| 1. |
- Karlson, Björn W., 1953, et al.
(författare)
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A Pharmacokinetic and Pharmacodynamic Comparison of Immediate-Release Metoprolol and Extended-Release Metoprolol CR/XL in Patients with Suspected Acute Myocardial Infarction : A Randomized, Open-Label Study
- 2014
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Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 127:2, s. 73-82
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous metoprolol studies in myocardial infarction patients were performed with immediate-release (IR) metoprolol. This study aims to evaluate if extended-release metoprolol CR/XL once daily gives a similar β-blockade over 24 h compared to multiple dosing of metoprolol IR. Methods: After 2 days of routine metoprolol treatment, 27 patients with suspected acute myocardial infarction were randomized to open-label treatment with metoprolol IR (50 mg four times daily or 100 mg twice daily) or metoprolol CR/XL 200 mg once daily for 3 days. Results: Metoprolol CR/XL 200 mg once daily gave more pronounced suppression of peak heart rate, with lower peak and less variation in peak to trough plasma levels. There were no differences in AUC between the CR/XL and IR formulations, although the trough plasma metoprolol levels were comparable for metoprolol CR/XL 200 mg once daily and metoprolol IR 50 mg four times daily, but lower for metoprolol IR 100 mg twice daily. Both treatments were well tolerated. Conclusions: Metoprolol CR/XL 200 mg once daily showed lower peak and less variation in peak to trough plasma levels compared to multiple dosing of metoprolol IR with the same AUC. This was accompanied by a more uniform β-blockade over time, which was reflected by heart rate, and a more pronounced suppression of peak heart rate with similar tolerability. This suggests metoprolol CR/XL may be used as an alternative to metoprolol IR in patients with myocardial infarction.
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| 2. |
- Lee, S. -K, et al.
(författare)
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Reduction of the barrier height and enhancement of tunneling current of titanium contacts using embedded Au nano-particles on 4H and 6H silicon carbide
- 2002
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Ingår i: Materials Science Forum. - : Trans Tech Publications Inc.. - 0255-5476 .- 1662-9752. ; 389-393:2, s. 937-940
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the electrical characteristics of Ti Schottky contacts with embedded Au nano-particles on various types of epilayers of SiC (4H- and 6H-SiC). From our current-voltage (I-V) and capacitance-voltage (C-V) measurements, we observed that Ti Schottky contacts with embedded Au nano-particles had 0.19 eV (n-4H-SiC) and 0.15 eV (n-6H-SiC) lower barrier height than those of particle free Ti Schottky contacts. In order to understand this reduction of the Schottky barrier height (SBH) for Ti Schottky contacts with embedded Au nano-particles, it has been proposed that SBH lowering is caused by an enhanced electric field due to the small size of the Au nano-particles and the large SBH difference. We have also tested these contacts on highly doped n-and p-type SiC material to study ohmic contacts using linear TLM measurements.
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| 3. |
- Ala-Laurinaho, J., et al.
(författare)
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TUMESA - MEMS tuneable metamaterials for smart wireless applications
- 2012
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Ingår i: European Microwave Week 2012: "Space for Microwaves", EuMW 2012, Conference Proceedings - 7th European Microwave Integrated Circuits Conference, EuMIC 2012. - : IEEE. - 9782874870286 ; , s. 95-98
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Konferensbidrag (refereegranskat)abstract
- This paper describes the main results of the EU FP7 project TUMESA - MEMS tuneable metamaterials for smart wireless applications. In this project, we studied several reconfigurable antenna approaches that combine the new technology of MEMS with the new concept of artificial electromagnetic materials and surfaces (metamaterials and metasurfaces) for realisation of millimetre wave phase shifters and beam-steering devices. MEMS technology allows to miniaturise electronic components, reduce their cost in batch production, and effectively compete with semiconductor and ferroelectric based technologies in terms of losses at millimetre wavelengths. Novel tuneable materials and components proposed in this project perform as smart beam steering devices. Fabricated with MEMS technology in batch and on a single chip, proposed tuneable devices allow substituting of larger and more complex sub-system of, e.g., a radar sensor. This substitution provides a dramatic cost reduction on a system level.
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| 4. |
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| 5. |
- Alvez, Maria Bueno, et al.
(författare)
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Next generation pan-cancer blood proteome profiling using proximity extension assay
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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| 6. |
- Andersson, Maria, et al.
(författare)
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Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia
- 2023
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Ingår i: Journal of Hematology. - : Elmer Press, Inc.. - 1927-1212 .- 1927-1220. ; 12:4, s. 170-175
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton’s tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluate the impact of the third-generation BTKi, zanubrutinib, on systemic and mucosal response to SARS-CoV-2 vaccination.Methods: Nine patients with CLL with ongoing zanubrutinib therapy were included and donated blood and saliva during SARS-CoV-2 vaccination, before vaccine doses 3 and 5 and 2 - 3 weeks after doses 3, 4, and 5. Ibrutinib-treated control patients (n = 7) and healthy aged-matched controls (n = 7) gave blood 2 - 3 weeks after vaccine dose 5. We quantified reactivity and neutralization capacity of SARS-CoV-2-specific IgG and IgA antibodies (Abs) in both serum and saliva, and reactivity of T cells activated with viral peptides.Results: Both zanubrutinib- and ibrutinib-treated patients had significantly, up to 1,000-fold, lower total spike-specific Ab levels after dose 5 compared to healthy controls (P < 0.01). Spike-IgG levels in serum from zanubrutinib-treated patients correlated well to neutralization capacity (r = 0.68; P < 0.0001) and were thus functional. Mucosal immunity (specific IgA in serum and saliva) was practically absent in zanubrutinib-treated patients even after five vaccine doses, whereas healthy controls had significantly higher levels (tested in serum after vaccine dose 5) (P < 0.05). In contrast, T-cell reactivity against SARS-CoV-2 peptides was equally high in zanubrutinib- and ibrutinib-treated patients as in healthy control donors.Conclusions: In our small cohort of zanubrutinib-treated CLL patients, we conclude that up to five doses of SARS-CoV-2 vaccination induced no detectable IgA mucosal immunity, which likely will impair the primary barrier defence against the infection. Systemic IgG responses were also impaired, whereas T-cell responses were normal. Further and larger studies are needed to evaluate the impact of these findings on disease protection.
