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The KASCADE-Grande experiment has significantly contributed to the current knowledge about the energy spectrum and composition of cosmic rays for energies between the knee and the ankle. Meanwhile, post-LHC versions of the hadronic interaction models are available and used to interpret the entire data set of KASCADE-Grande. In addition, a new, combined analysis of both arrays, KASCADE and Grande, was developed significantly increasing the accuracy of the shower observables. First results of the new analysis with the entire data set of the KASCADE-Grande experiment will be the focus of this contribution.
"Ja, Goethe über alles und immer!" : Benns "Doppelleben" in den Briefen an F. W. Oelze (1932-1956)
(2016)
"Goethe über alles"! Das will heißen, mit einer kaum versteckten Anspielung auf die deutsche Nationalhymne: Goethe vor allem über Deutschland! Diese emphatische Parole Gottfried Benns findet sich in seinem Brief vom 8. November 1950 an Friedrich Wilhelm Oelze.1 Zu dieser Zeit stand der Briefwechsel zwischen den beiden Männern schon in seinem achtzehnten Jahr, ausgelöst durch das Goethe-Jahr 1932, zu dem Benn seinen Essay "Goethe und die Naturwissenschaften" beigesteuert hatte. Er erschien in der "Neuen Rundschau" in einem "Sonderheft zum hundertsten Todestag Goethes" und enthielt u. a. Beiträge von Gerhart Hauptmann, Thomas Mann, Hermann Hesse, André Gide und Ortega y Gasset. Benn war zeitlebens stolz auf diese Leistung und ihre illustre Autoren-Nachbarschaft.
Nosological delineation of congenital ocular motor apraxia type Cogan : an observational study
(2016)
Background: The nosological assignment of congenital ocular motor apraxia type Cogan (COMA) is still controversial. While regarded as a distinct entity by some authorities including the Online Mendelian Inheritance in Man catalog of genetic disorders, others consider COMA merely a clinical symptom.
Methods: We performed a retrospective multicenter data collection study with re-evaluation of clinical and neuroimaging data of 21 previously unreported patients (8 female, 13 male, ages ranging from 2 to 24 years) diagnosed as having COMA.
Results: Ocular motor apraxia (OMA) was recognized during the first year of life and confined to horizontal pursuit in all patients. OMA attenuated over the years in most cases, regressed completely in two siblings, and persisted unimproved in one individual. Accompanying clinical features included early onset ataxia in most patients and cognitive impairment with learning disability (n = 6) or intellectual disability (n = 4). Re-evaluation of MRI data sets revealed a hitherto unrecognized molar tooth sign diagnostic for Joubert syndrome in 11 patients, neuroimaging features of Poretti-Boltshauser syndrome in one case and cerebral malformation suspicious of a tubulinopathy in another subject. In the remainder, MRI showed vermian hypo-/dysplasia in 4 and no abnormalities in another 4 patients. There was a strong trend to more severe cognitive impairment in patients with Joubert syndrome compared to those with inconclusive MRI, but otherwise no significant difference in clinical phenotypes between these two groups.
Conclusions: Systematical renewed analysis of neuroimaging data resulted in a diagnostic reappraisal in the majority of patients with early-onset OMA in the cohort reported here. This finding poses a further challenge to the notion of COMA constituting a separate entity and underlines the need for an expert assessment of neuroimaging in children with COMA, especially if they show cognitive impairment.
Auf der Basis von fast 500 eigenen Vegetationsaufnahmen haben wir die Pflanzengesellschaften grundwasserferner Säume in Nordostniedersachsen untersucht. Der vorliegende Beitrag beschäftigt sich davon mit den Gesellschaften der Klasse Trifolio-Geranietea sanguinei (inkl. Melampyro-Holcetea: 246 Aufnahmen). Wir unterscheiden 16 Assoziationen (bzw. assoziationsgleiche Einheiten). Zu diesen führen wir die diagnostische Artenkombination an, charakterisieren sie floristisch und strukturell, beschreiben ihren Standort sowie ihre Verbreitung und Häufigkeit im Gebiet und diskutieren ihre syntaxonomische Fassung bei anderen Autoren. Die Aufnahmen sind durch Einzeltabellen sowie in einer synoptischen Stetigkeitstabelle dokumentiert.
