The Role of IL-25 in Colitis-Associated Colon Cancer and Pulmonary Inflammation

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

Finite mixture regression model with random effects: application to neonatal hospital length of stay

A two-component mixture regression model that allows simultaneously for heterogeneity and dependency among observations is proposed. By specifying random effects explicitly in the linear predictor of the mixture probability and the mixture components, parameter estimation is achieved by maximising the corresponding best linear unbiased prediction type log-likelihood. Approximate residual maximum likelihood estimates are obtained via an EM algorithm in the manner of generalised linear mixed model (GLMM). The method can be extended to a g-component mixture regression model with the component density from the exponential family, leading to the development of the class of finite mixture GLMM. For illustration, the method is applied to analyse neonatal length of stay (LOS). It is shown that identification of pertinent factors that influence hospital LOS can provide important information for health care planning and resource allocation. (C) 2002 Elsevier Science B.V. All rights reserved.

Modelling inpatient length of stay by a hierarchical mixture regression via the EM algorithm

The modelling of inpatient length of stay (LOS) has important implications in health care studies. Finite mixture distributions are usually used to model the heterogeneous LOS distribution, due to a certain proportion of patients sustaining-a longer stay. However, the morbidity data are collected from hospitals, observations clustered within the same hospital are often correlated. The generalized linear mixed model approach is adopted to accommodate the inherent correlation via unobservable random effects. An EM algorithm is developed to obtain residual maximum quasi-likelihood estimation. The proposed hierarchical mixture regression approach enables the identification and assessment of factors influencing the long-stay proportion and the LOS for the long-stay patient subgroup. A neonatal LOS data set is used for illustration, (C) 2003 Elsevier Science Ltd. All rights reserved.

Prospective study of men's psychological and decision-related adjustment after treatment for localized prostate cancer

Objectives. To undertake a prospective longitudinal study to assess psychological and decision-related distress after the diagnosis of localized prostate cancer. Methods. A total of I 11 men (93% response rate) with localized prostate cancer were recruited from outpatient urology clinics and urologists' private practices. More than one half (56%) elected to undergo radical prostatectomy, 19% underwent external beam radiotherapy, and 25% chose watchful waiting. Men completed self-report measures before treatment and 2 and 12 months after treatment. The measures used included the University of California, Los Angeles, Prostate Cancer Index, International Prostate Symptom Score, Impact of Events Scale, Constructed Meaning Scale, Satisfaction with Life Scale, Health Care Orientation subscale, and Decisional Conflict Scale. Results. No statistically significant differences were found by medical treatment group in the psychological and decision-related adjustment at baseline or with time. Men who were undecided about their treatment choice had greater decisional conflict and a more negative healthcare orientation, but were not more psychologically distressed, compared with men who had decided. At diagnosis, 63% of men had high decision-related distress, and this persisted for 42% of men 12 months after treatment, despite high satisfaction with their treatment choice. At diagnosis, low-to-moderate psychological distress was most common, with distress decreasing after treatment. The overall quality of life was similar to community norms. Conclusions. The results of our study indicated that men who were undecided about what treatment to receive experienced greater decision-related distress. The final treatment choice was not related to psychological distress about prostate cancer. Psychological and decision-related distress decreased with time, independent of treatment modality. Interventions should target decision-related distress for all men and in-depth psychological support for those who experience ongoing difficulties. (C) 2004 Elsevier Inc.

Alternatives to conventional vaccines - Mediators of innate immunity

Vaccines have been described as weapons of mass protection. The eradication of many diseases is testament to their utility and effectiveness. Nevertheless, many vaccine preventable diseases remain prevalent because of political and economic barriers. Additionally, the effects of immaturity and old age, therapies that incapacitate the adaptive immune system and the multitude of strategies evolved by pathogens to evade immediate or sustained recognition by the mammalian immune system are barriers to the effectiveness of existing vaccines or development of new vaccines. In the front line of defence against the pervasiness of infection are the elements of the innate immune system. Innate immunity is under studied and poorly appreciated. However, in the first days after entry of a pathogen into the body, our entire protective response is dependant upon the various elements of our innate immune repertoire. In spite of, its place as our initial defence against infection, attention is only now turning to strategies which enhance or supplement innate immunity. This review examines the need for and potential of innate immune therapies.

