| 1. |
- Sandås, Kristofer, et al.
(författare)
-
Nanometa Live : a user-friendly application for real-time metagenomic data analysis and pathogen identification
- 2024
-
Ingår i: Bioinformatics. - : Oxford University Press. - 1367-4803 .- 1367-4811. ; 40:3
-
Tidskriftsartikel (refereegranskat)abstract
- Summary: Nanometa Live presents a user-friendly interface designed for real-time metagenomic data analysis and pathogen identification utilizing Oxford Nanopore Technologies’ MinION and Flongle flow cells. It offers an efficient workflow and graphical interface for the visualization and interpretation of metagenomic data as it is being generated. Key features include automated BLAST validation, streamlined handling of custom Kraken2 databases, and a simplified graphical user interface for enhanced user experience. Nanometa Live is particularly notable for its capability to run without constant internet or server access once installed, setting it apart from similar tools. It provides a comprehensive view of taxonomic composition and facilitates the detection of user-defined pathogens or other species of interest, catering to both researchers and clinicians.Availability and implementation: Nanometa Live has been implemented as a local web application using the Dash framework with Snakemake handling the data processing. The source code is freely accessible on the GitHub repository at https://github.com/FOIBioinformatics/nanometa_live and it is easily installable using Bioconda. It includes containerization support via Docker and Singularity, ensuring ease of use, reproducibility, and portability.
|
|
| 2. |
- Abdellah, Tebani, et al.
(författare)
-
Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
|
|
| 3. |
- Corman, Jessica R., et al.
(författare)
-
Response of lake metabolism to catchment inputs inferred using high-frequency lake and stream data from across the northern hemisphere
- 2023
-
Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 68:12, s. 2617-2631
-
Tidskriftsartikel (refereegranskat)abstract
- In lakes, the rates of gross primary production (GPP), ecosystem respiration (R), and net ecosystem production (NEP) are often controlled by resource availability. Herein, we explore how catchment vs. within lake predictors of metabolism compare using data from 16 lakes spanning 39°N to 64°N, a range of inflowing streams, and trophic status. For each lake, we combined stream loads of dissolved organic carbon (DOC), total nitrogen (TN), and total phosphorus (TP) with lake DOC, TN, and TP concentrations and high frequency in situ monitoring of dissolved oxygen. We found that stream load stoichiometry indicated lake stoichiometry for C : N and C : P (r2 = 0.74 and r2 = 0.84, respectively), but not for N : P (r2 = 0.04). As we found a strong positive correlation between TN and TP, we only used TP in our statistical models. For the catchment model, GPP and R were best predicted by DOC load, TP load, and load N : P (R2 = 0.85 and R2 = 0.82, respectively). For the lake model, GPP and R were best predicted by TP concentrations (R2 = 0.86 and R2 = 0.67, respectively). The inclusion of N : P in the catchment model, but not the lake model, suggests that both N and P regulate metabolism and that organisms may be responding more strongly to catchment inputs than lake resources. Our models predicted NEP poorly, though it is unclear why. Overall, our work stresses the importance of characterizing lake catchment loads to predict metabolic rates, a result that may be particularly important in catchments experiencing changing hydrologic regimes related to global environmental change.
|
|
| 4. |
- Ek, Kristine, 1975, et al.
