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This article explores and discusses one of the main findings of the author’s recent dissertation, namely that parents’ and pupils’ choice of language of instruction in formal schooling depends on its social prestige. The author first reviews the latest research on language in education in sub-Saharan Africa, and asks why indigenous languages are so rarely used in formal schooling in this region, despite political demands for their greater use and ample scientific research showing their positive effects. Burkina Faso exemplifies this seemingly contradictory situation. Indigenous languages and French are complementary in formal and non-formal schooling as well as in areas of informal education; however, a closer look at the areas of application of each language reveals that indigenous languages have lower prestige than French, as well as lower expected and required outcomes. This is one possible explanation for the low usage rates of indigenous languages in formal schooling and reveals the extent to which the choice of language of instruction depends on its social prestige.
Purpose: The aim of this study was to investigate characteristics associated with ectopic pregnancy (EP) that could be utilized for predicting morbidity or mortality.
Methods: This was a retrospective analysis of pregnancy-related records from a tertiary center over a period of ten years. Data on age, gravidity, parity, EP risk, amenorrhea duration, abdominal pain presence and location, β-human chorionic gonadotropin (β-HCG) level, ultrasound findings, therapeutic intervention, exact EP implantation site and length of hospital stay (LOS) were obtained from the database. The LOS was used as a proxy for morbidity and was tested for an association with all variables. All statistical analyses were conducted with Stata® (ver. 16.1, Texas, USA).
Results: The incidence of EP in a cohort of 30,247 pregnancies over a ten-year period was 1.05%. Patients presented with lower abdominal pain in 87.9% of cases, and the likelihood of experiencing pain was tenfold higher if fluid was detectable in the pouch of Douglas. Only 5.1% of patients had a detectable embryonic heartbeat, and 18.15% had one or more risk factors for EP. While most EPs were tubal, 2% were ovarian. The LOS was 1.9 days, and laparoscopic intervention was the main management procedure. The cohort included one genetically proven dizygotic heterotopic pregnancy (incidence, 3.3 × 10− 5) that was diagnosed in the 7th gestational week. The only association found was between the β-HCG level and LOS, with a linear regression β coefficient of 0.01 and a P-value of 0.04.
Conclusion: EP is a relatively common condition affecting approximately 1% of all pregnancies. β-HCG correlates with EP-related morbidity, but the overall morbidity rate of EP is low regardless of the implantation site. Laparoscopic surgery is an effective therapeutic procedure that is safe for managing EP, even in cases of heterotopic pregnancy.
The Miocene is a key time in the evolution of African mammals and their ecosystems witnessing the origin of the African apes and the isolation of eastern coastal forests through an expanding biogeographic arid corridor. Until recently, however, Miocene sites from the southeastern regions of the continent were unknown. Here we report discovery of the first Miocene fossil teeth from the shoulders of the Urema Rift in Gorongosa National Park, Mozambique, at the southern East African Rift System. We provide the first 1) radiometric age determinations of the fossiliferous Mazamba Formation, 2) reconstructions of past vegetation in the region based on pedogenic carbonates and fossil wood, and 3) description of fossil teeth from the southern rift. Gorongosa is unique in the East African Rift System in combining marine invertebrates, marine vertebrates, terrestrial mammals, and fossil woods in coastal paleoenvironments. The Gorongosa fossil sites offer the first evidence of persistent woodlands and forests on the coastal margins of southeastern Africa during the Miocene, and an exceptional assemblage of fossil vertebrates including new species. Further work will allow the testing of hypotheses positing the formation of a northeast-southwest arid corridor isolating species on the eastern coastal forests from those elsewhere in Africa.
Brief The Miocene is a key time in the evolution of African mammals and their ecosystems encompassing hominine origins and the establishment of an arid corridor that isolated eastern Africa’s coastal forests. Until now, however, Miocene sites from southeastern Africa have been unknown. We report the discovery of the first Miocene fossil sites from Gorongosa National Park, Mozambique, and show that these sites formed in coastal settings. We provide radiometric ages for the fossiliferous sediments, reconstructions of past vegetation based on stable isotopes and fossil wood, and a description of the first fossil teeth from the region. Gorongosa is the only paleontological site in the East African Rift that combines fossil woods, marine invertebrates, marine vertebrates, and terrestrial mammals. Gorongosa offers the first evidence of persistent woodlands and forests on the coastal margins of southeastern Africa during the Miocene.
Background: While the antidepressant efficacy of guided digital interventions has been proven in randomized controlled trials, findings from routine care are less clear. Low adherence rates are common and limit the potential effectiveness. Adherence has been linked to sociodemographic variables and the amount of guidance, but the role of the guide's profession and their work setting has not yet been studied for routine care.
Methods: Routinely collected log data from a digital intervention for depressed patients (iFightDepression tool) were analyzed in an exploratory manner. The sample is a convenience sample from routine care, where guidance is provided by general practitioners (GP), certified psychotherapists (PT) or medical doctors specialized in mental health. Log data from 2184 patients were analyzed and five usage parameters were extracted to measure adherence (first-to-last login, time on tool, number of sessions, workshops completed and minimal dose). Multiple logistic regression was used to analyze relations between the guide's profession and clinical context as well as other covariates and adherence and symptom change on a brief depression questionnaire (PHQ-9).
Results: The analyses showed a significant relation of guide profession and adherence. Guidance by PT was associated to the highest adherence scores (reference category). The odds ratios (ORs) of scoring above the median in each usage parameter for patients guided by GPs were 0.50–0.63 (all ps < 0.002) and 0.61–0.80 (p = .002–0.197) for MH. Higher age, initial PHQ-9 score and self-reported diagnosis of depression were also significantly associated with higher adherence scores. In a subsample providing enough data on the PHQ-9 (n = 347), no association of guide profession with symptom reduction was found. Instead, a greater reduction was observed for patients with a higher baseline PHQ-9 (β = −0. 39, t(341.75) = −8.814, p < .001) and for those who had achieved minimal dose (β = −2.42, t(340.34) = −4.174, P < .001) and those who had achieved minimal dose and scored high on time on tool (β = 0.22, t(341.75) = 1.965, P = .050).
Conclusion: Being guided by PT was associated with the highest adherence. The lowest adherence was observed in patients who were guided by GP. While no association of guide profession and symptom reduction was found in a subsample, greater adherence was associated with symptom reduction.
The detection of multiple biomolecule classes in one go is highly desirable for a wide variety of areas, and in particular for point-of-care diagnostics. For example, wound infections are a major problem for patient’s health and cause huge efforts in our healthcare system. In this regard, monitoring infected wounds through simultaneous detection of pathogens via nucleic acid analysis and detection of local inflammation biomarkers is key in order to enable a personalized therapy, improve the clinical outcome and thus, leading to a reduction of overall healthcare costs. In this regard, wound exudate offers an attractive sample material which can be collected in a non-invasive manner. Here, we report the development of a Multianalyte-Assay detecting inflammation biomarkers and pathogen DNA simultaneously from one sample within 35 min. Protein-compatible amplification and labeling transforms nucleic acid information into the measurement principle for protein detection. The combination with rapid detection via lateral flow immunoassay enables a fast and straightforward analysis of multiple biomolecule classes using identical assay conditions. To demonstrate the feasibility of the Multianalyte-Assay, the proinflammatory cytokine interleukin-6 (IL-6) and gDNA of the opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa) are used. The detection limits of 4 ng/mL IL-6 and 70 copies/reaction P. aeruginosa gDNA meet the clinically relevant range and thus, having tremendous potential to improve the wound management at the point-of-care.
At high pressures, autoionization – along with polymerization and metallization – is one of the responses of simple molecular systems to a rise in electron density. Nitrosonium nitrate (NO+NO3−), known for this property, has attracted a large interest in recent decades and was reported to be synthesized at high pressure and high temperature from a variety of nitrogen–oxygen precursors, such as N2O4, N2O and N2–O2 mixtures. However, its structure has not been determined unambiguously. Here, we present the first structure solution and refinement for nitrosonium nitrate on the basis of single-crystal X-ray diffraction at 7.0 and 37.0 GPa. The structure model (P21/m space group) contains the triple-bonded NO+ cation and the NO3− sp2-trigonal planar anion. Remarkably, crystal-chemical considerations and accompanying density-functional-theory calculations show that the oxygen atom of the NO+ unit is positively charged – a rare occurrence when in the presence of a less-electronegative element.
Synthesis, crystal structure and structure–property relations of strontium orthocarbonate, Sr2CO4
(2021)
Carbonates containing CO4 groups as building blocks have recently been discovered. A new orthocarbonate, Sr2CO4 is synthesized at 92 GPa and at a temperature of 2500 K. Its crystal structure was determined by in situ synchrotron single-crystal X-ray diffraction, selecting a grain from a polycrystalline sample. Strontium orthocarbonate crystallizes in the orthorhombic crystal system (space group Pnma) with CO4, SrO9 and SrO11 polyhedra as the main building blocks. It is isostructural to Ca2CO4. DFT calculations reproduce the experimental findings very well and have, therefore, been used to predict the equation of state, Raman and IR spectra, and to assist in the discussion of bonding in this compound.
Studies have demonstrated an increased risk of accidents and injuries in children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). However, little is known about how accident risk may alter over the lifespan. Additionally, it would be important to know if the most common types of accidents and injuries differ in ADHD patients over different age groups. Furthermore, there is increasing evidence of an ameliorating effect of ADHD medication on accident risk. Lastly, the underlying risk factors and causal mechanisms behind increased accident risk remain unclear. We therefore conducted a systematic review focusing on the above described research questions. Our results suggested that accident/injury type and overall risk changes in ADHD patients over the lifespan. ADHD medication appeared to be similarly effective at reducing accident risk in all age groups. However, studies with direct comparisons of accident/injuries and effects of medication at different age groups or in old age are still missing. Finally, comorbidities associated with ADHD such as substance abuse appear to further increase the accident/injury risk.
Purpose: To evaluate the potential impact of rebubbling on the anterior segment parameters and refractive outcomes in patients with graft detachment following uneventful DMEK for Fuchs endothelial dystrophy (FED).
Methods: Retrospective institutional cohort study of comparing 34 eyes of 31 patients with rebubbling for graft detachment following Descemet membrane endothelial keratoplasty (DMEK) to 33 eyes of 28 patients with uneventful DMEK. Main outcome parameters were various corneal parameters obtained by Scheimpflug imaging, refractive outcome, corrected distance visual acuity (CDVA), and endothelial cell density (ECD).
Results: Anterior and posterior corneal astigmatism, corneal densitometry, central corneal thickness, and anterior chamber depth and volume showed no significant differences. Preoperative distribution of astigmatism axis orientations showed a high proportion of anterior corneal with-the-rule astigmatism (71%) in eyes requiring rebubbling. Mean postoperative cylinder in the rebubbling group (1.21 ± 0.85 D) was significantly higher compared to the controls (p = 0.04), while differences in spherical equivalent (SE) were insignificant (p = 0.24). Postoperative CDVA was 0.11 ± 0.11 in the control group compared to 0.21 ± 0.17 in the rebubbling group (p = 0.03). Eyes with subsequent rebubbling demonstrated a significantly higher endothelial cell loss (56% versus 37%) (p < 0.001).
Conclusion: Apart from higher cylinder values, refractive outcome and corneal parameters assessed by Scheimpflug imaging were comparable in eyes with rebubbling and controls. However, a reduced visual acuity and an increased endothelial cell loss should be taken into consideration prior to rebubbling especially in eyes with circumscribed graft detachment.
Neurometabolic diseases (NMDs) are typically caused by genetic abnormalities affecting enzyme functions, which in turn interfere with normal development and activity of the nervous system. Although the individual disorders are rare, NMDs are collectively relatively common and often lead to lifelong difficulties and high societal costs. Neuropsychiatric manifestations, including ADHD symptoms, are prominent in many NMDs, also when the primary biochemical defect originates in cells and tissues outside the nervous system. ADHD symptoms have been described in phenylketonuria, tyrosinemias, alkaptonuria, succinic semialdehyde dehydrogenase deficiency, X-linked ichthyosis, maple syrup urine disease, and several mitochondrial disorders, but are probably present in many other NMDs and may pose diagnostic and therapeutic challenges. Here we review current literature linking NMDs with ADHD symptoms. We cite emerging evidence that many NMDs converge on common neurochemical mechanisms that interfere with monoamine neurotransmitter synthesis, transport, metabolism, or receptor functions, mechanisms that are also considered central in ADHD pathophysiology and treatment. Finally, we discuss the therapeutic implications of these findings and propose a path forward to increase our understanding of these relationships.
Background: An experienced life-threating anaphylactic reaction to hymenoptera venom can sustainably impair patients’ quality of life (QoL). Besides carrying emergency medication, venom-specific immunotherapy (VIT) exists as a causal treatment of allergy.
Objective: This study aimed to examine QoL, anxiety, depression, and physical and mental health in patients allergic to hymenoptera venom before and during VIT and the impact of a tolerated sting challenge (SC).
Methods: Between July 2017 and August 2017, 142 patients with venom allergy were analyzed using validated questionnaires as the: Vespid Allergy Quality for Life Questionnaire" (VQLQ-d), the "Hospital Anxiety and Depression Scale" (HADS-D) and the "Short Form 36" (SF-36). To evaluate the impact of VIT and SC on the QoL, patients were divided into 3 groups: (A) VIT and tolerated SC (n = 45), (B) VIT before carrying out SC (n = 73), and (C) therapy-naïve before VIT (n = 20). Further parameters like gender, age, insect species, and severity of the anaphylactic reaction were assessed.
Results: A significant correlation between the health-related QoL and the parameters of gender and state of treatment was seen. Especially male patients, as well as patients allergic to yellow jacket venom, benefit from a SC in terms of a significant increase in their QoL. In the total study cohort, a clear trend was observed towards a higher QoL in patients under VIT who tolerated a SC. Overall, neither the patients’ age nor the insect species exerted a relevant influence on QoL, depression or anxiety. However, women showed a lower QoL combined with higher anxiety and depression scores than men.
Conclusion: Immunotherapy leads to an improved QoL, which can be further increased by a SC. A tolerated SC conceivably reassures the patients by objectifying the treatment success. Female patients appear to have a stronger impaired QoL per se. Taken together, a SC can be performed during VIT to strengthen the patients’ QoL.
Background: Cirrhosis is known to have a high prevalence and mortality worldwide. However, in Europe, the epidemiology of cirrhosis is possibly undergoing demographic changes, and etiologies may have changed due to improvements in standard of care. The aim of this population-based study was to analyze the trends and the course of liver cirrhosis and its complications in recent years in Germany.
Methods: We analyzed the data of all hospital admissions in Germany within diagnosis-related groups from 2005 to 2018. The diagnostic records of cirrhosis and other categories of diseases were based on ICD-10-GM codes. The primary outcome measurement was in-hospital mortality. Trends were analyzed through Poisson regression of annual number of admissions. The impact of cirrhosis on overall in-hospital mortality were assessed through the multivariate multilevel logistic regression model adjusted for age, sex, and comorbidities.
Findings: Of the 248,085,936 admissions recorded between 2005 and 2018, a total of 2,302,171(0•94%) were admitted with the diagnosis of cirrhosis, mainly as a comorbidity. Compared with other chronic diseases, patients admitted with cirrhosis were younger, mainly male and had the highest in-hospital mortality rate. Diagnosis of cirrhosis was an independent risk factor of in-hospital mortality with the highest odds ratio (OR:6•2[95%CI:6.1-6•3]) among all diagnoses. The prevalence of non-alcoholic fatty liver disease has increased four times from 2005 to 2018, while alcoholic cirrhosis is 20 times than other etiologies. Bleeding was found to be decreasing over time, but ascites remained the most common complication and was increasing.
Interpretation: This nationwide study demonstrates that cirrhosis represents a considerable healthcare burden, as shown by the increasing in-hospital mortality, also in combination with other chronic diseases. Alcohol-related cirrhosis and complications are on the rise. More resources and better management strategies are warranted.
Aim: Formerly introduced for their presumed value in controlling mosquito-borne diseases, the two mosquitofish Gambusia affinis and G. holbrooki (Poeciliidae) are now among the world's most widespread invasive alien species, negatively impacting aquatic ecosystems around the world. These inconspicuous freshwater fish are, once their presence is noticed, difficult to eradicate. It is, therefore, of utmost importance to assess their geographic potential and to identify their likely ability to persist under novel climatic conditions.
Location Global.
Methods We build species distribution models using occurrence data from the native and introduced distribution ranges to identify putative niche shifts and further ascertain the areas climatically suitable for the establishment and possible spread of mosquitofish.
Results We found significant niche expansions into climatic regions outside their natural climatic conditions, emphasizing the importance of integrating climatic niches of both native and invasive ranges into projections. In particular, there was a marked shift toward tropical regions in Asia and a clear niche shift of European G. holbrooki. This ecological flexibility partly explains the massive success of the two species, and substantially increases the risk for further range expansion. We also showed that the potential for additional expansion resulting from climate change is enormous—especially in Europe.
Main conclusions Despite the successful invasion history and ongoing range expansions, many countries still lack proper preventive measures. Thus, we urge policy makers to carefully evaluate the risk both mosquitofish pose to a particular area and to initiate appropriate management strategies.
Background: Transfusion of red blood cells (RBC) in patients undergoing major elective cranial surgery is associated with increased morbidity, mortality and prolonged hospital length of stay (LOS). This retrospective single center study aims to identify the impact of RBC transfusions on skull-base and non-skull-base meningioma patients including the identification of risk factors for RBC transfusion.
Methods: From October 2009 - October 2016 we retrospectively analyzed 423 primary meningioma patients undergoing surgery for primary meningioma resection our department.
Results: Of these 423 patients, 68 (16.1%) received RBC transfusion and 355 (83.9%) did not receive RBC units. Preoperative anaemia rate was significantly higher in transfused patients (17.7%) compared to patients without RBC transfusion (6.2%; p = 0.0015). In transfused patients, postoperative complications as well as hospital LOS was significantly higher (p < 00001) compared to non-transfused patients. After multivariate analyses, risk factors for RBC transfusion were preoperative American Society of Anesthesiologists (ASA) physical status score (p = 0.0247), tumor size (p = 0.0006), surgical time (p = 0.0018) and intraoperative blood loss (p < 0.001). Kaplan-Meier curves revealed significant influence on overall survival by preoperative anaemia, RBC transfusion, smoking, cardiovascular disease, preoperative KPS ≤ 60% and age (elderly ≥ 75 years).
Conclusion: We concluded that blood loss due to large tumors or localization near large vessels are the main triggers for RBC transfusion in meningioma patients paired with a potential preselection that masks the effect of preoperative anaemia in multivariate analysis. Further studies evaluating the impact of preoperative anaemia management for reduction of RBC transfusion are needed to improve clinical outcomes of meningioma patients.
Study Design: Cross-sectional survey
Objective: To determine the influence of surgeons’ level of experience and subspeciality training on the reliability, reproducibility, and accuracy of sacral fracture classification using the AO Spine Sacral Injury Classification System.
Summary of Background Data: An ideal classification system is easily comprehensible and reliable amongst the diverse group of surgeons. A surgeons’ level of experience may have a significant effect on the reliability and accuracy of a classification system. Moreover, surgeons of different subspecialities may have various levels of comfort with imaging assessment of sacral injuries required for accurate diagnosis and classification.
Methods: High-resolution computerized tomography (CT) images from 26 cases were assessed by 172 investigators from a diverse array of surgical subspecialities (general orthopaedics, neurosurgery, orthopaedic spine, orthopaedic trauma) and experience (<5, 5-10, 11-20, >20 years). Validation assessments were performed via web conference using high-resolution images, as well as axial/sagittal/coronal CT scan sequences. Two assessments were performed by each investigator independently three weeks apart in randomized order. Reliability and reproducibility were calculated with cohen’s kappa coefficient (k) and gold standard classification agreement was determined for each fracture morphology and subtype and stratified by experience and subspeciality.
Results: Respondents achieved an overall k = 0.87 for morphology and k = 0.77 for subtype classification, representing excellent and substantial intraobserver reproducibility, respectively. Respondents from all four practice experience groups demonstrated excellent interobserver reliability when classifying overall morphology (k=0.842/0.850, Assessment 1/Assessment 2) and substantial interobserver reliability in overall subtype (k=0.719/0.751) in both assessments. General orthopaedists, neurosurgeons, and orthopaedic spine surgeons exhibited excellent interobserver reliability in overall morphology classification and substantial interobserver reliability in overall subtype classification. Surgeons in each experience category and subspecialty correctly classified fracture morphology in over 90% of cases and fracture subtype in over 80% of cases according to the gold standard. Correct overall classification of fracture morphology (Assessment 1: p= 0.024, Assessment 2: p=0.006) and subtype (p2<0.001) differed significantly with surgeons with >20 years of experience demonstrating increased difficulty correctly classifying all fracture subtypes overall in comparison to the other experience groups. Correct overall classification did not significantly differ by subspecialty.
Conclusions: Overall, the AO Spine Sacral Injury Classification System appears to be universally applicable among surgeons of various subspecialties and levels of experience with acceptable reliability, reproducibility, and accuracy.
Disclosures: author 1: none; author 2: consultant=Medtronic, Nuvasive, ISD, Asutra, Stryker, Bioventus, Zimmer, teledocs, Clinical Spine Surgery, AOSpine ; author 3: none; author 4: grants/research support=AOSpine, consultant=DPS, icotec; author 5: none; author 6: none; author 7: grants/research support=DPS; author 8: none; author 9: grants/research support=NIH, RTI, CSRS, royalties=Inion ; author 10: stock/shareholder=Advanced Spinal Intellectual Properties; Atlas Spine; Avaz Surgical; Bonovo Orthopaedics; Computational Biodynamics; Cytonics; Deep Health; Dimension Orthotics LLC; Electrocore; Flagship Surgical; FlowPharma; Globus; Innovative Surgical Design; Insight Therapeutics; Jushi; Nuvasive; Orthobullets; Paradigm Spine; Parvizi Surgical Innovation; Progressive Spinal Technologies; Replication Medica; Spine Medica; Spineology; Stout Medical; Vertiflex; ViewFi Health, royalties=Aesculap; Atlas Spine; Globus; Medtronics; SpineWave; Stryker Spine,other financial report=AO Spine
Background: To investigate whether patients with critical emergency conditions are seeking or receiving the medical care that they require we characterized the reality of care for patients presenting with Neuro-emergencies during the first phase of the COVID-19 pandemic.
Methods: In this observational, longitudinal cohort study, all neurosurgical admissions that presented to our Department between February 1st and April 15th during the COVID-19 pandemic and during the same time-period in 2019 were identified and categorized according to the presence of a Neuro-emergency, the route of admission, management, and the category of disease. Further, the clinical course of patients with chronic subdural hematoma (cSDH) was investigated as a Neuro-emergency representative for a wide variety of semi-urgent symptoms.
Results: During the pandemic, the percentage of Neuro-emergencies among all neurosurgical admissions remained similar as in 2019 but a larger proportion presented through the emergency department than through the outpatient clinic or by referral (*p=0.009). The total number of Neuro-emergencies was significantly reduced (*p=0.0007) across all types of disease, particularly in severe vascular (*p=0.036) but also in spinal (*p=0.007) and hydrocephalus (*p=0.048) emergencies. Strikingly, elderly patients with cSDH and mild to moderate symptoms presented less frequently, with more severe symptoms (*p=0.046) and were less likely to reach favorable outcome (*p=0.003).
Conclusions: Despite pandemic-related restrictive measures and reallocation of resources, patients with Neuro-emergencies should be encouraged to present regardless of the severity of symptoms because deferred presentation may result in adverse outcome. Thus, conservation of critical healthcare resources remains essential in spite fighting COVID-19.
We investigate the effectiveness of professional development (PD) aimed at promoting teachers' language-support skills in elementary school science instruction. In a 2-year quasi-experimental field trial study with 32 teachers in Germany, an intervention group (IG) and a control group (CG) received PD for teaching selected science topics; the IG additionally received PD for language support. Strong treatment effects emerged on teachers’ language-support skills and, to a lesser extent, on language support activities in classroom teaching. All teachers gained pedagogical content knowledge and self-efficacy for teaching elementary school science, thus pointing to the effectiveness of the PD.
The accessories perovskite, pyrochlore, zirconolite, calzirtite and melanite from carbonatites and carbonate-rich foidites from the Kaiserstuhl are variously suited for the in situ determination of their U–Pb ages and Sr, Nd- and Hf-isotope ratios by LA-ICP-MS. The 143Nd/144Nd ratios may be determined precisely in all five phases, the 176Hf/177Hf ratios only in calzirtite and the 87Sr/86Sr ratios in perovskites and pyrochlores. The carbonatites and carbonate-rich foidites belong to one of the three magmatic groups that Schleicher et al. (1990) distinguished in the Kaiserstuhl on the basis of their Sr, Nd and Pb isotope ratios. Tephrites, phonolites and essexites (nepheline monzogabbros) form the second and limburgites (nepheline basanites) and olivine nephelinites the third. Our 87Sr/86Sr isotope data from the accessories overlap with the carbonatite and olivine nephelinite fields defined by Schleicher et al. (1990) but exhibit a much narrower range. These and the εNd and εHf values plot along the mantle array in the field of oceanic island basalts relatively close to mid-ocean ridge basalts. Previously reported K–Ar, Ar–Ar and fission track ages for the Kaiserstuhl lie between 16.2 and 17.8 Ma. They stem entirely from the geologically older tephrites, phonolites and essexites. No ages existed so far for the geologically younger carbonatites and carbonate-rich foidites except for one apatite fission track age (15.8 Ma). We obtained precise U–Pb ages for zirconolites and calzirtites of 15.66, respectively 15.5 Ma (± 0.1 2σ) and for pyrochlores of 15.35 ± 0.24 Ma. Only the perovskites from the Badberg soevite yielded a U–P concordia age of 14.56 ± 0.86 Ma while the perovskites from bergalites (haüyne melilitites) only gave 206Pb/238U and 208Pb/232Th ages of 15.26 ± 0.21, respectively, 15.28 ± 0.48 Ma. The main Kaiserstuhl rock types were emplaced over a time span of 1.6 Ma almost 1 million years before the carbonatites and carbonate-rich foidites. These were emplaced within only 0.32 Ma.
Within the scope of this technical report, the feasibility of indocyanine green (ICG) as a fluorescent agent for postmortem angiography of the heart is tested. The study included 4 deceased persons with no respective medical history of heart diseases. The basic patterns of findings in ICG fluorescence angiography associated with healthy hearts are presented. The method can easily be integrated into a workflow without restricting the macroscopic or histologic diagnostics. This paper represents the fundamental technical and analytical basis for upcoming studies concerning the possibilities and limitations of fluorescence angiography in the diagnosis of heart pathology.
Motives motivate human behavior. Most behaviors are driven by more than one motive, yet it is unclear how different motives interact and how such motive combinations affect the neural computation of the behaviors they drive. To answer this question, we induced two prosocial motives simultaneously (multi-motive condition) and separately (single motive conditions). After the different motive inductions, participants performed the same choice task in which they allocated points in favor of the other person (prosocial choice) or in favor of themselves (egoistic choice). We used fMRI to assess prosocial choice-related brain responses and drift diffusion modeling to specify how motive combinations affect individual components of the choice process. Our results showed that the combination of the two motives in the multi-motive condition increased participants’ choice biases prior to the behavior itself. On the neural level, these changes in initial prosocial bias were associated with neural responses in the bilateral dorsal striatum. In contrast, the efficiency of the prosocial decision process was comparable between the multi-motive and the single-motive conditions. These findings provide insights into the computation of prosocial choices in complex motivational states, the motivational setting that drives most human behaviors.
Objective: Nationwide data on the epidemiology, treatment characteristics, and long-term outcome of severe traumatic brain injury (TBI) in Germany is not yet existing. Neurosurgeons from the German Neurosurgery Society (DGNC) and traumatologists from the German Trauma Society (DGU), therefore, joined forces in 2016 to conceptualize a TBI module for the well-established Trauma Register of the DGU (TR-DGU). Here, we report how this “German National TBI registry (GNTR)” has been developed, implemented, and tested in a recently completed pilot period.
Methods: The conception and implementation process of the GNTR from August 2016 to February 2019 is described, and results of its 23-months long pilot period from February 2019 to December 2020 are presented. For the pilot period, TBI patients were prospectively enrolled at nine neurosurgical and traumatological hospitals across Germany. Inclusion criteria were treatment on the ICU ≥ 24h, or an ISS score ≥ 16. A variety of clinical, imaging, and laboratory parameters were collected, and the GOSE score was used to assess the outcome at discharge and 6- and 12 months follow-up.
Results: Details on the structure and dataset of the GNTR as well as milestones and pitfalls during its conception and implementation, are outlined. During the pilot period, a total of 264 TBI patients were enrolled. Their demographic characteristics, clinical, imaging, and radiological findings, and their early mortality and functional outcome are described. Furthermore, factors associated with an unfavorable outcome (GOSE 1-4) are assessed using uni- and multivariate regression analyses. Finally, problems and future directions of the GNTR are discussed.
Conclusion: The pilot period of the GNTR offers a first glance at the current epidemiology and treatment characteristics of TBI patients in Germany. More importantly, they show how a national TBI registry yielding high-quality prospective data can be developed, implemented, and tested within four years
Background: Dexamethasone (Dex) is the most common corticosteroid to treat edema in glioblastoma (GBM) patients. Recent studies identified the addition of Dex to radiation therapy (RT) to be associated with poor survival. Independently, Tumor Treating Fields (TTFields) provides a novel anti-cancer modality for patients with primary and recurrent GBM. Whether Dex influences the efficacy of TTFields, however, remains elusive.
Methods: Human GBM cell lines MZ54 and U251 were treated with RT or TTFields in combination with Dex and the effects on cell counts and cell death were determined via flow cytometry. We further performed a retrospective analysis of GBM patients with TTFields treatment +/- concomitant Dex and analysed its impact on progression-free (PFS) and overall survival (OS).
Results: The addition of Dex significantly reduced the efficacy of RT in U251 and MZ54 cells. TTFields (200 kHz/250 kHz) induced massive cell death in both cell lines. Concomitant treatment of TTFields and Dex did not reduce the overall efficacy of TTFields. Further, in our retrospective clinical analysis, we found that the addition of Dex to TTFields therapy did not influence PFS nor OS.
