| 1. |
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| 2. |
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| 3. |
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| 4. |
- den Besten, C. A., et al.
(författare)
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Stability, Survival, and Tolerability of an Auditory Osseointegrated Implant for Bone Conduction Hearing: Long-Term Follow-Up of a Randomized Controlled Trial
- 2016
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Ingår i: Otology & Neurotology. - : Ovid Technologies (Wolters Kluwer Health). - 1531-7129. ; 37:8, s. 1077-1083
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare implant stability, survival, and soft tissue reactions for a novel (test) and previous generation (control) percutaneous auditory osseointegrated implant for bone conduction hearing at long-term follow-up of 5 years. Study Design: Single follow-up visit of a previously completed multicenter, randomized, controlled trial. Patients: Fifty-seven of the 77 participants of a completed randomized controlled trial on a new auditory osseointegrated implant underwent a single follow-up visit 5 years after implantation, which comprised implant stability measurements and collection of Holgers scores. Additionally, implant survival was recorded for all 77 patients from the original trial. Results: The test implant showed significantly higher implant stability quotient (ISQ) values compared with the control implant throughout the 5-year follow-up. Mean area under the curve of ISQ high from baseline to 5 years was 71.6 (standard deviation [SD] +/-2.0) and 66.7 (SD +/-3.4) for the test and control implant, respectively (p < 0.0001). For both implants, the mean ISQ value recorded at 5 years was higher compared with implantation (test group +2.03 [SD +/-2.55, within group p < 0.0001] and control group +2.25 [SD +/-4.95, within group p = 0.12]). No difference was noticed in increase from baseline between groups (p = 0.64). Furthermore, evaluation of soft tissue reactions continued to show superiority of the test implant. At the 5-year follow-up visit, one patient (2.5%) presented with a Holgers grade 2 in the test group, compared with four patients (23.5%) in the control group (p = 0.048); no patient presented with more severe soft tissue reactions. Excluding explantations, the survival rate was 95.8% for the test group and 95.0% for the control group. The corresponding rates including explantations were 93.9 and 90.0%. Conclusion: The test implant showed superiority in terms of higher mean ISQ values and less adverse soft tissue reactions, both at the single 5-year follow-up visit and during the complete follow-up. In addition, both implants showed an equally high implant survival.
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| 5. |
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| 6. |
- Gonçalves, Isabel, et al.
(författare)
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Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes
- 2016
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 16:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D. Methods: Renin was analyzed by the Proximity Extension Assay in subjects with (n = 985) and without (n = 515) T2D participating in the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study and in 205 carotid endarterectomy patients. Vascular changes were assessed by determining ankle-brachial pressure index (ABPI), carotid intima-media thickness (IMT), carotid plaque area, pulse wave velocity (PWV) and the reactivity hyperemia index (RHI). Results: Plasma renin was elevated in subjects with T2D and demonstrated risk factor-independent association with prevalent cardiovascular disease both in subjects with and without T2D. Renin levels increased with age, body mass index, HbA1c and correlated inversely with HDL. Subjects with T2D had more severe carotid disease, increased arterial stiffness, and impaired endothelial function. Risk factor-independent associations between renin and APBI, bulb IMT, carotid plaque area were observed in both T2D and non-T2D subjects. These associations were independent of treatment with RAAS inhibitors. Only weak associations existed between plasma renin and the expression of pro-inflammatory and fibrous components in plaques from 205 endarterectomy patients. Conclusions: Our findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.
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| 7. |
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| 8. |
- Mittler, Eva, et al.
(författare)
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Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:636
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Tidskriftsartikel (refereegranskat)abstract
- The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes virus (ANDV) and Sin Nombre virus, cause a distinct zoonotic disease, hantavirus cardiopulmonary syndrome (HCPS). Although these infections are severe and have substantial case fatality rates, no FDA-approved hantavirus countermeasures are available. Recent work suggests that monoclonal antibodies may have therapeutic utility. We describe here the isolation of human neutralizing antibodies (nAbs) against tetrameric Gn/Gc glycoprotein spikes from PUUV-experienced donors. We define a dominant class of nAbs recognizing the "capping loop" of Gn that masks the hydrophobic fusion loops in Gc. A subset of nAbs in this class, including ADI-42898, bound Gn/Gc complexes but not Gn alone, strongly suggesting that they recognize a quaternary epitope encompassing both Gn and Gc. ADI-42898 blocked the cell entry of seven HCPS- and HFRS-associated hantaviruses, and single doses of this nAb could protect Syrian hamsters and bank voles challenged with the highly virulent HCPS-causing ANDV and HFRS-causing PUUV, respectively. ADI-42898 is a promising candidate for clinical development as a countermeasure for both HCPS and HFRS, and its mode of Gn/Gc recognition informs the development of broadly protective hantavirus vaccines.
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| 9. |
- Notarnicola, A., et al.
