A Modified Newcastle-Ottawa Scale for Assessment of Study Quality in Genetic Urological Research

Our modification of the traditional Newcastle-Ottawa scale enables urological researchers to effectively appraise and communicate the quality of genetic-based research in urology

Genetic correlates of prostate cancer visibility (and invisibility) on mpMRI: It's time to take stock

Multiparametric magnetic resonance imaging (mpMRI) has enhanced risk stratification for men at risk of prostate cancer, through accurate pre‐biopsy detection of high‐risk disease. However, it has become apparent that not all clinically significant prostate cancer is detected by mpMRI. Approximately 10‐20% of significant disease is invisible to mpMRI, depending on the threshold set for significance, and on the quality of mpMRI acquisition and interpretation. The threshold for significance has recently been challenged by the 29‐year follow‐up of the SPCG‐4 study, in which men with overall Gleason score 3 + 4 did not suffer prostate‐cancer‐related death, whilst those with overall Gleason score 4 + 3 did suffer prostate‐cancer related death (adjusted relative risk 5.73; 95% CI 1.59–20.67) potentially suggesting a new threshold for clinically significant disease. This finding is important, given that in PROMIS, no men with overall Gleason score 4 + 3 had negative pre‐biopsy mpMRI, indicating that actually mpMRI may identify all truly significant cancer (if SPCG‐4 is used to guide our threshold). Nonetheless, over the past two years, there has been increasing drive to better understand the nature of mpMRI‐inconspicuous disease, particularly at the molecular level

Entrepreneurial capital, social values and Islamic traditions: exploring the growth of women-owned enterprises in Pakistan

Main ArticleThis study seeks to explore the variables contributing to the growth of women-owned enterprises in the Islamic Republic of Pakistan. Based on a previously established multivariate model, it uses two econometric approaches: first classifying variables into predetermined blocks; and second, using the general to specific approach. Statistical analyses and in-depth interviews confirm that women entrepreneurs’ personal resources and social capital have a significant role in their business growth. Further, it reveals that the moral support of immediate family, independent mobility and being allowed to meet with men play a decisive role in the sales and employment growth of women-owned enterprises in an Islamic country such as Pakistan

Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

CONTEXT: Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain. OBJECTIVE: To systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study. EVIDENCE ACQUISITION: We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment. EVIDENCE SYNTHESIS: We retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue (PTEN) loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours. CONCLUSIONS: Prostate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets. PATIENT SUMMARY: Prostate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility

Inequitable access to substance abuse treatment services in Cape Town, South Africa

BACKGROUND:Despite high levels of substance use disorders in Cape Town, substance abuse treatment utilization is low among people from disadvantaged communities in Cape Town, South Africa. To improve substance abuse treatment utilization, it is important to identify any potential barriers to treatment initiation so that interventions to reduce these barriers can be implemented. To date, substance abuse research has not examined the factors associated with substance abuse treatment utilization within developing countries. Using the Behavioural Model of Health Services Utilization as an analytic framework, this study aimed to redress this gap by examining whether access to substance abuse treatment is equitable and the profile of variables associated with treatment utilization for people from poor communities in Cape Town, South Africa. METHODS: This study used a case-control design to compare 434 individuals with substance use disorders from disadvantaged communities who had accessed treatment with 555 controls who had not accessed treatment on a range of predisposing, treatment need and enabling/restricting variables thought to be associated with treatment utilization. A hierarchical logistic regression was conducted to assess the unique contribution that the need for treatment, predisposing and enabling/restricting variable blocks made on substance abuse treatment utilization. RESULTS: Findings revealed that non-need enabling/restricting variables accounted for almost equal proportions of the variance in service utilization as the need for treatment variables. These enabling/restricting variables also attenuated the influence of the treatment need and predisposing variables domains on chances of treatment utilization. Several enabling/restricting variables emerged as powerful partial predictors of utilization including competing financial priorities, geographic access barriers and awareness of treatment services. Perceived severity of drug use, a need for treatment variable) was also a partial predictor of utilization. CONCLUSIONS: Findings point to inequitable access to substance abuse treatment services among people from poor South African communities, with non-need factors being significant determinants of treatment utilization. In these communities, treatment utilization can be enhanced by (i) expanding the existing repertoire of services to include low threshold services that target individuals with less severe problems; (ii) providing food and transport vouchers as part of contingency management efforts, thereby reducing some of the financial and geographic access barriers; (iii) introducing community-based mobile outpatient treatment services that are geographically accessible; and (iv) employing community-based outreach workers that focus on improving awareness of where, when and how to access existing treatment services

