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Reducing treatment burden is a priority for people with cystic fibrosis, whose health has benefited from using new modulators that substantially increase CFTR protein function. The SIMPLIFY study aimed to assess the effects of discontinuing nebulised hypertonic saline or dornase alfa in individuals using the CFTR modulator elexacaftor plus tezacaftor plus ivacaftor (ETI).The SIMPLIFY study included two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials at 80 participating clinics across the USA in the Cystic Fibrosis Therapeutics Development Network. We included individuals with cystic fibrosis aged 12-17 years with percent predicted FEVFrom Aug 25, 2020, to May 25, 2022, a total of 672 unique participants were screened for eligibility for one or both trials, resulting in 847 total random assignments across both trials with 594 unique participants. 370 participants were randomly assigned in the hypertonic saline trial and 477 in the dornase alfa trial. Participants across both trials had an average ppFEVIn individuals with cystic fibrosis on ETI with relatively well preserved pulmonary function, discontinuing daily hypertonic saline or dornase alfa for 6 weeks did not result in clinically meaningful differences in pulmonary function when compared with continuing treatment.

The relevance of electric drives in individual mobility is continuously increasing. This requires the use of new manufacturing processes in automotive production. In modern stators, the so-called hairpin winding is used. The production process entails rectangular copper conductors (hairpin) to be contacted by laser beam welding. To avoid temperature peaks due to resistance heating in the current-carrying wire, a high cross-sectional area in the welding seam is required. Therefore, the pore volume must be considered. This is proven by thermographic investigations of electrically stressed hairpin connections. To optimize the welding process, effects of the previous manufacturing steps and the welding parameters themselves must be taken into account. This paper analyses systematically the impact of all translational and rotational deviations on the corresponding welding quality. The tests are performed by using a disk laser. A laser spot with a focus diameter of 170 μm is compared to a statically shaped beam, capable of distributing power in core and ring beam. As an additional parameter, the influence of oxygen content in the copper wire is investigated by using electrolytic tough pitch copper (Cu-ETP) and oxygen-free copper (Cu-OF). Furthermore, the interaction between an additional cutting step before contacting and the welding path is considered. X-ray computed tomography (CT) is used to analyse the welding quality. The main finding of the studies is the significant influence of the gap and height offset between the wire ends on the resulting cross-sectional area. In addition, a low oxygen content of the copper and the use of static beam shaping reduce weld spatters, porosity and increase process stability. Three geometries in the welding path perform better in gap bridging and cause less spatters.

To present a deep learning algorithm for segmentation of geographic atrophy (GA) using en face swept-source OCT (SS-OCT) images that is accurate and reproducible for the assessment of GA growth over time.Retrospective review of images obtained as part of a prospective natural history study.Patients with GA (n = 90), patients with early or intermediate age-related macular degeneration (n = 32), and healthy controls (n = 16).An automated algorithm using scan volume data to generate 3 image inputs characterizing the main OCT features of GA-hypertransmission in subretinal pigment epithelium (sub-RPE) slab, regions of RPE loss, and loss of retinal thickness-was trained using 126 images (93 with GA and 33 without GA, from the same number of eyes) using a fivefold cross-validation method and data augmentation techniques. It was tested in an independent set of one hundred eighty 6 × 6-mmThe GA area, enlargement rate of GA area, square root of GA area, and square root of the enlargement rate of GA area measurements were calculated using the automated algorithm and compared with ground truth calculations performed by 2 manual graders. The repeatability of these measurements was determined using intraclass coefficients (ICCs).There were no significant differences in the GA areas, enlargement rates of GA area, square roots of GA area, and square roots of the enlargement rates of GA area between the graders and the automated algorithm. The algorithm showed high repeatability, with ICCs of 0.99 and 0.94 for the GA area measurements and the enlargement rates of GA area, respectively. The repeatability limit for the GA area measurements made by grader 1, grader 2, and the automated algorithm was 0.28, 0.33, and 0.92 mmWhen compared with manual methods, this proposed deep learning-based automated algorithm for GA segmentation using en face SS-OCT images was able to accurately delineate GA and produce reproducible measurements of the enlargement rates of GA.