(författare)
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Serum and balf-derived anti-JO1 autoantibodies exhibit high reactivity to distinct HISRS domains and associate with lung and joint involvement in patients with IIM/ASS
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 79, s. 1109-1110
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Autoantibodies that target aminoacyl transfer(t) RNA synthetases (aaRS) represent the serological marker of the anti-synthetase syndrome (ASS), a major subgroup of the idiopathic inflammatory myopathies (IIM) (1). Among the anti-aaRS, anti-histidyl tRNA synthetase (HisRS) autoantibodies (anti-Jo1) are the most common. Up to 90% of IIM/ASS patients diagnosed with interstitial lung disease (ILD) harbor anti-Jo1 autoantibodies (2).Objectives:Reactivity and affinity of anti-Jo1 autoantibodies from serum and broncheoalveolar lavage fluid (BALF) were investigated against HisRS autoantigen. Associations with clinical data from patients IIM/ASS were addressed.Methods:Total IgGs were purified by affinity chromatography. Samples and clinical data were obtained from: i) 26 anti-Jo1+patients (19 at diagnosis, 16/19 at follow-up, 7 BALF/matching serum at baseline; ii) 29 anti-Jo1-(25 serum at diagnosis, 4 BALF/matching serum at baseline); iii) 24 age/gender matched healthy controls. Anti-Jo1 IgG and IgA response against HisRS was evaluated by ELISA and western blot. Affinity was measured by surface plasmon resonance. HisRS full-length (HisRS-FL), two HisRS domains (ABD and CD), and two HisRS splice variants (WHEP and WHEP + ABD splice variant (SV)) were tested. Correlations between autoantibody reactivity and clinical data, at baseline and over disease course, were evaluated.Results:Anti-Jo1 autoantibodies from serum and lung bound HisRS-FL, WHEP and SV with high reactivity and affinity already at diagnosis and recognized both conformational and linear HisRS epitopes (Fig. 1). Levels of autoantibodies (against HisRS-FL, -domains and -splice variants) varied among patients and overtime. Patients with ILD, arthritis and less skin involvement presented higher anti-Jo1 titers compared to those with lower anti-Jo1 titers and to the anti-Jo1 negative group (Fig. 2). Anti-WHEP reactivity in BALF strongly correlated with poor pulmonary function.Conclusion:High reactivity and affinity at time of diagnosis indicates that autoimmunity against HisRS is most likely initiated before IIM/ASS diagnosis. Reactivity to specific splice variants of HisRS may be employed as diagnostic and prognostic markers.References:[1]Marguerie C, Bunn CC, Beynon HL, Bernstein RM, Hughes JM, So AK, Walport MJ: Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes. Q J Med 1990, 77(282):1019-1038[2]Richards TJ, Eggebeen A, Gibson K, Yousem S, Fuhrman C, Gochuico BR, Fertig N, Oddis CV, Kaminski N, Rosas IO et al: Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum 2009, 60(7):2183-2192.Fig. 1.Anti-Jo1 reactivity in total IgG purified from the first available serum sampleFig. 2.Reactivity of total anti-Jo1+ IgG purified from the first available serum close to IIM/ASS diagnosis in relation to clinical dataDisclosure of Interests:Antonella Notarnicola: None declared, Charlotta Preger: None declared, Susanna Lundström: None declared, Nuria Renard: None declared, Edvard Wigren: None declared, Eveline Van Gompel: None declared, Angeles Shunashy Galindo-Feria: None declared, Helena Persson: None declared, Maryam Fathi: None declared, Johan Grunewald: None declared, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Grant/research support from: Gesynta Pharma, AstraZeneca,, Susanne Gräslund: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Catia Cerqueira: None declared
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| 10. |
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| 11. |
- Preger, C., et al.
(författare)
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Characterization of anti-aminoacyl TRNA synthetase autoantibodies in patients with idiopathic inflammatory myopathies
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 79, s. 1084-1085
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Idiopathic inflammatory myopathies (IIM) are rare chronic inflammatory diseases associated with high mortality and morbidity [1]. One sub-group of IIM, anti-synthetase syndrome (ASS), is characterized by the presence of autoantibodies that target aminoacyl transfer(t) RNA synthetases (aaRS), together with specific clinical manifestations such as myositis, interstitial lung disease (ILD), arthritis, mechanic’s hand, Raynaud’s syndrome and fever [2]. The most common anti-aaRS autoantibody, anti-Jo1 targeting histidyl tRNA synthetase (HisRS), is present in up to 20-30% of patients with IIM, and up to 90% of patients with myositis and ILD [3, 4]. Besides Jo1, there are today seven other identified autoantigens within the aaRS family.Objectives:A large part of patients with IIM, including individuals with clinical manifestations indicating ASS, test seronegative to all known myositis specific autoantibodies. However, these patients could potentially harbor autoantibodies against targets not tested for in clinic. In this study, we aimed at extending the detection of autoantibodies by including all cytoplasmic aaRS in the analysis of patients with IIM. We hypothesized the existence of new potential autoantigens within this protein family.Methods:The presence of anti-aaRS autoantibodies was determined using a multiplex suspension bead array assay on 242 IIM patients from the Karolinska University Hospital myositis cohort. A panel of 186 recombinant constructs, representing 57 proteins that included full-length or partial sequence overlaps between constructs of all cytoplasmic aaRS as well as other myositis related proteins, were coupled to magnetic color-coded beads and each plasma sample was tested against the complete antigen panel.Results:By the use of this multiplex method we identified patients with autoantibodies against many of the tested aaRS. Autoantibodies binding to HisRS have previously been shown to bind with higher reactivity to the WHEP domain of HisRS and this was also confirmed in this study. We confirmed reactivity against three of the other aaRS tested for in the clinic (PL-12, PL-7, and EJ). In addition, we identified patients positive for anti-Zo, -KS and -HA, autoantibodies usually not screened for in routine. Finally, our data indicates that there are autoantibodies binding to other aaRS than the previously known eight autoantigens, which will be presented.Conclusion:In this study, we could detect autoantibodies in plasma from patients with IIM, both against the most common aaRS autoantigens, but also against other aaRS that are usually not tested for in clinic. We conclude that it is important to continue the studies of anti-aaRS autoantibodies, and their correlation to clinical manifestations, and in the long run also include more aaRS autoantigens in clinical practice.References:[1]Dobloug, G.C., et al., Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study. Ann Rheum Dis, 2018. 77(1): p. 40-47.[2]Barsotti, S. and I.E. Lundberg, Myositis an evolving spectrum of disease. Immunol Med, 2018. 41(2): p. 46-54.[3]Vencovsky, J., H. Alexanderson, and I.E. Lundberg, Idiopathic Inflammatory Myopathies. Rheum Dis Clin North Am, 2019. 45(4): p. 569-581.[4]Richards, T.J., et al., Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum, 2009. 60(7): p. 2183-92.Disclosure of Interests:Charlotta Preger: None declared, Antonella Notarnicola: None declared, Cecilia Hellström: None declared, Edvard Wigren: None declared, Catia Cerqueira: None declared, Peter Nilsson: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Helena Persson: None declared, Susanne Gräslund: None declared, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Grant/research support from: Gesynta Pharma, AstraZeneca,
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| 12. |
- Preger, C., et al.