(författare)
-
A harmonized method for automatable life cycle sustainability performance assessment and comparison of civil engineering works design concepts
- 2020
-
Ingår i: IOP Conference Series: Earth and Environmental Science. - : IOP Publishing. - 1755-1307 .- 1755-1315. ; 588:5
-
Konferensbidrag (refereegranskat)abstract
- The life cycle sustainability performance of civil engineering works is increasingly important. The possibility to influence the sustainability of a project design is larger in the conceptual stage than in later stages. Better-informed decisions regarding design choices’ impact on sustainability can be made by comparing conceptual project designs based on an assessment of their life cycle sustainability performance. It is essential that concepts are assessed in a harmonized way and compared impartially. Current standards provide the general framework for the assessment of sustainability performance, but do not give detailed guidance on calculation of sustainability indicators and their aggregation. Since design in automated systems is becoming increasingly common, there is a growing need for machine-readable data and automatable assessment methods. Assessment methods which can be applied using open-access data is important to achieve fair competition. This paper aims to provide a method for life cycle sustainability performance assessment and comparison of civil engineering works design concepts, possible to apply using open-access Environmental Product Declarations (EPDs) and life cycle assessment (LCA) data. The purpose is to enable fair and automatable sustainability assessments of design concepts, to facilitate impartial comparisons of such assessments as a basis for choosing sustainable designs. A literature review of relevant standards and scientific papers on sustainability assessment of construction and civil engineering works was performed. A harmonized, fair and automatable method for life cycle sustainability assessment and comparison of civil engineering works design concepts, well-suited for optimization purposes, is presented. However, the aim currently limits categories and indicators possible to include. The proposed method includes guidance on the calculation of environmental, social and economic indicators, based on LCA, life cycle costing (LCC) and external costs, and aggregation using normalisation and weighting factors of the Product Environmental Footprint (PEF). The proposed method allows for an impartial comparison of the sustainability of design concepts, resulting in better-informed decisions.
|
|
| 5. |
- Glise Sandblad, Katarina, 1982, et al.
(författare)
-
Prevalence of Cancer in Patients with Venous Thromboembolism: A Retrospective Nationwide Case-Control Study in Sweden.
- 2023
-
Ingår i: Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. - : SAGE Publications. - 1938-2723. ; 29
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is a risk factor for venous thromboembolism (VTE). We aimed to define sex-specific risk of preceding cancer in patients with a first-time VTE by conducting a nationwide Swedish registry-based study including 298172 patients with VTE and 1185079 matched controls. This included 44685 patients with a diagnosis of cancer at/or within 1 year before a VTE diagnosis. Female patients with VTE had a higher multivariable adjusted odds ratios of preceding cancer than male patients with VTE (5.5 [99% confidence interval 5.4-5.7] vs 3.9 [3.8-4.0]). The highest risk of cancer in patients with VTE were found for pancreatic cancer (women: 19.6 [15.8-24.4]; men: 17.2 [13.7-21.6]) and brain cancer (women: 17.4 [12.9-23.4]; men: 17.5 [13.8-22.2]). Weak associations were seen between VTE and bladder/urothelial cancer (women: 1.31 [1.12-1.53]; men: 1.34 [1.23-1.47]), prostate cancer (men: 2.17 [2.07-2.27]), malignant melanoma (women: 2.51 [2.07-3.05]; men: 2.67 [2.23-3.18]), and kidney cancer (women: 3.20 [2.49-4.11]; men: 3.33 [2.79-4.07]). In conclusion, associations with VTE were weak for bladder/urothelial cancer and kidney cancer, and strong for pancreatic, brain, and biliary cancers.
|
|
| 6. |
- Gösta, Alexander, et al.
(författare)
-
Data-Informed Urban Design: An Overview of the Use of Data and Digital Tools in Urban Planning and Design
- 2020
-
Ingår i: Built Environment. - : Alexandrine Press. - 0263-7960. ; 46:4, s. 620-636
-
Tidskriftsartikel (refereegranskat)abstract
- This article aims to map how different digital tools can be useful for architects and how they might affect their work processes. Researchers and professionals were interviewed to investigate what they found valuable to measure, which methods they used within their analyses, as well as the opportunities and risks they see for the future of the field with regards to digital tools. As part of the survey, a workshop was held with architects and project managers examining the possibilities of connecting existing methods and tools to the sustainability certification system, City Lab Action Guide, and through that, to achieve a more ambitious set of sustainability goals for the projects. Findings from the study indicate that there are risks associated with giving data an increasingly important role in the design work. A working model never provides the full truth but is inherently limited by its constraints. It is important to acknowledge that all angles and aspects of a problem can never be represented in a model. Another possible risk identified lies in the quality of, and access to, data. In a scenario where data plays an increasingly important role, it is not only the quality of the datasets that is of utmost importance, but it is equally important that the urban planners who request the analyses ask the questions first, and then collect the necessary data, instead of vice versa.
|
|
| 7. |
- Hirlekar, Geir, et al.
