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Abstract Background Cardiac positron emission tomography (PET) offers non-invasive assessment of perfusion and left ventricular (LV) function from a single dynamic scan. However, no prior assessment of mitral regurgitation severity by PET has been presented. Application of indicator dilution techniques and gated image analyses to PET data enables calculation of forward stroke volume and total LV stroke volume. We aimed to evaluate a combination of these methods for measurement of regurgitant volume (RegVol) and fraction (RegF) using dynamic 15O-water and 11C-acetate PET in comparison to cardiovascular magnetic resonance (CMR). Results Twenty-one patients with severe primary mitral valve regurgitation underwent same-day dynamic PET examinations (15O-water and 11C-acetate) and CMR. PET data were reconstructed into dynamic series with short time frames during the first pass, gated 15O-water blood pool images, and gated 11C-acetate myocardial uptake images. PET-based RegVol and RegF correlated strongly with CMR (RegVol: 15O-water r = 0.94, 11C-acetate r = 0.91 and RegF: 15O-water r = 0.88, 11C-acetate r = 0.84, p 30mL) was 95% for 15O-water and 92% for 11C-acetate. Conclusions LV regurgitation severity quantified using cardiac PET correlated with CMR and showed high accuracy for discriminating patients from healthy volunteers.

Abstract Background DNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as “mosaic”. Yet, the role and developmental dynamics of 5mC and how these explain interspecies differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla. Results Here, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, alongside a gradual and global, age-dependent demethylation in adult stages. Additionally, reducing 5mC levels with cytidine analogs during early development impairs normal embryogenesis and reactivates TEs in the annelid Owenia fusiformis. Conclusions Our study indicates that global epigenetic erosion during development and aging is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely more important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.

Abstract Background To strengthen palliative care for children in the Nordic countries, an updated status of current needs, resources, clinical services, education, and research is necessary to align and consolidate future research. A Nordic research collaboration initiative for children with palliative care needs was assembled in 2023. Building on this initiative, this paper presents an overview of pediatric palliative care (PPC) in the Nordic countries’ (a) population characteristics, (b) care models and setting of care, (c) education and training, and (d) research. Methods The Nordic initiative researchers collaboratively gathered and assessed available data on the characteristics of PPC within Denmark, Finland, Greenland, Iceland, Norway, the Faroe Islands, Sweden, and Åland. Data were compiled in a matrix with population characteristics, models- and setting of care, education and training, and areas of research in a Nordic context. The findings are narratively and descriptively presented, providing an overview of Nordic PPC. Results In total, the Nordic child population comprises around six million children (0–19 years), of which about 41.200 are estimated to be living with a life-limiting and/or life-threatening condition. Healthcare services are provided through various care models, ranging from specialized care to homecare settings. Overall, there remain few opportunities for education and training with some exceptions. Also, Nordic research within PPC has been shown to be a growing field although much remains to be done. Conclusion This overview is the first outline of the current PPC in Nordic countries. Although some differences remain important to acknowledge, overall, the strengths and challenges faced within PPC in the Nordic countries are comparable and call for joint action to increase evidence, services, and education to better serve the children, families, and healthcare personnel within PPC. Despite the varying structural premises for PPC, research endeavors aiming to provide evidence in this field seem increasing, timely and relevant for the Nordic countries, as well as the international context.

In general, innovation is considered a success element behind growth and competitiveness of manufacturing firms. This study investigated the impact of product and process innovation capability practices on competitiveness of manufacturing enterprises in Ethiopia. It also intended to test whether competitive advantage mediated the relationship between product innovation and competitiveness as well as process innovation and competitiveness. Quantitative research approach was used to collect questionnaire based data from 300 randomly selected manufacturing firms in Ethiopia; out of these, 270 were correctly completed and returned. Structural equation modeling with AMOS v23 was used for data analysis. Measurement model’s validation was done using confirmatory factor analysis in which all of the variables were assessed for convergent, composite and discriminant validity tests. The findings indicated that both product and process innovations had a significant direct effect on manufacturing firm’s competitiveness of manufacturing firms in Ethiopia. Moreover, both product and process innovations had a significant indirect effect on competitiveness through competitive advantage as the mediating variable. Competitive advantage as a mediating variable had a significant mediating role between product innovation and competitiveness, and between process innovation and competitiveness. These findings have substantial implications for manufacturing firms in Ethiopia to gear their energies towards improvement of products offered to market as well as those processes intended to produce quality products which outshines the internal and external competitions in the market. Hence, Ethiopian businesses are recommended to invest more in product and process innovations to build competitive advantage and competitiveness.