(författare)
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Generation and validation of recombinant antibodies to study human aminoacyl-tRNA synthetases
- 2020
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Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 295:41, s. 13981-13993
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Tidskriftsartikel (refereegranskat)abstract
- Aminoacyl-tRNA synthetases (aaRSs) have long been viewed as mere housekeeping proteins and have therefore often been overlooked in drug discovery. However, recent findings have revealed that many aaRSs have noncanonical functions, and several of the aaRSs have been linked to autoimmune diseases, cancer, and neurological disorders. Deciphering these roles has been challenging because of a lack of tools to enable their study. To help solve this problem, we have generated recombinant high-affinity antibodies for a collection of thirteen cytoplasmic and one mitochondrial aaRSs. Selected domains of these proteins were produced recombinantly in Escherichia coli and used as antigens in phage display selections using a synthetic human single-chain fragment variable library. All targets yielded large sets of antibody candidates that were validated through a panel of binding assays against the purified antigen. Furthermore, the top-performing binders were tested in immunoprecipitation followed by MS for their ability to capture the endogenous protein from mammalian cell lysates. For antibodies targeting individual members of the multi-tRNA synthetase complex, we were able to detect all members of the complex, co-immunoprecipitating with the target, in several cell types. The functionality of a subset of binders for each target was also confirmed using immunofluorescence. The sequences of these proteins have been deposited in publicly available databases and repositories. We anticipate that this open source resource, in the form of high-quality recombinant proteins and antibodies, will accelerate and empower future research of the role of aaRSs in health and disease.
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| 13. |
- TORNEVIK, C, et al.
(författare)
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ADSORPTION OF SN ON SI(111)7X7 - RECONSTRUCTIONS IN THE MONOLAYER REGIME
- 1994
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Ingår i: Surface Science. - : Elsevier BV. - 0039-6028 .- 1879-2758. ; 314:2, s. 179-187
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Tidskriftsartikel (refereegranskat)abstract
- Different monolayer phases of Sn on Si(111)7 x 7 have been studied by means of scanning tunneling microscopy (STM), core-level photoelectron spectroscopy (XPS), and Rutherford backscattering spectrometry (RBS). The STM results show that square-root 3 x square-root 3 reconstructions are obtained for room-temperature deposition of 1/3 ML of Sn followed by sample annealing in a broad temperature range. A T4 Sn adatom square-root 3 x square-root 3 phase is formed for temperatures between 500 and 800-degrees-C, with a concentration of defects that is strongly dependent on the temperature and which is as high as 25% for the lowest temperatures. Above 825-degrees-C a second square-root 3 x square-root 3 adatom reconstruction is formed, a mosaic-like phase with a 1: 1 mixture of Si and Sn atoms in T4 positions. The results from investigations of the higher coverage 2 square-root 3 x 2 square-root 3 reconstruction by XPS and RBS support the theory that this phase is a two-layer epitaxial Sn structure with all Si(111) dangling bonds saturated. The Sn coverage for this phase was determined to be between 1 and 1.2 ML.
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| 14. |
- Törnevik, C., et al.
(författare)
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Adsorption of Sn onSi(111)7 × 7 : reconstructions in the monolayer regime
- 1994
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Ingår i: Surface Science. - 0039-6028. ; 314:2, s. 179-187
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Tidskriftsartikel (refereegranskat)abstract
- Different monolayer phases of Sn on Si(111)7 × 7 have been studied by means of scanning tunneling microscopy (STM), core-level photoelectron spectroscopy (XPS), and Rutherford backscattering spectrometry (RBS). The STM results show that 3 × 3 reconstructions are obtained for room-temperature deposition of 1 3 ML of Sn followed by sample annealing in a broad temperature range. A T4 Sn adatom 3 ×3 phase is formed for temperatures between 500 and 800°C, with a concentration of defects that is strongly dependent on the temperature and which is as high as 25% for the lowest temperatures. Above 825°C a second 3×3 adatom reconstruction is formed, a mosaic-like phase with a 1:1 mixture of Si and Sn atoms in T4 positions. The results from investigations of the higher coverage 2 3 × 2 3 reconstruction by XPS and RBS support the theory that this phase is a two-layer epitaxial Sn structure with all Si(111) dangling bonds saturated. The Sn coverage for this phase was determined to be between 1 and 1.2 ML. © 1994.
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| 15. |
- Wigren, C., et al.
(författare)
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Sm- and Yb-induced reconstructions of the Si(111) surface
- 1993
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Ingår i: Physical Review B. - 0163-1829. ; 48:15, s. 11014-11019
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Tidskriftsartikel (refereegranskat)abstract
- Low-energy electron diffraction, scanning tunneling microscopy, and photoelectron spectroscopy results from the submonolayer Sm- and Yb-induced surface structures are presented. Several similar metal-induced surface reconstructions are found to exist for Yb and Sm on Si(111) for low submonolayer coverages: 3×2, 5×1, and 7×1. At higher submonolayer coverage, Yb induces a 2×1 reconstruction while Sm induces a (3 × 3) R30°-like reconstruction. Yb is found to be divalent in all structures, whereas the Sm valence increases with increasing coverage. In the 3×2 structure only divalent Sm is present, in the 5×1 and 7×1 structures a small amount of trivalent Sm appears, and, finally, in the (3 × 3) R30°structure approximately half of the Sm atoms are trivalent. The surface Fermi-level position in the band gap for the different Sm and Yb reconstructions has been measured. The difference in valence stability between Sm and Yb is suggested to be the cause of the difference in the high-coverage structures found and the differences in pinning level for the two elements observed for the 5×1 and 7×1 structures. © 1993 The American Physical Society.
