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In the first half of this article I will explore Van Helmont's philosophy of language and translation, in part by contextualizing it within the sixteenth- and seventeenth-century traditions upon which he drew. Since Van Helmont is so explicit about the philosophy of language and translation that he developed, I will investigate in this article if he turned his philosophy into practice. Therefore, the second half of this article will discuss Van Helmont's practices of using and translating between his two main languages (Dutch and Latin). The way in which he employed the languages in which he wrote raises questions about his practice of self-translation and the use of language. Did his mother tongue always figure as the first language into which his thoughts were translated, or could it also have been Latin as the first language for his profession? Van Helmont might have been switching primary languages for the different purposes of his writings. Before going into more detail about his philosophy and use of language, I will briefly introduce this relatively unknown author to the reader.
We examined the feedback between the major protein degradation pathway, the ubiquitin-proteasome system (UPS), and protein synthesis in rat and mouse neurons. When protein degradation was inhibited, we observed a coordinate dramatic reduction in nascent protein synthesis in neuronal cell bodies and dendrites. The mechanism for translation inhibition involved the phosphorylation of eIF2α, surprisingly mediated by eIF2α kinase 1, or heme-regulated kinase inhibitor (HRI). Under basal conditions, neuronal expression of HRI is barely detectable. Following proteasome inhibition, HRI protein levels increase owing to stabilization of HRI and enhanced translation, likely via the increased availability of tRNAs for its rare codons. Once expressed, HRI is constitutively active in neurons because endogenous heme levels are so low; HRI activity results in eIF2α phosphorylation and the resulting inhibition of translation. These data demonstrate a novel role for neuronal HRI that senses and responds to compromised function of the proteasome to restore proteostasis.
Protein turnover, the net result of protein synthesis and degradation, enables cells to remodel their proteomes in response to internal and external cues. Previously, we analyzed protein turnover rates in cultured brain cells under basal neuronal activity and found that protein turnover is influenced by subcellular localization, protein function, complex association, cell type of origin, and by the cellular environment (Dörrbaum et al., 2018). Here, we advanced our experimental approach to quantify changes in protein synthesis and degradation, as well as the resulting changes in protein turnover or abundance in rat primary hippocampal cultures during homeostatic scaling. Our data demonstrate that a large fraction of the neuronal proteome shows changes in protein synthesis and/or degradation during homeostatic up- and down-scaling. More than half of the quantified synaptic proteins were regulated, including pre- as well as postsynaptic proteins with diverse molecular functions.
Digital spatial processes have been widely explored and investigated in subject-specific geographic research. So far, however, this research has not been sufficiently reflected in classrooms or teacher education, and remains unconnected to notions of geographical digital literacy. Viral constructions of space – realities shaped in everyday life that are experienced and (re-)produced by students and teachers alike through social media – present an opportunity for Geography education to adapt to the digital society. This paper attempts to connect viral constructions of space, the digital society and the knowledge teachers need to include viral constructions of space in the classroom using Mishra and Koehler’s (2006) TPACK model, a well-established means for summarizing teachers’ technological, pedagogical and content knowledge for a specific topic. The paper focuses on content knowledge, identifies five sub-types of viral constructions of space, and extracts nine descriptors of teachers’ content knowledge. By focusing on content knowledge, the paper presents a starting point for future investigations of pedagogical and technological teacher knowledge as well as their intersections. It also raises awareness of viral constructions of space as both a new essential topic in the Geography classroom and a phenomenon already shaping learning environments for spatial acquisition.
During the 2016-17 and 2018-19 running periods, the BESIII experiment collected 7.5~fb−1 of e+e− collision data at center-of-mass energies ranging from 4.13 to 4.44~GeV. These data samples are primarily used for the study of excited charmonium and charmoniumlike states. By analyzing the di-muon process e+e−→(γISR/FSR)μ+μ−, we measure the center-of-mass energies of the data samples with a precision of 0.6 MeV. Through a run-by-run study, we find that the center-of-mass energies were stable throughout most of the data-taking period.