(författare)
-
Comorbidity and bystander cardiopulmonary resuscitation in out-of-hospital cardiac arrest.
- 2020
-
Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 106:14, s. 1087-1093
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cardiopulmonary resuscitation (CPR) performed before the arrival of emergency medical services (EMS) is associated with increased survival after out-of-hospital cardiac arrest (OHCA). The aim of this study was to determine whether patients who receive bystander CPR have a different comorbidity compared with patients who do not, and to determine the association between bystander CPR and 30-day survival when adjusting for such a possible difference. METHODS: Patients with witnessed OHCA in the Swedish Registry for Cardiopulmonary Resuscitation between 2011 and 2015 were included, and merged with the National Patient Registry. The Charlson Comorbidity Index (CCI) was used to measure comorbidity. Multiple logistic regression was used to examine the effect of CCI on the association between bystander CPR and outcome. RESULTS: In total, 11 955 patients with OHCA were included, 71% of whom received bystander CPR. Patients who received bystander CPR had somewhat lower comorbidity (CCI) than those who did not (mean±SD: 2.2±2.3 vs 2.5±2.4; p<0.0001). However, this difference in comorbidity had no influence on the association between bystander CPR and 30-day survival in a multivariable model including other possible confounders (OR 2.34 (95% CI 2.01 to 2.74) without adjustment for CCI and OR 2.32 (95% CI 1.98 to 2.71) with adjustment for CCI). CONCLUSION: Patients who undergo CPR before the arrival of EMS have a somewhat lower degree of comorbidity than those who do not. Taking this difference into account, bystander CPR is still associated with a marked increase in 30-day survival after OHCA.
|
|
| 8. |
- Johansson, Emil, et al.
(författare)
-
Hierarchical Clustering and Trajectory Analyses Reveal Viremia-Independent B-Cell Perturbations in HIV-2 Infection
- 2022
-
Ingår i: Cells. - : MDPI. - 2073-4409. ; 11:19
-
Tidskriftsartikel (refereegranskat)abstract
- Time to AIDS in HIV-2 infection is approximately twice as long compared to in HIV-1 infection. Despite reduced viremia, HIV-2-infected individuals display signs of chronic immune activation. In HIV-1-infected individuals, B-cell hyperactivation is driven by continuous antigen exposure. However, the contribution of viremia to B-cell perturbations in HIV-2-infected individuals remains largely unexplored. Here, we used polychromatic flow cytometry, consensus hierarchical clustering and pseudotime trajectory inference to characterize B-cells in HIV-1- or HIV-2-infected and in HIV seronegative individuals. We observed increased frequencies of clusters containing hyperactivated T-bethighCD95highCD27int and proliferating T-bet+CD95highCD27+CD71+ memory B-cells in viremic HIV-1 (p < 0.001 and p < 0.001, respectively), viremic HIV-2 (p < 0.001 and p = 0.014, respectively) and in treatment-naïve aviremic HIV-2 (p = 0.004 and p = 0.020, respectively)-infected individuals, compared to seronegative individuals. In contrast, these expansions were not observed in successfully treated HIV-1-infected individuals. Finally, pseudotime trajectory inference showed that T-bet-expressing hyperactivated and proliferating memory B-cell populations were located at the terminal end of two trajectories, in both HIV-1 and HIV-2 infections. As the treatment-naïve aviremic HIV-2-infected individuals, but not the successfully ART-treated HIV-1-infected individuals, showed B-cell perturbations, our data suggest that aviremic HIV-2-infected individuals would also benefit from antiretroviral treatment.
|
|
| 9. |
- Karlsson, Linda, et al.
(författare)
-
Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases.
- 2024
-
Ingår i: Nature Communications. - 2041-1723. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer's disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.
|
|
| 10. |
- Karlsson, Max, et al.
