215 research outputs found
RadarâSounding Characterization of the Subglacial Groundwater Table Beneath Hiawatha Glacier, Greenland
Radar-sounding surveys associated with the discovery of a large impact crater beneath Hiawatha Glacier, Greenland, revealed bright, flat subglacial reflections hypothesized to originate from a subglacial groundwater table. We test this hypothesis using radiometric and hydrologic analysis of those radar data. The dielectric loss between the reflection from the top of the basal layer and subglacial reflection and their reflectivity difference represent dual constraints upon the complex permittivity of the basal material. Either ice-cemented debris or fractured, well-drained bedrock explain the basal layer's radiometric properties. The subglacial reflector's geometry is parallel to isopotential hydraulic head contours, located 7.5â15.3 m below the interface, and 11 ± 7 dB brighter than the iceâbasal layer reflection. We conclude that this subglacial reflection is a groundwater table and that its detection was enabled by the wide bandwidth of the radar system and unusual geologic setting, suggesting a path for future direct radar detection of subglacial groundwater elsewhere
Estimates of array and pool-construction variance for planning efficient DNA-pooling genome wide association studies
<p>Abstract</p> <p>Background</p> <p>Until recently, genome-wide association studies (GWAS) have been restricted to research groups with the budget necessary to genotype hundreds, if not thousands, of samples. Replacing individual genotyping with genotyping of DNA pools in Phase I of a GWAS has proven successful, and dramatically altered the financial feasibility of this approach. When conducting a pool-based GWAS, how well SNP allele frequency is estimated from a DNA pool will influence a study's power to detect associations. Here we address how to control the variance in allele frequency estimation when DNAs are pooled, and how to plan and conduct the most efficient well-powered pool-based GWAS.</p> <p>Methods</p> <p>By examining the variation in allele frequency estimation on SNP arrays between and within DNA pools we determine how array variance [var(e<sub>array</sub>)] and pool-construction variance [var(e<sub>construction</sub>)] contribute to the total variance of allele frequency estimation. This information is useful in deciding whether replicate arrays or replicate pools are most useful in reducing variance. Our analysis is based on 27 DNA pools ranging in size from 74 to 446 individual samples, genotyped on a collective total of 128 Illumina beadarrays: 24 1M-Single, 32 1M-Duo, and 72 660-Quad.</p> <p>Results</p> <p>For all three Illumina SNP array types our estimates of var(e<sub>array</sub>) were similar, between 3-4 Ă 10<sup>-4 </sup>for normalized data. Var(e<sub>construction</sub>) accounted for between 20-40% of pooling variance across 27 pools in normalized data.</p> <p>Conclusions</p> <p>We conclude that relative to var(e<sub>array</sub>), var(e<sub>construction</sub>) is of less importance in reducing the variance in allele frequency estimation from DNA pools; however, our data suggests that on average it may be more important than previously thought. We have prepared a simple online tool, PoolingPlanner (available at <url>http://www.kchew.ca/PoolingPlanner/</url>), which calculates the effective sample size (ESS) of a DNA pool given a range of replicate array values. ESS can be used in a power calculator to perform pool-adjusted calculations. This allows one to quickly calculate the loss of power associated with a pooling experiment to make an informed decision on whether a pool-based GWAS is worth pursuing.</p
Presymptomatic risk assessment for chronic non-communicable diseases
The prevalence of common chronic non-communicable diseases (CNCDs) far
overshadows the prevalence of both monogenic and infectious diseases combined.
All CNCDs, also called complex genetic diseases, have a heritable genetic
component that can be used for pre-symptomatic risk assessment. Common single
nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome
currently account for a non-trivial portion of the germ-line genetic risk and
we will likely continue to identify the remaining missing heritability in the
form of rare variants, copy number variants and epigenetic modifications. Here,
we describe a novel measure for calculating the lifetime risk of a disease,
called the genetic composite index (GCI), and demonstrate its predictive value
as a clinical classifier. The GCI only considers summary statistics of the
effects of genetic variation and hence does not require the results of
large-scale studies simultaneously assessing multiple risk factors. Combining
GCI scores with environmental risk information provides an additional tool for
clinical decision-making. The GCI can be populated with heritable risk
information of any type, and thus represents a framework for CNCD
pre-symptomatic risk assessment that can be populated as additional risk
information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the
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Human blood PIG-A mutation and micronucleated reticulocyte flow cytometric assays: Method optimization and evaluation of intra- and inter-subject variation.
