University of Bergen

Background Although SARS-CoV-2 neutralising antibodies protect against severe COVID-19, whether circulating IgG titres reflect underlying host capacity to neutralise wild type (WT) and variants of concern (VOC) and what IgG threshold reflects sufficient neutralising capacity remains unclear. Methods In plasma from individuals in the All Ireland Infectious Diseases Cohort, we measured anti receptor binding domain (RBD) IgG and neutralising capacity by a micro-neutralisation assay, which determined the maximum plasma dilution to maintain 50% inhibition of replication (NT50) of live SARS-CoV-2, using WT and VOC (Beta and Omicron). We examined 3 groups sampled at 3 time periods: unvaccinated, prior infected (group 1, WT dominated), primary (2 dose) vaccinated (group 2) and group 3 with hybrid immunity (booster vaccine and Omicron infection). Although an NT50 ≥100 IU is considered sufficient protection in vaccine trials, as some VOC induce up to 6-fold reduction in NT50, we used NT50 ≥ 1000 IU as a cut off for WT neutralisation that would retain neutralisation against VOC. We used ROC curves to explore sensitivity and specificity and Youden Index to determine the RBD threshold associated with WT NT50 < 1000 IU. We validated the accuracy of this RBD threshold to predict NT50 < 100 IU against Beta and Omicron in groups 2 and 3 respectively. Results We included 255 participants across the 3 groups (table 1). In all groups, RBD highly correlated with WT NT50 (rho 0.81, 0.76 and 0.77 in groups 1, 2 and 3, all p< 0.001). In group 1 Youden’s Index determined RBD < 456 BAU/ml to best predict WT NT50 < 1000 IU (sensitivity 77% (95% CI 69, 84%), specificity 100% (95% CI 82, 100%)). All 99 samples with RBD < 456 BAU/ml had WT NT50 < 1000 IU; positive predictive value (PPV) 100%, (95% CI 95, 100%), and overall accuracy 80% (95% CI 73, 86%). When validated in groups 2 and 3, RBD < 456 BAU/ml retained good accuracy at predicting underlying neutralisation against VOC (group 2, accuracy 80% (95% CI 67, 90%) in predicting NT50 < 100 IU against Beta, and in group 3, overall accuracy of 87% (95% CI 77, 94%) to determine an NT50 of < 100 IU against Omicron.Table 1Participant Characteristics Conclusion Host RBD titres closely correlate with NT50. An RBD threshold of < 456 BAU/ml accurately predicts a clinically relevant neutralising capacity against both WT and common VOC. Disclosures Oliver A. Cornely, MD PhD, DZIF: Advisor/Consultant|DZIF: Board Member|DZIF: Grant/Research Support|DZIF: Honoraria|DZIF: Stocks/Bonds

Climate change affects all ecosystems, but subterranean ecosystems are repeatedly neglected from political and public agendas. Cave habitats are home to unknown and endangered species, with low trait variability and intrinsic vulnerability to recover from human-induced disturbances. We studied the annual variability and cyclicity of temperatures in caves vis-à-vis surface in different climatic areas. We hypothesize that cave temperatures follow the average temperature pattern at the surface for each location with a slight delay in the signal, but we found three different thermal patterns occurring in caves: (1) high positive correlation and a similar thermal pattern to the surface, (2) low correlation and a slight thermal delay of the signal from the surface, and (3) high negative correlation with an extreme delay from the surface. We found daily thermal cycles in some caves, which may potentially control the circadian rhythms of cave organisms. Our results show that caves had lower thermal amplitude than the surface, and that thermal averages within caves approximately correspond to the to the annual average of surface temperature. Caves buffer external temperature and act as refugia for biota in extreme climatic events. Likewise, temperature increases at surface will lead to increment in caves, threatening subterranean biota and ecosystem services.