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| 7. |
- Baghchehsaraei, Zargham, 1982-, et al.
(författare)
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Integration of microwave MEMS devices into rectangular waveguide with conductive polymer interposers
- 2013
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Ingår i: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 23:12, s. 125020-
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Tidskriftsartikel (refereegranskat)abstract
- This paper investigates a novel method of integrating microwave microelectromechanical systems (MEMS) chips into millimeter-wave rectangular waveguides. The fundamental difficulties of merging micromachined with macromachined microwave components, in particular, surface topography, roughness, mechanical stress points and air gaps interrupting the surface currents, are overcome by a double-side adhesive conductive polymer interposer. This interposer provides a uniform electrical contact, stable mechanical connection and a compliant stress distribution interlayer between the MEMS chip and a waveguide frame. The integration method is successfully implemented both for prototype devices of MEMS-tuneable reflective metamaterial surfaces and for MEMS reconfigurable transmissive surfaces. The measured insertion loss of the novel conductive polymer interface is less than 0.4 dB in the E-band (60-90 GHz), as compared to a conventional assembly with an air gap of 2.5 dB loss. Moreover, both dc biasing lines and mechanical feedthroughs to actuators outside the waveguide are demonstrated in this paper, which is achieved by structuring the polymer sheet xurographically. Finite element method simulations were carried out for analyzing the influence of different parameters on the radio frequency performance.
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| 8. |
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| 9. |
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| 10. |
- Bjornstad, Kristian, et al.
(författare)
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Validation of the Endopep-MS method for qualitative detection of active botulinum neurotoxins in human and chicken serum
- 2014
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 406:28, s. 7149-7161
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Tidskriftsartikel (refereegranskat)abstract
- Botulinum neurotoxins (BoNTs) are highly toxic proteases produced by anaerobic bacteria. Traditionally, a mouse bioassay (MBA) has been used for detection of BoNTs, but for a long time, laboratories have worked with alternative methods for their detection. One of the most promising in vitro methods is a combination of an enzymatic and mass spectrometric assay called Endopep-MS. However, no comprehensive validation of the method has been presented. The main purpose of this work was to perform a validation for the qualitative analysis of BoNT-A, B, C, C/D, D, D/C, and F in serum. The limit of detection (LOD), selectivity, precision, stability in matrix and solution, and correlation with the MBA were evaluated. The LOD was equal to or even better than that of the MBA for BoNT-A, B, D/C, E, and F. Furthermore, Endopep-MS was for the first time successfully used to differentiate between BoNT-C and D and their mosaics C/D and D/C by different combinations of antibodies and target peptides. In addition, sequential antibody capture was presented as a new way to multiplex the method when only a small sample volume is available. In the comparison with the MBA, all the samples analyzed were positive for BoNT-C/D with both methods. These results indicate that the Endopep-MS method is a valid alternative to the MBA as the gold standard for BoNT detection based on its sensitivity, selectivity, and speed and that it does not require experimental animals.
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| 11. |
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| 12. |
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| 13. |
- Bladh, Oscar, et al.
(författare)
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Comparison of SARS-CoV-2 spike-specific IgA and IgG in nasal secretions, saliva and serum
- 2024
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Several novel vaccine platforms aim at mucosal immunity in the respiratory tract to block SARS-CoV-2 transmission. Standardized methods for mucosal sample collection and quantification of mucosal antibodies are therefore urgently needed for harmonized comparisons and interpretations across mucosal vaccine trials and real-world data.Methods: Using commercial electrochemiluminescence antibody panels, we compared SARS-CoV-2 spike-specific IgA and IgG in paired saliva, nasal secretions, and serum from 1048 healthcare workers with and without prior infection.Results: Spike-specific IgA correlated well in nasal secretions and saliva (r>0.65, p<0.0001), but the levels were more than three-fold higher in nasal secretions as compared to in saliva (p<0.01). Correlations between the total population of spike-specific IgA and spike-specific secretory IgA (SIgA) were significantly stronger (p<0.0001) in nasal secretions (r=0.96, p<0.0001) as opposed to in saliva (r=0.77, p<0.0001), and spike-specific IgA correlated stronger (p<0.0001) between serum and saliva (r=0.73, p<0.001) as opposed to between serum and nasal secretions (r=0.54, p<0.001), suggesting transudation of monomeric spike specific IgA from the circulation to saliva. Notably, spike-specific SIgA had a markedly higher SARS-CoV-2 variant cross-binding capacity as compared to the total population of spike specific IgA and IgG in both nasal secretions, saliva and serum, (all p<0.0001), which emphasizes the importance of taking potential serum derived monomeric IgA into consideration when investigating mucosal immune responses.Discussion: Taken together, although spike-specific IgA can be reliably measured in both nasal secretions and saliva, our findings imply an advantage of higher levels and likely also a larger proportion of SIgA in nasal secretions as compared to in saliva. We further corroborate the superior variant cross-binding capacity of SIgA in mucosal secretions, highlighting the potential protective benefits of a vaccine targeting the upper respiratory tract.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Borgström, Magnus T., et al.
