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ABSTRACT Lower respiratory tract infections (LRTIs) remain a significant global cause of infectious disease-related mortality. Accurate discrimination between acute bacterial and viral LRTIs is crucial for optimal patient care, prevention of unnecessary antibiotic prescriptions, and resource allocation. Plasma samples from LRTI patients with bacterial (n = 36), viral (n = 27; excluding SARS-CoV-2), SARS-CoV-2 (n = 22), and mixed bacterial–viral (n = 38) etiology were analyzed for protein profiling. Whole-blood RNA samples from a subset of patients (bacterial, n = 8; viral, n = 8; and SARS-CoV-2, n = 8) were analyzed for transcriptional profiling. Lasso regression modeling identified a seven-protein signature (CRP, IL4, IL9, IP10, MIP1α, MIP1β, and TNFα) that discriminated between patients with bacterial (n = 36) vs viral (n = 27) infections with an area under the curve (AUC) of 0.98. When comparing patients with bacterial and mixed bacterial–viral infections (antibiotics clinically justified; n = 74) vs patients with viral and SARS-CoV-2 infections (antibiotics clinically not justified; n = 49), a 10-protein signature (CRP, bFGF, eotaxin, IFNγ, IL1β, IL7, IP10, MIP1α, MIP1β, and TNFα) with an AUC of 0.94 was identified. The transcriptional profiling analysis identified 232 differentially expressed genes distinguishing bacterial (n = 8) from viral and SARS-CoV-2 (n = 16) etiology. Protein–protein interaction enrichment analysis identified 20 genes that could be useful in the differentiation between bacterial and viral infections. Finally, we examined the performance of selected published gene signatures for bacterial–viral differentiation in our gene set, yielding promising results. Further validation of both protein and gene signatures in diverse clinical settings is warranted to establish their potential to guide the treatment of acute LRTIs.IMPORTANCEAccurate differentiation between bacterial and viral lower respiratory tract infections (LRTIs) is vital for effective patient care and resource allocation. This study investigated specific protein signatures and gene expression patterns in plasma and blood samples from LRTI patients that distinguished bacterial and viral infections. The identified signatures can inform the design of point-of-care tests that can aid healthcare providers in making informed decisions about antibiotic prescriptions in order to reduce unnecessary use, thereby contributing to reduced side effects and antibiotic resistance. Furthermore, the potential for faster and more accurate diagnoses for improved patient management in acute LRTIs is compelling.

ABSTRACT Sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes throughout the COVID-19 pandemic has generated a wealth of data on viral evolution across populations, but only a few studies have so far explored SARS-CoV-2 evolution across large connected transmission networks. Here, we couple data from SARS-CoV-2 sequencing with contact tracing data from an outbreak with a single origin in a rural Norwegian community where samples from all exposed persons were collected prospectively. A total of 134 nasopharyngeal samples were positive by PCR. Among the 121 retrievable genomes, 81 were identical to the genome of the introductor, thus demonstrating that genomics beyond clustering genotypically similar viral genomes to confirm relatedness offers limited additional value to manual contact tracing. In the cases where mutations were discovered, five small genetic clusters were identified. We observed a household secondary attack rate of 77%, with 92% of household members infected among households with secondary transmission, suggesting that SARS-CoV-2 introduction into large families is likely to affect all household members.IMPORTANCEIn outbreak investigations, obtaining a full overview of infected individuals within a population is seldom achieved. We here present an example where a single introduction of B1.1.7 SARS-CoV-2 within a rural community allowed for tracing of the virus from an introductor via dissemination through larger gatherings into households. The outbreak occurred before widespread vaccination, allowing for a “natural” outbreak development with community lockdown. We show through sequencing that the virus can infect up to five consecutive persons without gaining mutations, thereby showing that contact tracing seems more important than sequencing for local outbreak investigations in settings with few alternative introductory transmission pathways. We also show how larger households where a child introduced transmission appeared more likely to promote further spread of the virus compared to households with an adult as the primary introductor.

