High Average Gradient in a Laser-Gated Multistage Plasma Wakefield Accelerator.

Plasma wakefield accelerators driven by particle beams are capable of providing accelerating gradient several orders of magnitude higher than currently used radio-frequency technology, which could reduce the length of particle accelerators, with drastic influence on the development of future colliders at TeV energies and the minimization of x-ray free-electron lasers. Since interplasma components and distances are among the biggest contributors to the total accelerator length, the design of staged plasma accelerators is one of the most important outstanding questions in order to render this technology instrumental. Here, we present a novel concept to optimize interplasma distances in a staged beam-driven plasma accelerator by drive-beam coupling in the temporal domain and gating the accelerator via a femtosecond ionization laser.

Long-term evolution of the three-dimensional structure of string-fluid complex plasmas in the PK-4 experiment.

Microparticle suspensions in a polarity-switched discharge plasma of the Plasmakristall-4 facility on board the International Space Station exhibit string-like order. As pointed out in [Phys. Rev. Research 2, 033314 (2020)2643-156410.1103/PhysRevResearch.2.033314], the string-order is subject to evolution on the timescale of minutes at constant gas pressure and constant parameters of polarity switching. We perform a detailed analysis of this evolution using the pair correlations and length spectrum of the string-like clusters (SLCs). Average exponential decay rate of the SLC length spectrum is used as a measure of string order. The analysis shows that the improvement of the string-like order is accompanied by the decrease of the thickness of the microparticle suspension, microparticle number density, and total amount of microparticles in the field of view. This suggests that the observed long-term evolution of the string-like order is caused by the redistribution of the microparticles, which significantly modifies the plasma conditions.

ILEOSIGMOID POUCH AS A URINARY DIVERSION APPROACH FOLLOWING RADICAL CYSTECTOMY IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER.

Goal - to determine efficacy of the Ileosigmo-pouch (ISP) as a method of transrectal urinary diversion in invasive bladder cancer (BC) treatment. Retrospective analysis of clinical data of patients that undergone radical cystectomy (RC), followed by ISP method of urinary diversion. Study compared two groups of patients: the first group of 22 (23.6%) patients with ISP and the control group included 71 (76.4%) patients with Mainz pouch II (MP II) diversion. The groups were statistically comparable by major clinical parameters. Complication rates were evaluated with Clavien-Dindo classification. There were no significant differences in the duration of surgery procedure, - ISP 210 - 562 (380.4±38.4) minutes vs. 190 - 557 (311.3±49.5) minutes for MP II. Levels of intraoperative blood loss in both groups were comparable: 110 - 2850 (707.42±97.2) ml vs. 170 - 3000 (788.51±141.3) ml. Peroiperative complications after ISP and MP II (1 (4.5%) vs. 6 (4.8%)) did not exceed 3 grade according to Clavien-Dindo. The frequency of postoperative chronic pyelonephritis (CP) was higher in MP II 26 (24.3%) vs. ISP 3 (15.7%). Gas reflux into the kidneys was observed only in MP II 18 (16.8%). Metabolic acidosis was revealed in 27 (25.2%) after MP II and in 2 (10.5%) after ISP. During the ISP formation comparing to MP II, the pouch volume increased in average up to 1000 ml vs. 750 ml., the pressure in a sigmoid colon decreases to 18 cm of water column against 35 cm wc. Urination/defecation frequency was improved in patients after ISP - every 3-4 hours during the day and 5-6 hours at night vs. MP II every 2-3 hours during the day and 3-4 hours at night. The ISP method of urinary diversion in our study showed improvements of urodynamic parameters and eliminated the body metabolic disorders when compared to transrectal diversion with MP2. This viable option of diversion in patients with invasive bladder cancer who are not candidates for neobladder, but strongly afraid of cutaneous urinary stoma.

Efficacy of Neoadjuvant Targeted Therapy in Treatment of Patients with Localised Clear-Cell Renal Cell Carcinoma.

