[Voiding dysfunction after TVT: A 20-year experience TVT-placement under local anesthesia and sedation]. / Troubles mictionnelles après pose de TVT : 20 ans d'expérience de pose sous diazanalgésie et anesthésie locale.

BACKGROUND: Trans-vaginal tape has become the gold standard for the cure of urinary stress incontinence, but post-operative voiding dysfunction is frequently reported. The purpose of this study is to assess the incidence of voiding dysfunction, dysuria, chronic urinary retention, and necessity of reoperation after retropubic TVT placement under local anaesthesia and sedation. MATERIAL AND METHOD: We perform a retrospective study of a cohort of patient treated with the placement of a retropubic TVT under local anaesthesia and sedation between 1999 and 2019 for a SUI. Post-operative voiding dysfunction and necessity of reoperation were reviewed to access the principal aim of this study. RESULTS: Three hundred and two patients who met the eligibility criteria were included in the study. At 3 months, the dysuria rate and chronic urinary retention rate was 4.3% and 1%. At 12 months it was 2.6% and 0.3% respectively. The 12-month sling section rate was 1% and long-term self-catherization rate was 0.3%. The objective cure rate was 93% and subjective cure was 92%. CONCLUSION: TVT placement under local anaesthesia and sedation resulted in few voiding dysfunctions at medium/long-term, necessity of re-operation for refractory obstructive disorder and well functional results. Even if these results support more frequent use of this type of anaesthesia, it would be interesting to be able to follow them in a prospective study to conclude. LEVEL OF EVIDENCE: 4.

Side-effect management of chimeric antigen receptor (CAR) T-cell therapy.

Chimeric antigen receptor (CAR) T cells directed against the B-cell marker CD19 are currently changing the landscape for treatment of patients with refractory and/or relapsed B-cell malignancies. Due to the nature of CAR T cells as living drugs, they display a unique toxicity profile. As CAR T-cell therapy is extending towards other diseases and being more broadly employed in hematology and oncology, optimal management strategies of side-effects associated with CAR T-cell therapy are of high relevance. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias constitute challenges in the treatment of patients with CAR T cells. This review summarizes the current understanding of CAR T-cell toxicity and its management.

Disorder-Free Localization in an Interacting 2D Lattice Gauge Theory.

Disorder-free localization has been recently introduced as a mechanism for ergodicity breaking in low-dimensional homogeneous lattice gauge theories caused by local constraints imposed by gauge invariance. We show that also genuinely interacting systems in two spatial dimensions can become nonergodic as a consequence of this mechanism. This result is all the more surprising since the conventional many-body localization is conjectured to be unstable in two dimensions; hence the gauge invariance represents an alternative robust localization mechanism surviving in higher dimensions in the presence of interactions. Specifically, we demonstrate nonergodic behavior in the quantum link model by obtaining a bound on the localization-delocalization transition through a classical correlated percolation problem implying a fragmentation of Hilbert space on the nonergodic side of the transition. We study the quantum dynamics in this system by introducing the method of "variational classical networks," an efficient and perturbatively controlled representation of the wave function in terms of a network of classical spins akin to artificial neural networks. We identify a distinguishing dynamical signature by studying the propagation of line defects, yielding different light cone structures in the localized and ergodic phases, respectively. The methods we introduce in this work can be applied to any lattice gauge theory with finite-dimensional local Hilbert spaces irrespective of spatial dimensionality.

IgG antibody response against Plasmodium falciparum aminopeptidase 1 antigen in Gabonese children living in Makokou and Franceville.

