Refine
Year of publication
Document Type
- Article (892)
- Preprint (801)
- Part of Periodical (21)
- Conference Proceeding (9)
- Working Paper (8)
- Review (3)
- Book (1)
- Part of a Book (1)
- Contribution to a Periodical (1)
- Report (1)
Language
- English (1714)
- German (23)
- Multiple languages (1)
Has Fulltext
- yes (1738)
Is part of the Bibliography
- no (1738)
Keywords
- Heavy Ion Experiments (22)
- Hadron-Hadron Scattering (13)
- Hadron-Hadron scattering (experiments) (12)
- LHC (9)
- Jets (7)
- Heavy-ion collision (6)
- Heavy-ion collisions (5)
- ALICE experiment (4)
- Collective Flow (4)
- Heavy Ions (4)
- Heavy Quark Production (4)
- Inverse kinematics (4)
- Quark-Gluon Plasma (4)
- Quasi-free scattering (4)
- immunotherapy (4)
- ALICE (3)
- Breast cancer (3)
- COVID-19 (3)
- Diffraction (3)
- Elastic scattering (3)
- Jets and Jet Substructure (3)
- Nuclear reactions (3)
- Polarization (3)
- Quarkonium (3)
- Radiotherapy (3)
- Spectroscopic factors (3)
- acute myeloid leukemia (3)
- breast cancer (3)
- cirrhosis (3)
- cytokine-induced killer cells (3)
- global change (3)
- portal hypertension (3)
- pp collisions (3)
- screening (3)
- 140Ce (2)
- AML (2)
- Abdominal aortic aneurysm (2)
- Abdominelles Aortenaneurysma (2)
- Accelerators & Beams (2)
- Acute myeloid leukemia (2)
- Adaptive Erwartung (2)
- Aspergillus (2)
- Atomic, Molecular & Optical (2)
- Atrial fibrillation (2)
- Außenwirtschaftliches Gleichgewicht (2)
- Beam Energy Scan (2)
- Beauty production (2)
- Bipolar disorder (2)
- CIK cells (2)
- Charm physics (2)
- Chiral Magnetic Effect (2)
- Cirrhosis (2)
- Clinical Global Impression of Change (2)
- Collectivity (2)
- Community ecology (2)
- Correlation (2)
- Diagnostik (2)
- Dravet syndrome (2)
- Dynamisches Gleichgewicht (2)
- Ecological networks (2)
- Elliptic flow (2)
- Embryos (2)
- Endovascular repair (2)
- Endovaskuläre Behandlung (2)
- Erwartungsbildung (2)
- Ewing sarcoma (2)
- Experimental nuclear physics (2)
- Experimental particle physics (2)
- Früherkennung (2)
- Heavy-Ion Collision (2)
- Kalman filter (2)
- Klinische Ergebnisse (2)
- Konjunktur (2)
- Leistungsbilanz (2)
- Lepton-Nucleon Scattering (experiments) (2)
- Liver diseases (2)
- MRI (2)
- Mammakarzinom (2)
- NK cells (2)
- NK-92 (2)
- Nachsorge (2)
- Neutropenia (2)
- News and Business Cycles (2)
- Non-small cell lung cancer (2)
- Offene Versorgung (2)
- Offene Volkswirtschaft (2)
- Open Economy DSGE Models (2)
- Open repair (2)
- Outcome (2)
- PTEN (2)
- Particle Correlations and Fluctuations (2)
- Particle and resonance production (2)
- Particle correlations and fluctuations (2)
- Pb–Pb collisions (2)
- Pneumonia (2)
- Predictive markers (2)
- Produktivität (2)
- Psychiatric disorders (2)
- Pulmonary embolism (2)
- QCD (2)
- Quark Gluon Plasma (2)
- RHIC (2)
- Radiative capture (2)
- Real-time Data (2)
- Register (2)
- Registry (2)
- Relativistic heavy-ion collisions (2)
- Richtlinie (2)
- STAR (2)
- Shear viscosity (2)
- Shell model (2)
- Single electrons (2)
- Single-particle states (2)
- Suicide (2)
- Surgery (2)
- Surgical oncology (2)
- Treatment outcome (2)
- Trend Growth (2)
- USA (2)
- Umfrage (2)
- Wirtschaftswachstum (2)
- X-ray crystallography (2)
- Zahlungsbilanzausgleich (2)
- Zahlungsbilanzungleichgewicht (2)
- allogeneic stem cell transplantation (2)
- biodiversity protection (2)
- boryl anions (2)
- childhood acute myeloid leukemia (2)
- chimeric antigen receptor (2)
- conservation funding (2)
- conservation planning (2)
- convulsive seizures (2)
- decision making (2)
- dentate gyrus (2)
- diagnosis (2)
- elderly (2)
- fenfluramine (2)
- follow‑up (2)
- guideline (2)
- homeostatic plasticity (2)
- household finance (2)
- liver transplantation (2)
- lung cancer (2)
- meningioma (2)
- post-2020 biodiversity targets (2)
- real-world (2)
- refugees (2)
- relapse (2)
- salvage therapy (2)
- soft tissue sarcoma (2)
- spine head (2)
- stability (2)
- status epilepticus (2)
- storage rings (2)
- strategic site selection (2)
- synaptic plasticity (2)
- synaptopodin (2)
- tumor necrosis factor (2)
- 2-aminobenzimidazole (1)
- 3D tissue models (1)
- 5 lipoxygenase (1)
- 9-borafluorene (1)
- 900 GeV (1)
- AB-serum (1)
- ABC transporters (1)
- ABCB1 (1)
- ABCC1 (1)
- ABCG2 (1)
- ACLF (1)
- ACURATE neo (1)
- ADGRE1 (1)
- ADHD (1)
- AGN host galaxies (1)
- AIS (1)
- ALICE detector (1)
- ALL (1)
- APRI (1)
- ARDS (1)
- ATM (1)
- ATPases (1)
- Abdominal infections (1)
- Accelerators & storage rings (1)
- Acquired drug resistance (1)
- Active middle ear implants (1)
- Acute calcolous cholecystitis (1)
- Acute coronary syndrome (1)
- Acute-on-chronic subdural hematoma (1)
- Advanced biliary tract cancer (1)
- Afrotheria (1)
- Allogeneic hematopoietic stem (1)
- Amino acid analysis (1)
- Analysis and statistical methods (1)
- Angiogenesis (1)
- Animal flight (1)
- Animal phylogenetics (1)
- Anti-nuclei (1)
- Antibiotic (1)
- Antibiotic steward-ship (1)
- Antibiotics (1)
- Antiretroviral therapy (1)
- Aortic valve replacement (1)
- Arteria ophthalmica (1)
- Artesunate (1)
- Artificial Intelligence (1)
- Aspergillus fumigatus (1)
- Aspergillus species (1)
- Atomic & molecular beams (1)
- Atomic and Molecular Physics (1)
- Atoms (1)
- Auditory system (1)
- Autorschaft (1)
- B-slope (1)
- BI1361849 (1)
- BRAF (1)
- BRAF mutation (1)
- BRCA1 (1)
- BRCA2 (1)
- BTC (1)
- Beam energy scan (1)
- Beam loss (1)
- Bevacizumab (1)
- Big Data (1)
- Biliary tree stones (1)
- Biodiversity Data (1)
- Bioinformatics (1)
- Biological (1)
- Biological heart valves (1)
- Biomarker (1)
- Biomarkers (1)
- Biomonitoring (1)
- Bioprosthesis (1)
- Bird flight (1)
- Blindness (1)
- Blood plasma (1)
- Bloodstream infections (1)
- Bone conduction devices (1)
- Bone metastases (1)
- Boosted Jets (1)
- Botanical Collections (1)
- Business strategy in drug development (1)
- C3M (1)
- C4M (1)
- CAKUT (1)
- CAR (1)
- CBA (1)
- CD3/CD19 depletion (1)
- CD36 (1)
- CDI (1)
- CHRNA10 (1)
- CHRNA7 (1)
- CHRNA9 (1)
- CQL (1)
- CRVO (1)
- CTLA-4 (1)
- CV9202 (1)
- CVID (1)
- Caccoleptus (Bicaccoleptus) kacka, Nearctic region (1)
- Calorimeters (1)
- Cancer (1)
- Cancer detection (1)
- Cancer treatment (1)
- Candida (1)
- Canonical suppression (1)
- Canopy height model (1)
- Capecitabine (1)
- Cardiac troponin (1)
- Catheter ablation (1)
- Cell membranes (1)
- Cell proliferation (1)
- Cell signalling (1)
- Cell-to-Cell Spread (1)
- Central Europe (1)
- Centrality Class (1)
- Centrality Selection (1)
- Charge fluctuations (1)
- Charge-transfer collisions (1)
- Charged-particle multiplicity (1)
- Charm quark spatial diffusion coefficient (1)
- Charmonia (1)
- Chemotherapy (1)
- Cherenkov counter: lead-glass (1)
- Chickens (1)
- Chimerism (1)
- Chiral magnetic effect (1)
- Cholecystectomy (1)
- Circadian (1)
- Circular accelerators (1)
- Cleanliness level (1)
- Climate-change ecology (1)
- Clinical study (1)
- Clinical trial (1)
- Closure (1)
- Coalescence (1)
- Cohort studies (1)
- Coincidence measurement (1)
- Cold nuclear matter effects (1)
- Collective Flow, (1)
- Colon capsule endoscopy (1)
- Colorectal cancer (1)
- Combined immune checkpoint blockade (1)
- Compact astrophysical objects (1)
- Comparison with QCD (1)
- Complementation rate (1)
- Computer-aided drug design (1)
- Congenital anomalies (1)
- Consensus (1)
- Consensus statement (1)
- Conservation (1)
- Coronary heart disease (1)
- Couch tracking (1)
- Covid-19 (1)
- Critical care (1)
- Critical point (1)
- Cross sections (1)
- Cryoballoon (1)
- Cryoelectron microscopy (1)
- Cryoelectron tomography (1)
- Cultural Influences on Economic Behavior (1)
- Culture positive (1)
- Current Account (1)
- DNA sequence analysis (1)
- DNA-PK (1)
- DNA/LNA mixmers (1)
- DST (1)
- Data processing methods (1)
- Data sharing (1)
- De-isolation (1)
- Death rates (1)
- Dermis (1)
- Deuteron production (1)
- Di-hadron correlations (1)
- Diagnosis (1)
- Diagnostic differentiation (1)
- Diagnostic markers (1)
- Digestive system procedures (1)
- Digital (1)
- Digital breast tomosynthesis (DBT) (1)
- Digital mammography (1)
- Digitization (1)
- Direct nuclear reactions (1)
- Direct oral anticoagulation (1)
- Direct reactions (1)
- Drug susceptibility testing (1)
- Drug therapy (1)
- EGFR (1)
- EGFR inhibitor (1)
- EMR1 (1)
- EPR (1)
- ERBB2 (1)
- ERBB2 (HER2/neu) (1)
- ESBL (1)
- Earth sciences (1)
- Ecological modelling (1)
- Ecology (1)
- Economics (1)
- Ecosystem ecology (1)
- Eicosanoids (1)
- Electromagnetic transitions (1)
- Electron-pion identification (1)
- Electronic cigarettes (1)
- Electronic transitions (1)
- Electroweak interaction (1)
- Elephants (1)
- Ellenberg indicator values (1)
- Endocrinology (1)
- Endoscopic ultrasound (1)
- Endoscopy (1)
- Enterobacteriaceae (1)
- Epstein-Barr virus (1)
- Equity (1)
- Esophagectomy (1)
- Europe (1)
- European Dry Grassland Group (1)
- European Society for Immunodeficiencies (ESID) (1)
- Eutheria (1)
- Evidence-based guidelines (1)
- Evolutionary biology (1)
- Exosomes (1)
- Extended donor criteria (1)
- F4/80 (1)
- F508del homozygous (1)
- FDG-PET/CT (1)
- FHIR (1)
- FHIR Search (1)
- FIB-4 (1)
- Falciparum (1)
- Fast Healthcare Interoperability Resources (1)
- Fatty acids (1)
- Fatty liver (1)
- Fc receptor (1)
- Feathers (1)
- Femtoscopy (1)
- Festuco-Brometea (1)
- Fevers (1)
- Fibre/foam sandwich radiator (1)
- Fibroblast growth factor (1)
- Fibroblasts (1)
- Filler (1)
- Filovirus cell entry; attachment factors redundancy; SH-SY5Y cell line; host–pathogen interactions (1)
- Fistula (1)
- Flow (1)
- Fmoc solid phase peptide synthesis (1)
- Follow-up (1)
- Forward physics (1)
- Fusarium (1)
- GWAS (1)
- Gadobutrol (1)
- Gadopentate dimeglumine (1)
- Galaxies and clusters (1)
- Galietalia veri (1)
- Gallbladder percutaneous drainage (1)
- Gene expression (1)
- Genetics (1)
- Genetics research (1)
- German PID-NET registry (1)
- Gimbaled tracking (1)
- Glabella (1)
- Glioblastoma (1)
- Glioblastoma survival (1)
- Gouvernementalität (1)
- Gram negative bacteria (1)
- Green fluorescent protein (1)
- Groomed jet radius (1)
- Guadeloupe Archipelago (1)
- Guanine nucleotide exchange factors (1)
- Guanosine triphosphatase (1)
- Guidelines (1)
- HADES (1)
- HBT (1)
- HBV (1)
- HER2-positive (1)
- HER2/neu (1)
- HIPPO signalling (1)
- HIV (1)
- HL7 FHIR (1)
- HNSCC (1)
- Hadron production (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Hadronization (1)
- Haematopoietic stem cells (1)
- Hand-foot syndrome (1)
- Hard Scattering (1)
- Head and neck cancer (1)
- Head neck cancer (1)
- Health economics (1)
- Health policy (1)
- Heavy Ion Experiment (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ion collisions (1)
- Heavy ion storage ring (1)
- Heavy ions (1)
- Heavy-flavor decay electron (1)
- Heavy-flavour decay muons (1)
- Heavy-flavour production (1)
- Heavy-ion (1)
- Hegemonie (1)
- Hematopoietic stem cell transplantation (1)
- Hepatitis c (1)
- Hepatocellular carcinoma (1)
- Herbaria (1)
- Hereditary breast cancer (1)
- Hereditary ovarian cancer (1)
- Hif-1 alpha (1)
- Hif1α (1)
- High-energy astrophysics (1)
- High-energy neutron detection (1)
- Higher moments (1)
- Hospitals (1)
- Household Finance (1)
- Household Portfolios (1)
- Hsp70 (1)
- Human behaviour (1)
- Hypofractionated radiotherapy (1)
- Hyraxes (1)
- ICU (1)
- IHC (1)
- IL-15 (1)
- IL-21 (1)
- IL-6 (1)
- IR (1)
- ISS (1)
- IgG substitution therapy (1)
- Immune response (1)
- Immunity (1)
- Immunogenetics (1)
- Immunology (1)
- Immunology and Microbiology Section (1)
- Immunomonitoring (1)
- Immunotherapy (1)
- In vitro (1)
- Inclusive spectra (1)
- Incomplete colonoscopy (1)
- Induction chemotherapy (1)
- Induction therapy (1)
- Infection (1)
- Inflammation (1)
- Influenza (1)
- Intensity interferometry (1)
- Intensive care units (1)
- Interference fragmentation function (1)
- Interleukin-17A (1)
- Intra-abdominal infection (1)
- Invariant Mass Distribution (1)
- Ionisation energy loss (1)
- Ions (1)
- Ipilimumab (1)
- Isoscalar giant resonances (1)
- J/ψ suppression (1)
- Jet Physics (1)
- Jet Substructure (1)
- Jet substructure (1)
- KLK5 (1)
- KOOS IV (1)
- KPS (1)
- Kidney diseases (1)
- Koelerio-Corynephoretea (1)
- LCH (1)
- Langerhans cell histiocytosis (1)
- Laparostomy (1)
- Library screening (1)
- Lifestyle (1)
- Literarischer Stil (1)
- Literaturwissenschaft (1)
- Liver (1)
- Liver cancer (1)
- Low & intermediate-energy accelerators (1)
- Low volume prep (1)
- Low-molecular-weight heparin (1)
- Luciferase (1)
- M. Intracellulare (1)
- M. avium (1)
- M. avium complex (1)
- M. chimaera (1)
- MACS (1)
- MCP-1 (1)
- MGMT (1)
- MLC tracking (1)
- MLL (1)
- MMP9 (1)
- MRP4 (1)
- MYC (1)
- Machine learning (1)
- Macrotomini (1)
- Magnetic resonance (1)
- Malaria (1)
- Mammalian genomics (1)
- Mammals (1)
- Material budget (1)
- Mechanisms of disease (1)
- Medical imaging (1)
- Melanoma (1)
- Menthol (1)
- Mesh (1)
- Metabolism (1)
- Methicillin-resistant Staphylococcus aureus (1)
- MicroRNAs (1)
- Microscopy (1)
- Mid-rapidity (1)
- Minimal residual disease (1)
- Minimum Bias (1)
- Mitoxantrone (1)
- Mixed hearing loss (1)
- Models & methods for nuclear reactions (1)
- Molecular diagnostic testing (1)
- Molecular medicine (1)
- Molecular neuroscience (1)
- Monitoring (1)
- Monte Carlo (1)
- Moviprep (1)
- Multi-Parton Interactions (1)
- Multi-neutron detection (1)
- Multi-stakeholder approach (1)
- Multi-strange baryons (1)
- Multi-wire proportional drift chamber (1)
- Multidrug-resistant organisms (1)
- Multimodal imaging (1)
- Multiomics (1)
- Multiple parton interactions (1)
- Multivariate analysis (1)
- Mutation databases (1)
- Mycobacteria (1)
- Mycobacterium avium complex (1)
- Myocardial infarction (1)
- NADPH oxidase (1)
- NAFLD (1)
- NOTCH (1)
- NSCLC (1)
- NTM (1)
- Neoadjuvant therapy (1)
- Neoliberalismus (1)
- Neolithic (1)
- Net-charge correlations (1)
- Net-charge fluctuations (1)
- Network analysis (1)
- Neural network (1)
- Neutron physics (1)
- Nicotine (1)
- Nivolumab (1)
- Non-trauma (1)