Objectives: This study aimed to describe the microbial aetiology of community-acquired pneumonia (CAP) in adults admitted to a tertiary care hospital and assess the impact of syndromic polymerase chain reaction (PCR) panels on pathogen detection. Methods: Conducted at Haukeland University Hospital, Norway, from September 2020 to April 2023, this prospective study enrolled adults with suspected CAP. We analysed lower respiratory tract samples using both standard-of-care tests and the BIOFIRE® FILMARRAY® Pneumonia Plus Panel (FAP plus). The added value of FAP Plus in enhancing the detection of clinically relevant pathogens, alongside standard-of-care diagnostics, was assessed. Results: Of the 3238 patients screened, 640 met the inclusion criteria, with 384 confirmed to have CAP at discharge. In these patients, pathogens with proven or probable clinical significance were identified in 312 (81.3%) patients. Haemophilus influenzae was the most prevalent pathogen, found in 118 patients (30.7%), followed by SARS-CoV-2 in 74 (19.3%), and Streptococcus pneumoniae in 64 (16.7%). Respiratory viruses were detected in 186 (48.4%) patients. The use of FAP plus improved the pathogen detection rate from 62.8% with standard-of-care methods to 81.3%. Conclusions: Pathogens were identified in 81% of CAP patients, with Haemophilus influenzae and respiratory viruses being the most frequently detected pathogens. The addition of the FAP plus panel, markedly improved pathogen detection rates compared to standard-of-care diagnostics alone.

ObjectivesMentalizing difficulties are central to borderline personality disorder (BPD), have severe consequences, and are an explicit focus in mentalization-based treatment. The significance of mentalizing capacity as a predictor or mediator of change is however still uncertain due to a scarcity of research. The Mentalization Breakdown Interview (MBI) was developed as a time saving tool for studying psychotherapy processes and outcome in borderline pathology. This study aimed to investigate the convergent validity of reflective functioning (RF) ratings based on the MBI (MBI-RF) by a comparison with the gold standard, i.e., RF assessments based on the Adult Attachment Interview (AAI-RF). A secondary aim was to investigate how MBI-RF relates to core symptoms of BPD, levels of functional impairment and symptom distress compared with AAI-RF.MethodForty-five patients with BPD or significant BPD traits were included. MBI-RF and AAI-RF were rated using the Reflective Functioning Scale. Levels of MBI-RF and AAI-RF and the correlation between the measures were calculated, as well as their associations with the Difficulties in Emotion Regulation Scale, Levels of Personality Functioning-Brief Form 2.0, Work and Social Adjustment Scale, Patient Health Questionnaire, Depression, Generalized Anxiety Disorder-7, self-harm, suicide attempts, and PD diagnostics.ResultsThe correlation between MBI-RF and AAI-RF was 0.79 (p

ABSTRACT This prospective study assessed the value of initial microscopy evaluation of sputum samples submitted for rapid syndromic PCR-based testing. Bacterial detections by the BioFire FilmArray Pneumonia Panel plus in 126 high- and 108 low-quality sputum samples, based on initial microscopy evaluation in samples from patients with lower respiratory tract infections were compared. We found that high-quality samples had a higher proportion of bacterial detections compared to low-quality samples (P = 0.013). This included a higher proportion of detections of bacteria deemed clinically relevant by predefined criteria (70% and 55%, P = 0.016), as well as a higher proportion of detections of Haemophilus influenzae (36% and 20%, P = 0.010). High-quality samples also had more detections of bacteria with high semi-quantitative values. The study found no significant difference between high- and low-quality samples in the proportions of samples with a single species of bacteria detected, samples with a bacteria treated by the clinician, samples with detection of a proven etiology of community-acquired pneumonia by predefined criteria, the number of bacterial species detected, or the detection of Streptococcus pneumoniae, Moraxella catarrhalis, or Staphylococcus aureus. The results showed that 40% (95% CI 35%–47%) of the bacterial detections would have been missed if only high-quality samples were analyzed. This included 41% (27%–56%) of detections of S. pneumoniae, 33% (23%–45%) of detections of H. influenzae, 42% (28%–58%) of detections of S. aureus, and 37% (23%–54%) of detections of M. catarrhalis. These findings suggest that all sputum samples submitted for rapid syndromic PCR testing should be analyzed, regardless of initial microscopy quality assessment. (This study has been registered at ClinicalTrials.gov under registration no. NCT04660084.) IMPORTANCE Microscopic quality assessment of sputum samples was originally designed for sputum culture, and its applicability in today’s workflow, which includes syndromic PCR testing, may differ. Addressing this crucial gap, our study emphasizes the need to optimize the use and workflow of syndromic PCR panels, like the BioFire FilmArray Pneumonia plus (FAP plus), in microbiology laboratories. These advanced PCR-based tests offer rapid and comprehensive pathogen detection for respiratory infections, yet their full potential remains uncertain. By comparing bacterial detections in high- and low-quality sputum samples, we underscore the importance of including low-quality samples in testing. Our findings reveal a significant proportion of potentially clinically relevant bacterial detections that would have been missed if only high-quality samples were analyzed. These insights support the efficient implementation of syndromic PCR panels, ultimately enhancing patient care and outcomes.

