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- Rönnberg, Jerker, et al.
(författare)
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Hearing impairment, cognition and speech understanding : exploratory factor analyses of a comprehensive test battery for a group of hearing aid users, the n200 study
- 2016
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Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1499-2027 .- 1708-8186. ; 55:11, s. 623-642
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aims of the current n200 study were to assess the structural relations between three classes of test variables (i.e. HEARING, COGNITION and aided speech-in-noise OUTCOMES) and to describe the theoretical implications of these relations for the Ease of Language Understanding (ELU) model. Study sample: Participants were 200 hard-of-hearing hearing-aid users, with a mean age of 60.8 years. Forty-three percent were females and the mean hearing threshold in the better ear was 37.4 dB HL. Design: LEVEL1 factor analyses extracted one factor per test and/or cognitive function based on a priori conceptualizations. The more abstract LEVEL 2 factor analyses were performed separately for the three classes of test variables. Results: The HEARING test variables resulted in two LEVEL 2 factors, which we labelled SENSITIVITY and TEMPORAL FINE STRUCTURE; the COGNITIVE variables in one COGNITION factor only, and OUTCOMES in two factors, NO CONTEXT and CONTEXT. COGNITION predicted the NO CONTEXT factor to a stronger extent than the CONTEXT outcome factor. TEMPORAL FINE STRUCTURE and SENSITIVITY were associated with COGNITION and all three contributed significantly and independently to especially the NO CONTEXT outcome scores (R2 = 0.40). Conclusions: All LEVEL 2 factors are important theoretically as well as for clinical assessment.
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| 2. |
- Stenfelt, Stefan, 1969-, et al.
(författare)
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Auditory, signal processing, and cognitive factors influencing speech perception in persons with hearing loss fitted with hearing aids – the N200 study
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objective: The aim of the current study was to assess aided speech-in-noise outcomes and relate those measures to auditory sensitivity and processing, different types of cognitive processing abilities, and signal processing in hearing aids.Material and method: Participants were 200 hearing-aid wearers, with a mean age of 60.8 years, 43% females, with average hearing thresholds in the better ear of 37.4 dB HL. Tests of auditory functions were hearing thresholds, DPOAEs, tests of fine structure processing, IHC dead regions, spectro-temporal modulation, and speech recognition in quiet (PB words). Tests of cognitive processing function were tests of phonological skills, working memory, executive functions and inference making abilities, and general cognitive tests (e.g., tests of cognitive decline and IQ). The outcome test variables were the Hagerman sentences with 50 and 80% speech recognition levels, using two different noises (stationary speech weighted noise and 4-talker babble), and three types of signal processing (linear gain, fast acting compression, and linear gain plus a non-ideal binary mask). Another sentence test included typical and atypical sentences with contextual cues that were tested both audio-visually and in an auditory mode only. Moreover, HINT and SSQ were administrated.Analysis: Factor analyses were performed separate for the auditory, cognitive, and outcome tests.Results: The auditory tests resulted in two factors labeled SENSITIVITY and TEMPORAL FINE STRUCTURE, the cognitive tests in one factor (COGNITION), and the outcome tests in the two factors termed NO CONTEXT and CONTEXT that relates to the level of context in the different outcome tests. When age was partialled out, COGNITION was moderately correlated with the TEMPORAL FINE STRUCTURE and NO CONTEXT factors but only weakly correlated with the CONTEXT factor. SENSITIVITY correlated weakly with TEMPORAL FINE STRUCTURE and CONTEXT, and moderately with NO CONTEXT, while TEMPORAL FINE STRUCTURE showed weak correlation with CONTEXT and moderate correlation with NO CONTEXT. CONTEXT and NO CONTEXT had a moderate correlation. Moreover, the overall results of the Hagerman sentences showed 0.9 dB worse SNR with fast acting compression compared with linear gain and 5.5 dB better SNR with linear gain and noise reduction compared with only linear gain.Conclusions: For hearing aid wearers, the ability to recognize speech in noise is associated with both sensory and cognitive processing abilities when the speech materials have low internal context. These associations are less prominent when the speech material has contextual cues.
