RECENT PROGRESS TOWARD A MUON RECIRCULATING LINEAR ACCELERATOR

Both Neutrino Factories (NF) and Muon Colliders (MC) require very rapid acceleration due to the short lifetime of muons. After a capture and bunching section, a linac raises the energy to about 900 MeV, and is followed by one or more Recirculating Linear Accelerators (RLA), possibly followed by a Rapid Cycling Synchnotron (RCS) or Fixed-Field Alternating Gradient (FFAG) ring. A RLA reuses the expensive RF linac section for a number of passes at the price of having to deal with different energies within the same linac. Various techniques including pulsed focusing quadruopoles, beta frequency beating, and multipass arcs have been investigated via simulations to improve the performance and reduce the cost of such RLAs

Innovative Applications of Genetic Algorithms to Problems in Accelerator Physics

The genetic algorithm (GA) is a powerful technique that implements the principles nature uses in biological evolution to optimize a multidimensional nonlinear problem. The GA works especially well for problems with a large number of local extrema, where traditional methods (such as conjugate gradient, steepest descent, and others) fail or, at best, underperform. The field of accelerator physics, among others, abounds with problems which lend themselves to optimization via GAs. In this paper, we report on the successful application of GAs in several problems related to the existing Continuous Electron Beam Accelerator Facility nuclear physics machine, the proposed Medium-energy Electron-Ion Collider at Jefferson Lab, and a radio frequency gun-based injector. These encouraging results are a step forward in optimizing accelerator design and provide an impetus for application of GAs to other problems in the field. To that end, we discuss the details of the GAs used, include a newly devised enhancement which leads to improved convergence to the optimum, and make recommendations for future GA developments and accelerator applications

Beam-Beam Effect: Crab Dynamics Calculation in JLEIC

The electron and ion beams of a future Electron Ion Collider (EIC) must collide at an angle for detection, machine and engineering design reasons. To avoid associated luminosity reduction, a local crabbing scheme is used where each beam is crabbed before collision and de-crabbed after collision. The crab crossing scheme then provides a head-on collision for beams with a non-zero crossing angle. We develop a framework for accurate simulation of crabbing dynamics with beam-beam effects by combining symplectic particle tracking codes with a beam-beam model based on the Bassetti-Erskine analytic solution. We present simulation results using our implementation of such a framework where the beam dynamics around the ring is tracked using Elegant and the beam-beam kick is modeled in Python

Evolution of Endoscopic Lesions in Steroid-Refractory Acute Severe Ulcerative Colitis Responding to Infliximab or Cyclosporine

BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS >= 6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p CONCLUSION: In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.Peer reviewe

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls

Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance.Funder: The Canadian Cancer SocietyFunder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Calibrating transport lines using LOCO techniques

With the 12GeV upgrade underway at CEBAF, there is a need to re-characterize the beamlines after the modifications made to it to accommodate running at higher energies. We present a linear perturbation approach to calibrating the optics model of transport lines. This method is adapted from the LOCO method in use for storage rings. We consider the effect of quadrupole errors, dipole construction errors as well as beam position monitors and correctors calibrations. The ideal model is expanded to first order in Taylor series of the quadrupole errors. A set of difference orbits obtained by exciting the correctors along the beamline is taken, yielding the measured response matrix. An iterative procedure is invoked and the quadrupole errors as well as beam position monitors and corrector calibration factors are obtained. Here we present details of the method and results of first measurements at CEBAF in early 2011

Further Analysis of Real Beam Line Optics From A Synthetic Beam

Standard closed-orbit techniques for Twiss parameter measurement are not applicable to the open-ended Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab. The evolution of selected sets of real orbits in the accelerator models the behavior of a 'synthetic' beam. This process will be validated against beam profile-based Twiss parameter measurements and should provide the distributed optical information needed to optimize beamline tuning for an open-ended system. This work will discuss the current and future states of this technique, as well as an example of its use in the CEBAF machine