(författare)
-
A single-cell type transcriptomics map of human tissues
- 2021
-
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:31
-
Tidskriftsartikel (refereegranskat)abstract
- Advances in molecular profiling have opened up the possibility to map the expression of genes in cells, tissues, and organs in the human body. Here, we combined single-cell transcriptomics analysis with spatial antibody-based protein profiling to create a high-resolution single-cell type map of human tissues. An open access atlas has been launched to allow researchers to explore the expression of human protein-coding genes in 192 individual cell type clusters. An expression specificity classification was performed to determine the number of genes elevated in each cell type, allowing comparisons with bulk transcriptomics data. The analysis highlights distinct expression clusters corresponding to cell types sharing similar functions, both within the same organs and between organs.
|
|
| 11. |
- Karlsson, Simon, et al.
(författare)
-
An evaluation and shortening of the Cooking and Food Provisioning Action Scale (CAFPAS) using item response theory
- 2023
-
Ingår i: Food Quality and Preference. - : Elsevier Ltd. - 0950-3293 .- 1873-6343. ; 108
-
Tidskriftsartikel (refereegranskat)abstract
- The Cooking and Food Provisioning Action Scale (CAFPAS) is a 28-item validated tool for measuring food agency, a latent construct representing an individual's ability to make and achieve food-preparation and -provisioning goals. Here, key measurement parameters (targeting, threshold ordering, item fit, unidimensionality, differential item functioning, local dependency, and person reliability) of the CAFPAS are evaluated using a specific case of item response theory, Rasch analysis, on data from a development sample (N = 1853; 910 from Sweden; 943 from the US). Winsteps (v.5.1.7) is used for this analysis. The similarity of the Swedish version of the CAFPAS to the original is also assessed. Based on an iterative assessment of the measurement properties with different combinations of items in the development sample, ways to shorten the CAFPAS without jeopardizing construct validity or person reliability are examined. After removing items that do not fit the Rasch model, or that appear redundant in relation to other items, an 11-item version (CAFPAS-short) is suggested and tested using further Rasch analysis on both the development sample and an additional US-based validation sample (N = 1457). Scores of cooking confidence and attitudes are then modelled with measures from the CAFPAS and CAFPAS-short using frequentist and Bayesian analysis. Results suggest that the CAFPAS-short performs similarly to the full-length version, and potential future improvements to the CAFPAS are discussed. This study represents a successful application of item response theory to investigate and shorten a psychometric scale, reducing cognitive load on participants in studies using the CAFPAS whilst minimizing loss of data reliability. © 2023 The Author(s)
|
|
| 12. |
- Lewin, Harris A., et al.
(författare)
-
The Earth BioGenome Project 2020 : Starting the clock
- 2022
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:4
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 13. |
- Ludewig, Kristin, et al.
(författare)
-
Phenology and morphology of the invasive legume Lupinus polyphyllus along a latitudinal gradient in Europe
- 2022
-
Ingår i: NeoBiota. - : Pensoft Publishers. - 1619-0033 .- 1314-2488. ; 78
-
Tidskriftsartikel (refereegranskat)abstract
- Plant phenology, i. e. the timing of life cycle events, is related to individual fitness and species distributionranges. Temperature is one of the most important drivers of plant phenology together with day length.The adaptation of their phenology may be important for the success of invasive plant species. The presentstudy aims at understanding how the performance and the phenology of the invasive legume Lupinuspolyphyllus vary with latitude. We sampled data across a >2000 km latitudinal gradient from Centralto Northern Europe. We quantified variation in phenology of flowering and fruiting of L. polyphyllususing >1600 digital photos of inflorescences from 220 individual plants observed weekly at 22 sites. Theday of the year at which different phenological phases were reached, increased 1.3–1.8 days per degreelatitude, whereas the growing degree days (gdd) required for these phenological phases decreased 5–16 gddper degree latitude. However, this difference disappeared, when the day length of each day included inthe calculation of gdd was considered. The day of the year of the earliest and the latest climatic zone toreach any of the three studied phenological phases differed by 23–30 days and temperature requirementsto reach these stages differed between 62 and 236 gdd. Probably, the invasion of this species will furtherincrease in the northern part of Europe over the next decades due to climate warming. For invasive speciescontrol, our results suggest that in countries with a large latitudinal extent, the mowing date should shiftby ca. one week per 500 km at sites with similar elevations.
|
|
| 14. |
- Ludewig, Kristin, et al.
