International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Equity of access to NHS cancer services for members of minority ethnic groups. Report of findings of surveys of hospital medical and nursing staff at the Royal Marsden Hospital

Executive Summary 1. The NHS Cancer Plan draws attention to the inequity of access to cancer services for members of minority ethnic groups, according importance to such matters as culturally-sensitive information and different approaches to giving information. The Department of Health's latest Cancer Services: Update states that 'to improve the experience of patients from an ethnic background' is a significant area of risk within the development of cancer services. Again, improving access and providing information and more informed choice to ethnic minority communities is identified as a priority . 2. This research study focuses on one particular dimension of access: the attitudes of hospital medical and nursing staff to inequity of access to NHS cancer services for members of minority ethnic groups. 3. Postally-administered questionnaire surveys for hospital doctors and nurses achieved overall response rates (omitting exclusions) of 52% and 69%, respectively (valid responses, 44 and 55%, respectively). 4. 16% of doctors and nurses thought that patients from minority ethnic groups usually or sometimes presented with disease at a more advanced stage than the general population. Research is needed to establish whether members of minority ethnic groups are diagnosed in later disease stages than other patients, after controlling for socio-economic status and other confounding factors. 5. While only 5% of nurses and doctors thought that clinicians were less willing to recruit members of minority ethnic groups into clinical trials compared with other patients, 16% of doctors and 12% of nurses thought that members of minority ethnic groups were not as willing to participate in clinical trials. Significant proportions of doctors and nurses had greater concerns (compared with other patients) with respect to obtaining informed consent, fulfilling safety requirements, and ensuring follow-up. Linguistic and cultural constraints upon the participation of members of minority ethnic groups in cancer trials were identified by respondents. The extent to which ethnic minorities are excluded from trials requires investigation. 6. Between a quarter and a third of respondents perceived their gender as a barrier in treating/caring for members of minority ethnic groups, especially with respect to Muslim and Asian women and Arab/Middle Eastern men. 10% of nurses found their ethnicity a barrier

Time to listen

Gaining authentic voices in the production of research includes reflection on the process of research itself. The following paper reports on the work of an advisory group and raises issues about the extent to which it should be anticipated that such groups represent the feelings and interests of the wider community without the infrastructure and support to enable them to access these. Should we therefore conclude that advisory group members only speak for themselves? The process of developing the article also surfaced the emotional impact of recognizing that,whilst people may not share the same opinion or view, all views are valid. The paper provides important insights on the experience of contributing to the work of the group and the practices that support this. It was co-written using transcripts of discussion together with debate on symbol selection, to select key meanings to share with a wider audience. The paper is submitted here in both forms, without commentary or distancing academic argument, in recognition of the true value of such partnerships

Correlating the Bethesda System for Reporting Thyroid Cytopathology with Histology and Extent of Surgery : A Review of 21,746 Patients from Four Endocrine Surgery Registries Across Two Continents

Background: The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category. Methods: Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed. Results: Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31–35 years (52.1%, 95% confidence interval (CI) 37.9–66.2%), aged 36–40 years (55.9%, 95% CI 39.2–72.6%) and aged 41–45 years (46.9%, 95% CI 33–60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males. Conclusions: These data demonstrate that Bethesda categories 1–4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC