing body of evidence that integrated packages of community-based interventions, a form of programming often implemented by NGOs, can have substantial child mortality impact. More countries may be able to meet Millennium Development Goal (MDG) 4 targets by leveraging such programming. Analysis of the mortality effect of this type of programming is hampered by the cost and complexity of direct mortality measurement. The Lives Saved Tool (LiST) produces an estimate of mortality reduction by modelling the mortality effect of changes in population coverage of individual child health interventions. However, few studies to date have compared the LiST estimates of mortality reduction with those produced by direct measurement. Methods Using results of a recent review of evidence for community-based child health programming, a search was conducted for NGO child health projects implementing community-based interventions that had independently verified child mortality reduction estimates, as well as population coverage data for modelling in LiST. One child survival project fit inclusion criteria. Subsequent searches of the USAID Development Experience Clearinghouse and Child Survival Grants databases and interviews of staff from NGOs identified no additional projects. Eight coverage indicators, covering all the project’s technical interventions were modelled in LiST, along with indicator values for most other non-project interventions in LiST, mainly from DHS data from 1997 and 2003. Results The project studied was implemented by World Relief from 1999 to 2003 in Gaza Province, Mozambique. An independent evaluation collecting pregnancy history data estimated that under-five mortality declined 37% and infant mortality 48%. Using project-collected coverage data, LiST produced estimates of 39% and 34% decline, respectively. Conclusions LiST gives reasonably accurate estimates of infant and child mortality decline in an area where a package of community-based interventions was implemented. This and other validation exercises support use of LiST as an aid for program planning to tailor packages of community-based interventions to the epidemiological context and for project evaluation. Such targeted planning and assessments will be useful to accelerate progress in reaching MDG4 targets. PMID:21501454

Integration of lidar and Landsat ETM+ data for estimating and mapping forest canopy height.

Treesearch

Andrew T. Hudak; Michael A. Lefsky; Warren B. Cohen; Mercedes Berterretche

2002-01-01

Light detection and ranging (LIDAR) data provide accurate measurements of forest canopy structure in the vertical plane; however, current LIDAR sensors have limited coverage in the horizontal plane. Landsat data provide extensive coverage of generalized forest structural classes in the horizontal plane but are relatively insensitive to variation in forest canopy height...

Development and evaluation of a high density genotyping 'Axiom_Arachis' array with 58K SNPs for accelerating genetics and breeding in groundnut

USDA-ARS?s Scientific Manuscript database

Single nucleotide polymorphisms (SNPs) are the most abundant DNA sequence variation in the genomes which can be used to associate genotypic variation to the phenotype. Therefore, availability of a high-density SNP array with uniform genome coverage can advance genetic studies and breeding applicatio...

Australian attitudes to DNA sample banks and genetic screening.

PubMed

Williams, Carolyn

2005-11-01

An exploration via an anonymous questionnaire of Australian public attitudes towards medical genetics and sample banking revealed the overwhelming majority views these developments with thoughtful confidence. Continued public education and awareness of these issues will allow the public to make informed decisions and enhance vigilance towards the sometimes misleading coverage in the press and media.

A magnetic nanobead-based bioassay provides sensitive detection of single- and biplex bacterial DNA using a portable AC susceptometer.

PubMed

Strömberg, Mattias; Zardán Gómez de la Torre, Teresa; Nilsson, Mats; Svedlindh, Peter; Strømme, Maria

2014-01-01

Bioassays relying on magnetic read-out using probe-tagged magnetic nanobeads are potential platforms for low-cost biodiagnostic devices for pathogen detection. For optimal assay performance it is crucial to apply an easy, efficient and robust bead-probe conjugation protocol. In this paper, sensitive (1.5 pM) singleplex detection of bacterial DNA sequences is demonstrated in a portable AC susceptometer by a magnetic nanobead-based bioassay principle; the volume-amplified magnetic nanobead detection assay (VAM-NDA). Two bead sizes, 100 and 250 nm, are investigated along with a highly efficient, rapid, robust, and stable conjugation chemistry relying on the avidin-biotin interaction for bead-probe attachment. Avidin-biotin conjugation gives easy control of the number of detection probes per bead; thus allowing for systematic investigation of the impact of varying the detection probe surface coverage upon bead immobilization in rolling circle amplified DNA-coils. The existence of an optimal surface coverage is discussed. Biplex VAM-NDA detection is for the first time demonstrated in the susceptometer: Semi-quantitative results are obtained and it is concluded that the concentration of DNA-coils in the incubation volume is of crucial importance for target quantification. The present findings bring the development of commercial biodiagnostic devices relying on the VAM-NDA further towards implementation in point-of-care and outpatient settings. © 2013 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution-License, which permits use and distribution in any medium, provided the original work is properly cited.

An analytical framework for estimating aquatic species density from environmental DNA

USGS Publications Warehouse

Chambert, Thierry; Pilliod, David S.; Goldberg, Caren S.; Doi, Hideyuki; Takahara, Teruhiko

2018-01-01

Environmental DNA (eDNA) analysis of water samples is on the brink of becoming a standard monitoring method for aquatic species. This method has improved detection rates over conventional survey methods and thus has demonstrated effectiveness for estimation of site occupancy and species distribution. The frontier of eDNA applications, however, is to infer species density. Building upon previous studies, we present and assess a modeling approach that aims at inferring animal density from eDNA. The modeling combines eDNA and animal count data from a subset of sites to estimate species density (and associated uncertainties) at other sites where only eDNA data are available. As a proof of concept, we first perform a cross-validation study using experimental data on carp in mesocosms. In these data, fish densities are known without error, which allows us to test the performance of the method with known data. We then evaluate the model using field data from a study on a stream salamander species to assess the potential of this method to work in natural settings, where density can never be known with absolute certainty. Two alternative distributions (Normal and Negative Binomial) to model variability in eDNA concentration data are assessed. Assessment based on the proof of concept data (carp) revealed that the Negative Binomial model provided much more accurate estimates than the model based on a Normal distribution, likely because eDNA data tend to be overdispersed. Greater imprecision was found when we applied the method to the field data, but the Negative Binomial model still provided useful density estimates. We call for further model development in this direction, as well as further research targeted at sampling design optimization. It will be important to assess these approaches on a broad range of study systems.

Genomic treasure troves: complete genome sequencing of herbarium and insect museum specimens.

PubMed

Staats, Martijn; Erkens, Roy H J; van de Vossenberg, Bart; Wieringa, Jan J; Kraaijeveld, Ken; Stielow, Benjamin; Geml, József; Richardson, James E; Bakker, Freek T

2013-01-01

Unlocking the vast genomic diversity stored in natural history collections would create unprecedented opportunities for genome-scale evolutionary, phylogenetic, domestication and population genomic studies. Many researchers have been discouraged from using historical specimens in molecular studies because of both generally limited success of DNA extraction and the challenges associated with PCR-amplifying highly degraded DNA. In today's next-generation sequencing (NGS) world, opportunities and prospects for historical DNA have changed dramatically, as most NGS methods are actually designed for taking short fragmented DNA molecules as templates. Here we show that using a standard multiplex and paired-end Illumina sequencing approach, genome-scale sequence data can be generated reliably from dry-preserved plant, fungal and insect specimens collected up to 115 years ago, and with minimal destructive sampling. Using a reference-based assembly approach, we were able to produce the entire nuclear genome of a 43-year-old Arabidopsis thaliana (Brassicaceae) herbarium specimen with high and uniform sequence coverage. Nuclear genome sequences of three fungal specimens of 22-82 years of age (Agaricus bisporus, Laccaria bicolor, Pleurotus ostreatus) were generated with 81.4-97.9% exome coverage. Complete organellar genome sequences were assembled for all specimens. Using de novo assembly we retrieved between 16.2-71.0% of coding sequence regions, and hence remain somewhat cautious about prospects for de novo genome assembly from historical specimens. Non-target sequence contaminations were observed in 2 of our insect museum specimens. We anticipate that future museum genomics projects will perhaps not generate entire genome sequences in all cases (our specimens contained relatively small and low-complexity genomes), but at least generating vital comparative genomic data for testing (phylo)genetic, demographic and genetic hypotheses, that become increasingly more horizontal. Furthermore, NGS of historical DNA enables recovering crucial genetic information from old type specimens that to date have remained mostly unutilized and, thus, opens up a new frontier for taxonomic research as well.