Background and Objectives: Red blood cell (RBC) transfusions are needed by almost every acute myeloid leukaemia (AML) patient undergoing induction chemotherapy and constitute a cornerstone in supportive measures for cancer patients in general. Randomized controlled trials have shown non‐inferiority or even superiority of restrictive transfusion guidelines over liberal transfusion guidelines in specific clinical situations outside of medical oncology. In this study, we analysed whether more restrictive RBC transfusion reduces blood use without affecting hard outcomes.
Materials and Methods: A total of 352 AML patients diagnosed between 2007 and 2018 and undergoing intensive induction chemotherapy were included in this retrospective analysis. In the less restrictive transfusion group, patients received RBC transfusion for haemoglobin levels below 8 g/dl (2007–2014). In the restrictive transfusion group, patients received RBC transfusion for haemoglobin levels below 7 g/dl (2016–2018). Liberal transfusion triggers were never endorsed.
Results: A total of 268 (76·1%) and 84 (23·9%) AML patients fell into the less restrictive and restrictive transfusion groups, respectively. The less restrictive transfusion group had 1 g/dl higher mean haemoglobin levels, received their first RBC transfusions earlier and needed 1·5 more units of RBC during the hospital stay of induction chemotherapy. Febrile episodes, C‐reactive protein levels, admission to the intensive care unit, length of hospital stay as well as response and survival rates did not differ between the two cohorts.
Conclusion: From our retrospective analysis, we conclude that a more restrictive transfusion trigger does not affect important outcomes of AML patients. The opportunity to test possible effects of the more severe anaemia in the restrictive transfusion group on quality of life was missed.
There has recently been a dramatic renewal of interest in hadron spectroscopy and charm physics. This renaissance has been driven in part by the discovery of a plethora of charmonium-like XYZ states at BESIII and B factories, and the observation of an intriguing proton-antiproton threshold enhancement and the possibly related X(1835) meson state at BESIII, as well as the threshold measurements of charm mesons and charm baryons.
We present a detailed survey of the important topics in tau-charm physics and hadron physics that can be further explored at BESIII during the remaining operation period of BEPCII. This survey will help in the optimization of the data-taking plan over the coming years, and provides physics motivation for the possible upgrade of BEPCII to higher luminosity.
Cross sections of the process 𝑒+𝑒−→𝜋0𝜋0𝐽/𝜓 at center-of-mass energies between 3.808 and 4.600 GeV are measured with high precision by using 12.4 fb−1 of data samples collected with the BESIII detector operating at the BEPCII collider facility. A fit to the measured energy-dependent cross sections confirms the existence of the charmoniumlike state 𝑌(4220). The mass and width of the 𝑌(4220) are determined to be (4220.4±2.4±2.3) MeV/𝑐2 and (46.2±4.7±2.1) MeV, respectively, where the first uncertainties are statistical and the second systematic. The mass and width are consistent with those measured in the process 𝑒+𝑒−→𝜋+𝜋−𝐽/𝜓. The neutral charmonium-like state 𝑍𝑐(3900)0 is observed prominently in the 𝜋0𝐽/𝜓 invariant-mass spectrum, and, for the first time, an amplitude analysis is performed to study its properties. The spin-parity of 𝑍𝑐(3900)0 is determined to be 𝐽𝑃=1+, and the pole position is (3893.1±2.2±3.0)−𝑖(22.2±2.6±7.0) MeV/𝑐2, which is consistent with previous studies of electrically charged 𝑍𝑐(3900)±. In addition, cross sections of 𝑒+𝑒− → 𝜋0𝑍𝑐(3900)0 → 𝜋0𝜋0𝐽/𝜓 are extracted, and the corresponding line shape is found to agree with that of the 𝑌(4220).