(författare)
-
Phenology of Lupinus polyphyllus from Central to Northern Europe
- 2022
-
Annan publikationabstract
- Plant phenology, i. e. the timing of life cycle events, is related to individual fitness and species distribution ranges. Among the environmental factors, phenology is mostly driven by temperature and day length. Rapid adaptation of their phenology may also be important for the success of invasive plant species. Our main aim was to understand how the performance, timing, and temperature dependence of the phenology of the invasive legume Lupinus polyphyllus varies with latitude. L. polyphyllus is one of the most frequent invasive species in Europe, and the gained information may help to make management more effective by adjustments to latitude and phenology.Methods:We quantified variation in phenology across a >2000 km latitudinal gradient from Central to Northern Europe. We sampled data of flowering and fruiting of L. polyphyllus using >1600 digital photos of inflorescences from 220 individual plants observed weekly at 22 locations. We calculated the accumulated growing degree days for each observation date at each site from the temperature data of the meteorological stations, which are listed in the metadata of the dataset.
|
|
| 15. |
- Mulder, Jacob, et al.
(författare)
-
New Reference Materials, Analytical Procedures and Data Reduction Strategies for Sr Isotope Measurements in Geological Materials by LA‐MC‐ICP‐MS
- 2023
-
Ingår i: Geostandards and Geoanalytical Research. - : Wiley. - 1639-4488 .- 1751-908X. ; 47:2, s. 311-336
-
Tidskriftsartikel (refereegranskat)abstract
- Laser ablation multi-collector mass spectrometry (LA-MC-ICP-MS) has emerged as the technique of choice for in situ measurements of Sr isotopes in geological minerals. However, the method poses analytical challenges and there is no widely adopted standardised approach to collecting these data or correcting the numerous potential isobaric inferences. Here, we outline practical analytical procedures and data reduction strategies to help establish a consistent framework for collecting and correcting Sr isotope measurements in geological materials by LA-MC-ICP-MS. We characterise a new set of plagioclase reference materials, which are available for distribution to the community, and present a new data reduction scheme for the Iolite software package to correct isobaric interferences for different materials and analytical conditions. Our tests show that a combination of Kr-baseline subtraction, Rb-peak-stripping using βRb derived from a bracketing glass reference material, and a CaCa or CaAr correction for plagioclase and CaCa or CaAr + REE2+ correction for rock glasses, yields the most accurate and precise 87Sr/86Sr measurements for these materials. Using the analytical and correction procedures outlined herein, spot analyses using a beam diameter of 100 μm or rastering with a 50–65 μm diameter beam can readily achieve < 100 ppm 2SE repeatability ("internal") precision for 87Sr/86Sr measurements for materials with < 1000 μg g-1 Sr.
|
|
| 16. |
- Nilsson, Åsa, et al.
(författare)
-
Visualisering av råvaruflöden och hållbarhet för framtida svenskt skogsbruk : Från skog till produkt
- 2022
-
Rapport (refereegranskat)abstract
- Rapporten, som är framtagen inom Mistra Digital Forest, visar hur visualiseringsverktyget BioMapp kan användas för att analysera påverkan på olika aspekter av hållbarhet från tänkbara alternativa användningar av skogsråvara längs hela värdekedjan, från skog till produkt.BioMapp kan förse beslutsfattare med de underlag de behöver för att fatta faktabaserade beslut, för ökad hållbarhet inom svensk skoglig sektor. Rapporten visar exempel på den typ av resultat som kan genereras med BioMapp.
|
|
| 17. |
- Petersson, Alexandra, et al.
