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Abstract Background Given the rapid proliferation and use of online health resources, many of which may be of dubious quality, there is an increasing need to develop electronic health literacy (e-health literacy) skills among the population of internet users. E-health literacy encompasses the skills and abilities needed to access, understand, validate, evaluate, interpret, and apply online health-related information. Measuring e-health literacy has become crucial for developing targeted interventions, assessing their impact, and producing high-quality research findings that can inform health policy and clinical practice, which can lead to improved health outcomes and potentially reducing health inequalities. The scales need to be valid and reliable so that decisions are based on high-quality data. In this regard, the issue of the measurement invariance of scales across different demographic groups has been neglected. This is critical, as assessments should be valid across different sociodemographic groups to avoid bias when comparing them. The aim of this study was to validate the Extended e-health literacy scale (eHEALS-E) on general population and investigate its structural validity and internal consistency, construct validity in terms of convergent and discriminant validity, and examine its measurement invariance across gender, age, education and social status. Methods The data were collected as a part of a national health literacy survey conducted by the Slovenian National Institute of Public Health. For this survey the initial eHEALS-E scale was revised in order to address its limitations and applicability to general population. Based on a nationally representative sample, the final sample for the analysis comprised 1,944 individuals who at least occasionally used one of the various internet services to obtain health-related information. Multiple group confirmatory factor analysis was used to examine the measurement invariance of the scale. Results With some adjustments, the measurement model of the revised 6-dimensional eHEALS-E scale demonstrated a good fit to the data (χ2 = 2508, df = 282, RMSEA = 0.064, SRMR = 0.070, CFI = 0.90). The scale had good internal consistency (alpha = 0.89). Although evidence of the scale’s convergent and discriminant validity was partially provided, the analysis revealed robust measurement invariance across sociodemographic groups. Conclusions With a minor limitation, the scale ensures an unbiased e-health literacy assessment across different social groups, which is crucial for interventions that aim to reduce health-related social inequalities. This ensures that the interventions derived from the assessment of reality are equally valid and effective for everyone, regardless of their sociodemographic background.

V zadnjih 30 letih od prvega opisa v strokovni literaturi je sindrom takotsubo postal prepoznavna in uveljavljena klinična entiteta. Podatki kažejo, da znaša prevalenca bolnikov s sindromom takotsubo približno 1–3 % vseh bolnikov z elevacijami spojnice ST in simptomi, ki posnemajo akutni koronarni sindrom. Hkrati približno 4 % bolnikov po akutni fazi sindroma takotsubo vsaj enkrat ponovno zboli za to boleznijo. Gre za vrsto akutnega srčnega popuščanja neishemične etiologije s sorazmerno hitrim okrevanjem krčljivosti miokarda. Sindrom pogosto sproži močan stresni dogodek, ali fizični (npr. sepsa) oz. psihični (npr. izguba bližnjega), pri približno tretjini bolnikov pa jasnega sprožilnega dogodka ne uspemo zanesljivo opredeliti. Glede na klinični potek v akutni fazi bolezni bolnike s sindromom takotsubo delimo v 2 podskupini; bolnike s simptomi akutnega koronarnega sindroma in bolnike s simptomi, katerih simptomi niso v skladu z akutnim koronarnim sindromom. Zaradi nespecifičnih simptomov in znakov je prepoznavanje bolnikov s sindromom takotsubo še vedno diagnostični izziv. Hipoteze o hitrem okrevanju krčljivosti srčne mišice in ugodnem poteku bolezni so nedavno izzvali izsledki novejših raziskav, ki so pokazali primerljivo smrtnost in pogostost akutnih srčno-žilnih zapletov med bolniki s sindromom takotsubo in akutnim koronarnim sindromom. Prav tako novejši podatki kažejo, da podskupina bolnikov po akutni fazi sindroma takotsubo lahko razvije kronično srčno popuščanje. Sindrom takotsubo tako ni benigna bolezen in zahteva nove pristope k diagnostični in terapevtski obravnavi teh bolnikov. V članku želimo predstaviti novosti za razumevanje patogeneze in novosti pri obravnavi bolnikov s sindromom takotsubo in spremljati svoje izkušnje pri obravnavi teh bolnikov.

Abstract Background Recent data indicated similar growth performance of young calves fed solely high-quality hay instead of a starter diet based on starchy ingredients. Yet, providing exclusively such distinct carbohydrate sources during early life might specifically prime the microbiota and gene expression along the gut of young calves, which remains to be explored. We investigated the effects of starter diets differing in carbohydrate composition, that is medium- or high-quality hay and without or with 70% concentrate supplementation (on fresh matter basis), across the gastrointestinal tract (GIT) of weaned Holstein calves (100 ± 4 days of age) using 16 S rRNA gene sequencing and analyses of short-chain fatty acids and host epithelial gene expressions. Results The concentrate supplementation drastically decreased microbial diversity throughout the gut, which was also true to a much lesser extent for high-quality hay when compared to medium-quality hay in the foregut. Similarly, the factor concentrate strongly shaped the diet-associated common core microbiota, which was substantially more uniform along the gut with concentrate supplementation. The fermentation profile shifted towards less acetate but more propionate with concentrate supplementation in almost all gut sections, corresponding with higher abundances of starch-utilizing bacteria, while major fibrolytic clusters declined. Noteworthy, the n-butyrate proportion decreased in the rumen and increased in the colon with concentrate, showing an opposite, gut site-dependent effect. Both dietary factors modestly influenced the host epithelial gene expression. Conclusions Concentrate supplementation clearly primed the microbial ecosystem on a starch-targeted fermentation with characteristic genera occupying this niche along the entire GIT of calves, whereas the microbial differentiation due to hay quality was less distinct. Overall, changes in the microbial ecosystem were only marginally reflected in the targeted transcriptional profile of the host epithelium.

Abstract Since the onset of the coronavirus disease (COVID-19) pandemic in Belgium, UZ/KU Leuven has played a crucial role as the National Reference Centre (NRC) for respiratory pathogens, to be the first Belgian laboratory to develop and implement laboratory developed diagnostic assays for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and later to assess the quality of commercial kits. To meet the growing demand for decentralised testing, both clinical laboratories and government-supported high-throughput platforms were gradually deployed across Belgium. Consequently, the role of the NRC transitioned from a specialised testing laboratory to strengthening capacity and coordinating quality assurance. Here, we outline the measures taken by the NRC, the national public health institute Sciensano and the executing clinical laboratories to ensure effective quality management of molecular testing throughout the initial two years of the pandemic (March 2020 to March 2022).

In this paper, we analyze a perturbed formulation of bilevel optimization problems, which we refer to as δ-perturbed formulation. The δ-perturbed formulation allows to handle the lower level optimization problem efficiently when there are multiple lower level optimal solutions. By using an appropriate perturbation strategy for the optimistic or pessimistic formulation, one can ensure that the optimization problem at the lower level contains only a single (approximate) optimal solution for any given decision at the upper level. The optimistic or the pessimistic bilevel optimal solution can then be efficiently searched for by algorithms that rely on solving the lower level optimization problem multiple times during the solution search procedure. The δ-perturbed formulation is arrived at by adding the upper level objective function to the lower level objective function after multiplying the upper level objective by a small positive/negative δ. We provide a proof that the δ-perturbed formulation is approximately equivalent to the original optimistic or pessimistic formulation and give an error bound for the approximation. We apply this scheme to a class of algorithms that attempts to solve optimistic and pessimistic variants of bilevel optimization problems by repeatedly solving the lower level optimization problem.

