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This paper benchmarks the challenges involved with major sea, or fixed link, bridge crossings from their planning to final construction. An overview of existing major fixed link crossings globally, including statistical information such as length and inflation-adjusted project costs, is given. Data for well-known links such as the Øresund Crossing in Europe and the more recent Hong Kong–Zhuhai–Macau Bridge are included. The construction methods required to surmount the challenges of bridging such crossings and how advancements are making long-mooted crossings more feasible are discussed. Statistics on the construction durations of these crossings are presented and links between construction time, cost aspects and carbon dioxide emissions are considered. Finally, the paper looks to the future and considers how the data can be used to better bound estimates of time, costs, and emissions for fixed link projects. The viability of some of the more notable future fixed link projects is also addressed.

Background The risks associated with colonoscopy performed through the British Columbia Colon Screening Program (BCCSP) are not known. We aimed to determine the rate of colonoscopy-related serious adverse events within this program. Methods For this prospective observational study, we used the BCCSP database to identify participants 50 to 74 years of age who had a positive result on fecal immunochemical testing (FIT) between Nov. 15, 2013, and Dec. 31, 2017, followed by colonoscopy. Unplanned medical events were recorded at the time of colonoscopy and 14 days later. We reviewed the unplanned events and defined them as serious adverse events if they resulted in death, hospital admission or intervention; we also classified them as probably, possibly or unlikely related to the colonoscopy. The primary outcome was the overall rate of serious adverse events; the secondary outcomes were 14-day post-colonoscopy rates of perforation, bleeding and death. Results During the study period, a total of 96 192 colonoscopies were performed by 308 physicians at 50 sites. The median age of patients was 62 (10th-90th percentile 52-71) years, and 56% were male. Of these, 78 831 patients were contacted after the colonoscopy. Serious adverse events were deemed to have occurred in 350 colonoscopies (44 per 10 000, 95% confidence interval [CI] 39-50 per 10 000), with a number needed to harm of 225. Of the 332 (94.9%) serious adverse events that were probably or possibly related to colonoscopy, perforation occurred in 6 (95% CI 5-8) per 10 000 colonoscopies, bleeding in 26 (95% CI 22-30) per 10 000 colonoscopies and death in 3 (95% CI 1-10) per 100 000 colonoscopies. Interpretation The rate of serious adverse events associated with colonoscopy in the BCCSP was in keeping with previous publications and met accepted benchmarks. The findings of this study inform stakeholders of the risks associated with colonoscopy in an FIT-based colon screening program.

This paper benchmarks the challenges involved with major sea, or fixed link, crossings from their planning to final construction. Initially it gives an overview of existing major crossings globally, including statistical information such as length and inflation adjusted project costs. Well known links such as the UK Channel Tunnel and the more recent Hong Kong Zhuhai Macau crossing have been included in the data. The paper considers the construction methods required to surmount the challenges of bridging or tunnelling such crossings. The paper presents statistics on the construction time period for these crossings and considers links between construction time and cost. Finally, the paper looks to the future: How the data can be used to better bound estimates of time and costs for fixed link projects. The paper also considers other potentially important future benchmarking data such as carbon emissions.

Background The British Columbia Colon Screening Program (BCCSP) is a population-based program enrolling 50–74 year old individuals for biennial FIT (OC-Sensor, cut-off 10 mcg/g) with follow-up colonoscopy for positive FIT. The neoplasia detection rate is 50–55% and over 75% of colonoscopies have a specimen taken. Previously reported colonoscopy adverse event rates for FIT based screening programs vary widely: 0.03–6.2% and 0–2.7% for bleeding and perforation, respectively. Mortality as a result of colonoscopy is rare but has been reported in 0.0004%-0.0074% of colonoscopies. The rate of colonoscopy related adverse events in BCCSP participants is unknown. Aims To determine the rate of colonoscopy related serious adverse events within the BCCSP. Methods This is a retrospective cohort study of all participants undergoing colonoscopy in BCCSP from November 15, 2013 to December 31, 2017. BCCSP contacts screening participants by phone 14 days post colonoscopy to determine unplanned medical visits the day prior (during bowel preparation) or following the colonoscopy. Unplanned events underwent chart review if the event was a perforation, cardiovascular or respiratory event, or resulted in death, hospitalization, or significant intervention including repeat colonoscopy, interventional radiology, surgery, blood transfusion, cardioversion, casting of a fracture or suturing of a laceration. Chart review was conducted by a Colonoscopy Lead and reviewed by BCCSP Quality Committee. Unplanned events were defined as serious adverse events (SAE) if they resulted in death, hospitalization or significant intervention and further classified as probably, possibly, or unlikely related to the colonoscopy. Results A total of 108,004 colonoscopies were performed. Unplanned events were reported in 1753 participants, of which 586 met criteria for review. Of these, 578 were confirmed unplanned events and 409 were SAEs of which 367 (89.7%) were probably, 22 (5.4%) possibly and 20 (4.9%) unlikely associated with colonoscopy. 36/10,000 colonoscopies were associated with a SAE that was probably or possibly related: perforation in 5/10,000, bleeding 22/10,000. Three deaths occurred in the 14 days following colonoscopy that were probably (2 perforations) or possibly related to the colonoscopy (0.3/10,000). Conclusions The BCCSP has a colonoscopy SAE rate in keeping with previous publications, particularly in the context of a very high proportion of procedures associated with polypectomy, a known risk factor for perforation and bleeding. This study will help inform screening participants about the risks of colonoscopy in the BC program. Future studies are required to confirm these rates using hospital admission data. Funding Agencies None