Adsorption of parahydrogen on graphene

NASA Astrophysics Data System (ADS)

Dusseault, Marisa; Boninsegni, Massimo

2018-05-01

We study the low-temperature properties of a single layer of parahydrogen adsorbed on graphene, by means of quantum Monte Carlo simulations. The computed phase diagram is very similar to that of helium on the same substrate, featuring commensurate solid phases with fillings 1/3 and 7/16, as well as domain-wall phases at intermediate coverages. At higher coverage the system transitions to an incommensurate, compressible phase. Evidence of promotion of molecules to the second layer is observed at a coverage ˜0.112 Å-2, significantly above existing theoretical estimates.

Multiplex picoliter-droplet digital PCR for quantitative assessment of DNA integrity in clinical samples.

PubMed

Didelot, Audrey; Kotsopoulos, Steve K; Lupo, Audrey; Pekin, Deniz; Li, Xinyu; Atochin, Ivan; Srinivasan, Preethi; Zhong, Qun; Olson, Jeff; Link, Darren R; Laurent-Puig, Pierre; Blons, Hélène; Hutchison, J Brian; Taly, Valerie

2013-05-01

Assessment of DNA integrity and quantity remains a bottleneck for high-throughput molecular genotyping technologies, including next-generation sequencing. In particular, DNA extracted from paraffin-embedded tissues, a major potential source of tumor DNA, varies widely in quality, leading to unpredictable sequencing data. We describe a picoliter droplet-based digital PCR method that enables simultaneous detection of DNA integrity and the quantity of amplifiable DNA. Using a multiplex assay, we detected 4 different target lengths (78, 159, 197, and 550 bp). Assays were validated with human genomic DNA fragmented to sizes of 170 bp to 3000 bp. The technique was validated with DNA quantities as low as 1 ng. We evaluated 12 DNA samples extracted from paraffin-embedded lung adenocarcinoma tissues. One sample contained no amplifiable DNA. The fractions of amplifiable DNA for the 11 other samples were between 0.05% and 10.1% for 78-bp fragments and ≤1% for longer fragments. Four samples were chosen for enrichment and next-generation sequencing. The quality of the sequencing data was in agreement with the results of the DNA-integrity test. Specifically, DNA with low integrity yielded sequencing results with lower levels of coverage and uniformity and had higher levels of false-positive variants. The development of DNA-quality assays will enable researchers to downselect samples or process more DNA to achieve reliable genome sequencing with the highest possible efficiency of cost and effort, as well as minimize the waste of precious samples. © 2013 American Association for Clinical Chemistry.

Yellow Fever in Africa: estimating the burden of disease and impact of mass vaccination from outbreak and serological data.

PubMed

Garske, Tini; Van Kerkhove, Maria D; Yactayo, Sergio; Ronveaux, Olivier; Lewis, Rosamund F; Staples, J Erin; Perea, William; Ferguson, Neil M

2014-05-01

Yellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods. Generalised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone. The yellow fever burden in Africa was estimated for the year 2013 as 130,000 (95% CI 51,000-380,000) cases with fever and jaundice or haemorrhage including 78,000 (95% CI 19,000-180,000) deaths, taking into account the current level of vaccination coverage. The impact of the recent mass vaccination campaigns was assessed by evaluating the difference between the estimates obtained for the current vaccination coverage and for a hypothetical scenario excluding these vaccination campaigns. Vaccination campaigns were estimated to have reduced the number of cases and deaths by 27% (95% CI 22%-31%) across the region, achieving up to an 82% reduction in countries targeted by these campaigns. A limitation of our study is the high level of uncertainty in our estimates arising from the sparseness of data available from both surveillance and serological surveys. With the estimation method presented here, spatial estimates of transmission intensity can be combined with vaccination coverage levels to evaluate the impact of past or proposed vaccination campaigns, thereby helping to allocate resources efficiently for yellow fever control. This method has been used by the Global Alliance for Vaccines and Immunization (GAVI Alliance) to estimate the potential impact of future vaccination campaigns.

Yellow Fever in Africa: Estimating the Burden of Disease and Impact of Mass Vaccination from Outbreak and Serological Data

PubMed Central

Garske, Tini; Van Kerkhove, Maria D.; Yactayo, Sergio; Ronveaux, Olivier; Lewis, Rosamund F.; Staples, J. Erin; Perea, William; Ferguson, Neil M.

2014-01-01

Background Yellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods. Methods and Findings Generalised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone. The yellow fever burden in Africa was estimated for the year 2013 as 130,000 (95% CI 51,000–380,000) cases with fever and jaundice or haemorrhage including 78,000 (95% CI 19,000–180,000) deaths, taking into account the current level of vaccination coverage. The impact of the recent mass vaccination campaigns was assessed by evaluating the difference between the estimates obtained for the current vaccination coverage and for a hypothetical scenario excluding these vaccination campaigns. Vaccination campaigns were estimated to have reduced the number of cases and deaths by 27% (95% CI 22%–31%) across the region, achieving up to an 82% reduction in countries targeted by these campaigns. A limitation of our study is the high level of uncertainty in our estimates arising from the sparseness of data available from both surveillance and serological surveys. Conclusions With the estimation method presented here, spatial estimates of transmission intensity can be combined with vaccination coverage levels to evaluate the impact of past or proposed vaccination campaigns, thereby helping to allocate resources efficiently for yellow fever control. This method has been used by the Global Alliance for Vaccines and Immunization (GAVI Alliance) to estimate the potential impact of future vaccination campaigns. Please see later in the article for the Editors' Summary PMID:24800812

[National Health and Nutrition Survey 2012: design and coverage].

PubMed

Romero-Martínez, Martín; Shamah-Levy, Teresa; Franco-Núñez, Aurora; Villalpando, Salvador; Cuevas-Nasu, Lucía; Gutiérrez, Juan Pablo; Rivera-Dommarco, Juan Ángel

2013-01-01

To describe the design and population coverage of the National Health and Nutrition Survey 2012 (NHNS 2012). The design of the NHNS 2012 is reported, as a probabilistic population based survey with a multi-stage and stratified sampling, as well as the sample inferential properties, the logistical procedures, and the obtained coverage. Household response rate for the NHNS 2012 was 87%, completing data from 50,528 households, where 96 031 individual interviews selected by age and 14,104 of ambulatory health services users were also obtained. The probabilistic design of the NHNS 2012 as well as its coverage allowed to generate inferences about health and nutrition conditions, health programs coverage, and access to health services. Because of their complex designs, all estimations from the NHNS 2012 must use the survey design: weights, primary sampling units, and stratus variables.