ABSTRACTBiologics have revolutionized disease management in many therapeutic areas by addressing unmet medical needs and overcoming resistance to standard-of-care treatment in numerous patients. However, the development of unwanted immune responses directed against these drugs, humoral and/or cellular, can hinder their efficacy and have safety consequences with various degrees of severity. Health authorities ask that a thorough immunogenicity risk assessment be conducted during drug development to incorporate an appropriate monitoring and mitigation plan in clinical studies. With the rapid diversification and complexification of biologics, which today include modalities such as multi-domain antibodies, cell-based products, AAV delivery vectors, and nucleic acids, developers are faced with the challenge of establishing a risk assessment strategy sometimes in the absence of specific regulatory guidelines. The European Immunogenicity Platform (EIP) Open Symposium on Immunogenicity of Biopharmaceuticals and its one-day training course gives experts and newcomers across academia, industry, and regulatory agencies an opportunity to share experience and knowledge to overcome these challenges. Here, we report the discussions that took place at the EIP’s 14th Symposium, held in April 2023. The topics covered included immunogenicity monitoring and clinical relevance, non-clinical immunogenicity risk assessment, regulatory aspects of immunogenicity assessment and reporting, and the challenges associated with new modalities, which were discussed in a dedicated session.

An appropriately designed pharmacokinetic (PK) assay that is sensitive for anti-drug antibody (ADA) impact on relevant exposure is an alternative strategy to understand the neutralizing potential of ADAs. However, guidance on how to develop such PK assays and how to confirm the functional ADA impact on exposure is missing. Here, the PK assay of a T-cell-engaging bispecific antibody, cibisatamab, was developed based on its mechanism of action (MoA). Using critical monoclonal anti-idiotypic (anti-ID) antibody positive controls as ADA surrogates, the impact on exposure was evaluated pre-clinically. In a phase I clinical trial (NCT02324257), initial data suggest that the combination of ADA and PK assays for correlation of the ADA response with cibisatamab exposure. To understand the neutralizing potential of patient-derived ADAs on drug activity, advanced ADA characterization has been performed. Structural binding analysis of ADAs to antibody domains of the drug and its impact on targeting were assessed. For this purpose, relevant patient ADA binding features were identified and compared with the specific monoclonal anti-ID antibody-positive controls. Comparable results of target binding inhibition and similar impacts on exposure suggest that the observed reduction of Cmax and Ctrough levels in patients is caused by the neutralizing potential of ADAs and allows a correlation between ADA response and loss of exposure. Therefore, the described study provides important functional aspects for the development of an appropriately designed PK assay for bispecific antibodies as an alternative option towards understanding the neutralizing ADA impact on exposure.

Abstract One-way quantum repeaters where loss and operational errors are counteracted by quantum error-correcting codes can ensure fast and reliable qubit transmission in quantum networks. It is crucial that the resource requirements of such repeaters, for example, the number of qubits per repeater node and the complexity of the quantum error-correcting operations are kept to a minimum to allow for near-future implementations. To this end, we propose a one-way quantum repeater that targets both the loss and operational error rates in a communication channel in a resource-efficient manner using code concatenation. Specifically, we consider a tree-cluster code as an inner loss-tolerant code concatenated with an outer 5-qubit code for protection against Pauli errors. Adopting flag-based stabilizer measurements, we show that intercontinental distances of up to 10,000 km can be bridged with a minimized resource overhead by interspersing repeater nodes that each specialize in suppressing either loss or operational errors. Our work demonstrates how tailored error-correcting codes can significantly lower the experimental requirements for long-distance quantum communication.

Omejujoči dejavnik kratkoročnega preživetja pri bolnikih po presaditvi srca je zavrnitev presadka, dolgoročno preživetje pa omejuje predvsem vaskulopatija presadka. Za bolnike po presaditvi srca je ključnega pomena, da morebitno zavrnitveno reakcijo ali pa vaskulopatijo presadka odkrijemo v zgodnji fazi bolezni, ko so terapevtski ukrepi še učinkoviti in presadek še ni nepovratno poškodovan. Danes je prva izbira pri diagnosticiranju vaskulopatije koronarografija, zlati standard pri diagnosticiranju zavrnitvene reakcije pa je endomiokardna biopsija. Zaradi invazivnosti, potrebe po hospitalni obravnavi in suboptimalni občutljivosti obeh preiskav se vse več raziskav usmerja v neinvazivne diagnostične pristope, med katerimi se je kot obetajoča preiskava izkazalo zlasti magnetnoresonančno slikanje srca. V preglednem članku bomo predstavili uporabnost magnetnoresonančnega slikanja srca pri bolnikih s presajenim srcem, njegove prednosti in izhodišča za razvoj pri zgodnjem diagnosticiranju zavrnitvenih reakcij in vaskulopatije presadka v prihodnosti.

Nanocellulose is among the most promising materials for enhancing the mechanical properties of polymer composites. Broad application is, however, limited by inadequate surface properties. A standard technique for tailoring the surface composition and wettability of polymers is a brief treatment with non-equilibrium gaseous plasma, but it often fails when treating materials with a large surface-to-mass ratio, such as cellulose nanofibers. In this paper, the theoretical limitations are explained, the approaches reported by different groups are reviewed, and the results are interpreted. The treatment of dry nanocellulose is limited by the ability of uniform treatment, whereas the plasma treatment of nanocellulose dispersed in liquids is a slow process. The methods for enhancing the treatment efficiency for both dry and water-dispersed nanocellulose are explained.

Flavius Claudius Julianus, often referred to as “Julian the Apostate,” ruled the Roman Empire from early 360 AD until his death in battle on June 26th, 363 AD. Despite his brief reign, Julian undertook sig­nificant reforms targeting various aspects of public life, including the administration and provincial governance. This paper focuses on his administrative activities in Illyricum, where he resided in 361 AD while campaigning against Constantius II. While facing immediate tactical concerns during his campaign, Julian reportedly engaged in imperial administrative duties within Illyricum, as documented by historian Ammianus Marcellinus and panegyrist Claudius Mamertinus. This research delves into Ammianus’ account to analyze Julian’s adminis­trative acts in Illyricum and subsequently across the Roman Empire.

Precise knowledge of cropland productivity is relevant for farmers to enable optimizing managing practices; particularly with the perspective of anticipating crop yield ahead of harvest. The current availability of high spatiotemporal resolution Sentinel-2 satellite data offers a unique opportunity to monitor croplands over time. In this context, the recently introduced kernel NDVI (kNDVI) statistically optimizes the conventional NDVI formulation by applying a nonlinear function to the involved bands, and so maximizes the spectral information extraction. This study proposes a workflow for within-field yield forecasting from Sentinel-2 kNDVI time series analysis focusing on winter cereal croplands in Switzerland over three years, comparing with NDVI as baseline. For a temporally continuous modelling of crop yields, Gaussian Process Regression (GPR) was applied to reconstruct cloud-free time series of the complete crop growing seasons. Following, distinct machine learning regression models (GPR, Kernel Ridge Regression and Random Forest) were developed to forecast yield at any point in time throughout the cropland growing season. The integration of Growing Degree Days (GDD) information as temporal spacing reference of the time series considerably improved the accuracy and consistency of in-season yield forecasting. Training and testing within the same year demonstrated that yield can be accurately forecast approximately 2–2.5 months ahead of harvest, at crops’ anthesis (flowering) phase, with an RMSE up to 0.71 t/ha and a relative RMSE of 7.60%. Although the forecasting accuracy of the models decreased when predicting yield for the unseen years, still satisfactory results were obtained: RMSE = 0.97 t/ha, relative RMSE = 11.47%.

Scientific and philosophical accounts of cognition and perception have traditionally focused on the brain and external sense organs. The extended view of embodied cognition suggests including other parts of the body in these processes. However, one organ has often been overlooked: the gut. Frequently conceptualized as merely a tube for digesting food, there is much more to the gut than meets the eye. Having its own enteric nervous system, sometimes referred to as the “second brain,” the gut is also an immune organ and has a large surface area interacting with gut microbiota. The gut has been shown to play an important role in many physiological processes, and may arguably do so as well in perception and cognition. We argue that proposals of embodied perception and cognition should take into account the role of the “gut complex,” which considers the enteric nervous, endocrine, immune, and microbiota systems as well as gut tissue and mucosal structures. The gut complex is an interface between bodily tissues and the “internalized external environment” of the gut lumen, involved in many aspects of organismic activity beyond food intake. We thus extend current embodiment theories and suggest a more inclusive account of how to “mind the gut” in studying cognitive processes.

