Strategies for Colorectal Cancer Screening

The incidence of colorectal cancer (CRC) is increasing worldwide. CRC has high mortality when detected at advanced stages, yet it is also highly preventable. Given the difficulties in implementing major lifestyle changes or widespread primary prevention strategies to decrease CRC risk, screening is the most powerful public health tool to reduce mortality. Screening methods are effective but have limitations. Furthermore, many screen-eligible persons remain unscreened. We discuss established and emerging screening methods, and potential strategies to address current limitations in CRC screening. A quantum step in CRC prevention might come with the development of new screening strategies, but great gains can be made by deploying the available CRC screening modalities in ways that optimize outcomes while making judicious use of resources

Blow-up solutions for linear perturbations of the Yamabe equation

For a smooth, compact Riemannian manifold (M,g) of dimension N \geg 3, we are interested in the critical equation $$\Delta_g u+(N-2/4(N-1) S_g+\epsilon h)u=u^{N+2/N-2} in M, u>0 in M,$$ where \Delta_g is the Laplace--Beltrami operator, S_g is the Scalar curvature of (M,g), $h\in C^{0,\alpha}(M)$, and $\epsilon$ is a small parameter

BID mediates selective killing of APC-deficient cells in intestinal tumor suppression by nonsteroidal antiinflammatory drugs

Colorectal tumorigenesis is driven by genetic alterations in the adenomatous polyposis coli (APC) tumor suppressor pathway and effectively inhibited by nonsteroidal antiinflammatory drugs (NSAIDs). However, how NSAIDs prevent colorectal tumorigenesis has remained obscure. We found that the extrinsic apoptotic pathway and the BH3 interacting-domain death agonist (BID) are activated in adenomas from NSAID-treated patients. Loss of BID abolishes NSAID-mediated tumor suppression, survival benefit, and apoptosis in tumor-initiating stem cells in APC(Min/+) mice. BID-mediated cross-talk between the extrinsic and intrinsic apoptotic pathways is responsible for selective killing of neoplastic cells by NSAIDs. We further demonstrate that NSAIDs induce death receptor signaling in both cancer and normal cells, but only activate BID in cells with APC deficiency and ensuing c-Myc activation. Our results suggest that NSAIDs suppress intestinal tumorigenesis through BID-mediated synthetic lethality triggered by death receptor signaling and gatekeeper mutations, and provide a rationale for developing more effective cancer prevention strategies and agents

Gravitating Opposites Attract

Generalizing previous work by two of us, we prove the non-existence of certain stationary configurations in General Relativity having a spatial reflection symmetry across a non-compact surface disjoint from the matter region. Our results cover cases such that of two symmetrically arranged rotating bodies with anti-aligned spins in $n+1$ ($n \geq 3$) dimensions, or two symmetrically arranged static bodies with opposite charges in 3+1 dimensions. They also cover certain symmetric configurations in (3+1)-dimensional gravity coupled to a collection of scalars and abelian vector fields, such as arise in supergravity and Kaluza-Klein models. We also treat the bosonic sector of simple supergravity in 4+1 dimensions.Comment: 13 pages; slightly amended version, some references added, matches version to be published in Classical and Quantum Gravit

Developing a natural language processing application for measuring the quality of colonoscopy procedures

The quality of colonoscopy procedures for colorectal cancer screening is often inadequate and varies widely among physicians. Routine measurement of quality is limited by the costs of manual review of free-text patient charts. Our goal was to develop a natural language processing (NLP) application to measure colonoscopy quality

Applying a natural language processing tool to electronic health records to assess performance on colonoscopy quality measures

Gastroenterology specialty societies have advocated that providers routinely assess their performance on colonoscopy quality measures. Such routine measurement has been hampered by the costs and time required to manually review colonoscopy and pathology reports. Natural Language Processing (NLP) is a field of computer science in which programs are trained to extract relevant information from text reports in an automated fashion

Does backreaction enforce the averaged null energy condition in semiclassical gravity?

