| 1. |
- Lyxell, Björn, et al.
(författare)
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Cognitive and communicative development in deaf and hearing-impaired children with cochlear implants and/or hearing-aids
- 2011
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of the study was to examine neurophysiological, cognitive and linguistic development in deaf and hearing-impaired children (5–7 years of age) with CI and/or hearingaids and how a phonological intervention programme may influence this development. The deaf and hearing-impaired children were compared with age-matched hearing children. The results reveal that deaf and hearing-impaired children had equivalent or close to equivalent performance levels compared to hearing children for cognitive and linguistic tasks with relatively low demands on phonological processing, whereas there was a substantial and significant difference between the groups for cognitive tasks involving explicit phonological processing. The results indicate that there is a relationship between age at implant and neurophysiological, cognitive and linguistic development, where early implantation promotes faster development. The childrens´ cognitive performance increased as a function of phonological intervention.
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| 2. |
- Lyxell, Björn, et al.
(författare)
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Cognitive and communicative development in deaf and hearing-impaired children with cochlear implants and/or hearing-aids
- 2013
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of the study was to examine neurophysiological, cognitive and linguistic development in deaf and hearing-impaired children (5–7 years of age) with CI and/or hearingaids and how a phonological intervention programme may influence this development. The deaf and hearing-impaired children were compared with age-matched hearing children. The results reveal that deaf and hearing-impaired children had equivalent or close to equivalent performance levels compared to hearing children for cognitive and linguistic tasks with relatively low demands on phonological processing, whereas there was a substantial and significant difference between the groups for cognitive tasks involving explicit phonological processing. The results indicate that there is a relationship between age at implant and neurophysiological, cognitive and linguistic development, where early implantation promotes faster development. The childrens´ cognitive performance increased as a function of phonological intervention.
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| 8. |
- Nakeva von Mentzer, Cecilia, et al.
(författare)
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Computer-assisted intervention for children with hearing impairment : Cognitive factors and phonological change
- 2013
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Ingår i: CHSCOM2013. - : Linköping University Electronic Press.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Thirty-two children with hearing impairment (HI) using cochlear implants (CI) and/or hearing aids (HA), and sixteen with normal hearing (NH) participated in a computer-assisted intervention study that focused on perceiving and memorizing phonemic sounds. The first purpose was to study cognitive abilities in NH and HI children, how they related to phonological processing skills (PhPS) pre intervention and to phonological growth post intervention. The second purpose was to analyze children’s performance at different fine-grained levels of phonological processing, i.e. how they manipulated, stored and produced phonological entities of different size with or without semantic content. This was put in relation to children’s type of auditory stimulation (electrical; bilateral CI, bimodal: CI + HA and acoustical; bilateral HA). Results showed significant correlations between complex working memory and PhPS in children with HI but not in children with NH. This suggests different cognitive strategies in the children when dealing with phonological processing tasks. Poor phoneme discrimination was the strongest predictor of phonological growth in the children with HI as a function of training. Thus, the computer-assisted program was beneficial for HI children with weak initial phoneme discrimination skills. Children with CI showed reduced performance at fine-grained levels of receptive phonological processing but not on expressive phonological lexical tasks.
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| 9. |
- Nakeva von Mentzer, Cecilia, et al.
(författare)
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Computer-assisted intervention for Deaf and Hard of hearing (D/HH) children with cochlear implants or hearing aids : Cognitive factors and phonological change
- 2013
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aim: Study cognitive abilities; specifically working memory and lexical access in NH and DHH children, and their correlations to phonological processing skills (PhPS) pre intervention. Analyze how cognitive abilities related to phonological change post intervention. Material and Method: Tasks for lexical access, complex and visual working memory and Phpr were assessed pre and post intervention.Conclusion: DHH children performed at a lower level than NH children on lexical access but equally on complex and visual working memory. Significant correlations between complex working memory and PhPS were evident in DHH children but not in NH. This suggests that DHH children recruit more cognitive resources when performing PhPr tasks. Weak initial performance on a task for phonological representations (Phrep) was the only significant predictor of phonological change in DHH children. Weak PhRep was associated with a higher age at diagnosis, higher age at implant, and shorter usage-time with CI.
