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| 2. |
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| 3. |
- Clapham, Eric, et al.
(författare)
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The association between exposure to clozapine, olanzapine, and quetiapine and the outcomes perimyocarditis and heart failure : A population-based cohort study
- 2023
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Ingår i: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 326
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Tidskriftsartikel (refereegranskat)abstract
- The risk of cardiac adverse events following clozapine use is debated and is unknown for the chemically related and widely used antipsychotics olanzapine and quetiapine. National Swedish registers were used to identify all patients 16-75 years old with antipsychotic dispensations between 2005 and 2018. The short-term outcome was a diagnosis of perimyocarditis (pericarditis and/or myocarditis) within two months of first dispensation, and the long-term outcome was heart failure (including cardiomyopathy) within three years. Cox regressions with time varying exposure were used to estimate hazard rates (HR) and their 95% confidence intervals (CI). A total of 201,045 individuals were included in the cohort. The risk of developing perimyocarditis during clozapine treatment tripled compared to no antipsychotic treatment (HR 3.4, CI 1.6-7.3), although the absolute rate remained comparably low. The long-term risk of heart failure during clozapine treatment was also elevated (HR 1.3, CI 1.1-1.7). Treatment with either or both olanzapine or quetiapine was not associated with an increased relative risk of perimyocarditis, or heart failure compared to no antipsychotic treatment. Clozapine use is therefore associated with a substantially elevated short-term risk of perimyocarditis and an increased risk of heart failure within three years.
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| 4. |
- Holmström, Oscar, et al.
(författare)
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Point-of-care mobile digital microscopy and deep learning for the detection of soil-transmitted helminths and Schistosoma haematobium
- 2017
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 10:sup3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Microscopy remains the gold standard in the diagnosis of neglected tropical diseases. As resource limited, rural areas often lack laboratory equipment and trained personnel, new diagnostic techniques are needed. Low-cost, point-of-care imaging devices show potential in the diagnosis of these diseases. Novel, digital image analysis algorithms can be utilized to automate sample analysis.OBJECTIVE: Evaluation of the imaging performance of a miniature digital microscopy scanner for the diagnosis of soil-transmitted helminths and Schistosoma haematobium, and training of a deep learning-based image analysis algorithm for automated detection of soil-transmitted helminths in the captured images.METHODS: A total of 13 iodine-stained stool samples containing Ascaris lumbricoides, Trichuris trichiura and hookworm eggs and 4 urine samples containing Schistosoma haematobium were digitized using a reference whole slide-scanner and the mobile microscopy scanner. Parasites in the images were identified by visual examination and by analysis with a deep learning-based image analysis algorithm in the stool samples. Results were compared between the digital and visual analysis of the images showing helminth eggs.RESULTS: Parasite identification by visual analysis of digital slides captured with the mobile microscope was feasible for all analyzed parasites. Although the spatial resolution of the reference slide-scanner is higher, the resolution of the mobile microscope is sufficient for reliable identification and classification of all parasites studied. Digital image analysis of stool sample images captured with the mobile microscope showed high sensitivity for detection of all helminths studied (range of sensitivity = 83.3-100%) in the test set (n = 217) of manually labeled helminth eggs.CONCLUSIONS: In this proof-of-concept study, the imaging performance of a mobile, digital microscope was sufficient for visual detection of soil-transmitted helminths and Schistosoma haematobium. Furthermore, we show that deep learning-based image analysis can be utilized for the automated detection and classification of helminths in the captured images.
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| 5. |
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| 6. |
- Mohanty, Tirthankar, et al.
(författare)
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Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1667-1667
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophils are crucial mediators of host defense that are recruited to the central nervous system (CNS) in large numbers during acute bacterial meningitis caused by Streptococcus pneumoniae. Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures composed of decondensed DNA and neutrophil-derived antimicrobial proteins. Here we show NETs in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis, and their absence in other forms of meningitis with neutrophil influx into the CSF caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the CSF. Disrupting NETs using DNase I significantly reduces bacterial load, demonstrating that NETs contribute to pneumococcal meningitis pathogenesis in vivo. We conclude that NETs in the CNS reduce bacterial clearance and degrading NETs using DNase I may have significant therapeutic implications.
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| 7. |
- Ofverholm, Ingegerd, et al.
(författare)
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Comprehensive Genomic Profiling Alters Clinical Diagnoses in a Significant Fraction of Tumors Suspicious of Sarcoma
- 2024
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research (AACR). - 1078-0432 .- 1557-3265. ; 30:12, s. 2647-2658
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Tumor classification is a key component in personalized cancer care. For soft-tissue and bone tumors, this classification is currently based primarily on morphology assessment and IHC staining. However, these standard-of-care methods can pose challenges for pathologists. We therefore assessed how whole-genome and whole-transcriptome sequencing (WGTS) impacted tumor classification and clinical management when interpreted together with histomorphology.Experimental Design: We prospectively evaluated WGTS in routine diagnostics of 200 soft-tissue and bone tumors suspicious for malignancy, including DNA and RNA isolation from the tumor, and DNA isolation from a peripheral blood sample or any non-tumor tissue.Results: On the basis of specific genomic alterations or absence of presumed findings, WGTS resulted in reclassification of 7% (13/197) of the histopathologic diagnoses. Four cases were downgraded from low-grade sarcomas to benign lesions, and two cases were reclassified as metastatic malignant melanomas. Fusion genes associated with specific tumor entities were found in 30 samples. For malignant soft-tissue and bone tumors, we identified treatment relevant variants in 15% of cases. Germline pathogenic variants associated with a hereditary cancer syndrome were found in 22 participants (11%).Conclusions: WGTS provides an important dimension of data that aids in the classification of soft-tissue and bone tumors, correcting a significant fraction of clinical diagnoses, and identifies molecular targets relevant for precision medicine. However, genetic findings need to be evaluated in their morphopathologic context, just as germline findings need to be evaluated in the context of patient phenotype and family history.
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| 8. |
- Albaugh, Timothy J, et al.
(författare)
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Do biological expansion factors adequately estimate stand-scale aboveground component biomass for Norway spruce?
- 2009
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Ingår i: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 258:12, s. 2628-2637
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Tidskriftsartikel (refereegranskat)abstract
- We developed site specific component (stem, branch, and foliage) biomass functions for two sites in Sweden (64° and 57° North latitude) where four treatments (control, irrigated, fertilized, irrigated plus fertilized) were applied in the existing Norway spruce stands (Picea abies L. Karst.) for 17 years. We tested for site effects in the component biomass equations and compared site specific biomass estimates to those generated using published functions ( Lehtonen et al., 2004 and Wirth et al., 2004). Site effects were significant for all components and indicated it would be unlikely to generate equations that well estimate biomass across the Norway spruce range as implicitly indicated in our efforts to generate species biomass expansion factors. We rejected our hypothesis that the published functions would well estimate component biomass for control plots. The published functions did not compare well with site specific component biomass estimates for the other treatments; both published functions well estimated stem mass up to stem mass of 25 Mg ha−1, beyond which stem mass was overestimated, and both functions over and under estimated foliage and branch mass. Nor did the published functions compare well with each other, with stem, foliage and branch mass estimate differences of 12, 55, −8% and 11, 77, and 59% for the southern and northern sites, respectively, when averaged over all treatments and years. Adding limiting resources through fertilization increased stem, foliage and branch mass 57, 11, 18% and 120, 37, and 69% at the southern and northern sites, respectively, which would increase carbon sequestration and available stemwood and bioenergy materials. We recommend that more effort is spent in process-based modeling to better predict mass at a given site and ultimately provide better estimates of carbon sequestration and bioenergy material production changes.
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| 9. |
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| 10. |
- Arvola, Mattias, 1975-, et al.
