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The linear scaling divide–expand–consolidate (DEC) framework is expanded to include unrestricted Hartree–Fock references. By partitioning the orbital space and employing local molecular orbitals, the full molecular calculation can be performed as independent calculations on individual fragments, making the method well-suited for massively parallel implementations. This approach also incorporates error control through the fragment optimization threshold (FOT), which maintains precision and consistency throughout the calculations. A benchmark was conducted for correlation energies of open-shell systems and the relative energies of both open- and closed-shell molecules at the MP2 level of theory. The full calculation result is achieved as the FOT approaches zero. For correlation energies, an FOT of 10−3 is sufficient to recover over 98% of the full result in all cases. However, for relative energies and the electronic energy component of oxidation potentials, a tighter FOT of 10−4 is required to keep the DEC error within 10% for both open- and closed-shell molecules. This is likely due to a lack of systematic error cancellation for the molecules with vastly different chemical natures. Therefore, for accurate relative energies, the FOT should be an order of magnitude lower, and additional caution is needed, particularly for large systems. The DEC method extension to unrestricted references maintains favorable features of linear scaling and can be implemented in a massively parallel algorithm to calculate correlation energies for large open-shell systems. [ABSTRACT FROM AUTHOR]

Traditionally, excitation energies in coupled-cluster (CC) theory have been calculated by solving the CC Jacobian eigenvalue equation. However, based on our recent work [Jørgensen et al., Sci. Adv. 10, eadn3454 (2024)], we propose a reformulation of the calculation of excitation energies where excitation energies are determined as a conventional molecular property. To this end, we introduce an excitation-energy function that depends on the CC Jacobian and the right and left eigenvectors for the Jacobian eigenvalue problem. This excitation-energy function is variational with respect to the right and left eigenvectors but not with respect to the cluster amplitudes. Instead, the cluster amplitudes satisfy the cluster-amplitude equations, and we set up an excitation-energy Lagrangian by adding to the excitation-energy function the cluster-amplitude equations with an undetermined multiplier for each cluster-amplitude constraint. The excitation-energy Lagrangian is variational in all its parameters. Based on the variational property of the Lagrangian, we have determined two quadratically convergent excitation-energy series: the total-order cluster-perturbation (tCP) and variational cluster-perturbation (vCP) excitation-energy series. Calculations of the excitation energies of three small molecules have shown that the vCP series is to be preferred over the tCP series. The test calculations have been carried out for CPS(D) expansions [targeting the CC singles-and-doubles (CCSD) wave function from the CC singles wave function] and the CPSD(T) expansion [targeting the CC singles-doubles-triples (CCSDT) wave function from the CCSD wave function]. For the S(D) and SD(T) orbital excitation space calculations, we obtain in the second vCP iteration excitation energies with a mean deviation from CCSD excitation energies of about 0.04 eV for the S(D) orbital spaces, and for the SD(T) orbital space calculation, we obtain a mean deviation from the CCSDT excitation energies of 0.001 eV. [ABSTRACT FROM AUTHOR]

We describe an efficient implementation of cluster perturbation and Møller–Plesset Lagrangian energy series through the fifth order that targets the coupled cluster singles and doubles energy utilizing the resolution of the identity approximation. We illustrate the computational performance of the implementation by performing ground state energy calculations on systems with up to 1200 basis functions using a single node and by comparison to conventional coupled cluster singles and doubles calculations. We further show that our hybrid message passing interface/open multiprocessing parallel implementation that also utilizes graphical processing units can be used to obtain fifth order energies on systems with almost 1200 basis functions with a 90 min "time to solution" running on Frontier at Oak Ridge National Laboratory. [ABSTRACT FROM AUTHOR]

In this paper, we develop and analyze a number of perturbation series that target the coupled cluster singles and doubles (CCSD) ground state energy. We show how classical Møller–Plesset perturbation theory series can be restructured to target the CCSD energy based on a reference CCS calculation and how the corresponding cluster perturbation series differs from the classical Møller–Plesset perturbation series. Subsequently, we reformulate these series using the coupled cluster Lagrangian framework to obtain series, where fourth and fifth order energies are determined only using parameters through second order. To test the methods, we perform a series of test calculations on molecular photoswitches of both total energies and reaction energies. We find that the fifth order reaction energies are of CCSD quality and that they are of comparable accuracy to state-of-the-art approximations to the CCSD energy based on local pair natural orbitals. The advantage of the present approach over local correlation methods is the absence of user defined threshold parameters for neglecting or approximating contributions to the correlation energy. Fixed threshold parameters lead to discontinuous energy surfaces, although this effect is often small enough to be ignored, but the present approach has a differentiable energy that will facilitate derivation and implementation of gradients and higher derivatives. A further advantage is that the calculation of the perturbation correction is non-iterative and can, therefore, be calculated in parallel, leading to a short time-to-solution. [ABSTRACT FROM AUTHOR]

The recent progress in auditory attention decoding (AAD) methods is based on algorithms that find a relation between the audio envelope and the neurophysiological response. The most popular approach is based on the reconstruction of the audio envelope from electroencephalogram (EEG) signals. These methods are primarily based on the exogenous response driven by the physical characteristics of the stimuli. In this study, we specifically investigate higher-level cognitive responses influenced by auditory attention to natural speech events. We designed a series of four experimental paradigms with increasing levels of realism: a word category oddball paradigm, a word category oddball paradigm with competing speakers, and competing speech streams with and without specific targets. We recorded EEG data using 32 scalp electrodes, as well as 12 in-ear electrodes (ear-EEG) from 24 participants. By using natural speech events and cognitive tasks, a cognitive event-related potential (ERP) component, which we believe is related to the well-known P3b component, was observed at parietal electrode sites with a latency of ~625 ms. Importantly, the component decreases in strength but is still significantly observable in increasingly realistic paradigms of multi-talker environments. We also show that the component can be observed in the in-ear EEG signals by using spatial filtering. We believe that the P3b-like cognitive component modulated by auditory attention can contribute to improving auditory attention decoding from electrophysiological recordings. [ABSTRACT FROM AUTHOR]

The efficient utilization of solar energy as renewable source is a central pillar of societal future energy production. So-called molecular solar thermal energy storage (MOST) systems have attracted considerable attention as storage solution and heat release on demand. Substituted norbornadiene/quadricyclane (NBD/QC) derivatives have been shown to be well suited for this task, in particular when substituted with electron donating and accepting functional groups. The introduction of a hetero-atom in the main structural framework, however, has not been investigated thoroughly, yet. In this study, a previously established high-throughput screening procedure is used to investigate carbon, nitrogen and oxygen-bridged norbornadiene derivatives for their potential as MOST system employing their theoretical solar power conversion efficiency as scoring metric. Therefore, we explore a large chemical space considering also plausible synthetic availability and propose a set of 5 molecules per bridge head as best candidates for further experimental evaluation. [ABSTRACT FROM AUTHOR]