- Non-tuberculous mycobacteria (1)
- Nonflow (1)
- Noninferiority (1)
- Nontuberculous mycobacteria (1)
- Nox1 (1)
- NoxO1 (1)
- Nuclear astrophysics (1)
- Nuclear modification factor (1)
- Nuclear physics of explosive environments (1)
- Nuclear resonance fluorescence (1)
- Nuclear structure & decays (1)
- Nucleon induced nuclear reactions (1)
- Nutrition (1)
- Obesity (1)
- Occlusion (1)
- Omics (1)
- Oncogenes (1)
- Oncology (1)
- One-nucleon removal (1)
- Open abdomen (1)
- Open pulmonary tuberculosis (1)
- Ophthalmoplegia (1)
- Opportunistic infections (1)
- Orbital electron capture (1)
- Organ allocation (1)
- Organ motion (1)
- Osteoporosis (1)
- Oxaliplatin (1)
- P2X7 receptor (1)
- PD-1 (1)
- PDGFRβ (1)
- PELDOR (1)
- PGE2 (1)
- PI3K (1)
- PID prevalence (1)
- PLX4032 (1)
- PLX4720 (1)
- PYTHIA (1)
- Pancreas transplantation (1)
- Pancreatitis (1)
- Pandemic (1)
- Panel testing (1)
- Parainfluenza (1)
- Particle and Resonance Production (1)
- Particle production (1)
- Pathological complete response (1)
- Pathology (1)
- Patient safety (1)
- Patterns of care (1)
- Pb isotopes (1)
- Pb–Pb (1)
- Performance of High Energy Physics Detectors (1)
- Peritonitis (1)
- Personalized medicine (1)
- Perturbative methods (1)
- Phospho-soda (1)
- Phosphorylation (1)
- Photon counting (1)
- PillCamColon2 (1)
- Plant sciences (1)
- Plasmodium (1)
- Plastic scintillator array (1)
- Platelets (1)
- Polyps (1)
- Population-based screening (1)
- Portal veins (1)
- Post-Neoliberalismus (1)
- Poverty (1)
- Pre-emptive immunotherapy (1)
- Preoperative radiochemotherapy (1)
- Production Cross Section (1)
- Prognostic models (1)
- Properties of Hadrons (1)
- Prostaglandin (1)
- Prostate cancer (1)
- Protease inhibitor therapy (1)
- Proton-proton collisions (1)
- Proton–proton (1)
- Proton–proton collisions (1)
- Pseudo HE-images (1)
- Psoriasis vulgaris (1)
- Psychiatry (1)
- Pygmy Dipole Resonance (1)
- Pyogenic spondylodiscitis (1)
- QGP (1)
- Quark Deconfinement (1)
- Quark Production (1)
- Quark gluon plasma (1)
- Quark–gluon plasma (1)
- Quasi-particle phonon model (1)
- Quinine (1)
- RMS (1)
- RNA induced silencing complex (1)
- RNA recognition (1)
- RNA, long noncoding (1)
- Radiation detectors (1)
- Radio continuum emission (1)
- Radio jets (1)
- Radiofrequency (1)
- Raman spectroscopy (1)
- Rapidity Range (1)
- Re-exploration (1)
- Reactions with relativistic radioactive beams (1)
- Reactive oxygen species (1)
- Recall rate (1)
- Rectal cancer (1)
- Red blood cell transfusion (1)
- Registries (1)
- Rehabilitation (1)
- Rehospitalization (1)
- Reintervention (1)
- Rejection (1)
- Relativistic heavy ion physics (1)
- Renal lesions (1)
- Research Infrastructure (1)
- Resolution Parameter (1)
- Resonance reactions (1)
- Resonances (1)
- Respiratory infections (1)
- Respiratory syncytial virus (1)
- Retinal diseases (1)
- Rhaphipodini (1)
- Risk factor (1)
- Robotic tracking (1)
- Rome (1)
- SARS-CoV-2 (1)
- SCCHN (1)
- SD-OCT (1)
- SKALE score (1)
- SLC20A1 (1)
- SMAD (1)
- SPSS (1)
- SR-BI (1)
- STAMPE2 (1)
- SVR (1)
- Salivary gland carcinoma (1)
- Scattering of atoms, molecules, clusters & ions (1)
- Scattering theory (1)
- Seasonal variation (1)
- Second Punic War (1)
- Seed beetles (1)
- Seizure (1)
- Self-renewal (1)
- Semantics (1)
- Sequence alignment (1)
- Severe malaria (1)
- Single muons (1)
- Single particle decay spectroscopy (1)
- Small molecules (1)
- Social determinants (1)
- SoftDrop (1)
- Solar insolation (1)
- Sorafenib (1)
- Spectroscopic factors & electromagnetic moments (1)
- Spin alignment (1)
- Spine care (1)
- Splitting function (1)
- Sputum smear-negative (1)
- Standardization (1)
- Status epilepticus (1)
- Stenotrophomonas maltophilia (1)
- Stentoplasty (1)
- Storage ring (1)
- Strangeness enhancement (1)
- Sunlight (1)
- Superinfection (1)
- Supermassive black holes (1)
- Superoxide (1)
- Surgical risk (1)
- Survival (1)
- Survival analysis (1)
- Synthetic (1)
- Systematic Uncertainty (1)
- TAVR (1)
- TB-therapy (1)
- TEMPO (1)
- TGFB-induced factor homeobox 1 (1)
- TGFβ (1)
- TGIF (1)
- TGR(mREN2)27 (1)
- TOR signalling (1)
- TR (1)
- Tailored medicine (1)
- Taxonomy (1)
- Technical data (1)
- Technique (1)
- Temozolomide (1)
- Therapeutic anticoagulation (1)
- Thermal model (1)
- Thoracic trauma (1)
- Thrombosis (1)
- Thromboxane (1)
- Time Projection Chamber (1)
- Timing (1)
- Tracking (1)
- Transcriptome analysis (1)
- Transition radiation detector (1)
- Transverse momentum (1)
- Transversity (1)
- Trauma (1)
- Treatment (1)
- Trigger (1)
- Triple negative (1)
- Two body weak decay (1)
- Type 2 diabetes (1)
- UAV (1)
- USP28 (1)
- Upper respiratory tract infection (1)
- Uveal melanoma (1)
- VEGF (1)
- VEGFR (1)
- VEGFR-2 (1)
- VEGFR-3 (1)
- VRE (1)
- Vascular emergencies (1)
- Vector Boson Production (1)
- Veins (1)
- Vemurafenib (1)
- Vertebral augmentation (1)
- Vertebral body stenting (1)
- Vertebral fracture (1)
- Very long baseline interferometry (1)
- Vesicles (1)
- Vincristine (1)
- Vitreous samples (1)
- Wang resin (1)
- Western Mediterranean (1)
- Western blot (1)
- Western diet (1)
- WoMo score (1)
- X-rays (1)
- Xenon-based gas mixture (1)
- acneiform skin toxicity (1)
- acoustic radiation force impulse imaging (1)
- acute decompensation (1)
- acute leukemia (1)
- acute-on-chronic liver failure (1)
- adaptive cardiac remodelling (1)
- adenocarcinoma (1)
- adjuvant chemotherapy (1)
- age (1)
- age-related macular degeneration (1)
- aging (1)
- alleles (1)
- alternative oxidase (1)
- amphiregulin (1)
- anaemia (1)
- anaesthesia in orthopaedics (1)
- anaesthetics (1)
- angiogenesis (1)
- angiopoietin-2 (1)
- anterior chamber depth changes (1)
- antibiotic therapy (1)
- anticonvulsants (1)
- antiepileptic drugs (1)
- antifungal activity (1)
- antimicrobial stewardship (1)
- antiviral therapy (1)
- aortic stenosis (1)
- argonaute protein (1)
- artifacts (1)
- ascites (1)
- astrocyte heterogeneity (1)
- atherosclerosis (1)
- attention-deficit/hyperactivity disorder (ADHD) (1)
- autism spectrum disorder (1)
- autistic disorder (1)
- axions (1)
- beetle species (1)
- biogeographic legaciese (1)
- bioindication (1)
- biological maturation (1)
- bipolar disorder (1)
- bladder cancer (1)
- bladder exstrophy-epispadias complex (1)
- bone marrow metastasis (1)
- bone metastasis (1)
- boron (1)
- bryophyte (1)
- c-kit (1)
- cPLA2 (1)
- calcium-independent phospholipase A2β (1)
- calorimeter: electromagnetic (1)
- cancer (1)
- cancer immunotherapy (1)
- capture (1)
- carbapenem resistance (1)
- cardiac ischaemia‐reperfusion (1)
- cardiac magnetic resonance (1)
- cataract surgery (1)
- cell therapy (1)
- cell transplantation (1)
- cellular therapy (1)
- cerebral sinus and vein thrombosis (CVT) (1)
- cerium (1)
- chemiluminescence (1)
- child (1)
- children and adolescents (1)
- chromosomal translocations (1)
- chronic viral hepatitis (1)
- cleavage of large RNA molecules (1)
- cleavage site selection (1)
- cloacal malformation (1)
- cognitive decline (1)
- collagen degradation marker (1)
- colorectal cancer (1)
- computed tomography (1)
- cone-beam computed tomography (CBCT) (1)
- consensus data set (1)
- conservation (1)
- copy number polymorphism (1)
- coronary disease (1)
- coumarin-4-ylmethyl (1)
- cross-section (1)
- cryo-EM (1)
- cryopreservation (1)
- cyclosporin A (1)
- cystic fibrosis (1)
- cytarabine dose (1)
- cytokine (1)
- cytotoxic T cells (1)
- cytotoxicity (1)
- dE/dx (1)
- dark matter experiments (1)
- data quality (1)
- decompressive craniectomy (1)
- depression (1)
- detector (1)
- dexamethasone (1)
- diabetic macular edema (1)
- disease prevalence (1)
- disease progression (1)
- distributed analysis (1)
- domestication (1)
- drone (1)
- dye labeling (1)
- dysphagia (1)
- early recognition (1)
- ectosomes (1)
- education (1)
- effective lens position (1)
- elderly patients (1)
- electroencephalography (EEG) (1)
- electromagnetic navigation bronchoscopy (EMN, ENB) (1)
- electron transport chain (1)
- electronics: readout (1)
- energy-dispersive x-ray spectroscopy (1)
- epigenomics (1)
- epilepsy (1)
- epiregulin (1)
- eutrophication (1)
- evolution (1)
- ex vivo expansion (1)
- excitation (1)
- exhaustion (1)
- exosomes (1)
- experimental results (1)
- extracellular vesicles (1)
- extraskeletal (1)
- f-MLF (1)
- facial nerve functional outcome (1)
- feasibility study (1)
- federated feasibility queries (1)
- fibre: optical (1)
- fibrotest (1)
- financial literacy (1)
- fine spatial resolution remote sensing (1)
- fluocinolone acetonide (1)
- fluorescence in situ hybridization (FISH) (1)
- flurbiprofen (1)
- forest classification (1)
- forest functional similarity (1)
- formylation (1)
- fresh frozen plasma (1)
- functional genetics (1)
- functional outcome (1)
- fungal sinusitis (1)
- gap junction protein alpha 4-genotype (1)
- gene expression (1)
- gene flow (1)
- genes (1)
- genes for longevity (1)
- genetic generalized epilepsy (1)
- genetic phenotypes (1)
- genetics (1)
- genome (1)
- genotype (1)
- genotype determination (1)
- geriatric medicine (1)
- germ cell tumors (1)
- glioblastoma (1)
- glioblastoma survival (1)
- glioma microenvironment (1)
- growth inhibition (1)
- guanidine analogs (1)
- guidelines (1)
- habitat destruction (1)
- health data (1)
- hearing nerve (1)
- heavy ion experiments (1)
- heavy-ion collisions (1)
- hepatic encephalopathy (1)
- hepatitis c (1)
- high-dose chemotherapy (1)
- highly-charged ions (1)
- histology (1)
- host plants (1)
- human natural killer cell (1)
- hypertension and anti-hypertensive treatment (1)
- hypertension, pulmonary (1)
- immune checkpoint blockade (1)
- immune infiltration (1)
- immune therapy (1)
- immunity (1)
- immunocytochemistry (1)
- immunohistochemistry (1)
- immunosuppressive agent (1)
- improvement in quality of life (1)
- in silico simulation (1)
- infection control (1)
- inflammasome (1)
- inflammation (1)
- inflammatory markers (1)
- interferon regulatory factor 9 (IRF9) (1)
- interleukin-1β (1)
- interoperability (1)
- intracerebral hemorrhage (ICH) (1)
- invasive fungal infection (1)
- kidney formation (1)
- kidney function (1)
- lamotrigine (1)
- land use (1)
- lapatinib (1)
- levetiracetam (1)
- lichen (1)
- lichen extracts (1)
- liver (1)
- liver cirrhosis (1)
- liver fibrosis (1)
- liver metastasis (1)
- locked nucleic acids (1)
- long-term protection (1)
- long36 term protection (1)
- longitudinal follow-up after epilepsy surgery (1)
- lung disease phenotype (1)
- lung function (1)
- lymphoma (1)
- mRNA (1)
- mRNA active cancer immunotherapy (1)
- macrophage (1)
- magic-angle spinning (1)
- mechanical accuracy (1)
- medical informatics (1)
- membrane proteins (1)
- methylprednisolone (1)
- miRNAs (1)
- microdosing (1)
- microparticles (1)
- microsurgical treatment (1)
- microvesicles (1)
- migration (1)
- minimal clinically important difference (1)
- minimal information requirements (1)
- mixed infection (1)
- molecular machines (1)
- mouse (1)
- mucormycetes (1)
- multicenter study (1)
- multidrug resistance (1)
- multilevel latent polynomial regression analysis (1)
- mycophenolic acid (1)
- myocardial fibrosis (1)
- n_TOF (1)
- natural killer cell (1)
- neoadjuvant therapy (1)
- neovascularization, physiologic (1)
- neuroblastoma (1)
- neutron (1)
- neutrophils (1)
- new species (1)
- nitrogen deposition (1)
- nomenclatural revision (1)
- non-invasive fibrosis assessment (1)
- nucleophilic substitution (1)
- nucleosynthesis (1)
- oligonucleotide (1)
- oligonucleotides (1)
- opportunity (1)
- ovary (1)
- oxLDL (1)
- p+p collisions (1)
- p-hydroxyphenacyl (1)
- p47phox (1)
- pandemic (1)
- patient data (1)
- pediatric (1)
- pediatric cancer (1)
- pediatric patients (1)
- pediatric solid tumors (1)
- perforin (1)
- peritumoral edema (1)
- peritumoral edema zone (1)
- phantom study (1)
- pharmacoresistance (1)
- phenotype (1)
- phenotype/genotype relation (1)
- photoacid generator (1)
- photolabile protection (1)
- photolysis (1)
- phylogenetic community distance (1)
- phylogeny (1)
- plant height (1)
- platelet lysate (1)
- platinum-based chemotherapy (1)
- point shear wave elastography (1)
- polygenic risk score (1)
- portosystemic shunt (1)
- post-transplantation lymphoproliferative disease (1)
- precision medicine (1)
- predictive biomarkers (1)
- predictor (1)
- primary active transporters (1)
- primary immunodeficiency (PID) (1)
- prognosis (1)
- prognostic biomarker (1)
- propagation of inequality (1)
- proteasomal processing escape (1)
- proteasome (1)
- pseudoexfoliative syndrome (1)
- psoriasis (1)
- pull-down (1)
- pulmonary embolism (1)
- quantum electrodynamics test (1)
- quark gluon plasma (1)
- query (1)
- radical reactions (1)
- reactive oxygen species (1)
- recurrence pattern (1)
- redox chemistry (1)
- registry for primary immunodeficiency (1)
- relativistic collisions (1)
- reliable change index (1)
- renin-angiotensin system (1)
- reproducibility (1)
- retrospective trial (1)
- rhabdomyosarcoma (1)
- rigor (1)
- risk assessment (1)
- robot-guided stereotaxy (1)
- rosacea (1)
- s-process (1)
- scar (1)
- schizophrenia (1)
- screening routine (1)
- seizures (1)
- senescence (1)
- sequence alignment (1)
- sex (1)
- signal transduction (1)
- silver coinage (1)
- single nucleotide polymorphism (1)
- single subject classification (1)
- smart home (1)
- smart living (1)
- social identity (1)
- social interactions (1)
- sodium bituminosulfonate (1)
- soil nutrients (1)
- solar physics (1)
- solitary pulmonary nodule (1)
- species richness (1)
- specificity of cleavage (1)
- spectra (1)
- speech and language pathologist (1)
- spontaneous portosystemic shunt (1)
- squamous cell carcinoma (1)
- stage II/III colorectal cancer (1)
- standardization (1)
- standardized regression-based change norms (1)
- stereotactic frame (1)
- stereotactic neurosurgery (1)
- stratification (1)
- stroke (1)
- strong Coulomb field (1)
- structural biology (1)
- structure-from-motion photogrammetry (1)
- subdural hematoma (1)
- subvalent compounds (1)
