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Stored and cooled, highly-charged ions offer unprecedented capabilities for precision studies in the realm of atomic, nuclear structure and astrophysics[1]. After the successful investigation of the 96Ru(p,7)97Rh reaction cross section in 2009[2], the first measurement of the 124Xe(p,7)125Cs reaction cross section has been performed with decelerated, fully-ionized 124Xe ions in 2016 at the Experimental Storage Ring (ESR) of GSI[3]. Using a Double Sided Silicon Strip Detector, introduced directly into the ultra-high vacuum environment of a storage ring, the 125Cs proton-capture products have been successfully detected. The cross section has been measured at 5 different energies between 5.5AMeV and 8AMeV, on the high energy tail of the Gamow-window for hot, explosive scenarios such as supernovae and X-ray binaries. The elastic scattering on the H2 gas jet target is the major source of background to count the (p,7) events. Monte Carlo simulations show that an additional slit system in the ESR in combination with the energy information of the Si detector will enable background free measurements of the proton-capture products. The corresponding hardware is being prepared and will increase the sensitivity of the method tremendously.
Psychotherapists in mental health institutions as a professional group are part of the medical system, and from this perspective, as representing an occupation that serves the public health interests, as well as those of the individual seeking help. Despite the different existing therapeutic approaches and diverse forms of therapy deriving from these approaches critical theories, however, consider psychotherapy as a profession with a specific jurisdictional claim and own highly specific interests. In contrast to most of the recent discussion around therapy culture, in this article, I argue that sociology and social theory could benefit from an understanding of psychotherapy as a profession with a separate logic and claim for jurisdiction for mental health. Moreover, I present some general trends showing that, regarding psychotherapy, we face a concurrence of a professionalisation, and simultaneously, an already ongoing deprofessionalisation. To develop my argument, I first discuss the perspectives of sociology of the psychotherapy professions. Second, I present the potential lack of professionalism in four dimensions. Third, I discuss possible tendencies of deprofessionalisation. Finally, I conclude by pointing out the importance of theorising the psychotherapy professions for medical sociology.
Aims: The study aimed to evaluate the prevalence of mental distress in patients with newly diagnosed bladder cancer, the cancer-information search behavior, and the influence of information seeking on distress. Methods: One hundred and one bladder cancer patients answered 2 established questionnaires (“Hospital Anxiety and Depression Scale” [HADS] and the “Fragebogen zur Belastung von Krebskranken” [FBK-R23]) for evaluation of mental distress and a self-developed questionnaire with questions concerning information seeking and socioeconomic facts. Results: Regarding risk group stratification, 57.4% were classified as high-risk and 42.6% as low-risk tumor-bearing patients. Analysis of mental distress showed that 23.2% had a score above the HADS-A cutoff, 25.3% above the HADS-D cutoff, and 21.4% showed a pathologic FBK-R23 score. Overall, 75% felt well informed about their illness. Risk group stratification did not correlate with HADS-A, HADS-D, or FBK-R23 score. Furthermore, active search for information or the use of the Internet did not correlate with the HADS-A, HADS-D, or FBK-R23 score. However, the quality of the urologist’s information and the feeling of being informed correlated with the grade of mental distress. Conclusion: Besides the treatment of bladder cancer, informing the patient about the disease in a psychologically wholesome manner and working together with psycho-oncologically trained psychologists are essential tasks for the treating urologist.
Background: Data on the arrhythmic burden of women at risk for sudden cardiac death are limited, especially in patients using the wearable cardioverter-defibrillator (WCD).
Objective: We aimed to characterize WCD compliance, atrial and ventricular arrhythmic burden, and WCD outcomes by sex in patients enrolled in the Prospective Registry of Patients Using the Wearable Cardioverter Defibrillator (WEARIT-II U.S. Registry).
Methods: In the WEARIT-II Registry, we stratified 2000 patients by sex into women (n = 598) and men (n = 1402). WCD wear time, ventricular and atrial arrhythmic events during WCD use, and implantable cardioverter-defibrillator (ICD) implantation rates at the end of WCD use were evaluated.
Results: The mean WCD wear time was similar in women and men (94 days vs 90 days; P = .145), with longer daily use in women (21.4 h/d vs 20.7 h/d; P = .001). Burden of ventricular tachycardia or ventricular fibrillation was higher in women, with 30 events per 100 patient-years compared with 18 events per 100 patient-years in men (P = .017), with similar findings for treated and non-treated ventricular tachycardia/ventricular fibrillation. Recurrent atrial arrhythmias/sustained ventricular tachycardia was also more frequent in women than in men (167 events per 100 patient-years vs 73 events per 100 patient-years; P = .042). However, ICD implantation rate at the end of WCD use was similar in both women and men (41% vs 39%; P = .448).
Conclusion: In the WEARIT-II Registry, we have shown a higher burden of ventricular and atrial arrhythmic events in women than in men. ICD implantation rates at the end of WCD use were similar. Our findings warrant monitoring women at risk for sudden cardiac death who have a high burden of atrial and ventricular arrhythmias while using the WCD.
Determination of a minimal postmortem interval via age estimation of necrophagous diptera has been restricted to the juvenile stages and the time until emergence of the adult fly, i.e. up until 2–6 weeks depending on species and temperature. Age estimation of adult flies could extend this period by adding the age of the fly to the time needed for complete development. In this context pteridines are promising metabolites, as they accumulate in the eyes of flies with increasing age. We studied adults of the blow fly Lucilia sericata at constant temperatures of 16 °C and 25 °C up to an age of 25 days and estimated their pteridine levels by fluorescence spectroscopy. Age was given in accumulated degree days (ADD) across temperatures. Additionally, a mock case was set up to test the applicability of the method. Pteridine increases logarithmically with increasing ADD, but after 70–80 ADD the increase slows down and the curve approaches a maximum. Sex had a significant impact (p < 4.09 × 10−6) on pteridine fluorescence level, while body-size and head-width did not. The mock case demonstrated that a slight overestimation of the real age (in ADD) only occurred in two out of 30 samples. Age determination of L. sericata on the basis of pteridine levels seems to be limited to an age of about 70 ADD, but depending on the ambient temperature this could cover an extra amount of time of about 5–7 days after completion of the metamorphosis.
Aim: The primary aim of this study was to analyze frequency and characteristics of combined facial and peripheral trauma with consecutive hospitalization and treatment.
Materials and methods: The study included all patients with concomitant orthopedic-traumatolgical (OT) and craniomaxillofacial (CMF) injuries admitted to our level I trauma center in 2018. The data were collected by analysis of the institution’s database and radiological reviews and included age, sex, injury type, weekday and time of presentation. All patients were examined and treated by a team of surgeons specialized in OT and CMF directly after presentation.
Results: A total number of 1040 combined OT and CMF patients were identified. Mean age was 33.0 ± 26.2 years. 67.3% (n = 700) were male patients. Primary presentation happened most frequently on Sundays (n = 199) and between 7 and 8 pm (n = 74). 193 OT fractures were documented, where cervical spine injuries were most frequent (n = 30). 365 facial and skull fractures were recorded. 10.8% of the 204 patients with fractures of the viscerocranium presented with at least one fracture of the extremity, 7.8% (16/204) with cervical spine fractures, 33.3% (68/204) with signs of closed brain trauma and 9.8% (20/204) with intracranial hemorrhage.
Discussion: The study shows a high frequency of combined facial with OT-injuries and brain damage in a predominantly young and male cohort. Attendance by interdisciplinary teams of both CMF and OT surgeons specialized in cervical spine trauma surgery is highly advisable for adequate treatment.
Conclusion: Diagnostics and treatment should be performed by a highly specialized OT and CMF team, with a consulting neurosurgeon in a level-1 trauma center to avoid missed diagnoses and keep mortality low.
Corporate governance is the set of rules, be they legal or self-regulatory, practices and processes pursuant to which an insurance undertaking is administrated. Good corporate governance is not only key to establishing oneself and succeeding in a competitive environment but also to safeguarding the interests of all stakeholders in an insurance undertaking. It is insofar not surprising that mandatory requirements on the administration of insurance undertakings have become rather prolific in recent years, in an attempt by regulators to protect especially policyholders against perceived risks hailing from improperly governed insurance undertakings. In Germany this has been regarded by many undertakings as an overly paternalistic approach of the legislator, especially considering that the German insurance sector has experienced for decades if not centuries a remarkably low number of insolvencies and that German insurers were neither the trigger nor the (especially) endangered actors in the financial crisis commencing in 2007. Notwithstanding the true core of this criticism, that the insurance industry was taken to a certain degree hostage by the shortcomings within the banking sector, the reform of German Insurance Supervisory Law via implementation of the Solvency II-System has brought many advances in the sense of better governance of insurance undertakings and has also brought to light many deficiencies that the administration of some insurance undertakings may have suffered from in the past, which are now more properly addressed.
High-intensity functional training (HIFT) has become a popular method in the sports and fitness sector. In contrast to unimodal approaches such as strength or endurance training, it has been hypothesized to induce concurrent adaptations in multiple markers of motor function. However, to date, the effectiveness of HIFT in this regard has not been studied. The present systematic review quantified the chronic effects of HIFT on motor function in healthy individuals. A multilevel meta-analysis with a robust random effects meta-regession model was used to pool the standardized mean differences (SMD) between (a) HIFT and (b) no-exercise (NEX) as well as conventional endurance, resistance and balance training for outcomes of muscle strength, endurance capacity and balance. The influence of possible effect modifiers such as program duration, session duration, age or sex was examined in a moderator analysis. Seventeen papers with moderate to high methodological quality (PEDro scale) were identified. Compared to NEX, HIFT had small to moderate positive effects on endurance capacity (SMD: 0.42, 95% CI 0.07–0.78, p = 0.03) and strength (0.60, 95% CI 0.02–1.18, p = 0.04) but no effect on balance (SMD: − 0.10, 95% CI − 1.13 to 0.92, p = 0.42). Regarding endurance, HIFT showed similar effectiveness as moderate-intensity endurance training (SMD: − 0.11, 95% CI − 1.17 to 0.95, p = 0.75) and high-intensity interval endurance training (SMD: − 0.15, 95% CI − 1.4 to 1.1, p = 0.66). No comparisons of HIFT vs. classical resistance or balance training were found. Moderator analyses revealed no influence of most effect modifiers. However, regarding endurance, females seemed to respond more strongly to HIFT in the comparison to NEX (p < .05). HIFT appears to represent an appropriate method to induce chronic improvements in motor function. While being superior to NEX and non-inferior to endurance training, current evidence does not allow a comparison against resistance and balance training. The impact of possible effect moderators should be further elucidated in future research.
Hintergrund: Mit dem Masterplan 2020 und den an mehreren Universitäten eingeführten Modellstudiengängen befindet sich das Medizinstudium aktuell im Umbruch. Sowohl im Regel- als auch im Modellstudiengang werden medizinrechtliche Aspekte überwiegend im Rahmen rechtsmedizinischer Ausbildungsabschnitte unterrichtet. Allerdings werden Studierende bereits während Famulaturen oder im praktischen Jahr mit juristischen Fragen konfrontiert.
Ziel der Studie war es herauszufinden, ob und in welchem Umfang Studierende der Humanmedizin insbesondere zur ärztlichen Aufklärung und zu den ärztlichen Informationspflichten bis zum Beginn des 4. bzw. 5. klinischen Semesters auf medizinrechtliche Aspekte vorbereitet wurden, und ob Verbesserungen bei der medizinrechtlichen Lehre gewünscht werden.
Material und Methoden: Zwischen den Sommersemestern 2017 und 2019 wurde zu Beginn des Kurses für Rechtsmedizin eine quantitative, standardisierte Umfrage mit insgesamt 373 Studierenden durchgeführt.
Ergebnisse: Wenngleich 98,8 % der Studierenden angaben, Aufklärungsgespräche bereits (mehrfach) praktisch ausgeübt zu haben, bestanden deutliche Defizite in Bezug auf die juristischen Anforderungen an das ärztliche Aufklärungsgespräch und dessen Delegation. So gaben lediglich 5,1 % der Studierenden an, die rechtlichen Grundlagen der ärztlichen Aufklärung sowie die entsprechende Norm aus dem Zivilrecht zu kennen. Über 80 % der Befragten fühlten sich unzureichend auf die rechtlichen Aspekte des praktischen Jahres vorbereitet. Über 90 % der Studierenden wünschten sich eine bessere medizinrechtliche Ausbildung.
Diskussion: Eine fächerübergreifende Etablierung sowie eine über das gesamte Studium verteilte Lehre von Medizinrecht könnte die Vorbereitung auf das praktische Jahr verbessern und das Verständnis für die rechtlichen Anforderungen an die ärztliche Berufstätigkeit fördern. Nach dem derzeitigen Stand der Umsetzung des Masterplans 2020 soll das Medizinrecht in der Learning Opportunities, Objectives and Outcomes Platform (LOOOP) als verbindlicher Ausbildungs- und Lehrinhalt etabliert werden.
Background: The feedback given to students plays an important role in their efficiency related to learning practical skills. In the present study, diverse feedback modalities have been investigated. Our hypothesis is that individualized and unsupervised video feedback can produce a similar learning experience as performing practical skills in an oral and maxillofacial surgery setting with conventional direct expert feedback (control group).
Methods: This prospective, randomized, controlled, and blinded study compared direct expert feedback (DEF), individualized video feedback (IVF) and unsupervised video feedback (UVF). The participants were fourth-year dental students from University Goethe in Frankfurt. The students were assigned to one of the three feedback methods (n = 20 per group) using simple randomization. All participants watched an instruction video for an interdental (‘Ernst’) ligature and periphery venous catheterization. Next, the students were video recorded performing the tasks by themselves (pre-test). Following this, every student received feedback using one of the above-mentioned feedback modalities. The participants then performed the same task again while being video recorded (post-test) to measure the acquired competence. Six weeks later, the students participated in an objective structured clinical examination (OSCE) to evaluate their long-term knowledge retention. All examiners were blinded regarding the students’ instructional approach and their affiliation in terms of the learning group.
Results: For the interdental ligature, we found significant improvements in performance in each feedback modality group between the pre-test and post-test (p < 0.001). UVF had the strongest effect on performance time. The comparison between each group in the post-test showed no significant differences between the three groups.
Conclusion: This study showed that IVF and UVF can be considered an alternative or adjunct to conventional methods (i.e. DEF) when learning procedural skills in oral and maxillofacial surgery. However, DEF showed to be the most effective method of feedback and therefore preferable in teaching.
Background: Patients with rare diseases (RDs) are often diagnosed too late or not at all. Clinical decision support systems (CDSSs) could support the diagnosis in RDs. The MIRACUM (Medical Informatics in Research and Medicine) consortium, which is one of four funded consortia in the German Medical Informatics Initiative, will develop a CDSS for RDs based on distributed clinical data from ten university hospitals. This qualitative study aims to investigate (1) the relevant organizational conditions for the operation of a CDSS for RDs when diagnose patients (e.g. the diagnosis workflow), (2) which data is necessary for decision support, and (3) the appropriate user group for such a CDSS.
Methods: Interviews were carried out with RDs experts. Participants were recruited from staff physicians at the Rare Disease Centers (RDCs) at the MIRACUM locations, which offer diagnosis and treatment of RDs.
An interview guide was developed with a category-guided deductive approach. The interviews were recorded on an audio device and then transcribed into written form. We continued data collection until all interviews were completed. Afterwards, data analysis was performed using Mayring’s qualitative content analysis approach.
Results: A total of seven experts were included in the study. The results show that medical center guides and physicians from RDC B-centers (with a focus on different RDs) are involved in the diagnostic process. Furthermore, interdisciplinary case discussions between physicians are conducted.
The experts explained that RDs exist which cannot be fully differentiated, but rather described only by their overall symptoms or findings: diagnosis is dependent on the disease or disease group. At the end of the diagnostic process, most centers prepare a summary of the patient case. Furthermore, the experts considered both physicians and experts from the B-centers to be potential users of a CDSS. The experts also have different experiences with CDSS for RDs.
Conclusions: This qualitative study is a first step towards establishing the requirements for the development of a CDSS for RDs. Further research is necessary to create solutions by also including the experts on RDs.
We discuss the potential of light-nuclei measurements in heavy-ion collisions at intermediate energies for the search of the hypothetical QCD critical end-point. A previous proposal based on neutron density fluctuations has brought appealing experimental evidences of a maximum in the ratio of the number of tritons times protons, divided over deuterons square, O tpd. However these results are difficult to reconcile with the state-of-the-art statistical thermal model predictions. Based on the idea that the QCD critical point can lead to a substantial attraction among nucleons, we propose new light-nuclei multiplicity ratios involving He in which the maximum would be more noticeable. We argue that the experimental extraction is feasible by presenting these ratios formed from actual measurements of total and differential yields at low and high collision energies from FOPI and ALICE experiments, respectively. We also illustrate the possible behavior of these ratios at intermediate energies applying a semiclassical method based on flucton paths using the preliminary NA49 and STAR data for O tpd as input.
“Protection of the environment“ and “sustainability“ are more significant than ever. The legal system contributes an important share to the protection of the environment. However, an overview of the German private environmental liability law shows that conventional tort law is not a suitable basis for civil liability for the environmental consequences of officially approved emissions of greenhouse gases. In general, one of the main problems of private environmental liability law lies in proving the individual causality of the conduct of an emitter, as the lawsuit of a Peruvian homeowner against a German energy company pending before the Higher Regional Court of Hamm illustratively demonstrates. The outcome of this lawsuit, which may have an outstanding significance for the status and development of private environmental liability law in Germany, is awaited with great anticipation. The article also briefly examines recent developments in private environmental liability law outside Germany and the question to what extent insurance can be an instrument to protect the environment.
Background: Rare Diseases (RDs), which are defined as diseases affecting no more than 5 out of 10,000 people, are often severe, chronic and life-threatening. A main problem is the delay in diagnosing RDs. Clinical decision support systems (CDSSs) for RDs are software systems to support clinicians in the diagnosis of patients with RDs. Due to their clinical importance, we conducted a scoping review to determine which CDSSs are available to support the diagnosis of RDs patients, whether the CDSSs are available to be used by clinicians and which functionalities and data are used to provide decision support.
Methods: We searched PubMed for CDSSs in RDs published between December 16, 2008 and December 16, 2018. Only English articles, original peer reviewed journals and conference papers describing a clinical prototype or a routine use of CDSSs were included. For data charting, we used the data items “Objective and background of the publication/project”, “System or project name”, “Functionality”, “Type of clinical data”, “Rare Diseases covered”, “Development status”, “System availability”, “Data entry and integration”, “Last software update” and “Clinical usage”.
Results: The search identified 636 articles. After title and abstracting screening, as well as assessing the eligibility criteria for full-text screening, 22 articles describing 19 different CDSSs were identified. Three types of CDSSs were classified: “Analysis or comparison of genetic and phenotypic data,” “machine learning” and “information retrieval”. Twelve of nineteen CDSSs use phenotypic and genetic data, followed by clinical data, literature databases and patient questionnaires. Fourteen of nineteen CDSSs are fully developed systems and therefore publicly available. Data can be entered or uploaded manually in six CDSSs, whereas for four CDSSs no information for data integration was available. Only seven CDSSs allow further ways of data integration. thirteen CDSS do not provide information about clinical usage.
Conclusions: Different CDSS for various purposes are available, yet clinicians have to determine which is best for their patient. To allow a more precise usage, future research has to focus on CDSSs RDs data integration, clinical usage and updating clinical knowledge. It remains interesting which of the CDSSs will be used and maintained in the future.
Background: Combined inhibition of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) complexes may be an efficient treatment for acute leukemia. The primary objective of this phase I single center open label study was to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of the dual pan-class I PI3K and mTOR inhibitor BEZ235 in patients with advanced leukemia.
Methods: Herein patients > 18 years of age who had relapsed or showed refractory leukemia were treated with BEZ235 (orally at 300–400 mg BID (cohort − 1/1)) to assess safety, tolerability, preliminary efficacy and pharmacokinetic (PK). Adverse events data and serious adverse events were analyzed and haematological and clinical biochemistry toxicities were assessed from laboratory test parameters. Response was assessed for the first time at the end of cycle 1 (day 29) and after every subsequent cycle. Pharmacokinetic and pharmacodynamic analyses of BEZ235 were also included (BEZ235 plasma levels, phosphorylation of AKT, S6 and 4EBP1). On statistics this trial is a multiple ascending dose study in which a following variant of the 3 + 3 rule (“Rolling Six”), a minimum of 6 and a maximum of 12 patients was recruited for the dose escalation and another 5 were planned for the expansion phase.
Results: Twenty-four patients with ALL (n = 11) or AML (n = 12) or CML-BP (n = 1) were enrolled. All patients had failed one (n = 5) or more lines of therapy (n = 5) and 14 patients were in refractory / refractory relapse. No formal MTD was defined, stomatitis and gastrointestinal toxicity at 400 mg BID dose was considered incompatible with prolonged treatment. The RP2D of BEZ235 was defined as 300 mg BID. Four of 24 patients showed clinical benefit. Twenty-two of 24 patients discontinued because of progression, (median time to progression 27 days (4d-112d). There was no association between PK parameters and efficacy or tolerability.
Conclusions: Combined inhibition of PI3K and mTOR inhibits a clinically meaningful driver pathway in a small subset of patients with ALL, with no benefit in patients with AML.
Trial registration: ClinicalTrials.gov, identifier NCT01756118. retrospectively registered 19th December 2012, https://clinicaltrials.gov/ct2/show/NCT01756118.
Unter Endometriose versteht man das Auftreten von endometrialen Zellen und Zellverbänden außerhalb des Cavum uteri, welche dem hormonellen Zyklus unterliegen und zu rezidivierenden Beschwerden führen können. Die Inzidenz wird je nach Quelle mit 2–15 % der Frauen im reproduktionsfähigen Alter angegeben. Schmerzen und Fertilitätseinschränkung sind die führenden Symptome. Unter Kinderwunschpatientinnen liegt die Inzidenz bei 20–48 %.
Background: With refinements in diagnosis and therapy of gliomas, the importance of survival time as the sole outcome parameter has decreased, and patient-centered outcome parameters have gained interest. Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze the professional outcomes besides their neuro-oncological and functional evaluation after surgery for gliomas in eloquent areas.
Methods: We assessed neuro-oncological and functional outcomes of patients with gliomas WHO grades II and III undergoing surgery between 2012 and 2018. All patients underwent routine follow-up and adjuvant treatment. Treatment and survival parameters were collected prospectively. Repercussions of the disease on the patients’ professional status, socio-economic situation, and neurocognitive function were evaluated retrospectively with questionnaires.
Results: We analyzed data of 58 patients with gliomas (WHO II: 9; III: 49). Median patient age was 35.8 years (range 21–63 years). Awake surgery techniques were applied in 32 patients (55.2%). Gross total and subtotal tumor resections were achieved in 33 (56.9%) and 17 (29.3%) patients, respectively, whereas in 8 patients (13.8%) resection had to remain partial. Most patients (n = 46; 79.3%) received adjuvant treatment. Median follow up was 43.8 months (range 11–82 months). After treatment 41 patients (70.7%) were able to resume a working life. Median time until returning to work was 8.0 months (range 0.2–22.0 months). To be younger than 40 at the time of the surgery was associated with a higher probability to return to work (p < .001). Multivariable regression analysis showed that patient age < 40 years as well as occupational group and self-reported fatigue were factors independently associated with the ability to return to work.
Conclusion: The ability to resume professional activities following brain tumor surgery is an important patient-oriented outcome parameter. We found that the majority of patients with gliomas were able to return to work following surgical and adjuvant treatment. Preservation of neurological function is of utmost relevance for individual patients´ quality of life.
One current goal in native mass spectrometry is the assignment of binding affinities to noncovalent complexes. Here we introduce a novel implementation of the existing laser-induced liquid bead ion desorption (LILBID) mass spectrometry method: this new method, LILBID laser dissociation curves, assesses binding strengths quantitatively. In all LILBID applications, aqueous sample droplets are irradiated by 3 µm laser pulses. Variation of the laser energy transferred to the droplet during desorption affects the degree of complex dissociation. In LILBID laser dissociation curves, laser energy transfer is purposely varied, and a binding affinity is calculated from the resulting complex dissociation. A series of dsDNAs with different binding affinities was assessed using LILBID laser dissociation curves. The binding affinity results from the LILBID laser dissociation curves strongly correlated with the melting temperatures from UV melting curves and with dissociation constants from isothermal titration calorimetry, standard solution phase methods. LILBID laser dissociation curve data also showed good reproducibility and successfully predicted the melting temperatures and dissociation constants of three DNA sequences. LILBID laser dissociation curves are a promising native mass spectrometry binding affinity method, with reduced time and sample consumption compared to melting curves or titrations.
Background: Healthy volunteer registry donors have become the backbone of stem cell transplantation programs. While most registrants will never become actual donors, a small minority are called upon twice, most commonly for the same patient because of poor graft function. Anecdotal evidence provides no hard reasons to disallow second-time mobilized apheresis, but few centers have treated enough two-time donors for definitive conclusions. Moreover, for reasons unknown, the efficiency of G-CSF varies greatly between donations.
Methods: Comparison of outcomes of first vs. second donations can formally confirm G-CSF responsiveness as intrinsically, likely genetically, determined. In our database, we identified 60 donors (1.3%) who received two cycles of G-CSF 24 days to 4 years apart and systematically compared mobilization outcomes.
Results: First and second mobilization and collection proceeded without severe or unusual adverse effects. First-time mobilization efficiency was highly predictive of second-time mobilization. Neither mobilization efficiency nor time lag between donations affected the similarity of first- and second-time mobilization outcomes.
Conclusions: With the caveat that only donors with an unremarkable first donation were cleared for a second, our data indicate that a second donation is feasible, equally tolerable as a first donation, and efficient. Moreover, the data strongly support the notion of donor-intrinsic variables dictating mobilization response and argue against relevant damage to the stem cell compartment during mobilization with rhG-CSF.
The Izu–Bonin–Mariana volcanic arc is situated at a convergent plate margin where subduction initiation triggered the formation of MORB-like forearc basalts as a result of decompression melting and near-trench spreading. International Ocean Discovery Program (IODP) Expedition 352 recovered samples within the forearc basalt stratigraphy that contained unusual macroscopic globular textures hosted in andesitic glass (Unit 6, Hole 1440B). It is unclear how these andesites, which are unique in a stratigraphic sequence dominated by forearc basalts, and the globular textures therein may have formed. Here, we present detailed textural evidence, major and trace element analysis, as well as B and Sr isotope compositions, to investigate the genesis of these globular andesites. Samples consist of K2O-rich basaltic globules set in a glassy groundmass of andesitic composition. Between these two textural domains a likely hydrated interface of devitrified glass occurs, which, based on textural evidence, seems to be genetically linked to the formation of the globules. The andesitic groundmass is Cl rich (ca. 3000 µg/g ), whereas globules and the interface are Cl poor (ca. 300 µg/g ). Concentrations of fluid-mobile trace elements also appear to be fractionated in that globules and show enrichments in B, K, Rb, Cs, and Tl, but not in Ba and W relative to the andesitic groundmass, whereas the interface shows depletions in the latter, but is enriched in the former. Interestingly, globules and andesitic groundmass have identical Sr isotopic composition within analytical uncertainty ( 87Sr∕86Sr of 0.70580 ± 10 ), indicating that they likely formed from the same source. However, globules show high δ11 B (ca. + 7 ‰ ), whereas their host andesites are isotopically lighter (ca. – 1 ‰ ), potentially indicating that whatever process led to their formation either introduced heavier B isotopes to the globules, or induced stable isotope fractionation of B between globules and their groundmass. Based on the bulk of the textural information and geochemical data obtained from these samples, we conclude that these andesites likely formed as a result of the assimilation of shallowly altered oceanic crust (AOC) during forearc basaltic magmatism. Assimilation likely introduced radiogenic Sr, as well as heavier B isotopes to comparatively unradiogenic and low δ11B forearc basalt parental magmas (average 87Sr∕86Sr of 0.703284). Moreover, the globular textures are consistent with their formation being the result of fluid-melt immiscibility that was potentially induced by the rapid release of water from assimilated AOC whose escape likely formed the interface. If the globular textures present in these samples are indeed the result of fluid-melt immiscibility, then this process led to significant trace element and stable isotope fractionation. The textures and chemical compositions of the globules highlight the need for future experimental studies aimed at investigating the exsolution process with respect to potential trace element and isotopic fractionation in arc magmas that have perhaps not been previously considered.
1H, 13C, and 15N backbone chemical shift assignments of coronavirus-2 non-structural protein Nsp10
(2020)
The international Covid19-NMR consortium aims at the comprehensive spectroscopic characterization of SARS-CoV-2 RNA elements and proteins and will provide NMR chemical shift assignments of the molecular components of this virus. The SARS-CoV-2 genome encodes approximately 30 different proteins. Four of these proteins are involved in forming the viral envelope or in the packaging of the RNA genome and are therefore called structural proteins. The other proteins fulfill a variety of functions during the viral life cycle and comprise the so-called non-structural proteins (nsps). Here, we report the near-complete NMR resonance assignment for the backbone chemical shifts of the non-structural protein 10 (nsp10). Nsp10 is part of the viral replication-transcription complex (RTC). It aids in synthesizing and modifying the genomic and subgenomic RNAs. Via its interaction with nsp14, it ensures transcriptional fidelity of the RNA-dependent RNA polymerase, and through its stimulation of the methyltransferase activity of nsp16, it aids in synthesizing the RNA cap structures which protect the viral RNAs from being recognized by the innate immune system. Both of these functions can be potentially targeted by drugs. Our data will aid in performing additional NMR-based characterizations, and provide a basis for the identification of possible small molecule ligands interfering with nsp10 exerting its essential role in viral replication.
Background: The adequate allocation of inpatient care resources requires assumptions about the need for health care and how this need will be met. However, in current practice, these assumptions are often based on outdated methods (e.g. Hill-Burton Formula). This study evaluated floating catchment area (FCA) methods, which have been applied as measures of spatial accessibility, focusing on their ability to predict the need for health care in the inpatient sector in Germany.
Methods: We tested three FCA methods (enhanced (E2SFCA), modified (M2SFCA) and integrated (iFCA)) for their accuracy in predicting hospital visits regarding six medical diagnoses (atrial flutter/fibrillation, heart failure, femoral fracture, gonarthrosis, stroke, and epilepsy) on national level in Germany. We further used the closest provider approach for benchmark purposes. The predicted visits were compared with the actual visits for all six diagnoses using a correlation analysis and a maximum error from the actual visits of ± 5%, ± 10% and ± 15%.