Seismic reflection data and implicitly sonic velocity are undoubtedly the most important source of information for large-scale subsurface characterization. Yet, deriving reservoir and fluid flow properties from acoustic data is still challenging in carbonates, which display large acoustic velocity variations that contest many of the conventional assumptions regarding wave propagation in porous media. In this comprehensive study on 370 carbonate samples (247 limestones and 123 dolomites), we re-evaluate the impact of mineral velocity on bulk rock acoustic properties of dolomite and limestone by assessing the link between sonic velocity and the rock’s pore geometry. We quantify pore size and pore network complexity using parameters from both digital image analysis (DIA) and the extended Biot theory (EBT). We then compare DIA and EBT parameters to assess the impact of pore network geometry versus mineral velocity on the acoustic velocity of carbonate rocks. We explore the usefulness of EBT parameter γk in improving permeability estimates. Published values of velocity indicate that dolomites exhibit higher velocities than limestones at any given porosity. Our laboratory measurements of acoustic velocity, however, reveal that both dolomites and limestones show extreme variations in sonic velocities where samples with compressional velocity of ~5000 m/s may range in porosity from 5% to 25% and samples with porosity of ~20% may range in velocity from ~4000 m/s to 5700 m/s. Through the quantitative assessment of the pore network in our samples we document that pore network geometry has much more impact on the acoustic velocity of carbonates than variations in mineralogy, in this case dolomite and calcite. Most of the dolostone samples studied are dominated by small pores, resulting in relatively low velocities for their given porosity, while limestones with similar velocity–porosity values often possess simpler pore networks with larger pores. This pore size difference offsets the faster velocity of dolomite. The extended Biot theory parameter γk, captures this variation in pore size and internal geometry and exhibits a strong correlation to specific surface. Moreover, γk captures the impact of internal pore geometry on acoustic velocity, providing the basis for challenging existing assumptions regarding the importance of mineral velocity. By quantifying internal geometry, γk can improve permeability estimates in reservoir characterization and enhance evaluations of producibility and injectability. With that, it has direct implications on general geophysics, hydrocarbon exploration, and CCS initiatives.

Abstract Efficient traffic management is essential in modern urban areas. The development of intelligent traffic flow prediction systems can help to reduce travel times and maximize road capacity utilization. However, accurately modeling complex spatiotemporal dependencies can be a difficult task, especially when real-time data collection is not possible. This study aims to tackle this challenge by proposing a solution that incorporates extensive feature engineering to combine historical traffic patterns with covariates such as weather data and public holidays. The proposed approach is assessed using a new real-world data set of traffic patterns collected in Ljubljana, Slovenia. The constructed models are evaluated for their accuracy and hyperparameter sensitivity, providing insights into their performance. By providing practical solutions for real-world scenarios, the proposed approach offers an effective means to improve traffic flow prediction without relying on real-time data.

Carbon deposits consisting of vertically oriented multilayer graphene sheets on metallic foils represent an interesting alternative to activated carbon in electrical and electrochemical devices such as super-capacitors because of the superior electrical conductivity of graphene and huge surface–mass ratio. The graphene sheets were deposited on cobalt foils by plasma-enhanced chemical vapor deposition using propane as the carbon precursor. Plasma was sustained by an inductively coupled radiofrequency discharge in the H mode at a power of 500 W and a propane pressure of 17 Pa. The precursor effectively dissociated in plasma conditions and enabled the growth of porous films consisting of multilayer graphene sheets. The deposition rate varied with time and peaked at 100 nm/s. The evolution of surface wettability was determined by the sessile drop method. The untreated substrates were moderately hydrophobic at a water contact angle of about 110°. The contact angle dropped to about 50° after plasma treatment for less than a second and increased monotonously thereafter. The maximal contact angle of 130° appeared at a treatment time of about 30 s. Thereafter, it slowly decreased, with a prolonged deposition time. The evolution of the wettability was explained by surface composition and morphology. A brief treatment with oxygen plasma enabled a super-hydrophilic surface finish of the films consisting of multilayer graphene sheets.

Bonded permanent NdFeB magnets are useful in numerous applications, including electric vehicles, and the demand is steadily increasing. A major drawback is corrosion due to inadequate wetting of the magnetic particles by liquid polymers such as polyphenylene sulfide or polyamide. Recently reported methods for corrosion inhibition are summarized, and their applicability is critically evaluated. The phosphorylation of magnetic particles inhibits corrosion but does not enable appropriate properties in harsh environments. The same applies to metallic coatings, which usually contain aluminum and zinc. Advanced epoxy adhesives are a promising solution, although some authors have reported inadequate corrosion resistance. The application of composite coatings seems like an appropriate solution, but the exact mechanisms are yet to be studied.

This study presents a novel approach for improving the interfacial adhesion between Nd–Fe–B spherical magnetic powders and polyamide 12 (PA12) in polymer-bonded magnets using plasma treatments. By applying radio frequency plasma to the magnetic powder and low-pressure microwave plasma to PA12, we achieved a notable enhancement in the mechanical and environmental stability of fused deposition modeling (FDM)-printed Nd-Fe-B/PA12 magnets. The densities of the FDM-printed materials ranged from 92% to 94% of their theoretical values, with magnetic remanence (Br) ranging from 85% to 89% of the theoretical values across all batches. The dual plasma-treated batch demonstrated an optimal mechanical profile with an elastic modulus of 578 MPa and the highest ductility at 21%, along with a tensile strength range of 6 to 7 MPa across all batches. Flexural testing indicated that this batch also achieved the highest flexural strength of 15 MPa with a strain of 5%. Environmental stability assessments confirmed that applied plasma treatments did not compromise resistance to corrosion, evidenced by negligible flux loss in both hygrothermal and bulk corrosion tests. These results highlight plasma treatment’s potential to enhance mechanical strength, magnetic performance, and environmental stability.

The wettability of polymers is usually inadequate to ensure the appropriate spreading of polar liquids and thus enable the required adhesion of coatings. A standard ecologically benign method for increasing the polymer wettability is a brief treatment with a non-equilibrium plasma rich in reactive oxygen species and predominantly neutral oxygen atoms in the ground electronic state. The evolution of the surface wettability of selected aromatic polymers was investigated by water droplet contact angles deposited immediately after exposing polymer samples to fluxes of oxygen atoms between 3 × 1020 and 1 × 1023 m−2s−1. The treatment time varied between 0.01 and 1000 s. The wettability evolution versus the O-atom fluence for all aromatic polymers followed similar behavior regardless of the flux of O atoms or the type of polymer. In the range of fluences between approximately 5 × 1020 and 5 × 1023 m−2, the water contact angle decreased exponentially with increasing fluence and dropped to 1/e of the initial value after receiving the fluence close to 5 × 1022 m−2.

Unlike business process diagrams, where ISO/IEC 19510 (BPMN 2.0) prevails, high-level process landscape diagrams are being designed using a variety of standard- or semi-standard-based notations. Consequently, landscape diagrams differ among organizations, domains, and modeling tools. As (process landscape) diagrams need to be understandable in order to communicate effectively and thus form the basis for valid business decisions, this study aims to empirically validate the cognitive effectiveness of common landscape designs, including those BPMN-L-based, which represent a standardized extension of BPMN 2.0 specifically aimed at landscape modeling. Empirical research with 298 participants was conducted in which cognitive effectiveness was investigated by observing the speed, ease, accuracy, and efficiency of answering questions related to semantically equivalent process landscape diagrams modeled in three different notations: value chains, ArchiMate, and BPMN-L. The results demonstrate that BPMN-L-based diagrams performed better than value chain- and ArchiMate-based diagrams concerning speed, accuracy, and efficiency; however, subjects perceived BPMN-L-based diagrams as being less easy to use when compared to their counterparts. The results indicate that differences in cognitive effectiveness measures may result from the design principles of the underlying notations, specifically the complexity of the visual vocabulary and semiotic clarity, which states that modeling concepts should have unique visualizations.

