Search Results (95)

Draining wetland landscapes accelerates climate change, and multilateral support is therefore needed to speed up the transition to new land uses. This paper examines perceptions of ecosystem services (ES) in wetland areas in scientific and civic assessments. The case study area is Denmark’s largest drained wetland system, which is notable for its carbon sequestration potential. The area’s transformation efforts involving public participation offer a unique chance to examine differences between scientific and civic perceptions of ES. This exceptional case is ideal for revealing contextual differences, trade-offs, and controversies between scientific and civic perceptions of ES. Millennium ES Assessment and CICES are used as a conceptual framework for understanding and mapping human–nature interactions in a nature park. However, these systems are, in practice, not sufficiently developed to identify how citizens understand and value ES in real life. Therefore, we analyse perceptions using interviews, collaborative mapping, and media analysis. We compare these to scientific ES mappings based on local data, literature reviews, and fieldwork. The paper concludes that (1) scientific ES asymmetries are important; (2) environmental blind spots in scientific ES are due to its approach to knowledge collection; (3) citizens’ blind spots are due to their everyday life focus and tabooing the issue of local climate mitigation; and (4) science-based ES assessments and accounts are disconnected from local ES controversies. We argue that identifying ES controversies through various scientific methods may improve climate mitigation and restoration efforts if community planning becomes involved. Full article

Background/Objectives: Staphylococcus aureus is a leading cause of bacteraemia in Danish hospitals. Approximately 70% of clinical S. aureus isolates are penicillin-resistant, which is predominantly due to blaZ-mediated β-lactamase production. Methods: A collection of 489 S. aureus strains derived from bacteraemia were cultured and their genomes sequenced. Results: From this collection, 71% of isolates were methicillin-susceptible S. aureus (MSSA) harbouring blaZ. While most isolates contained the blaZ gene belonging to the well-characterised A, B, C and D variants, three strains (1%) produced a BlaZ protein characterised by having threonine residues on both positions 128 and 216 and, therefore, belonged to neither of the established blaZ variants. We named this variant, variant F. We report that clinical isolates expressing blaZ variant F were resistant to oxacillin. The β-lactamase production phenotype in isolates carrying either of the A, B, C or D variants was only weakly discernible on MIC gradient strip and disk diffusion tests. When the β-lactamases were expressed either from a T7 promoter or from their endogenous promoters in Escherichia coli, variant F was significantly better at degrading ampicillin than variant A. We also showed that variant F conferred oxacillin resistance when expressed in an isogenic S. aureus strain, while variant A did not. Finally, we demonstrated that the F variant threonine 216 played a role in the enzyme’s superior activity. Conclusions: Our findings demonstrate that the new F variant of BlaZ is sufficient to render S. aureus a BORSA strain, which is superior in the degradation of common anti-staphylococcal β-lactam antibiotics, such as benzylpenicillin, cloxacillin, and oxacillin. It is sensitive to β-lactamase inhibitors and rapidly degrades nitrocefin. We provide a genetic explanation for the borderline oxacillin-resistant S. aureus (BORSA) phenotype. Full article

Objective: Reliable reading and annotation of chest X-ray (CXR) images are essential for both clinical decision-making and AI model development. While most of the literature emphasizes pulmonary findings, this study evaluates the consistency and reliability of annotations for extrapulmonary findings, using a labelling scheme. Methods: Six clinicians with varying experience levels (novice, intermediate, and experienced) annotated 100 CXR images using a diagnostic labelling scheme, in two rounds, separated by a three-week washout period. Annotation consistency was assessed using Randolph’s free-marginal kappa (RK), prevalence- and bias-adjusted kappa (PABAK), proportion positive agreement (PPA), and proportion negative agreement (PNA). Pairwise comparisons and the McNemar’s test were conducted to assess inter-reader and intra-reader agreement. Results: PABAK values indicated high overall grouped labelling agreement (novice: 0.86, intermediate: 0.90, experienced: 0.91). PNA values demonstrated strong agreement on negative findings, while PPA values showed moderate-to-low consistency in positive findings. Significant differences in specific agreement emerged between novice and experienced clinicians for eight labels, but there were no significant variations in RK across experience levels. The McNemar’s test confirmed annotation stability between rounds. Conclusions: This study demonstrates that clinician annotations of extrapulmonary findings in CXR are consistent and reliable across different experience levels using a pre-defined diagnostic labelling scheme. These insights aid in optimizing training strategies for both clinicians and AI models. Full article