(författare)
-
Branching copy number evolution and parallel immune profiles across the regional tumor space of resected pancreatic cancer
- 2022
-
Ingår i: Molecular Cancer Research. - 1557-3125. ; 20:5, s. 749-761
-
Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease. The only option for curative treatment is resection of the tumor followed by standard adjuvant chemotherapy. Yet, early relapse due to chemoresistance is almost inevitable. Herein, we delineated the genetic intratumor heterogeneity in resected PDAC, with the aim to identify evolutionary patterns that may be associated with overall survival (OS) following treatment with curative intent. Potential relationships with the adjacent immune microenvironment were also examined. The genetic and immune landscapes of the regional tumor space were analyzed in nine patients with resected PDAC. Targeted deep sequencing and genome wide SNP array were followed by clonal deconvolution and phylogenetic analysis. A mathematical complexity score was developed to calculate the network extent of each phylogeny. Spatial variation in abundancy and tumor nest infiltration of immune cells was analyzed by double immunohistochemical staining. Copy number heterogeneity was denoted as the major contributing factor to the branching architectures of the produced phylogenetic trees. Increased tree complexity was significantly inversely associated with OS, and larger regional maximum aberrations (higher treetops) were associated with increased PD-L1 expression on tumor cells. Contrastingly, a FREM1 gene amplification, found in one patient, coincided with a particularly vigorous immune response. Findings from this limited case series suggest that complex evolutionary patterns may be associated with a shorter survival in surgically treated PDAC patients. Some hypothesis-generating associations with the surrounding immune microenvironment were also detected.Implications: Evolutionary copy number patterns may be associated with survival in patients with resected PDAC.
|
|
| 18. |
- Polyzoi, Maria, et al.
(författare)
-
Cost-Effectiveness Analysis of Adjuvant Olaparib Versus Watch and Wait in the Treatment of Germline BRCA1/2-Mutated, High-Risk, HER2-Negative Early Breast Cancer in Sweden
- 2024
-
Ingår i: PHARMACOECONOMICS-OPEN. - 2509-4262 .- 2509-4254. ; 8:2, s. 277-289
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction This study evaluated the cost effectiveness of adjuvant olaparib versus watch and wait (WaW) in patients with germline breast cancer susceptibility gene 1/2 (gBRCA1/2)-mutated, high-risk, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC), previously treated with neoadjuvant or adjuvant chemotherapy, from a Swedish healthcare perspective.Methods A five-state (invasive disease-free survival [IDFS], non-metastatic breast cancer [non-mBC], early-onset mBC, late-onset mBC, death) semi-Markov state transition model with a lifetime horizon was developed. Transition probabilities were informed by data from the Phase III OlympiA trial, supplemented with data from additional studies in BRCA-mutated, HER2-negative mBC. Health state utilities were derived via mapping of OlympiA data and supplemented by literature estimates. Treatment, adverse events and other medical costs were extracted from publicly available Swedish sources. Incremental cost per life-year (LY) and quality-adjusted life-year (QALY) gained were estimated. Costs and outcomes were discounted at 3% annually. One-way deterministic and probabilistic sensitivity analyses (PSA) were conducted.Results Over a lifetime horizon, adjuvant olaparib was associated with an additional 1.50 LYs and 1.22 QALYs, and incremental cost of 471,156 Swedish krona (SEK) versus WaW (discounted). The resulting ICER was 385,183SEK per QALY gained for olaparib versus WaW. ICERs remained below 1,000,000SEK across a range of scenarios, and were consistent across subgroups (hormone receptor [HR]-positive/HER2-negative and triple-negative breast cancer [TNBC]). In PSA, the probability of olaparib being cost effective at 1,000,000SEK per QALY was 99.8%.Conclusions At list price, adjuvant olaparib is a cost-effective alternative to WaW in patients with gBRCA1/2-mutated, high-risk, HER2-negative eBC in Sweden.
|
|
| 19. |
- Rangaiah, Pramod K. B., et al.