Abstract Background The COVID-19 pandemic was met with strict containment measures. We hypothesized that societal infection control measures would impact the number of hospital admissions for respiratory tract infections, as well as, the spectrum of pathogens detected in patients with suspected community acquired pneumonia (CAP). Methods This study is based on aggregated surveillance data from electronic health records of patients admitted to the hospitals in Bergen Hospital Trust from January 2017 through June 2021, as well as, two prospective studies of patients with suspected CAP conducted prior to and during the COVID-19 pandemic (pre-COVID cohort versus COVID cohort, respectively). In the prospective cohorts, microbiological detections were ascertained by comprehensive PCR-testing in lower respiratory tract specimens. Mann–Whitney’s U test was used to analyse continuous variables. Fisher’s exact test was used for analysing categorical data. The number of admissions before and during the outbreak of SARS-CoV-2 was compared using two-sample t-tests on logarithmic transformed values. Results Admissions for respiratory tract infections declined after the outbreak of SARS-CoV-2 (p

Abstract Background Community-acquired pneumonia (CAP) causes a large burden of disease. Due to difficulties in obtaining representative respiratory samples and insensitive standard microbiological methods, the microbiological aetiology of CAP is difficult to ascertain. With a few exceptions, standard-of-care diagnostics are too slow to influence initial decisions on antimicrobial therapy. The management of CAP is therefore largely based on empirical treatment guidelines. Empiric antimicrobial therapy is often initiated in the primary care setting, affecting diagnostic tests based on conventional bacterial culture in hospitalized patients. Implementing rapid molecular testing may improve both the proportion of positive tests and the time it takes to obtain test results. Both measures are important for initiation of pathogen-targeted antibiotics, involving rapid de-escalation or escalation of treatment, which may improve antimicrobial stewardship and potentially patient outcome. Methods Patients presenting to the emergency department of Haukeland University Hospital (HUH) in Bergen, Norway, will be screened for inclusion into a pragmatic randomised controlled trial (RCT). Eligible patients with a suspicion of CAP will be included and randomised to receive either standard-of-care methods (standard microbiological testing) or standard-of-care methods in addition to testing by the rapid and comprehensive real-time multiplex PCR panel, the BioFire® FilmArray® Pneumonia Panel plus (FAP plus) (bioMérieux S.A., Marcy-l’Etoile, France). The results of the FAP plus will be communicated directly to the treating staff within ~2 h of sampling. Discussion We will examine if rapid use of FAP plus panel in hospitalized patients with suspected CAP can improve both the time to and the proportion of patients receiving pathogen-directed treatment, thereby shortening the exposure to unnecessary antibiotics and the length of hospital admission, compared to the standard-of-care arm. The pragmatic design together with broad inclusion criteria and a straightforward intervention could make our results generalizable to other similar centres. Trial registration ClinicalTrials.gov NCT04660084 . Registered on December 9, 2020