Cross sections of the process 𝑒+𝑒−→𝜋0𝜋0𝐽/𝜓 at center-of-mass energies between 3.808 and 4.600 GeV are measured with high precision by using 12.4 fb−1 of data samples collected with the BESIII detector operating at the BEPCII collider facility. A fit to the measured energy-dependent cross sections confirms the existence of the charmoniumlike state 𝑌(4220). The mass and width of the 𝑌(4220) are determined to be (4220.4±2.4±2.3) MeV/𝑐2 and (46.2±4.7±2.1) MeV, respectively, where the first uncertainties are statistical and the second systematic. The mass and width are consistent with those measured in the process 𝑒+𝑒−→𝜋+𝜋−𝐽/𝜓. The neutral charmonium-like state 𝑍𝑐(3900)0 is observed prominently in the 𝜋0𝐽/𝜓 invariant-mass spectrum, and, for the first time, an amplitude analysis is performed to study its properties. The spin-parity of 𝑍𝑐(3900)0 is determined to be 𝐽𝑃=1+, and the pole position is (3893.1±2.2±3.0)−𝑖(22.2±2.6±7.0) MeV/𝑐2, which is consistent with previous studies of electrically charged 𝑍𝑐(3900)±. In addition, cross sections of 𝑒+𝑒− → 𝜋0𝑍𝑐(3900)0 → 𝜋0𝜋0𝐽/𝜓 are extracted, and the corresponding line shape is found to agree with that of the 𝑌(4220).
The process 𝑒+𝑒−→𝜙𝜂′ has been studied for the first time in detail using data sample collected with the BESIII detector at the BEPCII collider at center of mass energies from 2.05 to 3.08 GeV. A resonance with quantum numbers 𝐽𝑃𝐶=1−− is observed with mass 𝑀=(2177.5±4.8(stat)±19.5(syst))MeV/𝑐2 and width Γ=(149.0±15.6(stat)±8.9(syst)) MeV with a statistical significance larger than 10𝜎, including systematic uncertainties. If the observed structure is identified with the 𝜙(2170), then the ratio of partial width between the 𝜙𝜂′ by BESIII and 𝜙𝜂 by BABAR is (ℬ𝑅𝜙𝜂Γ𝑅𝑒𝑒)/(ℬ𝑅𝜙𝜂′Γ𝑅𝑒𝑒)=0.23±0.10(stat)±0.18(syst), which is smaller than the prediction of the 𝑠¯𝑠𝑔 hybrid models by several orders of magnitude.
By analyzing a data sample corresponding to an integrated luminosity of 2.93 fb−1 collected at a center-of-mass energy of 3.773 GeV with By analyzing a data sample corresponding to an integrated luminosity of 2.93 fb−1 collected at a center-of-mass energy of 3.773 GeV with the BESIII detector, we measure for the first time the absolute branching fraction of the 𝐷+→𝜂𝜇+𝜈𝜇 decay to be ℬ𝐷+→𝜂𝜇+𝜈𝜇=(10.4±1.0stat±0.5syst)×10−4. Using the world averaged value of ℬ𝐷+→𝜂𝑒+𝜈𝑒, the ratio of the two branching fractions is determined to be ℬ𝐷+→𝜂𝜇+𝜈𝜇/ℬ𝐷+→𝜂𝑒+𝜈𝑒=0.91±0.13(stat+syst), which agrees with the theoretical expectation of lepton flavor universality within uncertainty. By studying the differential decay rates in five four-momentum transfer intervals, we obtain the product of the hadronic form factor 𝑓𝜂+(0) and the 𝑐→𝑑 Cabibbo-Kobayashi-Maskawa matrix element |𝑉𝑐𝑑| to be 𝑓𝜂+(0)|𝑉𝑐𝑑|=0.087±0.008stat±0.002syst. Taking the input of |𝑉𝑐𝑑| from the global fit in the standard model, we determine 𝑓𝜂+(0)=0.39±0.04stat±0.01syst. On the other hand, using the value of 𝑓𝜂+(0) calculated in theory, we find |𝑉𝑐𝑑| = 0.242±0.022stat±0.006syst±0.033theory.
