We test the hypothesis that COVID-19 vaccine hesitancy is attributable to distrustful complacency—an interactive combination of low concern and low trust. Across two studies, 9,695 respondents from different parts of Britain reported their level of concern about COVID-19, trust in the UK government, and intention to accept or refuse the vaccine. Multilevel regression analysis, controlling for geographic area and relevant demographics, confirmed the predicted interactive effect of concern and trust. Across studies, respondents with both low trust and low concern were 10%–22% more vaccine hesitant than respondents with either high trust or high concern, and 26%–29% more hesitant than respondents with both high trust and high concern. Results hold equally among White, Black, and Muslim respondents, consistent with the view that regardless of mean-level differences, a common process underlies vaccine hesitancy, underlining the importance of tackling distrustful complacency both generally and specifically among unvaccinated individuals and populations.
Background: Adverse childhood experiences (ACEs) are highly prevalent and increase the risk for long-term adverse health outcomes. Next to well-known ACE-associated risks for morbidity, recent research is increasingly invested in exploring pathways towards health, overall functioning, and partaking in society following early adversity. Objectives: Thus, this study aims to assess the association between latent classes of ACEs with perceived social participation and health-related Quality of Life (QoL) in a large population-based sample and to explore potential moderators of these associations. Method: A representative sample of the German population (N = 2531; Mage = 48.7; 51 % women) was cross-sectionally investigated for ACEs, social participation (KsT-5), and health-related QoL (EuroQol-5D-5L). Latent Class Analysis (LCA) was performed to derive groups with similar ACE patterns. Multiple regression analyses were used to investigate the association of latent classes of ACEs with social participation and health-related QoL and to explore potential moderators. Results: Four distinct latent classes of ACEs were identified; "no/low ACEs" (N = 1968, 77.8 %); "household-dysfunction" (N = 259, 10.2 %), "child abuse and neglect" (N = 188, 7.4 %), and "polyadversity" (N = 116, 4.6 %). Compared to participants in the no/low ACE class, those in the ACE-exposed classes showed overall lower levels of perceived social participation and health-related QoL. The polyadversity class showed lower levels of social participation compared to the two other ACE-exposed classes. Chronic stress, living with a partner, education, current job/educational involvement, and gender were found to moderate these associations in exploratory analyses. Conclusions: This study shows people exposed to ACEs to have a higher risk for lower perceived social participation and lower health-related QoL - an increased risk, however, is not a deterministic uninventable fortune. Reduction of chronic stress, fostering of social support, and educational and vocational paths as interventional targets are discussed to enable those with precarious starting conditions to partake in society.
Chiari type 1 malformation (CIM) is defined as tonsillar ectopia of >5 mm, while syringomyelia (SM) is defined as a cerebrospinal fluid (CSF)-filled cavity larger than 3 mm dissecting the spinal cord. Over the last decades, our understanding of these pathologies has grown; however, many controversies still exist almost in every aspect of CIM and SM, including etiology, indication for treatment, timing of treatment, surgical technique, follow-up regime, and outcome. This chapter provides a comprehensive overview on different aspects of CIM and SM and on the still existing controversies, based on the evidence presently available. Future directions for clinical research concerning CIM and SM treatment and outcome are elaborated and discussed as well.
Targeted eradication of transformed or otherwise dysregulated cells using monoclonal antibodies (mAb), antibody–drug conjugates (ADC), T cell engagers (TCE), or chimeric antigen receptor (CAR) cells is very effective for hematologic diseases. Unlike the breakthrough progress achieved for B cell malignancies, there is a pressing need to find suitable antigens for myeloid malignancies. CD123, the interleukin-3 (IL-3) receptor alpha-chain, is highly expressed in various hematological malignancies, including acute myeloid leukemia (AML). However, shared CD123 expression on healthy hematopoietic stem and progenitor cells (HSPCs) bears the risk for myelotoxicity. We demonstrate that epitope-engineered HSPCs were shielded from CD123-targeted immunotherapy but remained functional, while CD123-deficient HSPCs displayed a competitive disadvantage. Transplantation of genome-edited HSPCs could enable tumor-selective targeted immunotherapy while rebuilding a fully functional hematopoietic system. We envision that this approach is broadly applicable to other targets and cells, could render hitherto undruggable targets accessible to immunotherapy, and will allow continued posttransplant therapy, for instance, to treat minimal residual disease (MRD).