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| 5. |
- Alterman, Mathias, et al.
(författare)
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P1/P1' modified HIV protease inhibitors as tools in two new sensitive surface plasmon resonance biosensor screening assays
- 2001
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 13:2, s. 203-212
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Tidskriftsartikel (refereegranskat)abstract
- The commonly used HIV-1 protease assays rely on measurements of the effect of inhibitions on the hydrolysis rate of synthetic peptides. Recently an assay based on surface plasmon resonance (SPR) was introduced. We have taken advantage of the fact that the SPR signal is proportional to the mass of the analyte interacting with the immobilised molecule and developed two new improved efficient competition assay methods. Thus, high molecular weight binders were used as amplifiers of the surface plasmon resonance signal. Linkers were attached by a Heck reaction to the para-positions of the P1/P1′ benzyloxy groups of a linear C2-symmetric C-terminal duplicated inhibitor to enable (a) biotin labelling or (b) direct immobilisation of the inhibitor to the biosensor surface matrix. The interaction properties of a series of 17 structurally diverse inhibitors was assessed and compared to previously reported data. The most sensitive assay was obtained by immobilising the enzyme and amplifying the signal with an antibody, giving a detection range between 0.1 nM and 10 μM. Immobilisation of the inhibitor resulted in a stable and durable surface but a narrower detection range (1–100 nM). The two competition assays are anticipated to be very suitable for fast screening of potential HIV inhibitors.
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| 9. |
- Ayesa, Susana, et al.
(författare)
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Solid-phase parallel synthesis and SAR of 4-amidofuran-3-one inhibitors of cathepsin S : Effect of sulfonamides P3 substituents on potency and selectivity.
- 2009
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier. - 0968-0896 .- 1464-3391. ; 17:3, s. 1307-1324
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Tidskriftsartikel (refereegranskat)abstract
- Highly potent and selective 4-amidofuran-3-one inhibitors of cathepsin S are described. The synthesis and structure–activity relationship of a series of inhibitors with a sulfonamide moiety in the P3 position is presented. Several members of the series show sub-nanomolar inhibition of the target enzyme as well as an excellent selectivity profile and good cellular potency. Molecular modeling of the most interesting inhibitors describes interactions in the extended S3 pocket and explains the observed selectivity towards cathepsin K.
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| 10. |
- Bäck, Marcus, et al.
(författare)
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Novel potent macrocyclic inhibitors of the hepatitis C virus NS3 protease : use of cyclopentane and cyclopentene P2-motifs
- 2007
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 15:22, s. 7184-7202
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Tidskriftsartikel (refereegranskat)abstract
- Several highly potent novel HCV NS3 protease inhibitors have been developed from two inhibitor series containing either a P2 trisubstituted macrocyclic cyclopentane- or a P2 cyclopentene dicarboxylic acid moiety as surrogates for the widely used N-acyl-(4R)-hydroxyproline in the P2 position. These inhibitors were optimized for anti HCV activities through examination of different ring sizes in the macrocyclic systems and further by exploring the effect of P4 substituent removal on potency. The target molecules were synthesized from readily available starting materials, furnishing the inhibitor compounds in good overall yields. It was found that the 14-membered ring system was the most potent in these two series and that the corresponding 13-, 15-, and 16-membered macrocyclic rings delivered less potent inhibitors. Moreover, the corresponding P1 acylsulfonamides had superior potencies over the corresponding P1 carboxylic acids. It is noteworthy that it has been possible to develop highly potent HCV protease inhibitors that altogether lack the P4 substituent. Thus the most potent inhibitor described in this work, inhibitor 20, displays a Ki value of 0.41 nM and an EC50 value of 9 nM in the subgenomic HCV replicon cell model on genotype 1b. To the best of our knowledge this is the first example described in the literature of a HCV protease inhibitor displaying high potency in the replicon assay and lacking the P4 substituent, a finding which should facilitate the development of orally active small molecule inhibitors against the HCV protease.
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