A prospective multicentre study of pharmacist initiated changes to drug therapy and patient management in acute care government funded hospitals

Aims To determine the cost savings of pharmacist initiated changes to hospitalized patients' drug therapy or management in eight major acute care government funded teaching hospitals in Australia. Methods This was a prospective study performed in eight hospitals examining resource implications of pharmacists' interventions assessed by an independent clinical panel. Pharmacists providing clinical services to inpatients recorded details of interventions, defined as any action that directly resulted in a change to patient management or therapy. An independent clinical review panel, convened at each participating centre, confirmed or rejected the clinical pharmacist's assessment of the impact on length of stay (LOS), readmission probability, medical procedures and laboratory monitoring and quantified the resultant changes, which were then costed. Results A total of 1399 interventions were documented. Eight hundred and thirty-five interventions impacted on drug costs alone. Five hundred and eleven interventions were evaluated by the independent panels with three quarters of these confirmed as having an impact on one or more of: length of stay, readmission probability, medical procedures or laboratory monitoring. There were 96 interventions deemed by the independent panels to have reduced LOS and 156 reduced the potential for readmission. The calculated savings was $263 221 for the eight hospitals during the period of the study. This included $150 307 for length of stay reduction, $111 848 for readmission reduction. Conclusions The annualized cost savings relating to length of stay, readmission, drugs, medical procedures and laboratory monitoring as a result of clinical pharmacist initiated changes to hospitalized patient management or therapy was $4 444 794 for eight major acute care government funded teaching hospitals in Australia.

Inhibition of interferon signaling by the New York 99 strain and Kunjin subtype of West Nile virus involves blockage of STAT1 and STAT2 activation by nonstructural proteins

The interferon (IFN) response is the first line of defense against viral infections, and the majority of viruses have developed different strategies to counteract IFN responses in order to ensure their survival in an infected host. In this study, the abilities to inhibit IFN signaling of two closely related West Nile viruses, the New York 99 strain (NY99) and Kunjin virus (KUN), strain MRM61C, were analyzed using reporter plasmid assays, as well as immunofluorescence and Western blot analyses. We have demonstrated that infections with both NY99 and KUN, as well as transient or stable transfections with their replicon RNAs, inhibited the signaling of both alpha/beta IFN (IFN-alpha/beta) and gamma IFN (IFN-gamma) by blocking the phosphorylation of STAT1 and its translocation to the nucleus. In addition, the phosphorylation of STAT2 and its translocation to the nucleus were also blocked by KUN, NY99, and their replicons in response to treatment with IFN-alpha. IFN-alpha signaling and STAT2 translocation to the nucleus was inhibited when the KUN nonstructural proteins NS2A, NS2B, NS3, NS4A, and NS4B, but not NS1 and NS5, were expressed individually from the pcDNA3 vector. The results clearly demonstrate that both NY99 and KUN inhibit IFN signaling by preventing STAT1 and STAT2 phosphorylation and identify nonstructural proteins. responsible for this inhibition.

The effect of depression on balance decline in mature women

Depression has been identified as a risk factor for falls, and a change in balance ability over time has yet to be investigated. This study aimed to identify if, over a 3-year period, balance ability changed in 26 women who were on medication for depression, compared to 26 non-depressed women. The two groups were matched for age, number of co-morbidities, activity level, medications, and height. All participants were simultaneously enrolled in a larger, longitudinal study of ageing. Balance measures included the Functional Reach (FR) test, Lateral Reach (LR) test, Step Test (ST), Timed Up and Go, and the Modified Clinical Test of Sensory Integration and Balance, Unilateral Stance (ULS) and Limit of Stability (LOS) laboratory tests. Results showed a significant difference between the groups on ST, right ULS (eyes closed) and forward end point excursion of the LOS. There was no difference in the number of falls between groups. Analysis of the depressed group alone showed that right FR declined significantly and left and right LR tended towards decline, but not differently between groups. There was no between-group differences for these measures. There was no significant decline in non-depressed women for any measurement. Depressed women have less ability to maintain their balance than non-depressed women, and should be encouraged to participate in appropriate activities known to improve or maintain balance.