The half-life of mRNAs, as well as their translation, increases in proportion to the optimal codons, indicating a tight coupling of codon-dependent differential translation and degradation. Little is known about the regulation of this coupling. We found that the mRNA stability gain in yeast depends on the mRNA coding sequence length. Below a critical length, codon optimality fails to affect the stability of mRNAs although they can be efficiently translated into short peptides and proteins. Above this threshold length, codon optimality–dependent differential mRNA stability emerges in a switch-like fashion, which coincides with a similar increase in the polysome propensity of the mRNAs. This threshold length can be tuned by the untranslated regions (UTR). Some of these UTRs can destabilize mRNAs without reducing translation, which plays a role in controlling the amplitude of the oscillatory expression of cell cycle genes. Our findings help understand the translation of short peptides from noncoding RNAs and the translation by localized monosomes in neurons.
Zusammenfassung Inwiefern Digitalisierung ein gesellschaftstransformatives Potenzial hat, ist umstritten. Diese Frage wird der empirischen Analyse zugänglich, wenn man die Steuerung von Verhalten in den Blick nimmt. Es fehlt jedoch bislang eine differenzierte sozialtheoretische Perspektive, mit der unterschiedliche Steuerungen von Verhalten präzise erfasst werden können. Der Beitrag geht von der Prämisse aus, dass Verhaltenssteuerung ausgehend von der Orientierung an Normen zu fassen ist, und macht einen Vorschlag, wie sich technische und soziale Normen in der Sozial‑, Sach- und Zeitdimension voneinander unterscheiden lassen und welche unterschiedlichen Modi der Verhaltenssteuerung mit ihnen korrespondieren. Am Beispiel assistiver Verkehrstechnologien werden zum einen die Fruchtbarkeit der Unterscheidung von sozialen und technischen Normen, zum anderen die sich ergebenden empirischen Anschlussfragen aufgezeigt.
Primary biological aerosol particles (PBAP) play an important role in the climate system, facilitating the formation of ice within clouds, consequently PBAP may be important in understanding the rapidly changing Arctic. Within this work, we use single-particle fluorescence spectroscopy to identify and quantify PBAP at an Arctic mountain site, with transmission electronic microscopy analysis supporting the presence of PBAP. We find that PBAP concentrations range between 10⁻³–10⁻¹ L⁻¹ and peak in summer. Evidences suggest that the terrestrial Arctic biosphere is an important regional source of PBAP, given the high correlation to air temperature, surface albedo, surface vegetation and PBAP tracers. PBAP clearly correlate with high-temperature ice nucleating particles (INP) (>-15 °C), of which a high a fraction (>90%) are proteinaceous in summer, implying biological origin. These findings will contribute to an improved understanding of sources and characteristics of Arctic PBAP and their links to INP.
Atmospheric mercury (Hg) is deposited to land surfaces mainly through vegetation uptake. Foliage stomatal gas exchange plays an important role for net vegetation Hg uptake, because foliage assimilates Hg via the stomata. Here, we use empirical relationships of foliar Hg uptake by forest tree species to produce a spatially highly resolved (1 km ² ) map of foliar Hg fluxes to European forests over one growing season. The modelled forest foliar Hg uptake flux is 23 ± 12 Mg Hg season ⁻¹ , which agrees with previous estimates from literature. We spatially compared forest Hg fluxes with modelled fluxes of the chemistry‐transport model GEOS‐Chem and find a good overall agreement. For European pine forests, stomatal Hg uptake was shown to be sensitive to prevailing conditions of relatively high ambient water vapor pressure deficit (VPD). We tested a stomatal uptake model for the total pine needle Hg uptake flux during four previous growing seasons (1994, 2003, 2015/2017, 2018) and two climate change scenarios (RCP 4.5 and RCP 8.5). The resulting modelled total European pine needle Hg uptake fluxes are in a range of 8.0 ‐ 9.3 Mg Hg season ⁻¹ (min ‐ max). The lowest pine forest needle Hg uptake flux to Europe (8 Mg Hg season ⁻¹ ) among all investigated growing seasons was associated with unusually hot and dry ambient conditions in the European summer 2018, highlighting the sensitivity of the investigated flux to prolonged high VPD. We conclude, that stomatal modelling is particularly useful to investigate changes in Hg deposition in the context of extreme climate events. This article is protected by copyright. All rights reserved.
