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To explore and describe attitudes and opinions towards suicidality in healthcare professionals (HCPs) working with oncological patients. Methods: A 48-item online questionnaire was developed and distributed to HCPs working with cancer patients. Three hundred fifty-four answered questionnaires were analyzed. Results: The majority of HCPs reported that they were able to understand why a cancer patient would commit suicide (87.8%) or would seek help from an assisted suicide organization (ASO; 83.9%). The understandable reasons were pain and physical impairments (51.4%), social isolation (19.8%), loss of control and autonomy (18.1%), terminal disease (17.2%), loss of meaning (15.3%), desperation (14.7%), and psychic distress (9.3%). Personal experiences with suicidality lead only 44.8% of HCPs to believe that thereby they would be better able to understand a patients’ wish for suicide. Religion was negatively associated with understanding of suicide and why a cancer patient would seek help from an ASO. Knowledge of suicidality was positively associated with why a cancer patient would seek help from an ASO. Conclusions: There is still little knowledge in oncology about the relation of HCPs’ attitudes toward suicidality in their patients and how those attitudes influence their behavior, especially care and treatment of patients. More research on this topic is needed. It stands to reason that more education about suicidality in cancer patients seems likely to improve understanding and attitudes and thereby influence care for cancer patients.
Objectives: Current treatments for chronic depression have focused on reducing interpersonal problems and negative affect, but paid little attention to promoting prosocial motivation and positive affect. Following this treatment focus, the objective of the present study was to examine whether the combination of metta (Loving Kindness) group meditation and subsequent tailored individual therapy focusing on kindness towards oneself and others (metta-based therapy, MBT) shows greater improvements in depressive symptoms than a wait list control group in patients with chronic depression. Methods: Forty-eight patients with DSM-5 persistent depressive disorder were randomly assigned to MBT or a wait list control condition. Outcome was assessed after group meditation, after subsequent individual therapy, and at 6-month follow-up. The primary outcome measure was an independent blind rating of depressive symptoms at post-test. Secondary outcome included changes in self-reported depression, behavioral activation, rumination, social functioning, mindfulness, compassion, and clinician-rated emotion regulation. Results: Mixed-design analyses showed significant differences between MBT and WLC in changes from pre- to post-test in clinician-rated and self-rated depression, behavioral activation, rumination, social functioning, mindfulness, and emotion regulation. Most of the changes occurred during group meditation and were associated with large effect sizes. Improvements were maintained at 6-month follow-up. Conclusions: The results provide preliminary support for the effectiveness of MBT in treating chronic depression. Trial Registration: ISRCTN, ISRCTN97264476.
Das Übergangstraining : Maßnahme in der betrieblichen Wiedereingliederung im professionellen Tanz
(2021)
Neben der Vorbeugung von akuten und chronischen Schäden ist im professionellen Bühnentanz bei gesundheitlichen Problemen am Muskel-Skelett-System eine intensive – dem Berufssport vergleichbare – Rehabilitation unter Berücksichtigung tanzspezifischer Bewegungselemente von großer Bedeutung. In Kombination mit anderen, die Leistungsfähigkeit wiederherstellenden Maßnahmen ist das in diesem Beitrag erläuterte sog. Übergangstraining („transition dance class“) als Trainingsform im Rahmen der stufenweisen beruflichen Wiedereingliederung von zentraler Bedeutung, da es die Übergangsphase zwischen allgemeinen Maßnahmen einer Rehabilitation und dem Wiedererreichen der vollständigen Arbeitsfähigkeit im Tanzberuf darstellt.
HADES is a fixed target experiment using SIS18 heavy-ion beams. It investigates the microscopic properties of matter formed in heavy-ion, proton and pion - induced reactions in the 1-3.5 GeV/u energy regime. In 2014 HADES used a secondary pion beam produced by interaction between high-intensity nitrogen primary beam and a beryllium target. In these conditions beam losses, generated by slow extraction and beam transport to the experimental area, led to activation of the beam line elements and triggered radiation alarms. The primary beam intensity had to be reduced and the beam optics modified in order to keep radiation levels within the allowed limits. Similar beam conditions are requested by HADES experiment for upcoming run in 2018 and in the following years. Therefore, a number of measures have been proposed to improve beam transmission and quality. These measures are: additional shielding, additional beam instrumentation, modification of beam optics and increase of vacuum chambers' apertures in critical locations. The optics study and preliminary results of FLUKA simulations for optimization of location of loss detectors are presented.
Natural products (NPs) from microorganisms have been important sources for discovering new therapeutic and chemical entities. While their corresponding biosynthetic gene clusters (BGCs) can be easily identified by gene-sequence-similarity-based bioinformatics strategies, the actual access to these NPs for structure elucidation and bioactivity testing remains difficult. Deletion of the gene encoding the RNA chaperone, Hfq, results in strains losing the production of most NPs. By exchanging the native promoter of a desired BGC against an inducible promoter in Δhfq mutants, almost exclusive production of the corresponding NP from the targeted BGC in Photorhabdus, Xenorhabdus and Pseudomonas was observed including the production of several new NPs derived from previously uncharacterized non-ribosomal peptide synthetases (NRPS). This easyPACId approach (easy Promoter Activated Compound Identification) facilitates NP identification due to low interference from other NPs. Moreover, it allows direct bioactivity testing of supernatants containing secreted NPs, without laborious purification.
Proteins encoded by small open reading frames (sORFs) have a widespread occurrence in diverse microorganisms and can be of high functional importance. However, due to annotation biases and their technically challenging direct detection, these small proteins have been overlooked for a long time and were only recently rediscovered. The currently rapidly growing number of such proteins requires efficient methods to investigate their structure–function relationship. Herein, a method is presented for fast determination of the conformational properties of small proteins. Their small size makes them perfectly amenable for solution-state NMR spectroscopy. NMR spectroscopy can provide detailed information about their conformational states (folded, partially folded, and unstructured). In the context of the priority program on small proteins funded by the German research foundation (SPP2002), 27 small proteins from 9 different bacterial and archaeal organisms have been investigated. It is found that most of these small proteins are unstructured or partially folded. Bioinformatics tools predict that some of these unstructured proteins can potentially fold upon complex formation. A protocol for fast NMR spectroscopy structure elucidation is described for the small proteins that adopt a persistently folded structure by implementation of new NMR technologies, including automated resonance assignment and nonuniform sampling in combination with targeted acquisition.
Acetogenic bacteria are a group of strictly anaerobic bacteria that may have been first life forms on Earth since they employ an ancient pathway for CO2 fixation into acetyl-CoA that is coupled to the synthesis of ATP, the Wood–Ljungdahl pathway. Electrons for CO2 reduction are derived from oxidation of H2 or CO and thus, these bacteria can grow lithotrophically on gases present on early Earth. Among the organic molecules present on early Earth is acetaldehyde, a highly volatile C2 compound. Here, we demonstrate that the acetogenic model bacterium Acetobacterium woodii grows on acetaldehyde. Acetaldehyde is dismutated to ethanol and acetyl-CoA, most likely by the bifunctional alcohol dehydrogenase AdhE. Acetyl-CoA is converted to acetate by two subsequent enzymes, phosphotransacetylase and acetate kinase, accompanied by the synthesis of ATP by substrate-level phosphorylation. Apparently, growth on acetaldehyde does not employ the Wood–Ljungdahl pathway. Our finding opens the possibility of a simple and ancient metabolic pathway with only three enzymes that allows for biomass (acetyl-CoA) and ATP formation on early Earth.
Photobleaching is a major challenge in fluorescence microscopy, in particular if high excitation light intensities are used. Signal-to-noise and spatial resolution may be compromised, which limits the amount of information that can be extracted from an image. Photobleaching can be bypassed by using exchangeable labels, which transiently bind to and dissociate from a target, thereby replenishing the destroyed labels with intact ones from a reservoir. Here, we demonstrate confocal and STED microscopy with short, fluorophore-labeled oligonucleotides that transiently bind to complementary oligonucleotides attached to protein-specific antibodies. The constant exchange of fluorophore labels in DNA-based STED imaging bypasses photobleaching that occurs with covalent labels. We show that this concept is suitable for targeted, two-color STED imaging of whole cells.
Frontal areas of the mammalian cortex are thought to be important for cognitive control and complex behaviour. These areas have been studied mostly in humans, non-human primates and rodents. In this article, we present a quantitative characterization of response properties of a frontal auditory area responsive to sound in the brain of Carollia perspicillata, the frontal auditory field (FAF). Bats are highly vocal animals, and they constitute an important experimental model for studying the auditory system. We combined electrophysiology experiments and computational simulations to compare the response properties of auditory neurons found in the bat FAF and auditory cortex (AC) to simple sounds (pure tones). Anatomical studies have shown that the latter provides feedforward inputs to the former. Our results show that bat FAF neurons are responsive to sounds, and however, when compared to AC neurons, they presented sparser, less precise spiking and longer-lasting responses. Based on the results of an integrate-and-fire neuronal model, we suggest that slow, subthreshold, synaptic dynamics can account for the activity pattern of neurons in the FAF. These properties reflect the general function of the frontal cortex and likely result from its connections with multiple brain regions, including cortico-cortical projections from the AC to the FAF.
Although researchers and practitioners increasingly focus on health promotion in organizations, research has been mainly fragmented and fails to integrate different organizational levels in terms of their effects on employee health. Drawing on organizational climate and social identity research, we present a cascading model of organizational health climate and demonstrate how and when leaders' perceptions of organizational health climate are linked to employee well-being. We tested our model in two multisource studies (NStudy 1 = 65 leaders and 291 employees; NStudy 2 = 401 leader–employee dyads). Results showed that leaders' perceptions of organizational health climate were positively related to their health mindsets (i.e., their health awareness). These in turn were positively associated with their health-promoting leadership behavior, which ultimately went along with better employee well-being. Additionally, in Study 1, the relationship between perceived organizational health climate and leaders' health mindsets was moderated by their organizational identification. High leader identification strengthened the relationship between perceived organizational health climate and leaders' health mindsets. These findings have important implications for theory and practice as they show how the dynamics of an organizational health climate can unfold in organizations and how it is related to employee well-being via the novel concept of health-promoting leadership.
Ribonucleic acid oligonucleotides (RNAs) play pivotal roles in cellular function (riboswitches), chemical biology applications (SELEX-derived aptamers), cell biology and biomedical applications (transcriptomics). Furthermore, a growing number of RNA forms (long non-coding RNAs, circular RNAs) but also RNA modifications are identified, showing the ever increasing functional diversity of RNAs. To describe and understand this functional diversity, structural studies of RNA are increasingly important. However, they are often more challenging than protein structural studies as RNAs are substantially more dynamic and their function is often linked to their structural transitions between alternative conformations. NMR is a prime technique to characterize these structural dynamics with atomic resolution. To extend the NMR size limitation and to characterize large RNAs and their complexes above 200 nucleotides, new NMR techniques have been developed. This Minireview reports on the development of NMR methods that utilize detection on low-γ nuclei (heteronuclei like 13C or 15N with lower gyromagnetic ratio than 1H) to obtain unique structural and dynamic information for large RNA molecules in solution. Experiments involve through-bond correlations of nucleobases and the phosphodiester backbone of RNA for chemical shift assignment and make information on hydrogen bonding uniquely accessible. Previously unobservable NMR resonances of amino groups in RNA nucleobases are now detected in experiments involving conformational exchange-resistant double-quantum 1H coherences, detected by 13C NMR spectroscopy. Furthermore, 13C and 15N chemical shifts provide valuable information on conformations. All the covered aspects point to the advantages of low-γ nuclei detection experiments in RNA.
Cancer stem cells (CSCs) are nowadays one of the major focuses in tumor research since this subpopulation was revealed to be a great obstacle for successful treatment. The identification of CSCs in pediatric solid tumors harbors major challenges because of the immature character of these tumors. Here, we present CD34, CD90, OV-6 and cell-surface vimentin (csVimentin) as reliable markers to identify CSCs in hepatoblastoma cell lines. We were able to identify CSC characteristics for the subset of CD34+CD90+OV-6+csVimentin+-co-expressing cells, such as pluripotency, self-renewal, increased expression of EMT markers and migration. Treatment with Cisplatin as the standard chemotherapeutic drug in hepatoblastoma therapy further revealed the chemo-resistance of this subset, which is a main characteristic of CSCs. When we treated the cells with the Hsp90 inhibitor 17-AAG, we observed a significant reduction in the CSC subset. With our study, we identified CSCs of hepatoblastoma using CD34, CD90, OV-6 and csVimentin. This set of markers could be helpful to estimate the success of novel therapeutic approaches, as resistant CSCs are responsible for tumor relapses.
Background: Dual-source dual-energy computed tomography (DECT) offers the potential for opportunistic osteoporosis screening by enabling phantomless bone mineral density (BMD) quantification. This study sought to assess the accuracy and precision of volumetric BMD measurement using dual-source DECT in comparison to quantitative CT (QCT). Methods: A validated spine phantom consisting of three lumbar vertebra equivalents with 50 (L1), 100 (L2), and 200 mg/cm3 (L3) calcium hydroxyapatite (HA) concentrations was scanned employing third-generation dual-source DECT and QCT. While BMD assessment based on QCT required an additional standardised bone density calibration phantom, the DECT technique operated by using a dedicated postprocessing software based on material decomposition without requiring calibration phantoms. Accuracy and precision of both modalities were compared by calculating measurement errors. In addition, correlation and agreement analyses were performed using Pearson correlation, linear regression, and Bland-Altman plots. Results: DECT-derived BMD values differed significantly from those obtained by QCT (p < 0.001) and were found to be closer to true HA concentrations. Relative measurement errors were significantly smaller for DECT in comparison to QCT (L1, 0.94% versus 9.68%; L2, 0.28% versus 5.74%; L3, 0.24% versus 3.67%, respectively). DECT demonstrated better BMD measurement repeatability compared to QCT (coefficient of variance < 4.29% for DECT, < 6.74% for QCT). Both methods correlated well to each other (r = 0.9993; 95% confidence interval 0.9984–0.9997; p < 0.001) and revealed substantial agreement in Bland-Altman plots. Conclusions: Phantomless dual-source DECT-based BMD assessment of lumbar vertebra equivalents using material decomposition showed higher diagnostic accuracy compared to QCT.