Length of Stay, Discharge Destination, and Functional Improvement: Utility of the Australian National Subacute and Nonacute Patient Casemix Classification

Background and Purpose - Although implemented in 1998, no research has examined how well the Australian National Subacute and Nonacute Patient (AN-SNAP) Casemix Classification predicts length of stay (LOS), discharge destination, and functional improvement in public hospital stroke rehabilitation units in Australia. Methods - 406 consecutive admissions to 3 stroke rehabilitation units in Queensland, Australia were studied. Sociode-mographic, clinical, and functional data were collected. General linear modeling and logistic regression were used to assess the ability of AN-SNAP to predict outcomes. Results - AN-SNAP significantly predicted each outcome. There were clear relationships between the outcomes of longer LOS, poorer functional improvement and discharge into care, and the AN-SNAP classes that reflected poorer functional ability and older age. Other predictors included living situation, acute LOS, comorbidity, and stroke type. Conclusions - AN-SNAP is a consistent predictor of LOS, functional change and discharge destination, and has utility in assisting clinicians to set rehabilitation goals and plan discharge.

Finite deformation model of simple shear of fault with microrotations: apparent strain localisation and en-echelon fracture pattern

Strain localisation is a widespread phenomenon often observed in shear and compressive loading of geomaterials, for example, the fault gouge. It is believed that the main mechanisms of strain localisation are strain softening and mismatch between dilatancy and pressure sensitivity. Observations show that gouge deformation is accompanied by considerable rotations of grains. In our previous work as a model for gouge material, we proposed a continuum description for an assembly of particles of equal radius in which the particle rotation is treated as an independent degree of freedom. We showed that there exist critical values of the model parameters for which the displacement gradient exhibits a pronounced localisation at the mid-surface layers of the fault, even in the absence of inelasticity. Here, we generalise the model to the case of finite deformations characteristic for the gouge deformation. We derive objective constitutive relationships relating the Jaumann rates of stress and moment stress to the relative strain and curvature rates, respectively. The model suggests that the pattern of localisation remains the same as in the linear case. However, the presence of the Jaumann terms leads to the emergence of non-zero normal stresses acting along and perpendicular to the shear layer (with zero hydrostatic pressure), and localised along the mid-line of the gouge; these stress components are absent in the linear model of simple shear. These additional normal stresses, albeit small, cause a change in the direction in which the maximal normal stresses act and in which en-echelon fracturing is formed.

Effects of group status on responses to sustainable land use campaigns

A number of survey studies were conducted with landholders throughout Queensland to assess the effectiveness and perceived influence of campaigns promotng sustainable land use. While previous studies have addressed the role of group membership in persuasive communications, the current line of research extends this by focusing on the intergroup context, namely, the perceptions of group status. Across a range of samples it was found that landholders' perceptions of lower status in relation to urban people were associated with increased support for ingroup messages and decreased support for outgroup messages. These results are broadly consistent with research that suggests that threats to group identity (such as an infiuence attempt by a higher status group) will be responded to in a negative way and highlights the importance of considering relations between groups when attempting to change attiutudes.