Conclusion: Our translational investigation indicates that the efficacy of TTFields therapy in patients with GBM and primary GBM cell lines is not affected by the addition of Dex.
Background: Epileptic seizures are common clinical features in patients with acute subdural hematoma (aSDH); however, diagnostic feasibility and therapeutic monitoring remain limited. Surface electroencephalography (EEG) is the major diagnostic tool for the detection of seizures but it might be not sensitive enough to detect all subclinical or nonconvulsive seizures or status epilepticus. Therefore, we have planned a clinical trial to evaluate a novel treatment modality by perioperatively implanting subdural EEG electrodes to diagnose seizures; we will then treat the seizures under therapeutic monitoring and analyze the clinical benefit.
Methods: In a prospective nonrandomized trial, we aim to include 110 patients with aSDH. Only patients undergoing surgical removal of aSDH will be included; one arm will be treated according to the guidelines of the Brain Trauma Foundation, while the other arm will additionally receive a subdural grid electrode. The study's primary outcome is the comparison of incidence of seizures and time-to-seizure between the interventional and control arms. Invasive therapeutic monitoring will guide treatment with antiseizure drugs (ASDs). The secondary outcome will be the functional outcome for both groups as assessed via the Glasgow Outcome Scale and modified Rankin Scale both at discharge and during 6 months of follow-up. The tertiary outcome will be the evaluation of chronic epilepsy within 2-4 years of follow-up.
Discussion: The implantation of a subdural EEG grid electrode in patients with aSDH is expected to be effective in diagnosing seizures in a timely manner, facilitating treatment with ASDs and monitoring of treatment success. Moreover, the occurrence of epileptiform discharges prior to the manifestation of seizure patterns could be evaluated in order to identify high-risk patients who might benefit from prophylactic treatment with ASDs.
Trial registration: ClinicalTrials.gov identifier no. NCT04211233.
Background: Unruptured intracranial aneurysm (UIA) poses a therapeutic dilemma in which the risk-benefit analysis of invasive intervention has to be balanced against the natural history of the disease. To date, there is no medical treatment to prevent aneurysm development and subsequent progression to rupture. We explored the vitamin D system because of its known anti-inflammatory and anti-tissue-remodeling effect as a potential treatment for UIA.
Methods: 25-vitaminD3 levels tested between 2008-2016 and data of SAH patients admitted during the months with a peak versus nadir of VitD3-values were analyzed, retrospectively. We prospectively correlated VitD3 with size and number of aneurysms at the rupture time in patients admitted between 2017-2019. An experimental mice shear stress model and cell culture model were used to investigate the effect of 1,25-dihydroxy-vitaminD3 (1,25-VitD3) and acting mediators in this mechanism.
Results: Based on the retrospective analysis demonstrating an increased frequency of aneurysm rupture rate in patients during the low vitamin D period in winter, we started the prospective study evaluating plasma vitamin D levels at admission. VitD levels were inversely correlated with aneurysm size as well as number of aneurysms. Low number of aneurysms was significantly associated with sufficient plasma Vitamin D level as an independent factor in a multivariate analysis.
From bedside back to bench, active 1,25-VitD3 hormone attenuated the natural history of remodeling in mice basilar artery. Deletion of the vitamin-D-receptor in myeloid cells decreased the protective 1,25-VitD3 effect. Cell-culture of vascular fibroblasts confirmed the anti-tissue remodeling effect of 1,25-VitD3.
Conclusion: 1,25-VitD3 attenuates aneurysm development and subsequent progression to rupture. However, VitD-administration should be tested as optional treatment in management of patients with UIA.
Background: Glioblastoma (GBM) is a cancer type with high thrombogenic potential and GBM patients are therefore at a particularly high risk for thrombotic events. To date only limited data on anticoagulation management after pulmonary embolism (PE) in GBM is available and the sporadic use of DOACs remains off-label.
Methods: A retrospective cohort analysis of patients with GBM and postoperative, thoracic CT-scan confirmed, PE was performed. Clinical course, follow-up at 6 and 12 months and the overall survival (OS) were evaluated using medical charts and neuroradiological data.
Results: Out of 584 GBM patients, 8% suffered from postoperative PE. Out of theses, 30% received direct oral anticoagulants (DOACs) and 70% low-molecular-weight heparin (LMWH) for therapeutic anticoagulation. There was no significant difference in major intracranial hemorrhage (ICH), re-thrombosis or re-embolism between the two cohorts. Although statistically non-significant, a tendency to reduced mRS at 6- and 12 months was observed in the LMWH cohort. Furthermore, patients receiving DOACs had a statistical benefit in OS.
Conclusion: In our analysis DOACs showed a satisfactory safety profile in terms of major ICH, re-thrombosis and re-embolism compared to LMWH in GBM patients with postoperative PE. Prospective, randomized trials are urgent to evaluate DOACs for therapeutic anticoagulation in GBM patients with PE.
Background: Dysphagia is a common and severe symptom of traumatic brain injury (TBI) affecting up to 78% of patients. It is associated with pneumonia, increased morbidity and mortality. Although subdural hematoma (SDH) accounts for over 50% of TBI, the occurrence of dysphagia in this subtype has not been investigated. This study investigates the overall frequency, clinical predictors of dysphagia and functional outcome of patients with SDH associated dysphagia.
Methods: All patients presenting in author ́s institution between 2007 and 2020 with SDH were included in the study. Patients with SDH and clinical suspicion for dysphagia received a clinical swallowing assessment by a speech and language pathologist (SLP). Furthermore the severity of dysphagia was rated according to swallowing disorder scale.Functional outcome was evaluated by Glasgow outcome scale (GOS).
Results: Of 545 patients with SDH, 71 patients had dysphagia (13%). The prevalence of dysphagia was significantly lower in the surgical arm compared to the conservative arm (11.8% vs 21.8%; OR 0.23; p=0.02). Independent predictors for dysphagia were GCS <13 at admission (p<0.001; OR 4.17), cardiovascular disease (p=0.002; OR 2.29) and pneumonia (p=0.002; OR 2.88) whereas operation was a protective factor (p<0.001; OR 0.2). All patients with dysphagia improved significantly under SLP treatment from initial diagnosis to hospital discharge (p<0.01). However, patients with most severe grade of dysphagia showed no significant improvement during the clinical course. Patients with dysphagia had significantly worse outcome (GOS 1-3) compared to those without dysphagia (48.8% vs 26.4%; p<0.001).
Conclusion: Dysphagia is a frequent symptom in SDH and the early identification of dysphagia is crucial regarding initiation of treatment and functional outcome. Surgery is effective in preventing dysphagia and should be considered in high-risked patients.
Background: Research on chronic subdural hematoma (cSDH) management has primarily focused on potential recurrence after surgical evacuation. Herein, we present a novel postoperative/non-invasive treatment that includes a supervised Valsalva maneuver (SVM), which may serve to reduce SDH recurrence. Accordingly, the aims of the study were to investigate the effects of SVM on SDH recurrence rates and functional outcomes.
Methods: A prospective study was conducted from December 2016 until December 2019 at the Goethe University Hospital Frankfurt. Of the 204 adult patients with surgically treated cSDH who had subdural drains placed, 94 patients were assigned to the SVM group and 82 patients were assigned to the control group. The SVM was performed by having patients blow into a self-made SVM device at least two times/h for 12 h/day. The primary end-point was SDH recurrence rate, while secondary outcomes were morbidity and functional outcomes at 3 months of follow-up.
Results: SDH recurrence was observed in 16 of 94 patients (17%) in the SVM group, which was a significant reduction as compared with the control group, which had 24 of 82 patients (29.3%; p = 0.05) develop recurrent SDHs. Further, the infection rate (e.g., pneumonia) was significantly lower in the SVM group (1.1%) than in the control group (13.4%; p < 0.001; odds ratio [OR] 0.1). At the 3-month follow-up, 85 of 94 patients (90.4%) achieved favorable outcomes in the SVM group compared with 62 of 82 patients (75.6%) in the control group (p = 0.008; OR 3.0). Independent predictors for favorable outcome at follow-up were age (OR 0.9) and infection (OR 0.2).
Conclusion: SVM appears to be safe and effective in the post-operative management of cSDHs, reducing both recurrence rates and infections after surgical evacuation, thereby resulting in favorable outcomes at follow-up.
Background: The extent of preoperative peritumoral edema in glioblastoma (GBM) has been negatively correlated with patient outcome. As several ongoing studies are investigating T-cell based immunotherapy in GBM, we conducted this study to assess whether peritumoral edema with potentially increased intracranial pressure, disrupted tissue homeostasis and reduced local blood flow has influence on immune infiltration and affects survival.
Methods: A volumetric analysis of preoperative imaging (gadolinium enhanced T1 weighted MRI sequences for tumor size and T2 weighted sequences for extent of edema (including the infiltrative zone, gliosis etc.) was conducted in 144 patients using the BrainlabÒ software. Immunohistochemical staining was analyzed for lymphocytic- (CD 3+) and myeloid (CD15+) tumor infiltration. A retrospective analysis of patient-, surgical-, and molecular characteristics was performed using medical records.
Results: The edema to tumor ratio was neither associated with progression-free nor overall survival (p=0.90, p=0.74). However, GBM patients displaying IDH-1 wildtype had significantly higher edema to tumor ratio than patients displaying an IDH-1 mutation (p=0.01). Immunohistopathological analysis did not show significant differences in lymphocytic or myeloid tumor infiltration (p=0.78, p=0.74) between these groups.
Conclusion: In our cohort, edema to tumor ratio had no significant correlation with immune infiltration and outcome. However, patients with an IDH-1wildtype GBM had a significantly higher edema to tumor ratio compared to their IDH-1 mutated peer group. Further studies are necessary to elucidate the underlying mechanisms.
DGK and DZHK position paper on genome editing: basic science applications and future perspective
(2021)
For a long time, gene editing had been a scientific concept, which was limited to a few applications. With recent developments, following the discovery of TALEN zinc-finger endonucleases and in particular the CRISPR/Cas system, gene editing has become a technique applicable in most laboratories. The current gain- and loss-of function models in basic science are revolutionary as they allow unbiased screens of unprecedented depth and complexity and rapid development of transgenic animals. Modifications of CRISPR/Cas have been developed to precisely interrogate epigenetic regulation or to visualize DNA complexes. Moreover, gene editing as a clinical treatment option is rapidly developing with first trials on the way. This article reviews the most recent progress in the field, covering expert opinions gathered during joint conferences on genome editing of the German Cardiac Society (DGK) and the German Center for Cardiovascular Research (DZHK). Particularly focusing on the translational aspect and the combination of cellular and animal applications, the authors aim to provide direction for the development of the field and the most frequent applications with their problems.
The present paper is concerned with the half-space Dirichlet problem [...] where ℝ𝑁+:={𝑥∈ℝ𝑁:𝑥𝑁>0} for some 𝑁≥1 and 𝑝>1, 𝑐>0 are constants. We analyse the existence, non-existence and multiplicity of bounded positive solutions to (𝑃𝑐). We prove that the existence and multiplicity of bounded positive solutions to (𝑃𝑐) depend in a striking way on the value of 𝑐>0 and also on the dimension N. We find an explicit number 𝑐𝑝∈(1,𝑒√), depending only on p, which determines the threshold between existence and non-existence. In particular, in dimensions 𝑁≥2, we prove that, for 0<𝑐<𝑐𝑝, problem (𝑃𝑐) admits infinitely many bounded positive solutions, whereas, for 𝑐>𝑐𝑝, there are no bounded positive solutions to (𝑃𝑐).
Background: The Global Burden of Diseases Study 2017 predicted that chronic obstructive pulmonary disease (COPD) is the second leading cause of death, the fourth leading cause of premature death, and the third cause for DALYs lost in Nepal. However, data on the population-based prevalence of COPD in Nepal are very limited. This study aims to assess the prevalence of COPD and factors associated with the occurrence of COPD in Nepal.
Methods: From a nationally representative, population-based cross-sectional study on chronic non-communicable diseases, the prevalence of COPD and its associated factors was determined. Of 12,557 participants aged over 20 years, 8945 participants completed a questionnaire and spirometry. Eligible participants were also asked to answer a COPD diagnostic questionnaire for screening COPD cases, and if needed underwent pre-bronchodilator and post-bronchodilator spirometry. COPD was defined as a post-bronchodilator FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio of < 0.70. Multivariate logistic regression was performed to identify factors associated with COPD. Sampling weights were used for all data analyses.
Results: The prevalence of COPD in Nepal was 11.7% (95% CI: 10.5% to 12.9 %), which increased with age, and higher in those with a low educational level, those who had smoked ≥ 50 pack-years, persons having a low body mass index (BMI), and residents of Karnali province. Multivariate analysis revealed that being aged 60 years and above, having a low BMI, low educational status, having smoked more than 50 pack-years, provincial distribution, and ethnicity were independent predictors of COPD.
Conclusion: COPD is a growing and serious public health issue in Nepal. Factor such as old age, cigarette smoking, low educational attainment, low BMI, ethnicity, and locality of residence (province-level variation) plays a vital role in the occurrence of COPD. Strategies aimed at targeting these risk factors through health promotion and education interventions are needed to decrease the burden of COPD.
Background: In the past, protease inhibitors (PIs) and the reverse transcriptase inhibitor abacavir were identified increasing the risk for thromboembolic complications and cardiovascular events (CVE) of HIV infected patients taking a combination antiretroviral therapy (cART). Results of the previous HIV-PLA I-study lead to the assumption that platelet activation could play a substantial role in increasing CVE risks.
Methods: The open label, monocentric HIV-PLA II-study investigated HIV-1-infected, therapy-naïve adults (n=45) starting with cART, consisting either of boosted PI (atazanavir, n= 6, darunavir, n=11), NNRTI (efavirenz, n=14) or integrase inhibitor (raltegravir, n=14), each plus tenofovir/emtricitabine co-medication. Main exclusion criteria were tobacco smoking, the intake of NSAIDs or abacavir or past CVE. Platelet adhesive molecule p-selectin (CD62P) and FITC anti-human Integrin α-IIb/Integrin β-3 (CD41/CD61) antibody (PAC-1) binding, monocyte CD11b/monocyte-associated CD41 expression and the endogenous thrombin potential (ETP) were assessed ex vivo-in vitro at baseline, weeks 4, 12 and 24. Therapy regimens were blinded to the investigators for laboratory and statistical analyses.
Results: CD11b and ETP showed no significant changes or differences between all study groups. In contrast, the mean + SD mean fluorescence units (MFI) of CD62P and PAC-1 increased significantly in patients taking PI, indicating an enhanced potential for thrombocyte activation and aggregation.
Conclusion: CD62P expression, detecting the ɑ-platelet degranulation of pro-inflammatory and pro-thrombotic factors and adhesive proteins, and PAC-1 expression, representing a marker for conformation changes of the GIIb/IIIa receptor, increased significantly in patients taking HIV protease inhibitors. The findings of this study revealed a yet unknown pathway of platelet activation, possibly contributing to the increased risk for CVE under HIV protease inhibitor containing cART.
Clinical Trial Registration No.: DRKS00000288.