- surgery (1)
- systematics (1)
- talent development (1)
- talent identification (1)
- targeted therapy (1)
- taxonomy (1)
- telmisartan (1)
- temporal classification (1)
- testis (1)
- therapeutic anticoagulation (1)
- tomography (1)
- trace elements (1)
- trans-Golgi network (1)
- transbronchial biopsy (TBB) (1)
- transcatheter aortic valve replacement (1)
- transfemoral (1)
- transient elastography (1)
- translocation partner genes (1)
- transmission (1)
- trastuzumab (1)
- treatment resistance (1)
- tropical forests (1)
- tumor microenvironment (1)
- tumor microenvironment (TME) (1)
- type I interferons (IFNs) (1)
- umpolung (1)
- urinary tract development (1)
- urothelial carcinoma (1)
- uveal melanoma (1)
- vaccination (1)
- vaccine-induced immune thrombotic thrombocytopenia (VITT) (1)
- valproic acid (1)
- vascular calcification (1)
- vascular dysfunction and inflammation (1)
- vascular endothelial growth factor (1)
- vegetation classification (1)
- vegetation-plot data (1)
- vemurafenib (1)
- versican (VCAN) (1)
- vestibular schwannoma (1)
- viability (1)
- water solubility (1)
- wealth inequality (1)
- web of things (1)
- white and brown dwarfs (1)
- whole-genome sequencing (1)
- women (1)
- x-ray techniques (1)
- youth football (1)
- zebrafish development (1)
- ΔNp63 (1)
- Υ suppression (1)
- γ-ray spectroscopy (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (1263)
- Frankfurt Institute for Advanced Studies (FIAS) (1116)
- Informatik (971)
- Medizin (214)
- Geowissenschaften (29)
- ELEMENTS (21)
- Biochemie und Chemie (17)
- Biowissenschaften (14)
- Senckenbergische Naturforschende Gesellschaft (10)
- Institut für Ökologie, Evolution und Diversität (9)
Background: Ribavirin (RBV) remains part of several interferon-free treatment strategies even though its mechanisms of action are still not fully understood. One hypothesis is that RBV increases responsiveness to type I interferons. Pegylated Interferon alpha (PEG-IFNa) has recently been shown to alter natural killer (NK) cell function possibly contributing to control of hepatitis C virus (HCV) infection. However, the effects of ribavirin alone or in combination with IFNa on NK cells are unknown.
Methods: Extensive ex vivo phenotyping and functional analysis of NK cells from hepatitis C patients was performed during antiviral therapy. Patients were treated for 6 weeks with RBV monotherapy (n = 11), placebo (n = 13) or PEG-IFNa-2a alone (n = 6) followed by PEG-IFNa/RBV combination therapy. The effects of RBV and PEG-IFNa-2a on NK cells were also studied in vitro after co-culture with K562 or Huh7.5 cells.
Results: Ribavirin monotherapy had no obvious effects on NK cell phenotype or function, neither ex vivo in patients nor in vitro. In contrast, PEG-IFNa-2a therapy was associated with an increase of CD56bright cells and distinct changes in expression profiles leading to an activated NK cell phenotype, increased functionality and decline of terminally differentiated NK cells. Ribavirin combination therapy reduced some of the IFN effects. An activated NK cell phenotype during therapy was inversely correlated with HCV viral load.
Conclusions: PEG-IFNa activates NK cells possibly contributing to virological responses independently of RBV. The role of NK cells during future IFN-free combination therapies including RBV remains to be determined.
Zielsetzung: Die Daten für das Jahr 2018 des Registers „Abdominelles Aortenaneurysma“ (AAA) des Deutschen Instituts für Gefäßmedizinische Gesundheitsforschung (DIGG) der Deutschen Gesellschaft für Gefäßchirurgie und Gefäßmedizin werden vorgestellt.
Methodik: Im Jahr 2018 beteiligten sich an dem Register insgesamt 135 Kliniken. Für die offene Versorgung (OR) des intakten AAA (iAAA) gaben 118 (87,4 %) Kliniken, für die endovaskuläre Versorgung (EVAR) des iAAA 133 (98,5 %) Kliniken Daten ein. Für das rupturierte AAA (rAAA) wurden von 80 Kliniken (59,3 %) (EVAR) bzw. 65 (48,1 %) Kliniken (OR) Patienten gemeldet. Ausgewertet wurden die Daten von 4051 stationär behandelten Patienten.
Ergebnisse: 2800 iAAA (75,8 %) wurden endovaskulär und 895 (24,2 %) offen versorgt. Bei den endovaskulär versorgten Patienten mit iAAA verlief der Eingriff in 86,4 % der Fälle komplikationslos. Es verstarben insgesamt 32 Patienten (1,1 %) bis zur Entlassung. Bei den offen versorgten Patienten wiesen 73,4 % der Patienten keine Komplikationen auf. Verstorben sind insgesamt 42 Patienten (4,7 %). Von den 356 Patienten mit rAAA wurden 192 (53,9 %) endovaskulär und 164 (46,1 %) offen versorgt. Nur 11,0 % der mit OR versorgten Patienten, aber 23,4 % bei EVAR wiesen freies Blut in der Bauchhöhle auf. Bei EVAR sind 30,7 % der Patienten während des stationären Aufenthalts verstorben, bei OR 20,1 %.
Schlussfolgerung: Die Ergebnisse des Jahres 2018 zu Klinikletalität und Morbidität bei endovaskulärer und offener Versorgung des iAAA bestätigen weitestgehend die publizierten Ergebnisse für die Jahre 2013 bis 2017. Beim rAAA wurde 2018 erstmals über mehr endovaskuläre als offene Versorgungen berichtet – mit Ergebnissen, die denen der Vorjahre diametral entgegengesetzt waren. Patienten mit EVAR wiesen die höhere Komorbidität als Patienten mit OR auf und die Klinikletalität war höher. Es bleiben die Ergebnisse der Folgejahre abzuwarten, um diesen Trend genauer bewerten zu können.
Introduction: Recent animal studies have shown that the alternate renin-angiotensin system (RAS) consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1–7) (Ang-(1–7)) and the Mas receptor is upregulated in cirrhosis and contributes to splanchnic vasodilatation and portal hypertension. To determine the potential relevance of these findings to human liver disease, we evaluated its expression and relationship to the patients’ clinical status in subjects with cirrhosis. Methods: Blood sampling from peripheral and central vascular beds was performed intra-operatively for cirrhotic patients at the time of liver transplantation (LT) or trans-jugular intra-hepatic portosystemic shunt (TIPS) procedures to measure angiotensin II (Ang II) and Ang-(1–7) peptide levels and ACE and ACE2 enzyme activity. Relevant clinical and hemodynamic data were recorded pre-operatively for all subjects and peripheral blood sampling was repeated 3 months or later post-operatively. Results: Ang-(1–-7) and ACE2 activity were up-regulated more than twofold in cirrhotic subjects both at the time of LT and TIPS and levels returned to comparable levels as control subjects post-transplantation. Ang-(1–7) levels correlated positively with the degree of liver disease severity, as measured by the model for an end-stage liver disease (MELD) and also with clinical parameters of pathological vasodilatation including cardiac output (CO). There were strong correlations found between the ACE2:ACE and the Ang-(1–7):Ang II ratio highlighting the inter-dependence of the alternate and classical arms of the RAS and thus their potential impact on vascular tone. Conclusions: In human cirrhosis, the alternate RAS is markedly upregulated and the activation of this system is associated strongly with features of the hyperdynamic circulation in advanced human cirrhosis.
Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially,thedevelopmentoffibrosisandportalhypertensioninNAFLDpatientsrequirestreatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertension but without obesity. This study investigated the additional role of obesity in this model on the development of portal hypertension and fibrosis. Obesity was induced in twelve-week old TGR(mREN2)27 rats after receiving Western diet (WD) for two or four weeks. Liver fibrosis was assessed using standard techniques. Hepatic expression of transforming growth factor-β1 (TGF-β1), collagen type Iα1, α-smooth muscle actin, and the macrophage markers Emr1, as well as the chemoattractant Ccl2, interleukin-1β (IL1β) and tumor necrosis factor-α (TNFα) were analyzed. Assessment of portal and systemic hemodynamics was performed using the colored microsphere technique. Asexpected,WDinducedobesityandliverfibrosisasconfirmedbySiriusRedandOilRed O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increasedduringfeedingofWD,indicatinginfiltrationofmacrophagesintotheliver,eventhoughthis increase was statistically not significant for the EGF module-containing mucin-like receptor (Emr1) mRNA expression levels. Of note, portal pressure increased with the duration of WD compared to animals that received a normal chow. Besides obesity, WD feeding increased systemic vascular resistance reflecting systemic endothelial and splanchnic vascular dysfunction. We conclude that transgenic TGR(mREN2)27 rats are a suitable model to investigate NAFLD development with liver fibrosis and portal hypertension. Tendency towards elevated expression of Emr1 is associated with macrophage activity point to a significant role of macrophages in NAFLD pathogenesis, probably due to a shift of the renin–angiotensin system towards a higher activation of the classical pathway. The hepatic injury induced by WD in TGR(mREN2)27 rats is suitable to evaluate different stages of fibrosis and portal hypertension in NAFLD with obesity.
Prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. Resulting fibrosis and portal hypertension, as a possible secondary event, may necessitate treatment. Overexpression of mouse renin in the transgenic rat model, TGR(mREN2)27, leads to spontaneous development of NAFLD. Therefore, we used TGR(mREN2)27 rats as a model of NAFLD where we hypothesized increased susceptibility and investigated fibrosis and portal hypertension and associated pathways. 12-week old TGR(mREN2)27 rats received either cholestatic (BDL) or toxic injury (CCl4 inhalation). Portal and systemic hemodynamic assessments were performed using microsphere technique with and without injection of the Janus-Kinase 2 (JAK2) inhibitor AG490 or the non-peptidic Ang(1-7) agonist, AVE0991. The extent of liver fibrosis was assessed in TGR(mREN2)27 and wild-type rats using standard techniques. Protein and mRNA levels of profibrotic, renin-angiotensin system components were assessed in liver and primary hepatic stellate cells (HSC) and hepatocytes. TGR(mREN2)27 rats developed spontaneous, but mild fibrosis and portal hypertension due to the activation of the JAK2/Arhgef1/ROCK pathway. AG490 decreased migration of HSC and portal pressure in isolated liver perfusions and in vivo. Fibrosis or portal hypertension after cholestatic (BDL) or toxic injury (CCl4) was not aggravated in TGR(mREN2)27 rats, probably due to decreased mouse renin expression in hepatocytes. Interestingly, portal hypertension was even blunted in TGR(mREN2)27 rats (with or without additional injury) by AVE0991. TGR(mREN2)27 rats are a suitable model of spontaneous liver fibrosis and portal hypertension but not with increased susceptibility to liver damage. After additional injury, the animals can be used to evaluate novel therapeutic strategies targeting Mas.
The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
Objective We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease.
Design Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12).
Results Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child–Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI −2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related.
Conclusions DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease.
Trial registration number NCT0209966.
We present the results of geochemical analysis of silver coinage issued by Rome and dated between the fourth and second century BCE, which are complemented by data of coinage issued by Carthage, the Brettii, and the Greek colony of Emporion. Each of these minting authorities represents one of the major parties involved in the struggle for hegemony in the fourth to second centuries BCE Western Mediterranean region. This study retraces how the metal supply shifts in response to the transforming power relations and how this change is related to Rome's rise to the virtually uncontested ruler of the region.
Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications, and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischaemia, putting it in the context of the human ‘diseasome’. Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischaemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischaemia/reperfusion injury and ischaemic heart failure in the post-genomic era.
Background and aims: Spontaneous bacterial peritonitis (SBP) is a severe complication of decompensated cirrhosis. The prevalence of multidrug-resistant organisms (MDROs) in patients with cirrhosis is increasing. Identification of patients at risk for SBP due to MDROs (ie, SBP with the evidence of MDROs or Stenotrophomonas maltophilia in ascitic culture, MDRO-SBP) is crucial to the early adaptation of antibiotic treatment in such patients. We therefore investigated whether MDROs found in ascitic cultures can also be found in specimens determined by noninvasive screening procedures.
Patients and methods: This retrospective study was conducted at the liver center of the University Hospital Frankfurt, Germany. Between 2011 and 2016, patients with cirrhosis were included upon diagnosis of SBP and sample collection of aerobic/anaerobic ascitic cultures. Furthermore, the performance of at least one complete MDRO screening was mandatory for study inclusion.
Results: Of 133 patients diagnosed with SBP, 75 (56.4%) had culture-positive SBP and 22 (16.5%) had MDRO-SBP. Multidrug-resistant Escherichia coli (10/22; 45.5%) and vancomycin-resistant enterococci (7/22; 36.4%) resembled the major causatives of MDRO-SBP. Rectal swabs identified MDROs in 17 of 22 patients (77.3%) who developed MDRO-SBP with a time-dependent sensitivity of 77% and 87% after 30 and 90 days upon testing, while negative predictive value was 83% and 76%, respectively. The majority of patients were included from intensive care unit or intermediate care unit.
