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Background: Since January 2018 performance of urethroplasties is done on regular basis at the University Hospital Frankfurt (UKF). We aimed to implement and transfer an institutional standardized perioperative algorithm for urethral surgery (established at the University Hospital Hamburg-Eppendorf—UKE) using a validated Urethral Stricture Surgery Patient-Reported Outcome Measure (USS-PROM) in patients undergoing urethroplasty at UKF. Materials and Methods: We retrospectively analyzed all patients who underwent urethroplasty for urethral stricture disease between January 2018 and January 2020 at UKF. All patients were offered to revisit for clinical follow-up (FU) and completion of USS-PROM. Primary end point was stricture recurrence-free survival (RFS). Secondary endpoints were functional outcomes, quality of life (QoL), and patient satisfaction. Results: In total, 50 patients underwent urethroplasty and 74 and 24% had a history of previous urethrotomy or urethroplasty, respectively. A buccal mucosal graft urethroplasty was performed in 86% (n = 43). After patient's exclusion due to lost of FU, FU <3 months, and/or a pending second stage procedure, 40 patients were eligible for final analysis. At median FU of 10 months (interquartile-range 5.0–18.0), RFS was 83%. After successful voiding trial, the postoperative median Qmax significantly improved (24.0 vs. 7.0 mL/s; p < 0.01). Conversely, median residual urine decreased significantly (78 vs. 10 mL; p < 0.01). Overall, 95% of patients stated that QoL improved and 90% were satisfied by the surgical outcome. Conclusions: We demonstrated a successful implementation and transfer of an institutional standardized perioperative algorithm for urethral surgery from one location (UKE) to another (UKF). In our short-term FU, urethroplasty showed excellent RFS, low complication rates, good functional results, improvement of QoL and high patient satisfaction. PROMs allow an objective comparison between different centers.
Prähistorische Eierschalenfragmente der Fundstelle Sulze bei Erfurt in Thüringen werden beschrieben und diskutiert. Die folgenden Arten werden nachgewiesen: Cygnus olor, Anser anser, Anas platyrhynchos und Gallus gallus forma domestica. Auf der Grundlage von Knochenresten gelten folgende Nachweise: Columba livia forma domestica, Tyto alba, Anser anser forma domestica, Anas platyrhynchos forma domestica, Gallus gallus forma domestica, Corvus corax, Coloelus monedula, Galerida cristata, Passer domesticus und Coccothraustes coccothraustes. Besonderes Gewicht wird auf die Bestimmungsmethoden an prähistorischen Eierschalen gelegt.
Der nachfolgende Bericht basiert auf dem Manuskript für einen Vortrag vor Mitgliedern des Verbandes ehemaliger Breslauer in Israel im September 2006. Viele der heute dort lebenden ehemaligen Breslauer waren Schülerinnen und Schüler der jüdischen Schulen in ihrer Heimatstadt. Das Ende des jüdischen Schulwesens wird im Folgenden vor allem nach den im (polnischen) Staatsarchiv zu Breslau [Archivum Panstwowe we Wrocławia] befindlichen Akten des Magistrats der schlesischen (Provinz) Hauptstadt Breslau und darunter insbesondere den der Magistratsschulverwaltung und soweit Dokumente darüber vorlagen für die Zeit zwischen 1933 und 1942 in groben Zügen aufgezeichnet. Auf die Wiederholung von Einzelheiten, die bereits in anderen Publikationen veröffentlicht wurden, und die breite Einbeziehung anderer Quellen wurde im Sinne, einen Überblick über die Ereignisse und die betroffenen Schüler und Lehrer zu vermitteln, verzichtet. Eine umfangreichere Arbeit mit vielen weiteren Details, die sich aus den Archivalien in Wrocław / Breslau ergeben und die auch anderes Quellenmaterial mit einschließt, ist unter dem Arbeitstitel „Breslaus jüdische Schüler, Lehrer und Schulen 1919 – 1943“ in Vorbereitung. Diese geplante Publikation und der vorliegende Artikel sollen dazu beitragen, dass das Andenken an die Opfer des nationalsozialistischen Regimes gewahrt wird. Deshalb werden auch die Namen der Lehrer, von denen viele ermordet wurden, genannt. Sie sollen unvergessen bleiben. Zugleich sollen über diese Veröffentlichung Kontakte zu anderen Forschern, die sich auch mit der Thematik der Jüdischen Schulen in der Zeit der Weimarer Republik und während der Herrschaft des Nationalsozialismus befassen, hergestellt und weitere Berichte von Zeitzeugen und Dokumente erschlossen werden, um dazu beizutragen, Einzelschicksale bzw. Lebenswege von Lehrern und Schülern und auch von jenen, die sich schuldig gemacht haben, aufzudecken.