The search for novel chemical classes of anti-malarial compounds to cope with the current state of chemoresistance of malaria parasites has led to the identification of Plasmodium falciparum aminopeptidase 1 (PfA-M1) as a new therapeutic target. PfA-M1, known to be involved in the hemoglobin digestion cascade which helps to provide most of the amino acids necessary to the parasite's metabolism, is currently considered as a promising target for anti-malarial chemotherapy. However, its immunogenic properties have not yet been tested in the Gabonese population. In Gabon, the prevalence of malaria remains three times higher in semi-urban areas (60·12%) than in urban areas (17·06%). We show that malaria-specific PfA-M1 antibodies are present in children and increase with the level of infection. Children living in semi-urban areas have higher anti-PfA-M1 antibody titers (0·14 ± 0·02 AU) than those living in urban areas (0·08 ± 0·02 AU, P = 0·03), and their antibody titers increase with age (P < 0·0001). Moreover, anti-PfA-M1 antibody titers decrease in children with hyperparasitemia (0·027 ± 0·055 AU) but they remain high in children with low parasite density (0·21 ± 0·034 AU, P = 0·034). In conclusion, our results suggest that malaria-specific PfA-M1 antibodies may play an important role in the immune response of the host against P. falciparum in Gabonese children. Further studies on the role of PfA-M1 during anemia are needed.

[VOTE versus ACLTE: comparison of two snoring noise classifications using machine learning methods]. / VOTE versus ACLTE: Vergleich zweier Schnarchgeräuschklassifikationen mit Methoden des maschinellen Lernens.

BACKGROUND: Acoustic snoring sound analysis is a noninvasive method for diagnosis of the mechanical mechanisms causing snoring that can be performed during natural sleep. The objective of this work is development and evaluation of classification schemes for snoring sounds that can provide meaningful diagnostic support. MATERIALS AND METHODS: Based on two annotated snoring noise databases with different classifications (s-VOTE with four classes versus ACLTE with five classes), identically structured machine classification systems were trained. The feature extractor openSMILE was used in combination with a linear support vector machine for classification. RESULTS: With an unweighted average recall (UAR) of 55.4% for the s­VOTE model and 49.1% for the ACLTE, the results are at a similar level. In both models, the best differentiation is achieved for epiglottic snoring, while velar and oropharyngeal snoring are more often confused. CONCLUSION: Automated acoustic methods can help diagnose sleep-disordered breathing. A reason for the restricted recognition performance is the limited size of the training datasets.

Primary T cells for mRNA-mediated immunotoxin delivery.

Immune cells become increasingly attractive as delivery system for immunotoxins in cancer therapy to reduce the intrinsic toxicity and severe side effects of chimeric protein toxins. In this study, we investigated the potential of human primary T cells to deliver a secreted immunotoxin through transient messenger RNA (mRNA) transfection. The chimeric protein toxin was directed toward the neovasculature of cancer cells by fusing a truncated version of Pseudomonas exotoxin A (PE38) to human vascular endothelial growth factor (VEGF) and to the single chain variable fragment (scFv) of anti-Her2/neu. Protocols for the transient transfection of human embryonic kidney cells (HEK293) as well as activated primary human T cells were established. Transient transfection with mRNA coding for the immunotoxins e23-PE38, VEGF-PE38 and its attenuated variant VEGF-PE38D yielded efficient expression and secretion. Mass spectrometry analysis endorsed that a fraction of VEGF-PE38D was properly translocated into the endoplasmic reticulum. Furthermore, cytotoxic activity of immunotoxin secreting T cells toward cancer cells was confirmed in co-culture with ovarian adenocarcinoma cells in the presence of a bispecific antibody (bsAb), highlighting the potential of primary T cells for mRNA-mediated immunotoxin delivery.

Intra- and inter-tooth variation in strontium isotope ratios from prehistoric seals by laser ablation multi-collector inductively coupled plasma mass spectrometry.

