Origin of basalts by hybridization in andesite-dominated arcs

Mafic magmas are common in subduction zone settings, yet their high density restricts their ascent to the surface. Once stalled in the crust, these magmas may differentiate, assimilate crust and other melts and mushes to produce hybridised intermediate magmas. The Soufriere Hills Volcano on Montserrat is a ‘type locality’ for these hybridisation processes and yet, just 3 km south of the crater, voluminous basalts have erupted from the South Soufriere Hills volcano within the same time period as the Soufriere Hills Volcano was erupting hybrid andesites (131 - 128 ka). Basaltic South Soufriere Hills magmas have 48 - 53 32 wt% SiO2 and 4 - 6 wt% MgO. They were hot (970 - 1160 °C), volatile-rich (melt inclusions contain up to 6.2 wt% H2O) and were stored at 8 – 13 km prior to eruption (based on olivine and pyroxene-hosted melt inclusion volatile geochemistry). Melt inclusions do not preserve basaltic liquids: they are andesitic to rhyolitic in composition, related to one another by a line of descent controlled by simple closed-system fractionation. Whole rock compositions, however, are best described by a hybridisation model involving “back”-mixing of andesitic to rhyolitic melts with mafic crystal phases such as magnetite, olivine, orthopyroxene and clinopyroxene. Phenocryst zoning illustrates repeated mixing events between evolved melts and mafic phenocrysts, which, when coupled with the heterogeneity of crystal compositions, strongly suggests that although the bulk composition is basalt (containing Fo80 olivine), they were assembled from disparate ingredients, likely derived from mafic crystal mushes and more evolved melt lenses of variable composition. The mixing events occur days to weeks prior to eruption. We propose that the South Soufriere Hills basaltic magmas, with their higher bulk density over andesites from neighbouring volcanoes, ultimately may have been eruptible owing to both the transtensional tectonics imposed by offshore grabens (related to the oblique subduction of the Lesser Antilles) and to surface unloading caused by large scale edifice collapse. Our observations support the idea that compositional changes in arcs might reflect not only changes in source compositions, but also effects caused by patterns in crustal strain and tectonics.MC and SFLW thank NERC for financial support via grant NE/K000403/1.This is the accepted manuscript. The final version is available from OUP at http://dx.doi.org/10.1093/petrology/egv00

The LLP risk model: an individual risk prediction model for lung cancer

Using a model-based approach, we estimated the probability that an individual, with a specified combination of risk factors, would develop lung cancer within a 5-year period

The Hippo pathway transcription factors YAP and TAZ play HPV-type dependent roles in cervical cancer

Human papillomaviruses (HPVs) cause most cervical cancers and an increasing number of anogenital and oral carcinomas, with most cases caused by HPV16 or HPV18. HPV hijacks host signalling pathways to promote carcinogenesis. Understanding these interactions could permit identification of much-needed therapeutics for HPV-driven malignancies. The Hippo signalling pathway is important in HPV+ cancers, with the downstream effector YAP playing a pro-oncogenic role. In contrast, the significance of its paralogue TAZ remains largely uncharacterised in these cancers. We demonstrate that TAZ is dysregulated in a HPV-type dependent manner by a distinct mechanism to that of YAP and controls proliferation via alternative cellular targets. Analysis of cervical cancer cell lines and patient biopsies revealed that TAZ expression was only significantly increased in HPV18+ and HPV18-like cells and TAZ knockdown reduced proliferation, migration and invasion only in HPV18+ cells. RNA-sequencing of HPV18+ cervical cells revealed that YAP and TAZ have distinct targets, suggesting they promote carcinogenesis by different mechanisms. Thus, in HPV18+ cancers, YAP and TAZ play non-redundant roles. This analysis identified TOGARAM2 as a previously uncharacterised TAZ target and demonstrates its role as a key effector of TAZ-mediated proliferation, migration and invasion in HPV18+ cancers

Male reproductive health and environmental xenoestrogens

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.Supported by EU Contract BMH4-CT96-0314

Emerging advantages and drawbacks of telephone surveying in public health research in Ireland and the U.K

BACKGROUND: Telephone surveys have been used widely in public health research internationally and are being increasingly used in Ireland and the U.K. METHODS: This study compared three telephone surveys conducted on the island of Ireland from 2000 to 2004, examining study methodology, outcome measures and the per unit cost of each completed survey. We critically examined these population-based surveys which all explored health related attitudes and behaviours. RESULTS: Over the period from 2000 to 2005 the percentage of calls which succeeded in contacting an eligible member of the public fell, from 52.9% to 31.8%. There was a drop in response rates to the surveys (once contact was established) from 58.6% to 17.7%. Costs per completed interview rose from €4.48 to €15.65. Respondents were prepared to spend 10–15 minutes being surveyed, but longer surveys yielded poorer completion rates. Respondents were willing to discuss issues of a sensitive nature. Interviews after 9 pm were less successful, with complaints about the lateness of the call. Randomisation from electronic residential telephone directory databases excluded all ex-directory numbers and thus was not as representative of the general population as number generation by the hundred-bank method. However the directory database was more efficient in excluding business and fax numbers. CONCLUSION: Researchers should take cognisance of under-representativeness of land-line telephone surveys, of the increasing difficulties in contacting the public and of mounting personnel costs. We conclude that telephone surveying now requires additional strategies such as a multimode approach, or incentivisation, to be a useful, cost-effective means of acquiring data on public health matters in Ireland and the U.K

A programme to spread eGFR graph surveillance for the early identification, support and treatment of people with progressive chronic kidney disease (ASSIST-CKD): protocol for the stepped wedge implementation and evaluation of an intervention to reduce late presentation for renal replacement therapy

Background Patients who start renal replacement therapy (RRT) for End-Stage Kidney Disease (ESKD) without having had timely access to specialist renal services have poor outcomes. At one NHS Trust in England, a community-wide CKD management system has led to a decline in the incident rate of RRT and the lowest percentage of patients presenting within 90 days of starting RRT in the UK. We describe the protocol for a quality improvement project to scale up and evaluate this innovation. Methods The intervention is based upon an off-line database that integrates laboratory results from blood samples taken in all settings stored under different identifying labels relating to the same patient. Graphs of estimated glomerular filtration rate (eGFR) over time are generated for patients 65 years with an incoming eGFR <40 ml/min/1.73 m2. Graphs where kidney function is deteriorating are flagged by a laboratory scientist and details sent to the primary care doctor (GP) with a prompt that further action may be needed. We will evaluate the impact of implementing this intervention across a large population served by a number of UK renal centres using a mixed methods approach. We are following a stepped-wedge design. The order of implementation among participating centres will be randomly allocated. Implementation will proceed with unidirectional steps from control group to intervention group until all centres are generating graphs of eGFR over time. The primary outcome for the quantitative evaluation is the proportion of patients referred to specialist renal services within 90 days of commencing RRT, using data collected routinely by the UK Renal Registry. The qualitative evaluation will investigate facilitators and barriers to adoption and spread of the intervention. It will include: semi-structured interviews with laboratory staff, renal centre staff and service commissioners; an online survey of GPs receiving the intervention; and focus groups of primary care staff. Discussion Late presentation to nephrology for patients with ESKD is a source of potentially avoidable harm. This protocol describes a robust quantitative and qualitative evaluation of a quality improvement intervention to reduce late presentation and improve the outcomes for patients with ESKD

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty