| 1. |
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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Shepherd, L., et al.
(författare)
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Infection-related and -unrelated malignancies, HIV and the aging population
- 2016
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Ingår i: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 17:8, s. 590-600
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. Methods: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. Results: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5–5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person-years over the same period. Conclusions: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV-infected populations.
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| 8. |
- Abolfathi, Bela, et al.
(författare)
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The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
- 2018
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Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
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Tidskriftsartikel (refereegranskat)abstract
- The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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| 10. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 11. |
- Borges, A. H., et al.
(författare)
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Nonnucleoside Reverse-transcriptase Inhibitor- vs Ritonavir-boosted Protease Inhibitor-based Regimens for Initial Treatment of HIV Infection: A Systematic Review and Metaanalysis of Randomized Trials
- 2016
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 63:2, s. 268-280
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Tidskriftsartikel (refereegranskat)abstract
- Background. Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors (PI/r) recover more CD4 cells. However, individual trials have not been powered to compare clinical outcomes. Methods. We searched databases to identify randomized trials that compared NNRTI-vs PI/r-based initial therapy. A meta-analysis calculated risk ratios (RRs) or mean differences (MDs), as appropriate. Primary outcome was death or progression to AIDS. Secondary outcomes were death, progression to AIDS, and treatment discontinuation. We calculated RR of virologic suppression and MD for an increase in CD4 cells at week 48. Results. We included 29 trials with 9047 participants. Death or progression to AIDS occurred in 226 participants in the NNRTI arm and in 221 in the PI/r arm (RR, 1.03; 95% confidence interval, .87-1.22; 12 trials; n = 3825), death in 205 participants in the NNRTI arm vs 198 in the PI/r arm (1.04; 0.86-1.25; 22 trials; n = 8311), and progression to AIDS in 140 participants in the NNRTI arm vs 144 in the PI/r arm (1.00; 0.80-1.25; 13 trials; n = 4740). Overall treatment discontinuation (1.12; 0.93-1.35; 24 trials; n = 8249) and from toxicity (1.21; 0.87-1.68; 21 trials; n = 6195) were comparable, but discontinuation due to virologic failure was more common with NNRTI (1.58; 0.91-2.74; 17 trials; n = 5371). At week 48, there was no difference between NNRTI and PI/r in virologic suppression (RR, 1.03; 0.98-1.09) or CD4(+) recovery (MD, -4.7 cells; -14.2 to 4.8). Conclusions. We found no difference in clinical and viro-immunologic outcomes between NNRTI-and PI/r-based therapy.
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| 15. |
- Martin, S., et al.
(författare)
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Multimolecule ALMA observations toward the Seyfert 1 galaxy NGC 1097
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 573
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Tidskriftsartikel (refereegranskat)abstract
- Context. The nearby Sy 1 galaxy NGC 1097 represents an ideal laboratory for exploring the molecular chemistry in the surroundings of an active galactic nucleus (AGN). Aims. Exploring the distribution of different molecular species allows us to understand the physical processes affecting the interstellar medium both in the AGN vicinity and in the outer star forming molecular ring. Methods. We carried out 3 mm ALMA observations that include seven different molecular species, namely HCN, HCO+, CCH, CS, HNCO, SiO, HC3N, and SO, as well as the C-13 isotopologues of the first two. Spectra were extracted from selected positions and all species were imaged over the central 2 kpc (similar to 30 '') of the galaxy at a resolution of similar to 2.2 '' x 1.5 '' (150 pc x 100 pc). Results. HCO+ and CS appear to be slightly enhanced in the star forming ring. CCH shows the largest variations across NGC 1097 and is suggested to be a good tracer of both obscured and early stage star formation. HNCO, SiO, and HC3N are significantly enhanced in the inner circumnuclear disk surrounding the AGN. Conclusions. Differences in the molecular abundances are observed between the star forming ring and the inner circumnuclear disk. We conclude that the HCN/HCO+ and HCN/CS differences observed between AGN-dominated and starburst (SB) galaxies are not due to a HCN enhancement due to X-rays, but rather this enhancement is produced by shocked material at distances of 200 pc from the AGN. Additionally, we claim that lower HCN/CS is a combination of a small underabundance of CS in AGNs, together with excitation effects, where a high density gas component (similar to 10(6) cm(-3)) may be more prominent in SB galaxies. However, the most promising are the differences found among the dense gas tracers that, at our modest spatial resolution, seem to outline the physical structure of the molecular disk around the AGN. In this picture, HNCO probes the well-shielded gas in the disk, surrounding the dense material moderately exposed to the X-ray radiation traced by HC3N. Finally SiO might be the innermost molecule in the disk structure.