We investigated the effects of sexual arousal induced by olfactory stimuli on the expression of neuromodulators, neurotransmitters and sexual steroid receptors in the suprachiasmatic nucleus (SCN, the circadian pacemaker of mammals) and other cerebral entities of Syrian hamsters (Mesocricetus auratus) compared to manual sleep deprivation and immobilization stress. The hamsters kept under a 12:12 hours (h) light:dark cycle were deprived of sleep by sexual stimulation, gentle manual handling or immobilization stress for 1 h at the beginning of the light phase and subsequently sacrificed at zeitgeber time 01:00, respectively; for comparison, hamsters were manually sleep deprived for 6 or 20 h or sacrificed after completing a full sleep phase. As demonstrated by immunohistochemistry, apart from various alterations after manual sleep deprivation, sexual stimulation caused down-regulation of arginine-vasopressin (AVP), vasointestinal peptide (VIP), serotonin (5-HT), substance P (SP), and met-enkephalin (ME) in the SCN. Somatostatin (SOM) was diminished in the medial periventricular nucleus (MPVN). In contrast, an increase in AVP was observed in the PVN, that of oxytocin (OXY) in the supraoptic nucleus (SON), of tyrosine-hydroxylase (TH) in the infundibular nucleus (IN), and dopamine beta-hydroxylase (DBH) in the A7 neuron population of the brain stem (A7), respectively. Testosterone in plasma was increased. The results indicate that sexual arousal extensively influences the neuropeptide systems of the SCN, suggesting an involvement of the SCN in reproductive behavior.
Strenuous and unaccustomed exercise frequently lead to what has been coined “delayed onset muscle soreness” (DOMS). As implied by this term, it has been proposed that the associated pain and stiffness stem from micro-lesions, inflammation, or metabolite accumulation within the skeletal muscle. However, recent research points towards a strong involvement of the connective tissue. First, according to anatomical studies, the deep fascia displays an intimate structural relationship with the underlying skeletal muscle and may therefore be damaged during excessive loading. Second, histological and experimental studies suggest a rich supply of algogenic nociceptors whose stimulation evokes stronger pain responses than muscle irritation. Taken together, the findings support the hypothesis that DOMS originates in the muscle-associated connective tissue rather than in the muscle itself. Sports and fitness professionals designing exercise programs should hence consider fascia-oriented methods and techniques (e.g., foam rolling, collagen supplementation) when aiming to treat or prevent DOMS.
Rodent models of Parkinson’s disease are based on transgenic expression of mutant synuclein, deletion of PD genes, injections of MPTP or rotenone, or seeding of synuclein fibrils. The models show histopathologic features of PD such as Lewi bodies but mostly only subtle in vivo manifestations or systemic toxicity. The models only partly mimic a predominant loss of dopaminergic neurons in the substantia nigra. We therefore generated mice that express the transgenic diphtheria toxin receptor (DTR) specifically in DA neurons by crossing DAT-Cre mice with Rosa26 loxP-STOP-loxP DTR mice. After defining a well-tolerated DTx dose, DAT-DTR and DTR-flfl controls were subjected to non-toxic DTx treatment (5 × 100 pg/g) and subsequent histology and behavioral tests. DAT protein levels were reduced in the midbrain, and tyrosine hydroxylase-positive neurons were reduced in the substantia nigra, whereas the pan-neuronal marker NeuN was not affected. Despite the promising histologic results, there was no difference in motor function tests or open field behavior. These are tests in which double mutant Pink1−/−SNCAA53T Parkinson mice show behavioral abnormalities. Higher doses of DTx were toxic in both groups. The data suggest that DTx treatment in mice with Cre/loxP-driven DAT-DTR expression leads to partial ablation of DA-neurons but without PD-reminiscent behavioral correlates.
Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we report our initial experience of peripheral blood stem-cell collection (PBSC) in patients with treatment-related cytopenia and therefore high risk of bone-marrow failure. Five patients with diffuse bone-marrow infiltration of NET and relevant myelosuppression (≥grade 2) received PBSC before one PRRT cycle with 177Lu-DOTATATE (7.6 ± 0.8 GBq/cycle). Standard stem-cell mobilization with Granulocyte-colony stimulating factor (G-CSF) was applied, and successful PBSC was defined as a collection of >2 × 106/kg CD34+ cells. In case of initial failure, Plerixafor was administered in addition to G-CSF prior to apheresis. PBSC was successfully performed in all patients with no adverse events. Median cumulative activity was 44.8 GBq (range, 21.3–62.4). Three patients had been previously treated with PRRT, two of which needed the addition of Plerixafor for stem-cell mobilization. Only one of five patients required autologous peripheral blood stem-cell transplantation during the median follow up time of 28 months. PBSC collection seems to be feasible in NET with bone-marrow involvement and might be worth considering as a backup strategy prior to PRRT, in order to overcome dose-limiting bone-marrow toxicity.
Gaining detailed knowledge about sex-related immunoregulation remains a crucial prerequisite for the development of adequate disease models and therapeutic strategies enabling personalized medicine. Here, the key parameter of the production of cytokines mediating disease resolution was investigated. Among these cytokines, STAT3-activating interleukin (IL)-22 is principally associated with recovery from tissue injury. By investigating paradigmatic acetaminophen-induced liver injury, we demonstrated that IL-22 expression is enhanced in female mice. Increased female IL-22 was confirmed at a cellular level using murine splenocytes stimulated by lipopolysaccharide or αCD3/CD28 to model innate or adaptive immunoactivation. Interestingly, testosterone or dihydrotestosterone reduced IL-22 production by female but not by male splenocytes. Mechanistic studies on PMA/PHA-stimulated T-cell-lymphoma EL-4 cells verified the capability of testosterone/dihydrotestosterone to reduce IL-22 production. Moreover, we demonstrated by chromatin immunoprecipitation that testosterone impairs binding of the aryl hydrocarbon receptor to xenobiotic responsive elements within the murine IL-22 promoter. Overall, female mice undergoing acute liver injury and cultured female splenocytes upon inflammatory activation display increased IL-22. This observation is likely related to the immunosuppressive effects of androgens in males. The data presented concur with more pronounced immunological alertness demonstrable in females, which may relate to the sex-specific course of some immunological disorders.
Chronic rhinosinusitis (CRS) is often treated by functional endoscopic paranasal sinus surgery, which improves endoscopic parameters and quality of life, while olfactory function was suggested as a further criterion of treatment success. In a prospective cohort study, 37 parameters from four categories were recorded from 60 men and 98 women before and four months after endoscopic sinus surgery, including endoscopic measures of nasal anatomy/pathology, assessments of olfactory function, quality of life, and socio-demographic or concomitant conditions. Parameters containing relevant information about changes associated with surgery were examined using unsupervised and supervised methods, including machine-learning techniques for feature selection. The analyzed cohort included 52 men and 38 women. Changes in the endoscopic Lildholdt score allowed separation of baseline from postoperative data with a cross-validated accuracy of 85%. Further relevant information included primary nasal symptoms from SNOT-20 assessments, and self-assessments of olfactory function. Overall improvement in these relevant parameters was observed in 95% of patients. A ranked list of criteria was developed as a proposal to assess the outcome of functional endoscopic sinus surgery in CRS patients with nasal polyposis. Three different facets were captured, including the Lildholdt score as an endoscopic measure and, in addition, disease-specific quality of life and subjectively perceived olfactory function.
The family of phytochrome photoreceptors contains proteins with different domain architectures and spectral properties. Knotless phytochromes are one of the three main subgroups classified by their distinct lack of the PAS domain in their photosensory core module, which is in contrast to the canonical PAS-GAF-PHY array. Despite intensive research on the ultrafast photodynamics of phytochromes, little is known about the primary kinetics in knotless phytochromes. Here, we present the ultrafast Pr ⇆ Pfr photodynamics of SynCph2, the best-known knotless phytochrome. Our results show that the excited state lifetime of Pr* (~200 ps) is similar to bacteriophytochromes, but much longer than in most canonical phytochromes. We assign the slow Pr* kinetics to relaxation processes of the chromophore-binding pocket that controls the bilin chromophore’s isomerization step. The Pfr photoconversion dynamics starts with a faster excited state relaxation than in canonical phytochromes, but, despite the differences in the respective domain architectures, proceeds via similar ground state intermediate steps up to Meta-F. Based on our observations, we propose that the kinetic features and overall dynamics of the ultrafast photoreaction are determined to a great extent by the geometrical context (i.e., available space and flexibility) within the binding pocket, while the general reaction steps following the photoexcitation are most likely conserved among the red/far-red phytochromes.
The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. However, the factors predisposing individuals to severe disease remain poorly understood. Here, we show that levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells, are elevated in SARS-CoV-2-infected Caco-2 cells, Calu-3 cells, and air−liquid interface cultures of primary human bronchial epithelial cells. Moreover, SARS-CoV-2 infection increases SIRPalpha levels, the binding partner of CD47, on primary human monocytes. Systematic literature searches further indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions that may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, age-related and virus-induced CD47 expression is a candidate mechanism potentially contributing to severe COVID-19, as well as a therapeutic target, which may be addressed by antibodies and small molecules. Further research will be needed to investigate the potential involvement of CD47 and SIRPalpha in COVID-19 pathology. Our data should encourage other research groups to consider the potential relevance of the CD47/ SIRPalpha axis in their COVID-19 research.
Deformation in the upper mantle is localized in shear zones. In order to localize strain, weakening has to occur, which can be achieved by a reduction in grain size. In order for grains to remain small and preserve shear zones, phases have to mix. Phase mixing leads to dragging or pinning of grain boundaries which slows down or halts grain growth. Multiple phase mixing processes have been suggested to be important during shear zone evolution. The importance of a phase mixing process depends on the geodynamic setting. This study presents detailed microstructural analysis of spinel bearing shear zones from the Erro-Tobbio peridotite (Italy) that formed during pre-alpine rifting. The first stage of deformation occurred under melt-free conditions, during which clinopyroxene and olivine porphyroclasts dynamically recrystallized. With ongoing extension, silica-undersaturated melt percolated through the shear zones and reacted with the clinopyroxene neoblasts, forming olivine–clinopyroxene layers. Furthermore, the melt reacted with orthopyroxene porphyroclasts, forming fine-grained polymineralic layers (ultramylonites) adjacent to the porphyroclasts. Strain rates in these layers are estimated to be about an order of magnitude faster than within the olivine-rich matrix. This study demonstrates the importance of melt-rock reactions for grain size reduction, phase mixing and strain localization in these shear zones.
A high incidence of thromboembolic events associated with high mortality has been reported in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections with respiratory failure. The present study characterized post-transcriptional gene regulation by global microRNA (miRNA) expression in relation to activated coagulation and inflammation in 21 critically ill SARS-CoV-2 patients. The cohort consisted of patients with moderate respiratory failure (n = 11) and severe respiratory failure (n = 10) at an acute stage (day 0–3) and in the later course of the disease (>7 days). All patients needed supplemental oxygen and severe patients were defined by the requirement of positive pressure ventilation (intubation). Levels of D-dimers, activated partial thromboplastin time (aPTT), C-reactive protein (CRP), and interleukin (IL)-6 were significantly higher in patients with severe compared with moderate respiratory failure. Concurrently, next generation sequencing (NGS) analysis demonstrated increased dysregulation of miRNA expression with progression of disease severity connected to extreme downregulation of miR-320a, miR-320b and miR-320c. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed involvement in the Hippo signaling pathway, the transforming growth factor (TGF)-β signaling pathway and in the regulation of adherens junctions. The expression of all miR-320 family members was significantly correlated with CRP, IL-6, and D-dimer levels. In conclusion, our analysis underlines the importance of thromboembolic processes in patients with respiratory failure and emphasizes miRNA-320s as potential biomarkers for severe progressive SARS-CoV-2 infection.
Background: To test the effect of urological primary cancers (bladder, kidney, testis, upper tract, penile, urethral) on overall mortality (OM) after secondary prostate cancer (PCa). Methods: Within the Surveillance, Epidemiology and End Results (SEER) database, patients with urological primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion with primary PCa controls. OM was compared between secondary and primary PCa patients and stratified according to primary urological cancer type, as well as to time interval between primary urological cancer versus secondary PCa diagnoses. Results: We identified 5,987 patients with primary urological and secondary PCa (bladder, n = 3,287; kidney, n = 2,127; testis, n = 391; upper tract, n = 125; penile, n = 47; urethral, n = 10) versus 531,732 primary PCa patients. Except for small proportions of Gleason grade group and age at diagnosis, PCa characteristics between secondary and primary PCa were comparable. Conversely, proportions of secondary PCa patients which received radical prostatectomy were smaller (29.0 vs. 33.5%), while no local treatment rates were higher (34.2 vs. 26.3%). After 1:4 matching, secondary PCa patients exhibited worse OM than primary PCa patients, except for primary testis cancer. Here, no OM differences were recorded. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis. Conclusions: After detailed matching for PCa characteristics, secondary PCa patients exhibit worse survival, except for testis cancer patients. The survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary urological cancer diagnosis.
