Many testicular germ cell cancers are curable despite metastatic disease, but about 10-15% of patients fail cisplatin-based first-line treatment. Immunotherapy is considered as additional treatment ...approach for these patients. Inhibition of the interaction between Programmed Death Receptor 1 (PD-1) and Programmed Death Receptor Ligand 1 (PD-L1) enhances T-cell responses in vitro and mediates clinical antitumour activity. We analysed the expression of PD-L1 in testicular germ cell tumours to evaluate its potential as target for immunotherapeutic strategies.
Immunohistochemistry was performed in 479 formalin-fixed paraffin-embedded specimens using a rabbit monoclonal antibody (E1L3N). The tissue microarray consisted of 208 pure seminomas, 121 non-seminomas, 20 intratubular germ cell neoplasia unclassified (IGCNU) and 20 specimens of non-neoplastic testicular tissue.
Programmed Death Receptor Ligand-1 expression was found in 73% of all seminomas and in 64% of all non-seminomas. None of 20 IGCNU and none of 20 normal tissue specimens exhibited PD-L1 expression. PD-L1 positive stromal cells were only detected in seminomas, but not in non-seminomas. The anti PD-L1 antibody showed a pre-dominantly membranous staining pattern in testicular tumour cells, as well as expression in stromal cells.
This frequent expression of PD-L1 in human testicular germ cell tumours suggests that patients with testicular germ cell tumours could profit from immunotherapeutic strategies using anti-PD1 and anti-PDL1 antibodies.
Liquid biopsy is a rapidly emerging tool of precision oncology enabling minimally invasive molecular diagnostics and longitudinal monitoring of treatment response. For the clinical management of ...advanced stage lung cancer patients, detection and quantification of circulating tumor DNA (ctDNA) is now widely adopted into clinical practice. Still, interpretation of results and validation of ctDNA-based treatment decisions remain challenging. We report here our experience implementing liquid biopsies into the clinical management of lung cancer. We discuss advantages and limitations of distinct ctDNA assay techniques and highlight our approach to the analysis of recurrent molecular alterations found in lung cancer. Moreover, we report three exemplary clinical cases illustrating the complexity of interpreting liquid biopsy results in clinical practice. These cases underscore the potential and current limitations of liquid biopsy, focusing on the difficulty of interpreting discordant findings. In our view, despite all current limitations, the analysis of ctDNA in lung cancer patients is an essential and highly versatile complementary diagnostic tool for the clinical management of lung cancer patients in the era of precision oncology.
Measurements of 55Fe activity in activated steel samples with GEMPix Curioni, A.; Dinar, N.; La Torre, F.P. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2017, Letnik:
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Journal Article
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In this paper we present a novel method, based on the recently developed GEMPix detector, to measure the 55Fe content in samples of metallic material activated during operation of CERN accelerators ...and experimental facilities. The GEMPix, a gas detector with highly pixelated read-out, has been obtained by coupling a triple Gas Electron Multiplier (GEM) to a quad Timepix ASIC. Sample preparation, measurements performed on 45 samples and data analysis are described. The calibration factor (counts per second per unit specific activity) has been obtained via measurements of the 55Fe activity determined by radiochemical analysis of the same samples. Detection limit and sensitivity to the current Swiss exemption limit are calculated. Comparison with radiochemical analysis shows inconsistency for the sensitivity for only two samples, most likely due to underestimated uncertainties of the GEMPix analysis. An operative test phase of this technique is already planned at CERN.
The COVID-19 pandemic has impacted all aspects of modern-day oncology, including how stakeholders communicate through social media. We surveyed oncology stakeholders in order to assess their ...attitudes pertaining to social media and how it has been affected during the pandemic.
A 40-item survey was distributed to stakeholders from 8 July to 22 July 2020 and was promoted through the European Society for Medical Oncology (ESMO) and the OncoAlert Network.
One thousand and seventy-six physicians and stakeholders took part in the survey. In total, 57.3% of respondents were medical oncologists, 50.6% aged <40 years, 50.8% of female gender and mostly practicing in Europe (51.5%). More than 90% of respondents considered social media a useful tool for distributing scientific information and for education. Most used social media to stay up to date on cancer care in general (62.5%) and cancer care during COVID-19 (61%) given the constant flow of information. Respondents also used social media to interact with other oncologists (78.8%) and with patients (34.4%). Overall, 61.1% of respondents were satisfied with the role that social media was playing during the COVID-19 pandemic. On the other hand, 41.1% of respondents reported trouble in discriminating between credible and less credible information and 30% stated social networks were a source of stress. For this reason, one-third of respondents reduced its use during the COVID-19 pandemic. Regarding meeting attendance, a total of 59.1% of responding physicians preferred in-person meetings to virtual ones, and 51.8% agreed that virtual meetings and social distancing could hamper effective collaboration.
Social media has a useful role in supporting cancer care and professional engagement in oncology. Although one-third of respondents reported reduced use of social media due to stress during the COVID-19 pandemic, the majority found social media useful to keep up to date and were satisfied with the role social media was playing during the pandemic.