Background/Objectives: The presence of antibiotic residues (ARs) in animal products such as milk can be an important driver of antimicrobial resistance in commensal and pathogenic bacteria. Previous studies on ARs in Nepal have demonstrated the presence of ARs in milk samples but without further characterization of the samples for risk factor analysis. This study aimed to quantify the prevalence and risk factors for the presence of ARs in 140 peri-urban dairy farms in Kathmandu, Nepal, included in a cross-sectional survey in 2019 to estimate farm-level AR prevalence. Results: Our results reveal the presence of ARs of sulfamethazine (61%), sulfamethoxazole (53%), ciprofloxacin (46%), and enrofloxacin (42%). Furthermore, of those samples positive for sulfamethazine, sulfamethoxazole, and ciprofloxacin, 81%, 42%, and 42%, respectively, exceeded the maximum residue limit (MRL). While samples taken from farms where staff administered antibiotics were less likely to have single drug residues and multidrug residues (two, three, and four drugs), farms with more workers were more likely to have single residues. Moreover, samples from farms with a higher number of calves and milking cows were more likely to contain single and multiple residues exceeding the MRL, while milk from farms with higher numbers of dry cows and farmers reported by a visiting chemist were less likely to have multidrug residues exceeding the MRL. Methods: High-performance liquid chromatography was conducted on bulk milk samples from farms for an AR analysis, revealing positive results. Additionally, a structured questionnaire and direct farmer interviews were used to collect data on farm biosecurity and farming practices, animal health and hygiene, antibiotic usage (AMU), and attitudes and practices towards antibiotic stewardship. Conclusions: Ultimately, this study provides evidence on the role of modifiable ARs risk factors in the peri-urban milk industry of Kathmandu, which can serve as a foundation for developing improved antimicrobial stewardship guidelines and designing intervention measures to reduce the public health risk posed by ARs in milk sold in Kathmandu, Nepal. [ABSTRACT FROM AUTHOR]

Background/Objectives: Infections in dogs caused by methicillin-resistant staphylococci (MRS) present limited treatment options. This study's objective was to investigate the molecular epidemiology of Staphylococcus spp. cultured exclusively from clinical canine skin and ear samples in Queensland, Australia, using whole-genome sequencing (WGS). Methods: Forty-two Staphylococcus spp. isolated from clinical canine skin and ear samples, from an unknown number of dogs, were sourced from two veterinary diagnostic laboratories between January 2022 and May 2023. These isolates underwent matrix-assisted laser desorption ionisation– time of flight bacterial identification, minimum inhibitory concentration testing using SensititreTM plates and WGS. Phylogenetic trees and core genome multilocus sequence typing (cgMLST) minimum spanning trees (MSTs) were constructed. Results: The isolates included methicillin-resistant and -sensitive S. pseudintermedius (MRSP: 57.1%, 24/42; and MSSP: 19.1%, 8/42), methicillin-resistant and -sensitive S. coagulans (MRSC: 14.3%, 6/42; and MSSC: 2.4%, 1/42) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS: 7.1%, 3/42). Thirty-nine isolates were included after WGS, where all MRS harboured the mecA gene. Eighteen sequence types (STs) were identified, including three novel MRSP and six novel MSSP STs. MRSP ST496-V-VII (23%; 9/39) and MRSP ST749-IV-(IVg) (12.8%; 5/39) were commonly isolated. Phylogenetic analysis of single nucleotide polymorphisms showed that MRSP, MRSC and MSSC were similar to globally isolated staphylococci from canine skin and ear infections. Using cgMLST MSTs, MRSP isolates were not closely related to global strains. Conclusions: Our findings revealed a genotypically diverse geographical distribution and phylogenetic relatedness of staphylococci cultured from clinical canine skin and ear samples across Queensland. This highlights the importance of ongoing surveillance to aid in evidence-based treatment decisions and antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Context Insulin-like growth factor (IGF) signaling is known to affect human ovarian follicular function during growth and development. However, the role of the IGF system is unknown during the ovulatory peak, which is characterized by profound changes in granulosa cell (GCs) mitosis and function. Objective How is the IGF system expressed and regulated during the midcycle surge in women? Methods Follicular fluid (FF) and GCs were collected during the ovulatory peak from 2 specific time points. One sample was obtained before oocyte pickup (OPU): before ovulation trigger (OT) (T = 0 hours) or at 12, 17, or 32 hours after OT, and 1 sample was obtained at OPU 36 hours after OT. Fifty women undergoing ovarian stimulation at a university hospital were included. Gene expression profiles were assessed by microarray analysis of GCs. IGF-related proteins in the FF were assessed by immunoassay or by determination of activity with a proteinase assay. Results Gene expression of proteins promoting IGF activity (ie, IGF2, PAPP-A, and IRS1) together with proliferation markers were downregulated on a transcriptional level in GCs after OT, whereas proteins inhibiting the IGF signal (ie, IGFBPs, IGF2, and STC1) were upregulated. STC1 gene expression and protein levels were greatly upregulated after OT with a parallel steep downregulation of PAPP-A proteolytic activity. Conclusion These data suggest that downregulation of IGF signaling mediated by increased STC1 expression is instrumental for the sudden cessation in GC proliferation and onset of differentiation during the ovulatory peak. [ABSTRACT FROM AUTHOR]

Aim: The Amazon rainforest is one of the most biodiverse regions on earth, but our understanding of the processes that have shaped its patterns of diversity remains incomplete. One hypothesis for Amazonian speciation is the river‐refuge hypothesis, which suggests that retraction of forests away from the periphery of Amazonia, where rivers are narrow, facilitated divergence of populations separated by wide rivers. Later re‐expansion of forests would have allowed secondary contact between these populations, and co‐occurring hybrid zones may reveal the location where expanding forests first reconnected. Here, we test whether a widespread Amazonian songbird species shows evidence of population contact zones in the eastern headwaters of the Tapajós river, hypothesised to be an area of secondary contact under the river‐refuge hypothesis. Location: Amazon and Atlantic forests of South America. Taxon: Ceratopipra rubrocapilla (Pipridae, Passeriformes). Methods: We sampled 147 C. rubrocapilla (Red‐headed Manakin) across its vast range, with 70 samples sequenced using reduced‐representation genomic sequencing and 139 sequenced at the mitochondrial gene cytochrome b. We use population genetic and phylogenetic analyses to investigate patterns of gene flow and population structure across the range, with a particular focus on samples from the headwaters of the Tapajós River to evaluate the potential role of the river‐refuge hypothesis. Results: We observe shallow population structure and evidence for widespread gene flow across the range of C. rubrocapilla. Patterns in the Tapajós headwaters match predictions of the river‐refuge hypothesis, with eastern headwater samples most similar to samples farther west on the opposite bank of the Tapajós River. Main Conclusions: The close co‐occurrence between population contact zones within C. rubrocapilla and other previously studied hybrid zones reinforces the hypothesis that the eastern Tapajós headwaters is where rainforest populations reconnected in the past, following predictions of the river‐refuge hypothesis of Amazonian speciation. [ABSTRACT FROM AUTHOR]

