Refine
Year of publication
- 2020 (2186) (remove)
Document Type
- Article (1417)
- Part of Periodical (253)
- Preprint (174)
- Doctoral Thesis (127)
- Working Paper (99)
- Part of a Book (58)
- Book (31)
- Conference Proceeding (15)
- Master's Thesis (3)
- Review (3)
Language
- English (2186) (remove)
Is part of the Bibliography
- no (2186) (remove)
Keywords
- taxonomy (87)
- new species (50)
- Spracherwerb (33)
- Sprachtest (33)
- COVID-19 (23)
- morphology (20)
- inflammation (18)
- ECB (16)
- SARS-CoV-2 (15)
- biodiversity (15)
Institute
- Medizin (637)
- Physik (255)
- Wirtschaftswissenschaften (158)
- Frankfurt Institute for Advanced Studies (FIAS) (152)
- Biowissenschaften (149)
- Sustainable Architecture for Finance in Europe (SAFE) (117)
- Informatik (116)
- Biochemie, Chemie und Pharmazie (97)
- Center for Financial Studies (CFS) (73)
- House of Finance (HoF) (62)
Density visualization pipeline: a tool for cellular and network density visualization and analysis
(2020)
Neuron classification is an important component in analyzing network structure and quantifying the effect of neuron topology on signal processing. Current quantification and classification approaches rely on morphology projection onto lower-dimensional spaces. In this paper a 3D visualization and quantification tool is presented. The Density Visualization Pipeline (DVP) computes, visualizes and quantifies the density distribution, i.e., the “mass” of interneurons. We use the DVP to characterize and classify a set of GABAergic interneurons. Classification of GABAergic interneurons is of crucial importance to understand on the one hand their various functions and on the other hand their ubiquitous appearance in the neocortex. 3D density map visualization and projection to the one-dimensional x, y, z subspaces show a clear distinction between the studied cells, based on these metrics. The DVP can be coupled to computational studies of the behavior of neurons and networks, in which network topology information is derived from DVP information. The DVP reads common neuromorphological file formats, e.g., Neurolucida XML files, NeuroMorpho.org SWC files and plain ASCII files. Full 3D visualization and projections of the density to 1D and 2D manifolds are supported by the DVP. All routines are embedded within the visual programming IDE VRL-Studio for Java which allows the definition and rapid modification of analysis workflows.
Recent research has identified significant correlations between traumatic events and depression in refugees. However, few studies have addressed the role of acculturation strategies in this relationship. This study explored the relationship between cultural orientation, traumatic events and depression in female refugees from Syria, Afghanistan, Eritrea, Iran, Iraq, and Somalia living in Germany. We expected acculturation strategies to moderate the effect of traumatic experiences on depression. The sample included 98 female refugees in Germany. The depression scale of the Hopkins Symptom Checklist (HSCL) represented the dependent measure. The trauma checklists derived from the Post-traumatic Diagnostic Scale (PDS) and the Harvard Trauma Questionnaire (HTQ) as well as the Frankfurt Acculturation Scale (FRACC) were used as independent measures for traumatic events and orientation toward the host culture as well as orientation toward the culture of origin, respectively. A moderation analysis was conducted to examine whether the relationship between the number of traumatic events and depression was influenced by the women’s orientation toward the culture of origin and the host culture. We identified a significant model explaining 26.85% of the variance in depressive symptoms (Cohen’s f2 = 0.37). The number of traumatic events and the orientation toward the host culture exerted significant effects on depressive symptoms. The moderating effect was not significant, indicating that the effect of the number of traumatic events was not influenced by cultural orientation. Based on our results, orientation toward the host culture as well as traumatic experiences exert independent effects on depressive symptoms in refugees.
Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially,thedevelopmentoffibrosisandportalhypertensioninNAFLDpatientsrequirestreatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertension but without obesity. This study investigated the additional role of obesity in this model on the development of portal hypertension and fibrosis. Obesity was induced in twelve-week old TGR(mREN2)27 rats after receiving Western diet (WD) for two or four weeks. Liver fibrosis was assessed using standard techniques. Hepatic expression of transforming growth factor-β1 (TGF-β1), collagen type Iα1, α-smooth muscle actin, and the macrophage markers Emr1, as well as the chemoattractant Ccl2, interleukin-1β (IL1β) and tumor necrosis factor-α (TNFα) were analyzed. Assessment of portal and systemic hemodynamics was performed using the colored microsphere technique. Asexpected,WDinducedobesityandliverfibrosisasconfirmedbySiriusRedandOilRed O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increasedduringfeedingofWD,indicatinginfiltrationofmacrophagesintotheliver,eventhoughthis increase was statistically not significant for the EGF module-containing mucin-like receptor (Emr1) mRNA expression levels. Of note, portal pressure increased with the duration of WD compared to animals that received a normal chow. Besides obesity, WD feeding increased systemic vascular resistance reflecting systemic endothelial and splanchnic vascular dysfunction. We conclude that transgenic TGR(mREN2)27 rats are a suitable model to investigate NAFLD development with liver fibrosis and portal hypertension. Tendency towards elevated expression of Emr1 is associated with macrophage activity point to a significant role of macrophages in NAFLD pathogenesis, probably due to a shift of the renin–angiotensin system towards a higher activation of the classical pathway. The hepatic injury induced by WD in TGR(mREN2)27 rats is suitable to evaluate different stages of fibrosis and portal hypertension in NAFLD with obesity.
Background: The purpose of this pilot study was to create a valid and reliable set of assessment questions for examining Evidence-based Dentistry (EbD) knowledge. For this reason, we adapted and validated for dental students the Berlin Questionnaire (BQ), which assesses Evidence-based Medicine (EbM) abilities.
Methods: The Berlin Questionnaire was validated with medical residents. We adapted it for use in a dentistry setting. An expert panel reviewed the adapted BQ for content validity. A cross-sectional cohort representing four training levels (EbD-novice dental students, EbD-trained dental students, dentists, and EbM−/EbD-expert faculty) completed the questionnaire. A total of 140 participants comprised the validation set. Internal reliability, item difficulty and item discrimination were assessed. Construct validity was assessed by comparing the mean total scores of students to faculty and comparing proportions of students and faculty who passed each item.
Results: Among the 133 participants (52 EbD-novice dental students, 53 EbD-trained dental students, 12 dentists, and 16 EbM-/ EbD-expert faculty), a statistically significant (p < 0.001) difference was evident in the total score corresponding to the training level. The total score reliability and psychometric properties of items modified for discipline-specific content were acceptable. Cronbach’s alpha was 0.648.
Conclusion: The adapted Berlin Questionnaire is a reliable and valid instrument to assess competence in Evidence-based Dentistry in dental students. Future research will focus on refining the instrument further.
Background: Radiotherapy dose and target volume prescriptions for anal squamous cell carcinoma (ASCC) vary considerably in daily practice and guidelines, including those from NCCN, UK, Australasian, and ESMO. We conducted a pattern-of-care survey to assess the patient management in German speaking countries.
Methods: We developed an anonymous questionnaire comprising 18 questions on diagnosis and treatment of ASCC. The survey was sent to 361 DEGRO-associated institutions, including 41 university hospitals, 118 non-university institutions, and 202 private practices.
Results: We received a total of 101 (28%) surveys, including 20 (19.8%) from university, 36 (35.6%) from non-university clinics, and 45 (44.6%) from private practices. A total of 28 (27.8%) institutions reported to treat more than 5 patients with early-stage ASCC and 42 (41.6%) institutions treat more than 5 patients with locoregionally-advanced ASCC per year. Biopsy of suspicious inguinal nodes was advocated in only 12 (11.8%) centers. Screening for human immunodeficiency virus (HIV) is done in 28 (27.7%). Intensity modulated radiotherapy or similar techniques are used in 97%. The elective lymph node dose ranged from 30.6 Gy to 52.8 Gy, whereas 87% prescribed 50.4–55. 8 Gy (range: 30.6 to 59.4 Gy) to the involved lymph nodes. The dose to gross disease of cT1 or cT2 ASCC ranged from 50 to ≥60 Gy. For cT3 or cT4 tumors the target dose ranged from 54 Gy to more than 60 Gy, with 76 (75.2%) institutions prescribing 59.4 Gy. The preferred concurrent chemotherapy regimen was 5-FU/Mitomycin C, whereas 6 (6%) prescribed Capecitabine/Mitomycin C. HIV-positive patients are treated with full-dose CRT in 87 (86.1%) institutions. First assessment for clinical response is reported to be performed at 4–6 weeks after completion of CRT in 2 (2%) institutions, at 6–8 weeks in 20 (19.8%), and 79 (78%) institutions wait up to 5 months.
Conclusions: We observed marked differences in radiotherapy doses and treatment technique in patients with ASCC, and also variable approaches for patients with HIV. These data underline the need for an consensus treatment guideline for ASCC.
Receptor tyrosine kinases (RTKs) orchestrate cell motility and differentiation. Deregulated RTKs may promote cancer and are prime targets for specific inhibitors. Increasing evidence indicates that resistance to inhibitor treatment involves receptor cross-interactions circumventing inhibition of one RTK by activating alternative signaling pathways. Here, we used single-molecule super-resolution microscopy to simultaneously visualize single MET and epidermal growth factor receptor (EGFR) clusters in two cancer cell lines, HeLa and BT-20, in fixed and living cells. We found heteromeric receptor clusters of EGFR and MET in both cell types, promoted by ligand activation. Single-protein tracking experiments in living cells revealed that both MET and EGFR respond to their cognate as well as non-cognate ligands by slower diffusion. In summary, for the first time, we present static as well as dynamic evidence of the presence of heteromeric clusters of MET and EGFR on the cell membrane that correlates with the relative surface expression levels of the two receptors
Direct acting antivirals (DAAs) revolutionized the therapy of chronic hepatitis C infection. However, unexpected high recurrence rates of hepatocellular carcinoma (HCC) after DAA treatment became an issue in patients with advanced cirrhosis and fibrosis. In this study, we aimed to investigate an impact of DAA treatment on the molecular changes related to HCC development and progression in hepatoma cell lines and primary human hepatocytes. We found that treatment with sofosbuvir (SOF), a backbone of DAA therapy, caused an increase in EGFR expression and phosphorylation. As a result, enhanced translocation of EGFR into the nucleus and transactivation of factors associated with cell cycle progression, B-MYB and Cyclin D1, was detected. Serine/threonine kinase profiling identified additional pathways, especially the MAPK pathway, also activated during SOF treatment. Importantly, the blocking of EGFR kinase activity by erlotinib during SOF treatment prevented all downstream events. Altogether, our findings suggest that SOF may have an impact on pathological processes in the liver via the induction of EGFR signaling. Notably, zidovudine, another nucleoside analogue, exerted a similar cell phenotype, suggesting that the observed effects may be induced by additional members of this drug class.
Background: Point of care devices for performing targeted coagulation substitution in bleeding patients have become increasingly important in recent years. New on the market is the Quantra® from HemoSonics (LC, Charlottesville, VA, US). It uses sonorheometry, a sonic estimation of elasticity via resonance (SEER), a novel ultrasound-based technology that measures viscoelastic properties of whole blood. Several studies have already shown the comparability with devices already established on the market such as the ROTEM® (TEM International GmbH, Munich, Germany).
Objective: In contrast to existing studies, the planned study will be the first prospective interventional study using the new Quantra® system in a cardiac surgical patient cohort. The aim is to investigate the non-inferiority between an already existing coagulation algorithm, based on ROTEM®/Multiplate®, and a new algorithm based on the Quantra®, 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 will be analyzed using both ROTEM®/Multiplate® and Quantra® obtained at three defined points of time (prior to surgery, after completion of cardiopulmonary bypass, on arrival in the intensive care unit). The obtained threshold values will be used to create an algorithm for hemotherapy. In a second intervention phase, the new algorithm will be tested against an algorithm used routineously for years at our department for non-inferiority.
Results: The main objective of the examination is the cumulative loss of blood within 24 hours after surgery. Statistical calculations based on literature and in-house data suggest that the new algorithm is not inferior if the difference in cumulative blood loss is < 150ml/24 h.
