Applying quantitative methods in the assessment of outcomes of pharmacotherapy of psoriasis

Healthcare providers and policy makers are faced with an ever-increasing number of medical publications. Searching for relevant information and keeping up to date with new research findings remains a constant challenge. It has been widely acknowledged that narrative reviews of the literature are susceptible to several types of bias and a systematic approach may protect against these biases. The aim of this thesis was to apply quantitative methods in the assessment of outcomes of topical therapies for psoriasis. In particular, to systematically examine the comparative efficacy, tolerability and cost-effectiveness of topical calcipotriol in the treatment of mild-to-moderate psoriasis. Over the years, a wide range of techniques have been used to evaluate the severity of psoriasis and the outcomes from treatment. This lack of standardisation complicates the direct comparison of results and ultimately the pooling of outcomes from different clinical trials. There is a clear requirement for more comprehensive tools for measuring drug efficacy and disease severity in psoriasis. Ideally, the outcome measures need to be simple, relevant, practical, and widely applicable, and the instruments should be reliable, valid and responsive. The results of the meta-analysis reported herein show that calcipotriol is an effective antipsoriatic agent. In the short-tenn, the pooled data found calcipotriol to be more effective than calcitriol, tacalcitol, coal tar and short-contact dithranol. Only potent corticosteroids appeared to have comparable efficacy, with less short-term side-effects. Potent corticosteroids also added to the antipsoriatic effect of calcipotriol, and appeared to suppress the occurrence of calcipotriol-induced irritation. There was insufficient evidence to support any large effects in favour of improvements in efficacy when calcipotriol is used in combination with systemic therapies in patients with severe psoriasis. However, there was a total absence of long-term morbidity data on the effectiveness of any of the interventions studied. Decision analysis showed that, from the perspective of the NHS as payer, the relatively small differences in efficacy between calcipotriol and short-contact dithranol lead to large differences in the direct cost of treating patients with mildto-moderate plaque psoriasis. Further research is needed to examine the clinical and economic issues affecting patients under treatment for psoriasis in the UK. In particular, the maintenance value and cost/benefit ratio for the various treatment strategies, and the assessment of patient's preferences has not yet been adequately addressed for this chronic recurring disease.

Quantitative methods in neuropathology

The last decade has seen a considerable increase in the application of quantitative methods in the study of histological sections of brain tissue and especially in the study of neurodegenerative disease. These disorders are characterised by the deposition and aggregation of abnormal or misfolded proteins in the form of extracellular protein deposits such as senile plaques (SP) and intracellular inclusions such as neurofibrillary tangles (NFT). Quantification of brain lesions and studying the relationships between lesions and normal anatomical features of the brain, including neurons, glial cells, and blood vessels, has become an important method of elucidating disease pathogenesis. This review describes methods for quantifying the abundance of a histological feature such as density, frequency, and 'load' and the sampling methods by which quantitative measures can be obtained including plot/quadrat sampling, transect sampling, and the point-quarter method. In addition, methods for determining the spatial pattern of a histological feature, i.e., whether the feature is distributed at random, regularly, or is aggregated into clusters, are described. These methods include the use of the Poisson and binomial distributions, pattern analysis by regression, Fourier analysis, and methods based on mapped point patterns. Finally, the statistical methods available for studying the degree of spatial correlation between pathological lesions and neurons, glial cells, and blood vessels are described.

Sociolinguistics:quantitative methods

Variationist sociolinguistics was one of the first branches of linguistics to adopt a quantitative approach to data analysis (e.g., Fischer, 1958; Labov, 1963, 1966, 1969; Wolfram, 1969).

Verstehen, was zählt. Ein Forschungsbericht über quantitative Arbeitsformen im Linguistik- und Deutsch-als-Fremdsprache-Unterricht in Großbritannien

UK schools and universities are trying to remedy a nationally recognized skills shortage in quantitative methods among graduates. This article describes and analyses a research project in German Studies funded by the Economic and Social Research Council (ESRC) aimed at addressing the issue. The interdisciplinary pilot project introduced quantitative methods into undergraduate curricula not only in Linguistics, but also in German Studies.

Quantifying the pathology of neurodegenerative disorders:Quantitative measurements, sampling strategies and data analysis

The use of quantitative methods has become increasingly important in the study of neurodegenerative disease. Disorders such as Alzheimer's disease (AD) are characterized by the formation of discrete, microscopic, pathological lesions which play an important role in pathological diagnosis. This article reviews the advantages and limitations of the different methods of quantifying the abundance of pathological lesions in histological sections, including estimates of density, frequency, coverage, and the use of semiquantitative scores. The major sampling methods by which these quantitative measures can be obtained from histological sections, including plot or quadrat sampling, transect sampling, and point-quarter sampling, are also described. In addition, the data analysis methods commonly used to analyse quantitative data in neuropathology, including analyses of variance (ANOVA) and principal components analysis (PCA), are discussed. These methods are illustrated with reference to particular problems in the pathological diagnosis of AD and dementia with Lewy bodies (DLB).