Radiology 24/7 In-House Attending Coverage: Do Benefits Outweigh Cost?

PubMed

Coleman, Stephanie; Holalkere, Nagaraj Setty; O׳Malley, Julie; Doherty, Gemma; Norbash, Alexander; Kadom, Nadja

2016-01-01

Many radiology practices, including academic centers, are moving to in-house 24/7 attending coverage. This could be costly and may not be easily accepted by radiology trainees and attending radiologists. In this article, we evaluated the effects of 24/7 in-house attending coverage on patient care, costs, and qualitative aspects such as trainee education. We retrospectively collected report turnaround times (TAT) and work relative value units (wRVU). We compared these parameters between the years before and after the implementation of 24/7 in-house attending coverage. The cost to provide additional attending coverage was estimated from departmental financial reports. A qualitative survey of radiology residents and faculty was performed to study perceived effects on trainee education. There were decreases in report TAT following 24/7 attending implementation: 69% reduction in computed tomography, 43% reduction in diagnostic radiography, 7% reduction in magnetic resonance imaging, and 43% reduction in ultrasound. There was an average daytime wRVU decrease of 9%, although this was compounded by a decrease in total RVUs of the 2013 calendar year. The financial investment by the institution was estimated at $850,000. Qualitative data demonstrated overall positive feedback from trainees and faculty in radiology, although loss of independence was reported as a negative effect. TAT and wRVU metrics changed with implementation of 24/7 attending coverage, although these metrics do not directly relate to patient outcomes. Additional clinical benefits may include fewer discrepancies between preliminary and final reports that may improve emergency and inpatient department workflows and liability exposure. Radiologists reported the impression that clinicians appreciated 24/7 in-house attending coverage, particularly surgical specialists. Loss of trainee independence on call was a perceived disadvantage of 24/7 attending coverage and raised a concern that residency education outcomes could be adversely affected. Copyright © 2016 Elsevier Inc. All rights reserved.

Detection limits of quantitative and digital PCR assays and their influence in presence-absence surveys of environmental DNA

USGS Publications Warehouse

Hunter, Margaret; Dorazio, Robert M.; Butterfield, John S.; Meigs-Friend, Gaia; Nico, Leo; Ferrante, Jason A.

2017-01-01

A set of universal guidelines is needed to determine the limit of detection (LOD) in PCR-based analyses of low concentration DNA. In particular, environmental DNA (eDNA) studies require sensitive and reliable methods to detect rare and cryptic species through shed genetic material in environmental samples. Current strategies for assessing detection limits of eDNA are either too stringent or subjective, possibly resulting in biased estimates of species’ presence. Here, a conservative LOD analysis grounded in analytical chemistry is proposed to correct for overestimated DNA concentrations predominantly caused by the concentration plateau, a nonlinear relationship between expected and measured DNA concentrations. We have used statistical criteria to establish formal mathematical models for both quantitative and droplet digital PCR. To assess the method, a new Grass Carp (Ctenopharyngodon idella) TaqMan assay was developed and tested on both PCR platforms using eDNA in water samples. The LOD adjustment reduced Grass Carp occupancy and detection estimates while increasing uncertainty – indicating that caution needs to be applied to eDNA data without LOD correction. Compared to quantitative PCR, digital PCR had higher occurrence estimates due to increased sensitivity and dilution of inhibitors at low concentrations. Without accurate LOD correction, species occurrence and detection probabilities based on eDNA estimates are prone to a source of bias that cannot be reduced by an increase in sample size or PCR replicates. Other applications also could benefit from a standardized LOD such as GMO food analysis, and forensic and clinical diagnostics.

Assessing the value of the NHIS for studying changes in state coverage policies: the case of New York.

PubMed

Long, Sharon K; Graves, John A; Zuckerman, Stephen

2007-12-01

(1) To assess the effects of New York's Health Care Reform Act of 2000 on the insurance coverage of eligible adults and (2) to explore the feasibility of using the National Health Interview Survey (NHIS) as opposed to the Current Population Survey (CPS) to conduct evaluations of state health reform initiatives. We take advantage of the natural experiment that occurred in New York to compare health insurance coverage for adults before and after the state implemented its coverage initiative using a difference-in-differences framework. We estimate the effects of New York's initiative on insurance coverage using the NHIS, comparing the results to estimates based on the CPS, the most widely used data source for studies of state coverage policy changes. Although the sample sizes are smaller in the NHIS, the NHIS addresses a key limitation of the CPS for such evaluations by providing a better measure of health insurance status. Given the complexity of the timing of the expansion efforts in New York (which encompassed the September 11, 2001 terrorist attacks), we allow for difference in the effects of the state's policy changes over time. In particular, we allow for differences between the period of Disaster Relief Medicaid (DRM), which was a temporary program implemented immediately after September 11th, and the original components of the state's reform efforts-Family Health Plus (FHP), an expansion of direct Medicaid coverage, and Healthy New York (HNY), an effort to make private coverage more affordable. 2000-2004 CPS; 1999-2004 NHIS. We find evidence of a significant reduction in uninsurance for parents in New York, particularly in the period following DRM. For childless adults, for whom the coverage expansion was more circumscribed, the program effects are less promising, as we find no evidence of a significant decline in uninsurance. The success of New York at reducing uninsurance for parents through expansions of both public and private coverage offers hope for new strategies to expand coverage. The NHIS is a strong data source for evaluations of many state health reform initiatives, providing a better measure of insurance status and supporting a more comprehensive study of state innovations than is possible with the CPS.

Assessment of Malawi's success in child mortality reduction through the lens of the Catalytic Initiative Integrated Health Systems Strengthening programme: Retrospective evaluation.

PubMed

Doherty, Tanya; Zembe, Wanga; Ngandu, Nobubelo; Kinney, Mary; Manda, Samuel; Besada, Donela; Jackson, Debra; Daniels, Karen; Rohde, Sarah; van Damme, Wim; Kerber, Kate; Daviaud, Emmanuelle; Rudan, Igor; Muniz, Maria; Oliphant, Nicholas P; Zamasiya, Texas; Rohde, Jon; Sanders, David

2015-12-01

Malawi is estimated to have achieved its Millennium Development Goal (MDG) 4 target. This paper explores factors influencing progress in child survival in Malawi including coverage of interventions and the role of key national policies. We performed a retrospective evaluation of the Catalytic Initiative (CI) programme of support (2007-2013). We developed estimates of child mortality using four population household surveys undertaken between 2000 and 2010. We recalculated coverage indicators for high impact child health interventions and documented child health programmes and policies. The Lives Saved Tool (LiST) was used to estimate child lives saved in 2013. The mortality rate in children under 5 years decreased rapidly in the 10 CI districts from 219 deaths per 1000 live births (95% confidence interval (CI) 189 to 249) in the period 1991-1995 to 119 deaths (95% CI 105 to 132) in the period 2006-2010. Coverage for all indicators except vitamin A supplementation increased in the 10 CI districts across the time period 2000 to 2013. The LiST analysis estimates that there were 10 800 child deaths averted in the 10 CI districts in 2013, primarily attributable to the introduction of the pneumococcal vaccine (24%) and increased household coverage of insecticide-treated bednets (19%). These improvements have taken place within a context of investment in child health policies and scale up of integrated community case management of childhood illnesses. Malawi provides a strong example for countries in sub-Saharan Africa of how high impact child health interventions implemented within a decentralised health system with an established community-based delivery platform, can lead to significant reductions in child mortality.