Background: Clinical trial registries increase transparency in medical research by making information and results of planned, ongoing, and completed studies publicly available. However, the registration of clinical trials remains a time-consuming manual task complicated by the fact that the same studies often need to be registered in different registries with different data entry requirements and interfaces.
Objective: This study investigates how Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) may be used as a standardized format for exchanging and storing clinical trial records.
Methods: We designed and prototypically implemented an open-source central trial registry containing records from university hospitals, which are automatically exported and updated by local study management systems.
Results: We provided an architecture and implementation of a multisite clinical trials registry based on HL7 FHIR as a data storage and exchange format.
Conclusions: The results show that FHIR resources establish a harmonized view of study information from heterogeneous sources by enabling automated data exchange between trial centers and central study registries.
Experimental work on highly pathogenic viruses such as Ebola virus (EBOV) and severe acute respiratory syndrome coronavirus-2 requires high-level biosafety facilities. Here, we provide a detailed step-by-step protocol which details the production and application of replication-incompetent murine leukemia virus-based pseudotyped particles to monitor and quantify the viral entry efficiency in human cell lines under biosafety level-2 conditions. We describe the use of viral particles encoding luciferase gene and the quantification of transduction efficiency by measuring luciferase activity.
Diagnostic value of dynamic magnetic resonance imaging of temporomandibular joint dysfunction
(2021)
Background: To estimate the diagnostic value of dynamic magnetic resonance imaging (MRI) for the assessment of the temporomandibular joint (TMJ) compared to standard static MRI sequences in patients with TMJ dysfunction (TMD).
Methods and materials: This retrospective study included 71 patients with clinical diagnose of TMD. We acquired 5 static T1- and T2-weighted sequences in parasagittal and paracoronal views and one dynamic sequence (trueFISP) in parasagittal view for each TMJ. Image analysis included evaluation of morphology and function of intra-articular structures and rating of the dynamic images as more, equally, or less informative compared to static MRI sequences.
Results: Mean age was 35.0 ± 14.7 years and 50/71 (70.4%) were female. 127/142 (89.4%) TMJs were of diagnostic quality. 42/127 (33.1%) TMJs showed no disc displacement (DD), 56 (44.1%) had DD with disc reduction (DDwR), and 29 (22.8%) had DD without disc reduction (DDwoR). In 38/127 (29.9%) TMJs, dynamic images were rated “more informative”, in 84/127 (66.2%) “equally informative”, and in 5/127 (3.9%) “less informative” compared to solely static images. Overall, 27/71 (38.0%) patients benefited from additional dynamic sequences compared to solely static images. Dynamic images were “more informative” in TMJs with DDwR (23/56 [41.1%], p < 0.001) and in TMJs with DDwoR (13/29 [44.8%], p = 0.007), while it had no beneficial value for TMJ without DD. For evaluation of joint effusion, static T2-weighted images were rated better in 102/127 (80.3%) TMJs compared to dynamic images (<0.001).
Conclusion: Dynamic MRI sequences are beneficial for the evaluation of morphology and function of the TMJ compared to static sequences, especially in patients with temporomandibular disc displacement.
Objectives: To investigate the diagnostic accuracy of color-coded contrast-enhanced dual-energy CT virtual noncalcium (VNCa) reconstructions for the assessment of lumbar disk herniation compared to unenhanced VNCa imaging.
Methods: A total of 91 patients were retrospectively evaluated (65 years ± 16; 43 women) who had undergone third-generation dual-source dual-energy CT and 3.0-T MRI within an examination interval up to 3 weeks between November 2019 and December 2020. Eight weeks after assessing unenhanced color-coded VNCa reconstructions for the presence and degree of lumbar disk herniation, corresponding contrast-enhanced portal venous phase color-coded VNCa reconstructions were independently analyzed by the same five radiologists. MRI series were additionally analyzed by one highly experienced musculoskeletal radiologist and served as reference standard.
Results: MRI depicted 210 herniated lumbar disks in 91 patients. VNCa reconstructions derived from contrast-enhanced CT scans showed similar high overall sensitivity (93% vs 95%), specificity (94% vs 95%), and accuracy (94% vs 95%) for the assessment of lumbar disk herniation compared to unenhanced VNCa images (all p > .05). Interrater agreement in VNCa imaging was excellent for both, unenhanced and contrast-enhanced CT (κ = 0.84 vs κ = 0.86; p > .05). Moreover, ratings for diagnostic confidence, image quality, and noise differed not significantly between unenhanced and contrast-enhanced VNCa series (all p > .05).
Conclusions: Color-coded VNCa reconstructions derived from contrast-enhanced dual-energy CT yield similar diagnostic accuracy for the depiction of lumbar disk herniation compared to unenhanced VNCa imaging and therefore may improve opportunistic retrospective lumbar disk herniation assessment, particularly in case of staging CT examinations.
Key Points
• Color-coded dual-source dual-energy CT virtual noncalcium (VNCa) reconstructions derived from portal venous phase yield similar high diagnostic accuracy for the assessment of lumbar disk herniation compared to unenhanced VNCa CT series (94% vs 95%) with MRI serving as a standard of reference.
• Diagnostic confidence, image quality, and noise levels differ not significantly between unenhanced and contrast-enhanced portal venous phase VNCa dual-energy CT series.
• Dual-source dual-energy CT might have the potential to improve opportunistic retrospective lumbar disk herniation assessment in CT examinations performed for other indications through reconstruction of VNCa images.
A remark on the bank cases
(2021)
Since their formulation by Keith DeRose (1992), the so-called bank cases have played a major role in the discussion about whether knowledge depends on practical factors. According to the proponents of pragmatic encroachment, the proper conclusion to be drawn from the bank cases and similar examples is that knowledge of a proposition p does not supervene on one’s evidence for or against p. In my view, this conclusion is ill-founded. The reason is that the bank cases and similar examples suffer from an ambiguity concerning the known proposition — an ambiguity that has so far been overlooked. When this ambiguity is made explicit, it becomes clear that the conclusion does not follow.
Childhood and adolescent sexual abuse (CSA) is a traumatic experience associated with a variety of short- and long-term negative consequences. Theoretical models assume that an abuse related and learned distorted image of sexuality might lead CSA survivors to feel obligated to provide sex or engage in unwanted sexual practices in order to gain affection or prevent abandonment. Dialectical behavioral therapy for posttraumatic stress disorder (DBT-PTSD) is tailored to people with PTSD and comorbid emotion regulation deficits. This case study presents the results of an outpatient DBT-PTSD treatment of an adult patient with posttraumatic stress disorder following sexual and physical abuse. DBT-PTSD was used to treat the patient’s complex psychopathological problems and to decrease her risky sexual behavior, which manifested itself in highly dangerous sexual practices with her partner. The treatment took place over a period of 18 months, with a total of 72 sessions. At the end of the treatment, the patient no longer met criteria for PTSD as indicated by large reductions in the assessments used. Furthermore, she managed to distance herself from risky sexual practices and to remain in a satisfying relationship.
Objective: To determine the early treatment response after microwave ablation (MWA) of inoperable lung neoplasms using the apparent diffusion coefficient (ADC) value calculated 24 h after the ablation.
Materials and methods: This retrospective study included 47 patients with 68 lung lesions, who underwent percutaneous MWA from January 2008 to December 2017. Evaluation of the lesions was done using MRI including DWI sequence with ADC value calculation pre-ablation and 24 h post-ablation. DWI-MR was performed with b values (50, 400, 800 mm2/s). The post-ablation follow-up was performed using chest CT and/or MRI within 24 h following the procedure; after 3, 6, 9, and 12 months; and every 6 months onwards to determine the local tumor response. The post-ablation ADC value changes were compared to the end response of the lesions.
Results: Forty-seven patients (mean age: 63.8 ± 14.2 years, 25 women) with 68 lesions having a mean tumor size of 1.5 ± 0.9 cm (range: 0.7–5 cm) were evaluated. Sixty-one lesions (89.7%) showed a complete treatment response, and the remaining 7 lesions (10.3%) showed a local progression (residual activity). There was a statistically significant difference regarding the ADC value measured 24 h after the ablation between the responding (1.7 ± 0.3 × 10−3 mm2/s) and non-responding groups (1.4 ± 0.3 × 10−3 mm2/s) with significantly higher values in the responding group (p = 0.001). A suggested ADC cut-off value of 1.42 could be used as a reference point for the post-ablation response prediction (sensitivity: 66.67%, specificity: 84.21%, PPV: 66.7%, and NPV: 84.2%). No significant difference was reported regarding the ADC value performed before the ablation as a factor for the prognosis of treatment response (p = 0.86).
Conclusion: ADC value assessment following ablation may allow the early prediction of treatment efficacy after MWA of inoperable lung neoplasms.
Key Points
• ADC value calculated 24 h post-treatment may allow the early prediction of MWA efficacy as a treatment of pulmonary tumors and can be used in the early immediate post-ablation imaging follow-up.
• The pre-treatment ADC value of lung neoplasms is not different between the responding and non-responding tumors.
This study explores the implications of rising markups for optimal Mirrleesian income and profit taxation. Using a stylized model with two individuals, the main forces shaping welfare-optimal policies are analytically characterized. Although a higher profit tax has redistributive benefits, it adversely affects market competition, leading to a greater equilibrium cost-of-living. Rising markups directly contribute to a decline in optimal marginal taxes on labor income. The optimal policy response to higher markups includes increasingly relying on the profit tax to fund redistribution. Declining optimal marginal income taxes assists the redistributive function of the profit tax by contributing to the expansion of the profit tax base. This response alone considerably increases the equilibrium cost-of-living. Nevertheless, a majority of the individuals become better off with the optimal policy. If it is not possible to tax profits optimally, due, for example, to profit shifting, increasing redistribution via income taxes is not optimal; every individual is worse off relative to the scenario with optimal profit taxation.
Background. Angiosarcomas are rare and heterogeneous tumors with poor prognosis. The clinical subtypes are classified depending on the primary site and etiology. Methods. We conducted a retrospective, monocentric study of 136 patients with localized AS between May 1985 and November 2018. Overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) were estimated using the Kaplan–Meier method. To identify prognostic factors, univariate and multivariate analyses were performed based on Cox regressions. Results. The median age was 67 years (19–72.8 years). Primary sites were cutaneous (27.2%), breast (38.2%), and deep soft tissue (34.6%). The majority was primary angiosarcomas (55.9%) followed by postradiation (40.4%) and chronic lymphedema angiosarcomas (2.9%). Prognosis significantly differed depending on the primary site and etiology. Shortest median OS and MFS were observed in deep soft tissue angiosarcomas, whereas cutaneous angiosarcomas, angiosarcomas of the breast, and radiation-associated angiosarcomas displayed worse median LRFS. Univariate analyses showed better OS for tumor size <10 cm (p = 0.009), negative surgical margins ( = 0.021), and negative lymph node status (p = 0.007). LRFS and MFS were longer for tumor size <10 cm (p = 0.012 and p = 0.013). In multivariate analyses, age <70 years was the only independent positive prognostic factor for OS in all subgroups. For LRFS, secondary AS of the breast was a negative prognostic factor (HR: 2.35; p = 0.035). Conclusions. Different behaviors and prognoses depending on the primary site and etiology should be considered for the treatment of this heterogeneous disease. In cutaneous angiosarcomas of the head/neck and postradiation angiosarcomas of the breast, local recurrence seems to have a crucial impact on OS. Therefore, improved local therapies and local tumor staging may have to be implemented. However, in deep soft tissue angiosarcomas, distant recurrence seems to have a major influence on prognosis, which indicates a benefit of additional perioperative chemotherapy.
A simple and sustainable one-step strategy for the preparation of electron-deficient aryl trifluoromethyl ethers (ArOCF3) from the corresponding phenols by electrochemical synthesis is presented. Anodic oxidation of trifluoromethane sulfinate (Langlois reagent) leads to direct O-trifluoromethylation of phenol-derivatives bearing fluorine, chlorine, bromine and nitrile substituents under mild conditions in yields up to 75% and in gram-scale. This electrochemical protocol provides an economic and green synthesis for an otherwise inaccessible class of molecules without the need for expensive or toxic reagents, oxidants or metal catalysts.
Reactive oxygen species (ROS) are derivatives of molecular oxygen (O2) involved in various physiological and pathological processes. In immune cells, ROS are mediators of pivotal functions such as phagocytosis, antigen presentation and recognition, cytolysis as well as phenotypical differentiation. Furthermore, ROS exert immunosuppressive effects on T and natural killer (NK) cells which is of particular importance in the so-called “tumor microenvironment” (TME) of solid tumors. This term describes the heterogenous group of non-malignant cells including tumor-associated fibroblasts and immune cells, vascular cells, bacteria etc. by which cancer cells are surrounded and with whom they engage in functional crosstalk. Importantly, pharmacological targeting of the TME and, specifically, tumor-associated immune cells utilizing immune checkpoint inhibitors - monoclonal antibodies that mitigate immunosuppression - turned out to be a major breakthrough in the treatment of malignant tumors. In this review, we aim to give an overview of the role that ROS produced in tumor-associated immune cells play during initiation, progression and metastatic outgrowth of solid cancers. Finally, we summarize findings on how ROS in the TME could be targeted therapeutically to increase the efficacy of cancer immunotherapy and discuss factors determining therapeutic success of redox modulation in tumors.
Introduction: There is limited awareness of von Willebrand disease (VWD), leading to challenges in both diagnosis and defining the optimal treatment approach for these patients. Patients with VWD are typically treated on-demand, with short-term prophylaxis used during surgery. In contrast, early initiation, and long-term use of prophylaxis is the standard of care in patients with severe haemophilia and can be successfully used to prevent joint bleeding and reduce chronic arthropathy.
Aim: To provide an understanding of the current evidence for the prophylactic treatment of patients with VWD and compare this to the management of patients with haemophilia.
Methods: Review of published literature using a non-systematic search of PubMed and reference lists of sourced articles.
Results: The successes seen with prophylaxis in haemophilia provide the rationale for long-term prophylaxis in patients with severe forms of VWD; preventing spontaneous, excessive and sometimes life-threatening bleeding, and reducing chronic joint disease. Currently, there are a few clinical trials assessing the long-term benefits of prophylaxis in VWD, and guidelines for the optimal prophylaxis treatment approach are lacking. Greater attempts to provide comprehensive, long-term care for patients with VWD are needed but still lacking within the community. This review highlights the success of prophylaxis in haemophilia and how this knowledge might be applied and translated to patients with VWD.
Conclusions: Lessons can be learned from the use of prophylaxis in haemophilia and prophylaxis should be considered the standard of care for a subgroup of patients with severe VWD.
Cryo-electron tomography is the only technique that can provide sub-nanometer resolved images of cell regions or even whole cells, without the need of labeling or staining methods. Technological advances over the past decade in electron microscope stability, cameras, stage precision and software have resulted in faster acquisition speeds and considerably improved resolution. In pursuit of even better image resolution, researchers seek to reduce noise – a crucial factor affecting the reliability of the tomogram interpretation and ultimately limiting the achieved resolution. Sub-tomogram averaging is the method of choice for reducing noise in repetitive objects. However, when averaging is not applicable, a trade-off between reducing noise and conserving genuine image details must be achieved. Thus, denoising is an important process that improves the interpretability of the tomogram not only directly but also by facilitating other downstream tasks, such as segmentation and 3D visualization. Here, I review contemporary denoising techniques for cryo-electron tomography by taking into account noise-specific properties of both reconstruction and detector noise. The outcomes of different techniques are compared, in order to help researchers select the most appropriate for each dataset and to achieve better and more reliable interpretation of the tomograms.