(författare)
-
Design of constant width branch line directional coupler for the microwave sensing application
- 2020
-
Ingår i: 14th European Conference on Antennas and Propagation (EuCAP). - 9788831299008 - 9781728137124
-
Konferensbidrag (refereegranskat)abstract
- This paper investigates the design of directional branch-line coupler using constant width multiple sections of series and open microstrip line stubs. This device is operating at the center frequency of 2.45 GHz. The designed coupler is having good performance for the frequency band 2-3 GHz. The proposed design is compared with a typical branch line coupler and shows the improved performance. The design is simulated and fabricated on the Fibreglass-resin laminate (FR4) substrate of height 1.5 mm. The results of simulated and experimented circuits are discussed and analyzed. The circuit is measured using Combination Analyzer N9918A Field Fox Handheld Microwave Analyzer. The proposed topology is easy to design and fabricate with a planar microstrip line technology. The designed coupler shows the good results at 2.45GHz i.e. S 11 = -61.26 dB, S 21 = -45 dB, S 31 = -2dB and S 41 = -4.5dB. The main target of this work is to design a coupler to differentiate between transmitted and reflected signals in the split ring resonator (SRR) sensor for Bone Density Measurement Analysis (BDAS) system.
|
|
| 20. |
- Robba, Chiara, et al.
(författare)
-
Oxygen targets and 6-month outcome after out of hospital cardiac arrest : a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial
- 2022
-
Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26, s. 1-13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.
|
|
| 21. |
- Robba, Chiara, et al.
(författare)
-
Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients : a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
- 2022
-
Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 48:8, s. 1024-1038
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2–8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5–9) cmH20, plateau pressure was 20 cmH20 (IQR = 17–23), driving pressure was 12 cmH20 (IQR = 10–15), mechanical power 16.2 J/min (IQR = 12.1–21.8), ventilatory ratio was 1.27 (IQR = 1.04–1.6), and respiratory rate was 17 breaths/minute (IQR = 14–20). Median partial pressure of oxygen was 87 mmHg (IQR = 75–105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36–45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003–1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001–1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. Conclusions: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.
|
|
| 22. |
- Scharf, Lydia, et al.
(författare)
-
Inverted CD8 T-Cell Exhaustion and Co-Stimulation Marker Balance Differentiate Aviremic HIV-2-Infected From Seronegative Individuals
- 2021
-
Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- HIV-2 is less pathogenic compared to HIV-1. Still, disease progression may develop in aviremic HIV-2 infection, but the driving forces and mechanisms behind such development are unclear. Here, we aimed to reveal the immunophenotypic pattern associated with CD8 T-cell pathology in HIV-2 infection, in relation to viremia and markers of disease progression. The relationships between pathological differences of the CD8 T-cell memory population and viremia were analyzed in blood samples obtained from an occupational cohort in Guinea-Bissau, including HIV-2 viremic and aviremic individuals. For comparison, samples from HIV-1- or dually HIV-1/2-infected and seronegative individuals were obtained from the same cohort. CD8 T-cell exhaustion was evaluated by the combined expression patterns of activation, stimulatory and inhibitory immune checkpoint markers analyzed using multicolor flow cytometry and advanced bioinformatics. Unsupervised multidimensional clustering analysis identified a cluster of late differentiated CD8 T-cells expressing activation (CD38+, HLA-DRint/high), co-stimulatory (CD226+/-), and immune inhibitory (2B4+, PD-1high, TIGIThigh) markers that distinguished aviremic from viremic HIV-2, and treated from untreated HIV-1-infected individuals. This CD8 T-cell population displayed close correlations to CD4%, viremia, and plasma levels of IP-10, sCD14 and beta-2 microglobulin in HIV-2 infection. Detailed analysis revealed that aviremic HIV-2-infected individuals had higher frequencies of exhausted TIGIT+ CD8 T-cell populations lacking CD226, while reduced percentage of stimulation-receptive TIGIT-CD226+ CD8 T-cells, compared to seronegative individuals. Our results suggest that HIV-2 infection, independent of viremia, skews CD8 T-cells towards exhaustion and reduced co-stimulation readiness. Further knowledge on CD8 T-cell phenotypes might provide help in therapy monitoring and identification of immunotherapy targets.
|
|