The Cyprinodon variegatus genome reveals gene expression changes underlying differences in skull morphology among closely related species

Genes in durophage intersection set at 15 dpf. This is a comma separated table of the genes in the 15 dpf durophage intersection set. Given are edgeR results for each pairwise comparison. Columns indicating whether a gene is included in the intersection set at a threshold of 1.5 or 2 fold are provided. (CSV 13 kb

Squaring the circle: a priority-setting method for evidence-based service development, reconciling research with multiple stakeholder views.

BACKGROUND: This study demonstrates a technique to aid the implementation of research findings through an example of improving services and self-management in longer-term depression. In common with other long-term conditions, policy in this field requires innovation to be undertaken in the context of a whole system of care, be cost-effective, evidence-based and to comply with national clinical guidelines. At the same time, successful service development must be acceptable to clinicians and service users and choices must be made within limited resources. This paper describes a novel way of resolving these competing requirements by reconciling different sources and types of evidence and systematically engaging multiple stakeholder views. METHODS: The study combined results from mathematical modelling of the care pathway, research evidence on effective interventions and findings from qualitative research with service users in a series of workshops to define, refine and select candidate service improvements. A final consensus-generating workshop used structured discussion and anonymised electronic voting. This was followed by an email survey to all stakeholders, to achieve a pre-defined criterion of consensus for six suggestions for implementation. RESULTS: An initial list of over 20 ideas was grouped into four main areas. At the final workshop, each idea was presented in person, visually and in writing to 40 people, who assigned themselves to one or more of five stakeholder groups: i) service users and carers, ii) clinicians, iii) managers, iv) commissioners and v) researchers. Many belonged to more than one group. After two rounds of voting, consensus was reached on seven ideas and one runner up. The survey then confirmed the top six ideas to be tested in practice. CONCLUSIONS: The method recruited and retained people with diverse experience and views within a health community and took account of a full range of evidence. It enabled a diverse group of stakeholders to travel together in a direction that converged with the messages coming out of the research and successfully yielded priorities for service improvement that met competing requirements

A through-life costing methodology for use in product-service-systems

Availability-based contracts which provide customers with the use of assets such as machines, ships, aircraft platforms or subsystems like engines and avionics are increasingly offered as an alternative to the purchase of an asset and separate support contracts. The cost of servicing a durable product can be addressed by Through-life Costing (TLC). Providers of advanced services are now concerned with the cost of delivering outcomes that meet customer requirements using combinations of assets and activities via a Product Service System (PSS). This paper addresses the question: To what extent are the current approaches to TLC methodologically appropriate for costing the provision of advanced services, particularly availability, through a PSS? A novel methodology for TLC is outlined addressing the challenges of PSS cost assessment with regard to 'what?' (cost object), 'why/to what extent?' (scope and boundaries), and 'how?' (computations). The research provides clarity for those seeking to cost availability in a performance-orientated contractual setting and provides insight to the measures that may be associated with it. In particular, a reductionist approach that focuses on one cost object at a time is not appropriate for a PSS. Costing an advanced service delivered through a PSS is a problem of attributing the value of means to the economic activities carried out for specific ends to be achieved. Cost results from the interplay between monetary and non-monetary metrics, and uncertainties thereof. Whilst seeking to ensure generality of the findings, the application of TLC examined here is limited to a military aircraft platform and subsystems. © 2014 Elsevier B.V. All rights reserved