In context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients with certain comorbidities and high age, as well as male sex are considered to represent the risk group for severe course of disease. Corona-virus disease 2019 (COVID-19) typical CT-patterns include bilateral, peripheral ground glass opacity (GGO), septal thickening, bronchiectasis, consolidation as well as associated pleural effusion. We report a 77-year-old heart transplanted patient with confirmed COVID-19 infection and coronary heart disease, diabetes type II and other risk factors. Notably, only slight clinical symptoms were reported and repeated computed tomography (CT) scans showed an atypical course of CT findings during his hospitalization.
Children from upper-class families have better cognitive outcomes and fewer behavioural problems than those from working-class families. Previous studies highlighted that the class gap in child development is partially driven by differences in parenting styles, but they rarely looked at multiple, more specific dimensions of parenting, i.e., inductive reasoning, parenting consistency, warmth and anger. This study provides a systematic account of how parental social class shapes these four dimensions of parenting, and how these dimensions affect children’s cognitive outcomes and behavioural problems. Using high-quality, longitudinal data, and both hybrid models and the generalized methods of moments, this study reports two main findings. First, upper-class parents significantly differ from lower-class parents in two parenting dimensions, displaying more inductive reasoning and parenting consistency, but no relevant class differences are found in the two emotion-type dimensions of parenting (i.e., warmth and anger). Second, all four parenting dimensions have a strong impact on children’s behavioural problems, while they do not affect cognitive outcomes. An exception is consistency, the only dimension that affects both types of child outcomes. The study underscores the relevance of analysing parenting and child development from a multidimensional approach to better understand how upper-class parents transmit advantage to children.
Nowadays, digitalization has an immense impact on the landscape of jobs. This technological revolution creates new industries and professions, promises greater efficiency and improves the quality of working life. However, emerging technologies such as robotics and artificial intelligence (AI) are reducing human intervention, thus advancing automation and eliminating thousands of jobs and whole occupational images. To prepare employees for the changing demands of work, adequate and timely training of the workforce and real-time support of workers in new positions is necessary. Therefore, it is investigated whether user-oriented technologies, such as augmented reality (AR) and virtual reality (VR) can be applied “on-the-job” for such training and support—also known as intelligence augmentation (IA). To address this problem, this work synthesizes results of a systematic literature review as well as a practically oriented search on augmented reality and virtual reality use cases within the IA context. A total of 150 papers and use cases are analyzed to identify suitable areas of application in which it is possible to enhance employees' capabilities. The results of both, theoretical and practical work, show that VR is primarily used to train employees without prior knowledge, whereas AR is used to expand the scope of competence of individuals in their field of expertise while on the job. Based on these results, a framework is derived which provides practitioners with guidelines as to how AR or VR can support workers at their job so that they can keep up with anticipated skill demands. Furthermore, it shows for which application areas AR or VR can provide workers with sufficient training to learn new job tasks. By that, this research provides practical recommendations in order to accompany the imminent distortions caused by AI and similar technologies and to alleviate associated negative effects on the German labor market.
An increasing number of voices highlight the need for science itself to transform and to engage in the co-production of knowledge and action, in order to enable the fundamental transformations needed to advance towards sustainable futures. But how can global sustainability-oriented research networks engage in co-production of knowledge and action? The present article introduces a strategic tool called the ‘network compass’ which highlights four generic, interrelated fields of action through which networks can strive to foster co-production. It is based on the networks’ particular functions and how these can be engaged for co-production processes. This tool aims to foster self-reflection and learning within and between networks in the process of (re)developing strategies and activity plans and effectively contributing to sustainability transformations.
Purpose: Epileptic seizures frequently result in distinct physical injuries, fractures, traumatic brain injuries and minor trauma. The aim of this study was to retrospectively determine the frequent injury patterns due to seizure episode and to analyze consecutive acute medical care.
Methods: This retrospective mono-center study was conducted at Frankfurt University Hospital, Frankfurt am Main, Germany between January 2007 and December 2017. Epilepsy patients with seizure-related fractures admitted to the emergency department were identified via a retrospective systematic query in the hospital information system using the ICD-10 German modification codes G40.0–G40.9. Patients with an unclear diagnosis of epilepsy were excluded. Sociodemographic as well as disease specific aspects were analyzed. Descriptive and Kruskal–Wallis one-way analysis of variance were used for statistical analysis.
Results: A total number of 62 epilepsy patients were included. The mean age was 58.1 years. Fractures concerned the upper extremity most frequently (43.5%, n = 20), and 70.0% (14/20) were humerus fractures. Admission to intensive care unit for acute trauma care was necessary in 29.0% patients (n = 18), and surgery in 45.2% patients (n = 28). Twenty-five patients (26.6%) showed clinical or radiological signs of traumatic brain injury. Provoking factors were identified in 20 patients (32.3%), i.e., acute withdrawal or excess of alcohol (n = 15), relevant sleep deprivation (n = 2), and intoxication or withdrawal of other illegal drugs or trivial infect (n = 1 for each) and non-compliance with anti-seizure drugs (n = 1). A decreased T-score (−1.04 ± 1.15) and Z-score (−0.84 ± 0.75) compared to healthy subjects were found.
Conclusion: Fractures in upper extremities, trunk and craniocerebral trauma occur frequently as seizure-induced injuries. Alcohol excess and withdrawal are important provoking factors and should be targeted with preventive measurements to avoid seizure related injuries and accidents.
We investigate how financial literacy shapes older Americans’ demand for financial advice. Using an experimental module fielded in the Health and Retirement Study, we show that financial literacy strongly improves the quality but not the quantity of financial advice sought. In particular, more financially literate people seek financial help from professionals. This effect is more pronounced among older people and those with more wealth and more complex financial positions. Our analysis result implies that financial literacy and financial advisory services are complementary with, rather than substitutes for, each other.
Vibrational energy transfer (VET) is essential for protein function. It is responsible for efficient energy dissipation in reaction sites, and has been linked to pathways of allosteric communication. While it is understood that VET occurs via backbone as well as via non-covalent contacts, little is known about the competition of these two transport channels, which determines the VET pathways. To tackle this problem, we equipped the β-hairpin fold of a tryptophan zipper with pairs of non-canonical amino acids, one serving as a VET injector and one as a VET sensor in a femtosecond pump probe experiment. Accompanying extensive non-equilibrium molecular dynamics simulations combined with a master equation analysis unravel the VET pathways. Our joint experimental/computational endeavor reveals the efficiency of backbone vs. contact transport, showing that even if cutting short backbone stretches of only 3 to 4 amino acids in a protein, hydrogen bonds are the dominant VET pathway.
In recent years, the clinical usefulness of the Wada test (WT) has been debated among researchers in the field. Therefore, we aimed to assess its contribution to the prediction of change in verbal learning and verbal memory function after epilepsy surgery. Data from 56 patients with temporal lobe epilepsy who underwent WT and subsequent surgery were analyzed retrospectively. Additionally, a standard neuropsychological assessment evaluating attentional, learning and memory, visuospatial, language, and executive function was performed both before and 12 months after surgery. Hierarchical linear regression analyses were used to determine the incremental value of WT results over socio-demographic, clinical, and neuropsychological characteristics in predicting postsurgical change in patients’ verbal learning and verbal memory function. The incorporation of WT results significantly improved the prediction models of postsurgical change in verbal learning (∆R2 = 0.233, p = .032) and verbal memory function (∆R2 = 0.386, p = .005). Presurgical performance and WT scores accounted for 41.8% of the variance in postsurgical change in verbal learning function, and 51.1% of the variance in postsurgical change in verbal memory function. Our findings confirm that WT results are of significant incremental value for the prediction of postsurgical change in verbal learning and verbal memory function. Thus, the WT contributes to determining the risks of epilepsy surgery and, therefore, remains an important part of the presurgical work-up of selected patients with clear clinical indications.
Purpose: We assessed contemporary incidence rates and trends of primary urethral cancer.
Methods: We identified urethral cancer patients within Surveillance, Epidemiology and End Results registry (SEER, 2004–2016). Age-standardized incidence rates per 1,000,000 (ASR) were calculated. Log linear regression analyses were used to compute average annual percent change (AAPC).
Results: From 2004 to 2016, 1907 patients with urethral cancer were diagnosed (ASR 1.69; AAPC: -0.98%, p = 0.3). ASR rates were higher in males than in females (2.70 vs. 0.55), respectively and did not change over the time (both p = 0.3). Highest incidence rates were recorded in respectively ≥75 (0.77), 55–74 (0.71) and ≤54 (0.19) years of age categories, in that order. African Americans exhibited highest incidence rate (3.33) followed by Caucasians (1.72), other race groups (1.57) and Hispanics (1.57), in that order. A significant decrease occurred over time in Hispanics, but not in other race groups. In African Americans, male and female sex-stratified incidence rates were higher than in any other race group. Urothelial histological subtype exhibited highest incidence rate (0.92), followed by squamous cell carcinoma (0.41), adenocarcinoma (0.29) and other histologies (0.20). In stage stratified analyses, T1N0M0 stage exhibited highest incidence rate. However, it decreased over time (−3.00%, p = 0.02) in favor of T1-4N1-2M0 stage (+ 2.11%, p = 0.02).
Conclusion: Urethral cancer is rare. Its incidence rates are highest in males, elderly patients, African Americans and in urothelial histological subtype. Most urethral cancer cases are T1N0M0, but over time, the incidence of T1N0M0 decreased in favor of T1-4N1-2M0.
Chimeric antigen receptor (CAR)-T cell therapies are on the verge of becoming powerful immunotherapeutic tools for combating hematological diseases confronted with pressing medical needs. Lately, CAR-NK cell therapies have also come into focus as novel therapeutic options to address hurdles related to CAR-T cell therapies, such as therapy-induced side effects. Currently, more than 500 CAR-T and 17 CAR-NK cell trials are being conducted worldwide including the four CAR-T cell products Kymriah, Yescarta, Tecartus and Breyanzi, which are already available on the market. Most CAR-T cell-based gene therapy products that are under clinical evaluation consist of autologous enriched T cells, whereas CAR-NK cell-based approaches can be generated from allogeneic donors. Besides modification based on a second-generation CAR, more advanced CAR-immune cell therapeutics are being tested, which utilize precise insertion of genes to circumvent graft-versus-host disease (GvHD) or employ a dual targeting approach and adapter CARs in order to avoid therapy resistance caused by antigen loss. In this review, we are going to take a closer look at the commercial CAR-T cell therapies, as well as on CAR-T and CAR-NK cell products, which are currently under evaluation in clinical trials, that are being conducted in Germany.
Artificial Intelligence (AI) and Machine Learning (ML) are currently hot topics in industry and business practice, while management-oriented research disciplines seem reluctant to adopt these sophisticated data analytics methods as research instruments. Even the Information Systems (IS) discipline with its close connections to Computer Science seems to be conservative when conducting empirical research endeavors. To assess the magnitude of the problem and to understand its causes, we conducted a bibliographic review on publications in high-level IS journals. We reviewed 1,838 articles that matched corresponding keyword-queries in journals from the AIS senior scholar basket, Electronic Markets and Decision Support Systems (Ranked B). In addition, we conducted a survey among IS researchers (N = 110). Based on the findings from our sample we evaluate different potential causes that could explain why ML methods are rather underrepresented in top-tier journals and discuss how the IS discipline could successfully incorporate ML methods in research undertakings.
Antigen presentation via major histocompatibility complex class I (MHC I) molecules is essential to mount an adaptive immune response against pathogens and cancerous cells. To this end, the transporter associated with antigen processing (TAP) delivers snippets of the cellular proteome, resulting from proteasomal degradation, into the ER lumen. After peptide loading and editing by the peptide-loading complex (PLC), stable peptide-MHC I complexes are released for cell surface presentation. Since the process of MHC I trafficking is poorly defined, we established an approach to control antigen presentation by introduction of a photo-caged amino acid in the catalytic ATP-binding site of TAP. By optical control, we initiate TAP-dependent antigen translocation, thus providing new insights into TAP function within the PLC and MHC I trafficking in living cells. Moreover, this versatile approach has the potential to be applied in the study of other cellular pathways controlled by P-loop ATP/GTPases.
Introduction: Stem cell transplantation is one of the most promising strategies to improve healing in chronic wounds as systemic administration of endothelial progenitor cells (EPC) enhances healing by promoting neovascularization and homing though a high amount of cells is needed. In the following study, we analysed whether local application can reduce the number of EPC needed achieving the same beneficial effect on wound healing.
Material and Methods: Wound healing after local or systemic treatment with EPC was monitored in vivo by creating standardized wounds on the dorsum of hairless mice measuring wound closure every second day. Systemic group received 2 × 106 EPC i.v. and locally treated group 2 × 105 EPC, locally injected. As control PBS injection was performed the same way. Expression of CD31, VEGF, CD90 and, SDF-1α was analysed immunohistochemically for evaluation of neovascularisation and amelioration of homing.
Results: Local (7.1 ± 0.45 SD) as well as systemic (6.1 ± 0.23 SD) EPC transplantation led to a significant acceleration of wound closure compared to controls (PBS local: 9.7 ± 0.5 SD, PBS systemic 10.9 ± 0.38 SD). Systemic application enhanced CD31 expression on day 6 after wounding and local EPC on 6 and 9 in comparison to control. VEGF expression was not significantly affected. Systemic and local EPC treatment resulted in a significantly enhanced SDF-1α and CD90 expression on all days investigated.
Conclusion: Local as well as systemic EPC treatment enhances wound healing. Moreover, beneficial effects are obtained with a tenfold decrease number of EPC when applied locally. Thus, local EPC treatment might be more convenient way to enhance wound healing as number of progenitor cells is limited.
Hintergrund: Die Ophthalmoskopie ist Bestandteil des medizinischen Curriculums, jedoch das Vermitteln der Inhalte oft unbefriedigend, da ein systematisches Lernen von Pathologien und deren Behandlungen dadurch erschwert ist, dass oftmals das passende Patientengut nicht zur Verfügung steht und dadurch gesunde Studenten einander untersuchen müssen. Aus diesem Grund haben wir eine Online-Plattform entwickelt, die in Kombination mit simulationsgestütztem Training sowohl das eigenständige als auch das angeleitete Lernen von Untersuchungsmethoden und Pathologien ermöglicht.
Ziel der Arbeit: Ziel der vorliegenden Arbeit war, ein Format für die Verbesserung der Lehre der direkten und indirekten Ophthalmoskopie im Studierendenunterricht zu evaluieren. Dabei wurden praktische Übungen an Virtual-Reality-basierten Simulatoren mit neu entwickelten und an den Lehrkatalog angepassten theoretischen Inhalten in der Online-Plattform EyesiNet verschränkt.
