Quasi-real-time range monitoring by in-beam PET: a case for 15O.

A fast and reliable range monitoring method is required to take full advantage of the high linear energy transfer provided by therapeutic ion beams like carbon and oxygen while minimizing damage to healthy tissue due to range uncertainties. Quasi-real-time range monitoring using in-beam positron emission tomography (PET) with therapeutic beams of positron-emitters of carbon and oxygen is a promising approach. The number of implanted ions and the time required for an unambiguous range verification are decisive factors for choosing a candidate isotope. An experimental study was performed at the FRS fragment-separator of GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany, to investigate the evolution of positron annihilation activity profiles during the implantation of [Formula: see text]O and [Formula: see text]O ion beams in a PMMA phantom. The positron activity profile was imaged by a dual-panel version of a Siemens Biograph mCT PET scanner. Results from a similar experiment using ion beams of carbon positron-emitters [Formula: see text]C and [Formula: see text]C performed at the same experimental setup were used for comparison. Owing to their shorter half-lives, the number of implanted ions required for a precise positron annihilation activity peak determination is lower for [Formula: see text]C compared to [Formula: see text]C and likewise for [Formula: see text]O compared to [Formula: see text]O, but their lower production cross-sections make it difficult to produce them at therapeutically relevant intensities. With a similar production cross-section and a 10 times shorter half-life than [Formula: see text]C, [Formula: see text]O provides a faster conclusive positron annihilation activity peak position determination for a lower number of implanted ions compared to [Formula: see text]C. A figure of merit formulation was developed for the quantitative comparison of therapy-relevant positron-emitting beams in the context of quasi-real-time beam monitoring. In conclusion, this study demonstrates that among the positron emitters of carbon and oxygen, [Formula: see text]O is the most feasible candidate for quasi-real-time range monitoring by in-beam PET that can be produced at therapeutically relevant intensities. Additionally, this study demonstrated that the in-flight production and separation method can produce beams of therapeutic quality, in terms of purity, energy, and energy spread.

Production and separation of positron emitters for hadron therapy at FRS-Cave M.

The FRagment Separator FRS at GSI is a versatile spectrometer and separator for experiments with relativistic in-flight separated short-lived exotic beams. One branch of the FRS is connected to the target hall where the bio-medical cave (Cave M) is located. Recently a joint activity between the experimental groups of the FRS and the biophysics at the GSI and Department of physics at LMU was started to perform biomedical experiments relevant for hadron therapy with positron emitting carbon and oxygen beams. This paper presents the new ion-optical mode and commissioning results of the FRS-Cave M branch where positron emitting 15O-ions were provided to the medical cave for the first time. An overall conversion efficiency of 2.9±0.2×10-4 15O fragments per primary 16O ion accelerated in the synchrotron SIS18 was reached.

BLEPHARITIS AND HELICOBACTER-ASSOCIATED GASTRODUODENAL DISEASES (REVIEW).

The aim of the study was to find the relationship between the inflammatory process on the eyelids (blepharitis) and Helicobascter pylori infection. The data of numerous studies are analyzed, which give grounds to suggest a possible pathogenetic or mediated role of H. pylori infection in the development and course of inflammatory eye diseases. Fundamental in these studies are the release of harmful compounds in the exhaled air of patients with H. pylori, such as ammonia, hydrogen nitrate and hydrogen cyanide, the restoration of impression cytology after H. Pylori eradication, the presence of H. pylori in the lacrimal fluid. In this regard, the authors conclude that there are three main possible pathogenetic mechanisms for the association between H. Pylori infection and blepharitis: chronic inflammation, endothelial dysfunction, and oxidative stress.

Precision of the PET activity range during irradiation with10C,11C, and12C beams.

Objective. Beams of stable ions have been a well-established tool for radiotherapy for many decades. In the case of ion beam therapy with stable12C ions, the positron emitters10,11C are produced via projectile and target fragmentation, and their decays enable visualization of the beam via positron emission tomography (PET). However, the PET activity peak matches the Bragg peak only roughly and PET counting statistics is low. These issues can be mitigated by using a short-lived positron emitter as a therapeutic beam.Approach.An experiment studying the precision of the measurement of ranges of positron-emitting carbon isotopes by means of PET has been performed at the FRS fragment-separator facility of GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany. The PET scanner used in the experiment is a dual-panel version of a Siemens Biograph mCT PET scanner.Main results.High-quality in-beam PET images and activity distributions have been measured from the in-flight produced positron emitting isotopes11C and10C implanted into homogeneous PMMA phantoms. Taking advantage of the high statistics obtained in this experiment, we investigated the time evolution of the uncertainty of the range determined by means of PET during the course of irradiation, and show that the uncertainty improves with the inverse square root of the number of PET counts. The uncertainty is thus fully determined by the PET counting statistics. During the delivery of 1.6 × 107ions in 4 spills for a total duration of 19.2 s, the PET activity range uncertainty for10C,11C and12C is 0.04 mm, 0.7 mm and 1.3 mm, respectively. The gain in precision related to the PET counting statistics is thus much larger when going from11C to10C than when going from12C to11C. The much better precision for10C is due to its much shorter half-life, which, contrary to the case of11C, also enables to include the in-spill data in the image formation.Significance. Our results can be used to estimate the contribution from PET counting statistics to the precision of range determination in a particular carbon therapy situation, taking into account the irradiation scenario, the required dose and the PET scanner characteristics.

