Emission characteristics of bulk aerosols excited by externally focused femtosecond filaments.

The bulk aerosol emissions excited by externally focused femtosecond laser filaments are characterized using time-resolved plasma imaging and spectroscopy. Images of N2 and N2+ plasma fluorescence are used to characterize the filament dimensions. Emission profiles from bulk Sr aerosols are studied, showing that several localized emission regions in the filament begin to develop for lower repetition rates and higher pulse energies. Plasma temperature and electron density profiles are determined using particle emissions along the length of short- and long-focused filaments, and results are compared for on-axis and side-collected spectra. The use of on-axis collection enables the sampling of light emitted over the entire length of the filament; however, the necessary back-propagation of light makes on-axis collection susceptible to self-absorption as the optical path is extended through the filament plasma column formed in bulk aerosols.

Generation of multiple obstruction-free channels for free space optical communication.

Multi-filament structures produced by vortical high-power femtosecond pulses propagating through clouds and fog can simultaneously clear two channels with cylindrical and annular profile. We present a method to achieve Free Space Optical (FSO) communications through such highly scattering media by propagating appropriately shaped laser modes through these channels. As a proof of concept, we implemented a Laguerre-Gaussian beam as information signal carrier to demonstrate transmission of 543-nm CW laser beam through a 1-m long cloud chamber using both channels. The low power of the information signal in this experiment allows considering applications in Earth-satellite FSO communication.

Iterative wavefront optimization of ultrafast laser beams carrying orbital angular momentum.

Structured intense laser beams offer degrees of freedom that are highly attractive for high-field science applications. However, the performance of high-power laser beams in these applications is often hindered by deviations from the desired spatiotemporal profile. This study reports the wavefront optimization of ultrafast Laguerre-Gaussian beams through the synergy of adaptive optics and genetic algorithm-guided feedback. The results indicate that the intensity fluctuations along the perimeter of the target ring-shaped profile can be reduced up to ∼15%. Furthermore, the radius of the ring beam profile can be tailored to a certain extent by establishing threshold fitting criteria. The versatility of this approach is experimentally demonstrated in conjunction with different focusing geometries.

AAV-mediated gene transfer of a checkpoint inhibitor in combination with HER2-targeted CAR-NK cells as experimental therapy for glioblastoma.

Glioblastoma (GB) is the most common primary brain tumor, which is characterized by low immunogenicity of tumor cells and prevalent immunosuppression in the tumor microenvironment (TME). Targeted local combination immunotherapy is a promising strategy to overcome these obstacles. Here, we evaluated tumor-cell specific delivery of an anti-PD-1 immunoadhesin (aPD-1) via a targeted adeno-associated viral vector (AAV) as well as HER2-specific NK-92/5.28.z (anti-HER2.CAR/NK-92) cells as components for a combination immunotherapy. In co-culture experiments, target-activated anti-HER2.CAR/NK-92 cells modified surrounding tumor cells and bystander immune cells by triggering the release of inflammatory cytokines and upregulation of PD-L1. Tumor cell-specific delivery of aPD-1 was achieved by displaying a HER2-specific designed ankyrin repeat protein (DARPin) on the AAV surface. HER2-AAV mediated gene transfer into GB cells correlated with HER2 expression levels, without inducing anti-viral responses in transduced cells. Furthermore, AAV-transduction did not interfere with anti-HER2.CAR/NK-92 cell-mediated tumor cell lysis. After selective transduction of HER2+ cells, aPD-1 expression was detected at the mRNA and protein level. The aPD-1 immunoadhesin was secreted in a time-dependent manner, bound its target on PD-1-expressing cells and was able to re-activate T cells by efficiently disrupting the PD-1/PD-L1 axis. Moreover, high intratumoral and low systemic aPD-1 concentrations were achieved following local injection of HER2-AAV into orthotopic tumor grafts in vivo. aPD-1 was selectively produced in tumor tissue and could be detected up to 10 days after a single HER2-AAV injection. In subcutaneous GL261-HER2 and Tu2449-HER2 immunocompetent mouse models, administration of the combination therapy significantly prolonged survival, including complete tumor control in several animals in the GL261-HER2 model. In summary, local therapy with aPD-1 encoding HER2-AAVs in combination with anti-HER2.CAR/NK-92 cells may be a promising novel strategy for GB immunotherapy with the potential to enhance efficacy and reduce systemic side effects of immune-checkpoint inhibitors.

Ultra-broadband long-wave-infrared pulse production using a chirped-pulse difference-frequency generation.

We present a broadband light source based on near-infrared chirped-pulse difference-frequency mixing that is suitable for seeding long-wave-infrared (LWIR) optical parametric chirped-pulse amplification (OPCPA). A nitrocellulose pellicle is used in a Ti:sapphire regenerative amplifier to generate dual-frequency output pulses, which are subsequently mixed in a 0.4-mm thick AgGaS2 crystal. LWIR pulses with ∼1 µm full width at half maximum (FWHM) bandwidth centered at 10.5 µm are generated by mixing transform-limited pulses. Assisted by genetic algorithm optimization, the bandwidth is broadened to ∼3 µm FWHM within the 8-12 µm atmospheric transmission window. The seed source paves the path towards tabletop ultrafast terawatt-class passively carrier-envelope-phase stabilized OPCPA in the LWIR region.

Tactile Stimulation in Adult Rats Modulates Dopaminergic Molecular Parameters in the Nucleus accumbens Preventing Amphetamine Relapse.

Amphetamine (AMPH) is a psychostimulant drug frequently related to addiction, which is characterized by functional and molecular changes in the brain reward system, favoring relapse development, and pharmacotherapies have shown low effectiveness. Considering the beneficial influences of tactile stimulation (TS) in different diseases that affect the central nervous system (CNS), here we evaluated if TS applied in adult rats could prevent or minimize the AMPH-relapse behavior also accessing molecular neuroadaptations in the nucleus accumbens (NAc). Following AMPH conditioning in the conditioned place preference (CPP) paradigm, male rats were submitted to TS (15-min session, 3 times a day, for 8 days) during the drug abstinence period, which were re-exposed to the drug in the CPP paradigm for additional 3 days for relapse observation and molecular assessment. Our findings showed that besides AMPH relapse, TS prevented the dopamine transporter (DAT), dopamine 1 receptor (D1R), tyrosine hydroxylase (TH), mu opioid receptor (MOR) increase, and AMPH-induced delta FosB (ΔFosB). Based on these outcomes, we propose TS as a useful tool to treat psychostimulant addiction, which is subsequent to clinical studies; it could be included in detoxification programs together with pharmacotherapies and psychological treatments already conventionally established.

Determination of strontium radioisotopes in routine and emergency samples.

We present the radioanalytical strategies used for the determination of strontium radioisotopes in routine and emergency samples. While in routine monitoring, the main goal is to achieve limits of detection as low as possible. In emergency, priority is given to the rapid procurement of data about a contamination. The parameters accuracy, precision and detection limit of the radiochemical methods are shown. We present the results obtained over the past 22 years in proficiency tests and in the analysis of reference materials.

The reliability of physical examination in diagnosing arterial injury in penetrating trauma to extremities: A first look at different anatomical regions and injury mechanisms.

BACKGROUND: The accuracy of physical examination to exclude arterial injury in penetrating trauma to extremities has been well established. OBJECTIVES: To determine whether the accuracy of physical examination to exclude arterial injury is similar to that of a computed tomography arteriogram (CTA) for different anatomical regions and mechanisms of injury, and in patients with concomitant fractures compared with those without. METHODS: A retrospective review was conducted on all patients who underwent CTA for penetrating injuries to an extremity between 1 June 2016 and 30 June 2017. The presence of arterial injuries was noted, and these were grouped into anatomical areas. Clinical notes were reviewed for the presence of hard signs of arterial injury at initial examination. RESULTS: A total of 220 lower limb and 133 upper limb CTAs were included. The mean patient age was 28.9 years (range 11 - 68). The overall sensitivity of physical examination in detecting a CTA-confirmed arterial injury was 95.3% (95% confidence interval (CI) 88.4 - 98.7), with a specificity of 93.9% (95% CI 90.2 - 96.4). Physical examination of the thigh had the highest specificity of 96.4% (95% CI 91.8 - 98.8), followed by the lower leg at 94.4% (95% CI 81.3 - 99.3), the upper arm at 89.6% (95% CI 79.7 - 95.7) and the forearm at 77.8% (95% CI 40.0 - 97.2). For gunshot wounds the specificity was 96.1% (95% CI 92.4 - 98.3), while for stab wounds it was 86.8% (95% CI 74.7 - 94.5). CONCLUSIONS: This study agrees with current literature indicating that physical examination has high specificity in detecting arterial injury in the setting of penetrating trauma to an extremity. However, it shows that the specificity is not equal for all anatomical regions or mechanisms of injury.

The incidence of fragility hip fractures in a subpopulation of South Africa.