Among Slovenian modernist composers, Darijan Božič dedicated the largest part of his work to musical theatre. The genre classifications of his works show that the composer constantly searched for a new form of musical theatre. It would appear that he finally settled on a medium that could almost be designated as a “radio play”, with an emphasis usually on the spoken word, accompanied by occasional interventions of instrumental music. Over time, these interventions appeared to lose their modernist edge (harmonic clusters) and approach postmodernism by juxtaposing diverse elements. Thus, a characteristic of Božic’s works is their double imbalance: the language strongly dominates the music, while at the same time, the composer’s desire to implement avant-garde theatrical procedures in an institutional opera house seems unusual.

Med slovenskimi skladateljskimi modernisti je glasbenemu gledališču največ pozornosti namenil Darijan Božič. Obravnavana so njegova glasbenogledališka dela, pri čemer je že iz žanrskih podnaslovov posameznih del razvidno, da je skladatelj ves čas iskal novo formo za glasbenogledališko delo. Zdi se, da jo je našel v nekakšnem napol »radijskem« mediju – nosilno težo ima po navadi govorjena beseda, ki jo v obliki zvočne opreme spremljajo redke instrumentalne zvočne intervencije. Te skozi čas izgubljajo modernistično ostrino (harmonski grozdi) in se s sopostavljanjem raznolikega približujejo postmodernizmu. Tako se za Božičeva dela kot značilna izkaže dvojna neuravnoteženost – beseda močno prevlada nad glasbo, hkrati pa se zdi nenavadna skladateljeva želja, da avantgardne gledališke postopke skuša uresničiti v institucionalnem opernem gledališču.

Abstract Early marine cementation is a fundamental process for many characteristics of carbonates, like the stabilisation of steep slopes. The genesis of early cements is often attributed to physicochemical processes but there is evidence for microbial mediation. To elucidate the role of microbes and associated organic material, in vitro experiments were undertaken in the presence and absence of indigenous microbiota in ooids from Schooner Cays, Bahamas and compared with native grapestones from Joulter Cays, Bahamas. Microscopic examinations by stereomicroscopy, scanning electron microscopy and thin section analysis of in vitro incubations with native flora document rapid grain fusion, resulting in the formation of grapestones within 30–60 days. The initial binding of the grains is primarily facilitated by exudates of extracellular polymeric substances and microbial communities acting as catalysts in the formation of micritic bridges, cements and encrusted aggregates. In vitro grapestones are similar to native grapestones from Joulter Cays with intergranular areas infested with extracellular polymeric substances, microbes, micritic cements, amorphous calcium carbonate nanograins and micritised outer surfaces. These similarities suggest that incubations with native flora follow similar mineralisation mechanisms as in the natural environment. In contrast, sterilised grains remain loose with little crystal formation after 60 days and are devoid of microbes and organic exudates. Owing to the near absence of precipitates, abiotic precipitation is not the driving force promoting early cements. In contrast, grain fusion is microbially mediated via both a passive mechanism, where extracellular polymeric substances and cell surfaces function as templates for crystal nucleation and generation of micritic cements, and through an active mechanism by which biofilm heterotrophs and autotrophs induce chemical alterations of a local environment, facilitating precipitation. This study underscores that microbially mediated cementation can occur at fast rates and that firmground to hardgrounds and slope stabilisation take place shortly after deposition of carbonate grains.

Abstract Background Hypoglycaemia and hyperglycaemia may develop during anaesthesia and surgery in children and can lead to severe adverse clinical outcomes. No study, as far as we know, has investigated glucose homeostasis in children undergoing surgery in Malawi. The aim of this study was to assess perioperative glucose levels of the children undergoing anaesthesia at Mercy James Centre (MJC) for Paediatric Surgery, Blantyre, Malawi. Methodology This was an observational cross-sectional study. We looked at 100 children aged 1 day to 15 years anaesthetised at MJC. Data were analysed using SPSS 28. Student t test and Analysis of the variance (ANOVA) were used to compare means. The level of significance was 5%. Results Male children represented 68%. The median age was 2.2 years. Sixten percents of patient were underweight. Fasting times were prolonged for 87%. Maintenance IV fluid with 2.5% dextrose was given to 14%. Overall, there was a significant increase of glycaemia from induction of anaesthesia to the end of the procedure. Hypoglycaemia was rare. The mean fasting glycaemia was 99.04 mg/dL ± 1.8, 116.95 mg/dL ± 34.2 at 30 min into the procedure and 127.62 mg/dL ± 46.8 at the end of the procedure. The differences in means were statistically significant (p

Po smrti skladatelja Janeza Matičiča (1926–2022) je del njegove zapuščine ostal tudi v njegovem pariškem stanovanju. Ta zapuščina zaobsega skladateljeve dokumente, korespondenco, arhiv fotografij, fonoteko, notni material in nekaj osebnih ter tehničnih predmetov. Najzanimivejši del gotovo predstavlja korespondenca, v kateri prevladujejo pisma, ki so jih skladatelju pisali člani družine, nato pa tudi intimni prijatelji in glasbeniški sopotniki. Iz teh pisem je bilo mogoče izluščiti nekatere nove podrobnosti o skladateljevem pariškem vsakdanu in tudi nekaj novih razlogov, zakaj je skladatelj namesto treh mesecev v Parizu ostal nekaj desetletij. Spoznanja o skladateljevi osebnosti je bilo mogoče povezati z nekateri njegovimi osrednjimi estetskimi in kompozicijsko-tehničnimi značilnostmi.

Water scarcity, one of the most pressing challenges we face today, has developed for many reasons, including the increasing number of waterborne pollutants that affect the safety of the water environment. Waterborne human, animal and plant viruses represent huge health, environmental, and financial burden and thus it is important to efficiently inactivate them. Therefore, the main objective of this study was to construct a unique device combining plasma with supercavitation and to evaluate its efficiency for water decontamination with the emphasis on inactivation of viruses. High inactivation (>5 log10 PFU/mL) of bacteriophage MS2, a human enteric virus surrogate, was achieved after treatment of 0.43 L of recirculating water for up to 4 min. The key factors in the inactivation were short-lived reactive plasma species that damaged viral RNA. Water treated with plasma for a short time required for successful virus inactivation did not cause cytotoxic effects in the in vitro HepG2 cell model system or adverse effects on potato plant physiology. Therefore, the combined plasma-supercavitation device represents an environmentally-friendly technology that could provide contamination-free and safe water.

Postopna digitalizacija družbe prinaša jasne spremembe tudi v krajino sodobne nove glasbe. Na podlagi zgodnjih teoretičnih premis o digitalizaciji nove glasbe sta analizirana prva festivala Forum nove glasbe. Analiza in primerjava s predhodnim Festivalom Slowind pokaže, da je novi festival jasno zaznamovan z digitalizacijo. Izkaže se, da je ta v prehodnem stadiju, kar se na estetski ravni kaže v številnih raznolikih kombinacijah digitalnega, »analognega«, konceptualnega, narativnega in abstraktnega.