This article presents a new perspective on the intersection of technology, biology, and politics in modern Germany by examining the history of biotechnics, a nonanthropocentric concept of technology that was developed in German-speaking Europe from the 1870s to the 1930s. Biotechnics challenged the traditional view of technology as exclusively a human creation, arguing that nature itself could also be a source of technical innovations. Our study focuses on the contributions of Ernst Kapp, Raoul Heinrich Francé, and Alf Giessler, highlighting the gradual shift in political perspectives that influenced the merging of nature and technology in their respective visions of biotechnics. From Kapp’s liberal radicalism to Francé’s social organicism and ultimately to Giessler’s totalitarian fascism, their writings increasingly vitalized technology by portraying it as a natural force independent from human influence. The history of biotechnics sheds light on previously unexplored aspects of debates surrounding the sciences and philosophy of technology in Germany, while also foreshadowing contemporary discussions on technocultural hybridity. As a genealogy of the idea of nonhuman technology, the article raises perturbing questions about the political implications of conflating nature and culture.
Blood culture diagnostics require rapid and accurate identification (ID) of pathogens and antimicrobial susceptibility testing (AST). Standard procedures, involving conventional cultivation on agar plates, may take up to 48 hours or more until AST completion. Recent approaches aim to shorten the processing time of positive blood cultures (PBC). The FAST System is a new technology, capable of purifying and concentrating bacterial/fungal pathogens from positive blood culture media and producing a bacterial suspension called “liquid colony” (LC), which can be further used in downstream analyses (e.g., ID and AST). Here, we evaluated the performance of the FAST System LC generated from PBC in comparison to our routine workflow including ID by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using Sepsityper, AST by automatized MicroScan WalkAway plus and directly inoculated disk diffusion (DD), and MICRONAUT-AM for yeast/fungi. A total of 261 samples were analyzed, of which 86.6% (226/261) were eligible for the comparative ID and AST analyses. In comparison to the reference technique (culture-grown colonies), ID concordance of the FAST System LC and Sepsityper was 150/154 (97.4%) and 123/154 (79.9%), respectively, for Gram positive; 67/70 (95.7%) and 64/70 (91.4%), respectively, for Gram negative. For AST, categorical agreement (CA) of the FAST System LC in comparison to the routine workflow for Gram-positive bacteria was 96.1% and 98.7% for MicroScan and DD, respectively. Similar results were obtained for Gram-negative bacteria with 96.6% and 97.5% of CA for MicroScan and DD, respectively. Taken together, the FAST System LC allowed the laboratory to significantly reduce the time to obtain correct ID and AST (automated MicroScan) results 1 day earlier and represents a promising tool to expedite the processing of PBC.
The Anthropocene is characterized by a rapid pace of environmental change and is causing a multitude of biotic responses, including those that affect the spatial distribution of species. Lagged responses are frequent and species distributions and assemblages are consequently pushed into a disequilibrium state. How the characteristics of environmental change—for example, gradual ‘press’ disturbances such as rising temperatures due to climate change versus infrequent ‘pulse’ disturbances such as extreme events—affect the magnitude of responses and the relaxation times of biota has been insufficiently explored. It is also not well understood how widely used approaches to assess or project the responses of species to changing environmental conditions can deal with time lags. It, therefore, remains unclear to what extent time lags in species distributions are accounted for in biodiversity assessments, scenarios and models; this has ramifications for policymaking and conservation science alike. This perspective piece reflects on lagged species responses to environmental change and discusses the potential consequences for species distribution models (SDMs), the tools of choice in biodiversity modelling. We suggest ways to better account for time lags in calibrating these models and to reduce their leverage effects in projections for improved biodiversity science and policy.