Assessment of Malawi’s success in child mortality reduction through the lens of the Catalytic Initiative Integrated Health Systems Strengthening programme: Retrospective evaluation

PubMed Central

Doherty, Tanya; Zembe, Wanga; Ngandu, Nobubelo; Kinney, Mary; Manda, Samuel; Besada, Donela; Jackson, Debra; Daniels, Karen; Rohde, Sarah; van Damme, Wim; Kerber, Kate; Daviaud, Emmanuelle; Rudan, Igor; Muniz, Maria; Oliphant, Nicholas P; Zamasiya, Texas; Rohde, Jon; Sanders, David

2015-01-01

Background Malawi is estimated to have achieved its Millennium Development Goal (MDG) 4 target. This paper explores factors influencing progress in child survival in Malawi including coverage of interventions and the role of key national policies. Methods We performed a retrospective evaluation of the Catalytic Initiative (CI) programme of support (2007–2013). We developed estimates of child mortality using four population household surveys undertaken between 2000 and 2010. We recalculated coverage indicators for high impact child health interventions and documented child health programmes and policies. The Lives Saved Tool (LiST) was used to estimate child lives saved in 2013. Results The mortality rate in children under 5 years decreased rapidly in the 10 CI districts from 219 deaths per 1000 live births (95% confidence interval (CI) 189 to 249) in the period 1991–1995 to 119 deaths (95% CI 105 to 132) in the period 2006–2010. Coverage for all indicators except vitamin A supplementation increased in the 10 CI districts across the time period 2000 to 2013. The LiST analysis estimates that there were 10 800 child deaths averted in the 10 CI districts in 2013, primarily attributable to the introduction of the pneumococcal vaccine (24%) and increased household coverage of insecticide–treated bednets (19%). These improvements have taken place within a context of investment in child health policies and scale up of integrated community case management of childhood illnesses. Conclusions Malawi provides a strong example for countries in sub–Saharan Africa of how high impact child health interventions implemented within a decentralised health system with an established community–based delivery platform, can lead to significant reductions in child mortality. PMID:26649176

Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast cancer

PubMed Central

Trabucco, S E; Priedigkeit, N; Parachoniak, C A; Vanden Borre, P; Morley, S; Rosenzweig, M; Gay, L M; Goldberg, M E; Suh, J; Ali, S M; Ross, J; Leyland-Jones, B; Young, B; Williams, C; Park, B; Tsai, M; Haley, B; Peguero, J; Callahan, R D; Sachelarie, I; Cho, J; Atkinson, J M; Bahreini, A; Nagle, A M; Puhalla, S L; Watters, R J; Erdogan-Yildirim, Z; Cao, L; Oesterreich, S; Mathew, A; Lucas, P C; Davidson, N E; Brufsky, A M; Frampton, G M; Stephens, P J; Chmielecki, J; Lee, A V

2018-01-01

Abstract Background Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. Patients and methods To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287–395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. Results We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3′ partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Conclusions Collectively, these data indicate that N-terminal ESR1 fusions involving exons 6–7 are a recurrent driver of endocrine therapy resistance and are impervious to ER-targeted therapies. PMID:29360925

A method for the estimate of the wall diffusion for non-axisymmetric fields using rotating external fields

NASA Astrophysics Data System (ADS)

Frassinetti, L.; Olofsson, K. E. J.; Fridström, R.; Setiadi, A. C.; Brunsell, P. R.; Volpe, F. A.; Drake, J.

2013-08-01

A new method for the estimate of the wall diffusion time of non-axisymmetric fields is developed. The method based on rotating external fields and on the measurement of the wall frequency response is developed and tested in EXTRAP T2R. The method allows the experimental estimate of the wall diffusion time for each Fourier harmonic and the estimate of the wall diffusion toroidal asymmetries. The method intrinsically considers the effects of three-dimensional structures and of the shell gaps. Far from the gaps, experimental results are in good agreement with the diffusion time estimated with a simple cylindrical model that assumes a homogeneous wall. The method is also applied with non-standard configurations of the coil array, in order to mimic tokamak-relevant settings with a partial wall coverage and active coils of large toroidal extent. The comparison with the full coverage results shows good agreement if the effects of the relevant sidebands are considered.

Mathematical Modeling of Programmatic Requirements for Yaws Eradication

PubMed Central

Mitjà, Oriol; Fitzpatrick, Christopher; Asiedu, Kingsley; Solomon, Anthony W.; Mabey, David C.W.; Funk, Sebastian

2017-01-01

Yaws is targeted for eradication by 2020. The mainstay of the eradication strategy is mass treatment followed by case finding. Modeling has been used to inform programmatic requirements for other neglected tropical diseases and could provide insights into yaws eradication. We developed a model of yaws transmission varying the coverage and number of rounds of treatment. The estimated number of cases arising from an index case (basic reproduction number [R0]) ranged from 1.08 to 3.32. To have 80% probability of achieving eradication, 8 rounds of treatment with 80% coverage were required at low estimates of R0 (1.45). This requirement increased to 95% at high estimates of R0 (2.47). Extending the treatment interval to 12 months increased requirements at all estimates of R0. At high estimates of R0 with 12 monthly rounds of treatment, no combination of variables achieved eradication. Models should be used to guide the scale-up of yaws eradication. PMID:27983500

Combining GOES-16 Geostationary Lightning Mapper with the ground based Earth Networks Total Lightning Network

NASA Astrophysics Data System (ADS)

Stock, M.; Lapierre, J. L.; Zhu, Y.

2017-12-01

Recently, the Geostationary Lightning Mapper (GLM) began collecting optical data to locate lightning events and flashes over the North and South American continents. This new instrument promises uniformly high detection efficiency (DE) over its entire field of view, with location accuracy on the order of 10 km. In comparison, Earth Networks Total Lightning Networks (ENTLN) has a less uniform coverage, with higher DE in regions with dense sensor coverage, and lower DE with sparse sensor coverage. ENTLN also offers better location accuracy, lightning classification, and peak current estimation for their lightning locations. It is desirable to produce an integrated dataset, combining the strong points of GLM and ENTLN. The easiest way to achieve this is to simply match located lightning processes from each system using time and distance criteria. This simple method will be limited in scope by the uneven coverage of the ground based network. Instead, we will use GLM group locations to look up the electric field change data recorded by ground sensors near each GLM group, vastly increasing the coverage of the ground network. The ground waveforms can then be used for: improvements to differentiation between glint and lightning for GLM, higher precision lighting location, current estimation, and lightning process classification. Presented is an initial implementation of this type of integration using preliminary GLM data, and waveforms from ENTLN.

A New Method for Estimating the Coverage of Mass Vaccination Campaigns Against Poliomyelitis From Surveillance Data.

PubMed

O'Reilly, K M; Cori, A; Durry, E; Wadood, M Z; Bosan, A; Aylward, R B; Grassly, N C

2015-12-01

Mass vaccination campaigns with the oral poliovirus vaccine targeting children aged <5 years are a critical component of the global poliomyelitis eradication effort. Monitoring the coverage of these campaigns is essential to allow corrective action, but current approaches are limited by their cross-sectional nature, nonrandom sampling, reporting biases, and accessibility issues. We describe a new Bayesian framework using data augmentation and Markov chain Monte Carlo methods to estimate variation in vaccination coverage from children's vaccination histories investigated during surveillance for acute flaccid paralysis. We tested the method using simulated data with at least 200 cases and were able to detect undervaccinated groups if they exceeded 10% of all children and temporal changes in coverage of ±10% with greater than 90% sensitivity. Application of the method to data from Pakistan for 2010-2011 identified undervaccinated groups within the Balochistan/Federally Administered Tribal Areas and Khyber Pakhtunkhwa regions, as well as temporal changes in coverage. The sizes of these groups are consistent with the multiple challenges faced by the program in these regions as a result of conflict and insecurity. Application of this new method to routinely collected data can be a useful tool for identifying poorly performing areas and assisting in eradication efforts. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

US health policy and prescription drug coverage of FDA-approved medications for the treatment of obesity.