RATIONALE: Strontium isotope ratios (87 Sr/86 Sr) in modern-day marine environments are considered to be homogeneous (~0.7092). However, in the Baltic Sea, the Sr ratios are controlled by mixing seawater and continental drainage from major rivers discharging into the Baltic. This pilot study explores if variations in Sr can be detected in marine mammals from archaeological sites in the Baltic Sea. METHODS: 87 Sr/86 Sr ratios were measured in tooth enamel from three seal species by laser ablation multi-collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS). The method enables micro-sampling of solid materials. This is the first time that the method has been applied to marine samples from archaeological collections. RESULTS: The analyses showed inter-tooth 87 Sr/86 Sr variation suggesting that different ratios can be detected in different regions of the Baltic Sea. Furthermore, the intra-tooth variation suggests possible different geographic origin or seasonal movement of seals within different regions in the Baltic Sea through their lifetime. CONCLUSIONS: The method was successfully applied to archaeological marine samples showing that: (1) the 87 Sr/86 Sr ratio in marine environments is not uniform, (2) 87 Sr/86 Sr differences might reflect differences in ecology and life history of different seal species, and (3) archaeological mobility studies based on 87 Sr/86 Sr ratios in humans should therefore be evaluated together with diet reconstruction.

The effect of different training exercises on the performance outcome on the da Vinci Skills Simulator.

BACKGROUND: Increasing usage of robotic surgery presents surgeons with the question of how to acquire the special skills required. This study aimed to analyze the effect of different exercises on their performance outcomes. METHODS: This prospective study was conducted on the da Vinci Skills Simulator from December 2014 till August 2015. Sixty robotic novices were included and randomized to three groups of 20 participants each. Each group performed three different exercises with comparable difficulty levels. The exercises were performed three times in a row within two training sessions, with an interval of 1 week in between. On the final training day, two new exercises were added and a questionnaire was completed. Technical metrics of performance (overall score, time to complete, economy of motion, instrument collisions, excessive instrument force, instruments out of view, master work space range, drops, missed targets, misapplied energy time, blood loss and broken vessels) were recorded by the simulator software for further analysis. RESULTS: Training with different exercises led to comparable results in performance metrics for the final exercises among the three groups. A significant skills gain was recorded between the first and last exercises, with improved performance in overall score, time to complete and economy of motion for all exercises in all three groups. CONCLUSIONS: As training with different exercises led to comparable results in robotic training, the type of exercise seems to play a minor role in the outcome. For a robotic training curriculum, it might be important to choose exercises with comparable difficulty levels. In addition, it seems to be advantageous to limit the duration of the training to maintain the concentration throughout the entire session.

Developments in spontaneous and coherent Raman scattering microscopic imaging for biomedical applications.

First, the potential role of Raman-based techniques in biomedicine is introduced. Second, an overview about the instrumentation for spontaneous and coherent Raman scattering microscopic imaging is given with a focus of recent developments. Third, imaging strategies are summarized including sequential registration with laser scanning microscopes, line imaging and global or wide-field imaging. Finally, examples of biomedical applications are presented in the context of single cells, laser tweezers, tissue sections, biopsies and whole animals.

Coexpression of human perforin improves yeast-mediated delivery of DNA and mRNA to mammalian antigen-presenting cells.

Previous studies underlined the capacity of recombinant yeast as efficient vehicle for the targeted delivery of functional nucleic acids as well as proteinaceous antigens to mammalian antigen-presenting cells (APCs). To improve this yeast-mediated cargo transport into APCs, we investigated the impact of coexpression of the human membrane-perturbing protein perforin in comparison with bacterial listeriolysin O (LLO) on the yeast-based delivery of DNA, mRNA and proteins to mammalian APCs. In contrast to LLO, a cholesterol-dependent pore-forming toxin of Listeria, intracellular expression of human perforin in Saccharomyces cerevisiae had no impact on yeast cell viability, while its coexpression significantly increased translocation of ovalbumin and subsequent activation of ovalbumin-specific T lymphocytes. Likewise, perforin improved the expression of the model antigen enhanced green fluorescent protein after yeast-mediated DNA and mRNA delivery, whereas LLO was only able to enhance DNA delivery. Taken together, our data show that human perforin, besides bacterial hemolysins, represents a promising means to improve the yeast-mediated delivery of functional nucleic acids and proteins to mammalian APCs.

Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA.

A record fuel hot-spot pressure P_{hs}=56±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition [A. Bose et al., Phys. Rev. E 93, 011201(R) (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.