Conclusion: MDRO screening may serve as a noninvasive diagnostic tool to identify patients at risk for MDRO-SBP. Patients with decompensated cirrhosis should be screened for MDROs from the first day of inpatient treatment onward.
Simple Summary
Seizures are among the most common symptoms of meningioma patients even after surgery. This study sought to identify risk factors for early and late seizures in meningioma patients and to evaluate a modified version of a score to predict postoperative seizures on an independent cohort. The data underline that there are distinct factors identifying patients with a high risk of postoperative seizures following meningioma surgery which has been already shown before. We could further show that the high proportion of 43% of postoperative seizures occur as late seizures which are more dangerous because they may happen out of hospital. The modified STAMPE2 score could predict postoperative seizures when reaching very high scores but was not generally transferable to our independent cohort.
Abstract
Seizures are among the most common symptoms of meningioma. This retrospective study sought to identify risk factors for early and late seizures in meningioma patients and to evaluate a modified STAMPE2 score. In 556 patients who underwent meningioma surgery, we correlated different risk factors with the occurrence of postoperative seizures. A modified STAMPE2 score was applied. Risk factors for preoperative seizures were edema (p = 0.039) and temporal location (p = 0.038). For postoperative seizures preoperative tumor size (p < 0.001), sensomotory deficit (p = 0.004) and sphenoid wing location (p = 0.032) were independent risk factors. In terms of postoperative status epilepticus; sphenoid wing location (p = 0.022), tumor volume (p = 0.045) and preoperative seizures (p < 0.001) were independent risk factors. Postoperative seizures lead to a KPS deterioration and thus an impaired quality of life (p < 0.001). Late seizures occurred in 43% of patients with postoperative seizures. The small sub-cohort of patients (2.7%) with a STAMPE2 score of more than six points had a significantly increased risk for seizures (p < 0.001, total risk 70%). We concluded that besides distinct risk factors, high scores of the modified STAMPE2 score could estimate the risk of postoperative seizures. However, it seems not transferable to our cohort
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers potential cure to acute myeloid leukemia (AML) patients. However, infections with commensal bacteria are an important cause for non-relapse mortality (NRM). We have previously described the impact of multidrug-resistant organism (MDRO) colonization on the survival of allo-HSCT patients. In the aforementioned publication, according to consensus, we there did not consider the opportunistic gram-negative bacterium Stenotrophomonas maltophilia (S. maltophilia) to be an MDRO. Since rate of S. maltophilia colonization is increasing, and it is not known whether this poses a risk for allo-HSCT patients, we here analyzed here its effect on the previously described and now extended patient cohort. We report on 291 AML patients undergoing allo-HSCT. Twenty of 291 patients (6.9%) were colonized with S. maltophilia. Colonized patients did not differ from non-colonized patients with respect to their age, remission status before allo-HSCT, donor type and HSCT-comorbidity index. S. maltophilia colonized patients had a worse overall survival (OS) from 6 months up to 60 months (85% vs. 88.1% and 24.7% vs. 59.7%; p = 0.007) due to a higher NRM after allo-HSCT (6 months: 15% vs. 4.8% and 60 months: 40.1% vs. 16.2% p = 0.003). The main cause of mortality in colonized patients was infection (46.2% of all deaths) and in non-colonized patients relapse (58.8% of all deaths). 5/20 colonized patients developed an invasive infection with S. maltophilia. The worse OS after allo-HSCT due to higher infection related mortality might implicate the screening of allo-HSCT patients for S. maltophilia and a closer observation of colonized patients as outpatients.
Organoboranes are among the most versatile and widely used reagents in synthetic chemistry. A significant further expansion of their application spectrum would be achievable if boron-containing reactive intermediates capable of inserting into C–H bonds or performing nucleophilic substitution reactions were readily available. However, current progress in the field is still hampered by a lack of universal design concepts and mechanistic understanding. Herein we report that the doubly arylene-bridged diborane(6) 1H2 and its B[double bond, length as m-dash]B-bonded formal deprotonation product Li2[1] can activate the particularly inert C(sp3)–H bonds of added H3CLi and H3CCl, respectively. The first case involves the attack of [H3C]− on a Lewis-acidic boron center, whereas the second case follows a polarity-inverted pathway with nucleophilic attack of the B[double bond, length as m-dash]B double bond on H3CCl. Mechanistic details were elucidated by means of deuterium-labeled reagents, a radical clock, α,ω-dihaloalkane substrates, the experimental identification of key intermediates, and quantum-chemical calculations. It turned out that both systems, H3CLi/1H2 and H3CCl/Li2[1], ultimately funnel into the same reaction pathway, which likely proceeds past a borylene-type intermediate and requires the cooperative interaction of both boron atoms.
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.
Selective BRAF inhibitors such as vemurafenib have become a treatment option in patients with Langerhans cell Histiocytosis (LCH). To date, only 14 patients receiving vemurafenib for LCH have been reported. Although vemurafenib can stabilize the clinical condition of these patients, it does not seem to cure the patients, and it is unknown, when and how to stop vemurafenib treatment. We present a girl with severe multisystem LCH who responded only to vemurafenib. After 8 months of treatment, vemurafenib was tapered and replaced by prednisone and vinblastine, a strategy which has not been described to date. Despite chemotherapy, early relapse occurred, but remission was achieved by re-institution of vemurafenib. Further investigation needs to address the optimal duration of vemurafenib therapy in LCH and whether and which chemotherapeutic regimen may prevent disease relapse after cessation of vemurafenib.
Double reduction of the THF adduct of 9H-9-borafluorene (1⋅THF) with excess alkali metal affords the dianion salts M2[1] in essentially quantitative yields (M=Li–K). Even though the added charge is stabilized through π delocalization, [1]2− acts as a formal boron nucleophile toward organoboron (1⋅THF) and tetrel halide electrophiles (MeCl, Et3SiCl, Me3SnCl) to form B−B/C/Si/Sn bonds. The substrate dependence of open-shell versus closed-shell pathways has been investigated.
Two subvalent, redox-active diborane(4) anions, [3]4− and [3]2−, carrying exceptionally high negative charge densities are reported: Reduction of 9-methoxy-9-borafluorene with Li granules without stirring leads to the crystallization of the B(sp3)−B(sp2) diborane(5) anion salt Li[5]. [5]− contains a 2,2′-biphenyldiyl-bridged B−B core, a chelating 2,2′-biphenyldiyl moiety, and a MeO substituent. Reduction of Li[5] with Na metal gives the Na+ salt of the tetraanion [3]4− in which two doubly reduced 9-borafluorenyl fragments are linked via a B−B single bond. Comproportionation of Li[5] and Na4[3] quantitatively furnishes the diborane(4) dianion salt Na2[3], the doubly boron-doped congener of 9,9′-bis(fluorenylidene). Under acid catalysis, Na2[3] undergoes a formal Stone–Wales rearrangement to yield a dibenzo[g,p]chrysene derivative with B=B core. Na2[3] shows boron-centered nucleophilicity toward n-butyl chloride. Na4[3] produces bright blue chemiluminescence when exposed to air.
Pediatric patients with recurrent, refractory or advanced soft tissue sarcoma (STS) who are simultaneously showing signs of cumulative treatment toxicity are in need of novel therapies. In this preclinical analysis, we identified ErbB2 as a targetable antigen on STS cells and used cytokine-induced killer (CIK) cells transduced with the lentiviral 2nd-generation chimeric antigen receptor (CAR) vector pS-5.28.z-IEW to target ErbB2-positive tumors. Solely CIK cell subsets with the CD3+ T cell phenotype showed up to 85% cell surface expression of the respective CAR. A comparison of wildtype (WT), mock-vector and ErbB2-CAR-CIK cells showed, that engineered cells exhibited diminished in vitro expansion, retained WT CIK cell phenotype with higher percentages of differentiated effector memory/effector cells. Activating natural killer (NK) cell receptor NKG2D-restricted target cell recognition and killing of WT and ErbB2-CAR-CIK cells was maintained against ErbB2-negative tumors, while ErbB2-CAR-CIK cells demonstrated significantly increased cytotoxicity against ErbB2-positive targets, including primary tumors. ErbB2-CAR- but not WT CIK cells proliferated, infiltrated and efficiently lysed tumor cell monolayers as well as 3D tumor spheroids.
Here, we demonstrate a potential cell therapeutic approach using ErbB2-CAR-CIK cells for the recognition and elimination of tumor cells expressing ErbB2, which we identified as a targetable antigen on high-risk STS cells.
Background: Prolonged immunosuppression or delayed T-cell recovery may favor Epstein-Barr virus (EBV) infection or reactivation after allogeneic hematopoietic stem cell transplantation (HSCT), which can lead to post-transplant lymphoproliferative disease (PTLD) and high-grade malignant B-cell lymphoma. Cytokine-induced killer (CIK) cells with dual specific anti-tumor and virus-specific cellular immunity may be applied in this context.
Methods: CIK cells with EBV-specificity were generated from peripheral blood mononuclear cells (PBMCs), expanded in the presence of interferon-γ, anti-CD3, interleukin (IL)-2 and IL-15 and were pulsed twice with EBV consensus peptide pool. CIK cells with EBV-specificity and conventional CIK cells were phenotypically and functionally analyzed. Additionally, CIK cells with EBV-specificity were applied to a patient with EBV-related PTLD rapidly progressing to highly aggressive B-cell lymphoma on a compassionate use basis after approval and agreement by the regulatory authorities.
Results: Pre-clinical analysis showed that generation of CIK cells with EBV-specificity was feasible. In vitro cytotoxicity analyses showed increased lysis of EBV-positive target cells, enhanced proliferative capacity and increased secretion of cytolytic and proinflammatory cytokines in the presence of EBV peptide-displaying target cells. In addition, 1 week after infusion of CIK cells with EBV-specificity, the patient's highly aggressive B-cell lymphoma persistently disappeared. CIK cells with EBV-specificity remained detectable for up to 32 days after infusion and infusion did not result in acute toxicity.
Discussion: The transfer of both anti-cancer potential and T-cell memory against EBV infection provided by EBV peptide-induced CIK cells might be considered a therapy for EBV-related PTLD.
Neuroblastoma (NB) is the most common solid extracranial tumor in childhood. Despite therapeutic progress, prognosis in high-risk NB is poor and innovative therapies are urgently needed. Therefore, we addressed the potential cytotoxic capacity of interleukin (IL)-activated natural killer (NK) cells compared to cytokine-induced killer (CIK) cells for the treatment of NB. NK cells were isolated from peripheral blood mononuclear cells (PBMCs) by indirect CD56-enrichment or CD3/CD19-depletion and expanded with different cytokine combinations, such as IL-2, IL-15, and/or IL-21 under feeder-cell free conditions. CIK cells were generated from PBMCs by ex vivo stimulation with interferon-γ, IL-2, OKT-3, and IL-15. Comparative analysis of expansion rate, purity, phenotype and cytotoxicity was performed. CD56-enriched NK cells showed a median expansion rate of 4.3-fold with up to 99% NK cell content. The cell product after CD3/CD19-depletion consisted of a median 43.5% NK cells that expanded significantly faster reaching also 99% of NK cell purity. After 10–12 days of expansion, both NK cell preparations showed a significantly higher median cytotoxic capacity against NB cells relative to CIK cells. Remarkably, these NK cells were also capable of efficiently killing NB spheroidal 3D culture in long-term cytotoxicity assays. Further optimization using a novel NK cell culture medium and a prolonged culturing procedure after CD3/CD19-depletion for up to 15 days enhanced the expansion rate up to 24.4-fold by maintaining the cytotoxic potential. Addition of an IL-21 boost prior to harvesting significantly increased the cytotoxicity. The final cell product consisted for the major part of CD16−, NCR-expressing, poly-functional NK cells with regard to cytokine production, CD107a degranulation and antitumor capacity. In summary, our study revealed that NK cells have a significantly higher cytotoxic potential to combat NB than CIK cell products, especially following the synergistic use of IL-15 and IL-21 for NK cell activation. Therefore, the use of IL-15+IL-21 expanded NK cells generated from CD3/CD19-depleted apheresis products seems to be highly promising as an immunotherapy in combination with haploidentical stem cell transplantation (SCT) for high-risk NB patients.
Multidrug-resistant Gram-negative bacteria (MDR GNB) were found to colonise 60.8% (95% confidence interval: 52.3–68.9) of 143 refugee patients mainly from Syria (47), Afghanistan (29), and Somalia (14) admitted to the University Hospital Frankfurt, Germany, between June and December 2015. This percentage exceeds the prevalence of MDR GNB in resident patients four–fold. Healthcare personnel should be aware of this and the need to implement or adapt adequate infection control measures.
Ecological networks are more sensitive to plant than to animal extinction under climate change
(2016)
Impacts of climate change on individual species are increasingly well documented, but we lack understanding of how these effects propagate through ecological communities. Here we combine species distribution models with ecological network analyses to test potential impacts of climate change on >700 plant and animal species in pollination and seed-dispersal networks from central Europe. We discover that animal species that interact with a low diversity of plant species have narrow climatic niches and are most vulnerable to climate change. In contrast, biotic specialization of plants is not related to climatic niche breadth and vulnerability. A simulation model incorporating different scenarios of species coextinction and capacities for partner switches shows that projected plant extinctions under climate change are more likely to trigger animal coextinctions than vice versa. This result demonstrates that impacts of climate change on biodiversity can be amplified via extinction cascades from plants to animals in ecological networks.
From July 2002 to March 2004 the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) aboard the European Space Agency´s Environmental Satellite (Envisat) measured nearly continuously mid infrared limb radiance spectra. These measurements are utilised to retrieve the global distribution of the chlorofluorocarbon CFC-11 by applying a new fast forward model for Envisat MIPAS and an accompanying optimal estimation retrieval processor. A detailed analysis shows that the total retrieval errors of the individual CFC-11 volume mixing ratios are typically below 10% in the altitude range 10 to 25 km and that the systematic components dominate. Contribution of a priori information to the retrieval results are less than 5 to 10% and the vertical resolution of the observations is about 3 to 4 km in the same vertical range. The data are successfully validated by comparison with several other space experiments, an air-borne in-situ instrument, measurements from ground-based networks, and independent Envisat MIPAS analyses. The retrieval results from 425 000 Envisat MIPAS limb scans are compiled to provide a new climatological data set of CFC-11. The climatology shows significantly lower CFC-11 abundances in the lower stratosphere compared with the Reference Atmospheres for MIPAS (RAMstan V3.1) climatology. Depending on the atmospheric conditions the differences between the climatologies are up to 30 to 110 ppt (45 to 150%) at 19 to 27 km altitude. Additionally, time series of CFC-11 mean abundance and variability for five latitudinal bands are presented. The observed CFC-11 distributions can be explained by the residual mean circulation and large-scale eddy-transports in the upper troposphere and lower stratosphere. The new CFC-11 data set is well suited for further scientific studies.
Background: The most frequent therapy of hydrocephalus is the implantation of ventriculoperitoneal shunts for diverting cerebrospinal fluid from the ventricles into the peritoneum. We compared two adjustable valves, the proGAV and proGAV 2.0, for complications which resulted in revision operations.
Methods: Four hundred patients who underwent primary shunt implantation between 2014 and 2020 were analyzed for overall revision rate, one-year revision rate, revision free survival and overall survival observing patient age group, gender, etiology of hydrocephalus, implantation site, prior diversion of cerebrospinal fluid and cause of revision.
Results: All data were available of all 400 patients (female/male 208/192). Overall, 99 patients underwent revision surgery after primary implantation. ProGAV valve was implanted in 283 patients, proGAV 2.0 in 117 patients. There was no significant difference between the two shunt valves concerning revision rate (p=0.8069), one-year revision rate (p=0.9077), revision free survival (p=0.6921) and overall survival (p=0.3232). Furthermore, regarding one-year revision rate, we observed no significant difference between the two shunt valves in pediatric patients (40.7% vs 27.6%; p=0.2247). Revision operation had to be performed more frequently in pediatric patients (46.6% vs 24.8%; p=0.0093) with a significant higher number of total revisions with proGAV than proGAV 2.0 (55.9% vs. 27.6%; p=0.0110) most likely due to longer follow up in the proGAV -group.