There is increasing interest in the use of edited proton magnetic resonance spectroscopy for the detection of GABA in the human brain. At a recent meeting held at Cardiff University, a number of spectroscopy groups met to discuss the acquisition, analysis and interpretation of GABA-edited MR spectra. This paper aims to set out the issues discussed at this meeting, reporting areas of consensus around parameters and procedures in the field and highlighting those areas where differences remain. It is hoped that this paper can fulfill two needs, providing a summary of the current ‘state-of-the-art’ in the field of GABA-edited MRS at 3 T using MEGA-PRESS and a basic guide to help researchers new to the field to avoid some of the pitfalls inherent in the acquisition and processing of edited MRS for GABA.

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P combined = 4.09 × 10-9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P combined = 2.74 × 10-10; OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus. © 2012 Nature America, Inc. All rights reserved.

This paper provides a comparison of the curricular recommendations for IT and a CS course in software engineering, including the specific topics covered in a recent class. The evolution of the semester project for this class, a web-based interface to a multimedia database for instructors and students, created in part by end users, is described and correlations are drawn to the IT curriculum recommendations. The course is proposed as appropriate, in general, as an elective in the IT curriculum that serves as a companion to the IT capstone.

Many of the programming principles taught in any programming fundamentals course are essentially the same. We will describe some of the principles and techniques that students learn in a first programming course using Alice 2.0 that is shared by programs in IS, IT, CS and liberal studies, drawing from the IT Computing Curricula 2005. We will then describe a set of nifty assignments that result in projects that exercise these principles and techniques and may be used to emphasize one or more in depth topical issues.

Recently, computer security has come to the forefront of public awareness. With the onslaught of worms such as Code Red, national (U.S.) concern has increased about cyber terrorism and the information infrastructure. One educational response has been the emergence of a number of computer security degree programs - at the undergraduate level, e.g., East Stroudsburg State University of PA, and at the graduate level, e.g., the Heinz School at Carnegie-Mellon University.The panel members were all participants in the Cyber security faculty development Workshop[1] held at Indiana University of PA in August, 2001. Among the goals of the workshop was the development of courses that would teach the theory and application of security, including the use of specially designed (quarantined) "attack" and "defend" computer labs. Additional goals include development of modules related to security for CS core courses, and an interdisciplinary minor for Computer Science and Criminology majors.It was the consensus of the panel participants that many institutions would be unable to implement special degree programs or tracks, and, in a significant number of cases, might be unable to immediately implement even one specialized course. Yet, all the participants also believed strongly that security-related content in our computer courses can, and should, be improved. Even if no security-based courses are added, major and non-major courses in computer science, CIS, etc., can do a better job of raising awareness of threats, vulnerabilities, and risks.Each panel member will address a specific course or sub discipline and describe how security was infused or added to the current curriculum. The intent is to foster discussion regarding appropriateness and pedagogy while relating individual experiences, successes and failures. Audience and panel members will be encouraged to discuss the relative merits of this approach.

The effect of selective group I metabotropic glutamate receptor subtype 5 (mGluR5) antagonists 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and (E)-2-methyl-6-(2-phenylethenyl)-pyridine (SIB-1893) on neuronal cell survival and post-traumatic recovery was examined using rat in vitro and in vivo trauma models. Treatment with MPEP and SIB-1893 showed significant neuroprotective effects in rat cortical neuronal cultures subjected to mechanical injury. Application of the antagonists also attenuated glutamate- and N-methyl-D-aspartate (NMDA)-induced neuronal cell death in vitro. Intracerebroventricular administration of MPEP to rats markedly improved motor recovery and reduced deficits of spatial learning after lateral fluid percussion-induced traumatic brain injury. Lesion volumes as assessed by magnetic resonance imaging were also substantially reduced by MPEP treatment. Although we show that MPEP acts as a potent mGluR5 antagonist in our culture system, where it completely blocks agonist-induced phosphoinositide hydrolysis, electrophysiological and pharmacological studies indicate that MPEP and SIB-1893 also inhibit NMDA receptor activity at higher concentrations that are neuroprotective. Taken together, these data suggest that MPEP and SIB-1893 may have therapeutic potential in brain injury, although the mechanisms of neuroprotective action for these drugs may reflect their ability to modulate NMDA receptor activity.