In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1 and TRPV1 induce inflammation and play a key role in the physiology of almost all organs. They may augment sensory or vagal nerve discharges to evoke pain and several symptoms of COVID-19, including cough, nasal obstruction, vomiting, diarrhea, and, at least partly, sudden and severe loss of smell and taste. TRPA1 can be activated by reactive oxygen species and may therefore be up-regulated in COVID-19. TRPA1 and TRPV1 channels can be activated by pungent compounds including many nuclear factor (erythroid-derived 2) (Nrf2)-interacting foods leading to channel desensitization. Interactions between Nrf2-associated nutrients and TRPA1/TRPV1 may be partly responsible for the severity of some of the COVID-19 symptoms. The regulation by Nrf2 of TRPA1/TRPV1 is still unclear, but suggested from very limited clinical evidence. In COVID-19, it is proposed that rapid desensitization of TRAP1/TRPV1 by some ingredients in foods could reduce symptom severity and provide new therapeutic strategies.View less
Introduction: Door-to-CT scan time (DCT) and door-to-needle time (DNT) are important process measures in acute ischemic stroke (AIS) patients undergoing intravenous thrombolysis (IVT). We examined the impact of a telemedical prenotification by emergency medical service (EMS) (called the “Stroke Angel” program) on DCT and DNT and IVT rate compared to standard of care.
Patients and Methods: Two prospective observational studies including AIS patients admitted via EMS from 2011 to 2013 (cohort I; n = 496) and from January 1, 2015 to May 31, 2018 (cohort II; n = 349) were conducted. After cohort I, the 4-Item Stroke Scale and a digital thrombolysis protocol were added. Multivariable logistic and linear regression analysis was performed.
Results: In cohort I, DCT was lower in the intervention group (13 vs. 26 min using standard of care; p < 0.001), but no significant difference in median DNT (35 vs. 39 min; p = 0.24) was observed. In cohort II, a reduction of DCT (8 vs. 15 min; p < 0.001) and DNT (25 vs. 29 min p = 0.003) was observed in the intervention group. Compared to standard of care, the likelihood of DCT ≤10 min or DNT ≤20 min in the intervention group was 2.7 (adjusted odds ratio [aOR] 2.7; 95% CI: 2.1–3.5) and 1.8 (aOR 1.8; 95% CI: 1.1–2.9), respectively. In cohort II, IVT rate was higher (aOR 1.4; 95% CI: 1.1–1.9) in the intervention group.
Conclusion: Although the positive effects of Stroke Angel in AIS provided a rationale for implementation in routine care, larger studies of practice implementation will be needed. Using Stroke Angel in the prehospital management of AIS impacts on important process measures of IVT delivery.View less
Background: Although transmission of pathogenic viruses through human tissue grafts is rare, it is still one of the most serious dreaded risks of transplantation. Therefore, in addition to the detailed medical and social history, a comprehensive serologic and molecular screening of the tissue donors for relevant viral markers for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) is necessary. In the case of reactive results in particular, clear decisions regarding follow-up testing and the criteria for tissue release must be made.
Methods: Based on the clinical relevance of the specific virus markers, the sensitivity of the serological and molecular biological methods used and the application of inactivation methods, algorithms for tissue release are suggested.
Results: Compliance with the preanalytical requirements and assessment of a possible hemodilution are mandatory requirements before testing the blood samples. While HIV testing follows defined algorithms, the procedures for HBV and HCV diagnostics are under discussion. Screening and decisions for HBV are often not as simple, e.g., due to cases of occult HBV infection, false-positive anti-HBc results, or early window period positive HBV NAT results. In the case of HCV diagnostics, modern therapies with direct-acting antivirals, which are often associated with successful treatment of the infection, should be included in the decision.