BACKGROUND: Fragility hip fractures (FHFs) are associated with significant morbidity, mortality and burden on the healthcare system. European and North American literature suggests that the worldwide incidence of FHFs is increasing, but very little is known about the incidence of FHFs in Africa and South Africa (SA). Historically FHFs were believed to be uncommon in black African populations, but recent studies have shown a marked increase in the incidence compared with the early literature. OBJECTIVES: To investigate the age-, gender- and population group-specific incidences of FHFs in a subpopulation in Eastern Cape Province, SA. METHODS: A retrospective review of all patients presenting with FHFs was performed at a tertiary hospital in the Eastern Cape over a 1-year period. Age-, gender- and population group-specific incidence rates were calculated for 5-year age intervals using the age distribution data of the western region of the Eastern Cape (WREC) as a denominator for each age group. Overall crude incidence rates were calculated by using the sum total of FHFs, divided by the study population. All incidences were calculated as number of fractures per 100 000 people annually. RESULTS: A total of 253 patients with FHFs were included. The crude incidence rate of low-energy hip fractures in the WREC was 19.3 per 100 000 (males 14.6, females 23.4) over the study period. Population group-specific incidences were 15.1, 18.7, 19.9 and 46.6 per 100 000 for black, coloured, Indian and white population groups, respectively. The highest number of low-energy hip fractures in females occurred in the ≥85-year (19.6%) and 70 - 74-year (16.5%) age groups, with the highest number of male cases observed in the 60 - 64-year group (20.2%). The highest frequency distribution of FHFs was observed in black males aged 60 - 64 years (5.5%; n=14) and black females aged 70 - 74 years (6.3%; n=16). CONCLUSIONS: The local incidence of FHFs is higher than initially reported, but when compared with other countries remains on the lower end of spectrum. A large proportion of FHFs are occurring in young patients (<65 years). These findings warrant further investigation that may prompt the development of preventive strategies and optimal treatment programmes.

Three months in a high-volume tertiary orthopaedic trauma unit: What is a registrar worth?

BACKGROUND: South Africa has a high burden of traumatic injuries that is predominantly managed in the public healthcare system, despite the relative disparity in human resources between the public and private sectors. Because of budget and theatre time constraints, the trauma waiting list often exceeds 50 - 60 patients who need urgent and emergent surgery in high-volume orthopaedic trauma centres. This situation is exacerbated by other surgical disciplines using orthopaedic theatre time for life-threatening injuries because of lack of own theatre availability. One of the proposed solutions to this problem is outsourcing of some of the cases to private medical facilities. OBJECTIVES: To establish the volume of work done by an orthopaedic registrar during a 3-month trauma rotation, and to calculate the implant and theatre costs, as well as compare the salary of a registrar with the theoretical private surgeon fees for procedures performed by the registrar in the 3-month period. METHODS: In a retrospective study, the surgical logbook of a single registrar during a 3-month rotation, from 14 January to 14 April 2019, was reviewed. Surgeon fees were calculated for these procedures, according to current medical aid rates, without additional modifier codes being added. RESULTS: During the 3-month study period, a total of 157 surgical procedures was performed, ranging from total hip arthroplasty to debridement of septic hands. Surgeon fees amounted to ZAR186 565.10 per month ‒ double the gross salary of a registrar. Total implant costs amounted to ZAR1 272 667. Theatre costs were ZAR1 301 976 for the 3-month period. CONCLUSIONS: Although this analysis was conducted over a short period, it highlights the significant amount of trauma work done by a single individual at a high-volume tertiary orthopaedic trauma unit. With increasing budget constraints, pressure on theatre time and a growing population, cost-effective expansion of resources is needed. From this study, it appears that increasing capacity in the state sector could be cheaper than private outsourcing, although a more in-depth analysis needs to be conducted.

Single-shot, double-pulse determination of the detonation energy in nanosecond-laser ablation using the blast model.

We demonstrate a novel single-shot method to determine the detonation energy of laser-induced plasma and investigate its performance. This approach can be used in cases where there are significant shot-to-shot variations in ablation conditions, such as laser fluctuations, target inhomogeneity, or multiple filamentation with ultrashort pulses. The Sedov blast model is used to fit two time-delayed shadowgrams measured with a double-pulse laser. We find that the reconstruction of detonation parameters is insensitive to the choice of interpulse delay in double-pulse shadowgraphy. In contrast, the initial assumption of expansion dimensionality has a large impact on the reconstructed detonation energy. The method allows for a reduction in the uncertainties of blast wave energy measurements as a diagnostic technique employed in various laser ablation applications.

[Early cystectomy-patient selection and technique]. / Indikationen und Technik der Frühzystektomie.