Quantitative neuropathology:data collection and statistical analysis

The use of quantitative methods has become increasingly important in the study of neuropathology and especially in neurodegenerative disease. Disorders such as Alzheimer's disease (AD) and the frontotemporal dementias (FTD) are characterized by the formation of discrete, microscopic, pathological lesions which play an important role in pathological diagnosis. This chapter reviews the advantages and limitations of the different methods of quantifying pathological lesions in histological sections including estimates of density, frequency, coverage, and the use of semi-quantitative scores. The sampling strategies by which these quantitative measures can be obtained from histological sections, including plot or quadrat sampling, transect sampling, and point-quarter sampling, are described. In addition, data analysis methods commonly used to analysis quantitative data in neuropathology, including analysis of variance (ANOVA), polynomial curve fitting, multiple regression, classification trees, and principal components analysis (PCA), are discussed. These methods are illustrated with reference to quantitative studies of a variety of neurodegenerative disorders.

Laminar distribution of the pathological changes in sporadic frontotemporal lobar degeneration with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy:a quantitative study using polynomial curve fitting

Aims: Previous data suggest heterogeneity in laminar distribution of the pathology in the molecular disorder frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy (FTLD-TDP). To study this heterogeneity, we quantified the changes in density across the cortical laminae of neuronal cytoplasmic inclusions, glial inclusions, neuronal intranuclear inclusions, dystrophic neurites, surviving neurones, abnormally enlarged neurones, and vacuoles in regions of the frontal and temporal lobe. Methods: Changes in density of histological features across cortical gyri were studied in 10 sporadic cases of FTLD-TDP using quantitative methods and polynomial curve fitting. Results: Our data suggest that laminar neuropathology in sporadic FTLD-TDP is highly variable. Most commonly, neuronal cytoplasmic inclusions, dystrophic neurites and vacuolation were abundant in the upper laminae and glial inclusions, neuronal intranuclear inclusions, abnormally enlarged neurones, and glial cell nuclei in the lower laminae. TDP-43-immunoreactive inclusions affected more of the cortical profile in longer duration cases; their distribution varied with disease subtype, but was unrelated to Braak tangle score. Different TDP-43-immunoreactive inclusions were not spatially correlated. Conclusions: Laminar distribution of pathological features in 10 sporadic cases of FTLD-TDP is heterogeneous and may be accounted for, in part, by disease subtype and disease duration. In addition, the feedforward and feedback cortico-cortical connections may be compromised in FTLD-TDP. © 2012 The Authors. Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society.

Chronic illness in non-heterosexual contexts: towards a critical LGBTQ health psychology

In this thesis, I contribute to the expansion of lesbian, gay, bisexual, trans and queer (LGBTQ) psychology by examining chronic illness within non-heterosexual contexts. Chronic illness, beyond the confines of HIV/AIDS, has been a neglected topic in LGBTQ psychology and sexual identity is often overlooked within health psychology. When the health of lesbian, gay and bisexual (LGB) people has been considered there has been an over-reliance on quantitative methods and comparative approaches which seek to compare LGB people?s health to their heterosexual counterparts. In contrast, I adopt a critical perspective and qualitative methods to explore LGBTQ health. My research brings together ideas from LGBTQ psychology and critical health psychology to explore non-heterosexuals? experiences of chronic illness and the discursive contexts within which LGB people live with chronic health conditions. I also highlight the heteronormativity which pervades academic health psychology as well as the „lay? health literature. The research presented in this thesis draws on three different sources of qualitative data: a qualitative online questionnaire (n=190), an online discussion within a newsgroup for people with diabetes, and semi-structured interviews with 20 LGB people with diabetes. These data are analysed using critical realist forms of thematic analysis and discourse analysis. In the first analytic chapter (Chapter 3), I report the perspectives of LGB people living with many different chronic illnesses and how they felt their sexuality shapes their experiences of illness. In Chapter 4, I examine heterosexism within an online discussion and consider the ways in which sexuality is constructed as (ir)relevant to a diabetes support forum. In Chapter 5, I analyse LGB people?s talk about the support family and partners provide in relation to their diabetes and how they negotiate wider discourses of gender, sexuality and individualism. In Chapter 6 I explore how diabetes intersects with gay and bisexual men?s sex lives. In the concluding chapter, I discuss the contributions of my research for a critical LGBTQ health psychology and identify some possible areas for future research.

