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Background: Point of care devices for performing targeted coagulation substitution in bleeding patients have become increasingly important in recent years. New on the market is the Quantra® from HemoSonics (LC, Charlottesville, VA, US). It uses sonorheometry, a sonic estimation of elasticity via resonance (SEER), a novel ultrasound-based technology that measures viscoelastic properties of whole blood. Several studies have already shown the comparability with devices already established on the market such as the ROTEM® (TEM International GmbH, Munich, Germany).
Objective: In contrast to existing studies, the planned study will be the first prospective interventional study using the new Quantra® system in a cardiac surgical patient cohort. The aim is to investigate the non-inferiority between an already existing coagulation algorithm, based on ROTEM®/Multiplate®, and a new algorithm based on the Quantra®, for the treatment of coagulopathic cardiac surgical patients.
Methods: The study is divided into two phases. In an initial observation phase, whole blood samples of 20 patients will be analyzed using both ROTEM®/Multiplate® and Quantra® obtained at three defined points of time (prior to surgery, after completion of cardiopulmonary bypass, on arrival in the intensive care unit). The obtained threshold values will be used to create an algorithm for hemotherapy. In a second intervention phase, the new algorithm will be tested against an algorithm used routineously for years at our department for non-inferiority.
Results: The main objective of the examination is the cumulative loss of blood within 24 hours after surgery. Statistical calculations based on literature and in-house data suggest that the new algorithm is not inferior if the difference in cumulative blood loss is < 150ml/24 h.
Conclusions: Because of the comparability of the Quantra® sonorheometry system with ROTEM® rotational thromboelastometric measurement methods, the existing hemotherapy treatment algorithm can be adapted to the Quantra device with a proof of non-inferiority. Clinical Trial: International Registered Report Identifier (IRRID): clinicaltrials.gov: NCT03902275
We present novel measurements of five short-lived brominated source gases (CH2Br2, CHBr3, CH2ClBr, CHCl2Br and CHClBr2) obtained using a gas chromatograph-mass spectrometer system on board the High Altitude and Long Range Research Aircraft (HALO). The instrument is extremely sensitive due to the use of chemical ionisation, allowing detection limits in the lower parts per quadrillion (10-15) range. Data from three campaigns using the HALO aircraft are presented, where the Upper Troposphere/Lower Stratosphere (UTLS) of the Northern Hemisphere mid to high latitudes were sampled during winter and during late summer to early fall. We show that an observed decrease with altitude in the stratosphere is consistent with the relative lifetimes of the different compounds. Distributions of the five source gases and total organic bromine just below the tropopause shows an increase in mixing ratio with latitude, in particular during polar winter. This increase in mixing ratio is explained by increasing lifetimes at higher latitudes during winter. As the mixing ratio at the extratropical tropopause are generally higher than those derived for the tropical tropopause, extratropical troposphere-to-stratosphere transport will result in elevated levels of organic bromine in comparison to air transported over the tropical tropopause. The observations are compared to model estimates using different emission scenarios. A scenario which has emissions most strongly concentrated to low latitudes cannot reproduce the observed latitudinal distributions and will tend to overestimate bromine input through the tropical tropopause from CH2Br2 and CHBr3. Consequently, the scenario also overestimates the amount of brominated organic gases in the stratosphere. The two scenarios with the highest overall emissions of CH2Br2 tend to overestimate mixing ratios at the tropical tropopause but are in much better agreement with extratropical tropopause values, showing that not only total emissions but also latitudinal distributions in the emissions are of importance. While an increase in tropopause values with latitude is reproduced with all emission scenarios during winter, the simulated extratropical tropopause values are on average lower than the observations during late summer to fall. We show that a good knowledge of the latitudinal distribution of tropopause mixing ratios and of the fractional contributions of tropical and extratropical air is needed to derive stratospheric inorganic bromine in the lowermost stratosphere from observations. Depending on the underlying emission scenario, differences of a factor 2 in reactive bromine derived from observations and model outputs are found for the lowermost stratosphere, based on source gas injection. We conclude that a good representation of the contributions of different source regions is required in models for a robust assessment of the role of short-lived halogen source gases on ozone depletion in the UTLS.
