Rare Exonic Minisatellite Alleles in MUC2 Influence Susceptibility to Gastric Carcinoma

BACKGROUND: Mucins are the major components of mucus and their genes share a common, centrally-located region of sequence that encodes tandem repeats. Mucins are well known genes with respect to their specific expression levels; however, their genomic levels are unclear because of complex genomic properties. In this study, we identified eight novel minisatellites from the entire MUC2 region and investigated how allelic variation in these minisatellites may affect susceptibility to gastrointestinal cancer. METHODOLOGY/PRINCIPLE FINDINGS: We analyzed genomic DNA from the blood of normal healthy individuals and multi-generational family groups. Six of the eight minisatellites exhibited polymorphism and were transmitted meiotically in seven families, following Mendelian inheritance. Furthermore, a case-control study was performed that compared genomic DNA from 457 cancer-free controls with DNA from individuals with gastric (455), colon (192) and rectal (271) cancers. A statistically significant association was identified between rare exonic MUC2-MS6 alleles and the occurrence of gastric cancer: odds ratio (OR), 2.56; 95% confidence interval (CI), 1.31-5.04; and p = 0.0047. We focused on an association between rare alleles and gastric cancer. Rare alleles were divided into short (40, 43 and 44) and long (47, 50 and 54), according to their TR (tandem repeats) lengths. Interestingly, short rare alleles were associated with gastric cancer (OR = 5.6, 95% CI: 1.93-16.42; p = 0.00036). Moreover, hypervariable MUC2 minisatellites were analyzed in matched blood and cancer tissue from 28 patients with gastric cancer and in 4 cases of MUC2-MS2, minisatellites were found to have undergone rearrangement. CONCLUSIONS/SIGNIFICANCE: Our observations suggest that the short rare MUC2-MS6 alleles could function as identifiers for risk of gastric cancer. Additionally, we suggest that minisatellite instability might be associated with MUC2 function in cancer cells

Declining Orangutan Encounter Rates from Wallace to the Present Suggest the Species Was Once More Abundant

BACKGROUND: Bornean orangutans (Pongo pygmaeus) currently occur at low densities and seeing a wild one is a rare event. Compared to present low encounter rates of orangutans, it is striking how many orangutan each day historic collectors like Alfred Russel Wallace were able to shoot continuously over weeks or even months. Does that indicate that some 150 years ago encounter rates with orangutans, or their densities, were higher than now? METHODOLOGY/PRINCIPAL FINDINGS: We test this hypothesis by quantifying encounter rates obtained from hunting accounts, museum collections, and recent field studies, and analysing whether there is a declining trend over time. Logistic regression analyses of our data support such a decline on Borneo between the mid-19th century and the present. Even when controlled for variation in the size of survey and hunting teams and the durations of expeditions, mean daily encounter rates appear to have declined about 6-fold in areas with little or no forest disturbance. CONCLUSIONS/SIGNIFICANCE: This finding has potential consequences for our understanding of orangutans, because it suggests that Bornean orangutans once occurred at higher densities. We explore potential explanations-habitat loss and degradation, hunting, and disease-and conclude that hunting fits the observed patterns best. This suggests that hunting has been underestimated as a key causal factor of orangutan density and distribution, and that species population declines have been more severe than previously estimated based on habitat loss only. Our findings may require us to rethink the biology of orangutans, with much of our ecological understanding possibly being based on field studies of animals living at lower densities than they did historically. Our approach of quantifying species encounter rates from historic data demonstrates that this method can yield valuable information about the ecology and population density of species in the past, providing new insight into species' conservation needs

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Recent advances in the surgical management of rhinosinusitis [version 1; referees: 4 approved]

Rhinosinusitis affects a significant portion of the US population, and its management imposes a substantial burden on the healthcare system. The treatment of chronic rhinosinusitis includes initial medical management prior to consideration of surgical intervention. However, if surgery does become necessary, several factors must be considered in order to optimize outcomes. This review evaluates surgical patient selection, perioperative medical management, and the extent of operative intervention, with the goal of improving surgical results, decreasing the need for revision surgery, and enhancing the patient’s quality of life. Specific variations in patient genotypes and phenotypes will be further explored with regard to their implications on surgical outcomes. Additionally, the evidence behind pre- and post-operative antibiotic and steroid use will be evaluated. Finally, we will review evolving surgical tools and techniques that are currently being utilized for the treatment of specific subsets of rhinosinusitis

Local Effect of Ballistic Fragments Embedded Along the Carotid Sheath of a Porcine Animal Model