CD163, a macrophage-specific receptor, plays a critical role in scavenging hemoglobin released during hemolysis, protecting against oxidative effects of heme iron. In the bloodstream, hemoglobin is bound by haptoglobin, leading to its immediate endocytosis by CD163. While haptoglobin's structure and function are well understood, CD163's structure and its interaction with the haptoglobin-hemoglobin complex have remained elusive. Here, we present the cryo-electron microscopy structure of the entire extracellular domain of human CD163 in complex with haptoglobin-hemoglobin. The structure reveals that CD163 assembles into trimers (and to some extent dimers), binding haptoglobin-hemoglobin in their center. Key acidic residues in CD163 interact with lysine residues from both haptoglobin and hemoglobin. Calcium-binding sites located near the haptoglobin-hemoglobin interface in CD163 provide explanation for the calcium dependence of the interaction. Furthermore, we show that the interaction facilitating CD163 oligomerization mimics ligand binding and is also calcium dependent. This structural insight into CD163 advances our understanding of its role in hemoglobin scavenging as well as its broader relevance to structurally related scavenger receptors. CD163, a macrophage receptor, is essential for clearing hemoglobin during hemolysis to prevent oxidative damage. Here, the authors reveal the cryo-electron microscopy structure of CD163 bound to haptoglobin-hemoglobin, uncovering calcium-dependent interactions critical for its function and oligomerization. [ABSTRACT FROM AUTHOR]

Ethical challenges are integral to health care and are associated with moral distress among health professionals. Moral distress can turn into burnout with a range of negative effects for professionals, patients, relatives, collaborators, and the organisation. Based on action research a focus group study was conducted inclucing prehospital personnel from the emergency services in the Region of Southern Denmark. Results showed that ethical challenges arise in contexts of (1) caring for patients, (2) managing organisational demands, (3) collaborating. Ethical challenges are addressed informally among personnel in emergency vehicles, at ambulance stations, outside working hours, and ocationally involve family or friends with a background in healthcare. Prehospital physicians have the added opportunity to address ethically sensitive issues during monthly meetings. Voicing ethical challenges presupposes confidence, trust, and feeling safe in relation to colleagues, management, and the organisation. Existing forms of ethics support do not lend themselves to the present organisational setup of the studied emergency services. Targeted clinical ethics support initiatives are needed to address moral distress, prevent burnout, and build a supportive working environment. Initiatives must be developed collaboratively and tested bottom-up to identify and eliminate barriers for implementation. [ABSTRACT FROM AUTHOR]

Background: The prehospital use of blood lactate measurements is increasing. However, the test's benefits have not been methodically evaluated in non-trauma patients. This study had three aims: (1) To assess the evidence of prehospital blood lactate measurements' prognostic value in non-trauma patients, (2) to investigate to what extent the test changed early patient treatment, and (3) to evaluate the healthcare personnel's attitude towards the test. Methods: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were systematically searched until Aug 26, 2023. Cohort and randomized controlled trials assessing ≥ 20 acute non-trauma patients with prehospital lactate measurements were included if they reported (1) prognostic outcomes such as short-term mortality or (2) changes in early patient treatments. All study designs were included to assess (3) the healthcare personnel's opinion on prehospital lactate measurements. The risks of bias were assessed using the QUIPS tool, the Newcastle–Ottawa Scale, and the RoB-2. Study registration number CRD42020167169 (PROSPERO). Results: We screened 6028 study reports. We included 15 studies on (1) the prognostic value of prehospital lactate measurements. Elevated blood lactate levels were correlated to a higher short-term mortality risk in most of the studies but not in studies with out-of-hospital cardiac arrest (OHCA) patients. The 15 prognostic studies were all cohort studies with moderate or high risks of bias. Four studies investigated (2) early treatment changes. They found that the prehospital lactate measurement may have changed early treatment in sepsis patients. However, all four studies on treatment changes were at high risk of bias. Four studies were included on (3) the healthcare personnel's attitude towards the lactate measurement. Evidence of the healthcare personnel's opinion on prehospital lactate measurements was scarce. Conclusion: Most acute non-trauma patients with elevated prehospital lactate levels had increased risks of short-term mortality, except OHCA patients. Few studies suggested that measuring prehospital lactate levels could change early patient care, particularly in patients with suspected sepsis. The certainty of the evidence is low in this systematic review. The included studies were heterogeneous, and many had high risks of bias. Further studies are needed to investigate the impact of prehospital lactate measurements on patient care. [ABSTRACT FROM AUTHOR]

Background: Workplace violence against healthcare workers has been a well-known problem for more than 40 years. This problem is also relevant for prehospital personnel who are at risk of physical and/or psychological violence during work. Violence and threats of violence can have physical and psychological consequences, including personal challenges in their everyday life, use of sick days, reports, and the need for professional help. Therefore, this study aimed to describe the extent of and subsequent reporting of physical and psychological workplace violence toward the prehospital healthcare workers in Denmark in a two-year period. Moreover, we wanted to elucidate any possible effect of workplace violence on the private and professional lives of the prehospital healthcare personnel. Methods: A nation-wide survey where a validated anonymised questionnaire was directed to all of the approximately 4500 Danish prehospital healthcare workers. Results: Out of 584 complete responses we found that 47.4% had experienced psychological violence on the job whereas 25.7% had experienced physical violence on the job within the past two years. The perpetrators were mainly patients or relatives of the patients. Physical violence was mostly reported as punching, pushing, and kicking, while psychological violence included threats of violence and other intimidation. After experiencing violence the respondents reported both physical and psychological harm, which for some prehospital healthcare workers had consequences for their professional and/or personal life. Furthermore, some prehospital healthcare workers reported that the violence had resulted in some patients receiving worse treatment afterwards. We found that violence was rarely reported to either employers or the police, because respondents believed the events were not important enough to merit reporting, or because a report was not considered to make any difference to the healthcare worker. The survey demonstrates that, as a minimum, at least one healthcare worker in 30 and one healthcare worker in 16 has been exposed to episodes of violence and threats of violence within the last two years. Conclusion: We suggest that the prehospital organisations emphasise reporting future episodes of physical and/or psychological violence. Knowing the extent of the problem is a prerequisite for addressing, debriefing, and/or other psychological follow-up. Trial registration: N/A. [ABSTRACT FROM AUTHOR]

In this work, the overarching goal of improving the photooxidative stability of organic components used in photovoltaic devices is addressed, focusing on the common problem of degradation mediated by singlet molecular oxygen. Through a systematic exploration of boron subphthalocyanines (SubPcs), the influence of donor and acceptor substituents on the SubPc's redox properties has been examined, including the SubPc's ability to (1) act as a photosensitizer for singlet oxygen generation and (2) deactivate singlet oxygen are examined. How singlet oxygen formation and removal are influenced by linking together three SubPcs in a compact structure and by linking a SubPc to another molecular unit of relevance for organic photovoltaics (indenofluorene‐extended tetrathiafulvalene) is also examined. Synthetic protocols rooted in acetylenic scaffolding, experimental and computational structure–property relationships (optical and redox properties, singlet oxygen quantum yields, and removal kinetics), and characteristics of a functional photovoltaic device using a SubPc molecule are presented, demonstrating that cyano functionalization results in remarkably enhanced organic photovoltaic device stability. [ABSTRACT FROM AUTHOR]

