Preferences for cancer investigation:a vignette-based study of primary-care attendees

SummaryBackgroundThe UK lags behind many European countries in terms of cancer survival. Initiatives to address this disparity have focused on barriers to presentation, symptom recognition, and referral for specialist investigation. Selection of patients for further investigation has come under particular scrutiny, although preferences for referral thresholds in the UK population have not been studied. We investigated preferences for diagnostic testing for colorectal, lung, and pancreatic cancers in primary-care attendees.MethodsIn a vignette-based study, researchers recruited individuals aged at least 40 years attending 26 general practices in three areas of England between Dec 6, 2011, and Aug 1, 2012. Participants completed up to three of 12 vignettes (four for each of lung, pancreatic, and colorectal cancers), which were randomly assigned. The vignettes outlined a set of symptoms, the risk that these symptoms might indicate cancer (1%, 2%, 5%, or 10%), the relevant testing process, probable treatment, possible alternative diagnoses, and prognosis if cancer were identified. Participants were asked whether they would opt for diagnostic testing on the basis of the information in the vignette.Findings3469 participants completed 6930 vignettes. 3052 individuals (88%) opted for investigation in their first vignette. We recorded no strong evidence that participants were more likely to opt for investigation with a 1% increase in risk of cancer (odds ratio [OR] 1·02, 95% CI 0·99–1·06; p=0·189), although the association between risk and opting for investigation was strong when colorectal cancer was analysed alone (1·08, 1·03–1·13; p=0·0001). In multivariable analysis, age had an effect in all three cancer models: participants aged 60–69 years were significantly more likely to opt for investigation than were those aged 40–59 years, and those aged 70 years or older were less likely. Other variables associated with increased likelihood of opting for investigation were shorter travel times to testing centre (colorectal and lung cancers), a family history of cancer (colorectal and lung cancers), and higher household income (colorectal and pancreatic cancers).InterpretationParticipants in our sample expressed a clear preference for diagnostic testing at all risk levels, and individuals want to be tested at risk levels well below those stipulated by UK guidelines. This willingness should be considered during design of cancer pathways, particularly in primary care. The public engagement with our study should encourage general practitioners to involve patients in referral decision making.FundingThe National Institute for Health Research Programme Grants for Applied Research programme

Lower Coverdale and Gaytons: Middle Devonian and possibly older anorthosite-ferronorite, gabbro, and quartz monzonite intrusions in southeastern New Brunswick

The Lower Coverdale intrusion near Moncton, New Brunswick, has been intersected in drill holes at depths of 100–200 m below unconformably overlying Carboniferous sandstone, onglomerate and, locally, limestone of the Windsor, Mabou, and Cumberland groups. A large positive aeromagnetic anomaly suggests that the intrusion has a subsurface area of at least 30–40 km2. As revealed by drill core and cuttings, the intrusion consists of interlayered coarse-grained anorthosite and ferronorite, both intruded by gabbro, quartz monzonite, and minor felsic dykes. The ferronorite is high in Ti and P, and contains interstitial patite and ilmenite/magnetite and layers of apatite-ilmenite rock (nelsonite) up to several metres thick. Much of the core shows pervasive effects of metamorphism and alteration but microprobe analyses of the freshest samples revealed that the plagioclase in both anorthosite and ferronorite has andesine composition. The anorthosite and ferronorite are chemically distinct, but their close spatial association suggests a genetic link. In contrast, the younger gabbroic rocks differ in mineralogy and chemistry from, and appear unrelated to, the anorthosite and ferronorite. They are altered but not metamorphosed, and preserve intergranular textures. They contain more calcic plagioclase and augite, and have low Ti and P. The deepest drill hole in the Lower Coverdale intrusion encountered highly altered coarse-grained quartz monzonite at a depth of 1095–1206 m. The quartz monzonite is mineralogically and chemically similar to quartz monzonite in quarries near Gaytons, 20 km to the east. Virtually identical Middle Devonian U-Pb zircon ages of 90.6 ± 1.0 Ma and 390.0 ± 0.5 Ma were obtained for samples from the Lower Coverdale and Gaytons quartz monzonite, espectively. However, the anorthosite-ferronoritegabbro is likely considerably older: perhaps ca. 540 Ma like gabbroic rocks elsewhere in the Brookville terrane; or possibly esoproterozoic, like intrusions with similar characteristics in Grenvillian parts of the Precambrian shield. RÉSUMÉ On a croisé l’intrusion de Lower Coverdale près de Moncton (Nouveau-Brunswick) dans des puits forés à des profondeurs de 100 à 200 m au-dessous de grès du Carbonifère sus-jacent non concordant, de conglomérat et, par endroits, de calcaire des groupes de Windsor, de Mabou et de Cumberland. Une anomalie aéromagnétique positive étendue permet de supposer que l’intrusion a une superficie souterraine d’au moins 30 à 40 kilomètres carrés. Les carottes de forage et les déblais révèlent que l’intrusion est constituée de ferronorite et d’anorthosite à grains grossiers interstratifiées, toutes deux pénétrées par du gabbro, de l’adamellite et des dykes felsiques secondaires. La ferronorite est riche en Ti et en P et renferme de ’ilménite/magnétite et de l’apatite interstitielles ainsi que des couches d’ilménite-apatite (nelsonite) pouvant avoir plusieurs mètres d’épaisseur. Une vaste part des carottes témoignent des effets intenses d’un métamorphisme et d’une altération, mais des analyses à la microsonde des échantillons les plus frais ont révélé que le plagioclase à l’intérieur de l’anorthosite et de la ferronorite est composé d’andésine. L’anorthosite et la ferronorite sont chimiquement distinctes, mais leur association spatiale étroite laisse supposer un lien génétique. Par contre, les roches gabbroïques plus récentes ont une composition minéralogique et chimique différant de celles de l’anorthosite et de la ferronorite et elles ne semblent pas y être apparentées. Elles sont altérées mais ne sont pas métamorphisées et elles conservent des textures intergranulaires. Elles renferment plus de plagioclase calcique et d’augite et ont une faible teneur en Ti et en P. Le puits de forage le plus profond dans l’intrusion de Lower Coverdale a recoupé de l’adamellite à grains grossiers fortement altérée à une profondeur de 1 095 à 1 206 m. L’adamellite est minéralogiquement et chimiquement similaire à l’adamellite des carrières situées près de Gaytons, à 20 kilomètres à l’est. On a obtenu des datations U-Pb sur zircon pratiquement identiques du Dévonien moyen de 390,6 ± 1,0 Ma et de 390,0 ± 0,5 Ma d’échantillons d’adamellite de Lower Coverdale et de Gaytons, respectivement. Le gabbro l’anorthosite-ferronorite, toutefois, est probablement beaucoup plus âgé : il a peut-être 540 Ma, comme les roches gabbroïques d’ailleurs à l’intérieur du terrane de Brookville, ou il pourrait remonter au Mésoprotérozoïque, comme les intrusions présentant des caractéristiques analogues dans les parties grenvilliennes du bouclier précambrien