Die Klassifikation erfolgte mittels einer in Axiomen gefassten Konkretisierung des Braun-Blanquet-Ansatzes. Parallel zur Bearbeitung des regionalen Datensatzes entwickelten wir ein europaweites Gliederungssystem, das auf insgesamt 246 Stetigkeitsspalten aus 15 Ländern beruht, die zusammen über 5.000 Aufnahmen umfassen. Das Ergebnis präsentieren wir in Form von zwei Stetigkeitstabellen (höhere Syntaxa der Trifolio-Geranietea, Assoziationen der Melamypro-Holcetalia mollis). Wir kommen zu dem Schluss, dass sämtliche Saumgesellschaften Europas von mageren Standorten in einer einzigen Klasse Trifolio-Geranietea zusammengefasst werden sollten, da diese floristisch besser charakterisiert ist als es die azidophytischen und basiphytischen Säume jeweils für sich genommen wären. Diese beiden Gruppen von Säumen, die von anderen Autoren als eigene Klassen gefasst werden, führen wir als Unterklassen, wobei die Melampyro pratensis-Holcenea mollis nur eine einzige Ordnung Melampyro- Holcetalia umfassen, während wir die Trifolio-Geranienea sanguinei in die beiden Ordnungen Origanetalia vulgaris s. str. (mesophytisch) und Antherico ramosi-Geranietalia sanguinei (xerophytisch) gliedern. Die Melampyro-Holcetalia umfassen vier Verbände, das Melampyrion pratensis (weit verbreitet: 3 Assoziationen im Gebiet), das Teucrion scorodoniae (atlantisch: 1 Assoziation), das Poion nemoralis all. nov. (steile, schattige Standorte: 2 Assoziationen: Aulacomnio androgynae-Polypodietum vulgaris ass. nov. und Veronica chamaedryos-Poetum nemoralis ass. nov.) und das Violo rivinianae-Stellarion holosteae (schwach saure, etwas nährstoffreichere Standorte: 2 Assoziationen). Die Origanetalia vulgaris sind im Gebiet nur mit dem Trifolion medii (6 Assoziationen) und die Antherico-Geranietalia nur mit dem Geranion sanguinei (2 Assoziationen, fragmentarisch) vertreten.
Wir unterziehen alle behandelten Syntaxa einer nomenklatorischen Revision, listen Synonyme und Typen auf und begründen vorgesehene Anträge an die Nomenklaturkommission. Das Agrimonio eupatoriae-Vicietum cassubicae Passarge 1967 nom. invers, propos, und das Geranio-Anemonetum sylvestris T. Müller 1962 werden neotypisiert. In einer abschließenden Diskussion beleuchten wir die überregionale Relevanz der von uns vorgeschlagenen syntaxonomischen Gliederung, diskutieren methodische Fragen und leiten aus unseren Erfahrungen generelle Empfehlungen für die pflanzensoziologische Arbeitsweise ab.
Ziel der Arbeit ist es, die nitrophytischen Saum- und Waldverlichtungsgesellschaften grundwasserferner Standorte in Nordostniedersachsen standörtlich, strukturell und floristisch zu charakterisieren, sie diesbezüglich untereinander und mit den in Teil I behandelten Säumen nährstoffarmer Standorte zu vergleichen und sie schließlich in eine überregional stimmige syntaxonomische Gliederung einzureihen. In Nordostniedersachsen konnten wir auf der Basis von 200 eigenen Vegetationsaufnahmen 16 Assoziationen (oder ranggleiche Einheiten) unterscheiden. Für das temperate Europa haben wir diese mit Aufnahmen und Stetigkeitslisten aus 63 weiteren Literaturquellen aus 16 Ländern zu einer synoptischen Tabelle aller ausdauernden Ruderal- und nitrophytischen Saumgesellschaften grundwasserferner Standorte zusammengestellt, die insgesamt auf 10.347 Einzelaufnahmen beruht.
