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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010; 20100921-20100925; Mannheim; DOCP1886 /20100916/
    Publication Date: 2010-09-17
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  88. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 20170524-20170527; Erfurt; DOC17hno212 /20170413/
    Publication Date: 2017-04-13
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; VOL: 13; DOC192 /20170426/
    Publication Date: 2017-04-26
    Description: Die Bestrahlung von Kopf-Hals-Tumore ist ein zentrales Element der Therapie. Für Zinkoxid-Nanopartikel konnte bereits in zahlreichen Studien eine tumorzellschädigende Wirkung nachgewiesen werden. Ziel unserer Untersuchungen war es daher zu evaluieren, ob Zinkoxid-Nanopartikel als Strahlensensitizer in der Therapie von Kopf-Hals-Tumoren nutzbar gemacht werden können. Dazu wurden Tumorzellen mit 0, 2, 4 oder 8 Gray bestrahlt, nachdem sie Zinkoxid-Nanopartikeln ausgesetzt waren (4h, 100 µg/ml). Im Anschluss wurde ein MTT Assay, das die metabolische Aktivität der Zellen nach Behandlung misst, durchgeführt und zusätzlich ein Koloniebildungstest, der eine Quantifizierung des klonogenen Überlebens der Tumorzellen erlaubt. Die Kombination aus einer Bestrahlung mit zwei bzw. vier Gray, entsprechend typischerweise in der Klinik applizierten Einzeldosen, und einer Behandlung von Tumorzellen mit 100 µg/ml Zinkoxid-Nanopartikeln führte zu einer deutlichen Reduktion der Zellviabilität verglichen mit Zellen, die nur bestrahlt wurden. Auch eine Reduktion der Koloniebildung nach Nanopartikelbehandlung zusätzlich zur Bestrahlung mit zwei oder vier Gray konnte nachgewiesen werden. Damit konnte gezeigt werden, dass eine Inkubation mit Zinkoxid-Nanopartikeln, den Bestrahlungserfolg in vitro - gemessen an klonogenem Überleben und Zellviabilität der Tumorzellen - verbessert.Die durchgeführten Untersuchungen belegen das Potential von Zinkoxid-Nanopartikeln zur Radiosensibilisierung von Tumorzellen.Unterstützt durch: Max-Planck Graduate Center MainzDer Erstautor gibt keinen Interessenkonflikt an.
    Keywords: ddc: 610
    Language: German
    Type: article
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  • 4
    Publication Date: 2018-06-08
    Description: Background Most patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival. Objective and design This observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age. Results 3119 patients were followed for a total of 24 475 years. Cumulative incidences at 75 years (risks) for colorectal cancer were 46%, 43% and 15% in path_ MLH1 , path_ MSH2 and path_ MSH6 carriers; for endometrial cancer 43%, 57% and 46%; for ovarian cancer 10%, 17% and 13%; for upper gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancers 21%, 10% and 7%; for urinary tract cancers 8%, 25% and 11%; for prostate cancer 17%, 32% and 18%; and for brain tumours 1%, 5% and 1%, respectively. Ovarian cancer occurred mainly premenopausally. By contrast, upper gastrointestinal, urinary tract and prostate cancers occurred predominantly at older ages. Overall 5-year survival for prostate cancer was 100%, urinary bladder 93%, ureter 85%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas 0%. Path_PMS2 carriers had lower risk for cancer. Conclusion Carriers of different path_MMR variants exhibit distinct patterns of cancer risk and survival as they age. Risk estimates for counselling and planning of surveillance and treatment should be tailored to each patient’s age, gender and path_MMR variant. We have updated our open-access website www.lscarisk.org to facilitate this.
    Keywords: Clinical trials (epidemiology), Open access, Gut
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 5
    Publication Date: 2018-04-12
    Description: We examine a static, spherically symmetric solution of the empty space field equations of general relativity with a non-orthogonal line element which gives rise to an opportunity that does not occur in the standard derivations of the Schwarzschild solution. In these derivations, convenient coordinate transformations and dynamical assumptions inevitably lead to the Schwarzschild solution. By relaxing these conditions, a new solution possibility arises and the resulting formalism embraces the Schwarzschild solution as a special case. The new solution avoids the coordinate singularity associated with the Schwarzschild solution and is achieved by obtaining a more suitable coordinate chart. The solution embodies two arbitrary constants, one of which can be identified as the Newtonian gravitational potential using the weak field limit. The additional arbitrary constant gives rise to a situation that allows for generalizations of the Eddington–Finkelstein transformation and the Kruskal–Szekeres coordinates.
    Keywords: relativity
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 6
    Publication Date: 2018-12-04
    Description: Saccharomyces cerevisiae target of rapamycin (TOR) complex 2 (TORC2) is an essential regulator of plasma membrane lipid and protein homeostasis. How TORC2 activity is modulated in response to changes in the status of the cell envelope is unclear. Here we document that TORC2 subunit Avo2 is a direct target of Slt2, the mitogen-activated protein kinase (MAPK) of the cell wall integrity pathway. Activation of Slt2 by overexpression of a constitutively active allele of an upstream Slt2 activator (Pkc1) or by auxin-induced degradation of a negative Slt2 regulator (Sln1) caused hyperphosphorylation of Avo2 at its MAPK phosphoacceptor sites in a Slt2-dependent manner and diminished TORC2-mediated phosphorylation of its major downstream effector, protein kinase Ypk1. Deletion of Avo2 or expression of a phosphomimetic Avo2 allele rendered cells sensitive to two stresses (myriocin treatment and elevated exogenous acetic acid) that the cell requires Ypk1 activation by TORC2 to survive. Thus, Avo2 is necessary for optimal TORC2 activity, and Slt2-mediated phosphorylation of Avo2 down-regulates TORC2 signaling. Compared with wild-type Avo2, phosphomimetic Avo2 shows significant displacement from the plasma membrane, suggesting that Slt2 inhibits TORC2 by promoting Avo2 dissociation. Our findings are the first demonstration that TORC2 function is regulated by MAPK-mediated phosphorylation.
