Transitivity conditions in infinite graphs

We study transitivity properties of graphs with more than one end. We completely classify the distance-transitive such graphs and, for all $k \geq 3$, the $k$-CS-transitive such graphs.Comment: 20 page

Edge-disjoint double rays in infinite graphs: a Halin type result

We show that any graph that contains k edge-disjoint double rays for any k>0 contains also infinitely many edge-disjoint double rays. This was conjectured by Andreae in 1981.Comment: 15 pages, 2 figure

Etablierung des „COPD Assessment Test“ zur Erfassung der Lebensqualität bei Patienten mit Cystischer Fibrose : Ein Vergleich zwischen Fragebögen und klinischen Parametern

Einleitung: Die Erfassung der Lebensqualität ist ein wichtiger Parameter zur Beurteilung des Gesundheitszustandes bei Personen mit Cystischer Fibrose. Sie hängt bei chronisch lungenkranken Menschen besonders von der Ausprägung der pulmonalen Symptomatik ab. Es gibt viele Fragebögen wie den „Cystic Fibrosis Questionnaire- Revised“ (CFQ-R) oder den „St George’s Respiratory Questionnaire“ (SGRQ), welche die Lebensqualität bei der Cystischen Fibrose erfassen, aber viel Zeit für die Bearbeitung und Auswertung in Anspruch nehmen. Bei der Behandlung der Chronisch Obstruktiven Lungenerkrankung (COPD) hat sich der „COPD Assessment Test“ (CAT) etabliert. Seine Vorteile liegen in der schnellen Bearbeitung, Auswertung und der leichten Integration in den klinischen Alltag. In dieser Studie sollte anhand der Testgütekriterien geklärt werden, ob der CAT für die routinemäßige Lebensqualitätserfassung bei Patienten mit Cystischer Fibrose geeignet ist und zusätzlich, ob es Zusammenhänge zwischen der Punktzahl des Tests und anderen klinischen Parametern gibt. Methoden: 42 Probanden mit Cystischer Fibrose wurden prospektiv in die PulmoHOM-Studie eingeschlossen. Es wurden verschiedene Fragebögen zur Bearbeitung ausgehändigt. Zudem wurden ein Lungenfunktionstest und eine Blutuntersuchung durchgeführt. Für die statistische Auswertung wurde der Spearmans Rangkorrelationskoeffizient und das Cronbachs α benutzt. Ergebnisse: Der CAT zeigte durchweg hohe Korrelationen mit den etablierten Fragebögen. Er korrelierte mit dem Totalscore des SGRQ (r = 0,851, p < 0,01), mit den meisten Scores des CFQ-R (Kraftscore: r = -0,874, p < 0,01) und mit dem „Clinical COPD Questionnaire“ (r = 0,837, p < 0,01). Es zeigten sich außerdem Zusammenhänge zu Parametern des klinischen Gesundheitszustandes. So korrelierte der Test mit der forcierten Einsekundenkapazität (% vom Sollwert) (r = -0,588, p < 0,01) und mit der Höhe des C-reaktiven Proteins im Blut (r = 0,318, p < 0,05). Durch ein Cronbachs α von 0,886 ließ sich eine hohe interne Konsistenz des CAT zeigen. Schlussfolgerung: Es konnte in dieser Studie zum ersten Mal gezeigt werden, dass der CAT bei der Anwendung in der Cystischen Fibrose durch die beschriebenen Zusammenhänge alle Testgütekriterien erfüllt. Es ist einValidation of the “COPD Assessment Test” (CAT) to evaluate the quality of life in patients with cystic fibrosis in clinical routine- a comparison between questionnaires and clinical parameters Background: Quality of life is an important parameter in assessing health in patients with cystic fibrosis. In individuals with chronic lung disease, there is a correlation between pulmonary symptoms and quality of life. There are many questionnaires like the “Cystic Fibrosis Questionnaire- Revised” (CFQ-R) and the “St George’s Respiratory questionnaire” (SGRQ), which evaluate the quality of life in cystic fibrosis. They aren’t used very often because of the length of the processing time involved. The “COPD Assessment Test” (CAT) was established for the treatment of chronic obstructive lung diseases. Its advantages are the fast and easy processing, evaluation and the easy integration into clinical routine. The aim of this study was to verify the CAT for routine use in cystic fibrosis and to examine whether there is a correlation between the score and clinical parameters. Methods: 42 individuals with cystic fibrosis were recruited into the prospective PulmoHOM-study and were given different questionnaires to respond to. They also had a lung function test and blood tests were carried out. For the statistical analysis Spearman’s rank correlation coefficient and the Cronbach’s α were used. Results: The CAT correlated with most of the scores of the established tests. There were high correlations with the total score of the SGRQ (r = 0.851, p < 0.01), with most of the scores of the CFQ-R (physical score: r = -0.874, p < 0.01) and with the “Clinical COPD Questionnaire” (r = 0.837, p < 0.01). Moreover, there were correlations between CAT and clinical parameters like the predicted forced expiratory volume in one second (r = -0.588, p < 0.01) as well as the amount of the C-reactive protein in the blood (r = 0.318, p < 0.05). The Cronbach’s α of 0,886 demonstrated a high internal consistency of the CAT. Conclusion: In conclusion, the CAT fulfils the criteria of validity and reliability regarding the correlations mentioned. It is a means of evaluating the quality of life of individuals with cystic fibrosis and might be applicable in the care of patients in daily clinical practice