Conclusions: Because of the comparability of the Quantra® sonorheometry system with ROTEM® rotational thromboelastometric measurement methods, the existing hemotherapy treatment algorithm can be adapted to the Quantra device with a proof of non-inferiority. Clinical Trial: International Registered Report Identifier (IRRID): clinicaltrials.gov: NCT03902275
The healthcare industry sees great potential in consolidating medical data on one and the same person which is currently distributed across various practices and hospitals. This would not only save costs on repeating procedures; physicians also hope that artificial intelligence will help them identify new connections and thereby treat diseases earlier, or even prevent them.
So far, personal feedback in the case of lectures with hundreds of students still seems utopic – even after the digitalization boom in times of the coronavirus. Tools from the research field of »learning analytics« could in future give students feedback and at the same time provide their supervisors with clues about where help is still needed.
A question of striking the right balance : how do digital media influence how we think and act?
(2020)
What influence do digital technologies have on human perception, thinking and action? Do computer games harm the development of young brains? And is there really such a thing as »digital dementia«, an increasing forgetfulness caused by the use of modern technologies? For some of these questions, answers are available that are empirically corroborated.
Through digitalization, the social importance of copyright law has grown considerably. Moreover, the culture of exclusivity established by copyright law conflicts fundamentally with the culture of access prevalent on the internet. An example for this is the dispute over the EU’s latest copyright directive. Does it ring in the end of the internet as we know it, or does it »only« see to fair remuneration for those working in the creative economy?
The issue of data security has become increasingly complex in the age of the internet and artificial intelligence. The developments seem to be almost unmanageable in some areas. Cooperation between jurisprudence and information technology is the only thing that can protect the individual and certain social groups from discrimination.
As a network researcher, sociologist Professor Christian Stegbauer also deals with communication in social media. That people prefer to stay in a bubble with like-minded others rather than get to grips with different opinions and ways of thinking was in his view inherent to digital communication from the outset. He considers many of the utopian ideas of a digital culture of participation to be exaggerated.
The early-diverging oomycetes contain a large number of holocarpic obligate parasites of diatoms, algae, aquatic phycomycetes, and invertebrate animals. These organisms are diverse and widespread. However, taxonomic placement most of the early-diverging oomycetes remains provisional and unresolved, since many have not been sequenced and studied for molecular phylogeny. Here, we report the taxonomy and phylogeny of several holocarpic oomycetes that we have rediscovered and newly classified, including several new species combinations. Phylogenetic reconstructions revealed that the type species of genus Ectrogella (E. bacillariacearum) is a member of the early-diverging Saprolegniales, while the type species of Olpidiopsis (O. saprolegniae) and Pontisma (P. lagenidioides) grouped within the early-diverging lineage of oomycetes forming distinct clades. Since the monophyletic red-algae parasitoids are unrelated to the Olpidiopsis, these were reclassified to the genus Pontisma, while genus Diatomophthora was introduced to accommodate all the diatom parasitoids that were previously assigned to Olpidiopsis. In addition, four new oomycete parasitoids, Miracula helgolandica, Miracula moenusica, Diatomophthora drebesii and Olpidiopsis parthenogenetica and a single rediscovered species, Diatomophthora gillii, are also classified here, including eight new species combinations of red-algae parasites (Pontisma bostrychiae, P. heterosiphoniae, P. muelleri, P. palmariae, P. porphyrae, P. pyropiae) and diatom parasitoids (Diatomophthora drebesii, D. gillii). The results obtained in this study have further improved the resolution and expanded the knowledge on the phylogeny of the earlydiverging oomycetes, leading to the establishment of three new orders (Miraculales, Diatomophthorales, Pontismatales) and one order (Anisolpidiales) being reintroduced.
Genotoxicity assessment is of high relevance for crude and refined petroleum products, since oil compounds are known to cause DNA damage with severe consequences for aquatic biota as demonstrated in long-term monitoring studies. This study aimed at the optimization and evaluation of small-scale higher-throughput assays (Ames fluctuation, micronucleus, Nrf2-CALUX®) covering different mechanistic endpoints as first screening tools for genotoxicity assessment of oils. Cells were exposed to native and chemically dispersed water-accommodated fractions (WAFs) of three oil types varying in their processing degree. Independent of an exogenous metabolic activation system, WAF compounds induced neither base exchange nor frame shift mutations in bacterial strains. However, significantly increased chromosomal aberrations in zebrafish liver (ZF-L) cells were observed. Oxidative stress was indicated for some treatments and was not correlated with observed DNA damage. Application of a chemical dispersant increased the genotoxic potential rather by the increased bioavailability of dissolved and particulate oil compounds. Nonetheless, the dispersant induced a clear oxidative stress response, indicating a relevance for general toxic stress. Results showed that the combination of different in vitro assays is important for a reliable genotoxicity assessment. Especially, the ZF-L capable of active metabolism and DNA repair seems to be a promising model for WAF testing.
Objective: Phenotypic (Sensititre Myco, pDST) and genotypic drug susceptibility testing (GenoType NTM DR, gDST) in M. avium complex (MAC) have become available as standardized assays, but comparable data is needed. This study aimed to investigate the phenotypic and genotypic drug susceptibility patterns in MAC clinical isolates.
Methods: Overall, 98 isolates from 85 patients were included. pDST and gDST were performed on all isolates and results compared regarding specificity and sensitivity using pDST as a reference method. The impact of drug instability on pDST results was studied using a biological assay over 14 days. In addition, the evolution of antimicrobial resistance was investigated in sequential isolates of 13 patients.
Results: Macrolide resistance was rare, 1.2% (95% CI 0.7–7.3) of isolates in the base cohort. No aminoglycoside resistances were found, but 14.1% of the studied isolates (95% CI 7.8–23.8) showed intermediate susceptibility. The GenoType NTM DR identified two out of four macrolide-resistant isolates. Antibiotic stability was demonstrated to be poor in rifampicin, rifabutin, and doxycycylin.
Conclusions: pDST results in NTM for unstable antibiotics must be interpreted with care. A combination of pDST and gDST will be useful for the guidance of antimicrobial therapy in MAC-disease.
Molecular and cellular research modalities for the study of liver pathologies have been tremendously improved over the recent decades. Advanced technologies offer novel opportunities to establish cell isolation techniques with excellent purity, paving the path for 2D and 3D microscopy and high-throughput assays (e.g., bulk or single-cell RNA sequencing). The use of stem cell and organoid research will help to decipher the pathophysiology of liver diseases and the interaction between various parenchymal and non-parenchymal liver cells. Furthermore, sophisticated animal models of liver disease allow for the in vivo assessment of fibrogenesis, portal hypertension and hepatocellular carcinoma (HCC) and for the preclinical testing of therapeutic strategies. The purpose of this review is to portray in detail novel in vitro and in vivo methods for the study of liver cell biology that had been presented at the workshop of the 8th meeting of the European Club for Liver Cell Biology (ECLCB-8) in October of 2018 in Bonn, Germany.
Radar technology in the millimeter-wave frequency band offers many interesting features for wind park surveillance, such as structural monitoring of rotor blades or the detection of bats and birds in the vicinity of wind turbines (WTs). Currently, the majority of WTs are affected by shutdown algorithms to minimize animal fatalities via direct collision with the rotor blades or barotrauma effects. The presence of rain is an important parameter in the definition of those algorithms together with wind speed, temperature, time of the day, and season of the year. A Ka-band frequency-modulated continuous-wave radar (33.4-36.0 GHz) installed at the tower of a 2-MW WT was used during a field study. We have observed characteristic rain-induced patterns, based on the range-Doppler algorithm. To better understand those signatures, we have developed a laboratory experiment and implemented a numerical modeling framework. Experimental and numerical results for rain detection and classification are presented and discussed here. Based on this article, a bat- and bird-friendly adaptive WT control can be developed for improved WT efficiency in periods of rain and, at the same time, reduced animal mortality.
Objective: To study the effect of total hip replacement (THR) on serum cartilage oligomeric matrix protein concentration (sCOMP) and its correlation with joint loading during gait in patients with unilateral hip osteoarthritis.
Design: In this prospective multimodal (clinical, biomechanical, biochemical) study blood samples from 15 patients were taken before and up to three times after THR (7 days, 3 months and 1 year), each after a resting period of at least 30 min, for analysis of sCOMP. Gait analysis was performed before and 1 year after THR to determine hip and knee joint moments.
Results: Seven days after THR, sCOMP decreased significantly compared to the preoperative measurement (p < 0.001). Three months and 1 year postoperatively, sCOMP reverted to concentrations in the range of the preoperative value. One year postoperatively, a linear correlation between sCOMP and the maximum hip flexion moment was indicated in the first half of the stance phase on the unaffected side (r = −0.736, p = 0.024). No further correlations could be determined.
Conclusions: Surprisingly, the removal of a joint affected by osteoarthritis did not have a sustained effect on sCOMP. Both before and after THR there was no scientifically substantiated correlation between sCOMP and joint moments from gait analysis. Consequently, the examination of sCOMP is not useful to detect altered joint loads that may influence degenerative changes of adjacent joints after THR.
The registration number in the German Registry of Clinical Trials is DRKS00015053.
With the rapid growth of technology in recent years, we are surrounded by or even dependent on the use of technological devices such as smartphones as they are now an indispensable part of our life. Smartphone applications (apps) provide a wide range of utilities such as navigation, entertainment, fitness, etc. To provide such context-sensitive services to users, apps need to access users' data including sensitive ones, which in turn, can potentially lead to privacy invasions. To protect users against potential privacy invasions in such a vulnerable ecosystem, legislation such as the European Union General Data Protection Regulation (EU GDPR) demands best privacy practices. Therefore, app developers are required to make their apps compatible with legal privacy principles enforced by law. However, this is not an easy task for app developers to comprehend purely legal principles to understand what needs to be implemented. Similarly, bridging the gap between legal principles and technical implementations to understand how legal principles need to be implemented is another barrier to develop privacy-friendly apps. To this end, this paper proposes a privacy and security design guide catalog for app developers to assist them in understanding and adopting the most relevant privacy and security principles in the context of smartphone apps. The presented catalog is aimed at mapping the identified legal principles to practical privacy and security solutions that can be implemented by developers to ensure enhanced privacy aligned with existing legislation. Through conducting a case study, it is confirmed that there is a significant gap between what developers are doing in reality and what they promise to do. This paper provides researchers and developers of privacy-related technicalities an overview of the characteristics of existing privacy requirements needed to be implemented in smartphone ecosystems, on which they can base their work.
Inclusions of breyite (previously known as walstromite-structured CaSiO3) in diamond are usually interpreted as retrogressed CaSiO3 perovskite trapped in the transition zone or the lower mantle. However, the thermodynamic stability field of breyite does not preclude its crystallization together with diamond under upper-mantle conditions (6–10 GPa). The possibility of breyite forming in subducted sedimentary material through the reaction CaCO3 + SiO2 = CaSiO3 + C + O2 was experimentally evaluated in the CaO–SiO2–C–O2 ± H2O system at 6–10 GPa, 900–1500 ∘C and oxygen fugacity 0.5–1.0 log units below the Fe–FeO (IW) buffer. One experimental series was conducted in the anhydrous subsystem and aimed at determining the melting temperature of the aragonite–coesite (or stishovite) assemblage. It was found that melting occurs at a lower temperature (∼1500 ∘C) than the decarbonation reaction, which indicates that breyite cannot be formed from aragonite and silica under anhydrous conditions and an oxygen fugacity above IW – 1. In the second experimental series, we investigated partial melting of an aragonite–coesite mixture under hydrous conditions at the same pressures and redox conditions. The melting temperature in the presence of water decreased strongly (to 900–1200 ∘C), and the melt had a hydrous silicate composition. The reduction of melt resulted in graphite crystallization in equilibrium with titanite-structured CaSi2O5 and breyite at ∼1000 ∘C. The maximum pressure of possible breyite formation is limited by the reaction CaSiO3 + SiO2 = CaSi2O5 at ∼8 GPa. Based on the experimental results, it is concluded that breyite inclusions found in natural diamond may be formed from an aragonite–coesite assemblage or carbonate melt at 6–8 GPa via reduction at high water activity.
Background: Experienced and anticipated regret influence physicians’ decision-making. In medicine, diagnostic decisions and diagnostic errors can have a severe impact on both patients and physicians. Little empirical research exists on regret experienced by physicians when they make diagnostic decisions in primary care that later prove inappropriate or incorrect. The aim of this study was to explore the experience of regret following diagnostic decisions in primary care.