(författare)
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Towards Nanowire Tandem Junction Solar Cells on Silicon
- 2018
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Ingår i: IEEE Journal of Photovoltaics. - 2156-3381. ; 8:3, s. 733-740
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Tidskriftsartikel (refereegranskat)abstract
- The development of photovoltaics as a serious means of producing renewable energy has accelerated greatly in the last ten years, with prices for silicon-based solar cell systems dropping dramatically in the last few years. The next great opportunity for photovoltaics following this competitiveness in prices will be to enhance the cell and panel efficiencies. It is quite generally seen that the most viable platform on which this should be realized will be as augmented silicon solar cells, in which a top cell will be combined with the silicon bottom cell in a tandem configuration, by which the efficiency can be enhanced by a factor from 20% to 50%, depending on details of the approach. In this paper, we report on the status of one such approach, namely, with a top cell comprising III-V nanowires, connected to the bottom silicon cell in a two-terminal or four-terminal configuration. Among the most important opportunities, we show that a substrate-free growth, called Aerotaxy, offers a radical reduction in the total price picture. Besides the description of the key technical approaches, we also discuss the environmental issues.
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| 20. |
- Broberg, Karin, et al.
(författare)
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Evaluation of 92 cardiovascular proteins in dried blood spots collected under field-conditions : Off-the-shelf affinity-based multiplexed assays work well, allowing for simplified sample collection
- 2021
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Ingår i: BioEssays. - : Wiley. - 0265-9247 .- 1521-1878. ; 43:9
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Tidskriftsartikel (refereegranskat)abstract
- Workplace-collected blood spots deposited on filter paper were analysed with multiplexed affinity-based protein assays and found to be suitable for proteomics analysis. The protein extension assay (PEA) was used to characterize 92 proteins using 1.2 mm punches in repeated samples collected from 20 workers. Overall, 97.8% of the samples and 91.3% of the analysed proteins passed quality control. Both within and between spot correlations using six replicates from the same individual were above 0.99, suggesting that comparable levels are obtained from multiple punches from the same spot and from consecutive spots. Protein levels from dried blood and wet serum from the same individuals were compared and the majority of the analysed proteins were found to be significantly correlated. These results open up for simplified sample collection of blood in field conditions for proteomic analysis, but also highlight that not all proteins can be robustly measured from dried whole blood.
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| 21. |
- Chen, Puran, et al.
(författare)
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Real-world assessment of immunogenicity in immunocompromised individuals following SARS-CoV-2 mRNA vaccination : a one-year follow-up of the prospective clinical trial COVAXID
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 94
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immunocompromised patients have varying responses to SARS-CoV-2 mRNA vaccination. However, there is limited information available from prospective clinical trial cohorts with respect to long-term immunogenicity-related responses in these patient groups following three or four vaccine doses, and in applicable cases infection.Methods: In a real-world setting, we assessed the long-term immunogenicity-related responses in patients with primary and secondary immunodeficiencies from the prospective open-label clinical trial COVAXID. The original clinical trial protocol included two vaccine doses given on days 0 and 21, with antibody titres measured at six different timepoints over six months. The study cohort has subsequently been followed for one year with antibody responses evaluated in relation to the third and fourth vaccine dose, and in applicable cases SARS-CoV-2 infection. In total 356/539 patients were included in the extended cohort. Blood samples were analysed for binding antibody titres and neutralisation against the Spike protein for all SARS-CoV-2 variants prevailing during the study period, including Omicron subvariants. SARS-CoV-2 infections that did not require hospital care were recorded through quarterly in-person, or phone-, interviews and assessment of IgG antibody titres against SARSCoV-2 Nucleocapsid. The original clinical trial was registered in EudraCT (2021-000175-37) and clinicaltrials.gov (NCT04780659).Findings: The third vaccine dose significantly increased Spike IgG titres against all the SARS-CoV-2 variants analysed in all immunocompromised patient groups. Similarly, neutralisation also increased against all variants studied, except for Omicron. Omicron-specific neutralisation, however, increased after a fourth dose as well as after three doses and infection in many of the patient subgroups. Noteworthy, however, while many patient groups mounted strong serological responses after three and four vaccine doses, comparably weak responders were found among patient subgroups with specific primary immunodeficiencies and subgroups with immunosuppressive medication.Interpretation: The study identifies particularly affected patient groups in terms of development of long-term immunity among a larger group of immunocompromised patients. In particular, the results highlight poor vaccine-elicited neutralising responses towards Omicron subvariants in specific subgroups. The results provide additional knowledge of relevance for future vaccination strategies.
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| 22. |
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| 23. |
- Chicherini, D., et al.
