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| 2. |
- Forssman, Linda, 1979-, et al.
(författare)
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Training basic visual attention leads to changes in responsiveness to social communication cues in 9-month-old infants
- 2018
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Ingår i: Child Development. - : Wiley. - 0009-3920 .- 1467-8624. ; 89:3, s. E199-E213
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated transfer effects of gaze‐interactive attention training to more complex social and cognitive skills in infancy. Seventy 9‐month‐olds were assigned to a training group (n = 35) or an active control group (n = 35). Before, after, and at 6‐week follow‐up both groups completed an assessment battery assessing transfer to nontrained aspects of attention control, including table top tasks assessing social attention in seminaturalistic contexts. Transfer effects were found on nontrained screen‐based tasks but importantly also on a structured observation task assessing the infants’ likelihood to respond to an adult's social‐communication cues. The results causally link basic attention skills and more complex social‐communicative skills and provide a principle for studying causal mechanisms of early development.
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| 5. |
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| 6. |
- Grankvist, A., et al.
(författare)
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Comparative Genomics of Clinical Isolates of the Emerging Tick-Borne Pathogen Neoehrlichia mikurensis
- 2021
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Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Tick-borne 'Neoehrlichia (N.) mikurensis' is the cause of neoehrlichiosis, an infectious vasculitis of humans. This strict intracellular pathogen is a member of the family Anaplasmataceae and has been unculturable until recently. The only available genetic data on this new pathogen are six partially sequenced housekeeping genes. The aim of this study was to advance the knowledge regarding 'N. mikurensis' genomic relatedness with other Anaplasmataceae members, intra-species genotypic variability and potential virulence factors explaining its tropism for vascular endothelium. Here, we present the de novo whole-genome sequences of three 'N. mikurensis' strains derived from Swedish patients diagnosed with neoehrlichiosis. The genomes were obtained by extraction of DNA from patient plasma, library preparation using 10x Chromium technology, and sequencing by Illumina Hiseq-4500. 'N. mikurensis' was found to have the next smallest genome of the Anaplasmataceae family (1.1 Mbp with 27% GC contents) consisting of 845 protein-coding genes, every third of which with unknown function. Comparative genomic analyses revealed that 'N. mikurensis' was more closely related to Ehrlichia chaffeensis than to Ehrlichia ruminantium, the opposite of what 16SrRNA sequence-based phylogenetic analyses determined. The genetic variability of the three whole-genome-sequenced 'N. mikurensis' strains was extremely low, between 0.14 and 0.22 parts per thousand, a variation that was associated with geographic origin. No protein-coding genes exclusively shared by N. mikurensis and E. ruminantium were identified to explain their common tropism for vascular endothelium.
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| 7. |
- Höper, Linnea, et al.
(författare)
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Vasculitis due to Candidatus Neoehrlichia mikurensis : a cohort study of 40 Swedish patients
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 73:7, s. e2372-e2378
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Candidatus (Ca.) Neoehrlichia (N.) mikurensis is an emerging tick-borne pathogen of humans that is closely related to Ehrlichia and Anaplasma species. This strict intracellular bacterium escapes detection by routine microbiologic diagnostic methods such as blood culture leading to considerable under-diagnosis of the infectious disease it causes, neoehrlichiosis.METHODS: Here, we describe the vascular and thromboembolic events afflicting a series of 40 patients diagnosed with neoehrlichiosis in Sweden during a 10-year period (2009-2019).RESULTS: The majority of the patients (60%) developed vascular events ranging from repeated thrombophlebitis, deep vein thrombosis, pulmonary embolism, transitory ischemic attacks to arteritis. Younger age was a risk factor for vascular complications. In contrast, there was no difference in the incidence of vascular events between immunosuppressed and immunocompetent patients. However, there were qualitative differences such that deep vein thrombosis exclusively afflicted the immunosuppressed patients whereas arteritis was restricted to the immunocompetent ones. We also present the case histories of two patients who developed vasculitis mimicking polyarteritis nodosa and giant cell arteritis. Both were cured by doxycycline treatment.CONCLUSIONS: Ca. N. mikurensis infection should be considered in patients living in tick-endemic areas of Europe and northern Asia who present with atypical vascular and/or thromboembolic events. Early diagnosis and antibiotics targeting this emerging infectious agent can eradicate the infection and prevent the development of new vascular events.
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| 8. |
- Leppänen, Jukka M, et al.