Methods: In this qualitative study, we used an online questionnaire on a sample of German primary care physicians. We asked participants to report on cases in which the final diagnosis differed from their original opinion, and in which treatment was at the very least delayed, possibly resulting in harm to the patient. We asked about original and final diagnoses, illness trajectories, and the reactions of other physicians, patients and relatives. We used thematic analysis to assess the data, supported by MAXQDA 11 and Microsoft Excel 2016.
Results: 29 GPs described one case each (14 female/15 male patients, aged 1.5–80 years, response rate < 1%). In 26 of 29 cases, the final diagnosis was more serious than the original diagnosis. In two cases, the diagnoses were equally serious, and in one case less serious. Clinical trajectories and the reactions of patients and relatives differed widely. Although only one third of cases involved preventable harm to patients, the vast majority (27 of 29) of physicians expressed deep feelings of regret.
Conclusion: Even if harm to patients is unavoidable, regret following diagnostic decisions can be devastating for clinicians, making them ‘second victims’. Procedures and tools are needed to analyse cases involving undesirable diagnostic events, so that ‘true’ diagnostic errors, in which harm could have been prevented, can be distinguished from others. Further studies should also explore how physicians can be supported in dealing with such events in order to prevent them from practicing defensive medicine.
We contribute to the foundations of tropical geometry with a view toward formulating tropical moduli problems, and with the moduli space of curves as our main example. We propose a moduli functor for the moduli space of curves and show that it is representable by a geometric stack over the category of rational polyhedral cones. In this framework, the natural forgetful morphisms between moduli spaces of curves with marked points function as universal curves.
Our approach to tropical geometry permits tropical moduli problems—moduli of curves or otherwise—to be extended to logarithmic schemes. We use this to construct a smooth tropicalization morphism from the moduli space of algebraic curves to the moduli space of tropical curves, and we show that this morphism commutes with all of the tautological morphisms.
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
The present paper aims at providing empirical evidence for dialectal variation concerning the perception of the central vowel [ɐ] in European Portuguese (EP). More concretely, this study compares the perception of the contrast between [a] and [ɐ] by native speakers of two varieties of EP: 23 speakers of a northern Portuguese dialect (from the city of Braga) and 23 speakers of the Littoral Center variety of EP (from the city of Lisbon, defined as Standard European Portuguese (SEP)). Based on a discrimination test, the results show that the two groups of speakers differ with respect to the perception of the contrast between the two central vowels under investigation. The speakers of the northern variety differentiate less between the two central vowels compared to the speakers from Lisbon.
Zoos attract millions of visitors every year, many of whom are schoolchildren. For this reason, zoos are important institutions for the environmental education of future generations. Empirical studies on the educational impact of environmental education programs in zoos are still rare. To address this issue, we conducted two studies: In study 1, we investigated students’ interests in different biological topics, including zoos (n = 1,587). Data analysis of individual topics revealed large differences of interest, with advanced students showing less interest in zoos. In study 2, we invited school classes of this age group to visit different guided tours at the zoo and tested connection to nature before and after each educational intervention (n = 608). The results showed that the guided tours are an effective tool to raise students’ connection to nature. Add-on components have the potential to further promote connection to nature. The education programs are most effective with students with a low initial nature connection.
Historic amphibian settlements in the northwestern Nile delta - a geoarchaeological perspective
(2020)
No concise picture of the archaeological and palaeoecological evolution can be drawn for the northwestern Nile delta, and archaeological records show significant population dynamics that still need explanation and spur the need for further palaeoenvironmental research. This study delivers a set of new methods especially in the fields of remote sensing and data analytics that can be regarded as important milestones and foundations for further palaeoenvironmental research in the area. Additionally, it shows new insights for individual time slices.
This geoarchaeological project is a cooperation with the archaeological excavations of the German Archaeological Institute (DAI) in Buto and Kom el’Gir. It expands the work of Wunderlich (1989) which laid important foundations in understanding the origin of the initial landscape that was later colonized in different cultural stages showing different dynamics, settlement intensities and even long phases of abandonment or breaks in between. This forms the starting point for relating the population dynamics of the different cultural phases reaching from Predynastic (prior to 3150 before Christ) up to the Greco-Roman era (~anno Domini 650) to the environmental history and events that occurred in the area. It is very likely that environmental changes such as the shifting of major water routes, inundation or paludification of larger areas or other environmental events affected settlements and human life in the area.
In the fields of remote sensing new methods are presented to complete information on the location of ancient settlements, and complex workflows are developed that allow the tracing of subsurface structures via indirect analysis of vegetation growth in larger time series data. It was verified that a relationship exists between vegetation performance, the appearance of archaeologic material in the topsoil, and the location of former Nile river branches.
Together with a new high resolution digital elevation model (DEM) based on TanDEM-X data, new interpretations with a high spatial significance are possible. For individual time slices, namely the Late Dynastic and Greco-Roman era, this work delivers a detailed landscape description suggesting a finely ramified subdelta, with all settlements placed on alluvial levees. This explains the massive increase in settlements in the Ptolemaic, Roman and in particular late Roman periods (4th century before Christ – anno Domini 7th century).
We sampled the Nile delta clays together with the channels and the material of the archaeologic excavations in vibracores and profile walls. This geologic inspection of the subsurface together with geochemical results from a handheld portable X-ray fluorescence device (pXRF) allowed new interpretations of the landscape and environmental history. For example, we used geochemical data to distinguish between artificial and natural channels as a measure for the anthropogenic influence, a proxy for past environmental characteristics and lastly as a basis for a new dating method. Many of the channels, for instance, were dated by our own 14C datings, comparisons with the previous work ofWunderlich (1989) and application of new dating approach based on machine learning with artificial neural networks. Additionally, we run a full methodological approach, and examine the applicability of pXRF methods in general, and test the quality of the data to detect distinct geochemical differences between the main settlement phases with advanced methods in data analytics. The dating is based, for example, on the training of artificial neural networks with pXRF data from archaeological material of well-dated context to date test data of cultural layers within the vibracores. With this method the homogeneous Nile alluvium, cultural layers and channels can be dated roughly and, as a result, fundamental changes in the landscape can be linked with the settlement history of Buto and neighboring tells.
This thesis discusses important questions of the beam dynamics in the proton-lead operation in the Large Hadron Collider (LHC) at CERN in Geneva. In two time blocks of several weeks in the years 2013 and 2016, proton-lead collisions have so far been successfully generated in the LHC and used by the experiments at the LHC. One reason for doubts regarding the successful operation in proton-lead configuration was the fact that the beams have to be accelerated with different revolution frequencies. There is long-range repulsion between the beams, since both beams share the beam chamber around the interaction points. Because of the different revolution frequencies, the positions of the interaction between the beams shift each revolution. This can lead to resonant excitation and to an increase in the transverse beam emittance, as was observed in the Relativistic Heavy-Ion Collider (RHIC). In this thesis, simulations for the LHC, RHIC and the High-Luminosity Large Hadron Collider (HL-LHC) are performed with a new model. The results for RHIC show relative growth rates of the emittances of the gold beam in gold-deuteron operation in RHIC from 0.1 %/s to 1.5 %/s. Growth rates of this magnitude were observed experimentally in RHIC. Simulations for the LHC show no significant increase of the emittance of the lead beam for different intensities of the counter-rotating beam. The simulation results confirm the measured stability of the beams in the LHC and the issue of strongly increasing emittances in RHIC is reproduced. Also, no significant increase of the emittance is predicted for the Future Circular Collider (FCC) and the HL-LHC.
Using a frequency-map analysis, this work verifies whether the interaction of the lead beam with the much smaller proton beam in the proton-lead operation of the LHC leads to diffusion within the lead beam. Experiences at HERA at DESY in Hamburg and at SppS at CERN have shown that the lifetime of the larger beam can rapidly decrease under certain circumstances. The results of the simulation show no chaotic dynamics near the beam centre of the lead beam. This result is supported by experimental observation.
A program code has been developed which calculates the beam evolution in the LHC by means of coupled differential equations. This study shows that the growth rates of the lead beam due to intra-beam scattering is overestimated and that particle bunches of the lead beam lose more intensity than assumed in the model. The analysis also shows that bunches colliding in a detector suffer additional losses that increase with decreasing crossing angle at the interaction point.
In this work, 2016 data from beam-loss monitors in combination with the luminosity and the loss rate of the beam intensity are used to determine the cross section of proton-lead collisions at the center-of-mass energy of 8.16 TeV. Beam-loss monitors that mainly detect beam losses that are not caused by the collision process itself are used to determine the total cross section via regression. An analysis of the data recorded in 2016 at the center-of-mass energy of 8.16 TeV resulted in a total cross section of σ=(2.32±0.01(stat.)±0.20(sys.)) b. This corresponds approximately to a hadronic cross section of σ(had)=(2.24±0.01(stat.)±0.21(sys.)) b. This value deviates only by 5.7 % from the theoretical value σ(had)=(2.12±0.01) b.
The simulation code for determining the beam evolution is also used to estimate the integrated luminosity of a future one-month run with proton-lead collisions. The result of the study shows that in the future the luminosity in the ATLAS and CMS experiments will increase from 15/nb per day in 2016 to 30/nb per day, which is a significant increase in terms of the performance. This operation, however, requires the use of the TCL collimators to protect the dispersion suppressors at ATLAS and CMS from collision fragments.
This work also gives an outlook on the expected luminosity production in proton-nucleus operation using ion species lighter than lead ions. For example, a change from proton-lead to proton-argon collisions would increase the integrated luminosity from monthly 0.8/nb to 9.4/nb in ATLAS and CMS. This is an increase of one order of magnitude and approximately a doubling of the integrated nucleon-nucleon luminosity. There may be a test operation with proton-oxygen collisions in 2023, which will last only a few days and will be operated with a low luminosity. The LHCf experiment (LHCb experiment) would achieve the desired integrated luminosity of 1.5/nb (2/nb) within 70h (35h) beam time.
The events of 1968/69 initiated a dispute between Adorno and Marcuse over the (alleged) separation of theory and praxis. While Marcuse “stood at the barricades” Adorno sought recluse in the “ivory tower”. Marcuse and German students perceived Adorno’s move as departure from fundamental postulates of critical theory as laid down in Horkheimer’s 1937 essay. Adorno died amidst the process of clarifying his differences with Marcuse and thus the “unlimited discussions” between the two remain unfinished. This paper sets to examine how both Marcuse and Adorno remained dedicated to the unity of theory and praxis, albeit in different ways. I argue that Adorno did not separate theory and praxis; instead, he perceived the gap between critical theory and concrete historical situation. Adorno rejected simple and unreflective translation of theory into praxis. Hence his attempt to recalibrate critical theory. Marcuse’s and Adorno’s differences lie in their different evaluation of the student movement and this (mis)evaluation was context related. My second argument is that Marcuse/Adorno disagreement is partly caused by the absence of the two from the concrete historical context.
In this review, we focus on the ubiquitination process within the endoplasmic reticulum associated protein degradation (ERAD) pathway. Approximately one third of all synthesized proteins in a cell are channeled into the endoplasmic reticulum (ER) lumen or are incorporated into the ER membrane. Since all newly synthesized proteins enter the ER in an unfolded manner, folding must occur within the ER lumen or co-translationally, rendering misfolding events a serious threat. To prevent the accumulation of misfolded protein in the ER, proteins that fail the quality control undergo retrotranslocation into the cytosol where they proceed with ubiquitination and degradation. The wide variety of misfolded targets requires on the one hand a promiscuity of the ubiquitination process and on the other hand a fast and highly processive mechanism. We present the various ERAD components involved in the ubiquitination process including the different E2 conjugating enzymes, E3 ligases, and E4 factors. The resulting K48-linked and K11-linked ubiquitin chains do not only represent a signal for degradation by the proteasome but are also recognized by the AAA+ ATPase Cdc48 and get in the process of retrotranslocation modified by enzymes bound to Cdc48. Lastly we discuss the conformations adopted in particular by K48-linked ubiquitin chains and their importance for degradation.