INTRODUCTION: Energized ballistic fragments from improvised explosive devices were the most common cause of injury to coalition service personnel during conflicts in Iraq and Afghanistan. Surgical excision of retained fragments is not routinely performed unless there is a concern for injury to vital structures. However, no clear guidelines dictate when or if a fragment should be removed, reflecting a lack of objective evidence of their long-term effects. Using a porcine model, we aimed to evaluate changes to the carotid artery produced by retained fragments over time. MATERIALS AND METHODS: Institutional Animal Care and Use Committee approval for all experiments was obtained before commencement of the study. Eighteen female swine (mean mass 62.0 ± 3.4 kg) were randomized into three study groups corresponding to the time of survival after implantation of ballistic fragments: 1, 6, and 12 weeks. Two animals from each group were randomly assigned to have one of the three different fragments implanted within the right carotid sheath in zones 1-3 of the neck. The left carotid served as the control. The vascular flow rate and arterial diameter were measured at each level before implantation and again after the survival interval. Baseline and interval angiograms were performed to identify gross vascular changes. RESULTS: No abnormalities were identified on baseline or interval angiograms. No significant difference was found when the baseline was compared to interval measurements or when compared to the control side for all gross and physiological measures at 1 and 6 weeks (P = .053-.855). After 12 weeks, the flow and diameter changed significantly (P \u3c .001-.03), but this significant change was found in both the control and affected carotid. CONCLUSIONS: The lack of significant gross anatomical and physiological changes at 6 weeks postimplantation lends evidence toward the current policy that early removal of retained ballistic fragments around cervical vessels is not required. Changes were significant after 12 weeks which suggest that surveillance may be required; however, such changes could be explained by physiological animal growth

Assessment of Sonic Waves and Tracer Gases as Non-Destructive Testing Methods to Evaluate the Condition and Integrity of In Situ Underground Mine Seals

Since the MINER Act of 2006, the minimum static load of in-situ underground mine seals has been increased from 20-psi to either 50-psi if monitoring is conducted or 120-psi if left unmonitored. These minimum strength requirements in seals must be designed, built, and maintained throughout the lifetime of the seal. Due to this, it has become necessary to assess the effectiveness of non-destructive testing (NDT) technologies to determine seal integrity, which in this case, are explored using sonic waves and tracer gases. Through both small and large scale testing, two NDT methods will be evaluated for their abilities to determine integrity of the seal. A sonic wave technique to observe a change in wave velocity to identify faults within the seal material. As a NDT method, tracer gases may be used as a potential indicator of a connection between both sides of the seal material through a series of faults and cracks within the material itself. This paper reviews the history of underground mine seals and discusses the overall assessment of sonic waves and tracer gases to serve as NDT methods for estimating the integrity of these seals

Monitor Height Ergonomics: A Comparison of Operating Room Video Display Terminals

A surgeon's eyes should be positioned 1 meter (m) distant and no more than 15° below the top of an operating monitor (0.27 m). We sought to determine which operating room video display terminal can best accommodate ergonomically optimized gaze during surgery. Floor to eye height was measured for surgeons in seated, perched, and standing positions. These ranges were then compared to vertical displacement ranges for monitors measured from floor to top of the screen. Eye height was measured for standing (1.56 −1.80 m), perched (1.40 −1.65 m), and seated (1.10 −1.32 m) positions. The minimum distance (min) between the floor and the top of the monitor and the vertical mobility range (VR) of the monitor were measured throughout a tertiary medical center including towers with boom arms (TcB) (min: 1.58 m, VR: 0.37 m), towers without booms (TsB) (min: 1.82 m, VR: 0.025 m), ceiling mounted booms (CMB) (min: 1.34 m:, VR: 1.04 m), and portable monitors (PM) (min: 1.73 m, VR: 0.04 m). The tangent of 15° declination was used to calculate a correction factor to determine the minimum optimal ergonomic display height. The correction factor was subtracted from the eye height at each position to determine the lowest target height and the highest target floor to eye distance for each position. Analysis of variance with least significant difference post hoc testing identified all minimum distances and vertical ranges to be statistically different (p < 0.001). Monitor vertical displacement varied between styles of carts. CMB video display terminal systems can accommodate standing, perched and the tallest seated surgeons. TcB, TsB and PM systems cannot adequately accommodate all standing, perched or seated surgeons

The Role of Simulation in Teaching Sinus Surgery in Otolaryngology Residency: A Survey of Rhinologists

Background Simulation is currently recognized as an effective surgical training tool. However, no standardized curriculum exists for endoscopic sinus surgery (ESS) simulation training. The goal of this study was to obtain an understanding of current ESS simulation use to aid the future development of an ESS training curriculum. Methods A 14-question survey regarding sinus simulation in residency training was developed through the education committee of the American Rhinologic Society. The survey was administered to academic American Rhinologic Society members in the United States, Canada, and Puerto Rico. The participants provided information regarding the type, amount, and effectiveness of simulation use in their residency program. Results Responses were received from 67 training programs; 45% of the programs endorsed using simulation training, although only 23.9% used ESS simulation, and all the programs used cadavers. Only 12.5% of respondent programs required ESS simulation training before operating on live patients, and trainees had an average of <6 hours of simulation training before live operations. A majority of respondents observed subjective improvement in residents' endoscope handling, dexterity, and understanding of anatomy after ESS simulation. The greatest obstacles identified were associated cost and lack of realistic simulators. Conclusion A majority of responders observed improved surgical technique and knowledge in residents after simulation training. However, <25% of the survey responders used ESS simulation and cited cost and limited availability as the most common barriers. A curriculum of validated simulators has potential to improve the quality of ESS training during residency