Making Rasch decisions: The use of Rasch analysis in the construction of preference based health related quality of life instruments

Objective: To set out the methodological process for using Rasch analysis alongside traditional psychometric methods in the development of a health state classification that is amenable to valuation. Methods: The overactive bladder questionnaire is used to illustrate a four step process for deriving a reduced health state classification from an existing nonpreference based health related quality of life instrument. Step I excludes items that do not meet the initial validation process and step II uses criteria based on Rasch analysis and psychometric testing to select the final items for the health state classification. In step III, item levels are examined and Rasch analysis is used to explore the possibility of reducing the number of item levels. Step IV repeats steps I to III on alternative data sets in order to validate the selection of items for the health state classification. Conclusions: The techniques described enable the construction of a health state classification amenable for valuation exercises that will allow the derivation of preference weights. Thus, the health related quality of life of patients with conditions, like overactive bladder, can be valued and quality adjustment weights such as quality adjusted life years derived

Making Rasch decisions: The use of Rasch analysis in the construction of preference based health related quality of life instruments

Objective: To set out the methodological process for using Rasch analysis alongside traditional psychometric methods in the development of a health state classification that is amenable to valuation. Methods: The overactive bladder questionnaire is used to illustrate a four step process for deriving a reduced health state classification from an existing nonpreference based health related quality of life instrument. Step I excludes items that do not meet the initial validation process and step II uses criteria based on Rasch analysis and psychometric testing to select the final items for the health state classification. In step III, item levels are examined and Rasch analysis is used to explore the possibility of reducing the number of item levels. Step IV repeats steps I to III on alternative data sets in order to validate the selection of items for the health state classification. Conclusions: The techniques described enable the construction of a health state classification amenable for valuation exercises that will allow the derivation of preference weights. Thus, the health related quality of life of patients with conditions, like overactive bladder, can be valued and quality adjustment weights such as quality adjusted life years derived

Making Rasch decisions: the use of Rasch analysis in the construction of preference based health related quality of life instruments

Objective: To set out the methodological process for using Rasch analysis alongside traditional psychometric methods in the development of a health state classification that is amenable to valuation. Methods: The overactive bladder questionnaire is used to illustrate a four step process for deriving a reduced health state classification from an existing nonpreference based health related quality of life instrument. Step I excludes items that do not meet the initial validation process and step II uses criteria based on Rasch analysis and psychometric testing to select the final items for the health state classification. In step III, item levels are examined and Rasch analysis is used to explore the possibility of reducing the number of item levels. Step IV repeats steps I to III on alternative data sets in order to validate the selection of items for the health state classification. Conclusions: The techniques described enable the construction of a health state classification amenable for valuation exercises that will allow the derivation of preference weights. Thus, the health related quality of life of patients with conditions, like overactive bladder, can be valued and quality adjustment weights such as quality adjusted life years derived.Rasch analysis; health related quality of life; condition specific measure; preference-based measures; overactive bladder syndrome

Phase transition in a mean-field model for sympatric speciation

We introduce an analytical model for population dynamics with intra-specific competition, mutation and assortative mating as basic ingredients. The set of equations that describes the time evolution of population size in a mean-field approximation may be decoupled. We find a phase transition leading to sympatric speciation as a parameter that quantifies competition strength is varied. This transition, previously found in a computational model, occurs to be of first order.Comment: accepted for Physica

Calcium signals and calpain-dependent necrosis are essential for release of coxsackievirus B from polarized intestinal epithelial cells

Coxsackievirus B (CVB), a member of the enterovirus family, targets the polarized epithelial cells lining the intestinal tract early in infection. Although the polarized epithelium functions as a protective barrier, this barrier is likely exploited by CVB to promote viral entry and subsequent egress. Here we show that, in contrast to nonpolarized cells, CVB-infected polarized intestinal Caco-2 cells undergo nonapoptotic necrotic cell death triggered by inositol 1,4,5-trisphosphate receptor-dependent calcium release. We further show that CVB-induced cellular necrosis depends on the Ca 2+-activated protease calpain-2 and that this protease is involved in CVB-induced disruption of the junctional complex and rearrangements of the actin cytoskeleton. Our study illustrates the cell signaling pathways hijacked by CVB, and perhaps other viral pathogens, to promote their replication and spread in polarized cell types. © 2011 Bozym et al.published_or_final_versio

Ferric Gluconate Yields Cost-Savings in Hemodialysis Patients with High Ferritin and Low TSAT: Results from the DRIVE Studies