Background/Objectives: Critical lung infection affects alveolar cells and probably also their ability to perform surfactant procedures, but bedside tools for monitoring lung surfactants are lacking. In this descriptive exploratory study, we aimed to evaluate lung surfactant levels in bronchial aspirate (BA) from patients admitted to the intensive care unit due to severe respiratory failure. Methods: Bronchial aspirates were collected from nine patients (median age: 72 years, range: 52–85) who required orotracheal intubation. Samples were obtained within 24 h of mechanical ventilation initiation (T1), after three days on a ventilator (T2), and on day seven (T3) for four patients. The concentration of dipalmitoylphosphatidylcholine (DPPC), a key surfactant component, was assessed in the lamellar body precipitate. Results: Across the nine patients at T1, the DPPC level was 12 µM (range: 3–20 µM). By T2, the DPPC level declined to 8 µM (range: 2–22 µM), with a statistically significant decrease from T1 (p = 0.0039). At T3, the DPPC level in four patients ranged from 2 to 5 µM, though the difference from T2 was not statistically significant. A surfactant biomarker would assist clinical decision-making when dealing with patients in severe respiratory failure where exogenous surfactant therapy may be considered. Conclusions: DPPC levels obtained from bronchial aspirate can be measured in patients with severe respiratory failure and may serve as a useful biomarker for lung surfactant status, which suggests the potential for bedside assessment in clinical practice with a dedicated test device. Full article

Passive maternal-fetal transfer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies has been demonstrated, whilst the degree of transfer depending on the trimester of infection is lacking. Due to neonates’ immature immune systems, this knowledge could be of interest when investigating the degree of early-life protection against SARS-CoV-2. For perinatal infections such as Rubella and Toxoplasmosis, the timing of infection related to gestational age is crucial for the severity of maternal-fetal outcomes; hence, the trimester of SARS-CoV-2 infection could potentially be crucial. So far, there is no stratification on all three trimesters of SARS-CoV-2 infection in relation to maternal antibody levels in SARS-CoV-2 positive women, and the degree of transfer of SARS-CoV-2 antibodies to the newborn nor on obstetric and neonatal outcomes, which we examined in this study. Eleven departments in Denmark invited women who tested SARS-CoV-2 positive during pregnancy to participate with a blood sample and a cord blood sample at delivery. 459 SARS-CoV-2 positive women and 2567 SARS-CoV-2 negative women were included. A percentage of 87.5%, 95.3%, and 60.3% of newborns of women who tested positive in their first, second, and third trimester, respectively, had a significantly higher immunoglobin G (IgG) antibody level than their mother at delivery, indicating that the fetus is able to concentrate antibody levels or maintain the level of IgG antibodies transferred. None of the examined maternal-fetal outcomes were increased in women infected with SARS-CoV-2. Full article

The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM’s composition to restore its organization and function. Across diverse organ diseases, there are common denominators and distinguishing factors in this fibroinflammatory axis, which may be used to foster new insights into drug development across disease indications. The 2nd Extracellular Matrix Pharmacology Congress took place in Copenhagen, Denmark, from 17 to 19 June 2024 and was hosted by the International Society of Extracellular Matrix Pharmacology. The event was attended by 450 participants from 35 countries, among whom were prominent scientists who brought together state-of-the-art research on organ diseases and asked important questions to facilitate drug development. We highlight key aspects of the ECM in the liver, kidney, skin, intestine, musculoskeletal system, lungs, and solid tumors to advance our understanding of the ECM and its central targets in drug development. We also highlight key advances in the tools and technology that enable this drug development, thereby supporting the ECM. Full article