Abstract Background To assess baseline characteristics, drug utilisation and healthcare use for oral anticoagulants (OACs) following the introduction of non-vitamin K antagonist oral anticoagulants among patients with atrial fibrillation in primary care in Norway. Methods In this retrospective longitudinal cohort study, 92,936 patients with atrial fibrillation were identified from the Norwegian Primary Care Registry between 2010 and 2018. Linking to the Norwegian Prescription Database, we identified 64,112 patients (69.0%) treated with OACs and 28,824 (31%) who were untreated. Participants were followed until 15 May 2019, death, or loss to follow-up, whichever came first. For each OAC, predictors of initiation were assessed by modelling the probability of initiating the OAC using logistic regression, and predictors of the first switch after index date were assessed using multivariable Cox proportional hazards models. The numbers of primary care visits per quarter by index OAC were plotted and analysed with negative binomial regression analyses offset for the log of days at risk. Results Patients treated with OACs were older, had more comorbidities, and higher CHA2DS2-VASc scores than untreated patients. However, the mean CHA2DS2-VASc in the non-OAC group was 1.58 for men and 3.13 for women, suggesting an indication for OAC therapy. The percentage of patients with atrial fibrillation initiating OACs increased from 59% in 2010 to 79% in 2018. Non-vitamin K antagonist oral anticoagulant use increased throughout the study period to 95% of new OAC-treated patients in 2018, and switches from warfarin to non-vitamin K antagonist oral anticoagulants were common. The persistence of OAC treatment was > 60% after four years, with greatest persistence for apixaban. Patients treated with non-vitamin K antagonist oral anticoagulants had fewer primary care visits compared with those treated with warfarin (incidence rate ratio: 0.73, 95% confidence interval 0.71 to 0.75). Conclusion In this Norwegian primary care study, we found that the shift from warfarin to non-vitamin K antagonist oral anticoagulants was successful with 95% use in patients initiating OACs in 2018, and associated with fewer general practitioner visits. Persistence with OACs was high, particularly for apixaban. However, many patients eligible for treatment with OACs remained untreated.

In recent years, the political approach to gender balance in academia has shifted from "fixing the women" to "fixing the system". Based on an action research (AR) project aimed at enabling more women to qualify for senior positions in the academic field and conducted at one of Norway's largest university colleges, this study explores the expectations of the participants during the initial phase of the project regarding what measures and strategies the project should offer. Using method triangulation, I have garnered insights into the priorities of these women, the polarizations that arose, and the consequences of these polarizations—all regarding the differences between the participants in strategic preferences and ways of doing gender. More specifically, this research unpacks conflicting norms of these women concerning factors such as community, support and care versus self-protection, individual competition, and professional goal-orientedness. This study mainly draws on the discourse analysis resources and theoretical contributions of Judith Butler and Michel Foucault. [ABSTRACT FROM AUTHOR]

ObjectiveEvidence-based personality disorder (PD) treatments are dominated by interventions targeting Borderline PD, although clinical populations characteristically include different PD features and severity. Personality functioning is a new concept intended to capture common features across PDs. This study aimed to investigate longitudinal improvement of personality functioning in a clinical sample assigned to PD treatment.MethodAn observational, large, longitudinal study of patients in PD treatments on specialist mental health service levels (N = 1,051). DSM-5 PDs were systematically assessed on referral. Personality functioning was repeatedly assessed (LPFS-BF-2.0), supplemented by symptom distress (anxiety: PHQ-GAD-7, depression: PHQ-9), and social/occupational activity (WSAS, work/study activity). Statistics were linear mixed models.ResultsThirty per cent had personality difficulties below PD threshold. Among PDs, 31% had Borderline (BPD), 39% Avoidant (AvPD), 15% not otherwise specified, 15% other PDs, and 24% > one PD. More severe initial LPFS-BF was associated with younger age, presence of PD and increasing number of total PD criteria. Across PD conditions, LPFS-BF, PHQ-9 and GAD-7 improved significantly (overall effect size 0.9). Mean duration of PD treatment was 15 (SD 9) months. Drop-out rates were low (12%). LPFS-BF improvement-rates were higher for BPD. Younger age was moderately associated with slower PHQ-9 improvement. Work/study activity was initially poor, poorer levels associated with AvPD and younger age, and improvement was non-significant across PD conditions. AvPD was associated with slower WSAS improvement-rates.ConclusionPersonality functioning improved across PD conditions. The results highlight BPD improvements. The study points to challenges concerning AvPD treatment, poor occupational activity and age-related differences.