Purpose: One third of hemodialysis patients have high serum ferritin levels and low transferrin saturation (TSAT). The purpose of this analysis was to determine the cost effectiveness of administering 1g of sodium ferric gluconate complex (SFGC: also referred to as ferric gluconate) to patients with serum ferritin \u3e500ng/mL and TSAT ≤25% based on the Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study and its 6-week observational extension (DRIVE-II). In these studies, IV iron administration resulted in reduced epoetin requirements. Methods: Decision analysis was performed using a time horizon of 12 weeks, consistent with the combined duration of DRIVE and DRIVE II. Treatment effectiveness was based on mean increase in hemoglobin (Hb) for each group (SFGC plus epoetin or epoetin alone) in the intention to treat populations. Costs included drugs (SFGC and epoetin) and hospitalizations due to serious adverse events (SAEs) reported. The primary cost effectiveness measure was cost per g/dL of Hb increase at 12 weeks. Costs were computed from a Medicare perspective using projected 2007 reimbursements. Sensitivity analyses were performed to test the impact of using the safety population, median epoetin and SFGC doses, actual 2005 Medicare reimbursements, median increases in Hb, and SAE rate changes. The model was constructed using TreeAge Pro software. Results: Total cost per patient receiving SFGC plus epoetin was $3675 per g/dL Hb increase, while the total cost per patient receiving epoetin alone was$5065 per g/dL Hb increase. Net savings for SFGC plus epoetin was $1390 per g/dL Hb increase over the 12 week period Sensitivity analyses affirmed the robustness of the model. Conclusion: Administering 1g of SFGC plus epoetin in patients with high ferritin and low TSAT as defined in the DRIVE studies resulted in significant cost-savings compared to epoetin alone

The interaction between supportive and unsupportive manager behaviors on employee work attitudes

Purpose: To use Social Exchange Theory (SET) to examine a model where supportive (SMB) and unsupportive (UMB) manager behaviors interact to predict employees’ engagement, job satisfaction and turnover intention. Design/Methodology: A cross-sectional online survey collected data from 252 UK based employees of a global data management company. Findings: Factor analysis confirmed manager behaviors to consist of two constructs: supportive and unsupportive behaviors. Structural equation modelling indicated SMB predicted job satisfaction and turnover intentions, but not engagement. Job satisfaction, but not engagement, mediated the SMB-turnover intention relationship. UMB only predicted job dissatisfaction. Neither job satisfaction nor engagement mediated the UMB-turnover intention relationship. UMB undermined the positive relationship between SMB and turnover intention. Implications: The behaviors assessed can be integrated into various stages of a manager’s development process to serve as guidelines of good practice. Crucially, findings suggest managers can exhibit both supportive and unsupportive behaviors, and that consistency in behaviors is important. The study also provides evidence that supportive managers can help reduce turnover intention through job satisfaction. Originality/value: SET was used as a framework for SMB, UMB and engagement. To our knowledge this is the first study to examine the interaction between SMB and UMB

Effect of DMSO on Protein Structure and Interactions Assessed by Collision-Induced Dissociation and Unfolding

Given the frequent use of DMSO in biochemical and biophysical assays, it is desirable to understand the influence of DMSO concentration on the dissociation or unfolding behavior of proteins. In this study, the effects of DMSO on the structure and interactions of avidin and Mycobacterium tuberculosis (Mtb) CYP142A1 were assessed through collision-induced dissociation (CID) and collision-induced unfolding (CIU) as monitored by nanoelectrospray ionization–ion mobility–mass spectrometry (nESI-IM-MS). DMSO concentrations higher than 4% (v/v) destabilize the avidin tetramer toward dissociation and unfolding, via both its effects on charge state distribution (CSD) as well as at the level of individual charge states. In contrast, DMSO both protects against heme loss and increases the stability of CYP142A1 toward unfolding even up to 40% DMSO. Tandem MS/MS experiments showed that DMSO could modify the dissociation pathway of CYP142A1, while CIU revealed the protective effect of the heme group on the structure of CYP142A1.D.S.-H.C. acknowledges the Croucher Foundation and the Cambridge Commonwealth, European and International Trust for receipt of a Croucher Cambridge International Scholarship. M.E.K. was supported by a Commonwealth (University of Cambridge) Scholarship awarded in conjunc-tion with the Cambridge Commonwealth Trust and Cam-bridge Overseas Trust. K.J.M. and A.G.C. were supported by grants from the UK BBSRC (Biotechnology and Biological Sciences Research Council (BB/I019669/1 and BB/I019227/1)