Results: The analysis of 229 million distances between hospitals and population locations revealed a high and significant correlation of predicted with actual visits for all three FCA methods across all six diagnoses up to ρ = 0.79 (p < 0.001). Overall, all FCA methods showed a substantially higher correlation with actual hospital visits compared to the closest provider approach (up to ρ = 0.51; p < 0.001). Allowing a 5% error of the absolute values, the analysis revealed up to 13.4% correctly predicted hospital visits using the FCA methods (15% error: up to 32.5% correctly predicted hospital). Finally, the potential of the FCA methods could be revealed by using the actual hospital visits as the measure of hospital attractiveness, which returned very strong correlations with the actual hospital visits up to ρ = 0.99 (p < 0.001).
Conclusion: We were able to demonstrate the impact of FCA measures regarding the prediction of hospital visits in non-emergency settings, and their superiority over commonly used methods (i.e. closest provider). However, hospital beds were inadequate as the measure of hospital attractiveness resulting in low accuracy of predicted hospital visits. More reliable measures must be integrated within the proposed methods. Still, this study strengthens the possibilities of FCA methods in health care planning beyond their original application in measuring spatial accessibility.
The first evidence of spin alignment of vector mesons (K*0 and ϕ) in heavy-ion collisions at the Large Hadron Collider (LHC) is reported. The spin density matrix element ρ00 is measured at midrapidity (|y|< 0.5) in Pb-Pb collisions at a center-of-mass energy (√sNN) of 2.76 TeV
with the ALICE detector. ρ00 values are found to be less than 1/3 (1/3 implies no spin alignment) at low transverse momentum (pT<2 GeV/c) for K*0 and ϕ at a level of 3σ and 2σ, respectively. No significant spin alignment is observed for the K0S meson (spin = 0) in Pb-Pb collisions and for the vector mesons in pp collisions. The measured spin alignment is unexpectedly large but qualitatively consistent with the expectation from models which attribute it to a polarization of quarks in the presence of angular momentum in heavy-ion collisions and a subsequent hadronization by the process of recombination.
The transverse momentum (pT) differential yields of (anti-)3He and (anti-)3H measured in p-Pb collisions at sNN−−−√ = 5.02 TeV with ALICE at the Large Hadron Collider (LHC) are presented. The ratios of the pT-integrated yields of (anti-)3He and (anti-)3H to the proton yields are reported, as well as the pT dependence of the coalescence parameters B3 for (anti-)3He and (anti-)3H. For (anti-)3He, the results obtained in four classes of the mean charged-particle multiplicity density are also discussed. These results are compared to predictions from a canonical statistical hadronization model and coalescence approaches. An upper limit on the total yield of 4He¯ is determined.
Inclusive ψ(2S) production is measured in p-Pb collisions at the centre-of-mass energy per nucleon-nucleon pair sNN−−−√=8.16 TeV, using the ALICE detector at the CERN LHC. The production of ψ(2S) is studied at forward (2.03<ycms<3.53) and backward (−4.46<ycms<−2.96) centre-of-mass rapidity and for transverse momentum pT < 12 GeV/c via the decay to muon pairs. In this paper, we report the integrated as well as the ycms- and pT-differential inclusive production cross sections. Nuclear effects on ψ(2S) production are studied via the determination of the nuclear modification factor that shows a strong suppression at both forward and backward centre-of-mass rapidities. Comparisons with corresponding results for inclusive J/ψ show a similar suppression for the two states at forward rapidity (p-going direction), but a stronger suppression for ψ(2S) at backward rapidity (Pb-going direction). As a function of pT, no clear dependence of the nuclear modification factor is found. The relative size of nuclear effects on ψ(2S) production compared to J/ψ is also studied via the double ratio of production cross sections [σψ(2S)/σJ/ψ]pPb/[σψ(2S)/σJ/ψ]pp between p-Pb and pp collisions. The results are compared with theoretical models that include various effects related to the initial and final state of the collision system and also with previous measurements at sNN−−−√ = 5.02 TeV.
The ALICE collaboration at the CERN LHC reports novel measurements of jet substructure in pp collisions at s√= 7 TeV and central Pb-Pb collisions at sNN−−−√ = 2.76 TeV. Jet substructure of track-based jets is explored via iterative declustering and grooming techniques. We present the measurement of the momentum sharing of two-prong substructure exposed via grooming, the zg, and its dependence on the opening angle, in both pp and Pb-Pb collisions. We also present the first measurement of the distribution of the number of branches obtained in the iterative declustering of the jet, which is interpreted as the number of its hard splittings. In Pb-Pb collisions, we observe a suppression of symmetric splittings at large opening angles and an enhancement of splittings at small opening angles relative to pp collisions, with no significant modification of the number of splittings. The results are compared to predictions from various Monte Carlo event generators to test the role of important concepts in the evolution of the jet in the medium such as color coherence.
One of the key challenges for nuclear physics today is to understand from first principles the effective interaction between hadrons with different quark content. First successes have been achieved using techniques that solve the dynamics of quarks and gluons on discrete space-time lattices1,2. Experimentally, the dynamics of the strong interaction have been studied by scattering hadrons off each other. Such scattering experiments are difficult or impossible for unstable hadrons3,4,5,6 and so high-quality measurements exist only for hadrons containing up and down quarks7. Here we demonstrate that measuring correlations in the momentum space between hadron pairs8,9,10,11,12 produced in ultrarelativistic proton–proton collisions at the CERN Large Hadron Collider (LHC) provides a precise method with which to obtain the missing information on the interaction dynamics between any pair of unstable hadrons. Specifically, we discuss the case of the interaction of baryons containing strange quarks (hyperons). We demonstrate how, using precision measurements of proton–omega baryon correlations, the effect of the strong interaction for this hadron–hadron pair can be studied with precision similar to, and compared with, predictions from lattice calculations13,14. The large number of hyperons identified in proton–proton collisions at the LHC, together with accurate modelling15 of the small (approximately one femtometre) inter-particle distance and exact predictions for the correlation functions, enables a detailed determination of the short-range part of the nucleon-hyperon interaction.
Scattering studies with low-energy kaon-proton femtoscopy in proton-proton collisions at the LHC
(2020)
The study of the strength and behaviour of the antikaon-nucleon (K¯¯¯¯N) interaction constitutes one of the key focuses of the strangeness sector in low-energy Quantum Chromodynamics (QCD). In this letter a unique high-precision measurement of the strong interaction between kaons and protons, close and above the kinematic threshold, is presented. The femtoscopic measurements of the correlation function at low pair-frame relative momentum of (K+ p ⊕ K− p¯¯¯) and (K− p ⊕ K+ p¯¯¯) pairs measured in pp collisions at s√ = 5, 7 and 13 TeV are reported. A structure observed around a relative momentum of 58 MeV/c in the measured correlation function of (K− p ⊕ K+ p¯¯¯) with a significance of 4.4. σ constitutes the first experimental evidence for the opening of the (K¯¯¯¯0n⊕K0n¯¯¯) isospin breaking channel due to the mass difference between charged and neutral kaons. The measured correlation functions have been compared to Jülich and Kyoto models in addition to the Coulomb potential. The high-precision data at low relative momenta presented in this work prove femtoscopy to be a powerful complementary tool to scattering experiments and provide new constraints above the K¯¯¯¯N threshold for low-energy QCD chiral models.
Scattering studies with low-energy kaon-proton femtoscopy in proton–proton collisions at the LHC
(2020)
The study of the strength and behaviour of the antikaon-nucleon (K¯¯¯¯N) interaction constitutes one of the key focuses of the strangeness sector in low-energy Quantum Chromodynamics (QCD). In this letter a unique high-precision measurement of the strong interaction between kaons and protons, close and above the kinematic threshold, is presented. The femtoscopic measurements of the correlation function at low pair-frame relative momentum of (K+ p ⊕ K− p¯¯¯) and (K− p ⊕ K+ p¯¯¯) pairs measured in pp collisions at s√ = 5, 7 and 13 TeV are reported. A structure observed around a relative momentum of 58 MeV/c in the measured correlation function of (K− p ⊕ K+ p¯¯¯) with a significance of 4.4. σ constitutes the first experimental evidence for the opening of the (K¯¯¯¯0n⊕K0n¯¯¯) isospin breaking channel due to the mass difference between charged and neutral kaons. The measured correlation functions have been compared to Jülich and Kyoto models in addition to the Coulomb potential. The high-precision data at low relative momenta presented in this work prove femtoscopy to be a powerful complementary tool to scattering experiments and provide new constraints above the K¯¯¯¯N threshold for low-energy QCD chiral models.
J/ψ production as a function of charged-particle multiplicity in p–Pb collisions at √sNN = 8.16 TeV
(2020)
Inclusive J/ψ yields and average transverse momenta in p-Pb collisions at a center-of-mass energy per nucleon pair sNN−−−√ = 8.16 TeV are measured as a function of the charged-particle pseudorapidity density with ALICE. The J/ψ mesons are reconstructed at forward (2.03<ycms<3.53) and backward (−4.46<ycms<−2.96) center-of-mass rapidity in their dimuon decay channel while the charged-particle pseudorapidity density is measured around midrapidity. The J/ψ yields at forward and backward rapidity normalized to their respective average values increase with the normalized charged-particle pseudorapidity density, the former showing a weaker increase than the latter. The normalized average transverse momenta at forward and backward rapidity manifest a steady increase from low to high charged-particle pseudorapidity density with a saturation beyond the average value.
Objective To evaluate the success of initiation of adjunctive brivaracetam in patients who required a change in antiepileptic drug (AED) regimen and substituted at least one AED with brivaracetam. Methods In this retrospective noninterventional study conducted in specialized epilepsy centers across Germany, patients initiated adjunctive brivaracetam between February 15, 2016, and August 31, 2016, as part of an intended change in AED regimen. The primary effectiveness variable was the proportion of patients who continued on brivaracetam after 3 months, and withdrew at least one AED either before or within 6 months after brivaracetam initiation. Results Five hundred and six patients had at least one brivaracetam dose and were included in the safety set (SS). Four hundred and seventy patients started to reduce the dose of one AED before/after brivaracetam initiation, had at least one concomitant AED at brivaracetam initiation, and were included in the full analysis set (FAS) for effectiveness analyses. At baseline, patients had a median of seven lifetime AEDs and a median of 3.8 seizures/28 days. In the SS, 85.2% of patients withdrew one AED before/after initiation of brivaracetam, most commonly levetiracetam (49.4%). 46.2% of patients substituted another AED with brivaracetam within 24 hours (fast withdrawal). The proportions of patients (FAS) who continued on brivaracetam after 3 and 6 months and withdrew one AED were 75.5% and 46.6%, respectively. After 6 months, 32.1% of patients were 50% responders; 13.0% were seizure‐free. In the SS, 34.6% of patients reported treatment‐emergent adverse events (TEAEs); 21.9% had TEAEs that were assessed by the treating physician as drug‐related. Incidences of behavioral AEs before (3‐month baseline) and after brivaracetam initiation in patients who withdrew levetiracetam were 19.2% and 8.0%, respectively (5.0% and 7.7% in patients who withdrew other AEDs). Significance Brivaracetam was effective and well‐tolerated in patients who required a change in AED drug regimen and initiated adjunctive brivaracetam in German clinical practice.
Synaptic plasticity is the activity dependent alteration of the composition, form and strength of synapses and believed to be the underlying mechanism of learning and memory formation. While initial changes in synaptic transmission are caused by second messenger signaling pathways and rapid modifications in the cytoskeleton, to achieve stable and persistent changes at individual synapses, the expression of new mRNAs and proteins is required. The central dogma postulated that the cell body is the only source of newly synthesized proteins. For neurons, with their unique morphology, this meant that proteins would need be transported long distances, often hundreds of microns, to reach their destined locations in dendrites and at spines. To overcome this limitation, neurons have developed a strategy to regulate protein synthesis locally by distributing thousands of mRNAs into neuronal processes and use them for local protein synthesis. Ample research has demonstrated the importance of local protein synthesis to many forms of long-term synaptic plasticity. One potential regulator of mRNA localization and local translation in neurons are non-coding RNAs. Intensive work over the past decades has highlighted the importance of non-coding RNAs in many aspects of brain function. The aim of this thesis is to obtain a better understanding of the role of non-coding RNAs in synaptic function and plasticity in the murine hippocampus. For this, we focused our studies on two classes of non-coding RNAs.
In the first part of my thesis, I describe our efforts on characterizing circular RNAs, a novel and peculiar family of non-coding RNAs, in the murine hippocampus by combining high throughput RNA-Sequencing with fluorescence in situ hybridization. Furthermore, we investigated the mechanisms of circular RNA biogenesis in hippocampal neurons by temporarily inhibiting spliceosome activity and analyzing the differentially regulated circular RNAs.
The compound class of the fabclavines was described as secondary or specialized metabolites (SM) for Xenorhabdus budapestensis and X. szentirmaii. Their corresponding structure was elucidated by NMR and further derivatives could be identified in both strains. Biochemically, fabclavines are hybrid SMs derived from two non-ribosomal-peptide-synthetases (NRPS), one type I polyketide-synthase (PKS) and polyunsaturated fatty acid (PUFA) synthases. In detail, a hexapeptide is connected via partially reduced polyketide units to an unsual polyamine. Structurally, they are related to the (pre-)zeamines, described for Serratia plymuthica and Dickeya zeae. Fabclavines exhibit a broad-spectrum bioactivity against a variety of different organisms like Grampositive and Gram-negative bacteria, fungi, protozoa but also against eukaryotic celllines.
In this work, the fabclavine biosynthesis was elucidated and assigned to two independently working assembly lines. The NRPS-PKS-pathway is initiated by the first NRPS FclI via generation of a tetrapeptide, which is elongated by the second NRPS FclJ, leading to a hexapeptide. Alternatively, FclJ can also act as direct start of the biosynthesis, resulting in the final formation of shortened fabclavine derivatives with a diinstead of a hexapeptide. In both cases, the peptide moiety is transferred to the iterative type I PKS FclK, leading to an elongation with partially reduced polyketide units. The resulting NRPS-PKS-intermediate is still enzyme-bound. The PUFA-homologues FclC, FclD and FclE in combination with FclF, FclG and FclH belong to the polyamine-forming pathway. Briefly, repeating decarboxylative Claisen thioester condensation reactions of acyl-coenzym A building blocks lead to the generation of an acyl chain in a PKS- or fatty acid biosynthesis-like manner. The corresponding β-keto-groups are either completely reduced or transaminated in a specific and repetitive way, resulting in the concatenation of so-called amine-units. The final β-keto-group is reduced to a hydroxy-group and the intermediate is reductively released by the thioester reductase FclG. A subsequent transamination step leads to the final polyamine. The NRPS-PKS- as well as the polyamine-pathway are connected by FclL. This condensation domain-like protein catalyzes the condensation of the polyamine with the NRPS-PKS-part, which results in the release of the final fabclavine. The results are described in detail in the first publication (first author).
Fabclavine biosynthesis gene cluster (BGC) are widely spread among the genus Xenorhabdus and Photorhabdus. In Xenorhabdus strains a high degree of conservation regarding the BGC synteny as well as the identity of single proteins can be observed. However, Photorhabdus strains harbor only the PUFA-homologues. While in Photorhabdus no product could be detected, our analysis revealed that the Xenorhabdus strains produce a large chemical diversity of different derivatives. Briefly, the general backbone of the fabclavines is conserved and only four chemical moieties are variable: The second and last amino acids of the NRPS-part, the number of incorporated polyketide units as well as the number of amine units in the polyamine. In combination with the elucidated biosynthesis, these variables could be assigned to single biosynthesis components as diversity mechanisms. Together with the 10 already described derivatives, a total of 32 derivatives could be detected. Interestingly, except for taxonomic closely related strains, all analyzed strains produce their own set of derivatives. Finally, we could confirm that the fabclavines are the major bioactive compound class in the analyzed strains under laboratory conditions. The results are described in detail in the second publication (first author).