The administration of insulin as a treatment for diabetes frequently leads to the formation of anti-insulin antibodies (IAs). The influence of these antibodies on the efficacy and safety of insulin therapy remains incompletely understood. This study presents a systematic, exploratory, cross-sectional analysis of the quantitative and qualitative properties of IAs in 101 patients with type 1 diabetes (T1D) and 101 patients with type 2 diabetes (T2D). The goal was to identify subpopulations of IAs that might impact glycemic control. We assessed the presence, titer, isotype, subclass, avidity, and in vitro neutralizing capacities of IAs, using glycated hemoglobin A1c (HbA1c) levels as an indicator of the clinical effectiveness of insulin. Our findings showed that 72% of individuals with T1D and 32% with T2D developed IAs, with IgG being the predominant isotype in both groups. Despite the presence of IAs, no in vitro neutralizing effect against insulin was observed, and there was no significant correlation between IA titer or avidity and HbA1c levels in either group. The results from this study demonstrate that while IAs are prevalent in both T1D and T2D, they do not have a significant clinical impact on the outcomes of insulin therapy in our study populations. Full article

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare hereditary cancer syndrome caused by pathogenic variants in the rearranged during transfection (RET) gene and is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), primary hyperparathyroidism (PHPT), cutaneous lichen amyloidosis (CLA), and Hirschsprung’s disease. Phenotypic data on the RET C611Y variant remain sparse. Consequently, we aimed to establish a clinical risk profile. Methods: We conducted a nationwide study of all cases (n = 128) born after 1 January 1930 and recognized as carrying the RET C611Y variant in Denmark before 1 April 2021. Results: The median follow-up after birth was 47 years (range, 3–92). Age-related penetrance at age 70 years for MTC was 98% (CI, 91–100), for PHEO 24% (CI, 16–37), and for PHPT 10% (CI, 5–20). None had CLA or Hirschsprung’s disease. The age-related progression of MTC was significant (p < 0.001). The mean age at T0N0M0 was 16 years (CI, 12–20), at T1-4N0M0 38 years (CI, 34–42), at TxN1M0 45 years (CI, 38–53) and at TxNxM1 49 years (CI, 36–61). At the last follow-up, 56% of thyroidectomized cases (n = 103) were biochemically cured. Overall survival at 70 years was 74% (CI, 59–84). Conclusions: RET C611Y is associated with a very high penetrance of MTC and a low penetrance of PHEO and PHPT. CLA and Hirschsprung’s disease almost never occur. MTC seems moderately aggressive, but large variability can be seen. Overall survival may be comparable to that of the general population. Full article

Accurate river hydraulic characterization is fundamental to assess flood risk, parametrize flood forecasting models, and develop river maintenance workflows. River hydraulic roughness and riverbed/floodplain geometry are the main factors controlling inundation extent and water levels. However, gauging stations providing hydrometric observations are declining worldwide, and they provide point measurements only. To describe hydraulic processes, spatially distributed data are required. In situ surveys are costly and time-consuming, and they are sometimes limited by local accessibility conditions. Satellite earth observation (EO) techniques can be used to measure spatially distributed hydrometric variables, reducing the time and cost of traditional surveys. Satellite EO provides high temporal and spatial frequency, but it can only measure large rivers (wider than ca. 50 m) and only provides water surface elevation (WSE), water surface slope (WSS), and surface water width data. UAS hydrometry can provide WSE, WSS, water surface velocity and riverbed geometry at a high spatial resolution, making it suitable for rivers of all sizes. The use of UAS hydrometry can enhance river management, with cost-effective surveys offering large coverage and high-resolution data, which are fundamental in flood risk assessment, especially in areas that difficult to access. In this study, we proposed a combination of UAS hydrometry techniques to fully characterize the hydraulic parameters of a river. The land elevation adjacent to the river channel was measured with LiDAR, the riverbed elevation was measured with a sonar payload, and the WSE was measured with a UAS radar altimetry payload. The survey provided 57 river cross-sections with riverbed elevation, and 8 km of WSE and land elevation and took around 2 days of survey work in the field. Simulated WSE values were compared to radar altimetry observations to fit hydraulic roughness, which cannot be directly observed. The riverbed elevation cross-sections have an average error of 32 cm relative to RTK GNSS ground-truth measurements. This error was a consequence of the dense vegetation on land that prevents the LiDAR signal from reaching the ground and underwater vegetation, which has an impact on the quality of the sonar measurements and could be mitigated by performing surveys during winter, when submerged vegetation is less prevalent. Despite the error of the riverbed elevation cross-sections, the hydraulic model gave good estimates of the WSE, with an RMSE below 3 cm. The estimated roughness is also in good agreement with the values measured at a gauging station, with a Gauckler–Manning–Strickler coefficient of M = 16–17 m^1/3/s. Hydraulic modeling results demonstrate that both bathymetry and roughness measurements are necessary to obtain a unique and robust hydraulic characterization of the river. Full article