(författare)
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Widely applicable MATLAB routines for automated analysis of saccadic reaction times
- 2015
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Ingår i: Behavior Research Methods. - : Springer Science and Business Media LLC. - 1554-351X .- 1554-3528. ; 47:2, s. 538-548
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Tidskriftsartikel (refereegranskat)abstract
- Saccadic reaction time (SRT) is a widely used dependent variable in eye-tracking studies of human cognition and its disorders. SRTs are also frequently measured in studies with special populations, such as infants and young children, who are limited in their ability to follow verbal instructions and remain in a stable position over time. In this article, we describe a library of MATLAB routines (Mathworks, Natick, MA) that are designed to (1) enable completely automated implementation of SRT analysis for multiple data sets and (2) cope with the unique challenges of analyzing SRTs from eye-tracking data collected from poorly cooperating participants. The library includes preprocessing and SRT analysis routines. The preprocessing routines (i.e., moving median filter and interpolation) are designed to remove technical artifacts and missing samples from raw eye-tracking data. The SRTs are detected by a simple algorithm that identifies the last point of gaze in the area of interest, but, critically, the extracted SRTs are further subjected to a number of postanalysis verification checks to exclude values contaminated by artifacts. Example analyses of data from 5- to 11-month-old infants demonstrated that SRTs extracted with the proposed routines were in high agreement with SRTs obtained manually from video records, robust against potential sources of artifact, and exhibited moderate to high test-retest stability. We propose that the present library has wide utility in standardizing and automating SRT-based cognitive testing in various populations. The MATLAB routines are open source and can be downloaded from http://www.uta.fi/med/icl/methods.html .
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| 9. |
- Wass, Linda, et al.
(författare)
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Cultivation of the causative agent of human neoehrlichiosis from clinical isolates identifies vascular endothelium as a target of infection.
- 2019
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Ingår i: Emerging microbes & infections. - : Informa UK Limited. - 2222-1751. ; 8:1, s. 413-425
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Tidskriftsartikel (refereegranskat)abstract
- Candidatus (Ca.) Neoehrlichia mikurensis is the cause of neoehrlichiosis, an emerging tick-borne infectious disease characterized by fever and vascular events. The bacterium belongs to the Anaplasmataceae, a family of obligate intracellular pathogens, but has not previously been cultivated, and it is uncertain which cell types it infects. The goals of this study were to cultivate Ca. N. mikurensis in cell lines and to identify possible target cells for human infection. Blood components derived from infected patients were inoculated into cell lines of both tick and human origin. Bacterial growth in the cell cultures was monitored by real-time PCR and imaging flow cytometry. Ca. N. mikurensis was successfully propagated from the blood of immunocompromised neoehrlichiosis patients in two Ixodes spp. tick cell lines following incubation periods of 7-20 weeks. Human primary endothelial cells derived from skin microvasculature as well as pulmonary artery were also susceptible to infection with tick cell-derived bacteria. Finally, Ca. N. mikurensis was visualized within circulating endothelial cells of two neoehrlichiosis patients. To conclude, we report the first successful isolation and propagation of Ca. N. mikurensis from clinical isolates and identify human vascular endothelial cells as a target of infection.
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| 10. |
- Wass, Linda, et al.
(författare)
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Cytokine responses of immunosuppressed and immunocompetent patients with Neoehrlichia mikurensis infection
- 2022
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Ingår i: Medical Microbiology and Immunology. - : Springer Science and Business Media LLC. - 0300-8584 .- 1432-1831. ; 211:2-3, s. 133-141
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The tick-borne bacterium Neoehrlichia mikurensis causes the infectious disease neoehrlichiosis in humans. Vascular endothelium is one of the target cells of the infection. Neoehrlichiosis patients with compromised B cell immunity present with more severe inflammation than immunocompetent patients. The aim of this study was to compare the cytokine profiles of immunocompetent and immunosuppressed patients with neoehrlichiosis. Methods Blood samples from Swedish and Norwegian immunosuppressed (N = 30) and immunocompetent (N = 16) patients with neoehrlichiosis were analyzed for the levels of 30 cytokines, using a multiplex cytokine assay and ELISA. A gender-matched healthy control group (N = 14) was analyzed in parallel. Data were analyzed using the multivariate method OPLS-DA. Results The multiplex cytokine analyses generated more cytokine results than did the uniplex ELISA analyses. Multivariate analysis of the multiplex cytokine results established that increased levels of FGF2, GM-CSF, CXCL10, and IFN-gamma were associated with immunosuppressed patients, whereas increased levels of IL-15 and VEGF were associated with immunocompetent neoehrlichiosis patients. When multivariate analysis findings were confirmed with uniplex ELISA, it was found that both groups of patients had similarly elevated levels of VEGF, FGF2 and IFN-gamma. In contrast, the immunosuppressed patients had clearly elevated levels of CXCL10, CXCL13 and BAFF, whereas the immunocompetent patients had the same levels as healthy controls. Conclusion Pro-angiogenic and type 1 cytokines were produced as part of the host response of neoehrlichiosis independent of immune status, whereas immunosuppressed neoehrlichiosis patients produced cytokines required for B cell-mediated defense.