Early radical cystectomy (RC) is a therapeutic option for non-muscle invasive bladder cancer (NMIBC). The 15-year overall survival after early RC in NMIBC patients is about 70%. Nevertheless, RC is associated with significant morbidity and mortality and therefore requires careful patient selection. The aim of the following review is to assess the selection process for early RC in NMIBC. Especially, the new European Association of Urology (EAU) risk calculator identifying NMIBC patients with very high risk for disease progression is described in detail. Furthermore, the technical aspects of the procedure are evaluated. A review of the current literature (PubMed) and national and international guideline recommendations was also conducted.

[Systemic treatment of bladder cancer]. / Blasenkarzinomsystemtherapie.

Cisplatin-based chemotherapy regimens represent the standard of care in patients with locally advanced or metastatic urothelial carcinoma of the bladder. However, many patients are ineligible for cisplatin due to comorbidities or performance status. Immunotherapy with checkpoint inhibitors (CPI) has become a well-established treatment alternative in metastatic bladder cancer. The following review discusses current literature and guideline recommendations based on two case studies, in order to provide practical know-how about therapy sequences and treatment processes.

The HELENA study: Hexvix®-TURB vs. white-light TURB followed by intravesical adjuvant chemotherapy-a prospective randomized controlled open-label multicenter non-inferiority study.

PURPOSE: Photodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix® TURB followed by immediate instillation compared to white-light TURB with immediate instillation followed by maintenance ICT. METHODS: Between 07/2010 and 12/2016, 129 patients with EORTC intermediate risk non-muscle invasive bladder cancer treated with TURB were included in this multicentre phase III study. Patients were randomized and received either white-light TURB with immediate ICT followed by maintenance ICT (n = 62, 20 mg Mitomycin weekly for 6 weeks as induction phase, afterwards 20 mg/month for 6 months) or Hexvix® TURB with immediate ICT only (n = 67, 40 mg Mitomycin). Primary study endpoint was RFS after 12 months. Hexvix® TURB was counted as non-inferior to white light alone if the upper limit of the one-sided 95% confidence interval of hazard ratio was lower than 1.676. Due to the non-inferiority design, the per-protocol population was used as the primary analysis population (n = 113) RESULTS: Median follow-up was 1.81 years. Hexvix® group showed more events (recurrence or death) than white-light group (19 vs. 10) resulting in a HR of 1.29 (upper limit of one-sided 95%-CI = 2.45; pnon-inferiority = 0.249). The ITT population yielded similar results (HR = 1.67); 3.18], pnon-inferiority = 0.493). There was no significant difference in overall survival between both groups (p = 0.257). CONCLUSION: Non-inferiority of Hexvix® TURB relative to white-light TURB with maintenance Mitomycin instillation in intermediate risk urothelial carcinoma of the bladder was not proven. Hence a higher effect of maintenance ICT is to assume compared to a Hexvix®-improved TURB only, confirming its important role in patient treatment.

Miniaturized percutaneous Nephrolithotomy without antibiotic prophylaxis: a single institution experience.

PURPOSE: To assess the feasibility of sparing routine antibiotic prophylaxis in patients without preoperative urinary tract infection (UTI) undergoing a miniaturized percutaneous nephrolithotomy (mPCNL). PATIENTS AND METHODS: A retrospective, monocentric study was conducted to evaluate the outcome of a modified perioperative antibiotic management strategy according to the principles of antibiotic stewardship (ABS). From December 2015 patients undergoing mPCNL for kidney stone with preoperative unremarkable urine culture no longer received an antibiotic prophylaxis (NoPAP). The NoPAP group was compared to mPCNL patients who received standard antibiotic prophylaxis (PAP) in the two years before. Analysis focused on postoperative complications. Logistic regression analysis was performed to identify potential risk factors. RESULTS: Postoperative fever occurred in 8% of the NoPAP and 9% of the PAP patients (p = 0.764). Clavien 1-3 complications did not differ between groups with 33% in the NoPAP and 41% in the PAP (p = 0.511). No Clavien 4-5 complications were seen. A (partial) staghorn stone (HR 5.587; p = 0.019) and an infectious stone component (HR 6.313; p = 0.003) were identified as significant risk factors for postoperative fever. By sparing routine antibiotic prophylaxis the overall antibiotic usage was reduced from 100% (PAP) to 9% (NoPAP). CONCLUSION: Patients with negative preoperative UC, a none-staghorn stone and no history of recurrent UTI or infectious stones may not need routine antibiotic prophylaxis prior to mPCNL. A prospective validation is warranted.