[Subclavian-carotid transposition and subclavian artery stenting for steal-syndrome]. / Podklyuchichno-sonnaya transpozitsiya i stentirovanie podklyuchichnoi arterii v lechenii stil-sindroma.

OBJECTIVE: To analyze in-hospital results of subclavian-carotid transposition and subclavian artery stenting in patients with steal-syndrome. MATERIAL AND METHODS: A retrospective open study included 137 patients with occlusion or severe stenosis of the first segment of subclavian artery and steal-syndrome. The 1st group included 50 patients who underwent stenting or recanalization with stenting of the first segment of subclavian artery between January 2010 and March 2020. The 2nd group included 87 patients who underwent subclavian-carotid transposition between January 2010 and March 2020. RESULTS: There were no in-hospital mortality, myocardial infarction, ischemic stroke or bleeding. In the second group, damage to recurrent laryngeal nerve with irreversible laryngeal paresis occurred in 6.9% of patients, and one patient had brachial plexus neuropathy. One patient developed lymphorrhea with chylothorax accompanied by shortness of breath on exertion. Conservative management with repeated pleural punctures was not accompanied by clinical compensation. The patient was discharged for outpatient treatment. Thromboembolism of the left branch of the aorto-femoral prosthesis and deep femoral artery on the left was diagnosed in the endovascular correction group after implantation of Protege GPS stent (10´60 mm) and post-dilation with a PowerFlex PRO balloon catheter (9´4 mm). Acute ischemia of the left lower limb required thrombectomy with patch repair of deep femoral artery. The patient was discharged after 5 days. In another case, vertebral artery dissection occurred after implantation of Protege GPS stent (10×40 mm) and post-dilatation with a PowerFlex PRO balloon catheter (8´20 mm). In this regard, the patient underwent stenting of the fourth segment of vertebral artery (Endeavor Resolute 4.0´24 mm stent) with post-dilation (Boston Scientific Samurai balloon catheter 0.014´190 cm). The patient was discharged after 3 days. CONCLUSION: Subclavian-carotid transposition and subclavian artery stenting are safe methods of revascularization that are not accompanied by myocardial infarction, ischemic stroke or mortality. However, subclavian-carotid transposition is characterized by higher risk of neurological disorders (laryngeal paresis, phrenic nerve paresis, brachial plexus neuropathy) and wound complications (lymphorrhea, chylothorax). In turn, subclavian artery stenting is associated with the risk of dissection and embolism. Therefore, the choice of treatment strategy in patients with occlusive-stenotic lesions of the first segment of subclavian artery should be personalized and carried out by a multidisciplinary team.

[In-hospital results of renal artery stenting in patients with multifocal atherosclerosis]. / Gospital'nye rezul'taty stentirovaniia pochechnykh arterii u patsientov s mul'tifokal'nym aterosklerozom.

OBJECTIVE: A retrospective analysis of in-hospital results of renal artery stenting in patients with multifocal atherosclerosis. MATERIAL AND METHODS: The study included 19 patients who underwent stenting for renal artery stenosis for the period 2011-2015 in the Kemerovo Cardiology Dispensary. Renal function was assessed considering glomerular filtration rate (GFR). Blood pressure and GFR were evaluated before the stenting procedure and at discharge. RESULTS: Stenting resulted optimal outcomes in all 19 patients. Severity of residual stenosis was 11±3%. In-hospital mortality was absent. Blood pressure in early postoperative period was similar to baseline values. One patient had a normalization of blood pressure up to 115-140/85-90 mm Hg without administration of antihypertensive drugs. Decrease of systolic blood pressure up to 155.3±32.6 mm Hg was noted in other patients at discharge. Blood creatinine levels decreased up to 0.167±0.56 mmol/L. In addition, mean GFR increased from 34.17 ml/min/1.69 m2 up to 37.16 ml/min/1.69 m2. CONCLUSION: Endovascular treatment of renal artery stenosis and secondary hypertension is effective and relatively safe approach.

[Long-term results of surgical and conservative treatment of patients with occlusive-stenotic lesions of carotid arteries]. / Otdalennye rezul'taty khirurgicheskogo i konservativnogo lecheniia patsientov s okkliuzionno-stenoticheskimi porazheniiami sonnykh arterii.