Pri več kot 85 % žensk med vaginalnim porodom pride do določene stopnje poškodbe presredka, pri čemer se obporodne poškodbe analnega sfinktra pojavljajo v povprečju pri 0,5–7 % vseh vaginalnih porodov. Kar 20–40 % primerov obporodnih poškodb analnega sfinktra je prikritih ali spregledanih, zato jih je izjemno pomembno prepoznati. Če odkrijemo poškodbo analnega sfinktra, jo je treba oskrbeti v operacijski dvorani. Pred kirurško oskrbo moramo zagotoviti ustrezno osvetlitev in analgezijo ter rano natančno pregledati. Anorektalno sluznico zašijemo s posameznimi ali kontinuiranimi šivi, notranji analni sfinkter pa s posameznimi ali t. i. šivi mattress. Pri poškodbah zunanjega analnega sfinktra, ki zajemajo celotno dolžino in debelino mišice, lahko uporabimo bodisi tehniko šivanja konec s koncem bodisi tehniko prekrivanja, pri delnih poškodbah pa tehniko konec s koncem. Na koncu zašijemo še mišice in kožo presredka. Perioperativno je treba uporabiti antibiotično zaščito in odvajala. Po obporodni poškodbi analnega sfinktra je potrebno bolnico spremljati. Prvi pregled naj bo 6 do 12 tednov po porodu. Najpogostejše posledice poškodb analnega sfinktra so bolečina v presredku, bolečine ob spolnih odnosih in druge težave v spolnosti ter analna inkontinenca, ki se pojavi v 15–61 % primerov. Potrebno je opraviti svetovanje glede načina poroda v naslednji nosečnosti, saj se ponovna poškodba analnega sfinktra pojavi v 4–8 %.

In this study, recent advances in tailoring the surface properties of polymers for the optimization of the adhesion of various coatings by non-equilibrium gaseous plasma are reviewed, and important findings are stressed. Different authors have used various experimental setups and reported results that scatter significantly and are sometimes contradictory. The correlations between the processing parameters and the adhesion are drawn, and discrepancies are explained. Many authors have explained improved adhesion with the adjustment of the surface free energy or wettability of the polymer substrate and the surface tension of liquids used for the deposition of thin films. The adhesion force between the polymer substrate and the coating does not always follow the evolution of the surface wettability, which is explained by several effects, including the aging effects due to the hydrophobic recovery and the formation of an interlayer rich in loosely bonded low molecular weight fragments.

Cellulose is an abundant natural polymer and is thus promising for enforcing biobased plastics. A broader application of cellulose fibers as a filler in polymer composites is limited because of their hydrophilicity and hygroscopicity. The recent scientific literature on plasma methods for the hydrophobization of cellulose materials is reviewed and critically evaluated. All authors focused on the application of plasmas sustained in fluorine or silicon-containing gases, particularly tetrafluoromethane, and hexamethyldisiloxane. The cellulose materials should be pre-treated with another plasma (typically oxygen) for better adhesion of the silicon-containing hydrophobic coating. In contrast, deposition of fluorine-containing coatings does not require pre-treatment, which is explained by mild etching of the cellulose upon treatment with F atoms and ions. The discrepancy between the results reported by different authors is explained by details in the gas phase and surface kinetics, including the heating of samples due to exothermic surface reactions, desorption of water vapor, competition between etching and deposition, the influence of plasma radiation, and formation of dusty plasma. Scientific and technological challenges are highlighted, and the directions for further research are provided.

Ad multos annos

Markomanske vojne so bile največji in najobsežnejši oboroženi spo­pad rimske vojske in barbarskih plemen ob osrednjem Podonavju – Markomanov, Kvadov in Sarmatov skupaj s še drugimi plemeni. Vojne z germanskimi plemeni so svoje prve kali kazale že v obdobju Antonina Pija, miroljubnega predhodnika Marka Avrelija, ki je težnje uzurpatorjev skrbno umirjal s konsistentnim pacifizmom. V Panonijo so prihajala poslanstva germanskih kraljevin izza Donave, ki so vznemirjala z vestmi o premikih barbarskih ljudstev s severa. Trgovanje barbarskih ljudstev z rimskimi državljani na mejah rimske države in migracije v germanskem bazenu plemen so v pasu ob limesu predstavljali težnje le-teh po dodatnem habitatu znotraj imperija. Apijan piše, da so poslanstva teh plemen prišla celo v Rim k cesarju Antoninu Piju in ga prosila za sprejem v imperij. Kontinuirani pritiski so eskalirali najverjetneje v l. 166, ko je bil velik del rimske garnizije stacioniran na vzhodni meji v boju s Parti. Limes je bil v tem obdobju slabo zavarovan, saj so bile čete legij, stacioniranih od Rena do Donave, poslane na fronto s Parti. Kljub prizadevanju cesarskih namestnikov v obeh Panonijah, da bi preprečili izbruh vojne na utrjeni državni meji z Donavo, je barbarom uspel preboj čez limes in posledično prodor vse do Akvileje in Opitergija. Boleča zavest o ranljivosti Italije, ki jo je avgustejski mir (Pax Romana) uspaval za več rodov, je prinesla nagel zasuk v obrambi. Pričujoče besedilo pretresa dva glavna vira za dogodke med germansko-sarmatsko vojno in postavlja vprašanja o odsotnosti omemb pomembnega obrambnega sistema, t.i. »Pre­tenture Italije in Alp«.

Introduction: Rising industrial emissions of carbon dioxide and methane highlight the important role of carbon sinks and sources in fast-changing northern landscapes. Northern lake systems play a key role in regulating organic carbon input by accumulating carbon in their sediment. Here we look at the lake history of 28 lakes (between 50°N and 80°N) over the past 21,000 years to explore the relationship between carbon accumulation in lakes and temperature changes.Method: For this study, we calculated organic carbon accumulation rates (OCAR) using measured and newly generated organic carbon and dry bulk density data. To estimate new data, we used and evaluated seven different regression techniques in addition to a log-linear model as our base model. We also used combined age-depth modeling to derive sedimentation rates and the TraCE-21ka climate reanalysis dataset to understand temperature development since the Last Glacial Maximum. We determined correlation between temperature and OCAR by using four different correlation coefficients.Results: In our data collection, we found a slightly positive association between OCAR and temperature. OCAR values peaked during warm periods Bølling Allerød (38.07 g·m−2·yr−1) and the Early Holocene (40.68 g·m−2·yr−1), while lowest values occurred during the cold phases of Last Glacial Maximum (9.47 g·m−2·yr−1) and Last Deglaciation (10.53 g·m−2·yr−1). However, high temperatures did not directly lead to high OCAR values.Discussion: We assume that rapid warming events lead to high carbon accumulation in lakes, but as warming progresses, this effect appears to change as increased microbial activity triggers greater outgassing. Despite the complexity of environmental forcing mechanisms affecting individual lake systems, our study showed statistical significance between measured OCAR and modelled paleotemperature for 11 out of 28 lakes. We concluded that air temperature alone appears to drive the carbon accumulation in lakes. We expected that other factors (catchment vegetation, permafrost, and lake characteristics) would influence accumulation rates, but could not discover a conclusive factor that had a statistical significant impact. More data available on long-term records from northern lake systems could lead to more confidence and accuracy on the matter.

Abstract The transition from milk to solid diets drastically impacts the gut microbiome of calves. We explored the microbial communities of ruminal fluid and feces of Holstein calves when fed milk on d 7 of life, and when fed solid feeds based on either medium- or high-quality hay with or without concentrate inclusion (70% in fresh matter) on d 91. Ruminal fluid and feces had distinct microbial compositions already on d 7, showing that niche specialization in early-life gut is rather diet-independent. Changes between d 7 and d 91 were accompanied by a general increase in microbial diversity. Solid diets differed largely in their carbohydrate composition, being reflected in major changes on d 91, whereby concentrate inclusion was the main driver for differences among groups and strongly decreased microbial diversity in both matrices. Fecal enterotyping revealed two clusters: concentrate-supplemented animals had an enterotype prevalent in Prevotella, Succinivibrio and Anaerovibrio, whereas the enterotype of animals without concentrate was dominated by fibrolytic Ruminococcaceae. Hay quality also affected microbial composition and, compared to medium-quality, high-quality hay reduced alpha-diversity metrics. Concluding, our study revealed that concentrate inclusion, more than hay quality, dictates the establishment of niche-specific, microbial communities in the rumen and feces of calves.

