[Nonimmunogenic staphylokinase in the treatment of acute ischemic stroke (FRIDA trial results)]. / Neimmunogennaya stafilokinaza ­ novyi tromboliticheskii preparat v lechenii ishemicheskogo insul'ta (rezul'taty issledovaniya FRIDA).

AIM OF THE STUDY: To investigate the efficacy and safety of non-immunogenic staphylokinase (NS) compared with alteplase (A) in patients with acute ischemic stroke (AIS) within 4.5 h after symptom onset. MATERIAL AND METHODS: 336 patients with IS within 4.5 h after symptom onset were included in a randomized, open-label, multicenter, parallel-group, non-inferiority comparative trial of NS vs A (168 patients in each group). NS was administered as an intravenous bolus in a dose of 10 mg, regardless of body weight, over 10 s, A was administered as a bolus infusion in a dose of 0.9 mg/kg, maximum 90 mg over 1 hour. The primary efficacy endpoint was a favorable outcome, defined as a modified Rankin scale (mRS) score of 0-1 on day 90. Safety endpoints included all-cause mortality on day 90, symptomatic intracranial haemorrhage, and other serious adverse events (SAEs). RESULTS: At day 90, 84 (50%) patients reached the primary endpoint (mRS 0-1) in the NS group, 68 (41%) patients - in the A group (p=0.10, OR=1.47, 95% CI=0.93-2.32). The difference between groups NS and A was 9.5% (95% CI= -1.7-20.7) and the lower limit of the 95% CI did not cross the margin of non-inferiority (pnon-inferiority<0.0001). There were no significant differences in the frequency of deaths between the groups: on day 90, 17 (10%) patients in the NS group and 24 (14%) in the A group had died (p=0.32). There was a trend towards significant differences in the frequency of symptomatic intracranial haemorrhage: NS group - 5 (3%) patients, A group - 13 (8%) patients (p=0.087, OR=0.37, 95% CI=0.1-1.13). There were significant differences in the number of patients with SAEs: in the NS group - 22 (13%) patients, in the A group - 37 (22%) patients (p=0.044, OR=0.53, 95% CI=0.28-0.98). CONCLUSION: The presented results of the FRIDA trial are the first in the world to use a drug based on NS in patients with IS. It has been shown that a single bolus (within 10 s) administration of NS at a standard dose of 10 mg, regardless of body weight, allows to conduct fast, effective and safe thrombolytic therapy in patients with IS within 4.5 h after symptom onset. In further clinical tials of NS, it is planned to expand the therapeutic window beyond 4.5 h after symptom onset in patients with IS.

Features of Housing Provision for Rural and Urban Populations.

The results of assessing the housing provision of the rural and urban populations of Russia are presented. On the basis of the author's methodology for identifying the level of housing provision, its actual characteristics were compared with social standards, that is, regulatory requirements for area, spaciousness, and comfort of a house or apartment. It is shown that in the city, in contrast to the countryside, housing conditions are characterized by a higher level of comforts but, at the same time, more constrained living conditions (in terms of the area of the dwelling and its spaciousness). The groups of the rural and urban populations differing in terms of housing provision have been identified. It was revealed that the share of rural residents living in housing poverty (in terms of area and living conditions) is more than two times higher (87.8%) than in the country as a whole (41.6%) and more than three times higher than residents of cities (25.1%). Ways to solve this problem are suggested.

New High-Confinement Regime with Fast Ions in the Core of Fusion Plasmas.

The key result of the present work is the theoretical prediction and observation of the formation of a new type of transport barrier in fusion plasmas, called F-ATB (fast ion-induced anomalous transport barrier). As demonstrated through state-of-the-art global electrostatic and electromagnetic simulations, the F-ATB is characterized by a full suppression of the turbulent transport-caused by strongly sheared, axisymmetric E×B flows-and an increase of the neoclassical counterpart, albeit keeping the overall fluxes at significantly reduced levels. The trigger mechanism is shown to be a mainly electrostatic resonant interaction between suprathermal particles, generated via ion-cyclotron-resonance heating, and plasma microturbulence. These findings are obtained by realistic simulations of the ASDEX Upgrade discharge No. 36637-properly designed to maximized the beneficial role of the wave-particle resonance interaction-which exhibits the expected properties of improved confinement produced by energetic particles.

Development of the ion cyclotron emission diagnostic for the W7-X stellarator.