On 10 June 2021, the Electronic Securities Act came into force in Germany, with which a great leap towards the modernization and dematerialization of German securities law was made. For the first time in Germany, the issue of securities in electronic form is possible without the need for a tangible securities certificate. With the emergence of two new types of (electronic) securities, new features were added to German (securities) law, which raise substantial questions, for instance, about the legal nature, issuance, and transference of electronic securities. By enabling electronic securities registers, the act also invites new actors into the ecosystem of the German financial market and modifies the role of already existing actors. As these registers can be based on distributed ledger technology (DLT), Germany has opened up to innovative technologies. Germany’s embrace of modern technology brings its securities law to the cutting edge (forefront) of the discipline and may create new opportunities for market participants but also pose new challenges for them as well as the regulator and supervisory authorities. The article addresses some of these issues and provides an overview of the legal framework for electronic securities. distributed ledger technology, electronic securities, Electronic Securities Act (Germany)

Migratory amphibians require movements to complete their biphasic life cycle, often across altered landscapes fragmented by roadways, which can have severe consequences on their populations. To manage this threat, transportation agencies have begun to implement exclusion fencing to separate natural areas from the roadway to prevent wildlife-vehicle collisions. Although fences are an effective conservation tool, the tendency of animals to access the road by circumventing the fence ends, known as the fence-end effect, threatens to jeopardize management efforts to reduce road associated mortality. One strategy to lessen the impacts of the fence-end effect is to construct fence-end treatments to block amphibian movement and guide the animals to safe crossing locations. By using experimental fence arenas, we examined how nine amphibian species responded to two alternative fence-end structures: horizontal v-shape and perpendicular fence-end treatments. Using a generalized linear model framework, we found both fence-end treatments to be an effective strategy to reduce the impacts of the fence-end effect, with our predictor variable, fence-end treatment, explaining most of the variation in amphibian response. Structure effectiveness also started to improve by 20% with each 7°C increase in temperature, however, this was not significant. Despite these promising findings, we also found for each additional 312 s an amphibians spent attempting to navigate around the experimental fence resulted in a 25% decline in structure effectiveness, suggesting longer fences are not an adequate protection measure to combat the fence-end effect for amphibians. In addition, Anaxyrus americanus was not found to differ in their response, performing equally well to both experimental fence-end treatments. In contrast, Rana spp., Pseudacris crucifer, and Notopthalmus viridescens showed a greater response to the horizontal v-shape fence-end treatment compared to the perpendicular fence-end treatment. Variation in response for Ambystoma spp. could not be detected due to a small sample size; however, no individuals responded positively to the perpendicular fence-end treatment. Guidelines for amphibian fences should continue to incorporate fence-end treatments into the design and implementation to mitigate for the fence-end effect, and preferably angle the fence-ends inward in the horizontal v-shape pattern with the fence ends diagonal to the road for migratory amphibians.

Coronavirus disease 2019 (COVID-19) has drastically increased the number of patients requiring extracorporeal life support. We investigate the efficacy and safety of low-dose recombinant tissue-type plasminogen activator (rtPA) injection into exhausted oxygenators to delay exchange in critically ill COVID-19 patients on veno-venous extracorporeal membrane oxygenation (V-V ECMO). Small doses of rtPA were injected directly into the draining section of a V-V ECMO circuit. We compared transmembrane pressure gradient, pump head efficiency, membrane arterial partial oxygen pressure, and membrane arterial partial carbon dioxide pressure before and after the procedure. Bleeding was compared with a matched control group of 20 COVID-19 patients on V-V ECMO receiving standard anticoagulation. Four patients received 16 oxygenator instillations with rtPA at 5, 10, or 20 mg per dose. Administration of rtPA significantly reduced transmembrane pressure gradient (Δ pm = 54.8 ± 18.1 mmHg before vs . 38.3 ± 13.3 mmHg after, p0.001) in a dose-dependent manner (Pearson's R -0.63, p = 0.023), allowing to delay oxygenator exchange, thus reducing the overall number of consumed oxygenators. rtPA increased blood flow efficiency η (1.20 ± 0.28 ml/revolution before vs . 1.24 ± 0.27 ml/r, p = 0.002). Lysis did not affect membrane blood gases or systemic coagulation. Minor bleeding occurred in 2 of 4 patients (50%) receiving oxygenator lysis as well as 19 of 20 control patients (95%). Lysis of ECMO oxygenators effectively delays oxygenator exchange, if exchange is indicated by an increase in transmembrane pressure gradient. Application of lysis did not result in higher bleeding incidences compared with anticoagulated patients on V-V ECMO for COVID-19.