Laufkäfer werden in ökologischen Studien zur Lebensraumbewertung sehr häufig als Bioindikatoren hinzugezogen (PLATEN & KOWARIK 1995, PLATNER et al. 1996, POSPISCHIL 1981), denn ihre Ökologie und die daraus resultierenden ökologischen Ansprüche sind durch zahlreiche Studien eingehend untersucht (u.a. BAEHR 1980, LINDROTH 1945, THIELE 1977). Unterschiede in der Artengemeinschaft bzw. Änderungen in der Abundanz der Carabiden lassen Rückschlüsse über Habitatqualität, Standortsfaktoren, Minimalareal- Fragen, Habitattradition und Vernetzung von Lebensräumen zu. Diese Tatsachen wurden ausgenutzt, um die Bestandstradition und die Naturnähe der Bestockung der Probeflächen zu untersuchen. Diese sind weitgehend naturnahe Wälder im südbayerischen Tertiärhügelland, einem insgesamt wenig naturnahen, forstlich durch Fichtenforste geprägten Landschaftsraum.
Osteosarcomas are aggressive bone tumours with a high degree of genetic heterogeneity, which has historically complicated driver gene discovery. Here we sequence exomes of 31 tumours and decipher their evolutionary landscape by inferring clonality of the individual mutation events. Exome findings are interpreted in the context of mutation and SNP array data from a replication set of 92 tumours. We identify 14 genes as the main drivers, of which some were formerly unknown in the context of osteosarcoma. None of the drivers is clearly responsible for the majority of tumours and even TP53 mutations are frequently mapped into subclones. However, >80% of osteosarcomas exhibit a specific combination of single-base substitutions, LOH, or large-scale genome instability signatures characteristic of BRCA1/2-deficient tumours. Our findings imply that multiple oncogenic pathways drive chromosomal instability during osteosarcoma evolution and result in the acquisition of BRCA-like traits, which could be therapeutically exploited.
A measurement of the transverse momentum spectra of jets in Pb-Pb collisions at sNN−−−√=2.76 TeV is reported. Jets are reconstructed from charged particles using the anti-kT jet algorithm with jet resolution parameters R of 0.2 and 0.3 in pseudo-rapidity |η|<0.5. The transverse momentum pT of charged particles is measured down to 0.15 GeV/c which gives access to the low pT fragments of the jet. Jets found in heavy-ion collisions are corrected event-by-event for average background density and on an inclusive basis (via unfolding) for residual background fluctuations and detector effects. A strong suppression of jet production in central events with respect to peripheral events is observed. The suppression is found to be similar to the suppression of charged hadrons, which suggests that substantial energy is radiated at angles larger than the jet resolution parameter R=0.3 considered in the analysis. The fragmentation bias introduced by selecting jets with a high pT leading particle, which rejects jets with a soft fragmentation pattern, has a similar effect on the jet yield for central and peripheral events. The ratio of jet spectra with R=0.2 and R=0.3 is found to be similar in Pb-Pb and simulated PYTHIA pp events, indicating no strong broadening of the radial jet structure in the reconstructed jets with R<0.3.
Die Weißtanne (Abies alba) – Symbol für naturnahe Waldwirtschaft – ist im Bayerischen Wald beheimatet. Die Tanne ist dort neben Fichte und Buche das prägende Element der Bergmischwälder auf Höhen von 600 bis 1250 m. Einstmals war sie mit etwa 20 % (ROTHE & BORCHERT 2003) am Waldaufbau beteiligt. Seit rund 150 Jahren ist jedoch ein drastischer Rückgang der Tanne - nicht nur im Bayerischen Wald – zu verzeichnen. Die Ursachen für den Rückgang der Tanne sind überwiegend anthropogen bedingt. In erster Linie ist hier die Forstwirtschaft zu erwähnen, die bestrebt ist durch waldbauliche Maßnahmen den Fichtenanteil anzuheben. An zweiter Stelle stehen die neuartigen Waldschäden, welche, bedingt durch Schadstoffimmissionen in den 70er und 80er Jahren des letzten Jahrhunderts, zu verstärktem Absterben der Tanne führten. Noch heute ist die Tanne die am stärksten geschädigte Baumart in Bayern (BAYSTMLF 2002). Ein weiterer nicht zu vergessender Faktor für den Rückgang der Tanne sind die z.T. hohen Wildbestände, durch deren Verbiss und Schälen junger Tannen das Heranwachsen einer neuen Generation verhindert wird. Mit dem Rückgang der Tanne verändert sich jedoch nicht nur die Baumartenzusammensetzung, sondern auch Tier- und Pflanzenarten sind direkt und indirekt betroffen. Die Arthropodenfauna der bisher kaum untersuchten Tanne wird als relativ artenarm beschrieben (BRÄNDLE & BRANDL 2001), jedoch gibt es wenige spezielle Untersuchungen an dieser Baumart (MÜLLER & GOßNER 2004).
