37 research outputs found
Eliciting health state utilities for Dupuytren's contracture using a discrete choice experiment
Background and purpose An internet-based discrete choice
experiment (DCE) was conducted to elicit preferences for a wide
range of Dupuytren’s contracture (DC)-related health states. An
algorithm was subsequently developed to convert these preferences
into health state utilities that can be used to assess DC’s
impact on quality of life and the value of its treatments.
Methods Health state preferences for varying levels of DC
hand severity were elicited via an internet survey from a sample
of the UK adult population. Severity levels were deined using a
combination of contractures (0, 45, or 90 degrees) in 8 proximal
interphalangeal and metacarpophalangeal joints of the index,
middle, ring, and little ingers. Right-handed, left-handed, and
ambidextrous respondents indicated which hand was preferable
in each of the 10 randomly-selected hand-pairings comparing
different DC severity levels. For consistency across comparisons,
anatomically precise digital hand drawings were used. To anchor
preferences onto the traditional 0–1 utility scale used in health
economic evaluations, unaffected hands were assigned a utility
of 1.0 whereas the utility for a maximally affected hand (i.e., all
8 joints set at 90 degrees of contracture) was derived by asking
respondents to indicate what combination of attributes and levels
of the EQ-5D-5L proile most accurately relects the impact of
living with such hand. Conditional logistic models were used to
estimate indirect utilities, then rescaled to the anchor points on
the EQ-5D-5L.
Results Estimated utilities based on the responses of 1,745
qualiied respondents were 0.49, 0.57, and 0.63 for completely
affected dominant hands, non-dominant hands, or ambidextrous
hands, respectively. Utility for a dominant hand with 90-degree
contracture in t h e metacarpophalangeal joints of the ring and
little ingers was estimated to be 0.89. Separately, reducing the
contracture of metacarpophalangeal joint for a little inger from
50 to 12 degrees would improve utility by 0.02.
Interpretation DC is associated with substantial utility decrements.
The algorithms presented herein provide a robust and lexible
framework to assess utility for varying degrees of DC severity
The performance of deterministic and stochastic interest rate risk measures : Another Question of Dimensions?
The efficiency of traditional and stochastic interest rate risk measures is compared under one-, two-, and three-factor no-arbitrage Gauss-Markov term structure models, and for different immunization periods. The empirical analysis, run on the German Treasury bond market from January 2000 to December 2010, suggests that: i) Stochastic interest rate risk measures provide better portfolio immunization than the Fisher-Weil duration; and ii) The superiority of the stochastic risk measures is more evident for multi-factor models and for longer investment horizons. These findings are supported by a first-order stochastic dominance analysis, and are robust against yield curve estimation errors.info:eu-repo/semantics/publishedVersio
A highly mutagenised barley (cv. Golden Promise) TILLING population coupled with strategies for screening-by-sequencing
Background:We developed and characterised a highly mutagenised TILLING population of the barley (Hordeum vulgare) cultivar Golden Promise. Golden Promise is the 'reference' genotype for barley transformation and a primary objective of using this cultivar was to be able to genetically complement observed mutations directly in order to prove gene function. Importantly, a reference genome assembly of Golden Promise has also recently been developed. As our primary interest was to identify mutations in genes involved in meiosis and recombination, to characterise the population we focused on a set of 46 genes from the literature that are possible meiosis gene candidates. Results:Sequencing 20 plants from the population using whole exome capture revealed that the mutation density in this population is high (one mutation every 154Â kb), and consequently even in this small number of plants we identified several interesting mutations. We also recorded some issues with seed availability and germination. We subsequently designed and applied a simple two-dimensional pooling strategy to identify mutations in varying numbers of specific target genes by Illumina short read pooled-amplicon sequencing and subsequent deconvolution. In parallel we assembled a collection of semi-sterile mutants from the population and used a custom exome capture array targeting the 46 candidate meiotic genes to identify potentially causal mutations. Conclusions:We developed a highly mutagenised barley TILLING population in the transformation competent cultivar Golden Promise. We used novel and cost-efficient screening approaches to successfully identify a broad range of potentially deleterious variants that were subsequently validated by Sanger sequencing. These resources combined with a high-quality genome reference sequence opens new possibilities for efficient functional gene validation.Miriam Schreiber, Abdellah Barakate, Nicola Uzrek, Malcolm Macaulay, Adeline Sourdille, Jenny Morris, Pete E. Hedley, Luke Ramsay and Robbie Waug