    Print ISSN: 0890-9369
    Topics: Biology
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  • 7
    Publication Date: 2018-03-12
    Description: Objective To determine the feasibility of a randomised controlled trial of an internet intervention for low back pain (LBP) using three arms: (1) usual care, (2) usual care plus an internet intervention or (3) usual care plus an internet intervention with additional physiotherapist telephone support. Design and setting A three-armed randomised controlled feasibility trial conducted in 12 general practices in England. Participants Primary care patients aged over 18 years, with current LBP, access to the internet and without indicators of serious spinal pathology or systemic illness. Interventions The ‘SupportBack’ internet intervention delivers a 6-week, tailored programme, focused on graded goal setting, self-monitoring and provision of tailored feedback to encourage physical activity. Additional physiotherapist telephone support consisted of three brief telephone calls over a 4-week period, to address any concerns and provide reassurance. Outcomes The primary outcomes were the feasibility of the trial design including recruitment, adherence and retention at follow-up. Secondary descriptive and exploratory analyses were conducted on clinical outcomes including LBP-related disability at 3 months follow-up. Results Primary outcomes: 87 patients with LBP were recruited (target 60–90) over 6 months, and there were 3 withdrawals. Adherence to the intervention was higher in the physiotherapist-supported arm, compared with the stand-alone internet intervention. Trial physiotherapists adhered to the support protocol. Overall follow-up rate on key clinical outcomes at 3 months follow-up was 84%. Conclusions This study demonstrated the feasibility of a future definitive randomised controlled trial to determine the clinical and cost-effectiveness of the SupportBack intervention in primary care patients with LBP. Trial registration number ISRCTN31034004 ; Results.
    Keywords: Open access, Rheumatology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 8
    Publication Date: 2018-01-05
    Description: Lymphodepletion chemotherapy with CD19-targeted chimeric antigen receptor–modified T (CAR-T)-cell immunotherapy is a novel treatment for refractory or relapsed B-cell malignancies. Infectious complications of this approach have not been systematically studied. We evaluated infections occurring between days 0 to 90 in 133 patients treated with CD19 CAR-T cells in a phase 1/2 study. We used Poisson and Cox regression to evaluate pre- and posttreatment risk factors for infection, respectively. The cohort included patients with acute lymphoblastic leukemia (ALL; n = 47), chronic lymphocytic leukemia (n = 24), and non-Hodgkin lymphoma (n = 62). There were 43 infections in 30 of 133 patients (23%) within 28 days after CAR–T-cell infusion with an infection density of 1.19 infections for every 100 days at risk. There was a lower infection density of 0.67 between days 29 and 90 ( P = .02). The first infection occurred a median of 6 days after CAR–T-cell infusion. Six patients (5%) developed invasive fungal infections and 5 patients (4%) had life-threatening or fatal infections. Patients with ALL, ≥4 prior antitumor regimens, and receipt of the highest CAR–T-cell dose (2 x 10 7 cells per kg) had a higher infection density within 28 days in an adjusted model of baseline characteristics. Cytokine release syndrome (CRS) severity was the only factor after CAR–T-cell infusion associated with infection in a multivariable analysis. The incidence of infections was comparable to observations from clinical trials of salvage chemoimmunotherapies in similar patients. This trial was registered at www.clinicaltrials.gov as #NCT01865617.
    Keywords: Immunobiology and Immunotherapy, Free Research Articles, Clinical Trials and Observations
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 9
    ISSN: 1573-6784
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary A simple standard-dilution method which obviates routine use of viable cell counts, feeder layers and time-consuming scale-up procedures is described. This method can be used to clone monoclonal antibody-producing hybridomas 9–14 days post-fusion. Each cloning cycle takes 5 min. Approximately 60% of the positive, monoclonal antibody-producing hybridomas were successfully cloned and established.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0044-2275
    Keywords: Key words.Plastic regimes, kinematically determined, granular materials, optimal systems, exact solutions.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics , Physics
    Notes: Abstract. For axially symmetric flow of dilatant granular materials, the velocity equations uncouple from the stress equations in certain plastic regimes, and assuming dilatant double shearing a set of three first order partial differential equations are obtained. These equations turn out to be deceptive because although simple in appearance, the determination of simple exact solutions is non-trivial. Here we show that all the known functional forms of existing solutions also arise systematically by consideration of the "optimal systems" of the classical Lie symmetries which indicates that any further solution types most likely arise from non-classical symmetries. For one of the known families we present a special case which admits a particularly simple closed form expression, which has not been previously given in the literature. For this particular special case the integral curves (streamlines) can be readily obtained as well as a simple analytical "approximation" for the particle paths. The streamlines and the validity of the analytical approximation are shown graphically.
    Type of Medium: Electronic Resource
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