Interlaboratory study on rheological properties of cement pastes and reference substances: comparability of measurements performed with different rheometers and measurement geometries

This paper presents the results of an interlaboratory study of the rheological properties of cement paste and ultrasound gel as reference substance. The goal was to quantify the comparability and reproducibility of measurements of the Bingham parameters yield stress and plastic viscosity when measured on one specific paste composition and one particular ultrasound gel in different laboratories using different rheometers and measurement geometries. The procedures for both in preparing the cement paste and carrying out the rheological measurements on cement paste and ultrasound gel were carefully defined for all of the study’s participants. Different conversion schemes for comparing the results obtained with the different measurement setups are presented here and critically discussed. The procedure proposed in this paper ensured a reasonable comparability of the results with a coefficient of variation for the yield stress of 27% and for the plastic viscosity of 24%, despite the individual measurement series’ having been performed in different labs with different rheometers and measurement geometries

SARS-CoV-2 variant Alpha has a spike-dependent replication advantage over the ancestral B.1 strain in human cells with low ACE2 expression

Epidemiological data demonstrate that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) Alpha and Delta are more transmissible, infectious, and pathogenic than previous variants. Phenotypic properties of VOC remain understudied. Here, we provide an extensive functional study of VOC Alpha replication and cell entry phenotypes assisted by reverse genetics, mutational mapping of spike in lentiviral pseudotypes, viral and cellular gene expression studies, and infectivity stability assays in an enhanced range of cell and epithelial culture models. In almost all models, VOC Alpha spread less or equally efficiently as ancestral (B.1) SARS-CoV-2. B.1. and VOC Alpha shared similar susceptibility to serum neutralization. Despite increased relative abundance of specific sgRNAs in the context of VOC Alpha infection, immune gene expression in infected cells did not differ between VOC Alpha and B.1. However, inferior spreading and entry efficiencies of VOC Alpha corresponded to lower abundance of proteolytically cleaved spike products presumably linked to the T716I mutation. In addition, we identified a bronchial cell line, NCI-H1299, which supported 24-fold increased growth of VOC Alpha and is to our knowledge the only cell line to recapitulate the fitness advantage of VOC Alpha compared to B.1. Interestingly, also VOC Delta showed a strong (595-fold) fitness advantage over B.1 in these cells. Comparative analysis of chimeric viruses expressing VOC Alpha spike in the backbone of B.1, and vice versa, showed that the specific replication phenotype of VOC Alpha in NCI-H1299 cells is largely determined by its spike protein. Despite undetectable ACE2 protein expression in NCI-H1299 cells, CRISPR/Cas9 knock-out and antibody-mediated blocking experiments revealed that multicycle spread of B.1 and VOC Alpha required ACE2 expression. Interestingly, entry of VOC Alpha, as opposed to B.1 virions, was largely unaffected by treatment with exogenous trypsin or saliva prior to infection, suggesting enhanced resistance of VOC Alpha spike to premature proteolytic cleavage in the extracellular environment of the human respiratory tract. This property may result in delayed degradation of VOC Alpha particle infectivity in conditions typical of mucosal fluids of the upper respiratory tract that may be recapitulated in NCI-H1299 cells closer than in highly ACE2-expressing cell lines and models. Our study highlights the importance of cell model evaluation and comparison for in-depth characterization of virus variant-specific phenotypes and uncovers a fine-tuned interrelationship between VOC Alpha- and host cell-specific determinants that may underlie the increased and prolonged virus shedding detected in patients infected with VOC Alpha

SARS-CoV-2 variant Alpha has a spike-dependent replication advantage over the ancestral B.1 strain in human cells with low ACE2 expression