We report the first observation of the semimuonic decay 𝐷+→𝜔𝜇+𝜈𝜇 using an 𝑒+𝑒− collision data sample corresponding to an integrated luminosity of 2.93 fb−1 collected with the BESIII detector at a center-of-mass energy of 3.773 GeV. The absolute branching fraction of the 𝐷+→𝜔𝜇+𝜈𝜇 decay is measured to be ℬ𝐷+→𝜔𝜇+𝜈𝜇=(17.7±1.8stat±1.1syst)×10−4. Its ratio with the world average value of the branching fraction of the 𝐷+→𝜔𝑒+𝜈𝑒 decay probes lepton flavor universality and it is determined to be ℬ𝐷+→𝜔𝜇+𝜈𝜇/ℬPDG 𝐷+→𝜔𝑒+𝜈𝑒=1.05±0.14, in agreement with the standard model expectation within one standard deviation.
Using 2.93 fb−1 of 𝑒+𝑒− collision data collected at a center-of-mass energy of 3.773 GeV with the BESIII detector, the first observation of the doubly Cabibbo-suppressed decay 𝐷+→𝐾+𝜋+𝜋−𝜋0 is reported. After removing decays that contain narrow intermediate resonances, including 𝐷+→𝐾+𝜂, 𝐷+→𝐾+𝜔, and 𝐷+→𝐾+𝜙, the branching fraction of the decay 𝐷+→𝐾+𝜋+𝜋−𝜋0 is measured to be (1.13±0.08stat±0.03syst)×10−3. The ratio of branching fractions of 𝐷+→𝐾+𝜋+𝜋−𝜋0 over 𝐷+→𝐾−𝜋+𝜋+𝜋0 is found to be (1.81±0.15)%, which corresponds to (6.28±0.52)tan4𝜃𝐶, where 𝜃𝐶 is the Cabibbo mixing angle. This ratio is significantly larger than the corresponding ratios for other doubly Cabibbo-suppressed decays. The asymmetry of the branching fractions of charge-conjugated decays 𝐷±→𝐾±𝜋±𝜋∓𝜋0 is also determined, and no evidence for 𝐶𝑃 violation is found. In addition, the first evidence for the 𝐷+→𝐾+𝜔 decay, with a statistical significance of 3.3𝜎, is presented and the branching fraction is measured to be ℬ(𝐷+→𝐾+𝜔) = (5.7+2.5−2.1stat±0.2syst)×10−5.
Using a sample of 106 million 𝜓(3686) decays, 𝜓(3686)→𝛾𝜒𝑐𝐽(𝐽=0,1,2) and 𝜓(3686)→𝛾𝜒𝑐𝐽,𝜒𝑐𝐽→𝛾𝐽/𝜓(𝐽=1,2) events are utilized to study inclusive 𝜒𝑐𝐽→anything, 𝜒𝑐𝐽→hadrons, and 𝐽/𝜓→anything distributions, including distributions of the number of charged tracks, electromagnetic calorimeter showers, and 𝜋0s, and to compare them with distributions obtained from the BESIII Monte Carlo simulation. Information from each Monte Carlo simulated decay event is used to construct matrices connecting the detected distributions to the input predetection “produced” distributions. Assuming these matrices also apply to data, they are used to predict the analogous produced distributions of the decay events. Using these, the charged particle multiplicities are compared with results from MARK I. Further, comparison of the distributions of the number of photons in data with those in Monte Carlo simulation indicates that G-parity conservation should be taken into consideration in the simulation.
The processes 𝑒+𝑒−→𝐷+ 𝑠𝐷𝑠1(2460)−+c.c. and 𝑒+𝑒−→𝐷*+ 𝑠𝐷𝑠1(2460)−+c.c. are studied for the first time using data samples collected with the BESIII detector at the BEPCII collider. The Born cross sections of 𝑒+𝑒−→𝐷+ 𝑠𝐷𝑠1(2460)−+c.c. at nine center-of-mass energies between 4.467 GeV and 4.600 GeV and those of 𝑒+𝑒−→𝐷*+ 𝑠𝐷𝑠1(2460)−+c.c. at √𝑠=4.590 GeV and 4.600 GeV are measured. No obvious charmonium or charmoniumlike structure is seen in the measured cross sections.
We report an amplitude analysis and branching fraction measurement of D+s→K+K−π+ decay using a data sample of 3.19 fb−1 recorded with BESIII detector at a center-of-mass energy of 4.178 GeV.
