Comparative analyses of multi-species sequences from targeted genomic regions

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.     

Predicting stock index volatility: can market volume help?

This paper explores a number of statistical models for predicting the daily stock return volatility of an aggregate of all stocks traded on the NYSE. An application of linear and non-linear Granger causality tests highlights evidence of bidirectional causality, although the relationship is stronger from volatility to volume than the other way around. The out-of-sample forecasting performance of various linear, GARCH, EGARCH, GJR and neural network models of volatility are evaluated and compared. The models are also augmented by the addition of a measure of lagged volume to form more general ex-ante forecasting models. The results indicate that augmenting models of volatility with measures of lagged volume leads only to very modest improvements, if any, in forecasting performance. © 1998 John Wiley & Sons, Ltd.     

Newly identified loci that influence lipid concentrations and risk of coronary artery disease

To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.     

Identification of ten loci associated with height highlights new biological pathways in human growth

Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for approximately 2% of the population variation in height. Individuals with < or =8 height-increasing alleles and > or =16 height-increasing alleles differ in height by approximately 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait.     

Evaluating organizations: A systems and contingency approach

It has become increasingly difficult to keep pace with the amount of information being generated about how to evaluate organizations. If it were not enough that the situation is made difficult by the sheer mass of material on evaluation, clarity is further hindered by many of the publications on the subject failing to make explicit the principles and assumptions upon which they are based. This was the situation confronting the authors when they began a national project with the National Association of Councils for Voluntary Service on the evaluation of the performance of Councils for Voluntary Service. In an attempt to bring some order to the field, this paper adopts a systems and contingency approach to elucidate the nature and practical usefulness of the different methods of evaluation. It first seeks, using some tools of Checkland's soft systems methodology, to present a systematic analysis of the subject of evaluation. Then, in the light of the analysis, an attempt is made to formulate a simple classification of approaches to evaluation which serves to match the different forms of evaluation to the contexts in which they are most appropriate for use.     

Total systems intervention: A research program

The development of TSI represents a real advance in management science in our view. Further developments are necessary however. This Research Note has outlined what we currently consider to be key issues in this development. We welcome other criticisms and suggestions. We invite you to join with us in this project.     

Assumptional analysis: An elucidation and appraisal for systems practitioners

The purpose of this paper is to review the ‘assumptional analysis’ methodology developed by R. O. Mason and I. I. Mitroff. The importance of this approach is that it was primarily constructed to deal with ill-structured problems at the strategic level in social systems. The 1980s has seen systems practitioners demonstrating an increased interest in exactly this type of problem. The principles and procedures of the approach are set out, its use in three organisations described, and an assessment of its potential contribution to systems practice provided.     

Population of households in England to 2021

This article outlines the methodology and results of the Department of the Environment, Transport and the Regions (DETR) 1996-based household projections for England, and its regions. It examines differences between this round of projections and the previous 1992-based round. The 1996-based projections indicate that between 1996 and 2021 a growth of 3.8 million households can be expected in England, if recent trends continue. Both the national and subnational methodology and results are covered.     

Insect communication: 'no entry' signal in ant foraging

Forager ants lay attractive trail pheromones to guide nestmates to food, but the effectiveness of foraging networks might be improved if pheromones could also be used to repel foragers from unrewarding routes. Here we present empirical evidence for such a negative trail pheromone, deployed by Pharaoh's ants (Monomorium pharaonis) as a 'no entry' signal to mark an unrewarding foraging path. This finding constitutes another example of the sophisticated control mechanisms used in self-organized ant colonies.