Background and aim Dental Public Health (DPH) education prepares future workforce to promote positive oral health behaviors, prevent oral diseases, and monitor disease distribution and trends taking into considerations best practices, needs and available resources. Scarce information is available about dental education in African countries and Egypt has the greatest number of dental schools in Africa. This study assessed the undergraduate DPH education in Egyptian universities including topics taught, methods of teaching, assessment, and the academics’ specialties. Methods A survey targeted 43 Egyptian universities with Bachelor of Dentistry (BDS) programs identified on the website of the Supreme Council of Egyptian Universities in 2022. Thirty-six deans could be reached by post and/ or email. The survey appraised the school profile and capacity, and methods of teaching and assessment in DPH courses in undergraduate dental programs. The survey also inquired who taught DPH courses and what was covered in the courses. Descriptive statistics were displayed. Results We received 21 (58.3%) responses from 36 deans/ senior officials. Of the universities, 52.4% were private and 47.6% were public. Most participants reported that DPH courses in BDS programs were taught by Pediatric Dentistry academics (71.4%) and DPH academics (57.1%) in 3rd, 4th and 5th years of the 5-year BDS programs. Teaching DPH consisted of face-to-face lectures (100%) and seminars (95.2%) and assessment included written exams with close ended questions (95.2%) and open-ended questions (71.4%). Twenty schools reported teaching the definition of DPH, definition of oral health, and determinants of oral diseases. Nine schools addressed the planning of oral health services and five schools taught about remuneration and payment systems. Conclusion Teaching and assessment of DPH in Egyptian dental schools use traditional methods with limited active engagement of the students. Variations among the schools exist in the DPH topics covered and most instructors were not primarily specialized in DPH. Development of dental/ oral health services calls for more emphasis on DPH education in the curriculum in Egypt.

Small bowel neuroendocrine tumors (SB-NETs) are increasingly identified and have become the most frequent entity among small bowel tumors. An increasing incidence, a high prevalence, and a prolonged survival with optimal modern multidisciplinary management makes SB-NETs a unique set of tumors to consider for surgical oncologists. The major goals of surgical treatment in the setting of SB-NET include control of tumor volume, control of endocrine secretion, and prevention of locoregional complications. Key considerations include assessment of multifocality and resection of mesenteric nodal masses with the use of mesenteric-sparing approaches and acceptance of R1 margins if necessary to clear disease while avoiding short bowel syndrome. A description through eight steps for consideration is presented to allow for systematic surgical planning and execution of resection. Moreover, some controversies and evolving considerations to the surgical principles and technical procedures remain. The role of primary tumor resection in the presence of (unresectable) liver metastasis is still unclear. Reports of feasibility of minimally invasive surgery are emerging, with undetermined selection criteria for appropriateness or long-term outcomes. Resection of SB-NETs should be considered in all patients fit for surgery and should follow principles to achieve surgical oncological control that is appropriate for the stage and tumor burden, considering the age and comorbidity of the individual patient.

The Jostedalsbreen ice cap is mainland Europe's largest ice cap and accommodates 20% (458 km ² in 2019) of the total glacier area of mainland Norway. Jostedalsbreen and its meltwater contribute to global sea-level rise and to local water management, hydropower and tourism economies and livelihoods. In this study, we construct a digital terrain model (DTM) of the ice cap from 1966 aerial photographs, which by comparing to an airborne LiDAR DTM from 2020, we compute changes in surface elevation and geodetic mass balances. The area mapped in both surveys cover about 3/4 of the ice cap area and 49 of 82 glaciers. The measured glacier area has decreased from 363.4 km ² in 1966 to 332.9 km ² in 2019, i.e. a change of −30 km ² or −8.4% (−0.16% a ⁻¹ ), which is in line with the percentage reduction in area for Jostedalsbreen as a whole. The mean geodetic mass balance over the 49 glaciers was −0.15 ± 0.01 m w.e. a ⁻¹ , however, large variability is evident between glaciers, e.g. Nigardsbreen (−0.05 m w.e. a ⁻¹ ), Austdalsbreen (−0.28 m w.e. a ⁻¹ ) and Tunsbergdalsbreen (−0.36 m w.e. a ⁻¹ ) confirming differences also found by the glaciological records for Nigardsbreen and Austdalsbreen.