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| 16. |
- Andersen, J. N., et al.
(författare)
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Surface core-level shifts as a probe of the local overlayer structure : CO on Pd(100)
- 1991
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Ingår i: Physical Review Letters. - 0031-9007. ; 67:20, s. 2822-2825
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Tidskriftsartikel (refereegranskat)abstract
- The bonding energies of the Pd 3d and the C 1s core levels have been studied for the p(2 S 2 × 2) R45°, p(3 s2 × S2) R45°, and p(4 S 2 × S 2) R45°structures of CO on Pd(100). Adsorption of CO shifts the Pd 3d surface emission to higher binding energies with the magnitude of the shift depending almost linearly on the number of Pd to CO bonds; the measured shift per bond is close to 0.5 eV. A direct relation is established between the detailed geometry of the CO overlayer and the changes in the Pd 3d spectra.
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| 17. |
- ANDERSEN, JN, et al.
(författare)
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SURFACE RELATED CORE LEVEL SHIFTS FOR THE SI(111)SQUARE-ROOT-3X SQUARE-ROOT-3 - AL SYSTEM
- 1991
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Ingår i: Journal of Vacuum Science & Technology B. - : American Vacuum Society. - 1071-1023 .- 1520-8567. ; 9:4, s. 2384-2387
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Tidskriftsartikel (refereegranskat)abstract
- The Si(111) square-root 3 x square-root 3:Al reconstruction has been studied by surface sensitive high resolution core level spectroscopy. It is shown that three components are needed to fit the Si 2p spectra. The Al2p emission is found to consist of more than one component and it is argued that this is related to defects in the overlayer.
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| 18. |
- Björneholm, O., et al.
(författare)
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Resonant photoemission at core-level shake-up thresholds : Valence-band satellites in nickel
- 1990
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Ingår i: Physical Review B (Condensed Matter). - 0163-1829. ; 41:15, s. 10408-10412
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Tidskriftsartikel (refereegranskat)abstract
- Three-hole satellites (3d7 final-state configuration) in the nickel valence-band photoelectron spectrum have been identified at 13 and 18 eV binding energy with use of synchrotron radiation from the MAX storage ring. The three-hole satellites show resonances at photon energies close to the threshold for excitation of 3p53d9 core-hole shake-up states. The 13-eV satellite also shows a resonance directly at the 3p threshold. This is interpreted as an interference between the direct three-hole ionization and a shake-up transition in the Auger decay of the 3p hole. This shake-up process is also identified directly in the M2,3M4,5M4,5 Auger spectrum.
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| 19. |
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| 20. |
- Brus, Linda, 1977-
(författare)
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Nonlinear Identification and Control with Solar Energy Applications
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nonlinear systems occur in industrial processes, economical systems, biotechnology and in many other areas. The thesis treats methods for system identification and control of such nonlinear systems, and applies the proposed methods to a solar heating/cooling plant. Two applications, an anaerobic digestion process and a domestic solar heating system are first used to illustrate properties of an existing nonlinear recursive prediction error identification algorithm. In both cases, the accuracy of the obtained nonlinear black-box models are comparable to the results of application specific grey-box models. Next a convergence analysis is performed, where conditions for convergence are formulated. The results, together with the examples, indicate the need of a method for providing initial parameters for the nonlinear prediction error algorithm. Such a method is then suggested and shown to increase the usefulness of the prediction error algorithm, significantly decreasing the risk for convergence to suboptimal minimum points. Next, the thesis treats model based control of systems with input signal dependent time delays. The approach taken is to develop a controller for systems with constant time delays, and embed it by input signal dependent resampling; the resampling acting as an interface between the system and the controller. Finally a solar collector field for combined cooling and heating of office buildings is used to illustrate the system identification and control strategies discussed earlier in the thesis, the control objective being to control the solar collector output temperature. The system has nonlinear dynamic behavior and large flow dependent time delays. The simulated evaluation using measured disturbances confirm that the controller works as intended. A significant reduction of the impact of variations in solar radiation on the collector outlet temperature is achieved, though the limited control range of the system itself prevents full exploitation of the proposed feedforward control. The methods and results contribute to a better utilization of solar power.
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| 21. |
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| 22. |
- Dao Nyesiga, Gillian, et al.
(författare)
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Tolerogenic dendritic cells generated in vitro using a novel protocol mimicking mucosal tolerance mechanisms represent a potential therapeutic cell platform for induction of immune tolerance.
