Photolumineszenz von Exzitonen in polaren ZnO/MgZnO-Quantengrabenstrukturen

Die vorliegende Arbeit befasst sich mit dem vertieften Verständnis der Rekombinationsdynamik von polaren ZnO/MgZnO-Quantengraben(QW)-Strukturen zur exakten Bestimmung des unabgeschirmten Grundzustandes und der Analyse der zugrundeliegenden Emissionsprozesse. Dafür werden ausgehend von Beobachtungen an ZnO-Dünnschichten die Eigenschaften von mittels PLD hergestellten QWs unter dem Einfluss des internen elektrischen Feldes mit Hilfe der zeitintegrierten (TI-) und zeitaufgelösten (TR-) Photolumineszenz(PL)-Spektroskopie untersucht. Die Differenz der spontanen und piezoelektrischen Polarisation zwischen ZnO und MgZnO führt zur Ausbildung eines internen elektrischen Feldes und damit zum Auftreten des quantum-confined Stark effect (QCSE). Es wird gezeigt, dass der QCSE durch eine Durchmischung der Grenzflächen stark vermindert wird. Für QWs mit schwachem QCSE ist die Übergangsenergie und Zerfallszeit des Grundzustandes experimentell gut bestimmbar. Bei starkem QCSE müssen jedoch bereits bei geringen Anregungsdichten (1E10 /cm²) Abschirmeffekte berücksichtigt werden. Dadurch ist es sehr schwierig, den unabgeschirmten Grundzustand mittels herkömmlicher experimenteller Methoden mit einem aussagekräftigen Signal-Rausch-Verhältnis zu bestimmen. Es wird gezeigt, dass für QWs mit einer Dicke > 4 nm die Übergangsenergie des unabgeschirmten Grundzustandes nicht durch TI-PL-Messungen bestimmt werden kann. TR-PL-Messungen zeigen energetisch tiefere Übergangsenergien, jedoch ebenfalls nicht den unabgeschirmten Grundzustand. Mit einem eingeführten Modell zur Beschreibung der zeitabhängigen Abschirmung des Grundzustandsniveaus wird die Zerfallszeit für QW-Dicken in einem Bereich von 1 - 10 nm bestimmt. Durch die selbstkonsistente Lösung von Schrödinger- und Poissongleichung werden die Übergangsenergie und Zerfallszeit der Exzitonen im QW in Abhängigkeit der Feldstärke und auch der Ladungsträgerdichte berechnet. Dadurch ist eine exaktere Bestimmung der Feldstärke möglich. Zusätzlich wird durch die vergleichende Untersuchung von QWs unterschiedlicher Dicke, Potentialhöhe und Wachstumsunterlage die spontane und piezoelektrische Polarisation der Materialien experimentell bestimmt. Mittels temperaturabhängiger Messungen wird der Ursprung der Lumineszenz für QW-Dicken > 2 nm der Rekombination freier Exzitonen im QW zugeschrieben. Für dünnere QWs ist der temperaturabhängige Verlauf des PL-Maximums durch Lokalisation der Exzitonen bestimmt

Die Verhandlungen über Schillers Berufung nach Berlin

DIE VERHANDLUNGEN ÜBER SCHILLERS BERUFUNG NACH BERLIN Die Verhandlungen über Schillers Berufung nach Berlin / Stölzel, Adolf (Public Domain) ( - ) Title page ( - ) Contents ( - ) I. ( - ) II. (7) III. (13) IV. (18) V. (64) VI. (69) VII. (83) VIII. (93) Advertising ( - ) ColorChart ( -

Comorbid symptoms occurring during acute low-tone hearing loss (AHLH) as potential predictors of Meniere's disease