We previously described flow cytometry-based methods for scoring the incidence of micronucleated reticulocytes (MN-RET) and PIG-A mutant phenotype reticulocytes (MUT RET) in rodent and human blood samples. The current report describes important methodological improvements for human blood analyses, including immunomagnetic enrichment of CD71-positive reticulocytes prior to MN-RET scoring, and procedures for storing frozen blood for later PIG-A analysis. Technical replicate variability in MN-RET and MUT RET frequencies based on blood specimens from 14 subjects, intra-subject variability based on serial blood draws from 6 subjects, and inter-subject variation based on up to 344 subjects age 0 to 73âyears were quantified. Inter-subject variation explained most of the variability observed for both endpoints (â„â77%), with much lower intra-subject and technical replicate variability. The relatively large degree of inter-subject variation is apparent from mean and standard deviation values for MN-RET (0.15 ±â0.10%) and MUT RET (4.7 ±â5.0 per million, after omission of two extreme outliers). The influences of age and sex on inter-subject variation were investigated, and neither factor affected MN-RET whereas both influenced MUT RET frequency. The lowest MUT RET values were observed for subjects <â11âyears old, and males had moderately higher frequencies than females. These results indicate that MN-RET and MUT RET are automation-compatible biomarkers of genotoxicity that bridge species of toxicological interest to include human populations. These data will be useful for appropriately designing future human studies that include these biomarkers of genotoxicity, and highlight the need for additional work aimed at identifying the sources of inter-individual variability reported herein
Dynamic early identification of hip replacement implants with high revision rates. Study based on the NJR data from UK during 2004-2012
BACKGROUND: Hip replacement and hip resurfacing are common surgical procedures with an estimated risk of revision of 4% over 10 year period. Approximately 58% of hip replacements will last 25 years. Some implants have higher revision rates and early identification of poorly performing hip replacement implant brands and cup/head brand combinations is vital. AIMS: Development of a dynamic monitoring method for the revision rates of hip implants. METHODS: Data on the outcomes following the hip replacement surgery between 2004 and 2012 was obtained from the National Joint Register (NJR) in the UK. A novel dynamic algorithm based on the CUmulative SUM (CUSUM) methodology with adjustment for casemix and random frailty for an operating unit was developed and implemented to monitor the revision rates over time. The Benjamini-Hochberg FDR method was used to adjust for multiple testing of numerous hip replacement implant brands and cup/ head combinations at each time point. RESULTS: Three poorly performing cup brands and two cup/ head brand combinations have been detected. Wright Medical UK Ltd Conserve Plus Resurfacing Cup (cup o), DePuy ASR Resurfacing Cup (cup e), and Endo Plus (UK) Limited EP-Fit Plus Polyethylene cup (cup g) showed stable multiple alarms over the period of a year or longer. An addition of a random frailty term did not change the list of underperforming components. The model with added random effect was more conservative, showing less and more delayed alarms. CONCLUSIONS: Our new algorithm is an efficient method for early detection of poorly performing components in hip replacement surgery. It can also be used for similar tasks of dynamic quality monitoring in healthcare
Socio-demographic factors and edentulism: the Nigerian experience
BACKGROUND: The rate of total edentulism is said to be increasing in developing countries and this had been attributed mainly to the high prevalence of periodontal diseases and caries. Several reports have shown that non-disease factors such as attitude, behavior, dental attendance, characteristics of health care systems and socio-demographic factors play important roles in the aetiopathogenesis of edentulism. The aim of this study was to assess the relationship between socio-demographic factors and edentulism. METHODS: A total of 152 patients made up of 80 (52.6%) males and 72 (47.4%) females who presented in two prosthetic clinics located in an urban and a rural area were included in the study. The relationship between gender, age, socio-economic status and edentulism in this study population was established. RESULTS: No significant relationship between gender and denture demand was noted in the study. The demand for complete dentures increased with age while the demand for removable partial dentures also increased with age until the 3(rd )decade and then started to decline. A significant relationship was found between denture demand and the level of education with a higher demand in lower educational groups (p < 0.001). In addition, the lower socio-economic group had a higher demand more for prostheses than the higher group. CONCLUSIONS: The findings in this study revealed a significant relationship between socio-demographic variables and edentulism with age, educational level and socio-economic status playing vital roles in edentulism and denture demand