Simple Summary: Pseudoprogression detection in glioblastoma patients remains a challenging task. Although pseudoprogression has only a moderate prevalence of 10–30% following first-line treatment of glioblastoma patients, it bears critical implications for affected patients. Non-invasive techniques, such as amino acid PET imaging using the tracer O-(2-[18F]-fluoroethyl)-L-tyrosine (FET), expose features that have been shown to provide useful information to distinguish tumor progression from pseudoprogression. The usefulness of FET-PET in IDH-wildtype glioblastoma exclusively, however, has not been investigated so far. Recently, machine learning (ML) algorithms have been shown to offer great potential particularly when multiparametric data is available. In this preliminary study, a Linear Discriminant Analysis-based ML algorithm was deployed in a cohort of newly diagnosed IDH-wildtype glioblastoma patients (n = 44) and demonstrated a significantly better diagnostic performance than conventional ROC analysis. This preliminary study is the first to assess the performance of ML in FET-PET for diagnosing pseudoprogression exclusively in IDH-wildtype glioblastoma and demonstrates its potential.
Abstract: Pseudoprogression (PSP) detection in glioblastoma remains challenging and has important clinical implications. We investigated the potential of machine learning (ML) in improving the performance of PET using O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) for differentiation of tumor progression from PSP in IDH-wildtype glioblastoma. We retrospectively evaluated the PET data of patients with newly diagnosed IDH-wildtype glioblastoma following chemoradiation. Contrast-enhanced MRI suspected PSP/TP and all patients underwent subsequently an additional dynamic FET-PET scan. The modified Response Assessment in Neuro-Oncology (RANO) criteria served to diagnose PSP. We trained a Linear Discriminant Analysis (LDA)-based classifier using FET-PET derived features on a hold-out validation set. The results of the ML model were compared with a conventional FET-PET analysis using the receiver-operating-characteristic (ROC) curve. Of the 44 patients included in this preliminary study, 14 patients were diagnosed with PSP. The mean (TBRmean) and maximum tumor-to-brain ratios (TBRmax) were significantly higher in the TP group as compared to the PSP group (p = 0.014 and p = 0.033, respectively). The area under the ROC curve (AUC) for TBRmax and TBRmean was 0.68 and 0.74, respectively. Using the LDA-based algorithm, the AUC (0.93) was significantly higher than the AUC for TBRmax. This preliminary study shows that in IDH-wildtype glioblastoma, ML-based PSP detection leads to better diagnostic performance.
Accurate multidimensional localization of isolated fluorescent emitters is a time consuming process in single-molecule based super-resolution microscopy. We demonstrate a functional method for real-time reconstruction with automatic feedback control, without compromising the localization accuracy. Compatible with high frame rates of EM-CCD cameras, it relies on a wavelet segmentation algorithm, together with a mix of CPU/GPU implementation. A combination with Gaussian fitting allows direct access to 3D localization. Automatic feedback control ensures optimal molecule density throughout the acquisition process. With this method, we significantly improve the efficiency and feasibility of localization-based super-resolution microscopy.
Feedforward inhibition and synaptic scaling are important adaptive processes that control the total input a neuron can receive from its afferents. While often studied in isolation, the two have been reported to co-occur in various brain regions. The functional implications of their interactions remain unclear, however. Based on a probabilistic modeling approach, we show here that fast feedforward inhibition and synaptic scaling interact synergistically during unsupervised learning. In technical terms, we model the input to a neural circuit using a normalized mixture model with Poisson noise. We demonstrate analytically and numerically that, in the presence of lateral inhibition introducing competition between different neurons, Hebbian plasticity and synaptic scaling approximate the optimal maximum likelihood solutions for this model. Our results suggest that, beyond its conventional use as a mechanism to remove undesired pattern variations, input normalization can make typical neural interaction and learning rules optimal on the stimulus subspace defined through feedforward inhibition. Furthermore, learning within this subspace is more efficient in practice, as it helps avoid locally optimal solutions. Our results suggest a close connection between feedforward inhibition and synaptic scaling which may have important functional implications for general cortical processing.
