A prickly problem: developing a volunteer-friendly tool for monitoring populations of a terrestrial urban mammal, the West European hedgehog (Erinaceus europaeus)

Across Europe, hedgehogs (Erinaceus europaeus) appear to be in decline in both urban and rural landscapes. Current methods used to monitor urban populations are, however, associated with several potential limitations. In this study, we conducted hedgehog footprint-tunnel surveys in 219 residential gardens across Reading, UK between May–September in 2013 and/or 2014; gardens were surveyed for five continuous days. Single-species occupancy models were used to investigate factors influencing hedgehog occupancy and two-species occupancy models were used to estimate a species interaction factor (SIF) between hedgehogs and (a) badgers (Meles meles), (b) foxes (Vulpes vulpes) and (c) dogs (Canis familiaris). The five-day survey protocol was associated with a false-absence error rate of 0.1–0.4%, indicating that it was a reliable method for determining hedgehog presence; conversely, 34.7% of householders were not able to correctly predict hedgehog presence or absence. Hedgehogs were widely distributed across Reading, but detected in only 32–40% of gardens. None of the within-garden or outside-garden factors investigated significantly affected hedgehog occupancy in the single-species models, but the two-species models indicated that badgers (SIF = 0.471 ± 0.188), but not foxes (SIF = 0.954 ± 0.048) or dogs (SIF = 0.780 ± 0.228), negatively affected the presence of hedgehogs in gardens, although not significantly. Overall, footprint-tunnels represent a viable field method for monitoring urban hedgehog populations, however, other approaches are required to identify factors that make gardens "hedgehog friendly"

Taking stock of cost-effectiveness analysis of healthcare in China

Introduction Cost-effectiveness analysis (CEA) is playing an increasingly important role in informing healthcare decision-making in China. This study aims to review the published literature on CEA in mainland China and describe its characteristics and evolution. We provide recommendations on the future direction of CEA as a methodology and as a tool to support healthcare decision-making in China. Methods English-language cost-per-quality-adjusted life-year (QALY) and cost-per-disability-adjusted life-year (DALY) publications relating to mainland China were reviewed using the Tufts Medical Center Cost-Effectiveness Analysis Registry and Global Health Cost-Effectiveness Analysis Registry through 2017. Study features were summarised using descriptive statistics. Changes in study methodology over time were analysed by trend test, and study characteristics influencing the incremental cost-effectiveness ratio (ICER) of cost-per-QALY studies were investigated using logistic regression. Results 170 studies were identified reporting CEA for mainland China (cost/QALY=125, cost/DALY=45) since 1998. The number and quality of studies has increased over the past two decades, with significantly more cost-per-QALY studies compared with cost-per-DALY studies (p<0.0001) and more studies with authors affiliated with Chinese institutions (p=0.0002). The average quality score was 5.04 out of 7 for cost-per-QALY and 4.70 for cost-per-DALY studies based on Registry reviewers’ subjective assessment of overall quality (methods, assumptions and reporting practices). The median ICER reported for interventions for oncology patients was higher (US$26 694 per QALY) than the median ICER reported for all interventions (US$11 503 per QALY). Oncology interventions were associated with the likelihood of reporting higher ICERs than the median ICER (p=0.003). Conclusion The number of English-language published CEA studies relating to China has grown rapidly over the past 20 years. In terms of quality, the China studies compare favourably with international studies, although they remain a small proportion of studies globally

Transforming growth factor-beta renders ageing microglia inhibitory to oligodendrocyte generation by CNS progenitors.

It is now well-established that the macrophage and microglial response to CNS demyelination influences remyelination by removing myelin debris and secreting a variety of signaling molecules that influence the behaviour of oligodendrocyte progenitor cells (OPCs). Previous studies have shown that changes in microglia contribute to the age-related decline in the efficiency of remyelination. In this study, we show that microglia increase their expression of the proteoglycan NG2 with age, and that this is associated with an altered micro-niche generated by aged, but not young, microglia that can divert the differentiation OPCs from oligodendrocytes into astrocytes in vitro. We further show that these changes in ageing microglia are generated by exposure to high levels of TGFβ. Thus, our findings suggest that the rising levels of circulating TGFβ known to occur with ageing contribute to the age-related decline in remyelination by impairing the ability of microglia to promote oligodendrocyte differentiation from OPCs, and therefore could be a potential therapeutic target to promote remyelination.This work was supported by funding from the UK Multiple Sclerosis Society, Medimmune, The Adelson Medical Research Foundation and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institut