We perform a model-independent partial wave analysis in the low K+K− mass region to determine the K+K− S-wave lineshape,
followed by an amplitude analysis of our very pure high-statistics sample.
The amplitude analysis provides an accurate determination of the detection efficiency allowing us to measure the branching fraction B(D+s→K+K−π+)=(5.47±0.08stat±0.13sys)%.
We report an amplitude analysis and branching fraction measurement of D+s→K+K−π+ decay using a data sample of 3.19 fb−1 recorded with BESIII detector at a center-of-mass energy of 4.178 GeV.
We perform a model-independent partial wave analysis in the low K+K− mass region to determine the K+K− S-wave lineshape, followed by an amplitude analysis of our very pure high-statistics sample.
The amplitude analysis provides an accurate determination of the detection efficiency allowing us to measure the branching fraction B(D+s→K+K−π+)=(5.47±0.08stat±0.13sys)%.
We report an amplitude analysis and branching fraction measurement of D+s→K+K−π+ decay using a data sample of 3.19 fb−1 recorded with BESIII detector at a center-of-mass energy of 4.178 GeV.
We perform a model-independent partial wave analysis in the low K+K− mass region to determine the K+K− S-wave lineshape, followed by an amplitude analysis of our very pure high-statistics sample.
The amplitude analysis provides an accurate determination of the detection efficiency allowing us to measure the branching fraction B(D+s→K+K−π+)=(5.47±0.08stat±0.13sys)%.
Healthy and degenerating intervertebral discs (IVDs) are innervated by sympathetic nerves, however, adrenoceptor (AR) expression and functionality have never been investigated systematically. Therefore, AR gene expression was analyzed in both tissue and isolated cells from degenerated human IVDs. Furthermore, human IVD samples and spine sections of wildtype mice (WT) and of a mouse line that develops spontaneous IVD degeneration (IVDD, in SM/J mice) were stained for ARs and extracellular matrix (ECM) components. In IVD homogenates and cells α1a-, α1b-, α2a-, α2b-, α2c-, β1-, and β2-AR genes were expressed. In human sections, β2-AR was detectable, and its localization parallels with ECM alterations. Similarly, in IVDs of WT mice, only β2-AR was expressed, and in IVDs of SM/J mice, β2AR expression was stronger accompanied by increased collagen II, collagen XII, decorin as well as decreased cartilage oligomeric matrix protein expression. In addition, norepinephrine stimulation of isolated human IVD cells induced intracellular signaling via ERK1/2 and PKA. For the first time, the existence and functionality of ARs were demonstrated in IVD tissue samples, suggesting that the sympathicus might play a role in IVDD. Further studies will address relevant cellular mechanisms and thereby help to develop novel therapeutic options for IVDD.
Shares of open-end real estate funds are typically traded directly between the investor and the fund management company. However, we provide empirical evidence for the growth of secondary market activities, i.e., the trading of shares on stock exchanges. We find high trading levels in situations where the fund management company suspends the issue or redemption of shares. Shares trade at a discount when the fund management company suspends the redemption, whereas shares trade at a premium when the fund management company suspends the issue. We also find evidence that secondary market trading activity is increasing since German regulation introduced a minimum holding period and a mandatory notice period for open-end real estate funds.
Measurement of cross sections for e⁺e⁻ → μ⁺μ⁻ at center-of-mass energies from 3.80 to 4.60 GeV
(2020)
The observed cross sections for 𝑒+𝑒−→𝜇+𝜇− at energies from 3.8 to 4.6 GeV are measured using data samples taken with the BESIII detector operated at the BEPCII collider. We measure the muonic widths and determine the branching fractions of the charmonium states 𝜓(4040), 𝜓(4160), and 𝜓(4415) decaying to 𝜇+𝜇−, as well as making a first determination of the phase of the amplitudes. In addition, we observe evidence for a structure in the dimuon cross section near 4.220 GeV/𝑐2, which we denote as 𝑆(4220). Analyzing a coherent sum of amplitudes yields eight solutions, one of which gives a mass of 𝑀𝑆(4220) = 4216.7±8.9±4.1 MeV/𝑐2, a total width of Γtot S(4220) = 47.2±22.8±10.5 MeV, and a muonic width of Γ𝜇𝜇 𝑆(4220) = 1.53±1.26±0.54 keV, where the first uncertainties are statistical and the second systematic. The eight solutions give the central values of the mass, total width, muonic width to be, respectively, in the range from 4212.8 to 4219.4 MeV/𝑐2, from 36.4 to 49.6 MeV, and from 1.09 to 1.53 keV. The statistical significance of the 𝑆(4220) signal is 3.9𝜎. Correcting the total dimuon cross section for radiative effects yields a statistical significance for this structure of 8.1𝜎.
