A multiple account framework for cost-benefit analysis

The paper presents a spreadsheet-based multiple account framework for cost-benefit analysis which incorporates all the usual concerns of cost-benefit analysts such as shadow-pricing to account for market failure. distribution of net benefits. sensitivity and risk analysis, cost of public funds, and environmental effects. The approach is generalizable to a wide range of projects and situations and offers a number of advantages to both analysts and decision-makers, including transparency, a check on internal consistency, and a detailed summary of project net benefits disaggregated by stakeholder group. Of particular importance is the ease with which this framework allows for a project to be evaluated from alternative decision-making perspectives and under alternative policy scenarios where the trade-offs among the project's stakeholders can readily be identified and quantified. (C) 2004 Elsevier Ltd. All rights reserved.

Use of the EM algorithm to detect QTL affecting multiple-traits in an across half-sib family analysis

QTL detection experiments in livestock species commonly use the half-sib design. Each male is mated to a number of females, each female producing a limited number of progeny. Analysis consists of attempting to detect associations between phenotype and genotype measured on the progeny. When family sizes are limiting experimenters may wish to incorporate as much information as possible into a single analysis. However, combining information across sires is problematic because of incomplete linkage disequilibrium between the markers and the QTL in the population. This study describes formulae for obtaining MLEs via the expectation maximization (EM) algorithm for use in a multiple-trait, multiple-family analysis. A model specifying a QTL with only two alleles, and a common within sire error variance is assumed. Compared to single-family analyses, power can be improved up to fourfold with multi-family analyses. The accuracy and precision of QTL location estimates are also substantially improved. With small family sizes, the multi-family, multi-trait analyses reduce substantially, but not totally remove, biases in QTL effect estimates. In situations where multiple QTL alleles are segregating the multi-family analysis will average out the effects of the different QTL alleles.

A polytope DNA vaccine elicits multiple effector and memory CTL responses and protects against human papillomavirus 16 E7-expressing tumour

Vaccine-induced CD8 T cells directed to tumourspecific antigens are recognised as important components of protective and therapeutic immunity against tumours. Where tumour antigens have pathogenic potential or where immunogenic epitopes are lost from tumours, development of subunit vaccines consisting of multiple individual epitopes is an attractive alternative to immunising with whole tumour antigen. In the present study we investigate the efficacy of two DNA-based multiepitope('polytope') vaccines containing murine (H-2(b)) and human (HLA-A* 0201)-restricted epitopes of the E7 oncoprotein of human papillomavirus type 16, in eliciting tumour-protective cytotoxic T-lymphocyte (CTL) responses. We show that the first of these polytopes elicited powerful effector CTL responses ( measured by IFN-gamma ELISpot) and long-lived memory CTL responses ( measured by functional CTL assay and tetramers) in immunised mice. The responses could be boosted by immunisation with a recombinant vaccinia virus expressing the polytope. Responses induced by immunisation with polytope DNA alone partially protected against infection with recombinant vaccinia virus expressing the polytope. Complete protection was afforded against challenge with an E7-expressing tumour, and reduced growth of nascent tumours was observed. A second polytope differing in the exact composition and order of CTL epitopes, and lacking an inserted endoplasmic reticulum targeting sequence and T-helper epitope, induced much poorer CTL responses and failed to protect against tumour challenge. These observations indicate the validity of a DNA polytope vaccine approach to human papillomavirus E7 - associated carcinoma, and underscore the importance of design in polytope vaccine construction.

How an enzyme answers. multiple-choice questions

Acetohydroxyacid synthase (AHAS) is the first common enzyme in the pathway for the biosynthesis of branched-chain amino acids. Interest in the enzyme has escalated over the past 20 years since it was discovered that AHAS is the target of the sulfonylurea and imidazolinone herbicides. However, several questions regarding the reaction mechanism have remained unanswered, particularly the way in which AHAS I chooses' its second substrate. A new method for the detection of reaction intermediates enables calculation of the microscopic rate constants required to explain this phenomenon.

Molecular characterization and cancer risk associated with BRCA1 and BRCA2 splice site variants identified in multiple-case breast cancer families

Genetic screening of women from multiple-case breast cancer families and other research-based endeavors have identified an extensive collection of germline variations of BRCA1 and BRCA2 that can be classified as deleterious and have clinical relevance. For some variants, such as those in the conserved intronic splice site regions which are highly likely to alter splicing, it is not possible to classify them based on the identified DNA sequence variation alone. We studied 11 multiple-case breast cancer families carrying seven distinct splice site region genetic alterations in BRCA1 or BRCA2 (BRCA1, c.IVS6-2delA, c.IVS9-2A>C, c.IVS4-1G>T, c.IVS20+1G>A and BRCA2, c.IVS17-1G>C, c.IVS20+1G>A, c.IVS7-1G>A) and applied SpliceSiteFinder to predict possible changes in efficiency of splice donor and acceptor sites, characterized the transcripts, and estimated the average age-specific cumulative risk (penetrance) using a modified segregation analysis. SpliceSiteFinder predicted and we identified transcipts that illustrated that all variants caused exon skipping, and all but two led to frameshifts. The risks of breast cancer to age 70 yrs, averaged over all variants, over BRCA1 variants alone, and over BRCA2 variants alone, were 73% (95% confidence interval 47-93), 64% (95%CI 28-96) and 79% (95%CI 48-98) respectively (all P

