Colonoscopic polyp detection rate is stable throughout the workday including evening colonoscopy sessions

Objective: Polyp detection rate (PDR) is an accepted measure of colonoscopy quality. Several factors may influence PDR including time of procedure and order of colonoscopy within a session. Our unit provides evening colonoscopy lists (6-9 pm). We examined whether colonoscopy performance declines in the evening. Design: Data for all National Health Service (NHS) outpatient colonoscopies performed at Norfolk and Norwich University Hospital in 2011 were examined. Timing, demographics, indication and colonoscopy findings were recorded. Statistical analysis was performed using multivariate regression. Results: Data from 2576 colonoscopies were included: 1163 (45.1%) in the morning, 1123 (43.6%) in the afternoon and 290 (11.3%) in the evening. Overall PDR was 40.80%. Males, increasing age and successful caecal intubation were all significantly associated with higher polyp detection. The indications ‘faecal occult blood screening’ (p<0.001) and ‘polyp surveillance’ (p<0.001) were strongly positively associated and ‘anaemia’ (p=0.01) was negatively associated with PDR. Following adjustment for covariates, there was no significant difference in PDR between sessions. With the morning as the reference value, the odds ratio for polyp detection in the afternoon and evening were 0.93 (95% CI = 0.72-1.18) and 1.15 (95%CI = 0.82-1.61) respectively. PDR was not affected by rank of colonoscopy within a list, sedation dose or trainee-involvement. Conclusions: Time of day did not affect polyp detection rate in clinical practice. Evening colonoscopy had equivalent efficacy and is an effective tool in meeting increasing demands for endoscopy. Standardisation was shown to have a considerable effect as demographics, indication and endoscopist varied substantially between sessions. Evening sessions were popular with a younger populatio

Focused Analysis of Exome Sequencing Data for Rare Germline Mutations in Familial and Sporadic Lung Cancer

AbstractIntroductionThe association between smoking-induced chronic obstructive pulmonary disease (COPD) and lung cancer (LC) is well documented. Recent genome-wide association studies (GWAS) have identified 28 susceptibility loci for LC, 10 for COPD, 32 for smoking behavior, and 63 for pulmonary function, totaling 107 nonoverlapping loci. Given that common variants have been found to be associated with LC in genome-wide association studies, exome sequencing of these high-priority regions has great potential to identify novel rare causal variants.MethodsTo search for disease-causing rare germline mutations, we used a variation of the extreme phenotype approach to select 48 patients with sporadic LC who reported histories of heavy smoking—37 of whom also exhibited carefully documented severe COPD (in whom smoking is considered the overwhelming determinant)—and 54 unique familial LC cases from families with at least three first-degree relatives with LC (who are likely enriched for genomic effects).ResultsBy focusing on exome profiles of the 107 target loci, we identified two key rare mutations. A heterozygous p.Arg696Cys variant in the coiled-coil domain containing 147 (CCDC147) gene at 10q25.1 was identified in one sporadic and two familial cases. The minor allele frequency (MAF) of this variant in the 1000 Genomes database is 0.0026. The p.Val26Met variant in the dopamine β-hydroxylase (DBH) gene at 9q34.2 was identified in two sporadic cases; the minor allele frequency of this mutation is 0.0034 according to the 1000 Genomes database. We also observed three suggestive rare mutations on 15q25.1: iron-responsive element binding protein neuronal 2 (IREB2); cholinergic receptor, nicotinic, alpha 5 (neuronal) (CHRNA5); and cholinergic receptor, nicotinic, beta 4 (CHRNB4).ConclusionsOur results demonstrated highly disruptive risk-conferring CCDC147 and DBH mutations