Objective: To evaluate the prognostic impact of gastrointestinal involvement on the survival of children with Langerhans cell histiocytosis (GI-LCH) registered with the international clinical trials of the Histiocyte Society. Study design: This was a retrospective analysis of 2414 pediatric patients registered onto the consecutive trials DAL-HX 83, DAL-HX 90, LCH-I, LCH-II, and LCH-III. Results: Among the 1289 patients with single-system LCH, there was no single case confined to the GI tract; 114 of 1125 (10%) patients with multisystem LCH (MS-LCH) had GI-LCH at initial presentation. GI-LCH was significantly more common in children aged <2 years at diagnosis (13% vs 6% in those aged >2 years; P < .001) and in those with risk organ involvement (15% vs 6% in those without risk organ involvement; P < .001). The 5-year overall survival (OS) in patients without risk organ involvement was excellent irrespective of GI disease (98% vs 97% in patients with GI-LCH; P = .789). In patients with risk organ involvement, the 5-year OS was 51% in 70 patients with GI-LCH vs 72% in 394 patients without GI-LCH (P < .001). Conclusions: GI-LCH has an additive unfavorable prognostic impact in children with MS-LCH and risk organ involvement. The emerding need for more intensive or alternative treatments mandates prospective evaluation.
With the Earth system being about to leave Holocene conditions and thus the known safe operating space for humanity, frameworks such as the Planetary Boundaries (PBs) and the Sustainable Development Goals (SDGs) provide quantitative metrics to guide sustainability transformations. In order to strive, not only for compliance with the PBs but also for societal well-being, some approaches attempt to combine both PBs and SDGs within a single assessment. We focus on two prominent examples, the “Doughnut” by Kate Raworth and the #SDGinPB project of the 2018 report to the Club of Rome, which are not only aimed at public outreach, but also at guiding policy-making. To meet these objectives, the approaches should possess a certain accuracy in determining the progress in achieving the SDGs and in complying with the PBs. We evaluate, by using a multi-indicator approach for comparison, whether both approaches’ limited set of indicators can still represent the SDGs’ complexity. This comparative approach estimates the progress in achieving SDGs, especially in the Global North, to be significantly lower. Based on these results and against the approaches’ purposes, we discuss their simplifications and at which point the results are no longer reliable. We conclude that global assessments can be an important factor in initiating transformative processes by stimulating public discourse, but that the actual implementation of these would require approaches with greater recognition of local particularities.
We combine structural analysis of fractures with 22 U–Pb dates measured in fracture-filling carbonate cements from bed-parallel fibrous calcite veins (beef), conjugated veins and faults within the Vaca Muerta Formation along the Andean fold and thrust belt in the Neuquén Basin. The measured ages constrain accurately the relationships between overpressures caused by hydrocarbon generation and Andean compression as mechanisms for natural fracturing and vein formation. Two generations of fibres have been identified in beef. The first one, consists of dark fibres from the inner zones, which are perpendicular to bedding and contain abundant cone-in-cone structures and hydrocarbon inclusions. U–Pb dating of these fibres yielded Early to Late Cretaceous ages from 116.7 ± 17.7 to 78.8 ± 10.2 Ma. The second generation of fibres corresponds to the outer zones and consists of white fibres oblique to bedding, indicating growth during layer-parallel shortening. Bed-perpendicular veins cutting beef yielded Late Cretaceous-late Palaeocene dates from 72.8 ± 22.4 to 60.9 ± 10.4 Ma. Eocene ages from 52.0 ± 2.9 to 42.2 ± 18.9 Ma were measured in bed-parallel slip surfaces and reverse and strike-slip faults, whereas Miocene dates from 13.9 ± 2.6 to 6.2 ± 1.1 Ma were measured in E-W calcite veins. U–Pb dating of veins, structural analysis of fractures and subsidence curves, indicate that beef inner zones formed in the oil window during burial of the Neuquén basin, and that tectonic stresses could enhance their formation. Beef outer zones and bed-perpendicular veins formed during E-W Late Cretaceous-late Palaeocene layer-parallel shortening. Contrarily, late Palaeocene-late Eocene bed-parallel slip surfaces and faults and Miocene E-W veins formed during NE-SW and E-W syn-to post-folding deformation, respectively. In both cases, syn-to post-folding compression occurred synchronously with forelandward migration of magmatic activity attributed to flat subduction of the Pacific slab beneath the Andes.
The impact of local environment characteristics on individual cycling behaviour has been discussed in transport research for several years. Many previous studies have, however, primarily focused on the presence and distribution of built environment elements, considered using georeferenced or census data. This paper argues that not only is the objectively measured environment an influencing factor, but also the individual perception of this environment. Furthermore, besides built elements, the evaluation of perceived non-built attributes, such as discourses and policies, as well as the environment’s impact on cycling attitudes, should be taken into account for a more comprehensive view. For this purpose, this study examines the responses to a household survey in the German city of Offenbach am Main (n = 701). The impact of the perceived local environment on cycling behaviour and cycling attitudes has been analysed using 21 perception items as well as socio-demographics, travel mode availability and general travel attitudes. For a more detailed view on cycling behaviour, this study applies the stage model of self-regulated behavioural change (SSBC) indicating a level of openness to use a bicycle frequently in everyday life. The results of the multivariate analysis show that the perceptions of built and non-built environment characteristics interrelate. Furthermore, certain perceptions encourage bicycle use and positive attitudes towards cycling, such as perceived cycling safety and pleasure. Primarily, these perceptions are safe and appropriate cycling infrastructures, cycling as a common practice and the absence of vandalism, dirt and high car pressure.
Objective: The term ‘precision medicine’ describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy. Methods: A systematic survey of patients with epilepsy with a molecular genetic diagnosis was conducted in six tertiary epilepsy centres including children and adults. A standardised questionnaire was used for data collection, including genetic findings and impact on clinical and therapeutic management. Results: We included 293 patients with genetic epilepsies, 137 children and 156 adults, 162 females and 131 males. Treatment changes were undertaken because of the genetic findings in 94 patients (32%), including rational precision medicine treatment and/or a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms. There was a rational precision medicine treatment for 56 patients (19%), and this was tried in 33/56 (59%) and was successful (ie, >50% seizure reduction) in 10/33 (30%) patients. In 73/293 (25%) patients there was a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms, and this was successful in 24/73 (33%). Significance: Our survey of clinical practice in specialised epilepsy centres shows high variability of clinical outcomes following the identification of a genetic cause for an epilepsy. Meaningful change in the treatment paradigm after genetic testing is not yet possible for many people with epilepsy. This systematic survey provides an overview of the current application of precision medicine in the epilepsies, and suggests the adoption of a more considered approach.
Abstract: Neurophysiological measures of preparation and attention are often atypical in ADHD. Still, replicated findings that these measures predict which patients improve after Neurofeedback (NF), reveal neurophysiological specificity, and reflect ADHD-severity are limited. Methods: We analyzed children’s preparatory (CNV) and attentional (Cue-P3) brain activity and behavioral performance during a cued Continuous Performance Task (CPT) before and after slow cortical potential (SCP)-NF or semi-active control treatment (electromyogram biofeedback). Mixed-effects models were performed with 103 participants at baseline and 77 were assessed for pre-post comparisons focusing on clinical outcome prediction, specific neurophysiological effects of NF, and associations with ADHD-severity. Results: Attentional and preparatory brain activity and performance were non-specifically reduced after treatment. Preparatory activity in the SCP-NF group increased with clinical improvement. Several performance and brain activity measures predicted non-specific treatment outcome. Conclusion: Specific neurophysiological effects after SCP-NF were limited to increased neural preparation associated with improvement on ADHD-subscales, but several performance and neurophysiological measures of attention predicted treatment outcome and reflected symptom severity in ADHD. The results may help to optimize treatment.
Korrektur zu: Roth C, Rettenmaier L and Behringer M (2021) High-Protein Energy-Restriction: Effects on Body Composition, Contractile Properties, Mood, and Sleep in Active Young College Students. Front. Sports Act. Living 3:683327. https://doi.org/10.3389/fspor.2021.683327
2-Aminobenzimidazole 10, although a weak catalyst in the monomeric state, is a successful building block for effective artificial ribonucleases. In an effort to identify new building blocks with improved catalytic potential, RNA cleavage by a variety of heterocyclic amidines and guanidines has been studied. In addition to pKa values and steric effects, the energy difference between tautomeric forms seems to be another important parameter for catalysis. This information is available from quantum chemical calculations on higher levels, but semiempirical methods are sufficient to get a first estimate. According to this assumption, imidazoimidazol 18, characterized by isoenergetic tautomeric forms, is superior to 2-aminoimidazol 6, the best candidate among the simple compounds. By far the largest effects are seen with 2-aminoperimidine 24, which rapidly cleaves RNA even in the micromolar concentration range. The impressive reactivity, however, is related to a tendency of compound 24 to form polycationic aggregates which are the actual catalysts.
Extremophilic prokaryotes live under harsh environmental conditions which require far-reaching cellular adaptations. The acquisition of novel genetic information via natural transformation plays an important role in bacterial adaptation. This mode of DNA transfer permits the transfer of genetic information between microorganisms of distant evolutionary lineages and even between members of different domains. This phenomenon, known as horizontal gene transfer (HGT), significantly contributes to genome plasticity over evolutionary history and is a driving force for the spread of fitness-enhancing functions including virulence genes and antibiotic resistances. In particular, HGT has played an important role for adaptation of bacteria to extreme environments. Here, we present a survey of the natural transformation systems in bacteria that live under extreme conditions: the thermophile Thermus thermophilus and two desiccation-resistant members of the genus Acinetobacter such as Acinetobacter baylyi and Acinetobacter baumannii. The latter is an opportunistic pathogen and has become a world-wide threat in health-care institutions. We highlight conserved and unique features of the DNA transporter in Thermus and Acinetobacter and present tentative models of both systems. The structure and function of both DNA transporter are described and the mechanism of DNA uptake is discussed.
Background: The promotion of healthy aging is one of the major challenges for healthcare systems in current times. The present study investigates the effects of a standardized physical activity intervention for older adults on cognitive capacity, self-reported health, fear of falls, balance, leg strength and gait under consideration of movement biography, sleep duration, and current activity behavior. Methods: This single-blinded, randomized controlled trial included 49 community-dwelling older adults (36 women; 82.9 ± 4.5 years of age (Mean [M] ± SD); intervention group = 25; control group = 24). Movement biography, sleep duration, cognitive capacity, self-reported health status, and fear of falls were assessed by means of questionnaires. Leg strength, gait, and current activity levels were captured using a pressure plate, accelerometers, and conducting the functional-reach and chair-rising-test. The multicomponent intervention took place twice a week for 45 min and lasted 16 weeks. Sub-cohorts of different sleep duration were formed to distinguish between intervention effects and benefits of healthy sleep durations. Change scores were evaluated in univariate analyses of covariances (ANCOVAs) between groups and sub-cohorts of different sleep duration in both groups. Changes in cognitive capacity, self-reported health, fear of falls, balance, leg strength, and gait were investigated using the respective baseline values, movement biography, and current activity levels as covariates. Analysis was by intention-to-treat (ITT). Results: We found sub-cohort differences in cognitive capacity change scores [F(3,48) = 5.498, p = 0.003, ηp2 = 0.287]. Effects on fear of falls [F(1,48) = 12.961, p = 0.001, ηp2 = 0.240] and balance change scores F(1,48) = 4.521, p = 0.040, ηp2 = (0.099) were modified by the level of current activity. Effects on gait cadence were modified by the movement biography [F(1,48) = 4.545; p = 0.039, ηp2 = 0.100]. Conclusions: Unlike for functional outcomes, our multicomponent intervention in combination with adequate sleep duration appears to provide combinable beneficial effects for cognitive capacity in older adults. Trainability of gait, fear of falls, and flexibility seems to be affected by movement biography and current physical activity levels. Trial registration: This study was registered at the DRKS (German Clinical Trials Register) on November 11, 2020 with the corresponding trial number: DRKS00020472.
We investigated whether dichotomous data showed the same latent structure as the interval-level data from which they originated. Given constancy of dimensionality and factor loadings reflecting the latent structure of data, the focus was on the variance of the latent variable of a confirmatory factor model. This variance was shown to summarize the information provided by the factor loadings. The results of a simulation study did not reveal exact correspondence of the variances of the latent variables derived from interval-level and dichotomous data but shrinkage. Since shrinkage occurred systematically, methods for recovering the original variance were fleshed out and evaluated.
The sudden impact of the COVID-19 pandemic challenged universities to provide students with online teaching and learning settings that were both immediately applicable and supportive of quality learning. This resulted in a broad variety of synchronous and asynchronous online settings of teaching and learning. While some courses balanced both kinds, others offered either predominantly synchronous or asynchronous teaching and learning. In a survey study with students (N=3,056) and teachers (N=396) from a large German university, we explored whether a predominance of synchronous or asynchronous teaching and learning settings in higher education was associated with certain student experiences and outcomes. Additionally, we examined how well these two types of teaching and learning settings support students’ basic psychological needs for autonomy, competence, and relatedness proposed by self-determination theory (SDT). Data were collected after the first online semester due to the COVID-19 pandemic. The results imply that from the students’ perspective, the teaching methods involved in the two settings of teaching and learning differ with regard to their potential to support social interaction and to support basic psychological needs as proposed by SDT. Students who studied mostly in synchronous settings reported more peer-centered activities such as feedback in comparison to students in mostly asynchronous settings. In contrast, teachers perceived fewer differences between teaching methods in synchronous and asynchronous settings, especially regarding feedback activities. Further, students in mostly synchronous settings reported greater support of their basic psychological needs for competence support and relatedness as well as a greater overall satisfaction with the online term compared to students in mostly asynchronous settings. Across all students, greater fulfillment of psychological needs and higher technology acceptance coincided with outcomes that are more favorable. Implications for the post-pandemic classroom are drawn.