Brain aging is one of the major risk factors for the development of several neurodegenerative diseases. Therefore, mitochondrial dysfunction plays an important role in processes of both, brain aging and neurodegeneration. Aged mice including NMRI mice are established model organisms to study physiological and molecular mechanisms of brain aging. However, longitudinal data evaluated in one cohort are rare but are important to understand the aging process of the brain throughout life, especially since pathological changes early in life might pave the way to neurodegeneration in advanced age. To assess the longitudinal course of brain aging, we used a cohort of female NMRI mice and measured brain mitochondrial function, cognitive performance, and molecular markers every 6 months until mice reached the age of 24 months. Furthermore, we measured citrate synthase activity and respiration of isolated brain mitochondria. Mice at the age of three months served as young controls. At six months of age, mitochondria-related genes (complex IV, creb-1, β-AMPK, and Tfam) were significantly elevated. Brain ATP levels were significantly reduced at an age of 18 months while mitochondria respiration was already reduced in middle-aged mice which is in accordance with the monitored impairments in cognitive tests. mRNA expression of genes involved in mitochondrial biogenesis (cAMP response element-binding protein 1 (creb-1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), nuclear respiratory factor-1 (Nrf-1), mitochondrial transcription factor A (Tfam), growth-associated protein 43 (GAP43), and synaptophysin 1 (SYP1)) and the antioxidative defense system (catalase (Cat) and superoxide dismutase 2 (SOD2)) was measured and showed significantly decreased expression patterns in the brain starting at an age of 18 months. BDNF expression reached, a maximum after 6 months. On the basis of longitudinal data, our results demonstrate a close connection between the age-related decline of cognitive performance, energy metabolism, and mitochondrial biogenesis during the physiological brain aging process.
The National Institutes of Health Stroke Scale (NIHSS) score is the most frequently used score worldwide for assessing the clinical severity of a stroke. Prior research suggested an association between acute symptomatic seizures after stroke and poorer outcome. We determined the frequency of acute seizures after ischemic stroke in a large population-based registry in a central European region between 2004 and 2016 and identified risk factors for acute seizures in univariate and multivariate analyses. Additionally, we determined the influence of seizures on morbidity and mortality in a matched case–control design. Our analysis of 135,117 cases demonstrated a seizure frequency of 1.3%. Seizure risk was 0.6% with an NIHSS score at admission <3 points and increased up to 7.0% with >31 score points. Seizure risk was significantly higher in the presence of acute non-neurological infections (odds ratio: 3.4; 95% confidence interval: 2.8–4.1). A lower premorbid functional level also significantly increased seizure risk (OR: 1.7; 95%CI: 1.4–2.0). Mortality in patients with acute symptomatic seizures was almost doubled when compared to controls matched for age, gender, and stroke severity. Acute symptomatic seizures increase morbidity and mortality in ischemic stroke. Their odds increase with a higher NIHSS score at admission.
As women's labor-force participation and earnings have grown, so has the likelihood that wives outearn their husbands. A common concern is that these couples may be at heightened risk of divorce. Yet with the rise of egalitarian marriage, wives' relative earnings may be more weakly associated with divorce than in the past. We examine trends in the association between wives' relative earnings and marital dissolution using data from the 1968–2009 Panel Study of Income Dynamics. We find that wives' relative earnings were positively associated with the risk of divorce among couples married in the late 1960s and 1970s, and that this was especially true for wives who outearned their husbands, but this was no longer the case for couples married in the 1990s. Change was concentrated among middle-earning husbands and those without college degrees, a finding consistent with the economic squeeze of the middle class over this period.
Background/Objectives: Sharing the bed with a partner is common among adults and impacts sleep quality with potential implications for mental health. However, hitherto findings are contradictory and particularly polysomnographic data on co-sleeping couples are extremely rare. The present study aimed to investigate the effects of a bed partner's presence on individual and dyadic sleep neurophysiology.
Methods: Young healthy heterosexual couples underwent sleep-lab-based polysomnography of two sleeping arrangements: individual sleep and co-sleep. Individual and dyadic sleep parameters (i.e., synchronization of sleep stages) were collected. The latter were assessed using cross-recurrence quantification analysis. Additionally, subjective sleep quality, relationship characteristics, and chronotype were monitored. Data were analyzed comparing co-sleep vs. individual sleep. Interaction effects of the sleeping arrangement with gender, chronotype, or relationship characteristics were moreover tested.
Results: As compared to sleeping individually, co-sleeping was associated with about 10% more REM sleep, less fragmented REM sleep (p = 0.008), longer undisturbed REM fragments (p = 0.0006), and more limb movements (p = 0.007). None of the other sleep stages was significantly altered. Social support interacted with sleeping arrangement in a way that individuals with suboptimal social support showed the biggest impact of the sleeping arrangement on REM sleep. Sleep architectures were more synchronized between partners during co-sleep (p = 0.005) even if wake phases were excluded (p = 0.022). Moreover, sleep architectures are significantly coupled across a lag of ± 5min. Depth of relationship represented an additional significant main effect regarding synchronization, reflecting a positive association between the two. Neither REM sleep nor synchronization was influenced by gender, chronotype, or other relationship characteristics.
Conclusion: Depending on the sleeping arrangement, couple's sleep architecture and synchronization show alterations that are modified by relationship characteristics. We discuss that these alterations could be part of a self-enhancing feedback loop of REM sleep and sociality and a mechanism through which sociality prevents mental illness.
Limbic encephalitis (LE) is an autoimmune syndrome often associated with temporal lobe epilepsy. Recent research suggests that particular structural changes in LE depend on the type of the associated antibody and occur in both mesiotemporal gray matter and white matter regions. However, it remains questionable to what degree conventional diffusion tensor imaging (DTI)-methods reflect alterations in white matter microstructure, since these methods do not account for crossing fibers. To address this methodological shortcoming, we applied fixel-based analysis as a novel technique modeling distinct fiber populations. For our study, 19 patients with LE associated with autoantibodies against glutamic acid decarboxylase 65 (GAD-LE, mean age = 35.9 years, 11 females), 4 patients with LE associated with autoantibodies against leucine-rich glioma-inactivated 1 (LGI1-LE, mean age = 63.3 years, 2 females), 5 patients with LE associated with contactin-associated protein-like 2 (CASPR2, mean age = 57.4, 0 females), 20 age- and gender-matched control patients with hippocampal sclerosis (19 GAD-LE control patients: mean age = 35.1 years, 11 females; 4 LGI1-LE control patients: mean age = 52.6 years, 2 females; 5 CASPR2-LE control patients: mean age = 42.7 years, 0 females; 10 patients are included in more than one group) and 33 age- and gender-matched healthy control subjects (19 GAD-LE healthy controls: mean age = 34.6 years, 11 females; 8 LGI1-LE healthy controls: mean age = 57.0 years, 4 females, 10 CASPR2-LE healthy controls: mean age = 57.2 years, 0 females; 4 subjects are included in more than one group) underwent structural imaging and DTI at 3 T and neuropsychological testing. Patient images were oriented according to lateralization in EEG resulting in an affected and unaffected hemisphere. Fixel-based metrics fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC = FD · FC) were calculated to retrieve information about white matter integrity both on the micro- and the macroscale. As compared to healthy controls, patients with GAD-LE showed significantly (family-wise error-corrected, p < 0.05) lower FDC in the superior longitudinal fascicle bilaterally and in the isthmus of the corpus callosum. In CASPR2-LE, lower FDC in the superior longitudinal fascicle was only present in the affected hemisphere. In LGI1-LE, we did not find any white matter alteration of the superior longitudinal fascicle. In an explorative tract-based correlation analysis within the GAD-LE group, only a correlation between the left/right ratio of FC values of the superior longitudinal fascicle and verbal memory performance (R = 0.64, Holm-Bonferroni corrected p < 0.048) remained significant after correcting for multiple comparisons. Our results underscore the concept of LE as a disease comprising a broad and heterogeneous group of entities and contribute novel aspects to the pathomechanistic understanding of this disease that may strengthen the role of MRI in the diagnosis of LE.
Advertising arbitrage
(2020)
Arbitrageurs with a short investment horizon gain from accelerating price discovery by advertising their private information. However, advertising many assets may overload investors' attention, reducing the number of informed traders per asset and slowing price discovery. So arbitrageurs optimally concentrate advertising on just a few assets, which they overweight in their portfolios. Unlike classic insiders, advertisers prefer assets with the least noise trading. If several arbitrageurs share information about the same assets, inefficient equilibria can arise, where investors' attention is overloaded and substantial mispricing persists. When they do not share, the overloading of investors' attention is maximal.
In fifteen European countries, China, and the US, stocks and business equity as a share of total household assets are represented by an increasing and convex function of income/wealth. A parsimonious model fitted to the data shows why background labor- income risk can explain much of this risk-taking pattern. Uncontrollable labor-income risk stresses middle-income households more because labor income is a larger fraction of their total lifetime resources compared with the rich. In response, middle-income households re-duce (controllable) financial risk. Richer households, having less pressure, can afford more risk-taking. The poor take low risk because they avoid jeopardizing their subsistence consumption.
The conspicuous Mediterranean brittle star Ophioderma longicauda (Bruzelius, 1805) has been discovered to represent a cryptic species complex, consisting of six nuclear clusters with contrasting reproductive modes (broadcast spawners and brooders). Here, O. longicauda is re-described. It is distinguished by a dark reddish-brown colouration both dorsally and on the ventral disc, and multiple tumid dorsal arm plates. One eastern Mediterranean brooding cluster is described as O. zibrowii sp. nov., characterized by a dark olive-green colour both dorsally and on the ventral disc, and single dorsal arm plates. Another brooder is described from Tunisia as O. hybrida sp. nov., with a highly variable morphology that reflects its origin by hybridization of O. longicauda and a brooder (possibly O. zibrowii sp. nov.), leaving the third brooding cluster as morphologically indistinguishable at this point and possibly conspecific with one of the others. The West-African O. guineense Greef, 1882 is resurrected as a valid species, differing morphologically from O. longicauda by predominantly single dorsal arm plates and light green or creamy white ventral side. Also from West Africa, O. africana sp. nov. is described, characterized by a dark brown colour, dorsally and ventrally, and single dorsal arm plates.
Eight new species of Ecuadorian Ptiliidae are described and figured: Nossidium harrietae sp. nov., Ptenidium robustum sp. nov., P. tauriforme sp. nov., P. triangulum sp. nov., Notoptenidium brunneum sp. nov., Americoptilium nigrescens sp. nov., Discheramocephalus nigerrimus sp. nov. and D. striatus sp. nov. The insects were collected by J. McClarin, 2017–2018, in the Napo Province to the southeast of the capital Quito.
The innate immune system is the first line of host defense that senses invading pathogens by various surveillance mechanisms, involving pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs). Furthermore, in response to stress, tissue injury or ischemia, cells release endogenous danger-associated molecular patterns (DAMPs) which activate PRRs in order to prompt an effective immune response. Activation of PRRs by DAMPs initiates signaling transduction pathways which drive sterile inflammation by the production of pro-inflammatory effector molecules. Biglycan, a class I small leucine-rich proteoglycan (SLRP), is proteolytically released from the extracellular matrix (ECM) in response to tissue stress and injury or de novo synthesized by activated macrophages. In its soluble form, biglycan operates as an ECM-derived DAMP and triggers a potent inflammatory response by engaging TLR2 and TLR4 on immune cells. By selective utilization of TLR2/4 and the TLR adaptor molecules adaptor molecule myeloid differentiation primary response gene 88 (MyD88) or TIR domain-containing adaptor-inducing interferon-β (TRIF) biglycan differentially regulates the production of TLR downstream mediators or inflammatory molecules. In this way, biglycan triggers the activation of mitogen-activated protein kinase (MAPK) p38, extracellular signal-regulated kinase (Erk) and nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) in a primarily MyD88-dependent manner. In contrast, biglycan induces the expression of (C–C motif) ligand (CCL)5 and chemokine (C-X-C motif) ligand (CXCL)10 over TLR4/TRIF, heat shock protein 70 (HSP70) production over TLR2 and the synthesis of tumor necrosis factor (TNF)-α, CCL2 and CCL20 by utilizing TLR2/4/MyD88. As a consequence, biglycan promotes the recruitment of immune cells such as neutrophils, T cells, B cells and macrophages into the inflamed tissue. Research over the past years showed that biglycan-induced inflammation is involved in the pathogenesis of various inflammatory diseases such as lupus nephritis (LN), sepsis and renal ischemia/reperfusion injury (IRI), whereby genetic deletion of biglycan or TLR2/4 alleviated disease outcome. Unfortunately, the selective interaction of biglycan to TLRs and TLR adaptors complicates the identification of an efficient pharmacological target in biglycan-mediated inflammation. Yet, the necessity of possible co-receptors in biglycan signaling such as cluster of differentiation 14 (CD14) which was found in a high molecular complex with biglycan was not addressed so far.
