Transposable elements promote the evolution of genome streamlining

Eukaryotes and prokaryotes have distinct genome architectures, withmarked differences in genome size, the ratio of coding/non-coding DNA,and the abundance of transposable elements (TEs). As TEs replicate inde-pendently of their hosts, the proliferation of TEs is thought to have drivengenome expansion in eukaryotes. However, prokaryotes also have TEs inintergenic spaces, so why do prokaryotes have small, streamlined genomes?Using anin silicomodel describing the genomes of single-celled asexualorganisms that coevolve with TEs, we show that TEs acquired from theenvironment by horizontal gene transfer can promote the evolution ofgenome streamlining. The process depends on local interactions and isunderpinned by rock–paper–scissors dynamics in which populations ofcells with streamlined genomes beat TEs, which beat non-streamlinedgenomes, which beat streamlined genomes, in continuous and repeatingcycles. Streamlining is maladaptive to individual cells, but improves lineageviability by hindering the proliferation of TEs. Streamlining does not evolvein sexually reproducing populations because recombination partially freesTEs from the deleterious effects they cause.This article is part of the theme issue‘The secret lives of microbial mobilegenetic elements’

Quality Control Process for EQ-5D-5L Valuation Studies

Background: The values of the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) are elicited using composite time trade-off and discrete choice experiments. Unfortunately, data quality issues and interviewer effects were observed in the first few EQ-5D-5L valuation studies. To prevent these issues from occurring in later studies, the EuroQol Group established a cyclic quality control (QC) process. Objectives: To describe this QC process and show its impact on data quality. Methods: A newly developed QC tool provided information about protocol compliance, interviewer effects, and mean values by health state severity. In a cyclic process, this information is initially used to evaluate whether new interviewers meet minimal quality requirements and later to provide feedback about how their performance may be improved. To investigate the impact of this cyclic process, we compared the quality of the data in Dutch and Spanish valuation studies that did not have this QC process with that in the follow-up studies in the same countries that used the QC process. Data quality was measured using protocol violations, variability between interviewers, the proportion of inconsistent responders, and clustering of composite time trade-off values. Results: In Spain, protocol violations were reduced from 87% in the valuation study to 5% in the follow-up study and in the Netherlands from 20% to 8%. In both countries, interviewers performed more homogeneously in the follow-up studies. The number of inconsistent respondents was reduced by 23.2% in Spain and 23.6% in the Netherlands. Values were less clustered in the follow-up studies. Conclusions: The implementation of a strict QC process in EQ-5D-5L valuation studies increases interviewer protocol compliance and promotes data quality

Overview, update, and lessons learned From the international EQ-5D-5L valuation work: version 2 of the EQ-5D-5L valuation protocol

A standardized 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L) valuation protocol was first used in national studies in the period 2012 to 2013. A set of problems encountered in this initial wave of valuation studies led to the subsequent refinement of the valuation protocol. To clarify lessons learned and how the protocol was updated when moving from version 1.0 to the current version 2.1 and 2.0, this article will (1) present the challenges faced in EQ-5D-5L valuation since 2012 and how these were resolved and (2) describe in depth a set of new challenges that have become central in currently ongoing research on how EQ-5D-5L health states should be valued and modeled

Balancing equity and efficiency in the Dutch basic benefits package using the principle of proportional shortfall

Economic evaluations are increasingly used to inform decisions regarding the allocation of scarce health care resources. To systematically incorporate societal preferences into these evaluations, quality-adjusted life year gains could be weighted according to some equity principle, the most suitable of which is a matter of frequent debate. While many countries still struggle with equity concerns for priority setting in health care, the Netherlands has reached a broad consensus to use the concept of proportional shortfall. Our study evaluates the concept and its support in the Dutch health care context. We discuss arguments in the Netherlands for using proportional shortfall and difficulties in transitioning from principle to practice. In doing so, we address universal issues leading to a systematic consideration of equity concerns for priority setting in health care. The article thus has relevance to all countries struggling with the formalization of equity concerns for priority setting

Liver function tests and risk prediction of incident type 2 diabetes:evaluation in two independent cohorts

BACKGROUND: Liver function tests might predict the risk of type 2 diabetes. An independent study evaluating utility of these markers compared with an existing prediction model is yet lacking. METHODS AND FINDINGS: We performed a case-cohort study, including random subcohort (6.5%) from 38,379 participants with 924 incident diabetes cases (the Dutch contribution to the European Prospective Investigation Into Cancer and Nutrition, EPIC-NL, the Netherlands), and another population-based cohort study including 7,952 participants with 503 incident cases (the Prevention of Renal and Vascular End-stage Disease, PREVEND, Groningen, the Netherlands). We examined predictive value of combination of the Liver function tests (gamma-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase and albumin) above validated models for 7.5-year risk of diabetes (the Cooperative Health Research in the Region of Augsburg, the KORA study). Basic model includes age, sex, BMI, smoking, hypertension and parental diabetes. Clinical models additionally include glucose and uric acid (model1) and HbA1c (model2). In both studies, addition of Liver function tests to the basic model improved the prediction (C-statistic by~0.020; NRI by~9.0%; P<0.001). In the EPIC-NL case-cohort study, addition to clinical model1 resulted in statistically significant improvement in the overall population (C-statistic = +0.009; P<0.001; NRI = 8.8%; P<0.001), while addition to clinical model 2 yielded marginal improvement limited to men (C-statistic = +0.007; P = 0.06; NRI = 3.3%; P = 0.04). In the PREVEND cohort study, addition to clinical model 1 resulted in significant improvement in the overall population (C-statistic change = 0.008; P = 0.003; NRI = 3.6%; P = 0.03), with largest improvement in men (C-statistic change = 0.013; P = 0.01; NRI = 5.4%; P = 0.04). In PREVEND, improvement compared to clinical model 2 could not be tested because of lack of HbA1c data. CONCLUSIONS: Liver function tests modestly improve prediction for medium-term risk of incident diabetes above basic and extended clinical prediction models, only if no HbA1c is incorporated. If data on HbA1c are available, Liver function tests have little incremental predictive value, although a small benefit may be present in men