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| 16. |
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| 17. |
- Nijkamp, P., et al.
(författare)
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Towards a regional science academy : A manifesto
- 2016
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Ingår i: Region. - : European Regional Science Association. - 2409-5370. ; 3:1, s. R1-R16
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Tidskriftsartikel (refereegranskat)abstract
- This Manifesto provides a joint proposal to create a Regional Science Academy as a think-tank support platform for a strategic development of the spatial sciences. The Regional Science Academy is a strategic spatial knowledge catalyst: it acts as a global intellectual powerhouse for new knowledge network initiatives and scholarly views on regions and cities as vital centrepieces of interconnected spatial systems. This contribution highlights its role and presents various activity plans.
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| 18. |
- Hardtke-Wolenski, Matthias, et al.
(författare)
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Autoimmune Hepatitis in a Murine Autoimmune Polyendocrine Syndrome Type 1 Model Is Directed Against Multiple Autoantigens
- 2015
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 61:4, s. 1295-1305
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS-1) is caused by mutations of the autoimmune regulator (AIRE) gene. Mouse studies have shown that this results in defective negative selection of T cells and defective early seeding of peripheral organs with regulatory T cells (Tregs). Aire deficiency in humans and mice manifests as spontaneous autoimmunity against multiple organs, and 20% of patients develop an autoimmune hepatitis (AIH). To study AIH in APS-1, we generated a murine model of human AIH on a BALB/c mouse background, in which Aire is truncated at exon 2. A subgroup of 24% of mice is affected by AIH, characterized by lymphoplasmacytic and periportal hepatic infiltrates, autoantibodies, elevated aminotransferases, and a chronic and progressive course of disease. Disease manifestation was dependent on specific Aire mutations and the genetic background of the mice. Though intrahepatic Treg numbers were increased and hyperproliferative, the intrahepatic CD4/CD8 ratio was decreased. The targets of the adaptive autoimmune response were polyspecific and not focussed on essential autoantigens, as described for other APS-1-related autoimmune diseases. The AIH could be treated with prednisolone or adoptive transfer of polyspecific Tregs. Conclusion: Development of AIH in APS-1 is dependent on specific Aire mutations and genetic background genes. Autoimmune response is polyspecific and can be controlled by steroids or transfer with Tregs. This might enable new treatment options for patients with AIH.
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| 19. |
- Landegren, Nils, et al.
(författare)
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Transglutaminase 4 as a prostate autoantigen in male subfertility
- 2015
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 7:292
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS1), a monogenic disorder caused by AIRE gene mutations, features multiple autoimmune disease components. Infertility is common in both males and females with APS1. Although female infertility can be explained by autoimmune ovarian failure, the mechanisms underlying male infertility have remained poorly understood. We performed a proteome-wide autoantibody screen in APS1 patient sera to assess the autoimmune response against the male reproductive organs. By screening human protein arrays with male and female patient sera and by selecting for gender-imbalanced autoantibody signals, we identified transglutaminase 4 (TGM4) as a male-specific autoantigen. Notably, TGM4 is a prostatic secretory molecule with critical role in male reproduction. TGM4 autoantibodies were detected in most of the adult male APS1 patients but were absent in all the young males. Consecutive serum samples further revealed that TGM4 autoantibodies first presented during pubertal age and subsequent to prostate maturation. We assessed the animal model for APS1, the Aire-deficient mouse, and found spontaneous development of TGM4 autoantibodies specifically in males. Aire-deficient mice failed to present TGM4 in the thymus, consistent with a defect in central tolerance for TGM4. In the mouse, we further link TGM4 immunity with a destructive prostatitis and compromised secretion of TGM4. Collectively, our findings in APS1 patients and Aire-deficient mice reveal prostate autoimmunity as a major manifestation of APS1 with potential role in male subfertility.
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| 20. |
- Pfaff, S., et al.
