To summarize the published literature on assessment of appropriateness of colonoscopy for screening for colorectal cancer (CRC) in asymptomatic individuals without personal history of CRC or polyps, ...and report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II.
A systematic search of guidelines, systematic reviews, and primary studies regarding colonoscopy for screening for colorectal cancer was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy in these circumstances.
Available evidence for CRC screening comes from small case-controlled studies, with heterogeneous results, and from indirect evidence from randomized controlled trials (RCTs) on fecal occult blood test (FOBT) screening and studies on flexible sigmoidoscopy screening. Most guidelines recommend screening colonoscopy every 10 years starting at age 50 in average-risk individuals. In individuals with a higher risk of CRC due to family history, there is a consensus that it is appropriate to offer screening colonoscopy at < 50 years. EPAGE II considered screening colonoscopy appropriate above 50 years in average-risk individuals. Panelists deemed screening colonoscopy appropriate for younger patients, with shorter surveillance intervals, where family or personal risk of colorectal cancer is higher. A positive FOBT or the discovery of adenomas at sigmoidoscopy are considered appropriate indications.
Despite the lack of evidence based on randomized controlled trials (RCTs), colonoscopy is recommended by most published guidelines and EPAGE II criteria available online (http://www.epage.ch), as a screening option for CRC in individuals at average risk of CRC, and undisputedly as the main screening tool for CRC in individuals at moderate and high risk of CRC.
Summary
Aim : To rationalize decision making around the use of different non‐steroidal anti‐inflammatory drug (NSAID) treatment strategies in patients with varying degrees of gastrointestinal and ...cardiovascular risk.
Methods : The panel comprised nine physicians (three rheumatologists, two internists, two gastroenterologists and two cardiologists) from geographically diverse areas practising in community‐based settings (n = 4) and academic institutions (n = 5). A literature review was performed by the authors on the risks, benefits and costs of NSAIDs, cyclo‐oxygenase‐2‐specific inhibitors and proton pump inhibitor co‐therapy. The RAND/UCLA Appropriateness Method was used to rate 304 clinical scenarios as ‘appropriate’, ‘uncertain’ or ‘inappropriate’.
Results : In patients with no previous gastrointestinal event and not concurrently on aspirin (low risk), the panel rated the use of an NSAID alone as ‘appropriate’ for those aged < 65 years, and the use of an NSAID +proton pump inhibitor or cyclo‐oxygenase‐2‐specific inhibitor + proton pump inhibitor as ‘inappropriate’. For patients aged > 65 years and at low risk, an NSAID or cyclo‐oxygenase‐2‐specific inhibitor alone was rated as ‘uncertain’. For patients with a previous gastrointestinal event or who concurrently received aspirin, an NSAID alone was rated as ‘inappropriate’, and either a cyclo‐oxygenase‐2‐specific inhibitor or an NSAID +proton pump inhibitor was rated as ‘appropriate’. Finally, for patients with a previous gastrointestinal event and on aspirin, an NSAID or cyclo‐oxygenase‐2‐specific inhibitor in conjunction with a proton pump inhibitor was rated as ‘appropriate’.
Conclusions : Clinicians and managed care entities need to balance the risks, benefits and costs of NSAIDs, cyclo‐oxygenase‐2‐specific inhibitors and the prophylactic use of proton pump inhibitors. The guidelines given here can assist this process.
We report on a study of the polarization transfer between transversely polarized incident electrons and the emitted x rays for electron-atom bremsstrahlung. By means of Compton polarimetry we ...performed for the first time an energy-differential measurement of the complete properties of bremsstrahlung emission related to linear polarization, i.e., the degree of linear polarization as well as the orientation of the polarization axis. For the high-energy end of the bremsstrahlung continuum the experimental results for both observables show a high sensitivity on the initial electron spin polarization and prove that the polarization orientation is virtually independent of the photon energy.
Background & Aims: Peroxisomal proliferator–activated receptor γ (PPARγ) is a nuclear hormone receptor that provides a direct link between fatty acid metabolism and control of gene transcription. The ...objective of this study was to determine the biological effect(s) of PPARγ activation in colorectal carcinoma cells.
Methods: PPARγ expression and activity were measured in 4 human colon cancer cell lines using reverse-transcription polymerase chain reaction, immunoprecipitation and immunoblotting, and transient reporter gene assays. The effects of activated PPARγ in these cell lines were assessed in cellular proliferation and anchorage-independent growth assays. Flow cytometry was used to determine the effects of PPARγ activation on progression through the cell cycle.
Results: PPARγ was expressed in all 4 colon cancer cell lines examined and was transcriptionally functional in 3 of the 4. Treatment of these cells with a selective PPARγ activator (BRL 49653) resulted in inhibition of anchorage-independent growth. The degree of growth inhibition correlated with the level of functional PPARγ present. Finally, activation of PPARγ resulted in G1 cell cycle arrest.
Conclusions: Activation of the PPARγ pathway in colon cancer cells has potent antiproliferative effects, suggesting that this nuclear hormone receptor may provide a novel target for prevention and treatment of colorectal cancer in humans.
GASTROENTEROLOGY 1998;115:1049-1055
The performance of a dual energy storage electric vehicle system mainly depends on the quality of its power and energy managements. A real-time management strategy supported by a model predictive ...control (MPC) using the nonuniform sampling time concept is developed and fully addressed in this paper. First, the overall multiple energy storage powertrain model including its inner control layer is represented with the energetic macroscopic representation and used to introduce the energy strategy level. The model of the system with its inner control layer is translated into the state-space domain in order to develop an MPC approach. The management algorithm based on mixed short- and long-term predictions is compared to rule-based and constant sampling time MPC strategies in order to assess its performance and its ability to be used in a real vehicle. The real-time simulation results indicate that, compared to other strategies, the proposed MPC strategy can balance the power and the energy of the dual energy storage system more effectively, and reduce the stress on batteries. Moreover, battery and supercapacitor key variables are kept within safety limits, increasing the lifetime of the overall system.