(författare)
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Analog type millimeter wave phase shifters based on MEMS tunable high-impedance surface in rectangular metal waveguide
- 2010
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Ingår i: 2010 IEEE MTT-S International Microwave Symposium. - : IEEE. - 9781424460571 ; , s. 61-64
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Konferensbidrag (refereegranskat)abstract
- Possibility of compact low loss analog type millimeter wave phase shifter was demonstrated. The phase shifter is controlled by a MEMS tunable high-impedance surface placed, e.g., as a backshort or as sidewall inclusions of a rectangular metal waveguide. Reflection type phase shifter can provide differential analog phase shift from O to up to 240. Reliable and tunable MEMS based high-impedance surface has been demonstrated for the first time. The insertion loss of the fabricated MEMS tunable high-impedance surface varies from 0.7 dB to a maximum of3.5 dB (at a resonance frequency), which is a dramatic improvement over our previous non-tunable prototype.
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| 24. |
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| 25. |
- Edén, Desireé, et al.
(författare)
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Adipocytes express tissue factor and FVII and are procoagulant in a TF/FVIIa-dependent manner
- 2019
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Ingår i: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 124:3, s. 158-167
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tissue factor (TF) combined with its ligand FVII initiates blood coagulation and intracellular signaling. Obese and type 2 diabetic subjects have increased TF expression in their adipose tissue and an increased risk for thrombotic complications. Here we address the role of TF/FVII on adipocyte functions.Materials and methods: Subcutaneous fat was obtained by means of needle aspiration from healthy volunteers, and adipocytes were isolated after collagenase digestion. 3T3-L1 fibroblasts kept in culture were differentiated into adipocytes by addition of IBMX, dexamethasone, rosiglitazone, and insulin to the media. Proteins and mRNA were analyzed by western blot and RT-PCR. Coagulation activity was determined by a colorimetric FX-assay. Lipolysis was measured as free glycerol using a colorimetric method. Glucose uptake was evaluated by scintillation counting of D-[U-C-14] glucose.Results: In isolated human primary adipocytes we found expression of TF and FVII. TF expression was confirmed in 3T3-L1 adipocytes, and both cell types were found to be procoagulant in a TF/FVIIa-dependent manner. FXa was generated without FVIIa added to the coagulation assay, and active site-inhibited FVIIa blocked FXa formation, supporting our finding of FVII production by human primary adipocytes. There was no evidence for a role of TF in either lipolysis or glucose uptake in our experimental settings.Conclusion: Human primary adipocytes express active TF and FVII, and the TF/FVIIa complex formed on the adipocyte surface can activate substrate FX. Whether the TF/FVIIa complex conveys signaling pathways leading to biological functions and has any biological activity in adipocytes beyond coagulation remains to be elucidated.
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| 26. |
- Gradin, Anna, et al.
(författare)
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Urinary cytokines correlate with acute kidney injury in critically ill COVID-19 patients
- 2021
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Ingår i: Cytokine. - : Springer Nature. - 1043-4666 .- 1096-0023. ; 146
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute kidney injury is common in COVID-19 patients admitted to the ICU. Urinary biomarkers are a non-invasive way of assaying renal damage, and so far, urinary cytokines are not fully investigated. The current study aimed to assess urinary cytokine levels in COVID-19 patients.METHODS: Urine was collected from COVID-19 patients (n = 29) in intensive care and compared to a preoperative group of patients (n = 9) with no critical illness. 92 urinary cytokines were analyzed in multiplex using the Olink Target 96 inflammation panel and compared to clinical characteristics, and urinary markers of kidney injury.RESULTS: There were strong correlations between proinflammatory cytokines and between urinary cytokines and urinary kidney injury markers in 29 COVID-19 patients. Several cytokines were correlated to kidney injury, 31 cytokines to AKI stage and 19 cytokines correlated to maximal creatinine.CONCLUSIONS: Urinary inflammatory cytokines from a wide range of immune cell lineages were significantly upregulated during COVID-19 and the upregulation correlated with acute kidney injury as well as urinary markers of kidney tissue damage.
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| 27. |
- Gunnarsson, Tommy, 1978-
(författare)
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MICROWAVE IMAGING OF BIOLOGICAL TISSUES: applied toward breast tumor detection
- 2007
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Microwave imaging is an efficient diagnostic modality for non-invasively visualizing dielectric contrasts of non-metallic bodies. An increasing interest of this field has been observed during the last decades. Many application areas in biomedicine have been issued, recently the breast tumor detection application using microwave imaging.Many groups are working in the field at the moment for several reasons. Breast cancer is a major health problem globally for women, while it is the second most common cancer form for women causing 0.3 % of the yearly female death in Sweden. Medical imaging is considered as the most effective way of diagnostic breast tumors, where X-ray mammography is the dominating technique. However, this imaging modality still suffers from some limitations. Many women, mostly young ones, have radiographically dense breasts, which means that the breast tissues containing high rates of fibroglandular tissues. In this case the density is very similar to the breast tumor and the diagnosis is very difficult. In this case alternative modalities like Magnetic Resonance Imaging (MRI) with contrast enhancement and Ultrasound imaging are used, however those are not suitable for large scale screening program.Another limitation is the false-negative and false-positive rate using mammography, in general 5–15 % of the tumors are not detected and many cases have to go though a breast biopsy to verify a tumor diagnosis. At last the mammography using breast compression sometimes painful, and utilizing ionizing X-rays. The big potential in microwave imaging is the reported high contrast of complex permittivity between fibroglandular tissues and tumor tissues in breasts and that it is a non-ionizing method which probably will be rather inexpensive.The goal with this work is to develop a microwave imaging system able to reconstruct quantitative images of a female breast. In the frame of this goal this Licentiate thesis contains a brief review of the ongoing research in the field of microwave imaging of biological tissues, with the major focus on the breast tumor application. Both imaging algorithms and experimental setups are included. A feasibility study is performed to analyze what response levels could be expected, in signal properties, in a breast tumor detection application. Also, the usability of a 3D microwave propagation simulator, (QW3D), in the setup development is investigated. This is done by using a simple antenna setup with a breast phantom with different tumor positions. From those results it is clear that strong responses are obtained by a tumor presence and the diffracted responses gives strong information about inhomogeneities inside the breast. The second part of this Licentiate thesis is done in collaboration between Mälardalen University and Supélec. Using the existing planar 2.45 GHz microwave camera and the iterative non-linear Newton Kantorovich code, developed at Département de Recherches en Electromagnétisme (DRE) at Supélec, as a starting point, a new platform for both real-time qualitative imaging and quantitative images of inhomogeneous objects are investigated. The focusing is related to breast tumor detection. For the moment the tomographic performance of the planar camera is verified in simulations through a comparison with other setups. Good calibration is observed, but still experimental work concerning phantom development etc. is needed before experimental results on breast tumor detection may be obtained.