Objectives The aim of this study was to provide real-world efficacy and safety data on niraparib maintenance treatment in patients with non-germline (gBRCA)1/2 mutated platinum-sensitive recurrent ovarian cancer. Methods This retrospective multi-center cohort study included 94 platinum-sensitive recurrent ovarian cancer patients without known gBRCA1/2 mutation treated in an individual patient access program in Norway. The primary outcome was time from start of niraparib treatment to first subsequent treatment. Secondary endpoints included progression-free survival, safety, and tolerability. Results After median follow-up of 13.4 months (95% confidence interval (CI) 10.0 to 16.8), 68.1% had progressed and 22.3% had died. Of the entire cohort, 61.7% had commenced a new line of treatment, and 24.5% were still receiving niraparib. The median duration of niraparib treatment was 5.0 months (range 0.4 to 27.3), and the median time to first subsequent treatment was 10.7 months (95% CI 8.4 to 13.0). Patients with elevated CA125 prior to start of niraparib had shorter time to first subsequent treatment (7.3 months, 95% CI 4.2 to 10.3) than patients with normalized CA125 (12.2 months, 95% CI 10.9 to 13.7 (p=0.002). Patients who started on individual dose based on weight and platelet counts had fewer dose reductions (p<0.001) and interruptions (p=0.02). Conclusion In a real-world setting, niraparib maintenance treatment in patients with non-gBRCA1/2 mutated recurrent platinum-sensitive ovarian cancer showed effectiveness comparable with published phase III studies and acceptable safety. Individualized dosing is essential to minimize adverse events. CA125 levels at start of niraparib treatment may help to estimate the individual prognosis.

Objective Growth differentiation factor-15 (GDF-15) is a predictor of death and cardiovascular events when measured during index hospitalisation in patients with acute chest pain. This study investigated the prognostic utility of measuring GDF-15 3 months after an admission with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS). Methods GDF-15 was measured at baseline and 3 months after admission in 758 patients admitted with suspected NSTE-ACS. Patients were followed for a median of 1540 (IQR: 1087–1776) days after the 3-month visit. The primary endpoint was all-cause mortality, while the secondary composite endpoint included all-cause mortality, incident myocardial infarction and heart failure hospitalisation during follow-up. Results In patients with GDF-15 ≥1200 pg/mL (n=248), 18% died and 25% met the composite endpoint. In patients with GDF-15 <1200 pg/mL (n=510), 1.7% died and 4% met the composite endpoint. The GDF-15 concentration (log2 transformed) at 3 months was significantly associated with all-cause mortality (adjusted HR: 2.2, 95% CI: 1.4 to 3.3, p<0.001) and the composite endpoint (adjusted HR: 1.9, 95% CI: 1.4 to 2.7, p<0.001), independently of traditional risk factors and baseline troponin T. A 10% change in GDF-15 concentration from baseline to the 3-month visit was associated with increased risk of all-cause mortality (HR: 1.06, 95% CI: 1.01 to 1.13, p=0.031), adjusting for baseline GDF-15 concentrations. Conclusions High GDF-15 concentrations 3 months after admission for suspected NSTE-ACS are associated with long-term mortality and cardiovascular events, independent of traditional risk factors and troponin T. A change in GDF-15 concentration can provide prognostic information.

A software product line (SPL) is a family of closely related software systems which capitalizes on the variability and reusability of the software products and can be formalised by a feature model. Feature model evolution plans (FMEP) capture the current SPL as well as the planned evolution of the SPL to ensure successful long-term development. As business requirements often change, FMEPs should support intermediate update. This modification may cause paradoxes in an FMEP, e.g., a node left without a parent, making the plan impossible to realise. Current tools exist to validate FMEPs, but require analysing the entire plan even when a modification affects only small parts of it. Hence, there is a need for a method that detects such paradoxes in a more efficient way. In this paper, we present an interval based feature model (IBFM), a representation for FMEPs, that allows local reasoning to validates only the parts of the plan affected by changes. We define operations for updating the FMEPs and the preconditions under which they preserve soundness, i.e., absence of paradoxes, and show the correctness of the method.