Multiple Merging Events in the Double Cluster A3128/A3125

Multi-fiber spectroscopy has been obtained for 335 galaxies in the field of the double cluster A3128/A3125, using the 2dF multi-fiber positioner on the AAT. A total of 532 objects in the double cluster now have known redshifts. We have also obtained a 20 ks Chandra ACIS-I image of A3128 and radio imaging with the MOST and the ATCA. The spatial-kinematic distribution of redshifts in the field of A3128/A3125, when combined with the Chandra image of A3128, reveals a variety of substructures present in the galaxy distribution and in the hot ICM. The most striking large-scale feature in the galaxy distribution is an underpopulated redshift zone ~4000 km/s on either side of the cluster velocity at ~17500 km/s. We attribute this depletion zone to the effect of the extensive Horologium-Reticulum Supercluster (HRS), within which A3128/A3125 is embedded. In addition, numerous smaller groups of galaxies are identified, particularly in the underpopulated region within +-4000 km/s of the cluster redshift. Due to the large gravitational influence of the HRS, these groups arrive at A3128 with a very high (hypersonic) infall velocity. Two of these groups appear as elongated filaments in position-velocity diagrams, indicating that they are tidally distended groups which have been disrupted after a close passage through A3128. We have identified a primary NE-SW merger axis connecting A3128 with A3125, along which the filaments are also oriented. In addition, the Chandra image reveals that the X-ray emission is split into two components, each with very small core radii, that are separated by ~1 Mpc along the NE-SW axis. We propose that the complex X-ray morphology is likely the result of the hypersonic infall of a relatively small group into A3128. The group produces a major disruption in the ICM due to its high infall velocity.Comment: 52 pages, 27 figures, accepted for publication in the Astronomical Journal. A more easily down-loaded version with full resolution figures is available at http://www.physics.unc.edu/~jim/a3128/LANL

90Y Radioembolization for Hepatic Malignancy in Patients with Previous Biliary Intervention: Multicenter Analysis of Hepatobiliary Infections

PurposeTo determine the frequency of hepatobiliary infections after transarterial radioembolization (TARE) with yttrium 90 (90Y) in patients with liver malignancy and a history of biliary intervention.Materials and MethodsFor this retrospective study, records of all consecutive patients with liver malignancy and history of biliary intervention treated with TARE at 14 centers between 2005 and 2015 were reviewed. Data regarding liver function, 90Y dosimetry, antibiotic prophylaxis, and bowel preparation prophylaxis were collected. Primary outcome was development of hepatobiliary infection.ResultsOne hundred twenty-six patients (84 men, 42 women; mean age, 68.8 years) with primary (n = 39) or metastatic (n = 87) liver malignancy and history of biliary intervention underwent 180 procedures with glass (92 procedures) or resin (88 procedures) microspheres. Hepatobiliary infections (liver abscesses in nine patients, cholangitis in five patients) developed in 10 of the 126 patients (7.9%) after 11 of the 180 procedures (6.1%; nine of those procedures were performed with glass microspheres). All patients required hospitalization (median stay, 12 days; range, 2–113 days). Ten patients required percutaneous abscess drainage, three patients underwent endoscopic stent placement and stone removal, and one patient needed insertion of percutaneous biliary drains. Infections resolved in five patients, four patients died (two from infection and two from cancer progression while infection was being treated), and one patient continued to receive suppressive antibiotics. Use of glass microspheres (P = .02), previous liver resection or ablation (P = .02), and younger age (P = .003) were independently predictive of higher infection risk.ConclusionInfectious complications such as liver abscess and cholangitis are uncommon but serious complications of transarterial radioembolization with 90Y in patients with liver malignancy and a history of biliary intervention.© RSNA, 2018Online supplemental material is available for this article

An Upstream Open Reading Frame Controls Translation of var2csa, a Gene Implicated in Placental Malaria

Malaria, caused by the parasite Plasmodium falciparum, is responsible for substantial morbidity, mortality and economic losses in tropical regions of the world. Pregnant women are exceptionally vulnerable to severe consequences of the infection, due to the specific adhesion of parasite-infected erythrocytes in the placenta. This adhesion is mediated by a unique variant of PfEMP1, a parasite encoded, hyper-variable antigen placed on the surface of infected cells. This variant, called VAR2CSA, binds to chondroitin sulfate A on syncytiotrophoblasts in the intervillous space of placentas. VAR2CSA appears to only be expressed in the presence of a placenta, suggesting that its expression is actively repressed in men, children or non-pregnant women; however, the mechanism of repression is not understood. Using cultured parasite lines and reporter gene constructs, we show that the gene encoding VAR2CSA contains a small upstream open reading frame that acts to repress translation of the resulting mRNA, revealing a novel form of gene regulation in malaria parasites. The mechanism underlying this translational repression is reversible, allowing high levels of protein translation upon selection, thus potentially enabling parasites to upregulate expression of this variant antigen in the presence of the appropriate host tissue

Investigating variation in replicability

Although replication is a central tenet of science, direct replications are rare in psychology. This research tested variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants. In the aggregate, 10 effects replicated consistently. One effect – imagined contact reducing prejudice – showed weak support for replicability. And two effects – flag priming influencing conservatism and currency priming influencing system justification – did not replicate. We compared whether the conditions such as lab versus online or US versus international sample predicted effect magnitudes. By and large they did not. The results of this small sample of effects suggest that replicability is more dependent on the effect itself than on the sample and setting used to investigate the effect