Zusammenfassung Hintergrund Atypische chondrogene Tumoren (ACT) der kurzen und langen Röhrenknochen, früher als Chondrosarkome G1 bezeichnet, verhalten sich lokal aggressiv, haben aber ein sehr geringes Metastasierungspotenzial. Die Abgrenzung zu benignen Enchondromen ist aus klinischer, radiologischer und histopathologischer Sicht komplex. Ziel der Arbeit Epidemiologie, Diagnostik und Therapie von ACT unter besonderer Berücksichtigung der Abgrenzung zu Enchondromen werden dargestellt. Material und Methoden Es erfolgt die Zusammenfassung der internationalen Fachliteratur zu ACT und Enchondromen. Ergebnisse Die Inzidenz von Enchondromen, und mehr noch von ACT, ist über die Jahre angestiegen, was auf häufiger werdende Diagnostik hinweist. Im Gegensatz zu Enchondromen können ACT mit Schmerzen verbunden sein und radiologische Zeichen aggressiven Wachstums, wie tiefes endosteales Scalloping, aufweisen. Die alleinige Biopsie zur Differenzierung zwischen Enchondromen und ACT ist oft nicht hilfreich, da aufgrund der punktuellen Probegewebsentnahme ein „sampling error“ resultieren kann. Die definitive operative Therapie von ACT der langen und kurzen Röhrenknochen hat sich über die letzten Jahre gewandelt, weg von einer radikalen Tumorentfernung hin zu intraläsionaler Kürettage. Ein Zuwarten ist bei radiologischem Verdacht auf das Vorliegen eines Enchondroms regelmäßigen Verlaufskontrollen mittels Magnetresonanztomographie (MRT) möglich. Schlussfolgerungen ACT weisen im Gegensatz zu Enchondromen radiologische Zeichen eines aggressiven Wachstums auf. Die heutzutage bevorzugte Therapie besteht aus einer intraläsionalen Kürettage. Sowohl Diagnostik als auch Therapie und Nachsorge von kartilaginären Tumoren sollten an einem spezialisierten Tumorzentrum erfolgen.

2020 hat die EU-Kommission zwei Vorschläge für die Regulierung der Digitalwirtschaft vorgelegt: den Digital Services Act (DSA)1 und den Digital Marktes Act (DMA). Diese beiden Verordnungen bilden die zwei Säulen des großen Digitalpakets, welches eine bis dahin beispiellose Regulierung des digitalen Raums bezweckt. Gemeinsam verfolgen sie das Ziel, ein angemessenes Gleichgewicht zu der Macht großer Internetplattformbetreiber zu schaffen, indem einerseits illegale Inhalte auf diesen Plattformen eingeschränkt werden und andererseits der Wettbewerb zwischen den einzelnen Plattformen reguliert wird. Nach der Zustimmung des Europäischen Parlaments zu Verordnungen am 5. Juli 2022 ist es nur noch eine Frage der Zeit, wann die Vorschriften in Kraft treten werden. Der nachfolgende Beitrag soll einen Überblick über die neuen Regelungen verschaffen und auch die Auswirkungen auf die deutsche Rechtslage thematisieren.

ObjectiveSchizophrenia is associated with widespread brain-morphological alterations, believed to be shaped by the underlying connectome architecture. This study tests whether large-scale structural reorganization in schizophrenia relates to normative network architecture, in particular regional centrality/hubness and connectivity patterns. We examine network effects in schizophrenia across different disease stages, and transdiagnostically explore consistency of such relationships in patients with bipolar and major depressive disorder.MethodsWe studied anatomical MRI scans from 2,439 adults with schizophrenia and 2,867 healthy controls from 26 ENIGMA sites. Case-control patterns of structural alterations were evaluated against two network susceptibility models: 1) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; 2) epicenter models, which identify regions whose typical connectivity profile most closely resembles the disease-related morphological alteration patterns. Both susceptibility models were tested across schizophrenia disease stages and compared to meta-analytic bipolar and major depressive disorder case-control maps.ResultsIn schizophrenia, regional gray matter reductions co-localized with interconnected hubs, in both the functional (r=0.58, pspinspin=0.01). Epicenters were identified in temporo-paralimbic regions, extending to frontal areas. We found unique epicenters for first-episode and early stages, and a shift from occipital to temporal-frontal epicenters in chronic stages. Transdiagnostic comparisons revealed shared epicenters in schizophrenia and bipolar, but not major depressive disorders.ConclusionsCortical reorganization over the course of schizophrenia closely reflects brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters. The observed overlapping epicenters for schizophrenia and bipolar disorder furthermore suggest shared pathophysiological processes within the schizophrenia-bipolar-spectrum.

We improve upon previous oblivious sketching and turnstile streaming results for $\ell_1$ and logistic regression, giving a much smaller sketching dimension achieving $O(1)$-approximation and yielding an efficient optimization problem in the sketch space. Namely, we achieve for any constant $c>0$ a sketching dimension of $\tilde{O}(d^{1+c})$ for $\ell_1$ regression and $\tilde{O}(\mu d^{1+c})$ for logistic regression, where $\mu$ is a standard measure that captures the complexity of compressing the data. For $\ell_1$-regression our sketching dimension is near-linear and improves previous work which either required $\Omega(\log d)$-approximation with this sketching dimension, or required a larger $\operatorname{poly}(d)$ number of rows. Similarly, for logistic regression previous work had worse $\operatorname{poly}(\mu d)$ factors in its sketching dimension. We also give a tradeoff that yields a $1+\varepsilon$ approximation in input sparsity time by increasing the total size to $(d\log(n)/\varepsilon)^{O(1/\varepsilon)}$ for $\ell_1$ and to $(\mu d\log(n)/\varepsilon)^{O(1/\varepsilon)}$ for logistic regression. Finally, we show that our sketch can be extended to approximate a regularized version of logistic regression where the data-dependent regularizer corresponds to the variance of the individual logistic losses., Comment: ICLR 2023