Granitoid plutons of the Brookville terrane, southern New Brunswick: petrology, age, and tectonic setting

Latest Neoproterozoic and Cambrian plutons in the Brookville terrane of southern New Brunswick are termed the Golden Grove Plutonic Suite. Four groups are recognized on the basis of composition: gabbro (2 plutons), diorite - granodiorite (17 plutons), granodiorite - monzogranite (8 plutons), and syenogranite - monzogranite (7 plutons). The dioritic to granodioritic and most of the granodioritic to monzogranitic plutons form linear trends on chemical variation diagrams, suggesting that magma evolution was dominated by plagioclase and amphibole fractionation. These plutons appear to constitute a typical I-type, calc-alkaline suite characteristic of continental margin subduction zones. This interpretation is supported by U-Pb zircon ages, which show that these plutons have ages between 540 Ma and 526 Ma. A new U-Pb age of 539.6 ± 1.2 Ma from one of the gabbroic plutons shows that the gabbroic plutons are co-genetic with the dioritic to granitic plutons, although they show varied ultramafic to anorthositic and dioritic compositions as a result of crystal accumulation. The syenogranitic to monzogranitic plutons and two of the granodioritic and monzogranitic plutons, as well as felsic volcanic rocks of the Dipper Harbour volcanic unit, show chemical trends that differ from the other plutons in having A-type characteristics. A U-Pb age of 548 ± 2 Ma for the Fairville Granite, as well as similar ages for a syenogranitic pluton and the Dipper Harbour volcanic unit, suggests that these units represent early stages of magmatism in the Golden Grove Plutonic Suite. RESUMÉ Les plutons du Cambrien et des périodes les plus anciennes du Néoprotérozoïque à l'intérieur du terrane de Brookville dans le Sud du Nouveau-Brunswick sont désignés sous le nom de « cortège plutonique de Golden Grove ». On y distingue quatre groupes en fonction de leur composition : ceux à base de gabbro (deux plutons), de diorite - granodiorite (17 plutons), de granodiorite - monzogranite (huit plutons) et de syénogranite - monzogranite (sept plutons). Les plutons dioritiques à granodioritiques et la majorité des plutons granodioritiques à monzogranitiques forment des tracés linéaires sur les schémas de diversité de la composition chimique, ce qui laisse supposer que l'évolution magmatique a été dominée par une cristallisation fractionnée des plagioclases et des amphiboles. Ces plutons semblent constituer un cortège calco-alcalin intrusif typique, caractéristique des zones de subduction de la marge continentale. Cette interprétation est corroborée par la datation au U-Pb, obtenue à partir de zircon, qui révèle que ces plutons ont des âges entre 540 Ma et 526 Ma. Une nouvelle datation au U-Pb obtenue à partir de zircon situant à 539,6 ± 1,2 Ma l'âge de l'un des plutons gabbroïques, signale que les plutons gabbroïques sont cogénétiques avec les plutons dioritiques à granitiques, même s'ils présentent des compositions ultramafi ques à anorthositiques et dioritiques diversifi ées par suite d'une accumulation de cristaux. Les plutons syénogranitiques à monzogranitiques et deux des plutons granodioritiques et monzogranitiques, de même que les roches volcanofelsiques de l'unité volcanique de Dipper Harbour, livrent des tracés chimiques différents des autres plutons du fait qu'ils possèdent les caractéristiques des plutons de type anorogénique. L'âge au U-Pb de 548 ± 2 Ma du granite de Fairville ainsi que les âges similaires d'un pluton syénogranitique et de l'unité volcanique de Dipper Harbour permettent de supposer que ces unités représentent les stades précoces du magmatisme à l'intérieur du cortège plutonique de Golden Grove

Using willingness-to-pay to establish patient preferences for cancer testing in primary care.