With frequent flaring activity of its relativistic jets, Cygnus X-3 (Cyg X-3) is one of the most active microquasars and is the only Galactic black hole candidate with confirmed high-energy γ-ray ...emission, thanks to detections by Fermi Large Area Telescope (Fermi/LAT) and AGILE. In 2011, Cyg X-3 was observed to transit to a soft X-ray state, which is known to be associated with high-energy γ-ray emission. We present the results of a multiwavelength campaign covering a quenched state, when radio emission from Cyg X-3 is at its weakest and the X-ray spectrum is very soft. A giant (∼20 Jy) optically thin radio flare marks the end of the quenched state, accompanied by rising non-thermal hard X-rays. Fermi/LAT observations (E≥ 100 MeV) reveal renewed γ-ray activity associated with this giant radio flare, suggesting a common origin for all non-thermal components. In addition, current observations unambiguously show that the γ-ray emission is not exclusively related to the rare giant radio flares. A three-week period of γ-ray emission is also detected when Cyg X-3 was weakly flaring in radio, right before transition to the radio quenched state. No γ-rays are observed during the ∼1-month long quenched state, when the radio flux is weakest. Our results suggest transitions into and out of the ultrasoft X-ray (radio-quenched) state trigger γ-ray emission, implying a connection to the accretion process, and also that the γ-ray activity is related to the level of radio flux (and possibly shock formation), strengthening the connection to the relativistic jets.
Ataxia telangiectasia-mutated (ATM) kinase is a master regulator of the DNA damage response. ATM is frequently inactivated in human B-cell non-Hodgkin lymphomas, including ~50% of mantle cell ...lymphomas (MCLs) characterized by ectopic expression of CyclinD1. Here we report that early and robust deletion of ATM in precursor/progenitor B cells causes cell autonomous, clonal mature B-cell lymphomas of both pre- and post-germinal center (GC) origins. Unexpectedly, naive B-cell-specific deletion of ATM is not sufficient to induce lymphomas in mice, highlighting the important tumor suppressor function of ATM in immature B cells. Although EμCyclinD1 is not sufficient to induce lymphomas, EμCyclinD1 accelerates the kinetics and increases the incidence of clonal lymphomas in ATM-deficient B-cells and skews the lymphomas toward pre-GC-derived small lymphocytic neoplasms, sharing morphological features of human MCL. This is in part due to CyclinD1-driven expansion of ATM-deficient naive B cells with genomic instability, which promotes the deletions of additional tumor suppressor genes (i.e. Trp53, Mll2, Rb1 and Cdkn2a). Together these findings define a synergistic function of ATM and CyclinD1 in pre-GC B-cell proliferation and lymphomagenesis and provide a prototypic animal model to study the pathogenesis of human MCL.
Persons infected with HIV are particularly vulnerable to a variety of oral microbial diseases. Although various study designs and detection approaches have been used to compare the oral microbiota of ...HIV-negative and HIV-positive persons, both with and without highly active antiretroviral therapy (HAART), methods have varied, and results have not been consistent or conclusive. The purpose of the present study was to compare the oral bacterial community composition in HIV-positive persons under HAART to an HIV-negative group using 16S rRNA gene sequence analysis. Extensive clinical data was collected, and efforts were made to balance the groups on clinical variables to minimize confounding. Multivariate analysis was used to assess the independent contribution of HIV status. Eighty-nine HIV-negative participants and 252 HIV-positive participants under HAART were sampled. The independent effect of HIV under HAART on the oral microbiome was statistically significant, but smaller than the effect of gingivitis, periodontal disease, smoking, caries, and other clinical variables. In conclusion, a multivariate comparison of a large sample of persons with HIV under HAART to an HIV-negative control group showed a complex set of clinical features that influenced oral bacterial community composition, including the presence of HIV under HAART.
Transmission of 1keV single charged nitrogen ions through a macroscopic tapered borosilicate glass capillary is studied theoretically and experimentally. Measured time trend of the transmission for ...different low beam intensities are given. They are compared to realistic microscopic calculation that allows simulating the transmission of charged particles through a conical capillary with macroscopic dimensions. We show clear evidence that a low energy ion beam with intensities in the pA range can be transmitted and focused through tapered macroscopic insulator capillaries.
Peroxisome proliferator-activated receptor γ (PPARγ) may serve as a useful target for drug development in non-diabetic diseases. However, some colorectal cancer cells are resistant to PPARγ agonists ...by mechanisms that are poorly understood. Here, we provide the first evidence that elevated PPARδ expression and/or activation of PPARδ antagonize the ability of PPARγ to induce colorectal carcinoma cell death. More importantly, the opposing effects of PPARδ and PPARγ in regulating programmed cell death are mediated by survivin and caspase-3. We found that activation of PPARγ results in decreased survivin expression and increased caspase-3 activity, whereas activation of PPARδ counteracts these effects. Our findings suggest that PPARδ and PPARγ coordinately regulate cancer cell fate by controlling the balance between the cell death and survival and demonstrate that inhibition of PPARδ can reprogram PPARγ ligand-resistant cells to respond to PPARγ agonists.
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