While co-creation is becoming increasingly popular among public sector institutions to solve problems and create public value, the question is, how the public sector institution can be successful when engaged in multiple (and often overlapping/competing) co-creation initiatives. In this article, we examine the theoretical terms of co-creation, meta-governance and portfolio management to analyse how portfolios of co-creation projects are best managed. We develop two propositions suggesting the link between different forms of portfolio management and co-creation and use the City of Espoo as an illustrative example of the value that can be derived from more adaptive approaches to portfolio management. [ABSTRACT FROM AUTHOR]

Background: Pediatric idiopathic intracranial hypertension (IIH) is a rare and challenging condition. As implied by the nomenclature, the etiologies remain unknown, and multiple etiologies are being investigated. In this study, we explored the potential role of increased systemic or cerebral venous pressure in the pathogenesis. Method: An observational cohort study following the STROBE guidelines, including prepubertal children with clinical symptoms and imaging findings consistent with IIH referred to the neurosurgical department, was conducted. The patients underwent a comprehensive diagnostic protocol, including MRI, continuous intracranial pressure (ICP) monitoring, and endovascular venography with venous pressure measurements. Results: The study included 11 consecutive patients (six boys and five girls) with an average age of 2.3 years, and an average BMI of 18.4. Among these, one patient was found to have venous stenosis with a gradient; the other 10 patients presented with normal intracranial anatomy. All patients exhibited elevated venous pressures, with an average superior sagittal sinus pressure of 18.9 mmHg, average internal jugular vein pressure of 17.0 mmHg, and average central venous pressure of 15.9 mmHg. Daytime ICP averaged 12.9 mmHg, whereas nighttime ICP averaged 17.2 mmHg with either A- or B-waves in 10 of the 11 patients. Despite pathological ICP, only three patients had papilledema. Conclusions: All patients had an increased systemic venous pressure, indicating a possible pathological factor for prepubertal IIH. Additionally, our findings show that young children often only partly meet the Friedman criteria due to a lack of papilledema, emphasizing the need for pediatric-specific diagnostic criteria. Further large-scale studies are needed to confirm these findings and to explore the underlying reasons for this increase in venous pressure and potential new treatment avenues. [ABSTRACT FROM AUTHOR]

This paper aims to enhance the understanding of how small and medium-sized enterprises (SMEs) can bolster their resilience to supply chain disruptions by engaging and aligning cross-functional staff in the process of developing supply chain resilience (SCRES). Employing process theory, the study adopts a multiple case-study methodology involving 18 Danish production SMEs across two iterative phases: an exploratory phase encompassing eight case companies, and a subsequent refinement phase involving an additional ten case companies. Utilizing a mixed-method approach comprising semi-structured interviews, card sorting exercises, observational studies, and a questionnaire survey, the research proposes a four-stage process for enhancing SCRES. This process includes: 1) mapping the supply chain, 2) identifying vulnerabilities and capabilities within each function, 3) prioritizing and creating cross-organizational alignment, and 4) developing action plans. The refined approach, validated through the ten Danish SMEs in the refinement phase, offers a practical and relevant framework for companies seeking to mitigate vulnerabilities and enhance capabilities in their supply chains. By strengthening SMEs' resilience against supply chain disruptions, this approach serves as a potential model for other companies striving to achieve SCRES. [ABSTRACT FROM AUTHOR]

This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings where dynamic sampling methods have been used. PubMed and Embase databases were systematically searched. English‐published studies between 2004 and 2024 involving systemic antibiotic administration in orthopedically relevant tissues and settings based on dynamic measurements were included. In total, 5385 titles were identified. After title and abstract screening, 97 eligible studies (43 different antibiotic drugs) were included. The studies covered both preclinical (42%) and clinical studies including healthy and infected tissues (21%) and prophylactic and steady‐state situations (35%). Microdialysis emerged as the predominant sampling method in 98% of the studies. Most of the presented antibiotics (80%) were only assessed once or twice. Among the most extensively studied antibiotics were cefuroxime (18 studies), linezolid (9 studies) and vancomycin (9 studies). This review presents valuable insights into the microenvironmental distribution of antibiotics in orthopedically relevant target tissues and settings and seeks to provide a basis for improving dosing recommendations and treatment outcomes. However, it is important to acknowledge that our findings are limited to the specific drug, dosing regimens, administration method and target tissue, and are crucially linked to the selected PK/PD target. [ABSTRACT FROM AUTHOR]

Background Glioblastoma and high-grade glioma (HGG) remain non-curable diseases. Symptoms and Quality-of-life (QoL) in the end-of-life (EoL) phase have not been prospectively studied with validated instruments. Therefore, we prospectively assessed symptom progression, symptom management, and hospice utilization in patients with treatment-refractory progressive HGG. Methods Patients failing bevacizumab and presenting with a Karnofsky performance score of ≤60, and their caregivers, were eligible. Symptoms, medication, and clinical management were tracked with serial telephone calls every 2 weeks until death utilizing clinical evaluations and the MD Anderson Symptom Inventory Brain Tumor Module (MDASI-BT). The MDASI-BT rates symptoms on a scale from 0 (no symptoms) to 10 (worst). Results Fifty-four patient-caregiver dyads were enrolled in the study. Amongst 50 evaluable patients, the most severe symptoms during the last 2 weeks prior to death were drowsiness (9.09 ± 1.44), difficulty with concentration (8.87 ± 2.29), fatigue (8.63 ± 2.03), difficulty speaking (8.44 ± 2.42), weakness (8.27 ± 3.44), and difficulty with understanding (7.71 ± 2.94). All symptoms, except weakness and memory impairment, which were high at baseline, showed statistically significant progression. Seizures were rare and did not progressively worsen near the end of life (1.38 ± 3.02). The decision-making composite score almost doubled during the EoL phase (8.58 ± 1.53). Conclusions This is the first prospective study describing symptoms and QoL issues in patients with HGG. Patients suffer from high morbidity in the EoL phase and should be offered early palliative and hospice care to assure proper symptom management and advance care planning. [ABSTRACT FROM AUTHOR]

Catheter-based intervention procedures contain complex maneuvers, and they are often performed using fluoroscopic guidance assisted by 2D and 3D echocardiography viewed on a flat screen that inherently limits depth perception. Emerging mixed reality (MR) technologies, combined with advanced rendering techniques, offer potential enhancement in depth perception and navigational support. The study aims to evaluate a MR-based guidance system for the atrial septal puncture (ASP) procedure utilizing a phantom anatomical model. A novel MR-based guidance system using a modified Monte Carlo-based rendering approach for 3D echocardiographic visualization was introduced and evaluated against standard clinical 3D echocardiographic display on a flat screen. The objective was to guide the ASP procedure by facilitating catheter placement and puncture across four specific atrial septum quadrants. To assess the system's feasibility and performance, a user study involving four experienced interventional cardiologists was conducted using a phantom model. Results show that participants accurately punctured the designated quadrant in 14 out of 16 punctures using MR and 15 out of 16 punctures using the flat screen of the ultrasound machine. The geometric mean puncture time for MR was 31 s and 26 s for flat screen guidance. User experience ratings indicated MR-based guidance to be easier to navigate and locate tents of the atrial septum. The study demonstrates the feasibility of MR-guided atrial septal puncture. User experience data, particularly with respect to navigation, imply potential benefits for more complex procedures and educational purposes. The observed performance difference suggests an associated learning curve for optimal MR utilization. [ABSTRACT FROM AUTHOR]