PubMed

Gomez, G; Stanford, F C

2018-03-01

Obesity is now the most prevalent chronic disease in the United States, which amounts to an estimated $147 billion in health care spending annually. The Affordable Care Act (ACA) enacted in 2010 included provisions for private and public health insurance plans that expanded coverage for lifestyle/behavior modification and bariatric surgery for the treatment of obesity. Pharmacotherapy, however, has not been included despite their evidence-based efficacy. We set out to investigate the coverage of Food and Drug Administration-approved medications for obesity within Medicare, Medicaid and ACA-established marketplace health insurance plans. We examined coverage for phentermine, diethylpropion, phendimetrazine, Benzphentamine, Lorcaserin, Phentermine/Topiramate (Qysmia), Liraglutide (Saxenda) and Buproprion/Naltrexone (Contrave) among Medicare, Medicaid and marketplace insurance plans in 34 states. Among 136 marketplace health insurance plans, 11% had some coverage for the specified drugs in only nine states. Medicare policy strictly excludes drug therapy for obesity. Only seven state Medicaid programs have drug coverage. Obesity requires an integrated approach to combat its public health threat. Broader coverage of pharmacotherapy can make a significant contribution to fighting this complex and chronic disease.

The Changing Dynamics Of US Health Insurance And Implications For The Future Of The Affordable Care Act.

PubMed

Graves, John A; Nikpay, Sayeh S

2017-02-01

The introduction of Medicaid expansions and state Marketplaces under the Affordable Care Act (ACA) have reduced the uninsurance rate to historic lows, changing the choices Americans make about coverage. In this article we shed light on these changing dynamics. We drew upon multistate transition models fit to nationally representative longitudinal data to estimate coverage transition probabilities between major insurance types in the years leading up to and including 2014. We found that the ACA's unprecedented coverage changes increased transitions to Medicaid and nongroup coverage among the uninsured, while strengthening the existing employer-sponsored insurance system and improving retention of public coverage. However, our results suggest possible weakness of state Marketplaces, since people gaining nongroup coverage were disproportionately older than other potential enrollees. We identified key opportunities for policy makers and insurers to improve underlying Marketplace risk pools by focusing on people transitioning from employer-sponsored coverage; these people are disproportionately younger and saw almost no change in their likelihood of becoming uninsured in 2014 compared to earlier years. Project HOPE—The People-to-People Health Foundation, Inc.

A Coalescent-Based Estimator of Admixture From DNA Sequences

PubMed Central

Wang, Jinliang

2006-01-01

A variety of estimators have been developed to use genetic marker information in inferring the admixture proportions (parental contributions) of a hybrid population. The majority of these estimators used allele frequency data, ignored molecular information that is available in markers such as microsatellites and DNA sequences, and assumed that mutations are absent since the admixture event. As a result, these estimators may fail to deliver an estimate or give rather poor estimates when admixture is ancient and thus mutations are not negligible. A previous molecular estimator based its inference of admixture proportions on the average coalescent times between pairs of genes taken from within and between populations. In this article I propose an estimator that considers the entire genealogy of all of the sampled genes and infers admixture proportions from the numbers of segregating sites in DNA sequence samples. By considering the genealogy of all sequences rather than pairs of sequences, this new estimator also allows the joint estimation of other interesting parameters in the admixture model, such as admixture time, divergence time, population size, and mutation rate. Comparative analyses of simulated data indicate that the new coalescent estimator generally yields better estimates of admixture proportions than the previous molecular estimator, especially when the parental populations are not highly differentiated. It also gives reasonably accurate estimates of other admixture parameters. A human mtDNA sequence data set was analyzed to demonstrate the method, and the analysis results are discussed and compared with those from previous studies. PMID:16624918

Reported community-level indoor residual spray coverage from two-stage cluster surveys in sub-Saharan Africa.

PubMed

Larsen, David A; Borrill, Lauren; Patel, Ryan; Fregosi, Lauren

2017-06-13

Malaria is an important cause of morbidity and mortality in malaria-endemic areas. Indoor residual spray is an effective intervention to control malaria, but high community-level coverage is needed to maximize its impact. Using thirty-four two-stage cluster surveys (e.g., demographic and health surveys) and lot quality assurance sampling, indoor residual spray was estimated at the community level (i.e. enumeration-area) across sub-Saharan Africa since 2010. For communities receiving indoor residual spray a logistic regression predicted whether community-level coverage exceeded 50% or not. Household-level coverage was equitable both in terms of wealth and urban/rural, with poorer and rural houses more likely to be sprayed than richer and urban houses. Coverage of indoor residual spray at the community level is poor across the continent, with 54% of communities receiving the intervention not reaching 50% coverage. Having >50% coverage at the community-level was not associated with increasing the number of houses sprayed in the country. Implementation and monitoring of indoor residual coverage at small geographical scales need to improve greatly to receive maximum benefit of the intervention.

Mathematical Methods for Studying DNA and Protein Interactions

NASA Astrophysics Data System (ADS)

LeGresley, Sarah

Deoxyribnucleic Acid (DNA) damage can lead to health related issues such as developmental disorders, aging, and cancer. It has been estimated that damage rates may be as high as 100,000 per cell per day. Because of the devastating effects that DNA damage can have, DNA repair mechanisms are of great interest yet are not completely understood. To gain a better understanding of possible DNA repair mechanisms, my dissertation focused on mathematical methods for understanding the interactions between DNA and proteins. I developed a damaged DNA model to estimate the probabilities of damaged DNA being located at specific positions. Experiments were then performed that suggested that the damaged DNA may be repositioned. These experimental results were consistent with the model's prediction that damaged DNA has preferred locations. To study how proteins might be moving along the DNA, I studied the use of the uniform motion "n-step" model. The n-step model has been used to determine the kinetics parameters (e.g. rates at which a protein moves along the DNA, how much energy is required to move a protein along a specified amount of DNA, etc.) of proteins moving along the DNA. Monte Carlo methods were used to simulate proteins moving with different types of non-uniform motion (e.g. backward, jumping, etc.) along the DNA. Estimates for the kinetics parameters in the n-step model were found by fitting of the Monte Carlo simulation data. Analysis indicated that non-uniform motion of the protein may lead to over or underestimation of the kinetic parameters of this n-step model.

[Influenza vaccination of hospital healthcare staff from the perspective of the employer: a positive balance].