Weather features, such as extratropical cyclones (ETC), atmospheric rivers (AR), and fronts, contribute to substantial amounts of precipitation globally. However, previous estimates of how much these individual features contribute to precipitation are very sensitive to subjectively chosen metrics. Furthermore, there is no information on how these weather features contribute to precipitation poleward of 60° latitude. To alleviate these shortcomings, we introduce a more robust attribution method applicable at all latitudes. Based on ERA5, we present the first global climatology of the contributions from cyclones, fronts, moisture transport axes (MTA; AR-like features), and cold air outbreaks, as well as their combinations to summer and winter precipitation as well as extreme precipitation. Most of the precipitation in the midlatitudes relates to the combination of ETC, fronts, and MTAs (28%), while in polar regions, most precipitation occurs within the ETC-only category (27%). Extreme precipitation events in all extratropical regions are predominantly associated with the combination of ETCs, fronts, and MTAs (46%). In the midlatitudes, the combination of ETCs, fronts, and MTAs occurs almost four times as often during extreme events compared to regular events.

Background Food insecurity is alarming in all four dimensions—availability, access, utilization, and stability—in Popokabaka, DR Congo. In such cases, a unique indicator may not help to develop adapted and local long-term actions. A comprehensive analysis of food insecurity is needed. We aimed to examine the burden and extent of food insecurity and suggest integrative pathways using a mixed approach for transformative actions at the local level. Methods We designed a convergent parallel mixed-methods study with four-level data sources collected in Popokabaka: (1) a household food survey (using the Household Food Insecurity Access Scale (HFIAS), a Household Dietary Diversity Score (HDDS) and the Food Consumption Score (FCS), (2) a market food census (assessing food availability and cost per 100 g), and (3) an exit food market survey (assessing buyers' food choices and client satisfaction), and (4) on-farm qualitative study among food producers (exploring challenges and opportunities). Descriptive statistics from our quantitative data were triangulated with themes emerging from qualitative data. Results Popokabaka experienced severe food access insecurity (89%), poor food consumption (40.7%), and low dietary diversity (30.2%) at the household level. The quantitative findings at the household level were linked to market characteristics and farmer-reported themes under three pathways: poor diet quality , culturally grounded diet , and risk perception . Conclusions The focus should be on improving livestock development, developing adapted communications about nutrition to change established dietary habits, and engaging the government and all stakeholders to empower local communities for improved food security.

Background In Norway, primary healthcare has first-line responsibility for all medical emergencies, including traumas and fractures. Normally, patients with suspected fractures are referred to specialist care in hospitals. However, the cooperating municipalities of Bykle and Valle have X-ray facilities and handle minor fractures locally. The aim of this study was to estimate the costs of X-ray diagnosis and initial treatment of fractures at the local primary care centre compared with initial transport and treatment in hospital. Methods We conducted a cost minimisation analysis by comparing expected costs of initial examination with X-ray and treatment of patients with fractures or suspected fractures at two possible sites, in the local municipality or at the hospital. A cost minimisation analysis is an economic evaluation based on the assumption that the outcomes of the two treatment procedure regimens are equal. Costs were estimated in Euros (EUR) using 2021 mean exchange rates. Results In 2019, we identified a total of 403 patients with suspected fractures in the two municipalities. Among these, 12 patients bypassed the primary care system as they needed urgent hospital care. A total of 391 injured patients were assessed with X-ray at the primary health care centres, 382 received their initial treatment there, and nine were referred to hospital. In an alternative hospital model, without X-ray and treatment possibilities in the municipality, the 382 patients would have been sent directly to hospital for radiological imaging and treatment. The total cost was estimated at EUR 367,756 in the hospital model and at EUR 69,835 in the primary care model, a cost saving of EUR 297,921. Conclusion Based on cost minimisation analysis, this study found that radiological diagnosis of suspected fractures and initial treatment of uncomplicated fractures in primary care cost substantially less than transport to and treatment in hospital.