Conclusion: According to the target variables we analyzed, aside from lifetime revision rate in pediatric patients there is no significant difference between the two shunt valves. From our subjective point of view, implantation of the newer proGAV 2.0 valve is preferable due to higher adjustment comfort for both patients and physicians.
This paper uses unique administrative data and a quasi-field experiment of exogenous allocation in Sweden to estimate medium- and longer-run effects on financial behavior from exposure to financially literate neighbors. It contributes evidence of causal impact of exposure and of a social multiplier of financial knowledge, but also of unfavorable distributional aspects of externalities. Exposure promotes saving in private retirement accounts and stockholding, especially when neighbors have economics or business education, but only for educated households and when interaction possibilities are substantial. Findings point to transfer of knowledge rather than mere imitation or effects through labor, education, or mobility channels.
The authors present evidence of a new propagation mechanism for wealth inequality, based on differential responses, by education, to greater inequality at the start of economic life. The paper is motivated by a novel positive cross-country relationship between wealth inequality and perceptions of opportunity and fairness, which holds only for the more educated. Using unique administrative micro data and a quasi-field experiment of exogenous allocation of households, the authors find that exposure to a greater top 10% wealth share at the start of economic life in the country leads only the more educated placed in locations with above-median wealth mobility to attain higher wealth levels and position in the cohort-specific wealth distribution later on. Underlying this effect is greater participation in risky financial and real assets and in self-employment, with no evidence for a labor income, unemployment risk, or human capital investment channel. This differential response is robust to controlling for initial exposure to fixed or other time-varying local features, including income inequality, and consistent with self-fulfilling responses of the more educated to perceived opportunities, without evidence of imitation or learning from those at the top.
The Eurozone fiscal crisis has created pressure for institutional harmonization, but skeptics argue that cultural predispositions can prevent convergence in behavior. Our paper derives a robust cultural classification of European countries and utilizes unique data on natives and immigrants to Sweden. Classification based on genetic distance or on Hofstede’s cultural dimensions fails to identify a single ‘southern’ culture but points to a ‘northern’ culture. Significant differences in financial behavior are found across cultural groups, controlling for household characteristics. Financial behavior tends to converge with longer exposure to common institutions, but is slowed down by longer exposure to original institutions.
Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 3-year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. (trial registered at www.clinicaltrials.gov: NCT00355862) (EudraCT Number: 2005-005362-36)
The New World genus Dysmerus Casey, currently with one valid species, is revised. Lectotypes are designated for two species, Dysmerus caseyi (Grouvelle), new status, and Dysmerus sulcicollis Grouvelle, new status. Both are revived from synonymy with D. basalis Casey. Twelve new species are described: Dysmerus boliviensis Thomas, new species, Dysmerus curvicornis Thomas, new species, Dysmerus genaspinosus Thomas, new species, Dysmerus hamaticornis Thomas, new species, Dysmerus impolitus Thomas, new species, Dysmerus skelleyi Thomas, new species, Dysmerus mexicanus Thomas, new species, Dysmerus monstrosus Thomas, new species, Dysmerus politus Thomas, new species, Dysmerus rondoniensis Thomas, new species, Dysmerus symphilus Thomas, new species, and Dysmerus trinidadensis Thomas, new species. A key to adults of the species and illustrations are provided.
Australophanus, new genus, is described and illustrated for Cryptamorpha redtenbacheri (Reitter). Platamus Erichson is synonymized under Telephanus Erichson, new synonymy. Euplatamus Sharp, new status, replaces Platamus Erichson as the genus name. Type species are designated for Aplatamus Grouvelle and Euplatamus Sharp. Telephanus velox (Haldeman) is synonymized under Telephanus atricapillus Erichson. A diagnosis of the tribe Telephanini, a key to the described telephanine genera of the world is presented, and a phylogeny of the family Silvanidae is proposed.
This article outlines changes in procedures and production policies for the journal Insecta Mundi. Background data and discussions leading to these necessary changes are explained. Updated instructions for authors are presented. A full current version of author instructions will be posted on the latest Center for Systematic Entomology URL.
The species of the genus Lathropus Erichson are reviewed for Florida and the West Indies, excluding the Lesser Antilles. Seven species are recorded from this region, three of which are described as new: Lathropus chickcharnie Thomas, new species, Lathropus jamaicensis Thomas, new species, and Lathropus rhabdophloeoides Thomas, new species. A lectotype is designated for Lathropus vernalis Casey, and Lathropus striatus Casey is synonymized under Lathropus vernalis Casey, new synonymy. Illustrations and a key to the species of this geographgic region are provided.
The key description and illustrations of mouthparts, ocelli, and terminal abdominal segments by Bovinq & Craighead (1931) have been the only information on the larval stages of the genus Hemipeplus Latreille, except for the observation by van Emden (1942) that individuals of the genus would not key properly in Boving & Craighead's key. Their example was of an undescribed species from Cuba. The semidiagrammatic illustrations make it difficult to identify the species illustrated, although it may be H. marginipennis (LeConte). This paper is based on larvae collected by the authors, in each case associated with adults. From the family diagnosis of larval Mycteridae (Crowson & Viedma 1964). Hemipeplus larvae differ noticeably in the form of the sensorium, which Crowson & Viedma describe as “very short, dome-shaped”; in Hemipeplus it is elongate and conical. From the larva of Mycterus (described by Crowson & Viedma 1964) those of Hemipeplus also differ in having five ocelli on each side (cf. two), mala with an uncus and medial pit (cf. without uncus or medial pit), mola ridged (cf. not ridged), cardines not divided (cf. distinctly divided, labial palpi with only one distinct palpomere (cf. with two palpomeres), abdominal asperities absent (cf. asperities present), and different form of spiracle (compare fig. 13 with fig. 4 in Crowson & Viedma 1964). Larvae of Hemipeplus are more similar to that of Eurypus muelleri Seldlitz (described by Costa & Vanin 1977) than to that of Mycterus. As in Hemipeplus, Eurypus larvae possess five ocelli arranged in rows of three and two on each side; two pairs of tubercles at posterior margin of abdominal sternite IX; mala with an uncus, and cardines divided. Hemipeplus larvae differ from those of Mycterus most notably in the form of abdominal tergite IX (see Costa & Vanin 1977:fig. 2 ) . The uncus is located on the mesal margin of the mala in Hemipeplus, whereas it is located on the ventral aspect of the mala in Eurypus.
The New World species of Cryptolestes Ganglbauer are revised and keys, diagnoses, descriptions, and illustrations are provided for the 13 non-economic species. Six stored products species of the genus are also keyed and illustrated. Two species, Laemophloeus pubescens Casey and L. bicolor Chevrolat, are reassigned to Cryptolestes. Eight new species are described: C. dissimulatus (southwestern United States); C. dybasi (Florida); C. mexicanus (Mexico and Guatemala); C. capillulus (Brazil); C. spatulifer (Argentina); C. trinidadensis (Trinidad); C. ampiyacus (Peru); and C. calabozus (Venezuela). Cryptolestes uncicornis (Reitter) is revived from synonymy under C. punctatus (LeConte), C. schwarzi (Casey) is revived from synonymy under C. weisei (Reitter), and four specific names are synonymized: C. quadratus (Casey) [ = C. uncicornis (Reitter)]; C. extricatus (Casey) and C. adumbratus Casey [ = C. punctatus (LeConte)]; and Laemophloeus concavus (Reitter) [ = C. bicolor (Chevrolat)]. Cyptolestes horni (Casey) and C. disseptus Casey are removed from Cryptolestes and reassigned to Rhabdophloeus Sharp. Lectotypes are designated for Laemophloeus geminatus LeConte, Cryptolestes adumbratus Casey, and Laemophloeus quadratus Casey.
A specimen of Rhizophagus sayi Schaeffer collected in a flight trap at 29°34½'N82°29'W in Alachua County, Florida, on 23-1-1993, by R.W. Lundgren prompted a search of unidentified specimens in the Florida State Collection of Arthropods. The search resulted in the discovery of seven additional Florida specimens with the following data: "FLA., Dixie Co. 3.5mi. N. Old Town 13-1-1980 Coll. M.C. Thomas", 2; "FLORIDA: Alachua Co. Gainesville 3-XII-1983 Coll. M.C. Thomas", 1; "FLORIDA: Alachua Co. San Felasco Hammock 4-11-1983 M.C. Thomasn, 3; same, except date is 12-II-1983. These specimens comprise a new state record for R. sayi, which Bousquet (1990) recorded from most of the eastern United States except for Florida and Georgia.
One of the rarest U.S. cerambycids, Romulus globosus, was described by Knull in 1948 based on four specimens collected in peninsular Florida. No new records have been reported in the literature since. Linsley (1963) apparently saw no specimens, since he merely quoted the original description, and gave the distribution as "Southern Florida."
Neoma, a new genus of Cerambycidae (Coleoptera: Cerambycidae: Prioninae: Macrotomini) is described for Mallodonopsis corrosus Bates, 1879, compared to related genera (Aplagiognathus Thomson, 1861; Archodontes Lameere, 1903; and Mallodonopsis Thomson, 1861), and its tribal position discussed. A lectotype for Mallodonopsis corrosus is here designated with the species redescribed and figured.
Several Coleopterists have been asked to revise the family sections, working from diskettes modified and provided from the original "Beetles of the United States." They will rewrite these sections, and will be recognized as the author of the section. They are asked to sign a writing contract with the publisher. Other Coleopterists have been asked to review the family sections of the new book. These persons are acknowledged in the family section text.
The Mesoamerican species of Telephanus distinguished by the presence eight lateral pronotal spines
and long temples are reviewed. The group includes T. serratus Nevermann and two previously undescribed species
that are described herein: T. bellus Thomas, new species, from Costa Rica, and the flightless T. monstrosus
Thomas, new species, from Mexico.
The Guadeloupe Archipelago, the French overseas Département de Guadeloupe, is a geographically associated group of islands and a natural biogeographic unit. The islands have been available for terrestrial colonization since the late Tertiary. From the viewpoint of beetle systematics and biodiversity, this is the most important set of islands of the Lesser Antilles because more species have been described or recorded from Guadeloupe than any other island or group in the Lesser Antilles. We present a summary of the 1338 beetle species recorded in the literature from the archipelago, in 60 families, and 719 genera. The families with the largest numbers of species are Curculionidae (420), Staphylinidae (153), Chrysomelidae (75), Cerambycidae (69), Scarabaeidae (64), and Tenebrionidae (59). Four hundred eighty two species are known only from one or more islands of the Guadeloupe group and likely speciated there. Guadeloupe is the type locality for an additional 59 species. At least 61 species have been accidentally introduced by human activities. A total of 261 species are known only from the Lesser Antilles including Guadeloupe. The remaining species are naturally more widespread in the Lesser Antilles, or the West Indies, and elsewhere in the New World. The actual number of species on the Guadeloupe Archipelago is estimated to be around 1850 or more species.
The genus Pediacus Shuckard is revised for America north of Mexico. Seven species are recorded: P. andrewsi Thomas, n. sp.; P. fuscus Erichson; P. gracilis Thomas, n. sp.; P. hesperoglaber Thomas, n. sp.; P. ommatodon Thomas, n. sp.; P. stephani Thomas, n. sp.; and P. subglaber LeConte, new status. The species are described and illustrated, and a key is presented for their identification. The described European and Neotropical species are reviewed and illustrated.
The following new species of Cryptolestes Ganglbauer are described and illustrated: Cryptolestes obesus Thomas, new species, Brazil; Cryptolestes turnbowi Thomas, new species, Honduras and Mexico; Cryptolestes inyoensis Thomas, new species, California; Cryptolestes spectabilis Thomas, new species, Ecuador. A revised key to the New World species is provided. The male genitalia are illustrated and the female of C. calabozus Thomas is characterized, and new distribution records are provided for it, C. cornutus Thomas and Zimmerman, C. trinidadensis Thomas, C. curus Lefkovitch, and C. hlapperichi Lefkovitch.
Four species of Anchonus Schonherr occur in Florida: A. flol'idanus Schwarz, A. dul'yi Blatchley, A. blatchleyi Sleeper, and A. suillus (Fabricius), which is recorded from Florida and the continental United States for the first time. The species are distinguished in a key and illustrated. A lectotype is selected for A. floridanus.
New distribution records for two species of Cryptolestes Ganglbauer (Coleoptera: Laemophloeidae)
(2005)
The nine Nearctic species of Laemophloeus Dejean (Coleoptera: Laemophloeidae) are reviewed, keyed, and illustrated. One species, L. apache Thomas, n. sp., is described as new. Two previously described species are synonymized: L. californicus Casey (= L. biguttatus (Say), n. syn.) and L. woodruffi Thomas (= L. fervidus Casey, n. syn.). A neotype is designated for L. biguttatus (Say), and lectotypes are designated for L. terminalis Casey and L. fervidus Casey. A checklist of the described world species is provided.
Eleven Neotropical species of Laemophloeus Dejean with antennal clubs composed of three antennomeres are reviewed, diagnosed, and illustrated. Six of the species are described as new: L. capitesculptus Thomas, n. sp., L. corporeflavus Thomas, n. sp., L. dozieri Thomas, n. sp., L. insulatestudinorum Thomas, n. sp., L. planaclavatus Thomas, n. sp., and L. taurus Thomas, n. sp. Four new synonymies are proposed: L. catharinensis Kessel (=L. incisus Sharp), new synonym; L. similans Kessel (=L. incisus Sharp), new synonym; L. distinguendus Sharp (=L. megacephalus Grouvelle), new synonym, and L. chevrolati Grouvelle (=L. lecontei Grouvelle), new synonym. A key to the species is provided.
A new species, Chrysobothris cerceripraeda Westcott and Thomas (Coleoptera: Buprestidae), is described from prey specimens found in nests of the ground-nesting wasp, Cerceris fumipennis Say (Hymenoptera: Crabronidae), near Jacksonville, Florida, USA. A listing for all species of Buprestidae taken as prey of the wasp in that state is provided, four of which, including the species described herein, are new. Notes are also given for
four new state records for Buprestidae.
The Brontini of the world : a generic review of the tribe (Coleoptera: Silvanidae: Brontinae)
(2003)
The genera of the tribe Brontini (Silvanidae: Brontinae) are reviewed. The tribe is considered here to be composed of 12 genera, Uleiota Latreille, Brontopriscus Sharp, and Dendrophagus Schönherr, plus nine new genera: Australodendrophagus, Australohyliota, Brontoliota, Dendrophagella, Macrohyliota, Megahyliota, Microhyliota, Parahyliota, and Protodendrophagus. Aplatamus Grouvelle is removed from the Brontini and placed in the Telephanini. Four new species are described: Protodendrophagus antipodes Thomas; Brontoliota indivisipennis Thomas; Brontoliota intermedius Thomas; and Brontoliota monteithi Thomas. Described species are assigned to genera with the following new combinations resulting: Australodendrophagus australis (Erichson); Australohyliota chilensis (Blanchard); Australohyliota macleayi (Olliff); Denrophagella capito (Pascoe); Macrohyliota truncatipennis (Heller); Macrohyliota bicolor Arrow; Macrohyliotagracilicornis (Arrow); Macrohyliota lucius (Pascoe); Macrohyliota militaris (Erichson); Macrohyliota spinicollis (Gory); Megahyliota feae (Grouvelle); Microhyliota integricollis (Fairmaire); Parahyliota africanus Grouvelle; Parahyliota alticola (Pal, Sen Gupta, and Crowson); Parahyliota atratus (Grouvelle); Parahyliota brevicollis (Arrow); Parahyliota cinamomeus (Fairmaire); Parahyliota costicollis (Reitter); Parahyliota fallax (Grouvelle); Parahyliota indicus (Arrow); Parahyliota pallidus (Arrow); Parahyliota puberulus (Reitter); Parahyliota serratus (Smith); Parahyliota serricollis (Candeze); Parahyliota siamensis (Arrow). Two new synonymies are proposed: Uleiota crenicollis Grouvelle (=Uleiota costicollis Grouvelle) and Uleiota texana Dajoz (=Uleiota dubius (Fabricius)). Uleiota truncatus Motschulsky, formerly treated as a subspecies of U. dubius (Fabricius), is elevated to a full species, new status.