Acute low-tone sensorineural hearing loss (ALHL) is a type of idiopathic sudden sensorineural hearing loss. ALHL is rarely a solitary condition but rather co-occurs with vertigo and tinnitus, being an element of contemporary diagnostic criteria for Meniere's disease (MD). The goal of our present study was to determine the value of ALHL for the early diagnosis of MD in patients presenting in the emergency room with AWL as a main complaint. The files of 106 patients with ALHL who were admitted to the emergency room over the period of 7 years and 104 patients with acute high- tone sensorineural hearing loss (AHHL) from the same period were included in this retrospective study. Forty ALHL patients presented with recurrent episode of hearing loss and 66 remaining patients presented with ALHL for the first time. Of the latter group, 25 patients gave consent for the follow-up. First, we analyzed the difference in the occurrence of tinnitus and vertigo between the ALHL and AHHL groups. In patients with ALHL, the incidence of vertigo with tinnitus and the number of recurrent episodes were statistically higher than in patients with AHHL. Next, we focused on the ALHL follow-up group (25 patients). In that group, two patients had all MD symptoms at presentation, 18 had ALHL and tinnitus and five ALHL only. Of 18 patients with ALHL and tinnitus at admission, five developed vertigo and thus the triad of Meniere's disease. None of the five patients with AHLH as a sole symptom developed MD during the follow-up time but four of them have developed tinnitus. Patients with recurrent ALHL had significantly higher incidence of MD than the patients with first episode. We conclude that some patients who present with ALHL and concomitant tinnitus or have recurrent episodes of ALHL are more likely to develop Meniere's disease than these patients, who present with ALHL as a sole symptom. Nonetheless, we recommend otological follow-up for all patients presenting with ALHL

Auricular Oedema and Dyshidrotic Eczema in a Patient with Acute Myeloid Leukaemia Treated with Cytarabine

Cytarabine is an effective drug in the treatment of haematological malignancies. The therapy is associated with various complications. Frequencies of dermatological side-effects range from 2–72% and occur most commonly after high-dose regimens. Although most cutaneous reactions are mild and resolve spontaneously within several days, they may result in an increased risk of infection and alterations in comfort. In some cases, severe life-threatening reactions have been reported. Here we describe the case of a patient with acute myeloid leukaemia, who developed severe exceptional skin toxicity in terms of auricular oedema and palmar dyshidrotic eczema after the application of low-dose cytarabine. Re-administration of the drug resulted in reduced skin toxicity during further cycles of chemotherapy. Negative epicutaneous patch-testing supported the existence of cytarabine-provoked toxicity

Acute porphyrias – A neurological perspective

Acute hepatic porphyrias (AHP) can cause severe neurological symptoms involving the central, autonomic, and peripheral nervous system. Due to their relative rarity and their chameleon-like presentation, delayed diagnosis and misdiagnosis are common. AHPs are genetically inherited disorders that result from heme biosynthesis enzyme deficiencies and comprise four forms: acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and ALA-dehydratase porphyria (ALADP). Depending on the clinical presentation, the main differential diagnoses are Guillain-Barré syndrome and autoimmune encephalitis. Red flags that could raise the suspicion of acute porphyria are neurological symptoms starting after severe (abdominal) pain, in association with reddish urine, hyponatremia or photodermatitis, and the presence of encephalopathy and/or axonal neuropathy. We highlight the diagnostic difficulties by presenting three cases from our neurological intensive care unit and give a comprehensive overview about the diagnostic findings in imaging, electrophysiology, and neuropathology

Case Report: ANXA2 Associated Life-Threatening Coagulopathy With Hyperfibrinolysis in a Patient With Non-APL Acute Myeloid Leukemia

Patients with acute promyelocytic leukemia (APL) often present with potentially lifethreatening hemorrhagic diathesis. The underlying pathomechanisms of APLassociated coagulopathy are complex. However, two pathways considered to be APLspecific had been identified: 1) annexin A2 (ANXA2)-associated hyperfibrinolysis and 2) podoplanin (PDPN)-mediated platelet activation and aggregation. In contrast, since disseminated intravascular coagulation (DIC) is far less frequent in patients with non- APL acute myeloid leukemia (AML), the pathophysiology of AML-associated hemorrhagic disorders is not well understood. Furthermore, the potential threat of coagulopathy in non- APL AML patients may be underestimated. Herein, we report a patient with non-APL AML presenting with severe coagulopathy with hyperfibrinolysis. Since his clinical course resembled a prototypical APL-associated hemorrhagic disorder, we hypothesized pathophysiological similarities. Performing multiparametric flow cytometry (MFC) and immunofluorescence imaging (IF) studies, we found the patient’s bone-marrow mononuclear cells (BM-MNC) to express ANXA2 - a biomarker previously thought to be APL-specific. In addition, whole-exome sequencing (WES) on sorted BM-MNC (leukemiaassociated immunophenotype (LAIP)1: ANXAlo, LAIP2: ANXAhi) demonstrated high intratumor heterogeneity. Since ANXA2 regulation is not well understood, further research to determine the coagulopathy-initiating events in AML and APL is indicated. Moreover, ANXA2 and PDPN MFC assessment as a tool to determine the risk of life-threatening DIC in AML and APL patients should be evaluated