Objective: We hypothesized that the insulin-sensitizing adipokine adiponectin (ADP) is upregulated in cystic fibrosis (CF) related diabetes (CFRD) and underweight adults with CF. We aimed to assess correlations between glucose metabolism, body composition and ADP in CF. Methods: We performed a cross-sectional study among adults with CF at the Copenhagen CF Center. The study included a fasting level of ADP, an oral glucose tolerance test (OGTT), and a dual energy-x-ray absorptiometry scan. Results: In total, 115 patients were included of whom 104 had an OGTT performed. Glucose intolerance was not correlated with ADP in multivariable analysis, while increased hepatic insulin resistance (i.e., HOMA-IR) was correlated with reduced ADP levels. ADP declined by 4% (eβ 0.96, 95% CI: 0.94, 0.98), 5% (eβ 0.95, 95% CI: 0.93, 0.98), 9% (eβ 0.91, 95% CI: 0.87, 0.95), and 83% (eβ 0.17, 95% CI: 0.08, 0.37) for each one unit (kg/m2) increase in body mass index, fat mass index, muscle mass index, and bone mineral content index, respectively. Conclusions: In CF, ADP was negatively correlated with hepatic insulin resistance as well as low fat, muscle, and bone mass, but not with glucose intolerance. This suggests that malnutrition leads to higher ADP levels in CF. [ABSTRACT FROM AUTHOR]

Non-conveyance refers to the practice of treating a patient on-site without transporting them to a medical facility. It may decrease unnecessary hospital transfers and improve patient satisfaction. Nonetheless, ensuring patient safety remains paramount. The objective of the study was to assess admission to hospital and mortality in non-conveyed patients. This population-based cohort study included all high-acuity dispatches in Region Zealand, Denmark between 2019 and 2022. The primary outcome was admission within 48 h, and the secondary outcome was 30-day mortality. Descriptive statistical analyses were conducted, and logistic regression models were used to estimate adjusted odds ratios and 95% confidence intervals. A non-conveyance rate of 14% was identified in 95,238 transports. Admission within 48 h was seen in 22% of non-conveyed patients vs. 95% in conveyed patients, p < 0.001. The adjusted analysis showed a decreased likelihood of admission within 48 h within non-conveyed patients, with an aOR of 0.01 95% CI (0.01–0.01). Non-conveyed patients had a crude 30-day mortality rate of 2 vs. 6% among conveyed patients, p < 0.001. The adjusted analysis showed an increased likelihood of 30-day mortality in non-conveyed patients with an odds ratio of 1.21, 95% CI (1.05–1.40). Non-conveyed patients constitute a substantial proportion of patients assessed by ambulances following high-acuity dispatch. Less than one in four non-conveyed patients were admitted within 48 h. Despite the low crude mortality in this study, an increased likelihood of mortality was found within the non-conveyed population. However, additional investigation is warranted in future research. [ABSTRACT FROM AUTHOR]

Background: Deep learning methods are revolutionizing natural science. In this study, we aim to apply such techniques to develop blood type prediction models based on cheap to analyze and easily scalable screening array genotyping platforms. Methods: Combining existing blood types from blood banks and imputed screening array genotypes for ~111,000 Danish and 1168 Finnish blood donors, we used deep learning techniques to train and validate blood type prediction models for 36 antigens in 15 blood group systems. To account for missing genotypes a denoising autoencoder initial step was utilized, followed by a convolutional neural network blood type classifier. Results: Two thirds of the trained blood type prediction models demonstrated an F1‐accuracy above 99%. Models for antigens with low or high frequencies like, for example, Cw, low training cohorts like, for example, Cob, or very complicated genetic underpinning like, for example, RhD, proved to be more challenging for high accuracy (>99%) DL modeling. However, in the Danish cohort only 4 out of 36 models (Cob, Cw, D‐weak, Kpa) failed to achieve a prediction F1‐accuracy above 97%. This high predictive performance was replicated in the Finnish cohort. Discussion: High accuracy in a variety of blood groups proves viability of deep learning‐based blood type prediction using array chip genotypes, even in blood groups with nontrivial genetic underpinnings. These techniques are suitable for aiding in identifying blood donors with rare blood types by greatly narrowing down the potential pool of candidate donors before clinical grade confirmation. [ABSTRACT FROM AUTHOR]

ConstructiCons are innovative digital dictionary-like resources that aim to represent large inventories of prominent linguistic patterns called grammatical constructions. Building constructiCon resources is a rapidly advancing emergent field of research that combines the practices of applied language description (lexicography) and theoretical insights of Construction Grammar (a subfield of Cognitive Linguistics). Constructions comprise both grammatical and lexical information and often contain elements that belong to different "levels" of language organization: morphology, syntax, semantics, prosody, etc. Inspired by advances of comparable resources developed for other languages, we propose that a thorough repository of multi-word semi-general constructions should be built for Norwegian and discuss ten crucial benefits of this endeavor. Many of our arguments are applicable to any language that lacks a constructiCon resource and can be of interest for a broader readership. [ABSTRACT FROM AUTHOR]

Background: Low back pain (LBP) is a highly prevalent condition that comprise a large portion of outpatient practice, challenging the diagnosis and treatment. However, the diagnostic tools are limited to clinical history, physical examination and imaging. Degenerative disc disease (DDD) is a significant cause of LBP, and emerging literature confirms the elevated levels of biomarkers in the discs. These biomarkers may serve as a tool for diagnosis, but may also be useful in predicting the treatment outcome. Here, we examine the expression of various cytokines on 1‐year recovery from patients with LBP. Methods: Patient‐reported outcome (PRO) in terms of pain intensity (VAS), disability (ODI), and quality of life (Eq‐5D) is collected from 44 patients at baseline and 12 months after surgery to study the influence of baseline TNF‐α, IL‐1β, and IL‐6 mRNA expression in both annulus fibrosus (AF) and nucleus pulposus (NP). Results: Between baseline and follow‐up, our cohort showed improvement in VAS back pain (p < 0.001), VAS leg pain (p < 0.001), ODI (p = 0.02), and Eq‐5D (p = 0.01). Baseline levels of IL‐1 β was positively correlated with VAS back pain scores in AF (p = 0.05) and NP (p = 0.01) at 1‐year follow‐up. TNF‐α expression at baseline was also positively correlated to ODI scores (p = 0.01) at follow‐up and inversely correlated to improvements in ODI score between baseline and follow‐up, suggesting that high TNF‐α expression at baseline is associated with poor outcomes from surgery. Conclusion: The results from our study support that TNF‐α expression at baseline can serve as a very important predictor of treatment response from lumbar fusion surgery. [ABSTRACT FROM AUTHOR]