Epidemiological data demonstrate that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) Alpha and Delta are more transmissible, infectious, and pathogenic than previous variants. Phenotypic properties of VOC remain understudied. Here, we provide an extensive functional study of VOC Alpha replication and cell entry phenotypes assisted by reverse genetics, mutational mapping of spike in lentiviral pseudotypes, viral and cellular gene expression studies, and infectivity stability assays in an enhanced range of cell and epithelial culture models. In almost all models, VOC Alpha spread less or equally efficiently as ancestral (B.1) SARS-CoV-2. B.1. and VOC Alpha shared similar susceptibility to serum neutralization. Despite increased relative abundance of specific sgRNAs in the context of VOC Alpha infection, immune gene expression in infected cells did not differ between VOC Alpha and B.1. However, inferior spreading and entry efficiencies of VOC Alpha corresponded to lower abundance of proteolytically cleaved spike products presumably linked to the T716I mutation. In addition, we identified a bronchial cell line, NCI-H1299, which supported 24-fold increased growth of VOC Alpha and is to our knowledge the only cell line to recapitulate the fitness advantage of VOC Alpha compared to B.1. Interestingly, also VOC Delta showed a strong (595-fold) fitness advantage over B.1 in these cells. Comparative analysis of chimeric viruses expressing VOC Alpha spike in the backbone of B.1, and vice versa, showed that the specific replication phenotype of VOC Alpha in NCI-H1299 cells is largely determined by its spike protein. Despite undetectable ACE2 protein expression in NCI-H1299 cells, CRISPR/Cas9 knock-out and antibody-mediated blocking experiments revealed that multicycle spread of B.1 and VOC Alpha required ACE2 expression. Interestingly, entry of VOC Alpha, as opposed to B.1 virions, was largely unaffected by treatment with exogenous trypsin or saliva prior to infection, suggesting enhanced resistance of VOC Alpha spike to premature proteolytic cleavage in the extracellular environment of the human respiratory tract. This property may result in delayed degradation of VOC Alpha particle infectivity in conditions typical of mucosal fluids of the upper respiratory tract that may be recapitulated in NCI-H1299 cells closer than in highly ACE2-expressing cell lines and models. Our study highlights the importance of cell model evaluation and comparison for in-depth characterization of virus variant-specific phenotypes and uncovers a fine-tuned interrelationship between VOC Alpha- and host cell-specific determinants that may underlie the increased and prolonged virus shedding detected in patients infected with VOC Alpha.Peer Reviewe

Phrenic Nerve Injury During Cryoballoon-Based Pulmonary Vein Isolation: Results of the Worldwide YETI Registry.

BackgroundCryoballoon-based pulmonary vein isolation (PVI) has emerged as an effective treatment for atrial fibrillation. The most frequent complication during cryoballoon-based PVI is phrenic nerve injury (PNI). However, data on PNI are scarce.MethodsThe YETI registry is a retrospective, multicenter, and multinational registry evaluating the incidence, characteristics, prognostic factors for PNI recovery and follow-up data of patients with PNI during cryoballoon-based PVI. Experienced electrophysiological centers were invited to participate. All patients with PNI during CB2 or third (CB3) and fourth-generation cryoballoon (CB4)-based PVI were eligible.ResultsA total of 17 356 patients underwent cryoballoon-based PVI in 33 centers from 10 countries. A total of 731 (4.2%) patients experienced PNI. The mean time to PNI was 127.7±50.4 seconds, and the mean temperature at the time of PNI was -49±8°C. At the end of the procedure, PNI recovered in 394/731 patients (53.9%). Recovery of PNI at 12 months of follow-up was found in 97.0% of patients (682/703, with 28 patients lost to follow-up). A total of 16/703 (2.3%) reported symptomatic PNI. Only 0.06% of the overall population showed symptomatic and permanent PNI. Prognostic factors improving PNI recovery are immediate stop at PNI by double-stop technique and utilization of a bonus-freeze protocol. Age, cryoballoon temperature at PNI, and compound motor action potential amplitude loss >30% were identified as factors decreasing PNI recovery. Based on these parameters, a score was calculated. The YETI score has a numerical value that will directly represent the probability of a specific patient of recovering from PNI within 12 months.ConclusionsThe incidence of PNI during cryoballoon-based PVI was 4.2%. Overall 97% of PNI recovered within 12 months. Symptomatic and permanent PNI is exceedingly rare in patients after cryoballoon-based PVI. The YETI score estimates the prognosis after iatrogenic cryoballoon-derived PNI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03645577. Graphic Abstract: A graphic abstract is available for this article