Even though Ethiopia recently adopted industrial park development as a policy instrument for fostering economic transformation, the effects of value chain management practices on firm performance has not been well researched. Thus, the study examined the effect of value chain management practices on the performance of manufacturing firms operating in Ethiopian industrial parks by using an explanatory research design. Employees of the industrial parks were considered as the target population and to select suitable respondents, a non-probability sampling technique was employed. The sample size was determined to be 382, which comprised of senior and middle managers. The study purified and validated scales for data collection by using Confirmatory Factor Analysis (CFA) and to test the hypothesis, Structural Equation Modeling (SEM) was used. The result of the study revealed that outbound logistics and marketing capabilities, statistically positively and significantly, affected financial and marketing performances. However, both inbound logistics and operations management capabilities did not significantly affect financial and marketing performance. Enhancing backward and forward linkage along the value chain and improving the efficiency of value chain management practices are paramount strategies. From the empirical evidence, the result of this study adds value to the existing knowledge of value chain management in industrial park contexts. Further, the paper significantly contributes to the field of industrial parks economic sustainability, in which the findings and suggestions can provide scientific knowledge to managers, practitioners, stakeholders, and policymakers.

The Hunga Tonga–Hunga Ha′apai volcano erupted on 15 January 2022, launching Lamb waves and gravity waves into the atmosphere. In this study, we present results using 13 globally distributed meteor radars and identify the volcanogenic gravity waves in the mesospheric/lower thermospheric winds. Leveraging the High-Altitude Mechanistic general Circulation Model (HIAMCM), we compare the global propagation of these gravity waves. We observed an eastward-propagating gravity wave packet with an observed phase speed of 240 ± 5.7 m s−1 and a westward-propagating gravity wave with an observed phase speed of 166.5 ± 6.4 m s−1. We identified these waves in HIAMCM and obtained very good agreement of the observed phase speeds of 239.5 ± 4.3 and 162.2 ± 6.1 m s−1 for the eastward the westward waves, respectively. Considering that HIAMCM perturbations in the mesosphere/lower thermosphere were the result of the secondary waves generated by the dissipation of the primary gravity waves from the volcanic eruption, this affirms the importance of higher-order wave generation. Furthermore, based on meteor radar observations of the gravity wave propagation around the globe, we estimate the eruption time to be within 6 min of the nominal value of 15 January 2022 04:15 UTC, and we localized the volcanic eruption to be within 78 km relative to the World Geodetic System 84 coordinates of the volcano, confirming our estimates to be realistic.

Abstract This systematic review aims to review the effect of innovation strategy on firm competitiveness and to establish a theoretical background for future studies in the innovation and firm competitiveness literature. A total of 40 studies covering the innovation strategy and firm competitiveness were from 2015 to 2023 and analysed via a PRISMA method using the descriptive content analysis. These studies were found in the Scopus, Web of Science, PubMed, and Taylor and Francis databases. The findings from this review show that a large majority of the reviewed studies has concluded that innovation strategy have a positive relationship and effect between firm competitiveness. This study offers the chance to empirically examine innovation strategy and firm competitiveness from various angles. Despite a rapid recent increase in publications and special issue calls, many opportune research avenues within the innovation strategy and firm competitiveness field require further investigation.

The paper describes technical characteristics and presents the first scientific results of a novel infrared imaging system (imager) for studies of nightglow emissions coming from the hydroxyl (OH) and molecular oxygen (O2) layers in the mesopause region (80–100 km) above northern Scandinavia. The OH imager was put into operation in November 2022 at the Swedish Institute of Space Physics in Kiruna (67.86° N, 20.42° E; 400 m altitude). The OH imager records selected emission lines in the OH(3-1) band near 1500 nm to obtain intensity and temperature maps at around 87 km altitude. In addition, the OH imager registers infrared emissions coming from the O2 IR A-band airglow at 1268.7 nm in order to obtain O2 intensity maps at a slightly higher altitude, around 94 km. This technique allows the tracing of wave disturbances in both horizontal and vertical domains in the mesopause region. Validation and comparison of the OH(3-1) rotational temperature with collocated lidar and Aura Microwave Limb Sounder (MLS) satellite temperatures are performed. The first scientific results obtained from the OH imager for the first winter season (2022–2023) are discussed.

Abstract Aims This study aimed to study the prognostic value of myocardial oxygen consumption (MVO2) and myocardial external efficiency (MEE) from 11C‐acetate positron emission tomography (PET) in cardiac amyloidosis (CA) patients. Methods and results Forty‐eight CA patients, both transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis, and 20 controls were included. All subjects were examined with 11C‐acetate PET and echocardiography. MVO2, forward stroke volume (FSV), and left ventricular mass (LVM) were derived from 11C‐acetate PET and used to calculate MEE. CA patients were followed for survival and the prognostic impact of clinical, echocardiographic, and 11C‐acetate PET parameters was analysed. MVO2 and MEE were reduced in CA compared with controls, but without significant difference between deceased and surviving CA patients. The ratio of 11C‐acetate PET‐derived FSV and LVM was also reduced in CA and significantly lowered in deceased patients compared with survivors. In univariate analysis, New York Heart Association class, N‐terminal pro‐brain natriuretic peptide, and the 11C‐acetate PET parameters FSV/LVM and MEE were the strongest prognostic factors. Of the 11C‐acetate PET parameters, FSV/LVM was the strongest survival predictor with hazard ratio of 0.56 per 0.1 mL/g (95% confidence interval 0.39–0.81, P = 0.002) and independently prognostic in a multivariate model. MEE significantly separated deceased from surviving CA patients with the cut‐off of 15.7% (P = 0.032). Survival was significantly shorter with FSV/LVM below 0.27 mL/g (P