PubMed

Hak, Eelko; Knol, Lisanne M; Wilschut, Jan C; Postma, Maarten J

2010-01-01

To assess the annual productivity loss among hospital healthcare workers attributable to influenza and to estimate the costs and economic benefits of a vaccination programme from the perspective of the the employer. Cost-benefit analysis. The percentage of work loss due to influenza was determined using monthly age and gender specific figures for productivity loss among healthcare workers of the University Medical Center Groningen (UMCG), the Netherlands over the period January 2006-June 2008. Influenza periods were determined on the basis of national surveillance data. The average increase in productivity loss in these periods was estimated by comparison with the periods outside influenza seasons. The direct costs of productivity loss from the perspective of the employer were estimated using the friction cost method. In the sensitivity analyses various modelling parameters were varied, such as the vaccination coverage. In the UMCG, with approximately 9,400 employees, the estimated annual costs associated with productivity loss due to influenza before the introduction of the yearly influenza vaccination program were € 675,242 or on average, € 72 per employee. The economic benefits of the current vaccination program with a vaccination coverage of 24% with a vaccine effectiveness of 71% were estimated at € 89,858 or € 10 per employee. The nett economic benefits of a vaccination program with a target vaccination coverage of 70% with a vaccine effectiveness of 71% were estimated at € 244,325 or € 26 per employee. This modelling study performed from the perspective of the employer showed that an annual influenza vaccination programme for hospital personnel can save costs.

Improving precipitation estimates over the western United States using GOES-R precipitation data

NASA Astrophysics Data System (ADS)

Karbalaee, N.; Kirstetter, P. E.; Gourley, J. J.

2017-12-01

Satellite remote sensing data with fine spatial and temporal resolution are widely used for precipitation estimation for different applications such as hydrological modeling, storm prediction, and flash flood monitoring. The Geostationary Operational Environmental Satellites-R series (GOES-R) is the next generation of environmental satellites that provides hydrologic, atmospheric, and climatic information every 30 seconds over the western hemisphere. The high-resolution and low-latency of GOES-R observations is essential for the monitoring and prediction of floods, specifically in the Western United States where the vantage point of space can complement the degraded weather radar coverage of the NEXRAD network. The GOES-R rainfall rate algorithm will yield deterministic quantitative precipitation estimates (QPE). Accounting for inherent uncertainties will further advance the GOES-R QPEs since with quantifiable error bars, the rainfall estimates can be more readily fused with ground radar products. On the ground, the high-resolution NEXRAD-based precipitation estimation from the Multi-Radar/Multi-Sensor (MRMS) system, which is now operational in the National Weather Service (NWS), is challenged due to a lack of suitable coverage of operational weather radars over complex terrain. Distribution of QPE uncertainties associated with the GOES-R deterministic retrievals are derived and analyzed using MRMS over regions with good radar coverage. They will be merged with MRMS-based probabilistic QPEs developed to advance multisensor QPE integration. This research aims at improving precipitation estimation over the CONUS by combining the observations from GOES-R and MRMS to provide consistent, accurate and fine resolution precipitation rates with uncertainties over the CONUS.

Duplicate Health Insurance Coverage: Determinants of Variation Across States

PubMed Central

Luft, Harold S.; Maerki, Susan C.

1982-01-01

Although it is recognized that many people have duplicate private health insurance coverage, either through separate purchase or as health benefits in multi-earner families, there has been little analysis of the factors determining duplicate coverage rates. A new data source, the Survey of Income and Education, offers a comparison with the only previous source of state level data, the estimates from the Health Insurance Association of America. The R2 between the two sets is only .3 and certain problems can be traced to the methodology underlying the HIAA figures. Using figures for gross and net coverage, the ratio of total policies to people with private coverage ranges from .94 in Utah to 1.53 in Illinois. Measures of industry distribution, per capita income and employment explain a large portion of the variance, but it appears that these factors operate in opposite directions for group and non-group policies. Similar sociodemographic variables also explain net coverage. These findings have substantial implications for research and the structuring of employee health benefits. PMID:10309638

Reporting of HIV-infected pregnant women: estimates from a Brazilian study.

PubMed

Domingues, Rosa Maria Soares Madeira; Saraceni, Valéria; Leal, Maria do Carmo

2018-01-01

To estimate the coverage of the reporting of cases of HIV-infected pregnant women, to estimate the increase in the coverage of the reporting with the routine search of data in other Brazilian health information systems, and to identify missed opportunities for identification of HIV-infected pregnant women in Brazilian maternity hospitals. This is a descriptive study on the linkage of Brazilian databases with primary data from the "Nascer no Brasil" study and secondary database collection from national health information systems. The "Nascer no Brasil" is a national-based study carried out in 2011-2012 with 23,894 pregnant women, which identified HIV-infected pregnant women using prenatal and medical records. We searched for cases of HIV-infected pregnant women identified in the "Nascer no Brasil" study in the Information System of Notifiable Diseases, the Control System for Laboratory Tests of the National CD4+/CD8+ Lymphocyte Count and HIV Viral Load Network, and the Logistics Control System for Medications. We used the OpenRecLink software for the linkage of databases. We estimated the notification coverage, with the respective confidence interval, of the evaluated Brazilian health information systems. We estimated the coverage of the reporting of HIV-infected pregnant women in the Information System of Notifiable Diseases as 57.1% (95%CI 42.9-70.2), and we located 89.3% of the HIV-infected pregnant women (95%CI 81.2-94.2) in some of the Brazilian health information systems researched. The search in other national health information systems would result in an increase of 57.1% of the reported cases. We identified no missed opportunities for the diagnosis of HIV+ in pregnant women in the maternity hospitals evaluated by the "Nascer no Brasil" study. The routine search for information in other Brazilian health information systems, a procedure carried out by the Ministry of Health for cases of AIDS in adults and children, should be adopted for cases of HIV in pregnancy.

The Effects of Cost Sharing on Adherence to Medications Prescribed for Concurrent Use: Do Definitions Matter?

PubMed

Sacks, Naomi C; Burgess, James F; Cabral, Howard J; McDonnell, Marie E; Pizer, Steven D

2015-08-01

Accurate estimates of the effects of cost sharing on adherence to medications prescribed for use together, also called concurrent adherence, are important for researchers, payers, and policymakers who want to reduce barriers to adherence for chronic condition patients prescribed multiple medications concurrently. But measure definition consensus is lacking, and the effects of different definitions on estimates of cost-related nonadherence are unevaluated. To (a) compare estimates of cost-related nonadherence using different measure definitions and (b) provide guidance for analyses of the effects of cost sharing on concurrent adherence. This is a retrospective cohort study of Medicare Part D beneficiaries aged 65 years and older who used multiple oral antidiabetics concurrently in 2008 and 2009. We compared patients with standard coverage, which contains cost-sharing requirements in deductible (100%), initial (25%), and coverage gap (100%) phases, to patients with a low-income subsidy (LIS) and minimal cost-sharing requirements. Data source was the IMS Health Longitudinal Prescription Database. Patients with standard coverage were propensity matched to controls with LIS coverage. Propensity score was developed using logistic regression to model likelihood of Part D standard enrollment, controlling for sociodemographic and health status characteristics. For analysis, 3 definitions were used for unadjusted and adjusted estimates of adherence: (1) patients adherent to All medications; (2) patients adherent on Average; and (3) patients adherent to Any medication. Analyses were conducted using the full study sample and then repeated in analytic subgroups where patients used (a) 1 or more costly branded oral antidiabetics or (b) inexpensive generics only. We identified 12,771 propensity matched patients with Medicare Part D standard (N = 6,298) or LIS (N = 6,473) coverage who used oral antidiabetics in 2 or more of the same classes in 2008 and 2009. In this sample, estimates of the effects of cost sharing on concurrent adherence varied by measure definition, coverage type, and proportion of patients using more costly branded drugs. Adherence rates ranged from 37% (All: standard patients using 1+ branded) to 97% (Any: LIS using generics only). In adjusted estimates, standard patients using branded drugs had 0.63 (95% CI = 0.57-0.70) and 0.70 (95% CI = 0.63-0.77) times the odds of concurrent adherence using All and Average definitions, respectively. The Any subgroup was not significant (OR = 0.89, 95% CI = 0.87-1.17). Estimates also varied in the full-study sample (All: OR = 0.79, 95% CI = 0.74-0.85; Average: OR = 0.83, 95% CI = 0.77-0.89) and generics-only subgroup, although cost-sharing effects were smaller. The Any subgroup generated no significant estimates. Different concurrent adherence measure definitions lead to markedly different findings of the effects of cost sharing on concurrent adherence, with All and Average subgroups sensitive to these effects. However, when more study patients use inexpensive generics, estimates of these effects on adherence to branded medications with higher cost-sharing requirements may be diluted. When selecting a measure definition, researchers, payers, and policy analysts should consider the range of medication prices patients face, use a measure sensitive to the effects of cost sharing on adherence, and perform subgroup analyses for patients prescribed more medications for which they must pay more, since these patients are most vulnerable to cost-related nonadherence.