Using a dedicated data sample taken in 2018 on the J/ψ peak, we perform a detailed study of the trigger efficiencies of the BESIII detector. The efficiencies are determined from three representative physics processes, namely Bhabha scattering, dimuon production and generic hadronic events with charged particles. The combined efficiency of all active triggers approaches 100% in most cases, with uncertainties small enough not to affect most physics analyses.
Ten hadronic final states of the ℎ𝑐 decays are investigated via the process 𝜓(3686)→𝜋0ℎ𝑐, using a data sample of (448.1±2.9)×106 𝜓(3686) events collected with the BESIII detector. The decay channel ℎ𝑐→𝐾+𝐾−𝜋+𝜋−𝜋0 is observed for the first time and has a measured significance of 6.0𝜎. The corresponding branching fraction is determined to be ℬ(ℎ𝑐→𝐾+𝐾−𝜋+𝜋−𝜋0)=(3.3±0.6±0.6)×10−3 (where the uncertainties are statistical and systematic, respectively). Evidence for the decays ℎ𝑐→𝜋+𝜋−𝜋0𝜂 and ℎ𝑐→𝐾0𝑆𝐾±𝜋∓𝜋+𝜋− is found with a significance of 3.6𝜎 and 3.8𝜎, respectively. The corresponding branching fractions (and upper limits) are obtained to be ℬ(ℎ𝑐→𝜋+𝜋−𝜋0𝜂)=(7.2±1.8±1.3)×10−3 (<1.8×10−2) and ℬ(ℎ𝑐→𝐾0𝑆𝐾±𝜋∓𝜋+𝜋−)=(2.8±0.9±0.5)×10−3 (<4.7×10−3). Upper limits on the branching fractions for the final states ℎ𝑐→𝐾+𝐾−𝜋0, 𝐾+𝐾−𝜂, 𝐾+𝐾−𝜋+𝜋−𝜂, 2(𝐾+𝐾−)𝜋0, 𝐾+𝐾−𝜋0𝜂, 𝐾0𝑆𝐾±𝜋∓, and 𝑝¯𝑝𝜋0𝜋0 are determined at a confidence level of 90%.
Background Coronavirus disease 2019 (COVID-19) represents a significant challenge to health care systems around the world. A well-functioning primary care system is crucial in epidemic situations as it plays an important role in the development of a system-wide response.
Methods 2,187 Austrian and German GPs answered an internet suvey on preparedness, testing, staff protection, perception of risk, self-confidence, a decrease in the number of patient contacts, and efforts to control the spread of the virus in the practice during the early phase of the COVID-pandemic (3rd to 30th April).
Results The completion rate of the questionnaire was high (90.9%). GPs gave low ratings to their preparedness for a pandemic, testing of suspected cases and efforts to protect staff. The provision of information to GPs and the perception of risk were rated as moderate. On the other hand, the participants rated their self-confidence, a decrease in patient contacts and their efforts to control the spread of the disease highly.
Conclusion Primary care is an important resource for dealing with a pandemic like COVID-19. The workforce is confident and willing to take an active role, but needs to be provided with the appropriate surrounding conditions. This will require that certain conditions are met.