Mobilization of autologous and allogeneic peripheral blood stem cells for transplantation in haematological malignancies using biosimilar G-CSF.

BACKGROUND AND OBJECTIVES: Biosimilars of the granulocyte colony stimulating factor (G-CSF) filgrastim were approved by the European Medicines Agency (EMA) for registered indications of the originator G-CSF, including prevention and treatment of neutropenia, as well as mobilization of peripheral blood stem cells in 2008. Nevertheless, there is still an ongoing debate regarding the quality, efficacy and safety of biosimilar G-CSF. MATERIALS AND METHODS: This article is a meta-analysis of clinical studies on the use of biosimilar G-CSF for mobilization and transplantation of haematopoietic stem cells as available in public databases. All data sets were weighted for the number of patients and parameters and then subjected to statistical meta-analysis employing the Mann-Whitney U-test followed by the Hodges-Lehmann estimator to assess differences between biosimilar and originator G-SCF. RESULTS: A total of 1892 individuals, mostly with haematological malignancies but also including 351 healthy donors have been successfully mobilized for autologous or allogeneic stem cell transplantation using biosimilar G-CSF (Zarzio(TM) : 1239 individuals; Ratiograstim(TM) /Tevagrastim(TM) : 653 individuals). A total of 740 patients with multiple myeloma, 491 with non-Hodgkin's lymphoma (NHL), 150 with Hodgkin's lymphoma (HL) and other diseases are included in this meta-analysis, as well as 161 siblings and 190 volunteer unrelated donors. For biosimilar and originator G-CSF, bioequivalence was observed for the yield of CD34+ stem cells as well as for the engraftment of the transplants. CONCLUSION: Biosimilar G-CSF has equivalent effects and safety as originator G-CSF.

The effect of neuropeptide FF in the amygdala kindling model.

OBJECTIVE: Neuropeptide FF (NPFF) and its receptors (NPFF1 R and NPFF2 R) are differentially distributed throughout the central nervous system. NPFF reduces cortical excitability in rats when administered intracerebroventricularly (i.c.v.), and both NPFF and NPFF1 R antagonists attenuate pilocarpine-induced limbic seizures. In this study, our aim was to determine whether NPFF exerts anticonvulsant or anti-epileptogenic effects in the rat amygdala kindling model for temporal lobe seizures. METHODS: Male Wistar rats were implanted with a recording/stimulation electrode in the right amygdala and a cannula in the left lateral ventricle. In a first group of animals, the afterdischarge threshold (ADT) was determined after a single i.c.v. infusion of saline (n = 8) or NPFF (1 nmol/h for 2 h; n = 10). Subsequently, daily infusion of saline (n = 8) or NPFF (1 nmol/h for 2 h; i.c.v.; n = 9) was performed, followed by a kindling stimulus (ADT+200 µA). Afterdischarge duration and seizure severity were evaluated after every kindling stimulus. A second group of rats (n = 7) were fully kindled, and the effect of saline or a high dose of NPFF (10 nmol/h for 2 h, i.c.v.) on ADT and the generalized seizure threshold (GST) was subsequently determined. RESULTS: In naive rats, NPFF significantly increased the ADT compared to control (435 ± 72 µA vs 131 ± 23 µA [P < 0.05]). When rats underwent daily stimulations above the ADT, NPFF did not delay or prevent kindling acquisition. Furthermore, a high dose of NPFF did not alter ADT or GST in fully kindled rats. CONCLUSIONS: I.c.v. administration of NPFF reduced excitability in the amygdala in naive, but not in fully kindled rats, and had no effect on kindling acquisition.

Active Brownian motion of emulsion droplets: Coarsening dynamics at the interface and rotational diffusion.

