Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Strong Roots 2 Climate Change Adaptation Project Report

Climate change is clearly a global issue, but also one that manifests itself locally. The global dimension requires an understanding of the world’s climate (i.e. physical science). Local adaptation requires a knowledge of projected physical impacts (i.e. physical science) but also a deep understanding of how (a) communities behave (i.e. social science) and (b) how to motivate behaviour change (i.e. psychology). Any project in this area must acknowledge this broad depth of factors and assemble an appropriate team of people to deal with them. The Strong Roots 2 project has aimed to achieve this blend. The 736 Community and Town Councils across Wales represent a direct interface between communities and government. Given the stark warnings of climate change for the future, both globally, and within Wales, Strong Roots 2 set out to further explore the potential of Community and Town Councils to engage with their communities and to address climate change adaptation and resilience at this level. As indicated in Strong Roots 1, the potential contribution of Councils has been somewhat overlooked; nonetheless, this tier of local government is closest to the community and, importantly, embodies the kind of locally-relevant knowledge, expertise and community networks that could support such action. Community and Town Councils across Wales are as individual as the communities they represent. Each Council has unique strengths, and it is important to acknowledge contextual factors when considering the contribution that each Council can make. Taking the local context into account and tailoring strategies are central to the Strong Roots research ethos, as is acknowledging and empowering community and town councillors as equal partners in the process. Moreover, the potential contribution of Community and Town Councils across Wales represents a significant step forward in developing innovative ways to tackle climate change impacts, increase resilience and engrain sustainable practices, both as a community and as a nation. This report builds on the findings of the previous Strong Roots 1 research project and details the findings of an investigation into the potential role of Community and Town Councils as local leaders of climate change adaptation, and the behaviours, resources and skills required to fulfil that role. Strong Roots is an initiative that aims to highlight the potential of Community and Town Councils as leaders in addressing climate change issues locally, and as supporting partners to the Welsh Assembly Government in its commitment to the development of sustainable, resilient low-carbon communities. This particular project is an aspect of this wider initiative.<br/

Neurons Expressing the Highest Levels of γ-Synuclein Are Unaffected by Targeted Inactivation of the Gene

Homologous recombination in ES cells was employed to generate mice with targeted deletion of the first three exons of the γ-synuclein gene. Complete inactivation of gene expression in null mutant mice was confirmed on the mRNA and protein levels. Null mutant mice are viable, are fertile, and do not display evident phenotypical abnormalities. The effects of γ-synuclein deficiency on motor and peripheral sensory neurons were studied by various methods in vivo and in vitro. These two types of neurons were selected because they both express high levels of γ-synuclein from the early stages of mouse embryonic development but later in the development they display different patterns of intracellular compartmentalization of the protein. We found no difference in the number of neurons between wild-type and null mutant animals in several brain stem motor nuclei, in lumbar dorsal root ganglia, and in the trigeminal ganglion. The survival of γ-synuclein-deficient trigeminal neurons in various culture conditions was not different from that of wild-type neurons. There was no difference in the numbers of myelinated and nonmyelinated fibers in the saphenous nerves of these animals, and sensory reflex thresholds were also intact in γ-synuclein null mutant mice. Nerve injury led to similar changes in sensory function in wild-type and mutant mice. Taken together, our data suggest that like α-synuclein, γ-synuclein is dispensable for the development and function of the nervous system