In the first part of the present study, by utilizing primary peritoneal murine macrophages we demonstrated that the biglycan-induced expression and synthesis of TNF-α and CCL2 via TLR2/4/MyD88, CCL5 through TLR4/TRIF and HSP70 over TLR2 is blunted in CD14 deficient mice, proving that CD14 is essential in TLR2- and TLR4-mediated biglycan signaling. Pre-incubation of macrophages with an anti-CD14 antibody significantly reduced the protein levels of TNF-α, CCL2, CCL5 and HSP70. In line with these data, pharmacological inhibition of CD14 alleviated the transcriptional activation of NF-κB by biglycan in HEK-Blue cells expressing hTLR2/CD14 as well as hTLR4/CD14/MD2 supporting CD14-dependency for biglycan/TLR2/4 signaling. Western blot analysis of phosphorylated p38, p44/42 and NF-κB in WT and CD14 deficient mice revealed that activation of biglycan-mediated TLR downstream signaling is CD14-dependent. Accordingly, biglycan-induced activation and nuclear translocation of p38, p44/42 and NF-κB was blocked in Cd14-/- mice as analyzed by confocal microscopy. Co-immunoprecipitation studies combined with microscale thermophoresis analysis showed that biglycan is in complex with CD14 in macrophages and in vitro binds directly with high affinity to CD14, thereby sustaining the concept that CD14 is a novel co-receptor in biglycan-mediated inflammation. Additionally, we provided proof-of-principle of our concept in an in vivo mouse model of renal IRI. Transient overexpression of biglycan in WT mice exacerbated the expression and production of TNF-α, CCL2, CCL5 and HSP70 in a CD14-dependent manner. Interestingly, pLIVE or pLIVE-hBGN-injected Cd14-/- mice displayed lower chemo- and cytokine levels in reperfused kidneys as compared to respective WT controls during renal IRI (30 h), indicating a renoprotective effect by CD14 deficiency. Flow cytometry analysis of kidney homogenates underlined the pivotal effect of CD14 in biglycan signaling as biglycan-mediated infiltration of CD11b- and F4/80-positive renal macrophages was abolished in Cd14-/- mice. Additionally, pLIVE or pLIVE-hBGN-injected CD14 deficient mice displayed lower numbers of renal CD11b- and F4/80-positive cells during renal IRI compared to WT mice. Analysis of F4/80- and CD38-positive cells isolated from mononuclear cell extracts from kidney homogenates of pLIVE or pLIVE-hBGN-injected WT and Cd14-/- mice revealed that biglycan triggers the polarization of pro-inflammatory M1 macrophages in a CD14-dependent manner. In line with this, Cd14-/- mice, either injected with pLIVE or pLIVE-hBGN, showed less F4/80- and CD38-positive cells during renal IRI than the respective WT control. As a corroboration of our data PAS-stained renal sections of pLIVE- or pLIVE-hBGN-injected WT or Cd14-/- mice uncovered that biglycan worsens tubular damage in IRI-subjected mice via CD14. At the same time, tubular damage was significantly reduced in IRI-subjected Cd14-/- mice as compared to WT mice. In correlation with these data, serum creatine levels were increased in pLIVE-hBGN-injected WT mice during renal IRI. In contrast, serum creatine levels were significantly less increased in pLIVE- or pLIVE-hBGN-injected Cd14-/- mice than in WT littermate controls. In conclusion we demonstrated that CD14 is a new high affinity ligand for biglycan-mediated pro-inflammatory signaling over TLR2 and TLR4 in macrophages. In vivo, soluble biglycan triggers the expression of various inflammatory mediators by utilizing the co-receptor CD14. Ablation of CD14 abolishes biglycan-induced renal macrophage infiltration and M1 macrophage polarization as well as overall kidney function by reduced tubular damage and serum creatinine levels. Therefore, this study identifies CD14 as a promising therapeutic target to ameliorate biglycan-induced inflammation.
...
A new species of praying mantis, Vates phoenix sp. nov. (Mantidae, Vatinae), is described from localities within Rio de Janeiro and São Paulo states, Brazil. This is the first record of Vates from the Atlantic Rainforest biome. The new species is unique among its congeners in having, among other features, strongly reduced cuticular projections above the lateral ocelli, structures otherwise well developed and produced in all other species of Vates. Remarks on the natural history and biogeography of Vates, in relation to this new finding, are further discussed.
Amphipod material collected from Brazil on Ilha do Arvoredo, (Santa Catarina), Campos Basin, (Rio de Janeiro) and Espírito Santo Basin (Espírito Santo) in the southwestern Atlantic Ocean yielded new taxonomic findings for the subfamily Phtisicinae Vassilenko, 1968. Hemiproto wigleyi McCain, 1968, previously recorded from the Gulf of Mexico to the Caribbean Sea, is herein redescribed and recorded for the first time from the Brazilian coast. The type material of Phtisica verae Quitete, 1979, a poorly described species recorded from Brazil and based only on its original description, was examined and considered herein as a junior synonym of P. marina Slabber, 1769, a well-known and widely distributed species from the Atlantic Ocean and the Mediterranean Sea. In this paper, Phtisica marina is redescribed, with its two morphotypes of male gnathopod two, and compared with previous descriptions. The geographic distribution of both H. wigleyi and P. marina is provided.
The taxa Cubicostissus palaeocaeni gen. et sp. nov. are described from the Paleocene of Menat (Central France) as the oldest representative of the family Issidae for which all currently known fossils are reviewed. With a unique combination of characters, the specimen represents the first fossil described for the tribe Hysteropterini. Its occurrence in the European Paleocene shows that its lineage, and therefore the Issidae, were already present at least some 60 Ma. It allows to discard the hypothesis of an Eocene origin for the family, which is in accordance with a recent molecular calibration of the family, reporting the tribe as old as the Upper Cretaceous.
During several sampling campaigns in the regions of Galicia and Andalusia in Spain and the Algarve region in Portugal, specimens of twelve species of schizorhynch rhabdocoels were collected. Four of these are new to science: three species of Proschizorhynchus (P. algarvensis sp. nov., P. arnautsae sp. nov. and P. troglodytus sp. nov.) and one species of Schizochilus (S. coninxae sp. nov.). The new species of Proschizorhynchus can be distinguished from their congeners by the curvature and length of their stylet, as well as the cirrus sheath and the organisation of the genital system. Schizochilus coninxae sp. nov. has a distinct two-part stylet that is unique within the genus. In addition to these new species, new data are reported for the diascorhynchid Diascorhynchus caligatus and the schizorhynchids Carcharodorhynchus multidentatus, C. tenuis, C. flavidus, Proschizorhynchus pectinatus and P. reniformis. Finally, new records for C. flavidus from the Hawaiian archipelago are presented.
Canthon (Peltecanthon) is revised in this work. The subgenus now includes four species: C. (P.) staigi (Pereira, 1953), C. (P.) haroldi nom. nov., C. (P.) splendidus Schmidt, 1922 and C. (P.) terciae sp. nov. All species occur in the Atlantic Forest. Maps, natural history information, specimen data and illustrations are provided.
The genus Rudolfina Roháček, 1987 is revised and redefined with the description of the following nine new species, all from the New World: R. bucki sp. nov. (Mexico), R. exuberata sp. nov. (widespread, from USA to Brazil), R. howdeni sp. nov. (Mexico), R. megepandria sp. nov. (Mexico), R. newtoni sp. nov. (Mexico), R. pauca sp. nov. (Guatemala, Mexico), R. pilosa sp. nov. (Mexico), R. remiforma sp. nov. (Mexico) and R. tumida sp. nov. (Mexico, USA). Rudolfina is compared to closely related genera in the Archiceroptera genus complex, which in turn is recognized as part of a large, mostly Neotropical clade including Robustagramma Marshall & Cui, 2005, Pterogramma Spuler, 1924, Aptilotella Duda, 1924, Bitheca Marshall, 1987, Bromeloecia Spuler, 1924 and Archiceroptera Papp, 1977.
This paper describes a novel species of the genus Heterophoxus Shoemaker, 1925 from Brazil. The material examined was collected during the Mini Biological Trawl Project, off southeast and southern Brazil's coast off the states of Rio de Janeiro, Santa Catarina, and Rio Grande do Sul, ranging in depth from 25 to 128 meters. The new species, H. shoemakeri sp. nov., is similar to H. videns K.H. Barnard, 1930; however, the former species can be distinguished by: pereopod 7 basis posterior margin serrate with acute teeth, merus posterior margin not produced; epimeral plate 3 posteroventral corner with a longer acute projection, posterior margin almost straight; uropod 3 outer ramus article 2 clearly notable in both sexes. For Brazilian waters, this is the second record of the genus and the first species described with type material from the country. Besides that, we provide an identification key for the world species of Heterophoxus and a distribution map for the new species.
Diplura is a group of entognathous hexapods, often considered a sister group to insects. They play an important role in recycling organic matter in soil and subterranean terrestrial ecosystems. The Campodeidae is the most diverse family, divided into four subfamilies. The subfamily Plusiocampinae has a subterranean life-style with many species distributed in the Euro-Mediterranean area. The incertae sedis tachycampoids ("lignée Tachycampoïde") is a group within the family Campodeidae that share with the Plusiocampinae a strong preference for subterranean habitats and several morphological characters, such as slender body shape, elongated appendages, considerable increment in the number of antennomeres and cercal articles, and complexity of sensorial structures. The present monograph provides a taxonomic revision of the subfamily Plusiocampinae and the genera belonging to the tachycampoid lineage from Europe and the Mediterranean region. It comprises detailed morphological descriptions and illustrations together with data on the habitats and distributions of 87 species, 10 subspecies and 11 affinis forms. Seven new species are described among those, namely: Plusiocampa (Plusiocampa) apollo Sendra, Giachino & Vailati sp. nov., P. (P.) chiosensis Sendra & Gasparo sp. nov., P. (P.) dublanskii Sendra & Turbanov sp. nov., P. (P.) hoffmanni Sendra & Paragamian sp. nov., P. (P.) rhea Sendra sp. nov., P. (P.) ternovensis Sendra & Borko sp. nov. and P. (Venetocampa) ferrani Sendra & Delić sp. nov.
Gliflozins are inhibitors of the renal proximal tubular sodium-glucose co-transporter-2 (SGLT-2), that inhibit reabsorption of urinary glucose and they are able to reduce hyperglycemia in patients with type 2 diabetes. A renoprotective function of gliflozins has been proven in diabetic nephropathy, but harmful side effects on the kidney have also been described. In the current project, primary highly purified human renal proximal tubular epithelial cells (PTCs) have been shown to express functional SGLT-2, and were used as an in vitro model to study possible cellular damage induced by two therapeutically used gliflozins: empagliflozin and dapagliflozin. Cell viability, proliferation, and cytotoxicity assays revealed that neither empagliflozin nor dapagliflozin induce effects in PTCs cultured in a hyperglycemic environment, or in co-medication with ramipril or hydro-chloro-thiazide. Oxidative stress was significantly lowered by dapagliflozin but not by empagliflozin. No effect of either inhibitor could be detected on mRNA and protein expression of the pro-inflammatory cytokine interleukin-6 and the renal injury markers KIM-1 and NGAL. In conclusion, empa- and dapagliflozin in therapeutic concentrations were shown to induce no direct cell injury in cultured primary renal PTCs in hyperglycemic conditions.
In higher concentrations, the blood pressure regulating hormone angiotensin II leads to vasoconstriction, hypertension, and oxidative stress by activating NADPH oxidases which are a major enzymatic source of reactive oxygen species (ROS). With the help of knockout animals, the impact of the three predominant NADPH oxidases present in the kidney, i.e., Nox1, Nox2 and Nox4 on angiotensin II-induced oxidative damage was studied. Male wildtype (WT) C57BL/6 mice, Nox1-, Nox2- and Nox4-deficient mice were equipped with osmotic minipumps, delivering either vehicle (PBS) or angiotensin II, for 28 days. Angiotensin II increased blood pressure and urinary albumin levels significantly in all treated mouse strains. In Nox1 knockout mice these increases were significantly lower than in WT, or Nox2 knockout mice. In WT mice, angiotensin II also raised systemic oxidative stress, ROS formation and DNA lesions in the kidney. A local significantly increased ROS production was also found in Nox2 and Nox4 knockout mice but not in Nox1 knockout mice who further had significantly lower systemic oxidative stress and DNA damage than WT animals. Nox2 and Nox4 knockout mice had increased basal DNA damage, concealing possible angiotensin II-induced increases. In conclusion, in the kidney, Nox1 seemed to play a role in angiotensin II-induced DNA damage.
