Refine
Year of publication
Document Type
- Preprint (701)
- Article (639)
- Book (2)
- Working Paper (2)
- Conference Proceeding (1)
- Part of Periodical (1)
Language
- English (1346)
Has Fulltext
- yes (1346)
Is part of the Bibliography
- no (1346)
Keywords
- Heavy Ion Experiments (21)
- Hadron-Hadron Scattering (11)
- Hadron-Hadron scattering (experiments) (11)
- LHC (9)
- Heavy-ion collision (6)
- ALICE experiment (4)
- Collective Flow (4)
- Genetics (4)
- Jets (4)
- Quark-Gluon Plasma (4)
- ALICE (3)
- CRISPR/Cas9 (3)
- Elastic scattering (3)
- Heavy Quark Production (3)
- Jets and Jet Substructure (3)
- Psychiatric disorders (3)
- Treatment (3)
- pp collisions (3)
- schizophrenia (3)
- ADHD (2)
- Beauty production (2)
- Biogeography (2)
- Bipolar disorder (2)
- Charm physics (2)
- Collectivity (2)
- Correlation (2)
- Diffraction (2)
- Elliptic flow (2)
- Experimental nuclear physics (2)
- Experimental particle physics (2)
- Guidelines (2)
- HER2/neu (2)
- HLA class I (2)
- Heavy Ions (2)
- Heavy-ion collisions (2)
- Human behaviour (2)
- Immunology (2)
- Lepton-Nucleon Scattering (experiments) (2)
- MHC (2)
- Neuroscience (2)
- Particle Correlations and Fluctuations (2)
- Particle and resonance production (2)
- Particle correlations and fluctuations (2)
- Pb–Pb collisions (2)
- Polarization (2)
- Quarkonium (2)
- RHIC (2)
- Shear viscosity (2)
- Single electrons (2)
- Sweden (2)
- Trauma (2)
- chemotherapy (2)
- epigenetics (2)
- 16S (1)
- 5-Aminolävulinsäure (5-ALA) (1)
- 5-aminolevulinic acid (5-ALA) (1)
- 900 GeV (1)
- ABC transporters (1)
- ALICE detector (1)
- APM (1)
- APP processing (1)
- ATAD2 (1)
- ATPases (1)
- Actin (1)
- Activities of daily living (1)
- Acute lymphocytic leukaemia (1)
- Adult (1)
- Adult-onset ADHD (1)
- Advanced biliary tract cancer (1)
- Advanced breast cancer (1)
- Aichi targets (1)
- Aiolochroia crassa (1)
- Alliaria petiolata (1)
- Alzheimer (1)
- Anti-nuclei (1)
- Antigens/Peptides/Epitopes (1)
- Antihormone therapy (1)
- Antiretroviral therapy (1)
- Antiretrovirals (1)
- Appendectomy (1)
- Appendicitis (1)
- Arbitrage (1)
- Asymptotically Even Nonlinearity (1)
- Ataxia-telangiectasia (1)
- Atherosclerosis (1)
- Atmospheric chemistry (1)
- Atmospheric science (1)
- B-slope (1)
- BET inhibitors (1)
- BRCA1 (1)
- BRCA2 (1)
- BRD2 (1)
- BRD4 (1)
- BROMO-10 (1)
- BTC (1)
- Babesia divergens (1)
- Babesia microti (1)
- Big Five (1)
- Biochemistry and chemical biology (1)
- Biodiversity conservation (1)
- Biodiversity tools and pipelines (1)
- Biological (1)
- Black and Scholes Option Price theory (1)
- Blocked Realized Kernel (1)
- Body temperature (1)
- Boosted Jets (1)
- Borrelia (1)
- Boundary Value Problems (1)
- Bromodomänen (1)
- CAR (1)
- CDH13 (1)
- CDK4/CDK6 (1)
- CNVs (1)
- COI (1)
- CVD biomarker (1)
- CVID (1)
- CYBA/p22phox (1)
- Cancer (1)
- Cancer genomics (1)
- Carbapenem-resistente Gram-negative Bakterien (CRGN) (1)
- Carbapenemasen (1)
- Cardiomyocyte signaling pathways (1)
- Cardiomyopathy (1)
- Cardioprotection (1)
- Cardiovascular disease (1)
- Cardiovascular diseases (1)
- Cell biology (1)
- Cell membranes (1)
- Centrality Class (1)
- Centrality Selection (1)
- Charged-particle multiplicity (1)
- Charm quark spatial diffusion coefficient (1)
- Charmonia (1)
- Chemische Sonden (1)
- Child health (1)
- Chronic hepatitis C (1)
- Circadian (1)
- Cirrhosis (1)
- Classification (1)
- Climate change (1)
- Clinical Trials and Observations (1)
- Clinical variation (1)
- Closure (1)
- Coalescence (1)
- Cognitive impairment (1)
- Cold nuclear matter effects (1)
- Collective Flow, (1)
- Community dynamics (1)
- Comorbidities (1)
- Comorbidity (1)
- Comparison with QCD (1)
- Complex I (1)
- Complicated appendicitis (1)
- Conformational trapping (1)
- Conservative (1)
- Covariance Prediction (1)
- Critical point (1)
- CspA (1)
- CspZ (1)
- Cytoskeleton (1)
- DIPSHIFT (1)
- Data sharing (1)
- Data standard (1)
- Data standards (1)
- Database searching (1)
- Degenerate Linear Part (1)
- Depression (1)
- Deuteron production (1)
- Developmental trajectory (1)
- Di-hadron correlations (1)
- Diagnostic differentiation (1)
- Diagnostic markers (1)
- Dilated cardiomyopathy (1)
- Discovery (1)
- Disease Activity (1)
- Dissemination (1)
- Drug targeting (1)
- E. colo (1)
- E/I-Balance (1)
- EMT (1)
- ERBB2 (1)
- ERBB2 (HER2/neu) (1)
- Early Rheumatoid Arthritis (1)