•More than 90% of the 1076 respondents believed in the role of social media promoting scientific information and education.•41% of respondents had trouble discriminating between credible and less credible information on social media.•61% of respondents used social media to stay up to date with scientific information regarding cancer care and COVID-19.•The flow of information on COVID-19 via social media was deemed useful for 49% of respondents but caused stress in 30%.•52% of respondents agreed that virtual meetings and social distancing could hamper effective collaboration.
Particle accelerators are invaluable tools for research in the basic and applied sciences, such as materials science, chemistry, the biosciences, particle physics, nuclear physics and medicine. The ...design, commissioning, and operation of accelerator facilities is a nontrivial task, due to the large number of control parameters and the complex interplay of several conflicting design goals. The Argonne Wakefield Accelerator facility has some unique challenges resulting from its purpose to carry out advanced accelerator R&D. Individual experiments often have challenging beam requirements, and the physical configuration of the beam lines is often changed to accommodate the variety of supported experiments. The need for rapid deployment of different operational settings further complicates the optimization work that must be done for multiple constraints and challenging operational regimes. One example of this is an independently staged two-beam acceleration experiment which requires the construction of an additional beam line (this is now in progress). The high charge drive beam, well into the space charge regime, must be threaded through small aperture (17.6 mm) decelerating structures. In addition, the bunch length must be sufficiently short to maximize power generation in the decelerator. We propose to tackle this problem by means of multiobjective optimization algorithms which also facilitate a parallel deployment. In order to compute solutions in a meaningful time frame, a fast and scalable software framework is required. In this paper, we present a general-purpose framework for simulation-based multiobjective optimization methods that allows the automatic investigation of optimal sets of machine parameters. Using evolutionary algorithms as the optimizer and opal as the forward solver, validation experiments and results of multiobjective optimization problems in the domain of beam dynamics are presented. Optimized solutions for the new high charge drive beam line found by the framework were used to finish the design of a two beam acceleration experiment. The selected solution along with the associated beam parameters is presented.
We present a more detailed account of our recently reported Hass, K. C.; Schneider, W. F.; Curioni, A.; Andreoni, W. Science 1998, 282, 265 first-principles molecular dynamics investigation of the ...static and dynamical behavior of adsorbed H2O on α-Al2O3 (0001). Al-terminated surfaces with varying degrees of H2O coverage are modeled using large periodic supercells. A predicted large relaxation of the clean surface agrees well with previous density functional theory calculations. Both molecular and dissociative H2O adsorption modes are identified, with the latter favored by ∼10 kcal mol-1. Complementary Al8O12 cluster results are shown to be unreliable because of their finite lateral extent. Constrained dynamical calculations of free-energy barriers indicate that the dissociation rate is very high, even in the absence of defects, but differs by 3 orders of magnitude for two equally exothermic pathways (proton transfer being more favorable across a six-membered ring than to the nearest O site). Unconstrained simulations at intermediate H2O coverages exhibit (1) spontaneous unimolecular and (2) H2O-mediated dissociation events, as well as (3) the diffusion and hydrogen bonding of physisorbed H2O and (4) an additional proton transfer reaction between adsorbed H2O and OH species. An experimentally observed decrease in H2O binding energies with coverage is explained in terms of a separation into defect-dominated, intrinsic (0001) terrace, and “hydrogen-bonding” regimes, with reasonable quantitative agreement throughout. Calculated O−H vibrational frequencies are consistent with known trends on aluminas but indicate a discrepancy between experimental observations for α-Al2O3 (0001) and models based on simple hydroxylation. Simulations for high H2O coverages suggest the possibility of more complicated behavior, including the interchange of adsorbed and lattice oxygen and the etching of surface Al. A “fully”-hydroxylated α-Al2O3 (0001) surface in which each surface Al is replaced by three protons to give uniform OH-termination, as in aluminum hydroxides, is the most likely result of prolonged exposure. Results for this surface confirm its anticipated stability, provide a reasonable explanation of observed vibrational spectra, and reveal a complex, dynamical structure with extensive intraplanar hydrogen bonding.
The Einstein classical Weak Equivalence Principle states that the trajectory of a particle is independent of its composition and internal structure when it is only submitted to gravitational forces. ...This fundamental principle has never been directly tested with antimatter. However, theoretical models such as supergravity may contain components inducing repulsive gravity, thus violating this principle. The GBAR project (Gravitational Behaviour of Antihydrogen at Rest) proposes to measure the free fall acceleration of ultracold neutral antihydrogen atoms in the terrestrial gravitational field. The experiment consists in preparing antihydrogen ions (one antiproton and two positrons) and sympathetically cool them with Be
+
ions to a few 10
μ
K. The ultracold ions will then be photoionized just above threshold, and the free-fall time over a known distance measured. In this work, the GBAR project is described as well as possible improvements that use quantum reflection of antihydrogen on surfaces to use quantum methods of measurements.
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