RATIONALE: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. OBJECTIVES: To test differing durations of intravenous antimicrobials for CF exacerbations. METHODS: STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7–10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days’ total antimicrobial duration; all others were randomized to 14 or 21 days’ duration. MEASUREMENTS AND MAIN RESULTS: The primary outcome was percent predicted FEV(1) (ppFEV(1)) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV(1) change was 12.8 and 13.4 for 10 and 14 days, respectively, a ‒0.65 difference (95% CI [‒3.3 to 2.0]), excluding the predefined noninferiority margin. The 21- and 14-day arms experienced 3.3 and 3.4 mean ppFEV(1) changes, a difference of ‒0.10 (‒1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive. CONCLUSIONS: Among adults with CF with early treatment improvement during exacerbation, ppFEV(1) after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days. Clinical trial registered with www.clinicaltrials.gov (NCT02781610).

Background Antibiotic-loaded polymethylmethacrylate (PMMA) bone cement spacers provide high local antibiotic concentrations and patient mobility during the interim period of two-stage revision for periprosthetic joint infection (PJI). This study compares mechanical characteristics of six dual antibiotic-loaded bone cement (dALBC) preparations made from three different PMMA bone cements. The study`s main objective was to determine the effect of time and antibiotic concentration on mechanical strength of dALBCs frequently used for spacer fabrication in the setting of two-stage revision for PJI. Methods A total of 84 dual antibiotic-loaded bone cement specimens made of either Copal spacem, Copal G + V or Palacos R + G were fabricated. Each specimen contained 0.5 g of gentamicin and either 2 g (low concentration) or 4 g (high concentration) of vancomycin powder per 40 g bone cement. The bending strength was determined at two different timepoints, 24 h and six weeks after spacer fabrication, using the four-point bending test. Results Preparations made from Copal G + V showed the highest bending strength after incubation for 24 h with a mean of 57.6 ± 1.2 MPa (low concentration) and 50.4 ± 4.4 MPa (high concentration). After incubation for six weeks the bending strength had decreased in all six preparations and Palacos R + G showed the highest bending strength in the high concentration group (39.4 ± 1.6 MPa). All low concentration preparations showed superior mechanical strength compared to their high concentration (4 g of vancomycin) counterpart. This difference was statistically significant for Copal spacem and Copal G + V (both p p = 0.09). Conclusions This study suggests that mechanical strength of antibiotic-loaded PMMA bone cement critically decreases even over the short time period of six weeks, which is the recommended interim period in the setting of two-stage revision. This potentially results in an increased risk for PMMA spacer fracture at the end of the interim period and especially in patients with prolonged interim periods. Finally, we conclude that intraoperative addition of 4 g of vancomycin powder per 40 g of gentamicin-premixed Palacos R + G (Group D) is mechanically the preparation of choice if a dual antibiotic-loaded bone cement spacer with high antibiotic concentrations and good stability is warranted. In any case the written and signed informed consent including the off-label use of custom-made antibiotic-loaded PMMA bone cement spacers must be obtained before surgery.

Short bowel syndrome (SBS) is a severe, life-threatening condition and one of the leading causes of intestinal failure in children. Here we were interested in changes in muscle layers and especially in the myenteric plexus of the enteric nervous system (ENS) of the small bowel in the context of intestinal adaptation. Twelve rats underwent a massive resection of the small intestine to induce an SBS. Sham laparotomy without small bowel transection was performed in 10 rats. Two weeks after surgery, the remaining jejunum and ileum were harvested and studied. Samples of human small bowel were obtained from patients who underwent resection of small bowel segments due to a medical indication. Morphological changes in the muscle layers and the expression of nestin, a marker for neuronal plasticity, were studied. Following a SBS, muscle tissue increases significantly in both parts of the small bowel, jejunum, and ileum. The leading pathophysiological mechanism of these changes is hypertrophy. Additionally, we observed an increased nestin expression in the myenteric plexus in the remaining bowel of SBS. Our human data also showed that in patients with SBS, the proportion of stem cells in the myenteric plexus have risen by more than two times. Our findings suggest that the ENS is tightly connected with changes in intestinal muscle layers and is critically involved in the intestinal adaptation process to SBS.