Be smart against cancer! A school-based program covering cancer-related risk behavior

Background: Several studies suggest that most school-age children are poorly informed about cancer risk factors. This study examines the effectiveness of the ‘Be smart against cancer’ (BSAC) program in promoting cancer awareness and intentions to engage in health-promoting behavior. Methods: 235 seventh-grade students were randomized to either the intervention (N = 152) or the wait-control group (N = 83). The intervention included the modules: “What is cancer?,” “Sun protection,” “Non smoking,” and “Physical activity, Healthy nutrition, and Limited alcohol consumption.” Outcomes measured at baseline and at the end of the one week BSAC program included knowledge of cancer and its behavioral risk factors, health-promoting intentions, and reported risk behavior. Results: BSAC was effective in increasing knowledge about cancer and risk factors for cancer (p < .001), as well as in increasing intentions to engage in health-promoting behavior (p < .001), independent of a student’s risk profile. Knowledge did not serve as a mediator for intention building. Conclusions: The BSAC is an effective school-based program for raising awareness of cancer, associated risk factors and intentions to engage in cancer-preventive behavior. The results indicate that the effectiveness of BSAC is independent of a student’s risk profile. Therefore, it holds considerable promise as a broadly applicable program to raise cancer awareness and promote healthy behavior intentions

The Role of Donor Selection for a Second Allogeneic Stem Cell Transplantation in Patients with AML Relapsing after a First Transplant; A Study on Behalf of the Acute Leukemia Working Party of EBMT

Abstract Introduction. Recurrent disease is the major cause of treatment failure after allogeneic stem cell transplantation (SCT) in patients with AML. Second SCT (SCT2) is a valid treatment option in this setting but outcome is relatively poor. Haplo-identical (haplo) SCT is increasingly used over the last decade due to the introduction of non T-depleted methods. Prior studies have shown similar outcome when using the same or different HLA-matched donor for SCT2. However, there is relatively limited data on the use of haplo-donors. Methods and Results. The study included 556 patients with AML relapsing after a first allogeneic SCT (SCT1) given in CR1 from an HLA-matched sibling (sib, n= 294) or a matched unrelated donor (MUD, n=262) and given SCT2 during the years 2006-2016. The median age at SCT2 was 46 years (20-73). 247 patients were in CR2 (44%) and 309 had active leukemia (55%) at the time of SCT2. The conditioning regimen was myeloablative (MAC, 66%) or reduced-intensity (RIC, 34%) for SCT1, and 41% and 59%, respectively for SCT2. 19% of all patients had acute GVHD grade II-IV and 20% had chronic GVHD after SCT1 and before relapse. Patients were divided into 3 groups based on the donor selected for SCT2; 1) same donor (n=163, sib/sib-112, MUD/MUD-51), 2) different HLA-matched donor (n=305, sib/different sib-44, sib/MUD-93, MUD/ different MUD- 168), 3) haplo-donor (n=88, sib/haplo-45, MUD/haplo-43). All haploSCT were non T-depleted. There were some differences between the 3 groups in the timing of relapse and SCT2. The median time from SCT1 to relapse was similar; 10.6, 12.5 and 9.3 months, respectively (P=0.14). However, the median time from relapse to SCT2 was shorter for the same donor group; 2.8, 3.7 and 3.5 months, respectively (P<0.001) and the median time between SCT1 and SCT2 was longer for the different donor group; 14.3, 17.5 and 13.8 months, respectively (P=0.03). There were no difference between the groups in patient age, gender, disease status at SCT2 or conditioning regimen intensity for SCT1 or SCT2. The 2-year leukemia-free survival (LFS) after SCT2 was 23.5%, 23.7% and 21.8%, respectively (unadjusted P=0.30). Multivariate analysis of factors predicting relapse after SCT2 showed no effect of the second donor type, hazard ratio (HR) 0.96 (P=0.83) and 1.20 (P=0.47) for different matched donor and haplo-donor compared to the same donor, respectively. MUD donor in SCT1, CR2 compared to active disease and chronic GVHD after SCT1 were associated with reduced relapse risk after SCT2, HR 0.70 (P=0.02), 0.60 (P=0.001) and 0.66 (P=0.03), respectively. Age, gender, conditioning regimen used for SCT1 or SCT2 and time to first relapse or to SCT2 did not predict relapse rate after SCT2. The second donor type did predict for non-relapse mortality (NRM) after SCT2; HR 1.26 (P=0.41) and 2.18 (P=0.02) for different matched donor and haplo-donor compared to same donor, respectively. Advanced age and MAC in SCT1 also predicted for NRM, HR 1.40 (P<0.001) and 0.61 (P=0.04), respectively. The second donor also predicted for LFS after SCT2; HR 1.05 (P=0.77) and 1.55 (P=0.03), respectively. Advanced age and SCT2 in CR2 also predicted for LFS; HR 1.11 (P=0.06) and 0.66 (P=0.002), respectively. In all, there were no differences between same or different matched donors in SCT2 outcomes, but haploSCT2 was associated with higher NRM and lower LFS. Significant interaction was detected between second donor type and conditioning for SCT1. The inferior outcome after SCT2 with a haplo-donor was limited to patients given MAC in SCT1. In this setting it was associated with higher relapse and NRM rates and lower LFS, HR 1.86 (P=0.05), 3.40 (P=0.005) and 2.25 (P=0.001), respectively. However, there was no difference in any of these outcomes in patients given RIC in SCT1. Unadjusted analysis showed that in patients with no chronic GVHD after SCT1, haploSCT2 was associated with lower LFS, due to higher NRM. However, LFS was similar in patients with prior chronic GVHD. Multivariate analysis was not feasible due to low patient numbers. Conclusions. Second SCT with the same donor or different matched donor is associated with similar outcomes in patients with relapsed AML after a first SCT. However, SCT2 with a haplo-donor is associated with higher NRM and lower LFS, mostly in patients given MAC in SCT1. Prior chronic GVHD after SCT1 is associated with lower relapse rate after SCT2. The role of prior chronic GVHD in donor selection should be further investigated. Disclosures Finke: Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding. Gramatzki:Affimed: Research Funding. Stelljes:Novartis: Honoraria; Amgen: Honoraria; JAZZ: Honoraria; MSD: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding. Stoelzel:Neovii: Speakers Bureau. Mohty:MaaT Pharma: Consultancy, Honoraria

Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised Double-blind Multicentre Phase 3B Study (BESIDE)

AbstractBackgroundIncontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic monotherapy.ObjectiveTo evaluate the efficacy and the safety and tolerability of combination (solifenacin 5mg and mirabegron 50mg) versus solifenacin 5 or 10mg in OAB patients remaining incontinent after 4 wk of solifenacin 5mg.Design, setting, and participantsOAB patients remaining incontinent despite daily solifenacin 5mg during 4-wk single-blind run-in were randomised 1:1:1 to double-blind daily combination or solifenacin 5 or 10mg for 12 wk. Patients receiving the combination were initiated on mirabegron 25mg increasing to 50mg after week 4.Outcome measurements and statistical analysisThe primary end point was a change from baseline to end of treatment (EOT) in the mean number of incontinence episodes per 24h (stratified rank analysis of covariance [ANCOVA]). Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h (ANCOVA) and number of incontinence episodes noted in a 3-d diary at EOT (mixed-effects Poisson regression). A trial (BESIDE) comparing combination treatment (solifenacin plus mirabegron) with one treatment alone (solifenacin) tested the superiority of combination versus solifenacin 5mg, noninferiority (and potential superiority) of combination versus solifenacin 10mg (key secondary end points), and the safety and tolerability of combination therapy versus solifenacin monotherapy.Results and limitationsA total of 2174 patients were randomised to combination (n=727), solifenacin 5mg (n=728), or solifenacin 10mg (n=719). At EOT, combination was superior to solifenacin 5mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p<0.001), and incontinence noted in a 3-d diary (p=0.014). Combination was noninferior to solifenacin 10mg for key secondary end points and superior to solifenacin 10mg for improving daily micturitions. All treatments were well tolerated.ConclusionsAdding mirabegron 50mg to solifenacin 5mg further improved OAB symptoms versus solifenacin 5 or 10mg, and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5mg.Patient summaryIn this 12-wk study, overactive bladder patients who remained incontinent despite initial solifenacin 5mg treatment received additional treatment with mirabegron 50mg. Combining mirabegron 50mg with solifenacin 5mg was superior to solifenacin 5mg alone in improving symptoms of incontinence and frequent urination, and it was well tolerated.Trial registrationClinicalTrials.gov NCT01908829