Together with our collaboration partner Prof. Selcuk Hazir a potent bioactivity against Enterococcus faecalis, which is associated with endodontic infections, could be contributed to X. cabanillasii. Here, we could confirm that this bioactivity can be assigned to the fabclavines. The results are described in detail in the third publication(co-author).
Among the genus Xenorhabdus, X. bovienii represents an exception as its NRPS and PKS genes of the fabclavine BGC are missing or truncated, resulting in the exclusive production of polyamines. Furthermore, its PUFA-homologue FclC harbors an additional dehydratase (DH) domain. Upon extensive analysis a yet unknown deoxy-polyamine was identified and assigned to this additional domain. Finally, the DH domain was transferred into other polyamine pathways. Regardless of an in cis or in trans integration, the chimeric pathways produced deoxy-derivatives of its naturally occurring polyamines, suggesting that this represents another diversification mechanism. The results are described in detail in the attached manuscript (first author).
Comprehensive analysis of tumour sub-volumes for radiomic risk modelling in locally advanced HNSCC
(2020)
Simple Summary: Radiomic risk models are usually based on imaging features, which are extracted from the entire gross tumour volume (GTV entire ). This approach does not explicitly consider the complex biological structure of the tumours. Therefore, in this retrospective study, we investigated the prognostic value of radiomic analyses based on different tumour sub-volumes using computed tomography imaging of patients with locally advanced head and neck squamous cell carcinoma who were treated with primary radio-chemotherapy. The GTV entire was cropped by different margins to define the rim and corresponding core sub-volumes of the tumour. Furthermore, the best performing tumour rim sub-volume was extended into surrounding tissue with different margins. As a result, the models based on the 5 mm tumour rim and on the 3 mm extended rim sub-volume showed an improved performance compared to models based on the corresponding tumour core. This indicates that the consideration of tumour sub-volumes may help to improve radiomic risk models.
Abstract: Imaging features for radiomic analyses are commonly calculated from the entire gross tumour volume (GTVentire). However, tumours are biologically complex and the consideration of different tumour regions in radiomic models may lead to an improved outcome prediction. Therefore, we investigated the prognostic value of radiomic analyses based on different tumour sub-volumes using computed tomography imaging of patients with locally advanced head and neck squamous cell carcinoma. The GTVentire was cropped by different margins to define the rim and the corresponding core sub-volumes of the tumour. Subsequently, the best performing tumour rim sub-volume was extended into surrounding tissue with different margins. Radiomic risk models were developed and validated using a retrospective cohort consisting of 291 patients in one of the six Partner Sites of the German Cancer Consortium Radiation Oncology Group treated between 2005 and 2013. The validation concordance index (C-index) averaged over all applied learning algorithms and feature selection methods using the GTVentire achieved a moderate prognostic performance for loco-regional tumour control (C-index: 0.61 ± 0.04 (mean ± std)). The models based on the 5 mm tumour rim and on the 3 mm extended rim sub-volume showed higher median performances (C-index: 0.65 ± 0.02 and 0.64 ± 0.05, respectively), while models based on the corresponding tumour core volumes performed less (C-index: 0.59 ± 0.01). The difference in C-index between the 5 mm tumour rim and the corresponding core volume showed a statistical trend (p = 0.10). After additional prospective validation, the consideration of tumour sub-volumes may be a promising way to improve prognostic radiomic risk models.
Purpose: To develop and validate a CT-based radiomics signature for the prognosis of loco-regional tumour control (LRC) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by primary radiochemotherapy (RCTx) based on retrospective data from 6 partner sites of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG).
Material and methods: Pre-treatment CT images of 318 patients with locally advanced HNSCC were collected. Four-hundred forty-six features were extracted from each primary tumour volume and then filtered through stability analysis and clustering. First, a baseline signature was developed from demographic and tumour-associated clinical parameters. This signature was then supplemented by CT imaging features. A final signature was derived using repeated 3-fold cross-validation on the discovery cohort. Performance in external validation was assessed by the concordance index (C-Index). Furthermore, calibration and patient stratification in groups with low and high risk for loco-regional recurrence were analysed.
Results: For the clinical baseline signature, only the primary tumour volume was selected. The final signature combined the tumour volume with two independent radiomics features. It achieved moderately good discriminatory performance (C-Index [95% confidence interval]: 0.66 [0.55–0.75]) on the validation cohort along with significant patient stratification (p = 0.005) and good calibration.
Conclusion: We identified and validated a clinical-radiomics signature for LRC of locally advanced HNSCC using a multi-centric retrospective dataset. Prospective validation will be performed on the primary cohort of the HNprädBio trial of the DKTK-ROG once follow-up is completed.
Degeneration of neurons, such as the inner ear spiral ganglion neurons (SGN), may be decelerated or even stopped by neurotrophic factor treatment, such as brain-derived neurotrophic factor (BDNF), as well as electrical stimulation (ES). In a clinical setting, drug treatment of the SGN could start directly during implantation of a cochlear implant, whereas electrical stimulation begins days to weeks later. The present study was conducted to determine the effects of consecutive BDNF and ES treatments on SGN density and electrical responsiveness. An electrode drug delivery device was implanted in guinea pigs 3 weeks after deafening and five experimental groups were established: two groups received intracochlear infusion of artificial perilymph (AP) or BDNF; two groups were treated with AP respectively BDNF in addition to ES (AP + ES, BDNF + ES); and one group received BDNF from the day of implantation until day 34 followed by ES (BDNF ⇨ ES). Electrically evoked auditory brainstem responses were recorded. After one month of treatment, the tissue was harvested and the SGN density was assessed. The results show that consecutive treatment with BDNF and ES was as successful as the simultaneous combined treatment in terms of enhanced SGN density compared to the untreated contralateral side but not in regard to the numbers of protected cells.
The two new species Phyllobaenus thomasi (Campeche, Oaxaca, Quintana Roo and Yucatán, Mexico, and Belize) and P. turnbowi (San Luis Potosi, Mexico), are described (Coleoptera: Cleridae: Hydnocerinae: Hydnocerini). The primary types are photographed and intrageneric relationships of the species are discussed.
Updated distributions are provided for all three species of Phlegyas Stål (Hemiptera: Heteroptera: Pachygronthidae) in the New World: Phlegyas abbreviatus (Uhler, 1876), P. annulicrus Stål, 1869, and P. patruelis Berg, 1883. In total, four new state records for the United States of America, four new state records for Mexico, one new Canadian provincial record, and one new country record (Nicaragua, P. annulicrus) are presented, along with remarks and corrections.
Sphingosine 1-phosphate (S1P), derived from membrane sphingolipids, is a pleiotropic bioactive lipid mediator capable of evoking complex immune phenomena. Studies have highlighted its importance regarding intracellular signaling cascades as well as membrane-bound S1P receptor (S1PR) engagement in various clinical conditions. In neurological disorders, the S1P–S1PR axis is acknowledged in neurodegenerative, neuroinflammatory, and cerebrovascular disorders. Modulators of S1P signaling have enabled an immense insight into fundamental pathological pathways, which were pivotal in identifying and improving the treatment of human diseases. However, its intricate molecular signaling pathways initiated upon receptor ligation are still poorly elucidated. In this review, the authors highlight the current evidence for S1P signaling in neurodegenerative and neuroinflammatory disorders as well as stroke and present an array of drugs targeting the S1P signaling pathway, which are being tested in clinical trials. Further insights on how the S1P–S1PR axis orchestrates disease initiation, progression, and recovery may hold a remarkable potential regarding therapeutic options in these neurological disorders.
Emerging evidence suggests a complex relationship between sphingosine 1-phosphate (S1P) signaling and stroke. Here, we show the kinetics of S1P in the acute phase of ischemic stroke and highlight accompanying changes in immune cells and S1P receptors (S1PR). Using a C57BL/6 mouse model of middle cerebral artery occlusion (MCAO), we assessed S1P concentrations in the brain, plasma, and spleen. We found a steep S1P gradient from the spleen towards the brain. Results obtained by qPCR suggested that cells expressing the S1PR type 1 (S1P1+) were the predominant population deserting the spleen. Here, we report the cerebral recruitment of T helper (TH) and regulatory T (TREG) cells to the ipsilateral hemisphere, which was associated with differential regulation of cerebral S1PR expression patterns in the brain after MCAO. This study provides insight that the S1P-S1PR axis facilitates splenic T cell egress and is linked to the cerebral recruitment of S1PR+ TH and TREG cells. Further insights by which means the S1P-S1PR-axis orchestrates neuronal positioning may offer new therapeutic perspectives after ischemic stroke.
Designed multitarget ligands are a popular approach to generating efficient and safe drugs, and fragment-based strategies have been postulated as a versatile avenue to discover multitarget ligand leads. To systematically probe the potential of fragment-based multiple ligand discovery, we have employed a large fragment library for comprehensive screening on five targets chosen from proteins for which multitarget ligands have been successfully developed previously (soluble epoxide hydrolase, leukotriene A4 hydrolase, 5-lipoxygenase, retinoid X receptor, farnesoid X receptor). Differential scanning fluorimetry served as primary screening method before fragments hitting at least two targets were validated in orthogonal assays. Thereby, we obtained valuable fragment leads with dual-target engagement for six out of ten target combinations. Our results demonstrate the applicability of fragment-based approaches to identify starting points for polypharmacological compound development with certain limitations.
Understanding effects of emotional valence and stress on children’s memory is important for educational and legal contexts. This study disentangles the effects of emotional content of to-be-remembered information (i.e., items differing in emotional valence and arousal), stress exposure, and associated cortisol secretion on children’s memory. We also examine whether girls’ memory is more affected by stress induction. 143 6-to-7-year-old children were randomly allocated to the Trier Social Stress Test for Children (n = 103) or a control condition (n = 40). 25 minutes after stressor onset, children incidentally encoded 75 objects varying in emotional valence (crossed with arousal) together with neutral scene backgrounds. We found that response-bias corrected memory was worse for low arousing negative items than neutral and positive items, with the latter two categories not being different from each other. Whilst boys’ memory was largely unaffected by stress, girls in the stress condition showed worse memory for negative items, especially the low arousing ones, than girls in the control condition. Girls, compared to boys, reported higher subjective stress increases following stress exposure, and had higher cortisol stress responses. Whilst a higher cortisol stress response was associated with better emotional memory in girls in the stress condition, boys’ memory was not associated with their cortisol secretion. Taken together, our study suggests that 6-to-7-year-old children, more so girls, show memory suppression for negative information. Girls’ memory for negative information, compared to boys, is also more strongly modulated by stress experience and the associated cortisol response.
Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving.
Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data.
Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR).
Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.
Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new VH1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC50 = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505SOSIP.664 Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection.
With a growing Muslim population, many European countries need to integrate Muslims into their societies. One aspect that can hinder successful integration are substantial differences in human values. This is because such values are consequential for attitudes as well as behavior. We compare basic human values between Muslim immigrants and non-Muslim natives in four European countries with distinct immigration histories and integration politics: Belgium, France, Germany, and Sweden. For most insightful comparisons, we contrast values of Muslim immigrants with those of Christian natives as well as those of non-religious natives. We employ data of more than 50,000 individuals based on the first eight waves of the European Social Survey. Our findings reveal significant differences in value priorities between Muslims, Christians and non-religious individuals in all four countries. Amongst other things, Muslim immigrants score particularly high in conservation values (security and tradition/conformity). At the same time, they also score higher in self-transcendence values (benevolence as well as universalism). While many of these findings are in line with theory and previous research, the higher score in universalism is unexpected. A potential explanation is the combination of religious traditionalism and discrimination experiences. In other words, religious traditions are associated with more conservative views, but being subject to marginalization can still result in an appreciation of equal opportunities. We find only limited support for differences in hedonism. Religiosity correlates with values of tradition/conformity for Muslim immigrants as well as for Christian natives. Thus, accounting for religiosity renders differences in these values between Muslims and other groups statistically insignificant. While most of these findings hold in all countries, differences are most pronounced in Sweden and lower in the other three countries, which is also true after accounting for differences in socio-economic status and religiosity between the three groups. This suggests that a combination of a country's history of diversity and national integration policies either encourages the convergence of values or leads to a solidification of value differences between groups. We discuss these political and social implications of our findings.
Auf das richtige Maß kommt es an : wie beeinflussen digitale Medien unser Denken und Handeln?
(2020)
Welchen Einfluss haben digitale Technologien auf das menschliche Wahrnehmen, Denken und Handeln? Schaden Computerspiele der Entwicklung junger Gehirne? Und gibt es tatsächlich so etwas wie eine »digitale Demenz«, eine durch die Nutzung moderner Technologien bedingte wachsende Vergesslichkeit? Auf einige dieser Fragen gibt es bereits Antworten, die empirisch belegt sind.
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.
Some anaerobic bacteria use biotin-dependent Na+-translocating decarboxylases (Bdc) of β-keto acids or their thioester analogs as key enzymes in their energy metabolism. Glutaconyl-CoA decarboxylase (Gcd), a member of this protein family, drives the endergonic translocation of Na+ across the membrane with the exergonic decarboxylation of glutaconyl-CoA (ΔG0’ ≈−30 kJ/mol) to crotonyl-CoA. Here, we report on the molecular characterization of Gcd from Clostridium symbiosum based on native PAGE, size exclusion chromatography (SEC) and laser-induced liquid bead ion desorption mass spectrometry (LILBID-MS). The obtained molecular mass of ca. 400 kDa fits to the DNA sequence-derived mass of 379 kDa with a subunit composition of 4 GcdA (65 kDa), 2 GcdB (35 kDa), GcdC1 (15 kDa), GcdC2 (14 kDa), and 2 GcdD (10 kDa). Low-resolution structural information was achieved from preliminary electron microscopic (EM) measurements, which resulted in a 3D reconstruction model based on negative-stained particles. The Gcd structure is built up of a membrane-spanning base primarily composed of the GcdB dimer and a solvent-exposed head with the GcdA tetramer as major component. Both globular parts are bridged by a linker presumably built up of segments of GcdC1, GcdC2 and the 2 GcdDs. The structure of the highly mobile Gcd complex represents a template for the global architecture of the Bdc family.
Bone vasculature provides protection and signals necessary to control stem cell quiescence and renewal1. Specifically, type H capillaries, which highly express Endomucin, constitute the endothelial niche supporting a microenvironment of osteoprogenitors and long-term hematopoietic stem cells2–4. The age-dependent decline in type H endothelial cells was shown to be associated with bone dysregulation and accumulation of hematopoietic stem cells, which display cell-intrinsic alterations and reduced functionality3. The regulation of bone vasculature by chronic diseases, such as heart failure is unknown. Here, we describe the effects of myocardial infarction and post-infarction heart failure on the vascular bone cell composition. We demonstrate an age-independent loss of type H bone endothelium in heart failure after myocardial infarction in both mice and in humans. Using single-cell RNA sequencing, we delineate the transcriptional heterogeneity of human bone marrow endothelium showing increased expression of inflammatory genes, including IL1B and MYC, in ischemic heart failure. Inhibition of NLRP3-dependent IL-1β production partially prevents the post-myocardial infarction loss of type H vasculature in mice. These results provide a rationale for using anti-inflammatory therapies to prevent or reverse the deterioration of vascular bone function in ischemic heart disease.
