Do Economic Evaluations in Primary Care Prevention and the Management of Hypertension Conform to Good Practice Guidelines? A Systematic Review

Background: Results of previous research have identified the need for further investigation into the compliance with good practice guidelines for current decision-analytic modeling (DAM). Objective: To identify the extent to which recent model-based economic evaluations of interventions focused on lowering the blood pressure (BP) of patients with hypertension conform to published guidelines for DAM in health care using a five-dimension framework developed to assess compliance to DAM guidelines. Methods: A systematic review of English language articles was undertaken to identify published model-based economic evaluations that examined interventions aimed at lowering BP. The review covered the period January 2000 to March 2015 and included the following electronic bibliographic databases: EMBASE and Medline via Ovid interface and the Centre for Reviews and Dissemination’s (CRD) NHS-EED. Data were extracted based on different components of good practice across five dimensions utilizing a framework to assess compliance to DAM guidelines. Results: Thirteen articles were included in this review. The review found limited compliance to good practice DAM guidelines, which was most frequently justified by the lack of data. Conclusions: The assessment of structural uncertainty cannot yet be considered common practice in primary prevention and management of hypertension, and researchers seem to face difficulties with identifying sources of structural uncertainty and then handling them correctly. Additional guidelines are needed to aid researchers in identifying and managing sources of potential structural uncertainty. Adherence to guidelines is not always possible and it does pose challenges, in particular when there are limitations due to data availability that restrict, for example, a validation process

Dense active matter model of motion patterns in confluent cell monolayers

Epithelial cell monolayers show remarkable displacement and velocity correlations over distances of ten or more cell sizes that are reminiscent of supercooled liquids and active nematics. We show that many observed features can be described within the framework of dense active matter, and argue that persistent uncoordinated cell motility coupled to the collective elastic modes of the cell sheet is sufficient to produce swirl-like correlations. We obtain this result using both continuum active linear elasticity and a normal modes formalism, and validate analytical predictions with numerical simulations of two agent-based cell models, soft elastic particles and the self-propelled Voronoi model together with in-vitro experiments of confluent corneal epithelial cell sheets. Simulations and normal mode analysis perfectly match when tissue-level reorganisation occurs on times longer than the persistence time of cell motility. Our analytical model quantitatively matches measured velocity correlation functions over more than a decade with a single fitting parameter.Comment: updated version accepted for publication in Nat. Com

Diameter-independent skyrmion Hall angle observed in chiral magnetic multilayers

Magnetic skyrmions are topologically non-trivial nanoscale objects. Their topology, which originates in their chiral domain wall winding, governs their unique response to a motion inducing force. When subjected to an electrical current, the chiral winding of the spin texture leads to a deflection of the skyrmion trajectory, characterised by an angle with respect to the applied force direction. This skyrmion Hall angle is predicted to be skyrmion diameter dependent. In contrast, our experimental study finds that the skyrmion Hall angle is diameter independent for skyrmions with diameters ranging from 35 to 825 nm. At an average velocity of 6 ± 1 ms−1, the average skyrmion Hall angle was measured to be 9° ± 2°. In fact, the skyrmion dynamics is dominated by the local energy landscape such as materials defects and the local magnetic configuration

Factors Influencing Continued Wearable Device Use in Older Adult Populations: Quantitative Study

Background: The increased use of wearable sensor technology has highlighted the potential for remote telehealth services such as rehabilitation. Telehealth services incorporating wearable sensors are most likely to appeal to the older adult population in remote and rural areas, who may struggle with long commutes to clinics. However, the usability of such systems often discourages patients from adopting these services. Objective: This study aimed to understand the usability factors that most influence whether an older adult will decide to continue using a wearable device. Methods: Older adults across 4 different regions (Northern Ireland, Ireland, Sweden, and Finland) wore an activity tracker for 7 days under a free-living environment protocol. In total, 4 surveys were administered, and biometrics were measured by the researchers before the trial began. At the end of the trial period, the researchers administered 2 further surveys to gain insights into the perceived usability of the wearable device. These were the standardized System Usability Scale (SUS) and a custom usability questionnaire designed by the research team. Statistical analyses were performed to identify the key factors that affect participants’ intention to continue using the wearable device in the future. Machine learning classifiers were used to provide an early prediction of the intention to continue using the wearable device. Results: The study was conducted with older adult volunteers (N=65; mean age 70.52, SD 5.65 years) wearing a Xiaomi Mi Band 3 activity tracker for 7 days in a free-living environment. The results from the SUS survey showed no notable difference in perceived system usability regardless of region, sex, or age, eliminating the notion that usability perception differs based on geographical location, sex, or deviation in participants’ age. There was also no statistically significant difference in SUS score between participants who had previously owned a wearable device and those who wore 1 or 2 devices during the trial. The bespoke usability questionnaire determined that the 2 most important factors that influenced an intention to continue device use in an older adult cohort were device comfort (τ=0.34) and whether the device was fit for purpose (τ=0.34). A computational model providing an early identifier of intention to continue device use was developed using these 2 features. Random forest classifiers were shown to provide the highest predictive performance (80% accuracy). After including the top 8 ranked questions from the bespoke questionnaire as features of our model, the accuracy increased to 88%. Conclusions: This study concludes that comfort and accuracy are the 2 main influencing factors in sustaining wearable device use. This study suggests that the reported factors influencing usability are transferable to other wearable sensor systems. Future work will aim to test this hypothesis using the same methodology on a cohort using other wearable technologies