AIM: This study aimed to evaluate the efficacy of neoadjuvant targeted therapy (TT) in patients with localised clear-cell renal cell carcinoma (RCC). MATERIALS AND METHODS: A special randomised trial was planned and conducted by the Research Department of Plastic and Reconstructive Oncology in the National Cancer Institute of Ukraine for testing the clinical efficacy of neoadjuvant TT in the treatment of clear-cell localised RCC, and the primary endpoint was tumour response evaluation after TT. The secondary endpoints included evaluation of dependence between the use of neoadjuvant TT and the probability of partial nephrectomy and the correlation between tumour size, stage, remaining functioning parenchyma volume, and response to systemic therapy. RESULTS: Overall, 118 patients met the inclusion criteria and were randomly assigned to receive combined treatment or surgery alone. The percentage of tumour regression ranged from 0% to 60%, and the median was (95% confidence interval) 20.5 ± 14.3 (16.8-24.3%). Most of the patients had a slightly positive response to TT (3%-29% decrease in tumour size); n = 44 (76.9%) cases. Partial response by the Response Evaluation Criteria in Solid Tumours, version 1.1, was observed in 14 (24.1%) patients and reached a maximum of 60% regression. Tumour reduction in the neoadjuvant TT group allowed kidney preservation in 53 (91.4%) patients. In the control group, the number of organ-sparing procedures was significantly lower (n = 20, 33.3%). The statistical difference was relevant (x 2 = 42.1; p < 0.001). CONCLUSION: The positive results of neoadjuvant TT obtained in our study indicate the clinical validity of combined treatment in patients with localised RCC.

Demonstration of a compact plasma accelerator powered by laser-accelerated electron beams.

Plasma wakefield accelerators are capable of sustaining gigavolt-per-centimeter accelerating fields, surpassing the electric breakdown threshold in state-of-the-art accelerator modules by 3-4 orders of magnitude. Beam-driven wakefields offer particularly attractive conditions for the generation and acceleration of high-quality beams. However, this scheme relies on kilometer-scale accelerators. Here, we report on the demonstration of a millimeter-scale plasma accelerator powered by laser-accelerated electron beams. We showcase the acceleration of electron beams to 128 MeV, consistent with simulations exhibiting accelerating gradients exceeding 100 GV m-1. This miniaturized accelerator is further explored by employing a controlled pair of drive and witness electron bunches, where a fraction of the driver energy is transferred to the accelerated witness through the plasma. Such a hybrid approach allows fundamental studies of beam-driven plasma accelerator concepts at widely accessible high-power laser facilities. It is anticipated to provide compact sources of energetic high-brightness electron beams for quality-demanding applications such as free-electron lasers.

Quality of life in patients after radical cystectomy with modified ureterocutaneostomy and Bricker urinary diversion.

BACKGROUND: Radical cystectomy (RC) has been used for over 100 years as an effective treatment of muscle invasive bladder cancer (MIBC). However, the main surgical challenge is not only to remove an affected organ but also to replace its functional component - urine diversion. The aim of our work is to study the efficacy of the modified ureterocutaneostomy technique by estimating the quality of life in post-RC patients with MIBC. MATERIALS AND METHODS: A retrospective analysis of the cases of 40 patients was provided. Two groups were delineated depending on urinary diversion: 20 patients with urinary derivation by the modified ureterocutaneostomy method, and 20 patients - with Bricker conduit. All patients were matched by mean age, gender, American Society of Anesthesiologists status, disease stage and duration. 16 (80%) and 15 (75%) patients from the study and control groups, respectively, passed 3 courses of standard preoperative polychemotherapy with gemcitabine-cisplatin. Quality of life was assessed using the health survey SF-36 form (developed at the US Medical Research Institute), adapted at the National Cancer Institute (Ukraine). RESULTS: Comparing patients after ureterocutaneostomy or Bricker surgery, no statistical discrepancy was noted before surgery and after 3 months. A statistical difference in perioperative parameters was noted only when comparing the surgery duration and length of stay in hospital. CONCLUSIONS: The modified ureterocutaneostomy technique contributes to performing surgery faster and more effectively since an intestinal stage is skipped in surgery. Our findings indicate that ureterocutaneostomy technique may be used as a standard of care for post-RC patients with MIBC.

Tunable High Spatio-Spectral Purity Undulator Radiation from a Transported Laser Plasma Accelerated Electron Beam.

Undulator based synchrotron light sources and Free Electron Lasers (FELs) are valuable modern probes of matter with high temporal and spatial resolution. Laser Plasma Accelerators (LPAs), delivering GeV electron beams in few centimeters, are good candidates for future compact light sources. However the barriers set by the large energy spread, divergence and shot-to-shot fluctuations require a specific transport line, to shape the electron beam phase space for achieving ultrashort undulator synchrotron radiation suitable for users and even for achieving FEL amplification. Proof-of-principle LPA based undulator emission, with strong electron focusing or transport, does not yet exhibit the full specific radiation properties. We report on the generation of undulator radiation with an LPA beam based manipulation in a dedicated transport line with versatile properties. After evidencing the specific spatio-spectral signature, we tune the resonant wavelength within 200-300 nm by modification of the electron beam energy and the undulator field. We achieve a wavelength stability of 2.6%. We demonstrate that we can control the spatio-spectral purity and spectral brightness by reducing the energy range inside the chicane. We have also observed the second harmonic emission of the undulator.

