Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes.

Listeria monocytogenes is an important cause of maternal-fetal infections and serves as a model organism to study these important but poorly understood events. L. monocytogenes can infect non-phagocytic cells by two means: direct invasion and cell-to-cell spread. The relative contribution of each method to placental infection is controversial, as is the anatomical site of invasion. Here, we report for the first time the use of first trimester placental organ cultures to quantitatively analyze L. monocytogenes infection of the human placenta. Contrary to previous reports, we found that the syncytiotrophoblast, which constitutes most of the placental surface and is bathed in maternal blood, was highly resistant to L. monocytogenes infection by either internalin-mediated invasion or cell-to-cell spread. Instead, extravillous cytotrophoblasts-which anchor the placenta in the decidua (uterine lining) and abundantly express E-cadherin-served as the primary portal of entry for L. monocytogenes from both extracellular and intracellular compartments. Subsequent bacterial dissemination to the villous stroma, where fetal capillaries are found, was hampered by further cellular and histological barriers. Our study suggests the placenta has evolved multiple mechanisms to resist pathogen infection, especially from maternal blood. These findings provide a novel explanation why almost all placental pathogens have intracellular life cycles: they may need maternal cells to reach the decidua and infect the placenta

Incremental fatigue damage model : Application to plane problems with non-proportional loading

Modern airframe aluminum structures are increasingly manufactured in large and complex integral parts. Suchparts are often exposed to in–plane, non–proportional loading and contain stress–raisers with complex geometry. Conventional methods, based on the stress concentration factor and cycle counting, are unsuitable forassessment of this type of problem. We present a fatigue damage model, based on the concept of movingendurance surface and incremental damage evolution. The fatigue damage is entirely dependent on the localstress history and the notch effect is accounted for by introduction of the relative stress gradient. Also, wepresent an automated and efficient implementation of the model, for the purpose of computing fatigue damageat stress raisers in plane problems with non–proportional loading. We demonstrate the implementation by anexample of a fatigue calculation in an aircraft frame.</p

Economic evaluations of screening strategies for the early detection of colorectal cancer in the average-risk population: a systematic literature review

Background: Colorectal cancer (CRC) screening has proven effective in reducing CRC mortality. This study aimed to systematically review, and evaluate the reporting quality, of the economic evidence regarding CRC screening in average-risk individuals. Methods: Databases searched included Medline, EMBASE, National Health Service Economic Evaluation, Database of Abstracts of Reviews of Effects, Cost-Effectiveness Analysis registry, EconLit, and Health Technology Assessment database. Eligible studies were cost-effectiveness and cost-utility analyses comparing CRC screening strategies in average-risk individuals, published in English or Spanish, between January 2012 and November 2018. Reporting quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results: Of 1,993 publications initially retrieved, 477 were excluded by duplicate review, 1,449 by title/abstract review, and 34 by full-text review. Finally, 33 publications were included in the qualitative synthesis. Most studies were conducted in Europe (36,4%), followed by United States (24,2%) and Asia (24,2%). The main screening modalities considered were fecal immunochemical tests (70%), colonoscopy (67%), guaiac fecal occult blood test (42%) and flexible sigmoidoscopy (30%). In most studies, CRC screening was deemed cost-effective compared to no screening. Sensitivity analyses indicated that cost of CRC screening tests, adherence to screening, screening test sensitivity, and cost of CRC treatment had the greatest impact on cost-effectiveness results across studies. The majority of studies (73%) adequately reported at least 50% of the items included in the CHEERS checklist. Least well reported items included setting, study perspective, discount rate, model choice, and methods to identify effectiveness data or to estimate resource use and costs. Conclusions: CRC screening is an efficient alternative to no screening. Nevertheless, it is not possible to conclude which strategy should be preferred for population-based screening programs. Although we observed an overall good adherence to CHEERS recommendations, there is still room for improvement in economic evaluations reporting in this field

Advances in fecal occult blood tests:The FIT revolution

There is a wide choice of fecal occult blood tests (FOBTs) for colorectal cancer screening. Goal: To highlight the issues applicable when choosing a FOBT, in particular which FOBT is best suited to the range of screening scenarios. Four scenarios characterize the constraints and expectations of screening programs: (1) limited colonoscopy resource with a need to constrain test positivity rate; (2) a priority for maximum colorectal neoplasia detection with little need to constrain colonoscopy workload; (3) an “adequate” endoscopy resource that allows balancing the benefits of detection with the burden of service provision; and (4) a need to maximize participation in screening. Guaiac-based FOBTs (gFOBTs) have significant deficiencies, and fecal immunochemical tests (FITs) for hemoglobin have emerged as better tests. gFOBTs are not sensitive to small bleeds, specificity can be affected by diet or drugs, participant acceptance can be low, laboratory quality control opportunities are limited, and they have a fixed hemoglobin concentration cutoff determining positivity. FITs are analytically more specific, capable of quantitation and hence provide flexibility to adjust cutoff concentration for positivity and the balance between sensitivity and specificity. FITs are clinically more sensitive for cancers and advanced adenomas, and because they are easier to use, acceptance rates are high. Conclusions: FOBT must be chosen carefully to meet the needs of the applicable screening scenario. Quantitative FIT can be adjusted to suit Scenarios 1, 2 and 3, and for each, they are the test of choice. FITs are superior to gFOBT for Scenario 4 and gFOBT is only suitable for Scenario 1