Arms positioning in post-mastectomy proton radiation:Feasibility and development of a new arms down contouring atlas

Background and purpose: Breast cancer patients receiving radiation are traditionally positioned with both arms up, but this may not be feasible or comfortable for all patients. We evaluated the treatment planning and positioning reproducibility differences between the arms up and arms down positions for patients receiving post-mastectomy radiation therapy (PMRT) using proton pencil beam scanning (PBS). Materials and methods: Ten PMRT patients who were scheduled to receive PBS underwent CT-based treatment planning in both an arms down and a standard arms up position. An arms down contouring atlas was developed for consistency in treatment planning. Treatment plans were performed on both scans. A Wilcoxon test was applied to compare arms up and arms down metrics across patients. Five patients received treatment in the arms-down position at our institution while others were treated with the arms up. Residual set-up errors were recorded for each patient's treatment fractions and compared between positions. Results: Target structure coverage remained consistent between the arms up and arms down positions. In regard to the OAR, the heart mean and maximum doses were statistically significantly lower in the arms up position versus the arms down position, however, the absolute differences were modest. Patients demonstrated similar setup errors, less than 0.5 mm differences, in all directions. Conclusions: PBS for PMRT in the arms down position appeared stable and reproducible compared to the traditional arms up positioning. The degree of OAR sparing in the arms down group was minimally less robust but still far superior to conventional photon therapy

Collagen Based Multicomponent Interpenetrating Networks as Promising Scaffolds for 3D Culture of Human Neural Stem Cells, Human Astrocytes, and Human Microglia

This work describes for the first time the fabrication and characterization of multicomponent interpenetrating networks composed of collagen I, hyaluronic acid, and poly(ethylene glycol) diacrylate for the 3D culture of human neural stem cells, astrocytes, and microglia. The chemical composition of the scaffolds can be modulated while maintaining values of complex moduli within the range of the mechanical performance of brain tissue (∼6.9 kPa) and having cell viability exceeding 84%. The developed scaffolds are a promising new family of biomaterials that can potentially serve as 3D in vitro models for studying the physiology and physiopathology of the central nervous system

Proton Therapy for Breast Cancer:A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research. (c) 2021 Elsevier Inc. All rights reserved

A TCR beta-Chain Motif Biases toward Recognition of Human CD1 Proteins

High-throughput TCR sequencing allows interrogation of the human TCR repertoire, potentially connecting TCR sequences to antigenic targets. Unlike the highly polymorphic MHC proteins, monomorphic Ag-presenting molecules such as MR1, CD1d, and CD1b present Ags to T cells with species-wide TCR motifs. CD1b tetramer studies and a survey of the 27 published CD1b-restricted TCRs demonstrated a TCR motif in humans defined by the TCR β-chain variable gene 4-1 (TRBV4-1) region. Unexpectedly, TRBV4-1 was involved in recognition of CD1b regardless of the chemical class of the carried lipid. Crystal structures of two CD1b-specific TRBV4-1+ TCRs show that germline-encoded residues in CDR1 and CDR3 regions of TRBV4-1–encoded sequences interact with each other and consolidate the surface of the TCR. Mutational studies identified a key positively charged residue in TRBV4-1 and a key negatively charged residue in CD1b that is shared with CD1c, which is also recognized by TRBV4-1 TCRs. These data show that one TCR V region can mediate a mechanism of recognition of two related monomorphic Ag-presenting molecules that does not rely on a defined lipid Ag

Sensitivity of the West Antarctic Ice Sheet to +2 °C (SWAIS 2C)

The West Antarctic Ice Sheet (WAIS) presently holds enough ice to raise global sea level by 4.3 m if completely melted. The unknown response of the WAIS to future warming remains a significant challenge for numerical models in quantifying predictions of future sea level rise. Sea level rise is one of the clearest planet-wide signals of human-induced climate change. The Sensitivity of the West Antarctic Ice Sheet to a Warming of 2 ∘C (SWAIS 2C) Project aims to understand past and current drivers and thresholds of WAIS dynamics to improve projections of the rate and size of ice sheet changes under a range of elevated greenhouse gas levels in the atmosphere as well as the associated average global temperature scenarios to and beyond the +2 ∘C target of the Paris Climate Agreement. Despite efforts through previous land and ship-based drilling on and along the Antarctic margin, unequivocal evidence of major WAIS retreat or collapse and its causes has remained elusive. To evaluate and plan for the interdisciplinary scientific opportunities and engineering challenges that an International Continental Drilling Program (ICDP) project along the Siple coast near the grounding zone of the WAIS could offer (Fig. 1), researchers, engineers, and logistics providers representing 10 countries held a virtual workshop in October 2020. This international partnership comprised of geologists, glaciologists, oceanographers, geophysicists, microbiologists, climate and ice sheet modelers, and engineers outlined specific research objectives and logistical challenges associated with the recovery of Neogene and Quaternary geological records from the West Antarctic interior adjacent to the Kamb Ice Stream and at Crary Ice Rise. New geophysical surveys at these locations have identified drilling targets in which new drilling technologies will allow for the recovery of up to 200 m of sediments beneath the ice sheet. Sub-ice-shelf records have so far proven difficult to obtain but are critical to better constrain marine ice sheet sensitivity to past and future increases in global mean surface temperature up to 2 ∘C above pre-industrial levels. Thus, the scientific and technological advances developed through this program will enable us to test whether WAIS collapsed during past intervals of warmth and determine its sensitivity to a +2 ∘C global warming threshold (UNFCCC, 2015)

International study on inter-reader variability for circulating tumor cells in breast cancer

Introduction: Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch® system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement.Methods: CellSearch® images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2- vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (κ) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test.Results: For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median κ of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and <3CTCs (median 87%, range 66 to 95%) compared to M0 and ≥3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2- vs HER2+), the median agreement was 87% (range 51 to 95%) with a median κ of 0.74 (range 0.25 to 0.90).Conclusions: The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London