An ion cyclotron emission (ICE) diagnostic is prepared for installation into the W7-X stellarator, with the aim to be operated in the 2022 experimental campaign. The design is based on the successful ICE diagnostic on the ASDEX Upgrade tokamak. The new diagnostic consists of four B-dot probes, mounted about 72° toroidally away (one module) from the neutral beam injector, with an unobstructed plasma view. Two of the B-dot probes are oriented parallel to the local magnetic field, aimed to detect fast magnetosonic waves. The remaining two probes are oriented poloidally, with the aim to detect slow waves. The radio frequency (RF) signals picked up by the probes are transferred via 50 Ω vacuum-compatible coaxial cables to RF detectors. Narrow band notch filters are used to protect the detectors from possible RF waves launched by the W7-X antenna. The signal will be sampled with a four-channel fast analog-to-digital converter with 14 bit depth and 1 GSample/s sampling rate. The diagnostic's phase-frequency characteristic is properly measured in order to allow measuring the wave vectors of the picked up waves.

Ion temperature measurement techniques using fast sweeping retarding field analyzer (RFA) in strongly intermittent ASDEX Upgrade tokamak plasmas.

This manuscript presents a new method of interpreting the ion temperature (Ti) measurement with a retarding field analyzer (RFA) that accounts for the intermittent/turbulent nature of the scrape off layer (SOL) plasmas in tokamaks. Fast measurements and statistical methods are desirable for an adequate description of random fluctuations caused by such intermittent events as edge localized modes (ELMs) and blobs. We use a RFA that can sweep its current-voltage (I-V) characteristics with up to 10 kHz. The RFA uses an electronics compensation stage to subtract the capacitive pickup due to the finite connecting cable capacitance, which greatly improves the signal-to-noise ratio. In the 10 kHz case, a single I-V characteristic is obtained in time, which is an order of magnitude faster than the ELM cycle. The fast sweeping frequency allows us to reconstruct the Ti probability density function (PDF), which we use as the Ti representation. The boundary conditions that we place on the I-V characteristics when calculating the Ti values impact the resulting Ti PDF. If the boundaries are insensitive to the plasma fluctuations, then the most probable Ti value of the PDF (20 eV-25 eV) is similar to the Ti value obtained via the classical conditional averaging method (20 eV-27 eV). However, if the boundary conditions follow the fluctuations, then the PDF-based method gives a substantially higher most probable Ti value (35 eV-60 eV). Overall, we show that a fast sweeping RFA diagnostic should be used in intermittent SOL plasmas to reconstruct the PDF for accurate Ti measurements.

Observations of core ion cyclotron emission on ASDEX Upgrade tokamak.

The B-dot probe diagnostic suite on the ASDEX Upgrade tokamak has recently been upgraded with a new 125 MHz, 14 bit resolution digitizer to study ion cyclotron emission (ICE). While classic edge emission from the low field side plasma is often observed, we also measure waves originating from the core with fast fusion protons or beam injected deuterons being a possible emission driver. Comparing the measured frequency values with ion cyclotron harmonics present in the plasma places the origin of this emission on the magnetic axis, with the fundamental hydrogen/second deuterium cyclotron harmonic matching the observed values. The actual values range from ∼27 MHz at the on-axis toroidal field BT = -1.79 T to ∼40 MHz at BT = -2.62 T. When the magnetic axis position evolves during this emission, the measured frequency values track the changes in the estimated on-axis cyclotron frequency values. Core ICE is usually a transient event lasting ∼100 ms during the neutral beam startup phase. However, in some cases, core emission occurs in steady-state plasmas and lasts for longer than 1 s. These observations suggest an attractive possibility of using a non-perturbing ICE-based diagnostic to passively monitor fusion alpha particles at the location of their birth in the plasma core, in deuterium-tritium burning devices such as ITER and DEMO.

Implementation of the new multichannel X-mode edge density profile reflectometer for the ICRF antenna on ASDEX Upgrade.

A new multichannel frequency modulated continuous-wave reflectometry diagnostic has been successfully installed and commissioned on ASDEX Upgrade to measure the plasma edge electron density profile evolution in front of the Ion Cyclotron Range of Frequencies (ICRF) antenna. The design of the new three-strap ICRF antenna integrates ten pairs (sending and receiving) of microwave reflectometry antennas. The multichannel reflectometer can use three of these to measure the edge electron density profiles up to 2 × 1019 m-3, at different poloidal locations, allowing the direct study of the local plasma layers in front of the ICRF antenna. ICRF power coupling, operational effects, and poloidal variations of the plasma density profile can be consistently studied for the first time. In this work the diagnostic hardware architecture is described and the obtained density profile measurements were used to track outer radial plasma position and plasma shape.