Chemical kinetic investigation of a commercial batch reactor process

The aim of this investigation was to study the chemical reactions occurring during the batchwise production of a butylated melamine-formaldehyde resin, in order to optimise the efficiency and economics of the batch processes. The batch process models are largely empirical in nature as the reaction mechanism is unknown. The process chemistry and the commercial manufacturing method are described. A small scale system was established in glass and the ability to produce laboratory resins with the required quality was demonstrated, simulating the full scale plant. During further experiments the chemical reactions of methylolation, condensation and butylation were studied. The important process stages were identified and studied separately. The effects of variation of certain process parameters on the chemical reactions were also studied. A published model of methylolation was modified and used to simulate the methylolation stage. A major result of this project was the development of an indirect method for studying the condensation and butylation reactions occurring during the dehydration and acid reaction stages, as direct quantitative methods were not available. A mass balance method was devised for this purpose and used to collect experimental data. The reaction scheme was verified using this data. The reactions stages were simulated using an empirical model. This has revealed new information regarding the mechanism and kinetics of the reactions. Laboratory results were shown to be comparable with plant scale results. This work has improved the understanding of the batch process, which can be used to improve product consistency. Future work has been identified and recommended to produce an optimum process and plant design to reduce the batch time.

Schoolgirls in a rural context

It is proposed that, for rural secondary schoolgirls, school is a site of contestation. Rural girls attempt to `use' school as a means of resisting traditional patriarchal definitions of a `woman's place'. In their efforts, the girls are thwarted by aspects of the school itself, the behaviour and attitudes of the boys in school, and also the `careers advice' which they receive. It is argued that the girls perceive school as being of greater importance to them than is the case for the boys, and that these gender differentiated perceptions are related to the `social' lives of the girls and boys, and also to their future employment prospects. Unlike the boys, the girls experience considerable restrictions concerning these two areas. This theory was grounded in an ethnographic study which was conducted in and around a village in a rural county in England. As well as developing the theory through ethnography, the thesis contains tests of certain hypotheses generated by the theory. These hypotheses relate to the gender differentiated perspectives of secondary school pupils with regard to the areas of school itself, life outside school, and expectations for the future. The quantitative methods used to test these hypotheses confirm that there is a tendency for girls to be more positively orientated to school than the boys; to feel less able to engage in preferred activities outside school time than the boys, and also to be more willing to move away from the area than the boys. For comparative purposes these hypotheses were tested in two other rural locations and the results indicate the need for further research of a quantitative kind into the context of girls' schooling in such locations. A critical review of literature is presented, as is a detailed discussion of the research process itself.

R.A. Armstrong

Richard Armstrong was educated at King’s College London (1968-1971) and subsequently at St. Catherine’s College Oxford (1972-1976). His early research involved the application of statistical methods to problems in botany and ecology. For the last 34 years, he has been a lecturer in Botany, Microbiology, Ecology, Neuroscience, and Optometry at the University of Aston. His current research interests include the application of quantitative methods to the study of neuropathology of neurodegenerative diseases with special reference to vision and the visual system.

How green is green? A framework for environmental performance assessment in operations

This paper presents a framework based upon a relationship between environmental benefits and the investments and costs needed to implement and run company operations. As the results of environmental management become more evident it is proposed that the benefits rather than the environmental impacts are measured in the analysis of environmental performance. Four categories, or stages, are defined in this paper: “creative-green”, “expensive-green”, “inefficient-green or beginner”, and finally, the “complacent” stage. The paper describes the characteristics of each category and provides examples of indicators that could be used to measure environmental benefits. Qualitative and quantitative methods are necessary to classify companies according to the framework. It is believed that this paper can assist companies and public organisations to assess operations and projects considering their level of sustainability. The proposed framework can impact FDI and environmental policies in the public arena, and foster innovation on environmental practices within the private sector.

Proteomics in vaccinology and immunobiology:an informatics perspective of the immunone

The postgenomic era, as manifest, inter alia, by proteomics, offers unparalleled opportunities for the efficient discovery of safe, efficacious, and novel subunit vaccines targeting a tranche of modern major diseases. A negative corollary of this opportunity is the risk of becoming overwhelmed by this embarrassment of riches. Informatics techniques, working to address issues of both data management and through prediction to shortcut the experimental process, can be of enormous benefit in leveraging the proteomic revolution.In this disquisition, we evaluate proteomic approaches to the discovery of subunit vaccines, focussing on viral, bacterial, fungal, and parasite systems. We also adumbrate the impact that proteomic analysis of host-pathogen interactions can have. Finally, we review relevant methods to the prediction of immunome, with special emphasis on quantitative methods, and the subcellular localization of proteins within bacteria.