Sowohl die nordostniedersächsischen als auch die europaweiten Daten sprechen dafür, alle diese Gesellschaften, und damit auch Teile der bisherigen Klassen Epilobietea angustifolii und Galio- Urticetea, in den Artemisietea vulgaris zusammenzufassen. Die nitrophytischen Säume gehören darin zu zwei der vier Unterklassen: Die azidophytischen „Schlagfluren“ (Senecioni sylvatici-Epilobienea angustifolii subcl. nov.) umfassen nach derzeitigem Kenntnisstand nur die Ordnung Galeopsio-Senecionetalia sylvatici mit dem einzigen Verband Epilobion angustifolii (2 Assoziationen in Nordostniedersachsen). Die übrigen nitrophytischen Säume gehören zu zwei Ordnungen innerhalb der Unterklasse Lamio albi-Urticenea dioicae. Die Circaeo-Stachyetalia umfassen das Atropion bellae-donnae (basiphytische „Schlagfluren“, 2 Assoziationen) und das Impatienti noli-tangere-Stachyion sylvaticae (staufeuchte Innensäume, 3 Assoziationen, darunter das Scutellario galericulatae-Circaeetum lutetianae ass. nov.), während die Galio-Alliarietalia aus Geo-Alliarion (frische Innensäume, 5 Assoziationen, darunter das Bromo sterilis-Chelidonietum majoris ass. nov.) und Aegopodion podagrariae (Außensäume, 4 Assoziationen) bestehen. Wir unterziehen alle im Untersuchungsgebiet vertretenen Syntaxa einer nomenklatorischen Revision, mit umfassender Auflistung von Synonymen, Typennachweis bzw. erforderlichenfalls Typisierung für alle gültigen Namen und Begründung vorgesehener Anträge an die Nomenklaturkommission.
In einer vergleichenden Betrachtung (meist auf Verbandsniveau) arbeiten wir abschließend Gemeinsamkeiten und Unterschiede aller nordostniedersächsischen Saumgesellschaften hinsichtlich Standortbedingungen, Vegetationsstruktur und Phytodiversität heraus. Die Säume weisen, verglichen mit anderen Gesellschaften der Region, durchschnittlich eine höhere Artendichte auf. Dabei sind die Syntaxa basenreicher Standorte im Allgemeinen artenreicher als jene saurer Standorte. Unter anderem aufgrund ihres großes Längen-Breiten-Verhältnisses beherbergen Säume entlang von Gehölzen in ihrer Gesamtheit auf sehr kleiner Fläche einen erheblichen Teil des regionalen Arteninventars an Gefäßpflanzen und besitzen so einen bedeutenden Naturschutzwert.
Iron deficiency, with or without anemia, is the most frequent hematological manifestation in individuals with cancer, and is especially common in patients with colorectal cancer. Iron is a vital micronutrient that plays an essential role in many biological functions, in the context of which it has been found to be intimately linked to cancer biology. To date, however, whereas a large number of studies have comprehensively investigated and reviewed the effects of excess iron on cancer initiation and progression, potential interrelations of iron deficiency with cancer have been largely neglected and are not well-defined. Emerging evidence indicates that reduced iron intake and low systemic iron levels are associated with the pathogenesis of colorectal cancer, suggesting that optimal iron intake must be carefully balanced to avoid both iron deficiency and iron excess. Since iron is vital in the maintenance of immunological functions, insufficient iron availability may enhance oncogenicity by impairing immunosurveillance for neoplastic changes and potentially altering the tumor immune microenvironment. Data from clinical studies support these concepts, showing that iron deficiency is associated with inferior outcomes and reduced response to therapy in patients with colorectal cancer. Here, we elucidate cancer-related effects of iron deficiency, examine preclinical and clinical evidence of its role in tumorigenesis, cancer progression and treatment response. and highlight the importance of adequate iron supplementation to limit these outcomes.