Abstract Microbialites and peloids are commonly associated throughout the geologic record. Proterozoic carbonate megafacies are composed predominantly of micritic and peloidal limestones often interbedded with stromatolitic textures. The association is also common throughout carbonate ramps and platforms during the Phanerozoic. Recent investigations reveal that Hamelin Pool, located in Shark Bay, Western Australia, is a microbial carbonate factory that provides a modern analog for the microbialite-micritic sediment facies associations that are so prevalent in the geologic record. Hamelin Pool contains the largest known living marine stromatolite system in the world. Although best known for the constructive microbial processes that lead to formation of these stromatolites, our comprehensive mapping has revealed that erosion and degradation of weakly lithified microbial mats in Hamelin Pool leads to the extensive production and accumulation of sand-sized micritic grains. Over 40 km2 of upper intertidal shoreline in the pool contain unlithified to weakly lithified microbial pustular sheet mats, which erode to release irregular peloidal grains. In addition, over 20 km2 of gelatinous microbial mats, with thin brittle layers of micrite, colonize subtidal pavements. When these gelatinous mats erode, the micritic layers break down to form platey, micritic intraclasts with irregular boundaries. Together, the irregular micritic grains from pustular sheet mats and gelatinous pavement mats make up nearly 26% of the total sediment in the pool, plausibly producing ~ 24,000 metric tons of microbial sediment per year. As such, Hamelin Pool can be seen as a microbial carbonate factory, with construction by lithifying microbial mats forming microbialites, and erosion and degradation of weakly lithified microbial mats resulting in extensive production of sand-sized micritic sediments. Insight from these modern examples may have direct applicability for recognition of sedimentary deposits of microbial origin in the geologic record.

Abstract Objectives The purpose of this study is to provide expert consensus recommendations to establish a global ultrasound curriculum for undergraduate medical students. Methods 64 multi-disciplinary ultrasound experts from 16 countries, 50 multi-disciplinary ultrasound consultants, and 21 medical students and residents contributed to these recommendations. A modified Delphi consensus method was used that included a systematic literature search, evaluation of the quality of literature by the GRADE system, and the RAND appropriateness method for panel judgment and consensus decisions. The process included four in-person international discussion sessions and two rounds of online voting. Results A total of 332 consensus conference statements in four curricular domains were considered: (1) curricular scope (4 statements), (2) curricular rationale (10 statements), (3) curricular characteristics (14 statements), and (4) curricular content (304 statements). Of these 332 statements, 145 were recommended, 126 were strongly recommended, and 61 were not recommended. Important aspects of an undergraduate ultrasound curriculum identified include curricular integration across the basic and clinical sciences and a competency and entrustable professional activity-based model. The curriculum should form the foundation of a life-long continuum of ultrasound education that prepares students for advanced training and patient care. In addition, the curriculum should complement and support the medical school curriculum as a whole with enhanced understanding of anatomy, physiology, pathophysiological processes and clinical practice without displacing other important undergraduate learning. The content of the curriculum should be appropriate for the medical student level of training, evidence and expert opinion based, and include ongoing collaborative research and development to ensure optimum educational value and patient care. Conclusions The international consensus conference has provided the first comprehensive document of recommendations for a basic ultrasound curriculum. The document reflects the opinion of a diverse and representative group of international expert ultrasound practitioners, educators, and learners. These recommendations can standardize undergraduate medical student ultrasound education while serving as a basis for additional research in medical education and the application of ultrasound in clinical practice.

Celem poniższego artykułu jest naszkicowanie przebiegu działań kasacyjnych Towarzystwa Jezusowego na Śląsku Austriackim na tle mało znanego w Polsce zespołu archiwalnego zgromadzonego przez Archiwum Ziemskie w Opawie (Zemský archiv v Opavě). Podział Śląska pomiędzy Prusy i monarchię habsburską, dokonany w wyniku I wojny śląskiej w 1742 roku, odbił się na strukturze organizacyjnej Towarzystwa Jezusowego na Śląsku. Kolegium jezuickie w Opawie oraz rezydencja w Cieszynie wraz z przynależnymi ośrodkami misyjnymi należały do Prowincji Czeskiej (Provincia Bohemiae), podległy zatem likwidacji bezpośrednio w 1773 roku – w przeciwieństwie do placówek jezuickich na Śląsku Pruskim, należących do odrębnej Prowincji Śląskiej (Provincia Silesiae). Działania kasacyjne dotknęły również częściowo nyskie kolegium jezuickie, które posiadało kilka wsi po stronie austriackiej. Głównym zamierzeniem poniższego opracowania jest przedstawienie charakterystyki działań centralnej austriackiej administracji nadwornej, zastosowanej nie tylko w ramach kasaty Towarzystwa Jezusowego na ziemiach austriackich, lecz również w tzw. kasatach józefińskich przeprowadzonych dekadę później, w latach 80. XVIII wieku. Sposób funkcjonowania biurokracji nadwornej w kwestii koordynacji prac przybliżono na podstawie opawskich dokumentów archiwalnych powstałych w bezpośrednim okresie kasaty. Historię omawianych placówek (do kasaty) naszkicowano jedynie pokrótce, ze względu na fakt, iż została ona już opracowana w literaturze. Zaprezentowano tabelaryczny wykaz archiwaliów zbioru Urzędu Królewskiego w Opawie oraz spis personalny jezuitów dotkniętych kasatą. Publikacja nie jest wyczerpującą analizą źródeł archiwalnych, lecz przyczynkiem do dalszych badań historii działalności Towarzystwa Jezusowego na Śląsku.

Background: We aimed to evaluate the feasibility of a non-contrast time-of-flight magnetic resonance angiography (TOF-MRA) protocol for the pre-procedural access route assessment of transcatheter aortic valve implantation (TAVI) in comparison with contrast-enhanced cardiac dual-source computed tomography angiography (CTA). Methods and Results: In total, 51 consecutive patients (mean age: 82.69 ± 5.69 years) who had undergone a pre-TAVI cardiac CTA received TOF-MRA for a pre-procedural access route assessment. The MRA image quality was rated as very good (median of 5 [IQR 4–5] on a five-point Likert scale), with only four examinations rated as non-diagnostic. The TOF-MRA systematically underestimated the minimal effective vessel diameter in comparison with CTA (for the effective vessel diameter in mm, the right common iliac artery (CIA)/external iliac artery (EIA)/common femoral artery (CFA) MRA vs. CTA was 8.04 ± 1.46 vs. 8.37 ± 1.54 (p < 0.0001) and the left CIA/EIA/CFA MRA vs. CTA was 8.07 ± 1.32 vs. 8.28 ± 1.34 (p < 0.0001)). The absolute difference between the MRA and CTA was small (for the Bland–Altman analyses in mm, the right CIA/EIA/CFA was −0.36 ± 0.77 and the left CIA/EIA/CFA was −0.25 ± 0.61). The overall correlation between the MRA and CTA measurements was very good (with a Pearson correlation coefficient of 0.87 (p < 0.0001) for the right CIA/EIA/CFA and a Pearson correlation coefficient of 0.9 (p < 0.0001) for the left CIA/EIA/CFA). The feasibility agreement between the MRA and CTA for transfemoral access was good (the right CIA/EIA/CFA agreement was 97.9% and the left CIA/EIA/CFA agreement was 95.7%, Kohen’s kappa: 0.477 (p = 0.001)). Conclusions: The TOF-MRA protocol was feasible for the assessment of the access route in an all-comer pre-TAVI population. This protocol might be a reliable technique for patients at an increased risk of contrast-induced nephropathy.

The disciplinary identity of molecular biology has frequently been called into question. Although the debates might sometimes have been more about creating or debunking myths, defending intellectual territory and the distribution of resources, there are interesting underlying questions about this area of biology and how it is conceptually organized. By looking at the history of molecular biology, its origins and development, I examine the possible criteria for its status as a scientific discipline. Doing so allows us to answer the title question in such a way that offers a reasonable middle ground, where molecular biology can be properly viewed as a viable interdisciplinary program that can very well be called a discipline in its own right, even if no strict boundaries can be established. In addition to this historical analysis, a couple of systematic issues from a philosophy of science perspective allow for some assessment of the current situation and the future of molecular biology.