(författare)
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Know thy users by interpretative phenomenological analysis
- 2018
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Ingår i: Journal of Interaction Science. - Germany : Journal of Interaction Science. - 2194-0827. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- One approach to getting to know a user and understanding the user experience (UX) is phenomenology. Currently, there is a lack of clearly defined methods for phenomenological analysis of user experience in design projects. Interpretative Phenomenological Analysis (IPA) is an approach developed in psychology, and in this article, it is adapted to the case of a pro bono design project at a UX design agency supporting a disadvantaged group of people, newly arrived immigrants to Sweden. The design project involved research on how the immigrants experienced a service that introduced them to the job market. The adapted method, UX IPA, contributed to the pro bono project with a focus on both experience and meaning, which is important in design projects that relate to major events in users’ lives. The method was considered less appropriate in UX projects for specific products with highly instrumental use. The method can, in many cases, be too costly. However, costs can possibly be reduced by top-down approaches. In commercial UX projects, the method may be appropriate for the fuzzy front-end of design and innovation, but clients may be unimpressed by the small sample size. This can potentially be alleviated by mixed-methods approaches.
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| 11. |
- Bakochi, Anahita, et al.
(författare)
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Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis
- 2021
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Ingår i: eLife. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Meningitis is a potentially life-threatening infection characterized by the inflammation of the leptomeningeal membranes. Many different viral and bacterial pathogens can cause meningitis, with differences in mortality rates, risk of developing neurological sequelae and treatment options. Here we constructed a compendium of digital cerebrospinal fluid (CSF) proteome maps to define pathogen-specific host response patterns in meningitis. The results revealed a drastic and pathogen-type specific influx of tissue-, cell- and plasma proteins in the CSF, where in particular a large increase of neutrophil derived proteins in the CSF correlated with acute bacterial meningitis. Additionally, both acute bacterial and viral meningitis result in marked reduction of brain-enriched proteins. Generation of a multi-protein LASSO regression model resulted in an 18-protein panel of cell and tissue associated proteins capable of classifying acute bacterial meningitis and viral meningitis. The same protein panel also enabled classification of tick-borne encephalitis, a subgroup of viral meningitis, with high sensitivity and specificity. The work provides insights into pathogen specific host response patterns in CSF from different disease etiologies to support future classification of pathogen-type based on host response patterns in meningitis.
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| 12. |
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| 13. |
- Bergh, Johan, et al.
(författare)
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Skogsbruket måste påbörja omställningen
- 2010
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Ingår i: Sverige i Nytt Klimat – våtvarm utmaning. - 9789154060405 ; , s. 185-202
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Bokkapitel (populärvet., debatt m.m.)
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| 14. |
- Brodin, Bertha A., et al.
(författare)
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Drug sensitivity testing on patient-derived sarcoma cells predicts patient response to treatment and identifies c-Sarc inhibitors as active drugs for translocation sarcomas
- 2019
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 120:4, s. 435-443
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Heterogeneity and low incidence comprise the biggest challenge in sarcoma diagnosis and treatment. Chemotherapy, although efficient for some sarcoma subtypes, generally results in poor clinical responses and is mostly recommended for advanced disease. Specific genomic aberrations have been identified in some sarcoma subtypes but few of them can be targeted with approved drugs. METHODS: We cultured and characterised patient-derived sarcoma cells and evaluated their sensitivity to 525 anti-cancer agents including both approved and non-approved drugs. In total, 14 sarcomas and 5 healthy mesenchymal primary cell cultures were studied. The sarcoma biopsies and derived cells were characterised by gene panel sequencing, cancer driver gene expression and by detecting specific fusion oncoproteins in situ in sarcomas with translocations. RESULTS: Soft tissue sarcoma cultures were established from patient biopsies with a success rate of 58%. The genomic profile and drug sensitivity testing on these samples helped to identify targeted inhibitors active on sarcomas. The cSrc inhibitor Dasatinib was identified as an active drug in sarcomas carrying chromosomal translocations. The drug sensitivity of the patient sarcoma cells ex vivo correlated with the response to the former treatment of the patient. CONCLUSIONS: Our results show that patient-derived sarcoma cells cultured in vitro are relevant and practical models for genotypic and phenotypic screens aiming to identify efficient drugs to treat sarcoma patients with poor treatment options.
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| 15. |
- Carlson, Johan, et al.
(författare)
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Projekt: SCOPE Norra
- 2011
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Annan publikation (populärvet., debatt m.m.)abstract
- SCOPE Norra är ett samarbetskonsortium för forskning och utveckling tillsammans med massa- och pappersindustrin i Norrbotten och Västerbotten. Projektet koordineras av centrumbildningen ProcessIT Innovations.Inom SCOPE Norra pågår ett flertal delprojekt, uppdelat på ett antal fokusområden.Huvudfinansiär för konsortiet är Tillväxtverket genom medel från EU:s strukturfonder.
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| 16. |
- Carlsson, Anna K, 1966, et al.
(författare)
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Design and Evaluation of the Initial 50th Percentile Female Prototype Rear Impact Dummy, BioRID P50F–Indications for the need of an additional dummy size
- 2021
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to present the design of a prototype rear impact crash test dummy, representing a 50th percentile female, and compare its performance to volunteer response data. The intention was to develop a first crude prototype as a first step toward a future biofidelic 50th percentile female rear impact dummy. The current rear impact crash test dummy, BioRID II, represents a 50th percentile male, which may limit the assessment and development of whiplash protection systems with regard to female occupants. Introduction of this new dummy size will facilitate evaluation of seat and head restraint (HR) responses in both the average sized female and male in rear impacts. A 50th percentile female rear impact prototype dummy, the BioRID P50F, was developed from modified body segments originating from the BioRID II. The mass and rough dimensions of the BioRID P50F is representative of a 50th percentile female. The prototype dummy was evaluated against low severity rear impact sled tests comprising six female volunteers closely resembling a 50th percentile female with regard to stature and mass. The head/neck response of the BioRID P50F prototype resembled the female volunteer response corridors. The stiffness of the thoracic and lumbar spinal joints remained the same as the average sized male BioRID II, and therefore likely stiffer than joints of an average female. Consequently, the peak rearward angular displacement of the head and T1, and the rearward displacement of the T1, were lesser for the BioRID P50F in comparison to the female volunteers. The biofidelity of the BioRID P50F prototype thus has some limitations. Based on a seat response comparison between the BioRID P50F and the BioRID II, it can be concluded that the male BioRID II is an insufficient representation of the average female in the assessment of the dynamic seat response and effectiveness of whiplash protection systems.
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| 17. |
- Carlsson, Anna K, 1966, et al.
(författare)
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Dynamic kinematic responses of female volunteers in rear impacts and comparison to previous male volunteer tests
- 2011
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Ingår i: Traffic Injury Prevention. - : Informa UK Limited. - 1538-9588 .- 1538-957X. ; 12:4, s. 347-357
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The objective was to quantify dynamic responses of 50th percentile females in rear impacts and compare to those from similar tests with males. The results will serve as a basis for future work with models, criteria, and safety systems.Methods: A rear impact sled test series with 8 female volunteers was performed at velocity changes of 5 and 7 km/h. The following dynamic response corridors were generated for the head, T1 (first thoracic vertebra) and head relative to T1: (1) accelerations in posterior-anterior direction, (2) horizontal and vertical displacements, (3) angular displacements for 6 females close to the 50th percentile in size. Additionally, the head-to-head restraint distance and contact time and neck injury criterion (NIC) were extracted from the data set. These data were compared to results from previously performed male volunteer tests, representing the 50th percentile male, in equivalent test conditions. T-tests were performed with the statistical significance level of.05 to quantify the significance of the parameter value differences for the males and females.Results: At 7 km/h, the females showed 29 percent earlier head-to-head restraint contact time (p =.0072); 27 percent shorter horizontal rearward head displacement (p =.0017); 36 percent narrower head extension angle (p =.0281); and 52 percent lower NIC value (p =.0239) than the males in previous tests. This was mainly due to 35 percent shorter initial head-to-head restraint distance for the females (p =.0125). The peak head acceleration in the posterior-anterior direction was higher and occurred earlier for the females.Conclusions: The overall result indicated differences in the dynamic response for the female and male volunteers. The results could be used in developing and evaluating a mechanical and/or mathematical average-sized female dummy model for rear impact safety assessment. These models can be used as a tool in the design of protective systems and for further development and evaluation of injury criteria. © 2011 Taylor & Francis Group, LLC.