Over the last decade, as molecular platforms have permitted the characterization of the genomic landscape of pediatric central nervous system (CNS) tumors, pediatric neuro-oncology has dramatically transformed. NTRK fusions are oncogenic driver alterations that have been found in a multitude of tumor types, including pediatric CNS tumors. In recent years, NTRK inhibitors have emerged as a promising class of targeted therapies for pediatric CNS tumors with NTRK gene fusions. The use of larotrectinib and entrectinib in the relapsed setting for pediatric CNS tumors has resulted in rapid and robust responses in an important fraction of patients. These agents are well tolerated, although close to 20% of patients have spontaneous bone fractures. Given the existing data for patients with relapsed disease, clinical trials using NTRK inhibitors in the upfront setting is the next natural progression of efficacy testing and many are currently underway. There are still several challenges that need to be addressed to optimize the use of NTRK inhibitors and identify the patients with NTRK fusion-positive CNS tumors who are most likely to benefit from them. As these agents are more broadly used, resistance will become a more pervasive issue and strategies will need to be determined for this scenario. This article summarizes the current status of NTRK inhibitors for pediatric CNS tumors and discusses the opportunities and challenges of their expanding use in the future. [ABSTRACT FROM AUTHOR]

Background: Viral infection is a common trigger of severe respiratory illnesses in early life and a risk factor for later asthma development. The mechanism leading to asthma could involve an aberrant airway immune response to viral infections, but this has rarely been studied in a human setting. Objectives: To investigate in situ virus‐specific differences in upper airway immune mediator levels during viral episodes of respiratory illnesses and the association with later asthma. Methods: We included 493 episodes of acute respiratory illnesses in 277 children aged 0–3 years from the COPSAC2010 mother–child cohort. Levels of 18 different immune mediators were assessed in nasal epithelial lining fluid using high‐sensitivity MesoScale Discovery kits and compared between children with and without viral PCR‐identification in nasopharyngeal samples. Finally, we investigated whether the virus‐specific immune response was associated with asthma by age 6 years. Results: Viral detection were associated with upregulation of several Type 1 and regulatory immune mediators, including IFN‐ɣ, TNF‐α, CCL4, CXCL10 and IL‐10 and downregulation of Type 2 and Type 17 immune mediators, including CCL13, and CXCL8 (FDR <0.05). Children developing asthma had decreased levels of IL‐10 (FDR <0.05) during viral episodes compared to children not developing asthma. Conclusion: We described the airway immune mediator profile during viral respiratory illnesses in early life and showed that children developing asthma by age 6 years have a reduced regulatory (IL‐10) immune mediator level. This provides insight into the interplay between early‐life viral infections, airway immunity and asthma development. [ABSTRACT FROM AUTHOR]

While significant progress has been made in understanding various aspects of liver regeneration, the molecular mechanisms responsible for the initiation and termination of cell proliferation in the liver following massive tissue loss or injury of liver remain unknown. As it was previously shown, the loss of liver mass affects putative hepatocyte‐specific mitogenic inhibitors in the blood. Although the presence of these putative inhibitors regulating precise liver regeneration has been described in numerous publications, they have never been identified. Extracellular vesicles (EVs) are nano‐sized, membrane‐limited structures secreted by cells into the extracellular space. Their proposed role is stable intercellular carriers of proteins and RNAs, predominantly micro‐RNA, from secreted to recipient cells. Upon uptake by the recipient cells, EVs can significantly modulate their biological functions. In the present study, using in vivo and in vitro models, we demonstrate that hepatocyte proliferation and liver regeneration are regulated by EVs secreted by hepatocytes into the bloodstream. This regulation occurs through a negative feedback mechanism, which explains the precise regeneration of liver tissue after massive damage. We also demonstrate that an essential component of this mechanism is RNA carried by hepatocyte‐derived EVs. Our findings open up a new and unexplored area of liver biology regarding the mechanisms involved in the precise regulation of liver regeneration after a massive tissue loss or injury. Further study of this mechanism will have a great influence on the development of new approaches to liver transplantation, various liver pathologies, and hepatic tumors. [ABSTRACT FROM AUTHOR]

Summary: The use of black soldier fly larvae (BSFL) to valorise different organic waste streams and the subsequent use of resulting larvae as a feedstock ingredient is increasing rapidly in several regions across the globe. The lack of knowledge about several safety issues including chemical contaminants (e.g. heavy metals) seems to affect the upscaling and commercialisation of this product. This study evaluates the safety of the BSFL against chemical contaminants including heavy metals and mycotoxins in both BSFL and frass samples reared with different food waste streams (e.g. soy waste, customised bread‐vegetable diet, food waste mixture, supermarket and childcare centre) from two commercial production facilities. The effect of larval instars and post‐harvest treatments (e.g. blanching and drying) on the safety of the BSFL was also investigated. The concentration of heavy metals was primarily influenced by the concentration in the food waste streams. The concentration was also higher in 6th instar compared to 5th instar larvae. The effect of blanching and drying have a varied effect on the concentration of heavy metals. Mycotoxins were found to be below the limit of quantification for all samples. The outcomes of this study indicated that BSFL grown on food waste streams and the resulting frass is safe against different heavy metals analysed. The findings of this study will assist the commercial BSFL manufacturers with the identification of relevant control points to ensure the chemical safety of their products. Therefore, encourage the use of different food waste streams as feedstock for rearing BSFL. [ABSTRACT FROM AUTHOR]

Background: The use of fertility indicators to predict ovulation has largely been studied for contraceptive purposes, while less so as fertility‐promoting tools. Objective: To investigate the association between fertility indicators and fecundability in Danish women trying to conceive. Methods: Web‐based preconception cohort study. We analysed data from 11,328 females aged 18–49 years trying to conceive without fertility treatment for ≤6 menstrual cycles, from the Danish SnartGravid.dk and SnartForældre.dk cohorts (2007–2023). Participants reported the use of fertility indicators (counting days since the last menstrual period, cervical fluid monitoring, urinary ovulation testing, feeling ovulation, using a smartphone fertility app and measuring basal body temperature [BBT]). Time to pregnancy was measured in menstrual cycles ascertained by self‐reported pregnancy status. We estimated fecundability ratios (FR) and 95% confidence intervals (CI) using proportional probabilities regression models adjusted for age, socio‐economic position, health indicators, reproductive history and gynaecological factors. Results: Fertility indicators were used by 63.3% of participants at study entry. Counting days was the most common (46.9%), while measuring BBT was the least (3.0%). Other indicators ranged from 17.0% to 23.6%, with 69.7% using more than one indicator. Compared with non‐use, use of any fertility indicator was associated with greater fecundability (adjusted FR 1.14, 95% CI 1.08, 1.19). Cervical fluid monitoring showed the strongest association (aFR 1.46, 95% CI 1.03, 2.07), followed by urinary ovulation testing (aFR 1.35, 95% CI 1.16, 1.58) and counting days (aFR 1.18, 95% CI 1.09, 1.29). Feeling ovulation and fertility apps were modestly associated with fecundability, while measuring BBT was not associated. Sensitivity analysis restricting to ≤2 cycles of attempt time and two cycles of follow‐up showed an aFR for any indicator use of 1.21 (95% CI 1.13, 1.31). Conclusion: In this Danish preconception cohort, use of fertility indicators was associated with a higher fecundability, varying by type of indicator. [ABSTRACT FROM AUTHOR]