The sedimentary signals of climatic and tectonic events are preserved in pristine condition by the hypersaline environment within brine pools discovered by remote observations, and core and brine sampling, in the Gulf of Aqaba, off the Saudi Arabian coast

Objective Informational social support is one of the main reasons for patients to visit online health communities (OHCs). Calls have been made to investigate the objective quality of such support in the light of a worrying number of inaccurate online health-related information. The main aim of this study is to conceptualize the Quality of Informational Social Support (QISS) and develop and test a measure of QISS for content analysis. A further aim is to investigate the level of QISS in cancer-related messages in the largest OHC in Slovenia and examine the differences among various types of discussion forums, namely, online consultation forums, online support group forums, and socializing forums. Methods A multidimensional measurement instrument was developed, which included 20 items in a coding scheme for a content analysis of cancer-related messages. On a set of almost three million posts published between 2015 and 2019, a machine-learning algorithm was used to detect cancer-related discussions in the OHC. We then identified the messages providing informational social support, and through quantitative content analysis, three experts coded a random sample of 403 cancer-related messages for the QISS. Results The results demonstrate a good level of interrater reliability and agreement for a QISS scale with six dimensions, each demonstrating good internal consistency. The results reveal large differences among the social support, socializing, and consultation forums, with the latter recording significantly higher quality in terms of accuracy (M = 4.48, P

Objective: Understanding factors that impaired mental health during the COVID-19 pandemic is extremely relevant in order to mitigate long-term consequences of the pandemic and to promote resilience in future crises. Method: Data were collected in southern Germany in a population-based survey study (CoKoS) with three times of measurement in May 2020, November 2020 and July 2021. Predictors of depressive and anxiety symptoms were measured with a short version of the Patient Health Questionnaire (PHQ-4) in the general population (N = 758) and individuals who were infected with SARS-CoV-2 in the beginning of the pandemic (N = 412). We investigated differences between both samples and how stress components (worry, tension, demands and joy) measured with the Perceived Stress Questionnaire (PSQ) varied with depressive and anxiety symptoms over time. Three linear mixed models (GLMMs) were fitted to predict the PHQ-4 stepwise, including sociodemographic variables and stress (PSQ). Results: Depressive and anxiety symptoms increased from May 2020 to November 2020 and remained stable until July 2021. There were no differences between people with SARS-CoV-2 infection and the general population. Those with a pre-existing disease and lower education reported higher levels of depressive and anxiety symptoms. Stress explained a substantial fraction of variance in depressive and anxiety symptoms. The stress component worry emerged as the strongest predictor of depressive and anxiety symptoms, whereas joy seemed to buffer these symptoms. Conclusions: The results suggest that mitigating people’s worry and increasing joy may promote resilience in future crises. Future studies should assess mental health interventions targeted at vulnerable groups, such as those with lower socioeconomic status and poorer health.

Calorimetry is a commonly used method in plasma characterization, but the accuracy of the method is tied to the accuracy of the recombination coefficient, which in turn depends on a number of surface effects. Surface effects also govern the kinetics in advanced methods such as atomic layer oxidation of inorganic materials and functionalization of organic materials. The flux of the reactive oxygen atoms for the controlled oxidation of such materials depends on the recombination coefficient of materials placed into the reaction chamber, which in turn depends on the surface morphology, temperature, and pressure in the processing chamber. The recombination coefficient of a well-oxidized cobalt surface was studied systematically in a range of temperatures from 300 to 800 K and pressures from 40 to 200 Pa. The coefficient increased monotonously with decreasing pressure and increasing temperature. The lowest value was about 0.05, and the highest was about 0.30. These values were measured for cobalt foils previously oxidized with oxygen plasma at the temperature of 1300 K. The oxidation caused a rich morphology with an average roughness as deduced from atomic force images of 0.9 µm. The results were compared with literature data, and the discrepancy between results reported by different authors was explained by taking into account the peculiarities of their experimental conditions.

BACKGROUND Results of many randomized trials on COVID-19 convalescent plasma (CCP) have been reported, but information on long-term outcome after CCP treatment is limited. The objectives of this extended observation of the randomized CAPSID trial are to assess long-term outcome and disease burden in patients initially treated with or without CCP.METHODS Of 105 randomized patients, 50 participated in the extended observation. Quality of life (QoL) was assessed by questionnaires and a structured interview. CCP donors (n = 113) with asymptomatic to moderate COVID-19 were included as a reference group.RESULTS The median follow-up of patients was 396 days, and the estimated 1-year survival was 78.7% in the CCP group and 60.2% in the control (P = 0.08). The subgroup treated with a higher cumulative amount of neutralizing antibodies showed a better 1-year survival compared with the control group (91.5% versus 60.2%, P = 0.01). Medical events and QoL assessments showed a consistent trend for better results in the CCP group without reaching statistical significance. There was no difference in the increase in neutralizing antibodies after vaccination between the CCP and control groups.CONCLUSION The trial demonstrated a trend toward better outcome in the CCP group without reaching statistical significance. A predefined subgroup analysis showed a significantly better outcome (long-term survival, time to discharge from ICU, and time to hospital discharge) among those who received a higher amount of neutralizing antibodies compared with the control group. A substantial long-term disease burden remains after severe COVID-19.Trial registration EudraCT 2020-001310-38 and ClinicalTrials.gov NCT04433910.Funding Bundesministerium für Gesundheit (German Federal Ministry of Health).

One of the most recognizable thinkers of the 16th century France, Jean Bodin, wrote what is perhaps the first methodological treatise of instructions and guidelines on how to not only read and write but also understand history. With his universal interest in all things human, Bodin predated Marc Bloch’s postulate that historians should ideally be interested in all forms of life if they were to perform their task as dutifully as possible. In 1566 Bodin published one of the most frequently reprinted works, the Methodus ad facilem historiarum cognitionem – “The Method for the Easy Understanding of History”. Although he expressed keen interest and good knowledge of a score of ancient historians, listing them in the fourth chapter of his work (De historicorum delectu – “On the Choice of Historians”), one of them was particularly close to his heart. The Roman historian Gaius Sallustius Crispus who is, according to Bodin, “a most honest author [who] possessed experience of important affairs”, provided Bodin and many of his colleagues with a model (stasis) narrative for discussing a changing world in turmoil – something Bodin was no stranger to in the time of the French religious wars. However, the explanation that it was the rhetorically efficient model narrative that inspired Bodin to copy Sallust’s argument seems unsatisfactory and biographically superficial. Instead, this paper closely analyses the Sallustian chapters that purportedly motivated Bodin’s thinking and proposes that there are little grounds in Sallust for Bodin’s legal and historical framing of absolutist sovereignty.