(författare)
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Combining high-energy X-ray diffraction with Surface Optical Reflectance and Planar Laser Induced Fluorescence for operando catalyst surface characterization
- 2019
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 90:3
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Tidskriftsartikel (refereegranskat)abstract
- We have combined three techniques, High Energy Surface X-Ray Diffraction (HESXRD), Surface Optical Reflectance, and Planar Laser Induced Fluorescence in an operando study of CO oxidation over a Pd(100) catalyst. We show that these techniques provide useful new insights such as the ability to verify that the finite region being probed by techniques such as HESXRD is representative of the sample surface as a whole. The combination is also suitable to determine when changes in gas composition or surface structure and/or morphology occur and to subsequently correlate them with high temporal resolution. In the study, we confirm previous results which show that the Pd(100) surface reaches high activity before an oxide can be detected. Furthermore, we show that the single crystal catalyst surface does not behave homogeneously, which we attribute to the surface being exposed to inhomogeneous gas conditions in mass transfer limited scenarios.
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| 21. |
- Andersson, G., et al.
(författare)
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Stromal progesterone receptor expression and long-term survival in patients with resected periampullary adenocarcinoma
- 2018
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 29:Suppl. 8, s. 262-263
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Early trials have reported a beneficial effect from tamoxifen treatment in patients with unresectable pancreatic cancer, in particular in women. However, the presence and prognostic significance of female hormone receptors in pancreatic or other periampullary cancers has not yet been described. Methods: Immunohistochemical screening of normal and malignant pancreatic tissue revealed that the predominantly expressed female hormone receptor was the progesterone receptor (PgR), in particular in the cancer-associated stroma. The impact of PgR expression on overall survival (OS) was further examined on tissue microarrays with primary tumours from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinoma. Results: Median follow-up time was 29.7 (range 1.9–185.1) months. Stromal PgR positivity (PgR+), allover denoted in 31% of the cases, was significantly higher in pancreatobiliary-type than in intestinal-type tumours (38.7% vs 19.0%, p = 0.008), with an equal distribution between sexes. Stromal PgR+ was significantly associated with a prolonged OS in KRAS-mutated tumours, whereas the opposite was seen in KRAS wild-type tumours (p for interaction =0.015). This association was particularly evident in women, with a median OS of 60.5 months for PgR+/KRAS mutated tumours and 9.9 months for PgR+/KRAS wild-type tumours (p for interaction <0.001). PgR expression was not prognostic in male patients. Conclusions: The finding of stromal PgR expression, and its link to clinical outcome in a considerable proportion of pancreatic and other periampullary cancers is novel. The concept of tamoxifen treatment for patients with unresectable disease, in particular elderly women, should be pursued, and PgR and KRAS may be relevant biomarkers for improved patient stratification.
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| 22. |
- Cakir, B., et al.
(författare)
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Thrombocytopenia is associated with severe retinopathy of prematurity
- 2018
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Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 3:19
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Tidskriftsartikel (refereegranskat)abstract
- Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (< 100 x 10(9)/l) at >= 30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.
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| 23. |
- Dahl, F, et al.
(författare)
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Imaging single DNA molecules for high precision NIPT
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 4549-
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Tidskriftsartikel (refereegranskat)abstract
- Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing. The primary objective of this study was to assess the Vanadis NIPT assay with respect to analytical precision and clinical feasibility. Analysis of reference DNA samples indicate that samples which are challenging to analyze with low fetal-fraction can be readily detected with a limit of detection determined at <2% fetal-fraction. In total of 286 clinical samples were analysed and 30 out of 30 pregnancies affected by trisomy 21 were classified correctly. This method has the potential to make cost effective NIPT more widely available with more women benefiting from superior detection and false positive rates.
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| 31. |
- Watanabe, M., et al.