Material und Methoden: Die Studierenden bearbeiteten am ersten sowie am letzten Praktikumstag zufällig ausgewählte Fälle, die ihnen von den Eyesi Direct- und Eyesi Indirect-Simulatoren präsentiert wurden. Zwischen diesen beiden Einheiten konnten sie sich auf freiwilliger Basis mit den theoretischen Grundlagen typischer ophthalmologischer Krankheitsbilder im EyesiNet beschäftigen.
Ergebnisse: Eyesi Direct: Die Bewertung des Simulators ergab am ersten Praktikumstag für beide Gruppen keinen signifikant unterschiedlichen Wissensstand (p = 0,29). In der Gruppe OHNE Training (n = 54) ergab sich am letzten Praktikumstag mit p = 0,02 eine signifikante Verbesserung dieser Bewertung, jedoch mit einer geringen Effektgröße von 0,1. In der Gruppe MIT Training (n = 32) konnte mit p = 0,0004 eine hoch signifikante Verbesserung mit einer Effektgröße von 0,3 nach Rosenthal festgestellt werden. Eyesi Indirect: Die simulatorgestützte Bewertung ergab am ersten Praktikumstag keinen signifikanten Unterschied im Wissensstand der beiden Gruppen (p = 0,1). Nach dem Training schnitten zwar beide Gruppen etwas besser ab, jedoch ohne signifikanten Unterschied (OHNE Training p = 0,41/MIT Training p = 0,17).
Diskussion: Die Online-Plattform EyesiNet unterstützt beim Erlernen der wichtigsten Erkrankungsbilder. Lerninhalte werden reproduzierbar und auf für alle Lernenden standardisierte Weise zur Verfügung gestellt. Die Fertigkeiten der direkten Ophthalmoskopie sind hierbei deutlich schneller als die der indirekten Ophthalmoskopie zu erlernen.
Aim: Radioiodine therapy (RIT) may trigger the development of Graves’ ophthalmopathy (GO) or exacerbate pre-existing subclinical GO. Therefore, glucocorticoid administration is recommended for patients with pre-existing GO. Aim of this study was to analyze the influence of glucocorticoid therapy with methylprednisolone on intratherapeutic effective half-life (EHL) of radioiodine-131 in patients with Graves’ disease (GD) as recent studies showed an effect for prednisolone.
Methods: In a retrospective study, 264 patients with GD who underwent RIT without any additional antithyroid medication were evaluated. Intrathyroidal EHL was determined pre- and intratherapeutically. Patients with co-existing GO (n = 43) received methylprednisolone according to a fixed scheme starting 1 day prior to RIT, patients without GO (n = 221) did not receive any protective glucocorticoid medication. The ratios of EHL during RIT and during radioiodine uptake test (RIUT) were compared.
Results: Patients receiving methylprednisolone showed a slight decrease of the mean EHL from 5.63 d (RIUT) to 5.39 d (RIT) (p > 0.05). A comparable result was obtained in patients without glucocorticoids (5.71 d (RIUT) to 5.47 d (RIT); p > 0.05). The ratios of the EHL between RIT and RIUT failed to show a significant difference between the two groups. EHL is therefore not significantly influenced by an additional protective treatment with methylprednisolone.
Conclusions: In the present study a decreased intrathyroidal EHL under glucocorticoid medication with methylprednisolone could not be detected. Therefore, co-medication with methylprednisolone in patients with GO may be preferred to avoid an intratherapeutic decrease of EHL by accompanying protective glucocorticoides.
Background: Low anterior resection (LAR) is often performed with diverting loop ileostomy (DLI) for anastomotic protection in patients with rectal cancer. We aim to analyze, if older patients are more prone to a decline in kidney function following creation and closure of DLI after LAR for rectal carcinoma versus younger patients.
Methods: A retrospective cohort study from a database including 151 patients undergoing LAR for rectal carcinoma with DLI was used. Patients were divided in two age groups (Group A: <65 years, n = 79; Group B: ≥65 years, n = 72). For 123 patients undergoing DLI reversal prognostic factors for an impairment of serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) 3 months after DLI reversal was analyzed using a multivariate linear regression analysis.
Results: SCr before LAR(T0) was significant higher in Group B (P = 0.04). Accordingly, the eGFR at T0 in group B was significantly lower (P < 0.001). No patients need to undergo hemodialysis after LAR or DLI reversal.
Age and SCr at T0were able to statistically significant predict an increase in SCr (P<0.001) and eGFR (P=0.001) three months after DLI reversal (The R2 for the overall model was .82 (adjusted R2 = .68).
Conclusion: DLI creation may result in a reduction of eGFR in older patients 3 months after DLI closure. Apart from this, patients do not have a higher morbidity after creation and closure of DLI resulting from LAR regardless of their age.
Mental imagery is a transdiagnostic feature that has been increasingly researched in mental disorders in the past years. This study is the first to investigate mental imagery in individuals suffering from Prolonged Grief Disorder (PGD), a new disorder which will be included into the new edition of the International Classification of Diseases and Related Health Problems (ICD-11).
Our objective was to find out to what extent patients suffering from PGD differ from healthy, but equally bereaved, controls in terms of mental imagery, and how mental imagery is related to psychopathology. Patients with PGD and matched bereaved healthy controls (n = 54) completed a mental imagery questionnaire specifically designed for the study, and other established measures of psychopathology. Patients suffering from PGD reported mental images more frequently, had less control over them, and described negative images as more vivid than did healthy controls. Also, in reaction to mental images, patients less frequently experienced joy, but more often grief, anger and guilt. Besides these group differences, significant correlations between mental imagery other psychopathological measures could be found. Mental imagery is clearly related to PGD. The underlying mechanisms on whether it is a developing or maintaining factor need to be addressed in future studies. Future research should also investigate in what way mental imagery might be used in therapeutic approaches.
Tail-correlation matrices are an important tool for aggregating risk measurements across risk categories, asset classes and/or business segments. This paper demonstrates that traditional tail-correlation matrices—which are conventionally assumed to have ones on the diagonal—can lead to substantial biases of the aggregate risk measurement’s sensitivities with respect to risk exposures. Due to these biases, decision-makers receive an odd view of the effects of portfolio changes and may be unable to identify the optimal portfolio from a risk-return perspective. To overcome these issues, we introduce the “sensitivity-implied tail-correlation matrix”. The proposed tail-correlation matrix allows for a simple deterministic risk aggregation approach which reasonably approximates the true aggregate risk measurement according to the complete multivariate risk distribution. Numerical examples demonstrate that our approach is a better basis for portfolio optimization than the Value-at-Risk implied tail-correlation matrix, especially if the calibration portfolio (or current portfolio) deviates from the optimal portfolio.
Experimental and theoretical studies of fluctuations in nucleus-nucleus interactions at high energies have started to play a major role in understanding of the concept of strong interactions. The elaborated procedures have been developed to disentangle different processes happening during nucleus-nucleus collisions. The fluctuations caused by a variation of the number of nucleons which participated in a collision are frequently considered the unwanted one. The methods to reduce the impact of these fluctuations in fixed-target experiments are reviewed and tested. They can be of key importance in the following ongoing fixed-target heavy-ion experiments: NA61/SHINE at the CERN SPS, STAR-FXT at the BNL RHIC, BMN at JINR Nuclotron, HADES at the GSI SIS18 and in future experiments such as NA60+ at the CERN SPS, CBM at the FAIR SIS100, JHITS at J-PARC-HI MR.
We empirically examine how systemic risk in the banking sector leads to correlated risk in office markets of global financial centers. In so doing, we compute an aggregated measure of systemic risk in financial centers as the cumulated expected capital shortfall of local financial institutions. Our identification strategy is based on a double counterfactual approach by comparing normal with financial distress periods as well as office with retail markets. We find that office market interconnectedness arises from systemic risk during financial turmoil periods. Office market performance in a financial center is affected by returns of systemically linked financial center office markets only during a systemic banking crisis. In contrast, there is no evidence of correlated risk during normal times and among the within-city counterfactual retail sector. The decline in office market returns during a banking crisis is larger in financial centers compared to non-financial centers.
CDK4/6 inhibitors have an established role in the treatment of hormone receptor positive HER2-negative advanced breast cancer. All studies conducted in metastatic breast cancer showed a benefit in delaying progression when added to standard endocrine therapy, regardless of therapy line, pretreatment, menopausal status, site of metastasis, CDK4/6 inhibitor used and associated endocrine therapy. A benefit in overall survival has also been demonstrated. In early breast cancer, only the MonarchE study has shown an improved invasive disease-free survival with abemaciclib taken for 2 years, whereas the Penelope-B did not meet the primary endpoint and the PALLAS study was terminated early for futility. Studies conducted in the neoadjuvant setting might help to explain the discordant results.
In this article, I question the use of the notion of ‘constituent power’ as a tool for the democratization of the European Union (EU). Rather than seeing the absence of a transnational constituent power as a cause of the EU’s ‘democratic deficit’, I identify it as an opportunity for unfettered democratic participation. Against the reification of power-in-action into a power-constituted-in-law, I argue that the democratization of the EU can only be achieved through the multiplication of ‘constituent moments’. I begin by deconstructing the normative justifications surrounding the concept of constituent power. Here I analyze the structural aporia of constituent power and question the autonomous and emancipatory dimension of this notion. I then test the theoretical hypothesis of this structural aporia of the popular constituent power by comparing it with the historical experiments of a European popular constituent power. Finally, based on these theoretical and empirical observations, I propose to replace the ambivalence of the concept of popular constituent power with a more cautious approach to the bottom-up democratization of European integration: that of a multiplication of transnational constituent moments.
A vast range of our everyday experiences seem to involve an immediate consciousness of value. We hear the rudeness of someone making offensive comments. In seeing someone risking her life to save another, we recognize her bravery. When we witness a person shouting at an innocent child, we feel the unfairness of this action. If, in learning of a close friend’s success, envy arises in us, we experience our own emotional response as wrong. How are these values apprehended? The three most common answers provided by contemporary philosophy explain the consciousness of value in terms of judgment, emotion, or perception. An alternative view endorsed mainly by authors inspired by the phenomenological tradition argues that values are apprehended by an intentional feeling. In this model, it is by virtue of a feeling that objects are presented as being in different degrees and nuances fair or unfair, boring or funny, good or bad. This paper offers an account of this model of feeling and its basic features, and defends it over alternative models. To this end, the paper discusses different versions of the model circulating in current research which until now have developed in parallel rather than in mutual exchange. The paper also applies the proposed account to the moral domain and examines how a feeling of values is presupposed by several moral experiences.
Having a gatekeeper position in a collaborative network offers firms great potential to gain competitive advantages. However, it is not well understood what kind of collaborations are associated with such a position. Conceptually grounded in social network theory, this study draws on the resource-based view and the relational factors view to investigate which types of collaboration characterize firms that are in a gatekeeper position, which ultimately could improve firm performance in subsequent periods. The empirical analysis utilizes a unique longitudinal data set to examine dynamic network formation. We used a data crawling approach to reconstruct collaboration networks among the 500 largest companies in Germany over nine years and matched these networks with performance data. The results indicate that firms in gatekeeper positions often engage in medium-intensity collaborations and less likely weak-intensity collaborations. Strong-intensity collaborations are not related to the likelihood of being a gatekeeper. Our study further reveals that a firm's knowledge base is an important moderator and that this knowledge base can increase the benefits of having a gatekeeper position in terms of firm performance.
Introduction: Arachidonoyl ethanolamide (AEA) and 2-arachidonoyl glycerol (2-AG) are central lipid mediators of the endocannabinoid system. They are highly relevant due to their involvement in a wide variety of inflammatory, metabolic or malign diseases. Further elucidation of their modes of action and use as biomarkers in an easily accessible matrix, like blood, is restricted by their susceptibility to deviations during blood sampling and physiological co-dependences, which results in high variability of reported concentrations in low ng/mL ranges.
Objectives: The objective of this review is the identification of critical parameters during the pre-analytical phase and proposal of minimum requirements for reliable determination of endocannabinoids (ECs) in blood samples.
Methods: Reported physiological processes influencing the EC concentrations were put into context with published pre-analytical research and stability data from bioanalytical method validation.
Results: The cause for variability in EC concentrations is versatile. In part, they are caused by inter-individual factors like sex, metabolic status and/or diurnal changes. Nevertheless, enzymatic activity in freshly drawn blood samples is the main reason for changing concentrations of AEA and 2-AG, besides additional non-enzymatic isomerization of the latter.
Conclusion: Blood samples for EC analyses require immediate processing at low temperatures (>0 °C) to maintain sample integrity. Standardization of the respective blood tube or anti-coagulant, sampling time point, applied centrifugal force and complete processing time can further decrease variability caused by sample handling. Nevertheless, extensive characterization of study participants is needed to reduce distortion of clinical data caused by co-variables and facilitate research on the endocannabinoid system.
Objectives: We explore the importance of SARS-CoV-2 sentinel surveillance testing in primary care during a regional COVID-19 outbreak in Austria.
Design: Prospective cohort study.
Setting: A single sentinel practice serving 22 829 people in the ski-resort of Schladming-Dachstein.
Participants: All 73 patients presenting with mild-to-moderate flu-like symptoms between 24 February and 03 April, 2020.
Intervention: Nasopharyngeal sampling to detect SARS-CoV-2 using real-time reverse transcriptase-quantitative PCR (RT-qPCR).
Outcome measures: We compared RT-qPCR at presentation with confirmed antibody status. We split the outbreak in two parts, by halving the period from the first to the last case, to characterise three cohorts of patients with confirmed infection: early acute (RT-qPCR reactive) in the first half; and late acute (reactive) and late convalescent (non-reactive) in the second half. For each cohort, we report the number of cases detected, the accuracy of RT-qPCR, the duration and variety of symptoms, and the number of viral clades present.
Results: Twenty-two patients were diagnosed with COVID-19 (eight early acute, seven late acute and seven late convalescent), 44 patients tested SARS-CoV-2 negative and 7 were excluded. The sensitivity of RT-qPCR was 100% among all acute cases, dropping to 68.1% when including convalescent. Test specificity was 100%. Mean duration of symptoms for each group were 2 days (range 1–4) among early acute, 4.4 days (1–7) among late acute and 8 days (2–12) among late convalescent. Confirmed infection was associated with loss of taste. Acute infection was associated with loss of taste, nausea/vomiting, breathlessness, sore throat and myalgia; but not anosmia, fever or cough. Transmission clusters of three viral clades (G, GR and L) were identified.
Conclusions: RT-qPCR testing in primary care can rapidly and accurately detect SARS-CoV-2 among people with flu-like illness in a heterogeneous viral outbreak. Targeted testing in primary care can support national sentinel surveillance of COVID-19.
Several past summer floods in Central Europe were associated with so-called Vb‑cyclones propagating from the Mediterranean Sea north-eastward to Central Europe. This study illustrates the usefulness of the parametric transfer entropy measure TE‑linear in investigating heavy Vb‑cyclone precipitation events in the Odra catchment (Poland). With the application of the TE‑linear approach, we confirm the impact of the Mediterranean Sea on precipitation intensification. Moreover, we also detect significant information exchange to Vb‑cyclone precipitation from evaporation over the European continent along the typical Vb‑cyclone pathway. Thus, the Mediterranean Sea could enhance the Vb‑cyclone precipitation by pre-moistening continental moisture source regions that contribute to precipitation downstream in the investigated catchments. Overall, the transfer entropy approach with the measure TE‑linear proved to be computationally effective and complementary to traditional methods such as Lagrangian and Eulerian diagnostics.