- Ecology (1)
- Ecophysiology (1)
- Ed Diener (1)
- Elderly (1)
- Electron-pion identification (1)
- Electrophysiology (1)
- Electroweak interaction (1)
- Embolization (1)
- Ena/VASP proteins (1)
- Endothelial permeability (1)
- Entomology (1)
- Epigenetik (1)
- Epilepsy (1)
- Erythrocytes (1)
- European Society for Immunodeficiencies (ESID) (1)
- Extracellular RNA (eRNA) (1)
- Factor H (1)
- Factor Model (1)
- Femtoscopy (1)
- Ferroelectrics and multiferroics (1)
- Fibre/foam sandwich radiator (1)
- Fibromyalgia (1)
- Finite temperature field theory (1)
- Fistula (1)
- Flow (1)
- Frailty (1)
- G protein-coupled receptors (1)
- GWAS (1)
- Gadobutrol (1)
- Gadopentate dimeglumine (1)
- Gamma-Band Activity (1)
- General practitioners (1)
- German PID-NET registry (1)
- Germany (1)
- Giraffa (1)
- Groomed jet radius (1)
- Guanine nucleotide exchange factors (1)
- Guanosine triphosphatase (1)
- HBT (1)
- HEOR (1)
- HER2 c-erbB2 (1)
- HIV (1)
- HIV-1 (1)
- Hadron production (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Hadronization (1)
- Hand-foot syndrome (1)
- Hard Scattering (1)
- Health risk analysis (1)
- Heart (1)
- Heart regeneration (1)
- Heart transplantation (1)
- Heavy Ion Experiment (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ion collisions (1)
- Heavy ions (1)
- Heavy-Ion Collision (1)
- Heavy-flavor decay electron (1)
- Heavy-flavour decay muons (1)
- Heavy-flavour production (1)
- Heavy-ion (1)
- Hepatitis C virus (1)
- Hereditary breast and ovarian cancer (1)
- Heregulin (1)
- Hif1α (1)
- Higher moments (1)
- Hippocampus (1)
- Human (1)
- Hypertension (1)
- IgA deficiency (1)
- IgG substitution therapy (1)
- Immunodeficiency (1)
- Immunogenetics (1)
- Immunoglobulins (1)
- Immunotherapy (1)
- In vitro selection (1)
- Inclusive spectra (1)
- Index at Infinity (1)
- Individual based modeling (1)
- Induced pluripotent stem cells (1)
- Inherited arrhythmic syndrome (1)
- Intensity interferometry (1)
- Interference fragmentation function (1)
- Intra-abdominal infection (1)
- Invariant Mass Distribution (1)
- Ionisation energy loss (1)
- Ischemia–reperfusion injury (1)
- Isoxazoline Alkaloids (1)
- Italy (1)
- J/ψ suppression (1)
- Jet Physics (1)
- Jet Substructure (1)
- Jet substructure (1)
- KCGS (1)
- Katze (1)
- Lactic acidosis (1)
- Landscape genetics (1)
- Landwirtschaftlicher Betrieb (1)
- Laparoscopic appendectomy (1)
- Laparostomy (1)
- Library screening (1)
- Lipid metabolism (1)
- Liver diseases (1)
- Liver transplantation (1)
- Long distance movement (1)
- Long-Range Dependence (1)
- Luciferase (1)
- Lymphocytes (1)
- Lymphoid tissues (1)
- Lymphopenia Mortality (1)
- MACE (1)
- MET (1)
- MM-121 (1)
- MRI (1)
- Magnetic properties and materials (1)
- Marine biodiversity (1)
- Material budget (1)
- Medizinische Chemie (1)
- Meldepflicht (1)
- Membrane protein (1)
- Mena/VASP (1)
- Mesh (1)
- Metaanalysis (1)
- Metastatic (1)
- MicroRNAs (miRNAs) (1)
- Mid-rapidity (1)
- Minimum Bias (1)
- Mitochondria (1)
- Mitochondrial disorder (1)
- Mixing Frequencies (1)
- Mobile links (1)
- Molecular autopsy (1)
- Molecular biology (1)
- Molecular neuroscience (1)
- Monte Carlo (1)
- Mortality (1)
- Multi-Parton Interactions (1)
- Multi-strange baryons (1)
- Multi-wire proportional drift chamber (1)
- Multiple parton interactions (1)
- Myeloid Neoplasia (1)
- Myocardial infarction (1)
- N-methyl-D-aspartate receptor (1)
- NADPH oxidase (1)
- NK-92 (1)
- NMR (1)
- NO (1)
- Nanobody (1)
- Neolithic (1)
- Neonatal (1)
- Net-charge correlations (1)
- Net-charge fluctuations (1)
- Neural network (1)
- Nitric oxide (1)
- Non-operative (1)
- Non-trauma (1)
- Nonflow (1)
- Noninferiority (1)
- Nonperturbative effects in field theory (1)
- Nuclear modification factor (1)
- Nutrition (1)
- Oldest-old (1)
- Oncology (1)
- Open abdomen (1)
- OspE (1)
- Outcomes research (1)
- PARK2 (1)
- PDGFRβ (1)
- PID prevalence (1)
- PYTHIA (1)
- Pancreatitis (1)
- Parkinson's disease (1)
- Particle and Resonance Production (1)
- Pb–Pb (1)
- Pediatric (1)
- Peer review (1)
- Peritonitis (1)
- Personalized medicine (1)
- Phage display (1)
- Phase transitions and critical phenomena (1)
- Phosphorylation (1)
- Photodynamische Therapie (PDT) (1)
- Phylogenomics (1)
- Physiology (1)
- Platelet (1)
- Population genetics (1)
- Portfolio Optimization (1)
- Portfolios (1)
- Post-mortem genetic screening (1)