Low flow extracorporeal carbon dioxide removal (ECCO2R) is a promising approach to correct hypercapnic lung failure, facilitate lung protective ventilation in acute respiratory distress syndrome and to possibly prevent the application of invasive ventilation. However, the predominant availability of adult membrane lungs (MLs) at most intensive care units are burdens for low flow ECCO2R that intends to reduce cannula size and promote the mobility of the patients. Herein, in a mock setup, we combine the idea of a low flow ECCO2R and the use of adult MLs by installing a recirculation channel into the circuit and comparing the new setup to an already clinically established setup, "the Homburg lung." Furthermore, to make stronger reference to hypercapnic respiratory failure, we investigate the influence of CO2 partial pressure in blood on CO2 removal of both setups. A linear association between CO2 partial pressure in blood and CO2 removal of the ML in the physiologically relevant range was observed. To understand this linear dependence, a simplified mathematical model was proposed. Our new ECCO2R mock setup combines the idea of a low flow ECCO2R and an adult size ML. It shows a reasonable alternative to the current available low flow setups based on pediatric MLs.

Introduction The Coronavirus Disease 2019 (COVID-19) pandemic highlighted the importance of understanding patients’ goals, values, and medical care preferences given the high morbidity and mortality. We aimed to examine rates of advance care planning (ACP) documentation along with hospital course differences in the absence or presence of ACP among hospitalized patients with COVID-19. Methods This retrospective cohort study was performed at a single tertiary academic medical center. All adults admitted between March 1, 2020, and June 30, 2020, for COVID-19 were included. Demographics, ACP documentation rates, presence of ACP forms, palliative care consultation (PCC) rates, code status, and hospital outcome data were collected. Data were analyzed with multivariable analysis to identify predictors of ACP documentation. Results Among 356 patients (mean age 60.0, 153 (43%) female), 97 (27.2%) had documented ACP and 20 (5.6%) had completed ACP forms. In patients with documented ACP, 52.4% (n = 55) de-escalated care to do-not-resuscitate (DNR)-limited or comfort measures. PCC occurred rarely (Conclusions This study found low ACP documentation and PCC rates in patients admitted for COVID-19. PCC and completion of ACP were associated with higher rates of care de-escalation. These results support the need for pro-active ACP and PCC for patients admitted for serious illnesses, like COVID-19, to improve goal-informed care.

As a consequence of the continued Covid-19 lockdown in Germany, in-hospital teaching for medical students was impossible. While lectures and other theoretical training were relatively easily converted into online sessions using platforms such as Moodle, Zoom and Microsoft Teams, this was not the case for practical skills and clinical interventions, such as bronchoscopy or colonoscopy. This study describes a workaround that was implemented at the Saarland University Hospital utilizing virtual reality equipment to convey the impressions of shadowing clinical procedures to the students without physical presence. To achieve this, 3D 180° videos of key clinical interventions of various internal medicine specialities were recorded, cut, and censored. The videos were uploaded to the e-learning YouTube channel of our institution and shared with the students via the private share function. The students could choose whether to use a VR-viewer to watch the videos immersively or to watch them without a viewer on a screen non-immersively. At the end of the course after 1 week, the students completed a questionnaire anonymously focusing on learning-success regarding the presented topics, a self-assessment, and an evaluation of the course. A total of 27 students watched the videos with a VR-Viewer and 74 watched non-immersively. Although the VR-viewer group self-assessed their expertise higher, there was no significant difference between the two groups in the learning-success test score. However, students in the VR-viewer group rated the learning atmosphere, comprehensibility, and overall recommendation of the course significantly higher. They also agreed significantly more to the statement, that they gained a better conception of the presented procedures, and that virtual reality might be an appropriate tool for online teaching. Video-assisted teaching facilitates learning and might be a valuable add-on to conventional teaching.

Zusammenfassung Die gegenwärtige Niedrigzinsphase hat der Lückenfüllung bei wegen Verstoßes gegen das AGB-Recht unwirksamen Zinsanpassungskauseln in Sparverträgen zu einer enormen Praxisbedeutung in rechtlicher wie wirtschaftlicher Hinsicht verholfen; diese zeigt sich nicht zuletzt in zwei Musterfeststellungsklagen, einer anstehenden Befassung des BGH und jüngst einer öffentlichen Intervention der BaFin. Der nachfolgende Beitrag beleuchtet daher am Beispiel des Sparkassen-Prämiensparens die bisherige BGH-Judikatur. Dabei wird ein Korrekturbedarf aufgezeigt, der gerade auch aus einem Fortschreiten der höchstrichterlichen Rechtsprechung in teleologisch verwandten Bereichen – konkret: Bearbeitungsentgelte bei Darlehensverträgen, Negativzinsen und Anpassung langfristiger Energieversorgungsverträge – folgt.

In late 2020, during the second wave of COVID-19 in Germany, we started using the MobyBox, which is a novel fully pneumatically driven ECMO device, on a regular basis to meet the increasing demand for ECMO therapy. In this case series, we performed a retrospective chart review of seven patients with severe COVID-19-related acute respiratory distress syndrome (ARDS) requiring veno-venous (vv)-ECMO support with the MobyBox. During ECMO treatments we have observed no disadvantages in comparison to conventional ECMO systems. There were no system failures or adverse events directly attributable to the MobyBox system. Our data support that providing vv-ECMO with the MobyBox device is safe and feasible. Furthermore, our findings suggest that the MobyBox device might represent an advantage in terms of biocompatibility. Therefore, more data on this issue is needed to better understand how the pneumatically driven pump affects cellular blood components.

