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Osimertinib is the current recommended treatment for EGFRT790M–positive NSCLC after EGFR tyrosine kinase inhibitor therapy. However, resistance to osimertinib therapy is inevitably acquired after a period of effective treatment. We had a patient with EGFRL858R/T790M–positive NSCLC who initially responded to osimertinib therapy but eventually experienced development of resistance. Plasma cell–free DNA analysis revealed the occurrence of exon 16–skipping HER2, which may have resulted in the erb-b2 receptor tyrosine kinase 2 gene (HER2) splice variant HER2D16. HER2D16 has never been reported in lung cancer, and HER2D16-driven signaling is known to be regulated by Src kinase in breast cancer. We investigated the role of HER2D16 as an osimertinib-resistant mechanism.

EGFR mutated (EGFRm) NSCLC tumors occasionally express programmed cell death ligand 1 (PD-L1), although frequency and clinical relevance are not fully characterized. We report PD-L1 expression in patients with EGFRm advanced NSCLC and association with clinical outcomes following treatment with osimertinib or comparator EGFR tyrosine kinase inhibitors in the FLAURA trial (phase III, NCT02296125).

EGFR tyrosine kinase inhibitor (EGFR-TKI)-sensitizing and -resistance mutations may be detected in plasma through circulating tumor DNA (ctDNA). Circulating tumor DNA level changes reflect alterations in tumor burden and could be a dynamic indicator of treatment effect. This analysis aimed to determine whether longitudinal EGFR-mutation ctDNA testing could detect progressive disease (PD) before radiologic detection.

Abstract: This paper examines the phenology and biometrics of Bluethroats staging in the Eilat region. This is of special interest because of the extreme conditions with which this temperate zone breeding species has to contend because Eilat is a desert habitat and is the last green area before the crossing of the deserts in autumn or after it in spring. Data were collected during 20 spring and 18 autumn migration seasons in the years 1984–2003, and a total of 7,464 Bluethroat were recorded. The number of trapped birds was much higher in autumn than in spring. The majority of Bluethroats caught in both the autumn and spring migrations were juveniles. We found differences in sex ratio in the individual age classes only in the autumn wherein among both adults and juveniles, males were in greater numbers. We also found significant differences in the dates of ringed birds from different sex–age classes in the spring and in autumn migrations. In spring, males from both age classes were caught earlier than females. In autumn, adult birds arrived earlier than juveniles. We think that it is important to identify and conserve the high quality stopover habitats such as Eilat wherein not only Bluethroats have been shown to stopover but also several hundred other species.

Abstract: For the last decade, owing to methods of computerized neuroradiology, it has been established that the process of the human organism natural aging is accompanied by a gradual atrophic reduction of the brain tissue volume and a decrease of the cerebral blood flow level, while the intracranial cerebrospinal fluid volume increases. The goal of the present study was to elucidate functional significance of the above changes in terms of interaction of intracranial hemo- and liquorocirculation systems at various stages of ontogenesis of practically healthy people. The total of 122 people aged from 6 to 100 years were examined at rest and during performance of goal-oriented functional physiological tests with simultaneous continuous recording of parameters of cerebral blood flow and liquorodynamics by methods of transcranial dopplerography and rheoencephalography. The obtained data are processed by means of the pattern and phasic two-dimensional analysis with use of special computer programs. In the same age groups, the brain neurophysiological activity was evaluated by applying special psychological tests. It has been shown that with age, on the background of a decrease of hemodynamic parameters of cerebral blood supply, there is observed an enhancement of the liquorodynamic factor of cerebral blood circulation due to an increase of the liquor volume and facilitation of its translocation in the single craniospinal cavity. The enhancement of the liquor-dependent mechanism of compensation of intracranial pulse oscillations of the blood volume is particularly expressed both in children and in elderly people due to a relatively high liquor volume. Owing to the improvement of intracranial liquorodynamic processes, the change of the cerebral blood circulation is compensated, which is confirmed by results of performed psychophysiological studies.