A micron-sized droplet of bromine water immersed in a surfactant-laden oil phase can swim (S. Thutupalli, R. Seemann, S. Herminghaus, New J. Phys. 13 073021 (2011). The bromine reacts with the surfactant at the droplet interface and generates a surfactant mixture. It can spontaneously phase-separate due to solutocapillary Marangoni flow, which propels the droplet. We model the system by a diffusion-advection-reaction equation for the mixture order parameter at the interface including thermal noise and couple it to fluid flow. Going beyond previous work, we illustrate the coarsening dynamics of the surfactant mixture towards phase separation in the axisymmetric swimming state. Coarsening proceeds in two steps: an initially slow growth of domain size followed by a nearly ballistic regime. On larger time scales thermal fluctuations in the local surfactant composition initiates random changes in the swimming direction and the droplet performs a persistent random walk, as observed in experiments. Numerical solutions show that the rotational correlation time scales with the square of the inverse noise strength. We confirm this scaling by a perturbation theory for the fluctuations in the mixture order parameter and thereby identify the active emulsion droplet as an active Brownian particle.

Molecular self-healing mechanisms between C60-fullerene and anthracene unveiled by Raman and two-dimensional correlation spectroscopy.

The self-healing polymer P(LMA-co-MeAMMA) crosslinked with C60-fullerene has been studied by FT-Raman spectroscopy in combination with two-dimensional (2D) correlation analysis and density functional theory calculations. To unveil the molecular changes during the self-healing process mediated by the Diels-Alder equilibrium between 10-methyl-9-anthracenyl groups and C60-fullerene different anthracene-C60-fullerene adducts have been synthesized and characterized by time-, concentration- and temperature-dependent FT-Raman measurements. The self-healing process could be monitored via the C60-fullerene vibrations at 270, 432 and 1469 cm(-1). Furthermore, the detailed analysis of the concentration-dependent FT-Raman spectra point towards the formation of anthracene-C60-fullerene adducts with an unusual high amount of anthracene bound to C60-fullerene in the polymer film, while the 2D correlation analysis of the temperature-dependent Raman spectra suggests a stepwise dissociation of anthracene-C60-fullerene adducts, which are responsible for the self-healing of the polymer.

Individuals with impaired glucose tolerance demonstrate normal cardiac sympathetic innervation using I-123 mIBG scintigraphy.

BACKGROUND: Impaired glucose tolerance (IGT) is associated with an increased risk of type 2 diabetes (T2DM) and cardiovascular disease. Some but not all studies have reported cardiac autonomic dysfunction in subjects with IGT and there is only one direct study of cardiac innervation in subjects with IGT. The purpose of this study was to assess global and regional cardiac sympathetic innervation and cardiac autonomic function in individuals with IGT. METHODS AND RESULTS: We undertook (123)I-mIBG scintigraphy and cardiac autonomic function in 15 subjects with IGT and 15 age and sex-matched healthy controls. Early heart to mediastinum ratio (HMR) (1.71 ± 0.17 vs 1.67 ± 0.13, P = .49), late HMR (1.73 ± 0.18 vs 1.73 ± 0.16, P = .97) and washout rate (WR) (18.6 ± 4.2 vs 19.1 ± 7.6%, P = .84), did not differ between subjects with IGT and control subjects. More detailed regional analysis revealed reduced tracer uptake at the apex, base and inferior wall in all subjects and the anterior wall in a minority of subjects. There were no differences in total score (56.6 ± 4.0 vs 53.3 ± 8.4, P = .193), modified score (48.5 ± 3.3 vs 46.2 ± 6.0, P = .215), anterior wall score (10.2 ± 1.3 vs 10.1 ± 1.6, P = .898), inferior wall score (8.9 ± 1.9 vs 7.7 ± 2.6, P = .163), basal score (18.7 ± 1.9 vs 18.2 ± 3.3, P = .636) and tests of cardiac autonomic function between the groups. CONCLUSION: Global and regional measures of MIBG uptake and washout as well as cardiac autonomic function did not differ between subjects with IGT and healthy controls.

Two-dimensional Raman correlation spectroscopy reveals molecular structural changes during temperature-induced self-healing in polymers based on the Diels-Alder reaction.

