Erdafitinib, an inhibitor of fibroblast growth factor receptor, was tested in previously treated patients with advanced urothelial cancer with
FGFR
alterations. The objective response rate was 40%, ...with treatment-related adverse events of grade 3 or higher reported in nearly half the patients.
There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status ...measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC.
We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial).
In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS hazard ratio (HR), 3.98; 95% CI 1.74–9.10; P < 0.001 and HR 3.81; 95% CI 2.28–6.37; P < 0.001, respectively, PFS (HR 2.18; 95% CI 1.08–4.39; P = 0.03, and HR 1.95; 95% CI 1.23–3.11; P = 0.01, respectively) and rate of PSA decline≥50% odds ratio (OR), 4.7; 95% CI 1.17–19.17; P = 0.035 and OR, 5.0; 95% CI 1.70–14.91; P = 0.003, respectively. AR mutations 2105T>A (p.L702H) and 2632A>G (p.T878A) were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47–not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94–9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26–19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16–56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts.
Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required.
NCT02288936 (PREMIERE trial).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Novel considerations are presented on the physics, apparatus and accelerator designs for a future, luminous, energy frontier electron-hadron (
eh
) scattering experiment at the LHC in the thirties ...for which key physics topics and their relation to the hadron-hadron HL-LHC physics programme are discussed. Demands are derived set by these physics topics on the design of the LHeC detector, a corresponding update of which is described. Optimisations on the accelerator design, especially the interaction region (IR), are presented. Initial accelerator considerations indicate that a common IR is possible to be built which alternately could serve
eh
and
hh
collisions while other experiments would stay on
hh
in either condition. A forward-backward symmetrised option of the LHeC detector is sketched which would permit extending the LHeC physics programme to also include aspects of hadron-hadron physics. The vision of a joint
eh
and
hh
physics experiment is shown to open new prospects for solving fundamental problems of high energy heavy-ion physics including the partonic structure of nuclei and the emergence of hydrodynamics in quantum field theory while the genuine TeV scale DIS physics is of unprecedented rank.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Determining the spin and the parity quantum numbers of the recently discovered Higgs-like boson at the LHC is a matter of great importance. In this Letter, we consider the possibility of using the ...kinematics of the tagging jets in Higgs production via the vector boson fusion (VBF) process to test the tensor structure of the Higgs–vector boson (HVV) interaction and to determine the spin and CP properties of the observed resonance. We show that an anomalous HVV vertex, in particular its explicit momentum dependence, drastically affects the rapidity between the two scattered quarks and their transverse momenta and, hence, the acceptance of the kinematical cuts that allow to select the VBF topology. The sensitivity of these observables to different spin–parity assignments, including the dependence on the LHC center of mass energy, are evaluated. In addition, we show that in associated Higgs production with a vector boson some kinematical variables, such as the invariant mass of the system and the transverse momenta of the two bosons and their separation in rapidity, are also sensitive to the spin–parity assignments of the Higgs-like boson.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
DRESS syndrome due to iodinated contrast media. A case report Zambrano Ibarra, G; Noguerado Mellado, B; Tornero Molina, P ...
Allergy, asthma & clinical immunology/Allergy, asthma, and clinical immunology,
02/2023, Volume:
19, Issue:
1
Journal Article
Peer reviewed
Open access
The most frequent non-immediate reactions described with iodinated contrast media (ICM) are mild to moderate, however, some cases of patients with severe non-immediate reactions, such as drug ...eruption with eosinophilia and systemic symptoms (DRESS) have been described.
An 84-year-old patient developed DRESS syndrome after administration of ICM ioversol. The patient fullfilled the RegiSCAR diagnostic criteria for DRESS (definite score = 6). He underwent intradermal skin testing (IDT) with the widest panel of ICM available at our center. IDT was positive with ioversol and iomeprol. A punch biopsy was performed on the positive IDT with the culprit drug (ioversol) and histopathology was compatible with a T-cell mediated mechanism.
In this case, the IDT-positive biopsy was consistent with DRESS syndrome caused by T-lymphocyte activation, supporting the clinical diagnosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We hypothesized that the abundance of PD1 mRNA in tumor samples might explain the differences in overall response rates (ORR) observed following anti-PD1 monotherapy across cancer types.
RNASeqv2 ...data from 10078 tumor samples representing 34 different cancer types was analyzed from TCGA. Eighteen immune-related gene signatures and 547 immune-related genes, including PD1, were explored. Correlations between each gene/signature and ORRs reported in the literature following anti-PD1 monotherapy were calculated. To translate the in silico findings to the clinical setting, we analyzed the expression of PD1 mRNA using the nCounter platform in 773 formalin-fixed paraffin embedded (FFPE) tumor samples across 17 cancer types. To test the direct relationship between PD1 mRNA, PDL1 immunohistochemistry (IHC), stromal tumor-infiltrating lymphocytes (sTILs) and ORR, we evaluated an independent FFPE-based dataset of 117 patients with advanced disease treated with anti-PD1 monotherapy.