Registration Trial registration at the German Clinical Trials Register: DRKS00021231
Background: The health status, health awareness and health behavior of persons with a migration background often differ from the autochthonous population. Little is known about the proportion of patients with a migration background (PMB) that participate in primary care studies on oral antithrombotic treatment (OAT) in Germany, and whether the quality of their antithrombotic care differs from patients without a migration background. The aim of this paper was to use the results of a cluster-randomized controlled trial (PICANT) to determine the proportion of PMB at different stages of recruitment, and to compare the results in terms of sociodemographic characteristics and antithrombotic treatment.
Methods: This study used screening and baseline data from the PICANT trial on oral anticoagulation management in GP practices. For this analysis, we determined the proportion of PMB during the recruitment period at stage 1 (screening of potentially eligible patients), stage 2 (eligible patients invited to participate in the trial), and stage 3 (assessment of baseline characteristics of patients participating in the PICANT trial). In addition, we compared patients in terms of sociodemographic characteristics and quality of anticoagulant treatment. Statistical analysis comprised descriptive and bivariate analyses.
Results: The proportion of PMB at each recruitment stage declined from 9.1% at stage 1 to 7.9% at stage 2 and 7.3% at stage 3). A lack of German language skills led to the exclusion of half the otherwise eligible PMB. At stages 1 and 3, PMB were younger (stage 1: 70.7 vs. 75.0 years, p<0.001; stage 3: 70.2 vs. 73.5 years, p = 0.013), but did not differ in terms of gender. The quality of their anticoagulant care was comparable (100.0% vs. 99.1% were receiving appropriate OAT, 94.4% vs. 95.7% took phenprocoumon, or warfarin, and the most recent INR measurement of 60.8% vs. 69.3% was within their individual INR range).
Conclusions: In the potentially eligible population and among participants at baseline, the quality of anticoagulant care was high in all groups of patients, which is reassuring. To enable the inclusion of more PMB, future primary care research on OAT in Germany should address how best to overcome language barriers. This will be challenging, particularly because the heterogeneity of PMB means the resulting sample sizes for each specific language group are small.
Trial registration: Current Controlled Trials ISRCTN41847489.
Background & Aims: NAFLD is a growing health concern. The aim of the Fatty Liver Assessment in Germany (FLAG) study was to assess disease burden and provide data on the standard of care from secondary care. Methods: The FLAG study is an observational real-world study in patients with NAFLD enrolled at 13 centres across Germany. Severity of disease was assessed by non-invasive surrogate scores and data recorded at baseline and 12 months. Results: In this study, 507 patients (mean age 53 years; 47% women) were enrolled. According to fibrosis-4 index, 64%, 26%, and 10% of the patients had no significant fibrosis, indeterminate stage, and advanced fibrosis, respectively. Patients with advanced fibrosis were older, had higher waist circumferences, and higher aspartate aminotransferase and gamma-glutamyltransferase as well as ferritin levels. The prevalence of obesity, arterial hypertension, and type 2 diabetes increased with fibrosis stages. Standard of care included physical exercise >2 times per week in 17% (no significant fibrosis), 19% (indeterminate), and 6% (advanced fibrosis) of patients. Medication with either vitamin E, silymarin, or ursodeoxycholic acid was reported in 5%. Approximately 25% of the patients received nutritional counselling. According to the FibroScan-AST score, 17% of patients presented with progressive non-alcoholic steatohepatitis (n = 107). On follow-up at year 1 (n = 117), weight loss occurred in 47% of patients, of whom 17% lost more than 5% of body weight. In the weight loss group, alanine aminotransferase activities were reduced by 20%. Conclusions: This is the first report on NAFLD from a secondary-care real-world cohort in Germany. Every 10th patient presented with advanced fibrosis at baseline. Management consisted of best supportive care and lifestyle recommendations. The data highlight the urgent need for systematic health agenda in NAFLD patients. Lay summary: FLAG is a real-world cohort study that examined the liver disease burden in secondary and tertiary care. Herein, 10% of patients referred to secondary care for NAFLD exhibited advanced liver disease, whilst 64% had no significant liver scarring. These findings underline the urgent need to define patient referral pathways for suspected liver disease.