ICRF wave field measurements in the presence of scrape off layer turbulence on the ASDEX Upgrade tokamak (invited).

A new array of B-dot probes was installed on ASDEX Upgrade. The purpose of the new diagnostic is to study Ion Cyclotron Range-off Frequencies (ICRF) wave field distributions in the evanescent scrape-off layer (SOL) plasma region on the low field side of ASDEX Upgrade. The vacuum measurements (no gas, BT = 0 T) reveal ICRF wave field measurements consistent with the profiles expected from the newly installed 3-strap ICRF antennas outside the antenna box: the shape of the toroidal distribution of both the amplitude and the phase is the same for the case of only the central straps being active, as for the case of only the side straps being active. These profiles become strongly modified during plasma operations. The modifications can be separated into two types: "Inter-edge localized mode (ELM)" and "During-ELM" periods. The phase distribution of the ICRF wave fields remains well-defined during the Inter-ELM period; however, it becomes more spread out over the entire 360° range during ELMs. The observed modulations cannot be explained by the observed changes in the ICRF power, as monitored in the transmission line. However, they are consistent with ICRF coupling changes introduced by plasma filaments: the plasma density perturbations due to the filaments are high enough to change the nature of the fast ICRF wave field from evanescent to propagating. The coverage of the present diagnostic is being expanded to include both the low field side and the high field side probes. Additionally, a manipulator probe head is being developed to measure ICRF wave field radial profiles across the SOL region.

A new B-dot probe-based diagnostic for amplitude, polarization, and wavenumber measurements of ion cyclotron range-of frequency fields on ASDEX Upgrade.

A new B-dot probe-based diagnostic has been installed on an ASDEX Upgrade tokamak to characterize ion cyclotron range-of frequency (ICRF) wave generation and interaction with magnetized plasma. The diagnostic consists of a field-aligned array of B-dot probes, oriented to measure fast and slow ICRF wave fields and their field-aligned wavenumber (k(//)) spectrum on the low field side of ASDEX Upgrade. A thorough description of the diagnostic and the supporting electronics is provided. In order to compare the measured dominant wavenumber of the local ICRF fields with the expected spectrum of the launched ICRF waves, in-air near-field measurements were performed on the newly installed 3-strap ICRF antenna to reconstruct the dominant launched toroidal wavenumbers (k(tor)). Measurements during a strap current phasing scan in tokamak discharges reveal an upshift in k(//) as strap phasing is moved away from the dipole configuration. This result is the opposite of the k(tor) trend expected from in-air near-field measurements; however, the near-field based reconstruction routine does not account for the effect of induced radiofrequency (RF) currents in the passive antenna structures. The measured exponential increase in the local ICRF wave field amplitude is in agreement with the upshifted k(//), as strap phasing moves away from the dipole configuration. An examination of discharges heated with two ICRF antennas simultaneously reveals the existence of beat waves at 1 kHz, as expected from the difference of the two antennas' operating frequencies. Beats are observed on both the fast and the slow wave probes suggesting that the two waves are coupled outside the active antennas. Although the new diagnostic shows consistent trends between the amplitude and the phase measurements in response to changes applied by the ICRF antennas, the disagreement with the in-air near-field measurements remains. An electromagnetic model is currently under development to address this issue.

Convective and diffusive energetic particle losses induced by shear Alfvén waves in the ASDEX upgrade tokamak.

We present here the first phase-space characterization of convective and diffusive energetic particle losses induced by shear Alfvén waves in a magnetically confined fusion plasma. While single toroidal Alfvén eigenmodes (TAE) and Alfvén cascades (AC) eject resonant fast ions in a convective process, an overlapping of AC and TAE spatial structures leads to a large fast-ion diffusion and loss. Diffusive fast-ion losses have been observed with a single TAE above a certain threshold in the fluctuation amplitude.

Convective transport suppression in the scrape-off layer using ion cyclotron resonance heating on the ASDEX Upgrade Tokamak.