- Prediction (1)
- Predictive markers (1)
- Production Cross Section (1)
- Prognosis (1)
- Properties of Hadrons (1)
- Proton-proton collisions (1)
- Proton–proton (1)
- Proton–proton collisions (1)
- Psychiatry (1)
- QCD (1)
- Quantum field theory (1)
- Quark Deconfinement (1)
- Quark Gluon Plasma (1)
- Quark Production (1)
- Questionnaires (1)
- RMS (1)
- Rapidity Range (1)
- Re-exploration (1)
- Red blood cell transfusion (1)
- Red blood cells (1)
- Reintervention (1)
- Relativistic heavy ion physics (1)
- Relativistic heavy-ion collisions (1)
- Remote ischemic conditioning (1)
- Renal lesions (1)
- Research Article (1)
- Resolution Parameter (1)
- Rheumatoid Arthritis (1)
- Ribosome display (1)
- SNP (1)
- STAR (1)
- SVR (1)
- Safety (1)
- Schizophrenia (1)
- Seasonal variation (1)
- Seribantumab (1)
- Single muons (1)
- Small molecules (1)
- SoftDrop (1)
- Solar insolation (1)
- Sorafenib (1)
- Sozialverhalten (1)
- Species coexistence (1)
- Spectral Decomposition (1)
- Spectrin (1)
- Spin alignment (1)
- Spleen (1)
- Splitting function (1)
- Sponges (1)
- Stewardship (1)
- Stewardship and dissemination (1)
- Stochastic Analysis of Square Zero Variation Processes (1)
- Stroke (1)
- Structural biology and molecular biophysics (1)
- Structure Elucidation (1)
- Strukturbasiertes Design (1)
- Sudden cardiac death (1)
- Sudden death (1)
- Suicide (1)
- Sunlight (1)
- Surgery (1)
- Synaptic plasticity (1)
- Synthetic (1)
- Systematic Uncertainty (1)
- Systematic reviews (1)
- T-DM1 (1)
- TGF-β (1)
- TR (1)
- Technique (1)
- Thermal model (1)
- Tick-Borne diseases (1)
- Time Projection Chamber (1)
- Timing (1)
- Tools and pipelines (1)
- Tools and ressources (1)
- Tracking (1)
- Transition radiation detector (1)
- Transverse momentum (1)
- Transversity (1)
- Trigger (1)
- Triple-negative breast cancer (1)
- Uncomplicated appendicitis (1)
- VEGF receptor 2 internalization and signaling (1)
- VEGFR-2 (1)
- VEGFR-3 (1)
- VUS (1)
- Vascular emergencies (1)
- Vector Boson Production (1)
- Vesicles (1)
- Vitamin (1)
- Warzen (1)
- X-ray crystallography (1)
- Xenon-based gas mixture (1)
- acute coronary syndromes (1)
- advanced breast cancer (1)
- agreeableness (1)
- algebraic cluster model (1)
- alirocumab (1)
- alleles (1)
- anaemia (1)
- anchialine cave (1)
- androgen receptor (1)
- anticoagulants (1)
- antigen presentation (1)
- antigen processing and presentation (1)
- antihormone therapy (1)
- antiseizure medication (1)
- atherosclerosis (1)
- atrial fibrillation (1)
- autism spectrum disorder (1)
- autistic disorder (1)
- axions (1)
- azacitidine (1)
- binary nucleation (1)
- biobank (1)
- biogeographic legaciese (1)
- biomarkers (1)
- bioprinting (1)
- body-on-a-chip (1)
- bromodomain (1)
- bromodomain inhibitor (1)
- bromodomains (1)
- burden of illness (1)
- c-kit (1)
- cancer immunotherapy (1)
- carbapenem-resistant Gram-negative bacteria (CRGN) (1)
- carbapenemases (1)
- cardiocerebral resuscitation (1)
- cardiopulmonary resuscitation (1)
- cardiovascular disease (1)
- castration-resistant prostate cancer (1)
- cell-free expression (1)
- cellular therapy (1)
- chemical probes (1)
- chemogenomic set (1)
- child (1)
- children (1)
- chimeric antigen receptor (1)
- chromatin (1)
- chromium de novo assembly (1)
- citizen science (1)
- common genetic variation (1)
- complement (1)
- complexity (1)
- copy number polymorphism (1)
- cost containment (1)
- cross-linking (1)
- cryo-EM (1)
- cytokine-induced killer cells (1)
- cytotoxicity (1)
- dE/dx (1)
- dark matter experiments (1)
- demographic inference (1)
- detector (1)
- diagnosis (1)
- direct-acting antivirals (DAAs) (1)
- disease prevalence (1)
- domestication (1)
- drug discovery (1)
- druggable genome (1)
- dynamics (1)
- eNOS (1)
- early childhood (1)
- ectosomes (1)
- elderly patients (1)
- electrocardiography (1)
- endothelial cells (1)
- epigenetic (1)
- evolution (1)
- executive functions (1)
- exosomes (1)
- experimental results (1)
- extracellular vesicles (1)
- follow-up (1)
- forest classification (1)
- forest functional similarity (1)
- functional connectivity (1)
- galunisertib monohydrate (LY2157299) (1)
- gastric cancer (1)
- gene flow (1)
- genes (1)
- genetic distance (1)
- genetic diversity (1)
- genetics (1)
- genome (1)
- genome-wide association study (1)
- genotype (1)
- genotype determination (1)
- giraffe (1)
- gliomas (1)
