Spin-outs

The subject of this report is spin-outs in the Netherlands compared to those in the Cambridge area. The differences between the two areas have been found to be fewer than expected. The same type of initiatives are to be found in both areas, and the same type of problems are also encountered in both areas In general it seems that it would be advisable for universities to have spin-out stimulation added to the performance criteria to help the better facilitation of spin-outs.

The M 4 Core Project with HST - III. Search for variable stars in the primary field

We present the results of a photometric search for variable stars in the core of the Galactic globular cluster Messier 4 (M 4). The input data are a large and unprecedented set of deep Hubble Space Telescope WFC3 images (large programme GO-12911; 120 orbits allocated), primarily aimed at probing binaries with massive companions by detecting their astrometric wobbles. Though these data were not optimized to carry out a time-resolved photometric survey, their exquisite precision, spatial resolution and dynamic range enabled us to firmly detect 38 variable stars, of which 20 were previously unpublished. They include 19 clustermember eclipsing binaries (confirming the large binary fraction ofM4), RR Lyrae and objects with known X-ray counterparts. We improved and revised the parameters of some among published variables

Optimised Dirac Operators on the Lattice: Construction, Properties and Applications

We review a number of topics related to block variable renormalisation group transformations of quantum fields on the lattice, and to the emerging perfect lattice actions. We first illustrate this procedure by considering scalar fields. Then we proceed to lattice fermions, where we discuss perfect actions for free fields, for the Gross-Neveu model and for a supersymmetric spin model. We also consider the extension to perfect lattice perturbation theory, in particular regarding the axial anomaly and the quark gluon vertex function. Next we deal with properties and applications of truncated perfect fermions, and their chiral correction by means of the overlap formula. This yields a formulation of lattice fermions, which combines exact chiral symmetry with an optimisation of further essential properties. We summarise simulation results for these so-called overlap-hypercube fermions in the two-flavour Schwinger model and in quenched QCD. In the latter framework we establish a link to Chiral Perturbation Theory, both, in the p-regime and in the epsilon-regime. In particular we present an evaluation of the leading Low Energy Constants of the chiral Lagrangian - the chiral condensate and the pion decay constant - from QCD simulations with extremely light quarks.Comment: published version (plus slight extension), 120 pages, 41 figure

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Saving Human Lives: What Complexity Science and Information Systems can Contribute

We discuss models and data of crowd disasters, crime, terrorism, war and disease spreading to show that conventional recipes, such as deterrence strategies, are often not effective and sufficient to contain them. Many common approaches do not provide a good picture of the actual system behavior, because they neglect feedback loops, instabilities and cascade effects. The complex and often counter-intuitive behavior of social systems and their macro-level collective dynamics can be better understood by means of complexity science. We highlight that a suitable system design and management can help to stop undesirable cascade effects and to enable favorable kinds of self-organization in the system. In such a way, complexity science can help to save human lives.Comment: 67 pages, 25 figures; accepted for publication in Journal of Statistical Physics [for related work see http://www.futurict.eu/

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