Selfish genetic elements that act as post-segregation distorters cause lethality in non-carrier individuals after fertilization. Two post-segregation distorters have been previously identified in Caenorhabditis elegans, the peel-1/zeel-1 and the sup-35/pha-1 elements. These elements seem to act as modification-rescue systems, also called toxin/antidote pairs. Here we show that the maternal-effect toxin/zygotic antidote pair sup-35/pha-1 is required for proper expression of apical junction (AJ) components in epithelia and that sup-35 toxicity increases when pathways that establish and maintain basal epithelial characteristics, die-1, elt-1, lin-26, and vab-10, are compromised. We demonstrate that pha-1(e2123) embryos, which lack the antidote, are defective in epidermal morphogenesis and frequently fail to elongate. Moreover, seam cells are frequently misshaped and mispositioned and cell bond tension is reduced in pha-1(e2123) embryos, suggesting altered tissue material properties in the epidermis. Several aspects of this phenotype can also be induced in wild-type embryos by exerting mechanical stress through uniaxial loading. Seam cell shape, tissue mechanics, and elongation can be restored in pha-1(e2123) embryos if expression of the AJ molecule DLG-1/Discs large is reduced. Thus, our experiments suggest that maternal-effect toxicity disrupts proper development of the epidermis which involves distinct transcriptional regulators and AJ components.
Background: This study aims to test the effect of the 10 most common nonurological primary cancers (skin, rectal, colon, lymphoma, leukemia, pancreas, stomach, esophagus, liver, lung) on overall mortality (OM) after secondary prostate cancer (PCa). Material and Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database, patients with 10 most common primary cancers and concomitant secondary PCa (diagnosed 2004–2016) were identified and were matched in 1:4 fashion (age, year at diagnosis, race/ethnicity, treatment type, TNM stage) with primary PCa controls. OM was compared between secondary and primary PCa patients and was stratified according to primary cancer type, as well as according to time interval between primary cancer vs. secondary PCa diagnoses. Results: We identified 24,848 secondary PCa patients (skin, n = 3,871; rectal, n = 798; colon, n = 3,665; lymphoma, n = 2,583; leukemia, n = 1,102; pancreatic, n = 118; stomach, n = 361; esophagus, n = 219; liver, n = 160; lung, n = 1,328) vs. 531,732 primary PCa patients. Secondary PCa characteristics were less favorable than those of primary PCa patients (PSA and grade), and smaller proportions of secondary PCa patients received active treatment. After 1:4 matching, all secondary PCa exhibited worse OM than primary PCa patients. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis and subsequent secondary PCa. Conclusion: Patients with secondary PCa are diagnosed with less favorable PSA and grade. Even after matching for PCa characteristics, secondary PCa patients still exhibit worse survival. However, the survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary cancer diagnosis.
Muscular fatigue can affect postural control processes by impacting on the neuromuscular and somatosensory system. It is assumed that this leads to an increased risk of injury, especially in sports such as alpine skiing that expose the body to strong and rapidly changing external forces. In this context, posture constraints and contraction-related muscular pressure may lead to muscular deoxygenation. This study investigates whether these constraints and pressure affect static and dynamic postural control. To simulate impaired blood flow in sports within a laboratory task, oxygen saturation was manipulated locally by using an inflatable cuff to induce blood flow restriction (BFR). Twenty-three subjects were asked to stand on a perturbatable platform used to assess postural-related movements. Using a 2 × 2 within-subject design, each participant performed postural control tasks both with and without BFR. BFR resulted in lower oxygenation of the m. quadriceps femoris (p = 0.024) and was associated with a significantly lower time to exhaustion (TTE) compared to the non-restricted condition [F(1,19) = 16.22, p < 0.001, ηp2 = 0.46]. Perturbation resulted in a significantly increased TTE [F(1,19) = 7.28, p = 0.014, ηp2 = 0.277]. There were no significant effects on static and dynamic postural control within the saturation conditions. The present data indicate that BFR conditions leads to deoxygenation and a reduced TTE. Postural control and the ability to regain stability after perturbation were not affected within this investigation.
he ubiquity of microplastics in aquatic ecosystems has raised concerns over their interaction with biota. However,microplastics research on freshwater species, especially mollusks, is still scarce. We, therefore, investigated the factorsaffecting microplastics ingestion in the freshwater musselDreissena polymorpha. Using polystyrene spheres (5, 10, 45,90μm), we determined the body burden of microplastics in the mussels in relation to 1) exposure and depuration time, 2)body size, 3) food abundance, and 4) microplastic concentrations.D. polymorpharapidly ingested microplastics and ex-creted most particles within 12 h. A few microplastics were retained for up to 1 wk. Smaller individuals had a higher relativebody burden of microplastics than larger individuals. The uptake of microplastics was concentration‐dependent, whereas anadditional food supply (algae) reduced it. We also compared the ingestion of microplastics byD. polymorphawith 2 otherfreshwater species (Anodonta anatina,Sinanodonta woodiana), highlighting that absolute and relative uptake depends onthe species and the size of the mussels. In addition, we determined toxicity of polystyrene fragments (≤63μm,6.4–100 000 p mL–1) and diatomite (natural particle, 100 000 p mL–1)inD. polymorphaafter 1, 3, 7, and 42 d of exposure,investigating clearance rate, energy reserves, and oxidative stress. Despite ingesting large quantities, exposure to poly-styrene fragments only affected the clearance rate ofD. polymorpha. Further, results of the microplastic and diatomiteexposure did not differ significantly. Therefore,D. polymorphais unaffected by or can compensate for polystyrene fragmenttoxicity even at concentrations above current environmental levels.Environ Toxicol Chem2021;40:2247–2260. © 2021 TheAuthors.Environmental Toxicology and Chemistrypublished by Wiley Periodicals LLC on behalf of SETAC.Keywords:Microplastics; Toxic effects; Mollusk toxicity
Aquatic ecosystems are globally contaminated with microplastics (MP). However, comparative data on MP levels in freshwater systems is still scarce. Therefore, the aim of this study is to quantify MP abundance in water and sediment of the German river Elbe using visual, spectroscopic (Fourier-transform infrared spectroscopy) and thermo analytical (pyrolysis gas chromatography mass spectrometry) methods. Samples from eleven German sites along the German part of the Elbe were collected, both in the water and sediment phase, in order to better understand MP sinks and transport mechanisms. MP concentrations differed between the water and sediment phase. Sediment concentrations (mean: 3,350,000 particles m−3, 125–5000 μm MP) were in average 600,000-fold higher than water concentrations (mean: 5.57 particles m−3, 150–5000 μm MP). The abundance varied between the sampling sites: In sediments, the abundance decreased in the course of the river while in water samples no such clear trend was observed. This may be explained by a barrage retaining sediments and limiting tidal influence in the upstream parts of the river. Particle shape differed site-specifically with one site having exceptionally high quantities of spheres, most probably due to industrial emissions of PS-DVB resin beads. Suspended MP consisted predominantly of polyethylene and polypropylene whereas sediments contained a higher diversity of polymer types. Determined MP concentrations correspond well to previous results from other European rivers. In a global context, MP levels in the Elbe relate to the lower (water) to middle section (sediment) of the global range of MP concentrations determined for rivers worldwide. This highlights that elevated MP levels are not only found in single countries or continents, but that MP pollution is an issue of global concern.
With our research, we contribute to the research on proactive work behavior in two ways. First, we examine a person's gender as a boundary condition for proactive behavior at work. Based on social role theory, we argue that women are less likely to receive credit for showing personal initiative (PI) than men. Second, we examine agency and communion as underlying mechanisms that translate PI into a person's evaluation and drive backlash effects. The hypotheses were tested in two complementary experimental studies (Study 1; N = 114, Study 2: N = 163) using simulated job interviews. Our results show that PI relates to better evaluations (likeability, perceived competence, performance evaluations, expected success and hireability) of the job applicant and that these effects are mediated by agency and communion. Further, we find backlash effects for women high in agency and men high in communion on likeability (Study 2). The implications of these results for organizations and future research are discussed.
Background: Patients with colorectal carcinoma and high-grade microsatellite instability (MSI-H) or deficiency in mismatch repair (dMMR) exceptionally respond to immune checkpoint inhibitors (ICIs). ICIs are more active in treatment-naïve patients than in patients with refractory MSI-H/dMMR metastatic colorectal cancer and even more active in patients with locally advanced tumors. Material and Methods: A 33-year-old male patient with Lynch syndrome was diagnosed with a locally advanced rectal cancer and refused standard neoadjuvant chemoradiation because of the potential harm of sexual dysfunction. MMR and microsatellite instability status were analyzed by immunohistochemistry and fragment length polymerase chain reaction followed by capillary electrophoresis. Results: After MSI-H/dMMR was confirmed, the patient was treated with ICIs (1 mg/kg ipilimumab at day 1 and 3 mg/kg nivolumab at day 1 and 15). A complete clinical response was documented at day 21 after start of treatment. The patient underwent a total mesorectal excision at day 30. In the extirpated tissue, a complete pathological response was confirmed. Conclusion: In MSI-H/dMMR locally advanced rectal cancer short-course ICI treatment is highly effective and may be discussed in patients with dMMR locally advanced rectal cancer.
Background: To analyze postoperative, in-hospital, complication rates in patients with organ transplantation before radical prostatectomy (RP). Methods: From National Inpatient Sample (NIS) database (2000–2015) prostate cancer patients treated with RP were abstracted and stratified according to prior organ transplant versus nontransplant. Multivariable logistic regression models predicted in-hospital complications. Results: Of all eligible 202,419 RP patients, 216 (0.1%) underwent RP after prior organ transplantation. Transplant RP patients exhibited higher proportions of Charlson comorbidity index ≥2 (13.0% vs. 3.0%), obesity (9.3% vs. 5.6%, both p < 0.05), versus to nontransplant RP. Of transplant RP patients, 96 underwent kidney (44.4%), 44 heart (20.4%), 40 liver (18.5%), 30 (13.9%) bone marrow, <11 lung (<5%), and <11 pancreatic (<5%) transplantation before RP. Within transplant RP patients, rates of lymph node dissection ranged from 37.5% (kidney transplant) to 60.0% (bone marrow transplant, p < 0.01) versus 51% in nontransplant patients. Regarding in-hospital complications, transplant patients more frequently exhibited, diabetic (31.5% vs. 11.6%, p < 0.001), major (7.9% vs. 2.9%) cardiac complications (3.2% vs. 1.2%, p = 0.01), and acute kidney failure (5.1% vs. 0.9%, p < 0.001), versus nontransplant RP. In multivariable logistic regression models, transplant RP patients were at higher risk of acute kidney failure (odds ratio [OR]: 4.83), diabetic (OR: 2.81), major (OR: 2.39), intraoperative (OR: 2.38), cardiac (OR: 2.16), transfusion (OR: 1.37), and overall complications (1.36, all p < 0.001). No in-hospital mortalities were recorded in transplant patients after RP. Conclusions: Of all transplants before RP, kidney ranks first. RP patients with prior transplantation have an increased risk of in-hospital complications. The highest risk, relative to nontransplant RP patients appears to acute kidney failure.
Model frameworks, based on Floquet theory, have been shown to produce effective tools for accurately predicting phase-noise response of single (free-running) oscillator systems. This method of approach, referred to herein as macro-modeling, has been discussed in several highly influential papers and now constitutes an established branch of modern circuit theory. The increased application of, for example, injection-locked oscillators and oscillator arrays in modern communication systems has subsequently exposed the demand for similar rigorous analysis tools aimed at coupled oscillating systems. This paper presents a novel solution in terms of a macro-model characterizing the phase-response of synchronized coupled oscillator circuits and systems perturbed by weak noise sources. The framework is generalized and hence applicable to all circuit configurations and coupling topologies generating a synchronized steady-state. It advances and replaces the phenomenological descriptions currently found in the published literature pertaining to this topic and, as such, represents a significant breakthrough w.r.t. coupled oscillator noise modeling. The proposed model is readily implemented numerically using standard routines.
The majority of excitatory synapses terminating on cortical neurons are found on dendritic spines. The geometry of spines, in particular the size of the spine head, tightly correlates with the strength of the excitatory synapse formed with the spine. Under conditions of synaptic plasticity, spine geometry may change, reflecting functional adaptations. Since the cytokine tumor necrosis factor (TNF) has been shown to influence synaptic transmission as well as Hebbian and homeostatic forms of synaptic plasticity, we speculated that TNF-deficiency may cause concomitant structural changes at the level of dendritic spines. To address this question, we analyzed spine density and spine head area of Alexa568-filled granule cells in the dentate gyrus of adult C57BL/6J and TNF-deficient (TNF-KO) mice. Tissue sections were double-stained for the actin-modulating and plasticity-related protein synaptopodin (SP), a molecular marker for strong and stable spines. Dendritic segments of TNF-deficient granule cells exhibited ∼20% fewer spines in the outer molecular layer of the dentate gyrus compared to controls, indicating a reduced afferent innervation. Of note, these segments also had larger spines containing larger SP-clusters. This pattern of changes is strikingly similar to the one seen after denervation-associated spine loss following experimental entorhinal denervation of granule cells: Denervated granule cells increase the SP-content and strength of their remaining spines to homeostatically compensate for those that were lost. Our data suggest a similar compensatory mechanism in TNF-deficient granule cells in response to a reduction in their afferent innervation.