Iteroparity represents an important but often overlooked component of life history in anadromous Atlantic salmon. Here, we combined individual DNA profiling and scale reading to identify repeat spawners among ~8000 adult salmon captured in a fish trap in the river Etne, Norway, in the period 2015–2019. Additionally, 171 outward migrating kelts were captured in the spring of 2018–2020 and identified using molecular methods to estimate weight loss since ascending the river to spawn. The overall frequency of repeat spawners identified using molecular methods and scale reading combined was 7% in females and 3% in males (5% in total). Most of these (83%) spent one full year reconditioning at sea before returning for their second spawning, with a larger body size compared with their size at first spawning, gaining on average 15.9 cm. A single female migrating back into the river for a fifth breeding season was also identified. On average, kelts lost 40% bodyweight in the river, and more female than male kelts were captured during outward migration. The date of arrival in the upstream fish trap was significantly but moderately correlated between maiden and second entry to the river for alternate and consecutive spawners. The estimated contribution from repeat spawners to the total number of eggs deposited in the river each year varied between 2% and 17% (average 12%). Molecular‐based methods marginally underestimated the number of repeat spawners compared with scale reading (5% vs 7%) likely due to a small number of returning spawners not being trapped and sampled. Differences between the methods were most evident when classifying the spawning strategy (alternate or consecutive‐year repeat spawners), where the scale method identified proportionally more consecutive‐year repeat spawners than the molecular method. This unique data set reveals previously unstudied components of this life history strategy and demonstrates the importance of repeat spawners in population recruitment.

The rapid diversification and high species richness of flowering plants is regarded as ‘Darwin’s second abominable mystery’. Today the global spatiotemporal pattern of plant diversification remains elusive. Using a newly generated genus-level phylogeny and global distribution data for 14,244 flowering plant genera, we describe the diversification dynamics of angiosperms through space and time. Our analyses show that diversification rates increased throughout the early Cretaceous and then slightly decreased or remained mostly stable until the end of the Cretaceous–Paleogene mass extinction event 66 million years ago. After that, diversification rates increased again towards the present. Younger genera with high diversification rates dominate temperate and dryland regions, whereas old genera with low diversification dominate the tropics. This leads to a negative correlation between spatial patterns of diversification and genus diversity. Our findings suggest that global changes since the Cenozoic shaped the patterns of flowering plant diversity and support an emerging consensus that diversification rates are higher outside the tropics.

The evolution of dispersal modes has been proposed to promote the diversification of angiosperms. However, little is known about the relative impact of different dispersal modes on plant diversification. We test the association between dispersal modes and diversification rates using Rhamnaceae, the cosmopolitan buckthorn family, as a model. We found that species with diplochory have the highest diversification rates followed by those with myrmecochory and ballistic dispersal, while lineages dispersed by vertebrates and wind have relatively low diversification rates. The difference in diversification rates may be closely linked to the difference in dispersal distance and ecological interactions implied by each dispersal mode. Species which disperse over larger geographical distances may have much higher speciation rates due to the increased chance of establishing isolated populations due to geological barriers or habitat fragmentation. However, long-distance dispersal may also increase the chance of extinction. By contrast, species with short-distance dispersal modes may have low speciation rates. Complex interactions with the surrounding environment may, however, impact diversification rates positively by increasing plant survival and reproductive success.

We study the question of how visual analysis can support the comparison of spatio-temporal ensemble data of liquid and gas flow in porous media. To this end, we focus on a case study, in which nine different research groups concurrently simulated the process of injecting CO2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$_2$$\end{document} into the subsurface. We explore different data aggregation and interactive visualization approaches to compare and analyze these nine simulations. In terms of data aggregation, one key component is the choice of similarity metrics that define the relationship between different simulations. We test different metrics and find that using the machine-learning model “S4” (tailored to the present study) as metric provides the best visualization results. Based on that, we propose different visualization methods. For overviewing the data, we use dimensionality reduction methods that allow us to plot and compare the different simulations in a scatterplot. To show details about the spatio-temporal data of each individual simulation, we employ a space-time cube volume rendering. All views support linking and brushing interaction to allow users to select and highlight subsets of the data simultaneously across multiple views. We use the resulting interactive, multi-view visual analysis tool to explore the nine simulations and also to compare them to data from experimental setups. Our main findings include new insights into ranking of simulation results with respect to experimental data, and the development of gravity fingers in simulations.