Background: The elderly population deals with multimorbidity (three chronic conditions) and increasinged drug use with age. A comprehensive characterisation of the medication – including prescription and over-the-counter (OTC) drugs – of elderly patients in primary care is still insufficient.
Objectives: This study aims to characterise the medication (prescription and OTC) of multimorbid elderly patients in primary care and living at home by identifying drug patterns to evaluate the relationship between drugs and drug groups and reveal associations with recently published multimorbidity clusters of the same cohort.
Methods: MultiCare was a multicentre, prospective, observational cohort study of 3189 multimorbid patients aged 65 to 85 years in primary care in Germany. Patients and general practitioners were interviewed between 2008 and 2009. Drug patterns were identified using exploratory factor analysis. The relations between the drug patterns with the three multimorbidity clusters were analysed with Spearman-Rank-Correlation.
Results: Patients (59.3% female) used in mean 7.7 drugs; in total 24,535 drugs (23.7% OTC) were detected. Five drug patterns for men (drugs for obstructive pulmonary diseases (D-OPD), drugs for coronary heart diseases and hypertension (D-CHD), drugs for osteoporosis (D-Osteo), drugs for heart failure and drugs for pain) and four drug patterns for women (D-Osteo, D-CHD, D-OPD and drugs for diuretics and gout) were detected. Significant associations between multimorbidity clusters and drug patterns were detectable (D-CHD and CMD: male: ρ = 0.376, CI 0.322–0.430; female: ρ = 0.301, CI 0.624–0.340).
Conclusion: The drug patterns demonstrate non-random relations in drug use in multimorbid elderly patients and systematic associations between drug patterns and multimorbidity clusters were found in primary care.
Objectives The aims of our study were to examine the anticholinergic drug use and to assess the association between anticholinergic burden and cognitive function in the multimorbid elderly patients of the MultiCare cohort.
Setting MultiCare was conducted as a longitudinal cohort study in primary care, located in eight different study centres in Germany.
Participants 3189 patients (59.3% female).
Primary and secondary outcome measures Baseline data were used for the following analyses. Drugs were classified according to the well-established anticholinergic drug scale (ADS) and the recently published German anticholinergic burden (German ACB). Cognitive function was measured using a letter digit substitution test (LDST) and a mixed-effect multivariate linear regression was performed to calculate the influence of anticholinergic burden on the cognitive function.
Results Patients used 1764 anticholinergic drugs according to ADS and 2750 anticholinergics according to the German ACB score (prevalence 38.4% and 53.7%, respectively). The mean ADS score was 0.8 (±1.3), and the mean German ACB score was 1.2 (±1.6) per patient. The most common ADS anticholinergic was furosemide (5.8%) and the most common ACB anticholinergic was metformin (13.7%). The majority of the identified anticholinergics were drugs with low anticholinergic potential: 80.2% (ADS) and 73.4% (ACB), respectively. An increasing ADS and German ACB score was associated with reduced cognitive function according to the LDST (−0.26; p=0.008 and −0.24; p=0.003, respectively).
Conclusion Multimorbid elderly patients are in a high risk for using anticholinergic drugs according to ADS and German ACB score. We especially need to gain greater awareness for the contribution of drugs with low anticholinergic potential from the cardiovascular system. As anticholinergic drug use is associated with reduced cognitive function in multimorbid elderly patients, the importance of rational prescribing and also deprescribing needs to be further evaluated.
Trial registration number ISRCTN89818205.
Supported by the German Alliance Against Depression, 82 regions in Germany launched their own community-based multi-level intervention programs targeting both depression and suicidal behavior prior to January 2016. Sixteen of these regions have implemented the full 4-level intervention program comprising 1) training of General Practitioners, 2) a public awareness campaign, 3) training of community facilitators and 4) support for depressed patients and their relatives for at least three years. The aim of the study was to examine possible suicide prevention effects in these sixteen 4-level intervention regions (comprising a population of 6,976,309) by 1) comparing the annual suicide rates during the 3-year intervention period to a 10-year baseline and 2) comparing these differences to corresponding trends in Germany after excluding all intervention regions (Germany-IR). Primary outcome was the annual rate of suicides. Analyses included negative binomial regression models. When examining differences between suicide rates during the intervention period compared to the baseline period, only a trend towards a significant reduction was found. This reduction of suicides in the sixteen 4-level intervention regions did not differ from that in Germany-IR as control. The interpretation of these findings has to take into account that the training of General Practitioners, police and other community facilitators might have improved the recognition of suicides, thus increasing detection rates. Furthermore, destigmatizing effects of the public awareness campaigns might have increased the number of suicides by lowering suicide threshold (“normalization”) for those at risk and by decreasing the rate of suicides deliberately hidden by suicide victims or their relatives.
The infrastructure for parking and parked cars themselves (e.g., parked cars blocking bike lanes and sidewalks or the visibility range) can lead to conflicts for pedestrians and cyclists. The perception of conflicts could discourage walking and cycling in neighborhoods and undermine municipalities’ efforts to provide more sustainable urban mobility. The aim of this study was therefore to analyze the effect of on-street car parking in urban neighborhoods on perceived parking and traffic-related conflicts. In addition, it examines in what way the intention to reduce one’s car use influences the perception of the conflicts (Stage Model of Self-Regulated Behavior Change (SSBC)). A household survey was conducted in the inner-city neighborhood of Frankfurt-Bornheim, Germany (N=1027). The residents most often observed the conflicts in which parked cars impeded walking and cycling as well as situations in which pedestrians felt threatened by cyclists biking on the sidewalk. Results from multiple linear regression models revealed that the influencing factors for the perception of conflicts were the use of different means of transportation and the intention to change one’s behavior (SSBC model) to reduce car use rather than car ownership. In addition, a resident’s age and household structure seemed to affect awareness of conflicts in which pedestrians and cyclists were involved. The results suggest a group-serving bias, meaning that the residents mostly observed those conflicts that they did not cause. A separate infrastructure for pedestrians and cyclists could help prevent most of the conflicts described in this study.
Monoacylglycerol lipase (MGL) expressed in cancer cells influences cancer pathogenesis but the role of MGL in the tumor microenvironment (TME) is less known. Using a syngeneic tumor model with KP cells (KrasLSL-G12D/p53fl/fl; from mouse lung adenocarcinoma), we investigated whether TME-expressed MGL plays a role in tumor growth of non-small cell lung cancer (NSCLC).
In sections of human and experimental NSCLC, MGL was found in tumor cells and various cells of the TME including macrophages and stromal cells. Mice treated with the MGL inhibitor JZL184 as well as MGL knock-out (KO) mice exhibited a lower tumor burden than the controls. The reduction in tumor growth was accompanied by an increased number of CD8+ T cells and eosinophils. Naïve CD8+ T cells showed a shift toward more effector cells in MGL KOs and an increased expression of granzyme-B and interferon-γ, indicative of enhanced tumoricidal activity. 2-arachidonoyl glycerol (2-AG) was increased in tumors of MGL KO mice, and dose-dependently induced differentiation and migration of CD8+ T cells as well as migration and activation of eosinophils in vitro.
Our results suggest that next to cancer cell-derived MGL, TME cells expressing MGL are responsible for maintaining a pro-tumorigenic environment in tumors of NSCLC.
We review the properties of the strongly interacting quark-gluon plasma (QGP) at finite temperature T and baryon chemical potential µB as created in heavy-ion collisions at ultrarelativistic energies. The description of the strongly interacting (non-perturbative) QGP in equilibrium is based on the effective propagators and couplings from the Dynamical QuasiParticle Model (DQPM) that is matched to reproduce the equation-of-state of the partonic system above the deconfinement temperature Tc from lattice QCD. Based on a microscopic transport description of heavy-ion collisions, we discuss which observables are sensitive to the QGP creation and its properties.
A deep convolutional neural network (CNN) is developed to study symmetry energy (Esym(ρ)) effects by learning the mapping between the symmetry energy and the two-dimensional (transverse momentum and rapidity) distributions of protons and neutrons in heavy-ion collisions. Supervised training is performed with labeled data-set from the ultrarelativistic quantum molecular dynamics (UrQMD) model simulation. It is found that, by using proton spectra on event-by-event basis as input, the accuracy for classifying the soft and stiff Esym(ρ) is about 60% due to large event-by-event fluctuations, while by setting event-summed proton spectra as input, the classification accuracy increases to 98%. The accuracies for 5-label (5 different Esym(ρ)) classification task are about 58% and 72% by using proton and neutron spectra, respectively. For the regression task, the mean absolute errors (MAE) which measure the average magnitude of the absolute differences between the predicted and actual L (the slope parameter of Esym(ρ)) are about 20.4 and 14.8 MeV by using proton and neutron spectra, respectively. Fingerprints of the density-dependent nuclear symmetry energy on the transverse momentum and rapidity distributions of protons and neutrons can be identified by convolutional neural network algorithm.
Adaptive threshold estimation procedures sample close to a subject’s perceptual threshold by dynamically adapting the stimulation based on the subject’s performance. Yet, perceptual thresholds not only depend on the observers’ sensory capabilities but also on any bias in terms of their expectations and response preferences, thus distorting the precision of the threshold estimates. Using the framework of signal detection theory (SDT), independent estimates of both, an observer’s sensitivity and internal processing bias can be delineated from threshold estimates. While this approach is commonly available for estimation procedures engaging the method of constant stimuli (MCS), correction procedures for adaptive methods (AM) are only scarcely applied. In this article, we introduce a new AM that takes individual biases into account, and that allows for a bias-corrected assessment of subjects’ sensitivity. This novel AM is validated with simulations and compared to a typical MCS-procedure, for which the implementation of bias correction has been previously demonstrated.
Comparing AM and MCS demonstrates the viability of the presented AM. Besides its feasibility, the results of the simulation reveal both, advantages, and limitations of the proposed AM. The procedure has considerable practical implications, in particular for the design of shaping procedures in sensory training experiments, in which task difficulty has to be constantly adapted to an observer’s performance, to improve training efficiency.
Thermoanaerobacter kivui is a thermophilic acetogen that can grow on carbon monoxide as sole carbon and energy source. To identify the gene(s) involved in CO oxidation, the genome sequence was analyzed. Two genes potentially encoding CO dehydrogenases were identified. One, cooS, potentially encodes a monofunctional CO dehydrogenase, whereas another, acsA, potentially encodes the CODH component of the CODH/ACS complex. Both genes were cloned, a His-tag encoding sequence was added, and the proteins were produced from a plasmid in T. kivui. His-AcsA copurified by affinity chromatography with AcsB, the acetyl-CoA synthase of the CO dehydrogenase/acetyl CoA synthase complex. His-CooS copurified with CooF1, a small iron-sulfur center containing protein likely involved in electron transport. Both protein complexes had CO:ferredoxin oxidoreductase as well as CO:methyl viologen oxidoreductase activity, but the activity of CooSF1 was 15-times and 231-times lower, respectively. To underline the importance of CooS, the gene was deleted in the CO-adapted strain. Interestingly, the ∆cooS deletion mutant did not grow on CO anymore. These experiments clearly demonstrated that CooS is essential for growth of T. kivui on CO. This is in line with the hypothesis that CooS is the CO-oxidizing enzyme in cells growing on CO.
Neuroligin-3 (Nlgn3), a neuronal adhesion protein implicated in autism spectrum disorder (ASD), is expressed at excitatory and inhibitory postsynapses and hence may regulate neuronal excitation/inhibition balance. To test this hypothesis, we recorded field excitatory postsynaptic potentials (fEPSPs) in the dentate gyrus of Nlgn3 knockout (KO) and wild-type mice. Synaptic transmission evoked by perforant path stimulation was reduced in KO mice, but coupling of the fEPSP to the population spike was increased, suggesting a compensatory change in granule cell excitability. These findings closely resemble those in neuroligin-1 (Nlgn1) KO mice and could be partially explained by the reduction in Nlgn1 levels we observed in hippocampal synaptosomes from Nlgn3 KO mice. However, unlike Nlgn1, Nlgn3 is not necessary for long-term potentiation. We conclude that while Nlgn1 and Nlgn3 have distinct functions, both are required for intact synaptic transmission in the mouse dentate gyrus. Our results indicate that interactions between neuroligins may play an important role in regulating synaptic transmission and that ASD-related neuroligin mutations may also affect the synaptic availability of other neuroligins.
Research on collective resilience processes still lacks a detailed understanding of psychological mechanisms at work when groups cope with adverse conditions, i.e., long-term processes, and how such mechanisms affect physical and mental well-being. As collective resilience will play a crucial part in facing looming climate change-related events such as floods, it is important to investigate these processes further. To this end, this study takes a novel holistic approach by combining resilience research, social psychology, and an archeological perspective to investigate the role of social identity as a collective resilience factor in the past and present. We hypothesize that social identification buffers against the negative effects of environmental threats in participants, which increases somatic symptoms related to stress, in a North Sea region historically prone to floods. A cross-sectional study (N = 182) was conducted to analyze the moderating effects of social identification on the relations between perceived threat of North Sea floods and both well-being and life satisfaction. The results support our hypothesis that social identification attenuates the relationship between threat perception and well-being, such that the relation is weaker for more strongly identified individuals. Contrary to our expectations, we did not find this buffering effect to be present for life satisfaction. Future resilience studies should further explore social identity as a resilience factor and how it operates in reducing environmental stress put on individuals and groups. Further, to help communities living in flood-prone areas better cope with future environmental stress, we recommend implementing interventions strengthening their social identities and hence collective resilience.
Intention attribution in children and adolescents with autism spectrum disorder: an EEG study
(2021)
The ability to infer intentions from observed behavior and predict actions based on this inference, known as intention attribution (IA), has been hypothesized to be impaired in individuals with autism spectrum disorder (ASD). The underlying neural processes, however, have not been conclusively determined. The aim of this study was to examine the neural signature of IA in children and adolescents with ASD, and to elucidate potential links to contextual updating processes using electroencephalography. Results did not indicate that IA or early contextual updating was impaired in ASD. However, there was evidence of aberrant processing of expectation violations in ASD, particularly if the expectation was based on IA. Results are discussed within the context of impaired predictive coding in ASD.
First crystal structure of a Pigment Red 52 compound: DMSO solvate hydrate of the monosodium salt
(2021)
Pigment Red 52, Na2[C18H11ClN2O6S], is an industrially produced hydrazone-laked pigment. It serves as an intermediate in the synthesis of the corresponding Ca2+ and Mn2+ salts, which are used commercially for printing inks and lacquers. Hitherto, no crystal structure of any salt of Pigment Red 52 is known. Now, single crystals have been obtained of a dimethyl sulfoxide solvate hydrate of the monosodium salt of Pigment Red 52, namely, monosodium 2-[2-(3-carboxy-2-oxo-1,2-dihydronaphthalen-1-ylidene)hydrazin-1-yl]-5-chloro-4-methylbenzenesulfonate dimethyl sulfoxide monosolvate monohydrate, Na+·C18H12ClN2O6S−·H2O·C2H6OS, obtained from in-house synthesized Pigment Red 52. The crystal structure was determined by single-crystal X-ray diffraction at 173 K. In this monosodium salt, the SO3− group is deprotonated, whereas the COOH group is protonated. The residues form chains via ionic interactions and hydrogen bonds. The chains are arranged in polar/non-polar double layers.