Natürlicherweise war die Tanne (Abies alba) in den bayerischen Wäldern mit Anteilen von bis zu 20% vertreten (nach ROTHE & BORCHERT 2003). Seit 150 Jahren aber gehen die Tannenbestände in drastischem Ausmaß zurück, was nicht nur auf die wachsende Schadstoffbelastung der Luft, sondern auch auf hohe Wildbestände und die einseitige Waldbewirtschaftung zugunsten der Fichte (Picea abies) zurückzuführen ist. In jüngster Zeit wird seitens der Staatsforstverwaltung angestrebt, der Tanne ihren angestammten Platz in unseren Wäldern wieder einzuräumen (BAYERISCHES STAATSMINISTERIUM FÜR LANDWIRTSCHAFT UND FORSTEN 1993). Es stellt sich die Frage, welchen Beitrag die Tanne zur Biodiversität in Wäldern und speziell in Mischwäldern leistet. Frühere Untersuchungen beschrieben die Tannenfauna als artenarm im Vergleich mit anderen Baumarten (BÖHME 2001, BUCKING 1998), allerdings wurde die Kronenfauna dabei stets vernachlässigt. Da aber 90% eines Hochwaldes über der Reichhöhe eines Menschen liegt (BUßLER et al. 2004), sind Untersuchungen im Kronenraum höheren Straten für eine umfassende Aussage über die Fauna auf Bäumen von großer Bedeutung. Bis jetzt gibt es trotz des generell wachsenden Interesses an der Kronenfauna keine umfassenden Untersuchungen an Tanne (MÜLLER & GOSSNER 2004). Mit dem hier vorgestellten Projekt sollte begonnen werden, die Wissenslücke um die Insektenfauna in Tannenkronen zu schließen. Den xylobionten Käfern galt besondere Aufmerksamkeit, da sie als eine baumartengebundene Insektengruppe für vergleichendeUntersuchungen sehr gut geeignet und sowohl taxonomisch als auch ökologisch gut untersucht sind. Daneben wurden Heteroptera, Neuropterida und Hymenoptera bearbeitet .
Oligonucleotides suppress PKB/Akt and act as superinductors of apoptosis in human keratinocytes
(2009)
DNA oligonucleotides (ODN) applied to an organism are known to modulate the innate and adaptive immune system. Previous studies showed that a CpG-containing ODN (CpG-1-PTO) and interestingly, also a non-CpG-containing ODN (nCpG- 5-PTO) suppress inflammatory markers in skin. In the present study it was investigated whether these molecules also influence cell apoptosis. Here we show that CpG-1-PTO, nCpG-5-PTO, and also natural DNA suppress the phosphorylation of PKB/Akt in a cell-type-specific manner. Interestingly, only epithelial cells of the skin (normal human keratinocytes, HaCaT and A-431) show a suppression of PKB/Akt. This suppressive effect depends from ODN lengths, sequence and backbone. Moreover, it was found that TGFa-induced levels of PKB/Akt and EGFR were suppressed by the ODN tested. We hypothesize that this suppression might facilitate programmed cell death. By testing this hypothesis we found an increase of apoptosis markers (caspase 3/7, 8, 9, cytosolic cytochrome c, histone associated DNA fragments, apoptotic bodies) when cells were treated with ODN in combination with low doses of staurosporin, a wellknown pro-apoptotic stimulus. In summary the present data demonstrate DNA as a modulator of apoptosis which specifically targets skin epithelial cells.
Objective: Pancreatic ductal adenocarcinoma (PDAC) still carries a dismal prognosis with an overall 5-year survival rate of 9%. Conventional combination chemotherapies are a clear advance in the treatment of PDAC; however, subtypes of the disease exist, which exhibit extensive resistance to such therapies. Genomic MYC amplifications represent a distinct subset of PDAC with an aggressive tumour biology. It is clear that hyperactivation of MYC generates dependencies that can be exploited therapeutically. The aim of the study was to find and to target MYC-associated dependencies.
Design: We analysed human PDAC gene expression datasets. Results were corroborated by the analysis of the small ubiquitin-like modifier (SUMO) pathway in a large PDAC cohort using immunohistochemistry. A SUMO inhibitor was used and characterised using human and murine two-dimensional, organoid and in vivo models of PDAC.