Chronic intestinal failure (CIF) is a rare but feared complication of Crohn’s disease. Depending on the remaining length of the small intestine, the affected intestinal segment, and the residual bowel function, CIF can result in a wide spectrum of symptoms, from single micronutrient malabsorption to complete intestinal failure. Management of CIF has improved significantly in recent years. Advances in home-based parenteral nutrition, in particular, have translated into increased survival and improved quality of life. Nevertheless, 60% of patients are permanently reliant on parenteral nutrition. Encouraging results with new drugs such as teduglutide have added a new dimension to CIF therapy. The outcomes of patients with CIF could be greatly improved by more effective prevention, understanding, and treatment. In complex cases, the care of patients with CIF requires a multidisciplinary approach involving not only physicians but also dietitians and nurses to provide optimal intestinal rehabilitation, nutritional support, and an improved quality of life. Here, we summarize current literature on CIF and short bowel syndrome, encompassing epidemiology, pathophysiology, and advances in surgical and medical management, and elucidate advances in the understanding and therapy of CIF-related complications such as catheter-related bloodstream infections and intestinal failure-associated liver disease.
Background: Preclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects and promoting immune responses. BI1361849 (CV9202) is an active cancer immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1), intended to induce targeted immune responses.
Methods: We describe a phase Ib clinical trial evaluating treatment with BI1361849 combined with local radiation in 26 stage IV NSCLC patients with partial response (PR)/stable disease (SD) after standard first-line therapy. Patients were stratified into three strata (1: non-squamous NSCLC, no epidermal growth factor receptor (EGFR) mutation, PR/SD after ≥4 cycles of platinum- and pemetrexed-based treatment [n = 16]; 2: squamous NSCLC, PR/SD after ≥4 cycles of platinum-based and non-platinum compound treatment [n = 8]; 3: non-squamous NSCLC, EGFR mutation, PR/SD after ≥3 and ≤ 6 months EGFR-tyrosine kinase inhibitor (TKI) treatment [n = 2]). Patients received intradermal BI1361849, local radiation (4 × 5 Gy), then BI1361849 until disease progression. Strata 1 and 3 also had maintenance pemetrexed or continued EGFR-TKI therapy, respectively. The primary endpoint was evaluation of safety; secondary objectives included assessment of clinical efficacy (every 6 weeks during treatment) and of immune response (on Days 1 [baseline], 19 and 61).
Results: Study treatment was well tolerated; injection site reactions and flu-like symptoms were the most common BI1361849-related adverse events. Three patients had grade 3 BI1361849-related adverse events (fatigue, pyrexia); there was one grade 3 radiation-related event (dysphagia). In comparison to baseline, immunomonitoring revealed increased BI1361849 antigen-specific immune responses in the majority of patients (84%), whereby antigen-specific antibody levels were increased in 80% and functional T cells in 40% of patients, and involvement of multiple antigen specificities was evident in 52% of patients. One patient had a partial response in combination with pemetrexed maintenance, and 46.2% achieved stable disease as best overall response. Best overall response was SD in 57.7% for target lesions.
Conclusion: The results support further investigation of mRNA-based immunotherapy in NSCLC including combinations with immune checkpoint inhibitors.
Trial registration: ClinicalTrials.gov identifier: NCT01915524.
Prostaglandin (PG) E2 (PGE2) plays a predominant role in promoting colorectal carcinogenesis. The biosynthesis of PGE2 is accomplished by conversion of the cyclooxygenase (COX) product PGH2 by several terminal prostaglandin E synthases (PGES). Among the known PGES isoforms, microsomal PGES type 1 (mPGES-1) and type 2 (mPGES-2) were found to be overexpressed in colorectal cancer (CRC); however, the role and regulation of these enzymes in this malignancy are not yet fully understood. Here, we report that the cyclopentenone prostaglandins (CyPGs) 15-deoxy-Δ12,14-PGJ2 and PGA2 downregulate mPGES-2 expression in the colorectal carcinoma cell lines Caco-2 and HCT 116 without affecting the expression of any other PGES or COX. Inhibition of mPGES-2 was subsequently followed by decreased microsomal PGES activity. These effects were mediated via modulation of the cellular thiol-disulfide redox status but did not involve activation of the peroxisome proliferator-activated receptor γ or PGD2 receptors. CyPGs had antiproliferative properties in vitro; however, this biological activity could not be directly attributed to decreased PGES activity because it could not be reversed by adding PGE2. Our data suggest that there is a feedback mechanism between PGE2 and CyPGs that implicates mPGES-2 as a new potential target for pharmacological intervention in CRC.