Clinical anti-drug-antibody (ADA) responses represent a substantial obstacle to the development of efficacious therapeutic antibodies. The enhanced ADA production against the idiotype (Id) often displayed by cancer immunotherapy antibodies (CitAbs) can lead to exposure loss and subsequently affect anti-tumor efficacy and cause undesired effects on safety. Thus, ADA responses contribute to prolonged clinical development and high attrition rates. Most conventional therapeutic antibodies are now of human origin or humanized proteins, and are hence immunologically tolerized in most patients. In contrast, the contribution of additional factors, other than the protein sequence, to the higher rates of clinical ADA to certain CitAbs, remains poorly understood. Here, we used human immunoglobulin gamma 1 (IgG1) transgenic mice (named “hIgG1 transgenic mice” or “TG”), which are immunologically tolerant to human IgG1, to study the immunogenicity of 13 conventional antibodies and 2 CitAbs. We found that tolerance to non-germline encoded Ids is maintained in part by the function of neonatal Fc-receptor (FcRn). Additionally, the incorporation of T cell-engaging moieties like an interleukin 2 (IL-2)-based immunocytokine or a CD3ε-specific antigen-binding fragment (Fab) was sufficient to revert tolerance and trigger ADA production directed to the Id of these compounds. We postulate that T cell receptor or IL-2 receptor activation may result in activation of unresponsive T cells specific for the crystallizable fragment (Fc) that typically inactivate Id-specific B cells and mediate “linked-antigen tolerance”. Reversal of this unresponsiveness by the action of CitAbs on T cells may be the cause of undesired ADA responses.Abbreviations ADA Anti-Drug Antibodies; BCR B Cell Receptor; BId Idiotype-specific B Cell; BiTE Bispecific T cell Engager; BMC Bone Marrow Chimeric Mice; BSA Bovine Serum Albumin; CDR Complementary Determining Region; CEA Carcinoembryonic Antigen; CIT Cancer Immunotherapy; CitAbs Cancer Immunotherapy Antibodies; DC Dendritic Cell; ELISA Enzyme-Linked Immunosorbent Assay; FcRn Neonatal Fc Receptor; FcyR Fc gamma Receptor; GM-CSF Granulocyte-Macrophage Colony Stimulating Factor; gMFI Geometric Mean Fluorescence Intensity; H Heavy Chain; IC Immune Complex; Id Idiotype; IgA Immunoglobulin alpha; IgG1 Immunoglobulin gamma 1; IL-2 Interleukin 2; IL-2R Interleukin 2 Receptor; IL2v Interleukin 2 Variant; IVIG1 Intravenous Immunoglobulin 1; KLH Keyhole Limpet Hemocyanin; L Light Chain; MAPPs MHC-associated Peptide Proteomics; MHC Major Histocompatibility Complex; PBMC Peripheral Blood Mononuclear Cells; PBS Phosphate Buffered Saline; SHM Somatic Hypermutation; scFv Single-chain Variable Fragment; TCR T cell Receptor; TFc Fc-specific T cell; TId Id-specific T cell; UV Ultraviolet; V Variable.

Decompensation episodes in chronic heart failure patients frequently result in unplanned outpatient or emergency room visits or even hospitalizations. Early detection of these episodes in their pre-symptomatic phase would likely enable the clinicians to manage this patient cohort with the appropriate modification of medical therapy which would in turn prevent the development of more severe heart failure decompensation thus avoiding the need for heart failure-related hospitalizations. Currently, heart failure worsening is recognized by the clinicians through characteristic changes of heart failure-related symptoms and signs, including the changes in heart sounds. The latter has proven to be largely unreliable as its interpretation is highly subjective and dependent on the clinicians’ skills and preferences. Previous studies have indicated that the algorithms of artificial intelligence are promising in distinguishing the heart sounds of heart failure patients from those of healthy individuals. In this manuscript, we focus on the analysis of heart sounds of chronic heart failure patients in their decompensated and recompensated phase. The data was recorded on 37 patients using two types of electronic stethoscopes. Using a combination of machine learning approaches, we obtained up to 72% classification accuracy between the two phases, which is better than the accuracy of the interpretation by cardiologists, which reached 50%. Our results demonstrate that machine learning algorithms are promising in improving early detection of heart failure decompensation episodes.

Cold-water corals mounds develop over millennial timescales as a result of sustained coral growth and concurrent with sediment deposition within their coral frameworks. So far, coral mounds have been primarily investigated as deep-sea biodiversity hotspots and geo-biological paleo-archives, whereas their morphological appearance and spatial arrangement have received much less attention. Here, we analysed the spatial distribution and the morphometry of coral mounds that developed on the Namibian shelf during a single short period dating back to the Early. The spatial distribution of these “early-stage” mounds and their morphological characteristics revealed a hierarchy of three different patterns. These comprise an alongslope mound distribution at a regional scale (first-order pattern), a topography-steered downslope alignment of mounds at a local scale (second-order pattern), and a hydrodynamic-controlled downslope orientation of the individual mounds at a mound scale (third-order pattern). In addition, because the Namibian mounds rarely exceed 20 m in height, key steps in the development of early-stage coral mounds (e.g. elongation, merging, limited gain in height compared to lateral extension) have been identified. With increasing size, coral mounds are more elongated, parallel to the prevailing tidal system, which is interpreted to reflect the transition from an “inherited” to a “developed” mound morphology. Besides supporting this earlier hypothesis on mound development, we could show that this transition takes place when the Namibian coral mounds reach ~150 m in length and ~8 m in height. This study reveals that the spatial-morphological appearance of coral mounds, often treated as a descriptive information, can provide valid information to understand their formation.

The stress response to the COVID-19 pandemic might differ between early and later stages. Longitudinal data on the development of population mental health during COVID-19 pandemic is scarce. We have investigated mental health trajectories and predictors for change in a probability sample of the general population in Germany at the beginning and after 6 months of the pandemic. We conducted a longitudinal survey in a population-based probability sample of German adults. The current study analyzed data from a first assessment in May 2020 (T1; N = 1,412) and a second in November 2020 (T2; N = 743). Mental health was assessed in terms of anxiety and depression using the Patient Health Questionnaire-4 (PHQ-4). Mental health outcomes at T1 were compared with PHQ-4 norm data. Trajectories over time were investigated based on outcome classifications of PHQ-4 scores. Predictors of mental health outcomes and change were identified using multiple regression analysis. In spring 2020, participants showed significantly higher PHQ-4 scores as compared to the norm data, however, overall anxiety and depression remained low also 6 months later. 6.6% of respondents showed a mental health deterioration in autumn 2020, entering subclinical and clinical ranges, outweighing the proportion of people with improved outcomes. Sociodemographic variables associated with mental distress at T1 were mainly not predictive for change at T2. Even under prolonged pandemic-related stress, mental health remained mainly stable in the general population. Further development of the considerable subgroup experiencing deterioration of depression and anxiety should be monitored, in order to tailor prevention and intervention efforts.

ObjectivesTo determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP).MethodsPatients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT04433910). The primary outcome was a dichotomous composite outcome (survival and no longer severe COVID-19 on day 21). Time to clinical improvement was a key secondary endpoint. The concentrations of 27 cytokines were measured (baseline, day 7). We analyzed the change and the correlation between serum cytokine levels over time in different subgroups and the prediction of outcome in receiver operating characteristics (ROC) analyses and in multivariate models.ResultsThe majority of cytokines showed significant changes from baseline to day 7. Some were strongly correlated amongst each other (at baseline the cluster IL-1ß, IL-2, IL-6, IL-8, G-CSF, MIP-1α, the cluster PDGF-BB, RANTES or the cluster IL-4, IL-17, Eotaxin, bFGF, TNF-α). The correlation matrix substantially changed from baseline to day 7. The heatmaps of the absolute values of the correlation matrix indicated an association of CCP treatment and clinical outcome with the cytokine pattern. Low levels of IP-10, IFN-γ, MCP-1 and IL-1ß on day 0 were predictive of treatment success in a ROC analysis. In multivariate models, low levels of IL-1ß, IFN-γ and MCP-1 on day 0 were significantly associated with both treatment success and shorter time to clinical improvement. Low levels of IP-10, IL-1RA, IL-6, MCP-1 and IFN-γ on day 7 and high levels of IL-9, PDGF and RANTES on day 7 were predictive of treatment success in ROC analyses. Low levels of IP-10, MCP-1 and high levels of RANTES, on day 7 were associated with both treatment success and shorter time to clinical improvement in multivariate models.ConclusionThis analysis demonstrates a considerable dynamic of cytokines over time, which is influenced by both treatment and clinical course of COVID-19. Levels of IL-1ß and MCP-1 at baseline and MCP-1, IP-10 and RANTES on day 7 were associated with a favorable outcome across several endpoints. These cytokines should be included in future trials for further evaluation as predictive factors.