Turbulence properties in the scrape-off layer (SOL) in the presence of ion cyclotron frequency heating (ICRH) are compared to instances where it is absent. The discharges are all in a high-confinement mode (H-mode) regime. During ICRH, the SOL plasma density increases whereas turbulence large-scale and convective structures are shown to be suppressed. The probability distribution function is thus recorded to be closer to a Gaussian, and a net decrease in the low-frequency density fluctuations is reflected in the power spectra. Consequently, the level of turbulent fluctuations decreases significantly. Turbulence suppression is also reported during edge localized modes (ELMs) where both the ELMs-induced transport and duration are strongly affected. The increase of neutrals by gas puffing did not alter this behavior. We deduce that ICRH can be used as to suppress convective transport and reduce the ELM's amplitude.

[Indications to the formation of arteriovenous fistulas in performing reconstructive operations in patients with atherosclerotic lesions of the main arteries of the femur and shin at the stage of critical ischemia].

Causes of early shunt thromboses were studied retrospectively in 35 patients with occlusion of the femoro-popliteal segment and critical ischemia, in whom the operation of distal femoro-tibial shunt with the autovein had been performed by the method in situ without an application of the arteio-venous fistula (AVF). Early thromboses of the shunts took place in 8 patients (22.9%). The main cause of the early thromboses of the femorotibial shunts was shown to be a critical occlusive-stenotic lesion of the main arteries of the shin and foot with dysfunction of the plantar arch as well as decompensation of the microcirculation system. Objective criteria of the formation of AVF were worked out. The application of the criteria in operative treatment of 25 patients allowed the number of early thromboses to be reduced to 4%.

[Choice of optimal surgical reconstruction at patients with critical limb ischemia due to infrainguinal atherosclerotic arterial occlusive disease].

One hundred and four patients with atherosclerotic lesion of femoro-popliteal segment and III-IV stage of ischemia underwent vascular surgical procedures. Results of these operations were analyzed depending on state of distal arterial bed. Autovenous femoro-popliteal bypass (FPB) with reversed autovein was performed at 49 (47.1%) patients, femoro-tibial bypass (FTB) with autovein in situ - at 55 (52.9%). Clinical and angiographic variants of favorable and unfavorable prognosis of FBP and FTB are described. It is demonstrated that severe lesion of outflow distal arteries is the main cause of bypasses thrombosis. Protective arteriovenous fistula in the region of FTB distal anastomosis improves significantly short-term results of operation.

[Features of microcirculatory disorders in acute and recurrent hemorrhagic vasculitis (Schönlein-Henoch disease)]. / Osobennosti mikrotsirkuliatornykh narushenii pri ostrom i retsidiviruiushchem gemorragicheskom vaskulite (bolezni Shenleina-Genokha).

AIM: To study microcirculatory disturbances in acute and chronic hemorrhagic vasculitis (HV). MATERIAL AND METHODS: The examination of 44 HV patients included clinical and immunological examinations, conjunctival biomicroscopy, tests for blood viscosity, aggregation of erythrocytes, coagulation parameters. In 8 patients morphological examination of skin microvessels was made (light microscopy and electron microscopy). RESULTS: Changes in microcirculation of patients with acute HV were characterized by increased IgA and red cell aggregation, tendency to hypercoagulation. Morphologically, there was high permeability of the microvessels wall. In patients with chronic HV laboratory parameters normalized except elevated level of circulating immune complexes and red cell aggregation. Morphological picture of microcirculatory disturbances in patients with chronic HV was characterized by productive vasculitis. CONCLUSION: In HV patients microcirculatory disorders caused by immunologic mechanisms are realized through increased permeability of microvessel wall, high aggregation of erythrocytes in microvessels and hypercoagulation in acute HV. In patients with chronic HV productive vasculitis and high aggregation of erythrocytes are registered.

[Acid-base balance parameters of the synovial fluid in patients with early-stage rheumatoid arthritis]. / Pokazateli kislotno-osnovnogo sostoianiia sinovial'noi zhidkosti u bol'nykh revmatoidnym artritom v rannei stadii.

AIM: To study changes in acid-base balance (ABB) of synovial fluid (SF) in rheumatoid arthritis (RA) patients in respect of the disease duration, clinical symptoms and treatment. MATERIAL AND METHODS: The examination of verified RA patients included clinical, x-ray, immunological and special tests. The patients received nonsteroid antiinflammatory drugs, 2 weeks later--physiotherapy followed by 10-day basic treatment (tauredon, methotrexate or cyclophosphamide). RESULTS: Before the treatment, SF acidotic shift was found in all the patients. The shift correlated with activity of the inflammation, serologic affiliation to the rheumatoid factor, presence of systemic manifestations, x-ray signs of the articular changes in response to the treatment. Attenuation of the inflammatory process accompanies an increase in SF acidotic shift. In administration of methotrexate SF pH was higher than in the use of other drugs. CONCLUSION: Adjuvant ABB correctors are recommended for RA patients.