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| 11. |
- Wass, Linda
(författare)
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Neoehrlichiosis - latent infection of endothelium and immune defense
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is a study of the tick-borne pathogen Neoehrlichia (N.) mikurensis that causes the infectious disease neoehrlichiosis in humans. The disease affects both individuals with competent and suppressed immune defense with the majority of the affected being immunosuppressed. The most common symptoms of neoehrlichiosis are recurrent fever, nightly sweats as well as muscle and joint pain. The most prominent clinical features are vascular events with thrombosis and arteritis. The aims of this thesis were to identify the target cells of the infection and get a deeper understanding of the immune responses evoked by N. mikurensis. In the first paper, it is described how some patients diagnosed with neoehrlichiosis also have antibodies targeted against another member of the Anaplasmataceae family, Anaplasma phagocytophilum. This can lead to patients with neoehrlichiosis mistakenly being diagnosed with anaplasmosis. In the second paper we describe for the first time that N. mikurensis can be cultivated and propagated both in tick cells and human endothelial cells. N. mikurensis was also demonstrated inside of circulating endothelial cells isolated from the blood of patients with neoehrlichiosis. These findings indicate that endothelial cells are a target cell of the infection, which could also explain the many vascular events affecting patients. In paper III we show that immunosuppressed patients with N. mikurensis infection had increased serum levels of cytokines involved in B-cell responses (CXCL13 and B-cell activating factor), the pro-inflammatory cytokine CXCL10 as well as cytokines associated with growth of blood vessels (vascular endothelial growth factor and fibroblast growth factor basic). We also show the importance of confirming results obtained with multiplex cytokine assays with single plex tests. In the last paper IV, we lend support to the hypothesis that N. mikurensis infections in humans are latent infections that can reactivate when B-cell responses are suppressed in patients with B-cell lymphomas. Out of 97 patients treated with anti-CD20 antibody therapy, 8 % had a latent N. mikurensis infection, it was only the patients with latent infection that had T cells specific for N. mikurensis. These T cells were of the gamma delta type, T-helper 1 and cytotoxic T lymphocyte types and expressed the cytolytic protein perforin. This work and future N. mikurensis projects will lead to a greater understanding of the infectious disease neoehrlichiosis.
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| 12. |
- Wass, Linda, et al.
(författare)
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Serological reactivity to Anaplasma phagocytophilum in neoehrlichiosis patients
- 2018
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Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 37:9, s. 1673-1678
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Tidskriftsartikel (refereegranskat)abstract
- The tick-borne bacterium Candidatus (Ca.) Neoehrlichia (N.) mikurensis is a cause of "fever of unknown origin" because this strict intracellular pathogen escapes detection by routine blood cultures. Case reports suggest that neoehrlichiosis patients may display serological reactivity to Anaplasma (A.) phagocytophilum. Since Anaplasma serology is part of the diagnostic work-up of undetermined fever in European tick-exposed patients, we wanted to investigate (1) the prevalence of A. phagocytophilum seropositivity among neoehrlichiosis patients, (2) the frequency of misdiagnosed neoehrlichiosis patients among A. phagocytophilum seropositive patients, and (3) the frequency of A. phagocytophilum and Ca. N. mikurensis co-infections. Neoehrlichiosis patients (n = 18) were analyzed for A. phagocytophilum IgM and IgG serum antibodies by indirect immunofluorescence assay. Serum samples from suspected anaplasmosis patients (n = 101) were analyzed for bacterial DNA contents by singleplex PCR specific for A. phagocytophilum and Ca. N. mikurensis, respectively. One fifth of the neoehrlichiosis patients (4/18) were seropositive for IgM and/or IgG to A. phagocytophilum at the time of diagnosis. Among the patients with suspected anaplasmosis, 2% (2/101) were positive for Ca. N. mikurensis by PCR whereas none (0/101) had detectable A. phagocytophilum DNA in the serum. To conclude, patients with suspected anaplasmosis may in fact have neoehrlichiosis. We found no evidence of A. phagocytophilum and Ca. N. mikurensis co-infections in humans with suspected anaplasmosis or confirmed neoehrlichiosis.
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| 13. |
- Wass, Malin, et al.