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| 10. |
- Nakeva von Mentzer, Cecilia, et al.
(författare)
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Computer-assisted reading intervention with a phonics approach for children using cochlear implants or hearing aids
- 2014
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 55:5, s. 448-455
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Tidskriftsartikel (refereegranskat)abstract
- The present study examined computer-assisted reading intervention with a phonics approach for deaf and hard of hearing (DHH) children in Sweden using cochlear implants or hearing aids, or a combination of both. The study included 48 children, 5, 6 and 7years of age. Sixteen children with normal hearing (NH) served as a reference group. The first purpose of the study was to compare NH and DHH children's reading ability at pre and post-intervention. The second purpose was to investigate effects of the intervention. Cognitive and demographic factors were analyzed in relation to reading improvement. Results showed no statistically significant difference for reading ability at the group level, although NH children showed overall higher reading scores at both test points. Age comparisons revealed a statistically significant higher reading ability in the NH 7-year-olds compared to the DHH 7-year-olds. The intervention proved successful for word decoding accuracy, passage comprehension and as a reduction of nonword decoding errors in both NH and DHH children. Reading improvement was associated with complex working memory and phonological processing skills in NH children. Correspondent associations were observed with visual working memory and letter knowledge in the DHH children. Age was the only demographic factor that was significantly correlated with reading improvement. The results suggest that DHH children's beginning reading may be influenced by visual strategies that might explain the reading delay in the older children.
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| 11. |
- Nakeva von Mentzer, Cecilia, 1968-, et al.
(författare)
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Computer-assisted training of phoneme-grapheme correspondence for children who are deaf and hard of hearing : Effects on phonological processing skills
- 2013
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Ingår i: International Journal of Pediatric Otorhinolaryngology. - Amsterdam, Netherlands : Elsevier. - 0165-5876 .- 1872-8464. ; 77:12, s. 2049-2057
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Examine deaf and hard of hearing (DHH) children's phonological processing skills in relation to a reference group of children with normal hearing (NH) at two baselines pre intervention. Study the effects of computer-assisted phoneme-grapheme correspondence training in the children. Specifically analyze possible effects on DHH children's phonological processing skills.Methods: The study included 48 children who participated in a computer-assisted intervention study, which focuses on phoneme-grapheme correspondence. Children were 5, 6, and 7 years of age. There were 32 DHH children using cochlear implants (CI) or hearing aids (HA), or both in combination, and 16 children with NH. The study had a quasi-experimental design with three test occasions separated in time by four weeks; baseline 1 and 2 pre intervention, and 3 post intervention. Children performed tasks measuring lexical access, phonological processing, and letter knowledge. All children were asked to practice ten minutes per day at home supported by their parents.Results: NH children outperformed DHH children on the majority of tasks. All children improved their accuracy in phoneme-grapheme correspondence and output phonology as a function of the computer-assisted intervention. For the whole group of children, and specifically for children with CI, a lower initial phonological composite score was associated with a larger phonological change between baseline 2 and post intervention. Finally, 18 DHH children, whereof 11 children with CI, showed specific intervention effects on their phonological processing skills, and strong effect sizes for their improved accuracy of phoneme-grapheme correspondence.Conclusion: For some DHH children phonological processing skills are boosted relatively more by phoneme-grapheme correspondence training. This reflects the reciprocal relationship between phonological change and exposure to and manipulations of letters.
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| 13. |
- Nakeva von Mentzer, Cecilia, et al.