In pan-cancer TCGA, PD1 mRNA expression was found strongly correlated (r>0.80) with CD8 T-cell genes and signatures and the proportion of PD1 mRNA-high tumors (80th percentile) within a given cancer type was variable (0%–84%). Strikingly, the PD1-high proportions across cancer types were found strongly correlated (r=0.91) with the ORR following anti-PD1 monotherapy reported in the literature. Lower correlations were found with other immune-related genes/signatures, including PDL1. Using the same population-based cutoff (80th percentile), similar proportions of PD1-high disease in a given cancer type were identified in our in-house 773 tumor dataset as compared with TCGA. Finally, the pre-established PD1 mRNA FFPE-based cutoff was found significantly associated with anti-PD1 response in 117 patients with advanced disease (PD1-high 51.5%, PD1-intermediate 26.6% and PD1-low 15.0%; odds ratio between PD1-high and PD1-intermediate/low=8.31; P<0.001). In this same dataset, PDL1 tumor expression by IHC or percentage of sTILs was not found associated with response.
Our study provides a clinically applicable assay that links PD1 mRNA abundance, activated CD8 T-cells and anti-PD1 efficacy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Dentro de un marco de interdependencia por la internacionalización de los mercados y la conectividad global, resultan las mudanzas que sufriera el capitalismo mundial con la aceleración vertiginosa ...de los cambios tecnológicos digitales que continúan transformándolo, al tiempo que crean oportunidades económicas y generan poderosos gigantes en el mercado poniendo en riesgo la intimidad de las personas y los derechos ciudadanos. Este escenario conduce a plantear ciertos interrogantes claves: cómo enfrentar el desafío que conlleva la digitalización y el surgimiento de empresas oferentes de plataformas virtuales; cuáles serán las políticas a adoptar en consecuencia, particularmente las tributarias por los problemas inéditos que se plantean en la materia, a partir de considerar a los datos como clave de la generación del valor y el rol de las plataformas digitales para capitalizarlos. Asimismo, la incertidumbre se constituye en la variable contextual por efecto de tensiones geopolíticas y estratégicas, tanto en Estados Unidos y China como en Europa del Este, que permitirían afianzar el predominio de las principales potencias mundiales como impulsoras de la Economía digital.
ALBA y MERCOSUR en cuestión Mellado, Noemí B.
Aportes para la integración latinoamericana,
12/2021
45
Journal Article
Peer reviewed
Open access
Los procesos de integración, como todo proceso, se gestan con la consigna de iniciar un camino evolutivo en función de los objetivos que se plantean al momento de nacer. Dicho progreso se ve ...condicionado por el acompañamiento de los diferentes actores o agentes, tanto internos como externos, que conforman el ámbito de acción en el cual se desarrollan.
A su vez, las variables endógenas y exógenas de influencia pueden llegar a generar modificaciones que indefectiblemente impactarán en la consecución de los objetivos planteados desde el inicio, derivando en algunos casos a un mayor impulso o a sus crisis. La historia de la integración latinoamericana exhibe un camino sinuoso, algunas veces de certezas y otras de incertidumbre, que lleva a analizar y replantear por parte de académicos a dos procesos de integración en marcha: “MERCOSUR Y ALBA-TCP”.
Abstract
The Tile PreProcessor (TilePPr) is the core element of the Tile Calorimeter (TileCal) off-detector electronics for High-luminosity Large Hadron Collider (HL-LHC). The TilePPr comprises ...FPGA-based boards to operate and read out the TileCal on-detector electronics. The Tile Computer on Module (TileCoM) mezzanine is embedded within TilePPr to carry out three main functionalities. These include remote configuration of on-detector electronics and TilePPr FPGAs, interface the TilePPr with the ATLAS Trigger and Data Acquisition (TDAQ) system, and interfacing the TilePPr with the ATLAS Detector Control System (DCS) by providing monitoring data. The TileCoM is a 10-layer board with a Zynq UltraScale+ ZU2CG for processing data, interface components to integrate with TilePPr and the power supply to be connected to the Advanced Telecommunication Computing Architecture carrier. A CentOS embedded Linux is deployed on the TileCoM to implement the required functionalities for the HL-LHC. In this paper we present the hardware and firmware developments of the TileCoM system in terms of remote programming, interface with ATLAS TDAQ system and DCS system.
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