This rapid communication reports on a novel method of determining electron transport coefficients in dense gases and liquids using a nanosecond discharge. The breakdown occurs in the plane–plane discharge gap with variable interelectrode distance. The impulse applications are of only a few nanoseconds in duration, thus allowing measuring procedures with no perturbation in the medium thermodynamic state. To record discharge voltages and currents the pulsed reflectometry method is applied. The focus is on the time dependence of the discharge admittance and conducting channel propagation velocity. The latter is determined by a purpose-developed method of movable electrode. The obtained discharge characteristics are then used to derive electron multiplication rates and electron drift velocities, which finally result in the First Townsend coefficient and other related ionization coefficients. The assessment of the reduced electric field strength at the front of a conducting discharge channel allows the correlation between this quantity and the measured transport coefficients to be established. The approach developed is applied to gaseous and liquid nitrogen at atmospheric pressure and temperature of 77 K.

The results are given of observations of regions of closure of current on the electrodes of an atmospheric-pressure low-current carbon arc, performed using a laser monitor immediately during the time of burning of the arc. It is found that the time of existence of a cathode crater on a graphite cathode is 0.2–0.3 s. An analysis of images of the region of closure of current on a pyrographite cathode reveals evidence of melting of pyrographite. A comparison of images of the region of closure of current on the electrodes of a carbon arc with the available literature data on the conditions of closure of current on the anode and cathode enables one to establish the origins of the various details of images of the region of closure of current on the cathode and anode of a low-current carbon arc. The results of this comparison further lead one to conclude that a low-current electric arc is an arc with liquid cathode and anode spots, and that the melting process is a stabilizing factor as regards the current density in those spots.

Slow rhythmic oscillations in the human cranial cavity were studied using two noninvasive methods: the bioimpedance method (volume ratios between liquid media in the cranial cavity) and transcranial ultrasound Doppler echography (variation in the blood flow in the middle cerebral artery). The combination of these methods made it possible to estimate the intracranial hemodynamics. Simultaneous recording of these parameters and their spectral analysis were carried out in healthy subjects and patients with intracranial hypertension syndrome and disturbed cerebrospinal fluid (CSF) flow. The parameters were recorded at rest and immediately after manual (osteopathic) correction. The recording and analysis were performed using a Macintosh-IIsi PC and the Chart-3.52, Cricket Graph-3.32, and Canvas-3.5 software. It was found that slow oscillations of the bioimpedance (BIM) in the frequency range 0.08–0.2 Hz were of intracranial origin and were related to the mechanisms of regulation of the blood supply to and oxygen consumption by cerebral tissue, as well as with the dynamics of the CSF circulation.

1.Through cold hardening has a negative effect on the strength of alloys at high temperatures; the higher the degree of cold hardening the lower the strength.2.A critical degree of deformation (about 8%) decreases the strenghth of the KhN70VMYuT alloy, at high temperatures. A deformation of 16% produces a peak of strength; higher degrees of deformation decrease the strength again.3.It is important to avoid the critical degree of deformation in the manufacture of articles operating at 715°C.

Conclusions 1.The effect of the structure of alloys VT3-1 and VT-18 on their cyclic strength depends on the conditions of loading.2.Under loading with a pulsating cycle (extension, R=0) at room temperature, rods of alloys VT3-1 and VT-18 with a fine-grained equiaxial structure are superior in cyclic streghth to metal with a lamellar structure.3.At 450°C under asymmetrical tension with a mean stress sn=30 kgf/mm2, the fine-grained equiaxial and the lamellar structures behave in the same way; in the case of alloy VT-18 the lamellar structure gives a higher resistance to fatigue failure at 600°C and sn=25.0 kgf/mm2.

1.The nature of the depedence of maximal uniform strain ep and of the strain-hardening coefficient n on the degree of strain hardening and on the heat-treatment regimes is analogous.2.Strain ep can be calculated by the formula ep=(n -2)/(n -1), where n is determined from the results of two indentations of a spherical indentor.