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) are mediators between innate and adaptive immunity and vital in initiating and modulating antigen-specific immune responses. The most important site for induction of tolerance is the gut mucosa, where TGF-β, retinoic acid, and aryl hydrocarbon receptors collaborate in DCs to induce a tolerogenic phenotype. To mimic this, a novel combination of compounds – the synthetic aryl hydrocarbon receptor (AhR) agonist IGN-512 together with TGF-β and retinoic acid – was developed to create a platform technology for induction of tolerogenic DCs intended for treatment of several conditions caused by unwanted immune activation. These in vitro-generated cells, designated ItolDCs, are phenotypically characterized by their low expression of co-stimulatory and activating molecules along with high expression of tolerance-associated markers such as ILT3, CD103, and LAP, and a weak pro-inflammatory cytokine profile. When co-cultured with T cells and/or B cells, ItolDC-cultures contain higher frequencies of CD25+Foxp3+ regulatory T cells (Tregs), CD49b+LAG3+ ‘type 1 regulatory (Tr1) T cells, and IL-10-producing B cells and are less T cell stimulatory compared to cultures with matured DCs. Factor VIII (FVIII) and tetanus toxoid (TT) were used as model antigens to study ItolDC antigen-loading. ItolDCs can take up FVIII, process, and present FVIII peptides on HLA-DR. By loading both ItolDCs and mDCs with TT, antigen-specific T cell proliferation was observed. Cryo-preserved ItolDCs showed a stable tolerogenic phenotype that was maintained after stimulation with LPS, CD40L, or a pro-inflammatory cocktail. Moreover, exposure to other immune cells did not negatively impact ItolDCs’ expression of tolerogenic markers. In summary, a novel protocol was developed supporting the generation of a stable population of human DCs in vitro that exhibited a tolerogenic phenotype with an ability to increase proportions of induced regulatory T and B cells in mixed cultures. This protocol has the potential to constitute the base of a tolDC platform for inducing antigen-specific tolerance in disorders caused by undesired antigen-specific immune cell activation.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Fernandes-Cerqueira, C, et al.
(författare)
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Patients with anti-Jo1 antibodies display a characteristic IgG Fc-glycan profile which is further enhanced in anti-Jo1 autoantibodies
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 17958-
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Tidskriftsartikel (refereegranskat)abstract
- IgG Fc-glycans affect IgG function and are altered in autoimmune diseases and autoantibodies. Anti-histidyl tRNA synthetase autoantibodies (anti-Jo1) are frequent in patients with idiopathic inflammatory myopathies (IIM) and anti-synthetase syndrome (ASS) with associated interstitial lung disease (ILD). Thus, we hypothesized that the total-IgG Fc-glycans from Jo1+ versus Jo1− patients and anti-Jo1-IgG would show characteristic differences, and that particular Fc-glycan features would be associated with specific clinical manifestations. By proteomics based mass spectrometry we observed a high abundance of agalactosylated IgG1 Fc-glycans in ASS/IIM patients (n = 44) compared to healthy age matched controls (n = 24). Using intra-individual normalization of the main agalactosylated glycan (FA2) of IgG1 vs FA2-IgG2, ASS/IIM and controls were distinguished with an area under the curve (AUC) of 79 ± 6%. For Jo1+ patients (n = 19) the AUCs went up to 88 ± 6%. Bisected and afucosylated Fc-glycans were significantly lower in Jo1+ compared to Jo1− patients. Anti-Jo1-IgG enriched from eleven patients contained even significantly lower abundances of bisected, afucosylated and galactosylated forms compared to matched total-IgG. ASS and ILD diagnosis, as well as lysozyme and thrombospondin correlated with Jo1+ characteristic Fc-glycan features. These results suggest that the anti-Jo1+ patient Fc-glycan profile contains phenotype specific features which may underlie the pathogenic role of Jo1 autoantibodies.
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| 28. |
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| 31. |
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| 32. |
- Girard, R T, et al.
(författare)
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Electronic structure of ZnO(0001) studied by angle-resolved photoelectron spectroscopy
- 1997
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Ingår i: Surface Science. - 0039-6028 .- 1879-2758. ; 373:2-3, s. 409-417
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structure of the ZnO(0001) surface was studied by angle-resolved photoelectron spectroscopy. The recorded normal emission spectra give information about the Valence band states as well as the Zn 3d states. The dispersions of the four valence bands observed in the (0001) direction were compared with theory and are in good agreement with recent calculations which consider the Zn 3d electrons as part of the valence band. The Zn 3d states are seen to separate into two groups of four and six bands, which show dispersion with k(perpendicular to). This is in agreement with theoretical results but the location of these states were not accurately predicted. The present photoemission results show that they lie around 10.5 eV below E(F). Two surface states were observed on the (0001) surface. One, at 7.5 eV binding energy, was predicted by theory and is interpreted as arising from the ''back-bondings'' of the Zn 4s-O 2p mixed bulk states. The other one at 4.5 eV below E(F), most likely Zn 4p-0 2p derived, was not predicted by theoretical calculations and this is discussed further in the text. (C) 1997 Elsevier Science B.V.
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| 33. |
- Gothelid, M, et al.
(författare)
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Etching and a disordered overlayer on the Ge(100)-S surface
- 1997
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Ingår i: Applied Surface Science. - 0169-4332 .- 1873-5584. ; 115:1, s. 87-95
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Tidskriftsartikel (refereegranskat)abstract
- High resolution core level photoelectron spectroscopy (PES) and scanning tunneling microscopy (STM) have been used to study the adsorption and desorption of S on and off the Ge(100) surface. The previously proposed bridge adsorption site of S is consistent with our results at low coverage. At saturation the substrate contains several GeSx species, with x = 0.5 to 4. Both photoemission and STM reveals a non-ideal surface, with a saturation coverage above one monolayer. Furthermore, S is found to etch the substrate. The reaction products forms a disordered overlayer on top of the interface. This overlayer is transparent in the filled state STM images.
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| 34. |
- GOTHELID, M, et al.
(författare)
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GEOMETRY OF THE GE(111)-AU(ROOT-3X-ROOT-3)R 30-DEGREES RECONSTRUCTION
- 1994
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 50:7, s. 4470-4475
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Tidskriftsartikel (refereegranskat)abstract
- A structure model for the Ge(111)-Au(root 3X root 3)R30 degrees surface reconstruction is proposed based on scanning tunneling microscopy (STM) and photoelectron spectroscopy on the Ge 3d and Au 4f core lines. The basic unit is a Au3Ge molecule binding in one-third of the T-1 substrate sites with a gold trimer pointing out of the surface. This leaves two-thirds of a monolayer of unoccupied T-1 sites which make up a hexagonal honeycomb pattern. Two types of STM images have been obtained which are explained within this model, where either the trimers or the substrate Ge atoms are probed depending on the specific tip conditions in combination with the sample bias voltage. Furthermore, small insets of a metallic (1X1) structure are found at low gold coverage together with a distorted (2X2) surface structure.