Five Neotropical species of Laemophloeus Dejean (s. str.) (Coleoptera: Laemophloeidae) with antennal clubs of more than three antennomeres are reviewed: L. buenavista Thomas, n.sp.; L. concinnus Thomas, n.sp.; L. germaini Grouvelle; L. macrognathus Reitter; and L. sexarticulatus Kessel. Diagnoses, descriptions of the new species, illustrations, and a key are provided. Laemophloeus prominens Hetschko, proposed as a replacement name for Laemophloeus notabilis Kessel, is synonymized under L. germaini, new synonymy.
Species descriptions, keys to genera and species, and geographical distributions are presented for 43 species of the family Bruchidae (Coleoptera: Chrysomeloidea) for Chile. Of these species, seven are described as new:
Acanthoscelides aricae sp. nov., Lithraeus chillan sp. nov., L. comptus sp. nov., L. elguetai sp. nov., L. limari sp. nov., L. lonquimay sp. nov., and L. penai sp. nov. Eight species are endemic to Chile. A list of true host plants and floral records for those with known host associations is presented. Habitus photographs and drawings of pertinent body parts, including male genitalia, are provided. References pertaining to the previously described species are listed.
This report provides a brief review of the 20th annual meeting of the German Language Branch of the Society of Environmental Toxicology and Chemistry (SETAC GLB) held from September 7th to 10th 2015 at ETH (Swiss Technical University) in Zurich, Switzerland. The event was chaired by Inge Werner, Director of the Swiss Centre for Applied Ecotoxicology (Ecotox Centre) Eawag-EPFL, and organized by a team from Ecotox Centre, Eawag, Federal Office of the Environment, Federal Office of Agriculture, and Mesocosm GmbH (Germany). Over 200 delegates from academia, public agencies and private industry of Germany, Switzerland and Austria attended and discussed the current state of science and its application presented in 75 talks and 83 posters. In addition, three invited keynote speakers provided new insights into scientific knowledge ‘brokering’, and—as it was the International Year of Soil—the important role of healthy soil ecosystems. Awards were presented to young scientists for best oral and poster presentations, and for best 2014 master and doctoral theses. Program and abstracts of the meeting (mostly in German) are provided as Additional file 1.
The Iranian fauna of Cucujidae, Laemophloeidae, and Silvanidae (Coleoptera: Cucujoidea) are summarized in this paper. In total 2 species of Cucujidae (1 genus: Pediacus Shuckard), 6 species of Laemophloeidae (3 genera: Cryptolestes Ganglbauer, Laemophloeus Dejean, and Placonotus MacLeay) and 7 species of Silvanidae (6 genera: Uleiota Latreille, Psammoecus Latreille, Ahasverus Gozis, Nausibius Lentz, Oryzaephilus Ganglbauer, Psammoecus Latreille, and Silvanus Latreille) are listed in this paper. Synonymies and distribution data are given.
The genus Paraphloeolaemus Thomas (Coleoptera: Cucujoidea: Laemophloeidae) is described for two new Neotropical species, P. vorticosus Thomas, new species, and P. pterosiagon Thomas, new species. Diagnoses and illustrations are provided.
The following 16 species are transferred from Laemophloeus Dejean (s. l.) to Phloeolaemus Casey: Phloeolaemus anticus (Sharp, 1899: 518) [= Laemophloeus anticus Sharp, 1899], new combination; Phloeolaemus boops (Sharp, 1899: 517) [= Laemophloeus boops Sharp, 1899], new combination; Phloeolaemus castaneipennis (Grouvelle, 1876: 494) [= Laemophloeus castaneipennis Grouvelle, 1876: 494], new combination; Phloeolaemus championi (Sharp, 1899: 516) [= Laemophloeus championi Sharp, 1899], new combination; Phloeolaemus curtus (Grouvelle, 1876: xxxiii) [= Laemophloeus curtus Grouvelle, 1876], new combination; Phloeolaemus endomychus (Sharp, 1899: 519) [= Laemophloeus endomychus Sharp, 1899], new combination; Phloeolaemus hoplites (Sharp, 1899: 517) [= Laemophloeus hoplites Sharp, 1899], new combination; Phloeolaemus ignobilis (Sharp, 1899: 518) [= Laemophloeus ignobilis Sharp, 1899], new combination; Phloeolaemus impressus (Grouvelle, 1876: xxxiii) [= Laemophloeus impressus Grouvelle, 1876], new combination; Phloeolaemus lacerdae (Grouvelle, 1877: 211) [= Laemophloeus lacerdae Grouvelle, 1877], new combination; Phloeolaemus macrocephalus (Schaeffer, 1910: 214) [= Laemophloeus macrocephalus Schaeffer, 1910], new combination; Phloeolaemus punctulaticollis (Hetschko, 1929: 94) [= Laemophloeus punctulaticollis Hetschko, 1929], new combination; Phloeolaemus reitteri (Grouvelle, 1877: 210) [= Laemophloeus reitteri Grouvelle, 1877], new combination; Phloeolaemus semiflavus (Grouvelle, 1876: 497) [= Laemophloeus semiflavus Grouvelle, 1876], new combination; Phloeolaemus sharpi (Hetschko, 1929: 41) [= Laemophloeus sharpi Hetschko, 1929], new combination; Phloeolaemus straminipennis (Reitter, 1876: 47) [= Laemophloeus straminipennis Reitter, 1876], new combination; Phloeolaemus teapensis (Grouvelle, 1876: 494) [= Laemophloeus teapensis Grouvelle, 1876], new combination.
The genus Rhinolaemus Steel is revised. A new island and a new country record are presented for the type species, R. maculatus Steel. A new species, R. niueensis Thomas, new species, is described from Niue, and Rhinolaemus tuberculatus (Grouvelle), new combination, is transferred from Laemophloeus (sens. lat.). The members of the genus are illustrated and a key to their identification is presented.
The ENVISAT validation programme for the atmospheric instruments MIPAS, SCIAMACHY and GOMOS is based on a number of balloon-borne, aircraft, satellite and ground-based correlative measurements. In particular the activities of validation scientists were coordinated by ESA within the ENVISAT Stratospheric Aircraft and Balloon Campaign or ESABC. As part of a series of similar papers on other species [this issue] and in parallel to the contribution of the individual validation teams, the present paper provides a synthesis of comparisons performed between MIPAS CH4 and N2O profiles produced by the current ESA operational software (Instrument Processing Facility version 4.61 or IPF v4.61, full resolution MIPAS data covering the period 9 July 2002 to 26 March 2004) and correlative measurements obtained from balloon and aircraft experiments as well as from satellite sensors or from ground-based instruments. In the middle stratosphere, no significant bias is observed between MIPAS and correlative measurements, and MIPAS is providing a very consistent and global picture of the distribution of CH4 and N2O in this region. In average, the MIPAS CH4 values show a small positive bias in the lower stratosphere of about 5%. A similar situation is observed for N2O with a positive bias of 4%. In the lower stratosphere/upper troposphere (UT/LS) the individual used MIPAS data version 4.61 still exhibits some unphysical oscillations in individual CH4 and N2O profiles caused by the processing algorithm (with almost no regularization). Taking these problems into account, the MIPAS CH4 and N2O profiles are behaving as expected from the internal error estimation of IPF v4.61 and the estimated errors of the correlative measurements.
Estimates of the recovery time of stratospheric ozone heavily rely on the exact knowledge of the processes that lead to the decomposition of the relevant halogenated source gases. Crucial parameters in this context are Fractional Release Factors (FRFs) as well as stratospheric lifetimes and Ozone Depletion Potentials (ODPs). We here present data from the analysis of air samples collected between 2009 and 2011 on board research aircraft flying in the mid- and high latitudinal stratosphere and infer the above-mentioned parameters for ten major source gases:CFCl3 (CFC-11), CF2Cl2 (CFC-12), CF2ClCFCl2(CFC-113), CCl4 (carbon tetrachloride),CH3CCl3 (methyl chloroform), CHF2Cl (HCFC-22), CH3CFCl2 (HCFC-141b), CH3CF2Cl (HCFC-142b), CF2ClBr (H-1211), and CF3Br (H-1301). The inferred correlations of their FRFs with mean ages of air reveal less decomposition as compared to previous studies for most compounds. When using the calculated set of FRFs to infer equivalent stratospheric chlorine we find a reduction of more than 20% as compared to the values inferred in the most recent Scientific Assessment of Ozone Depletion by the World Meteorological Organisation (WMO, 2011). We also note that FRFs and their correlations with mean age are not generally time-independent as often assumed. The stratospheric lifetimes were calculated relative to that of CFC-11. Within our uncertainties the inferred ratios between lifetimes agree with those between stratospheric lifetimes from recent WMO reports except for CFC-11, CFC-12 and CH3CCl3. Finally we calculate lower ODPs than WMO for six out of ten compounds with changes most pronounced for the three HCFCs. Collectively these newly calculated values may have important implications for the severity and recovery time of stratospheric ozone loss.
The ENVISAT validation programme for the atmospheric instruments MIPAS, SCIAMACHY and GOMOS is based on a number of balloon-borne, aircraft, satellite and ground-based correlative measurements. In particular the activities of validation scientists were coordinated by ESA within the ENVISAT Stratospheric Aircraft and Balloon Campaign or ESABC. As part of a series of similar papers on other species [this issue] and in parallel to the contribution of the individual validation teams, the present paper provides a synthesis of comparisons performed between MIPAS CH4 and N2O profiles produced by the current ESA operational software (Instrument Processing Facility version 4.61 or IPF v4.61, full resolution MIPAS data covering the period 9 July 2002 to 26 March 2004) and correlative measurements obtained from balloon and aircraft experiments as well as from satellite sensors or from ground-based instruments. In the middle stratosphere, no significant bias is observed between MIPAS and correlative measurements, and MIPAS is providing a very consistent and global picture of the distribution of CH4 and N2O in this region. In average, the MIPAS CH4 values show a small positive bias in the lower stratosphere of about 5%. A similar situation is observed for N2O with a positive bias of 4%. In the lower stratosphere/upper troposphere (UT/LS) the individual used MIPAS data version 4.61 still exhibits some unphysical oscillations in individual CH4 and N2O profiles caused by the processing algorithm (with almost no regularization). Taking these problems into account, the MIPAS CH4 and N2O profiles are behaving as expected from the internal error estimation of IPF v4.61 and the estimated errors of the correlative measurements.
Estimates of the recovery time of stratospheric ozone heavily rely on the exact knowledge of the processes that lead to the decomposition of the relevant halogenated source gases. Crucial parameters in this context are fractional release factors (FRFs) as well as stratospheric lifetimes and ozone depletion potentials (ODPs). We here present data from the analysis of air samples collected between 2009 and 2011 on board research aircraft flying in the mid- and high-latitude stratosphere and infer the above-mentioned parameters for ten major source gases: CFCl3 (CFC-11), CF2Cl2 (CFC-12), CF2ClCFCl2 (CFC-113), CCl4 (carbon tetrachloride), CH3CCl3 (methyl chloroform), CHF2Cl (HCFC-22), CH3CFCl2 (HCFC-141b), CH3CF2Cl (HCFC-142b), CF2ClBr (H-1211), and CF3Br (H-1301). The inferred correlations of their FRFs with mean ages of air reveal less decomposition as compared to previous studies for most compounds. When using the calculated set of FRFs to infer equivalent stratospheric chlorine, we find a reduction of more than 20% as compared to the values inferred in the most recent Scientific Assessment of Ozone Depletion by the World Meteorological Organisation (WMO, 2011). We also note that FRFs and their correlations with mean age are not generally time-independent as often assumed. The stratospheric lifetimes were calculated relative to that of CFC-11. Within our uncertainties the ratios between stratospheric lifetimes inferred here agree with the values in recent WMO reports except for CFC-11, CFC-12 and CH3CCl3. Finally, we calculate lower ODPs than recommended by WMO for six out of ten compounds, with changes most pronounced for the three HCFCs. Collectively these newly calculated values may have important implications for the severity and recovery time of stratospheric ozone loss.
Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of lymphocytes, macrophages, debris and the implants degradation products. Therefore the lymphatic vessels are involved in implant integration and fracture healing.
We report on HCFC-22 data acquired by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) in the reduced spectral resolution nominal observation mode. The data cover the period from January 2005 to April 2012 and the altitude range from the upper troposphere (above cloud top altitude) to about 50 km. The profile retrieval was performed by constrained nonlinear least squares fitting of modelled spectra to the measured limb spectral radiances. The spectral ν4-band at 816.5 ± 13 cm−1 was used for the retrieval. A Tikhonov-type smoothing constraint was applied to stabilise the retrieval. In the lower stratosphere, we find a global volume mixing ratio of HCFC-22 of about 185 pptv in January 2005. The rate of linear growth in the lower latitudes lower stratosphere was about 6 to 7 pptv year−1 in the period 2005–2012. The profiles obtained were compared with ACE-FTS satellite data v3.5, as well as with MkIV balloon profiles and cryosampler balloon measurements. Between 13 and 22 km, average agreement within −3 to +5 pptv (MIPAS – ACE) with ACE-FTS v3.5 profiles is demonstrated. Agreement with MkIV solar occultation balloon-borne measurements is within 10–20 pptv below 30 km and worse above, while in situ cryosampler balloon measurements are systematically lower over their full altitude range by 15–50 pptv below 24 km and less than 10 pptv above 28 km. MIPAS HCFC-22 time series below 10 km altitude are shown to agree mostly well to corresponding time series of near-surface abundances from the NOAA/ESRL and AGAGE networks, although a more pronounced seasonal cycle is obvious in the satellite data. This is attributed to tropopause altitude fluctuations and subsidence of polar winter stratospheric air into the troposphere. A parametric model consisting of constant, linear, quasi-biennial oscillation (QBO) and several sine and cosine terms with different periods has been fitted to the temporal variation of stratospheric HCFC-22 for all 10°-latitude/1-to-2-km-altitude bins. The relative linear variation was always positive, with relative increases of 40–70 % decade−1 in the tropics and global lower stratosphere, and up to 120 % decade−1 in the upper stratosphere of the northern polar region and the southern extratropical hemisphere. Asian HCFC-22 emissions have become the major source of global upper tropospheric HCFC-22. In the upper troposphere, monsoon air, rich in HCFC-22, is instantaneously mixed into the tropics. In the middle stratosphere, between 20 and 30 km, the observed trend is inconsistent with the trend at the surface (corrected for the age of stratospheric air), hinting at circulation changes. There exists a stronger positive trend in HCFC-22 in the Southern Hemisphere and a more muted positive trend in the Northern Hemisphere, implying a potential change in the stratospheric circulation over the observation period.
We report on HCFC-22 data acquired by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) in reduced spectral resolution nominal mode in the period from January 2005 to April 2012 from version 5.02 level-1b spectral data and covering an altitude range from the upper troposphere (above cloud top altitude) to about 50 km. The profile retrieval was performed by constrained nonlinear least squares fitting of measured limb spectral radiances to modelled spectra. The spectral v4-band at 816.5 ± 13 cm-1 was used for the retrieval. A Tikhonov-type smoothing constraint was applied to stabilise the retrieval. In the lower stratosphere, we find a global volume mixing ratio of HCFC-22 of about 185 pptv in January 2005. The linear growth rate in the lower latitudes lower stratosphere was about 6 to 7 pptv yr-1 in the period 2005–2012. The obtained profiles were compared with ACE-FTS satellite data v3.5, as well as with MkIV balloon profiles and in situ cryosampler balloon measurements. Between 13 and 22 km, average agreement within -3 to +5 pptv (MIPAS–ACE) with ACE-FTS v3.5 pro files is demonstrated. Agreement with MkIV solar occultation balloon-borne measurements is within 10–20 pptv below 30 km and worse above, while in situ cryosampler balloon measurements are systematically lower over their full altitude range by 15– 50 pptv below 24 km and less than 10 pptv above 28 km. Obtained MIPAS HCFC-22 time series below 10 km altitude are shown to agree mostly well to corresponding time series of near-surface abundances from NOAA/ESRL and AGAGE networks, although a more pronounced seasonal cycle is obvious in the satellite data, probably due to tropopause altitude fluctuations and subsidence of polar winter stratospheric air into the troposphere. A parametric model consisting of constant, linear, quasi-biennial oscillation (QBO) and several sine and cosine terms with different periods has been fitted to the temporal variation of stratospheric HCFC-22 for all 10° latitude/1 to 2 km altitude bins. The relative linear variation was always positive, with relative increases of 40–70%decade-1 in the tropics and global lower stratosphere, and up to 120%decade-1 in the upper stratosphere of the northern polar region and the southern extratropical hemisphere. In the middle stratosphere between 20 and 30 km, the observed trend is not consistent with the age of stratospheric air-corrected trend at ground, but stronger positive at the Southern Hemisphere and less strong increasing in the Northern Hemisphere, hinting towards changes in the stratospheric circulation over the observation period.