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| 28. |
- Gyllensten, Ulf B., et al.
(författare)
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Next Generation Plasma Proteomics Identifies High-Precision Biomarker Candidates for Ovarian Cancer
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. The aim of our study was to broadly measure protein biomarkers to find tests for the early detection of ovarian cancer. We found that combinations of 4-7 protein biomarkers can provide highly accurate detection of early- and late-stage ovarian cancer compared to benign conditions. The performance of the tests was then validated in a second independent cohort. Background: Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. Methods: We employed the Explore PEA technology for high-precision analysis of 1463 plasma proteins and conducted a discovery and replication study using two clinical cohorts of previously untreated patients with benign or malignant ovarian tumours (N = 111 and N = 37). Results: The discovery analysis identified 32 proteins that had significantly higher levels in malignant cases as compared to benign diagnoses, and for 28 of these, the association was replicated in the second cohort. Multivariate modelling identified three highly accurate models based on 4 to 7 proteins each for separating benign tumours from early-stage and/or late-stage ovarian cancers, all with AUCs above 0.96 in the replication cohort. We also developed a model for separating the early-stage from the late-stage achieving an AUC of 0.81 in the replication cohort. These models were based on eleven proteins in total (ALPP, CXCL8, DPY30, IL6, IL12, KRT19, PAEP, TSPAN1, SIGLEC5, VTCN1, and WFDC2), notably without MUCIN-16. The majority of the associated proteins have been connected to ovarian cancer but not identified as potential biomarkers. Conclusions: The results show the ability of using high-precision proteomics for the identification of novel plasma protein biomarker candidates for the early detection of ovarian cancer.
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| 29. |
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| 30. |
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| 31. |
- Havervall, Sebastian, et al.
(författare)
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Antibody responses after a single dose of ChAdOx1 nCoV-19 vaccine in healthcare workers previously infected with SARS-CoV-2
- 2021
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent reports demonstrate robust serological responses to a single dose of messenger RNA (mRNA) vaccines in individuals previously infected with SARS-CoV-2. Data on immune responses following a single-dose adenovirus-vectored vaccine expressing the SARS-CoV-2 spike protein (ChAdOx1 nCoV-19) in individuals with previous SARS-CoV-2 infection are however limited, and current guidelines recommend a two-dose regimen regardless of preexisting immunity. Methods: We compared RBD-specific IgG and RBD-ACE2 blocking antibodies against SARS-CoV-2 wild type and variants of concern following two doses of the mRNA vaccine BNT162b2 in SARS-CoV-2 naive healthcare workers (n=65) and a single dose of the adenovector vaccine ChAdOx1 nCoV-19 in 82 healthcare workers more than (n=45) and less than (n=37) 11 months post mild SARS-CoV-2 infection at time of vaccination. Findings: The post-vaccine levels of RBD-specific IgG and neutralizing antibodies against the SARS-CoV-2 wild type and variants of concern including Delta lineage 1.617.2 were similar or higher in participants receiving a single dose of ChAdOx1 nCoV-19 vaccine post SARS-CoV-2 infection (both more than and less than 11 months post infection) compared to SARS-CoV-2 naive participants who received two doses of BNT162b2 vaccine. Interpretation: Our data support that a single dose ChAdOx1 nCoV-19 vaccine that is administered up to at least 11 months post SARS-CoV-2 infection serves as an effective immune booster. This provides a possible rationale for a single-dose vaccine regimen. (C) 2021 The Author(s). Published by Elsevier B.V.
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| 32. |
- Havervall, Sebastian, et al.
