The utility of ductal lavage in breast cancer detection and risk assessment

Ductal lavage (DL) permits noninvasive retrieval of epithelial cells from the breast. Clinical development of this technique has been fueled largely by its potential, as yet unproven, to improve detection of breast cancer and definition of individual risk for development of breast cancer. Early studies demonstrate the feasibility of performing this technique, provide data on cellular yield and findings, and demonstrate the ability to measure molecular markers in DL fluid. However, the sensitivity and specificity of DL for the detection of breast cancer remains unknown, as does the significance of atypia, particularly mild atypia, when found in DL fluid. Although DL appears safe and the device is approved by the US Food and Drug Administration, DL is still best utilized in the setting of clinical trials designed to resolve issues of sensitivity, specificity, and localization

Statistical practices of educational researchers: An analysis of their ANOVA, MANOVA, and ANCOVA analyses

Articles published in several prominent educational journals were examined to investigate the use of data-analysis tools by researchers in four research paradigms: between-subjects univariate designs, between-subjects multivariate designs, repeated measures designs, and covariance designs. In addition to examining specific details pertaining to the research design (e.g., sample size, group size equality/inequality) and methods employed for data analysis, we also catalogued whether: (a) validity assumptions were examined, (b) effect size indices were reported, (c) sample sizes were selected based on power considerations, and (d) appropriate textbooks and/or articles were cited to communicate the nature of the analyses that were performed. Our analyses imply that researchers rarely verify that validity assumptions are satisfied and accordingly typically use analyses that are nonrobust to assumption violations. In addition, researchers rarely report effect size statistics, nor do they routinely perform power analyses to determine sample size requirements. We offer many recommendations to rectify these shortcomings.Social Sciences and Humanities Research Counci

Genomic DNA Pooling Strategy for Next-Generation Sequencing-Based Rare Variant Discovery in Abdominal Aortic Aneurysm Regions of Interest—Challenges and Limitations

The costs and efforts for sample preparation of hundreds of individuals, their genomic enrichment for regions of interest, and sufficient deep sequencing bring a significant burden to next-generation sequencing-based experiments. We investigated whether pooling of samples at the level of genomic DNA would be a more versatile strategy for lowering the costs and efforts for common disease-associated rare variant detection in candidate genes or associated loci in a substantial patient cohort. We performed a pilot experiment using five pools of 20 abdominal aortic aneurysm (AAA) patients that were enriched on separate microarrays for the reported 9p21.3 associated locus and 42 additional AAA candidate genes, and sequenced on the SOLiD platform. Here, we discuss challenges and limitations connected to this approach and show that the high number of novel variants detected per pool and allele frequency deviations to the usually highly false positive cut-off region for variant detection in non-pooled samples can be limiting factors for successful variant prioritization and confirmation. We conclude that barcode indexing of individual samples before pooling followed by a multiplexed enrichment strategy should be preferred for detection of rare genetic variants in larger sample sets rather than a genomic DNA pooling strategy

Should women under 50 be screened for breast cancer?

Should women under 50 be screened for breast cancer? Despite some controversy in recent years, the majority of experts agree on the evidence for effectiveness of breast screening by mammography for women aged 50 years and above, but for those under 50 years, the picture is much less clear. However, the issue remains of importance both to policy makers and to individual women; although the incidence of breast cancer is lower at younger ages, the life years lost due to cancers diagnosed below 50 years amount to a third of all those lost due to the disease

Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations.

BACKGROUND AND PURPOSE: Currently, there are no licensed vaccines and limited antivirals for the treatment of COVID-19. Heparin (delivered systemically) is currently used to treat anticoagulant anomalies in COVID-19 patients. Additionally, in the United Kingdom, Brazil and Australia, nebulised unfractionated heparin (UFH) is being trialled in COVID-19 patients as a potential treatment. A systematic comparison of the potential antiviral effect of various heparin preparations on live wild type SARS-CoV-2, in vitro, is needed. EXPERIMENTAL APPROACH: Seven different heparin preparations including UFH and low MW heparins (LMWH) of porcine or bovine origin were screened for antiviral activity against live SARS-CoV-2 (Australia/VIC01/2020) using a plaque inhibition assay with Vero E6 cells. Interaction of heparin with spike protein RBD was studied using differential scanning fluorimetry and the inhibition of RBD binding to human ACE2 protein using elisa assays was examined. KEY RESULTS: All the UFH preparations had potent antiviral effects, with IC50 values ranging between 25 and 41 μg·ml-1 , whereas LMWHs were less inhibitory by ~150-fold (IC50 range 3.4-7.8 mg·ml-1 ). Mechanistically, we observed that heparin binds and destabilizes the RBD protein and furthermore, we show heparin directly inhibits the binding of RBD to the human ACE2 protein receptor. CONCLUSION AND IMPLICATIONS: This comparison of clinically relevant heparins shows that UFH has significantly stronger SARS-CoV-2 antiviral activity compared to LMWHs. UFH acts to directly inhibit binding of spike protein to the human ACE2 protein receptor. Overall, the data strongly support further clinical investigation of UFH as a potential treatment for patients with COVID-19