Asteroseismology and Interferometry
Asteroseismology provides us with a unique opportunity to improve our
understanding of stellar structure and evolution. Recent developments,
including the first systematic studies of solar-like pulsators, have boosted
the impact of this field of research within Astrophysics and have led to a
significant increase in the size of the research community. In the present
paper we start by reviewing the basic observational and theoretical properties
of classical and solar-like pulsators and present results from some of the most
recent and outstanding studies of these stars. We centre our review on those
classes of pulsators for which interferometric studies are expected to provide
a significant input. We discuss current limitations to asteroseismic studies,
including difficulties in mode identification and in the accurate determination
of global parameters of pulsating stars, and, after a brief review of those
aspects of interferometry that are most relevant in this context, anticipate
how interferometric observations may contribute to overcome these limitations.
Moreover, we present results of recent pilot studies of pulsating stars
involving both asteroseismic and interferometric constraints and look into the
future, summarizing ongoing efforts concerning the development of future
instruments and satellite missions which are expected to have an impact in this
field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume
14, Issue 3-4, pp. 217-36
Selecting Forecasting Methods
I examined six ways of selecting forecasting methods: Convenience, âwhatâs easy,â is inexpensive, but risky. Market popularity, âwhat others do,â sounds appealing but is unlikely to be of value because popularity and success may not be related and because it overlooks some methods. Structured judgment, âwhat experts advise,â which is to rate methods against prespecified criteria, is promising. Statistical criteria, âwhat should work,â are widely used and valuable, but risky if applied narrowly. Relative track records, âwhat has worked in this situation,â are expensive because they depend on conducting evaluation studies. Guidelines from prior research, âwhat works in this type of situation,â relies on published research and offers a low-cost, effective approach to selection. Using a systematic review of prior research, I developed a flow chart to guide forecasters in selecting among ten forecasting methods. Some key findings: Given enough data, quantitative methods are more accurate than judgmental methods. When large changes are expected, causal methods are more accurate than naive methods. Simple methods are preferable to complex methods; they are easier to understand, less expensive, and seldom less accurate. To select a judgmental method, determine whether there are large changes, frequent forecasts, conflicts among decision makers, and policy considerations. To select a quantitative method, consider the level of knowledge about relationships, the amount of change involved, the type of data, the need for policy analysis, and the extent of domain knowledge. When selection is difficult, combine forecasts from different methods
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Management and resistance in the digital newsroom
What happens when there is conflict between the profit motivations of a news outlet and the professional values of its journalists? Questions of managerial influence and journalistic autonomy have interested media scholars from the seminal work of Warren Breed onwards. However, there have only been a handful of studies since the introduction of audience metrics which, this research suggests, allow managers to more efficiently monitor and discipline their journalists. This article presents an ethnographic case study of a Reuters newswire bureau during a time of conflict between the management and journalists. The article outlines the strategies that management used to incentivize their journalists to change their reporting priorities. These included the strategic dissemination of audience metrics and praise, and the hiring and promotion of âappropriateâ journalists to positions of influence. These interventions changed who was considered a âgood journalistâ at the newswire, disrupting existing hierarchies, and eventually changing the culture of the newsroom. The article draws on the insights of Pierre Bourdieuâs field theory to help explain how managerial power operates, and the role that individual journalists play producing and reinforcing newsroom norms
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