The expected stress-energy tensor of quantum fields generically violates the local positive energy conditions of general relativity. However, may satisfy some nonlocal conditions such as the averaged null energy condition (ANEC), which would rule out traversable wormholes. Although ANEC holds in Minkowski spacetime, it can be violated in curved spacetimes if one is allowed to choose the spacetime and quantum state arbitrarily, without imposition of the semiclassical Einstein equation G_{ab} = 8 \pi . In this paper we investigate whether ANEC holds for solutions to this equation, by studying a free, massless scalar field with arbitrary curvature coupling in perturbation theory to second order about the flat spacetime/vacuum solution. We "reduce the order" of the perturbation equations to eliminate spurious solutions, and consider the limit in which the lengthscales determined by the incoming state are much larger than the Planck length. We also need to assume that incoming classical gravitational radiation does not dominate the first order metric perturbation. We find that although the ANEC integral can be negative, if we average the ANEC integral transverse to the geodesic with a suitable Planck scale smearing function, then a strictly positive result is obtained in all cases except for the flat spacetime/vacuum solution. This result suggests --- in agreement with conclusions drawn by Ford and Roman from entirely independent arguments --- that if traversable wormholes do exist as solutions to the semiclassical equations, they cannot be macroscopic but must be ``Planck scale''. A large portion of our paper is devoted to the analysis of general issues concerning the nature of the semiclassical Einstein equation and of prescriptions for extracting physically relevant solutions.Comment: 54 pages, 3 figures, uses revtex macros and epsf.tex, to appear in Phys Rev D. A new appendix has been added showing consistency of our results with recent results of Visser [gr-qc/9604008]. Some corrections were made to Appendix A, and several other minor changes to the body of the paper also were mad

Recommendations for a step-wise comparative approach to the evaluation of new screening tests for colorectal cancer

BACKGROUND: New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain.METHODS: A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on how to compare new screening tests with proven screening tests.RESULTS: Findings and recommendations from the review included the following: Adoption of a new screening test requires evidence of effectiveness relative to a proven comparator test. Clinical accuracy supported by programmatic population evaluation in the screening context on an intention-to-screen basis, including acceptability, is essential. Cancer-specific mortality is not essential as an endpoint provided that the mortality benefit of the comparator has been demonstrated and that the biologic basis of detection is similar. Effectiveness of the guaiac-based fecal occult blood test provides the minimum standard to be achieved by a new test. A 4-phase evaluation is recommended. An initial retrospective evaluation in cancer cases and controls (Phase 1) is followed by a prospective evaluation of performance across the continuum of neoplastic lesions (Phase 2). Phase 3 follows the demonstration of adequate accuracy in these 2 prescreening phases and addresses programmatic outcomes at 1 screening round on an intention-to-screen basis. Phase 4 involves more comprehensive evaluation of ongoing screening over multiple rounds. Key information is provided from the following parameters: the test positivity rate in a screening population, the true-positive and false-positive rates, and the number needed to colonoscope to detect a target lesion.CONCLUSIONS: New screening tests can be evaluated efficiently by this stepwise comparative approach. Cancer 2016;122:826-39. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.</p

Declining Rates in Male Circumcision amidst Increasing Evidence of its Public Health Benefit

BACKGROUND: Recent experimental evidence has demonstrated the benefits of male circumcision for the prevention of human immunodeficiency virus (HIV) infection. Studies have also shown that male circumcision is cost-effective and reduces the risk for certain ulcerative sexually transmitted diseases (STDs). The epidemiology of male circumcision in the United States is poorly studied and most prior reports were limited by self-reported measures. The study objective was to describe male circumcision trends among men attending the San Francisco municipal STD clinic, and to correlate the findings with HIV, syphilis and sexual orientation. METHODS AND FINDINGS: A cross sectional study was performed by reviewing all electronic records of males attending the San Francisco municipal STD clinic between 1996 and 2005. The prevalence of circumcision over time and by subpopulation such as race/ethnicity and sexual orientation were measured. The findings were further correlated with the presence of syphilis and HIV infection. Circumcision status was determined by physical examination and disease status by clinical evaluation with laboratory confirmation. Among 58,598 male patients, 32,613 (55.7%, 95% Confidence Interval (CI) 55.2-56.1) were circumcised. Male circumcision varied significantly by decade of birth (increasing between 1920 and 1950 and declining overall since the 1960's), race/ethnicity (Black: 62.2%, 95% CI 61.2-63.2, White: 60.0%, 95% CI 59.46-60.5, Asian Pacific Islander: 48.2%, 46.9-49.5 95% CI, and Hispanic: 42.2%, 95% CI 41.3-43.1), and sexual orientation (gay/bisexual: 73.0%, 95% CI 72.6-73.4; heterosexual: 66.0%, 65.5-66.5). Male circumcision may have been modestly protective against syphilis in HIV-uninfected heterosexual men (PR 0.92, 95% C.I. 0.83-1.02, P = 0.06). CONCLUSIONS: Male circumcision was common among men seeking STD services in San Francisco but has declined substantially in recent decades. Male circumcision rates differed by race/ethnicity and sexual orientation. Given recent studies suggesting the public health benefits of male circumcision, a reconsideration of national male circumcision policy is needed to respond to current trends