Abstract A minequake of magnitude ML 4.1 occurred on 18 May 2020 early in the morning at the LKAB underground iron ore mine in Kiruna, Sweden. This is the largest mining‐induced earthquake in Scandinavia. It generated acoustic signals observed at three infrasound arrays at 9.3 (KRIS, Sweden), 155 (IS37, Norway), and 286 km (ARCI, Norway) distance. We perform full‐waveform focal mechanism inversion based on regional seismic data and local infrasound data. These independently highlight that this event was dominated by a shallow‐depth collapse in agreement with in‐mine seismic station data. However, regional infrasound data cannot inform the inversion process without an accurate model of atmospheric winds and temperatures. Yet, our numerical simulations demonstrate a potential of using local and regional infrasound data to constrain an event's focal mechanism and depth.

This work is dedicated to developing a laboratory method for assessing emissions of polycyclic aromatic hydrocarbons (PAHs) from different carbon-based materials at elevated temperatures. The method will additionally contribute to enhancing the fundamental knowledge about the formation and decomposition of these compounds during various process conditions. Developing a method entails designing a setup for laboratory-scale experiments utilizing different furnace configurations and off-gas capturing media. To demonstrate the method's applicability, different carbon materials were tested under identical conditions, and analysis results for the same material in different furnace setups were compared. In this article, we have focused on the procedure for obtaining the “fingerprint” of PAH emissions under conditions characteristic of industrial processes. • Two setups for investigation of the influence of temperature on PAH emissions were designed and tested for three types of carbon materials. • The collected off-gas samples underwent analysis in two different laboratories to capture intra-laboratory differences and to evaluate the significance of the instrument detection limit. • The results of PAH 16 (16 EPA PAH) and PAH 42 analysis were compared to showcase the influence of the expanded list on the overall emission of PAH.The novel methodology enables the determination and comparison of PAH emissions during the thermal treatment of individual carbon materials under laboratory conditions. This could potentially be a new approach for predicting the PAH emissions in metallurgical industries that use these carbon materials as reducing agents in their processes and their control by optimizing process parameters and raw materials used. In addition to being suitable for simulating various conditions in the metallurgical industry, the utilization of low-hazard PAH solvents makes it a promising method.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer's disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese-American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia-broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with "frequent" neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer's disease neuropathology.

Analysis of pesticide residue levels in juice beverages is important to ensure safe consumption and avoid global trade concerns associated to pesticide contaminations. A simple, inexpensive and effective method was developed for the determination of organochlorine pesticides (OCPs) in bottled juice drinks using GC-MS. Sample pretreatment was performed using dispersive solid-phase microextraction (D-μ-SPE) for matrix desorption and dispersive liquid-liquid microextraction (DLLME) for analyte enrichment. In this study, an affordable and effective sorbent for the adsorption of OCPs from juice samples was synthesized from avocado seeds mixed with magnetic precursors for D-μSPE. The ground avocado seeds combined with a magnetic precursor nanocomposite were characterized using various instruments including scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Brunauer-Emmett-Teller (BET) analysis. The solution obtained from D-μ-SPE desorption was used as a dispersant for the subsequent DLLME, which made the combination of D-μ-SPE with DLLME much easier. The effectiveness of the method was enhanced by optimizing the influential parameters in both D-μ-SPE and DLLME. Then after, the optimal values were determined for the real sample analysis. Accordingly, there was good linear dynamic range with a coefficient of determination (r2) ≥ 0.9989. The limit of detection and quantification were 0.02–0.69 and 0.06–2.10 ng/L respectively. The method showed high enrichment factors ranging from 96 to 313 with recoveries of 87–100 %. Intraday and interday precisions were ≤4 %. Compared with other reported methods, this method is a one-step, simple, cheap, fast, and environmentally friendly alternative and straightforward method for adsorbing organochlorine pesticides from sample solutions. These results demonstrates the high potential of the proposed method for the extraction and cleanup of contaminants in selected juices and other related samples.

The hope of reaching diverse and large target groups has motivated civic education practitioners to offer their content on social media. The question has therefore long ceased to be whether civic education should take place on the internet, but rather how civic education goals can be implemented digitally to foster civic literacy. At first glance, the possibility of reaching a broad audience in a short time seems tempting. At a second glance, social media reveals several challenges that can impair educational processes. The present paper discusses the following questions: What are the opportunities and pitfalls of civic education in social media? How can we ensure successful civic education in a digitalized world? In our article, we want to provide an interdisciplinary perspective on the topic by drawing among others from the literature in the fields of media psychology, communication studies, and education science. By integrating insights from various disciplines, our paper seeks to enrich the academic dialogue and to promote a nuanced understanding of the evolving dynamics of civic education in the digital realm. With its practical focus, our paper further aims to underscore the applicability of scientific research.