The specific temporal evolution of bacterial and phage population sizes, in particular bacterial depletion and the emergence of a resistant bacterial population, can be seen as a kinetic fingerprint that depends on the manifold interactions of the specific phage–host pair during the course of infection. We have elaborated such a kinetic fingerprint for a human urinary tract Klebsiella pneumoniae isolate and its phage vB_KpnP_Lessing by a modeling approach based on data from in vitro co-culture. We found a faster depletion of the initially sensitive bacterial population than expected from simple mass action kinetics. A possible explanation for the rapid decline of the bacterial population is a synergistic interaction of phages which can be a favorable feature for phage therapies. In addition to this interaction characteristic, analysis of the kinetic fingerprint of this bacteria and phage combination revealed several relevant aspects of their population dynamics: A reduction of the bacterial concentration can be achieved only at high multiplicity of infection whereas bacterial extinction is hardly accomplished. Furthermore the binding affinity of the phage to bacteria is identified as one of the most crucial parameters for the reduction of the bacterial population size. Thus, kinetic fingerprinting can be used to infer phage–host interactions and to explore emergent dynamics which facilitates a rational design of phage therapies.
Background: Ataxia telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition and altered body composition. In addition, evidence is rising for endocrine dysfunction.
Objectives: To determine the evolution of diabetes and its prevalence in a larger A-T cohort.
Methods: A retrospective analysis of the patient charts of 39 subjects from the Frankfurt A-T cohort was performed between August 2002 and 2018 concerning HbA1c and oral glucose tolerance (OGTT). The median follow-up period was 4 years (1–16 years). In addition, in 31 A-T patients aged 1 to 38 years HbA1c and fasting glucose were studied prospectively from 2018 to 2019.
Results: In the retrospective analysis, we could demonstrate a longitudinal increase of HbA1c. The prospective analysis showed a significant increase of HbA1c and fasting glucose with age (r = 0.79, p ≤ 0.0001). OGTT has a good sensitivity for insulin resistance screening, whereas HbA1c can be used to evaluate individual courses and therapy response. Seven out of 39 (17.9%) patients suffered from diabetes. Metformin did not always lead to sufficient diabetes control; one patient was treated successfully with repaglinide.
Conclusion: Diabetes is a common finding in older A-T patients and often starts in puberty. Our data clearly demonstrate the need for an annual diabetes screening in patients > 12 years.
Background: The newly introduced German pediatric screening examination at the end of the third year of life (U7a) incorporates visual function testing in particular; there is no ophthalmic screening during childhood in Germany. The purpose of this study is to investigate the relationship between participation in U7a and visual function at the preschool health examination (PHE) in the sixth year of life. Methods: This study evaluated PHE data from school enrollment years 2009/2010 to 2014/2015 of Rhineland-Palatinate, Germany. Visual acuity (VA) at PHE was assessed with Rodenstock visual acuity test device (tumbling E) wearing glasses if present. The relationship between participation in U7a and VA <0.7 at PHE was calculated for reduced monocular and binocular VA using multiple logistic regression adjusted for potential confounders. Results: Data from 189,704 children (91,041 girls) in 35 out of 36 districts were included. The first children to participate in U7a were enrolled in 2011/2012 school year. In total, 90,339 children (47.6%) had U7a before PHE, while 99,365 (52.4%) had not. VA <0.7 in at least one eye was measured at PHE in 8429 (4.4%) children, and in both eyes in 4345 (2.3%) children. Participation in U7a was not associated with VA <0.7 at PHE (odds ratio 0.99; 95% confidence interval: 0.94–1.04). Conclusions: The proportion of children with VA <0.7 at PHE was high. No beneficial effect of newly introduced German U7a pediatric screening examination was found for reduced VA at PHE.
Background: Children who are frequently aggressive or lack empathy show various deficits in their social information processing. Several findings suggest that children with conduct problems (CP) show a tendency to interpret ambiguous situations as hostile (hostile attribution bias) and have difficulties to disengage from negative stimuli (attentional bias). The role that additional callous-unemotional traits (CU-traits) play in these biases is yet unclear. Investigating both attentional and attributional aspects of social information processing in children can help us to understand where anomalies in the processing pathway occur and whether the biases are associated with CP and CU-traits separately or in an interactive manner.
Methods: We compared three groups of children: (a) 25 children with CP and low levels of CU-traits (b) 25 children with CP and elevated levels of CU-traits (c) 50 gender (68% male), age (8–17 years) and intelligence score-matched typically developing children, on a pictorial emotional stroop task and a hostile attribution bias task.
Results: In contrast to our predictions, there were no significant group differences regarding attentional biases or hostile attribution biases. Boys with CP and high levels of CU-traits showed a significantly higher hostile attribution bias compared to girls with CP and high levels of CU-traits. The attention bias to angry stimuli significantly correlated with the hostile attribution bias. Compared to the control group the CP group with low levels of CU-traits showed a significantly stronger association between the attention bias to angry stimuli and the hostile attribution bias.
Conclusions: The current study provides evidence that boys with CP and high levels of CU-traits interpret ambiguous situations as more hostile than girls do. Our results further provide indications that the interaction of attentional and attributional biases in children with CP might contribute to their increased aggressive behavior.
Making agriculture sustainable is a global challenge. In the European Union (EU), the Common Agricultural Policy (CAP) is failing with respect to biodiversity, climate, soil, land degradation as well as socio‐economic challenges.
The European Commission's proposal for a CAP post‐2020 provides a scope for enhanced sustainability. However, it also allows Member States to choose low‐ambition implementation pathways. It therefore remains essential to address citizens' demands for sustainable agriculture and rectify systemic weaknesses in the CAP, using the full breadth of available scientific evidence and knowledge.
Concerned about current attempts to dilute the environmental ambition of the future CAP, and the lack of concrete proposals for improving the CAP in the draft of the European Green Deal, we call on the European Parliament, Council and Commission to adopt 10 urgent action points for delivering sustainable food production, biodiversity conservation and climate mitigation.
Knowledge is available to help moving towards evidence‐based, sustainable European agriculture that can benefit people, nature and their joint futures.
The statements made in this article have the broad support of the scientific community, as expressed by above 3,600 signatories to the preprint version of this manuscript. The list can be found here (https://doi.org/10.5281/zenodo.3685632).
A free Plain Language Summary can be found within the Supporting Information of this article.
Mutations in the actively expressed, maternal allele of the imprinted KCNK9 gene cause Birk-Barel intellectual disability syndrome (BBIDS). Using a BBIDS mouse model, we identify here a partial rescue of the BBIDS-like behavioral and neuronal phenotypes mediated via residual expression from the paternal Kcnk9 (Kcnk9pat) allele. We further demonstrate that the second-generation HDAC inhibitor CI-994 induces enhanced expression from the paternally silenced Kcnk9 allele and leads to a full rescue of the behavioral phenotype suggesting CI-994 as a promising molecule for BBIDS therapy. Thus, these findings suggest a potential approach to improve cognitive dysfunction in a mouse model of an imprinting disorder.
This paper explores how refugee families in Germany draw on me-diational repertoires to accomplish a range of digital literacy prac-tices on their smartphones. We introduce the concept of ‘mediation-al repertoire’, i.e. a socially and individually structured configuration of semiotic and technological resources for communication, and use it in an ethnographic case study with participants from Syria and Af-ghanistan in a refugee residence in Hamburg in 2017/18. The collect-ed data includes nine semi-directed interviews, video demonstra-tions of smartphone usage, and ethnographic fieldnotes. Qualitative analysis draws on mediagrams, i.e. visualizations of mediational re-pertoires in two families. Findings suggest that individual mediation-al repertoires in these families differ especially by generation and other factors, such as literacy competence, type of social relation-ship and purpose of online use, including smartphone-based lang-uage-learning.
Inhibitor-kappaB kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) are non-canonical IκB kinases, both described as contributors to tumor growth and metastasis in different cancer types. Several hints indicate that they are also involved in the pathogenesis of melanoma; however, the impact of their inhibition as a potential therapeutic measure in this “difficult-to-treat” cancer type has not been investigated so far. We assessed IKKε and TBK1 expression in human malignant melanoma cells, primary tumors and the metastasis of melanoma patients. Both kinases were expressed in the primary tumor and in metastasis and showed a significant overexpression in tumor cells in comparison to melanocytes. The pharmacological inhibition of IKKε/TBK1 by the approved drug amlexanox reduced cell proliferation, migration and invasion. Amlexanox did not affect the cell cycle progression nor apoptosis induction but significantly suppressed autophagy in melanoma cells. The analysis of potential functional downstream targets revealed that NF-кB and ERK pathways might be involved in kinase-mediated effects. In an in vivo xenograft model in nude mice, amlexanox treatment significantly reduced tumor growth. In conclusion, amlexanox was able to suppress tumor progression potentially by the inhibition of autophagy as well as NF-кB and MAP kinase pathways and might therefore constitute a promising candidate for melanoma therapy.
The macrophage-inducible C-type lectin (mincle) is part of the innate immune system and acts as a pattern recognition receptor for pathogen-associated molecular patterns (PAMPS) and damage-associated molecular patterns (DAMPs). Ligand binding induces mincle activation which consequently interacts with the signaling adapter Fc receptor, SYK, and NF-kappa-B. There is also evidence that mincle expressed on macrophages promotes intestinal barrier integrity. However, little is known about the role of mincle in hepatic fibrosis, especially in more advanced disease stages. Mincle expression was measured in human liver samples from cirrhotic patients and donors collected at liver transplantation and in patients undergoing bariatric surgery. Human results were confirmed in rodent models of cirrhosis and acute-on-chronic liver failure (ACLF). In these models, the role of mincle was investigated in liver samples as well as in peripheral blood monocytes (PBMC), tissues from the kidney, spleen, small intestine, and heart. Additionally, mincle activation was stimulated in experimental non-alcoholic steatohepatitis (NASH) by treatment with mincle agonist trehalose-6,6-dibehenate (TDB). In human NASH, mincle is upregulated with increased collagen production. In ApoE deficient mice fed high-fat western diet (NASH model), mincle activation significantly increases hepatic collagen production. In human cirrhosis, mincle expression is also significantly upregulated. Furthermore, mincle expression is associated with the stage of chronic liver disease. This could be confirmed in rat models of cirrhosis and ACLF. ACLF was induced by LPS injection in cirrhotic rats. While mincle expression and downstream signaling via FC receptor gamma, SYK, and NF-kappa-B are upregulated in the liver, they are downregulated in PBMCs of these rats. Although mincle expressed on macrophages might be beneficial for intestinal barrier integrity, it seems to contribute to inflammation and fibrosis once the intestinal barrier becomes leaky in advanced stages of chronic liver disease.
Software updates are a critical success factor in mobile app ecosystems. Through publishing regular updates, platform providers enhance their operating systems for the benefit of both end users and third-party developers. It is also a way of attracting new customers. However, this platform evolution poses the risk of inadvertently introducing software problems, which can severely disturb the ecosystem’s balance by compromising its foundational technologies. So far, little to no research has addressed this issue from a user-centered perspective. The thesis at hand draws on IS post-adoption literature to investigate the potential negative influences of operating system updates on mobile app users. The release of Apple’s iOS 13 update serves as research object. Based on over half a million user reviews from the AppStore, data mining techniques are applied to study the impact of the new platform version. The results show that iOS 13 caused complications with a large number of popular apps, leading to a significant decline in user ratings and an uptrend in negative sentiment. Feature requests, functional complaints, and device compatibility are identified as the three major issue categories. These issue types are compared in terms of their quantifiable negative effect on users’ continuance intention. In essence, the findings contribute to IS research on post-adoption behavior and provide guidance to ecosystem participants in dealing with update-induced platform issues.
