Computed tomography colonography: Radiographer independent preliminary clinical evaluation for intraluminal pathology

This is the author accepted manuscript; the final version is available from Elsevier via the DOI in this recordIntroduction: We evaluated the reporting competency of radiographers providing preliminary clinical evaluations (PCE) for intraluminal pathology of computed tomography colonography (CTC). Method: Following validation of a suitable tool, audit was undertaken to compare radiographer PCE against radiology reports. A database was designed to capture radiographer and radiologist report data. The radiographer's PCE of intraluminal pathology was given a score, the “pathology discrepancy and significance” (PDS) score based on the pathology present, any discrepancy between the PCE and the final report, and the significance of that discrepancy on the management of the patient. Agreement was assessed using percentage agreement and Kappa coefficient. Significant discrepancies between findings were compared against endoscopy and pathology reports. Results: There was agreement or insignificant discrepancy between the radiographer PCE and the radiology report for 1736 patients, representing 97.0% of cases. There was a significant discrepancy between findings in 2.8% of cases and a major discrepancy recorded for 0.2% of cases. There was a 98.4% agreement in the 229 cases where significant pathologies were present. Conclusion: From a database of 1815 studies acquired over three years and representing work done in a clinical environment, this study indicates a potential for trained radiographers to provide a PCE of intraluminal pathology

Individualized Angiotensin‐Converting Enzyme (ACE)‐Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model

Patients with stable coronary artery disease (CAD) constitute a heterogeneous group in which the treatment benefits by angiotensin-converting enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to integrate clinical and pharmacogenetic determinants in an ultimate combined risk prediction model.Clinical, genetic, and outcomes data were used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of perindopril versus placebo. Multivariable analysis of phenotype data resulted in a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in the bradykinin type I-receptor gene) were used to construct a pharmacogenetic risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow-up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients with PGXscore of 0 to 2. As a consequence, estimated annual numbers needed to treat ranged from as low as 29 (clinical risk score ≥10 and PGXscore of 0) to 521 (clinical risk score ≤6 and PGXscore of 2). Furthermore, our data suggest that long-term perindopril prescription in patients with a PGXscore of 0 to 2 is cost-effective.Both baseline clinical phenotype, as well as genotype determine the efficacy of widely prescribed ACE inhibition in stable CAD. Integration of clinical and pharmacogenetic determinants in a combined risk prediction model demonstrated a very wide range of gradients of absolute treatment benefit

Late Cenozoic deepening of Yosemite Valley, USA

Although Yosemite Valley, USA, catalyzed the modern environmental movement and fueled foundational debates in geomorphology, a century of investigation has failed to definitively determine when it formed. The non-depositional nature of the landscape and homogeneous bedrock have prevented direct geological assessments. Indirect assumptions about the age of downcutting have ranged from pre-Eocene to Pleistocene. Clarity on this issue would not only satisfy public interest but also provide a new constraint for contentious debates about the Cenozoic tectonic and geomorphologic history of the Sierra Nevada in California. Here we use thermochronometric analysis of radiogenic helium in apatite crystals, coupled with numerical models of crustal temperatures beneath evolving topography, to demonstrate significant late Cenozoic deepening of Tenaya Canyon, Yosemite’s northeastern branch. Approximately 40%–90% of the current relief has developed since 10 Ma and most likely since 5 Ma. This coincides with renewed regional tectonism, which is a long-hypothesized but much debated driver of Sierran canyon development. Pleistocene glaciation caused spatially variable incision and valley widening in Yosemite Valley, whereas little contemporaneous erosion occurred in the adjacent upper Tuolumne watershed. Such variations probably arise from glacial erosion’s dependence on topographic focusing of ice discharge into zones of rapid flow, and on the abundance of pre-existing fractures in the substrate. All available data, including those from our study, are consistent with a moderately high and slowly eroding mid-Cenozoic Sierra Nevada followed by significant late Cenozoic incision of some, but not all, west-side canyon

Should I stay or should I go? Fitness costs and benefits of prolonged parent-offspring and sibling-sibling associations in an Arctic-nesting goose population.

This is the final version of the article. Available from the publisher via the DOI in this record.Theory predicts persistence of long-term family relationships in vertebrates will occur until perceived fitness costs exceed benefits to either parents or offspring. We examined whether increased breeding probability and survival were associated with prolonged parent-offspring and sibling-sibling relationships in a long-lived Arctic migrant herbivore, the Greenland white-fronted goose (Anser albifrons flavirostris). Although offspring associated with parents for 1-13 years, 79 % of these associations lasted two or less years. Only 65 (9.9 %) of the 656 marked offspring bred once in their lifetime, and just 16 (2.4 %) bred twice or more. The probability of birds with siblings breeding successfully in a subsequent year was credibly greater than that of independent birds at ages 5, 6, and 7. Survival of offspring with parents was credibly greater than that of independent/nonbreeder birds at all possible ages (i.e., ages 2-7+). A cost-benefit matrix model utilizing breeding and survival probabilities showed that staying with family groups was favored over leaving until age 3, after which there were no credible differences between staying and leaving strategies until the oldest ages, when leaving family groups was favored. Thus, most birds in this study either departed family groups early (e.g., at age 2, when the "stay" strategy was favored) or as predicted by our cost-benefit model (i.e., at age 3). Although extended family associations are a feature of this population, we contend that the survival benefits are not sufficient enough to yield clear fitness benefits, and associations only persist because parents and offspring mutually benefit from their persistence.This research was funded through a joint PhD studentship from the Wildfowl & Wetlands Trust and the University of Exeter undertaken by MDW