- global change (1)
- guidelines (1)
- habitat destruction (1)
- happiness (1)
- heart-on-a-chip (1)
- heavy ion experiments (1)
- hematopoietic stem cell transplantation (1)
- hemodialysis (1)
- host-pathogen interaction (1)
- human (1)
- human papilloma virus (HPV) (1)
- humanes Papillomvirus (HPV) (1)
- insertable cardiac monitor (1)
- inter-individual variability (1)
- ion‐induced nucleation (1)
- iron metabolism (1)
- juvenile myelomonocytic leukemia (1)
- kidney disease (1)
- kidney-on-a-chip (1)
- kinase inhibitor (1)
- knapsack cryptosystems (1)
- knockout (1)
- land use (1)
- lapatinib (1)
- lattice basis reduction (1)
- lattices (1)
- leukemia (1)
- leukopenia (1)
- life satisfaction (1)
- liver-on-a-chip (1)
- low-density lipoprotein cholesterol (1)
- lung-on-a-chip (1)
- macrophage polarization (1)
- magic angle spinning (1)
- magnetoencephalography (1)
- major adverse cardiovascular events (1)
- mandatory reporting system (1)
- medicinal chemistry (1)
- membrane proteins (1)
- mentalizing (1)
- metastatic (1)
- miRNA (1)
- micro-physiological systems (1)
- microparticles (1)
- microvesicles (1)
- minimal information requirements (1)
- model system (1)
- molecular machines (1)
- multidrug-resistant Gram-negative bacteria (MRGN) (1)
- multiresistente Gram-negativen Stäbchenbakterien (MRGN) (1)
- multispecies coalescent (1)
- mutation (1)
- neural oscillations (1)
- neurodevelopment (1)
- neutropenia (1)
- next-generation sequencing (1)
- non-autonomous dynamical systems (1)
- nuclear collective model (1)
- obituary (1)
- obituary announcement (1)
- organs-on-a-chip (1)
- p+p collisions (1)
- pSMAD2 (1)
- pauli principle (1)
- perceptual closure (1)
- pericytes (1)
- pertuzumab (1)
- pharmacokinetics (1)
- phenotype (1)
- phenotypic screening (1)
- photodynamic therapy (PDT) (1)
- phylogenetic analysis (1)
- phylogenetic community distance (1)
- phylogenetic network (1)
- phylogeny (1)
- plant invasion (1)
- polymeric micelle (1)
- polymorphism (1)
- polypept(o)ide (1)
- population structure (1)
- positive psychology (1)
- precision weighting (1)
- predictive coding (1)
- primary active transporters (1)
- primary immunodeficiency (PID) (1)
- proprotein convertase subtilisin/kexin type 9 inhibition (1)
- prosocial behavior (1)
- protein kinase (1)
- quark gluon plasma (1)
- registry for primary immunodeficiency (1)
- reproducibility (1)
- research network (1)
- resistance-associated substitutions (RAS) (1)
- rhabdomyosarcoma (1)
- rigor (1)
- risk factor progression (1)
- risk factors (1)
- runs of homozygosity (1)
- seizures (1)
- sequence alignment (1)
- set-valued pullback attractors (1)
- single nucleotide polymorphism (1)
- single subject classification (1)
- skin-on-a-chip (1)
- small molecules (1)
- social exclusion (1)
- sofosbuvir (1)
- solar physics (1)
- speciation (1)
- spectra (1)
- sprouting angiogenesis (1)
- standardization (1)
- stroke prevention (1)
- structural biology (1)
- structure-based design (1)
- subjective well-being (1)
- subset sum problems (1)
- superparamagnetic iron oxide nanoparticles (1)
- surgery (1)
- switching systems (1)
- synaesthesia (1)
- temporal classification (1)
- theory of mind (1)
- tick (1)
- tip cell filopodia formation (1)
- topological entropy (1)
- trastuzumab (1)
- tropical forests (1)
- understudied kinase (1)
- velpatasvir (1)
- vessel-associated mural cells (1)
- voxilaprevir (1)
- warts (1)
- wassergefiltertes Infrarot A (wIRA) (1)
- waterfiltered infrared A (wIRA) (1)
- white and brown dwarfs (1)
- whole-genome sequencing (1)
- working memory (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (1133)
- Frankfurt Institute for Advanced Studies (FIAS) (981)
- Informatik (906)
- Medizin (106)
- Geowissenschaften (15)
- Biochemie und Chemie (11)
- Biowissenschaften (10)
- Institut für Ökologie, Evolution und Diversität (7)
- Biodiversität und Klima Forschungszentrum (BiK-F) (5)
- Senckenbergische Naturforschende Gesellschaft (5)