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| 18. |
- Carlsson, Anna K, 1966, et al.
(författare)
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Dynamic Responses of Female Volunteers in Rear Impact Sled Tests at Two Head Restraint Distances
- 2021
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to assess the biomechanical and kinematic responses of female volunteers with two different head restraint (HR) configurations when exposed to a low-speed rear loading environment. A series of rear impact sled tests comprising eight belted, near 50th percentile female volunteers, seated on a simplified laboratory seat, was performed with a mean sled acceleration of 2.1 g and a velocity change of 6.8 km/h. Each volunteer underwent two tests; the first test configuration, HR10, was performed at the initial HR distance ∼10 cm and the second test configuration, HR15, was performed at ∼15 cm. Time histories, peak values and their timing were derived from accelerometer data and video analysis, and response corridors were also generated. The results were separated into three different categories, HR10C (N = 8), HR15C (N = 6), and HR15NC (N= 2), based on: (1) the targeted initial HR distance [10 cm or 15 cm] and (2) whether the volunteers’ head had made contact with the HR [Contact (C) or No Contact (NC)] during the test event. The results in the three categories deviated significantly. The greatest differences were found for the average peak head angular displacements, ranging from 10° to 64°. Furthermore, the average neck injury criteria (NIC) value was 22% lower in HR10C (3.9 m2/s2), and 49% greater in HR15NC (7.4 m2/s2) in comparison to HR15C (5.0 m2/s2). This study supplies new data suitable for validation of mechanical or mathematical models of a 50th percentile female. A model of a 50th percentile female remains to be developed and is urgently required to complement the average male models to enhance equality in safety assessments. Hence, it is important that future protection systems are developed and evaluated with female properties taken into consideration too. It is likely that the HR15 test configuration is close to the limit for avoiding HR contact for this specific seat setup. Using both datasets (HR15C and HR15NC), each with its corresponding HR contact condition, will be possible in future dummy or model evaluation.
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| 19. |
- Carlsson, Anna K, 1966, et al.
(författare)
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Female volunteer motion in rear impact sled tests in comparison to results from earlier male volunteer tests
- 2008
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Ingår i: 2008 INTERNATIONAL IRCOBI CONFERENCEONTHE BIOMECHANICS OF INJURY17. – 19. September 2008– BERN (Switzerland)PROCEEDINGS. ; , s. 461-464, s. 461-464
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Konferensbidrag (refereegranskat)abstract
- Vehicle related crashes causing neck injuries (whiplash) are costly and common, and injury statistic data shows a larger risk of neck injuries for females than for males. This study aims at investigating differences between female and male dynamic response in rear impacts. Rear impact sled tests with female volunteers were carried out and the results were compared with previously performed tests with males in matching test conditions. The volunteer tests were performed at a change of velocity of 7 km/h. The comparison of the average response of the males and the females and their response corridors showed several differences. The horizontal head acceleration peak value was on average 40% higher and occurred on average 18% earlier for the female volunteers compared to the male volunteers. The NIC value was 45% lower and 30% earlier for the females, probably due to a 27% smaller initial head-to-head restraint distance and thereby a 24% earlier head restraint contact. The results provide characteristic differences between dynamic responses of females and males in low speed rear impacts. These results contribute to the understanding of human dynamic response in rear impacts. In addition, they can be used in the process of future development if numerical and/or mechanical human models for crash testing.
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| 20. |
- Casetou, Sophie, et al.
(författare)
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Current, steady-state and historical weathering rates of base cations at two forest sites in northern and southern Sweden: a comparison of three methods
- 2020
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 17, s. 281-304
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Tidskriftsartikel (refereegranskat)abstract
- Reliable and accurate methods for estimating soil mineral weathering rates are required tools in evaluating the sustainability of increased harvesting of forest biomass and assessments of critical loads of acidity. A variety of methods that differ in concept, temporal and spatial scale, and data requirements are available for measuring weathering rates. In this study, causes of discrepancies in weathering rates between methods were analysed and were classified as being either conceptual (inevitable) or random. The release rates of base cations (BCs; Ca, Mg, K, Na) by weathering were estimated in podzolised glacial tills at two experimental forest sites, Asa and Flakaliden, in southern and northern Sweden, respectively. Three different methods were used: (i) historical weathering since deglaciation estimated by the depletion method, using Zr as the assumed inert reference; (ii) steady-state weathering rate estimated with the PROFILE model, based on quantitative analysis of soil mineralogy; and (iii) BC budget at stand scale, using measured deposition, leaching and changes in base cation stocks in biomass and soil over a period of 12 years. In the 050 cm soil horizon historical weathering of BCs was 10.6 and 34.1 mmolc m(-2) yr(-1), at Asa and Flakaliden, respectively. Corresponding values of PROFILE weathering rates were 37.1 and 42.7 mmolc m(-2) yr(-1). The PROFILE results indi- cated that steady-state weathering rate increased with soil depth as a function of exposed mineral surface area, reaching a maximum rate at 80 cm (Asa) and 60 cm (Flakaliden). In contrast, the depletion method indicated that the largest postglacial losses were in upper soil horizons, particularly at Flakaliden.With the exception of Mg and Ca in shallow soil horizons, PROFILE produced higher weathering rates than the depletion method, particularly of K and Na in deeper soil horizons. The lower weathering rates of the depletion method were partly explained by natural and anthropogenic variability in Zr gradients. The base cation budget approach produced significantly higher weathering rates of BCs, 134.6 mmolc m(-2) yr(-1) at Asa and 73.2 mmolc m(-2) yr(-1) at Flakaliden, due to high rates estimated for the nutrient elements Ca, Mg and K, whereas weathering rates were lower and similar to those for the depletion method (6.6 and 2.2 mmolc m(-2) yr(-1) at Asa and Flakaliden). The large discrepancy in weathering rates for Ca, Mg and K between the base cation budget approach and the other methods suggests additional sources for tree uptake in the soil not captured by measurements.
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| 21. |
- Chang, Fred, et al.
(författare)
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EvaRID: a dummy model representing females in rear end impacts
- 2010
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Ingår i: Proc. Whiplash 2010, 3rd International Conference, Munich, November 18 – 20, 2010.
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Konferensbidrag (refereegranskat)abstract
- The Seventh Framework project ADSEAT (Adaptive Seat to Reduce Neck Injuries for Female andMale Occupants) aims at establishing the properties for a model of an average female and toimplement those in a computational model in order to provide an improved tool for the developmentand evaluation of adaptive systems with special focus on protection against whiplash injuries. As suchthe project will result in a computational model of a female, in addition to the male model that alreadyexists, for low severity testing. Both the female and the male model will then be used in be used instudies to design and evaluate adaptive seat systems that provide enhanced neck injury protection.This paper will present the first version of the female dummy model, called EvaRID, as developedduring the first year of the ADSEAT project. Background information on the size selection,anthropometry and the scaling method used will be described. The performance of the EvaRID V1.0release is shown by comparing simulation results with volunteer data.
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| 22. |
- Dankiewicz, Josef, et al.
(författare)
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Infectious complications after out-of-hospital cardiac arrest—A comparison between two target temperatures
- 2017
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 113, s. 70-76
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Tidskriftsartikel (refereegranskat)abstract
- Background It has been suggested that target temperature management (TTM) increases the probability of infectious complications after cardiac arrest. We aimed to compare the incidence of pneumonia, severe sepsis and septic shock after out-of-hospital cardiac arrest (OHCA) in patients with two target temperatures and to describe changes in biomarkers and possible mortality associated with these infectious complications. Methods Post-hoc analysis of the TTM-trial which randomized patients resuscitated from OHCA to a target temperature of 33 °C or 36 °C. Prospective data on infectious complications were recorded daily during the ICU-stay. Pneumonia, severe sepsis and septic shock were considered infectious complications. Procalcitonin (PCT) and C-reactive-protein (CRP) levels were measured at 24 h, 48 h and 72 h after cardiac arrest. Results There were 939 patients in the modified intention-to-treat population. Five-hundred patients (53%) developed pneumonia, severe sepsis or septic shock which was associated with mortality in multivariate analysis (Hazard ratio [HR] 1.39; 95%CI 1.13–1.70; p = 0.001). There was no statistically significant difference in the incidence of infectious complications between temperature groups (sub-distribution hazard ratio [SHR] 0.88; 95%CI 0.75–1.03; p = 0.12). PCT and CRP were significantly higher for patients with infections at all times (p < 0.001), but there was considerable overlap. Conclusions Patients who develop pneumonia, severe sepsis or septic shock after OHCA might have an increased mortality. A target temperature of 33 °C after OHCA was not associated with an increased risk of infectious complications compared to a target temperature of 36 °C. PCT and CRP are of limited value for diagnosing infectious complications after cardiac arrest.
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| 23. |
- Dardashti, Alain, et al.
(författare)
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Impact of cardiopulmonary bypass and surgical complexity on plasma soluble urokinase-type plasminogen activator receptor levels after cardiac surgery
- 2021
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 81:8, s. 634-640
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating soluble urokinase plasminogen activator receptor (suPAR) is a marker of inflammation with prognostic value for elevated risk of morbidity and mortality. It has not yet been shown how the inflammatory process induced by cardiac surgery affects suPAR concentrations postoperatively Methods: In a prospective observational study, plasma suPAR levels were measured in 30 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), pre-, peri, post-operatively, and 3–5 days after surgery. Fifteen patients underwent coronary artery bypass grafting (CABG) and 15 underwent complex procedures with longer CPB duration. Concentrations of suPAR at each time point were compared to the preoperative levels and compared between the two groups. Results: In both groups, plasma suPAR concentrations were significantly higher on the first postoperative day (3.27 (interquartile range (IQR) 2.75–3.86) µg/L compared to baseline (2.62 (1.98–3.86)) µg/L, p <.001. There were no significant differences in suPAR concentrations between the groups at any time point. Preoperatively, the median suPAR concentration was 2.57 (2.01–3.60) µg/L in the CABG group versus 2.67 (1.89–3.97) µg/L in the complex group (p =.567). At ICU arrival 2.48 (2.34–3.23) µg/L versus 2.73 (2.28–3.44) µg/L in CABG and complex patients, respectively (p =.914). There was no difference in suPAR concentrations between the groups on postoperative day 1 (3.34 (2.89–3.89) versus 3.19 (2.57–3.62) p =.967) or 3–5 days after surgery (2.72 (1.98–3.16) versus 2.96 (2.39–4.28) p =.085. Conclusions: After a transient rise on the first postoperative day, the suPAR levels returned to the preoperative levels by the third postoperative day. There was no significant difference in suPAR levels between the routine CABG and complex group with longer CPB time.
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| 24. |
- Davidsson, Johan, 1967, et al.
(författare)
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Human Volunteer Kinematics in Rear-End Sled Collisions
- 1998
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Ingår i: Proceeding of the 1998 International IRCOBI Conference on the Biomechanics of Impact. ; , s. 289-301
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Konferensbidrag (refereegranskat)abstract
- A number of current projects are developing new crash test dummies for rear-end impact testing. The validation of such a dummy design requires human response data from pertinent test situations. The objectives of this study are to quantify human head, neck, chest, pelvis and femur mechanical response in a well defined test seat. Another aim is to see how the response varies with seat design and sled speed change during low-speed rear-end collisions. This data is intended to be used in the validation of the crash test dummy (BioRID I) in rear-end impact situations, with a focus on low delta V (velocity change) collisions. Thirteen human subjects were exposed to 28 rear-end collision sled impacts with velocity changes close to 5 and 7 krn/h respectively. The results showed vertical motion of the subjects' H-point caused by ramping up along the seat, a forward rotat ion of the subjects' femur and maybe a contraction of the subjects' gluteus muscles. A vertical motion of the subjects' torso and head was also observed. This motion was caused by a combination of ramping up along the seat back and the straightening of the thoracic kyphosis. In the first 100 ms after impact, several subjects flexed their head relative T1. These new data have proven to be useful as validation data for new rear-end impact dummies.
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| 25. |
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| 26. |
- Falk, Johan
(författare)
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Students' depictions of quantum mechanics : a contemporary review and some implications for research and teaching
- 2007
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents a comprehensive review of research into students’ depictions of quantum mechanics. A taxonomy to describe and compare quantum mechanics education research is presented, and this taxonomy is used to highlight the foci of prior research. A brief history of quantum mechanics education research is also presented. Research implications of the review are discussed, and several areas for future research are proposed. In particular, this thesis highlights the need for investigations into what interpretations of quantum mechanics are employed in teaching, and that classical physics – in particular the classical particle model – appears to be a common theme in students’ inappropriate depictions of quantum mechanics. Two future research projects are presented in detail: one concerning interpretations of quantum mechanics, the other concerning students’ depictions of the quantum mechanical wave function.This thesis also discusses teaching implications of the review. This is done both through a discussion on how Paper 1 can be used as a resource for lecturers and through a number of teaching suggestions based on a merging of the contents of the review and personal teaching experience.
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| 27. |
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| 28. |
- Fisher, Jane, et al.
(författare)
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Proteome profiling of recombinant DNase therapy in reducing NETs and aiding recovery in COVID-19 patients
- 2021
-
Ingår i: Molecular and Cellular Proteomics. - : Elsevier BV. - 1535-9484 .- 1535-9476. ; 20
-
Tidskriftsartikel (refereegranskat)abstract
- Severe COVID-19 can result in pneumonia and acute respiratory failure. Accumulation of mucus in the airways is a hall mark of the disease and can result in hypoxemia. Here, we show that quantitative proteome analysis of the sputum from severe COVID-19 patients reveal high levels of neutrophil extracellular trap(s) (NETs) components, which was confirmed by microscopy. Extracellular DNA from excessive NET formation can increase sputum viscosity and can lead to acute respiratory distress syndrome (ARDS). Recombinant human DNase (rhDNase/Pulmozyme) has been shown to be beneficial in reducing sputum viscosity and improve lung function. We treated 5 COVID-19 patients presenting acute symptoms with clinically approved aerosolized Pulmozyme. No adverse reactions to the drug were seen, and improved oxygen saturation and recovery in all severely ill COVID-19 patients was observed after therapy. Immunofluorescence and proteome analysis of sputum and blood plasma samples after treatment revealed a marked reduction of NETs and a set of statistically significant proteome changes that indicate reduction of haemorrhage, plasma leakage and inflammation in the airways, and reduced systemic inflammatory state in the blood plasma of patients. Taken together, the results indicate that NETs contribute to acute respiratory failure in COVID-19 and that degrading NETs may reduce dependency on external high flow oxygen therapy in patients. Targeting NETs using rhDNase may have significant therapeutic implications in COVID-19 disease and warrants further studies.