(författare)
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Ex Vivo Generation of Donor Antigen-Specific Immunomodulatory Cells A Comparison Study of Anti-CD80/86 mAbs and CTLA4-lg Costimulatory Blockade
- 2018
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Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 27:11, s. 1692-1704
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Tidskriftsartikel (refereegranskat)abstract
- Adoptive transfer of alloantigen-specific immunomodulatory cells generated ex vivo with anti-CD80/CD86 mAbs (2D10.4/IT2.2) holds promise for operational tolerance after transplantation. However, good manufacturing practice is required to allow widespread clinical application. Belatacept, a clinically approved cytotoxic T-lymphocyte antigen 4-immunoglobulin that also binds CD80/CD86, could be an alternative agent for 2D10.4/IT2.2. With the goal of generating an optimal cell treatment with clinically approved reagents, we evaluated the donor-specific immunomodulatory effects of belatacept- and 2D10.4/IT2.2-generated immunomodulatory cells. Immunomodulatory cells were generated by coculturing responder human peripheral blood mononuclear cells (PBMCs) (50 x 10(6) cells) with irradiated donor PBMCs (20 x 10(6) cells) from eight human leukocyte antigen-mismatched responder-donor pairs in the presence of either 2D10.4/IT2.2 (3 mu g/10(6) cells) or belatacept (40 mu g/10(6) cells). After 14 days of coculture, the frequencies of CD4(+) T cells, CD8(+) T cells, and natural killer cells as well as interferon gamma (IFN-gamma) production in the 2D10.4/IT2.2- and belatacept-treated groups were lower than those in the control group. The percentage of CD19(+) B cells was higher in the 2D10.4/IT2.2- and belatacept-treated groups than in the control group. The frequency of CD4(+)CD25(+)CD127(low)FOXP3(+) T cells increased from 4.1 +/- 1.0% (preculture) to 7.1 +/- 2.6% and 7.3 +/- 2.6% (day 14) in the 2D10.4/IT2.2- and belatacept-treated groups, respectively (p<0.05). Concurrently, delta-2 FOXP3 mRNA expression increased significantly. Compared with cells derived from the no-antibody treated control group, cells generated from both the 2D10.4/IT2.2- and belatacept-treated groups produced lower IFN-gamma and higher interleukin-10 levels in response to donor-antigens, as detected by enzyme-linked immunospot. Most importantly, 2D10.4/IT2.2- and belatacept-generated cells effectively impeded the proliferative responses of freshly isolated responder PBMCs against donor-antigens. Our results indicate that belatacept-generated donor-specific immunomodulatory cells possess comparable phenotypes and immunomodulatory efficacies to those generated with 2D10.4/IT2.2. We suggest that belatacept could be used for ex vivo generation of clinical grade alloantigen-specific immunomodulatory cells for tolerance induction after transplantation.
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| 32. |
- Akhtar, M., et al.
(författare)
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Evaluation of the safety and immunogenicity of the oral inactivated multivalent enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi adults in a double-blind, randomized, placebo-controlled Phase I trial using electrochemiluminescence and ELISA assays for immunogenicity analyses
- 2019
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 37:37, s. 5645-5656
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Tidskriftsartikel (refereegranskat)abstract
- The safety and immunogenicity of the second generation oral enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX, consisting of inactivated recombinant E. coli strains over-expressing the colonization factors (CFs) CFA/I, CS3, CS5 and CS6 and the heat labile toxoid LCTBA, were evaluated in Bangladeshi volunteers. To enable analysis of antibody responses against multiple vaccine antigens for subsequent use in small sample volumes from children, a sensitive electrochemiluminescence (ECL) assay for analysis of intestine-derived antibody-secreting cell responses using the antibodies in lymphocyte secretions (ALS) assay was established using Meso Scale Discovery technology. Three groups of Bangladeshi adults (n = 15 per group) received two oral doses of ETVAX with or without double mutant LT (dmLT) adjuvant or placebo in the initial part of a randomized, double-blind, placebo-controlled, age-descending, dose-escalation trial. CF- and LTB-specific ALS and plasma IgA responses were analyzed by ECL and/or ELISA. ETVAX was safe and well tolerated in the adults. Magnitudes of IgA ALS responses determined by ECL and ELISA correlated well (r = 0.85 to 0.98 for the five primary antigens, P < 0.001) and ECL was selected as the ALS readout method. ALS IgA responses against each of the primary antigens were detected in 87-100% of vaccinees after the first and in 100% after the second vaccine dose. Plasma IgA responses against different CFs and LTB were observed in 62-93% and 100% of vaccinees, respectively. No statistically significant adjuvant effect of dmLT on antibody responses to any antigen was detected, but the overall anti-genic breadth of the plasma IgA response tended to favor the adjuvanted vaccine when responses to 4 or more or 5 vaccine antigens were considered. Responses in placebo recipients were infrequent and mainly detected against single antigens. The promising results in adults supported testing ETVAX in descending age groups of children.
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| 33. |
- Akhtar, M., et al.