A hygroscopicity tandem differential mobility analyzer (HTDMA) was used to measure the water uptake (hygroscopicity) of secondary organic aerosol (SOA) formed during the chemical and photochemical oxidation of several organic precursors in a smog chamber. Electron ionization mass spectra of the non-refractory submicron aerosol were simultaneously determined with an aerosol mass spectrometer (AMS), and correlations between the two different signals were investigated. SOA hygroscopicity was found to strongly correlate with the relative abundance of the ion signal m/z 44 expressed as a fraction of total organic signal (f44). m/z 44 is due mostly to the ion fragment CO2+ for all types of SOA systems studied, and has been previously shown to strongly correlate with organic O/C for ambient and chamber OA. The analysis was also performed on ambient OA from two field experiments at the remote site Jungfraujoch, and the megacity Mexico City, where similar results were found. A simple empirical linear relation between the hygroscopicity of OA at subsaturated RH, as given by the hygroscopic growth factor (GF) or "ϰorg" parameter, and f44 was determined and is given by ϰorg = 2.2 × f44 − 0.13. This approximation can be further verified and refined as the database for AMS and HTDMA measurements is constantly being expanded around the world. The use of this approximation could introduce an important simplification in the parameterization of hygroscopicity of OA in atmospheric models, since f44 is correlated with the photochemical age of an air mass.
We present measurements of exclusive ensuremathπ+,0 and η production in pp reactions at 1.25GeV and 2.2GeV beam kinetic energy in hadron and dielectron channels. In the case of π+ and π0 , high-statistics invariant-mass and angular distributions are obtained within the HADES acceptance as well as acceptance-corrected distributions, which are compared to a resonance model. The sensitivity of the data to the yield and production angular distribution of Δ (1232) and higher-lying baryon resonances is shown, and an improved parameterization is proposed. The extracted cross-sections are of special interest in the case of pp → pp η , since controversial data exist at 2.0GeV; we find \ensuremathσ=0.142±0.022 mb. Using the dielectron channels, the π0 and η Dalitz decay signals are reconstructed with yields fully consistent with the hadronic channels. The electron invariant masses and acceptance-corrected helicity angle distributions are found in good agreement with model predictions.
Background Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights.
Objective To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion.
Methods A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived.
Results The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10).
Conclusions The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA.
Chickpea (Cicer arietinum L.) is the third most important cool season food legume, cultivated in arid and semi-arid regions of the world. The goal of this study was to develop novel molecular markers such as microsatellite or simple sequence repeat (SSR) markers from bacterial artificial chromosome (BAC)-end sequences (BESs) and diversity arrays technology (DArT) markers, and to construct a high-density genetic map based on recombinant inbred line (RIL) population ICC 4958 (C. arietinum)×PI 489777 (C. reticulatum). A BAC-library comprising 55,680 clones was constructed and 46,270 BESs were generated. Mining of these BESs provided 6,845 SSRs, and primer pairs were designed for 1,344 SSRs. In parallel, DArT arrays with ca. 15,000 clones were developed, and 5,397 clones were found polymorphic among 94 genotypes tested. Screening of newly developed BES-SSR markers and DArT arrays on the parental genotypes of the RIL mapping population showed polymorphism with 253 BES-SSR markers and 675 DArT markers. Segregation data obtained for these polymorphic markers and 494 markers data compiled from published reports or collaborators were used for constructing the genetic map. As a result, a comprehensive genetic map comprising 1,291 markers on eight linkage groups (LGs) spanning a total of 845.56 cM distance was developed (http://cmap.icrisat.ac.in/cmap/sm/cp/thudi/). The number of markers per linkage group ranged from 68 (LG 8) to 218 (LG 3) with an average inter-marker distance of 0.65 cM. While the developed resource of molecular markers will be useful for genetic diversity, genetic mapping and molecular breeding applications, the comprehensive genetic map with integrated BES-SSR markers will facilitate its anchoring to the physical map (under construction) to accelerate map-based cloning of genes in chickpea and comparative genome evolution studies in legumes.