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| 29. |
- Fortino, Vittorio, et al.
(författare)
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Machine-learning-driven biomarker discovery for the discrimination between allergic and irritant contact dermatitis
- 2020
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:52, s. 33474-33485
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Tidskriftsartikel (refereegranskat)abstract
- Contact dermatitis tremendously impacts the quality of life of suffering patients. Currently, diagnostic regimes rely on allergy testing, exposure specification, and follow-up visits; however, distinguishing the clinical phenotype of irritant and allergic contact dermatitis remains challenging. Employing integrative transcriptomic analysis and machine-learning approaches, we aimed to decipher disease-related signature genes to find suitable sets of biomarkers. A total of 89 positive patch-test reaction biopsies against four contact allergens and two irritants were analyzed via microarray. Coexpression network analysis and Random Forest classification were used to discover potential biomarkers and selected biomarker models were validated in an independent patient group. Differential gene-expression analysis identified major gene-expression changes depending on the stimulus. Random Forest classification identified CD47, BATF, FASLG, RGS16, SYNPO, SELE, PTPN7, WARS, PRC1, EXO1, RRM2, PBK, RAD54L, KIFC1, SPC25, PKMYT, HISTH1A, TPX2, DLGAP5, TPX2, CH25H, and IL37 as potential biomarkers to distinguish allergic and irritant contact dermatitis in human skin. Validation experiments and prediction performances on external testing datasets demonstrated potential applicability of the identified biomarker models in the clinic. Capitalizing on this knowledge, novel diagnostic tools can be developed to guide clinical diagnosis of contact allergies.
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| 30. |
- Gimsing, Peter, et al.
(författare)
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Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial
- 2010
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Ingår i: LANCET ONCOLOGY. - : Elsevier Science B.V., Amsterdam.. - 1470-2045 .- 1474-5488. ; 11:10, s. 973-982
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Tidskriftsartikel (refereegranskat)abstract
- Background Compared with placebo, prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma. However, because of toxicity associated with long-term bisphosphonate treatment, establishing the lowest effective dose is important. This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in patients with newly diagnosed multiple myeloma. Methods This double-blind, randomised, phase 3 trial was undertaken at 37 clinics in Denmark, Norway, and Sweden. Patients with multiple myeloma who were starting antimyeloma treatment were randomly assigned in a 1:1 ratio to receive one of two doses of pamidronate (30 mg or 90 mg) given by intravenous infusion once a month for at least 3 years. Randomisation was done by use of a central, computerised minimisation system. Primary outcome was physical function after 12 months estimated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire (scale 0-100). All patients who returned questionnaires at 12 months and were still on study treatment were included in the analysis of the primary endpoint. This study is registered with ClinicalTrials. gov, number NCT00376883. Findings From January, 2001, until August, 2005, 504 patients were randomly assigned to pamidronate 30 mg or 90 mg (252 in each group). 157 patients in the 90 mg group and 156 in the 30 mg group were included in the primary analysis. Mean physical function at 12 months was 66 points (95% CI 62.9-70.0) in the 90 mg group and 68 points (64.6-71.4) in the 30 mg group (95% CI of difference -6.6 to 3.3; p=0.52). Median time to first skeletal-related event in patients who had such an event was 9.2 months (8.1-10.7) in the 90 mg group and 10-2 months (7.3-14.0) in the 30 mg group (p=0.63). In a retrospective analysis, eight patients in the pamidronate 90 mg group developed osteonecrosis of the jaw compared with two patients in the 30 mg group. Interpretation Monthly infusion of pamidronate 30 mg should be the recommended dose for prevention of bone disease in patients with multiple myeloma.
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| 31. |
- Hartman, Erik, et al.
(författare)
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Interpreting biologically informed neural networks for enhanced proteomic biomarker discovery and pathway analysis
- 2023
-
Ingår i: Nature Communications. - 2041-1723. ; 14, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- The incorporation of machine learning methods into proteomics workflows improves the identification of disease-relevant biomarkers and biological pathways. However, machine learning models, such as deep neural networks, typically suffer from lack of interpretability. Here, we present a deep learning approach to combine biological pathway analysis and biomarker identification to increase the interpretability of proteomics experiments. Our approach integrates a priori knowledge of the relationships between proteins and biological pathways and biological processes into sparse neural networks to create biologically informed neural networks. We employ these networks to differentiate between clinical subphenotypes of septic acute kidney injury and COVID-19, as well as acute respiratory distress syndrome of different aetiologies. To gain biological insight into the complex syndromes, we utilize feature attribution-methods to introspect the networks for the identification of proteins and pathways important for distinguishing between subtypes. The algorithms are implemented in a freely available open source Python-package ( https://github.com/InfectionMedicineProteomics/BINN ).
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| 32. |
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| 33. |
- Hasper, Thomas Berg, et al.
(författare)
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Water use by Swedish boreal forests in a changing climate
- 2016
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Ingår i: Functional Ecology. - : Wiley. - 0269-8463 .- 1365-2435. ; 30:5, s. 690-699
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Tidskriftsartikel (refereegranskat)abstract
- The rising levels of atmospheric carbon dioxide concentration ([CO2]) and temperature have the potential to substantially affect the terrestrial water and energy balance by altering the stomatal conductance and transpiration of trees. Many models assume decreases in stomatal conductance and plant water use under rising [CO2], which has been used as a plausible explanation for the positive global trend in river run-off over the past century. Plant water use is, however, also affected by changes in temperature, precipitation and land use, and there is yet no consensus about the contribution of different drivers to temporal trends of evapotranspiration (ET) and river run-off. In this study, we assessed water-use responses to climate change by using both long-term monitoring and experimental data in Swedish boreal forests. Historical trends and patterns in ET of large-scale boreal landscapes were determined using climate and run-off data from the past 50 years, while explicit tree water-use responses to elevated [CO2] and/or air temperature were examined in a whole-tree chamber experiment using mature Norway spruce (Picea abies (L.) Karst.) trees. The results demonstrated that ET estimated from water budgets at the catchment scale increased by 18% over the past 50 years while run-off did not significantly change. The increase in ET was related to increasing precipitation and a steady increase in forest standing biomass over time. The whole-tree chamber experiment showed that Norway spruce trees did not save water under elevated [CO2] and that experimentally elevated air temperature did not increase transpiration as decreased stomatal conductance cancelled the effect of higher vapour pressure deficit in warmed air. Our findings have important implications for projections of future water use of European boreal coniferous forests, indicating that changes in precipitation and standing biomass are more important than the effects of elevated [CO2] or temperature on transpiration rates.
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| 34. |
- Hayden, Brian, et al.
(författare)
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The HST See Change Program. I. Survey Design, Pipeline, and Supernova Discoveries
- 2021
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 912:2
-
Tidskriftsartikel (refereegranskat)abstract
- The See Change survey was designed to make z > 1 cosmological measurements by efficiently discovering high-redshift Type Ia supernovae (SNe Ia) and improving cluster mass measurements through weak lensing. This survey observed twelve galaxy clusters with the Hubble Space Telescope (HST) spanning the redshift range z = 1.13-1.75, discovering 57 likely transients and 27 likely SNe Ia at z similar to 0.8-2.3. As in similar previous surveys, this proved to be a highly efficient use of HST for supernova observations; the See Change survey additionally tested the feasibility of maintaining, or further increasing, the efficiency at yet higher redshifts, where we have less detailed information on the expected cluster masses and star formation rates. We find that the resulting number of SNe Ia per orbit is a factor of similar to 8 higher than for a field search, and 45% of our orbits contained an active SN Ia within 22 rest-frame days of peak, with one of the clusters by itself yielding 6 of the SNe Ia. We present the survey design, pipeline, and supernova discoveries. Novel features include fully blinded supernova searches, the first random forest candidate classifier for undersampled IR data (with a 50% detection threshold within 0.05 mag of human searchers), real-time forward-modeling photometry of candidates, and semi-automated photometric classifications and follow-up forecasts. We also describe the spectroscopic follow-up, instrumental in measuring host galaxy redshifts. The cosmology analysis of our sample will be presented in a companion paper.