Producing multi-coloured bunches through beam-induced ionization injection in plasma wakefield accelerator.

This paper discusses the properties of electron beams formed in plasma wakefield accelerators through ionization injection. In particular, the potential for generating a beam composed of co-located multi-colour beamlets is demonstrated in the case where the ionization is initiated by the evolving charge field of the drive beam itself. The physics of the processes of ionization and injection are explored through OSIRIS simulations. Experimental evidence showing similar features are presented from the data obtained in the E217 experiment at the FACET facility of the SLAC National Laboratory. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Betatron radiation and emittance growth in plasma wakefield accelerators.

Beam-driven plasma wakefield acceleration (PWFA) has demonstrated significant progress during the past two decades of research. The new Facility for Advanced Accelerator Experimental Tests (FACET) II, currently under construction, will provide 10 GeV electron beams with unprecedented parameters for the next generation of PWFA experiments. In the context of the FACET II facility, we present simulation results on expected betatron radiation and its potential application to diagnose emittance preservation and hosing instability in the upcoming PWFA experiments. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Hybrid LWFA-PWFA staging as a beam energy and brightness transformer: conceptual design and simulations.

We present a conceptual design for a hybrid laser-driven plasma wakefield accelerator (LWFA) to beam-driven plasma wakefield accelerator (PWFA). In this set-up, the output beams from an LWFA stage are used as input beams of a new PWFA stage. In the PWFA stage, a new witness beam of largely increased quality can be produced and accelerated to higher energies. The feasibility and the potential of this concept is shown through exemplary particle-in-cell simulations. In addition, preliminary simulation results for a proof-of-concept experiment in Helmholtz-Zentrum Dresden-Rossendorf (Germany) are shown. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

A case of synchronous bilateral calyx urothelial carcinoma: combined treatment approach.

Upper urinary tract urothelial carcinoma is a rare tumor. Data about its correct management are controversial. Investigational technology development made it possible to diagnose asymptomatic small tumors, which can be successfully managed endoscopically. We report the case of bilateral urothelial cancer and hydronephrosis in patient aged 38. After management of acute post-renal kidney insufficiency, the neoadjuvant platinum-based chemotherapy was used followed by the kidney-sparing surgery split in two interventions on both sides. The patient does not have any relapse or further progression after one year of initial treatment with good performance status and high life quality level. We believe that the kidney preserving strategy can be considered as an option even in high-risk patients. The renal function in such cases is a crucial parameter affecting the outcome.

Expression pattern of genes associated with tumor microenvironment in prostate cancer.

AIM: To assess relative expression (RE) levels of CAF-, TAM-specific, immune defense-associated genes in prostate tumors and to show correlation of RE with clinical, pathological and molecular characteristics, with the aim to define clinically significant specific alterations in a gene expression pattern. METHODS: RE of 23 genes was analyzed by a quantitative polymerase chain reaction in 37 freshly frozen samples of prostate cancer tissues of a different Gleason score (GS) and at various tumor stages, compared with RE in 37 paired conventionally normal prostate tissue (CNT) samples and 20 samples of prostate adenomas. RESULTS: Differences in RE were shown for 11 genes out of 23 studied, when tumor samples were compared with corresponding CNTs. 7 genes, namely ACTA2, CXCL14, CTGF, THY1, FAP, CD163, CCL17 were upregulated in tumors. 4 genes, namely CCR4, NOS2A, MSMB, IL1R1 were downregulated in tumors. 14 genes demonstrated different RE in TNA at different stages: CXCL12, CXCL14, CTGF, FAP, HIF1A, THY1, CCL17, CCL22, CCR4, CD68, CD163, NOS2A, CTLA4, IL1R1. RE changes of 9 genes - CXCL12, CXCL14, HIF1A, CCR4, CCL17, NOS2A, CTLA4, IL1R1, IL2RA - were found in tumors with different GS. Moreover, 9 genes showed differences in RE in TNA, dependently on the presence or absence of the TMPRSS2/ERG fusion and 7 genes showed differences in RE of groups with differential PTEN expression. Significant correlations were calculated between RE of 9 genes in adenocarcinomas and the stage, and GS; also, between RE of 2 genes and the fusion presence; and between RE of 4 genes and PTEN expression. CONCLUSIONS: Several gene expression patterns were identified that correlated with the GS, stage and molecular characteristics of tumors, i.e. presence of the TMPRSS2/ERG fusion and alterations in PTEN expression. These expression patterns can be used for molecular profiling of prostate tumors, with the aim to develop personalized medicine approaches. However, the proposed profiling requires a more detailed analysis and a larger cohort of patients with prostate tumor.