(författare)
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Kinetics of antibody-secreting cell and fecal IgA responses after oral cholera vaccination in different age groups in a cholera endemic country
- 2017
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 35:2, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- Immune responses to oral enteric vaccines in children and infants may be influenced by factors such as age, previous priming with related microorganisms and breast feeding. In this study, we aimed to determine optimal time points to assess immune responses to oral enteric vaccines in different clinical specimens. This was done by investigating antibody secreting cell (ASC) and fecal antibody responses on different days after vaccination using the licensed oral cholera vaccine Dukoral, containing cholera toxin B-subunit (rCTB) and inactivated Vibrio cholerae bacteria, as a model vaccine. Two vaccine doses were given 2 weeks apart to infants (6-11 months), young children (12-18 months), toddlers (19 months-5 years) and adults in a cholera endemic country (Bangladesh). IgA ASC responses, as determined by the antibodies in lymphocyte supernatant (ALS) assay, plasma IgA and IgG responses and secretory IgA (SIgA) responses in extracts of fecal samples were evaluated 4/5 and 7 days after each vaccination. After the first vaccine dose, anti-CTB ALS IgA responses in adults and toddlers were high and comparable on day 5 and 7, while responses were low and infrequent in young children. After the second dose, highest ALS responses were detected on day 5 among the time points studied in all age groups and the responses declined until day 7. In contrast, plasma IgA and IgG anti-CTB responses were high both on day 5 and 7 after the second dose. Fecal SIgA responses in young children and infants were highest on day 7 after the second dose. Our results suggest that ASC/ALS responses to two doses of the oral cholera vaccine Dukoral and related oral vaccines should be analyzed earlier than previously recommended (day 7) at all ages. Fecal antibody responses should preferably be analyzed later than ASC/ALS responses to detect the highest antibody responses. (C) 2016 Elsevier Ltd. All rights reserved.
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| 34. |
- Akter, S., et al.
(författare)
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The frequency of circulating integrin alpha 4 beta 7(+) cells correlates with protection against Helicobacter pylori infection in immunized mice
- 2019
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Ingår i: Helicobacter. - : Wiley. - 1083-4389 .- 1523-5378. ; 24:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Chronic Helicobacter pylori infection is the cause of peptic ulcers in a subpopulation of individuals and a risk factor for the development of gastric cancer. A vaccine against H pylori infection can prevent the acquisition of the infection and protect against reinfections. Clinical trials to date evaluating the efficacy of H pylori vaccines in human challenge models have shown moderate to poor protection with difficulties in predicting efficacy. Thus, while further studies are needed to design an effective vaccine, we also need to find relevant correlates for vaccine efficacy. Objective To find immune correlates to vaccine efficacy, the frequencies of neutrophils, eosinophils and inflammatory monocytes and CD4(+) T-cell memory and mucosa homing integrin alpha 4 beta 7(+) cells were assessed by flow cytometry in the blood of mice after vaccination. Materials and Methods H pylori antigens and cholera toxin or the multiple mutant CT (mmCT) were administered via the sublingual (SL) and intragastric route (IG). The vaccinated mice were infected with H pylori strain SS1 bacteria, and colonization in the stomach and immune responses were evaluated. Results The H pylori vaccine was effective in reducing bacterial load in the stomach of mice and enhancing immune responses compared to unvaccinated infection controls. In the blood of mice after SL or IG route of vaccination, we observed changes in frequencies of innate and adaptive immune cell subsets compared to infection controls. Remarkably, the frequency of circulating mucosal homing alpha 4 beta 7(+)CD4(+) T cells after vaccination correlated with low bacterial load in the stomach of individual mice irrespective of the immunization route. Conclusions Our study shows that the innate and adaptive immune cell subsets can be measured in the blood after vaccination and that increased frequency of alpha 4 beta 7(+)CD4(+) in the blood after immunization could be used as a predictive marker for the efficacy of vaccine against H pylori infection.
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| 36. |
- Blomberg, S., et al.