Atmospheric gravity waves and traveling ionospheric disturbances can be observed in the neutral atmosphere and the ionosphere at a wide range of spatial and temporal scales. Especially at medium scales, these oscillations are often not resolved in general circulation models and are parameterized. We show that ionospheric disturbances forced by upward-propagating atmospheric gravity waves can be simultaneously observed with the EISCAT very high frequency incoherent scatter radar and the Nordic Meteor Radar Cluster. From combined multi-static measurements, both vertical and horizontal wave parameters can be determined by applying a specially developed Fourier filter analysis method. This method is demonstrated using the example of a strongly pronounced wave mode that occurred during the EISCAT experiment on 7 July 2020. Leveraging the developed technique, we show that the wave characteristics of traveling ionospheric disturbances are notably impacted by the fall transition of the mesosphere and lower thermosphere. We also demonstrate the application of using the determined wave parameters to infer the thermospheric neutral wind velocities. Applying the dissipative anelastic gravity wave dispersion relation, we obtain vertical wind profiles in the lower thermosphere.

Objective: Nonautoimmune hyperthyroidism (NAH) is rare and occurs due to a constitutively activating thyroid stimulating hormone receptor (TSHR) mutation. In contrast to other thyroid nodules, no further evaluation for malignancy is recommended for hot thyroid nodules. In the first model for NAH in mice nearly all homozygous mice had developed papillary thyroid cancer by 12 months of age. Methods: To further evaluate these mice, whole exome sequencing and phosphoproteome analysis were employed in a further generation of mice to identify any other mutations potentially responsible and to identify the pathways involved in thyroid carcinoma development. Results: Only three genes (Nrg1, Rrs1, Rasal2) were mutated in all mice examined, none of which were known primary drivers of papillary thyroid cancer development. Wild-type and homozygous TSHR D633H knockin mice showed distinct phosphoproteome profiles with an enrichment of altered phosphosites found in ERK/mitogen-activated protein kinase (MAPK) signaling. Most importantly, phosphosites with known downstream effects included BRAF p.S766, which forms an inhibitory site: a decrease of phosphorylation at this site suggests an increase in MEK/ERK pathway activation. The decreased phosphorylation at BRAF p.S766 would suggest decreased AMP-activated protein kinase (AMPK) signaling, which is supported by the decreased phosphorylation of STIM1 p.S257, a downstream AMPK target. Conclusion: The modified phosphoproteome profile of the homozygous mice in combination with human literature suggests a potential signaling pathway from constitutive TSHR signaling and cAMP activation to the activation of ERK/MAPK signaling. This is the first time that a specific mechanism has been identified for a possible involvement of TSH signaling in thyroid carcinoma development.

The aim of the paper is to present a structure for nursing education simulation that incorporates elements of blended and online simulation in a socially constructivist, culturally sensitive environment. To develop the structure for nursing education, a descriptive literature review was conducted in spring 2022 on simulations implemented in mental health nursing education. Nurses require the skills and knowledge to provide mental health care in every area of health care. According to the descriptive literature review, simulation-based learning such as high-fidelity mental health simulation resulted in increased confidence, knowledge gains and improved communication skills. Simulation is a wide concept and allows nurse lecturers to implement the pedagogy as they see it best. The Simulation structure helps especially beginners to follow the simulation as a process. The structure eases the planning phase as well as the debriefing part of the simulation. As it has been shown in the analysis of the literature simulation can be effectively implemented in a blended and / or online environment. It is expected that in the future, simulation games and virtual, online simulations will be more typical ways to conduct a simulation.

Abstract Aim To explore nurses' perceptions to alleviate dyspnoea in inpatients with advanced cancer while receiving palliative care. Design A descriptive qualitative design. Methods Seven focus groups were conducted with nurses (n = 27) from five specialized palliative care wards in four hospitals in south and southwest Finland. The focus groups were conducted between June and November 2019, and the transcripts were analysed using inductive analysis. Results The findings revealed three categories: recognizing dyspnoea is a multi‐faceted problem, dealing with the complexity of assessment of dyspnoea and strategies for relieving dyspnoea. Nurses perceived the complexity of dyspnoea as a symptom and emphasized the importance of utilizing patients' subjective experiences and consistent assessment scales to determine its severity. Furthermore, nonpharmacological interventions are as pertinent as pharmacological and medical interventions. The findings can assist nurses in selecting appropriate interventions for dyspnoea care, ultimately enhancing the quality of patient care and patient safety.