Two-probe atomic-force microscope manipulator and its applications.

We report on a manipulator based on a two-probe atomic force microscope (AFM) with an individual feedback system for each probe. This manipulator works under an upright optical microscope with 3 mm focal distance. The design of the microscope helps us tomanipulate nanowires using the microscope probes as a two-prong fork. The AFM feedback is realized based on the dynamic full-time contact mode. The applications of the manipulator and advantages of its two-probe design are presented.

[PECULIARITIES OF METHOD AND RESULTS OF PLASTY, USING INTESTINAL SEGMENT, FOR IATROGENIC INJURY OF URETER].

Basing on analysis of the examination and treatment results in 53 patients, suffering iatrogenic injury of ureter (IIU), the indications for ureteric reconstruction using intestinal segment were the ureter long irreversible changes, while renal function preserved. A segmental ureteric plasty was done in 8 (15.1%) patients, a subtotal one--in 16 (30.2%), total--in 14 (26.4%), and bilateral--in 15 (28.3%). With the objective to prevent the bladder-intestinal reflux occurrence a distal part of the intestinal transplant was modeled. In 35 (66%) patients 2 - 3 cm of distal part of intestinal mucosa were turned out with the wrap formation. In 18 (34%) patients the creation of antireflux wrap was added by its modeling in a kind of intraileal plasty with formation of two separate channels in the intestinal-bladder anastomosis region. While performance of intraileal plasty of the bladder-intestinal reflux have occurred in 2 (11.1%) patients, and after procedure with the wrap formation--in 13 (37.1%).

[TACTICS OF TREATMENT OF PATIENTS FOR ONCOLOGICAL DISEASES IN IATROGENIC INJURY OF UPPER URINARY WAYS].

Results of examination and treatment of 119 patients for oncological diseases were analyzed, in whom iatrogenic injury of ureter (IIU) have occurred. Remission of oncological diseases plastic operations were performed in 48 (40.3%) patients, reconstructive - in 23 (19.3%), restoration - in 3 (2.5%); while a progress - palliative nephrostomy in 41 (34.5%) patients. In 4 (3.4%) patients dynamical observation was conducted. The method of operative treatment was selected, taking into account efficacy of treatment of oncological diseases; mechanism of IIU; level of obstruction and irreversibility of changes in wall of ureter; character of injury (one-sided, bilateral, injury of ureter of a single kidney); anatomo-functional changes of upper and lower urinary ways; the patient state severity.

[CRITERIA OF ESTIMATION AND RESULTS OF TREATMENT OF IATROGENIC INJURIES OF URETERS IN ONCOLOGICAL PATIENTS].

Clinical analysis was conducted in 74 oncological patients, in whom 103 iatrogenic injuries of ureter (IIU) were revealed and for which they were treated in Scientific-nvestigative Department of Plastic and Reconstructive Oncourology. Restoration of renal and ureteric function were noted in terms up to 6 mo, in these terms were revealed all complications, caused by recurrence of obstruction. Late follow-up results of III were positive in 95.2% patients, unsatisfactory result was revealed in 3 (4.8%) patients, what have demanded conduction of surgical secondary correction of urodynamics. Quality of life after restoration operative treatment have improved in 31.70%patients in comparison of such before the operation.

[NEOADJUVANT TARGET THERAPY IN A RENAL-CELL CANCER].

There were observed 30 patients (32 tumors), to whom preoperatively for renal-cell cancer (ROC) a neoadjuvant target therapy (NATTH) was conducted. In 19 (66.7%) of them a pazopanib (800 mg per os once a day through 2 mo) was applied, and in 10 (33.3%)--sunitinib (50 mg per os once a day through 28 days, the gap--14 days, repeated course--28 days). The indications for the NATTH conduction were: in 7 (21.9%) patients--a locally--spread RCC with the objective to localize a tumor and to search a further possibility of radical surgical intervention performance, and in 25 (78.1%)--the tumor reduction and searching possibility of the organpreserving treatment conduction. The NATTH conduction in the patients, suffering RCC, have guaranteed a primary pathological focus reduction in 90% of observations, and a partial regression in accordance to the RECIST criteria--in 28.1%. A tumor reduction by (22.9 ± 17.8)% at average have permitted to perform a renal resection in 75% of observations, concerning localized RCC, when indication of preservation of enough functioning renal parenchyma was secured.