Aim: It can be challenging to distinguish COVID-19 in children from other common infections. We set out to determine the rate at which children consulting a primary care paediatrician with an acute infection are infected with SARS-CoV-2 and to compare distinct findings. Method: In seven out-patient clinics, children aged 0–13 years with any new respiratory or gastrointestinal symptoms and presumed infection were invited to be tested for SARS-CoV-2. Factors that were correlated with testing positive were determined. Samples were collected from 25 January 2021 to 01 April 2021. Results: Seven hundred and eighty-three children participated in the study (median age 3 years and 0 months, range 1 month to 12 years and 11 months). Three hundred and fifty-eight were female (45.7%). SARS-CoV-2 RNA was detected in 19 (2.4%). The most common symptoms in children with as well as without detectable SARS-CoV-2 RNA were rhinitis, fever and cough. Known recent exposure to a case of COVID-19 was significantly correlated with testing positive, but symptoms or clinical findings were not. Conclusion: COVID-19 among the children with symptoms of an acute infection was uncommon, and the clinical presentation did not differ significantly between children with and without evidence of an infection with SARS-CoV-2.
Ever since Hegel highlighted the difference between morality and ethical life or ‘Sittlichkeit’, philosophical discourse concerning morality and law in the traditions that developed subsequently, up to and including the Frankfurt School, has oscillated between those poles. This paper opens with a short exposition of autonomy as one of the few large-scale innovations in the history of philosophy and proceeds to discuss Hegel's concept of ethical life and the objections that can be raised against it from a Kantian point of view. Political theory, however, has to move beyond pure normativism and consider actual social relations of power, as Marx disclosed. Tracing this winding trajectory from Kant to Marx provides some perspective that may be illuminating concerning present-day challenges.
Introduction: Adeno-associated virus (AAV)-based gene therapy for haemophilia presents a challenge to the existing structure of haemophilia centres and requires a rethink of current collaboration and information exchange with the aim of ensuring a system that is fit-for-purpose for advanced therapies to maximise benefits and minimise risks. In Europe, a certification process based on the number of patients and facilities is offered to the haemophilia centres by European Haemophilia Network (EUHANET). Aim and methods: This joint European Association for Haemophilia and Allied Disorders (EAHAD) and European Haemophilia Consortium (EHC) publication describes criteria for centres participating in gene therapy care that require a reassessment of the infrastructure of comprehensive care and provides an outlook on how these criteria can be implemented in the future work of haemophilia centres. Results: The core definition of a haemophilia treatment centre remains, but additional roles could be implemented. A modifiable ‘hub-and-spoke’ model addresses all aspects associated with gene therapy, including preparation and administration of the gene therapy product, determination of coagulation and immunological parameters, joint.
2-Aminobenzimidazole 10, although a weak catalyst in the monomeric state, is a successful building block for effective artificial ribonucleases. In an effort to identify new building blocks with improved catalytic potential, RNA cleavage by a variety of heterocyclic amidines and guanidines has been studied. In addition to pKa values and steric effects, the energy difference between tautomeric forms seems to be another important parameter for catalysis. This information is available from quantum chemical calculations on higher levels, but semiempirical methods are sufficient to get a first estimate. According to this assumption, imidazoimidazol 18, characterized by isoenergetic tautomeric forms, is superior to 2-aminoimidazol 6, the best candidate among the simple compounds. By far the largest effects are seen with 2-aminoperimidine 24, which rapidly cleaves RNA even in the micromolar concentration range. The impressive reactivity, however, is related to a tendency of compound 24 to form polycationic aggregates which are the actual catalysts.
Introduction: Over the last decade, multiple clinical trials demonstrated improved survival after chemotherapy for metastatic prostate cancer (mPCa). However, real-world data validating this effect within large-scale epidemiological data sets are scarce. We addressed this void. Materials and Methods: Men with de novo mPCa were identified and systemic chemotherapy status was ascertained within the Surveillance, Epidemiology, and End Results database (2004–2016). Patients were divided between historical (2004–2013) versus contemporary (2014–2016). Chemotherapy rates were plotted over time. Kaplan–Meier plots and Cox regression models with additional multivariable adjustments addressed overall and cancer-specific mortality. All tests were repeated in propensity-matched analyses. Results: Overall, 19,913 patients had de novo mPCa between 2004 and 2016. Of those, 1838 patients received chemotherapy. Of 1838 chemotherapy-exposed patients, 903 were historical, whereas 905 were contemporary. Chemotherapy rates increased from 5% to 25% over time. Median overall survival was not reached in contemporary patients versus was 24 months in historical patients (hazard ratio [HR]: 0.55, p < 0.001). After propensity score matching and additional multivariable adjustment (age, prostate-specific antigen, GGG, cT-stage, cN-stage, cM-stage, and local treatment) a HR of 0.55 (p < 0.001) was recorded. Analyses were repeated for cancer-specific mortality after adjustment for other cause mortality in competing risks regression models and recorded virtually the same findings before and after propensity score matching (HR: 0.55, p < 0.001). Conclusions: In mPCa patients, chemotherapy rates increased over time. A concomitant increase in survival was also recorded.
Purpose: To evaluate the impact of testing asymptomatic cancer patients, we analyzed all tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) before and during radiotherapy at a tertiary cancer center throughout the second wave of the pandemic in Germany. Methods: Results of all real-time polymerase chain reaction (RT-PCR) tests for SARS-CoV 2 performed at our radio-oncology department between 13 October 2020 and 11 March 2021 were included. Clinical data and anamnestic information at the time of testing were documented and examined for (i) the presence of COVID-19-related symptoms and (ii) virus-related anamnesis (high-risk [prior positive test or contact to a positive tested person within the last 14 days] or low-risk [inconspicuous anamnesis within the last 14 days]). Results: A total of 1056 SARS-CoV 2 tests in 543 patients were analyzed. Of those, 1015 tests were performed in asymptomatic patients and 41 tests in patients with COVID-19-associated symptoms. Two of 940 (0.2%) tests in asymptomatic patients with low-risk anamnesis and three of 75 (4.0%) tests in asymptomatic patients with high-risk anamnesis showed a positive result. For symptomatic patients, SARS-CoV 2 was detected in three of 36 (8.3%) low-risk and three of five (60.0%) high-risk tests. Conclusion: To the best of our knowledge, this is the first study evaluating the correlation between individual risk factors and positivity rates of SARS-CoV 2 tests in cancer patients. The data demonstrate that clinical and anamnestic assessment is a simple and effective measure to distinctly increase SARS-CoV 2 test efficiency. This might enable cancer centers to adjust test strategies in asymptomatic patients, especially when test resources are scarce.
Interpretation bias and dysfunctional social assumptions are proposed to play a pivotal role in the development and maintenance of social phobia (SP), especially in youth. In this study, we aimed to investigate disorder-specific implicit assumptions of rejection and implicit interpretation bias in youth with severe, chronic SP and healthy controls (CG). Twenty-seven youth with SP in inpatient/day-care treatment (M age = 15.6 years, 74% female) and 24 healthy controls (M age = 15.7 years, 54% female) were included. The Implicit Association Test (IAT) and the Affect Misattribution Procedure (AMP) were completed to assess implicit assumptions and interpretation bias related to the processing of social and affective stimuli. No group differences were observed for the IAT controlling for depressive symptoms in the analyses. However, group differences were found regarding interpretation bias (p = .017, η2p = .137). Correlations between implicit scores and explicit questionnaire results were medium to large in the SP group (r =|.28| to |.54|, pall ≤ .05), but lower in the control group (r =|.04| to |.46|, pall ≤ .05). Our results confirm the finding of an interpretation bias in youth SP, especially regarding the implicit processing of faces, whereas implicit dysfunctional social assumptions of being rejected do not seem to be specific for SP. Future research should investigate the causal relationship of assumptions/interpretation bias and SP.
Estimating the age of the developmental stages of the blow fly Calliphora vicina (Diptera: Calliphoridae) is of forensic relevance for the determination of the minimum post-mortem interval (PMImin). Fly eggs and larvae can be aged using anatomical and morphological characters and their modification during development. However, such methods can only hardly be applied for aging fly pupae. Previous study described age estimation of C. vicina pupae using gene expression, but just when reared at constant temperatures, but fluctuating temperatures represent a more realistic scenario at a crime scene. Therefore, age-dependent gene expression of C. vicina pupae were compared at 3 fluctuating and 3 constant temperatures, the latter representing the mean values of the fluctuating profiles. The chosen marker genes showed uniform expression patterns during metamorphosis of C. vicina pupae bred at different temperature conditions (constant or fluctuating) but the same mean temperature (e.g. constant 10 °C vs. fluctuating 5–15 °C). We present an R-based statistical tool, which enables estimation of the age of the examined pupa based on the analysed gene expression data.
Sprach- und Sprechstörungen kommen bei zahlreichen Kindern vor und werden in der ICD-11 analog zur ICD-10 als Entwicklungsstörungen im Kapitel 6 (Psychische, Verhaltens- und Entwicklungsstörungen) klassifiziert. International sind bislang die ICD-10-Kriterien nicht von allen Professionen, die sich mit Sprach- und Sprechstörungen klinisch oder im Rahmen der Forschung beschäftigen, akzeptiert. Sie werden einerseits als zu wenig differenziert hinsichtlich der unterschiedlichen Sprachkomponenten vonseiten der Linguistik, Sprachtherapie oder Logopädie erlebt. Zum anderen wird die unklare Abgrenzung organisch bedingter Sprach- und Sprechprobleme von der Sprachentwicklungsstörung vonseiten der Medizin teilweise kritisch bewertet. In dem vorliegenden Artikel wird deshalb einerseits die Klassifikation von Sprach- und Sprechproblemen und -störungen in der ICD-11 im Vergleich zur ICD-10 vorgenommen. Wesentlich erscheint hier die in der ICD-11 neu eingeführte Differenzierung in „primäre“ und „sekundäre“ Neuroentwicklungsstörungen. Zum anderen erfolgt aber auch eine Auseinandersetzung mit dem DSM-5 sowie anderen Klassifikationsvorschlägen vonseiten der englischsprachigen Sprachtherapie (CATALISE-2) und der deutschsprachigen Pädaudiologie („phonologische Wahrnehmungsstörung“) sowie der Vorschlag einer Ergänzung der aktuellen ICD-11-Klassifikation hinsichtlich konkreter sprachlicher Einschränkungen bei einem Kind mit Sprachentwicklungsstörung, basierend auf einer ausführlichen Diagnostik. Wir hoffen, mit dem Artikel so den Weg für eine berufsübergreifende Klassifikation von Sprach- und Sprechstörungen nach ICD-11 zu bahnen, damit perspektivisch alle Berufsgruppen, die Diagnostik und Therapie der betroffenen Personen anbieten, eine vergleichbare Terminologie verwenden. Diese vergleichbare Terminologie soll sowohl die klinische Versorgung verbessern als auch die unterschiedlichen Forschungsansätze und -richtungen vergleichbarer machen.
Criminal law exceptionalism, or so I suggest, has turned into an ideology in German and Continental criminal law theory. It rests on interrelated claims about the (ideal or real) extraordinary qualities and properties of the criminal law and has led to exceptional doctrines in constitutional criminal law and criminal law theory. It prima facie paradoxically perpetuates and conserves the criminal law, and all too often leads to ideological thoughtlessness, which may blind us to the dark sides of criminal laws in action.
The single crystal growth of 19 different intermetallic compounds within the LnT2X2 family (with Ln = lanthanides, T = Co, Ru, Rh, Ir, and X = Si, P) is presented, by employing a high-temperature metal-flux technique. The habitus of the obtained crystals is platelet-like with the crystallographic c direction perpendicular to the surface and with individual masses between 1 and 100 mg. The magnetic properties of these crystals are characterized by magnetization, heat-capacity, and resistivity measurements. These crystals form the materials basis for a thorough study of exciting surface properties by angle-resolved photoemission spectroscopy.
Motions on planetary spatial scales in the atmosphere are governed by the planetary geostrophic equations. However, little attention has been paid to the interaction between the baroclinic and barotropic flows within the planetary geostrophic scaling. This is the focus of the present study, which utilizes planetary geostrophic equations for a Boussinesq fluid supplemented by a novel evolution equation for the barotropic flow. The latter is affected by meridional momentum flux due to baroclinic flow and drag by the surface wind. The barotropic wind, on the other hand, affects the baroclinic flow through buoyancy advection. Via a relaxation towards a prescribed buoyancy profile the model produces realistic major features of the zonally symmetric wind and temperature fields. We show that there is considerable cancellation between the barotropic and the baroclinic surface zonal mean zonal winds. Linear and nonlinear model responses to steady diabatic zonally asymmetric forcing are investigated, and the arising stationary waves are interpreted in terms of analytical solutions. We also study the problem of baroclinic instability on the sphere within the present model.
The locus coeruleus (LC) contains the majority of central noradrenergic neurons sending wide projections throughout the entire CNS. The LC is considered to be essential for multiple key brain functions including arousal, attention and adaptive stress responses as well as higher cognitive functions and memory. Electrophysiological studies of LC neurons have identified several characteristic functional features such as low-frequency pacemaker activity with broad action potentials, transient high-frequency burst discharges in response to salient stimuli and an apparently homogeneous inhibition of firing by activation of somatodendritic α2 autoreceptors (α2AR). While stress-mediated plasticity of the α2AR response has been described, it is currently unclear whether different LC neurons projecting to distinct axonal targets display differences in α2AR function. Using fluorescent beads-mediated retrograde tracing in adult C57Bl6/N mice, we compared the anatomical distributions and functional in vitro properties of identified LC neurons projecting either to medial prefrontal cortex, hippocampus or cerebellum. The functional in vitro analysis of LC neurons confirmed their mostly uniform functional properties regarding action potential generation and pacemaker firing. However, we identified significant differences in tonic and evoked α2AR-mediated responses. While hippocampal-projecting LC neurons were partially inhibited by endogenous levels of norepinephrine and almost completely silenced by application of saturating concentrations of the α2 agonist clonidine, prefrontal-projecting LC neurons were not affected by endogenous levels of norepinephrine and only partially inhibited by saturating concentrations of clonidine. Thus, we identified a limited α2AR control of electrical activity for prefrontal-projecting LC neurons indicative of functional heterogeneity in the LC-noradrenergic system.