(författare)
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Comparison of AP-XPS and PLIF Measurements during CO Oxidation over Pd Single Crystals
- 2016
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Ingår i: Topics in Catalysis. - : Springer Science and Business Media LLC. - 1022-5528 .- 1572-9028. ; 59:5-7, s. 478-486
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between the gas-phase molecules and a catalyst surface is crucial for the surface structure and are therefore important to consider when the active phase of a catalyst is studied. In this study we have used two different techniques to study the gas phase during CO oxidation over Pd single crystals. Gas-phase imaging by planar laser-induced fluorescence (PLIF) shows that a spherical boundary layer with a decreasing gradient of CO2 concentration out from the surface, is present close to the surface when the Pd crystal is highly active. Within this boundary layer the gas composition is completely different than that detected at the outlet of the chamber. The PLIF images of the gas-phase distribution are used to achieve a better understanding of the gas composition between the surface and the detector of a set-up for ambient pressure X-ray photoelectron spectroscopy (AP-XPS), a common technique for surface structure determination of model catalysts. The results show that also the gas-phase peaks present in the AP-XPS spectra truly represent the gas closest to the surface, which facilitates the interpretation of the AP-XPS spectra and thereby also the understanding of the mechanism behind the reaction process.
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| 37. |
- Brundin, L., et al.
(författare)
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An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation
- 2016
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-D-aspartate receptor agonist, are increased. The enzyme amino-beta-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Asberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.
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| 38. |
- Carreras-Puigvert, Jordi, et al.
(författare)
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A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family
- 2017
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes. To a certain extent, their substrate preference redundancies correlate with structural classes, thus linking structure and activity relationships. To elucidate interdependence among the NUDIX hydrolases, we pairwise deplete them generating an epistatic interaction map, evaluate cell cycle perturbations upon knockdown in normal and cancer cells, and analyse their protein and mRNA expression in normal and cancer tissues. Using a novel FUSION algorithm, we integrate all data creating a comprehensive NUDIX enzyme profile map, which will prove fundamental to understanding their biological functionality.
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| 39. |
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| 40. |
- Derraik, Jose G. B., et al.
(författare)
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Association Between Preterm Birth and Lower Adult Height in Women
- 2017
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Ingår i: American Journal of Epidemiology. - : OXFORD UNIV PRESS INC. - 0002-9262 .- 1476-6256. ; 185:1, s. 48-53
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Tidskriftsartikel (refereegranskat)abstract
- We examined whether being born preterm was associated with changes in adult anthropometry in women. We assessed data on 201,382 women (born in 1973-1988) from the Swedish Birth Register. The mean age was 26.0 years. Of the women in our cohort, 663 were born very preterm (< 32 weeks of gestation), 8,247 were born moderately preterm (at least 32 weeks but < 37 weeks), and 192,472 were born at term (37-41 weeks). Subgroup analyses were carried out among siblings and also after adjustment for maternal anthropometric data. Statistical tests were 2-sided. Decreasing gestational age was associated with lower height (-1.1 mm per week of gestation; P < 0.0001), so that women who were born very preterm were on average 12 mm shorter than women who were born moderately preterm (P < 0.0001) and 17 mm shorter than women born at term (P < 0.0001). Compared with women who were born at term, those who were born very preterm had 2.9 times higher odds of short stature (< 155.4 cm), and those born moderately preterm had 1.43 times higher odds. Subgroup analyses showed no differences between women born moderately preterm and those born at term but accentuated differences from women born very preterm. Among siblings (n = 2,388), very preterm women were 23 mm shorter than those born at term (P = 0.003), with a 20-mm difference observed in subgroup analyses (n = 27,395) that were adjusted for maternal stature (P < 0.001). A shorter final height was associated with decreasing gestational age, and this association was particularly marked in women born very preterm.
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| 41. |
- Derraik, Jose G. B., et al.
(författare)
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Body Mass Index, Overweight, and Obesity in Swedish Women Born Post-term
- 2016
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Ingår i: Paediatric and Perinatal Epidemiology. - : Wiley. - 0269-5022 .- 1365-3016. ; 30:4, s. 320-324
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThere is increasing evidence that post-term birth (42 weeks of gestation) is associated with adverse long-term outcomes. We assessed whether women born post-term displayed increased risk of overweight and obesity in adulthood. MethodsData were collected at first antenatal visit (similar to 10-12 weeks of gestation) on singleton Swedish women aged 18 years in 1991-2009 (mean age 26.1 years), who were born post-term (n = 27 153) or at term (37-41 weeks of gestation; n = 184 245). Study outcomes were evaluated for continuous associations with gestational age. Stratified analyses were carried out comparing women born post-term or at term. Analyses were also run with a 2-week buffer between groups to account for possible errors in gestational age estimation, comparing women born very post-term (43 weeks of gestation; n = 5761) to those born within a narrower term window (38-40 weeks of gestation; n = 130 110). ResultsIncreasing gestational age was associated with greater adult weight and body mass index (BMI). Stratified analyses showed that women born post-term were 0.5 kg heavier and had BMI 0.2 kg/m(2) greater than those born at term. Differences were more marked between women born very post-term (43 weeks) vs. a narrower term group (38-40 weeks): 1.0 kg and 0.3 kg/m(2). The adjusted relative risks of overweight/obesity and obesity in women born very post-term were 1.13 and 1.12 times higher, respectively, than in those born at term. ConclusionsPost-term birth is associated with greater BMI and increased risk of overweight and obesity in adulthood, particularly among women born 43 weeks of gestation.