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| 35. |
- Gothelid, M, et al.
(författare)
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Iodine reaction and passivation of the Ge(111) surface
- 1997
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Ingår i: Surface Science. - 0039-6028 .- 1879-2758. ; 371:2-3, s. 264-276
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Tidskriftsartikel (refereegranskat)abstract
- The Ge(111)-I surface has been studied at different I coverages ranging from 0.05 hit up to saturation, and different annealing temperatures, using photoelectron spectroscopy (PES) and scanning tunneling microscopy (STM). At saturation the surface is covered with I in the top site and Gel, species in the bridge site, coexisting with small islands/clusters comprising GeI2, giving a total coverage of I in GeIx species of 1.15 ML. The chemically induced shifts in the Ge 3d core level are 0.39 eV per attached I atom. The coverage determined from the I 4d core level is higher than 1.15 ML, which we explain by the presence of I not bound to Ge. Annealing at 200 degrees C decreases the iodine coverage, whereas the I 4d and Ge 3d line profiles are practically unchanged. Further heating desorbs the iodide species and restores the virgin c(2 x 8) structure.
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| 36. |
- GOTHELID, M, et al.
(författare)
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STRUCTURAL AND ELECTRONIC EVOLUTION ON THE GE(111)-AG SURFACE
- 1995
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 52:19, s. 14104-14110
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Tidskriftsartikel (refereegranskat)abstract
- High-resolution core-level photoelectron spectroscopy has been used to study three different silver induced surface reconstructions on the Ge(111) surface. At the lowest coverage a (4 X 4) structure is formed, which displays a similar Ge 3d core-level line shape as the clean c(2 X 8) surface. Details in the spectra are discussed with respect to possible models. The Ge(111)-Ag (root 3 X root 3)R30 degrees structure Ge 3d spectrum is dominated by a very strong contribution assigned to the two topmost Ge layers in a missing top layer structure, similar to the Si(111)-Ag (root 3 X root 3)R30 degrees surface. A weak bulk peak is present on the high-binding-energy side of the spectrum, while a third contribution assigned to Ge in phase boundaries is included in the fit on the lower-binding-energy side. A comparison with results obtained from the Ge(111)-Au root 3 structure points to substantial differences between the two noble-metal-induced root 3 reconstructions on the Ge(111) surface. Finally, after further deposition of silver at room temperature, the root 3 geometry is locally broken creating a (6 X 6) structure and a new surface-related peak emerges on the low-binding-energy side of the Ge 3d spectrum, which was interpreted as being due to Ge atoms floating on top of the outermost surface layer. The valence band also revealed the existence of small metallic silver islands.
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| 37. |
- Ilver, L, et al.
(författare)
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Quantum size effects in epitaxial ErAs on GaAs(001)
- 1996
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 77:24, s. 4946-4949
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structure of very thin epitaxial ErAs layers on GaAs(100) is studied with angle resolved photoelectron spectroscopy. Clear evidence is found for confinement induced quantization of states around the Fermi level. From the dispersive properties of the quantum well states effective masses are obtained, representing electron motion parallel to the surface layers and orthogonal to the layers. We find, for the first time, that effective masses along equivalent bulk directions (XW) are significantly different in the thin layers. Furthermore, the bottom of the highest occupied band shifts towards the Fermi level when going from very thin to thick ErAs layers.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
- Lloyd-Spets, Anita, et al.
(författare)
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SiC based field effect gas sensors for industrial applications
- 2001
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Ingår i: Physica status solidi. A, Applied research. - 0031-8965 .- 1521-396X. ; 185:1, s. 15-25
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Tidskriftsartikel (refereegranskat)abstract
- The development and field-testing of high-temperature sensors based on silicon carbide devices have shown promising results in several application areas. Silicon carbide based field-effect sensors can be operated over a large temperature range, 100-600 degreesC, and since silicon carbide is a chemically very inert material these sensors can be used in environments like exhaust gases and flue gases from boilers. The sensors respond to reducing gases like hydrogen, hydrocarbons and carbon monoxide. The use of different temperatures, different catalytic metals and different structures of the gate metal gives selectivity to different gases and arrays of sensors can be used to identify and monitor several components in gas mixtures. MOSFET sensors based on SIC combine the advantage of simple circuitry with a thicker insulator, which increases the long term stability of the devices. In this paper we describe silicon carbide MOSFET sensors and their performance and give: examples of industrial applications such as monitoring of car exhausts and flue gases. Chemometric methods have been used for the evaluation of the data.
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| 43. |
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| 44. |
- Nyholm, R., et al.
(författare)
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The surface core-level shift of the Pd(100) single-crystal surface
- 1992
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Ingår i: Journal of Physics: Condensed Matter. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 4:1, s. 277-283
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Tidskriftsartikel (refereegranskat)abstract
- The surface core-level shift of the Pd(100) single-crystal surface has been measured from high-resolution Pd 3d core-level spectra. The surface atoms are found to have 0.44+or-0.03 eV lower binding energy than the bulk atoms. The result is compared with theoretical estimates.
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| 45. |
- Preger, C., et al.
