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Abstract: Dusty plasma coagulation controlled by external cooling of discharge was studied experimentally. [Copyright &y& Elsevier]

Background In the phase III FLAURA study (NCT02296125), the 3rd-generation EGFR-TKI osimertinib showed superior efficacy to comparator EGFR-TKIs in previously untreated EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC). Here we report results from an exploratory analysis of ctDNA for the early detection of disease progression (PD) in FLAURA. Methods Treatment-naïve patients (pts) with EGFRm (ex19del/L858R) locally advanced/metastatic NSCLC (n = 556) were randomised 1:1 (osimertinib 80 mg qd: comparator [gefitinib 250 mg qd/erlotinib 150 mg qd]). Plasma samples were collected on Days 1, 8 and 15, then every 21 days for weeks (W) 3–18, then every 6W thereafter. In pts who had a plasma sample on PD and/or discontinuation, ctDNA droplet digital PCR (ddPCR; Biodesix) for EGFRm (ex19del/L858R/T790M) was performed at all available time points and C797S for post-W6 time points. C797S and T790M were the only resistance mutations assayed. ctDNA progression was defined with respect to the nadir ctDNA result and its proximity to the ddPCR detection and quantification limits. Results The ctDNA progression analysis included 122/556 (22%) pts with valid longitudinal monitoring ddPCR data and RECIST PD by DCO1 (12 June 2017). Across both arms, ctDNA progression preceded or co-occurred with PD in 80/122 (66%) pts with 2.7 months (mo) median lead time; 9.5 mo median progression-free survival (mPFS; n = 80). Acquired C797S or T790M was detected in 57/122 (47%) pts with ctDNA progression (osimertinib 4/50 [8%] C797S, comparator 53/72 [74%] T790M); median time to detection was 16.7 and 8.4 mo for the osimertinib and comparator arms, respectively, mirroring overall mPFS. In pts with ctDNA progression and PD (n = 106), acquired T790M and C797S were detected either at the same time as, or earlier than PD in 41/106 (38%) pts (osimertinib 2/39 [5%], comparator 39/67 [58%]); median lead time was 1.4 mo. Conclusions ctDNA monitoring may allow for earlier identification of pts who progress on first-line EGFR-TKI therapy and the detection of EGFR-mediated resistance mechanisms in advance of PD in EGFRm NSCLC. Future work aims to explore early detection of non-EGFR-mediated resistance. Clinical trial identification NCT02296125. Editorial acknowledgement Donna Tillotson, PhD, of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines. Legal entity responsible for the study AstraZeneca. Funding AstraZeneca. Disclosure J.E. Gray: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Array; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Takeda. A. Markovets: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. N. Nogami: Honoraria (self): Pfizer Inc. Chugai Pharmaceutical Co. Ltd, Eli Lilly, Taiho Pharmaceutical Co. Ltd. AstraZeneca, Kyowa Hakko Kirin, Ono Pharmaceutical Co. Ltd. Bristol-Myers Squibb, MSD. B.C. Cho: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Janssen, Yuhan, Ono Pharmaceutical, Dizal Pharma, MSD; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Licensing / Royalties: Champions Oncology; Honoraria (institution), Advisory / Consultancy: Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Eli Lilly, Takeda; Shareholder / Stockholder / Stock options: TheraCanVac Inc. B. Chewaskulyong: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca. M. Majem: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy: Tesaro; Speaker Bureau / Expert testimony: Hellsin; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony: Amgen. N. Peled: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche, Takeda; Advisory / Consultancy: Eli Lilly; Honoraria (self): Foundation Medicine; Shareholder / Stockholder / Stock options: Novellus Dx; Honoraria (self): Guardant360. K. Vishwanathan: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. A. Todd: Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Johnson: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. C. Barrett: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Chmielecki: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. R. Hartmaier: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options, Licensing / Royalties, Nfe2l2 exon 2 ano/or exon 3 loss from work conducted at Foundation Medicine; provisional patent filed: Foundation Medicine. S.S. Ramalingam: Advisory / Consultancy, Research grant / Funding (self): Amgen, AstraZeneca, Bristol-Myers Squibb, Merck; Advisory / Consultancy: AbbVie, Celgene, Genentech, Lilly, Loxo, Takeda; Research grant / Funding (self): Tesaro. [ABSTRACT FROM AUTHOR]

