Pedestrian accidents occurring on freeways: an investigation of causative factors, accident data collection and analysis. Volume II. Final report, phases III and IV.

Federal Highway Administration, Washington, D.C.

Safety status data collection methodology. Volume II - technical report on development and validation of evaluation procedures. Final report.

National Highway Traffic Safety Administration, Crash Avoidance Research Division, Washington, D.C.

Causative factors and countermeasures for rural and suburban pedestrian accidents: accident data collection and analysis - appendices. Phase I and II.

Federal Highway Administration, Washington, D.C.

Methods to Control for Bias in Observational Studies

Thesis (Master's)--University of Washington, 2016-06

Development and Application of Improvements to the Tile-based Fisher Ratio Method and Fundamental Instrument Considerations for Non-targeted Analysis using Two-dimensional Gas Chromatography

Thesis (Ph.D.)--University of Washington, 2016-06

CYP2D6: a global analysis of phenotypic and genotypic variation in search of radical cure of Plasmodium vivax malaria

Thesis (Master's)--University of Washington, 2016-06

Constructing internationally comparable real income aggregates by combining sparse benchmark data with annual national accounts data: A state-space approach

The importance of availability of comparable real income aggregates and their components to applied economic research is highlighted by the popularity of the Penn World Tables. Any methodology designed to achieve such a task requires the combination of data from several sources. The first is purchasing power parities (PPP) data available from the International Comparisons Project roughly every five years since the 1970s. The second is national level data on a range of variables that explain the behaviour of the ratio of PPP to market exchange rates. The final source of data is the national accounts publications of different countries which include estimates of gross domestic product and various price deflators. In this paper we present a method to construct a consistent panel of comparable real incomes by specifying the problem in state-space form. We present our completed work as well as briefly indicate our work in progress.

The use of multivariate methods in the identification of subtypes of Alzheimer's disease: a comparison of principal components and cluster analysis

Two contrasting multivariate statistical methods, viz., principal components analysis (PCA) and cluster analysis were applied to the study of neuropathological variations between cases of Alzheimer's disease (AD). To compare the two methods, 78 cases of AD were analyzed, each characterised by measurements of 47 neuropathological variables. Both methods of analysis revealed significant variations between AD cases. These variations were related primarily to differences in the distribution and abundance of senile plaques (SP) and neurofibrillary tangles (NFT) in the brain. Cluster analysis classified the majority of AD cases into five groups which could represent subtypes of AD. However, PCA suggested that variation between cases was more continuous with no distinct subtypes. Hence, PCA may be a more appropriate method than cluster analysis in the study of neuropathological variations between AD cases.

Statistical analysis in microbiology:statnotes

This book is aimed primarily at microbiologists who are undertaking research and who require a basic knowledge of statistics to analyse their experimental data. Computer software employing a wide range of data analysis methods is widely available to experimental scientists. The availability of this software, however, makes it essential that investigators understand the basic principles of statistics. Statistical analysis of data can be complex with many different methods of approach, each of which applies in a particular experimental circumstance. Hence, it is possible to apply an incorrect statistical method to data and to draw the wrong conclusions from an experiment. The purpose of this book, which has its origin in a series of articles published in the Society for Applied Microbiology journal ‘The Microbiologist’, is an attempt to present the basic logic of statistics as clearly as possible and therefore, to dispel some of the myths that often surround the subject. The 28 ‘Statnotes’ deal with various topics that are likely to be encountered, including the nature of variables, the comparison of means of two or more groups, non-parametric statistics, analysis of variance, correlating variables, and more complex methods such as multiple linear regression and principal components analysis. In each case, the relevant statistical method is illustrated with examples drawn from experiments in microbiological research. The text incorporates a glossary of the most commonly used statistical terms and there are two appendices designed to aid the investigator in the selection of the most appropriate test.

House building productivity : a study of labour requirements on Scottish house building sites using activity sampling methods

This study is concerned with labour productivity in traditional house building in Scotland. Productivity is a measure of the effective use of resources and provides vital benefits that can be combined in a number of ways. The introduction gives the background to two Scottish house building sites (Blantyre and Greenfield) that were surveyed by the Building Research Establishment (BEE) activity sampling method to provide the data for the study. The study had two main objectives; (1) summary data analysis in average manhours per house between all the houses on the site, and (2) detailed data analysis in average manhours for each house block on the site. The introduction also provides a literature review related to the objectives. The method is outlined in Chapter 2, the sites are discussed in Chapter 3, and Chapter 4 covers the method application on each site and a method development made in the study. The summary data analysis (Chapter 5) compares Blantyre and Greenfield, and two previous BEE surveys in England. The main detailed data analysis consisted of three forms, (Chapters 6, 7 and 8) each applied to a set of operations. The three forms of analysis were variations in average manhours per house for each house block on the site compared with; (1) block construction order, (2) average number of separate visits per house made by operatives to each block to complete an operation, and (3) average number of different operatives per house employed on an operation in each block. Three miscellaneous items of detail data analysis are discussed in Chapter 9. The conclusions to the whole study state that considerable variations in manhours for repeated operations were discovered, that the numbers of visits by operatives to complete operations were large and that the numbers of different operatives employed in some operations were a factor related to productivity. A critique of the activity sampling method suggests that the data produced is reliable in summary form and can give a good context for more detailed data collection. For future work, this could take the form of selected operations, with the context of an activity sampling survey, that wuld be intensively surveyed by other methods.