Background: Patient Blood Management (PBM) is a systematic quality improving clinical model to reduce anemia and avoid transfusions in all kinds of clinical settings. Here, we investigated the potential of PBM in oncologic surgery and hypothesized that PBM improves 2-year overall survival (OS).
Methods: Retrospective analysis of patients 2 years before and after PBM implementation. The primary endpoint was OS at 2 years after surgery. We identified a sample size of 824 to detect a 10% improvement in survival in the PBM group.
Results: The analysis comprised of 836 patients that underwent oncologic surgery, 389 before and 447 after PBM, was implemented. Patients in the PBM+ presented significantly more frequent with normal hemoglobin values before surgery than PBM− (56.6 vs. 35.7%; p < 0.001). The number of transfusions was significantly reduced from 5.5 ± 11.1 to 3.0 ± 6.9 units/patient (p < 0.001); moreover, the percentage of patients being transfused during the clinic stay was significantly reduced from 62.4 to 40.9% (p < 0.001). Two-year OS was significantly better in the PBM+ and increased from 67.0 to 80.1% (p = 0.001). A normal hemoglobin value (> 12 g/dl in female and > 13 g/dl in male) before surgery (HR 0.43, 95% CI 0.29–0.65, p < 0.001) was the only independent predictive factor positively affecting survival.
Conclusions: PBM is a quality improvement tool that is associated with better mid-term surgical oncologic outcome. The root cause for improvement is the increase of patients entering surgery with normal hemoglobin values.
Ovaj se rad bavi položajem zanaglasnica u kontekstu njegove obrade u nastavi hrvatskoga jezika u srednjim školama. S obzirom na to da pisani korpus pokazuje velika odstupanja od klasičnoga tumačenja Wackernagelova pravila (Peti-Stantić 2007), htjele smo ovu pojavu istražiti u kontekstu odnosa nastavnika hrvatskoga jezika prema poučavanju pravila o položaju zanaglasnica. Dosadašnji radovi u ovome području pokazuju različite težnje. Dok većina suvremenih gramatika (Babić i dr. 2007, Barić i dr. 2005, Težak i Babić 1994) staje u prilog prozodijskome tumačenju Wackernagelova pravila, prema kojemu se zanaglasnica uvrštava iza prve naglašene riječi u rečenici, neki suvremeni jezikoslovci (Peti-Stantić 2002, 2002a, 2006, 2007) zagovaraju sintaktičko tumačenje ovoga pravila u hrvatskome jeziku, prema kojemu se zanaglasnice smještaju iza prve naglašene sintaktičke jedinice. Ovi drugi svoje tvrdnje podupiru neskladom između propisanih pravila i stvarne uporabe, tj. korpusa, a naše se istraživanje bavi sličnim problemom – odnosom između načelnih i praktičnih elemenata poučavanja ovoga pravila. Ispitivanje predodžbe nastavnika o pravilu o položaju zanaglasnica u hrvatskome jeziku te prakse poučavanja toga pravila otkrilo je da nastavnici daju prednost prozodijskom tumačenju Wackernagelova pravila, no nisu skloni ispravljanju učenika koji ga drugačije primjenjuju.
Background: In March 2020, the COVID-19 outbreak led to the declaration of a pandemic. The accompanying restrictions on public life caused a change in the training routines of athletes worldwide. The present study aimed to investigate the effects of a 13-week supervised home training program on physical performance, sleep quality, and health-related quality of life in professional youth soccer players during the first COVID-19 lockdown in Germany.