Conclusion: In HBV and HCV testing, a high-sensitivity virus genome test should play a central role in diagnostics, especially in the case of equivocal serology, and it should be the basis for the decision to release the tissue. The proposed test algorithms and decisions are also based on current European recommendations and standards for safety and quality assurance in tissue and cell banking.View less
Mechanical ventilation (MV) is an essential part of modern intensive care medicine. MV is performed in patients with severe respiratory failure caused by respiratory muscle insufficiency and/or lung parenchymal disease; that is, when other treatments such as medication, oxygen administration, secretion management, continuous positive airway pressure (CPAP), or nasal high-flow therapy have failed. MV is required for maintaining gas exchange and allows more time to curatively treat the underlying cause of respiratory failure. In the majority of ventilated patients, liberation or "weaning" from MV is routine, without the occurrence of any major problems. However, approximately 20% of patients require ongoing MV, despite amelioration of the conditions that precipitated the need for it in the first place. Approximately 40-50% of the time spent on MV is required to liberate the patient from the ventilator, a process called "weaning". In addition to acute respiratory failure, numerous factors can influence the duration and success rate of the weaning process; these include age, comorbidities, and conditions and complications acquired during the ICU stay. According to international consensus, "prolonged weaning" is defined as the weaning process in patients who have failed at least 3 weaning attempts, or require more than 7 days of weaning after the first spontaneous breathing trial (SBT). Given that prolonged weaning is a complex process, an interdisciplinary approach is essential for it to be successful. In specialised weaning centres, approximately 50% of patients with initial weaning failure can be liberated from MV after prolonged weaning. However, the heterogeneity of patients undergoing prolonged weaning precludes the direct comparison of individual centres. Patients with persistent weaning failure either die during the weaning process, or are discharged back to their home or to a long-term care facility with ongoing MV. Urged by the growing importance of prolonged weaning, this Sk2 Guideline was first published in 2014 as an initiative of the German Respiratory Society (DGP), in conjunction with other scientific societies involved in prolonged weaning. The emergence of new research, clinical study findings and registry data, as well as the accumulation of experience in daily practice, have made the revision of this guideline necessary. The following topics are dealt with in the present guideline: Definitions, epidemiology, weaning categories, underlying pathophysiology, prevention of prolonged weaning, treatment strategies in prolonged weaning, the weaning unit, discharge from hospital on MV, and recommendations for end-of-life decisions. Special emphasis was placed on the following themes: (1) A new classification of patient sub-groups in prolonged weaning. (2) Important aspects of pulmonary rehabilitation and neurorehabilitation in prolonged weaning. (3) Infrastructure and process organisation in the care of patients in prolonged weaning based on a continuous treatment concept. (4) Changes in therapeutic goals and communication with relatives. Aspects of paediatric weaning are addressed separately within individual chapters. The main aim of the revised guideline was to summarize both current evidence and expert-based knowledge on the topic of "prolonged weaning", and to use this information as a foundation for formulating recommendations related to "prolonged weaning", not only in acute medicine but also in the field of chronic intensive care medicine. The following professionals served as important addressees for this guideline: intensivists, pulmonary medicine specialists, anaesthesiologists, internists, cardiologists, surgeons, neurologists, paediatricians, geriatricians, palliative care clinicians, rehabilitation physicians, intensive/chronic care nurses, physiotherapists, respiratory therapists, speech therapists, medical service of health insurance, and associated ventilator manufacturers.View less
There are large country variations in COVID-19 death rates that may be partly explained by diet. Many countries with low COVID-19 death rates have a common feature of eating large quantities of fermented vegetables such as cabbage and, in some continents, various spices. Fermented vegetables and spices are agonists of the antioxidant transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and spices are transient receptor potential ankyrin 1 and vanillin 1 (TRPA1/V1) agonists. These mechanisms may explain many COVID-19 symptoms and severity. It appears that there is a synergy between Nrf2 and TRPA1/V1 foods that may explain the role of diet in COVID-19. One of the mechanisms of COVID-19 appears to be an oxygen species (ROS)-mediated process in synergy with TRP channels, modulated by Nrf2 pathways. Spicy foods are likely to desensitize TRP channels and act in synergy with exogenous antioxidants that activate the Nrf2 pathway.View less