The COVID-19 pandemic created stress and trauma for many individuals. Traumatic experiences often trigger reflection on meaning in life, with subsequent growth or despair. This study evaluates the role of meaning in life in buffering stressors in the early stages of the COVID-19 pandemic. The purpose of this study was to determine the extent to which the negative effects of COVID-19 stressors (self-perceived stress, emotional state, and cognitive adaptation to stress in the pandemic) are influenced by meaning in life in the context of the early stages of the pandemic. Further, this study described differences in meaning in life observed across demographic groups.Web-based surveys were completed by 831 Slovenian participants in April of 2020. Demographic data; perceptions of stressors related to lacking necessities, movement restrictions, and concerns at home; meaning in life; perceived overall health status; anxiety; emotional state; and perceived stress were measured.A moderately strong sense of meaning in life (M = 5.0, SD = 0.74, range 1–7) was reported by participants, and meaning in life was associated with enhanced wellbeing (B = 0.06-0.28, p < .01). Both direct and indirect relationships were observed between stressors and wellbeing outcomes. The indirect effects of meaning in life were especially prominent in the relationship between stressors related to lacking necessities and concerns at home and outcomes of anxiety, perceived stress, and negative emotions, contributing 13–27% of the total observed effects. Increased meaning in life was observed across older age groups (F(5, 825) = 4.8, p < .001) and for those in partnered relationships (t(829) = -3.397, p

Objectives The aim included investigation of the associations between sedentary (SED), low-intensity physical activity (LIPA), moderate-to-vigorous intensity PA (MVPA) and the prevalence of subclinical atherosclerosis in both coronaries and carotids and the estimated difference in prevalence by theoretical reallocation of time in different PA behaviours.Design Cross-sectional.Setting Multisite study at university hospitals.Participants A total of 22 670 participants without cardiovascular disease (51% women, 57.4 years, SD 4.3) from the population-based Swedish CArdioPulmonary bioImage study were included. SED, LIPA and MVPA were assessed by hip-worn accelerometer.Primary and secondary outcomes Any and significant subclinical coronary atherosclerosis (CA), Coronary Artery Calcium Score (CACS) and carotid atherosclerosis (CarA) were derived from imaging data from coronary CT angiography and carotid ultrasound.Results High daily SED (>70% ≈10.5 hours/day) associated with a higher OR 1.44 (95% CI 1.09 to 1.91), for significant CA, and with lower OR 0.77 (95% CI 0.63 to 0.95), for significant CarA. High LIPA (>55% ≈8 hours/day) associated with lower OR for significant CA 0.70 (95% CI 0.51 to 0.96), and CACS, 0.71 (95% CI 0.51 to 0.97), but with higher OR for CarA 1.41 (95% CI 1.12 to 1.76). MVPA above reference level, >2% ≈20 min/day, associated with lower OR for significant CA (OR range 0.61–0.67), CACS (OR range 0.71–0.75) and CarA (OR range 0.72–0.79). Theoretical replacement of 30 min of SED into an equal amount of MVPA associated with lower OR for significant CA, especially in participants with high SED 0.84 (95% CI 0.76 to 0.96) or low MVPA 0.51 (0.36 to 0.73).Conclusions MVPA was associated with a lower risk for significant atherosclerosis in both coronaries and carotids, while the association varied in strength and direction for SED and LIPA, respectively. If causal, clinical implications include avoiding high levels of daily SED and low levels of MVPA to reduce the risk of developing significant subclinical atherosclerosis.

The Hunga Tonga–Hunga Ha′apai volcano eruption was a unique event that caused many atmospheric phenomena around the globe. In this study, we investigate the atmospheric gravity waves in the mesosphere/lower-thermosphere (MLT) launched by the volcanic explosion in the Pacific, leveraging multistatic meteor radar observations from the Chilean Observation Network De Meteor Radars (CONDOR) and the Nordic Meteor Radar Cluster in Fennoscandia. MLT winds are computed using a recently developed 3DVAR+DIV algorithm. We found eastward- and westward-traveling gravity waves in the CONDOR zonal and meridional wind measurements, which arrived 12 and 48 h after the eruption, and we found one in the Nordic Meteor Radar Cluster that arrived 27.5 h after the volcanic detonation. We obtained observed phase speeds for the eastward great circle path at both locations of about 250 m s−1, and they were 170–150 m s−1 for the opposite propagation direction. The intrinsic phase speed was estimated to be 200–212 m s−1. Furthermore, we identified a potential lamb wave signature in the MLT winds using 5 min resolved 3DVAR+DIV retrievals.

Abstract Universal testing for microsatellite instability (MSI) is recommended in colorectal cancer (CRC) to screen for Lynch syndrome and to guide optimal treatment and follow-up of the patients. Especially in neoadjuvant setting, where immuno-oncological treatments have recently shown excellent responses, identification of MSI status at biopsy is a prerequisite. Idylla MSI test offers a rapid and automated test to assess MSI-status from formalin-fixed paraffin-embedded tumor tissue sections. In this study, we compared the performance of the Idylla MSI test to mismatch repair (MMR) protein immunohistochemistry (IHC) using 117 CRC biopsies with previously known deficient MMR status. The concordance between Idylla and IHC was 99.0% (95/96) for biopsies with the recommended ≥ 20% tumor cell content. Further, 85.7% (18/21) of suboptimal CRC biopsy specimens (tumor cell content 5–15%) were diagnosed as MSI. Overall, we identified four discrepant cases of which three had tumor cell content less than 20%, explaining the discordant result. Our study shows that the Idylla MSI test offers a competent tool for MSI screening in CRC biopsy specimens.