Non-destructive monitoring of viability in an ex vivo organ culture model of osteochondral tissue

Organ culture is an increasingly important tool in research, with advantages over monolayer cell culture due to the inherent natural environment of tissues. Successful organ cultures must retain cell viability. The aim of this study was to produce viable and non-viable osteochondral organ cultures to assess the accumulation of soluble markers in the conditioned medium for predicting tissue viability. Porcine femoral osteochondral plugs were cultured for 20 days, with the addition on day 6, of Triton X-100 (to induce necrosis), camptothecin (to induce apoptosis) or no toxic additives. Tissue viability was assessed by the tissue destructive XTT (sodium 3'-[1-[(phenylamino)-carbonyl]-3,4-tetrazolium]-bis(4-methoxy-6-nitro)benzene-sulfonic acid hydrate) assay method and LIVE/DEAD® staining of the cartilage at days 0, 6 and 20. Tissue structure was assessed by histological evaluation using haematoxylin & eosin and safranin O. Conditioned medium was assessed every 3-4 days for glucose depletion, and levels of lactate dehydrogenase (LDH), alkaline phosphatase (AP), glycosaminoglycans (GAGs), and matrix metalloproteinase (MMP)-2 and MMP-9. Necrotic cultures immediately showed a reduction in glucose consumption, and an immediate increase in LDH, GAG, MMP-2 and MMP-9 levels. Apoptotic cultures showed a delayed reduction in glucose consumption and delayed increase in LDH, a small rise in MMP-2 and MMP-9, but no significant effect on GAGs released into the conditioned medium. The data showed that tissue viability could be monitored by assessing the conditioned medium for the aforementioned markers, negating the need for tissue destructive assays. Physiologically relevant whole- or part-joint organ culture models, necessary for research and pre-clinical assessment of therapies, could be monitored this way, reducing the need to sacrifice tissues to determine viability, and hence reducing the sample numbers necessary

Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of reninangiotensinaldosterone system inhibitors involving 158 998 patients

AimsRenin-Angiotensin-Aldosterone system (RAAS) inhibitors are well established for the reduction in cardiovascular morbidity, but their impact on all-cause mortality in hypertensive patients is uncertain. Our objective was to analyse the effects of RAAS inhibitors as a class of drugs, as well as of angiotensin-converting enzyme (ACE) inhibitors and AT1 receptor blockers (ARBs) separately, on all-cause mortality. Methods and resultsWe performed a pooled analysis of 20 cardiovascular morbiditymortality trials. In each trial at least two-thirds of the patients had to be diagnosed with hypertension, according to the trial-specific definition, and randomized to treatment with an RAAS inhibitor or control treatment. The cohort included 158 998 patients (71 401 RAAS inhibitor; 87 597 control). The incidence of all-cause death was 20.9 and 23.3 per 1000 patient-years in patients randomized to RAAS inhibition and controls, respectively. Overall, RAAS inhibition was associated with a 5 reduction in all-cause mortality (HR: 0.95, 95 CI: 0.911.00, P = 0.032), and a 7 reduction in cardiovascular mortality (HR: 0.93, 95 CI: 0.880.99, P = 0.018). The observed treatment effect resulted entirely from the class of ACE inhibitors, which were associated with a significant 10 reduction in all-cause mortality (HR: 0.90, 95 CI: 0.840.97, P = 0.004), whereas no mortality reduction could be demonstrated with ARB treatment (HR: 0.99, 95 CI: 0.941.04, P = 0.683). This difference in treatment effect between ACE inhibitors and ARBs on all-cause mortality was statistically significant (P-value for heterogeneity 0.036). ConclusionIn patients with hypertension, treatment with an ACE inhibitor results in a significant further reduction in all-cause mortality. Because of the high prevalence of hypertension, the widespread use of ACE inhibitors may result in an important gain in lives saved

The development and evaluation of an audit tool for measuring reporting accuracy of radiographers compared with radiologists for intra-luminal pathology detected at computed tomography colonography (CTC)

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Objective: To design and test an audit tool to measure the reporting accuracy of radiographers using radiologist reports as the gold standard. Design: A database was designed to capture radiographer and radiologist report data. The radiographer preliminary evaluation of intraluminal pathology was given a score (PDS score) by the reporting radiologist based on the pathology present, the discrepancy between the preliminary evaluation and the final report and the significance of that discrepancy on the clinical management of the patient. To test the reliability of this scoring system, 30 randomly selected cases (n=1815) were retrospectively compared and assessed for accuracy using the PDS score by 3 independent practitioners. Inter rater reliability was assessed using percentage agreement and kappa scores. Results: There was 100% agreement between participants for all significant pathologies. Inter rater agreement was 80-93% for normal studies and insignificant pathologies. Conclusion: Results indicate that the tool provides a practical, easy to use and reliable method to record, monitor and evaluate a preliminary evaluation of the colon by radiographers