Methods: Eight professional soccer players (age range 16–19; height: 1.81 ± 0.07 m; body weight: 72.05 ± 6.96 kg) from a Bundesliga team in Germany participated in this study. During the lockdown, they trained 5–6 days per week with home-based training plans and were monitored via tracking apps and video training. To determine the effects of home training, measurements were taken before (March 2020) and after (June 2020) the home training period. Bioelectrical impedance analysis was used to determine body composition, and an isokinetic strength test and a treadmill step test, including lactate measurements, were used to measure physical performance. Two questionnaires were responded to in order to assess health-related quality of life [Short-Form 36 Health Survey (SF-36)] and sleep quality (Pittsburgh Sleep Quality Index).
Results: When comparing measurements before and after the home training period, we observed significant increases in the following variables: body weight (72.05 ± 6.96 kg vs. 73.50 ± 6.68 kg, p = 0.034), fat mass (11.99 ± 3.13 % vs. 13.98 ± 3.92 %, p = 0.030), body mass index (22.04 ± 0.85 kg/m2 vs. 22.49 ± 0.92 kg/m2, p = 0.049), and mental health component summary score (MCS) of the questionnaire SF-36 (53.95 ± 3.47 vs. 58.33 ± 4.50, p = 0.044). Scores on the general health (77.88 ± 14.56 vs. 89.75 ± 13.76, p = 0.025) and mental health (81.50 ± 9.30 vs. 90.00 ± 11.71, p = 0.018) subscales of the SF-36 also increased significantly.
Conclusion: The COVID-19 lockdown led to an increase in body composition parameters and showed an improvement in the MCS and scores on the general and mental health subscales of the SF-36. Physical performance and sleep quality could be maintained during the home training period. These observations may help trainers for future training planning during longer interruptions in soccer training.
Introduction: Our aim was to highlight the characteristics of pediatric Meckel's diverticulum with a special focus on its complications.
Methods: We report a group of seven patients with Meckel's diverticulum and its resection from the Department of Pediatric Surgery between 2012 and 2017. We reviewed all patient records, clinical presentation, and intraoperative findings. The diagnosis was confirmed by surgery and pathology. For a systematic literature review, we used PubMed, Medline and Google Scholar search engines to locate articles containing terms such as Meckel's diverticulum, children, pediatric, complications and symptomatic. We included article reporting on case series in English and German on pediatric patients only.
Results: All included patients (n = 7) were symptomatic. Some patients showed isolated symptoms, and others presented with a combination of symptoms that consisted of abdominal pain, bloody stool or vomiting. The median age of our seven cases was 3.5 years, including 4 male and 3 female patients. Intestinal obstruction was the most common complication; it was seen in 5 out of 7 patients (intussusception in 4 cases, volvulus in 1 case). Ectopic gastric tissue was identified in 3 cases, and inclusion of pancreatic tissue was observed in 1 case. The literature review identified 8 articles for a total of 641 patients aged between 1 day and 17 years and a male:female ratio of 2.6:1. From this group, 528 patients showed clinical symptoms related to Meckel's diverticulum. The most common symptom was abdominal pain and bloody stool. The most common surgical finding in symptomatic patients was intestinal obstruction (41%), followed by intestinal hemorrhage (34%). Complications such as perforation (10%) and diverticulitis (13%) were less frequently reported. Heterotopic tissue was confirmed on histopathology in 53% of all patients enclosing gastric, pancreatic, and both gastric and pancreatic mucosae. In one case, large intestine tissue could be found. Overall, one death was reported.
Conclusion: The presented case series and literature review found similar clinical presentations and complications of Meckel's diverticulum in children. Intestinal obstruction and bleeding are more frequent than inflammation in pediatric Meckel's diverticulum. Bowel obstruction is the leading cause for complicated Meckel's diverticulum in patients younger than 12 years.
We report a case of a 2-day-old neonate with bilious vomiting and abdominal distension. A small bowel obstruction with ileal perforation due to a misplaced clamping of the umbilical cord was apparent before laparotomy. This complication was a sequala after clamping the cord too close to the abdominal wall in a case where there was a hernia into the cord with intestinal content. A herniation of abdominal contents due to an omphalocele minor or a hernia must be taken into consideration during the inspection of the umbilical cord before clamping.