A spatial explanation for synchrony biases in perceptual grouping: Consequences for the temporal-binding hypothesis

If two images are shown in rapid sequential order, they are perceived as a single, fused image. Despite this, recent studies have revealed that fundamental perceptual processes are influenced by extremely brief temporal offsets in stimulus presentation. Some researchers have suggested that this is due to the action of a cortical temporal-binding mechanism, which would serve to keep multiple mental representations of one object distinct from those of other objects. There is now gathering evidence that these studies should be reassessed. This article describes evidence for sensitivity to fixational eye and head movements, which provides a purely spatial explanation for the earlier results. Taken in conjunction with other studies, the work serves to undermine the current body of behavioral evidence for a temporal-binding mechanism.

Testing multiple mapping conditioning mixing for Monte Carlo probability density function simulations

Mitarai [Phys. Fluids 17, 047101 (2005)] compared turbulent combustion models against homogeneous direct numerical simulations with extinction/recognition phenomena. The recently suggested multiple mapping conditioning (MMC) was not considered and is simulated here for the same case with favorable results. Implementation issues crucial for successful MMC simulations are also discussed.

On multiple solutions of the exterior neumann problem involving critical sobolev exponent

In this paper we consider the exterior Neumann problem involving a critical Sobolev exponent. We establish the existence of two solutions having a prescribed limit at infinity.

Lessons from the National Mental Health Integration Program

Three projects were funded under the national Mental Health Integration Program (MHIP) in 1999, each of which employed a different model aimed at improving linkages between disparate parts of the mental health system. A national evaluation framework guided local evaluations of these projects, and this paper presents a synthesis of the findings. For providers, the projects improved working relationships, created learning opportunities and increased referral and shared care opportunities. For consumers and carers, the projects resulted in a greater range of options and increased continuity of care. For the wider system, the projects achieved significant structural and cultural change. Cost-wise, there were no increases in expenditure, and even some reductions. Many of the lessons from the projects (and their evaluations) may be generalised to other mental health settings and beyond.

The role of orthographic-motor integration in the production of creative and well-structured written text for students in secondary school

There is a strong relationship between orthographic-motor integration related to handwriting and students' ability to produce creative and well-structured written text. This relationship is thought to be due to the cognitive load which results when attention is required by writers to write letters and words on the page. Lack of automaticity in orthographic-motor integration means that writers do not have sufficient cognitive resources to accomplish the more demanding aspects of text production such as ideation, text monitoring, and pragmatic awareness. A systematic handwriting program can significantly improve the quality of written text by young children experiencing problems with orthographic-motor integration. This study investigated the effectiveness of a handwriting program in remediating older students' problems in orthographic-motor integration and consequently enhancing their written language skills. Two groups of students in Grades 8 and 9 were provided with either practice in handwriting or daily completion of a written journal. There were no differences between the two groups at pre-test. However, at post-test, the handwriting group had significantly higher scores in orthographic-motor integration as well as for the length and quality of the text they wrote.

Pseudomonas aeruginosa fimL regulates multiple virulence functions by intersecting with Vfr-modulated pathways

Virulence of Pseudomonas aeruginosa involves the co-ordinate expression of a range of factors including type IV pili (tfp), the type III secretion system (TTSS) and quorum sensing. Tfp are required for twitching motility, efficient biofilm formation, and for adhesion and type III secretion (TTS)-mediated damage to mammalian cells. We describe a novel gene (fimL) that is required for tfp biogenesis and function, for TTS and for normal biofilm development in P. aeruginosa. The predicted product of fimL is homologous to the N-terminal domain of ChpA, except that its putative histidine and threonine phosphotransfer sites have been replaced with glutamine. fimL mutants resemble vfr mutants in many aspects including increased autolysis, reduced levels of surface-assembled tfp and diminished production of type III secreted effectors. Expression of vfr in trans can complement fimL mutants. vfr transcription and production is reduced in fimL mutants whereas cAMP levels are unaffected. Deletion and insertion mutants of fimL frequently revert to wild-type phenotypes suggesting that an extragenic suppressor mutation is able to overcome the loss of fimL. vfr transcription and production, as well as cAMP levels, are elevated in these revertants, while Pseudomonas quinolone signal (PQS) production is reduced. These results suggest that the site(s) of spontaneous mutation is in a gene(s) which lies upstream of vfr transcription, cAMP, production, and PQS synthesis. Our studies indicate that Vfr and FimL are components of intersecting pathways that control twitching motility, TTSS and autolysis in P. aeruginosa.