Transfer of patients from health care centres to special care services:analysis of travel distances in Nordic countries

Objectives: This paper highlights the importance of analysing patient transportation in Nordic circumpolar areas. The research questions we asked are as follows: How many Finnish patients have been transferred to special care intra-country and inter-country in 2009? Does it make any difference to health care policymakers if patients are transferred inter-country? Study design: We analysed the differences in distances from health care centres to special care services within Finland, Sweden and Norway and considered the health care policy implica tions. Methods: An analysis of the time required to drive between service providers using the "Google distance meter" (http://maps.google.com/); conducting interviews with key Finnish stakeholders; and undertaking a quantitative analyses of referral data from the Lapland Hospital District. Results: Finnish patients are generally not transferred for health care services across national borders even if the distances are shorter. Conclusion: Finnish patients have limited access to health care services in circumpolar are as across the Nordic countries for 2 reasons. First, health professionals in Norway and Sweden do not speak Finnish, which presents a language problem. Second, The Social Insurance Institution of Finland does not cover the expenditures of travel or the costs of medicine. In addition, it seems that in circumpolar areas the density of Finnish service providers is greater than Swedish ones, causing many Swedish citizens to transfer to Finnish health care providers every year. However, future research is needed to determine the precise reasons for this.

Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The cytotoxic effects of 6-mercaptopurine (6-MP) were found to be due to drug-derived intracellular metabolites (mainly 6-thioguanine nucleotides and to some extent 6-methylmercaptopurine nucleotides) rather than the drug itself. • Current empirical dosing methods for oral 6-MP result in highly variable drug and metabolite concentrations and hence variability in treatment outcome. WHAT THIS STUDY ADDS • The first population pharmacokinetic model has been developed for 6-MP active metabolites in paediatric patients with acute lymphoblastic leukaemia and the potential demographic and genetically controlled factors that could lead to interpatient pharmacokinetic variability among this population have been assessed. • The model shows a large reduction in interindividual variability of pharmacokinetic parameters when body surface area and thiopurine methyltransferase polymorphism are incorporated into the model as covariates. • The developed model offers a more rational dosing approach for 6-MP than the traditional empirical method (based on body surface area) through combining it with pharmacogenetically guided dosing based on thiopurine methyltransferase genotype. AIMS - To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites. METHODS - Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m−2 day−1). All patients were genotyped for polymorphisms in three enzymes involved in 6-MP metabolism. Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites. RESULTS - The developed model revealed considerable interindividual variability (IIV) in the clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-mMPNs)]. Body surface area explained a significant part of 6-TGNs clearance IIV when incorporated in the model (IIV reduced from 69.9 to 29.3%). The most influential covariate examined, however, was thiopurine methyltransferase (TPMT) genotype, which resulted in the greatest reduction in the model's objective function (P < 0.005) when incorporated as a covariate affecting the fractional metabolic transformation of 6-MP into 6-TGNs. The other genetic covariates tested were not statistically significant and therefore were not included in the final model. CONCLUSIONS - The developed pharmacokinetic model (if successful at external validation) would offer a more rational dosing approach for 6-MP than the traditional empirical method since it combines the current practice of using body surface area in 6-MP dosing with a pharmacogenetically guided dosing based on TPMT genotype.

Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder:protocol for a systematic review and meta-analysis

INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

Oxidiative lipidomics coming of age:advances in analysis of oxidized phospholipids in physiology and pathology

Significance: Oxidized phospholipids are now well-recognized as markers of biological oxidative stress and bioactive molecules with both pro-inflammatory and anti-inflammatory effects. While analytical methods continue to be developed for studies of generic lipid oxidation, mass spectrometry (MS) has underpinned the advances in knowledge of specific oxidized phospholipids by allowing their identification and characterization, and is responsible for the expansion of oxidative lipidomics. Recent Advances: Studies of oxidized phospholipids in biological samples, both from animal models and clinical samples, have been facilitated by the recent improvements in MS, especially targeted routines that depend on the fragmentation pattern of the parent molecular ion and improved resolution and mass accuracy. MS can be used to identify selectively individual compounds or groups of compounds with common features, which greatly improves the sensitivity and specificity of detection. Application of these methods have enabled important advances in understanding the mechanisms of inflammatory diseases such as atherosclerosis, steatohepatitis, leprosy and cystic fibrosis, and offer potential for developing biomarkers of molecular aspects of the diseases. Critical Issues and Future Directions: The future in this field will depend on development of improved MS technologies, such as ion mobility, novel enrichment methods and databases and software for data analysis, owing to the very large amount of data generated in these experiments. Imaging of oxidized phospholipids in tissue MS is an additional exciting direction emerging that can be expected to advance understanding of physiology and disease.

Application of Artificial Intelligence Methods to Computer Design of Inorganic Compounds

In this paper the main problems for computer design of materials, which would have predefined properties, with the use of artificial intelligence methods are presented. The DB on inorganic compound properties and the system of DBs on materials for electronics with completely assessed information: phase diagram DB of material systems with semiconducting phases and DB on acousto-optical, electro-optical, and nonlinear optical properties are considered. These DBs are a source of information for data analysis. Using the DBs and artificial intelligence methods we have predicted thousands of new compounds in ternary, quaternary and more complicated chemical systems and estimated some of their properties (crystal structure type, melting point, homogeneity region etc.). The comparison of our predictions with experimental data, obtained later, showed that the average reliability of predicted inorganic compounds exceeds 80%. The perspectives of computational material design with the use of artificial intelligence methods are considered.