(författare)
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Coputer based phonological intervention : Effects on phonological processing
- 2012
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Konferensbidrag (refereegranskat)abstract
- Children with mild to profound hearing impairment (HI) using cochlear implants (CI) and/or hearingaids (HA), and children with normal hearing (NH) participated in a phonological intervention study, bymeans of a computer‐based intervention program (Graphogame, Lyytinen et al., 2009). Children were 5,6 and 7 years of age. Thirty‐two of the children used CI and/or HA. 16 children with NH served as thecontrol group. The main design was a quasi‐experimental 3 x 3 design. Each test session was separatedin time with four weeks. All children were asked to practice 10 minutes per day at home supported bytheir parents, with an intervention program primarily developed to enhance phonemic differentiation.Results showed that the children with HI displayed a heterogeneous pattern of results, specifically withrespect to their performance on the phonological tasks. Approximately 20 percent performed within therange of NH children; these were all children with HA except one child with CI/HA. Children with CIdisplayed considerable difficulty with phonological working memory whereas children with HAshowed less knowledge in letter tasks. Intervention revealed positive effects on accuracy of phonemegraphemecorrespondence for all children and a significant positive change on phonological processingskills for children with weak initial phonological skills. Enhanced phoneme‐grapheme connections maybuild associations between the phonological lexicon and the sub‐lexical phonological representations,thereby improving underlying skills essential for word learning and the development of literacy. Implicationsof this are discussed within theoretical models of phonological and lexical processing (Goswami,2000; Ramus, 2001).
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| 14. |
- Nakeva von Mentzer, Cecilia, 1968-, et al.
(författare)
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Datorbaserad fonologisk intervention för barn med cochleaimplantat (CI) och/eller hörapparat (HA) : effekter på fonologiska färdigheter
- 2012
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Ingår i: Logopednytt. - Stockholm, Sweden : Svenska Logopedförbundet (SLOF). - 1102-500X. ; :3, s. 18-23
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Children with mild to profound hearing impairment 5, 6 and 7 years of age, thirty-two using cochlear implants and/or hearing aids, and sixteen normal hearing children participated in a computer based phonological intervention study.The main design was a quasi-experimental design with three test sessions separated in time with four weeks. Each test session included tasks for phonological skills and letter knowledge. All children were asked to practice 10 minutes per day.Results showed that children with HI displayed a heterogeneous pattern of results with respect to phonological skills. Only 20 percent performed within the range of NH children; these were children with HA, except one child with CI/HA.Group comparisons at the first and last test session revealed that children with CI displayed difficulty with phonological working memory whereas children with HA showed less letter knowledge. Intervention revealed positive effects on accuracy of phoneme-grapheme correspondence for all children and a significant positive change on phonological processing skills for children with weak initial phonological skills.
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| 21. |
- Nakeva von Mentzer, Cecilia, et al.
(författare)
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Predictors of phonological change in deaf and hard of hearing children who use cochlear implants or hearing aids
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: The purpose of the present study was to examine cognitive abilities (i.e., working memory (WM), lexical access, phonological processing skills (PhPS), and letter knowledge) in deaf and hard of hearing (D/HH) children in relation to a reference group with normal hearing (NH) children pre intervention with a computer-assisted program that focused on phonological coding. A more specific purpose was to explore how cognitive abilities were associated to PhPS pre intervention and to phonological change post intervention in D/HH children in general, and specifically in D/HH children with weak initial PhPS.Methods: Participants were thirty-two children using cochlear implants or hearing aids, or both in combination, and sixteen children with NH 5, 6 and 7 years of age. Children practiced with phonological coding 10 min per day for 4 weeks with support by their parents. Cognitive abilities were examined pre and post intervention.Results: NH and D/HH children displayed a similar performance level on the majority of cognitive tasks, but the D/HH children demonstrated weaker lexical access and PhPS. A significant correlation between complex WM and PhPS pre intervention was only observed in D/HH children. Weak initial performance on one phonological processing task capturing both lower level and higher level auditory processing was the main significant predictor of phonological change in all D/HH children. In D/HH children with weak initial PhPS letter naming was associated with phonological change.Conclusions: The associations between complex working memory and PhPS in D/HH children and the lack of such associations in children with NH may indicate that phonological processing skills require more cognitive resources in the D/HH children. Letter knowledge can act as a driving force for phonological change following intervention in D/HH children with weak PhPS.