(författare)
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Impact of SARS-CoV-2 infection on vaccine-induced immune responses over time
- 2022
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Ingår i: Clinical & Translational Immunology (CTI). - : Wiley. - 2050-0068. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To determine the long-term impact of prior SARS-CoV-2 infection on immune responses after COVID-19 vaccination. Methods. Using longitudinally collected blood samples from the COMMUNITY study, we determined binding (WHO BAU mL(-1)) and neutralising antibody titres against ten SARS-CoV-2 variants over 7 months following BNT162b2 in SARS-CoV-2-recovered (n = 118) and SARS-CoV-2-naive (n = 289) healthcare workers with confirmed prior SARS-CoV-2 infection. A smaller group with (n = 47) and without (n = 60) confirmed prior SARS-CoV-2 infection receiving ChAdOx1 nCoV-19 was followed for 3 months. SARS-CoV-2-specific memory T-cell responses were investigated in a subset of SARS-CoV-2-naive and SARS-CoV-2-recovered vaccinees. Results. Vaccination with both vaccine platforms resulted in substantially enhanced T-cell responses, anti-spike IgG responses and neutralising antibodies effective against ten SARS-CoV-2 variants in SARS-CoV-2-recovered participants as compared to SARS-CoV-2-naive participants. The enhanced immune responses sustained over 7 months following vaccination. Conclusion. These findings imply that prior SARS-CoV-2 infection should be taken into consideration when planning booster doses and design of current and future COVID-19 vaccine programmes.
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| 33. |
- Havervall, Sebastian, et al.
(författare)
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Robust humoral and cellular immune responses and low risk for reinfection at least 8 months following asymptomatic to mild COVID-19
- 2022
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 291:1, s. 72-80
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Tidskriftsartikel (refereegranskat)abstract
- Background: Emerging data support detectable immune responses for months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, but it is not yet established to what degree and for how long protection against reinfection lasts.Methods: We investigated SARS-CoV-2-specific humoral and cellular immune responses more than 8 months post-asymptomatic, mild and severe infection in a cohort of 1884 healthcare workers (HCW) and 51 hospitalized COVID-19 patients. Possible protection against SARS-CoV-2 reinfection was analyzed by a weekly 3-month polymerase chain reaction (PCR) screening of 252 HCW that had seroconverted 7 months prior to start of screening and 48 HCW that had remained seronegative at multiple time points.Results: All COVID-19 patients and 96% (355/370) of HCW who were anti-spike IgG positive at inclusion remained anti-spike IgG positive at the 8-month follow-up. Circulating SARS-CoV-2-specific memory T cell responses were detected in 88% (45/51) of COVID-19 patients and in 63% (233/370) of seropositive HCW. The cumulative incidence of PCR-confirmed SARS-CoV-2 infection was 1% (3/252) among anti-spike IgG positive HCW (0.13 cases per 100 weeks at risk) compared to 23% (11/48) among anti-spike IgG negative HCW (2.78 cases per 100 weeks at risk), resulting in a protective effect of 95.2% (95% CI 81.9%-99.1%).Conclusions: The vast majority of anti-spike IgG positive individuals remain anti-spike IgG positive for at least 8 months regardless of initial COVID-19 disease severity. The presence of anti-spike IgG antibodies is associated with a substantially reduced risk of reinfection up to 9 months following asymptomatic to mild COVID-19.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Khandagale, Avinash, et al.
(författare)
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Role of Extracellular Vesicles in Pulmonary Arterial Hypertension Modulation of Pulmonary Endothelial Function and Angiogenesis
- 2020
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : LIPPINCOTT WILLIAMS & WILKINS. - 1079-5642 .- 1524-4636. ; 40:9, s. 2293-2309
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Extracellular vesicles (EVs) have the potential to act as intercellular communicators. The aims were to characterize circulating EVs in patients with pulmonary arterial hypertension (PAH) and to explore whether these EVs contribute to endothelial activation and angiogenesis. Approach and Results: Patients with PAH (n=70) and healthy controls (HC; n=20) were included in this cross-sectional study. EVs were characterized and human pulmonary endothelial cells (hPAECs) were incubated with purified EVs. Endothelial cell activity and proangiogenic markers were analyzed. Tube formation analysis was performed for hPAECs, and the involvement of PSGL-1 (P-selectin glycoprotein ligand 1) was evaluated. The numbers of CD62P(+), CD144(+), and CD235a EVs were higher in blood from PAH compared with HC. Thirteen proteins were differently expressed in PAH and HC EVs, where complement fragment C1q was the most significantly elevated protein (P=0.0009) in PAH EVs. Upon EVs-internalization in hPAECs, more PAH compared with HC EVs evaded lysosomes (P<0.01). As oppose to HC, PAH EVs stimulated hPAEC activation and induced transcription and translation of VEGF-A (vascular endothelial growth factor A;P<0.05) and FGF (fibroblast growth factor;P<0.005) which were released in the cell supernatant. These proangiogenic proteins were higher in patient with PAH plasma compered with HC. PAH EVs induced a complex network of angiotubes in vitro, which was abolished by inhibitory PSGL-1antibody. Anti-PSGL-1 also inhibited EV-induced endothelial cell activation and PAH EV dependent increase of VEGF-A. Conclusions: Patients with PAH have higher levels of EVs harboring increased amounts of angiogenic proteins, which induce activation of hPAECs and in vitro angiogenesis. These effects were partly because of platelet-derived EVs evasion of lysosomes upon internalization within hPAEC and through possible involvement of P-selectin-PSGL-1 pathway.
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| 38. |
- Kindborg, Mikael, et al.
