Although EGFR mutant tumors exhibit low response rates to immune checkpoint blockade overall, some EGFR mutant tumors do respond to these therapies; however, there is a lack of understanding of the ...characteristics of EGFR mutant lung tumors responsive to immune checkpoint blockade.
We retrospectively analyzed de-identified clinical and molecular data on 171 cases of EGFR mutant lung tumors treated with immune checkpoint inhibitors from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, University of California Los Angeles, and Dana Farber Cancer Institute. A separate cohort of 383 EGFR mutant lung cancer cases with sequencing data available from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, and The Cancer Genome Atlas was compiled to assess the relationship between tumor mutation burden and specific EGFR alterations.
Compared with 212 EGFR wild-type lung cancers, outcomes with programmed cell death 1 or programmed death-ligand 1 (PD-(L)1) blockade were worse in patients with lung tumors harboring alterations in exon 19 of EGFR (EGFRΔ19) but similar for EGFRL858R lung tumors. EGFRT790M status and PD-L1 expression did not impact response or survival outcomes to immune checkpoint blockade. PD-L1 expression was similar across EGFR alleles. Lung tumors with EGFRΔ19 alterations harbored a lower tumor mutation burden compared with EGFRL858R lung tumors despite similar smoking history.
EGFR mutant tumors have generally low response to immune checkpoint inhibitors, but outcomes vary by allele. Understanding the heterogeneity of EGFR mutant tumors may be informative for establishing the benefits and uses of PD-(L)1 therapies for patients with this disease.
The study of open charm meson production provides an efficient tool for the investigation of the properties of hot and dense matter formed in nucleus–nucleus collisions. The interpretation of the ...existing di-muon data from the CERN SPS suffers from a lack of knowledge on the mechanism and properties of the open charm particle production. Due to this, the heavy-ion programme of the NA61/SHINE experiment at the CERN SPS has been extended by precise measurements of charm hadrons with short lifetimes. A new Vertex Detector for measurements of the rare processes of open charm production in nucleus–nucleus collisions was designed to meet the challenges of track registration and high resolution in primary and secondary vertex reconstruction. A small-acceptance version of the vertex detector was installed in 2016 and tested with Pb + Pb collisions at 150
A
GeV
/
c
. It was also operating during the physics data taking on Xe + La and Pb + Pb collisions at 150
A
GeV
/
c
conducted in 2017 and 2018. This paper presents the detector design and construction, data calibration, event reconstruction, and analysis procedure.
The Compressed Baryonic Matter (CBM) experiment is to explore the properties of strongly interacting matter in the regime of highest net baryon densities. It aims to find experimental evidence for ...numerous predicted effects like a first order phase transition between hadronic and partonic matter, the existence of a critical endpoint of this phase transition and the expected onset of chiral symmetry restoration. The 8-45 AGeV heavy ion beam needed to create the hot and dense matter in the fixed target experiment will be provided by the SIS100 and the SIS300 synchrotron of the future FAIR facility in Darmstadt, Germany. The paper provides an introduction into the measurement challenges and the technological concept of CBM-experiment from an instrumentalist's point of view.
Measurements of multiplicity and transverse momentum fluctuations of charged particles were performed in inelastic p+p interactions at 20, 31, 40, 80, and 158
GeV
/
c
beam momentum. Results for the ...scaled variance of the multiplicity distribution and for three strongly intensive measures of multiplicity and transverse momentum fluctuations
Δ
P
T
,
N
,
Σ
P
T
,
N
and
Φ
p
T
are presented. For the first time the results on fluctuations are fully corrected for experimental biases. The results on multiplicity and transverse momentum fluctuations significantly deviate from expectations for the independent particle production. They also depend on charges of selected hadrons. The string-resonance Monte Carlo models
Epos
and
U
r
qmd
do not describe the data. The scaled variance of multiplicity fluctuations is significantly higher in inelastic p+p interactions than in central Pb+Pb collisions measured by NA49 at the same energy per nucleon. This is in qualitative disagreement with the predictions of the Wounded Nucleon Model. Within the statistical framework the enhanced multiplicity fluctuations in inelastic p+p interactions can be interpreted as due to event-by-event fluctuations of the fireball energy and/or volume.