Background and Aims: Monocyte chemotactic protein-1 (MCP-1) is a potent chemoattractant for monocytes. It is involved in pathogenesis of several inflammatory diseases. Hepatic MCP-1 is a readout of macrophage activation. While inflammation is a major driver of liver disease progression, the origin and role of circulating MCP-1 as a biomarker remains unclear.
Methods: Hepatic CC-chemokine ligand 2 (CCL2) expression and F4/80 staining for Kupffer cells were measured and correlated in a mouse model of chronic liver disease (inhalative CCl4 for 7 weeks). Next, hepatic RNA levels of CCL2 were measured in explanted livers of 39 patients after transplantation and correlated with severity of disease. Changes in MCP-1 were further evaluated in a rat model of experimental cirrhosis and acute-on-chronic liver failure (ACLF). Finally, we analyzed portal and hepatic vein levels of MCP-1 in patients receiving transjugular intrahepatic portosystemic shunt insertion for complications of portal hypertension.
Results: In this mouse model of fibrotic hepatitis, hepatic expression of CCL2 (P = 0.009) and the amount of F4/80 positive cells in the liver (P < 0.001) significantly increased after induction of hepatitis by CCl4 compared to control animals. Moreover, strong correlation of hepatic CCL2 expression and F4/80 positive cells were seen (P = 0.023). Furthermore, in human liver explants, hepatic transcription levels of CCL2 correlated with the MELD score of the patients, and thus disease severity (P = 0.007). The experimental model of ACLF in rats revealed significantly higher levels of MCP-1 plasma (P = 0.028) and correlation of hepatic CCL2 expression (R = 0.69, P = 0.003). Particularly, plasma MCP-1 levels did not correlate with peripheral blood monocyte CCL2 expression. Finally, higher levels of MCP-1 were observed in the hepatic compared to the portal vein (P = 0.01) in patients receiving TIPS. Similarly, a positive correlation of MCP-1 with Child-Pugh score was observed (P = 0.018). Further, in the presence of ACLF, portal and hepatic vein levels of MCP-1 were significantly higher compared to patients without ACLF (both P = 0.039).
Conclusion: Circulating levels of MCP-1 mainly derive from the injured liver and are associated with severity of liver disease. Therefore, liver macrophages contribute significantly to disease progression. Circulating MCP-1 may reflect the extent of hepatic macrophage activation.
Background: Point of care devices for performing targeted coagulation substitution in patients who are bleeding have become increasingly important in recent years. New on the market is the Quantra. It is a device that uses sonorheometry, a sonic estimation of elasticity via resonance, which is a novel ultrasound-based technology that measures viscoelastic properties of whole blood. Several studies have already shown the comparability of the Quantra with devices already established on the market, such as the rotational thromboelastometry (ROTEM) device.
Objective: In contrast to existing studies, this study is the first prospective interventional study using this new system in a cardiac surgical patient cohort. We will investigate the noninferiority between an already existing coagulation algorithm based on the ROTEM/Multiplate system and a new algorithm based on the Quantra system for the treatment of coagulopathic cardiac surgical patients.
Methods: The study is divided into two phases. In an initial observation phase, whole blood samples of 20 patients obtained at three defined time points (prior to surgery, after completion of cardiopulmonary bypass, and on arrival in the intensive care unit) will be analyzed using both the ROTEM/Multiplate and Quantra systems. The obtained threshold values will be used to develop a novel algorithm for hemotherapy. In a second intervention phase, the new algorithm will be tested for noninferiority against an algorithm used routinely for years in our department.
Results: The main objective of the examination is the cumulative loss of blood within 24 hours after surgery. Statistical calculations based on the literature and in-house data suggest that the new algorithm is not inferior if the difference in cumulative blood loss is <150 mL/24 hours.
Conclusions: Because of the comparability of the Quantra sonorheometry system with the ROTEM measurement methods, the existing hemotherapy treatment algorithm can be adapted to the Quantra device with proof of noninferiority.
Trial Registration: ClinicalTrials.gov NCT03902275; https://clinicaltrials.gov/ct2/show/NCT03902275
International Registered Report Identifier (IRRID): DERR1-10.2196/17206