(författare)
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A lightweight agent framework for interactive multi-agent applications
- 1999. - 1
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Ingår i: Proceedings of Fourth International Conference on the Practical Application of Intelligent Agents and Multi-Agents. ; , s. 123-142
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Konferensbidrag (refereegranskat)abstract
- Usability issues are traditionally associated with user interfaces rather than with agent frameworks. We argue that the metaphors and models used in a framework will affect the thinking of the developer, and will influence the application design. Therefore, usability is of central importance for successful software development, and for reducing development and maintenance costs. We discuss the design and implementation of a lightweight agent framework for interactive multi-agent applications. A lightweight framework is advantageous for distributed interactive applications, for instance applications running on hand-held devices with limited memory. The design is based on minimalism and simplicity. We present the results from a usability study of the framework, where issues such as learnability and attitude have been evaluated. The study shows that minimalist design principles are useful for achieving understandable and navigable frameworks.
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| 39. |
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| 40. |
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| 41. |
- Lantz, Mikael, et al.
(författare)
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Thyrostimulin (a TSH-like Hormone) Expression in Orbital and Thyroid Tissue.
- 2007
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1557-9077 .- 1050-7256. ; 17:2, s. 113-118
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate gene expression of thyrostimulin in orbital and thyroid tissue from patients with and without Graves' disease. Design: Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used for detection of thyrostimulin gene expression in intraorbital adipose tissue from patients with severe ophthalmopathy and thyroid healthy controls in addition to thyrostimulin expression in normal thyroid tissue, multinodular goiter tissue, and Graves' thyroid tissue. Main Outcome: In intraorbital tissue, thyrostimulin expression was identified in both patients and controls with fluorescence intensities varying between 0.23 and 0.88 in patients and 0.29 and 8.9 in controls before treatment with DNase. The signal of thyrostimulin was weak or absent in intraorbital adipose tissue from patients with ophthalmopathy and thyroid healthy controls after treatment of samples with DNase. This was in contrast to the expression of the thyroid-stimulating hormone (TSH) receptor and the housekeeping gene cyclophilin A that were detected both before and after DNase treatment. Similar results were found when analyzing human and rat thyroid tissue. Conclusions: Neither did we demonstrate gene expression of thyrostimulin in intraorbital adipose tissue or in thyroid tissue, nor could we confirm earlier findings in rat thyroid tissue. Whether thyrostimulin is a regulator of thyroid function has to be further investigated in future studies.
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| 42. |
- Lindahl, Hannes, et al.
(författare)
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SARS-CoV-2 Antibodies in Commercial Immunoglobulin Products Show Markedly Reduced Cross-reactivities Against Omicron Variants
- 2023
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Ingår i: Journal of Clinical Immunology. - : Springer Nature. - 0271-9142 .- 1573-2592. ; 43:6, s. 1075-1082
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Tidskriftsartikel (refereegranskat)abstract
- PurposePatients with antibody deficiencies often receive maintenance treatment with donor plasma-derived immunoglobulin (Ig) preparations to decrease the incidence and severity of infections. We have previously shown that IgG antibodies to the original SARS-CoV-2 strain were not consistently present in off-the-shelf Ig batches produced up to approximately 18 months after the first identified case of COVID-19 in the USA and that Ig batches with anti-SARS-CoV-2 IgG primarily contained vaccine-induced spike specific antibodies. This study aimed to investigate the degree of cross-reactivity between vaccine-induced anti-SARS-CoV-2 antibodies against Wuhan strain and subsequent viral variants.MethodsSamples were collected from 74 Ig batches supplied by three different commercial manufacturers. All batches were used at the Immunodeficiency Unit at the Karolinska University Hospital from the start of the SARS-CoV-2 pandemic until September 2022. Antibody quantity and potential to neutralize virus entry into host cells were assessed against the original SARS-CoV-2 Wuhan strain and the following nine variants: Alpha, Beta, Delta, IHU, and the Omicron BA.1, BA.1.1, BA.1 with spike mutation L452R, BA.2, and BA.3.ResultsIg batches produced approximately 18 months after the SARS-CoV-2 outbreak (from around July 2021) and later consistently contained high quantities of antibodies that bind the Wuhan strain. The Ig batches had overall low reactivity to the SARS-CoV-2 nucleocapsid, which implies that plasma donor spike IgG essentially is the result of vaccination. We assessed the degree of cross-reactivity towards each virus variant by plotting the variant/Wuhan strain ratio, which was consistent regardless of production date, suggesting cross-reactivity with vaccine-induced antibodies rather than virus exposure in the plasma donor population. Viral variants that emerged later during the pandemic systematically had a lower reactivity ratio, except for the Delta and IHU variants. The Ig batches displayed markedly low neutralizing potential towards the Beta variant and all tested Omicron variants.ConclusionCommercial Ig batches currently contain large quantities of SARS-CoV-2 vaccine-induced antibodies. Cross-reactivity with variant strains is evident but varies, with markedly low neutralizing potential observed against Omicron variants.
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| 43. |
- Ljung Aust, Mikael, 1973, et al.
(författare)
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Close Calls on the Road : A Study of Drivers’ Near-misses
- 2004
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Ingår i: Proceedings of the 3rd International Conference on Traffic and Transportation Psychology.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Joining a longstanding tradition in the field of industrial accident prevention, traffic accident research has begun to extend the study of accidents and serious incidents to include also near-misses and unsafe conditions. As part of a Swedish project called FICA (FactorsInfluencing the Causation of Incidents and Accidents), a study has been conducted to investigate near-misses, with the aim of clarifying different types and frequencies, as well as possible causes at the blunt and sharp end. The near-miss study made use of an analysis method called Driving Reliability and Error Analysis Method. The purpose of the method is to uncover the main socio-technical MTO factors involved in scenarios leading to traffic accidents. The study resulted in valuable understanding of near-misses in traffic and their aetiology, suggestions for improvements of the analysis method, and a basis for further,more extensive, near-miss studies.