Extracorporeal membrane oxygenation (ECMO) has become an important therapeutic approach in the COVID-19 pandemic. The development and research in this field strongly relies on animal models; however, efforts are being made to find alternatives. In this work, we present a new mock circuit for ECMO that allows measurements of the oxygen transfer rate of a membrane lung at full ECMO blood flow. The mock utilizes a large reservoir of heparinized porcine blood to measure the oxygen transfer rate of the membrane lung in a single passage. The oxygen transfer rate is calculated from blood flow, hemoglobin value, venous saturation, and post-membrane arterial oxygen pressure. Before the next measuring sequence, the blood is regenerated to a venous condition with a sweep gas of nitrogen and carbon dioxide. The presented mock was applied to investigate the effect of a recirculation loop on the oxygen transfer rate of an ECMO setup. The recirculation loop caused a significant increase in post-membrane arterial oxygen pressure (paO2). The effect was strongest for the highest recirculation flow. This was attributed to a smaller boundary layer on gas fibers due to the increased blood velocity. However, the increase in paO2 did not translate to significant increases in the oxygen transfer rate because of the minor significance of physically dissolved oxygen for gas transfer. In conclusion, our results regarding a new ECMO mock setup demonstrate that recirculation loops can improve ECMO performance, but not enough to be clinically relevant.

Hyperfine interactions 243(1), 16 (2022). doi:10.1007/s10751-022-01798-y, Within this work, we report the results of nuclear inelastic scattering experiments of the low-spin phase of the iron(II) mononuclear SCO complex Fe[HBpz$_3$]$_2$ and density functional theory based calculations performed on a model molecule of the complex. We show that the calculated partial density of vibrational states based on the structure of a single iron(II) center which is linked by three pyrazole rings to borat is in good accordance with the experimentally obtained $^{57}$Fe-pDOS and assign the molecular vibrations to the prominent optical phonons., Published by Springer Science + Business Media B.V, Dordrecht [u.a.]

EnglishOn July 9, 2018, the 4th Amendment Directive to the 4th Money Laundering Directive (the so-called 5th Money Laundering Directive) came into force. It brings changes in the area of virtualcurrencies and continues the 4th Money Laundering Directive in the area of the transparency regis-ter. The European legislature thereby aims to achieve a complete coverage of legal arrangementsunder company law in order to effectively and comprehensively curb money laundering throughoutthe European Union. The German legislature has transposed the 5th Money Laundering Directiveby the Act Implementing the Amending Directive to the Fourth EU Money Laundering Directiveof 12 December 20192. When applying the latest Directive, problems arise in the context of determi-ning the beneficial owner of the trust who has a notification and registration obligation under the5th Money Laundering Directive. In regard to the scope of application, it needs to be determinedwhich legal arrangements have a structure or functions similar to trusts. Moreover, this article focu-ses on the interaction with the Ordinance on the Formulation of the List of Shareholders (Sharehol-der List Ordinance) in the area of limited liability companies (GmbH). DeutschAm 9. Juli 2018 ist mit zahlreichen Neuerungen die Anderungsrichtlinie zur 4. Geldwaschericht-linie–konsolidiert die sog. 5. Geldwascherichtlinie–in Kraft getreten. Diese bringt Anderungen imBereich der virtuellen Wahrungen mit sich und schreibt die 4. Geldwascherichtlinie im Bereich desTransparenzregisters fort. Der Richtliniengeber will eine moglichst luckenlose Erfassung von gesell-schaftsrechtlich gepragten Rechtsvereinbarungen erreichen, um Geldwasche effektiv, aber auch fla-chendeckend und einheitlich in der ganzen Europaischen Union einzudammen. Durch das Gesetzzur Umsetzung der Anderungsrichtlinie zur Vierten EU-Geldwascherichtlinie vom 12.12.20191setzte der deutsche Gesetzgeber die 5. Geldwascherichtlinie um. Probleme bereiten weiterhin die Einordnung der melde- und registerpflichtigen„wirtschaftlichen Eigentumer“sowie insbesonderedie Einordnung von Trusts und vergleichbaren Gebilden. Der Beitrag geht zudem auf das Zusam-menspiel mit der Gesellschafterlistenverordnung von 2018 ein