(författare)
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Abundant autoantibody isotypes in idiopathic inflammatory myopathies
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:Suppl 1, s. 242.2-243
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Anti-synthetase syndrome (ASSD), a sub-group of idiopathic inflammatory myopathies (IIM) is characterized by the presence of autoantibodies targeting aminoacyl tRNA synthetases (aaRS) and specific clinical manifestations such as myositis and interstitial lung disease (ILD) [1]. Some of the most common anti-aaRS autoantibodies in ASSD are anti-Jo1, -PL7, -PL12 and-EJ. In addition, many anti-aaRS positive patients are also positive for anti-Ro52. Having the combination of anti-Jo1 and anti-Ro52 increases the risk of developing ILD [2]. The presence of autoantibodies is an important part of the classification of ASSD, however only autoantibodies of IgG isotype are usually analyzed in the clinical setting. In rheumatoid arthritis there is evidence that anti-citrullinated protein/peptide antibodies (ACPA) can be found as IgG, IgA and IgM, and importantly, specific isotypes might correlate with disease activity [3, 4].ObjectivesTo verify if other autoantibody isotypes, besides IgG, might be present in sera of patients with IIM/ASSD and to compare with the corresponding frequencies in population controls (PC).MethodsStored sera collected from consecutive 366 IIM patients and 156 age/gender matched PC at Karolinska University Hospital were retrospectively selected. The serum samples were screened for the presence of autoantibodies of isotypes IgG, IgA and IgM, against a panel of 20 antigens representing Jo1 (HisRS), PL7 (ThrRS), PL12 (AlaRS), EJ (GlyRS), and Ro52 (TRIM21) using a multiplex bead array assay.ResultsWe identified IIM patients with autoantibodies of different isotypes, and a low frequency in PC (Figure 1). For anti-Jo1 autoantibodies we could detect IIM patients with only IgG (n=13), only IgM (n=8) and only IgA (n=4), but the majority had a combination of two (n=32) or three isotypes (n=16). For the other anti-aaRS autoantibodies the distribution was more equal to each of the three isotypes with anti-PL12 and anti-PL7 being represented by a slightly higher frequency of IgG and only a few patients had antibodies of more than one isotype targeting PL12, PL7 or EJ. The majority of anti-Ro52 positive IIM patients (n=52) only harbored IgG isotype. The combination of anti-Ro52 and anti-aaRS autoantibodies was identified in 28 patients (anti-Jo1 (n=19), -PL12 (n=2), -PL7 (n=3), and -EJ (n=4)). Most patients with such combination had anti-Ro52 IgG together with anti-aaRS IgG or IgG in combination with IgA and/or IgM. The exception was observed for three anti-Jo1 positive patients who had the combination anti-Ro52 IgG with only anti-Jo1 IgM and one anti-PL7 positive patient who had anti-Ro52 IgA together with anti-PL7 IgA and IgG.Figure 1.Venn diagrams showing reactivity in idiopathic inflammatory myopathies (IIM) (top) and population controls (PC) (bottom) for the three autoantibody isotypes IgG, IgA and IgM against five myositis antigens: Jo1 (HisRS), PL12 (AlaRS), ThrRS (PL7), EJ (GlyRS) and Ro52 (TRIM21).ConclusionThe frequency of the different autoantibody isotypes seems to be autoantigen dependent. Our results suggest that for anti-aaRS autoantibodies it could be important to investigate additional autoantibody isotypes, as some patients only harbor autoantibodies of IgM or IgA isotypes but not IgG. The clinical relevance of the different antibody isotypes still needs to be determined.References[1]Mahler, M., et al., Rev, 2014. 13(4-5): p. 367-71.[2]Huang, H.L., et al., J Clin Neurosci, 2020.[3]Arlestig, L., et al., Ann Rheum Dis, 2012. 71(6): p. 825-9.[4]Roos Ljungberg, K., et al., Arthritis Res Ther, 2020. 22(1): p. 274.Table 1.Total number of individuals and percentage (n (%)) in each group for each of the isotypes and antigens.anti-Jo1anti-PL12anti-PL7anti-EJanti-Ro52IIMPCIIMPCIIMPCIIMPCIIMPCIgG61 (16.7)1 (0.6)7 (1.9)0 (0.0)7 (1.9)0 (0.0)3 (0.8)0 (0.0)54 (14.8)5 (3.2)IgA20 (5.5)0 (0.0)2 (1.2)1 (0.6)3 (0.8)2 (1.3)1 (0.3)1 (0.6)3 (0.8)1 (0.6)IgM56 (15.3)1 (0.6)1 (0.3)2 (1.3)7 (1.9)0 (0.0)1 (0.3)0 (0.0)3 (0.8)2 (1.3)AcknowledgementsSciLifeLab facilities Autoimmunity and Serology Profiling and Human Antibody Therapeutics (Drug Discovery and Development). IMI project EUbOPEN, This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875510. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and Ontario Institute for Cancer Research, Royal Institution for the Advancement of Learning McGill University, Kungliga Tekniska Hoegskolan, Diamond Light Source Limited.Disclosure of InterestsCharlotta Preger Grant/research support from: IMI project EUbOPEN, Grant no 875510, Antonella Notarnicola: None declared, Cecilia Hellström: None declared, Edvard Wigren Grant/research support from: IMI project EUbOPEN, Grant no 875510, Ingrid E. Lundberg Shareholder of: Roche and Novartis, Consultant of: Corbus Pharmaceuticals Inc, Astra Zeneca, Bristol Myer´s Squibb, Corbus Pharmaceutical, EMD Serono Research & Development Institute, Argenx, Octapharma, Kezaar, Orphazyme, and Janssen, Grant/research support from: Astra Zeneca, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Consultant of: UCB, Grant/research support from: Gesynta Pharma, Helena Persson Employee of: Affibody AB, Susanne Gräslund Grant/research support from: IMI project EUbOPEN, Grant no 875510
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| 46. |
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| 47. |
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| 48. |
- Van Gompel, E, et al.