The burden of non-communicable diseases is increasing, with risk factors emerging early in life. Physical activity reduces cardiovascular risk, but limited evidence exists for children from lower-income countries and mostly relies on self-reported methods that might be inaccurate and biased. We aimed to compare self-reported and accelerometer-measured physical activity in relation to cardiovascular risk markers in children from underserved communities in South Africa. We analysed cross-sectional data from 594 children aged 8 to 13. Physical activity was measured via accelerometry and the Physical Activity Questionnaire for Older Children (PAQ-C). Correlation analyses and linear regression models examined the relationship between accelerometer-measured and self-reported physical activity and their association with cardiovascular risk markers (body mass index, blood pressure, blood lipid profile and glycated haemoglobin). Results show a positive but weak correlation between PAQ-C scores and accelerometer-measured moderate-to-vigorous physical activity (MVPA). MVPA was inversely associated with body mass index, whilst sedentary behaviour correlated positively with lipid levels. PAQ-C scores were inversely associated with systolic blood pressure. The comparison of self-reported and accelerometer-measured physical activity in children from Gqeberha, South Africa, revealed inconsistencies in their correlation and association with cardiovascular risk markers. Accelerometry provided a more accurate cardiovascular risk estimation than PAQ-C, although associations were weak. Further, longitudinal studies should investigate the predictive power of both methodologies. These findings inform researchers and public health practitioners in the choice of method for physical activity appraisal beyond practical considerations, especially when combined with cardiovascular risk and in lower-income settings. Significance: We explore two widely used methods to assess physical activity levels in children. By comparing both methods, we expose inconsistencies in their correlation and association with cardiovascular risk markers. These data can guide researchers and public health practitioners in the use of one method beyond practical considerations. Whilst this work focuses on children from marginalised areas of South Africa, the issues explored are of relevance to other lower-income settings. Open data set: https://doi.org/10.5281/zenodo.7217145
Background Interventions such as advance care planning (ACP), technology, or access to euthanasia may increase the sense of control over the end of life. In people with advanced dementia, the loss of cognitive and physical function limits the ability to control care. To date, little is known about the acceptability of these interventions from the perspective of persons with dementia and others involved. This study will examine the cross-cultural acceptability, and factors associated with acceptability, of four end-of-life interventions in dementia which contain an element of striving for control. Also, we report on the development and pilot testing of animation video vignettes that explain the interventions in a standardized manner. Methods Cross-sectional mixed-methods vignette study. We assess acceptability of two ACP approaches, technology use at the end of life and euthanasia in persons with dementia, their family caregivers and physicians in six countries (Netherlands, Japan, Israel, USA, Germany, Switzerland). We aim to include 80 participants per country, 50 physicians, 15 persons with dementia, and 15 family caregivers. After viewing each animation video, participants are interviewed about acceptability of the intervention. We will examine differences in acceptability between group and country and explore other potentially associated factors including variables indicating life view, personality, view on dementia and demographics. In the pilot study, participants commented on the understandability and clarity of the vignettes and instruments. Based on their feedback, the scripts of the animation videos were clarified, simplified and adapted to being less slanted in a specific direction. Discussion In the pilot study, the persons with dementia, their family caregivers and other older adults found the adapted animation videos and instruments understandable, acceptable, feasible, and not burdensome. The CONT-END acceptability study will provide insight into cross-cultural acceptability of interventions in dementia care from the perspective of important stakeholders. This can help to better align interventions with preferences. The study will also result in a more fundamental understanding as to how and when having control at the end of life in dementia is perceived as beneficial or perhaps harmful. Trial registration The CONT-END acceptability study was originally registered at the Netherlands Trial Register (NL7985) at 31 August, 2019, and can be found on the International Clinical Trials Registry Platform.
The urban community faces a significant obstacle in effectively utilising Earth Observation (EO) intelligence, particularly the Copernicus EO program of the European Union, to address the multifaceted aspects of urban sustainability and bolster urban resilience in the face of climate change challenges. In this context, here we present the efforts of the CURE project, which received funding under the European Union’s Horizon 2020 Research and Innovation Framework Programme, to leverage the Copernicus Core Services (CCS) in supporting urban resilience. CURE provides spatially disaggregated environmental intelligence at a local scale, demonstrating that CCS can facilitate urban planning and management strategies to improve the resilience of cities. With a strong emphasis on stakeholder engagement, CURE has identified eleven cross-cutting applications between CCS that correspond to the major dimensions of urban sustainability and align with user needs. These applications have been integrated into a cloud-based platform known as DIAS (Data and Information Access Services), which is capable of delivering reliable, usable and relevant intelligence to support the development of downstream services towards enhancing resilience planning of cities throughout Europe.