Abstract Vector or reservoir species of three diseases of crustaceans listed in the Animal Health Law were identified based on evidence generated through an extensive literature review, to support a possible updating of Regulation (EU) 2018/1882. Crustacean species on or in which Taura syndrome virus (TSV), Yellow head virus (YHV) or White spot syndrome virus (WSSV) were identified, in the field or during experiments, were classified as reservoir species with different levels of certainty depending on the diagnostic tests used. Where experimental evidence indicated transmission of the pathogen from a studied species to another known susceptible species, the studied species was classified as vector species. Although the quantification of the risk of spread of the pathogens by the vectors or reservoir species was not part of the terms of reference, such risks do exist for the vector species, since transmission from infected vector species to susceptible species was proven. Where evidence for transmission from infected crustaceans was not found, these were defined as reservoirs. Nonetheless, the risk of the spread of the pathogens from infected reservoir species cannot be excluded. Evidence identifying conditions that may prevent transmission by vectors during transport was collected from scientific literature. It was concluded that it is very likely to almost certain (90–100%) that WSSV, TSV and YHV will remain infective at any possible transport condition. Therefore, vector or reservoir species that may have been exposed to these pathogens in an affected area in the wild or aquaculture establishments or by water supply can possibly transmit WSSV, TSV and YHV.

Abstract Vector or reservoir species of five mollusc diseases listed in the Animal Health Law were identified, based on evidence generated through an extensive literature review, to support a possible updating of Regulation (EU) 2018/1882. Mollusc species on or in which Mikrocytos mackini, Perkinsus marinus, Bonamia exitiosa, Bonamia ostreae and Marteilia refringens were detected, in the field or during experiments, were classified as reservoir species with different levels of certainty depending on the diagnostic tests used. Where experimental evidence indicated transmission of the pathogen from a studied species to another known susceptible species, this studied species was classified as a vector species. Although the quantification of the risk of spread of the pathogens by the vectors or reservoir species was not part of the terms of reference, such risks do exist for the vector species, since transmission from infected vector species to susceptible species was proven. Where evidence for transmission from infected molluscs was not found, these were defined as reservoir. Nonetheless, the risk of the spread of the pathogens from infected reservoir species cannot be excluded. Evidence identifying conditions that may prevent transmission by vectors or reservoir mollusc species during transport was collected from scientific literature. It was concluded that it is very likely to almost certain (90–100%) that M. mackini, P. marinus, B. exitiosa B. ostreae and M. refringens will remain infective at any possible transport condition. Therefore, vector or reservoir species that may have been exposed to these pathogens in an affected area in the wild or at aquaculture establishments or through contaminated water supply can possibly transmit these pathogens. For transmission of M. refringens, the presence of an intermediate host, a copepod, is necessary.

Abstract Vector or reservoir species of five fish diseases listed in the Animal Health Law were identified, based on evidence generated through an extensive literature review (ELR), to support a possible updating of Regulation (EU) 2018/1882. Fish species on or in which highly polymorphic region‐deleted infectious salmon anaemia virus (HPR∆ ISAV), Koi herpes virus (KHV), epizootic haematopoietic necrosis virus (EHNV), infectious haematopoietic necrosis virus (IHNV) or viral haemorrhagic septicaemia virus (VHSV) were detected, in the field or during experiments, were classified as reservoir species with different levels of certainty depending on the diagnostic tests used. Where experimental evidence indicated transmission of the pathogen from a studied species to another known susceptible species, the studied species was classified as a vector species. Although the quantification of the risk of spread of the pathogens by the vectors or reservoir species was not part of the terms or reference, such risks do exist for the vector species, since transmission from infected vector species to susceptible species was proven. Where evidence for transmission from infected fish was not found, these were defined as reservoirs. Nonetheless, the risk of the spread of the pathogens from infected reservoir species cannot be excluded. Evidence identifying conditions that may prevent transmission by vectors or reservoir fish species during transport was collected from scientific literature. For VHSV, IHNV or HPR∆ ISAV, it was concluded that under transport conditions at temperatures below 25°C, it is likely (66–90%) they will remain infective. Therefore, vector or reservoir species that may have been exposed to these pathogens in an affected area in the wild, aquaculture establishments or through water supply can possibly transmit VHSV, IHNV or HPR∆ ISAV into a non‐affected area when transported at a temperature below 25°C. The conclusion was the same for EHN and KHV; however, they are likely to remain infective under all transport temperatures.