The Islamic conquest of the seventh century marked the beginning of a process that pulled the Far and Central Maghreb into the emerging Islamic world. This process was, however, not straightforward. Step by step, commercial, political and intellectual bonds linked the Maghreb with the Middle Eastern centers, while religious missionaries and political dissidents arrived there and sought for adepts amongst the newly converted population. Umayyads and Fatimids used this territory to fight their battles. The conflicts between these rival regional macro-powers forced the Berber imamates to increase their dependence on the Western Umayyads in Al-Andalus. Economically the Maghreb had become part of a transregional commercial network (slave- trade) and eventually became part of the Islamicate world sharing legal practices, religious doctrines and globally connected scholarly elites. The growing influence of Maliki scholars and practices prepared the terrain for the adoption of the Maliki legal school and the marginalization of local forms of Islam. Finally, the Maghreb became part of a “Sunni” mainstream Islam throughout the tenth and eleventh centuries.View less
Empirical evidence demonstrates that lakes and reservoirs are warming across the globe. Consequently, there is an increased need to project future changes in lake thermal structure and resulting changes in lake biogeochemistry in order to plan for the likely impacts. Previous studies of the impacts of climate change on lakes have often relied on a single model forced with limited scenario-driven projections of future climate for a relatively small number of lakes. As a result, our understanding of the effects of climate change on lakes is fragmentary, based on scattered studies using different data sources and modelling protocols, and mainly focused on individual lakes or lake regions. This has precluded identification of the main impacts of climate change on lakes at global and regional scales and has likely contributed to the lack of lake water quality considerations in policy-relevant documents, such as the Assessment Reports of the Intergovernmental Panel on Climate Change (IPCC). Here, we describe a simulation protocol developed by the Lake Sector of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP) for simulating climate change impacts on lakes using an ensemble of lake models and climate change scenarios for ISIMIP phases 2 and 3. The protocol prescribes lake simulations driven by climate forcing from gridded observations and different Earth system models under various representative greenhouse gas concentration pathways (RCPs), all consistently bias-corrected on a 0.5∘ × 0.5∘ global grid. In ISIMIP phase 2, 11 lake models were forced with these data to project the thermal structure of 62 well-studied lakes where data were available for calibration under historical conditions, and using uncalibrated models for 17 500 lakes defined for all global grid cells containing lakes. In ISIMIP phase 3, this approach was expanded to consider more lakes, more models, and more processes. The ISIMIP Lake Sector is the largest international effort to project future water temperature, thermal structure, and ice phenology of lakes at local and global scales and paves the way for future simulations of the impacts of climate change on water quality and biogeochemistry in lakes.View less
EBLM J0113+31 is a moderately bright (V = 10.1), metal-poor ([Fe/H] ≈−0.3) G0V star with a much fainter M dwarf companion on a wide, eccentric orbit (= 14.3 d). We have used near-infrared spectroscopy obtained with the SPIRou spectrograph to measure the semi-amplitude of the M dwarf’s spectroscopic orbit, and high-precision photometry of the eclipse and transit from the CHEOPS and TESS space missions to measure the geometry of this binary system. From the combined analysis of these data together with previously published observations, we obtain the following model-independent masses and radii: M1 = 1.029 ± 0.025 M⊙, M2 = 0.197 ± 0.003 M⊙, R1 = 1.417 ± 0.014 R⊙, R2 = 0.215 ± 0.002 R⊙. Using R1 and the parallax from Gaia EDR3 we find that this star’s angular diameter is θ = 0.0745 ± 0.0007 mas. The apparent bolometric flux of the G0V star corrected for both extinction and the contribution from the M dwarf (<0.2 per cent) is F⊕,0=(2.62±0.05)×10−9 erg cm−2 s−1. Hence, this G0V star has an effective temperature Teff,1=6124K±40K(rnd.)±10K(sys.). EBLM J0113+31 is an ideal benchmark star that can be used for ‘end-to-end’ tests of the stellar parameters measured by large-scale spectroscopic surveys, or stellar parameters derived from asteroseismology with PLATO. The techniques developed here can be applied to many other eclipsing binaries in order to create a network of such benchmark stars.View less
Little is known about changes of mental health during the COVID-19 pandemic in potentially disadvantaged groups. We investigated changes in anxiety and depression symptoms during the first year of the pandemic in six European countries and Australia by prior mental disorders and migration status.
Overall, 4674 adults answered a web-based survey in May–June 2020 and were followed by three repeated surveys up to February 2021. Information on psychosocial, financial and demographic, living conditions, prior mental disorders, depression and anxiety symptoms during the pandemic and migration status was collected. Weighted general estimation equations modelling was used to investigate the association between prior mental disorders, migration status, and symptoms over time.
Most participants were <40 years old (48%), women (78%) and highly educated (62%). The baseline prevalence of depressive and anxiety symptoms ranged between 19%–45% and 13%–35%, respectively. In most countries, prevalence rates remained unchanged throughout the pandemic and were higher among people with prior mental disorders than without even after adjustment for several factors. We observed interactions between previous mental disorders and symptoms of anxiety or depression over time in two countries. No difference by migration status was noted.
