Increasing the quality of seismic interpretation

Acknowledgments E. Macrae was funded by an NERC Open CASE Ph.D. award (NE/F013728/1) with Midland Valley Exploration Ltd. as the industry partner. We thank 763 geoscientists for their participation, and in particular, the REs who gave their time freely to the project. M. Scott (University of Glasgow, UK) is thanked for assisting with the statistical analysis. Four reviewers are thanked for their constructive comments that improved the manuscript.Peer reviewedPublisher PD

Using a hypothetical scenario to assess public preferences for colorectal surveillance following screening-detected, intermediate-risk adenomas: annual home-based stool test vs. triennial colonoscopy

Background To assess public preferences for colorectal cancer (CRC) surveillance tests for intermediate-risk adenomas, using a hypothetical scenario. Methods Adults aged 45–54 years without CRC were identified from three General Practices in England (two in Cumbria, one in London). A postal survey was carried out during a separate study on preferences for different first-line CRC screening modalities (non- or full-laxative computed tomographic colonography, flexible sigmoidoscopy, or colonoscopy). Individuals were allocated at random to receive a pack containing information on one first-line test, and a paragraph describing CRC surveillance recommendations for people who are diagnosed with intermediate-risk adenomas during screening. All participants received a description of two surveillance options: annual single-sample, home-based stool testing (consistent with Faecal Immunochemical Tests; FIT) or triennial colonoscopy. Invitees were asked to imagine they had been diagnosed with intermediate-risk adenomas, and then complete a questionnaire on their surveillance preferences. Results 22.1 % (686/3,100) questionnaires were returned. 491 (15.8 %) were eligible for analysis. The majority of participants stated a surveillance preference for the stool test over colonoscopy (60.8 % vs 31.0 %; no preference: 8.1 %; no surveillance: 0.2 %). Women were more likely to prefer the stool test than men (66.7 % vs. 53.6 %; p = .011). The primary reason for preferring the stool test was that it would be done more frequently. The main reason to prefer colonoscopy was its superiority at finding polyps. Conclusions A majority of participants stated a preference for a surveillance test resembling FIT over colonoscopy. Future research should test whether this translates to greater adherence in a real surveillance setting

Differing calcification processes in cultured vascular smooth muscle cells and osteoblasts

© 2019 Published by Elsevier Inc.Arterial medial calcification (AMC) is the deposition of calcium phosphate mineral, often as hydroxyapatite, inthe medial layer of the arteries. AMC shares some similarities to skeletal mineralisation and has been associatedwith the transdifferentiation of vascular smooth muscle cells (VSMCs) towards an osteoblast-like phenotype. Thisstudy used primary mouse VSMCs and calvarial osteoblasts to directly compare the established and widely usedin vitromodels of AMC and bone formation. Significant differences were identified between osteoblasts andcalcifying VSMCs. First, osteoblasts formed large mineralised bone nodules that were associated with widespreaddeposition of an extracellular collagenous matrix. In contrast, VSMCs formed small discrete regions of calcifi-cation that were not associated with collagen deposition and did not resemble bone. Second, calcifying VSMCsdisplayed a progressive reduction in cell viability over time (≤7-fold), with a 50% increase in apoptosis,whereas osteoblast and control VSMCs viability remained unchanged. Third, osteoblasts expressed high levels ofalkaline phosphatase (TNAP) activity and TNAP inhibition reduced bone formation by to 90%. TNAP activity incalcifying VSMCs was∼100-fold lower than that of bone-forming osteoblasts and cultures treated withβ-gly-cerophosphate, a TNAP substrate, did not calcify. Furthermore, TNAP inhibition had no effect on VSMC calci-fication. Although, VSMC calcification was associated with increased mRNA expression of osteoblast-relatedgenes (e.g. Runx2, osterix, osteocalcin, osteopontin), the relative expression of these genes was up to 40-foldlower in calcifying VSMCs versus bone-forming osteoblasts. In summary, calcifying VSMCsin vitrodisplay somelimited osteoblast-like characteristics but also differ in several key respects: 1) their inability to form collagen-containing bone; 2) their lack of reliance on TNAP to promote mineral deposition; and, 3) the deleterious effectof calcification on their viability.Peer reviewedFinal Published versio

Identification of the growth arrest and DNA damage protein GADD34 in the normal human heart and demonstration of alterations in expression following myocardial ischaemia

Growth arrest and DNA damage protein 34 (GADD34) is a multifunctional protein upregulated in response to cellular stress and is believed to mediate DNA repair and restore protein synthesis. In the present study we have examined GADD34 immunoreactivity in human myocardial tissue at defined survival times following cardiac arrest and determined alterations in expression following ischaemia. In the normal human heart, GADD34 immunoreactivity was generally intense and present within most cells. GADD34 immunoreactivity was downregulated in tissue displaying ischaemic damage and remained intense in adjacent non-infarcted tissue. Unlike brain, GADD34 was not found to be upregulated in the peri-infarct zone. Cells displaying apoptotic changes were located in regions displaying reduced GADD34 immunoreactivity. In the brain, it is thought that GADD34 supports re-initiation of protein synthesis following ischaemia. Similarly, GADD34 may perform important functions in cardiac tissue in response to ischaemia

Metformin ameliorates valve interstitial cell calcification by promoting autophagic flux.

Calcific aortic valve disease (CAVD) is the most common heart disease of the developed world. It has previously been established that metformin administration reduces arterial calcification via autophagy; however, whether metformin directly regulates CAVD has yet to be elucidated. In the present study we investigated whether metformin alleviates valvular calcification through the autophagy-mediated recycling of Runx2.Calcification was reduced in rat valve interstitial cells (RVICs) by metformin treatment (0.5mM - 1.5mM) (P&lt;0.01), with a marked decrease in Runx2 protein expression compared to control cells (P&lt;0.05). Additionally, upregulated expression of Atg3 and Atg7 (key proteins required for autophagosome formation), was observed following metformin treatment (1mM). Blocking autophagic flux using Bafilomycin-A1 revealed colocalisation of Runx2 with LC3 puncta in metformin treated RVICs (P&lt;0.001). Comparable Runx2 accumulation was seen in LC3 positive autolysosomes present within cells that had been treated with both metformin and hydroxychloroquine in combination (P&lt;0.001). Mechanistic studies employing three-way co-immunoprecipitation with Runx2, p62 and LC3 suggested that Runx2 binds to LC3-II upon metformin treatment in VICs.Together these studies suggest that the utilisation of metformin may represent a novel strategy for the treatment of CAVD.<br/