In memory of Edward Diener: reflections on his career, contributions and the science of happiness
(2021)
Prof. Edward (Ed) Diener (1946-2021), a pioneer in positive psychology, passed away on the 27th of April 2021 at his home in Salt Lake City, Utah (Salt Lake City Tribune, 2021). As one of the most influential psychologists of the discipline, Ed Diener pushed the boundaries of our understanding of positive psychological functioning, subjective well-being, and happiness (Layous, 2020). As one of the Top 200 most cited researchers across all disciplines and fields, he will be most remembered for founding the scientific study of subjective well-being (SWB) and happiness (Bakshi, 2019). Diener developed the concept of subjective well-being by exploring the factors that influence people's life satisfaction (Diener et al., 2017a). He studied the individual causes of subjective well-being, such as close social relationships, income, meaning and purpose, personality, and societal causes, such as economic development, low corruption and crime, and a healthy environment (Diener et al., 2018). His research has discovered both universal and culture-specific causes and consequences of SWB and influenced governmental policy (Oishi et al., 1999). In respect of his memory, the purpose of this paper is threefold: (a) to reflect upon his career journey, (b) to celebrate his significant contributions to the discipline, and (c) to provide personal reflections of those who worked closely with him over the past 50 years.
Saccharomyces cerevisiae CEN.PK 113-7D is widely used for metabolic engineering and systems biology research in industry and academia. We sequenced, assembled, annotated and analyzed its genome. Single-nucleotide variations (SNV), insertions/deletions (indels) and differences in genome organization compared to the reference strain S. cerevisiae S288C were analyzed. In addition to a few large deletions and duplications, nearly 3000 indels were identified in the CEN.PK113-7D genome relative to S288C. These differences were overrepresented in genes whose functions are related to transcriptional regulation and chromatin remodelling. Some of these variations were caused by unstable tandem repeats, suggesting an innate evolvability of the corresponding genes. Besides a previously characterized mutation in adenylate cyclase, the CEN.PK113-7D genome sequence revealed a significant enrichment of non-synonymous mutations in genes encoding for components of the cAMP signalling pathway. Some phenotypic characteristics of the CEN.PK113-7D strains were explained by the presence of additional specific metabolic genes relative to S288C. In particular, the presence of the BIO1 and BIO6 genes correlated with a biotin prototrophy of CEN.PK113-7D. Furthermore, the copy number, chromosomal location and sequences of the MAL loci were resolved. The assembled sequence reveals that CEN.PK113-7D has a mosaic genome that combines characteristics of laboratory strains and wild-industrial strains.
A list of authors and their affiliations appears at the end of the paper New-particle formation is a major contributor to urban smog, but how it occurs in cities is often puzzling. If the growth rates of urban particles are similar to those found in cleaner environments (1–10 nanometres per hour), then existing understanding suggests that new urban particles should be rapidly scavenged by the high concentration of pre-existing particles. Here we show, through experiments performed under atmospheric conditions in the CLOUD chamber at CERN, that below about +5 degrees Celsius, nitric acid and ammonia vapours can condense onto freshly nucleated particles as small as a few nanometres in diameter. Moreover, when it is cold enough (below −15 degrees Celsius), nitric acid and ammonia can nucleate directly through an acid–base stabilization mechanism to form ammonium nitrate particles. Given that these vapours are often one thousand times more abundant than sulfuric acid, the resulting particle growth rates can be extremely high, reaching well above 100 nanometres per hour. However, these high growth rates require the gas-particle ammonium nitrate system to be out of equilibrium in order to sustain gas-phase supersaturations. In view of the strong temperature dependence that we measure for the gas-phase supersaturations, we expect such transient conditions to occur in inhomogeneous urban settings, especially in wintertime, driven by vertical mixing and by strong local sources such as traffic. Even though rapid growth from nitric acid and ammonia condensation may last for only a few minutes, it is nonetheless fast enough to shepherd freshly nucleated particles through the smallest size range where they are most vulnerable to scavenging loss, thus greatly increasing their survival probability. We also expect nitric acid and ammonia nucleation and rapid growth to be important in the relatively clean and cold upper free troposphere, where ammonia can be convected from the continental boundary layer and nitric acid is abundant from electrical storms.
Triple differential cross sections d3 sigma /dp3 for charged pions produced in symmetric heavy-ion collisions were measured with the KaoS magnetic spectrometer at the heavy-ion synchrotron facility SIS at GSI. The correlations between the momentum vectors of charged pions and the reaction plane in 197Au+197Au collisions at an incident energy of 1 GeV/nucleon were determined. We observe, for the first time, an azimuthally anisotropic distribution of pions, with enhanced emission perpendicular to the reaction plane. The anisotropy is most pronounced for pions of high transverse momentum in semicentral collisions.