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| 22. |
- Nakeva von Mentzer, Cecilia, et al.
(författare)
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The Phonics Approach in Swedish Children using Cochlear Implants or Hearing Aids : Inspecting Phonological Gain
- 2014
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Ingår i: Journal of Communication Disorders, Deaf Studies & Hearing Aids. - : OMICS Publishing Group. - 2375-4427. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated cognitive abilities (i.e. Phonological Processing Skills (PhPS), lexical access, complex and visual Working Memory (WM), and letter knowledge) in Deaf and Hard of Hearing children (DHH) 5, 6 and 7 years of age using cochlear implants or hearing aids. Children with Normal Hearing (NH) served as a reference group. All children took part of a computer-assisted intervention with a phonics approach for 4 weeks aimed to support PhPS. The first aim of the study was to examine associations between cognitive abilities and Phonological Processing Skills (PhPS) pre intervention in DHH and NH children respectively. The second aim was to examine cognitive predictors of phonological gain post intervention. Finally, the influence of background variables on phonological gain was examined in NH and DHH respectively and in DHH children with weak PhPS particularly. Results showed comparable performance level in NH and DHH children on the majority of cognitive tasks, but weaker PhPS and lexical access in the DHH children. A significant association between PhPS and complex WM was only evident in DHH children. This finding suggests that DHH recruit more cognitive resources in phonological processing. A phonological representation task was the single predictor of phonological gain in DHH children. Children with initial weak performance on this task but had letter-naming skills, displayed relatively more phonological gain from the phonics training. Children with difficulties with the phonological representation task were older when diagnosed and had an older age at amplification. Further, these children displayed broader cognitive difficulties, suggesting that reduced access to auditory stimulation may have wide ranging effects on cognitive development.
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| 23. |
- Schwarz, Iris-Corinna, 1976-, et al.
(författare)
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Towards a contingent anticipatory infant hearing test using eye-tracking
- 2014
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Ingår i: Proceedings from FONETIK 2014. - Stockholm : Department of Linguistics, Stockholm University. - 9789163756627 - 9789163756634 ; , s. 35-40
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Early identification of infant hearing impairment is imperative to prevent developmental language difficulties. The current diagnostic method is Visual Reinforcement Audiometry (VRA) in which infant response to sound isobserved to establish hearing thresholds. Together with the Karolinska Institute, we are developing an observer-independent contingent anticipatory infant hearing test using eye-tracking to increase reliability and significance levels of the current clinical practice. The present pilot study addresses in particular the first phase of the test in which the eye response is conditioned to occur at sound detection. The aim is to establish how well 6.5-month-olds associate the presence of sound to a certain location via a visual reward.