Genetic markers associated with abstinence length in alcohol-dependent subjects treated with acamprosate.

Acamprosate supports abstinence in some alcohol-dependent subjects, yet predictors of response are unknown. To identify response biomarkers, we investigated associations of abstinence length with polymorphisms in candidate genes in glycine and glutamate neurotransmission pathways and genes previously implicated in acamprosate response. Association analyses were conducted in the discovery sample of 225 alcohol-dependent subjects treated with acamprosate for 3 months in community-based treatment programs in the United States. Data from 110 alcohol-dependent males treated with acamprosate in the study PREDICT were used for replication of the top association findings. Statistical models were adjusted for relevant covariates, including recruitment site and baseline clinical variables associated with response. In the discovery sample, shorter abstinence was associated with increased intensity of alcohol craving and lower number of days between the last drink and initiation of acamprosate treatment. After adjustment for covariates, length of abstinence was associated with the GRIN2B rs2058878 (P=4.6 × 10(-5)). In the replication sample, shorter abstinence was associated with increased craving, increased depressive mood score and higher alcohol consumption. Association of abstinence length with GRIN2B rs2058878 was marginally significant (P=0.0675); as in the discovery sample, the minor A allele was associated with longer abstinence. Furthermore, rs2300272, which is in strong linkage disequilibrium with rs2058878, was also associated with abstinence length (P=0.049). This is the first report of a replicated association of genetic markers with the length of abstinence in acamprosate-treated alcoholics. Investigation of the underlying mechanisms of this association and its usefulness for individualized treatment selection should follow.

Comparative pharmacodynamics of moxifloxacin and levofloxacin in an in vitro dynamic model: prediction of the equivalent AUC/MIC breakpoints and equiefficient doses.

To demonstrate the impact of the different pharmacokinetics of moxifloxacin and levofloxacin on their antimicrobial effects (AMEs), killing and regrowth kinetics of two clinical isolates of Staphylococcus aureus and one each of Escherichia coli and Klebsiella pneumoniae were studied. With each organism, a series of monoexponential pharmacokinetic profiles of single doses of moxifloxacin (T:1/2 = 12.1 h) and levofloxacin (T:(1/2) = 6.8 h) were simulated. The respective eight-fold ranges of the ratios of area under the concentration-time curve (AUC) to the MIC were 58-475 and 114-934. Species- and strain-independent linear relationships observed between the intensity of AME (I:(E)) and log AUC/MIC were not superimposed for moxifloxacin and levofloxacin (r(2) = 0.99 in both cases). The predicted AUC/MIC ratios for moxifloxacin and levofloxacin that might be equivalent to Schentag's AUC/MIC breakpoint for ciprofloxacin (125) were estimated at 80 and 130, respectively. The respective equivalent MIC breakpoints were 0.41 mg/L (for a 400 mg dose of moxifloxacin) and 0.35 mg/L (for a 500 mg dose of levofloxacin). Based on the I:(E)-log AUC/MIC relationships, equiefficient 24 h doses (D:(24)s) of moxifloxacin and levofloxacin were calculated for hypothetical strains of S. aureus, E. coli and K. pneumoniae with MICs equal to the respective MIC50s (weighted geometric means of reported values). To provide an 'acceptable' I:(E) = 200 (log cfu/mL)*h, the D:(24)s of moxifloxacin for all three organisms were much lower (150, 30 and 60 mg, respectively) than the clinically proposed 400 mg dose. Although the usual dose of levofloxacin (500 mg) would be in excess for E. coli and K. pneumoniae (D:(24) = 36 and 220 mg, respectively), it might be insufficient for S. aureus (the estimated D:(24) = 850 mg). Moreover, to provide the same effect as a 400 mg D:(24) of moxifloxacin against staphylococci, levofloxacin would have to be given in a 5000 mg D:(24), which is 10-fold higher than its clinically accepted dose. The described method of generalization of data obtained with specific organisms to other representatives of the same species might be useful to predict the AMEs of new quinolones.