Introduction: Endovascular aortic repair, if technically feasible, is the treatment of choice for patients with a contained ruptured aortic aneurysm who are unfit for open surgery. Case presentation: We report the case of an 80-year-old Caucasian man who presented with an unusually configured, symptomatic infrarenal aortic aneurysm. His aneurysm showed an erosion of the fourth lumbar vertebra and a severely arteriosclerotic pelvic axis. A high thigh amputation of his right leg had been performed 15 months previously. On his right side, occlusion of his external iliac artery, common femoral artery, and deep femoral artery had occurred. His aneurysm was treated by a left-sided aortomonoiliac stent graft without femorofemoral revascularization, resulting in occlusions of both internal iliac arteries. No ischemic symptoms appeared, although perfusion of his right side was maintained only over epigastric collaterals. Conclusions: The placement of aortomonoiliac stent grafts for endovascular treatment of infrarenal aortic aneurysms without contralateral revascularization is a feasible treatment option in isolated cases. In this report, access problems and revascularization options in endovascular aneurysm repair are discussed.
STADT FÜR ALLE! steht in großen rosa Buchstaben auf der Fassade des verlassenen Amerika Instituts. Das mit Graffiti überzogene Gebäude ist den meisten Bewohner:innen des Frankfurter Westends eher ein Dorn im Auge. Was aber vielen Frankfurter:innen nicht mehr bekannt sein dürfte, ist die enorme politische Aufladung, die der Bau als öffentlicher Schauplatz in sich birgt. Ein historischer Rückblick.
Artificial splitting of a non‐ribosomal peptide synthetase by inserting natural docking domains
(2020)
The interaction in multisubunit non‐ribosomal peptide synthetases (NRPSs) is mediated by docking domains that ensure the correct subunit‐to‐subunit interaction. We introduced natural docking domains into the three‐module xefoampeptide synthetase (XfpS) to create two to three artificial NRPS XfpS subunits. The enzymatic performance of the split biosynthesis was measured by absolute quantification of the products by HPLC‐ESI‐MS. The connecting role of the docking domains was probed by deleting integral parts of them. The peptide production data was compared to soluble protein amounts of the NRPS using SDS‐PAGE. Reduced peptide synthesis was not a result of reduced soluble NRPS concentration but a consequence of the deletion of vital docking domain parts. Splitting the xefoampeptide biosynthesis polypeptide by introducing docking domains was feasible and resulted in higher amounts of product in one of the two tested split‐module cases compared to the full‐length wild‐type enzyme.
Weiden (Salix spp., Salicaceae) gehören zu den typischen Gehölzarten der Flussauen in Mitteleuropa. Viele Arten dieser Gattung haben ähnliche Eigenschaften (life history traits) und Strategien bei der Besiedelung frisch entstandener Rohböden. In Auenhabitaten kommen deshalb häufig mehrere Weidenarten gemeinsam vor und treten deshalb miteinander in Konkurrenz. In der vorliegenden Arbeit wurde untersucht, ob interspezifische phänologische Unterschiede in der Zeit der Samenausbreitung in Verbindung mit wechselnden Pegelständen des Flusses dazu führen, dass sich koexistierende Weidenarten räumlich differenziert ansiedeln und so die interspezifische Konkurrenz zwischen den Weiden reduziert wird. Auf frisch sedimentierten Auenböden an der Rodach und am Oberlauf des Mains (Oberfranken, Nordostbayern) wurde der Einfluss der Zeit des Samenfluges und der Schwankung der Pegelstände auf die räumliche Verteilung der Keimlinge von Salix fragilis s.l., S. purpurea, S. triandra und S. viminalis auf zwei Aufnahmeflächen untersucht. Ergänzt wurden diese Freilandstudien durch Untersuchungen zur Keimfähigkeit von Samen dieser Arten unter verschiedenen Bedingungen im Labor. Die Keimfähigkeit der Samen betrug unmittelbar nach ihrer Reife mindestens 80-100%. Bei trockener Lagerung (20 °C) erlosch die Keimfähigkeit von S. fragilis und S. triandra nach 4 Wochen, bei S. purpurea und S. viminalis nach spätestens 6 Wochen. Die Samen aller Arten können auch im Wasser keimen.