Coverage percentage and raman measurement of cross-tile and scaffold cross-tile based DNA nanostructures.

PubMed

Gnapareddy, Bramaramba; Ahn, Sang Jung; Dugasani, Sreekantha Reddy; Kim, Jang Ah; Amin, Rashid; Mitta, Sekhar Babu; Vellampatti, Srivithya; Kim, Byeonghoon; Kulkarni, Atul; Kim, Taesung; Yun, Kyusik; LaBean, Thomas H; Park, Sung Ha

2015-11-01

We present two free-solution annealed DNA nanostructures consisting of either cross-tile CT1 or CT2. The proposed nanostructures exhibit two distinct structural morphologies, with one-dimensional (1D) nanotubes for CT1 and 2D nanolattices for CT2. When we perform mica-assisted growth annealing with CT1, a dramatic dimensional change occurs where the 1D nanotubes transform into 2D nanolattices due to the presence of the substrate. We assessed the coverage percentage of the 2D nanolattices grown on the mica substrate with CT1 and CT2 as a function of the concentration of the DNA monomer. Furthermore, we fabricated a scaffold cross-tile (SCT), which is a new design of a modified cross-tile that consists of four four-arm junctions with a square aspect ratio. For SCT, eight oligonucleotides are designed in such a way that adjacent strands with sticky ends can produce continuous arms in both the horizontal and vertical directions. The SCT was fabricated via free-solution annealing, and self-assembled SCT produces 2D nanolattices with periodic square cavities. All structures were observed via atomic force microscopy. Finally, we fabricated divalent nickel ion (Ni(2+))- and trivalent dysprosium ion (Dy(3+))-modified 2D nanolattices constructed with CT2 on a quartz substrate, and the ion coordinations were examined via Raman spectroscopy. Copyright © 2015 Elsevier B.V. All rights reserved.

Existing and emerging detection technologies for DNA (Deoxyribonucleic Acid) finger printing, sequencing, bio- and analytical chips: a multidisciplinary development unifying molecular biology, chemical and electronics engineering.

PubMed

Kumar Khanna, Vinod

2007-01-01

The current status and research trends of detection techniques for DNA-based analysis such as DNA finger printing, sequencing, biochips and allied fields are examined. An overview of main detectors is presented vis-à-vis these DNA operations. The biochip method is explained, the role of micro- and nanoelectronic technologies in biochip realization is highlighted, various optical and electrical detection principles employed in biochips are indicated, and the operational mechanisms of these detection devices are described. Although a diversity of biochips for diagnostic and therapeutic applications has been demonstrated in research laboratories worldwide, only some of these chips have entered the clinical market, and more chips are awaiting commercialization. The necessity of tagging is eliminated in refractive-index change based devices, but the basic flaw of indirect nature of most detection methodologies can only be overcome by generic and/or reagentless DNA sensors such as the conductance-based approach and the DNA-single electron transistor (DNA-SET) structure. Devices of the electrical detection-based category are expected to pave the pathway for the next-generation DNA chips. The review provides a comprehensive coverage of the detection technologies for DNA finger printing, sequencing and related techniques, encompassing a variety of methods from the primitive art to the state-of-the-art scenario as well as promising methods for the future.

Aquatic environmental DNA detects seasonal fish abundance and habitat preference in an urban estuary

PubMed Central

Soboleva, Lyubov; Charlop-Powers, Zachary

2017-01-01

The difficulty of censusing marine animal populations hampers effective ocean management. Analyzing water for DNA traces shed by organisms may aid assessment. Here we tested aquatic environmental DNA (eDNA) as an indicator of fish presence in the lower Hudson River estuary. A checklist of local marine fish and their relative abundance was prepared by compiling 12 traditional surveys conducted between 1988–2015. To improve eDNA identification success, 31 specimens representing 18 marine fish species were sequenced for two mitochondrial gene regions, boosting coverage of the 12S eDNA target sequence to 80% of local taxa. We collected 76 one-liter shoreline surface water samples at two contrasting estuary locations over six months beginning in January 2016. eDNA was amplified with vertebrate-specific 12S primers. Bioinformatic analysis of amplified DNA, using a reference library of GenBank and our newly generated 12S sequences, detected most (81%) locally abundant or common species and relatively few (23%) uncommon taxa, and corresponded to seasonal presence and habitat preference as determined by traditional surveys. Approximately 2% of fish reads were commonly consumed species that are rare or absent in local waters, consistent with wastewater input. Freshwater species were rarely detected despite Hudson River inflow. These results support further exploration and suggest eDNA will facilitate fine-scale geographic and temporal mapping of marine fish populations at relatively low cost. PMID:28403183

NSW annual immunisation coverage report, 2010.

PubMed

Hull, Brynley; Dey, Aditi; Campbell-Lloyd, Sue; Menzies, Robert I; McIntyre, Peter B

2011-11-01

This annual report, the second in the series, documents trends in immunisation coverage in NSW for children, adolescents and the elderly, to the end of 2010. Data from the Australian Childhood Immunisation Register, the NSW School Immunisation Program and the NSW Population Health Survey were used to calculate various measures of population coverage, coverage for Aboriginal children and vaccination timeliness for all children. Over 90% coverage has been reached for children at 12 and 24 months of age. For children at 5 years of age there was an improvement during 2010 in timeliness for vaccines due at 4 years and coverage almost reached 90%. Delayed receipt of vaccines is still an issue for Aboriginal children. For adolescents, there is good coverage for the first and second doses of human papillomavirus vaccine and the dose of diphtheria, tetanus and acellular pertussis. The pneumococcal vaccination rate in the elderly has been steadily rising, although it has remained lower than the influenza coverage estimates. Completion of the recommended immunisation schedule at the earliest appropriate age should be the next public health goal at both the state and local health district level. Official coverage assessments for 'fully immunised' should include the 7-valent pneumococcal conjugate and meningococcal C vaccines, and wider dissemination should be considered.

Extending Medicare coverage to medically necessary dental care.