Mapping and assessment of ecosystems and their services. Urban ecosystems

Action 5 of the EU Biodiversity Strategy to 2020 requires member states to Map and Assess the state of Ecosystems and their Services (MAES). This report provides guidance for mapping and assessment of urban ecosystems. The MAES urban pilot is a collaboration between the European Commission, the European Environment Agency, volunteering Member States and cities, and stakeholders. Its ultimate goal is to deliver a knowledge base for policy and management of urban ecosystems by analysing urban green infrastructure, condition of urban ecosystems and ecosystem services. This report presents guidance for mapping urban ecosystems and includes an indicator framework to assess the condition of urban ecosystems and urban ecosystem services. The scientific framework of mapping and assessment is designed to support in particular urban planning policy and policy on green infrastructure at urban, metropolitan and regional scales. The results are based on the following different sources of information: a literature survey of 54 scientific articles, an online-survey (on urban ecosystems, related policies and planning instruments and with participation of 42 cities), ten case studies (Portugal: Cascais, Oeiras, Lisbon; Italy: Padua, Trento, Rome; The Netherlands: Utrecht; Poland: Poznań; Spain: Barcelona; Norway: Oslo), and a two-day expert workshop. The case studies constituted the core of the MAES urban pilot. They provided real examples and applications of how mapping and assessment can be organized to support policy; on top, they provided the necessary expertise to select a set of final indicators for condition and ecosystem services. Urban ecosystems or cities are defined here as socio-ecological systems which are composed of green infrastructure and built infrastructure. Urban green infrastructure (GI) is understood in this report as the multi-functional network of urban green spaces situated within the boundary of the urban ecosystem. Urban green spaces are the structural components of urban GI. This study has shown that there is a large scope for urban ecosystem assessments. Firstly, urban policies increasingly use urban green infrastructure and nature-based solutions in their planning process. Secondly, an increasing amount of data at multiple spatial scales is becoming available to support these policies, to provide a baseline, and to compare or benchmark cities with respect to the extent and management of the urban ecosystem. Concrete examples are given on how to delineate urban ecosystems, how to choose an appropriate spatial scale, and how to map urban ecosystems based on a combination of national or European datasets (including Urban Atlas) and locally collected information (e.g., location of trees). Also examples of typologies for urban green spaces are presented. This report presents an indicator framework which is composed of indicators to assess for urban ecosystem condition and for urban ecosystem services. These are the result of a rigorous selection process and ensure consistent mapping and assessment across Europe. The MAES urban pilot will continue with work on the interface between research and policy. The framework presented in this report needs to be tested and validated across Europe, e.g. on its applicability at city scale, on how far the methodology for measuring ecosystem condition and ecosystem service delivery in urban areas can be used to assess urban green infrastructure and nature-based solutions

Mapping the disease-specific LupusQoL to the SF-6D

Purpose To derive a mapping algorithm to predict SF-6D utility scores from the non-preference-based LupusQoL and test the performance of the developed algorithm on a separate independent validation data set. Method LupusQoL and SF-6D data were collected from 320 patients with systemic lupus erythematosus (SLE) attending routine rheumatology outpatient appointments at seven centres in the UK. Ordinary least squares (OLS) regression was used to estimate models of increasing complexity in order to predict individuals’ SF-6D utility scores from their responses to the LupusQoL questionnaire. Model performance was judged on predictive ability through the size and pattern of prediction errors generated. The performance of the selected model was externally validated on an independent data set containing 113 female SLE patients who had again completed both the LupusQoL and SF-36 questionnaires. Results Four of the eight LupusQoL domains (physical health, pain, emotional health, and fatigue) were selected as dependent variables in the final model. Overall model fit was good, with R2 0.7219, MAE 0.0557, and RMSE 0.0706 when applied to the estimation data set, and R2 0.7431, MAE 0.0528, and RMSE 0.0663 when applied to the validation sample. Conclusion This study provides a method by which health state utility values can be estimated from patient responses to the non-preference-based LupusQoL, generalisable beyond the data set upon which it was estimated. Despite concerns over the use of OLS to develop mapping algorithms, we find this method to be suitable in this case due to the normality of the SF-6D data

VEZF1 elements mediate protection from DNA methylation

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin stat

Limits to the Rate of Adaptive Substitution in Sexual Populations

In large populations, many beneficial mutations may be simultaneously available and may compete with one another, slowing adaptation. By finding the probability of fixation of a favorable allele in a simple model of a haploid sexual population, we find limits to the rate of adaptive substitution, , that depend on simple parameter combinations. When variance in fitness is low and linkage is loose, the baseline rate of substitution is , where is the population size, is the rate of beneficial mutations per genome, and is their mean selective advantage. Heritable variance in log fitness due to unlinked loci reduces by under polygamy and under monogamy. With a linear genetic map of length Morgans, interference is yet stronger. We use a scaling argument to show that the density of adaptive substitutions depends on , , , and only through the baseline density: . Under the approximation that the interference due to different sweeps adds up, we show that , implying that interference prevents the rate of adaptive substitution from exceeding one per centimorgan per 200 generations. Simulations and numerical calculations confirm the scaling argument and confirm the additive approximation for ; for higher , the rate of adaptation grows above , but only very slowly. We also consider the effect of sweeps on neutral diversity and show that, while even occasional sweeps can greatly reduce neutral diversity, this effect saturates as sweeps become more common—diversity can be maintained even in populations experiencing very strong interference. Our results indicate that for some organisms the rate of adaptive substitution may be primarily recombination-limited, depending only weakly on the mutation supply and the strength of selection