Mapping EQ-5D Utility Scores from the Incontinence Quality of Life Questionnaire among Patients with Neurogenic and Idiopathic Overactive Bladder

AbstractObjectivesTo provide a mapping algorithm for estimating EuroQol five-dimensional (EQ-5D) questionnaire index scores from the Incontinence-specific Quality of Life questionnaire (I-QOL) based on nationally representative samples of patients with idiopathic or neurogenic overactive bladder (OAB) using EQ-5D questionnaire preference valuations based on both the UK and US general populations.MethodsAnalyses were conducted for 2505 patients from the Adelphi Overactive Bladder Disease Specific Programme, a cross-sectional study of patients with idiopathic or neurogenic OAB, undertaken in the United States and Europe in 2010. A range of statistical modeling techniques was used. Tenfold cross-validation techniques were used to calculate mean absolute error (MAE) and root mean squared error (RMSE) goodness-of-fit statistics. Various predictor lists, together with a method combining stepwise selection with multivariable fractional polynomial techniques to allow nonlinear relationships to feature, were pursued.ResultsChoice of predictors was consistent for both the UK and US EQ-5D questionnaire tariffs. For idiopathic, the best model included the I-QOL total score and age (both modeled nonlinearly.) For neurogenic, the best model was the I-QOL social embarrassment domain score modeled linearly only. Best-fit results were better in the idiopathic (n = 2351; MAE = 0.10; RMSE = 0.14) than in the neurogenic sample (n = 254; MAE = 0.17; RMSE = 0.22).ConclusionsThis research provides algorithms for mapping EQ-5D questionnaire index scores from the I-QOL, allowing calculation of appropriate preference-based health-related quality-of-life scores for use in cost-effectiveness analyses when only I-QOL data are available. The strongest results were for idiopathic patients, but those for neurogenic are consistent with those of other published mapping studies

Social control in online communities of consumption: a framework for community management

Online communities of consumption (OCCs) represent highly diverse groups of consumers whose interests are not always aligned. Social control in OCCs aims to effectively manage problems arising from this heterogeneity. Extant literature on social control in OCCs is fragmented as some studies focus on the principles of social control, while others focus on the implementation. Moreover, the domain is undertheorized. This article integrates the disparate literature on social control in OCCs providing a first unified conceptualization of the topic. The authors conceptualize social control as a system, or configuration, of moderation practices. Moderation practices are executed during interactions operating under different governance structures (market, hierarchy, and clan) and serving different purposes (interaction initiation, maintenance, and termination). From this conceptualization, important areas of future research emerge and research questions are developed. The framework also serves as a community management tool for OCC managers, enabling the diagnosis of social control problems and the elaboration of strategies and tactics to address them

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11

The proteasome is a vital cellular machine that maintains protein homeostasis, which is of particular importance in multiple myeloma and possibly other cancers. Targeting of proteasome 20S peptidase activity with bortezomib and carfilzomib has been widely used to treat myeloma. However, not all patients respond to these compounds, and those who do eventually suffer relapse. Therefore, there is an urgent and unmet need to develop new drugs that target proteostasis through different mechanisms. We identified quinoline-8-thiol (8TQ) as a first-in-class inhibitor of the proteasome 19S subunit Rpn11. A derivative of 8TQ, capzimin, shows >5-fold selectivity for Rpn11 over the related JAMM proteases and >2 logs selectivity over several other metalloenzymes. Capzimin stabilized proteasome substrates, induced an unfolded protein response, and blocked proliferation of cancer cells, including those resistant to bortezomib. Proteomic analysis revealed that capzimin stabilized a subset of polyubiquitinated substrates. Identification of capzimin offers an alternative path to develop proteasome inhibitors for cancer therapy