The ultra-thin and highly granular CMOS Monolithic Active Pixel Sensors (MAPS) are typically optimized for high rate high precision tracking, which implies the use of a very thin active medium and ...digital readout. Both features hamper using the devices for identifying low momentum particles by means of dE/dx. Still, MAPS feature charge sharing and typically clusters of more than one fired pixel per impinging particles are formed. It was previously shown that the number of fired pixels per cluster scales with the dE/dx, which allowed identifying highly ionizing nuclear fragments 1. Assuming a sufficiently strong response to different dE/dx, this approach could also be considered for distinguishing minimum ionizing particles (MIP) from light fragments like alpha particles in tracking detectors. In this work, we study this response with particle beams with a dE/dx of up to four times the ones of MIPs, for non-irradiated and irradiated chips, with different sensing nodes as implemented in the MIMOSIS-1 prototype used for the vertex detector of the CBM experiment.
Measurements of multiplicity fluctuations of identified hadrons produced in inelastic p+p interactions at 31, 40, 80, and 158 Formula omitted beam momentum are presented. Three different measures of ...multiplicity fluctuations are used: the scaled variance Formula omitted and strongly intensive measures Formula omitted and Formula omitted. These fluctuation measures involve second and first moments of joint multiplicity distributions. Data analysis is preformed using the Identity method which corrects for incomplete particle identification. Strongly intensive quantities are calculated in order to allow for a direct comparison to corresponding results on nucleus-nucleus collisions. The results for different hadron types are shown as a function of collision energy. A comparison with predictions of string-resonance Monte-Carlo models: Epos, Smash and Venus, is also presented.
The effect of biodiversity declines on human health is currently debated, but empirical assessments are lacking. Lyme disease provides a model system to assess relationships between biodiversity and ...human disease because the etiologic agent, Borrelia burgdorferi, is transmitted in the United States by the generalist black-legged tick (Ixodes scapularis) among a wide range of mammalian and avian hosts. The 'dilution effect' hypothesis predicts that species-poor host communities dominated by white-footed mice (Peromyscus leucopus) will pose the greatest human risk because P. leucopus infects the largest numbers of ticks, resulting in higher human exposure to infected I. scapularis ticks. P. leucopus-dominated communities are also expected to maintain a higher frequency of those B. burgdorferi outer surface protein C (ospC) genotypes that this host species more efficiently transmits ('multiple niche polymorphism' hypothesis). Because some of these genotypes are human invasive, an additive increase in human disease risk is expected in species-poor settings. We assessed these theoretical predictions by comparing I. scapularis nymphal infection prevalence, density of infected nymphs and B. burgdorferi genotype diversity at sites on Block Island, RI, where P. leucopus dominates the mammalian host community, to species-diverse sites in northeastern Connecticut. We found no support for the dilution effect hypothesis; B. burgdorferi nymphal infection prevalence was similar between island and mainland and the density of B. burgdorferi infected nymphs was higher on the mainland, contrary to what is predicted by the dilution effect hypothesis. Evidence for the multiple niche polymorphism hypothesis was mixed: there was lower ospC genotype diversity at island than mainland sites, but no overrepresentation of genotypes with higher fitness in P. leucopus or that are more invasive in humans. We conclude that other mechanisms explain similar nymphal infection prevalence in both communities and that high ospC genotype diversity can be maintained in both species-poor and species-rich communities.
CMOS pixel sensors are foreseen to equip the vertex detector (called PXL) of the upgraded inner tracking system of the STAR experiment at RHIC. The sensors (called ULTIMATE) are being designed and ...their architecture is being optimized for the PXL specifications, extrapolating from the MIMOSA-26 sensor realized for the EUDET beam telescope.
The paper gives an overview of the ULTIMATE sensor specifications and of the adaptation of its forerunner, MIMOSA-26, to the PXL specifications.
One of the main changes between MIMOSA-26 and ULTIMATE is the use of a high resistivity epitaxial layer. Recent performance assessments obtained with MIMOSA-26 sensors manufactured on such an epitaxial layer are presented, as well as results of beam tests obtained with a prototype probing improved versions of the MIMOSA-26 pixel design. They show drastic improvements of the pixel signal-to-noise ratio and of the sensor radiation tolerance with respect to the performances achieved with a standard, i.e. low resistivity, layer.
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