Anhand des Zeitraumes der Samenausbreitung lassen sich die im Freiland untersuchten Weiden in eine früh (S. purpurea und S. viminalis) und in eine spät fruktifizierende Gruppe (S. fragilis s.l. und S. triandra) unterscheiden. Die Keimlinge aller Arten traten jeweils nur in einem schmalen Saum entlang des Ufers auf. Die Pegel von Main und Rodach an den Untersuchungsflächen waren während des Samenfluges der früh fruktifizierenden Gruppe höher als während des Samenfluges der spät fruktifizierenden Gruppe. Keimlinge beider Gruppen etablierten sich deshalb in unterschiedlichen Reliefbereichen und in unterschiedlicher Entfernung zum Ufer: bezogen auf einen sommerlichen Tiefstand des Wassers waren die Keimlinge der früh fruktifizierenden Arten (S. purpurea und S. viminalis) höher auf der Kiesbank und weiter vom Ufer entfernt als die der spät fruktifizierenden Arten (S. fragilis s.l. und S. triandra). Phänologische Unterschiede ermöglichen somit in Kombination mit sinkenden Wasserständen eine räumlich differenzierte Verteilung von Keimlingen verschiedener Weidenarten auf engstem Raum. Dies trägt zur Verringerung interspezifischer Konkurrenz und zu einer hohen Diversität von Salix-Arten in alluvialen Habitaten bei.
The article presents two surgical texts written in Strasbourg around 1500. The author of the first text is Hieronymus Brunschwig, and the second is by Hans Gersdorff. Although Gersdorff's book is more like a teaching text, a set of normative instructions in the manner of (legally binding) municipal records, it was published under the name 'Feldbuch'. The publisher may have chosen this designation under the influence of texts named Feldbücher, originating in the Moravian-Silesian region, which were originally intended as manuals for barber surgeons working on battlefields
Asplenium adiantum-nigrum (Aspleniaceae, Pteridophyta) breitet sich seit ca. 20 Jahren von seinem Arealrand im Rheinisch-Westfälischen Mittelgebirge ins Tiefland hinein aus. Die bislang in Nordrhein-Westfalen collin-montan verbreitete Farnart besaß dort bis zum Ende der 1980er Jahre eine stabile Verbreitungsgrenze mit Vorkommen an Felsstandorten des Ruhrtals (südliches Ruhrgebiet). Ausbreitungsgeschichte, Populationsentwicklung, Gesellschaftsanschluss sowie die neuen Wuchsorte werden dargestellt. Insgesamt konnten seit 1990 25 Neufunde, 16 davon im planaren Raum des Niederrheinischen Tieflandes und der Westfälischen Bucht, mit einer Gesamtpopulation von über 580 Individuen verzeichnet werden. Die Ursachen der Arealerweiterung werden anhand von vier Hypothesen und unter Berücksichtigung von Untersuchungsergebnissen aus West- und Nordwesteuropa diskutiert. Eine derzeit häufig diskutierte mögliche Ursache der Arealerweiterung ist die seit Jahren erkennbare Klimaerwärmung, bei der insbesondere die milderen Winter und wärmeren Sommer u.a. zu einer Veränderung der Luftfeuchtigkeit führen. Diese scheidet jedoch im Falle von Asplenium adiatum-nigrum zumindest als monokausale Erklärung aus. Die veränderten klimatischen Faktoren überlagern sich zeitgleich mit einer einhergehenden Luftverbesserung (insbesondere Verringerung der SO2-Immissionen) und höheren Stickstoffimmissionen, welche letztlich die Wuchsbedingungen des Farntaxons insgesamt positiv beeinflussen können. Ein belegbarer Zusammenhang zwischen Ausbreitung des Taxons und den veränderten Klima- sowie Umweltbedingungen ist derzeit allerdings nicht gegeben.