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| 42. |
- Derraik, José G B, et al.
(författare)
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First-borns have greater BMI and are more likely to be overweight or obese : a study of sibling pairs among 26 812 Swedish women
- 2016
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 70:1, s. 78-81
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A number of large studies have shown phenotypic differences between first-borns and later-borns among adult men. In this study, we aimed to assess whether birth order was associated with height and BMI in a large cohort of Swedish women.METHODS: Information was obtained from antenatal clinic records from the Swedish National Birth Register over 20 years (1991-2009). Maternal anthropometric data early in pregnancy (at approximately 10-12 weeks of gestation) were analysed on 13 406 pairs of sisters who were either first-born or second-born (n=26 812).RESULTS: Early in pregnancy, first-born women were of BMI that was 0.57 kg/m(2) (2.4%) greater than their second-born sisters (p<0.0001). In addition, first-borns had greater odds of being overweight (OR 1.29; p<0.0001) or obese (OR 1.40; p<0.0001) than second-borns. First-borns were also negligibly taller (+1.2 mm) than their second-born sisters. Of note, there was a considerable increase in BMI over the 18-year period covered by this study, with an increment of 0.11 kg/m(2) per year (p<0.0001).CONCLUSIONS: Our study corroborates other large studies on men, and the steady reduction in family size may contribute to the observed increase in adult BMI worldwide.
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| 43. |
- Derraik, Jose G. B., et al.
(författare)
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Maternal Height and Preterm Birth : A Study on 192,432 Swedish Women
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Background There is increasing evidence that lower maternal stature is associated with shorter gestational length in the offspring. We examined the association between maternal height and the likelihood of delivering preterm babies in a large and homogeneous cohort of Swedish women. Methods This study covers antenatal data from the Swedish Medical Birth Register on 192,432 women (aged 26.0 years on average) born at term, from singleton pregnancies, and of Nordic ethnicity. Continuous associations between women's heights and the likelihood of preterm birth in the offspring were evaluated. Stratified analyses were also carried out, separating women into different height categories. Results Every cm decrease in maternal stature was associated with 0.2 days shortening of gestational age in the offspring (p<0.0001) and increasing odds of having a child born preterm (OR 1.03), very preterm (OR 1.03), or extremely preterm (OR 1.04). Besides, odds of all categories of preterm birth were highest among the shortest women but lowest among the tallest mothers. Specifically, women of short stature (<= 155 cm or <=-2.0 SDS below the population mean) had greater odds of having preterm (OR 1.65) or very preterm (OR 1.47) infants than women of average stature (-0.5 to 0.5 SDS). When compared to women of tall stature (>= 19 cm), mothers of short stature had even greater odds of giving birth to preterm (OR 2.07) or very preterm (OR 2.16) infants. Conclusions Among Swedish women, decreasing height was associated with a progressive increase in the odds of having an infant born preterm. Maternal short stature is a likely contributing factor to idiopathic preterm births worldwide, possibly due to maternal anatomical constraints.
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| 44. |
- Egerstedt, Anna, et al.
(författare)
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Profiling of the plasma proteome across different stages of human heart failure
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 5830-
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a major public health problem characterized by inability of the heart to maintain sufficient output of blood. The systematic characterization of circulating proteins across different stages of HF may provide pathophysiological insights and identify therapeutic targets. Here we report application of aptamer-based proteomics to identify proteins associated with prospective HF incidence in a population-based cohort, implicating modulation of immunological, complement, coagulation, natriuretic and matrix remodeling pathways up to two decades prior to overt disease onset. We observe further divergence of these proteins from the general population in advanced HF, and regression after heart transplantation. By leveraging coronary sinus samples and transcriptomic tools, we describe likely cardiac and specific cellular origins for several of the proteins, including Nt-proBNP, thrombospondin-2, interleukin-18 receptor, gelsolin, and activated C5. Our findings provide a broad perspective on both cardiac and systemic factors associated with HF development.