Background The role of the Fcgamma receptor IIa (FcgammaRIIa), a receptor for C-reactive protein (CRP), the classical acute phase protein, in atherosclerosis is not yet clear. We sought to investigate the association of FcgammaRIIa genotype with risk of coronary heart disease (CHD) in two large population-based samples. Methods FcgammaRIIa-R/H131 polymorphisms were determined in a population of 527 patients with a history of myocardial infarction and 527 age and gender matched controls drawn from a population-based MONICA- Augsburg survey. In the LURIC population, 2227 patients with angiographically proven CHD, defined as having at least one stenosis [greater than or equal to]50%, were compared with 1032 individuals with stenosis <50%. Results In both populations genotype frequencies of the FcgammaRIIa gene did not show a significant departure from the Hardy-Weinberg equilibrium. FcgammaRIIa R(-131)->H genotype was not independently associated with lower risk of CHD after multivariable adjustments, neither in the MONICA population (odds ratio (OR) 1.08; 95% confidence interval (CI) 0.81 to 1.44), nor in LURIC (OR 0.96; 95% CI 0.81 to 1.14). Conclusion Our results do not confirm an independent relationship between FcgammaRIIa genotypes and risk of CHD in these populations.
Purpose: Surgery of KOOS IV vestibular schwannoma remains challenging regarding the balance of extent of tumor resection (EoR) and functional outcome. Our aim was to evaluate the outcome of surgical resection and define a cut-off value for safe resection with low risk for tumor regrowth of KOOS IV vestibular schwannoma.
Methods: All patients presenting at the authors’ institution between 2000 and 2019 with surgically treated KOOS IV vestibular schwannoma were included. Outcome measures included EoR, facial/hearing nerve function, surgical complications and progression of residual tumor during the median follow-up period of 28 months.
Results: In 58 patients, mean tumor volume was 17.1 ± 9.2 cm3, and mean EoR of 81.6 ± 16.8% could be achieved. Fifty-one patients were available for the follow-up analysis. Growth of residual tumor was observed in 11 patients (21.6%) followed by adjuvant treatment with stereotactic radiosurgery or repeat surgery in 15 patients (29.4%). Overall serviceable hearing preservation was achieved in 38 patients (74.5%) and good facial outcome at discharge was observed in 66.7% of patients, significantly increasing to 82.4% at follow-up. Independent predictors for residual tumor growth was EoR ≤ 87% (OR11.1) with a higher EoR being associated with a very low number of residual tumor progression amounting to 7.1% at follow-up (p=0.008).
Conclusions: Subtotal tumor resection is a good therapeutic concept in patients with KOOS IV vestibular schwannoma resulting in a high rate of good hearing and facial nerve function and a very low rate of subsequent tumor progression. The goal of surgery should be to achieve more than 87% of tumor resection to keep residual tumor progression low.
Angiogenesis, the process by which endothelial cells (ECs) form new blood vessels from existing ones, is intimately linked to the tissue’s metabolic milieu and often occurs at nutrient-deficient sites. However, ECs rely on sufficient metabolic resources to support growth and proliferation. How endothelial nutrient acquisition and usage are regulated is unknown. Here we show that these processes are instructed by Yes-associated protein 1 (YAP)/WW domain-containing transcription regulator 1 (WWTR1/TAZ)-transcriptional enhanced associate domain (TEAD): a transcriptional module whose function is highly responsive to changes in the tissue environment. ECs lacking YAP/TAZ or their transcriptional partners, TEAD1, 2 and 4 fail to divide, resulting in stunted vascular growth in mice. Conversely, activation of TAZ, the more abundant paralogue in ECs, boosts proliferation, leading to vascular hyperplasia. We find that YAP/TAZ promote angiogenesis by fuelling nutrient-dependent mTORC1 signalling. By orchestrating the transcription of a repertoire of cell-surface transporters, including the large neutral amino acid transporter SLC7A5, YAP/TAZ-TEAD stimulate the import of amino acids and other essential nutrients, thereby enabling mTORC1 activation. Dissociating mTORC1 from these nutrient inputs—elicited by the loss of Rag GTPases—inhibits mTORC1 activity and prevents YAP/TAZ-dependent vascular growth. Together, these findings define a pivotal role for YAP/TAZ-TEAD in controlling endothelial mTORC1 and illustrate the essentiality of coordinated nutrient fluxes in the vasculature.
Purpose: Filler injections for aesthetic purposes are very popular, but can have far-reaching and irreversible consequences. This report describes the course of a patient with devastating complications after glabellar hyaluronic acid injection, their pathomechanism, management and outcome.
Observations: A healthy, 43-year-old woman underwent her first hyaluronic acid injection in the glabella and went blind on her left eye immediately thereafter. Massaging of the injection area and observation were performed, before she presented with swelling of the left forehead and upper lid, ptosis, complete ophthalmoplegia and blindness in our hospital. Immediate massaging of the globe and systemic therapy including acetylsalicylic acid, tinzaparin sodium and cortisone was initiated and hyaluronidase injections in the injection area were performed. In the further course, the patient developed necrotic and hemorrhagic skin and mucosal lesions, lagophthalmos, anterior and posterior segment ischemia and globe hypotonia with consecutive globe deformation. In the follow-up of 2.5 months, lid swelling, lagophthalmos and ptosis resolved and keratopathy improved but blindness, skin lesions and strabismus with reduced eye motility were still present and madarosis and early enophthalmos were detected.
Conclusions and Importance: The outcome of ophthalmic artery occlusion after hyaluronic acid filler injection is poor. Sufficient knowledge about facial anatomy, the implementation of filler injections and the management of complications is essential for the practitioner. The patient should be clarified about potential and even rare risks of these procedures.
There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation.
Background: Liver cirrhosis is associated with profound immunodysfunction, i.e. a parallel presence of chronic systemic inflammation and immunosuppression, which can result in acute-on-chronic liver failure (ACLF). Omega-3 fatty acids are precursors of pro-resolving mediators and support the resolution of inflammation.
Objective: The aim of this study was to determine plasma levels of omega-3 fatty acids in patients with liver cirrhosis and ACLF.
Methods: Patients with liver cirrhosis with and without ACLF were enrolled in a prospective cohort study and analyzed post-hoc for the present sub-study. Clinical data and biomaterials were collected at baseline and at day 7, 28 and after 3 months of follow-up. Plasma concentrations of arachidonic acid (ARA) and docosahexaenoic acid (DHA), which represent key omega-6 and -3 fatty acids, respectively, were quantified and associated with markers of systemic inflammation and severity of liver cirrhosis.
Results: A total of 117 patients were included in the present analyses. Of those, 26 (22.2%), 51 (43.6%) and 40 (34.2%) patients had compensated or decompensated liver cirrhosis, and ACLF. Plasma levels of ARA and DHA were similar in patients with compensated cirrhosis, decompensated cirrhosis, and ACLF. Furthermore, no significant association between plasma ARA or DHA and C-reactive protein or peripheral blood leukocytes were observed (P>0.05).
Conclusion: In our study plasma levels of key omega-3 and omega-6 fatty acid are neither associated with the severity of liver cirrhosis nor with liver-cirrhosis-associated systemic inflammation.
Electromagnetic calorimeter (ECAL) is being developed to complement dilepton spectrometer HADES. ECAL will enable the HADES@FAIR experiment to measure data on neutral meson production in heavy ion collisions at the energy range of 2-10 AGeV on the beam of future accelerator SIS100@FAIR. We will report results of the last beam test with quasi-monoenergetic photons carried out in MAMI facility at Johannes Gutenberg Universität Mainz.
Activation of TRPC6 channels is essential for lung ischaemia–reperfusion induced oedema in mice
(2012)
Lung ischaemia–reperfusion-induced oedema (LIRE) is a life-threatening condition that causes pulmonary oedema induced by endothelial dysfunction. Here we show that lungs from mice lacking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox2y/−) or the classical transient receptor potential channel 6 (TRPC6−/−) are protected from LIR-induced oedema (LIRE). Generation of chimeric mice by bone marrow cell transplantation and endothelial-specific Nox2 deletion showed that endothelial Nox2, but not leukocytic Nox2 or TRPC6, are responsible for LIRE. Lung endothelial cells from Nox2- or TRPC6-deficient mice showed attenuated ischaemia-induced Ca2+ influx, cellular shape changes and impaired barrier function. Production of reactive oxygen species was completely abolished in Nox2y/− cells. A novel mechanistic model comprising endothelial Nox2-derived production of superoxide, activation of phospholipase C-γ, inhibition of diacylglycerol (DAG) kinase, DAG-mediated activation of TRPC6 and ensuing LIRE is supported by pharmacological and molecular evidence. This mechanism highlights novel pharmacological targets for the treatment of LIRE.
Invasive fungal disease (IFD) in hematopoietic stem cell transplantation is associatedwith high morbidity and mortality. As the antifungal host response determines risk and outcomeof IFD, there is growing interest in adoptive immunotherapy using T cells or natural killer (NK)cells. Although the NK-92 cell line has been tested as anticancer therapy in clinical trials, data onthe antifungal activity of NK-92 cells are lacking. Here, we show that the NK-92 cell line exhibitsconsiderable fungal damage on all medically important fungi tested, such as different species ofAspergillus,Candida, mucormycetes, andFusarium. The extent of fungal damage differs acrossvarious species of mucormycetes andFusarium, whereas it is comparable across different species ofAspergillusandCandida. Interferon (IFN)-γlevels in the supernatant were lower when NK-92 cells areco-incubated withAspergillus fumigatus,Candida albicans, orRhizopus arrhizuscompared to the levelswhen NK-92 cells are incubated alone. Different to primary human NK cells, no increase of perforinlevels in the supernatant was observed when the fungi were added to NK-92 cells. Ourin vitrodatademonstrated that the NK-92 cell line could be a feasible tool for antifungal immunotherapy, butdata of animal models are warranted prior to clinical trials.
The Tarim River Basin, located in Xinjiang, NW China, is the largest endorheic river basin of China and one of the largest in whole Central Asia. Due to the extremely arid climate with an annual precipitation of less than 100 mm, the water supply along the Aksu and Tarim River solely depends on river water. This applies for anthropogenic activities (e.g. agriculture) as well as for the natural ecosystems so that both compete for water. The on-going increase of water consumption by agriculture and other human activities in this region has been enhancing the competition for water between human needs and nature. Against this background, 11 German and 6 Chinese universities and research institutes formed the consortium SuMaRiO (www.sumario.de), which aims at gaining a holistic picture of the availability of water resources in the Tarim River Basin and the impacts on anthropogenic activities and natural ecosystems caused by the water distribution within the Tarim River Basin. The discharge of the Aksu River, which is the major tributary to the Tarim, has been increasing over the past 6 decades due to enhanced glacier melt. Alone from 1989 to 2011, the area under agriculture more than doubled. Thereby, cotton became the major crop and there was a shift from small-scale farming to large-scale intensive farming. The major natural ecosystems along the Aksu and Tarim River are riparian ecosystems: Riparian (Tugai) forests, shrub vegetation, reed beds, and other grassland. Within the SuMaRiO Cluster the focus was laid on the Tugai forests, with Populus euphratica as dominant tree, because the most productive and species-rich natural ecosystems can be found among those forests. On sites with groundwater distance of less than 7.5 m the annual increments correlated with river runoffs of the previous year. But, the further downstream along the Tarim River, the more the natural river dynamics ceased, which impacts on the recruitment of Populus euphratica. Household surveys revealed that there is a considerable willingness to pay for conservation of those riparian forests with the mitigation of dust and sandstorms considered as the most important ecosystem service. This interdisciplinary project will result in a decision support tool (DST), build on the participation of regional stakeholders and models based on results and field experiments. This DST finally shall assist stakeholders in balancing the water competition acknowledging the major external effects of any water allocation.
Schriftenschau
(2006)
The adaptive response of Sorghum bicolor landraces from Egypt to drought stress and following recovery was analyzed using two-dimensional difference gel electrophoresis, 2D-DIGE. Physiological measurements and proteome alterations of accession number 11434, drought tolerant, and accession number 11431, drought sensitive, were compared to their relative control values after drought stress and following recovery. Differentially expressed proteins were analysed by Matrix assisted laser desorption ionisation time-of-flight mass spectrometry, MALDI-TOF-MS. Alterations in protein contents related to the energy balance, metabolism (sensu Mewes et al. 1997), and chaperons were the most apparent features to elucidate the differences between the drought tolerant and sensitive accessions. Further alterations in the levels of proteins related to transcription and protein synthesis are discussed.
Zielsetzung: Die Daten für das Jahr 2019 des Registers „Abdominelles Aortenaneurysma“ (AAA) des Deutschen Instituts für Gefäßmedizinische Gesundheitsforschung (DIGG) der Deutschen Gesellschaft für Gefäßchirurgie und Gefäßmedizin werden vorgestellt.
Methodik: Im Jahr 2019 beteiligten sich an dem Register insgesamt 109 Kliniken. Für die offene Versorgung (OR) des intakten AAA (iAAA) gaben 78 (71,6 %) Kliniken, für die endovaskuläre Versorgung (EVAR) des iAAA 102 (93,6 %) Kliniken Daten ein. Für das rupturierte AAA (rAAA) wurden von 36 Kliniken (33,0 %) (EVAR) bzw. 50 (45,9 %) Kliniken (OR) Patienten gemeldet. Ausgewertet wurden die Daten von 1967 stationär behandelten Patienten. Von den insgesamt 1793 iAAA waren 1501 infrarenal (83,7 %) und 292 (16,3 %) juxtarenal gelegen.
Ergebnisse: 1429 iAAA (79,7 %) wurden endovaskulär und 364 (20,3 %) offen versorgt. Bei den endovaskulär versorgten Patienten mit iAAA verlief der Eingriff in 86,3 % der Fälle komplikationslos. Es verstarben insgesamt 15 Patienten (1,0 %) bis zur Entlassung. Bei den offen versorgten Patienten wiesen 67,0 % der Patienten keine Komplikationen auf. Verstorben sind insgesamt 20 Patienten (5,5 %). Bei EVAR war die Klinikletalität bei Versorgung juxtarenaler AAA mit 3,7 % signifikant höher als bei Versorgung infrarenaler AAA mit 0,6 % (p = 0,002), bei OR konnten hingegen keine signifikanten Unterschiede hinsichtlich der Klinikletalität aufgezeigt werden (juxtarenal 4,8 %, infrarenal 5,8 %; p = 0,470). Von den 174 Patienten mit rAAA wurden 80 (46,0 %) endovaskulär und 94 (54,0 %) offen versorgt. Bei EVAR sind 20,0 % der Patienten während des stationären Aufenthalts verstorben, bei OR 36,2 %.
Schlussfolgerung: Die Ergebnisse des Jahres 2019 zu Klinikletalität und Morbidität bei endovaskulärer und offener Versorgung des iAAA bestätigen weitgehend die publizierten Ergebnisse für die Jahre 2013 bis 2018. Beim rAAA sind die Ergebnisse der einzelnen Jahresberichte hingegen widersprüchlich, die kleinen berichteten jährlichen Fallzahlen erlauben nur Aussagen über größere Zeiträume.