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| 35. |
- Hedwall, Per-Ola, et al.
(författare)
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Effects of clear-cutting and slash removal on soil water chemistry and forest-floor vegetation in a nutrient optimised Norway spruce stand
- 2013
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Ingår i: Silva Fennica. - : Finnish Society of Forest Science. - 0037-5330 .- 2242-4075. ; 47
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Tidskriftsartikel (refereegranskat)abstract
- Fertilisation with nutrient optimisation has in Sweden resulted in large increases in volume growth in young stands of Norway spruce. There are, however, environmental concerns about repeated fertilisation and one is the risk of nutrient leakage to ground water resources and aquatic ecosystems after clear-cutting of such forests. The present study followed soil-water chemistry in optimised fertilised stands after clear-cutting, as well as effects of harvest of slash on nutrient leakage. Parts of a 30-year-old stand of Norway spruce, which had been subject to a nutrient optimisation experiment for 17 years, were clear-cut. A split-plot design with whole-tree harvesting as the sub-plot treatment was applied. Lysimeters were installed and soil-water sampled at nine occasions during the following four years. No significant effects of fertilisation on nitrate leaching were found, while harvest of slash affected the concentration of Ca, DOC, DON, K, Mg, ammonium and nitrate, as well as pH in the soil solution. While no effects of fertilisation could be seen on the soil water concentration of N, the results indicate an interaction between fertilisation and harvest of slash on the concentration of nitrate in the soil solution. The results indicate that forest-floor vegetation plays an important role in the retention of N after clear-cutting of fertilised forests.
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| 36. |
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| 37. |
- Hofmann, Robin, et al.
(författare)
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Oxygen therapy in ST-elevation myocardial infarction.
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:29, s. 2730-2739
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To determine whether supplemental oxygen in patients with ST-elevation myocardial infarction (STEMI) impacts on procedure-related and clinical outcomes.Methods and results: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized patients with suspected myocardial infarction (MI) to receive oxygen at 6 L/min for 6-12 h or ambient air. In this pre-specified analysis, we included only STEMI patients who underwent percutaneous coronary intervention (PCI). In total, 2807 patients were included, 1361 assigned to receive oxygen, and 1446 assigned to ambient air. The pre-specified primary composite endpoint of all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis at 1 year occurred in 6.3% (86 of 1361) of patients allocated to oxygen compared to 7.5% (108 of 1446) allocated to ambient air [hazard ratio (HR) 0.85, 95% confidence interval (95% CI) 0.64-1.13; P = 0.27]. There was no difference in the rate of death from any cause (HR 0.86, 95% CI 0.61-1.22; P = 0.41), rate of rehospitalization for MI (HR 0.92, 95% CI 0.57-1.48; P = 0.73), rehospitalization for cardiogenic shock (HR 1.05, 95% CI 0.21-5.22; P = 0.95), or stent thrombosis (HR 1.27, 95% CI 0.46-3.51; P = 0.64). The primary composite endpoint was consistent across all subgroups, as well as at different time points, such as during hospital stay, at 30 days and the total duration of follow-up up to 1356 days.Conclusions: Routine use of supplemental oxygen in normoxemic patients with STEMI undergoing primary PCI did not significantly affect 1-year all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis.
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| 38. |
- Hofmann, Robin, et al.
(författare)
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Oxygen therapy in suspected acute myocardial infarction
- 2017
-
Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 377:13, s. 1240-1249
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS: In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS: A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. CONCLUSIONS: Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart–Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110.)
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| 39. |
- Holmstrom, Oscar, et al.
(författare)
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Detection of breast cancer lymph node metastases in frozen sections with a point-of care low-cost microscope scanner
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Detection of lymph node metastases is essential in breast cancer diagnostics and staging, affecting treatment and prognosis. lntraoperative microscopy analysis of sentinel lymph node frozen sections is standard for detection of axillary metastases but requires access to a pathologist for sample analysis. Remote analysis of digitized samples is an alternative solution but is limited by the requirement for high-end slide scanning equipment.Objective To determine whether the image quality achievable with a low-cost, miniature digital microscope scanner is sufficient for detection of metastases in breast cancer lymph node frozen sections.Methods Lymph node frozen sections from 79 breast cancer patients were digitized using a prototype miniature microscope scanner and a high-end slide scanner. Images were independently reviewed by two pathologists and results compared between devices with conventional light microscopy analysis as ground truth.Results Detection of metastases in the images acquired with the miniature scanner yielded an overall sensitivity of 91% and specificity of 99% and showed strong agreement when compared to light microscopy (k = 0.91). Strong agreement was also observed when results were compared to results from the high-end slide scanner (k = 0.94). A majority of discrepant cases were micrometastases and sections of which no anticytokeratin staining was available.ConclusionAccuracy of detection of metastatic cells in breast cancer sentinel lymph node frozen sections by visual analysis of samples digitized using low-cost, point-of-care microscopy is comparable to analysis of digital samples scanned using a high-end, whole slide scanner. This technique could potentially provide a workflow for digital diagnostics in resource-limited settings, facilitate sample analysis at the point-of-care and reduce the need for trained experts on-site during surgical procedures.
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| 40. |
- Holmström, Oscar, et al.
(författare)
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A novel deep learning-based point-of-care diagnostic method for detecting Plasmodium falciparum with fluorescence digital microscopy.
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:11
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Malaria remains a major global health problem with a need for improved field-usable diagnostic tests. We have developed a portable, low-cost digital microscope scanner, capable of both brightfield and fluorescence imaging. Here, we used the instrument to digitize blood smears, and applied deep learning (DL) algorithms to detect Plasmodium falciparum parasites.METHODS: Thin blood smears (n = 125) were collected from patients with microscopy-confirmed P. falciparum infections in rural Tanzania, prior to and after initiation of artemisinin-based combination therapy. The samples were stained using the 4',6-diamidino-2-phenylindole fluorogen and digitized using the prototype microscope scanner. Two DL algorithms were trained to detect malaria parasites in the samples, and results compared to the visual assessment of both the digitized samples, and the Giemsa-stained thick smears.RESULTS: Detection of P. falciparum parasites in the digitized thin blood smears was possible both by visual assessment and by DL-based analysis with a strong correlation in results (r = 0.99, p < 0.01). A moderately strong correlation was observed between the DL-based thin smear analysis and the visual thick smear-analysis (r = 0.74, p < 0.01). Low levels of parasites were detected by DL-based analysis on day three following treatment initiation, but a small number of fluorescent signals were detected also in microscopy-negative samples.CONCLUSION: Quantification of P. falciparum parasites in DAPI-stained thin smears is feasible using DL-supported, point-of-care digital microscopy, with a high correlation to visual assessment of samples. Fluorescent signals from artefacts in samples with low infection levels represented the main challenge for the digital analysis, thus highlighting the importance of minimizing sample contaminations. The proposed method could support malaria diagnostics and monitoring of treatment response through automated quantification of parasitaemia and is likely to be applicable also for diagnostics of other Plasmodium species and other infectious diseases.
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| 41. |
- Holmström, Oscar, et al.