Individual differences in general cognitive ability (i.e., intelligence) have been linked to individual variations in the modular organization of functional brain networks. However, these analyses have been limited to static (time-averaged) connectivity, and have not yet addressed whether dynamic changes in the configuration of brain networks relate to general intelligence. Here, we used multiband functional MRI resting-state data (N = 281) and estimated subject-specific time-varying functional connectivity networks. Modularity optimization was applied to determine individual time-variant module partitions and to assess fluctuations in modularity across time. We show that higher intelligence, indexed by an established composite measure, the Wechsler Abbreviated Scale of Intelligence (WASI), is associated with higher temporal stability (lower temporal variability) of brain network modularity. Post-hoc analyses reveal that subjects with higher intelligence scores engage in fewer periods of extremely high modularity — which are characterized by greater disconnection of task-positive from task-negative networks. Further, we show that brain regions of the dorsal attention network contribute most to the observed effect. In sum, our study suggests that investigating the temporal dynamics of functional brain network topology contributes to our understanding of the neural bases of general cognitive abilities.
The precise understanding of the dopaminergic (DA) system and its pharmacological modifications is crucial for diagnosis and treatment of neuropsychiatric disorders, as well as for understanding basic processes, such as motivation and reward. We probed the functional connectivity (FC) of subcortical nuclei related to the DA system according to seed regions defined according to an atlas of subcortical nuclei. We conducted a large pharmaco-fMRI study using a double-blind, placebo-controlled design, where we examined the effect of l -DOPA, a dopamine precursor, and amisulpride, a D2/D3-receptor antagonist on resting-state FC in 45 healthy young adults using a cross-over design. We examined the FC of subcortical nuclei with connection to the reward system and their reaction to opposing pharmacological probing. Amisulpride increased FC from the putamen to the precuneus and from ventral striatum to precentral gyrus. l -DOPA increased FC from the ventral tegmental area (VTA) to the insula/operculum and between ventral striatum and ventrolateral prefrontal cortex and it disrupted ventral striatal and dorsal caudate FC with the medial prefrontal cortex. In an exploratory analysis, we demonstrated that higher self-rated impulsivity goes together with a significant increase in VTA-mid-cingulate gyrus FC during l -DOPA-challenge. Therefore, our DA challenge modulated distinct large-scale subcortical connectivity networks. A dopamine-boost can increase midbrain DA nuclei connectivity to the cortex. The involvement of the VTA-cingulum connectivity in dependence of impulsivity has implications for diagnosis and therapy in disorders like ADHD.
Positive psychological coaching (PPC) has emerged as a popular “paradigm” for practitioners interested in the professional development of people. A recent review consolidated the literature on PPC and produced a 5-phase positive psychological coaching model aimed at facilitating professional growth. However, little is known about practically operationalizing each phase of the coaching process (i.e., how to facilitate each phase and which underlying tools and techniques could be employed to do so). As such, the purpose of this systematic review was to address this limitation by (a) determining which coaching tools and techniques are proposed within the coaching literature and (b) classifying the identified tools and techniques into the respective phases of PPC model. The investigation used a two-step approach by conducting a systematic literature review (to identify various PPC tools/techniques) followed by an iterative heuristic classification process (to assign these PPC tools/techniques to a known PPC model). The systematic literature review resulted in 24 peer-reviewed publications on positive psychological coaching, providing 117 different coaching tools that could be condensed into 18 overarching coaching techniques. The iterative classification process showed that most techniques and tools are useful in at least two phases. Interestingly, experts still vary in opinion on the timing and application of these specific techniques and tools within the positive psychological coaching process. This study provides researchers and practitioners with practical guidelines to facilitate a positive psychological coaching process.
The physiotherapist plays an essential role for people with haemophilia, an inherited bleeding disease responsible for musculoskeletal complications. Yet, with the advent of new and advanced therapies, the medical landscape is changing, and physiotherapy must adapt alongside. This paper considers whether there will still be a need for physiotherapy in the era of advanced therapies, and discusses ways in which services should evolve to complement emerging treatment paradigms for haemostasis in people with haemophilia. Ultimately, physiotherapy will remain an important element of care, even for people with little joint damage and low risks in the era of the new mild phenotype. However, competencies will need to evolve, and physiotherapists in both primary care and specialist treatment centres should work with haematology colleagues to develop more sensitive tools for detecting early joint changes. Physiotherapists will also play a crucial role in counselling and physically coaching, monitoring the musculoskeletal status of people with haemophilia who have transitioned to new treatments.
Given the ongoing global SARS-CoV-2-vaccination efforts, clinical awareness needs to be raised regarding the possibility of an increased incidence of SARS-CoV-2-vaccine-related immune-mediated thrombocytopenia in patients with intracerebral hemorrhage (ICH) secondary to cerebral sinus and vein thrombosis (CVT) requiring (emergency) neurosurgical treatment in the context of vaccine-induced immune thrombotic thrombocytopenia (VITT). Only recently, an association of vaccinations and cerebral sinus and vein thrombosis has been described. In a number of cases, neurosurgical treatment is warranted for these patients and special considerations are warranted when addressing the perioperative coagulation. We, herein, describe the past management of patients with VITT and established a literature-guided algorithm for the treatment of patients when addressing the impaired coagulation in these patients. Increasing insights addressing the pathophysiology of SARS-CoV-2-vaccine-related immune-mediated thrombocytopenia guide physicians in developing an interdisciplinary algorithm taking into account the special considerations of this disease.
Background: Both selective mutism (SM) and social anxiety disorder (SAD) are severe pediatric anxiety disorders with the common trait of behavioral inhibition (BI). The underlying pathophysiology of these disorders remains poorly understood, however converging evidence suggests that alterations in several peripheral molecular pathways might be involved. In a pilot study, we investigated alterations in plasma molecular markers (dipeptidyl peptidase-4 [DPPIV], interleukin-6 [IL-6], tumor necrosis factor-β [TNF-β] and neuropeptide-Y [NPY]) in children with SM, SAD, and healthy controls, as well as the correlation of these markers to symptom severity. Methods: We included 51 children and adolescents (aged 5–18 years; n = 29 girls): n = 20 children in the SM-, n = 16 in the SAD- and n = 15 in the control-group (CG). Peripheral blood samples were analyzed for DPPIV, IL-6, TNF-β, and NPY concentrations. Diverse psychometric measures were used for BI, anxiety, and mutism symptoms. Results: Lower DPPIV-levels were correlated with more anxiety symptoms. However, we could not find a difference in any molecular marker between the patients with SAD and SM in comparison to the CG. Conclusion: DPPIV is proposed as relevant marker for child and adolescent anxiety. Investigating the pathophysiology of SM and SAD focusing on state and trait variables as anxiety or BI might help better understanding the underlying mechanisms of these disorders. Further studies with especially larger cohorts are needed to validate the current pilot-findings.
Extremophilic prokaryotes live under harsh environmental conditions which require far-reaching cellular adaptations. The acquisition of novel genetic information via natural transformation plays an important role in bacterial adaptation. This mode of DNA transfer permits the transfer of genetic information between microorganisms of distant evolutionary lineages and even between members of different domains. This phenomenon, known as horizontal gene transfer (HGT), significantly contributes to genome plasticity over evolutionary history and is a driving force for the spread of fitness-enhancing functions including virulence genes and antibiotic resistances. In particular, HGT has played an important role for adaptation of bacteria to extreme environments. Here, we present a survey of the natural transformation systems in bacteria that live under extreme conditions: the thermophile Thermus thermophilus and two desiccation-resistant members of the genus Acinetobacter such as Acinetobacter baylyi and Acinetobacter baumannii. The latter is an opportunistic pathogen and has become a world-wide threat in health-care institutions. We highlight conserved and unique features of the DNA transporter in Thermus and Acinetobacter and present tentative models of both systems. The structure and function of both DNA transporter are described and the mechanism of DNA uptake is discussed.
Since the survival rates of pediatric patients undergoing cancer treatment or hematopoietic stem cell transplantation (HSCT) have increased rapidly in recent decades, the late effects of treatment are now an important focus of patient care. Access to fertility preservation (FP) procedures as well as their financing differs considerably across Europe. However, some countries in Europe have recently changed the legal basis for financing FP procedures; therefore, the implementation of structures is mandatory to give patients access to FP. In this prospective cohort study, we characterized the process for establishing pediatric fertility counseling, including the development of an in-house standard procedure for recommendations regarding FP with potentially gonadotoxic treatment and valuating data from all FP counseling sessions. All data concerning patient characteristics (pubertal status, disease group) and recommendation of FP measures were prospectively collected and adoption of FP measures analyzed. Prior to the establishment of a structured process for FP in our pediatric oncology and stem cell transplantation center, there was no standardized FP counseling. We demonstrate that with the establishment of an inhouse standard procedure, it is possible to give consistent yet individualized FP counseling to approximately 90% of our patients facing gonadotoxic treatment, counseling over 200 patients between 2017 and 2019. This pilot study could potentially be adapted in other pediatric hematology, oncology, and stem cell transplantation centers to allow a more standardized handling of FP counseling for all patients facing gonadotoxic treatment.
Purpose: To investigate short-term (3 months follow-up) changes in visual quality following Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial dystrophy (FED). Methods: In this prospective institutional case series, 51 patients that underwent DMEK for FED were included. Assessment included the Quality of Vision (QoV) questionnaire preoperatively, at 1 month, and 3 months after surgery. Secondary outcome measures were anterior segment parameters acquired by Scheimpflug imaging, corrected distance visual acuity (CDVA), and endothelial cell density (ECD). Results: Glare, hazy vision, blurred vision, and daily fluctuation in vision were the symptoms mostly reported preoperatively. All symptoms demonstrated a significant reduction of item scores for severity, frequency, and bothersome in the course after DMEK (P < 0.01). Glare and fluctuation in vision remained to some extent during the follow-up period (median score = 1). Preoperatively, corneal densitometry correlated moderately to weakly with severity of hazy vision (rs = 0.39; P = 0.03) and frequency (rs = 0.26; P = 0.02) as well as severity (rs = 0.27; P = 0.03) of blurry vision. CDVA and central corneal thickness (CCT) did not correlate with visual complains. Conclusions: Following DMEK for FED, patient-reported visual symptoms assessed by the QoV questionnaire represent a useful tool providing valuable information on the impact of DMEK on visual quality that cannot be directly estimated by morphological parameters and visual acuity only.
Background: SAMHD1 mediates resistance to anti-cancer nucleoside analogues, including cytarabine, decitabine, and nelarabine that are commonly used for the treatment of leukaemia, through cleavage of their triphosphorylated forms. Hence, SAMHD1 inhibitors are promising candidates for the sensitisation of leukaemia cells to nucleoside analogue-based therapy. Here, we investigated the effects of the cytosine analogue CNDAC, which has been proposed to be a SAMHD1 inhibitor, in the context of SAMHD1. Methods: CNDAC was tested in 13 acute myeloid leukaemia (AML) cell lines, in 26 acute lymphoblastic leukaemia (ALL) cell lines, ten AML sublines adapted to various antileukaemic drugs, 24 single cell-derived clonal AML sublines, and primary leukaemic blasts from 24 AML patients. Moreover, 24 CNDAC-resistant sublines of the AML cell lines HL-60 and PL-21 were established. The SAMHD1 gene was disrupted using CRISPR/Cas9 and SAMHD1 depleted using RNAi, and the viral Vpx protein. Forced DCK expression was achieved by lentiviral transduction. SAMHD1 promoter methylation was determined by PCR after treatment of genomic DNA with the methylation-sensitive HpaII endonuclease. Nucleoside (analogue) triphosphate levels were determined by LC-MS/MS. CNDAC interaction with SAMHD1 was analysed by an enzymatic assay and by crystallisation. Results: Although the cytosine analogue CNDAC was anticipated to inhibit SAMHD1, SAMHD1 mediated intrinsic CNDAC resistance in leukaemia cells. Accordingly, SAMHD1 depletion increased CNDAC triphosphate (CNDAC-TP) levels and CNDAC toxicity. Enzymatic assays and crystallisation studies confirmed CNDAC-TP to be a SAMHD1 substrate. In 24 CNDAC-adapted acute myeloid leukaemia (AML) sublines, resistance was driven by DCK (catalyses initial nucleoside phosphorylation) loss. CNDAC-adapted sublines displayed cross-resistance only to other DCK substrates (e.g. cytarabine, decitabine). Cell lines adapted to drugs not affected by DCK or SAMHD1 remained CNDAC sensitive. In cytarabine-adapted AML cells, increased SAMHD1 and reduced DCK levels contributed to cytarabine and CNDAC resistance. Conclusion: Intrinsic and acquired resistance to CNDAC and related nucleoside analogues are driven by different mechanisms. The lack of cross-resistance between SAMHD1/ DCK substrates and non-substrates provides scope for next-line therapies after treatment failure.