Background and Aim: Several studies observed alterations in the gut microbiota in patients with non‐alcoholic fatty liver disease (NAFLD). However, analyzed patient populations and methods strongly differ among these studies. The aim of this study was to prove the reproducibility of published results and to provide a detailed overview of all findings in our NAFLD cohort using next generation sequencing methods.
Methods: The individual taxonomic microbiota composition of fecal samples from 90 NAFLD patients and 21 healthy controls was analyzed using 16S rRNA gene sequencing. Study participants were grouped according to their disease stage and compared regarding their gut microbiota composition. Studies were identified from PubMed listed publications, and the results were compared with the findings in our cohort.
Results: Results from 13 identified studies were compared with our data. A decreased abundance of the Bacteroidetes and Ruminococcaceae as well as an increased abundance of Lactobacillaceae and Veillonellaceae and Dorea were the most frequently reported changes among NAFLD patients in 4/13, 5/13, 4/13, 2/13, and 3/13 studies, respectively. Even though these alterations in the gut microbiota composition were also observed in our patient cohort, the majority of published differences could not be reproduced, neither in our own nor in other NAFLD cohort studies.
Conclusion: Despite repeatedly reproduced abundance patterns of specific bacteria, the heterogeneous study results did not reveal a consistent disease specific gut microbiota signature. Further prospective studies with homogenous patient cohorts and standardized methods are necessary to phenotype NAFLD by the gut microbiota.
Overconsumption of carbohydrates and lipids are well known to cause nonalcoholic fatty liver disease (NAFLD), while the role of nutritional protein intake is less clear. In Western diet, meat and other animal products are the main protein source, with varying concentrations of specific amino acids. Whether the amount or composition of protein intake is associated with a higher risk for disease severity has not yet been examined. In this study, we investigated associations of dietary components with histological disease activity by analyzing detailed 14‐day food records in a cohort of 61 patients with biopsy‐proven NAFLD. Furthermore, we used 16S ribosomal RNA gene sequencing to detect associations with different abundances of the gut microbiota with dietary patterns. Patients with definite nonalcoholic steatohepatitis (NAFLD activity score of 5‐8 on liver biopsy) had a significantly higher daily relative intake of protein compared with patients with a NAFLD activity score of 0‐4 (18.0% vs. 15.8% of daily protein‐based calories, P = 0.018). After adjustment for several potentially confounding factors, a higher protein intake (≥17.3% of daily protein‐based calories) remained associated with definite nonalcoholic steatohepatitis, with an odds ratio of 5.09 (95% confidence interval 1.22‐21.25, P = 0.026). This association was driven primarily by serine, glycine, arginine, proline, phenylalanine, and methionine. A higher protein intake correlated with a lower Bacteroides abundance and an altered abundance of several other bacterial taxa. Conclusion: A high protein intake was independently associated with more active and severe histological disease activity in patients with NAFLD. Further studies are needed to investigate the potential harmful role of dietary amino acids on NAFLD, with special attention to meat as their major source.
Es ist schon merkwürdig: Für keines der großen Konzilien des Spätmittelalters schien in den letzten Jahren eine Gesamtdarstellung so nah wie im Fall des Pisanum. Dieter Girgensohn und Hélenè Millet legten eine Fülle von Einzelstudien vor, doch keiner der beiden goss sie in die Form eines opus magnum, sieht man von einem Aufsatzband der französischen Kollegin ab. Durch Mona Kirsch erfuhr die Synode 2016 eine zwar viele Facetten erfassende Würdigung im Rahmen einer ritualgeschichtlich grundierten Geschichte des allgemeinen Konzils im Spätmittelalter, zu der für sie aber die auf Pisa folgenden und damit eng verbundenen Versammlungen von Konstanz und Basel nicht gehörten. Und nun erklärt Florian Eßer gleich mehrfach, bei seinem hier anzuzeigenden, immerhin 874-seitigen Werk handele es sich keinesfalls um eine Gesamtdarstellung. Was die Frage aufwirft, wer angesichts einer solch zerklüfteten Landschaft partieller Monumente das finale Wagnis überhaupt noch angehen mag.
Am ehesten wohl Florian Eßer selbst, der eine auf umfassender Kenntnis der ungedruckten wie gedruckten Quellen beruhende und die gesamte Forschung zum Thema rezipierende Studie vorgelegt hat, die weniger als Dissertation – die sie ist – denn fast schon als Habilitationsschrift gelten darf. Nur wünscht man sich und ihm, dass er sich künftig in der Kunst des Kürzens und Streichens übt. Denn hier wird viel in der Sache wohlgemerkt Treffendes derart breit bis in die feinsten Einzelheiten und Verästelungen ausgeführt, ja ausgewalzt, dass dem Autor am Ende dabei offensichtlich selbst nicht mehr so recht wohl war, widmet er sein Opus doch Freundin, Eltern und Freunden, "auch wenn (beziehungsweise weil) sie es vermutlich nie lesen werden" (S. 14). ...
We use holography to study the dynamics of a strongly-coupled gauge theory in four-dimensional de Sitter space with Hubble rate H. The gauge theory is non-conformal with a characteristic mass scale M. We solve Einstein’s equations numerically and determine the time evolution of homogeneous gauge theory states. If their initial energy density is high compared with H4 then the early-time evolution is well described by viscous hydrodynamics with a non-zero bulk viscosity. At late times the dynamics is always far from equilibrium. The asymptotic late-time state preserves the full de Sitter symmetry group and its dual geometry is a domain-wall in AdS5. The approach to this state is characterised by an emergent relation of the form P = w E that is different from the equilibrium equation of state in flat space. The constant w does not depend on the initial conditions but only on H/M and is negative if the ratio H/M is close to unity. The event and the apparent horizons of the late-time solution do not coincide with one another, reflecting its non-equilibrium nature. In between them lies an “entanglement horizon” that cannot be penetrated by extremal surfaces anchored at the boundary, which we use to compute the entanglement entropy of boundary regions. If the entangling region equals the observable universe then the extremal surface coincides with a bulk cosmological horizon that just touches the event horizon, while for larger regions the extremal surface probes behind the event horizon.
We use the quantum null energy condition in strongly coupled two-dimensional field theories (QNEC2) as diagnostic tool to study a variety of phase structures, including crossover, second and first order phase transitions. We find a universal QNEC2 constraint for first order phase transitions with kinked entanglement entropy and discuss in general the relation between the QNEC2-inequality and monotonicity of the Casini-Huerta c-function. We then focus on a specific example, the holographic dual of which is modelled by three-dimensional Einstein gravity plus a massive scalar field with one free parameter in the self-interaction potential. We study translation invariant stationary states dual to domain walls and black branes. Depending on the value of the free parameter we find crossover, second and first order phase transitions between such states, and the c-function either flows to zero or to a finite value in the infrared. Strikingly, evaluating QNEC2 for ground state solutions allows to predict the existence of phase transitions at finite temperature.
We use the quantum null energy condition in strongly coupled two-dimensional field theories (QNEC2) as diagnostic tool to study a variety of phase structures, including crossover, second and first order phase transitions. We find a universal QNEC2 constraint for first order phase transitions with kinked entanglement entropy and discuss in general the relation between the QNEC2-inequality and monotonicity of the Casini-Huerta c-function. We then focus on a specific example, the holographic dual of which is modelled by three-dimensional Einstein gravity plus a massive scalar field with one free parameter in the self-interaction potential. We study translation invariant stationary states dual to domain walls and black branes. Depending on the value of the free parameter we find crossover, second and first order phase transitions between such states, and the c-function either flows to zero or to a finite value in the infrared. Strikingly, evaluating QNEC2 for ground state solutions allows to predict the existence of phase transitions at finite temperature.
Für ausgewählten Patienten mit Aortenklappeninsuffizienz (AI) bietet die Aortenklappenrekonstruktion eine sehr attraktive Alternative zum Klappenersatz, wodurch mögliche prothesenbezogene Komplikationen vermieden werden können.
Die begrenzte Zahl der Langzeitstudien sowie das Fehlen von standardisierten Verfahren machen die klappenerhaltende Aortenklappenchirurgie technisch anspruchsvoll.
Ziel dieser Arbeit ist es, die Langzeitergebnisse nach Aortenklappenrekonstruktion zu erfassen und die Haltbarkeit sowie die klappenbezogenen Komplikationen nach klappenerhaltender Aortenklappenchirurgie zu untersuchen.
Hierzu analysierten wir die klinischen Daten von 560 Patienten, die eine operative Versorgung mittels Aortenklappenrekonstruktion erhielten. Dabei wurden sowohl Segelpathologien (bikuspid sowie trikuspid) als auch Aortenwurzelpathologien berücksichtigt. Bei 56% der Patienten (n=313) wurde eine Reimplantation nach David durchgeführt. Bei 247 Patienten wurde bei isolierter Segelpathologie ohne Aortenwurzelbeteiligung eine Segelrekonstruktion durchgeführt. Pathologien der Aortenwurzel konnten mit subkommissuralen Nähten (bei 62 Patienten) oder mit Rekonstruktion des sinotubulären Übergangs (bei 60 Patienten) behoben werden. Begleitende Aorteneingriffe bei Aneurysma oder Dissektion der thorakalen Aorta wurden ebenfalls durchgeführt. So wurden bei 78 Patienten ein partieller Aortenbogenersatz, bei 12 Patienten ein kompletter Aortenbogenersatz und bei 14 Patienten ein Bogenersatz mit „Elephant Trunk“ Technik durchgeführt.
Die Nachuntersuchungen erfolgten anhand eines standardisierten Fragebogens 5 sowie durch transthorakal echokardiographische Verlaufskontrollen. Die durchschnittliche Nachuntersuchungszeit betrug 6.3 ± 4.6 Jahre, 97% der Patienten konnten dabei erfasst werden.
Die 30-Tage-Mortalität betrug 1,4%. Im Langzeitverlauf wurden 132 Verstorbene beobachtet, wobei 13 Patienten aufgrund eines kardiovaskulären Ereignisses verstarben. Das 10-Jahres-Überleben betrug 70%. Eine Reoperation war bei 39 Patienten notwendig, in 25 Fällen aufgrund von signifikanter Restinsuffizienz der Aortenklappe, in 5 Fällen aufgrund eines kombinierten Aortenklappenvitium. Endokarditis führte in 9 Fällen zur Reoperation (0,2% pro Patientenjahr). Die Freiheit von Reoperation betrug 88% nach 10 Jahren. Die klappenbezogenen Komplikationen ergaben eine kumulative linearisierte Inzidenz von 2% pro Patientenjahr.
Schlussfolgernd kann man sagen, dass die Aortenklappenrekonstruktion für ausgewählte Patienten eine gute Alternative zum Aortenklappenersatz darstellt. Die Haltbarkeit der Klappenfunktion erwies sich in der Langzeitbeobachtung als gut. Die adäquate Wahl der Operationstechnik bezogen auf die Pathologie führen zu guten Ergebnissen der Aortenklappenrekonstruktion mit akzeptabler Mortalität und Morbidität im Langzeitverlauf.
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.
Highlights
• German patients with LGS identified using most specific algorithm to date.
• Prevalence of probable LGS with epilepsy diagnosis before age 6 was 6.5 per 100,000.
• High healthcare costs of €22,787 PPY; mostly due to inpatient and home nursing care.
• Costs were greater in patients prescribed rescue medications.
• Over 10 years, LGS patients had significant mortality vs. controls (2.88 vs. 0.01%).
Abstract
Objective: This retrospective study examined patients with probable Lennox-Gastaut syndrome (LGS) identified from German healthcare data.
Methods: This 10-year study (2007–2016) assessed healthcare insurance claims information from the Vilua Healthcare research database. A selection algorithm considering diagnoses and drug prescriptions identified patients with probable LGS. To increase the sensitivity of the identification algorithm, two populations were defined: all patients with probable LGS (broadly defined) and only those with a documented epilepsy diagnosis before 6 years of age (narrowly defined). This specific criterion was used as LGS typically has a peak seizure onset between age 3 and 5 years. Primary analyses were prevalence and demographics; secondary analyses included healthcare costs, hospitalization rate and length of stay (LOS), medication use, and mortality.
Results: In the final year of the study, 545 patients with broadly defined probable LGS (mean [range] age: 31.4 [2–89] years; male: 53%) were identified. Using the narrowly defined probable LGS definition, the number of patients was reduced to 102 (mean [range] age: 7.4 [2–14] years; male: 52%). Prevalence of broadly defined and narrowly defined probable LGS was 39.2 and 6.5 per 100,000 people. During the 10-year study, 208 patients with narrowly defined probable LGS were identified and followed up for 1379 patient-years. The mean annual cost of healthcare was €22,787 per patient-year (PPY); greatest costs were attributable to inpatient care (33%), home nursing care (13%), and medication (10%). Mean annual healthcare costs were significantly greater for those with prescribed rescue medication (45% of patient-years) versus those without (€33,872 vs. €13,785 PPY, p < 0.001). Mean (standard deviation [SD]) annual hospitalization rate was 1.6 (2.0) PPY with mean (SD) annual LOS of 22.7 (46.0) days. Annual hospitalization rate was significantly greater in those who were prescribed rescue medication versus those who were not (2.2 [2.3] vs. 1.1 [1.6] PPY, p < 0.001). The mean (SD) number of different medications prescribed was 11.3 (7.3) PPY and 33.8 (17.0) over the entire observable time per patient (OET); antiepileptic drugs only accounted for 2.1 (1.1) of the medications prescribed PPY and 3.8 (2.0) OET. Over the 10-year study period, mortality in patients with narrowly defined probable LGS was significantly higher than the matched control population (six events [2.88%] vs. one event [0.01%], p < 0.001).
Conclusion: Annual healthcare costs incurred by patients with probable LGS in Germany were substantial, and mostly attributable to inpatient care, home nursing care, and medication. Patients prescribed with rescue medication incurred significantly greater costs than those who were not. Patients with narrowly defined probable LGS had a higher mortality rate versus control populations.
Metabolic differences between symbiont subpopulations in the deep-sea tubeworm Riftia pachyptila
(2020)
The hydrothermal vent tube worm Riftia pachyptila lives in intimate symbiosis with intracellular sulfur-oxidizing gammaproteobacteria. Although the symbiont population consists of a single 16S rRNA phylotype, bacteria in the same host animal exhibit a remarkable degree of metabolic diversity: They simultaneously utilize two carbon fixation pathways and various energy sources and electron acceptors. Whether these multiple metabolic routes are employed in the same symbiont cells, or rather in distinct symbiont subpopulations, was unclear. As Riftia symbionts vary considerably in cell size and shape, we enriched individual symbiont cell sizes by density gradient centrifugation in order to test whether symbiont cells of different sizes show different metabolic profiles. Metaproteomic analysis and statistical evaluation using clustering and random forests, supported by microscopy and flow cytometry, strongly suggest that Riftia symbiont cells of different sizes represent metabolically dissimilar stages of a physiological differentiation process: Small symbionts actively divide and may establish cellular symbiont-host interaction, as indicated by highest abundance of the cell division key protein FtsZ and highly abundant chaperones and porins in this initial phase. Large symbionts, on the other hand, apparently do not divide, but still replicate DNA, leading to DNA endoreduplication. Highest abundance of enzymes for CO2 fixation, carbon storage and biosynthesis in large symbionts indicates that in this late differentiation stage the symbiont’s metabolism is efficiently geared towards the production of organic material. We propose that this division of labor between smaller and larger symbionts benefits the productivity of the symbiosis as a whole.
