The use of happiness research for public policy

Research on happiness tends to follow a "benevolent dictator" approach where politicians pursue people's happiness. This paper takes an antithetic approach based on the insights of public choice theory. First, we inquire how the results of happiness research may be used to improve the choice of institutions. Second, we show that the policy approach matters for the choice of research questions and the kind of knowledge happiness research aims to provide. Third, we emphasize that there is no shortcut to an optimal policy maximizing some happiness indicator or social welfare function since governments have an incentive to manipulate this indicator

Protocol for the immediate delivery versus expectant care of women with preterm prelabour rupture of the membranes close to term (PPROMT) Trial [ISRCTN44485060]

BACKGROUND: Preterm prelabour rupture of membranes (PPROM) complicates up to 2% of all pregnancies and is the cause of 40% of all preterm births. The optimal management of women with PPROM prior to 37 weeks, is not known. Furthermore, diversity in current clinical practice suggests uncertainty about the appropriate clinical management. There are two options for managing PPROM, expectant management (a wait and see approach) or early planned birth. Infection is the main risk for women in which management is expectant. This risk need to be balanced against the risk of iatrogenic prematurity if early delivery is planned. The different treatment options may also have different health care costs. Expectant management results in prolonged antenatal hospitalisation while planned early delivery may necessitate intensive care of the neonate for problems associated with prematurity. METHODS/DESIGN: We aim to evaluate the effectiveness of early planned birth compared with expectant management for women with PPROM between 34 weeks and 36(6 )weeks gestation, in a randomised controlled trial. A secondary aim is a cost analysis to establish the economic impact of the two treatment options and establish the treatment preferences of women with PPROM close to term. The early planned birth group will be delivered within 24 hours according to local management protocols. In the expectant management group birth will occur after spontaneous labour, at term or when the attending clinician feels that birth is indicated according to usual care. Approximately 1812 women with PPROM at 34–36(6 )weeks gestation will be recruited for the trial. The primary outcome of the study is neonatal sepsis. Secondary infant outcomes include respiratory distress, perinatal mortality, neonatal intensive care unit admission, assisted ventilation and early infant development. Secondary maternal outcomes include chorioamnionitis, postpartum infection treated with antibiotics, antepartum haemorrhage, induction of labour, mode of delivery, maternal satisfaction with care, duration of hospitalisation, and maternal wellbeing at four months postpartum. DISCUSSION: This trial will provide evidence on the optimal care for women with PPROM close to term (34–37 weeks gestation). Consideration of both the clinical and economic sequelae of the management of PPROM will enable informed decision making and guideline development

A Naturally Occurring Mutation in ropB Suppresses SpeB Expression and Reduces M1T1 Group A Streptococcal Systemic Virulence

Epidemiological studies of group A streptococcus (GAS) have noted an inverse relationship between SpeB expression and invasive disease. However, the role of SpeB in the course of infection is still unclear. In this study we utilize a SpeB-negative M1T1 clinical isolate, 5628, with a naturally occurring mutation in the gene encoding the regulator RopB, to elucidate the role of RopB and SpeB in systemic virulence. Allelic exchange mutagenesis was used to replace the mutated ropB allele in 5628 with the intact allele from the well characterized isolate 5448. The inverse allelic exchange was also performed to replace the intact ropB in 5448 with the mutated allele from 5628. An intact ropB was found to be essential for SpeB expression. While the ropB mutation was shown to have no effect on hemolysis of RBC's, extracellular DNase activity or survival in the presence of neutrophils, strains with the mutated ropB allele were less virulent in murine systemic models of infection. An isogenic SpeB knockout strain containing an intact RopB showed similarly reduced virulence. Microarray analysis found genes of the SpeB operon to be the primary target of RopB regulation. These data show that an intact RopB and efficient SpeB production are necessary for systemic infection with GAS

A framework and a measurement instrument for sustainability of work practices in long-term care

<p>Abstract</p> <p>Background</p> <p>In health care, many organizations are working on quality improvement and/or innovation of their care practices. Although the effectiveness of improvement processes has been studied extensively, little attention has been given to sustainability of the changed work practices after implementation. The objective of this study is to develop a theoretical framework and measurement instrument for sustainability. To this end sustainability is conceptualized with two dimensions: routinization and institutionalization.</p> <p>Methods</p> <p>The exploratory methodological design consisted of three phases: a) framework development; b) instrument development; and c) field testing in former improvement teams in a quality improvement program for health care (N _teams= 63, N _individual= 112). Data were collected not until at least one year had passed after implementation.</p> <p>Underlying constructs and their interrelations were explored using Structural Equation Modeling and Principal Component Analyses. Internal consistency was computed with Cronbach's alpha coefficient. A long and a short version of the instrument are proposed.</p> <p>Results</p> <p>The χ²- difference test of the -2 Log Likelihood estimates demonstrated that the hierarchical two factor model with routinization and institutionalization as separate constructs showed a better fit than the one factor model (p < .01). Secondly, construct validity of the instrument was strong as indicated by the high factor loadings of the items. Finally, the internal consistency of the subscales was good.</p> <p>Conclusions</p> <p>The theoretical framework offers a valuable starting point for the analysis of sustainability on the level of actual changed work practices. Even though the two dimensions routinization and institutionalization are related, they are clearly distinguishable and each has distinct value in the discussion of sustainability. Finally, the subscales conformed to psychometric properties defined in literature. The instrument can be used in the evaluation of improvement projects.</p