OBJECTIVE: To compare long-term outcomes in patients after carotid endarterectomy and those who refused surgical correction and received only conservative treatment. MATERIAL AND METHODS: There were 1035 carotid endarterectomies performed at the Kemerovo Regional Clinical Hospital and Kemerovo Regional Clinical Cardiology Dispensary for the period 2014-2017. Surgery was refused by 136 patients for the same time. Thus, two groups of patients were formed: 1 - carotid endarterectomy group; 2 - conservative treatment group. INCLUSION CRITERIA: significant carotid stenosis, absence of severe neurological deficit (over 25 scores by the National Institutes of Health Stroke Scale), absence of concomitant diseases limiting long-term follow-up. RESULTS: Lethal outcome (p=0.0038) and fatal acute cerebrovascular accident (p=0.0005) were significantly more common in the 2nd group in long-term follow-up period. Thus, combined endpoint took the greatest values in patients who refused surgery compared with patients who received surgical treatment (p=0.0001). It should be noted that ischemic stroke de novo occurred in 9 (6.6%) patients of the 2nd group after 10.8 ± 2.5 months. This complication required subsequent hospitalization for carotid endarterectomy. CONCLUSION: Preventive role of carotid endarterectomy was convincingly proved in comparison with drug therapy regarding mortality and fatal ischemic stroke in patients with significant carotid stenoses within 2.5 years of follow-up period.

[Local population of Eritrichium caucasicum as an object of mathematical modelling. I. Life cycle graph and a nonautonomous matrix model].

For the plant species, which is considered a short-lived perennial, we have composed a scale of ontogenetic stages and the life cycle graph (LCG) according to annual observations on permanent sample plots in an Alpine lichen heath during the 2009-2014 period. The LCG that reflects seed reproduction has been reduced to the one that avoids the stage of soil seed bank, yet preserves the arcs of annual recruitment. The corresponding matrix model of stage-structured population dynamics has four stages: juvenile plants (including seedlings), virginal, generative, and 'terminally generative' (the plants die after seed production). Model calibration reduces to directly calculating the rates of transition between stages and those of delays within stages from the data of only one time step, while keeping the two reproduction rates uncertain, yet confined to the quantitative bounds of observed recruitment. This has enabled us to determine a feasible range for the dominant eigenvalue of the model matrix, i.e., the quantitative bounds for the measure of how the local population adapts to its environment, at each of the five time steps, resulting in aformally nonautonomous model. To obtain 'age-specific parameters' from a stage-classified model, we have applied the technique that constructs a virtual absorbing Markov chain and calculates its fundamental matrix. In a nonautonomous model, the estimates of life expectancy also depend on the time of observation (that fixes certain environmental conditions), and vary from two to nearly seven years. The estimates reveal how specifically short lives the short-lived perennial, while their range motivates the task to average the model matrices over the whole period of observation. The model indicates that Eritrichium caucasicum plants spend the most part of their life span in the virginal stage under each of the environment conditions observed, thus revealing the place retention strategy by C. K6rner (2003), or the delayed-development strategy by L.A. Zhukova (1995). We discuss the prospects of model experiments with a logically nonautonomous model to forecast the long-term dynamics of E. caucasicum under a scenario of climate changes.

Deoxyribonucleotide-containing RNAs: a novel class of templates for HIV-1 reverse transcriptase.

Deoxyribonucleotide-containing RNA-like polynucleotides (dcRNAs) were synthesized by mutant T7 RNA polymerase and their structures confirmed by sequencing. dcRNAs annealed with a 20mer oligodeoxyribonucleotide primer were tested as templates/primers in the reverse transcription reaction catalyzed by HIV-1 reverse transcriptase (RT). All dcRNAs were shown to be efficient templates for both wild-type RT and RT mutants, containing 'AZT-resistant' mutations. Differences in the patterns of the DNA products of RNA- and dcRNA-driven reverse transcription were demonstrated. The kinetic characteristics for dcRNAs utilization were compared with the corresponding parameters for RNA/DNA and DNA/DNA templates/primers. The respective K m values for dcRNAs appear to be intermediate between those for RNA and DNA templates. A correlation equation connecting apparent K m value for template/primer and the number of deoxyribonucleotide substitutions in RNA template is proposed.

[The manifestations of a scarlatina epidemic process in a large city and their interpretation]. / Proiavleniia épidemicheskogo protsessa skarlatiny v krupnom gorode i ikh interpretatsiia.

The average morbidity level in scarlet fever for the period of 1972-1990 in Moscow was 230.9 cases per 100,000 of the population and the annual economic damage was 2-2.5 million rubles. The highest morbidity rate values were registered among children attending children's institutions, and in this group among children aged 3-6 years. Cohort and disperse analysis revealed that age-dependent fluctuations of morbidity rate had a regular character and significantly differed. An increase in scarlet fever morbidity was registered simultaneously with elevated levels of morbidity in tonsillitis and acute respiratory diseases and occurred several weeks after a rise in tonsillitis morbidity. Contamination with group A streptococci was higher among "organized" children of preschool age than among other groups of the population. T serovars 4/28, 8/29/Imp.19, 3/13/B3254 and 1, constituting 44% of all isolated Streptococcus pyogenes strains, and OF type 2 (44%) and 22 (20%) occurred most frequently. Among the strains isolated from patients T-4 and OF-2 types prevailed.