[Urologic cancer care during the first wave of the COVID-19 pandemic : Role of federal cancer registration in Germany]. / Uroonkologische Therapie in der ersten Welle der COVID-19-Pandemie : Was sagen uns die Krebsregister der deutschen Bundesländer?

Urologic cancer care needs to be prioritized despite multiple health care restrictions during the coronavirus disease 2019 (COVID-19) pandemic. However, therapies and procedures may be delayed and complicated. In Germany, analysis of the multiple cancer registries provides insights into the actual numbers of treated patients. We provide a review on the registration of urologic cancer care during the first wave of the COVID-19 pandemic in Germany and on potential surgical complications of urologic interventions. We found that during the year 2020 there were generally fewer registrations of newly diagnosed patients with major urologic neoplasms in a representative federal database. The number of surgical interventions in patients with renal cell carcinoma and urothelial bladder cancer decreased, whereas equal numbers of radical prostatectomies were performed when compared to the year 2019. COVID-19 may increase non-urological postoperative complications following surgical treatment of urologic malignancies; however, available data are still very limited.

[Quality assessment of radical cystectomy-opportunities, risks, challenges]. / Qualitätsparameter bei der radikalen Zystektomie ­ Chancen, Risiken, Herausforderungen.

Radical cystectomy (RC) is the standard treatment for nonmetastatic muscle-invasive urothelial carcinoma of the urinary bladder. It is associated with relevant morbidity and mortality. After RC, the 5­year overall survival rate is approximately 60%. In the context of the present work, quality parameters of RC divided into oncological/functional criteria and freedom from complications are identified and summarized. A PubMed search was performed. In addition to early criteria such as negative surgical margins, performance of pelvic lymphadenectomy, creation of a continent urinary diversion or preservation of sexual function, long-term criteria were identified such as the absence of higher-grade postoperative complications, recurrence-free survival and the preservation of health-related quality of life. The early criteria are suitable for individualized therapy planning, whereas the long-term criteria can be used for quality monitoring.

Effect of cerebral palsy and dental caries on dental plaque index, salivary parameters and oxidative stress in children and adolescents.

PURPOSE: The aim of the present study was to investigate the effect of cerebral palsy and dental caries on dental plaque index, salivary parameters and oxidative stress in children and adolescents. METHODS: Seventy children and adolescents aged 2-20 years were divided into four groups: neurotypical controls-inactive caries (NCIC; n = 19); neurotypical controls-active caries (NCAC; n = 16); cerebral palsy-inactive caries (CPIC; n = 19); and cerebral palsy-active caries (CPAC; n = 16). The visible dental plaque index was determined after drying the tooth surfaces and without any mechanical or chemical disclosing methods. Salivary pH and buffer capacity were measured 1 hour after collection using a digital pH meter. Saliva was used to evaluate oxidative status based on the levels of reactive species, lipid peroxidation and non-enzymatic antioxidants (reduced glutathione and vitamin C). RESULTS: The CPIC and CPAC groups had lower salivary pH and a higher visible dental plaque index. CP was also associated with an increase in salivary levels of markers of oxidative stress and the modulation of salivary levels of non-enzymatic antioxidants. CONCLUSION: Cerebral palsy exerts an influence on the salivary profile, oral health and oxidative stress. The individuals with CP had more acidic saliva and a higher dental plaque index, which were positively correlated with caries activity. CP was associated with high salivary levels of reactive species and lipid peroxidation, demonstrating an imbalance in salivary redox that was particularly associated with caries activity. These factors facilitate the development of oral diseases in individuals with cerebral palsy.

Filament-induced breakdown spectroscopy with structured beams.

Filament-induced ablation represents an attractive scheme for long-range material identification via optical spectroscopy. However, the delivery of laser energy to the target can be severely hindered by the stochastic nature of multiple-filamentation, ionization of ambient gas, and atmospheric turbulence. In order to mitigate some of these adverse effects, we examine the utility of beam shaping for femtosecond filament-induced breakdown spectroscopy with Gaussian and structured (Laguerre-Gaussian, Airy, and Bessel-Gaussian) beams in the nonlinear regime. Interaction of filaments with copper, zinc, and brass targets was studied by recording axially-resolved broadband emission from the filament-induced plasma. The laser-solid coupling efficacy was assessed by inferring thermodynamic parameters such as excitation temperature and electron density. While under our experimental conditions the ablation rate with Gaussian- and Laguerre-Gaussian beams is found to be similar, the Airy and Bessel-Gaussian beams offer the advantage of longitudinally extended working zones. These results provide insights into potential benefits of structuring ultrafast laser beams for standoff sensing applications.