This article examines whether restrictions on access to welfare rights for EU immigrants are justifiable on grounds of reciprocity. Recently political theorists have supported some robust restrictions on the basis of fairness. They argue that if EU immigrants do not immediately contribute sufficiently to the provision of basic collective goods in the host state, restrictions on their access to the welfare state are justified. I argue that these accounts of the principle of reciprocity rely on an ambiguous conception of contribution that cannot deliver the restrictions it advocates. Several strategies open to those advocating reciprocity-based restrictions are considered and found wanting. This article defends that verdict from a number of objections.
In sports and clinical settings, roller massage (RM) interventions are used to acutely increase range of motion (ROM); however, the underlying mechanisms are unclear. Apart from changes in soft tissue properties (i.e., reduced passive stiffness), neurophysiological alterations such as decreased spinal excitability have been described. However, to date, no study has investigated both jointly. The purpose of this trial was to examine RM’s effects on neurophysiological markers and passive tissue properties of the plantar flexors in the treated (ROLL) and non-treated (NO- ROLL) leg. Fifteen healthy individuals (23 ± 3 years, eight females) performed three unilateral 60-s bouts of calf RM. This procedure was repeated four times on separate days to allow independent assessments of the following outcomes without reciprocal interactions: dorsiflexion ROM, passive torque during passive dorsiflexion, shear elastic modulus of the medial gastrocnemius muscle, and spinal excitability. Following RM, dorsiflexion ROM increased in both ROLL (+19.7%) and NO-ROLL (+13.9%). Similarly, also passive torque at dorsiflexion ROM increased in ROLL (+15.0%) and NO-ROLL (+15.2%). However, there were no significant changes in shear elastic modulus and spinal excitability (p > 0.05). Moreover, significant correlations were observed between the changes in DF ROM and passive torque at DF ROM in both ROLL and NO-ROLL. Changes in ROM after RM appear to be the result of sensory changes (e.g., passive torque at DF ROM), affecting both rolled and non-rolled body regions. Thus, therapists and exercise professionals may consider applying remote treatments if local loading is contraindicated.
MANY PEOPLE CLAIM THAT FIRMS NEED TO EMBRACE DIGITAL TECHNOLOGIES. YET, WE KNOW LITTLE ABOUT DIGITAL EMBRACEMENT, ITS ANTECEDENTS, AND ECONOMIC CONSEQUENCES. THIS ARTICLE PROPOSES A TEXTUAL APPROACH TO MEASURE DIGITAL EMBRACEMENT AND APPLIES IT IN AN EMPIRICAL STUDY COVERING 2,278 PUBLICLY LISTED U.S. FIRMS OVER 17 YEARS. THE RESULTS OUTLINE A VAST HETEROGENEITY IN FIRMS’ DIGITAL EMBRACEMENT IN AND ACROSS INDUSTRIES. REMARKABLY, A HIGHER DIGITAL EMBRACEMENT PREDICTS HIGHER FINANCIAL PERFORMANCE.
RECENTLY, A NEW CLASS OF SYSTEMS FOR SHARED AND COLLABORATIVE DATA MANAGEMENT HAS GAINED MORE AND MORE TRACTION. IN CONTRAST TO CLASSICAL DATA BASE MANAGEMENT SYSTEMS (DBMS), SYSTEMS FOR SHARED DATA NEED TO PROVIDE ADDITIONAL GUARANTEES TO ENSURE THE INTEGRITY OF DATA AND TRANSACTION EXECUTION. IN THIS PAPER, WE PRESENT TRUSTDBLE, A NEW DBMS THAT EXTENDS THE ACID PROPERTIES (I.E., ATOMICITY, CONSISTENCY, ISOLATION, DURABILITY) USED BY CLASSICAL DBMSS WITH A NEW VERIFIABILITY COMPONENT TO ADDRESS THESE NEW REQUIREMENTS.
With Empire of the Black Sea: the Rise and Fall of the Mithridatic World (2020), Duane Roller has published the first English monograph meant to cover the Pontic Kingdom of the Mithradatid dynasty. Although he falls short of presenting an up-to-date bibliography, the book is likely to become an influential reference work. The present chapter aims at closing several of the bibliographical gaps, by surveying recent (and forthcoming) scholarship especially on the kingdom’s history prior to Mithradates VI Eupator. Topics include the Achaemenid ancestry of Mithradates of Kios, the flight of Mithradates I Ktistes to Kimiata, the role of the Galatians in the rise of the kingdom, the historicity of Mithradates III, the wars and diplomacy of Pharnakes I, the putative sibling marriage of Mithradates IV, chronological aspects of the rule of Mithradates V, and the continuity of Mithradatid foreign policies.
Den Münzen der römischen Republik verpflichtet – Der Numismatiker Max von Bahrfeldt (1856-1936)
(2021)
Kriegslärm und seine Wirkungen auf die ‚Akteure‘ sind für die Antike ein noch ungenutzter Betrachtungsgegenstand. „Sensory History“ darf als innovativer Beitrag zur Geschichtswissenschaft insgesamt gelten. Schlachtbeschreibungen thematisieren Sinneseindrücke aller Art: Die Geräusche des Krieges gehören zu den lautesten, die sich in der Menschheitsgeschichte finden lassen, der Kampf war eine multisensorische Angelegenheit mit Geschrei und Musik. Im Beitrag soll die Aufmerksamkeit auf diese Phänomene und ihre literarische Verarbeitung gelegt werden. Was bedeuteten Geräusche und Eindrücke des Krieges für die Beteiligten? Die in der Antike verbreitete Auffassung, dass „in jeder Schlacht zuerst die Augen erliegen würden“ (Tac. Germ. 43,5), ist zu relativieren! Die Kakophonie der Schlacht blieb nicht ohne Wirkung: sie bedeutete "terror" und konnte Menschen paralysieren!
This study offers a contribution to the reception analysis of TV documentaries by focusing on viewer opinions expressed on social media. It analyses German and English comments from YouTube and Facebook in order to find out what aspects of documentaries the audience comments on. More specifically, it describes how the viewers evaluate strategies that the producers use for simplifying complex content while still creating an appealing and entertaining media product. The results imply that most viewers appreciate informative shows that are entertaining at the same time. They also show that viewers tend to focus on the music and image, rather than on the spoken text, and that documentaries where nature plays an important role are judged more positively than science and history documentaries.
Playing videogames is a popular social activity; people play videogames in different places, on different media, in different situations, alone or with partners, online or offline. Unsurprisingly, they thereby share space (physically or virtually) with other playing or non-playing people. The special issue investigates through different contexts and settings how non-players become participants of the gaming interaction and how players and non-players co-construct presence. The introduction provides a problem-related context for the individual contributions and then briefly presents them.
This study explores how ‘gatherings’ turn into ‘encounters’ in a virtual world (VW) context. Most communication technologies enable only focused encounters between distributed participants, but in VWs both gatherings and encounters can occur. We present close sequential analysis of moments when after a silent gathering, interaction among participants in a VW is gradually resumed, and also investigate the social actions in the verbal (re-)opening turns. Our findings show that like in face-to-face situations, also in VWs participants often use different types of embodied resources to achieve the transition, rather than rely on verbal means only. However, the transition process in VWs has distinctive characteristics compared to the one in face-to-face situations. We discuss how participants in a VW use virtually embodied pre-beginnings to display what we call encounter-readiness, instead of displaying lack of presence by avatar stillness. The data comprise 40 episodes of video-recorded team interactions in a VW.
In so-called Let’s Plays, video gaming is presented and verbally commented by Let’s Players on the internet for an audience. When only watched but not played, the most attractive features of video games, immersion and interactivity, get lost – at least for the internet audience. We assume that the accompanying reactions (transmitted via a so-called facecam) and verbal comments of Let’s Players on their game for an audience contribute to an embodiment of their avatars which makes watching a video game more attractive. Following an ethnomethodological conversation analytical (EMCA) approach, our paper focusses on two practices of embodying avatars. A first practice is that Let’s Players verbally formulate their actions in the game. By that, they make their experiences and the 'actions' of avatars more transparent. Secondly, they produce response cries (Goffman) in reaction to game events. By that, they enhance the liveliness of their avatars. Both practices contribute to a co-construction of a specific kind of (tele-)presence.
This study analyzes how participants playing VR games construct co-presence and shared gameplay. The analysis focuses on instances of play where one person is wearing the VR equipment, and other participants are located nearby without the ability to directly interact with the game. We first show how the active player using the VR equipment draws on talk and embodied activity to signal their presence in the shared physical environment, while simultaneously conducting actions in the virtual space, and thus creates spaces for the other participants to take part in gameplay. Second, we describe how other participants draw on the contextual configurations of the moment in displaying co-presence and position themselves as active and consequential co-players. The analysis demonstrates how gameplay can be communicatively constructed even in situations where the participants have differential rights and possibilities to act and influence the game.
The paper presents research results emerging from the analysis of Intelligent Personal Assistants (IPA) log data. Based on the assumption that media and data, as part of practice, are produced and used cooperatively, the paper discusses how IPA log data can be used to analyze (1) how the IPA systems operate through their connection to platforms and infrastructures, (2) how the dialog systems are designed today and (3) how users integrate them into their everyday social interaction. It also asks in which everyday practical contexts the IPA are placed on the system side and on the user side, and how privacy issues in particular are negotiated. It is argued that, in order to be able to investigate these questions, the technical-institutional and the cultural-theoretical perspective on media, which is common in German media linguistics, has to be complemented by a more fundamental, i.e. social-theoretical and interactionist perspective.
This paper investigates situations in French videogame interactions where non-players who share the same physical space as players, participate in the gaming activities as spectators. Through a detailed multimodal and sequential analysis, we show that being a spectator is a local achievement of all co-present participants - players and non-players.
In the present article we argue that all communication is medial in the sense that every human sign-based interaction is shaped by medial aspects from the outset. We propose a dynamic, semiotic concept of media that focuses on the process-related aspect of mediality, and we test the applicability of this concept using as an example the second presidential debate between Clinton and Trump in 2016. The analysis shows in detail how the sign processing during the debate is continuously shaped by structural aspects of television and specific traits of political communication in television. This includes how the camerawork creates meaning and how the protagonists both use the affordances of this special mediality. Therefore, it is not adequate in our view to separate the technical aspects of the medium, the ‘hardware’, from the processual aspects and the structural conditions of communication. While some aspects of the interaction are directly constituted by the medium, others are more indirectly shaped and influenced by it, especially by its institutional dimension – we understand them as second-order media effects. The whole medial procedure with its specific mediality is a necessary, but not a sufficient condition of meaning-making. We distinguish the medial procedure from the semiotic modes employed, the language games played and the competence of the players involved.
Der Einfluss extremistischer Gewaltereignisse auf das Framing von Extremismen auf SPIEGEL Online
(2020)
In diesem Beitrag untersuchen wir die Darstellung von Rechtsextremismus, Linksextremismus und Islamismus im medialen Diskurs am Beispiel von SPIEGEL Online, einem der deutschen Leitmedien. Wir leiten vier zentrale Dimensionen für die Konzeptualisierung von Extremismen ab: Ideologie und Organisation, Herkunft der Akteure, Stellung zur Gesellschaft und Typische Handlungen. Wir beobachten die Entwicklung der Darstellung der drei Extremismen an möglichen Bruchpunkten: Wir untersuchen das assoziative Framing der drei Extremismen vor und nach prominenten extremismusbezogenen Gewaltereignissen, namentlich die Anschläge des 11. September, die Veröffentlichung des NSU-Skandals und linksextremistische Aktivitäten während des G20-Gipfels in Hamburg. Mittels einer Kollokationsanalyse identifizieren wir mit den Extremismen assoziierte Aspekte und ordnen diese den Konzeptualisierungsdimensionen zu. Wir beobachten Veränderungen im Framing, die durch die ausgewählten Ereignisse bedingt sind, und vergleichen das resultierende Framing mit den Kerndefinitionen des Verfassungsschutzes aus dem Bericht des Jahres 2017, um mögliche Unterschiede in der Konzeptualisierung von Extremismen mit möglicherweise unterschiedlichen Handlungslogiken als Resultat divergierender Konzeptualisierungen herauszuarbeiten.
Der Einfluss extremistischer Gewaltereignisse auf das Framing von Extremismen auf SPIEGEL Online
(2020)
In diesem Beitrag untersuchen wir die Darstellung von Rechtsextremismus, Linksextremismus und Islamismus im medialen Diskurs am Beispiel von SPIEGEL Online, einem der deutschen Leitmedien. Wir leiten vier zentrale Dimensionen für die Konzeptualisierung von Extremismen ab: Ideologie und Organisation, Herkunft der Akteure, Stellung zur Gesellschaft und Typische Handlungen. Wir beobachten die Entwicklung der Darstellung der drei Extremismen an möglichen Bruchpunkten: Wir untersuchen das assoziative Framing der drei Extremismen vor und nach prominenten extremismusbezogenen Gewaltereignissen, namentlich die Anschläge des 11. September, die Veröffentlichung des NSU-Skandals und linksextremistische Aktivitäten während des G20-Gipfels in Hamburg. Mittels einer Kollokationsanalyse identifizieren wir mit den Extremismen assoziierte Aspekte und ordnen diese den Konzeptualisierungsdimensionen zu. Wir beobachten Veränderungen im Framing, die durch die ausgewählten Ereignisse bedingt sind, und vergleichen das resultierende Framing mit den Kerndefinitionen des Verfassungsschutzes aus dem Bericht des Jahres 2017, um mögliche Unterschiede in der Konzeptualisierung von Extremismen mit möglicherweise unterschiedlichen Handlungslogiken als Resultat divergierender Konzeptualisierungen herauszuarbeiten.