HEE-GER: a systematic review of German economic evaluations of health care published 1990–2004

BACKGROUND: Studies published in non-English languages are systematically missing in systematic reviews of growth and quality of economic evaluations of health care. The aims of this study were: to characterize German evaluations, published in English or German-language, in terms of various key parameters; to investigate methods to derive quality-of-life weights in cost-utility studies; and to examine changes in study characteristics over the years. METHODS: We conducted a country-specific systematic review of the German and English-language literature of German economic evaluations (assessment of or application to the German health care system) published 1990–2004. Generic and specialized health economic databases were searched. Two independent reviewers verified fulfillment of inclusion criteria and extracted study characteristics. RESULTS: The fulltexts of 730 articles were reviewed of which 283 fulfilled all entry criteria. 32% of included studies were published in German-language. 51% of studies evaluated pharmaceuticals and 63% were cost-effectiveness analyses. Economic appraisals concentrate on few disease categories and important health areas are strongly underrepresented. Declaration of sponsorship was associated with article language (49% English articles vs. 29% German articles, p < 0.001). The methodology used to obtain quality-of-life weights in published cost-utility studies was very diverse, poorly reported and most studies did not use German patients' or community health state valuations. CONCLUSION: Many of the German-language evaluations included in our study are likely to be missing in international reviews and may be systematically different from English-language reviews from Germany. Lack of transparency and adherence to recommended reporting practices constitute a serious problem in German economic evaluations

Interpersonal and affective dimensions of psychopathic traits in adolescents : development and validation of a self-report instrument

We report the development and psychometric evaluations of a self-report instrument designed to screen for psychopathic traits among mainstream community adolescents. Tests of item functioning were initially conducted with 26 adolescents. In a second study the new instrument was administered to 150 high school adolescents, 73 of who had school records of suspension for antisocial behavior. Exploratory factor analysis yielded a 4-factor structure (Impulsivity α = .73, Self-Centredness α = .70, Callous-Unemotional α = .69, and Manipulativeness α = .83). In a third study involving 328 high school adolescents, 130 with records of suspension for antisocial behaviour, competing measurement models were evaluated using confirmatory factor analysis. The superiority of a first-order model represented by four correlated factors that was invariant across gender and age was confirmed. The findings provide researchers and clinicians with a psychometrically strong, self-report instrument and a greater understanding of psychopathic traits in mainstream adolescents

FAS-dependent cell death in α-synuclein transgenic oligodendrocyte models of multiple system atrophy

Multiple system atrophy is a parkinsonian neurodegenerative disorder. It is cytopathologically characterized by accumulation of the protein p25α in cell bodies of oligodendrocytes followed by accumulation of aggregated α-synuclein in so-called glial cytoplasmic inclusions. p25α is a stimulator of α-synuclein aggregation, and coexpression of α-synuclein and p25α in the oligodendroglial OLN-t40-AS cell line causes α-synuclein aggregate-dependent toxicity. In this study, we investigated whether the FAS system is involved in α-synuclein aggregate dependent degeneration in oligodendrocytes and may play a role in multiple system atrophy. Using rat oligodendroglial OLN-t40-AS cells we demonstrate that the cytotoxicity caused by coexpressing α-synuclein and p25α relies on stimulation of the death domain receptor FAS and caspase-8 activation. Using primary oligodendrocytes derived from PLP-α-synuclein transgenic mice we demonstrate that they exist in a sensitized state expressing pro-apoptotic FAS receptor, which makes them sensitive to FAS ligand-mediated apoptosis. Immunoblot analysis shows an increase in FAS in brain extracts from multiple system atrophy cases. Immunohistochemical analysis demonstrated enhanced FAS expression in multiple system atrophy brains notably in oligodendrocytes harboring the earliest stages of glial cytoplasmic inclusion formation. Oligodendroglial FAS expression is an early hallmark of oligodendroglial pathology in multiple system atrophy that mechanistically may be coupled to α-synuclein dependent degeneration and thus represent a potential target for protective intervention

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