Convenience sampling limits generalizability. Self-assessed symptoms of depression and anxiety might involve some misclassification.
Depression and anxiety symptoms were worse among individuals with prior mental disorders than without, but there was no clear trend of worsening mental health in the observed groups during the observed period.View less
Objectives: Detectability experiments performed to assess the diagnostic performance of computed tomography (CT) images should represent the clinical situation realistically. The purpose was to develop anatomically realistic phantoms with low-contrast lesions for detectability experiments.
Methods: Low-contrast lesions were digitally inserted into a neck CT image of a patient. The original and the manipulated CT images were used to create five phantoms: four phantoms with lesions of 10, 20, 30, and 40 HU contrast and one phantom without any lesion. Radiopaque 3D printing with potassium-iodide-doped ink (600 mg/mL) was used. The phantoms were scanned with different CT settings. Lesion contrast was analyzed using HU measurement. A 2-alternative forced choice experiment was performed with seven radiologists to study the impact of lesion contrast on detection accuracy and reader confidence (1 = lowest, 5 = highest).
Results: The phantoms reproduced patient size, shape, and anatomy. Mean ± SD contrast values of the low-contrast lesions were 9.7 ± 1.2, 18.2 ± 2, 30.2 ± 2.7, and 37.7 ± 3.1 HU for the 10, 20, 30, and 40 HU contrast lesions, respectively. Mean ± SD detection accuracy and confidence values were not significantly different for 10 and 20 HU lesion contrast (82.1 ± 6.3% vs. 83.9 ± 9.4%, p = 0.863 and 1.7 ± 0.4 vs. 1.8 ± 0.5, p = 0.159). They increased to 95 ± 5.7% and 2.6 ± 0.7 for 30 HU lesion contrast and 99.5 ± 0.9% and 3.8 ± 0.7 for 40 HU lesion contrast (p < 0.005).
Conclusions: A CT image was manipulated to produce anatomically realistic phantoms for low-contrast detectability experiments. The phantoms and our initial experiments provide a groundwork for the assessment of CT image quality in a clinical context.View less
Objectives: To assess the discriminatory power of lexicon terms used in PI-RADS version 2 to describe MRI features of prostate lesions.
Methods: Four hundred fifty-four patients were included in this retrospective, institutional review board-approved study. Patients received multiparametric (mp) MRI and subsequent prostate biopsy including MRI/transrectal ultrasound fusion biopsy and 10-core systematic biopsy. PI-RADS lexicon terms describing lesion characteristics on mpMRI were assigned to lesions by experienced readers. Positive and negative predictive values (PPV, NPV) of each lexicon term were assessed using biopsy results as a reference standard.
Results: From a total of 501 lesions, clinically significant prostate cancer (csPCa) was present in 175 lesions (34.9%). Terms related to findings of restricted diffusion showed PPVs of up to 52.0%/43.9% and NPV of up to 91.8%/89.7% (peripheral zone or PZ/transition zone or TZ). T2-weighted imaging (T2W)-related terms showed a wide range of predictive values. For PZ lesions, high PPVs were found for "markedly hypointense," "lenticular," "lobulated," and "spiculated" (PPVs between 67.2 and 56.7%). For TZ lesions, high PPVs were found for "water-drop-shaped" and "erased charcoal sign" (78.6% and 61.0%). The terms "encapsulated," "organized chaos," and "linear" showed to be good predictors for benignity with distinctively low PPVs between 5.4 and 6.9%. Most T2WI-related terms showed improved predictive values for TZ lesions when combined with DWI-related findings.
