PhysioZoo: The Open Digital Physiological Biomarkers Resource

PhysioZoo is a collaborative platform designed for the analysis of continuous physiological time series. The platform currently comprises four modules, each consisting of a library, a user interface, and a set of tutorials: (1) PhysioZoo HRV, dedicated to studying heart rate variability (HRV) in humans and other mammals; (2) PhysioZoo SPO2, which focuses on the analysis of digital oximetry biomarkers (OBM) using continuous oximetry (SpO2) measurements from humans; (3) PhysioZoo ECG, dedicated to the analysis of electrocardiogram (ECG) time series; (4) PhysioZoo PPG, designed to study photoplethysmography (PPG) time series. In this proceeding, we introduce the PhysioZoo platform as an open resource for digital physiological biomarkers engineering, facilitating streamlined analysis and data visualization of physiological time series while ensuring the reproducibility of published experiments. We welcome researchers to contribute new libraries for the analysis of various physiological time series, such as electroencephalography, blood pressure, and phonocardiography. You can access the resource at physiozoo.com. We encourage researchers to explore and utilize this platform to advance their studies in the field of continuous physiological time-series analysis.Comment: 4 pages, 2 figure, 50th Computing in Cardiology conference in Atlanta, Georgia, USA on 1st - 4th October 202

Activating mTOR Mutations in a Patient with an Extraordinary Response on a Phase I Trial of Everolimus and Pazopanib

Understanding the genetic mechanisms of sensitivity to targeted anticancer therapies may improve patient selection, response to therapy, and rational treatment designs. One approach to increase this understanding involves detailed studies of exceptional responders: rare patients with unexpected exquisite sensitivity or durable responses to therapy. We identified an exceptional responder in a phase I study of pazopanib and everolimus in advanced solid tumors. Whole-exome sequencing of a patient with a 14-month complete response on this trial revealed two concurrent mutations in mTOR, the target of everolimus. In vitro experiments demonstrate that both mutations are activating, suggesting a biologic mechanism for exquisite sensitivity to everolimus in this patient. The use of precision (or “personalized”) medicine approaches to screen patients with cancer for alterations in the mTOR pathway may help to identify subsets of patients who may benefit from targeted therapies directed against mTOR.National Human Genome Research Institute (U.S.) (5U54HG003067-11

The GenoChip: A New Tool for Genetic Anthropology

The Genographic Project is an international effort aimed at charting human migratory history. The project is nonprofit and nonmedical, and, through its Legacy Fund, supports locally led efforts to preserve indigenous and traditional cultures. Although the first phase of the project was focused on uniparentally inherited markers on the Y-chromosome and mitochondrial DNA (mtDNA), the current phase focuses on markers from across the entire genome to obtain a more complete understanding of human genetic variation. Although many commercial arrays exist for genome-wide single-nucleotide polymorphism (SNP) genotyping, they were designed for medical genetic studies and contain medically related markers that are inappropriate for global population genetic studies. GenoChip, the Genographic Project’s new genotyping array, was designed to resolve these issues and enable higher resolution research into outstanding questions in genetic anthropology. The GenoChip includes ancestry informative markers obtained for over 450 human populations, an ancient human (Saqqaq), and two archaic hominins (Neanderthal and Denisovan) and was designed to identify all known Y-chromosome and mtDNA haplogroups. The chip was carefully vetted to avoid inclusion of medically relevant markers. To demonstrate its capabilities, we compared the FST distributions of GenoChip SNPs to those of two commercial arrays. Although all arrays yielded similarly shaped (inverse J) FST distributions, the GenoChip autosomal and X-chromosomal distributions had the highest mean FST, attesting to its ability to discern subpopulations. The chip performances are illustrated in a principal component analysis for 14 worldwide populations. In summary, the GenoChip is a dedicated genotyping platform for genetic anthropology. With an unprecedented number of approximately 12,000 Y-chromosomal and approximately 3,300 mtDNA SNPs and over 130,000 autosomal and X-chromosomal SNPs without any known health, medical, or phenotypic relevance, the GenoChip is a useful tool for genetic anthropology and population genetics

Expansion and Characterization of Human Melanoma Tumor-Infiltrating Lymphocytes (TILs)

Various immunotherapeutic strategies for cancer are aimed at augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT), where T cells are manipulated ex vivo and subsequently re-infused in an autologous manner, has been performed using T cells from various sources. Some of the highest clinical response rates for metastatic melanoma have been reported in trials using tumor-infiltrating lymphocytes (TILs). These protocols still have room for improvement and furthermore are currently only performed at a limited number of institutions. The goal of this work was to develop TILs as a therapeutic product at our institution.TILs from 40 melanoma tissue specimens were expanded and characterized. Under optimized culture conditions, 72% of specimens yielded rapidly proliferating TILs as defined as at least one culture reaching ≥3×10(7) TILs within 4 weeks. Flow cytometric analyses showed that cultures were predominantly CD3+ T cells, with highly variable CD4+:CD8+ T cell ratios. In total, 148 independent bulk TIL cultures were assayed for tumor reactivity. Thirty-four percent (50/148) exhibited tumor reactivity based on IFN-γ production and/or cytotoxic activity. Thirteen percent (19/148) showed specific cytotoxic activity but not IFN-γ production and only 1% (2/148) showed specific IFN-γ production but not cytotoxic activity. Further expansion of TILs using a 14-day "rapid expansion protocol" (REP) is required to induce a 500- to 2000-fold expansion of TILs in order to generate sufficient numbers of cells for current ACT protocols. Thirty-eight consecutive test REPs were performed with an average 1865-fold expansion (+/- 1034-fold) after 14 days.TILs generally expanded efficiently and tumor reactivity could be detected in vitro. These preclinical data from melanoma TILs lay the groundwork for clinical trials of ACT

Signaling and mediation in games with common interest

International audiencePlayers who have a common interest are engaged in a game with incomplete information. Before playing they get differential stochastic signals that depend on the actual state of nature. These signals provide the players with partial information about the state of nature and may also serve as a means of correlation. Different information structures induce different outcomes. An information structure is better than another, with respect to a certain solution concept, if the highest solution payoff it induces is at least that induced by the other structure. This paper characterizes the situation where one information structure is better than another with respect to various solution concepts: Nash equilibrium, strategic-normal-form correlated equilibrium, agent-normal-form correlated equilibrium and belief-invariant Bayesian solution. These solution concepts differ from one another in the scope of communication allowed between the players. The characterizations use maps that stochastically translate signals of one structure to signals of another

Signaling and mediation in games with common interests

Players who have a common interest are engaged in a game with incomplete information. Before playing they get differential stochastic signals that depend on the actual state of nature. These signals provide the players with partial information about the state of nature and may also serve as a means of correlation. Different information structures induce different outcomes. An information structure is better than another, with respect to a certain solution concept, if the highest solution payoff it induces is at least that induced by the other structure. This paper characterizes the situation where one information structure is better than another with respect to various solution concepts: Nash equilibrium, strategic-normal-form correlated equilibrium, agent-normal-form correlated equilibrium and belief-invariant Bayesian solution. These solution concepts differ from one another in the scope of communication allowed between the players. The characterizations use maps that stochastically translate signals of one structure to signals of another.