(författare)
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Point-of-Care Digital Cytology With Artificial Intelligence for Cervical Cancer Screening in a Resource-Limited Setting
- 2021
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Cervical cancer is highly preventable but remains a common and deadly cancer in areas without screening programs. The creation of a diagnostic system to digitize Papanicolaou test samples and analyze them using a cloud-based deep learning system (DLS) may provide needed cervical cancer screening to resource-limited areas.Objective: To determine whether artificial intelligence-supported digital microscopy diagnostics can be implemented in a resource-limited setting and used for analysis of Papanicolaou tests.Design, Setting, and Participants: In this diagnostic study, cervical smears from 740 HIV-positive women aged between 18 and 64 years were collected between September 1, 2018, and September 30, 2019. The smears were digitized with a portable slide scanner, uploaded to a cloud server using mobile networks, and used to train and validate a DLS for the detection of atypical cervical cells. This single-center study was conducted at a local health care center in rural Kenya.Exposures: Detection of squamous cell atypia in the digital samples by analysis with the DLS.Main Outcomes and Measures: The accuracy of the DLS in the detection of low- and high-grade squamous intraepithelial lesions in Papanicolaou test whole-slide images.Results: Papanicolaou test results from 740 HIV-positive women (mean [SD] age, 41.8 [10.3] years) were collected. The DLS was trained using 350 whole-slide images and validated on 361 whole-slide images (average size, 100 387 x 47 560 pixels). For detection of cervical cellular atypia, sensitivities were 95.7% (95% CI, 85.5%-99.5%) and 100% (95% CI, 82.4%-100%), and specificities were 84.7% (95% CI, 80.2%-88.5%) and 78.4% (95% CI, 73.6%-82.4%), compared with the pathologist assessment of digital and physical slides, respectively. Areas under the receiver operating characteristic curve were 0.94 and 0.96, respectively. Negative predictive values were high (99%-100%), and accuracy was high, particularly for the detection of high-grade lesions. Interrater agreement was substantial compared with the pathologist assessment of digital slides (kappa = 0.72) and fair compared with the assessment of glass slides (kappa = 0.36). No samples that were classified as high grade by manual sample analysis had false-negative assessments by the DLS.Conclusions and Relevance: In this study, digital microscopy with artificial intelligence was implemented at a rural clinic and used to detect atypical cervical smears with a high sensitivity compared with visual sample analysis.
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| 42. |
- Huhn, Evelyn Annegret, et al.
(författare)
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Effectiveness of real-time continuous glucose monitoring to improve glycaemic control and pregnancy outcome in patients with gestational diabetes mellitus : a study protocol for a randomised controlled trial
- 2020
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 10:11
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Real-time continuous glucose monitoring (rt-CGM) informs users about current interstitial glucose levels and allows early detection of glycaemic excursions and timely adaptation by behavioural change or pharmacological intervention. Randomised controlled studies adequately powered to evaluate the impact of long-term application of rt-CGM systems on the reduction of adverse obstetric outcomes in women with gestational diabetes (GDM) are missing. We aim to assess differences in the proportion of large for gestational age newborns in women using rt-CGM as compared with women with self-monitored blood glucose (primary outcome). Rates of neonatal hypoglycaemia, caesarean section and shoulder dystocia are secondary outcomes. A comparison of glucose metabolism and quality of life during and after pregnancy completes the scope of this study.METHODS AND ANALYSIS: Open-label multicentre randomised controlled trial with two parallel groups including 372 female patients with a recent diagnosis of GDM (between 24+0 until 31+6 weeks of gestation): 186 with rt-CGM (Dexcom G6) and 186 with self-monitored blood glucose (SMBG). Women with GDM will be consecutively recruited and randomised to rt-CGM or control (SMBG) group after a run-in period of 6-8 days. The third visit will be scheduled 8-10 days later and then every 2 weeks. At every visit, glucose measurements will be evaluated and all patients will be treated according to the standard care. The control group will receive a blinded CGM for 10 days between the second and third visit and between week 36+0 and 38+6. Cord blood will be sampled immediately after delivery. 48 hours after delivery neonatal biometry and maternal glycosylated haemoglobin A1c (HbA1c) will be assessed, and between weeks 8 and 16 after delivery all patients receive a re-examination of glucose metabolism including blinded CGM for 8-10 days.ETHICS AND DISSEMINATION: This study received ethical approval from the main ethic committee in Vienna. Data will be presented at international conferences and published in peer-reviewed journals.TRIAL REGISTRATION NUMBER: NCT03981328; Pre-results.
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| 43. |
- Jarl, Johan, et al.
(författare)
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Heterogeneity in the associations between common mental disorders and labour outcomes - a population study from southern Sweden
- 2020
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous research has shown that Common Mental Disorders (CMD) are unequally distributed between population subgroups, but we know less about how labour outcomes following such disorders are distributed. Our aim is to investigate how the labour outcomes following a CMD diagnosis differ over sex, age, schooling and country of birth.METHODS: We use a population sample from southern Sweden of patients diagnosed with CMD during calendar years 2009-2011, and a matched general population control group, to study labour market outcomes three years following diagnosis. Logistic regression is used to study the associations between a CMD diagnosis and outcomes in employment, sick leave, and disability pension. Interaction analysis is used to study heterogeneity in these associations.RESULTS: CMD diagnosis is associated with reduced employment and increased odds of sick leave and disability pension. Following a CMD diagnosis, men and higher educated individuals have higher odds of non-employment and sick leave compared to women and the lower educated. Foreign-born individuals have higher odds of non-employment and lower odds of sick leave, compared to individuals born in Sweden. Heterogeneity appears to be present also based on age. Younger age is associated with higher odds of non-employment and disability pension and lower odds of sick leave, following a CMD diagnosis.CONCLUSIONS: Heterogeneity in labour outcomes following a CMD diagnosis sometimes contributes to and sometimes mitigates inequalities in employment, sick leave and disability pension between population subgroups. When developing new strategies to tackle mental ill-health in the population, it may therefore be motivated to consider not only inequalities in the prevalence of mental disorders but also heterogeneity in associated adverse labour outcomes.
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| 44. |
- Jarl, Johan, et al.
(författare)
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Inequalities in labour market consequences of common mental disorders
- 2018
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The burden of mental disorders continues to grow and is now a leading cause of disability worldwide. The prevalence of mental disorders is unequal between population subgroups, and these disorders are associated with unfavourable consequences in social and economic conditions, health and survival. However, how the negative effects of mental disorders are distributed among population subgroups is less studied. Our aim is to investigate how labour market consequences of Common Mental Disorders (CMD) differ over gender, age, education, and country of birth. We use a population sample from southern Sweden of patients diagnosed with CMD 2009-2012 and a matched general population control group with linked register information on employment, long-term sick leave, and disability pension. Logistic regression with interaction effects between CMD and sociodemographic indicators are used to estimate labour market consequences of CMD in the different population subgroups. CMD have a negative impact on all labour market outcomes studied, reducing employment while increasing the risk of long term sick leave and disability pension. However, the associated effect is found to be stronger for men than women, except for disability pension where consequences are similar. Surprisingly, high educated individuals suffer worse labour market consequences than low educated. Consequences of CMD in labour market outcomes are not consistent across different age-groups and country of birth. Inequalities in the labour market consequences of common mental disorders sometimes contributes to, and sometimes mitigates, societal inequalities in employment, long term sick leave and disability pension. When developing new strategies to tackle mental ill health in the population, it may therefore be motivated to consider not only inequalities in the prevalence of mental disorders, but also inequalities in the consequences of these disorders.
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| 45. |
- Johan, Linder, et al.