The treatment of childhood cancer is challenged by toxic side effects mainly due to chemotherapy-induced organ damage and infections, which are accompanied by severe systemic inflammation. Insulin-like growth factor I (IGF-I) is a key regulating factor in tissue repair. This study investigated associations between the circulating IGF-I levels and chemotherapy-related toxicity in pediatric acute lymphoblastic leukemia (ALL). In this prospective study, we included 114 patients (age: 1–17 years) with newly diagnosed ALL treated according to The Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol between 2013 and 2018. The patients’ plasma levels of IGF-I, and the primary binding protein, IGFBP-3, were measured weekly during the first six weeks of treatment, including the induction therapy. The patients’ systemic inflammation was monitored by their C-reactive protein (CRP) and interleukin (IL)-6 levels and their intestinal epithelial damage by their plasma citrulline levels. IGF-I and IGFBP-3 were converted into sex-and age-adjusted standard deviation scores (SDS) using 1621 healthy children as reference. At ALL diagnosis, IGF-I levels were decreased (median (quartiles): −1.2 SDS (−1.9 to −0.5), p = 0.001), but increased significantly following the initiation of chemotherapy, peaking on day 8 (0.0 SDS (from −0.8 to 0.7), p < 0.001). This increase correlated with the levels of CRP (rho = 0.37, p < 0.001) and IL-6 (rho = 0.39, p = 0.03) on day 15, when these markers reached maximum levels. A larger IGF-I increase from day 1 to 15 correlated with a slower recovery rate of the intestinal damage marker citrulline from day 15 to 29 (rho = −0.28, p = 0.01). Likewise, IGFBP-3 was reduced at diagnosis, followed by an increase after treatment initiation, and was highly correlated with same-day IGF-I levels. This study demonstrates a chemotherapy-induced increase in IGF-I, with a response that appears to reflect the severity of tissue damage and systemic inflammation, preceding CRP and IL-6 increases. IGF-I may have potential as an early reactive biomarker for acute toxicity in patients with ALL. Full article

This study aimed to enhance our understanding of the agreement between two sampling methods for the detection of bovine respiratory disease (BRD) pathogens in calves using high-throughput real-time qPCR (ht-RT-qPCR). In total, 233 paired nasal swab (NS) and non-endoscopic bronchoalveolar lavage (nBAL) samples were collected from 152 calves from 12 Danish cattle herds. In 202 of the observations, the calves were examined using a standardized clinical protocol. Samples were tested for three viruses (bovine respiratory syncytial virus, bovine corona virus, and influenza D virus) and six bacteria (Histophilus somni, Mannheimia haemolytica, Mycoplasma bovis, Mycoplasma species, Pasteurella multocida, and Truepurella pyogenes). The results showed age-related differences in disease and pathogen occurrence, with the highest detection rates in calves aged 35 days or older. Poor to moderate agreement was found between the NS and nBAL results. The presence of Mannheimia haemolytica in both NS and nBAL in younger calves and in nBAL in older calves was associated with clinical BRD. There was a potential link between BRD and influenza D virus in older calves, although it was only found in one herd in a small sample size. Overall, NS was a relatively poor predictor of pathogens in the lower respiratory tract. The present study confirms the complexity of pathogen detection in BRD, with marked influences of age and the sampling method on pathogen detection and disease associations. Full article

Indirect evaporative coolers (IECs) for air conditioning rely on liquid water being sprayed into the exhaust stream of used air to induce evaporation and cool down the incoming stream of fresh air in an indirect heat exchanger. This paper describes a computational fluid dynamics analysis that makes use of the particle transport model to simulate the evaporation of the water droplets at the exhaust side of an IEC using a pre-implemented spray dryer model. Critical parameters include the average size of the droplets and the amount of water sprayed into the system. In addition to droplet evaporation, the evaporation of water from the wet wall on the exhaust side is accounted for. The results show the calculated temperature field in both air streams, the pressure distribution, the relative humidity distribution at the exhaust side and the particle tracks. The predicted wet bulb efficiency of around 30–35% is moderate but in agreement with the literature to date, and it can be attributed to the small heat exchanger size. A parametric study investigated the effect of the droplet size and mass flow rate. At an average size of 50 microns and below, the effect of the mass flow rate is quite strong, while at a higher droplet size the mass flow effect is small. Overall, the model can be used to shed fundamental understanding in order to increase the performance of the IEC while maintaining its compactness. Full article