Objectives To compare the rates and injury sites among competitors in European and Swiss karate tournaments and to identify differences in these incidence rates by sex and age. Methods This prospective cohort study collected data from two European and four national tournaments in Switzerland between 2011 and 2019. The on-site medical staff completed an anonymised report sheet with demographic data and injury characteristics in all injuries requiring medical treatment. The incidence rates per 1000 exposed athletes (AoE) and 1000 min of exposition (MoE) were analysed. Furthermore, the relative risk of injury related to sex and age was calculated and compared. Results In total, 228 injuries were observed in 2404 fights, for an incidence rate of 47.4 per 1000 AoE (95% CI 41.5 to 54.0) or 22.5 injuries per 1000 MoE (95% CI 19.7 to 25.6), respectively. The oldest age group (senior) of both sexes had a 3.6-fold (95% CI 2.7 to 4.8) significantly higher relative risk of injury than younger participants. Furthermore, there was a 2.9-fold (95% CI 1.6 to 5.6) statistically higher risk of injury for males in the senior age group compared with senior females. The most injured body part was the head, followed by the lower extremity, trunk and upper extremity. Conclusion Senior athletes, especially senior males, had significantly more injuries compared with younger and female senior competitors. Medical staff should be aware of the increased propensity for injury among this age and sex group to facilitate injury prevention and intervention.
Malaria surveillance is hampered by the widespread use of diagnostic tests with low sensitivity. Adequate molecular malaria diagnostics are often only available in centralized laboratories. PlasmoPod is a novel cartridge-based nucleic acid amplification test for rapid, sensitive, and quantitative detection of malaria parasites. PlasmoPod is based on reverse-transcription quantitative polymerase chain reaction (RT-qPCR) of the highly abundant Plasmodium spp. 18S ribosomal RNA/DNA biomarker and is run on a portable qPCR instrument which allows diagnosis in less than 30 minutes. Our analytical performance evaluation indicates that a limit-of-detection as low as 0.02 parasites/μL can be achieved and no cross-reactivity with other pathogens common in malaria endemic regions was observed. In a cohort of 102 asymptomatic individuals from Bioko Island with low malaria parasite densities, PlasmoPod accurately detected 83 cases, resulting in an overall detection rate of 81.4%. Notably, there was a strong correlation between the Cq values obtained from the reference RT-qPCR assay and those obtained from PlasmoPod. In an independent cohort, using dried blood spots from malaria symptomatic children living in the Central African Republic, we demonstrated that PlasmoPod outperforms malaria rapid diagnostic tests based on the PfHRP2 and panLDH antigens as well as thick blood smear microscopy. Our data suggest that this 30-minute sample-to-result RT-qPCR procedure is likely to achieve a diagnostic performance comparable to a standard laboratory-based RT-qPCR setup. We believe that the PlasmoPod rapid NAAT could enable widespread accessibility of high-quality and cost-effective molecular malaria surveillance data through decentralization of testing and surveillance activities, especially in elimination settings.