Redirection of miRNA‐argonaute complexes to specific target sites by synthetic adaptor molecules
(2020)
Dysregulation of miRNAs is connected with a multitude of diseases for which antagomirs and miRNA replacement are discussed as therapeutic options. Here, we suggest an alternative concept based on the redirection of RISCs to non‐native target sites. Metabolically stable DNA‐LNA mixmers are used to mediate the binding of RISCs to mRNAs without any direct base complementarity to the presented guide RNA strand. Physical redirection of a dye‐labeled miRNA model and of specific miRNA‐programmed RISC fractions present in HeLa extracts is demonstrated by pull‐down experiments with biotinylated capture oligonucleotides.
Background: There are several ways to conduct a job task analysis in medical work environments including pencil-paper observations, interviews and questionnaires. However these methods implicate bias problems such as high inter-individual deviations and risks of misjudgement. Computer-based observation helps to reduce these problems. The aim of this paper is to give an overview of the development process of a computer-based job task analysis instrument for real-time observations to quantify the job tasks performed by physicians working in different medical settings. In addition reliability and validity data of this instrument will be demonstrated.
Methods: This instrument was developed in consequential steps. First, lists comprising tasks performed by physicians in different care settings were classified. Afterwards content validity of task lists was proved. After establishing the final task categories, computer software was programmed and implemented in a mobile personal computer. At least inter-observer reliability was evaluated. Two trained observers recorded simultaneously tasks of the same physician.
Results: Content validity of the task lists was confirmed by observations and experienced specialists of each medical area. Development process of the job task analysis instrument was completed successfully. Simultaneous records showed adequate interrater reliability.
Conclusion: Initial results of this analysis supported the validity and reliability of this developed method for assessing physicians' working routines as well as organizational context factors. Based on results using this method, possible improvements for health professionals' work organisation can be identified.
Site-specific cleavage of RNAs derived from the PIM1 3′-UTR by a metal-free artificial ribonuclease
(2019)
Oligonucleotide conjugates of tris(2-aminobenzimidazole) have been reported previously to cleave complementary RNA strands with high levels of sequence and site specificity. The RNA substrates used in these studies were oligonucleotides not longer than 29-mers. Here we show that ~150–400-mer model transcripts derived from the 3′-untranslated region of the PIM1 mRNA reacted with rates and specificities comparable to those of short oligonucleotide substrates. The replacement of DNA by DNA/LNA mixmers further increased the cleavage rate. Tris(2-aminobenzimidazoles) were designed to interact with phosphates and phosphate esters. A cell, however, contains large amounts of phosphorylated species that may cause competitive inhibition of RNA cleavage. It is thus important to note that no loss in reaction rates was observed in phosphate buffer. This opens the way to in-cell applications for this type of artificial nuclease. Furthermore, we disclose a new synthetic method giving access to tris(2-aminobenzimidazoles) in multigram amounts.
Seven different instruments and measurement methods were used to examine the immersion freezing of bacterial ice nuclei from Snomax® (hereafter Snomax), a product containing ice active protein complexes from non-viable Pseudomonas syringae bacteria. The experimental conditions were kept as similar as possible for the different measurements. Of the participating instruments, some examined droplets which had been made from suspensions directly, and the others examined droplets activated on previously generated Snomax particles, with particle diameters of mostly a few hundred nanometers and up to a few micrometers in some cases. Data were obtained in the temperature range from −2 to −38 °C, and it was found that all ice active protein complexes were already activated above −12 °C. Droplets with different Snomax mass concentrations covering 10 orders of magnitude were examined. Some instruments had very short ice nucleation times down to below 1 s, while others had comparably slow cooling rates around 1 K min−1. Displaying data from the different instruments in terms of numbers of ice active protein complexes per dry mass of Snomax, nm, showed that within their uncertainty the data agree well with each other as well as to previously reported literature results. Two parameterizations were taken from literature for a direct comparison to our results, and these were a time dependent approach based on a contact angle distribution Niedermeier et al. (2014) and a modification of the parameterization presented in Hartmann et~al.~(2013) representing a time independent approach. The agreement between these and the measured data were good, i.e. they agreed within a temperature range of 0.6 K or equivalently a range in nm of a factor of 2. From the results presented herein, we propose that Snomax, at least when carefully shared and prepared, is a suitable material to test and compare different instruments for their accuracy of measuring immersion freezing.
Seven different instruments and measurement methods were used to examine the immersion freezing of bacterial ice nuclei from Snomax® (hereafter Snomax), a product containing ice-active protein complexes from non-viable Pseudomonas syringae bacteria. The experimental conditions were kept as similar as possible for the different measurements. Of the participating instruments, some examined droplets which had been made from suspensions directly, and the others examined droplets activated on previously generated Snomax particles, with particle diameters of mostly a few hundred nanometers and up to a few micrometers in some cases. Data were obtained in the temperature range from −2 to −38 °C, and it was found that all ice-active protein complexes were already activated above −12 °C. Droplets with different Snomax mass concentrations covering 10 orders of magnitude were examined. Some instruments had very short ice nucleation times down to below 1 s, while others had comparably slow cooling rates around 1 K min−1. Displaying data from the different instruments in terms of numbers of ice-active protein complexes per dry mass of Snomax, nm, showed that within their uncertainty, the data agree well with each other as well as to previously reported literature results. Two parameterizations were taken from literature for a direct comparison to our results, and these were a time-dependent approach based on a contact angle distribution (Niedermeier et al., 2014) and a modification of the parameterization presented in Hartmann et al. (2013) representing a time-independent approach. The agreement between these and the measured data were good; i.e., they agreed within a temperature range of 0.6 K or equivalently a range in nm of a factor of 2. From the results presented herein, we propose that Snomax, at least when carefully shared and prepared, is a suitable material to test and compare different instruments for their accuracy of measuring immersion freezing.
Investigations of the micro- and nanostructures and chemical composition of the sponge skeletons as examples for natural structural biocomposites are of fundamental scientific relevance. Recently, we show that some demosponges (Verongula gigantea, Aplysina sp.) and glass sponges (Farrea occa, Euplectella aspergillum) possess chitin as a component of their skeletons. The main practical approach we used for chitin isolation was based on alkali treatment of corresponding external layers of spicules sponge material with the aim of obtaining alkali-resistant compounds for detailed analysis. Here, we present a detailed study of the structural and physicochemical properties of spicules of the glass sponge Rossella fibulata. The structural similarity of chitin derived from this sponge to invertebrate alpha chitin has been confirmed by us unambiguously using physicochemical and biochemical methods. This is the first report of a silica-chitin composite biomaterial found in Rossella species. Finally, the present work includes a discussion related to strategies for the practical application of silica-chitin-based composites as biomaterials.
Lichen-forming fungi are symbiotic organisms that synthesize unique natural products with potential for new drug leads. Here, we explored the pharmacological activity of six lichen extracts (Evernia prunastri, Pseudevernia furfuracea, Umbilicaria pustulata, Umbilicaria crustulosa, Flavoparmelia caperata, Platismatia glauca) in the context of cancer and inflammation using a comprehensive set of 11 functional and biochemical in vitro screening assays. We assayed intracellular Ca2+ levels and cell migration. For cancer, we measured tumor cell proliferation, cell cycle distribution and apoptosis, as well as the angiogenesis-associated proliferation of endothelial cells (ECs). Targeting inflammation, we assayed leukocyte adhesion onto ECs, EC adhesion molecule expression, as well as nitric oxide production and prostaglandin (PG)E2 synthesis in leukocytes. Remarkably, none of the lichen extracts showed any detrimental influence on the viability of ECs. We showed for the first time that extracts of F. caperata induce Ca2+ signaling. Furthermore, extracts from E. prunastri, P. furfuracea, F. caperata, and P. glauca reduced cell migration. Interestingly, F. caperata extracts strongly decreased tumor cell survival. The proliferation of ECs was significantly reduced by E. prunastri, P. furfuracea, and F. caperata extracts. The extracts did not inhibit the activity of inflammatory processes in ECs. However, the pro-inflammatory activation of leukocytes was inhibited by extracts from E. prunastri, P. furfuracea, F. caperata, and P. glauca. After revealing the potential biological activities of lichen extracts by an array of screening tests, a correlation analysis was performed to evaluate particular roles of abundant lichen secondary metabolites, such as atranorin, physodic acid, and protocetraric acid as well as usnic acid in various combinations. Overall, some of the lichen extracts tested in this study exhibit significant pharmacological activity in the context of inflammation and/or cancer, indicating that the group lichen-forming fungi includes promising members for further testing.
Rezensionen [2020]
(2020)
Verzeichnis
Einzelrezensionen
148 Bäni Rigler, Petra: Bilderbuch – Lesebuch – Künstlerbuch. Elsa Beskows Ästhetik des Materiellen (Heinz-Jürgen Kliewer)
149 Barilaro, Christina/Oetken, Mareile(Hg.): Erzähl mir vom Tier. Tiere in der Kinderliteratur und in der Natur (Kurt Franz)
151 Bieker, Nadine: Erzählanfänge und Erzählschlüsse im Adoleszenzroman (Astrid Henning-Mohr)
153 Blumesberger, Susanne/Seibert, Ernst (Hg.): Kinderliteratur in Wien um 1800 (Michael Stierstorfer)
154 Brons, Patricia/Nickel, Artur /Nicolai, Matthias (Hg.): Kästneriaden zum 120. Geburtstag (Sabine Planka)
156 Dallmann, Christine/Hartung, Anja/Aigner, Alfons /Buchele, Kai-Thorsten (Hg.): Comics. Interdisziplinäre Perspektiven aus Theorie und Praxis auf ein Stiefkind der Medienpädagogik (Carolin Führer)
157 Darr, Yael: The Nation and the Child. Nation Building in Hebrew Children’s Literature, 1930–1970 (Susanne Blumesberger)
159 Dingelmaier, Theresia: Das Märchen vom Märchen. Eine kultur- und literaturwissenschaftliche Untersuchung des deutschsprachigen jüdischen Volks- und Kindermärchens (Kurt Franz)
161 Field, Hannah: Playing with the Book. Victorian Movable Picture Books and the Child Reader (Petra Bäni Rigler)
163 Gittinger, Kerstin/ Loidl, Sonja (Hg.): Unter Wölfen. Käthe Recheis – Literatur und Politik (Lena Hoffmann)
164 Giuriato, Davide/Hubmann, Philipp/Schildmann, Mareike (Hg.): Kindheit und Literatur. Konzepte – Poetik – Wissen (Ernst Seibert)
166 Glasenapp, Gabriele von/Pecher, Claudia Maria/Anker, Martin (Hg.): Martin Luther und die Reformation in der Kinder- und Jugendliteratur. Beiträge zur literarhistorischen und literarästhetischen Praxis (Roland Issler)
169 Gruner, Elizabeth Rose: Constructing the Adolescent Reader in Contemporary Young Adult Fiction (Thomas Kullmann)
171 Harde, Roxanne/Kokkola, Lydia (Hg.): The Embodied Child. Readings in Children’s Literature and Culture (Thomas Kullmann)
172 Holzen, Aleta-Amirée von: Maskierte Helden. Zur Doppelidentität in Pulp-Novels und Superheldencomics (Maike Paiska)
174 Hubli, Kathrin: Kunstprojekt (Mumin-)Buch. Tove Janssons prozessuale Ästhetik und materielle Transmission (Ben Dammers)
175 Jantzen, Christoph/ Josting, Petra/Ritter, Michael (Hg.): Ästhetik – Leserbezug – Wirkung. Ansprüche an Kinder- und Jugendliteratur im Wandel der Zeit (Nadine Bieker)
177 Jung, Britta C.: Komplexe Lebenswelten – multidirektionale Erinnerungsdiskurse. Jugendliteratur zum Nationalsozialismus, Zweiten Weltkrieg und Holocaust im Spiegel des postmemorialen Wandels (Susanne Blumesberger)
179 Meyer, Christina: Producing Mass Entertainment. The Serial Life of the Yellow Kid (Aleta-Amirée von Holzen)
181 Rox-Helmer, Monika: Der historische Jugendroman als geschichtskulturelle Gattung. Fiktionalisierung von Geschichte und ihr didaktisches Potential (Annette Kliewer)
182 Seidel, Nadine Maria: Adoleszenz, Geschlecht, Identität. Queere Konstruktionen in Romanen nach der Jahrtausendwende (Annette Kliewer)
184 Sonyem, Alain Belmond: Kinder- und Jugendliteratur als Gegendiskurs? Zu Afrikavorstellungen in neueren deutschen und deutschafrikanischen Kinder- und Jugendbüchern (Astrid Henning-Mohr)
186 Sprenger, Karoline: Bertolt Brechts Kinderlyrik. Hintergründe, Analysen und fachdidaktische Perspektiven (Kurt Franz)
188 Uhlig, Bettina/ Lieber, Gabriele/Pieper, Irene (Hg.): Erzählen zwischen Bild und Text (Heinz-Jürgen Kliewer) 190 Van Nahl, Ruth: Jugendkrimis im 21. Jahrhundert. Eine Typologie (Sabine Fuchs)
192 Wietersheim, Annegret von: »Später einmal werde ich es dir erzählen«. Leerstellen in der Kinder- und Jugendliteratur der 1950er Jahre (Susanne Blumesberger)
While interleukin (IL)-1β is a potent pro-inflammatory cytokine involved in host defense, high levels can cause life-threatening sterile inflammation including systemic inflammatory response syndrome. Hence, the control of IL-1β secretion is of outstanding biomedical importance. In response to a first inflammatory stimulus such as lipopolysaccharide, pro-IL-1β is synthesized as a cytoplasmic inactive pro-form. Extracellular ATP originating from injured cells is a prototypical second signal for inflammasome-dependent maturation and release of IL-1β. The human anti-protease alpha-1 antitrypsin (AAT) and IL-1β regulate each other via mechanisms that are only partially understood. Here, we demonstrate that physiological concentrations of AAT efficiently inhibit ATP-induced release of IL-1β from primary human blood mononuclear cells, monocytic U937 cells, and rat lung tissue, whereas ATP-independent IL-1β release is not impaired. Both, native and oxidized AAT are active, suggesting that the inhibition of IL-1β release is independent of the anti-elastase activity of AAT. Signaling of AAT in monocytic cells involves the lipid scavenger receptor CD36, calcium-independent phospholipase A2β, and the release of a small soluble mediator. This mediator leads to the activation of nicotinic acetylcholine receptors, which efficiently inhibit ATP-induced P2X7 receptor activation and inflammasome assembly. We suggest that AAT controls ATP-induced IL-1β release from human mononuclear blood cells by a novel triple-membrane-passing signaling pathway. This pathway may have clinical implications for the prevention of sterile pulmonary and systemic inflammation.
Recent clinical data support the clinical use of oral lavender oil in patients suffering from subsyndromal anxiety. We identified the molecular mechanism of action that will alter the perception of lavender oil as a nonspecific ingredient of aromatherapy to a potent anxiolytic inhibiting voltage dependent calcium channels (VOCCs) as highly selective drug target. In contrast to previous publications where exorbitant high concentrations were used, the effects of lavender oil in behavioral, biochemical, and electrophysiological experiments were investigated in physiological concentrations in the nanomolar range, which correlate to a single dosage of 80 mg/d in humans that was used in clinical trials. We show for the first time that lavender oil bears some similarities with the established anxiolytic pregabalin. Lavender oil inhibits VOCCs in synaptosomes, primary hippocampal neurons and stably overexpressing cell lines in the same range such as pregabalin. Interestingly, Silexan does not primarily bind to P/Q type calcium channels such as pregabalin and does not interact with the binding site of pregabalin, the α2δ subunit of VOCCs. Lavender oil reduces non-selectively the calcium influx through several different types of VOCCs such as the N-type, P/Q-type and T-type VOCCs. In the hippocampus, one brain region important for anxiety disorders, we show that inhibition by lavender oil is mainly mediated via N-type and P/Q-type VOCCs. Taken together, we provide a pharmacological and molecular rationale for the clinical use of the oral application of lavender oil in patients suffering from anxiety.