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| 45. |
- Evertsson, Jonas, et al.
(författare)
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Self-organization of porous anodic alumina films studied in situ by grazing-incidence transmission small-angle X-ray scattering
- 2018
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Ingår i: RSC Advances. - 2046-2069. ; 8:34, s. 18980-18991
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Tidskriftsartikel (refereegranskat)abstract
- Self-ordered porous anodic alumina (PAA) films are studied extensively due to a large number of possible applications in nanotechnology and low cost of production. Whereas empirical relationships between growth conditions and produced oxides have been established, fundamental aspects regarding pore formation and self-organization are still under debate. We present in situ structural studies of PAA films using grazing-incidence transmission small-angle X-ray scattering. We have considered the two most used recipes where the pores self-organize: 0.3 M H2SO4 at 25 V and 0.3 M C2H2O4 at 40 V. During anodization we have followed the evolution of the structural parameters: average interpore distance, length of ordered pores domains, and thickness of the porous oxide layer. Compared to the extensively used ex situ investigations, our approach gives an unprecedented temporal accuracy in determination of the parameters. By using of Al(100), Al(110) and Al(111) surfaces, the influence of surface orientation on the structural evolution was studied, and no significant differences in the interpore distance and domain length could be observed. However, the rate of oxide growth in 0.3 M C2H2O4 at 40 V was significantly influenced by the surface orientation, where the slowest growth occurs for Al(111). In 0.3 M H2SO4 at 25 V, the growth rates were higher, but the influence of surface orientation was not obvious. The structural evolution was also studied on pre-patterned aluminum surfaces. These studies show that although the initial structures of the oxides are governed by pre-patterning geometry, the final structures are dictated by the anodization conditions.
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| 46. |
- Ferstl, P., et al.
(författare)
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Adsorption and Activation of CO on Co3O4(111) Thin Films
- 2015
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 119:29, s. 16688-16699
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Tidskriftsartikel (refereegranskat)abstract
- To explore the catalytic properties of cobalt oxide at the atomic level, we have studied the interaction of CO and O-2 with well-ordered Co3O4(111) thin films using scanning tunneling microscopy (STM), high-resolution X-ray photoelectron spectroscopy (HR-XPS), infrared reflection absorption spectroscopy (IRAS), and temperature-programmed desorption spectroscopy (TPD) under ultrahigh vacuum (UHV) conditions. At low coverage and temperature, CO binds to surface Co2+ ions on the (111) facets. At larger exposure, a compressed phase is formed in which additional CO is located at sites in between the Co2+ ions. In addition, a bridging carbonate species forms that is associated with defects such as step edges of Co3O4(111) terraces or the side facets of the (111) oriented grains. Preadsorbed oxygen neither affects CO adsorption at low coverage nor the formation of the surface carbonate, but it blocks formation of the high coverage CO phase. Desorption of the molecularly bound CO occurs up to 180 K, whereas the surface carbonate decomposes in a broad temperature range up to 400 K under the release of CO and, to a lesser extent, of CO2. Upon strong loss of crystalline oxygen, the Co3O4 grains eventually switch to the CoO rocksalt structure.
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| 47. |
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| 48. |
- Harlow, Gary S., et al.
(författare)
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Observing growth under confinement : Sn nanopillars in porous alumina templates
- 2019
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Ingår i: Nanoscale Advances. - : Royal Society of Chemistry (RSC). - 2516-0230. ; 1:12, s. 4764-4771
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Tidskriftsartikel (refereegranskat)abstract
- Using a micro-focused high-energy X-ray beam, we have performed in situ time-resolved depth profiling during the electrochemical deposition of Sn into an ordered porous anodic alumina template. Combined with micro-diffraction we are able to follow the variation of the structure at the atomic scale as a function of depth and time. We show that Sn initially deposits at the bottom of the pores, and forms metallic nanopillars with a preferred [100] orientation and a relatively low mosaicity. The lattice strain is found to differ from previous ex situ measurements where the Sn had been removed from the porous support. The dendritic nature of the pore bottom affects the Sn growth mode and results in a variation of Sn grain size, strain and mosaicity. Such atomic scale information of nano-templated materials during electrodeposition may improve the future fabrication of devices.
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| 49. |
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| 50. |
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