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| 24. |
- Seijsing, Johan, 1986-
(författare)
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Rational and Combinatorial Engineering of Affinity Proteins Towards Therapeutical Applications
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Protein engineering has had an immense impact on the development of biological drugs, including replacement therapies with engineered versions of insulin or factor VIII to treat diabetes or bleeding disorders, and monoclonal antibodies to treat cancer and various other malignancies. Now, with the next generation of treatment modalities coming up, including monoclonal reagents based on alternative scaffolds, gene and cell therapies, the importance of protein engineering to tailor-make these treatments is likely to increase further.The neonatal Fc receptor (FcRn) is widely expressed in the body. One of the receptor's interesting functions is to rescue immunoglobulin G (IgG) and serum albumin (SA) from degradation by cells in contact with blood. When serum proteins are endocytosed by a cell, they are transported via the endosome to the lysosome for degradation. However, IgG and SA associate with the FcRn already at the slightly acidic pH of the endosome followed by transport back to the cell surface. There the complex encounters the neutral pH of the blood, at which the binding affinity to FcRn is lost, and IgG and SA are released back into circulation. In the main part of this thesis, efforts are described aiming to take use of, or block, the FcRn recycling mechanism to control the serum circulation half-life of proteins.In the first study (Study I), a robust expression strategy for human FcRn was designed and evaluated. The extracellular domain was produced in the human SKOV3 cell-line after facile lentiviral delivery of the expression cassettes. This lead to continuous expression of secreted protein that could be purified to homogeneity by a single affinity chromatographic step, using the intrinsic pH-dependent interaction between FcRn and IgG, where the latter was immobilized in a column. The amount of purified protein was 1.4 mg per liter medium. The protein was characterized by SDS-PAGE, western blotting, circular dichroism spectroscopy, ELISA, surface plasmon resonance and a temperature stability assay. The results suggested a fully functional and stable protein of high purity. In addition, the gene encoding full-length FcRn as a fusion to eGFP was delivered to HeLa cells utilizing the same lentiviral system. Subsequent analysis by flow cytometry and confocal fluorescence microscopy indicated a wide distribution of eGFP/FcRn expression among the cells. Binding of IgG and HSA was found to correlate well with the amount of eGFP/FcRn expressed by the cells.In a following study (Study II), the goal was to generate affinity proteins interacting with human FcRn in a pH-dependent manner similar to that of FcRn's natural ligands. The affinity proteins used are denoted affibody molecules, a class of small alternative scaffold proteins with a three-helical structure. Affibody molecules were selected from a combinatorial library displayed on phage where binding took place at pH 5.5 and elution was performed at pH 2.2 or 8.0. Selected variants were characterized by developed in vitro and cell based assays, and some were found to have the desired pH-dependent binding to FcRn. In vivo studies in mice showed that the serum half-life of a model protein, genetically fused to the FcRn binding affibody molecules, was extended up to almost three-fold compared to a control protein (from 33 to 91 hours).In a subsequent study (Study III), the use of a FcRn binding affibody molecule to reduce, rather than prolong, the serum half-life of proteins was explored. Here, the rationale was to investigate if injection of a FcRn binding affibody could hinder endogenous IgG from being rescued by FcRn, which could lead to depletion of IgGs by lysosomal degradation. In autoimmune diseases, such depletion of IgG would include also pathogenic IgG and could thus mitigate the symptoms of the disease. Using cell based assays, it was found that one affibody molecule, selected in Study II, could readily block IgG from binding both human and murine FcRn. A following in vivo study in mice showed that systemic injection of the molecule reduced the amount of endogenous IgG by 39%.In a fourth study (Study IV), the goal was to use a different class of affinity proteins to regulate the level of an enzyme in the brain. More specifically, artificial zinc finger-based transcription factors regulating the level of GAD67, which is the rate-limiting enzyme in synthesis of gamma-aminobutyric acid (GABA), were designed. Imbalances in GABA-signaling is involved in different diseases, including Parkinson's disease and epilepsy, and regulation of GAD67 at particular sites in the brain might be a route to ameliorate symptoms associated with such diseases. ELISA-based investigation showed that one of the designed zinc fingers, denoted G3, bound selectively to its intended target DNA sequence. A construct encoding G3 fused to a general transcriptional activator (VP64) was delivered to PC12-cells, using a lentivirus-based gene delivery system, resulting in a significant up-regulation of endogenous GAD67 expression. The same construct was subsequently delivered to the striatum of rats, with an induced disease model of Parkinson's disease. Western blot of striatal samples showed a significant up-regulation of GAD67 expression in lesioned striatum compared to intact striatum, and a tendency towards up-regulation compared to lesioned striatum.Taken together, the protein engineering efforts described in this thesis concerning affinity proteins binding other proteins or DNA, has the potential to find use in drug development and may benefit patients in the future.
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