Die Behandlung von primar malignen Knochentumoren erfolgt interdisziplinar und individuell angepasst an den Patienten. Heutzutage ist eine extremitatenerhaltende extralasionale Tumorresektion meistens moglich und die anschliesende Defektuberbruckung wird entweder uber die Implantation von modularen Tumormegaprothesen oder uber biologische Rekonstruktionsverfahren durchgefuhrt. Hierbei sind spezielle operationstypische und sekundare Komplikationen zu beachten. Indikation und Erlauterung von verschiedenen biologische Rekonstruktionsverfahren und Aufzeigen der speziellen peri- und postoperativen Komplikationen. Es erfolgte eine adaptierte Literaturrecherche und das Einbringen von eigenen Therapieerfahrungen und Fallbeispielen zur Prasentation von biologischen Rekonstruktionen und deren Komplikationsmanagement. Bei biologischen Rekonstruktionen werden Autografts, Allografts oder eine Kombination aus Auto- und Allografts verwendet. Eine Stabilisierung erfolgt uber Schrauben- und Plattenosteosynthesen. Zu den haufigsten sekundaren Komplikationen gehoren die Pseudarthrose, die Interponatfraktur, die Transplantatnekrose und sekundare Fehlstellungen. In ausgewahlten Fallen, insbesondere an der oberen Extremitat und bei dia- oder metaphysarer Tumorlage, ist die biologische Rekonstruktion nach extralasionaler Tumorresektion die chirurgische Therapie der Wahl. Die Rate an langfristigen Revisionseingriffen ist im Vergleich zu modularen Tumormegaprothesen deutlich geringer. Die Anwendung biologischer Rekonstruktionen und das Behandeln der spezifischen Komplikationen obliegt spezialisierten Zentren fur muskuloskelettale Onkochirurgie oder Tumororthopadie.

The comprehensive “PJI-TNM classification” for the description of periprosthetic joint infections (PJI) was introduced in 2020. Its structure is based on the well-known oncological TNM classification to appreciate the complexity, severity, and diversity of PJIs. The main goal of this study is to implement the new PJI-TNM classification into the clinical setting to determine its therapeutic and prognostic value and suggest modifications to further improve the classification for clinical routine use. A retrospective cohort study was conducted at our institution between 2017 and 2020. A total of 80 consecutive patients treated with a two-stage revision for periprosthetic knee joint infection were included. We retrospectively assessed correlations between patients’ preoperative PJI-TNM classification and their therapy and outcome and identified several statistically significant correlations for both classifications, the original and our modified version. We have demonstrated that both classifications provide reliable predictions already at the time of diagnosis regarding the invasiveness of surgery (duration of surgery, blood and bone loss during surgery), likelihood of reimplantation, and patient mortality during the first 12 months after diagnosis. Orthopedic surgeons can use the classification system preoperatively as an objective and comprehensive tool for therapeutic decisions and patient information (informed consent). In the future, comparisons between different treatment options for truly similar preoperative baseline situations can be obtained for the first time. Clinicians and researchers should be familiar with the new PJI-TNM classification and start implementing it into their routine practice. Our adjusted and simplified version (“PJI-pTNM”) might be a more convenient alternative for the clinical setting.

Background The concomitant occurrence of the symptoms intravascular hypovolemia, peripheral edema and hemodynamic instability is typically named Capillary Leak Syndrome (CLS) and often occurs in surgical critical ill patients. However, neither a unitary definition nor standardized diagnostic criteria exist so far. We aimed to investigate common characteristics of this phenomenon with a subsequent scoring system, determining whether CLS contributes to mortality. Methods We conducted this single-center, observational, multidisciplinary, prospective trial in two separately run surgical ICUs of a tertiary academic medical center. 200 surgical patients admitted to the ICU and 30 healthy volunteers were included. Patients were clinically diagnosed as CLS or No-CLS group (each N = 100) according to the grade of edema, intravascular hypovolemia, hemodynamic instability, and positive fluid balance by two independent attending physicians with > 10 years of experience in ICU. We performed daily measurements with non-invasive body impedance electrical analysis, ultrasound and analysis of serum biomarkers to generate objective diagnostic criteria. Receiver operating characteristics were used, while we developed machine learning models to increase diagnostic specifications for our scoring model. Results The 30-day mortility was increased among CLS patients (12 vs. 1%, P = 0.002), while showing higher SOFA-scores. Extracellular water was increased in patients with CLS with higher echogenicity of subcutaneous tissue [29(24–31) vs. 19(16–21), P P P Conclusions Diagnosis of CLS in critically ill patients is feasible by objective, non-invasive parameters using the CLS-Score. A simplified two-parameter diagnostic approach can enhance clinical utility. CLS contributes to mortality and should, therefore, classified as an independent entity. Trial Registration: German Clinical Trials Registry (DRKS No. 00012713), Date of registration 10/05/2017, www.drks.de Graphical Abstract

The progress of scientific research and technology development greatly depends upon effective imaging solutions for characterizing the properties and behaviors of materials. Revealing details of microstructure, ideally in 3D, is a critical part of this understanding, whether the goal is to develop and confirm models that describe material properties and behaviors or simply to visualize structural details. ZEISS offers 3D X-ray microscopes (XRM): advanced imaging solutions that have removed major hurdles for three-dimensional imaging by achieving high contrast and submicron resolution imaging even for relatively large samples. These groundbreaking advances in non-destructive, three-dimensional (3D) imaging empower a broad range of technical disciplines.