(författare)
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IPA in UX Research : Interpretative Phenomenological Analysis in a User Experience Design Practice
- 2017
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Konferensbidrag (refereegranskat)abstract
- One approach to user experience (UX) is phenomenology, but there are no well-defined methods for how to conduct UX research using phenomenology, especially not in a professional design practice. One well-defined approach developed in psychology is Interpretative Phenomenological Analysis (IPA), which in this paper is adapted to professional UX research practice. The adaptation is put to test in the case of understanding how newly-arrived immigrants to Sweden experience a start-up service that introduce them to the job market. Contributions and shortcomings of the method in the views of professional UX researchers and designers are documented and discussed. It is concluded that IPA contributes to UX research by investigating both experience and meaning, and by providing holistic insights appropriate for service design and the fuzzy front-end of innovation.
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| 46. |
- Johannesson, Emilia, et al.
(författare)
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Utility of heparin-binding protein following cardiothoracic surgery using cardiopulmonary bypass
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Cardiothoracic surgery using cardiopulmonary bypass (CPB) triggers an inflammatory state that may be difficult to differentiate from infection. Heparin-binding protein (HBP) is a candidate biomarker for sepsis. As data indicates that HBP normalizes rapidly after cardiothoracic surgery, it may be a suitable early marker of postoperative infection. We therefore aimed to investigate which variables influence postoperative HBP levels and whether elevated HBP concentration is associated with poor surgical outcome. This exploratory, prospective, observational study enrolled 1475 patients undergoing cardiothoracic surgery using CPB, where HBP was measured at ICU arrival. Patients with HBP in the highest tercile were compared to remaining patients. Multivariable logistic regressions were performed to identify factors predictive of elevated HBP and 30-day mortality. Overall median HBP was 30.0 ng/mL. Patients undergoing isolated CABG or surgery with CPB-duration ≤ 60 min had a median HBP of 24.9 ng/mL and 23.2 ng/mL, respectively. Independent predictors of elevated postoperative HBP included increased EuroSCORE, prolonged CPB-duration and high intraoperative temperature. Increased HBP was an independent predictor of 30-day mortality. This study confirms the promising characteristics of HBP as a biomarker for identification of postoperative sepsis, especially after routine procedures. Further studies are required to investigate whether HBP may detect postoperative infections.
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| 47. |
- Johansson, Linda, et al.
(författare)
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HMGB1 in severe soft tissue infections caused by Streptococcus pyogenes.
- 2014
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Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 4:Jan 30
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular High Mobility Group Box 1 (HMGB1) has been associated with acute and chronic inflammatory conditions. However, little is known about HMGB1 in necrotizing bacterial infections. We hypothesized that the local HMGB1 response is excessive in severe soft tissue infections (STIs), which are characterized by necrosis and hyperinflammation. To explore this, tissue biopsies were collected from patients with varying severity of Streptococcus pyogenes skin and STIs, including erysipelas, cellulitis, and necrotizing fasciitis. Tissue sections were immunostained for HMGB1, S. pyogenes, and inflammatory cell infiltrates and results quantified by acquired computerized image analysis (ACIA). HMGB1 expression increased in parallel to disease severity and was significantly higher in necrotizing fasciitis than in erysipelas (p = 0.0023). Confocal microscopy of sections co-stained for HMGB1 and cell markers revealed both extracellular and cytoplasmic HMGB1, the latter of which was found predominantly in macrophages. To further verify macrophages as main source of activation triggered HMGB1 release, human macrophages were infected with clinical S. pyogenes isolates. The results demonstrated infection triggered release of HMGB1. Dual staining's visualized HMGB1 in areas close to, but not overlapping, with neutrophils, indicating a potential chemotactic role. In vitro transmigration experiments showed a chemotactic effect of HMGB1 on neutrophils. The data furthermore provided in vivo support that HGMB1 may form immunostimulatory complexes with IL-1β. Taken together, the findings provide the first in vivo evidence that HMGB1 is abundant at the local site of severe bacterial STIs and its levels correlated to severity of infections; hence, indicating its potential value as a biomarker for tissue pathology.
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| 48. |
- Kaprio, Tuomas, et al.
(författare)
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Human leukocyte antigen-G expression correlates with histological grade but not with prognosis in colorectal carcinoma
- 2021
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Ingår i: HLA. - : John Wiley & Sons. - 2059-2302 .- 2059-2310. ; 98:3, s. 213-217
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Tidskriftsartikel (refereegranskat)abstract
- Trophoblast-specific expression of human leukocyte antigen-G (HLA-G) induces immune tolerance for the developing fetus. Pathological HLA-G expression later in life might contribute to immune escape of various cancers. We studied the still controversial role of HLA-G in colorectal carcinoma (CRC) using the MEM-G/1 antibody and a tissue microarray series of CRC tumors (n = 317). HLA-G expression appeared in 20% of the tumors and showed high intratumoral heterogeneity. HLA-G positivity was associated with better differentiation (p = 0.002) and non-mucinous histology (p = 0.008). However, HLA-G expression alone showed no prognostic value: 5-years disease-specific survival among patients with HLA-G expression was 68.9% (95% CI: 62.7%-75.0%) compared to 74.8% (95% CI: 63.2%-86.3%) among those without expression. These results support a modulatory role of HLA-G in CRC.
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| 49. |
- Karlsson, Christofer A.Q., et al.
(författare)
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Streptococcus pyogenes Infection and the Human Proteome with a Special Focus on the Immunoglobulin G-cleaving Enzyme IdeS
- 2018
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Ingår i: Molecular and Cellular Proteomics. - 1535-9476. ; 17:6, s. 1097-1111
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Tidskriftsartikel (refereegranskat)abstract
- Infectious diseases are characterized by a complex interplay between host and pathogen, but how these interactions impact the host proteome is unclear. Here we applied a combined mass spectrometry-based proteomics strategy to investigate how the human proteome is transiently modified by the pathogen Streptococcus pyogenes, with a particular focus on bacterial cleavage of IgG in vivo. In invasive diseases, S. pyogenes evokes a massive host response in blood, whereas superficial diseases are characterized by a local leakage of several blood plasma proteins at the site of infection including IgG. S. pyogenes produces IdeS, a protease cleaving IgG in the lower hinge region and we find highly effective IdeS-cleavage of IgG in samples from local IgG poor microenvironments. The results show that IdeS contributes to the adaptation of S. pyogenes to its normal ecological niches. Additionally, the work identifies novel clinical opportunities for in vivo pathogen detection.
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| 50. |
- Kessel, Klaus, et al.
(författare)
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Deep Learning Algorithms for Corneal Amyloid Deposition Quantitation in Familial Amyloidosis
- 2020
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Ingår i: OCULAR ONCOLOGY AND PATHOLOGY. - : KARGER. - 2296-4681 .- 2296-4657. ; 6:1, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to train and validate deep learning algorithms to quantitate relative amyloid deposition (RAD; mean amyloid deposited area per stromal area) in corneal sections from patients with familial amyloidosis, Finnish (FAF), and assess its relationship with visual acuity.Methods: Corneal specimens were obtained from 42 patients undergoing penetrating keratoplasty, stained with Congo red, and digitally scanned. Areas of amyloid deposits and areas of stromal tissue were labeled on a pixel level for training and validation. The algorithms were used to quantify RAD in each cornea, and the association of RAD with visual acuity was assessed.Results: In the validation of the amyloid area classification, sensitivity was 86%, specificity 92%, and F-score 81. For corneal stromal area classification, sensitivity was 74%, specificity 82%, and F-score 73. There was insufficient evidence to demonstrate correlation (Spearman's rank correlation, -0.264, p = 0.091) between RAD and visual acuity (logMAR).Conclusions: Deep learning algorithms can achieve a high sensitivity and specificity in pixel-level classification of amyloid and corneal stromal area. Further modeling and development of algorithms to assess earlier stages of deposition from clinical images is necessary to better assess the correlation between amyloid deposition and visual acuity. The method might be applied to corneal dystrophies as well.
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