Results: We observed that MYC is connected to the SUMOylation machinery in PDAC. Components of the SUMO pathway characterise a PDAC subtype with a dismal prognosis and we provide evidence that hyperactivation of MYC is connected to an increased sensitivity to pharmacological SUMO inhibition.
Conclusion: SUMO inhibitor-based therapies should be further developed for an aggressive PDAC subtype.
The transverse momentum (pT) spectrum and nuclear modification factor (RAA) of reconstructed jets in 0–10% and 10–30% central Pb–Pb collisions at √sNN = 2.76 TeV were measured. Jets were reconstructed using the anti-kT jet algorithm with a resolution parameter of R = 0.2 from charged and neutral particles, utilizing the ALICE tracking detectors and Electromagnetic Calorimeter (EMCal). The jet pT spectra are reported in the pseudorapidity interval of |ηjet| < 0.5 for 40 < pT, jet < 120 GeV/c in 0–10% and for 30 < pT, jet < 100 GeV/c in 10–30% collisions. Reconstructed jets were required to contain a leading charged particle with pT > 5 GeV/c to suppress jets constructed from the combinatorial background in Pb–Pb collisions. The leading charged particle requirement applied to jet spectra both in pp and Pb–Pb collisions had a negligible effect on the RAA. The nuclear modification factor RAA was found to be 0.28 ± 0.04 in 0–10% and 0.35 ± 0.04 in 10–30% collisions, independent of pT, jet within the uncertainties of the measurement. The observed suppression is in fair agreement with expectations from two model calculations with different approaches to jet quenching.
We have performed the first measurement of the coherent ψ(2S) photo production cross section in ultraperipheral Pb–Pb collisions at the LHC. This charmonium excited state is reconstructed via the ψ(2S) → l +l − and ψ(2S) → J/ψπ+π− decays, where the J/ψ decays into two leptons. The analysis is based on an event sample corresponding to an integrated luminosity of about 22 μb−1. The cross section for coherent ψ(2S) production in the rapidity interval −0.9 < y < 0.9 is dσcoh ψ(2S)/dy = 0.83±0.19 stat+syst mb. The ψ(2S) to J/ψ coherent cross section ratio is 0.34+0.08 −0.07(stat + syst). The obtained results are compared to predictions from theoretical models.
A measurement of dijet correlations in p–Pb collisions at √sNN = 5.02 TeV with the ALICE detector is presented. Jets are reconstructed from charged particles measured in the central tracking detectors and neutral energy deposited in the electromagnetic calorimeter. The transverse momentum of the full jet (clustered from charged and neutral constituents) and charged jet (clustered from charged particles only) is corrected event-by-event for the contribution of the underlying event, while corrections for underlying event fluctuations and finite detector resolution are applied on an inclusive basis. A projection of the dijet transverse momentum, kTy = pch+ne T,jet sin(ϕdijet) with ϕdijet the azimuthal angle between a full and charged jet and pch+ne T,jet the transverse momentum of the full jet, is used to study nuclear matter effects in p–Pb collisions. This observable is sensitive to the acoplanarity of dijet production and its potential modification in p–Pb collisions with respect to pp collisions. Measurements of the dijet kTy as a function of the transverse momentum of the full and recoil charged jet, and the event multiplicity are presented. No significant modification of kTy due to nuclear matter effects in p–Pb collisions with respect to the event multiplicity or a PYTHIA8 reference is observed.
The measurement of the mass differences for systems bound by the strong force has reached a very high precision with protons and anti-protons1,2. The extension of such measurement from (anti-)baryons to (anti-)nuclei allows one to probe any difference in the interactions between nucleons and anti-nucleons encoded in the (anti-)nuclei masses. This force is a remnant of the underlying strong interaction among quarks and gluons and can be described by effective theories3, but cannot yet be directly derived from quantum chromodynamics. Here we report a measurement of the difference between the ratios of the mass and charge of deuterons (d) and anti-deuterons (), and 3He and nuclei carried out with the ALICE (A Large Ion Collider Experiment)4 detector in Pb–Pb collisions at a centre-of-mass energy per nucleon pair of 2.76 TeV. Our direct measurement of the mass-over-charge differences confirms CPT invariance to an unprecedented precision in the sector of light nuclei5,6. This fundamental symmetry of nature, which exchanges particles with anti-particles, implies that all physics laws are the same under the simultaneous reversal of charge(s) (charge conjugation C), reflection of spatial coordinates (parity transformation P) and time inversion (T).