PubMed

Patton, L L; White, B A; Field, M J

2001-09-01

Periodically, Congress considers expanding Medicare coverage to include some currently excluded health care services. In 1999 and 2000, an Institute of Medicine committee studied the issues related to coverage for certain services, including "medically necessary dental services." The committee conducted a literature search for dental care studies in five areas: head and neck cancer, leukemia, lymphoma, organ transplantation, and heart valve repair or replacement. The committee examined evidence to support Medicare coverage for dental services related to these conditions and estimated the cost to Medicare of such coverage. Evidence supported Medicare coverage for preventive dental care before jaw radiation therapy for head or neck cancer and coverage for treatment to prevent or eliminate acute oral infections for patients with leukemia before chemotherapy. Insufficient evidence supported dental coverage for patients with lymphoma or organ transplants and for patients who had undergone heart valve repair or replacement. The committee suggested that Congress update statutory language to permit Medicare coverage of effective dental services needed in conjunction with surgery, chemotherapy, radiation therapy or pharmacological treatment for life-threatening medical conditions. Dental care is important for members of all age groups. More direct, research-based evidence on the efficacy of medically necessary dental care is needed both to guide treatment and to support Medicare payment policy.

Value for money: protecting endangered species on Danish heathland.

PubMed

Strange, Niels; Jacobsen, Jette B; Thorsen, Bo J; Tarp, Peter

2007-11-01

Biodiversity policies in the European Union (EU) are mainly implemented through the Birds and Habitats Directives as well as the establishment of Natura 2000, a network of protected areas throughout the EU. Considerable resources must be allocated for fulfilling the Directives and the question of optimal allocation is as important as it is difficult. In general, economic evaluations of conservation targets at most consider the costs and seldom the welfare economic benefits. In the present study, we use welfare economic benefit estimates concerning the willingness-to-pay for preserving endangered species and for the aggregate area of heathland preserved in Denmark. Similarly, we obtain estimates of the welfare economic cost of habitat restoration and maintenance. Combining these welfare economic measures with expected species coverage, we are able to estimate the potential welfare economic contribution of a conservation network. We compare three simple nonprobabilistic strategies likely to be used in day-to-day policy implementation: i) a maximum selected area strategy, ii) a hotspot selection strategy, and iii) a minimizing cost strategy, and two more advanced and informed probabilistic strategies: i) a maximum expected coverage strategy and ii) a strategy for maximum expected welfare economic gain. We show that the welfare economic performance of the strategies differ considerably. The comparison between the expected coverage and expected welfare shows that for the case considered, one may identify an optimal protection level above which additional coverage only comes at increasing welfare economic loss.

MARTA: a suite of Java-based tools for assigning taxonomic status to DNA sequences.

PubMed

Horton, Matthew; Bodenhausen, Natacha; Bergelson, Joy

2010-02-15

We have created a suite of Java-based software to better provide taxonomic assignments to DNA sequences. We anticipate that the program will be useful for protistologists, virologists, mycologists and other microbial ecologists. The program relies on NCBI utilities including the BLAST software and Taxonomy database and is easily manipulated at the command-line to specify a BLAST candidate's query-coverage or percent identity requirements; other options include the ability to set minimal consensus requirements (%) for each of the eight major taxonomic ranks (Domain, Kingdom, Phylum, ...) and whether to consider lower scoring candidates when the top-hit lacks taxonomic classification.

Income, Poverty, and Health Insurance Coverage in the United States: 2012. Current Population Reports P60-245

ERIC Educational Resources Information Center

DeNavas-Walt, Carmen; Proctor, Bernadette D.; Smith, Jessica C.

2013-01-01

This report presents data on income, poverty, and health insurance coverage in the United States based on information collected in the 2013 and earlier Current Population Survey Annual Social and Economic Supplements (CPS ASEC) conducted by the U.S. Census Bureau. For most groups, the 2012 income, poverty, and health insurance estimates were not…

Disability, Health Insurance Coverage, and Utilization of Acute Health Services in the United States. Disability Statistics Report 4.

ERIC Educational Resources Information Center

LaPlante, Mitchell P.

This report uses data from the 1989 National Health Interview Survey to estimate health insurance coverage of children and nonelderly adults with disabilities and their utilization of physician and hospital care as a function of health insurance status. In part 1, national statistics on disability and insurance status are provided for different…

Balancing investments in Federally Qualified Health Centers and Medicaid for improved access and coverage in Pennsylvania.

PubMed

Griffin, Paul M; Lee, Hyunji; Scherrer, Christina; Swann, Julie L

2014-12-01

Two common health disparities in the US include a lack of access to care and a lack of insurance coverage. To help address these disparities, healthcare reform will provide $11B to expand Federally Qualified Health Centers (FQHCs) over the next 5 years. In 2014, Medicaid rules will be modified so that more people will become eligible. There are, however, important tradeoffs in the investment in these two programs. We find a balanced investment between FQHC expansion and relaxing Medicaid eligibility to improve both access (by increasing the number of FQHCs) and coverage (by FQHC and Medicaid expansion) for the state of Pennsylvania. The comparison is achieved by integrating multi-objective mathematical models with several public data sets that allow for specific estimations of healthcare need. Demand is estimated based on current access and coverage status in order to target groups to be considered preferentially. Results show that for Pennsylvania, FQHCs are more cost effective than Medicaid if we invest all of the resources in just one policy. However, we find a better investment point balancing those two policies. This point is approximately where the additional expenses incurred from relaxing Medicaid eligibility equals the investment in FQHC expansion.

Dental Use and Expenditures for Older Uninsured Americans: The Simulated Impact of Expanded Coverage

PubMed Central

Manski, Richard J; Moeller, John F; Chen, Haiyan; Schimmel, Jody; Pepper, John V; St Clair, Patricia A

2015-01-01

Objective To determine if providing dental insurance to older Americans would close the current gaps in dental use and expenditure between insured and uninsured older Americans. Data Sources/Study Setting We used data from the 2008 Health and Retirement Survey (HRS) supplemented by data from the 2006 Medical Expenditure Panel Survey (MEPS). Study Design We compared the simulated dental use and expenditures rates of newly insured persons against the corresponding rates for those previously insured. Data Collection/Extraction Methods The HRS is a nationally representative survey administered by the Institute for Social Research (ISR). The MEPS is a nationally representative household survey sponsored by the Agency for Healthcare Research and Quality (AHRQ). Principal Findings We found that expanding dental coverage to older uninsured Americans would close previous gaps in dental use and expense between uninsured and insured noninstitutionalized Americans 55 years and older. Conclusions Providing dental coverage to previously uninsured older adults would produce estimated monthly costs net of markups for administrative costs that comport closely to current market rates. Estimates also suggest that the total cost of providing dental coverage targeted specifically to nonusers of dental care may be less than similar costs for prior users. PMID:25040355

Integration, Validation, and Application of a PV Snow Coverage Model in SAM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryberg, David; Freeman, Janine

2015-09-01

Due to the increasing deployment of PV systems in snowy climates, there is significant interest in a method capable of estimating PV losses resulting from snow coverage that has been verified for a wide variety of system designs and locations. A scattering of independent snow coverage models have been developed over the last 15 years; however, there has been very little effort spent on verifying these models beyond the system design and location on which they were based. Moreover, none of the major PV modeling software products have incorporated any of these models into their workflow. In response to thismore » deficiency, we have integrated the methodology of the snow model developed in the paper by Marion et al. [1] into the National Renewable Energy Laboratory's (NREL) System Advisor Model (SAM). In this work we describe how the snow model is implemented in SAM and discuss our demonstration of the model's effectiveness at reducing error in annual estimations for two PV arrays. Following this, we use this new functionality in conjunction with a long term historical dataset to estimate average snow losses across the United States for a typical PV system design. The open availability of the snow loss estimation capability in SAM to the PV modeling community, coupled with our results of the nation-wide study, will better equip the industry to accurately estimate PV energy production in areas affected by snowfall.« less