A RELAÇÃO ENTRE CAPITAL HUMANO E CAPITAL PSICOLÓGICO

Os ativos intangíveis receberam atenção especial de estudiosos nos últimos anos, no contexto organizacional de gestão de pessoas, visto que foram desenvolvidas propostas teóricas para compreendê-los e mensurá-los. Ancorados nesta linha de investigação, encontram-se o capital humano e o capital psicológico. Enquanto o capital humano representa o que os trabalhadores sabem fazer, o capital psicológico compreende um estado mental positivo composto por autoeficácia, esperança, otimismo e resiliência. Este estudo teve, como objetivo geral, analisar as relações entre capital humano e capital psicológico. Tratou-se de um estudo quantitativo do qual participaram 60 trabalhadores, estudantes do último período do Curso de Administração, com idade média de 23,85 anos, sendo a maioria do sexo feminino, solteira e empregada. Os dados para o estudo foram coletados em salas de aula de uma universidade particular, situada na Região do Grande ABC, por meio de um instrumento auto aplicável, contendo uma medida intervalar de capital psicológico com 12 itens, validada para o Brasil, e uma de capital humano com seis questões, sendo duas para medir a dimensão experiência e quatro para aferir educação. Foi criado um banco eletrônico, o qual foi submetido a análises descritivas e de correlação (r de Pearson) por meio do SPSS, versão 19.0. Os resultados revelaram que os participantes detinham um capital humano representado por 4,38 anos médios de experiência de trabalho , e que a maioria (75%) havia revelado possuir no máximo cinco anos neste quesito. Quanto à dimensão educação do capital humano, a maioria (96,70%) não havia concluído nenhum curso de graduação, se dedicou entre 11 a 20 anos aos estudos (81,60%), não realizou intercâmbios de estudos (93%), enquanto 86,70% já incluíram, em seu currículo acadêmico, atividades complementares previstas no Plano Pedagógico do Curso de Administração que cursavam, bem como 73,30% realizaram entre um a três estágios curriculares. As análises indicaram um escore mediano de capital psicológico, acentuado pela dificuldade dos participantes para reconhecerem que estavam em uma fase de sucesso no trabalho e de conseguirem enxergar o lado brilhante das coisas relativas ao trabalho. Ao se investigar as relações entre o capital humano e capital psicológico não foram encontradas correlações significativas. Diante de tais resultados, pareceu provável que os participantes do estudo, por serem predominantemente jovens trabalhadores que ainda não concluíram um curso de graduação, embora tivessem em seu percurso de vida mais de 10 anos dedicados aos estudos e trabalhado por volta de cinco anos em média, ainda não reconheciam, em si, a presença de um consistente capital humano nem psicológico. A ausência de relação observada entre os dois ativos intangíveis preconizados por teóricos como importantes, para que o trabalhador pudesse contribuir com a empresa no alcance de suas metas, pareceu revelar que ainda eram necessários mais estudos e desenvolvimento de teorização, para sustentar não somente as hipóteses acerca de ativos intangíveis, como também permitir identificar a relação de dependência que pudesse existir entre as categorias de capital humano e psicológico.

The targeting of corticosteroids to inflamed tissues

In recent years, much interest has focused on the beneficial effects of administering potentially harmful therapeutic agents in drug carriers so as to reduce their toxic side effects. Rheumatoid arthritis is a chronic systemic disease with progressive destruction of the Joints and long term patient disability, Corticosteroids have been shown to retard the progression of Joint destruction but are limited in their use due to adverse side effects,This project, following the line of investigation started by other workers, was designed to study the use of microspheres to deliver corticosteroids to inflamed tissues by both the oral and intravenous routes. Hydrocortisone (HC)-loaded albumin microspheres were prepared by three different methods, by direct incorporation of HC within the particles, by indirect incorporation of HC by the enzymatic conversion of hydrocortisone-21-phosphate (H-21-P) to HC within the particles, and by the adsorption of HC onto the surface. HC was also loaded with PLA microspheres. The level of corticosteriod loading and in vitro release from microspheres was determined by HPLC analysis. A reversed-phase, ion-pairing HPLC method was developed to simultaneously measure both HC and H-21-P. The highest level of corticosteroid loading was achieved using the incorporation of H-21-P with enzymatic conversion to HC method. However, HPLC analysis showed only 5% of the incorporated steroid was HC. In vitro release rates of steroid from albumin microspheres showed >95% of incorporated steroid was released within 2 hours of dissolution. Increasing the protein:steroid ratio, and the temperature and duration of microsphere stabilization, had little effect on prolonging drug release. In vivo studies, using the carrageenan-induced rat hind-paw model of inflammation, indicated steroid-incorporated microspheres administered both orally and intraperitoneally were not therapeutically advantageous when compared to equivalent free steroid doses. The ability of orally and intravenously dosed [125I]~albumin microspheres (2.67 μm mean diameter) to accumulate in acutely and chronically inflamed tissues was investigated, The subcutaneous air-pouch was the model of inflammation used, with carrageenan as the inflammatory stimulus. Acute and chronic inflammation was shown to be consistently formed  in pouch tissues in terms of cell infiltration and fluid exudate formation in the pouch cavity. Albumin microspheres were shown to accumulate in the inflamed tissues and pouch fluids after both oral and intravenous administration. Preliminary, confirmatory studies using latex microspheres and quantitation by GPC analysis, also indicated microsphere accumulation in both acutely and chronically inflamed air-pouch tissues. tntl lUr"'poucbtis,sues; The results indicate the uptake and transfer of microspheres across the gastrointestinal tract into the circulation and their migration through disrupted endothelium and basement membranes at the inflamed sites. , .