Headache disorders are the most common disorders of the nervous system. The lifetime prevalence of headache disorders show that some individuals never experience headache. The etiology of complete freedom from headache is not known. To assess genetic variants associated with complete freedom from headache, we performed a genome-wide association study of individuals who have never experienced a headache. We included 63,992 individuals (2,998 individuals with complete freedom from headache and 60,994 controls) from the Danish Blood Donor Study Genomic Cohort. Participants were included in two rounds, from 2015 to 2018 and in 2020. We discovered a genome-wide significant association, with the lead variant rs7904615[G] in ADARB2 (EAF = 27%, OR = 1.20 [1.13–1.27], p = 3.92 × 10−9). The genomic locus was replicated in a non-overlapping cohort of 13,032 individuals (539 individuals with complete freedom from headache and 12,493 controls) from the Danish Blood Donor Study Genomic Cohort (p < 0.05, two-sided). Participants for the replication were included from 2015 to 2020. In conclusion, we show that complete freedom from headache has a genetic component, and we suggest that ADARB2 is involved in complete freedom from headache. The genomic locus was specific for complete freedom from headache and was not associated with any primary headache disorders. A genome-wide association study in a cohort of 63,992 Danish blood donors identified an association between complete freedom from headache and a locus in the ADARB2 gene. The association was replicated in a cohort of 13,032 Danish blood donors. [ABSTRACT FROM AUTHOR]

The objective of this study was to measure the aerodynamic characteristics of the NACA 0018 airfoil across a range of low Reynolds numbers, with a particular focus on the unique behaviours observed in this regime. The experiments were conducted primarily in a low-turbulence wind tunnel using wall pressure taps, a pressure rake, and a force gauge. The Reynolds numbers investigated ranged from 30.000 to 160.000, with angles of attack spanning from -190 to +20 degrees. A major achievement of this research was the successful acquisition of data at Re = 30.000, where the lift behaviour significantly deviated from that observed at higher Reynolds numbers. The results demonstrated a strong dependency of aerodynamic characteristics on Reynolds number, with the drag coefficient at zero angle of attack decreasing by over 700 percent when Re increased from 30.000 to 160.000. Additionally, two independent techniques for measuring lift force were employed, both yielding consistent results despite the low Reynolds number. The experimental results were also compared with XFOIL and 2-D CFD simulations, which, although not perfectly accurate, provided reasonably good predictions. [ABSTRACT FROM AUTHOR]

Aims: Based on selected themes from a national survey, the study aims to describe and analyse similarities and differences in community-based palliative care provided to people living at home in two different care settings – the nursing home setting and the home care setting. Methods: Responses from four palliative care themes covered by a national survey sent to 717 managers in municipality-based care units were used. The themes were: (a) target groups in palliative care; (b) wishes for end-of-life care; (c) tools/guidelines in palliative care; and (d) palliative care provided to relatives. Results: The response rates were 53% in the nursing home setting and 69% in the home care setting (69%). Both settings had target groups for palliative care, in which significantly more units in the home care settings cared for people with other cultural backgrounds or children. Wishes for end-of-life care were addressed by more than 90% of the units in both settings. There were significantly more nursing home units that addressed questions regarding resuscitation, decision making when you are incapable of making decisions for yourself, and the level of medication. In both settings, around half of the units did not use or did not know if they used tools/guidelines to identify palliative care needs. Half of home care and 65% of nursing home settings did not/were unaware of providing palliative care to relatives. Conclusions: Both settings serve target populations for palliative care with few differences. Identifying palliative care needs seemed to be a low priority in both settings. A difference was found between the settings regarding end-of-life care questions and palliative care promotion to relatives. [ABSTRACT FROM AUTHOR]

Molecular solar thermal systems, which absorb light, store it, and release it as heat, have been extensively researched, yet many potential candidates remain unexplored. To expand this range, five specifically designed ortho-dianthrylbenzenes were investigated. Anthracene dimers have been underexplored due to issues like photooxidation and varying photodimerization efficiency. The presented systems address these challenges by aryl-linking two anthracene moieties, achieving photodimerization quantum yields ranging from 11.5% to 16% in mesitylene. The impact of donor or acceptor groups on energy storage time (9–37 years), energy storage density (0.14–0.2 MJ kg−1), and solar energy storage efficiency (0.38–0.66%) was evaluated. The experimental results, supported by density functional theory-based modeling, highlight the potential of anthracene-based photoswitches for molecular solar thermal applications and encourage further exploration of similar systems. [ABSTRACT FROM AUTHOR]

This study presents in situ, high-resolution optical measurements of particle size distributions (PSD) within sediment plumes generated by a pre-prototype deep seabed nodule collector vehicle operating in the abyssal Pacific Ocean. These measurements were obtained using a cutting-edge instrument, the LISST-RTSSV sensor. The data collected in situ reveal marked differences compared to previously reported laboratory-based, ex situ measurements. The grain size and other key particle shape characteristics are found to be dependent on multiple factors, including the collector vehicle maneuvers, the time elapsed following sediment discharge, and the complex hydrodynamic processes that generate the sediment in suspension. Significantly, the PSD from a highly complex succession of straight-line maneuvers converges to that of the canonical case of a simple straight-line driving maneuver within a timescale of ten minutes. Our results underscore the importance of parameterizing sediment plume transport models based on well-informed, comprehensive PSDs of detrained suspended sediment measured in situ at adequate timescales and in regions no longer strongly influenced by active and complex hydrodynamic processes. [ABSTRACT FROM AUTHOR]

Implementation of standardized protocols in neurooncology during the surgical resection of brain tumors is needed to advance the clinical treatment paradigms that use tissue for diagnosis, prognosis, bio-banking, and treatment. Currently recommendations on intraoperative tissue procurement only exist for diffuse gliomas but management of other brain tumor subtypes can also benefit from these protocols. Fresh tissue from surgical resection can now be used for intraoperative diagnostics and functional precision medicine assays. A multidisciplinary neuro-oncology perspective is critical to develop the best avenues for practical standardization. This perspective from the multidisciplinary Oncology Tissue Advisory Board (OTAB) discusses current advances, future directions, and the imperative of adopting standardized protocols for diverse brain tumor entities. There is a growing need for consistent operating room practices to enhance patient care, streamline research efforts, and optimize outcomes. [ABSTRACT FROM AUTHOR]

Wastewater treatment plants (WWTPs) connected to combined sewer systems must cope with high flows during wet-weather conditions, often leading to bypass and thus pollution of water bodies. Radar rainfall forecasts coupled with a rainfall-runoff model provides flow and volume forecasts that can be used for deciding when to switch from normal to wet-weather operation, which temporarily allows for higher inflow. However, forecasts are by definition uncertain and may lead to potential mismanagement, e.g., false alarms and misses. Our study focused on two years of operational data from the Damhuså sewer catchment and WWTP. We used the Relative Economic Value (REV) framework to optimize the control parameters of a baseline control strategy (thresholds on flow measurements and radar flow prognosis) and to test new control strategies based on volume instead of flow thresholds. We investigated two situations with different objective functions, considering higher negative impact from misses than false alarms and vice versa, and obtained in both cases a reduction of the rate of false alarms, higher flow thresholds and lower bypass compared to the baseline control. We also assess a new control strategy that employs thresholds of predicted accumulated volume instead of predicted flow and achieved even better results. [ABSTRACT FROM AUTHOR]