Abstract: Recently, the lineage hTURDUS2 of Haemoproteus minutus (Haemosporida, Haemoproteidae) was reported to cause mortality in captive parrots. This parasite lineage is widespread and prevalent in the blackbird Turdus merula throughout its entire distribution range. Species identity of other closely related lineages recently reported in dead parrots remains unclear, but will be important to determine for a better understanding of the epidemiology of haemoproteosis. Using polymerase chain reaction (PCR)-based and microscopic methods, we analyzed 265 blood samples collected from 52 species of wild birds in Eurasia (23 samples from Kamchatka Peninsula, 73 from Sakhalin Island, 150 from Ekaterinburg and 19 from Irkutsk regions of Russia). Single infections of the lineages hTURDUS2 (hosts are redwing Turdus iliacus and fieldfare Turdus pilaris), hTUPHI1 (song thrush Turdus philomelos) and hTUCHR01 (fieldfare, redwing, song thrush and brown-headed thrush Turdus chysolaus) were detected. We identified species of these haemoproteids based on morphology of their blood stages and conclude that these lineages belong to H. minutus, a widespread parasite of different species of thrushes (genus Turdus), which serve as reservoir hosts of this haemoproteid infection. Phylogenetic analysis shows that the lineages hTURDUS2, hTUCHR01 and hTUPHI1 of H. minutus are closely related to Haemoproteus pallidus (lineages hPFC1 and hCOLL2), Haemoproteus pallidulus (hSYAT03), and Haemoproteus sp. (hMEUND3); genetic distance among their mitochondrial cytochrome b (cyt b) lineages is small (<1% or<4 nucleotides). All these blood parasites are different in many morphological characters, but are similar due to one feature, which is the pale staining of their macrogametocytes' cytoplasm with Giemsa. Because of the recent publications about mortality caused by the lineages hTUPHI1 and hTURDUS2 of H. minutus in captive parrots in Europe, H. minutus and the closely related H. pallidus and H. pallidulus are worth more attention as these are possible agents of haemoproteosis in exotic birds. The present study provides barcodes for molecular detection of different lineages of H. minutus, and extends information about the distribution of this blood parasite. [Copyright &y& Elsevier]

Kinetics of sapphire single crystals charging under electron beam irradiation has been studied. The electron beam energy was 5 and 15 keV. The sapphire was preliminary irradiated with Ar N + cluster ions with the energy of 7–15 keV. The charging characteristics of virgin sapphire samples and those of the samples irradiated with atomic Ar+ and cluster Ar N + ions were compared. It was found that cluster ion preirradiation reduces the charging time of sapphire by almost two orders of magnitude. Possible explanations of the phenomenon are discussed. ∙ Cluster ion irradiation results in faster electron beam charging of sapphire ∙Charging kinetics varies with the cluster irradiation dose ∙On the first stage of electron irradiation, partial discharging may take place ∙Defect layer supposed to determine the emission characteristic and charging pattern [ABSTRACT FROM AUTHOR]

We present an experimental study of charging of dielectrics and ferroelectrics under Ar+ ion beam irradiation. Complex measurements of ion emission yield, accumulated charges and a surface charging potential have been carried out. It has been found an effective charging of dielectrics to high positive potentials closed to the potential of an ion gun. The experimental data show that the ion emission coefficient from charged dielectrics may differ significantly from the one from uncharged dielectrics and conductive samples. The specific features of ion charging of ferroelectrics are interpreted by taking into account the polarization switching of ferroelectric crystals. • Charging of dielectrics and ferroelectrics under Ar+ ion beam irradiation was investigated experimentally. • Dielectric bulk samples charge up to high positive potentials close to the potential of an ion gun. • Mechanisms of ion and electron emission may differ strongly for charged and uncharged dielectrics. • Specific feature of charging kinetics of ferroelectrics can be interpreted by polarization switching under ion irradiation. [ABSTRACT FROM AUTHOR]