Aim: Left ventricular non-compaction (LVNC) is perceived as a rare high-risk cardiomyopathy characterized by excess left ventricular (LV) trabeculation. However, there is increasing evidence contesting the clinical significance of LV hyper-trabeculation and the existence of LVNC as a distinct cardiomyopathy. The aim of this study is to assess the association of LV trabeculation extent with cardiovascular morbidity and all-cause mortality in patients undergoing clinical cardiac magnetic resonance (CMR) scans across 57 European centers from the EuroCMR registry.
Methods and Results: We studied 822 randomly selected cases from the EuroCMR registry. Image acquisition was according to international guidelines. We manually segmented images for LV chamber quantification and measurement of LV trabeculation (as per Petersen criteria). We report the association between LV trabeculation extent and important cardiovascular morbidities (stroke, atrial fibrillation, heart failure) and all-cause mortality prospectively recorded over 404 ± 82 days of follow-up. Maximal non-compaction to compaction ratio (NC/C) was mean (standard deviation) 1.81 ± 0.67, from these, 17% were above the threshold for hyper-trabeculation (NC/C > 2.3). LV trabeculation extent was not associated with increased risk of the defined outcomes (morbidities, mortality, LV CMR indices) in the whole cohort, or in sub-analyses of individuals without ischaemic heart disease, or those with NC/C > 2.3.
Conclusion: Among 882 patients undergoing clinical CMR, excess LV trabeculation was not associated with a range of important cardiovascular morbidities or all-cause mortality over ~12 months of prospective follow-up. These findings suggest that LV hyper-trabeculation alone is not an indicator for worse cardiovascular prognosis.
Evoked potentials in the amplitude-time spectrum of the electroencephalogram are commonly used to assess the extent of brain responses to stimulation with noxious contact heat. The magnitude of the N- and P-waves are used as a semi-objective measure of the response to the painful stimulus: the higher the magnitude, the more painful the stimulus has been perceived. The strength of the N-P-wave response is also largely dependent on the chosen reference electrode site. The goal of this study was to examine which reference technique excels both in practical and theoretical terms when analyzing noxious contact heat evoked potentials (CHEPS) in the amplitude-time spectrum. We recruited 21 subjects (10 male, 11 female, mean age of 55.79 years). We applied seven noxious contact heat stimuli using two temperatures, 51°C, and 54°C, to each subject. During EEG analysis, we aimed to identify the referencing technique which produces the highest N-wave and P-wave amplitudes with as little artifactual influence as possible. For this purpose, we applied the following six referencing techniques: mathematically linked A1/A2 (earlobes), average reference, REST, AFz, Pz, and mathematically linked PO7/PO8. We evaluated how these techniques impact the N-P amplitudes of CHEPS based on our data from healthy subjects. Considering all factors, we found that mathematically linked earlobes to be the ideal referencing site to use when displaying and evaluating CHEPS in the amplitude-time spectrum.
Recent studies have shown that the speciose Holarctic genera of Leiobunum C.L. Koch, 1839 and Nelima Roewer, 1910 are polyphyletic taxa, and therefore, the traditional diagnostic characters for these European genera of Leiobuninae Banks, 1893 (respectively, the presence or absence of tubercle rows on leg coxae) are unsuitable. We present the description of Leiolima iberica gen. et sp. nov., a new endemic harvestman from the north-western part of the Iberian Peninsula. The newly established genus shows intermediate characters between Leiobunum and Nelima. In addition, the new genus is characterized by shorter legs compared to Leiobunum and the presence of trichomes on all leg femora and pedipalpal patellae, a structure that is absent in all other western Palearctic genera of the subfamily Leiobuninae.
Recent samplings in cavities of the Iberian Peninsula led to the discovery of a new millipede species of the order Callipodida in one cave in the region of El Bierzo (León, Spain): Lusitanipus xanin sp. nov. In additional samplings (near that cave), more specimens of this new species were discovered in surface habitats. The species has various distinctive characteristics, such as its green colour, but the morphology of the gonopod has several similarities with that of Lusitanipus alternans (Verhoeff, 1893), indicating a close relationship between them. The diagnosis of the genus Lusitanipus Mauriès, 1978 has to be changed to accommodate the new species. The presence of crests in two different sizes is no longer a diagnostic character of the genus Lusitanipus, but of the species L. alternans. Lusitanipus xanin sp. nov. is the fourth species of the order Callipodida for the Iberian Peninsula, and the second species for the genus. Lusitanipus xanin sp. nov. seems to be an epigean but troglophile species.
Consuming dividends
(2020)
This paper studies why investors buy dividend-paying assets and how they time their consumption accordingly. We combine administrative bank data linking customers’ consumption transactions and income to detailed portfolio data and survey responses on financial behavior. We find that private consumption is excessively sensitive to dividend income. Investors across wealth, income, and age distributions increase spending precisely around days of dividend receipt. Importantly, the consumption response is driven by financially prudent investors who select dividend portfolios, anticipate dividend income, and plan consumption accordingly. Our results contribute to the literature on a dividend clientele and provide evidence of ‘planned’ excess sensitivity.
This article demonstrates the use of guided elastic waves (GEW) for multiple-in and multiple-out (MIMO) data communication in the framework of a structural health monitoring (SHM) system. Therefore, miniaturized low-voltage communication nodes have been developed. They are arranged in a spatially distributed and permanently installed network. Wireless exchange of encoded information across a metallic plate and a stiffened carbon-fiber reinforced plastics (CFRP) structure is investigated. A combination of square-wave excitation sequences and frequency-division multiplexing (FDM) is explored for parallel communication with multiple nodes. Moreover, the impact of the excitation-sequence length on the reliability of information transmission is studied in view of future energy-aware application scenarios. The presented system achieves in both studied structures error-free transmission at a data rate of 0.17 kbps (per carrier frequency) with a power consumption of 224 mW.
The third dataset dedicated to the Open Guided Waves platform aims at carbon fiber composite plates with an additional omega stringer at constant temperature conditions. The two structures used in this work are representative for real aircraft components. Comprehensive measurements were recorded in order to study (I) the impact of the omega stringer on guided wave propagation, and (II) elliptical reference damages of different sizes located at three separate positions on the structure. Measurements were recorded for narrowband excitation (5-cycle toneburst with varying carrier frequencies) and broadband excitation (using chirp waveforms). The paper presents the results of a technical validation including numerical modelling, and enables further research, for example related to probability of detection (POD) analysis.
A central motivation for the development of x-ray free-electron lasers has been the prospect of time-resolved single-molecule imaging with atomic resolution. Here, we show that x-ray photoelectron diffraction—where a photoelectron emitted after x-ray absorption illuminates the molecular structure from within—can be used to image the increase of the internuclear distance during the x-ray-induced fragmentation of an O2 molecule. By measuring the molecular-frame photoelectron emission patterns for a two-photon sequential K-shell ionization in coincidence with the fragment ions, and by sorting the data as a function of the measured kinetic energy release, we can resolve the elongation of the molecular bond by approximately 1.2 a.u. within the duration of the x-ray pulse. The experiment paves the road toward time-resolved pump-probe photoelectron diffraction imaging at high-repetition-rate x-ray free-electron lasers.
The retinoid X receptor (RXR) is a ligand-sensing transcription factor acting mainly as a universal heterodimer partner for other nuclear receptors. Despite presenting as a potential therapeutic target for cancer and neurodegeneration, adverse effects typically observed for RXR agonists, likely due to the lack of isoform selectivity, limit chemotherapeutic application of currently available RXR ligands. The three human RXR isoforms exhibit different expression patterns; however, they share high sequence similarity, presenting a major obstacle toward the development of subtype-selective ligands. Here, we report the discovery of the saturated fatty acid, palmitic acid, as an RXR ligand and disclose a uniform set of crystal structures of all three RXR isoforms in an active conformation induced by palmitic acid. A structural comparison revealed subtle differences among the RXR subtypes. We also observed an ability of palmitic acid as well as myristic acid and stearic acid to induce recruitment of steroid receptor co-activator 1 to the RXR ligand-binding domain with low micromolar potencies. With the high, millimolar endogenous concentrations of these highly abundant lipids, our results suggest their potential involvement in RXR signaling.
A new species of Limnophilinae (Diptera: Limoniidae), Dicranophragma (Brachylimnophila) relictum Mederos sp. nov., is described. This is the third species of this genus recorded from the Iberian Peninsula. This new species was discovered in a cave in the Sant Llorenç del Munt i Serra de l’Obac Natural Park, Barcelona Province (Catalonia) and it is the first record of a species of this genus from a hypogeous environment. The absence of suitable ecological conditions for the survival of this new species, particularly in the vicinity of the cave, suggests that this population of D. relictum Mederos sp. nov. is isolated. Dicranophragma relictum Mederos sp. nov. is characterized by the following features: a general grey-to-greenish-grey coloration on its thorax and a dark-grey abdomen; wings more than four times longer than wide; pale-brown-to-yellowish tinted wings, with brown veins and a well-marked stigma; in the male genitalia the upper part of the aedeagus is acute when viewed laterally and is longer than the lower part. A key is provided for separating the three species of Dicranophragma known to be present in the Iberian Peninsula.
Non-alcoholic steatohepatitis (NASH) - a hepatic manifestation of the metabolic syndrome - is a multifactorial disease with alarming global prevalence. It involves steatosis, inflammation and fibrosis in the liver, thus demanding multiple modes of action for robust therapeutic efficacy. Aiming to fuse complementary validated anti-NASH strategies in a single molecule, we have designed and systematically optimized a scaffold for triple activation of farnesoid X receptor (FXR), peroxisome proliferator-activated receptor (PPAR) α and PPARδ. Pilot profiling of the resulting triple modulator demonstrated target engagement in native cellular settings and in mice, rendering it a suitable tool to probe the triple modulator concept in vivo. In DIO NASH in mice, the triple agonist counteracted hepatic inflammation and reversed hepatic fibrosis highlighting the potential of designed polypharmacology in NASH.
Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development.
Methods: To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal.
Results: In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants.
Conclusion: Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.
Pathogenic variants in PRRT2, encoding the proline-rich transmembrane protein 2, have been associated with an evolving spectrum of paroxysmal neurologic disorders. Based on a cohort of children with PRRT2-related infantile epilepsy, this study aimed at delineating the broad clinical spectrum of PRRT2-associated phenotypes in these children and their relatives. Only a few recent larger cohort studies are on record and findings from single reports were not confirmed so far. We collected detailed genetic and phenotypic data of 40 previously unreported patients from 36 families. All patients had benign infantile epilepsy and harbored pathogenic variants in PRRT2 (core cohort). Clinical data of 62 family members were included, comprising a cohort of 102 individuals (extended cohort) with PRRT2-associated neurological disease. Additional phenotypes in the cohort of patients with benign sporadic and familial infantile epilepsy consist of movement disorders with paroxysmal kinesigenic dyskinesia in six patients, infantile-onset movement disorders in 2 of 40 individuals, and episodic ataxia after mild head trauma in one girl with bi-allelic variants in PRRT2. The same girl displayed a focal cortical dysplasia upon brain imaging. Familial hemiplegic migraine and migraine with aura were reported in nine families. A single individual developed epilepsy with continuous spikes and waves during sleep. In addition to known variants, we report the novel variant c.843G>T, p.(Trp281Cys) that co-segregated with benign infantile epilepsy and migraine in one family. Our study highlights the variability of clinical presentations of patients harboring pathogenic PRRT2 variants and expands the associated phenotypic spectrum.
Coherent photoproduction of ρ⁰ vector mesons in ultra-peripheral Pb-Pb collisions at √sNN = 5.02 TeV
(2020)
Cross sections for the coherent photoproduction of ρ0 vector mesons in ultra-peripheral Pb-Pb collisions at sNN−−−√ = 5.02 TeV are reported. The measurements, which rely on the π+π− decay channel, are presented in three regions of rapidity covering the range |y| < 0.8. For each rapidity interval, cross sections are shown for different nuclear-breakup classes defined according to the presence of neutrons measured in the zero-degree calorimeters. The results are compared with predictions based on different models of nuclear shadowing. Finally, the observation of a coherently produced resonance-like structure with a mass around 1.7 GeV/c2 and a width of about 140 MeV/c2 is reported and compared with similar observations from other experiments.
CO2 has been electrochemically reduced to the intermediate formate, which was subsequently used as sole substrate for the production of the polymer polyhydroxybutyrate (PHB) by the microorganism Cupriavidus necator. Faradaic efficiencies (FE) up to 54 % have been reached with Sn‐based gas‐diffusion electrodes in physiological electrolyte. The formate containing electrolyte can be used directly as drop‐in solution in the following biological polymer production by resting cells. 56 mg PHB L−1 and a ratio of 34 % PHB per cell dry weight were achieved. The calculated overall FE for the process was as high as 4 %. The direct use of the electrolyte as drop‐in media in the bioconversion enables simplified processes with a minimum of intermediate purification effort. Thus, an optimal coupling between electrochemical and biotechnological processes can be realized.
We use recent results by Bainbridge–Chen–Gendron–Grushevsky–Möller on compactifications of strata of abelian differentials to give a comprehensive solution to the realizability problem for effective tropical canonical divisors in equicharacteristic zero. Given a pair (Γ,D) consisting of a stable tropical curve Γ and a divisor D in the canonical linear system on Γ, we give a purely combinatorial condition to decide whether there is a smooth curve X over a non-Archimedean field whose stable reduction has Γ as its dual tropical curve together with an effective canonical divisor KX that specializes to D.
Purpose: COVID-19 pandemic had multiple influences on the social, industrial, and medical situation in all affected countries. Measures of obligatory medical confinement were suspensions of scheduled non-emergent surgical procedures and outpatients’ clinics as well as overall access restrictions to hospitals and medical practices. The aim of this retrospective study was to assess if the obligatory confinement (lockdown) had an effect on the number of appendectomies (during and after the period of lockdown).
Methods: This retrospective study was based on anonymized nationwide administrative claims data of the German Local General Sickness Fund (AOK). Patients admitted for diseases of the appendix (ICD-10: K35-K38) or abdominal and pelvic pain (ICD-10: R10) who underwent an appendectomy (OPS: 5-470) were included. The study period included 6 weeks of German lockdown (16 March–26 April 2020) as well as 6 weeks before (03 February–15 March 2020) and after (27 April–07 June 2020). These periods were compared to the respective one in 2018 and 2019.
Results: The overall number of appendectomies was significantly reduced during the lockdown time in 2020 compared to that in 2018 and 2019. This decrease affects only appendectomies due to acute simple (ICD-10: K35.30, K35.8) and non-acute appendicitis (ICD-10: K36-K38, R10). Numbers for appendectomies in acute complex appendicitis remained unchanged. Female patients and in the age group 1–18 years showed the strongest decrease in number of cases.
Conclusion: The lockdown in Germany resulted in a decreased number of appendectomies. This affected mainly appendectomies in simple acute and non-acute appendicitis, but not complicated acute appendicitis. The study gives no evidence that the confinement measures resulted in a deterioration of medical care for appendicitis.