Cerebral lesions may cause degeneration and neuroplastic reorganization in both the ipsi- and the contralesional hemisphere, presumably creating an imbalance of primarily inhibitory interhemispheric influences produced via transcallosal pathways. The two hemispheres are thought to mutually hamper neuroplastic reorganization of the other hemisphere. The results of preceding degeneration and neuroplastic reorganization of white matter may be reflected by Diffusion Tensor Imaging-derived diffusivity parameters such as fractional anisotropy (FA). In this study, we applied Diffusion Tensor Imaging (DTI) to contrast the white matter status of the contralesional hemisphere of young lesioned brains with and without contralateral influences by comparing patients after hemispherotomy to those who had not undergone neurosurgery. DTI was applied to 43 healthy controls (26 females, mean age ± SD: 25.07 ± 11.33 years) and two groups of in total 51 epilepsy patients with comparable juvenile brain lesions (32 females, mean age ± SD: 25.69 ± 12.77 years) either after hemispherotomy (30 of 51 patients) or without neurosurgery (21 of 51 patients), respectively. FA values were compared between these groups using the unbiased tract-based spatial statistics approach. A voxel-wise ANCOVA controlling for age at scan yielded significant group differences in FA. A post hoc t-test between hemispherotomy patients and healthy controls revealed widespread supra-threshold voxels in the contralesional hemisphere of hemispherotomy patients indicating comparatively higher FA values (p < 0.05, FWE-corrected). The non-surgery group, in contrast, showed extensive supra-threshold voxels indicating lower FA values in the contralesional hemisphere as compared to healthy controls (p < 0.05, FWE-corrected). Whereas lower FA values are suggestive of pronounced contralesional degeneration in the non-surgery group, higher FA values in the hemispherotomy group may be interpreted as a result of preceding plastic remodeling. We conclude that, whether juvenile brain lesions are associated with contralesional degeneration or reorganization partly depends on the ipsilesional hemisphere. Contralesional reorganization as observed in hemispherotomy patients was most likely enabled by the complete neurosurgical deafferentation of the ipsilesional hemisphere and, thereby, the disinhibition of the neuroplastic potential of the contralesional hemisphere. The main argument of this study is that hemispherotomy may be seen as a major plastic stimulus and as a prerequisite for contralesional neuroplastic remodeling in patients with juvenile brain lesions.
Multicentre comparison of quantitative PCR-based assays to detect SARS-CoV-2, Germany, March 2020
(2020)
Containment strategies and clinical management of coronavirus disease (COVID-19) patients during the current pandemic depend on reliable diagnostic PCR assays for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we compare 11 different RT-PCR test systems used in seven diagnostic laboratories in Germany in March 2020. While most assays performed well, we identified detection problems in a commonly used assay that may have resulted in false-negative test results during the first weeks of the pandemic.
Chronic coronary artery disease remains an unconquered clinical problem, affecting an increasing number of people worldwide. Despite the improved understanding of the disease development, the implementation of the many advances in diagnosis and therapy is lacking. Many clinicians continue to rely on patient's symptoms and diagnostic methods, which do not enable optimal clinical decisions. For example, echocardiography and invasive coronary catheterisation remain the mainstay investigations for stable angina patients in many places, despite the evidence on their limitations and availability of better diagnostic options. Cardiac MRI is a powerful diagnostic method, supporting robust measurements of crucial markers of cardiac structure and function, myocardial perfusion and scar, as well as providing detailed insight into myocardial tissue. Accurate and informative diagnostic readouts can help with guiding therapy, monitoring disease progress and tailoring the response to treatment. In this article, the authors outline the evidence supporting the state-of-art applications based on cardiovascular magnetic resonance, allowing the clinician optimal use of this insightful diagnostic method in everyday clinical practice.
Purpose: The prevalence of "ocal allergic rhinitis" within individuals suffering from perennial rhinitis remains uncertain, and patients usually are diagnosed with non-allergic rhinitis. The aim of this study was to evaluate the prevalence of a potential "local allergic rhinitis" in subjects suffering from non-allergic rhinitis in a non-selected group of young students.
Methods: 131 students (age 25.0 ± 5.1 years) with a possible allergic rhinitis and 25 non-allergic controls without rhinitis symptoms (age 22.0 ± 2.0 years) were recruited by public postings. 97 of 131 students with rhinitis were tested positive (≥3 mm) to prick testing with 17 frequent allergens at visit 1. Twenty-four 24 subjects with a house dust mite allergy, 21 subjects with a non-allergic rhinitis, and 18 non-allergic controls were further investigated at visit 2. Blood samples were taken, and nasal secretion was examined. In addition, all groups performed a nasal provocation test with house dust mite (HDM).
Results: In serum and nasal secretion, total IgE and house dust mite specific IgE significantly differed between HDM positive subjects and controls. However, no differences between non-allergic subjects and control subjects were quantifiable. Neither a nasal provocation test nor a nasal IgE to HDM allergens showed a measurable positive response in any of the non-allergic rhinitis subjects as well as the healthy controls, whilst being positive in 13 subjects with HDM allergy.
Conclusions: Nasal IgE is present in subjects with HDM allergy, but not in non-allergic rhinitis. In the investigated non-selected population, exclusive local production of IgE is absent. By implication, therefore, our findings challenge the emerging concept of local allergic rhinitis.
Study identifier at ClinicalTrials.gov: NCT 02810535.
The novel coronavirus SARS-CoV-2 is the causative agent of the acute respiratory disease COVID-19, which has become a global concern due to its rapid spread. Meanwhile, increased demand for testing has led to a shortage of reagents and supplies and compromised the performance of diagnostic laboratories in many countries. Both the World Health Organization (WHO) and the Center for Disease Control and Prevention (CDC) recommend multi-step RT-PCR assays using multiple primer and probe pairs, which might complicate the interpretation of the test results, especially for borderline cases. In this study, we describe an alternative RT-PCR approach for the detection of SARS-CoV-2 RNA that can be used for the probe-based detection of clinical isolates in diagnostics as well as in research labs using a low-cost SYBR green method. For the evaluation, we used samples from patients with confirmed SARS-CoV-2 infections and performed RT-PCR assays along with successive dilutions of RNA standards to determine the limit of detection. We identified an M-gene binding primer and probe pair highly suitable for the quantitative detection of SARS-CoV-2 RNA for diagnostic and research purposes.
The Wirecard scandal is a wake-up call alerting German politics to the importance of securities market integrity. The role of market supervision is to ensure the smooth functioning of capital markets and their integrity, creating trust among and acceptance by investors locally and globally. The existing patchwork of national supervisory practice in Europe is under discussion today, in the wake of Brexit that will end the role of London as a de-facto lead supervisor in stock and bond markets. A fundamental overhaul of a fragmented securities markets supervisory regime in Europe would offer the potential to lead to the establishment of an independent European Single Market Supervisor (ESMS). Endowed with strong enforcement powers, and supported by the existing national agencies, the ESMS would be entrusted with ensuring a uniform market standard as to transparency and other issues of market integrity across Europe. This would not rule out maintaining a variety of market organization structures at the national level. The ESMS would need executive powers in the world of markets (i.e. securities and trading), much like the SSM in the world of banking. To fill this new role, ESMS would have to be established as a new, independent institution, including an enormously scaled up staff if compared, e.g., to ESMA.
Accounting for financial stability: Bank disclosure and loss recognition in the financial crisis
(2020)
This paper examines banks’ disclosures and loss recognition in the financial crisis and identifies several core issues for the link between accounting and financial stability. Our analysis suggests that, going into the financial crisis, banks’ disclosures about relevant risk exposures were relatively sparse. Such disclosures came later after major concerns about banks’ exposures had arisen in markets. Similarly, the recognition of loan losses was relatively slow and delayed relative to prevailing market expectations. Among the possible explanations for this evidence, our analysis suggests that banks’ reporting incentives played a key role, which has important implications for bank supervision and the new expected loss model for loan accounting. We also provide evidence that shielding regulatory capital from accounting losses through prudential filters can dampen banks’ incentives for corrective actions. Overall, our analysis reveals several important challenges if accounting and financial reporting are to contribute to financial stability.
Background/aims: Hepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT) worldwide. Early identification of patients at risk for HCC recurrence is of paramount importance since early treatment of recurrent HCC after LT may be associated with increased survival. We evaluated incidence of and predictors for HCC recurrence, with a focus on the course of AFP levels.
Methods: We performed a retrospective, single-center study of 99 HCC patients who underwent LT between January 28th, 1997 and May 11th, 2016. A multi-stage proportional hazards model with three stages was used to evaluate potential predictive markers, both by univariate and multivariable analysis, for influences on 1) recurrence after transplantation, 2) mortality without HCC recurrence, and 3) mortality after recurrence.
Results: 19/99 HCC patients showed recurrence after LT. Waiting time was not associated with overall HCC recurrence (HR = 1, p = 0.979). Similarly, waiting time did not affect mortality in LT recipients both with (HR = 0.97, p = 0.282) or without (HR = 0.99, p = 0.685) HCC recurrence. Log10-transformed AFP values at the time of LT (HR 1.75, p = 0.023) as well as after LT (HR 2.07, p = 0.037) were significantly associated with recurrence. Median survival in patients with a ratio (AFP at recurrence divided by AFP 3 months before recurrence) of 0.5 was greater than 70 months, as compared to a median of only 8 months in patients with a ratio of 5.
Conclusion: A rise in AFP levels rather than an absolute threshold could help to identify patients at short-term risk for HCC recurrence post LT, which may allow intensification of the surveillance strategy on an individualized basis.
Background: Fingolimod is used for immune therapy in patients with multiple sclerosis. Long-term treatment is associated with a small increase in the risk of herpes virus reactivation and respiratory tract infections. Patients with coronavirus disease 2019 (COVID-19) under Fingolimod treatment have not been described.
Methods and results. We report a 57-year old female patient with a relapsing remitting multiple sclerosis under fingolimod treatment who experienced a severe COVID-19 infection in March 2020 (Extended Disability Status Scale: 2.0). Having peripheral lymphopenia typical for fingolimod treatment (total lymphocytes 0.39/nL [reference range 1.22-3.56]), the patient developed bilateral interstitial pneumonia with multiple ground-glass opacities on chest CT. Fingolimod medication was stopped. On the intensive care unit, non-invasive ventilation was used to provide oxygen and ventilation support regularly. Over the following two days, oxygenation improved, and the patient was transferred to a normal ward five days after admission.
Conclusion: The implications fingolimod has on COVID-19 are complex. As an S1P analogue, fingolimod might enhance lung endothelial cell integrity. In addition, in case of a so-called cytokine storm, immunomodulation might be beneficial to reduce mortality. Future studies are needed to explore the risks and therapeutic effects of fingolimod in COVID-19 patients.
Microthlaspi erraticum is widely distributed in temperate Eurasia, but restricted to Ca2+-rich habitats, predominantly on white Jurassic limestone, which is made up by calcium carbonate, with little other minerals. Thus, naturally occurring Microthlaspi erraticum individuals are confronted with a high concentration of Ca2+ ions while Mg2+ ion concentration is relatively low. As there is a competitive uptake between these two ions, adaptation to the soil condition can be expected. In this study, it was the aim to explore the genomic consequences of this adaptation by sequencing and analysing the genome of Microthlaspi erraticum. Its genome size is comparable with other diploid Brassicaceae, while more genes were predicted. Two Mg2+ transporters known to be expressed in roots were duplicated and one showed a significant degree of positive selection. It is speculated that this evolved due to the pressure to take up Mg2+ ions efficiently in the presence of an overwhelming amount of Ca2+ ions. Future studies on plants specialized on similar soils and affinity tests of the transporters are needed to provide unequivocal evidence for this hypothesis. If verified, the transporters found in this study might be useful for breeding Brassicaceae crops for higher yield on Ca2+-rich and Mg2+ -poor soils.
Considering the microbiome in stress-related and neurodevelopmental trajectories to schizophrenia
(2020)
Early life adversity and prenatal stress are consistently associated with an increased risk for schizophrenia, although the exact pathogenic mechanisms linking the exposures with the disease remain elusive. Our previous view of the HPA stress axis as an elegant but simple negative feedback loop, orchestrating adaptation to stressors among the hypothalamus, pituitary, and adrenal glands, needs to be updated. Research in the last two decades shows that important bidirectional signaling between the HPA axis and intestinal mucosa modulates brain function and neurochemistry, including effects on glucocorticoid hormones and brain-derived neurotrophic factor (BDNF). The intestinal microbiome in earliest life, which is seeded by the vaginal microbiome during delivery, programs the development of the HPA axis in a critical developmental window, determining stress sensitivity and HPA function as well as immune system development. The crosstalk between the HPA and the Microbiome Gut Brain Axis (MGBA) is particularly high in the hippocampus, the most consistently disrupted neural region in persons with schizophrenia. Animal models suggest that the MGBA remains influential on behavior and physiology across developmental stages, including the perinatal window, early childhood, adolescence, and young adulthood. Understanding the role of the microbiome on critical risk related stressors may enhance or transform of understanding of the origins of schizophrenia and offer new approaches to increase resilience against stress effects for preventing and treating schizophrenia.