The thermally healable polymer P(LMA-co-FMA-co-MIMA) has been studied by temperature-dependent FT-Raman spectroscopy, two-dimensional Raman correlation analysis and density functional theory (DFT) calculations. To the best of our knowledge this study reports for the first time on the investigation of a self-healing polymer by means of two-dimensional correlation techniques. The synchronous correlation spectrum reveals that the spectrally overlapping C[double bond, length as m-dash]C stretching vibrations at 1501, 1575, 1585 and 1600 cm(-1) are perfect marker bands to monitor the healing process which is based on a Diels-Alder reaction of furan and maleimide. The comparison between experimental and calculated Raman spectra as well as their correlation spectra showed a good agreement between experiment and theory. The data presented within this study nicely demonstrate that Raman correlation analysis combined with a band assignment based on DFT calculations presents a powerful tool to study the healing process of self-healing polymers.

Factors associated with conversion from laparoscopic to open colectomy using the National Surgical Quality Improvement Program (NSQIP) database.

AIM: Conversion rates from laparoscopic to open colectomy and associated factors are traditionally reported in clinical trials or reviews of outcomes from experienced institutions. Indications and selection criteria for laparoscopic colectomy may be more narrowly defined in these circumstances. With the increased adoption of laparoscopy, conversion rates using national data need to be closely examined. The purpose of this study was to use data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) to identify factors associated with conversion of laparoscopic to open colectomy at a national scale in the United States. METHOD: The ACS-NSQIP Participant Use Data Files for 2006-2011 were used to identify patients who had undergone laparoscopic colectomy. Converted cases were identified using open colectomy as the primary procedure and laparoscopic colectomy as 'other procedure'. Preoperative variables were identified and statistics were calculated using sas version 9.3. Logistic regression was used to model the multivariate relationship between patient variables and conversion status. RESULTS: Laparoscopy was successfully performed in 41 585 patients, of whom 2508 (5.8%) required conversion to an open procedure. On univariate analysis the following factors were significant: age, body mass index (BMI), American Society of Anesthesiologists (ASA) class, presence of diabetes, smoking, chronic obstructive pulmonary disease, ascites, stroke, weight loss and chemotherapy (P < 0.05). The following factors remained significant on multivariate analysis: age, BMI, ASA class, smoking, ascites and weight loss. CONCLUSION: Multiple significant factors for conversion from laparoscopic to open colectomy were identified. A novel finding was the increased risk of conversion for underweight patients. As laparoscopic colectomy is become increasingly utilized, factors predictive of conversion to open procedures should be sought via large national cohorts.

Narrow-line magneto-optical trap for dysprosium atoms.

We present our technique to create a magneto-optical trap (MOT) for dysprosium atoms using the narrow-line cooling transition at 626 nm to achieve suitable conditions for direct loading into an optical dipole trap. The MOT is loaded from an atomic beam via a Zeeman slower using the strongest atomic transition at 421 nm. With this combination of two cooling transitions we can trap up to 2.0·10(8) atoms at temperatures down to 6 µK. This cooling approach is simpler than present work with ultracold dysprosium and provides similar starting conditions for a transfer to an optical dipole trap.

Transition from spherical to irregular dispersed phase in water/oil emulsions.

Bulk properties of transparent and dilute water in paraffin oil emulsions stabilized with sodium dodecyl sulfate (SDS) are analyzed by optical scanning tomography. Each scanning shot of the considered emulsions has a precision of 1 µm. The influence of aluminum oxide nanoparticles in the structure of the water droplets is investigated. Depending on concentrations of SDS and nanoparticles, a transition occurs in their shape that changes from spherical to polymorphous. This transition is controlled by the SDS/alumina nanoparticles mixing ratio and is described using an identification procedure of the topology of the gray level contours extracted from each images. The transition occurs for a critical mixing ratio of Rcrit ≈ 0.05 which does not significantly depend on temperature and electrolyte concentration. This structural change seems to be a general feature when emulsifying dispersions and most probably involves both interfacial and bulk phenomena.