Conclusions: Lexicon terms with high discriminatory power were identified (e.g., "markedly hypointense," "water-drop-shaped," "organized chaos"). DWI-related terms can be useful for excluding TZ cancer. Combining T2WI- with DWI findings in TZ lesions markedly improved predictive values.View less
There is lack of standardization of practices and limited evidence on efficacy and safety of nebulization of antimicrobials. We sought to determine inhalation practices in one tertiary care hospital by performing a cross-sectional survey. Eleven adult ICUs were included in the analysis. Three units followed established protocols. Ventilation circuit filters were exchanged at least daily in all but one units. Dosages of aminoglycosides and CMS depended on indication and unit. Nebulization of antimicrobials was generally regarded as safe and efficacious. Our data indicate that approach to nebulization of antimicrobials may be heterogeneous even in a single center.View less
Klassische Autonomiekonzepte, die Kunst als selbstbestimmt und selbstzweckhaft denken, werden einer in ökonomische, politische, soziale und ökologische Zusammenhänge verwickelten künstlerischen Praxis der Gegenwart kaum gerecht – und bleiben doch für ein Verständnis dieser Kunst unerlässlich. Aus verschiedenen disziplinären Perspektiven gehen die Beiträger*innen des Bandes den Widersprüchlichkeiten einer falschen Gegenüberstellung von Autonomie und Engagement nach und bestimmen gegen Tendenzen einer einseitigen Funktionalisierung differenzielle Strategien und heteronome Verflechtungen künstlerischer Praxis neu.View less
Sie ist die Heldin der heimlichen Nationalhymne und das hiesige Äquivalent zum Waffenwahn der USA. Schon in ihren Anfängen war sie ein rechter Raum für die vom Futurismus besungene neue Männlichkeit: die Autobahn. Mussolini und Hitler machten sie nicht zufällig zu Staatsprojekten ersten Ranges und ihre Propaganda überdauert versteckt bis heute – und zeigt sich zunehmend wieder ganz offen. Mit dem drohenden Klimakollaps ist überdeutlich, dass Auto und Autobahn historische Fehler waren. Conrad Kunze liefert eine Handreichung für alle, die davon träumen, diese Form der fossilen Moderne zugunsten einer Moderne von Klimaschutz und Emanzipation zu überwinden.View less
Germany's debate on nuclear energy is characterized by a potential for conflict. With the Repository Site Selection Act, a new strategy was adopted for a participatory search process for the best possible repository site for high-level radioactive waste in Germany. To gain insights into how a Public Participatory GIS application (PPGIS) can contribute to this strategy, a transdisciplinary approach was adopted. By involving a citizen group to take part in the research process, we co-designed and addressed three research questions regarding the role of the PPGIS, its usability and ability to enable dialogue. Key findings include the need for guidance on how to interpret the data provided. Although the potential of a PPGIS to support dialogue is recognized, the need for content moderation emerged as a significant challenge. The transdisciplinary approach was useful in capturing multiple viewpoints and providing new insights into how a PPGIS should be designed to maximize its usefulness.View less
Quantum channels breaking entanglement, incompatibility, or nonlocality are defined as such because they are not useful for entanglement-based, one-sided device-independent, or device-independent quantum-information processing, respectively. Here, we show that such breaking channels are related to complementary tests of macrorealism, i.e., temporal separability, channel unsteerability, temporal unsteerability, and the temporal Bell inequality. To demonstrate this we first define a steerability-breaking channel, which is conceptually similar to entanglement and nonlocality-breaking channels and prove that it is identical to an incompatibility-breaking channel. A hierarchy of quantum nonbreaking channels is derived, akin to the existing hierarchy relations for temporal and spatial quantum correlations. We then introduce the concept of channels that break temporal correlations, explain how they are related to the standard breaking channels, and prove the following results. (1) A robustness-based measure for non-entanglement-breaking channels can be probed by temporal nonseparability. (2) A non-steerability-breaking channel can be quantified by channel steering. (3) Temporal steerability and nonmacrorealism can be used for, respectively, distinguishing unital steerability-breaking channels and nonlocality-breaking channels for a maximally entangled state. Finally, a two-dimensional depolarizing channel is experimentally implemented as a proof-of-principle example to demonstrate the hierarchy relation of nonbreaking channels using temporal quantum correlations.View less
Emerging infectious diseases, especially if caused by bat-borne viruses, significantly affect public health and the global economy. There is an urgent need to understand the mechanism of interspecies transmission, particularly to humans. Viral genetics; host factors, including polymorphisms in the receptors; and ecological, environmental, and population dynamics are major parameters to consider. Here, we describe the taxonomy, geographic distribution, and unique traits of bats associated with their importance as virus reservoirs. Then, we summarize the origin, intermediate hosts, and the current understanding of interspecies transmission of Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, Nipah, Hendra, Ebola, Marburg virus, and rotaviruses. Finally, the molecular interactions of viral surface proteins with host cell receptors are examined, and a comparison of these interactions in humans, intermediate hosts, and bats is conducted. This uncovers adaptive mutations in virus spike protein that facilitate cross-species transmission and risk factors associated with the emergence of novel viruses from bats.View less