Defects and their interactions in crystalline solids often underpin materialproperties and functionality as they are decisive for stability, result inenhanced diffusion, and act as a reservoir of vacancies. Recently, lithium-richlayered oxides have emerged among the leading candidates for thenext-generation energy storage cathode material, delivering 50 % excesscapacity over commercially used compounds. Oxygen-redox reactions are believedto be responsible for the excess capacity, however, voltage fading hasprevented commercialization of these new materials. Despite extensive researchthe understanding of the mechanisms underpinning oxygen-redox reactions andvoltage fade remain incomplete. Here, using operando three-dimensional Braggcoherent diffractive imaging, we directly observe nucleation of a mobiledislocation network in nanoparticles of lithium-rich layered oxide material.Surprisingly, we find that dislocations form more readily in the lithium-richlayered oxide material as compared with a conventional layered oxide material,suggesting a link between the defects and the anomalously high capacity inlithium-rich layered oxides. The formation of a network of partial dislocationsdramatically alters the local lithium environment and contributes to thevoltage fade. Based on our findings we design and demonstrate a method torecover the original high voltage functionality. Our findings reveal that thevoltage fade in lithium-rich layered oxides is reversible and call for newparadigms for improved design of oxygen-redox active materials.

I akademia har det vært tradisjon for å assosiere karriere og avansement med personlig talent og særlige kompetanser, og noe som gjerne har blitt forstått som den enkeltes ansvar. Karriereutvikling i Norge blir imidlertid, i stadig større grad, definert som et ansvar for universitetet som organisasjon, og noe som alle bør delta i. Siden kvinner utgjør 31 % (DBH, 2019) av professorer og dosenter, er organiserte kvinnenettverk et av de tiltak som blir brukt for å bidra til karriereutvikling. I denne artikkelen viser vi hva kvinnelige førsteamanuensiser og førstelektorer som deltok i et slikt nettverk selv la vekt på som betydningsfulle sider ved nettverksdeltakelsen, og hvordan det bidro til deres karriereutvikling. Vi analyserer refleksjonslogger som kvinnene skrev mens de deltok i et karrierenettverk. Resultatene viser at deltakelsen rommet både sosial og faglig støtte, noe som bidro til et stort engasjement og bevissthet om egne strategiske valg. Det går imidlertid også fram at støtte fra kvinnenes ledere ble opplevd som en viktig premiss i karriereutvikling. Ut fra ulike teoretiske perspektiver diskuterer vi hvordan meningsskaping blant kvinner i karrierenettverk har betydning for den enkelte, men vi tydeliggjør også spenninger mellom det individuelle ansvaret og organisasjonens ansvar for karriereutvikling.

Background: Hospital-acquired pneumonia (HAP) is the most common hospital-acquired infection (HAI). HAP is associated with a high burden of morbidity and mortality, but the diagnosis is difficult to establish and the incidence uncertain. Methods: Patients aged ≥ 18 years hospitalised with radiologically verified non-ventilator hospital acquired pneumonia (NV-HAP) during 2018 were retrospectively identified at Drammen Hospital, a Norwegian general hospital. Infectious Diseases Society of America and the American Thoracic Society's definition of HAP was used. Results: In total 119 cases of NV-HAP were identified among 27,701 admissions. The incidence was 4.3 per 1000 admissions and 1.2 per 1000 patient-days. The median age was 74 years, 63% were male and median Charlson comorbidity index was 5. Coronary heart disease (42%) was the most common comorbidity. Median length of stay was 17.2 days. A blood culture was obtained in 53.8% of patients, while samples from lower airways were seldom obtained (10.9%). In-hospital mortality was 21%, accumulated 30-day mortality was 27.7% and accumulated 1-year mortality was 39.5%. Thirty-day readmission rate among survivors was 39.4%. Conclusion: NV-HAP was present in approximately 1 in 250 hospitalisations, most had multiple comorbidities, and 1 in 5 died in hospital. Although thorough microbiological sampling is recommended when NV-HAP is suspected, our data indicate that airway sampling is infrequent in clinical practice. Our findings underscore the need to develop microbiological diagnostic strategies to achieve targeted antimicrobial treatment that may improve patient outcomes and reduce broad-spectrum antibiotic usage. [ABSTRACT FROM AUTHOR]