Summary: Background: People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down. Methods: Biological age was estimated through patterns of sugar molecules attached to plasma immunoglobulin-G (IgG-glycans, an established “biological-ageing-clock”) in n = 246 individuals with DS from three European populations, clinically characterised for the presence of co-morbidities, and compared to n = 256 age-, sex- and demography-matched healthy controls. Isogenic human induced pluripotent stem cell (hiPSCs) models of full and partial trisomy-21 with CRISPR-Cas9 gene editing and two kinase inhibitors were studied prior and after differentiation to cerebral organoids. Findings: Biological age in adults with DS is (on average) 18.4–19.1 years older than in chronological-age-matched controls independent of co-morbidities, and this shift remains constant throughout lifespan. Changes are detectable from early childhood, and do not require a supernumerary chromosome, but are seen in segmental duplication of only 31 genes, along with increased DNA damage and decreased levels of LaminB1 in nucleated blood cells. We demonstrate that these cell-autonomous phenotypes can be gene-dose-modelled and pharmacologically corrected in hiPSCs and derived cerebral organoids. Using isogenic hiPSC models we show that chromosome-21 gene DYRK1A overdose is sufficient and necessary to cause excess unrepaired DNA damage. Interpretation: Explanation of hitherto observed accelerated ageing in DS as a developmental progeroid syndrome driven by DYRK1A overdose provides a target for early pharmacological preventative intervention strategies. Funding: Main funding came from the “Research Cooperability” Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014–2020, Project PZS-2019-02-4277, and the Wellcome Trust Grants 098330/Z/12/Z and 217199/Z/19/Z (UK). All other funding is described in details in the “Acknowledgements”.

Prilikom pregledavanja novovjekovne arhivske građe povezane s Biogradom i okolnim prostorom u fondu Bilježnici Zadra u Državnom arhivu u Zadru uočeno je kako se u devetom svežnju zadarskog bilježnika Tomassa de Franceschija nalazi neobično velik broj neobjavljenih glagoljičnih dokumenata. Dodatnim je pregledom primijećeno da se više od polovice svih glagoljičnih dokumenata u tom svežnju odnosi upravo na Biograd. U ovom se radu objavljuju transliteracije tih dokumenata, koje će zasigurno pružiti relevantne podatke budućim istraživačima demografije i zemljišnih odnosa na području Biograda i njegove okolice u ranom novom vijeku. Pritom je važno naglasiti da se u ovom radu pod biogradskim glagoljičnim ispravama uz isprave biogradskih pisara podrazumijevaju i dokumenti pisani u Biogradu bez obzira na provenijenciju pisara te dokumenti u kojima su stranke ili barem jedna od stranaka iz Biograda.

Abstract Evolving evidence has supported the existence of two anatomically distinct Lewy-related pathology (LRP) types. Investigation of spinal cord and peripheral LRP can elucidate mechanisms of Lewy body disorders and origins of synuclein accumulation. Still, very few unselected studies have focused on LRP in these regions. Here we analysed LRP in spinal cord, dorsal root ganglion, and adrenal gland in the population-based Vantaa 85 + study, including every ≥ 85 years old citizen living in the city of Vantaa in 1991 (n = 601). Samples from spinal cord (C6-7, TH3-4, L3-4, S1-2) were available from 303, lumbar dorsal root ganglion from 219, and adrenal gland from 164 subjects. Semiquantitative scores of LRP were determined from immunohistochemically stained sections (anti-alpha-synuclein antibody 5G4). LRP in the ventral and dorsal horns of spinal cord, thoracic intermediolateral column, dorsal root ganglion and adrenal gland were compared with brain LRP, previously determined according to DLB Consortium criteria and by caudo-rostral versus amygdala-based LRP classification. Spinal LRP was found in 28% of the total population and in 61% of those who had LRP in the brain. Spinal cord LRP was found only in those subjects with LRP in the brain, and the quantity of spinal cord LRP was associated with the severity of brain LRP (p

Meteor radars have become widely used instruments to study atmospheric dynamics, particularly in the 70 to 110 km altitude region. These systems have been proven to provide reliable and continuous measurements of horizontal winds in the mesosphere and lower thermosphere. Recently, there have been many attempts to utilize specular and/or transverse scatter meteor measurements to estimate vertical winds and vertical wind variability. In this study we investigate potential biases in vertical wind estimation that are intrinsic to the meteor radar observation geometry and scattering mechanism, and we introduce a mathematical debiasing process to mitigate them. This process makes use of a spatiotemporal Laplace filter, which is based on a generalized Tikhonov regularization. Vertical winds obtained from this retrieval algorithm are compared to UA-ICON model data. This comparison reveals good agreement in the statistical moments of the vertical velocity distributions. Furthermore, we present the first observational indications of a forward scatter wind bias. It appears to be caused by the scattering center's apparent motion along the meteor trajectory when the meteoric plasma column is drifted by the wind. The hypothesis is tested by a radiant mapping of two meteor showers. Finally, we introduce a new retrieval algorithm providing a physically and mathematically sound solution to derive vertical winds and wind variability from multistatic meteor radar networks such as the Nordic Meteor Radar Cluster (NORDIC) and the Chilean Observation Network De meteOr Radars (CONDOR). The new retrieval is called 3DVAR+DIV and includes additional diagnostics such as the horizontal divergence and relative vorticity to ensure a physically consistent solution for all 3D winds in spatially resolved domains. Based on this new algorithm we obtained vertical velocities in the range of w = ± 1–2 m s−1 for most of the analyzed data during 2 years of collection, which is consistent with the values reported from general circulation models (GCMs) for this timescale and spatial resolution.