[Changes in the acid-base status of the synovial fluid in rheumatoid arthritis patients]. / Izmenenie kislotno-osnovnogo sostoianiia sinovial'noi zhidkosti u bol'nykh revmatoidnym artritom.

AIM: The study of changes in joint fluid (JF) acid-base balance in RA patients to evaluate severity of joint lesions, efficacy of on-going therapy and to predict appearance and persistence of RA remission. MATERIALS AND METHODS: A routine examination and measurements of JF pH of the affected joints and venous blood before and during the treatment were performed in 65 RA patients with articular or articular-visceral forms (46 and 19 patients, respectively). 19 patients were seropositive and 20 seronegative by rheumatoid factor. A group of 17 patients suffering from osteoarthritis deformans with synovitis served control. RESULTS: Inflammation in RA is running with lowering of JF pH in the affected joints and with acidic shift in the acid-base balance manifesting as compensated metabolic acidosis in blood. JF pH of the affected joints inversely correlated with activity of the inflammation. Its changes were more pronounced in RA systemic lesions and in the seropositive variant. CONCLUSION: JF pH may be used for assessment of inflammation activity in RA.

[The role of an imbalance of sex and calcium-regulating hormones in osteoarthrosis deformans in women]. / O roli disbalansa polovykh i kal'tsiireguliruiushchikh gormonov pri deformiruiushchem osteoartroze u zhenshchin.

AIM: Determination of essential changes in hormonal background in evaluation of sex and calcium-regulating hormones levels in women of different age with osteoarthrosis deformans (OAD). MATERIALS AND METHODS: 30-34-year-old and 45-60-year-old females (60 premenopausal and 51 menopausal) with x-ray confirmed OAD and 34 control healthy women (23 premenopausal and 11 in menopause) were examined with radioimmunoassay for the baseline serum levels of calcitonin, parathyrine, osteocalcin, estradiol, testosterone, progesterone, dehydroepiandrosterone-sulfate (DHAS). RESULTS: Both age-groups patients had abnormal levels of testosterone and its metabolite DHAS. Significant deviations were found in menopausal women. With age, both patients and healthy women exhibited increasing levels of parathyrine and calcitonine. Compared to controls, OAD women had lower parathyrine, osteocalcine and higher calcitonine levels. With OAD progression, serum osteocalcin tended to lowering while testosterone was on the increase. CONCLUSION: Changes in blood levels of calcium-regulating hormones observed in osteoarthrosis may result in stimulation of cartilage degeneration. Calcitonine was low in premenopausal and menopausal OAD patients indicating impairment of bone metabolism in osteoarthrosis.

[Antibodies to cardiolipin and hemostasis in rheumatic patients during development of rheumatic valvular disease]. / Antitela k kardiolipinu i pokazateli gemostaza u bol'nykh revmatizmom pri formirovanii revmaticheskikh porokov serdtsa.

The observational study included 79 rheumatic patients aged 14-49 years. The diagnosis of acute rheumatic fever (ARF) was made in 29 patients (13-first attack, 16-recurrence), 50 patients had rheumatic heart disease (RHD) without signs of activity, 40 healthy donors served control. Antibodies to cardiolipin (a-CL) in the blood were determined by enzyme immunoassay, hemostasis was assessed by the level of antithrombin III, platelet aggregation, readings of electrocoagulograms. ARF patients were examined throughout the year, RHD patients--only once. Compared to the controls, both ARF and RHD patients demonstrated higher occurrence of a-CL, enhanced platelet aggregation, low antithrombin III level, hypercoagulation on electrocoagulogram, a-CL in ARF patients were detectable from the first month of the attack. By month 7-12 their count decreased, hemostasis normalized. In the onset and progression of RHD in the presence of ARF a-CL occurred more frequently. A direct relationship was found between the time of a-CL detection in the blood and severity, duration of rheumatic carditis. The data obtained validate feasibility of using a-CL for diagnosis of rheumatic carditis severity and prognosis of RHD development.