Introduction Two-stage revision remains the gold standard treatment for most chronically infected and complex total hip arthroplasty infections. To improve patient outcome and reduce complication rates, we have developed a novel custom-made articulating hip spacer technique and present our short-term results. Materials and methods Between November 2017 and November 2019, 27 patients (mean age 70 years) underwent two-stage revision for periprosthetic joint infection of the hip using the articulating spacer design described here. We retrospectively analyzed spacer-related complications as well as rates for complication, infection control, and implant survivorship after final reimplantation. Furthermore, we prospectively collected patient-reported health-related quality of life (HRQoL) scores prior to spacer implantation, with the spacer and after reimplantation of the new prosthesis. Results An additional round of spacer exchange was performed in two patients (8.3%), persistent wound discharge was the reason in both cases. We had one (4.2%) spacer-related mechanical complication, a dislocation that was treated with closed reduction. After reimplantation, infection control was achieved in 96% with an implant survivorship of 92% after a mean follow-up time of 19 (range 7–32, SD 7.2) months. While the scores for VR-12 MCS, VAS hip pain and patient-reported overall satisfaction significantly improved after first stage surgery, the scores for WOMAC, UCLA and VR-12 PCS significantly improved after second stage surgery. Conclusions Our two-stage approach for periprosthetic joint infection shows high infection eradication and implant survivorship rates at short-term follow-up. Spacer-related complication rates were low, and we achieved high patient satisfaction rates and low pain levels already during the spacer period. To further simplify comparison between different spacer designs, we propose a new hip spacer classification system.

Ninety per cent of the Spanish Republicans who were deported by the Nazis during the Second World War ended up in the concentration camp of Mauthausen in Austria. Sara Brenneis’s focus on this part...

The enteric nervous system (ENS) controls gastrointestinal key functions and is mainly characterized by two ganglionated plexus located in the gut wall: the myenteric plexus and the submucous plexus. The ENS harbors a high number and diversity of enteric neurons and glial cells, which generate neuronal circuitry to regulate intestinal physiology. In the past few years, the pivotal role of enteric neurons in the underlying mechanism of several intestinal diseases was revealed. Intestinal diseases are associated with neuronal death that could in turn compromise intestinal functionality. Enteric neurogenesis and regeneration is therefore a crucial aspect within the ENS and could be revealed not only during embryogenesis and early postnatal periods, but also in the adulthood. Enteric glia and/or enteric neural precursor/progenitor cells differentiate into enteric neurons, both under homeostatic and pathologic conditions beyond the perinatal period. The unique role of the intestinal microbiota and serotonin signaling in postnatal and adult neurogenesis has been shown by several studies in health and disease. In this review article, we will mainly focus on different recent studies, which advanced the concept of postnatal and adult ENS neurogenesis. Moreover, we will discuss the key factors and underlying mechanisms, which promote enteric neurogenesis. Finally, we will shortly describe neurogenesis of transplanted enteric neural progenitor cells. Anat Rec, 302:1345-1353, 2019. © 2019 Wiley Periodicals, Inc.

Since several years, the enteric nervous system (ENS) is getting more and more in the focus of gastrointestinal research. While the main interest was credited for years to the enteric neurons and their functional properties, less attention has been paid on the enteric glial cells (EGCs). Although the similarity of EGCs to central nervous system (CNS) astrocytes has been demonstrated a long time ago, EGCs were investigated in more detail only recently. Similar to the CNS, there is not "the" EGC, but also a broad range of diversity. Based on morphology and protein expression, such as glial fibrillary acidic protein (GFAP), S100, or Proteolipid-protein-1 (PLP1), several distinct glial types can be differentiated. Their heterogeneity in morphology, localization, and transcription as well as interaction with surrounding cells indicate versatile functional properties of these cells for gut function in health and disease. Although NG2 is found in a subset of CNS glial cells, it did not colocalize with the glial marker S100 or GFAP in the ENS. Instead, it in part colocalize with PDGFRα, as it does in the CNS, which do stain fibroblast-like cells in the gastrointestinal tract. Moreover, there seem to be species dependent differences. While GFAP is always found in the rodent ENS, this is completely different for the human gut. Only the compromised human ENS shows a significant amount of GFAP-positive glial cells. So, in general we can conclude that the EGC population is species specific and as complex as CNS glia. Anat Rec, 302:1333-1344, 2019. © 2019 Wiley Periodicals, Inc.