Hintergrund: Das Kindesalter wurde bei der Entwicklung von wirksamen Präventions- und Interventionsprogrammen bei Computerspiel- und Internetabhängigkeit bisher kaum berücksichtigt. PROTECTdissonanz wurde daher als 1-stündiges dissonanzbasiertes universelles Primärpräventionsprogramm für die Klassenstufe 5 konzipiert. Die vorliegende Pilotstudie überprüft die unmittelbaren Effekte der Dissonanzinduktion auf die Einstellung zum Gaming. Methodik: In einem einarmigen A+B-Design mit drei Messzeitpunkten (T0, T1, T2) wurde die Einstellung zum Gaming anhand des Gaming Attitude Test (GAT) erfasst. In die Baselinesequenz (Sequenz A, T0 bis T1, Teilstichprobe) wurden N = 83 Schüler_innen eingeschlossen (Alter: M = 10.27; SD = 0.48) und in die Interventionssequenz (Sequenz B, T1 bis T2, Gesamtstichprobe) N = 200 Schüler_innen (Alter: M = 10.24; SD = 0.47). Akzeptanz und Zufriedenheit wurden nach der Intervention erfasst. Ergebnisse: Hierarchisch lineare Wachstumsmodelle zeigten eine signifikante Reduktion der GAT-Symptome durch die Intervention, sowohl im Gesamtwert des GAT als auch auf der Subskala „Bagatellisierung negativer Konsequenzen“. Im natürlichen Verlauf (Baselinesequenz A) zeigten sich keine Veränderungen. Die Schüler_innen bewerteten PROTECTdissonanz zudem mit einer hohen Zufriedenheit. Schlussfolgerungen: Eine kurze, gezielte übung zur Dissonanzinduktion zeigt unmittelbare Effekte auf ein Einstellungsmaß zum Gaming. Zur Weiterverfolgung dieses vielversprechenden Ansatzes sollte in künftigen Studien untersucht werden, ob sich eine verringerte Bagatellisierung negativer Konsequenzen von Gaming im Sinne der kognitiven Dissonanztheorie auch tatsächlich in einer Verhaltensänderung widerspiegelt.
An automated NMR chemical shift assignment algorithm was developed using multi-objective optimization techniques. The problem is modeled as a combinatorial optimization problem and its objective parameters are defined separately in different score functions. Some of the heuristic approaches of evolutionary optimization are employed in this problem model. Both, a conventional genetic algorithm and multi-objective methods, i.e., the non-dominated sorting genetic algorithms II and III (NSGA2 and NSGA3), are applied to the problem. The multi-objective approaches consider each objective parameter separately, whereas the genetic algorithm followed a conventional way, where all objectives are combined in one score function. Several improvement steps and repetitions on these algorithms are performed and their combinations are also created as a hyper-heuristic approach to the problem. Additionally, a hill-climbing algorithm is also applied after the evolutionary algorithm steps. The algorithms are tested on several different datasets with a set of 11 commonly used spectra. The test results showed that our algorithm could assign both sidechain and backbone atoms fully automatically without any manual interactions. Our approaches could provide around a 65% success rate and could assign some of the atoms that could not be assigned by other methods.
An accurate measurement of the 140Ce(n,γ) energy-dependent cross-section was performed at the n_TOF facility at CERN. This cross-section is of great importance because it represents a bottleneck for the s-process nucleosynthesis and determines to a large extent the cerium abundance in stars. The measurement was motivated by the significant difference between the cerium abundance measured in globular clusters and the value predicted by theoretical stellar models. This discrepancy can be ascribed to an overestimation of the 140Ce capture cross-section due to a lack of accurate nuclear data. For this measurement, we used a sample of cerium oxide enriched in 140Ce to 99.4%. The experimental apparatus consisted of four deuterated benzene liquid scintillator detectors, which allowed us to overcome the difficulties present in the previous measurements, thanks to their very low neutron sensitivity. The accurate analysis of the p-wave resonances and the calculation of their average parameters are fundamental to improve the evaluation of the 140Ce Maxwellian-averaged cross-section.
Transcatheter left atrial appendage occlusion (LAAO) is non-inferior to vitamin K antagonists (VKAs) in preventing thromboembolic events in atrial fibrillation (AF). Non-vitamin K antagonists (NOACs) have an improved safety profile over VKAs; however, evidence regarding their effect on cardiovascular and neurological outcomes relative to LAAO is limited. Up-to-date randomized trials or propensity-score-matched data comparing LAAO vs. NOACs in high-risk patients with AF were pooled in our study. A total of 2849 AF patients (LAAO: 1368, NOACs: 1481, mean age: 75 ± 7.5 yrs, 63.5% male) were enrolled. The mean CHA2DS2-VASc score was 4.3 ± 1.7, and the mean HAS-BLED score was 3.4 ± 1.2. The baseline characteristics were comparable between the two groups. In the LAAO group, the success rate of device implantation was 98.8%. During a mean follow-up of 2 years, as compared with NOACs, LAAO was associated with a significant reduction of ISTH major bleeding (p = 0.0002). There were no significant differences in terms of ischemic stroke (p = 0.61), ischemic stroke/thromboembolism (p = 0.63), ISTH major and clinically relevant minor bleeding (p = 0.73), cardiovascular death (p = 0.63), and all-cause mortality (p = 0.71). There was a trend toward reduction of combined major cardiovascular and neurological endpoints in the LAAO group (OR: 0.84, 95% CI: 0.64–1.11, p = 0.12). In conclusion, for high-risk AF patients, LAAO is associated with a significant reduction of ISTH major bleeding without increased ischemic events, as compared to “contemporary NOACs”. The present data show the superior role of LAAO over NOACs among high-risk AF patients in terms of reduction of major bleeding; however, more randomized controlled trials are warranted.
Simple Summary: The role of transcriptionally deregulated miRNAs (microRNAs) in classical Hodgkin lymphoma (cHL) is still not fully understood. To address this issue, we have performed global miRNA expression profiling of commonly used cHL cell lines and we present a complete cHL miRNome (microRNome). Within this group, we identify miRNAs recurrently deregulated in cHL cell lines, and compare them to non-Hodgkin lymphoma cell lines and sorted normal CD77+ germinal centre B-cells. Moreover, we show that several of the recurrently overexpressed miRNAs in cHL cell lines, and also primary microdissected HRS (Hodgkin and Reed-Sternberg) cells, target known B-cell-related transcription factors and NF-κB inhibitors. These findings provide evidence that deregulated miRNAs contribute to the loss of B-cell phenotype and NF-κB activation observed in this lymphoma.
Abstract: A hallmark of classical Hodgkin lymphoma (cHL) is the attenuation of B-cell transcription factors leading to global transcriptional reprogramming. The role of miRNAs (microRNAs) involved in this process is poorly studied. Therefore, we performed global miRNA expression profiling using RNA-seq on commonly used cHL cell lines, non-Hodgkin lymphoma cell lines and sorted normal CD77+ germinal centre B-cells as controls and characterized the cHL miRNome (microRNome). Among the 298 miRNAs expressed in cHL, 56 were significantly overexpressed and 23 downregulated (p < 0.05) compared to the controls. Moreover, we identified five miRNAs (hsa-miR-9-5p, hsa-miR-24-3p, hsa-miR-196a-5p, hsa-miR-21-5p, hsa-miR-155-5p) as especially important in the pathogenesis of this lymphoma. Target genes of the overexpressed miRNAs in cHL were significantly enriched (p < 0.05) in gene ontologies related to transcription factor activity. Therefore, we further focused on selected interactions with the SPI1 and ELF1 transcription factors attenuated in cHL and the NF-ĸB inhibitor TNFAIP3. We confirmed the interactions between hsa-miR-27a-5p:SPI1, hsa-miR-330-3p:ELF-1, hsa-miR-450b-5p:ELF-1 and hsa-miR-23a-3p:TNFAIP3, which suggest that overexpression of these miRNAs contributes to silencing of the respective genes. Moreover, by analyzing microdissected HRS cells, we demonstrated that these miRNAs are also overexpressed in primary tumor cells. Therefore, these miRNAs play a role in silencing the B-cell phenotype in cHL.
In this roadmap article, we have focused on the most recent advances in terahertz (THz) imaging with particular attention paid to the optimization and miniaturization of the THz imaging systems. Such systems entail enhanced functionality, reduced power consumption, and increased convenience, thus being geared toward the implementation of THz imaging systems in real operational conditions. The article will touch upon the advanced solid-state-based THz imaging systems, including room temperature THz sensors and arrays, as well as their on-chip integration with diffractive THz optical components. We will cover the current-state of compact room temperature THz emission sources, both optolectronic and electrically driven; particular emphasis is attributed to the beam-forming role in THz imaging, THz holography and spatial filtering, THz nano-imaging, and computational imaging. A number of advanced THz techniques, such as light-field THz imaging, homodyne spectroscopy, and phase sensitive spectrometry, THz modulated continuous wave imaging, room temperature THz frequency combs, and passive THz imaging, as well as the use of artificial intelligence in THz data processing and optics development, will be reviewed. This roadmap presents a structured snapshot of current advances in THz imaging as of 2021 and provides an opinion on contemporary scientific and technological challenges in this field, as well as extrapolations of possible further evolution in THz imaging.
Presolar grains and their isotopic compositions provide valuable constraints to AGB star nucleosynthesis. However, there is a sample of O- and Al-rich dust, known as group 2 oxide grains, whose origin is difficult to address. On the one hand, the 17O/16O isotopic ratios shown by those grains are similar to the ones observed in low-mass red giant stars. On the other hand, their large 18O depletion and 26Al enrichment are challenging to account for. Two different classes of AGB stars have been proposed as progenitors of this kind of stellar dust: intermediate mass AGBs with hot bottom burning, or low mass AGBs where deep mixing is at play. Our models of low-mass AGB stars with a bottom-up deep mixing are shown to be likely progenitors of group 2 grains, reproducing together the 17O/16O, 18O/16O and 26Al/27Al values found in those grains and being less sensitive to nuclear physics inputs than our intermediate-mass models with hot bottom burning.
Introduction: Cancer patients tend to prefer oral instead of parenteral chemotherapy. To date, there is little evidence on the medication adherence in cancer patients. We investigated medication adherence to tyrosine kinase inhibitors in patients suffering from non-small cell lung cancer. Methods: Tyrosine kinase inhibitor adherence was measured electronically by MEMS® (medication event monitoring system) over at least six months. Adherence rates were calculated in terms of Dosing Compliance, Timing Compliance, Taking Compliance, and Drug Holidays. Patients were dichotomized as adherent when Dosing Compliance and Timing Compliance were ≥80%, Taking Compliance ranged between 90 and 110%, and <1 Drug Holiday was registered. Quality of life was assessed by two questionnaires (EORTC QLQ-C30 version 3.0, EORTC QLQ-LC13) at three time points. Adverse drug events were reported via patient diaries. Results: Out of 32 patients enrolled, data from 23 patients were evaluable. Median Dosing Compliance, Taking Compliance, and Timing Compliance adherence rates of tyrosine kinase inhibitor intake amounted to 100%, 98%, and 99%, respectively; Drug Holidays were observed in three patients. Four patients were dichotomized as non-adherent. Three of them had a twice-daily tyrosine kinase inhibitor regimen. Median quality of life scores amounted to 67 (max. 100) and remained unchanged over the study period. Fatigue and rash were the most frequently reported adverse drug events. Conclusion: Medication adherence of non-small cell lung cancer patients treated with tyrosine kinase inhibitors was extraordinarily high and is likely to support the effectiveness of tyrosine kinase inhibitor treatment and a good quality of life over a long period of time. Adherence facilitating information and education is especially relevant for patients taking tyrosine kinase inhibitors in a twice-daily regimen.
This essay explores the problem of legitimation crises in deliberative systems. For some time now, theorists of deliberative democracy have started to embrace a “systemic approach.” But if deliberative democracy is to be understood in the context of a system of multiple moving parts, then we must confront the possibility that that system’s dynamics may admit of breakdowns, contradictions, and tendencies toward crisis. Yet such crisis potentials remain largely unexplored in deliberative theory. The present article works toward rectifying this lacuna, using the 2016 Brexit and Trump votes as examples of a particular kind of “legitimation crisis” that results in a sequence of failures in the deliberative system. Drawing on recent work of Rainer Forst, I identify this particular kind of legitimation crisis as a “justification crisis.”
The strengths use scale: psychometric properties, longitudinal invariance and criterion validity
(2021)
Strengths use is an essential personal resource to consider when designing higher-educational programs and interventions. Strengths use is associated with positive outcomes for both the student (e.g., study engagement) and the university (e.g., academic throughput/performance). The Strengths Use Scale (SUS) has become a popular psychometric instrument to measure strengths use in educational settings, yet its use has been subjected to limited psychometric scrutiny outside of the U.S. Further, its longitudinal stability has not yet been established. Given the wide use of this instrument, the goals of this study were to investigate (a) longitudinal factorial validity and the internal consistency of the scale, (b) its equivalence over time, and (c) criterion validity through its relationship with study engagement over time. Data were gathered at two-time points, 3 months apart, from a sample of students in the Netherlands (n = 360). Longitudinal confirmatory factor analyses showed support for a two-factor model for overall strengths use, comprised of Affinity for Strengths and Strengths Use Behaviors. The SUS demonstrated high levels of internal consistency at both the lower- and upper bound limits at both time points. Further, strict longitudinal measurement invariance was established, which confirmed the instrument's temporal stability. Finally, criterion validity was established through relating strengths use to study engagement at different time stamps. These findings support the use of the SUS in practice to measure strengths use and to track the effectiveness of strengths use interventions within the higher education sector.