Earth's lower ionosphere is the region where terrestrial weather and space weather come together. Here, between 60 and 100 km altitude, solar radiation governs the diurnal cycle of the ionized species. This altitude range is also the place where nanometre-sized dust particles, recondensed from ablated meteoric material, exist and interact with free electrons and ions of the ionosphere. This study reports electron density measurements from the Arecibo incoherent-scatter radar being performed during sunset and sunrise conditions. An asymmetry of the electron density is observed, with higher electron density during sunset than during sunrise. This asymmetry extends from solar zenith angles (SZAs) of 80 to 100∘. This D-region asymmetry can be observed between 95 and 75 km altitude. The electron density observations are compared to the one-dimensional Sodankylä Ion and Neutral Chemistry (SIC) model and a variant of the Whole Atmosphere Community Climate Model incorporating a subset SIC's ion chemistry (WACCM-D). Both models also show a D-region sunrise–sunset asymmetry. However, WACCM-D compares slightly better to the observations than SIC, especially during sunset, when the electron density gradually fades away. An investigation of the electron density continuity equation reveals a higher electron–ion recombination rate than the fading ionization rate during sunset. The recombination reactions are not fast enough to closely match the fading ionization rate during sunset, resulting in excess electron density. At lower altitudes electron attachment to neutrals and their detachment from negative ions play a significant role in the asymmetry as well. A comparison of a specific SIC version incorporating meteoric smoke particles (MSPs) to the observations revealed no sudden changes in electron density as predicted by the model. However, the expected electron density jump (drop) during sunrise (sunset) occurs at 100∘ SZA when the radar signal is close to the noise floor, making a clear falsification of MSPs' influence on the D region impossible.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is an unparalleled challenge for the international community. Subsequently, an extraordinary effort has been made to contain SARS-CoV-2. However, this has been largely limited to behavioral changes and vaccination. To make the containment strategies effective, behavioral changes and vaccination need to be complemented with alternative prevention methods and curative treatments. This work reports the antiviral properties of some of the commonly known edible medicinal plants that can be used as potential remedies to suppress coronaviruses. A growing body of evidence substantiates that edible medicinal plants with antiviral properties that have been proven effective against sibling coronaviruses likely contain the spread of SARS-CoV-2, and they may also suppress the fatality of COVID-19 (coronavirus disease 2019). The secondary metabolites found in herbal medicines do not cause pathogens to develop drug resistance, which is a common problem in conventional medicines. The use of edible medicinal plants is much safer and causes less panic, thereby avoiding the fear associated with the use of herbal medicines. Right dosages and mixtures of edible medicinal plants need to be rigorously investigated to circumvent unanticipated side effects and chronic health risks.

Abstract Background Individuals with multiple islet autoantibodies are at increased risk for clinical type 1 diabetes and may proceed gradually from stage to stage complicating the recruitment to secondary prevention studies. We evaluated multiple islet autoantibody positive subjects before randomisation for a clinical trial 1 month apart for beta-cell function, glucose metabolism and continuous glucose monitoring (CGM). We hypothesized that the number and type of islet autoantibodies in combination with different measures of glucose metabolism including fasting glucose, HbA1c, oral glucose tolerance test (OGTT), intra venous glucose tolerance test (IvGTT) and CGM allows for more precise staging of autoimmune type 1 diabetes than the number of islet autoantibodies alone. Methods Subjects (n = 57) at 2–50 years of age, positive for two or more islet autoantibodies were assessed by fasting plasma insulin, glucose, HbA1c as well as First Phase Insulin Response (FPIR) in IvGTT, followed 1 month later by OGTT, and 1 week of CGM (n = 24). Results Autoantibodies against GAD65 (GADA; n = 52), ZnT8 (ZnT8A; n = 40), IA-2 (IA-2A; n = 38) and insulin (IAA; n = 28) were present in 9 different combinations of 2–4 autoantibodies. Fasting glucose and HbA1c did not differ between the two visits. The estimate of the linear relationship between log2-transformed FPIR as the outcome and log2-transformed area under the OGTT glucose curve (AUC) as the predictor, adjusting for age and sex was − 1.88 (− 2.71, − 1.05) p = 3.49 × 10–5. The direction of the estimates for all glucose metabolism measures was positive except for FPIR, which was negative. FPIR was associated with higher blood glucose. Both the median and the spread of the CGM glucose data were significantly associated with higher glucose values based on OGTT, higher HbA1c, and lower FPIR. There was no association between glucose metabolism, autoantibody number and type except that there was an indication that the presence of at least one of ZnT8(Q/R/W) A was associated with a lower log2-transformed FPIR (− 0.80 (− 1.58, − 0.02), p = 0.046). Conclusions The sole use of two or more islet autoantibodies as inclusion criterion for Stage 1 diabetes in prevention trials is unsatisfactory. Staging type 1 diabetes needs to take the heterogeneity in beta-cell function and glucose metabolism into account. Trial registration ClinicalTrials.gov identifier: NCT02605148 , November 16, 2015