BACKGROUND: Shared decision making is a stated aim of several healthcare systems. In the area of cancer, patients' views have informed policy on screening and treatment but there is little information about their views on diagnostic testing in relation to symptom severity. METHODS: We used the technique of willingness-to-pay to determine public preferences around diagnostic testing for colorectal, lung, and pancreatic cancer in primary care in the UK. Participants were approached in general practice waiting rooms and asked to complete a two-stage electronic survey that described symptoms of cancer, the likelihood that the symptoms indicate cancer, and information about the appropriate diagnostic test. Part 1 asked for a binary response (yes/no) as to whether they would choose to have a test if it were offered. Part 2 elicited willingness-to-pay values of the tests using a payment scale followed by a bidding exercise, with the aim that these values would provide a strength of preference not detectable using the binary approach. RESULTS: A large majority of participants chose to be tested for all cancers, with only colonoscopy (colorectal cancer) demonstrating a risk gradient. In the willingness-to-pay exercise participants placed a lower value on an X-ray (lung cancer) than the tests for colorectal or pancreatic cancer and X-ray was the only test where risk was clearly related to the willingness-to-pay value. CONCLUSION: Willingness-to-pay values did not enhance the binary responses in the way intended; participants appeared to be motivated differently when responding to the two parts of the questionnaire. More work is needed to understand how participants perceive risk in this context and how they respond to questions about willingness-to-pay. Qualitative methods could provide useful insights

Transmission of Salmonella enteritidis after endoscopic retrograde cholangiopancreatography because of inadequate endoscope decontamination

We report a historic nosocomial outbreak of Salmonella enteritidis affecting 4 inpatients who underwent endoscopic retrograde cholangiopancreatography. The cause was attributed to inadequate decontamination of an on-loan endoscope used over a weekend. This report highlights the risks of using on-loan endoscopes, particularly regarding their commissioning and adherence to disinfection protocols. In an era of increasing antibiotic resistance, transmission of Enterobacteriaceae by endoscopes remains a significant concern

Identification of the major proteins of an immune modulating fraction from adult Fasciola hepatica released by Nonidet P40

Fasciola hepatica NP-40 released antigens (FhTeg) exhibit potent Th1 immunosuppressive properties in vitro and in vivo. However, the protein composition of this active fraction, responsible for Th1 immune modulatory activity, has yet to be resolved. Therefore, FhTeg, a Nonidet P-40 extract, was subjected to a proteomic analysis in order to identify individual protein components. This was performed using an in house F. hepatica EST database following 2D electrophoresis combined with de novo sequencing based mass spectrometry. The identified proteins, a mixture of excretory/secretory and membrane-associated proteins, are associated with stress response and chaperoning, energy metabolism and cytoskeletal components. The immune modulatory properties of these identified protein(s) is discussed and HSP70 from F. hepatica is highlighted as a potential host immune modulator for future study

Connectivity mapping using a combined gene signature from multiple colorectal cancer datasets identified candidate drugs including existing chemotherapies

BACKGROUND: While the discovery of new drugs is a complex, lengthy and costly process, identifying new uses for existing drugs is a cost-effective approach to therapeutic discovery. Connectivity mapping integrates gene expression profiling with advanced algorithms to connect genes, diseases and small molecule compounds and has been applied in a large number of studies to identify potential drugs, particularly to facilitate drug repurposing. Colorectal cancer (CRC) is a commonly diagnosed cancer with high mortality rates, presenting a worldwide health problem. With the advancement of high throughput omics technologies, a number of large scale gene expression profiling studies have been conducted on CRCs, providing multiple datasets in gene expression data repositories. In this work, we systematically apply gene expression connectivity mapping to multiple CRC datasets to identify candidate therapeutics to this disease. RESULTS: We developed a robust method to compile a combined gene signature for colorectal cancer across multiple datasets. Connectivity mapping analysis with this signature of 148 genes identified 10 candidate compounds, including irinotecan and etoposide, which are chemotherapy drugs currently used to treat CRCs. These results indicate that we have discovered high quality connections between the CRC disease state and the candidate compounds, and that the gene signature we created may be used as a potential therapeutic target in treating the disease. The method we proposed is highly effective in generating quality gene signature through multiple datasets; the publication of the combined CRC gene signature and the list of candidate compounds from this work will benefit both cancer and systems biology research communities for further development and investigations