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

Anamneses-Based Internet Information Supply: Can a Combination of an Expert System and Meta-Search Engine Help Consumers find the Health Information they Require?

An increasing number of people search for health information online. During the last 10 years various researchers have determined the requirements for an ideal consumer health information system. The aim of this study was to figure out, whether medical laymen can find a more accurate diagnosis for a given anamnesis via the developed prototype health information system than via ordinary internet search

Interpreting linear support vector machine models with heat map molecule coloring

<p>Abstract</p> <p>Background</p> <p>Model-based virtual screening plays an important role in the early drug discovery stage. The outcomes of high-throughput screenings are a valuable source for machine learning algorithms to infer such models. Besides a strong performance, the interpretability of a machine learning model is a desired property to guide the optimization of a compound in later drug discovery stages. Linear support vector machines showed to have a convincing performance on large-scale data sets. The goal of this study is to present a heat map molecule coloring technique to interpret linear support vector machine models. Based on the weights of a linear model, the visualization approach colors each atom and bond of a compound according to its importance for activity.</p> <p>Results</p> <p>We evaluated our approach on a toxicity data set, a chromosome aberration data set, and the maximum unbiased validation data sets. The experiments show that our method sensibly visualizes structure-property and structure-activity relationships of a linear support vector machine model. The coloring of ligands in the binding pocket of several crystal structures of a maximum unbiased validation data set target indicates that our approach assists to determine the correct ligand orientation in the binding pocket. Additionally, the heat map coloring enables the identification of substructures important for the binding of an inhibitor.</p> <p>Conclusions</p> <p>In combination with heat map coloring, linear support vector machine models can help to guide the modification of a compound in later stages of drug discovery. Particularly substructures identified as important by our method might be a starting point for optimization of a lead compound. The heat map coloring should be considered as complementary to structure based modeling approaches. As such, it helps to get a better understanding of the binding mode of an inhibitor.</p

c-Src Regulates Akt Signaling in Response to Ghrelin via β-Arrestin Signaling-Independent and -Dependent Mechanisms

The aim of the present study was to identify the signaling mechanisms to ghrelin-stimulated activation of the serine/threonine kinase Akt. In human embryonic kidney 293 (HEK293) cells transfected with GHS-R1a, ghrelin leads to the activation of Akt through the interplay of distinct signaling mechanisms: an early Gi/o protein-dependent pathway and a late pathway mediated by β-arrestins. The starting point is the Gi/o-protein dependent PI3K activation that leads to the membrane recruitment of Akt, which is phosphorylated at Y by c-Src with the subsequent phosphorylation at A-loop (T308) and HM (S473) by PDK1 and mTORC2, respectively. Once the receptor is activated, a second signaling pathway is mediated by β-arrestins 1 and 2, involving the recruitment of at least β-arrestins, c-Src and Akt. This β-arrestin-scaffolded complex leads to full activation of Akt through PDK1 and mTORC2, which are not associated to the complex. In agreement with these results, assays performed in 3T3-L1 preadipocyte cells indicate that β-arrestins and c-Src are implicated in the activation of Akt in response to ghrelin through the GHS-R1a. In summary this work reveals that c-Src is crucially involved in the ghrelin-mediated Akt activation. Furthermore, the results support the view that β-arrestins act as both scaffolding proteins and signal transducers on Akt activation

Effectiveness of an online curriculum for medical students on genetics, genetic testing and counseling

Background: It is increasingly important that physicians have a thorough understanding of the basic science of human genetics and the ethical, legal and social implications (ELSI) associated with genetic testing and counseling. Methods: The authors developed a series of web-based courses for medical students on these topics. The course modules are interactive, emphasize clinical case studies, and can easily be incorporated into existing medical school curricula. Results: Results of a &#x2018;real world&#x2019; effectiveness trial indicate that the courses have a statistically significant effect on knowledge, attitude, intended behavior and self-efficacy related to genetic testing (p&#60;0.001; N varies between 163 and 596 for each course). Conclusions: The results indicate that this curriculum is an effective tool for educating medical students on the ELSI associated with genetic testing and for promoting positive changes in students&#x0027; confidence, counseling attitudes and behaviors