Background: Biotin, a water-soluble B vitamin, has demonstrable anti-inflammatory properties. A biotin-deficient diet induced a colitis-like phenotype in mice, alleviable by biotin substitution. Mice with dextran sulfate sodium (DSS)-induced colitis showed biotin deficiency and diminished levels of sodium-dependent multivitamin transporter, a protein involved in biotin absorption. Biotin substitution induced remission by reducing activation of NF-κB, a transcription factor involved in intestinal permeability and inflammatory bowel disease (IBD). We investigated for the first time a possible clinical role of biotin status in IBD. Methods: In a comparative, retrospective, cross-sectional study, serum samples of 138 patients with IBD (67 female; 72 Crohn’s disease (CD), 66 ulcerative colitis (UC)) aged 18–65 years and with a mean age (±SD) of 42.5 ± 14.3 years as well as 80 healthy blood donors (40 female; 40.0 ± 10.0 years; range 20–60 years) were analyzed. Inflammation was defined as hsCRP ≥5 mg/L, and to determine biotin status, serum 3-hydroxyisovaleryl carnitine (3HIVc) levels were measured by LC-MS/MS. Results: A total of 138 patients with IBD (67f; 72CD/66 UC; 42.5 ± 14.3 years) were enrolled: 83/138 had inflammation. Mean serum 3HIVc levels were significantly higher in IBD patients but unaffected by inflammation. Biotin deficiency (95th percentile of controls: >30 nmol/L 3HIVc) was significantly more common in IBD patients versus controls. Conclusion: High serum 3HIVc levels and biotin deficiency were associated with IBD but not inflammatory activity or disease type. Our findings suggest biotin may play a role as cause or effect in IBD pathogenesis. Routine assessment and supplementation of biotin may ameliorate IBD and support intestinal integrity.
Background: To assess late toxicity, quality of life and oncological outcome after consolidative whole abdominal radiotherapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high risk patients with advanced ovarian cancer FIGO stage III using IMRT (Intensity modulated radiation therapy).
Methods: The OVAR-IMRT-02 study is a multi-center single-arm phase-II-trial. Twenty patients with optimally debulked ovarian cancer stage FIGO III with complete remission after chemotherapy were treated with intensity modulated WART. A total dose of 30 Gy in 20 fractions was applied to the entire peritoneal cavity. Primary endpoint was treatment tolerability; secondary objectives were acute and chronic toxicities, quality of life, rates of therapy disruption/abortion, progression-free survival (PFS) and overall survival (OS).
Results: All patients completed treatment and 10/20 patients (50%) reached the final study follow-up of 36 months. Late side effects consisted of °1-°2 lower limb edema (44.5%), with one patient (5.6%) showing °3 edema. Three patients (16.7%) showed elevated gamma-Glutamyltransferase. There were no severe late side effects regarding
renal or hepatic function or any gastrointestinal toxicity greater than °2. During WART, mean global health status
decreased by 18.1 points (95%-CI: 7.1–29.0), but completely normalized after 6 months. The same trend was observed for the function scale scores. Kaplan-Meier-estimated 1-, 2- and 3-year PFS was 74, 51 and 40%, respectively. 1-, 2- and 3-year OS was 89, 83 and 83%, respectively.
Conclusions: Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late toxicity and minor impact on long-term quality of life. Together
with the promising results for PFS and OS, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer.
Trial registration: The study is registered with ClinicalTrials.gov (NCT01180504). Registered 12 August 2010 – retrospectively registered.