(författare)
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Orthographic Learning in Children Who Are Deaf or Hard of Hearing
- 2018
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Ingår i: Language, speech & hearing services in schools. - : American Speech-Language-Hearing Association (ASHA). - 0161-1461 .- 1558-9129. ; 50:1, s. 99-112
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The purpose of the current study was to investigate the relationship between orthographic learning and language, reading, and cognitive skills in 9-year-old children who are deaf or hard of hearing (DHH) and to compare their performance to age-matched typically hearing (TH) controls.Method Eighteen children diagnosed with moderate-to-profound hearing loss who use hearing aids and/or cochlear implants participated. Their performance was compared with 35 age-matched controls with typical hearing. Orthographic learning was evaluated using a spelling task and a recognition task. The children were assessed on measures of reading ability, language, working memory, and paired-associate learning.Results On average, the DHH group performed more poorly than the TH controls on the spelling measure of orthographic learning, but not on the recognition measure. For both groups of children, there were significant correlations between orthographic learning and phonological decoding and between visual–verbal paired-associate learning and orthographic learning.Conclusions Although the children who are DHH had lower scores in the spelling test of orthographic learning than their TH peers, measures of their reading ability revealed that they acquired orthographic representations successfully. The results are consistent with the self-teaching hypothesis in suggesting that phonological decoding is important for orthographic learning.
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| 14. |
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| 15. |
- Wass, Sam, et al.
(författare)
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Robustness and Precision : How Data Quality May Influence Key Dependent Variables in Infant Eye-Tracker Analyses
- 2014
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Ingår i: Infancy. - : Wiley. - 1525-0008 .- 1532-7078. ; 19:5, s. 427-460
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, eye-tracking has become a popular method for drawing conclusions about infant cognition. Relatively little attention has been paid, however, to methodological issues associated with infant eye-tracking. Here, we consider the possibility that systematic differences in the quality of raw eye-tracking data obtained from different populations and individuals might create the impression of differences in gaze behavior, without this actually being the case. First, we show that lower quality eye-tracking data are obtained from populations who are younger and populations who are more fidgety and that data quality declines during the testing session. Second, we assess how these differences in data quality might influence key dependent variables in eye-tracking analyses. We show that lower precision data can appear to suggest a reduced likelihood to look at the eyes in a face relative to the mouth. We also show that less robust tracking may manifest as slower reaction time latencies (e.g., time to first fixation). Finally, we show that less robust data can manifest as shorter first look/visit duration. We argue that data quality should be reported in all analyses of infant eye-tracking data and/or that steps should be taken to control for data quality before performing final analyses.
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| 16. |
- Wennerås, Christine, 1963, et al.
(författare)
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Infection with Neoehrlichia mikurensis promotes the development of malignant B- cell lymphomas
- 2023
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 201:3, s. 480-488
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Tidskriftsartikel (refereegranskat)abstract
- The tick-borne pathogen Neoehrlichia (N.) mikurensis is implicated in persistent infection of the vascular endothelium. B cells are crucial for the host defence to this infection. Chronic stimulation of B cells may result in B-cell transformation and lymphoma. Five patients with malignant B-cell lymphoma and concomitant N. mikurensis infection were investigated regarding clinical picture, lymphoma subtype, B-cell lymphoma immunophenotype and IGHV (variable region of the immunoglobulin heavy) gene repertoire. Three of the five patients improved markedly and ceased lymphoma treatment after doxycycline treatment to eliminate N. mikurensis. Sequencing the B-cell lymphoma IGHV genes revealed preferred usage of the IGHV1 (IGHV1-2, and -69) and IGHV3 (IGHV3-15, -21, -23) families. In conclusion, N. mikurensis infection may drive the development of malignant B-cell lymphomas. Eradication of the pathogen appears to induce remission with apparent curing of the lymphoma in some cases.
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| 17. |
- Wennerås, Christine, 1963, et al.
(författare)
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Natural IgM antibodies in the immune defence against neoehrlichiosis
- 2017
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 49:11-12, s. 809-816
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neoehrlichiosis is an infectious disease caused by the tick-borne bacterium Candidatus Neoehrlichia mikurensis. Splenectomy and rituximab therapies are risk factors for severe neoehrlichiosis. Our aim was to examine if neoehrlichiosis patients had low levels of natural IgM antibodies and/or were hypogammaglobulinemic, and if such deficiencies were associated with asplenia and vascular complications. Methods: Neoehrlichiosis patients (n=9) and control subjects (n=10) were investigated for serum levels of IgG, IgA, and IgM, and for levels of natural IgM antibodies to pneumococcal polysaccharides (6B, 14), and to the malondialdehyde acetaldehyde epitope of oxidized LDL. The multivariate method Projection to Latent Structures was used to analyze the data. Results: The levels of natural IgM antibodies of various specificities were decreased or not measurable in half of the studied patients with neoehrlichiosis. Only one patient and one control subject were hypogammaglobulinemic. An inverse relationship was noted between the levels of natural IgM antibodies and the development of deep vein thrombosis. Unexpectedly, no association was seen between having or not having a spleen and the levels of natural IgM antibody levels in the circulation. Conclusions: Neither hypogammaglobulinemia nor lack of natural IgM antibodies alone predisposes for severe neoehrlichiosis. The importance of the spleen in the immune defence against Ca. N. mikurensis probably lies in its capacity to generate or maintain specific antibodies.
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