Fossil records of early solar irradiation and cosmolocation of the CAI factory: a reappraisal
(2021)
Calcium-aluminum–rich inclusions (CAIs) in meteorites carry crucial information about the environmental conditions of the nascent Solar System prior to planet formation. Based on models of 50V–10Be co-production by in-situ irradiation, CAIs are considered to have formed within ~0.1 AU from the proto-Sun. Here, we present vanadium (V) and strontium (Sr) isotopic co-variations in fine- and coarse-grained CAIs and demonstrate that kinetic isotope effects during partial condensation and evaporation best explain V isotope anomalies previously attributed to solar particle irradiation. We also report initial excesses of 10Be and argue that CV CAIs possess essentially a homogeneous level of 10Be, inherited during their formation. Based on numerical modeling of 50V–10Be co-production by irradiation, we show that CAI formation during protoplanetary disk build-up likely occurred at greater heliocentric distances than previously considered, up to planet-forming regions (~1AU), where solar particle fluxes were sufficiently low to avoid substantial in-situ irradiation of CAIs.
Bisphenols and phthalates, chemicals frequently used in plastic products, promote obesity in cell and animal models. However, these well-known metabolism disrupting chemicals (MDCs) represent only a minute fraction of all compounds found in plastics. To gain a comprehensive understanding of plastics as a source of exposure to MDCs, we characterized all chemicals present in 34 everyday products using nontarget high-resolution mass spectrometry and analyzed their joint adipogenic activities by high-content imaging. We detected 55,300 chemical features and tentatively identified 629 unique compounds, including 11 known MDCs. Importantly, chemicals that induced proliferation, growth, and triglyceride accumulation in 3T3-L1 adipocytes were found in one third of the products. Since the majority did not target peroxisome proliferator-activated receptor γ, the effects are likely to be caused by unknown MDCs. Our study demonstrates that daily-use plastics contain potent mixtures of MDCs and can, therefore, be a relevant yet underestimated environmental factor contributing to obesity.
Teaser Plastics contain a potent mixture of chemicals promoting adipogenesis, a key process in developing obesity.
Recently, a 15-valent (PCV15) and a 20-valent pneumococcal conjugate vaccine (PCV20) have been licensed by the US Food and Drug Administration and are under evaluation by the European Medicines Agency. PCV15 contains all serotypes of the 13-valent conjugate vaccine (PCV13) plus serotype 22F and 33F and PCV20 includes PCV13 serotypes plus serotypes 8, 10A, 11A, 12F, 15B, 22F, 33F. We investigated pneumococcal serotype distribution, secular trends and proportion of pneumonia caused by serotypes included in PCV13, PCV15, PCV20, and the 23-valent pneumococcal polysaccharide vaccine (PPV23) among adult patients with all-cause community-acquired pneumonia (CAP) between 2013 and 2019. We applied logistic mixed regression modelling to assess annual trends. Urine samples from adult patients with CAP treated in the community or hospital in Germany and included in the CAPNETZ study, a prospective multi-centre cohort study, were analysed by two serotype-specific multiplex urinary antigen detection assays (UAD1/UAD2) at Pfizer’s Vaccines Research and Development Laboratory. UAD1 detects serotypes in PCV13, UAD2 detects additional serotypes in PCV20 plus serotypes 2, 9N, 17F and 20. Out of 1,831 patients screened, urine samples with a valid UAD test result were available for 1,343 patients (73.3%). Among those patients, 829 patients (61.7%) were male, 792 patients (59.0%) were aged ≥60 years, 1038 patients (77.3%) had at least one comorbidity and 1,204 patients (89.7%) were treated in the hospital. The overall proportion of vaccine-type pneumonia among all-cause CAP for PCV13, PCV15, PCV20 and PPV23 was 7.7% (n=103), 9.1% (n=122), 12.3% (n=165) and 13.3% (n=178). Over the entire observation period, we did not observe evidence for significant annual trends in pneumococcal vaccine serotype coverage against pneumonia in adults (PCV13: OR 0.94, 95% CI 0.83-1.05; PCV15: OR 0.93, 95% CI 0.84-1.03; PCV20: OR 0.95, 95% CI 0.86-1.04; PPV23: OR 0.99, 95% CI 0.90-1.08). In conclusion, our data show that i) the infant vaccination program of PCV13, which started in Germany 2010 did not result in a relevant and sustained decrease of PCV13 serotypes in pneumonia in adults and ii) that the gap in the coverage between PCV20 and PPV23 was small and did not increase over the entire observation time.
Recently, a 15-valent (PCV15) and a 20-valent pneumococcal conjugate vaccine (PCV20) have been licensed by the US Food and Drug Administration and are under evaluation by the European Medicines Agency. PCV15 contains all serotypes of the 13-valent conjugate vaccine (PCV13) plus serotype 22F and 33F and PCV20 includes PCV13 serotypes plus serotypes 8, 10A, 11A, 12F, 15B, 22F, 33F. We investigated pneumococcal serotype distribution, secular trends and proportion of pneumonia caused by serotypes included in PCV13, PCV15, PCV20, and the 23-valent pneumococcal polysaccharide vaccine (PPV23) among adult patients with all-cause community-acquired pneumonia (CAP) between 2013 and 2019. We applied logistic mixed regression modelling to assess annual trends. Urine samples from adult patients with CAP treated in the community or hospital in Germany and included in the CAPNETZ study, a prospective multi-centre cohort study, were analysed by two serotype-specific multiplex urinary antigen detection assays (UAD1/UAD2) at Pfizer’s Vaccines Research and Development Laboratory. UAD1 detects serotypes in PCV13, UAD2 detects additional serotypes in PCV20 plus serotypes 2, 9N, 17F and 20. Out of 1,831 patients screened, urine samples with a valid UAD test result were available for 1,343 patients (73.3%). Among those patients, 829 patients (61.7%) were male, 792 patients (59.0%) were aged ≥60 years, 1038 patients (77.3%) had at least one comorbidity and 1,204 patients (89.7%) were treated in the hospital. The overall proportion of vaccine-type pneumonia among all-cause CAP for PCV13, PCV15, PCV20 and PPV23 was 7.7% (n=103), 9.1% (n=122), 12.3% (n=165) and 13.3% (n=178). Over the entire observation period, we did not observe evidence for significant annual trends in pneumococcal vaccine serotype coverage against pneumonia in adults (PCV13: OR 0.94, 95% CI 0.83-1.05; PCV15: OR 0.93, 95% CI 0.84-1.03; PCV20: OR 0.95, 95% CI 0.86-1.04; PPV23: OR 0.99, 95% CI 0.90-1.08). In conclusion, our data show i) no decline of PCV13 serotypes in all-cause CAP between 2013-2019 mainly due to a persistently high proportion of serotype 3 suggesting no meaningful effect of childhood PCV13 vaccination on PCV13 coverage in pneumonia in adults during this time period and ii) that the gap in the coverage between PCV20 and PPV23 was small and did not increase over the entire observation time.
Background: School attendance during the COVID-19 pandemic is intensely debated.
Aim: In November 2020, we assessed SARS-CoV-2 infections and seroreactivity in 24 randomly selected school classes and connected households in Berlin, Germany.
Methods: We collected oro-nasopharyngeal swabs and blood samples, examining SARS-CoV-2 infection and IgG antibodies by RT-PCR and ELISA. Household members self-swabbed. We assessed individual and institutional prevention measures. Classes with SARS-CoV-2 infection and connected households were retested after 1 week.
Results: We examined 1,119 participants, including 177 primary and 175 secondary school students, 142 staff and 625 household members. SARS-CoV-2 infection occurred in eight classes, affecting each 1–2 individuals. Infection prevalence was 2.7% (95% confidence interval (CI): 1.2–5.0; 9/338), 1.4% (95% CI: 0.2–5.1; 2/140), and 2.3% (95% CI: 1.3–3.8; 14/611) among students, staff and household members. Six of nine infected students were asymptomatic at testing. We detected IgG antibodies in 2.0% (95%CI: 0.8–4.1; 7/347), 1.4% (95% CI: 0.2–5.0; 2/141) and 1.4% (95% CI: 0.6–2.7; 8/576). Prevalence increased with inconsistent facemask-use in school, walking to school, and case-contacts outside school. For three of nine households with infection(s), origin in school seemed possible. After 1 week, no school-related secondary infections appeared in affected classes; the attack rate in connected households was 1.1%.
Conclusion: School attendance under rigorously implemented preventive measures seems reasonable. Balancing risks and benefits of school closures need to consider possible spill-over infection into households. Deeper insight is required into the infection risks due to being a schoolchild vs attending school.
Background: School attendance during the SARS-CoV-2 pandemic is intensely debated. Modelling studies suggest that school closures contribute to community transmission reduction. However, data among school-attending students and staff are scarce. In November 2020, we examined SARS-CoV-2 infections and seroreactivity in 24 randomly selected school classes and connected households in Berlin, Germany.
Methods: Students and school staff were examined, oro-nasopharyngeal swabs and blood samples collected, and SARS-CoV-2 infection and IgG antibodies detected by RT-PCR and ELISA. Household members performed self-swabs. Individual and institutional infection prevention and control measures were assessed. Classes with SARS-CoV-2 infection and connected household members were re-tested after one week.
Findings: 1119 participants were examined, including 177 primary and 175 secondary school students, 142 staff, and 625 household members. Participants reported mainly cold symptoms (19·4%). SARS-CoV-2 infection occurred in eight of 24 classes affecting each 1-2 individuals. Infection prevalence was 2·7% (95%CI; 1·2-5·0%; 9/338), 1·4% (0·2-5·1%; 2/140), and 2·3% (1·3-3·8%; 14/611) among students, staff and household members, respectively, including quarantined persons. Six of nine infected students were asymptomatic. Prevalence increased with inconsistent facemask use in school, way to school on foot, and case-contacts outside school. IgG antibodies were detected in 2·0% (0·8-4·1%; 7/347), 1·4% (0·2-5·0%; 2/141) and 1·4% (0·6-2·7%; 8/576), respectively. For three of nine households with infection(s) detected at cross-sectional assessment, origin in school seemed possible. After one week, no school-related, secondary infections appeared in affected classes; the attack rate in connected households was 1·1%.
Interpretation: These data suggest that school attendance under preventive measures is feasible, provided their rigorous implementation. In balancing threats and benefits of open versus closed schools during the pandemic, parents and society need to consider possible spill-overs into their households. Deeper insight is needed into the infection risks due to being a schoolchild as compared to attending school.
Sound discrimination is essential in many species for communicating and foraging. Bats, for example, use sounds for echolocation and communication. In the bat auditory cortex there are neurons that process both sound categories, but how these neurons respond to acoustic transitions, that is, echolocation streams followed by a communication sound, remains unknown. Here, we show that the acoustic context, a leading sound sequence followed by a target sound, changes neuronal discriminability of echolocation versus communication calls in the cortex of awake bats of both sexes. Nonselective neurons that fire equally well to both echolocation and communication calls in the absence of context become category selective when leading context is present. On the contrary, neurons that prefer communication sounds in the absence of context turn into nonselective ones when context is added. The presence of context leads to an overall response suppression, but the strength of this suppression is stimulus specific. Suppression is strongest when context and target sounds belong to the same category, e.g.,echolocation followed by echolocation. A neuron model of stimulus-specific adaptation replicated our results in silico The model predicts selectivity to communication and echolocation sounds in the inputs arriving to the auditory cortex, as well as two forms of adaptation, presynaptic frequency-specific adaptation acting in cortical inputs and stimulus-unspecific postsynaptic adaptation. In addition, the model predicted that context effects can last up to 1.5 s after context offset and that synaptic inputs tuned to low-frequency sounds (communication signals) have the shortest decay constant of presynaptic adaptation.SIGNIFICANCE STATEMENT We studied cortical responses to isolated calls and call mixtures in awake bats and show that (1) two neuronal populations coexist in the bat cortex, including neurons that discriminate social from echolocation sounds well and neurons that are equally driven by these two ethologically different sound types; (2) acoustic context (i.e., other natural sounds preceding the target sound) affects natural sound selectivity in a manner that could not be predicted based on responses to isolated sounds; and (3) a computational model similar to those used for explaining stimulus-specific adaptation in rodents can account for the responses observed in the bat cortex to natural sounds. This model depends on segregated feedforward inputs, synaptic depression, and postsynaptic neuronal adaptation.
Background: The most recent overall survival (OS) and adverse event (AE) data have not been compared for the three guideline-recommended high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) treatment alternatives.
Methods: We performed a systematic review and network meta-analysis focusing on OS and AE according to the most recent apalutamide, enzalutamide, and darolutamide reports. We systematically examined and compared apalutamide vs. enzalutamide vs. darolutamide efficacy and toxicity, relative to ADT according to PRISMA. We relied on PubMed search for most recent reports addressing prospective randomized trials with proven predefined OS benefit, relative to ADT: SPARTAN, PROSPER, and ARAMIS. OS represented the primary outcome and AEs represented secondary outcomes.
Results: Overall, data originated from 4117 observations made within the three trials that were analyzed. Regarding OS benefit relative to ADT, darolutamide ranked first, followed by enzalutamide and apalutamide, in that order. In the subgroup of PSA-doubling time (PSA-DT) ≤ 6 months patients, enzalutamide ranked first, followed by darolutamide and apalutamide in that order. Conversely, in the subgroup of PSA-DT 6–10 months patients, darolutamide ranked first, followed by apalutamide and enzalutamide, in that order. Regarding grade 3+ AEs, darolutamide was most favorable, followed by enzalutamide and apalutamide, in that order.
Conclusion: The current network meta-analysis suggests the highest OS efficacy and lowest grade 3+ toxicity for darolutamide. However, in the PSA-DT ≤ 6 months subgroup, the highest efficacy was recorded for enzalutamide. It is noteworthy that study design, study population, and follow-up duration represent some of the potentially critical differences that distinguish between the three studies and remained statistically unaccounted for using the network meta-analysis methodology. Those differences should be strongly considered in the interpretation of the current and any network meta-analyses.
The deuteron coalescence parameter 𝐵2 in proton+proton and nucleus+nucleus collisions in the energy range of √s N N = 900–7000 GeV for proton + proton and √s N N = 2–2760 GeV for nucleus + nucleus collisions is analyzed with the Ultrarelativistic Quantum Molecular Dynamics (UrQMD) transport model, supplemented by an event-by-event phase space coalescence model for deuteron and anti-deuteron production. The results are compared to data by the E866, E877, PHENIX, STAR and ALICE experiments. The 𝐵2 values are calculated from the final spectra of protons and deuterons. At lower energies, √s N N ≤ 20 GeV, B2 drops drastically with increasing energy. The calculations confirm that this is due to the increasing freeze-out volume reflected in B2 ∼ 1/V . At higher energies, √s N N ≥ 20 GeV, B2 saturates at a constant level. This qualitative change and the vanishing of the volume suppression is shown to be due to the development of strong radial flow with increasing energy. The flow leads to strong space-momentum correlations which counteract the volume effect.