Hematotoxicity is one of the major side effects of chemotherapy. The aim of this study was to examine the association between single nucleotide polymorphisms (SNPs) and hematotoxicity in breast cancer patients in a subset of patients of the SUCCESS prospective phase III chemotherapy study. All patients (n = 1678) received three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by three cycles of docetaxel or docetaxel/gemcitabine, depending on randomization. Germline DNA was genotyped for 246 SNPs selected from a previous genome-wide association study (GWAS) in a panel of lymphoblastoid cell lines, with gemcitabine toxicity as the phenotype. All SNPs were tested for their value in predicting grade 3 or 4 neutropenic or leukopenic events (NLEs). Their prognostic value in relation to overall survival and disease-free survival was also tested.
None of the SNPs was found to be predictive for NLEs during treatment with docetaxel/gemcitabine. Two SNPs in and close to the PIGB gene significantly improved the prediction of NLEs after FEC, in addition to the factors of age and body surface area. The top SNP (rs12050587) had an odds ratio of 1.38 per minor allele (95% confidence interval, 1.17 to 1.62). No associations were identified for predicting disease-free or overall survival.
Genetic variance in the PIGB gene may play a role in determining interindividual differences in relation to hematotoxicity after FEC chemotherapy.
A hygroscopicity tandem differential mobility analyzer (HTDMA) was used to measure the water uptake (hygroscopicity) of secondary organic aerosol (SOA) formed during the chemical and photochemical oxidation of several organic precursors in a smog chamber. Electron ionization mass spectra of the non-refractory submicron aerosol were simultaneously determined with an aerosol mass spectrometer (AMS), and correlations between the two different signals were investigated. SOA hygroscopicity was found to strongly correlate with the relative abundance of the ion signal m/z 44 expressed as a fraction of total organic signal (f44). m/z 44 is due mostly to the ion fragment CO2+ for all types of SOA systems studied, and has been previously shown to strongly correlate with organic O/C for ambient and chamber OA. The analysis was also performed on ambient OA from two field experiments at the remote site Jungfraujoch, and the megacity Mexico City, where similar results were found. A simple empirical linear relation between the hygroscopicity of OA at subsaturated RH, as given by the hygroscopic growth factor (GF) or "κorg" parameter, and f44 was determined and is given by κorg=2.2×f44−0.13. This approximation can be further verified and refined as the database for AMS and HTDMA measurements is constantly being expanded around the world. The use of this approximation could introduce an important simplification in the parameterization of hygroscopicity of OA in atmospheric models, since f44 is correlated with the photochemical age of an air mass.
Rationale: RBPs (RNA binding proteins) play critical roles in the cell by regulating mRNA transport, splicing, editing, and stability. The RBP SRSF3 (serine/arginine-rich splicing factor 3) is essential for blastocyst formation and for proper liver development and function. However, its role in the heart has not been explored.
Objective:To investigate the role of SRSF3 in cardiac function.
Methods and Results: Cardiac SRSF3 expression was high at mid gestation and decreased during late embryonic development. Mice lacking SRSF3 in the embryonic heart showed impaired cardiomyocyte proliferation and died in utero. In the adult heart, SRSF3 expression was reduced after myocardial infarction, suggesting a possible role in cardiac homeostasis. To determine the role of this RBP in the adult heart, we used an inducible, cardiomyocyte-specific SRSF3 knockout mouse model. After SRSF3 depletion in cardiomyocytes, mice developed severe systolic dysfunction that resulted in death within 8 days. RNA-Seq analysis revealed downregulation of mRNAs encoding sarcomeric and calcium handling proteins. Cardiomyocyte-specific SRSF3 knockout mice also showed evidence of alternative splicing of mTOR (mammalian target of rapamycin) mRNA, generating a shorter protein isoform lacking catalytic activity. This was associated with decreased phosphorylation of 4E-BP1 (eIF4E-binding protein 1), a protein that binds to eIF4E (eukaryotic translation initiation factor 4E) and prevents mRNA decapping. Consequently, we found increased decapping of mRNAs encoding proteins involved in cardiac contraction. Decapping was partially reversed by mTOR activation.
Conclusions: We show that cardiomyocyte-specific loss of SRSF3 expression results in decapping of critical mRNAs involved in cardiac contraction. The molecular mechanism underlying this effect likely involves the generation of a short mTOR isoform by alternative splicing, resulting in reduced 4E-BP1 phosphorylation. The identification of mRNA decapping as a mechanism of systolic heart failure may open the way to the development of urgently needed therapeutic tools.
Background: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography.
Methods: In a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known.
Findings: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07).
Interpretation: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials.
Funding: UK Medical Research Council and British Heart Foundation.
