Surgical options for Chinese patients with early invasive breast cancer: Data from the Hong Kong Breast Cancer Registry

Background: Breast conserving surgery (BCS) is preferred for suitable candidates, while mastectomy (MTX) with reconstruction (MTX + R) is considered a better option for patients requiring MTX. In Hong Kong, the rates of BCS and breast reconstruction are relatively low. This paper aims to study the surgical options and their predictors among Hong Kong breast cancer patients. Methods: Data is retrieved from the Hong Kong Breast Cancer Registry (HKBCR) from 2007 to 2013. A total of 4519 Stage I–II breast cancer patients who had surgical treatments were included in this retrospective study. Results: Our multivariate logistic regression shows that people who were younger (age < 40 years: OR, 1.5; 95% CI, 1.1–2.1; p = 0.010), more educated (undergraduate/postgraduate: OR, 2.8; 95% CI, 1.7–4.4; p < 0.0001), never married (OR, 1.5; 95% CI, 1.1–1.9; p = 0.002), had regular mammography screening (OR, 1.5; 95% CI, 1.3–1.8; p < 0.0001), had screen-detected cancers (OR, 1.3; 95% CI, 1.0–1.6; p = 0.031), and who underwent surgery at a private medical service facility (OR, 1.8; 95% CI, 1.6–2.2; p < 0.0001) were more likely to receive BCS. In addition, people who were younger (age < 40 years: OR, 15.9; 95% CI, 6.5–39.2; p < 0.0001), more educated (undergraduate/postgraduate: OR, 26.8; 95% CI, 3.6–201.4; p = 0.001), had regular mammography screening (OR, 1.6; 95% CI, 1.1–2.3; p = 0.008), had screen-detected cancers (OR, 2.1; 95% CI, 1.4–3.3; p = 0.001), and had smaller tumor (≤ 2.0 cm: OR, 0.39; 95% CI, 0.20–0.76; p = 0.005) were more likely to have reconstruction after MTX. Conclusion: Chinese patients have lower BCS and breast reconstruction rate. Besides cultural difference, patient-related factors such as age, education, marital status, mammography screening, the use of private medical facilities, and clinical characteristics including smaller tumor size and peripherally located tumor were significant predictors for type of surgical treatments in Chinese women with early breast cancer

Exploration of the intercellular heterogeneity of topotecan uptake into human breast cancer cells through compartmental modelling

A mathematical multi-cell model for the in vitro kinetics of the anti-cancer agent topotecan (TPT) following administration into a culture medium containing a population of human breast cancer cells (MCF-7 cell line) is described. This non-linear compartmental model is an extension of an earlier single-cell type model and has been validated using experimental data obtained using two-photon laser scanning microscopy (TPLSM). A structural identifiability analysis is performed prior to parameter estimation to test whether the unknown parameters within the model are uniquely determined by the model outputs. The full model has 43 compartments, with 107 unknown parameters, and it was found that the structural identifiability result could not be established even when using the latest version of the symbolic computation software MATHEMATICA. However, by assuming that a priori knowledge is available for certain parameters, it was possible to reduce the number of parameters to 81, and it was found that this (Stage Two) model was globally (uniquely) structurally identifiable. The identifiability analysis demonstrated how valuable symbolic computation is in this context, as the analysis is far too lengthy and difficult to be performed by hand. (C) 2008 Elsevier Inc. All rights reserved

Moving towards a question‐centric approach for regulatory decision‐making in the context of drug assessment

The most intuitive question for market access for medicinal products is the benefit/risk (B/R) balance. The B/R assessment can conceptually be divided into subquestions related to establishing efficacy and safety. There are additional layers to the B/R ratio for medical products, including questions related to dose selection, clinical and nonclinical pharmacology, and drug quality. Explicitly stating the actual questions and how they contribute to the overall B/R provides a structure that fosters better informed cross-domain discussions. There is currently no systematic approach in the regulatory setting to assess and establish the acceptability of alternative methods and data sources. In most cases, the medicinal product sponsors tend to prioritize traditional data types and methods, which are well accepted by regulators for inclusion in regulatory submissions. This, in addition to the absence of rigor in the use and validation of new data types and methods, and the limited training of assessors in related fields can lead to increased regulatory skepticism toward new data types and methods. A data-knowledge backbone is needed to mitigate the uncertainty in efficacy and safety characterization. This white paper discusses the value of explicitly redefining and restructuring the regulatory scientific decision making around the scientific question to be addressed. The ecosystem proposed is based on three pillars: (i) a repository connecting questions, data, and methods; (ii) the development and validation of high-quality standards for data and methods; and (iii) credibility assessment. The ecosystem is applied to four use cases for illustration. The need for training and regulatory guidance is also discussed

Observation of WWWWWW Production in pppp Collisions at s\sqrt s =13 TeV with the ATLAS Detector

International audienceThis Letter reports the observation of $WWW$ production and a measurement of its cross section using 139 fb$^{-1}$ of proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider. Events with two same-sign leptons (electrons or muons) and at least two jets, as well as events with three charged leptons, are selected. A multivariate technique is then used to discriminate between signal and background events. Events from $WWW$ production are observed with a significance of 8.0 standard deviations, where the expectation is 5.4 standard deviations. The inclusive $WWW$ production cross section is measured to be $820 \pm 100\,\text{(stat)} \pm 80\,\text{(syst)}$ fb, approximately 2.6 standard deviations from the predicted cross section of $511 \pm 18$ fb calculated at next-to-leading-order QCD and leading-order electroweak accuracy

Observation of WWWWWW Production in pppp Collisions at s\sqrt s =13 TeV with the ATLAS Detector

International audienceThis Letter reports the observation of $WWW$ production and a measurement of its cross section using 139 fb$^{-1}$ of proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider. Events with two same-sign leptons (electrons or muons) and at least two jets, as well as events with three charged leptons, are selected. A multivariate technique is then used to discriminate between signal and background events. Events from $WWW$ production are observed with a significance of 8.0 standard deviations, where the expectation is 5.4 standard deviations. The inclusive $WWW$ production cross section is measured to be $820 \pm 100\,\text{(stat)} \pm 80\,\text{(syst)}$ fb, approximately 2.6 standard deviations from the predicted cross section of $511 \pm 18$ fb calculated at next-to-leading-order QCD and leading-order electroweak accuracy

Observation of WWWWWW Production in pppp Collisions at s\sqrt s =13 TeV with the ATLAS Detector

International audienceThis Letter reports the observation of $WWW$ production and a measurement of its cross section using 139 fb$^{-1}$ of proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider. Events with two same-sign leptons (electrons or muons) and at least two jets, as well as events with three charged leptons, are selected. A multivariate technique is then used to discriminate between signal and background events. Events from $WWW$ production are observed with a significance of 8.0 standard deviations, where the expectation is 5.4 standard deviations. The inclusive $WWW$ production cross section is measured to be $820 \pm 100\,\text{(stat)} \pm 80\,\text{(syst)}$ fb, approximately 2.6 standard deviations from the predicted cross section of $511 \pm 18$ fb calculated at next-to-leading-order QCD and leading-order electroweak accuracy