Evaluation of a rapid turn-over, fully-automated ADAMTS13 activity assay: a method comparison study
(2020)
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy caused by severely reduced activity of the von-Willebrand factor-cleaving protease ADAMTS13, mainly caused by anti-ADAMTS-13 antibodies. Although several test systems for ADAMTS13 measurement exist, long turn-around times hamper the usability in daily practice. We performed a method comparison study for two commercially available ADAMTS13 assays and evaluated the agreement between the fully-automated rapid turn-over HemosIL AcuStar ADAMTS13 Activity assay and the manually performed TECHNOZYM ADAMTS-13 Activity assay. Twenty-four paired test samples derived from 10 consecutively recruited patients (n = 8, acquired TTP; n = 1, atypical hemolytic uremic syndrome; n = 1, control), of which nine test samples were collected in case of clinically apparent TTP and 13 samples were collected from TTP patients in clinical remission were included. Overall correlation between the TECHNOZYM and AcuStar assay was good with a Pearson R of 0.93 (p < 0.001). Agreement between the assays assessed with the Passing–Bablok analysis showed high agreement with an Intercept of − 2.56 (95% confidence interval [CI], − 5.07 to − 0.86) and Slope of 1.04 (95% CI 0.84–1.17). The absolute mean bias was 2.54% (standard difference [SD], 6.38%; 95% CI to 10.0–15.05%). Intra-method reliability was high with an absolute mean bias of − 0.13% (SD 3.21%; 95% CI to 6.42–6.16%). The observer agreement for categorial thresholds (> or < 10% ADAMTS3 activity) was kappa = 0.82 (95% CI 0.59–1.0). Conclusively, overall agreement between the testing methods was sufficient and we support previously published data suggesting the AcuStar assay being a valuable and accurate tool for ADAMTS13 activity testing and TTP diagnostics.
Icacinaceae Miers are a well-described family. However, the family lacks a comprehensive guide to endocarp morphology, which would be an important tool for interpreting the family's extensive fossil record of endocarp remains. In this survey, we describe fruits and endocarps of 88 species of Icacinaceae s. str., four of Icacinaceae s. lat. (now Metteniusaceae) and one of Oncothecaceae. We investigated the value of the endocarp in species recognition. In addition, we generated an Xper3 database with an associated e-key to increase the availability of raw data and the understanding of the characters used. This study documents great diversity in epicarp hairs, mesocarp thickness, endocarp ornamentation, tubercle shape (if present), endocarp structure and thickness, and the locule lining. Some morphological features appear diagnostic for individual genera. In particular, the genus Iodes Blume, which is very common in the fossil record, is the only clade with the three following characters: papillae on the inner locule lining, ridged ornamentation on the endocarp surface, and a vascular bundle embedded within the endocarp wall. Finally, we discuss issues related to the preservation of fruit material in herbarium collections.
We show explicit formulas for the evaluation of (possibly higher-order) fractional Laplacians (-△)ˢ of some functions supported on ellipsoids. In particular, we derive the explicit expression of the torsion function and give examples of s-harmonic functions. As an application, we infer that the weak maximum principle fails in eccentric ellipsoids for s ∈ (1; √3 + 3/2) in any dimension n ≥ 2. We build a counterexample in terms of the torsion function times a polynomial of degree 2. Using point inversion transformations, it follows that a variety of bounded and unbounded domains do not satisfy positivity preserving properties either and we give some examples.
The electron-capture process was studied for Xe54+ colliding with H2 molecules at the internal gas target of the Experimental Storage Ring (ESR) at GSI, Darmstadt. Cross-section values for electron capture into excited projectile states were deduced from the observed emission cross section of Lyman radiation, being emitted by the hydrogenlike ions subsequent to the capture of a target electron. The ion beam energy range was varied between 5.5 and 30.9 MeV/u by applying the deceleration mode of the ESR. Thus, electron-capture data were recorded at the intermediate and, in particular, the low-collision-energy regime, well below the beam energy necessary to produce bare xenon ions. The obtained data are found to be in reasonable qualitative agreement with theoretical approaches, while a commonly applied empirical formula significantly overestimates the experimental findings.
The metasomatised continental mantle may play a key role in the generation of some ore deposits, in particular mineral systems enriched in platinum-group elements (PGE) and Au. The cratonic lithosphere is the longest-lived potential source for these elements, but the processes that facilitate their pre-concentration in the mantle and their later remobilisation to the crust are not yet well-established. Here, we report new results on the petrography, major-element, and siderophile- and chalcophile-element composition of native Ni, base metal sulphides (BMS), and spinels in a suite of well-characterised, highly metasomatised and weakly serpentinised peridotite xenoliths from the Bultfontein kimberlite in the Kaapvaal Craton, and integrate these data with published analyses. Pentlandite in polymict breccias (failed kimberlite intrusions at mantle depth) has lower trace-element contents (e.g., median total PGE 0.72 ppm) than pentlandite in phlogopite peridotites and Mica-Amphibole-Rutile-Ilmenite-Diopside (MARID) rocks (median 1.6 ppm). Spinel is an insignificant host for all elements except Zn, and BMS and native Ni account for typically <25% of the bulk-rock PGE and Au. High bulk-rock Te/S suggest a role for PGE-bearing tellurides, which, along with other compounds of metasomatic origin, may host the missing As, Ag, Cd, Sb, Te and, in part, Bi that are unaccounted for by the main assemblage.
The close spatial relationship between BMS and metasomatic minerals (e.g., phlogopite, ilmenite) indicates that the lithospheric mantle beneath Bultfontein was resulphidised by metasomatism after initial melt depletion during stabilisation of the cratonic lithosphere. Newly-formed BMS are markedly PGE-poor, as total PGE contents are <4.2 ppm in pentlandite from seven samples, compared to >26 ppm in BMS in other peridotite xenoliths from the Kaapvaal craton. This represents a strong dilution of the original PGE abundances at the mineral scale, perhaps starting from precursor PGE alloy and small volumes of residual BMS. The latter may have been the precursor to native Ni, which occurs in an unusual Ni-enriched zone in a harzburgite and displays strongly variable, but overall high PGE abundances (up to 81 ppm). In strongly metasomatised peridotites, Au is enriched relative to Pd, and was probably added along with S. A combination of net introduction of S, Au +/− PGE from the asthenosphere and intra-lithospheric redistribution, in part sourced from subducted materials, during metasomatic events may have led to sulphide precipitation at ~80–120 km beneath Bultfontein. This process locally enhanced the metallogenic fertility of this lithospheric reservoir. Further mobilisation of the metal budget stored in these S-rich domains and upwards transport into the crust may require interaction with sulphide-undersaturated melts that can dissolve sulphides along with the metals they store.
Three species of Lophogastrida and eight Mysida are documented for samples from 5161–5497 m bottom depth in the Angola Basin. Previously known latitudinal ranges are extended southward for five species, and bathymetric ranges extended beyond 5000 m for six species. Upon revision of the subfamily Petalophthalminae (Mysidae), four species previously attributed to the genus Petalophthalmus are integrated into Ipirophthalmus gen. nov. as I. liui gen. et comb. nov., I. caribbeanus gen. et comb. nov., I. oculatus gen. et comb. nov., and I. macrops gen. et comb. nov., mainly based on the structure of eyes and presence of setae on the telson. Petalophthalmus cristatus sp. nov. is described based on its reduced cornea and the structure of eyestalks, rostrum, mandibles, and telson. The structure of mouthparts, foregut and maxillipeds suggests an omnivorous mode of life. The diagnosis of the tribe Calyptommini (Mysidae: Erythropinae) is widened to cover the 3-segmented, uniramous fourth male pleopod and the non-incised eyeplate with horn-like rudiments of eyestalks in Abyssomysis cornuta gen. et sp. nov. The structure of mandibles, foregut, and second maxilliped suggest detritus feeding in this species. Keys to the Calyptommini and Petalophthalminae are given.
Ziel dieser Untersuchung ist es, die Legitimität der Kriminalisierung des Glücksspiels in Brasilien zu hinterfragen. Dies geschieht mit besonderem Augenmerk auf das spezifische brasilianische Glücksspiel, das „Spiel der Tiere“ (Jogo do bicho), das Ende des 19. Jahrhunderts in der Stadt Rio de Janeiro, der Hauptstadt des damaligen kaiserlichen Brasiliens, entstand. Es handelt sich um eine Form des Glücksspiels, die sich in ganz Brasilien verbreitet hat und bereits Gegenstand mehrerer akademischer Studien in den Bereichen Anthropologie und Soziologie war. Das Verbot dieser Art von Glücksspiel, seine Kriminalisierung, seine große Beliebtheit und seine gesellschaftliche Toleranz sind jedoch Gründe dafür, dass das Spiel der Tiere im Besonderen und das Glücksspiel im Allgemeinen auch im juristischen Bereich, insbesondere im Strafrecht, ein bisher vernachlässigter Forschungsgegenstand von großem Interesse ist.
Das Hauptaugenmerk dieser Arbeit liegt auf der Analyse der Kriminalisierung des Glücksspiels, das in Brasilien seit über einem Jahrhundert unter freiem Himmel praktiziert wird. Bei dieser Analyse werden die Gründe für die Kriminalisierung und die Legitimität des Verbots in Frage gestellt. Zu diesem Zweck ist der Text, abgesehen von der Einleitung und der Schlussfolgerung, in sechs Kapitel unterteilt.
Kapitel 1 beschreibt die Geschichte des brasilianischen Tierspiels, die Ursprünge seines Verbots und seiner Kriminalisierung. In Kapitel 2 wird über die Wirklichkeit der Strafverfolgung in diesem „Kriminalitätsbereich“ berichtet. Kapitel 3 stellt den ent-sprechenden Straftatbestand des brasilianischen „Código Penal“ im Kontext der Systematik des brasilianischen Strafgesetzbuches vor. Kapitel 4 widmet sich zunächst den verfassungsrechtlichen Grenzen der Kriminalisierung, und danach einem Überblick über das deutsche Glücksspielverbot und die Glücksspielregulierung. Ergänzt wird diese Suche in Kapitel 5, in dem die Forschung das strafrechtliche Glücksspielverbot in den Kontext der Debatte über die Abgrenzung zwischen und den Zusammenhang von Recht und Moral. Im abschließenden Kapitel 6 wird das (strafrechtlich sanktionierte) Glücksspielverbot mit den klassischen Legitimations-anforderungen konfrontiert.
Was in der strafrechtlichen Literatur der ersten Hälfte des 20. Jahrhunderts zur Rechtfertigung des Verbots zu lesen ist, deutet auf einen großen Einfluss moralischer Argumente hin. Diese Argumente haben bis heute an Gewicht nicht verloren, auch wenn die Befürworter der Beibehaltung der Kriminalisierung versuchen, ihre letztlich moralistische Ideologie gegen das Glücksspiel mit Argumenten wie der Begleitkriminalität des Glückspiels zu verschleiern, die eher eine Folge als eine Ursache der Kriminalisierung ist.
Das Staatsangehörigkeitsrecht verankert rechtlich Vorstellungen über Zugehörigkeit und bestimmt wer vollumfängliche Rechte in einer Gesellschaft hat und wer nicht. Jahrzehntelang wurde Migration in Deutschland als etwas temporäres betrachtet. Im Staatsangehörigkeitsrecht galt bis zur Reform 1999/2000 weitgehend das „ius sanguinis“, das Abstammungsrecht, das auf einem rassistischen und völkischen Staatsverständnis beruht. Diese Reform bedeutete somit mehr als eine reine Gesetzesänderung. Sie war eine Anerkennung Deutschlands als Einwanderungsland und die Veränderung der Vorstellung deutscher Identität. Als Reaktion entbrannte infolge der Reformpläne eine hitzige, rassistische Debatte in der Öffentlichkeit über ebendiese Fragen, die unter dem polarisierten Schlagwort „Doppelpass“ verhandelt wurde. Es war die lauteste migrationspolitische Debatte dieser Zeit.
Kurze Zeit vor Beginn dieser Debatte war die rechtsterroristische Gruppe „Nationalsozialistischer Untergrund“ (NSU) abgetaucht, um einem Haftbefehl zu entgehen. Der NSU war ein deutsches, neonazistisches Netzwerk, in dessen Mittelpunkt drei Terrorist*innen standen. Sie verübten über einen Zeitraum von zwölf Jahren eine rassistische Mordserie an neun Personen türkischer, kurdischer und griechischer Herkunft sowie drei Sprengstoffanschläge auf migrantische Orte und ermordeten eine Polizistin. Den ersten ihrer Sprengstoffanschläge begingen sie nur einen Monat nach der Unterzeichnung der Reform. Wenige Monate nach dem Inkrafttreten des Gesetzes begannen sie mit dem Anschlag auf Enver Şimşek ihre rassistische Mordserie.
Diese Arbeit untersucht anhand der Struktur der Historisch-Materialistischen Politikanalyse das Migrationsregime um die Staatsangehörigkeitsreform von 1999/2000 und wie der NSU darin verortet werden kann.
Die Kontextanalyse stellt auf der Grundlage einer Literaturrecherche die relevanten historischen und strukturellen Faktoren der Debatte sowie des NSU dar. Im nächsten Schritt werden mithilfe einer Analyse von Zeitungsartikel aus dieser Zeit die relevanten Akteur*innen identifiziert und in die vier Hegemonieprojekte neoliberal, sozial, linksliberal-alternativ und konservativ gruppiert. Darauffolgend wird der Ablauf der Debatte in vier Phasen darstellt und als Aushandlung der vier Hegemonieprojekte rekonstruiert. Dabei zeigt sich, dass kein Projekt sich vollumfänglich durchsetzen und Hegemonie erreichen konnte, sie jedoch unterschiedlich stark in den Medien repräsentiert wurden.
Im letzten Schritt betrachtet diese Arbeit Verbindungen dieser Migrationsregime-Analyse zum NSU. Sie kommt zu dem Ergebnis, dass der NSU kein Akteur im Migrationsregime um die Staatsangehörigkeitsdebatte von 1998/99 war. Aufgrund der geringen Erkenntnisse über spezifische Meinungen des NSU zum Staatsangehörigkeitsrecht, können keine kausalen Beziehungen hergestellt werden. Dennoch zeigt diese Arbeit Gemeinsamkeiten in den Weltbildern, Annahmen und migrationspolitischen Zielen des NSU, des konservativen Hegemonieprojektes sowie Teilen der Bevölkerung auf. Dadurch wird ein Beitrag dazu geleistet den NSU als Produkt und Teil der deutschen Gesellschaft zu begreifen.
100 Jahre Dieter Janz
(2020)
The 20 April 2020 marks the centenary of Dieter Janz’s birth. This issue of Zeitschrift für Epileptologie is published in his honor with the aim of tracing the work of Dieter Janz over the last five decades and summarizing new findings on the Janz syndrome (Juvenile Myoclonic Epilepsy), which is named after him.
Relationship between regional white matter hyperintensities and alpha oscillations in older adults
(2020)
White matter hyperintensities (WMHs) in the cerebral white matter and attenuation of alpha oscillations (AO; 7–13 Hz) occur with the advancing age. However, a crucial question remains, whether changes in AO relate to aging per se or they rather reflect the impact of age-related neuropathology like WMHs. In this study, using a large cohort (N=907) of elderly participants (60-80 years), we assessed relative alpha power (AP), individual alpha peak frequency (IAPF) and long-range temporal correlations (LRTC) from resting-state EEG. We further associated these parameters with voxel-wise WMHs from 3T MRI. We found that higher prevalence of WMHs in the superior and posterior corona radiata was related to elevated relative AP, with strongest correlations in the bilateral occipital cortex, even after controlling for potential confounding factors. In contrast, we observed no significant relation of probability of WMH occurrence with IAPF and LRTC. We argue that the WMH-associated increase of AP reflects generalized and likely compensatory changes of AO leading to a larger number of synchronously recruited neurons.
Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity are frequently comorbid, genetically correlated, and share brain substrates. The biological mechanisms driving this association are unclear, but candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the genetic link between ADHD and obesity measures and investigate associations of overlapping genes with brain volumes. We tested the association of dopaminergic and circadian rhythm gene sets with ADHD, body mass index (BMI), and obesity (using GWAS data of N = 53,293, N = 681,275, and N = 98,697, respectively). We then conducted genome-wide ADHD–BMI and ADHD–obesity gene-based meta-analyses, followed by pathway enrichment analyses. Finally, we tested the association of ADHD–BMI overlapping genes with brain volumes (primary GWAS data N = 10,720–10,928; replication data N = 9428). The dopaminergic gene set was associated with both ADHD (P = 5.81 × 10−3) and BMI (P = 1.63 × 10−5); the circadian rhythm was associated with BMI (P = 1.28 × 10−3). The genome-wide approach also implicated the dopaminergic system, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was enriched in both ADHD–BMI and ADHD–obesity results. The ADHD–BMI overlapping genes were associated with putamen volume (P = 7.7 × 10−3; replication data P = 3.9 × 10−2)—a brain region with volumetric reductions in ADHD and BMI and linked to inhibitory control. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling and involving the putamen, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering shared etiological factors underlying the frequently observed ADHD–obesity comorbidity may have important implications in terms of prevention and/or efficient treatment of these conditions.
Relationship between regional white matter hyperintensities and alpha oscillations in older adults
(2020)
Objective: To investigate whether regional white matter hyperintensities (WMHs) relate to alpha oscillations (AO) in a large population-based sample of elderly individuals.
Methods: We associated voxel-wise WMHs from high-resolution 3-Tesla MRI with neuronal alpha oscillations (AO) from resting-state multichannel EEG at sensor (N=907) and source space (N=855) in older participants of the LIFE-Adult study (60–80 years). In EEG, we computed relative alpha power (AP), individual alpha peak frequency (IAPF), as well as long-range temporal correlations (LRTC) that represent dynamic properties of the signal. We implemented whole-brain voxel-wise regression models to identify regions where parameters of AO were linked to probability of WMH occurrence. We further used mediation analyses to examine whether WMH volume mediated the relationship between age and AO.
Results: Higher prevalence of WMHs in the superior and posterior corona radiata was related to elevated relative AP, with strongest correlations in the bilateral occipital cortex, even after controlling for potential confounding factors. The age-related increase of relative AP in the right temporal brain region was shown to be mediated by total WMH volume.
Conclusion: A high relative AP corresponding to increased regional WMHs was not associated with age per se, in fact, this relationship was mediated by WMHs. We argue that the WMH-associated increase of AP reflects a generalized and likely compensatory spread of AO leading to a larger number of synchronously recruited neurons. Our findings thus suggest that longitudinal EEG recordings might be sensitive to detect functional changes due to WMHs.
Markeninszenierung in Japan - zur narrativen Konstruktion der Lifestyle-Marken "Muji" und "Uniqlo"
(2020)
Die Einzelhandelsketten "Muji" und "Uniqlo" gelten als Musterbeispiele für international erfolgreiche Lifestyle-Marken aus Japan. Aus einer interdisziplinären Perspektive heraus identifiziert Christiane Rühle die Strukturen und Akteure dieser spezifischen Markeninszenierungen und arbeitet die dazugehörigen Positionen, Mittel und zentralen Motive heraus. Sie fragt im Kontext von unternehmensbezogener und nationalstaatlicher Imagebildung nach den Bezügen zwischen Konsum, Kultur und Identität und fokussiert dabei auf die Rolle, die privatwirtschaftliche Unternehmen innerhalb dieses Prozesses einnehmen.
A growing body of experimental syntactic research has revealed substantial variation in the magnitude of island effects, not only across languages but also across different grammatical constructions. Adopting a well-established experimental design, the present study examines island effects in Spanish using a speeded acceptability judgment task. To quantify variation across grammatical constructions, we tested extraction from four different types of structure (subjects, complex noun phrases, adjuncts and interrogative clauses). The results of Bayesian mixed effects modelling showed that the size of island effects varied between constructions, such that there was clear evidence of subject, adjunct and interrogative island effects, but not of complex noun phrase island effects. We also failed to find evidence that island effects were modulated by participants’ working memory capacity as measured by an operation span task. To account for our results, we suggest that variability in island effects across constructions may be due to the interaction of syntactic, semantic-pragmatic and processing factors, which may affect island types differentially due to their idiosyncratic properties.
The tremendous diversity of life in the ocean has proven to be a rich source of inspiration for drug discovery, with success rates for marine natural products up to 4 times higher than other naturally derived compounds. Yet the marine biodiscovery pipeline is characterized by chronic underfunding, bottlenecks and, ultimately, untapped potential. For instance, a lack of taxonomic capacity means that, on average, 20 years pass between the discovery of new organisms and the formal publication of scientific names, a prerequisite to proceed with detecting and isolating promising bioactive metabolites. The need for “edge” research that can spur novel lines of discovery and lengthy high-risk drug discovery processes, are poorly matched with research grant cycles. Here we propose five concrete pathways to broaden the biodiscovery pipeline and open the social and economic potential of the ocean genome for global benefit: (1) investing in fundamental research, even when the links to industry are not immediately apparent; (2) cultivating equitable collaborations between academia and industry that share both risks and benefits for these foundational research stages; (3) providing new opportunities for early-career researchers and under-represented groups to engage in high-risk research without risking their careers; (4) sharing data with global networks; and (5) protecting genetic diversity at its source through strong conservation efforts. The treasures of the ocean have provided fundamental breakthroughs in human health and still remain under-utilised for human benefit, yet that potential may be lost if we allow the biodiscovery pipeline to become blocked in a search for quick-fix solutions.
Objectives: Lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH) are often accompanied by frequently occurring leg cramps severely affecting patients’ life and sleep quality. Recent evidence suggests that neuromuscular electric stimulation (NMES) of cramp-prone muscles may prevent cramps in lumbar disorders.
Materials and Methods: Thirty-two men and women (63 ± 9 years) with LSS and/or LDH suffering from cramps were randomly allocated to four different groups. Unilateral stimulation of the gastrocnemius was applied twice a week over four weeks (3 × 6 × 5 sec stimulation trains at 30 Hz above the individual cramp threshold frequency [CTF]). Three groups received either 85%, 55%, or 25% of their maximum tolerated stimulation intensity, whereas one group only received pseudo-stimulation.
Results: The number of reported leg cramps decreased in the 25% (25 ± 14 to 7 ± 4; p = 0.002), 55% (24 ± 10 to 10 ± 11; p = 0.014) and 85%NMES (23 ± 17 to 1 ± 1; p < 0.001) group, whereas it remained unchanged after pseudo-stimulation (20 ± 32 to 19 ± 33; p > 0.999). In the 25% and 85%NMES group, this improvement was accompanied by an increased CTF (p < 0.001).
Conclusion: Regularly applied NMES of the calf muscles reduces leg cramps in patients with LSS/LDH even at low stimulation intensity.
We report results on the total and elastic cross sections in proton-proton collisions at √s = 200 GeV obtained with the Roman Pot setup of the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The elastic differential cross section was measured in the squared four-momentum transfer range 0.045 ≤ −t ≤ 0.135 GeV2. The value of the exponential slope parameter B of the elastic differential cross section dσ/dt ∼ e−Bt in the measured −t range was found to be B = 14.32 ± 0.09(stat.)+0.13 −0.28(syst.) GeV−2. The total cross section σtot, obtained from extrapolation of the dσ/dt to the optical point at −t = 0, is σtot = 54.67 ± 0.21(stat.)+1.28 −1.38(syst.) mb. We also present the values of the elastic cross section σel = 10.85 ± 0.03(stat.)+0..49 −0.41(syst.) mb, the elastic cross section integrated within the STAR t-range σ det el = 4.05 ± 0.01(stat.)+0.18−0.17(syst.) mb, and the inelastic cross section σinel = 43.82 ± 0.21(stat.)+1.37−1.44(syst.) mb. The results are compared with the world data
Background: Vacuum cleaning, which is associated with musculoskeletal complaints, is frequently carried out in private households and by professional cleaners. The aim of this pilot study was to quantify the movements during habitual vacuuming and to characterize the movement profile with regard to its variability. Methods: The data were collected from 31 subjects (21 f/10 m) using a 3D motion analysis system (XSens). Eight vacuum cleaners were used to vacuum polyvinyl chloride (PVC) and carpet floors. In 15 joints of the right upper extremity, the trunk and the lower extremities, Principal Component Analysis was used to determine the predominantly varying joints during vacuuming. Results: The movements of the trunk and the lower extremities were relatively constant and, therefore, had less influence. The shoulder, elbow and wrist joints were identified as joints that can be decisive for the movement profile and that can be influenced. These joints were represented in the course of the vacuuming cycle by the mean movement with its standard deviation. Conclusion: In summary, the generalization of a movement profile is possible for the trunk and the lower extremities due to the relative homogeneity. In future it will be necessary to identify factors influencing variability in order to draw conclusions about movement ergonomics.
Background: Dentists are at a higher risk of suffering from musculoskeletal disorders (MSD) than the general population. However, the latest study investigating MSD in the dental profession in Germany was published about 20 years ago. Therefore, the aim of this study was to reveal the current prevalence of MSD in dentists and dental students in Germany. Methods: The final study size contained 450 (287 f/163 m) subjects of different areas of specialization. The age of the participants ranged from 23 to 75 years. The questionnaire consisted of a modified version of the Nordic Questionnaire, work-related questions from the latest questionnaire of German dentists, typical medical conditions and self-developed questions. Results: The overall prevalence showed that dentists suffered frequently from MSD (seven days: 65.6%, twelve months: 92%, lifetime: 95.8%). The most affected body regions included the neck (42.7%–70.9%–78.4%), shoulders (29.8%–55.6%–66.2%) and lower back (22.9%–45.8%–58.7%). Overall, female participants stated that they suffered from pain significantly more frequently, especially in the neck, shoulders and upper back. Conclusion: The prevalence of MSD among dentists, especially in the neck, shoulder and back area, was significantly higher than in the general population. In addition, women suffered more frequently from MSD than men in almost all body regions.
Background & Aims: NAFLD is a growing health concern. The aim of the Fatty Liver Assessment in Germany (FLAG) study was to assess disease burden and provide data on the standard of care from secondary care. Methods: The FLAG study is an observational real-world study in patients with NAFLD enrolled at 13 centres across Germany. Severity of disease was assessed by non-invasive surrogate scores and data recorded at baseline and 12 months. Results: In this study, 507 patients (mean age 53 years; 47% women) were enrolled. According to fibrosis-4 index, 64%, 26%, and 10% of the patients had no significant fibrosis, indeterminate stage, and advanced fibrosis, respectively. Patients with advanced fibrosis were older, had higher waist circumferences, and higher aspartate aminotransferase and gamma-glutamyltransferase as well as ferritin levels. The prevalence of obesity, arterial hypertension, and type 2 diabetes increased with fibrosis stages. Standard of care included physical exercise >2 times per week in 17% (no significant fibrosis), 19% (indeterminate), and 6% (advanced fibrosis) of patients. Medication with either vitamin E, silymarin, or ursodeoxycholic acid was reported in 5%. Approximately 25% of the patients received nutritional counselling. According to the FibroScan-AST score, 17% of patients presented with progressive non-alcoholic steatohepatitis (n = 107). On follow-up at year 1 (n = 117), weight loss occurred in 47% of patients, of whom 17% lost more than 5% of body weight. In the weight loss group, alanine aminotransferase activities were reduced by 20%. Conclusions: This is the first report on NAFLD from a secondary-care real-world cohort in Germany. Every 10th patient presented with advanced fibrosis at baseline. Management consisted of best supportive care and lifestyle recommendations. The data highlight the urgent need for systematic health agenda in NAFLD patients. Lay summary: FLAG is a real-world cohort study that examined the liver disease burden in secondary and tertiary care. Herein, 10% of patients referred to secondary care for NAFLD exhibited advanced liver disease, whilst 64% had no significant liver scarring. These findings underline the urgent need to define patient referral pathways for suspected liver disease.
Background Coronavirus disease 2019 (COVID-19) represents a significant challenge to health care systems around the world. A well-functioning primary care system is crucial in epidemic situations as it plays an important role in the development of a system-wide response.
Methods 2,187 Austrian and German GPs answered an internet suvey on preparedness, testing, staff protection, perception of risk, self-confidence, a decrease in the number of patient contacts, and efforts to control the spread of the virus in the practice during the early phase of the COVID-pandemic (3rd to 30th April).
Results The completion rate of the questionnaire was high (90.9%). GPs gave low ratings to their preparedness for a pandemic, testing of suspected cases and efforts to protect staff. The provision of information to GPs and the perception of risk were rated as moderate. On the other hand, the participants rated their self-confidence, a decrease in patient contacts and their efforts to control the spread of the disease highly.
Conclusion Primary care is an important resource for dealing with a pandemic like COVID-19. The workforce is confident and willing to take an active role, but needs to be provided with the appropriate surrounding conditions. This will require that certain conditions are met.
Registration Trial registration at the German Clinical Trials Register: DRKS00021231
Background: The health status, health awareness and health behavior of persons with a migration background often differ from the autochthonous population. Little is known about the proportion of patients with a migration background (PMB) that participate in primary care studies on oral antithrombotic treatment (OAT) in Germany, and whether the quality of their antithrombotic care differs from patients without a migration background. The aim of this paper was to use the results of a cluster-randomized controlled trial (PICANT) to determine the proportion of PMB at different stages of recruitment, and to compare the results in terms of sociodemographic characteristics and antithrombotic treatment.
Methods: This study used screening and baseline data from the PICANT trial on oral anticoagulation management in GP practices. For this analysis, we determined the proportion of PMB during the recruitment period at stage 1 (screening of potentially eligible patients), stage 2 (eligible patients invited to participate in the trial), and stage 3 (assessment of baseline characteristics of patients participating in the PICANT trial). In addition, we compared patients in terms of sociodemographic characteristics and quality of anticoagulant treatment. Statistical analysis comprised descriptive and bivariate analyses.
Results: The proportion of PMB at each recruitment stage declined from 9.1% at stage 1 to 7.9% at stage 2 and 7.3% at stage 3). A lack of German language skills led to the exclusion of half the otherwise eligible PMB. At stages 1 and 3, PMB were younger (stage 1: 70.7 vs. 75.0 years, p<0.001; stage 3: 70.2 vs. 73.5 years, p = 0.013), but did not differ in terms of gender. The quality of their anticoagulant care was comparable (100.0% vs. 99.1% were receiving appropriate OAT, 94.4% vs. 95.7% took phenprocoumon, or warfarin, and the most recent INR measurement of 60.8% vs. 69.3% was within their individual INR range).
Conclusions: In the potentially eligible population and among participants at baseline, the quality of anticoagulant care was high in all groups of patients, which is reassuring. To enable the inclusion of more PMB, future primary care research on OAT in Germany should address how best to overcome language barriers. This will be challenging, particularly because the heterogeneity of PMB means the resulting sample sizes for each specific language group are small.
Trial registration: Current Controlled Trials ISRCTN41847489.