Anaphylaxis is an allergic manifestation characterised by rapid onset and progression. Rapid treatment may be challenging in patients with atypical symptoms or no previous history of anaphylaxis. This study aimed to describe the clinical prehospital presentation of first-time anaphylactic patients. To help target educational initiatives, we sought to identify which groups of medical professionals are most likely to encounter first-time anaphylactic patients and investigated the referral pattern for suspected anaphylactic patients for specialised treatment. A retrospective register-based study from the Region of Southern Denmark. Patients referred to the Allergy Centre, Odense University Hospital, from 2019 to 2021 were included. The medical records were manually reviewed for first contact with the emergency departments or the emergency medical service. 444 patients with suspected anaphylaxis were referred. 226 patients had grade 3–5 systemic allergic reactions as classified by the World Allergy Organisation; 90% had cutaneous symptoms, 63% symptoms from the central nervous system, 42% gastrointestinal symptoms, 40% cardiovascular symptoms, 36% had upper-airway symptoms, and 36% had lower-airway symptoms. Patients treated prehospitally had a significantly more severe degree of anaphylaxis than patients only treated within the hospital. More than half of the patients with suspected anaphylaxis were referred to the Allergy Centre from the emergency departments. Patients with allergies progressing to severe anaphylaxis most often are treated prehospitally before transport to emergency departments. From the emergency departments, they are referred to the allergy centre. Education concerning the immediate treatment of severe anaphylaxis should primarily be targeted towards prehospital care providers. [ABSTRACT FROM AUTHOR]

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) is increasing, and translational animal models are needed to develop novel treatments for this disease. The physiology and metabolism of pigs have a relatively high resemblance to humans, and the present study aimed to characterize choline-deficient and high-fat diet (CDAHFD)-fed Göttingen Minipigs as a novel animal model of MASLD/MASH. Göttingen Minipigs were fed CDAHFD for up to 5 mo, and the phenotype was investigated by the analysis of plasma parameters and repeated collection of liver biopsies. Furthermore, changes in hepatic gene expression during the experiment were explored by RNA sequencing. For a subset of the minipigs, the diet was changed from CDAHFD back to chow to investigate whether the liver pathology was reversible. Göttingen Minipigs on CDAHFD gained body weight, and plasma levels of cholesterol, AST, ALT, ALP, and GGT were increased. CDAHFD-fed minipigs developed hepatic steatosis, inflammation, and fibrosis, which in 5 of 16 animals progressed to cirrhosis. During an 11-wk chow reversal period, steatosis regressed, while fibrosis persisted. Regarding inflammation, the findings were less clear, depending on the type of readout. MASH Human Proximity Scoring (combined evaluation of transcriptional, phenotypic, and histopathological parameters) showed that CDAHFD-fed Göttingen Minipigs resemble human MASLD/MASH better than most rodent models. In conclusion, CDAHFD-fed minipigs develop a MASH-like phenotype, which, in several aspects, resembles the changes observed in human patients with MASLD/MASH. Furthermore, repeated collection of liver biopsies allows detailed characterization of histopathological changes over time in individual animals. NEW & NOTEWORTHY: The physiology and metabolism of pigs have a relatively high resemblance to humans. This study characterizes a new animal model of MASLD/MASH using CDAHFD-fed Göttingen Minipigs. Göttingen Minipigs fed CDAHFD gained weight and developed hepatic steatosis, inflammation, fibrosis, and cirrhosis. After an 11-wk chow-reversal period, hepatic steatosis and some inflammatory parameters reversed. Combined evaluation of phenotypic, transcriptional, and histological parameters revealed the minipig model showed a higher resemblance to human disease than many rodent models. [ABSTRACT FROM AUTHOR]

* OBJECTIVE: To investigate how a global rating of change (GROC) score corresponds to change in Knee injury and Osteoarthritis Outcome Score (KOOS) subscales in people with patellofemoral pain (PFP). * DESIGN: Secondary analysis of data from 3 clinical trials. * METHODS: Four hundred ninety adolescents (10-18 years old) and adults (19-40 years old) with PFP completed KOOS (5 subscales, 0-100) at baseline and 3-month follow-up as well as GROC at 3-month follow-up. GROC category descriptors were mapped to 5 categories: worse, no change, a bit better, better, and much better. Gaussian approximation was then used to calculate the change in KOOS scores for each GROC category. * RESULTS: Due to overlap between KOOS scores in "no change" and "a bit better," all analyses were performed on 4 categories. For all KOOS subscales, patients who reported being "worse" had negative KOOS scale change scores (≤ -2); patients reporting "no change" had KOOS scale change scores that ranged from -5 to 14; and patients feeling "better" or "much better" had positive KOOS scale change scores that ranged from 4 to 26 and ≥16, respectively. * CONCLUSION: When patients with PFP reported feeling "worse," "better," or "much better," there was a small-to-substantial change across the different KOOS scales. This is in contrast to no difference between reporting "a bit better" or "no change" in KOOS. When patients say they feel a little better, clinicians should be less confident about whether change has truly occurred. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of expansive and contractive body displays on adaptive behavior and affective outcomes. Addressing limitations in past research, the effects were investigated in two different contexts (i.e., fear context and sadness context), compared with two types of control conditions and the moderating effects of motivational traits and symptoms of psychopathology were accounted for. A sample of 186 adults completed a fear experiment involving a mock job interview and a sadness experiment involving sad mood induction. For each experiment, participants were randomly assigned to one of four body manipulations: (1) expansive; (2) contractive; (3) active control (i.e., running in place); or 4) passive control (i.e., doing nothing). The primary outcome was adaptive behavior (i.e., appropriate job‐interview behavior and positive recall bias). Secondary affective outcomes were emotions, action tendencies, and appraisals. Results revealed small, non‐significant effects of body displays on primary outcomes (ds = 0.19–0.28). For secondary outcomes, significant effects were identified for positive emotions (ds = 0.33). Across secondary outcomes, pairwise comparisons revealed that expansive displays led to more favorable outcomes than contractive displays. For participants with the highest levels of depression, body display conditions led to less favorable affective outcomes than control conditions. The results suggest that body displays do not influence adaptive behavior within the investigated contexts. When compared to contractive displays, expansive displays were found to yield more favorable affective changes. Lastly, the findings indicate that further investigations into body manipulations in the context of psychopathology are warranted. [ABSTRACT FROM AUTHOR]

Evidence suggests that separate spheres gender norms discourage girls from maths. We therefore examine a policy that counteracts such norms among parents, and investigate whether it increases girls' participation in maths‐intensive studies. Specifically, we examine a parental leave reform that reserved one month of leave for fathers, and estimate its effect on children's study choices. We find that the reform increases the probability of doing a maths‐intensive programme in upper secondary education among girls whose father was otherwise reluctant to take leave. There is no effect on boys. We also conduct heterogeneity analyses to investigate whether the results can be explained by human capital transmission or the gender norms mechanism. The results of our analyses suggest that the gender norms mechanism is at play. [ABSTRACT FROM AUTHOR]