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| 44. |
- Lundahl, Anna, et al.
(författare)
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High-resolution mass spectrometric investigation of the phase I and II metabolites of finasteride in pig plasma, urine and bile
- 2014
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Ingår i: Xenobiotica. - : Informa UK Limited. - 0049-8254 .- 1366-5928. ; 44:6, s. 498-510
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Tidskriftsartikel (refereegranskat)abstract
- 1. The metabolite profile of the 5 alpha-reductase type II inhibitor finasteride has been studied in pig plasma, urine and bile using high-resolution mass spectrometry. The porcine biotransformation products were compared to those formed by human liver microsomes and to literature data of recently identified human in vivo metabolites. The objective of this study was to gain further evidence for the validity of using pigs for advanced, invasive drug-drug interaction studies that are not possible to perform in humans. 2. The use of high-resolution mass spectrometry with accurate mass measurements enabled identification of the metabolites by calculation of their elemental compositions as well as their fragmentation patterns. 3. There was an excellent match between the porcine and human metabolic profiles, corroborating the pig as a model of human drug metabolism. The glucuronides of the two recently described human hydroxylated metabolites MX and MY and the carboxylated metabolite M3 were identified as the major biotransformation products of finasteride in pig urine and bile. 4. Furthermore, the CYP enzymes involved in the formation of the hydroxylated metabolites were characterized. Human recombinant CYP3A4 could produce the two major hydroxylated metabolites MX and MY, whereas human recombinant CYP2D6 formed MY only.
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| 45. |
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| 46. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 47. |
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| 48. |
- Marking, Ulrika, et al.
(författare)
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Correlates of protection and viral load trajectories in omicron breakthrough infections in triple vaccinated healthcare workers
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Vaccination offers protection against severe COVID-19 caused by SARS-CoV-2 omicron but is less effective against infection. Characteristics such as serum antibody titer correlation to protection, viral abundance and clearance of omicron infection in vaccinated individuals are scarce. We present a 4-week twice-weekly SARS-CoV-2 qPCR screening in 368 triple vaccinated healthcare workers. Spike-specific IgG levels, neutralization titers and mucosal spike-specific IgA-levels were determined at study start and qPCR-positive participants were sampled repeatedly for two weeks. 81 (cumulative incidence 22%) BA.1, BA.1.1 and BA.2 infections were detected. High serum antibody titers are shown to be protective against infection (p < 0.01), linked to reduced viral load (p < 0.01) and time to viral clearance (p < 0.05). Pre-omicron SARS-CoV-2 infection is independently associated to increased protection against omicron, largely mediated by mucosal spike specific IgA responses (nested models lr test p = 0.02 and 0.008). Only 10% of infected participants remain asymptomatic through the course of their infection. We demonstrate that high levels of vaccine-induced spike-specific WT antibodies are linked to increased protection against infection and to reduced viral load if infected, and suggest that the additional protection offered by pre-omicron SARS-CoV-2 infection largely is mediated by mucosal spike-specific IgA.
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| 49. |
- Marking, Ulrika, et al.
(författare)
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Duration of SARS-CoV-2 Immune Responses Up to Six Months Following Homologous or Heterologous Primary Immunization with ChAdOx1 nCoV-19 and BNT162b2 mRNA Vaccines
- 2022
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Ingår i: Vaccines. - : MDPI AG. - 2076-393X. ; 10:3, s. 359-
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Tidskriftsartikel (refereegranskat)abstract
- Heterologous primary immunization against SARS-CoV-2 is part of applied recommendations. However, little is known about duration of immune responses after heterologous vaccine regimens. To evaluate duration of immune responses after primary vaccination with homologous adeno-vectored ChAdOx1 nCoV-19 vaccine (ChAd) or heterologous ChAd/BNT162b2 mRNA vaccine (BNT), anti-spike-IgG and SARS-CoV-2 VOC-neutralizing antibody responses were measured in 354 healthcare workers (HCW) at 2 weeks, 3 months, 5 months and 6 months after the second vaccine dose. T-cell responses were investigated using a whole blood interferon gamma (IFN-gamma) release assay 2 weeks and 3 months post second vaccine dose. Two hundred and ten HCW immunized with homologous BNT were enrolled for comparison of antibody responses. In study participants naive to SARS-CoV-2 prior to vaccination, heterologous ChAd/BNT resulted in 6-fold higher peak anti-spike IgG antibody titers compared to homologous ChAd vaccination. The half-life of antibody titers was 3.1 months (95% CI 2.8-3.6) following homologous ChAd vaccination and 1.9 months (95% CI 1.7-2.1) after heterologous vaccination, reducing the GMT difference between the groups to 3-fold 6 months post vaccination. Peak T-cell responses were stronger in ChAd/BNT vaccinees, but no significant difference was observed 3 months post vaccination. SARS-CoV-2 infection prior to vaccination resulted in substantially higher peak GMTs and IFN-gamma levels and enhanced SARS-CoV-2 specific antibody and T cell responses over time. Heterologous primary SARS-CoV-2 immunization with ChAd and BNT elicits a stronger initial immune response compared to homologous vaccination with ChAd. However, although the differences in humoral responses remain over 6 months, the difference in SARS-CoV-2 specific T cell responses are no longer significant three months after vaccination.
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| 50. |
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