In this article, we build on research arguing that linguistic self-representation on social media can be viewed as a form of face-work and that the strategies employed by users are influenced by both a desire to connect with others and a need to preserve privacy. Drawing on our own analyses of usernames as well as that of others which were conducted as part of a large-scale project investigating usernames in 14 languages (Schlobinski/T. Siever 2018a), we argue that these conflicting goals of wanting to be recognised as an authentic member of an in-group while retaining a degree of anonymity are also observable in the choice of username. Online self-naming can thus be viewed as a key practice in the debate of face-work on social media platforms, because names and naming strategies can be studied more readily than broader and more complex aspects, such as stylistic variation or text-image interdependence, while at the same time forming part of these.
Downy mildew of common sage (Salvia officinalis), caused by Peronospora salviae-officinalis, has become a serious problem in sage production worldwide. The causal agent of the disease belongs to the Pe. belbahrii species complex and was described as a species of its own in 2009. Nevertheless, very little is known about its infection biology and epidemiology. The aims of the current study were therefore to unravel the life cycle of this downy mildew and gain deeper insights into the epidemiology of the disease, as well as to clarify the species boundaries in the Pe. belbahrii species complex.
Infection studies showed that temperatures between 15 and 20 °C were most favourable for infection and disease progress. At 5 °C Pe. salviae-officinalis is still able to infect sage plants, but sporulation was only observed at higher temperatures. Furthermore, Pe. salviae-officinalis needs two events of leaf wetness or high humidity, a first one of at least three hours for conidial germination and penetration of the host, and a second one for sporulation. Additionally, contamination of sage seeds by Pe. salviae-officinalis was proven by seed washing and by PCR and DNA sequence comparisons, suggesting that infested seeds might play a major role in the fast spread of sage downy mildew, which is an important finding for phytosanitary or quarantine measures.
A protocol for fluorescence staining and confocal laser scanning microscopy was established and the whole life cycle of Pe. salviae-officinalis was tracked including oospore formation. The method was also used to examine samples of Pe. lamii on Lamium purpureum and Pe. belbahrii on Ocimum basilicum demonstrating the usefulness of this method for studying the infection process of downy mildews in general.
Peronospora species parasitizing S. sclarea, S. pratensis, O. basilicum, and Plectranthus scutellarioides were studied using light microscopy and molecular phylogenetic analyses based on six loci (ITS rDNA, cox1, cox2, ef1a, hsp90 and β-tubulin). The downy mildew on S. pratensis was shown to be distinct from Pe. salviae-officinalis and closely related to Pe. glechomae, and is herein described as a new taxon, Peronospora salviae-pratensis. The downy mildew on S. sclarea was found to be caused by Peronospora salviae-officinalis. The multi-gene phylogeny revealed that the causal agent of downy mildew on coleus is distinct from Pe. belbahrii on basil, and is herein described as a new taxon, Pe. choii.
Interest in time-resolved connectivity in fMRI has grown rapidly in recent years. The most widely used technique for studying connectivity changes over time utilizes a sliding windows approach. There has been some debate about the utility of shorter versus longer windows, the use of fixed versus adaptive windows, as well as whether observed resting state dynamics during wakefulness may be predominantly due to changes in sleep state and subject head motion. In this work we use an independent component analysis (ICA)-based pipeline applied to concurrent EEG/fMRI data collected during wakefulness and various sleep stages and show: 1) connectivity states obtained from clustering sliding windowed correlations of resting state functional network time courses well classify the sleep states obtained from EEG data, 2) using shorter sliding windows instead of longer non-overlapping windows improves the ability to capture transition dynamics even at windows as short as 30 s, 3) motion appears to be mostly associated with one of the states rather than spread across all of them 4) a fixed tapered sliding window approach outperforms an adaptive dynamic conditional correlation approach, and 5) consistent with prior EEG/fMRI work, we identify evidence of multiple states within the wakeful condition which are able to be classified with high accuracy. Classification of wakeful only states suggest the presence of time-varying changes in connectivity in fMRI data beyond sleep state or motion. Results also inform about advantageous technical choices, and the identification of different clusters within wakefulness that are separable suggest further studies in this direction.
Most living organisms possess varying degrees of regenerative capabilities but how these regenerative processes are controlled is still poorly understood. Naturally occurring bioelectric voltages (like Vmem) are thought to be playing instructive role in tissue regeneration, as well as embryonic development. The different distribution of ions on the either side of the cell membrane results in intra- and extra-cellular voltage differences, known as membrane potential or Vmem. The relationship between Vmem and cell physiology is conserved in a wide range of cell types and suggests that Vmem regulation is a fundamental control mechanism for regeneration related processes e.g., proliferation and differentiation. In the present study we measured Vmem in three different cell types (human osteogenic sarcoma cell line (OSC), rat bone marrow derived mesenchymal stem cells (BM-MSC), and rat dermal fibroblasts) and characterized the relationship between their Vmem and proliferation. In order to find out if Vmem controls proliferation, or visa-versa, we blocked and then unblocked Na+/K+-exchanging ATPase using ouabain and measured the proliferation. Our results demonstrate that Vmem can be pharmacologically manipulated to control proliferation in certain cell types like BM-MSC. Taken together, it is clear that control of bioelectrical properties in non-excitable cells could prove to be potentially a useful tool in regenerative medicine efforts.
Spatial and temporal processes shaping microbial communities are inseparably linked but rarely studied together. By Illumina 16S rRNA sequencing, we monitored soil bacteria in 360 stations on a 100 square meter plot distributed across six intra-annual samplings in a rarely managed, temperate grassland. Using a multi-tiered approach, we tested the extent to which stochastic or deterministic processes influenced the composition of local communities. A combination of phylogenetic turnover analysis and null modeling demonstrated that either homogenization by unlimited stochastic dispersal or scenarios, in which neither stochastic processes nor deterministic forces dominated, explained local assembly processes. Thus, the majority of all sampled communities (82%) was rather homogeneous with no significant changes in abundance-weighted composition. However, we detected strong and uniform taxonomic shifts within just nine samples in early summer. Thus, community snapshots sampled from single points in time or space do not necessarily reflect a representative community state. The potential for change despite the overall homogeneity was further demonstrated when the focus shifted to the rare biosphere. Rare OTU turnover, rather than nestedness, characterized abundance-independent β-diversity. Accordingly, boosted generalized additive models encompassing spatial, temporal and environmental variables revealed strong and highly diverse effects of space on OTU abundance, even within the same genus. This pure spatial effect increased with decreasing OTU abundance and frequency, whereas soil moisture – the most important environmental variable – had an opposite effect by impacting abundant OTUs more than the rare ones. These results indicate that – despite considerable oscillation in space and time – the abundant and resident OTUs provide a community backbone that supports much higher β-diversity of a dynamic rare biosphere. Our findings reveal complex interactions among space, time, and environmental filters within bacterial communities in a long-established temperate grassland.
Perspectives on participation in continuous vocational education training - an interview study
(2020)
In European industrialized countries, a large number of companies in the healthcare, hotel, and catering sectors, as well as in the technology sector, are affected by demographic, political, and technological developments resulting in a greater need of skilled workers with a simultaneous shortage of skilled workers (CEDEFOP, 2015, 2016). Consequently, employers have to address workers who have not been taken into account such as low-skilled workers, workers returning from a career break, people with a migrant background, older people, and jobseekers and train them, in order to guarantee the professionalization of this workforce (Festing and Harsch, 2018). Continuing vocational education and training (CVET) is seen as an indispensable tool; because CVET has advantages for both employers and employees, it helps to increase the productivity of companies (Barrett and O’Connell, 2001), to prevent the widening of socioeconomic disparities (Dieckhoff, 2007), and to open up career opportunities for the workforce (Rubenson and Desjardins, 2009). However, participation rate on CVET seems to differ, depending on institutional factors (such as sector and size of the company) and individual characteristics (such as qualification level, migration background, age and time of absence from work) (e.g., Rubenson and Desjardins, 2009; Wiseman and Parry, 2017). In contrast to previous research, our study aims to provide a holistic view of reasons for and against CVET, combining the different perspectives of employers and (potential) employees. The analysis of reasons and barriers was carried out based on semi-structured interviews. Fifty-seven employers, 73 employees, and 42 jobseekers (potential employees) from the sectors retail, healthcare and social services, hotels and catering, and technology were interviewed. Results point to considerable differences in the reasons and barriers mentioned by the disadvantaged groups. These differences are particularly significant between employees on the one side and employers, as well as jobseekers, on the other side, while the reasons to attend CVET of jobseekers are more similar to those of employers. The results can be used to tailor CVET more closely to the needs of (potential) employees and thus strengthen both the qualification and career opportunities of (potential) employees and the competitiveness and productivity of companies.
Diversity and psychological health issues at the workplace are pressing issues in today’s organizations. However, research linking two fields is scant. To bridge this gap, drawing from team faultline research, social categorization theory, and the job-demands resources model, we propose that perceiving one’s team as fragmented into subgroups increases strain. We further argue that this relationship is mediated by task conflict and relationship conflict and that it is moderated by psychological empowerment and task interdependence. Multilevel structural equation models on a two-wave sample consisting of 536 participants from 107 work teams across various industries and work contexts partially supported the hypotheses: task conflict did indeed mediate the positive relationships between perceived subgroups and emotional exhaustion while relationship conflict did not; effects on stress symptoms were absent. Moreover, contrary to our expectations, neither empowerment, nor task interdependence moderated the mediation. Results indicate that team diversity can constitute a job demand that can affect psychological health. Focusing on the mediating role of task conflict, we offer a preliminary process model to guide future research at the crossroads of diversity and psychological health at work.
When Christine Lagarde announced her first, moderate rescue package, she called upon member states to provide fiscal aid. But the markets showed to have lost confidence in fiscal policy. In the absence of strong monetary policy signals, the slide continued until Lagarde in her second attempt opened the floodgates.
Governments, economists and intellectuals have called for common European bonds or increased own EU funds to address the recession induced by Covid19. Unfortunately, the German government, joined by the other members of the “Frugal Four” (Austria, Finland, the Netherlands), has categorically rejected to look into any such measures and favours using the ESM. This reaction created a déjà vu experience for citizens and governments of the heavily affected southern Member States of the EU. The proposal to use the ESM raises fears of another wave of austerity amounting to yet another lost decade for economic, social, and ecological development in Europe.
The recovery plan of the Commission entitled "Next Generation EU" proposes a compromise that goes beyond the ominous lowest common denominator. With a package of EUR 750bn in total, comprising EUR 250bn in loans and the rest in grants, the Commission paves the way for both forward-looking public finance and constitutional innovation. The proposals are masterpieces of high-tech legal engineering. Again, European constitutional law evolves through crisis. Yet, again, it stands to reason how far the proposed instruments will shift the European Union towards enhancing solidarity and democracy.
The nucleoside analogue nelarabine, the prodrug of arabinosylguanine (AraG), is effective against T-cell acute lymphoblastic leukaemia (T-ALL) but not against B-cell ALL (B-ALL). The underlying mechanisms have remained elusive. Here, data from pharmacogenomics studies and a panel of ALL cell lines reveal an inverse correlation between nelarabine sensitivity and the expression of SAMHD1, which can hydrolyse and inactivate triphosphorylated nucleoside analogues. Lower SAMHD1 abundance is detected in T-ALL than in B-ALL in cell lines and patient-derived leukaemic blasts. Mechanistically, T-ALL cells display increased SAMHD1 promoter methylation without increased global DNA methylation. SAMHD1 depletion sensitises B-ALL cells to AraG, while ectopic SAMHD1 expression in SAMHD1-null T-ALL cells induces AraG resistance. SAMHD1 has a larger impact on nelarabine/AraG than on cytarabine in ALL cells. Opposite effects are observed in acute myeloid leukaemia cells, indicating entity-specific differences. In conclusion, SAMHD1 promoter methylation and, in turn, SAMHD1 expression levels determine ALL cell response to nelarabine.