A prediction of outcomes: a psychological investigation into cognitive and affective development within the framework of adult literacy provision

This investigation seeks to explore the hypothesis, derived from observation and practice, that there is a strong relationship between the development of literacy skills and the growth of confidence in adult literacy students. Implicit in the developmental approach is the notion of progression towards some cognitive goal. Such a goal necessitates the establishment of a base line of existing attainment, together with subsequent assessment so that progress and development can be measured. The study includes an evaluation of existing formal and informal methods of initial and subsequent assessment and diagnosis available at the time for Adult Literacy Scheme Co-ordinators. Underlying the funding by Cheshire County Council for the project is the assumption that the results will be available for all practitioners and that the tools of measurement may be used by other Adult Literacy Co-ordinators in the County. It is intended, therefore, that this research should result in practical outcomes in which methods of assessment will involve active participation by students as well as by tutors, becoming part of the learning process. It is hypothesised that this kind of co-operation could lead ultimately to self-directed learning and student-independence. For the purposes of this research, a balance is attempted in the use of assessment tools, between standardised tests and informal methods. The study provides facts about students! reading habits; as well as their reading levels, their spelling levels, their handwriting, their writing skills and their writing habits. The study seeks to show the students' feelings towards education, their educational attainments and the type of school which they attended. The study also attempts to come to some measurement of those aspects of student personality which relate to confidence, by means of tests and questionnaires. The study concludes with an examination of the link between cognitive and affective progress.

Theoretical perspectives in purchasing and supply chain management:an analysis of the literature

Purpose – This paper attempts to seek answers to four questions. Two of these questions have been borrowed (but adapted) from the work of Defee et al.: RQ1. To what extent is theory used in purchasing and supply chain management (P&SCM) research? RQ2. What are the prevalent theories to be found in P&SCM research? Following on from these questions an additional question is posed: RQ3. Are theory-based papers more highly cited than papers with no theoretical foundation? Finally, drawing on the work of Harland et al., the authors have added a fourth question: RQ4. To what extent does P&SCM meet the tests of coherence, breadth and depth, and quality necessary to make it a scientific discipline? Design/methodology/approach – A systematic literature review was conducted in accordance with the model outlined by Tranfield et al. for three journals within the field of “purchasing and supply chain management”. In total 1,113 articles were reviewed. In addition a citation analysis was completed covering 806 articles in total. Findings – The headline features from the results suggest that nearly a decade-and-a-half on from its development, the field still lacks coherence. There is the absence of theory in much of the work and although theory-based articles achieved on average a higher number of citations than non-theoretical papers, there is no obvious contender as an emergent paradigm for the discipline. Furthermore, it is evident that P&SCM does not meet Fabian's test necessary to make it a scientific discipline and is still some way from being a normal science. Research limitations/implications – This study would have benefited from the analysis of further journals, however the analysis of 1,113 articles from three leading journals in the field of P&SCM was deemed sufficient in scope. In addition, a further significant line of enquiry to follow is the rigour vs relevance debate. Practical implications – This article is of interest to both an academic and practitioner audience as it highlights the use theories in P&SCM. Furthermore, this article raises a number of important questions. Should research in this area draw more heavily on theory and if so which theories are appropriate? Social implications – The broader social implications relate to the discussion of how a scientific discipline develops and builds on the work of Fabian and Amundson. Originality/value – The data set for this study is significant and builds on a number of previous literature reviews. This review is both greater in scope than previous reviews and is broader in its subject focus. In addition, the citation analysis (not previously conducted in any of the reviews) and statistical test highlights that theory-based articles are more highly cited than non-theoretically based papers. This could indicate that researchers are attempting to build on one another's work.