The ALICE Collaboration at the LHC reports measurement of the inclusive production cross section of electrons from semi-leptonic decays of beauty hadrons with rapidity |y| < 0.8 and transverse momentum 1 < pT < 10 GeV/c, in pp collisions at √s = 2.76 TeV. Electrons not originating from semi-electronic decay of beauty hadrons are suppressed using the impact parameter of the corresponding tracks. The production cross section of beauty decay electrons is compared to the result obtained with an alternative method which uses the distribution of the azimuthal angle between heavy-flavour decay electrons and charged hadrons. Perturbative QCD predictions agree with the measured cross section within the experimental and theoretical uncertainties. The integrated visible cross section, σb→e = 3.47 ± 0.40(stat) +1.12 −1.33(sys) ± 0.07(norm) μb, was extrapolated to full phase space using Fixed Order plus Next-to-Leading Log (FONLL) calculations to obtain the total bb production ¯ cross section, σbb¯ = 130 ± 15.1(stat) +42.1 −49.8(sys) +3.4 −3.1(extr) ± 2.5(norm) ± 4.4(BR) μb.
Transverse momentum spectra of π±, K± and p(p¯) up to pT = 20 GeV/c at mid-rapidity in pp, peripheral (60–80%) and central (0–5%) Pb–Pb collisions at √sNN = 2.76 TeV have been measured using the ALICE detector at the Large Hadron Collider. The proton-to-pion and the kaon-to-pion ratios both show a distinct peak at pT ≈ 3 GeV/c in central Pb–Pb collisions. Below the peak, pT < 3 GeV/c, both ratios are in good agreement with hydrodynamical calculations, suggesting that the peak itself is dominantly the result of radial flow rather than anomalous hadronization processes. For pT > 10 GeV/c particle ratios in pp and Pb–Pb collisions are in agreement and the nuclear modification factors for π±, K± and p(p¯) indicate that, within the systematic and statistical uncertainties, the suppression is the same. This suggests that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets.
We report on the production of inclusive Υ (1S) and Υ (2S) in p–Pb collisions at √sNN = 5.02 TeV at the LHC. The measurement is performed with the ALICE detector at backward (−4.46 < ycms < −2.96) and forward (2.03 .< ycms < 3.53) rapidity down to zero transverse momentum. The production cross sections of the Υ (1S) and Υ (2S) are presented, as well as the nuclear modification factor and the ratio of the forward to backward yields of Υ (1S). A suppression of the inclusive Υ (1S) yield in p–Pb collisions with respect to the yield from pp collisions scaled by the number of binary nucleon–nucleon collisions is observed at forward rapidity but not at backward rapidity. The results are compared to theoretical model calculations including nuclear shadowing or partonic energy loss effect.
Background: Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy.
Methods: The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2470 elderly (≥ 70 years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ≤9 g/dl during surgery or within 3 days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb ≤ 9 g/dl with a target range for the post-transfusion Hb level of 9–10.5 g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb ≤ 7.5 g/dl with a target range for the post-transfusion Hb level of 7.5–9 g/dl). The intervention per patient will be followed until hospital discharge or up to 30 days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90 days after surgery. Infections requiring iv antibiotics with re-hospitalisation are assessed as important secondary endpoint. The primary endpoint will be analysed by logistic regression adjusting for age, cancer surgery (y/n), type of surgery (intermediate- or high-risk), and incorporating centres as random effect.
Discussion: The LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90 days after surgery.
Trial registration: ClinicalTrials.gov (identifier: NCT03369210).
The differential charged jet cross sections, jet fragmentation distributions, and jet shapes are measured in minimum bias proton-proton collisions at centre-of-mass energy s√=7 TeV using the ALICE detector at the LHC. Jets are reconstructed from charged particle momenta in the mid-rapidity region using the sequential recombination kT and anti-kT as well as the SISCone jet finding algorithms with several resolution parameters in the range R=0.2 to 0.6. Differential jet production cross sections measured with the three jet finders are in agreement in the transverse momentum (pT) interval 20<pjet,chT<100 GeV/c. They are also consistent with prior measurements carried out at the LHC by the ATLAS collaboration. The jet charged particle multiplicity rises monotonically with increasing jet pT, in qualitative agreement with prior observations at lower energies. The transverse profiles of leading jets are investigated using radial momentum density distributions as well as distributions of the average radius containing 80% (⟨R80⟩) of the reconstructed jet pT. The fragmentation of leading jets with R=0.4 using scaled pT spectra of the jet constituents is studied. The measurements are compared to model calculations from event generators (PYTHIA, PHOJET, HERWIG). The measured radial density distributions and ⟨R80⟩ distributions are well described by the PYTHIA model (tune Perugia-2011). The fragmentation distributions are better described by HERWIG.