Genetic biomarkers could potentially lower the risk of treatment failure in chronic inflammatory diseases (CID) like psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) and response to biologics. Odds ratio (OR) with 95% confidence interval (CI) meta-analyses were performed. In total, 185 studies examining 62,774 individuals were included. For the diseases combined, the minor allele of MYD88 (rs7744) was associated with good response to TNFi (OR: 1.24 [1.02–1.51], 6 studies, 3158 patients with psoriasis or RA) and the minor alleles of NLRP3 (rs4612666) (OR: 0.71 [0.58–0.87], 5 studies, 3819 patients with RA or IBD), TNF-308 (rs1800629) (OR: 0.71 [0.55–0.92], 25 studies, 4341 patients with psoriasis, RA, or IBD), FCGR3A (rs396991) (OR: 0.77 [0.65–0.93], 18 studies, 2562 patients with psoriasis, PsA, RA, or IBD), and TNF-238 (rs361525) (OR: 0.57 [0.34–0.96]), 7 studies, 818 patients with psoriasis, RA, or IBD) were associated with poor response to TNFi together or infliximab alone. Genetic variants in TNFα, NLRP3, MYD88, and FcRγ genes are associated with response to TNFi across several inflammatory diseases. Most other genetic variants associated with response were observed in a few studies, and further validation is needed. Full article

Aging has been associated with a changed composition and function of the gut microbiota (GM). Here, we investigate the effects of the multi-strain probiotic HOWARU^® Restore on GM composition and function in seniors. Ninety-eight healthy adult volunteers aged ≥75 years were enrolled in a randomised, double-blinded intervention (NCT02207140), where they received HOWARU Restore (10¹⁰ CFU) or the placebo daily for 24 weeks, with 45 volunteers from each group completing the intervention. Questionnaires monitoring the effects on gastro-intestinal discomfort and bowel movements were collected. Faecal samples for GM characterisation (qPCR, 16S rRNA gene amplicon sequencing) and metabolomics (GC-FID, ¹H NMR) were collected at the baseline and after 24 weeks. In the probiotic group, self-reported gastro-intestinal discomfort in the form of flatulence was significantly decreased during the intervention. At the baseline, 151 ‘core species’ (present in ≥95% of samples) were identified. Most core species belonged to the Lachnospiraceae and Ruminococcaceae families. Neither alpha diversity nor beta diversity or faecal metabolites was affected by probiotic intake. On the contrary, we observed high intra-individual GM stability, with ‘individual’ accounting for 72–75% of variation. In conclusion, 24 weeks of HOWARU Restore intake reduced gastro-intestinal discomfort in the form of flatulence in healthy seniors without significantly influencing GM composition or activity. Full article

This paper presents methodologies and equipment for SI-traceable inline measurements of water content (a critical quality parameter) in solid biofuels. Inline measurement systems for water content are commonly used at CHP plants, providing continuous real-time data. However, the accuracy of these systems is in most cases unsatisfactory, mainly because the systems are not calibrated representatively for the relevant material, and until now, calibrations traceable to the SI system have not been available. To provide reliable and accurate inline water content data, new procedures and equipment for calibrating measurement systems were developed. Two reference methods for the determination of water content were developed; one measures the airflow and dewpoint of desorbed water in the air passing a test sample, while the other uses a P₂O₅-sensor. Additionally, a transfer standard based on a cavity resonance sensor was developed for fast onsite calibration of the inline sensor at the power plant. This new instrument allows for quick and accurate measurements. The transfer standard is made metrologically traceable to the primary measurement standards. The entire system was demonstrated by calibrating an inline microwave-based (MW) sensor at the CHP plant of VERDO in Randers, Denmark. Thus, a complete metrological traceability chain was established from an industrial to a primary standard. Full article