Objectives: Mentalizing difficulties are central to borderline personality disorder (BPD), have severe consequences, and are an explicit focus in mentalizationbased treatment. The significance of mentalizing capacity as a predictor or mediator of change is however still uncertain due to a scarcity of research. The Mentalization Breakdown Interview (MBI) was developed as a time saving tool for studying psychotherapy processes and outcome in borderline pathology. This study aimed to investigate the convergent validity of reflective functioning (RF) ratings based on the MBI (MBI-RF) by a comparison with the gold standard, i.e., RF assessments based on the Adult Attachment Interview (AAI-RF). A secondary aim was to investigate how MBI-RF relates to core symptoms of BPD, levels of functional impairment and symptom distress compared with AAI-RF. Method: Forty-five patients with BPD or significant BPD traits were included. MBI-RF and AAI-RF were rated using the Reflective Functioning Scale. Levels of MBI-RF and AAI-RF and the correlation between the measures were calculated, as well as their associations with the Difficulties in Emotion Regulation Scale, Levels of Personality Functioning-Brief Form 2.0, Work and Social Adjustment Scale, Patient Health Questionnaire, Depression, Generalized Anxiety Disorder-7, self-harm, suicide attempts, and PD diagnostics. Results: The correlation between MBI-RF and AAI-RF was 0.79 (p<0.01), indicating high convergent validity. There were few significant associations between MBI-RF and AAI-RF and clinical measures. Conclusions: The study provides support for the convergent validity of the MBI as a BPD-focused RF assessment method. The MBI has the potential as a time saving, reliable and valid method to be applied in treatment research on patients with borderline pathology. The results indicate that measures of MBI-RF and AAIRF are different from clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: Current approaches for pathogen identification in community-acquired pneumonia (CAP) remain suboptimal, leaving most patients without a microbiological diagnosis. If better diagnostic tools were available for differentiating between viral and bacterial CAP, unnecessary antibacterial therapy could be avoided in viral CAP patients. Methods: In 156 adults hospitalized with CAP classified to have bacterial, viral, or mixed viral-bacterial infection based on microbiological testing or both microbiological testing and procalcitonin (PCT) levels, we aimed to identify discriminatory host transcriptional signatures in peripheral blood samples acquired at hospital admission, by applying Dual-color-Reverse-Transcriptase-Multiplex-Ligation-dependent-Probe-Amplification (dc-RT MLPA). Results: In patients classified by microbiological testing, a 9-transcript signature showed high accuracy for discriminating bacterial from viral CAP (AUC 0.91, 95% CI 0.85-0.96), while a 10-transcript signature similarly discriminated mixed viral-bacterial from viral CAP (AUC 0.91, 95% CI 0.86-0.96). In patients classified by both microbiological testing and PCT levels, a 13-transcript signature showed excellent accuracy for discriminating bacterial from viral CAP (AUC 1.00, 95% CI 1.00-1.00), while a 7-transcript signature similarly discriminated mixed viral-bacterial from viral CAP (AUC 0.93, 95% CI 0.87-0.98). Conclusion: Our findings support host transcriptional signatures in peripheral blood samples as a potential tool for guiding clinical decision-making and antibiotic stewardship in CAP.

Abstract Cascade impactors are useful tools in the measurement of particle size mass distribution of workplace aerosols. The application of cascade impactors, however, is sometimes challenging. Personal aerosol samples were collected by Sioutas cascade impactors and respirable cyclones in parallel in a silicon (Si) metal smelter to investigate the different particulate matter (PM) fractions. In a second campaign, nine new air samples were collected with the Sioutas personal cascade impactors using stationary sampling. It was found that wall deposition was substantial in the upper stages of the Sioutas cascade impactors, which meant that quite often more PM was deposited on the inner walls of the impactor than on the filter substrates. At the same time, wall deposition did most probably not affect the collection of the finest particles (< 0.25 µm). Besides wall deposition of the particles, the effect of high PM concentration on the impactor performance, particle bouncing and blow off, high particle mass loading and impact fragmentation of the particle agglomerates were considered for explaining the malfunctioning of the Sioutas impactors in the Si metal smelter. Furthermore, concentrations of the finest PM fraction (< 0.25 µm) and respirable fraction both collected by personal sampling are reported and discussed in the paper.