The purpose of this study is to evaluate the association between perinatal asphyxia, neonatal encephalopathy, and childhood hearing impairment. This is a population-based study including all Norwegian infants born ≥ 36 weeks gestation between 1999 and 2014 and alive at 2 years (n = 866,232). Data was linked from five national health registries with follow-up through 2019. Perinatal asphyxia was defined as need for neonatal intensive care unit (NICU) admission and an Apgar 5-min score of 4–6 (moderate) or 0–3 (severe). We coined infants with seizures and an Apgar 5-min score < 7 as neonatal encephalopathy with seizures. Infants who received therapeutic hypothermia were considered to have moderate-severe hypoxic-ischemic encephalopathy (HIE). The reference group for comparisons were non-admitted infants with Apgar 5-min score ≥ 7. We used logistic regression models and present data as adjusted odds ratios (aORs) with 95% confidence intervals (CI). The aOR for hearing impairment was increased in all infants admitted to NICU: moderate asphyxia aOR 2.2 (95% CI 1.7–2.9), severe asphyxia aOR 5.2 (95% CI 3.6–7.5), neonatal encephalopathy with seizures aOR 7.0 (95% CI 2.6–19.0), and moderate-severe HIE aOR 10.7 (95% CI 5.3–22.0). However, non-admitted infants with Apgar 5-min scores < 7 did not have increased OR of hearing impairment. The aOR for hearing impairment for individual Apgar 5-min scores in NICU infants increased with decreasing Apgar scores and was 13.6 (95% CI 5.9–31.3) when the score was 0. Conclusions: An Apgar 5-min score < 7 in combination with NICU admission is an independent risk factor for hearing impairment. Children with moderate-severe HIE had the highest risk for hearing impairment. What is Known: • Perinatal asphyxia and neonatal encephalopathy are associated with an increased risk of hearing impairment. • The strength of the association, and how other co-morbidities affect the risk of hearing impairment, is poorly defined. What is New: • Among neonates admitted to a neonatal intensive care unit (NICU), decreased Apgar 5-min scores, and increased severity of neonatal encephalopathy, were associated with a gradual rise in risk of hearing impairment. • Neonates with an Apgar 5-min score 7, but without NICU admission, did not have an increased risk of hearing impairment.

The sperm-specific Na ⁺ /H ⁺ exchanger SLC9C1 stands out by its unique tripartite domain composition. It is the first known secondary-active transporter which is directly activated by membrane voltage via a voltage-sensing domain (VSD). Our cryo-EM structures of sea urchin SLC9C1 reveal the domain arrangement and new structural coupling elements, allowing us to propose a mechanism for a voltage-activated alternative access mechanism.

Humans infer motion direction from noisy sensory signals. We hypothesize that to make these inferences more precise, the visual system computes motion direction not only from velocity but also spatial orientation signals – a ‘streak’ created by moving objects. We implement this hypothesis in a Bayesian model, which quantifies knowledge with probability distributions, and test its predictions using psychophysics and fMRI. Using a probabilistic pattern-based analysis, we decode probability distributions of motion direction from trial-by-trial activity in the human visual cortex. Corroborating the predictions, the decoded distributions have a bimodal shape, with peaks that predict the direction and magnitude of behavioral errors. Interestingly, we observe similar bimodality in the distribution of the observers’ behavioral responses across trials. Together, these results suggest that observers use spatial orientation signals when estimating motion direction. More broadly, our findings indicate that the cortical representation of low-level visual features, such as motion direction, can reflect a combination of several qualitatively distinct signals.