Externalized histones erupt from the nucleus as extracellular traps, are associated with several acute and chronic lung disorders, but their implications in the molecular pathogenesis of interstitial lung disease are incompletely defined. To investigate the role and molecular mechanisms of externalized histones within the immunologic networks of pulmonary fibrosis, we studied externalized histones in human and animal bronchoalveolar lavage (BAL) samples of lung fibrosis. Neutralizing anti-histone antibodies were administered in bleomycin-induced fibrosis of C57BL/6 J mice, and subsequent studies used conditional/constitutive knockout mouse strains for TGFβ and IL-27 signaling along with isolated platelets and cultured macrophages. We found that externalized histones (citH3) were significantly ( P < 0.01) increased in cell-free BAL fluids of patients with idiopathic pulmonary fibrosis (IPF; n = 29) as compared to healthy controls ( n = 10). The pulmonary sources of externalized histones were Ly6G ⁺ CD11b ⁺ neutrophils and nonhematopoietic cells after bleomycin in mice. Neutralizing monoclonal anti-histone H2A/H4 antibodies reduced the pulmonary collagen accumulation and hydroxyproline concentration. Histones activated platelets to release TGFβ1, which signaled through the TGFbRI/TGFbRII receptor complex on LysM ⁺ cells to antagonize macrophage-derived IL-27 production. TGFβ1 evoked multiple downstream mechanisms in macrophages, including p38 MAPK, tristetraprolin, IL-10, and binding of SMAD3 to the IL-27 promotor regions. IL-27RA-deficient mice displayed more severe collagen depositions suggesting that intact IL-27 signaling limits fibrosis. In conclusion, externalized histones inactivate a safety switch of antifibrotic, macrophage-derived IL-27 by boosting platelet-derived TGFβ1. Externalized histones are accessible to neutralizing antibodies for improving the severity of experimental pulmonary fibrosis.
Despite its importance, few validated scales exist to measure aesthetics in HCI. One notable exception, the Visual Aesthetics of Websites Inventory (VisAWI), has never been validated in English. Furthermore, the VisAWI contains negatively formulated items, which adversely impact the psychometric quality of survey scales. Consequently, this paper’s aim was the development of a positive-item version of the VisAWI, the VisAWI-pos, as a viable alternative to the original scale. Positive alternatives for the negative items of the VisAWI scale were developed and evaluated in a first study (N = 41). Afterward, a pre-registered second study (N = 966) was conducted to validate the VisAWI-pos. In addition, the VisAWI’s English version was formally validated for the first time. Results showed that the English VisAWI has comparable psychometric qualities to validated versions in other languages. Furthermore, the VisAWI-pos provided matching results to the original VisAWI while exhibiting equal or improved psychometric quality.
Background Identifying factors associated with delayed diagnosis of cerebral venous thrombosis (CVT) can inform future strategies for early detection. Methods and Results We conducted a retrospective cohort study including all participants from ACTION‐CVT (Anticoagulation in the Treatment of Cerebral Venous Thrombosis) study who had dates of neurologic symptom onset and CVT diagnosis available. Delayed diagnosis was defined as CVT diagnosis occurring in the fourth (final) quartile of days from symptom onset. The primary study outcome was modified Rankin Scale score of ≤1 at 90 days; secondary outcomes included partial/complete CVT recanalization on last available imaging and modified Rankin Scale score of ≤2. Logistic regression analyses were used to identify independent variables associated with delayed diagnosis and to assess the association of delayed diagnosis and outcomes. A total of 935 patients were included in our study. Median time from symptom onset to diagnosis was 4 days (interquartile range, 1–10 days). Delayed CVT diagnosis (time to diagnosis >10 days) occurred in 212 patients (23%). Isolated headache (adjusted odds ratio [aOR], 2.36 [95% CI, 1.50–3.73]; P <0.001), older age (aOR by 1 year, 1.02 [95% CI, 1.004–1.03]; P =0.01), and papilledema (aOR, 2.00 [95% CI, 1.03–3.89]; P =0.04) were associated with diagnostic delay, whereas higher National Institutes of Health Stroke Scale score was inversely associated with diagnostic delay (aOR by 1 point, 0.95 [95% CI, 0.89–1.00]; P =0.049). Delayed diagnosis was not associated with modified Rankin Scale score of ≤1 at 90 days (aOR, 1.08 [95% CI, 0.60–1.96]; P =0.79). Conclusions In a large multicenter cohort, a quarter of included patients with CVT were diagnosed >10 days after symptom onset. Delayed CVT diagnosis was associated with the symptom of isolated headache and was not associated with adverse clinical outcomes.
Institution pages aggregate content on ResearchGate related to an institution. The members listed on this page have self-identified as being affiliated with this institution. Publications listed on this page were identified by our algorithms as relating to this institution. This page was not created or approved by the institution. If you represent an institution and have questions about these pages or wish to report inaccurate content, you can contact us here.
Klingelbergstrasse 61, 4056, Basel, Basel, Switzerland
Head of institution
Prof. Dr. Eberhard Parlow