A new global synthesis and biomization of long (> 40 kyr) pollen-data records is presented, and used with simulations from the HadCM3 and FAMOUS climate models to analyse the dynamics of the global terrestrial biosphere and carbon storage over the last glacial–interglacial cycle. Global modelled (BIOME4) biome distributions over time generally agree well with those inferred from pollen data. The two climate models show good agreement in global net primary productivity (NPP). NPP is strongly influenced by atmospheric carbon dioxide (CO2) concentrations through CO2 fertilization. The combined effects of modelled changes in vegetation and (via a simple model) soil carbon result in a global terrestrial carbon storage at the Last Glacial Maximum that is 210–470 Pg C less than in pre-industrial time. Without the contribution from exposed glacial continental shelves the reduction would be larger, 330–960 Pg C. Other intervals of low terrestrial carbon storage include stadial intervals at 108 and 85 kaBP, and between 60 and 65 kaBP during Marine Isotope Stage 4. Terrestrial carbon storage, determined by the balance of global NPP and decomposition, influences the stable carbon isotope composition (δ 13C) of seawater because terrestrial organic carbon is depleted in 13C. Using a simple carbon-isotope mass balance equation we find agreement in trends between modelled ocean δ 13C based on modelled land carbon storage, and palaeo-archives of ocean δ 13C, confirming that terrestrial carbon storage variations may be important drivers of ocean δ 13 C changes.
A new global synthesis and biomization of long (> 40 kyr) pollen-data records is presented and used with simulations from the HadCM3 and FAMOUS climate models and the BIOME4 vegetation model to analyse the dynamics of the global terrestrial biosphere and carbon storage over the last glacial–interglacial cycle. Simulated biome distributions using BIOME4 driven by HadCM3 and FAMOUS at the global scale over time generally agree well with those inferred from pollen data. Global average areas of grassland and dry shrubland, desert, and tundra biomes show large-scale increases during the Last Glacial Maximum, between ca. 64 and 74 ka BP and cool substages of Marine Isotope Stage 5, at the expense of the tropical forest, warm-temperate forest, and temperate forest biomes. These changes are reflected in BIOME4 simulations of global net primary productivity, showing good agreement between the two models. Such changes are likely to affect terrestrial carbon storage, which in turn influences the stable carbon isotopic composition of seawater as terrestrial carbon is depleted in 13C.
The Coulomb Dissociation (CD) cross sections of the stable isotopes 92,94,100Mo and of the unstable isotope 93Mo were measured at the LAND/R3B setup at GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. Experimental data on these isotopes may help to explain the problem of the underproduction of 92,94Mo and 96,98Ru in the models of p-process nucleosynthesis. The CD cross sections obtained for the stable Mo isotopes are in good agreement with experiments performed with real photons, thus validating the method of Coulomb Dissociation. The result for the reaction 93Mo(γ,n) is especially important since the corresponding cross section has not been measured before. A preliminary integral Coulomb Dissociation cross section of the 94Mo(γ,n) reaction is presented. Further analysis will complete the experimental database for the (γ,n) production chain of the p-isotopes of molybdenum.
There is a need for diagnostic biomarkers of epilepsy and status epilepticus to support clinical examination, electroencephalography and neuroimaging. Extracellular microRNAs may be potentially ideal biomarkers since some are expressed uniquely within specific brain regions and cell types. Cerebrospinal fluid offers a source of microRNA biomarkers with the advantage of being in close contact with the target tissue and sites of pathology. Here we profiled microRNA levels in cerebrospinal fluid from patients with temporal lobe epilepsy or status epilepticus, and compared findings to matched controls. Differential expression of 20 microRNAs was detected between patient groups and controls. A validation phase included an expanded cohort and samples from patients with other neurological diseases. This identified lower levels of miR-19b in temporal lobe epilepsy compared to controls, status epilepticus and other neurological diseases. Levels of miR-451a were higher in status epilepticus compared to other groups whereas miR-21-5p differed in status epilepticus compared to temporal lobe epilepsy but not to other neurological diseases. Targets of these microRNAs include proteins regulating neuronal death, tissue remodelling, gliosis and inflammation. The present study indicates cerebrospinal fluid contains microRNAs that can support differential diagnosis of temporal lobe epilepsy and status epilepticus from other neurological and non-neurological diseases.
Introduction. Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin.
Material and methods. Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa2a (40KD) 180 or 90 Mg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns.
Results. The percentage of patients with undetectable HCV RNA was consistently higher in all balapiravir groups from week 2 to 12. However, high rates of dose modifications and discontinuations of one/all study drugs compromised the efficacy assessment and resulted in similar sustained virological response rates in the balapiravir groups (range 32-50%) and the peginterferon alfa-2a (40KD)/ribavirin group (43%). Balapiravir was discontinued for safety reasons in 28-36% of patients (most often for lymphopenia) and the percentage of patients with serious adverse events (especially hematological, infection, ocular events) was dose related. Serious hematological adverse events (particularly neutropenia, lymphopenia) were more common in balapiravir recipients. Two deaths in the balapiravir/peginterferon alfa-2a/ribavirin combination groups were considered possibly related to study medication.
Conclusion. Further development of balapiravir for the treatment of chronic hepatitis C has been halted because of the unacceptable benefit to risk ratio revealed in this study (www.ClinicalTrials.gov NCT 00517439).
Knowledge about the biogeographic affinities of the world’s tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world’s tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.
Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.
Aims: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.
Methods and results: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies.
In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95–1.02) in group A, 0.98 (0.93–1.04) in group B, and 0.95 (0.89–1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07–1.23) in group A, 1.13 (1.05–1.22) in group B, and 1.12 (1.05–1.20) in group C.
Conclusions: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.