(författare)
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DELINEATING THE IMMUNOGENIC DOMAINS OF MDA5 USING PATIENT DERIVED AUTOANTIBODIES
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 196-197
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The presence of myositis specific anti-melanoma differentiation associated protein 5 (MDA5) autoantibodies is associated with mucocutaneous ulcerations, rapidly progressing interstitial lung disease (RPILD), arthritis and mild muscle involvement in patients. RPILD is the major cause of mortality. At present it is unknown which domain of the MDA5 protein is the main elicitor of an immunogenic response.Objectives:The aim of this study is to delineate the domains in the MDA5 protein that are the target of autoantibodies.Methods:Anti-MDA5 IgG were isolated from MDA5(+) patient plasma (7 UPMC, 1 KI and 1 KULeuven) by affinity chromatography using an in-house affinity column as described earlier in Ossipova et al, 2014(1). 8 constructs covering different regions of the MDA5 protein were recombinantly produced in E.coli (Uniprot ID Q9BYX4, Figure 1). An in-house ELISA was developed to identify the domains with the main epitope(s) by measuring the reactivity of the plasma samples and purified autoantibodies against these MDA5 protein constructs, similar to what was reported by Fernandes-Cerqueira et al, 2018(2). The biotinylated MDA5 proteins were immobilized on streptavidin coated plates and subsequently incubated with primary antibodies (purified autoantibodies(2) or original plasma) and a HRP-conjugated secondary antibody. The ELISA was developed by the addition of TMB substrate and the optical density (OD) was measured at 450 nm.Figure 1.Graphical presentation of the constructs representing different (combinations of) domains of the MDA5 protein.Results:The preliminary data suggest the main reactivity of the plasma samples and the corresponding purified autoantibodies is directed towards the helicase domains and that there is variability between the patients in the reactivity towards domains located at the end of the protein.Conclusion:The study aims to resolve the main immunogenic domain of the MDA5 protein, which will lead to more insight in the disease mechanisms. The preliminary results suggest this domain is in the center of the MDA5 protein, but further experiments are necessary. We will use this set up to study differences in reactivity between patients (from different cohorts) and assess if differences in antibody reactivity could be linked to clinical features such as RPILD. Such correlations might be beneficial to predict the disease progression and to apply personal treatment approaches.References:[1]Ossipova E, Cerqueira CF, Reed E, Kharlamova N, Israelsson L, et al. Affinity purified anti-citrullinated protein/peptide antibodies target antigens expressed in the rheumatoid joint. Arthritis Res Ther. 2014;16(4):R167.[2]Fernandes-Cerqueira C, Renard N, Notarnicola A, Wigren E, Gräslund S, et al. Patients with anti-Jo1 antibodies display a characteristic IgG Fc-glycan profile which is further enhanced in anti-Jo1 autoantibodies. Scientific reports. 2018;8(1):17958.Disclosure of Interests:Eveline Van Gompel: None declared, Catia Cerqueira: None declared, Edvard Wigren: None declared, Susanne Gräslund: None declared, Karine Chemin: None declared, Begum Horuluoglu: None declared, Ellen De Langhe: None declared, Olivier Benveniste: None declared, Ingrid E. Lundberg Consultant of: Consulting fees from Corbus Pharmaceuticals, Inc, Grant/research support from: Research grants from Bristol Myers Squibb and AstraZeneca.
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| 49. |
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| 50. |
- van Hoof, M., et al.
(författare)
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Clinical Outcomes of Soft Tissue Preservation Surgery With Hydroxyapatite-Coated Abutments Compared to Traditional Percutaneous Bone Conduction Hearing Implant Surgery-A Pragmatic Multi-Center Randomized Controlled Trial
- 2020
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Ingår i: Frontiers in Surgery. - : Frontiers Media SA. - 2296-875X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Soft tissue preservation using a hydroxyapatite-coated abutment in bone conduction hearing implant surgery may lead to improved clinical outcomes over the short (1 year) and long term (3 years). Methods: In this open multi-center, randomized (1:1), controlled clinical trial, subjects with conductive, mixed hearing loss or single-sided sensorineural deafness were randomly assigned to receive the conventional intervention, a titanium abutment with soft tissue reduction surgery (control), or a new intervention, a hydroxyapatite-coated abutment with soft tissue preservation surgery (test). The primary efficacy outcome was the combined endpoint of numbness, pain, peri-abutment dermatitis, and soft tissue thickening/overgrowth after 1 and 3 years. Results: The Intention-to-treat (ITT) population consisted of 52 control subjects and 51 test subjects. The difference between the groups after 1 year of follow-up as measured by the primary efficacy outcome was not statistically significant (p = 0.12) in the ITT population (n = 103), but did reach statistical significance (p = 0.03) in the per-protocol (PP) population (n = 96). It showed an advantage for the test group, with over twice as many subjects (29%) without these medical events during the first year compared to the control group (13%). After 3 years, the difference between the two groups had declined and did not reach statistical significance (24 vs. 10%, ITT p = 0.45). Secondary outcome measures which showed a statistical significant difference during the first year, such as surgical time (15 vs. 25 minutes, p < 0.0001), numbness (90 vs. 69% of subjects experienced no numbness at 1 year, p < 0.01), neuropathic pain at 3 months (p = 0.0087) and the overall opinion of the esthetic outcome (observer POSAS scale at 3 months, p < 0.01) were favorable for the test group. More soft tissue thickening/overgrowth was observed at 3 weeks for the test group (p = 0.016). Similar results were achieved for the long term follow up. Conclusions: Soft tissue preservation with a hydroxyapatite-coated abutment leads to a reduction in the combined occurrence of complications over the first year which is not statistically significant in the ITT population but is in the PP population. This effect decreased for the long-term study follow up of 3 years and did also not reach statistical significance.
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