Advances in characterisation, calibration and data processing speed of optical coherence tomography systems

This thesis describes advances in the characterisation, calibration and data processing of optical coherence tomography (OCT) systems. Femtosecond (fs) laser inscription was used for producing OCT-phantoms. Transparent materials are generally inert to infra-red radiations, but with fs lasers material modification occurs via non-linear processes when the highly focused light source interacts with the materials. This modification is confined to the focal volume and is highly reproducible. In order to select the best inscription parameters, combination of different inscription parameters were tested, using three fs laser systems, with different operating properties, on a variety of materials. This facilitated the understanding of the key characteristics of the produced structures with the aim of producing viable OCT-phantoms. Finally, OCT-phantoms were successfully designed and fabricated in fused silica. The use of these phantoms to characterise many properties (resolution, distortion, sensitivity decay, scan linearity) of an OCT system was demonstrated. Quantitative methods were developed to support the characterisation of an OCT system collecting images from phantoms and also to improve the quality of the OCT images. Characterisation methods include the measurement of the spatially variant resolution (point spread function (PSF) and modulation transfer function (MTF)), sensitivity and distortion. Processing of OCT data is a computer intensive process. Standard central processing unit (CPU) based processing might take several minutes to a few hours to process acquired data, thus data processing is a significant bottleneck. An alternative choice is to use expensive hardware-based processing such as field programmable gate arrays (FPGAs). However, recently graphics processing unit (GPU) based data processing methods have been developed to minimize this data processing and rendering time. These processing techniques include standard-processing methods which includes a set of algorithms to process the raw data (interference) obtained by the detector and generate A-scans. The work presented here describes accelerated data processing and post processing techniques for OCT systems. The GPU based processing developed, during the PhD, was later implemented into a custom built Fourier domain optical coherence tomography (FD-OCT) system. This system currently processes and renders data in real time. Processing throughput of this system is currently limited by the camera capture rate. OCTphantoms have been heavily used for the qualitative characterization and adjustment/ fine tuning of the operating conditions of OCT system. Currently, investigations are under way to characterize OCT systems using our phantoms. The work presented in this thesis demonstrate several novel techniques of fabricating OCT-phantoms and accelerating OCT data processing using GPUs. In the process of developing phantoms and quantitative methods, a thorough understanding and practical knowledge of OCT and fs laser processing systems was developed. This understanding leads to several novel pieces of research that are not only relevant to OCT but have broader importance. For example, extensive understanding of the properties of fs inscribed structures will be useful in other photonic application such as making of phase mask, wave guides and microfluidic channels. Acceleration of data processing with GPUs is also useful in other fields.

From icon to naturalised icon:a linguistic analysis of media representations of the BP Deepwater Horizon crisis

This research explores how news media reports construct representations of a business crisis through language. In an innovative approach to dealing with the vast pool of potentially relevant texts, media texts concerning the BP Deepwater Horizon oil spill are gathered from three different time points: immediately after the explosion in 2010, one year later in 2011 and again in 2012. The three sets of 'BP texts' are investigated using discourse analysis and semi-quantitative methods within a semiotic framework that gives an account of language at the semiotic levels of sign, code, mythical meaning and ideology. The research finds in the texts three discourses of representation concerning the crisis that show a movement from the ostensibly representational to the symbolic and conventional: a discourse of 'objective factuality', a discourse of 'positioning' and a discourse of 'redeployment'. This progression can be shown to have useful parallels with Peirce's sign classes of Icon, Index and Symbol, with their implied movement from a clear motivation by the Object (in this case the disaster events), to an arbitrary, socially-agreed connection. However, the naturalisation of signs, whereby ideologies are encoded in ways of speaking and writing that present them as 'taken for granted' is at its most complete when it is least discernible. The findings suggest that media coverage is likely to move on from symbolic representation to a new kind of iconicity, through a fourth discourse of 'naturalisation'. Here the representation turns back towards ostensible factuality or iconicity, to become the 'naturalised icon'. This work adds to the study of media representation a heuristic for understanding how the meaning-making of a news story progresses. It offers a detailed account of what the stages of this progression 'look like' linguistically, and suggests scope for future research into both language characteristics of phases and different news-reported phenomena.