| 1. |
- Hägglund, Patricia, et al.
(author)
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The Timed Water Swallow Test (TWST) : normative data on swallowing capacity for healthy people aged 60 years and older
- 2023
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In: International Journal of Speech-Language Pathology. - : Taylor & Francis. - 1754-9507 .- 1754-9515. ; 25:4, s. 479-485
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Journal article (peer-reviewed)abstract
- Purpose: To provide normative data on swallowing capacity (mL/s) in people older than 60 years using the Timed Water Swallow Test (TWST), stratified by sex. Intra- and inter-rater reliability for swallowing time in TWST was further investigated.Method: A total of 165 participants, aged 60 years and above, were included in the study. The time taken to consume 150 mL of tap water and the swallowing capacity (mL/s) was observed in a clinical context using the TWST. Video recordings of the performances were collected for 118 of the 165 participants for inter-rater reliability testing, of which a random set of 25 performances were assessed for intra-rater reliability. Analysis of the agreement between TWST rated by an in-person clinician and rated from a video recording was further evaluated.Result: There were significant age and sex effects observed for swallowing capacity. The average reduction in swallowing capacity in the investigated age range (60-92 years) was 8.8 and 7.3 mL/s for women and men respectively. The results showed high inter-and intra-rater reliability and agreement between the clinical assessment and the video recording.Conclusion: The presented measurements indicate a clear effect of age on swallowing capacity and that women may be expected to have lower capacity scores than men when tested using TWST. The provided norms can be used as reference points in the clinical identification of people at risk of dysphagia in the older population.
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| 2. |
- Islam, Md Mafijul, et al.
(author)
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Towards benchmarking of functional safety in the automotive industry
- 2013
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In: Lecture Notes in Computr Science. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 1611-3349 .- 0302-9743. - 9783642387883 ; , s. 111-125
-
Conference paper (peer-reviewed)abstract
- Functional safety is becoming increasingly important in the automotive industry to deal with the growing reliance on the electrical and/or electronic (E/E) systems and the associated complexities. The introduction of ISO 26262, a new standard for functional safety in road vehicles, has made it even more important to adopt a systematic approach of evaluating functional safety. However, standard assessment methods of benchmarking functional safety of automotive systems are not available as of today. This is where the BeSafe (Benchmarking of Functional Safety) project comes into the picture. BeSafe project aims to lay the foundation for benchmarking functional safety of automotive E/E systems. In this paper, we present a brief overview of the project along with the benchmark targets that we have identified as relevant for the automotive industry, assuming three abstraction layers (model, software, hardware). We then define and discuss a set of benchmark measures. Next, we propose a benchmark framework encompassing fault/error models, methods and the required tool support. This paper primarily focuses on functional safety benchmarking from the Safety Element out of Context (SEooC) viewpoint. Finally, we present some preliminary results and highlight potential future works.
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| 3. |
- Karlsson, Fredrik, 1984, et al.
(author)
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Symptomatic atherosclerosis is associated with an altered gut metagenome
- 2012
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 3
-
Journal article (peer-reviewed)abstract
- Recent findings have implicated the gut microbiota as a contributor of metabolic diseases through the modulation of host metabolism and inflammation. Atherosclerosis is associated with lipid accumulation and inflammation in the arterial wall, and bacteria have been suggested as a causative agent of this disease. Here we use shotgun sequencing of the gut metagenome to demonstrate that the genus Collinsella was enriched in patients with symptomatic atherosclerosis, defined as stenotic atherosclerotic plaques in the carotid artery leading to cerebrovascular events, whereas Roseburia and Eubacterium were enriched in healthy controls. Further characterization of the functional capacity of the metagenomes revealed that patient gut metagenomes were enriched in genes encoding peptidoglycan synthesis and depleted in phytoene dehydrogenase; patients also had reduced serum levels of β-carotene. Our findings suggest that the gut metagenome is associated with the inflammatory status of the host and patients with symptomatic atherosclerosis harbor characteristic changes in the gut metagenome.
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| 4. |
- Karlsson, Roger, 1975, et al.
(author)
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Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping
- 2020
-
In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 19:3, s. 518-528
-
Journal article (peer-reviewed)abstract
- Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases.
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| 5. |
- Karlsson, Roger, 1975, et al.
(author)
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Proteotyping bacteria: Characterization, differentiation and identification of pneumococcus and other species within the Mitis Group of the genus Streptococcus by tandem mass spectrometry proteomics
- 2018
-
In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
-
Journal article (peer-reviewed)abstract
- A range of methodologies may be used for analyzing bacteria, depending on the purpose and the level of resolution needed. The capability for recognition of species distinctions within the complex spectrum of bacterial diversity is necessary for progress in microbiological research. In clinical settings, accurate, rapid and cost-effective methods are essential for early and efficient treatment of infections. Characterization and identification of microorganisms, using, bottom-up proteomics, or "proteotyping", relies on recognition of species-unique or associated peptides, by tandem mass spectrometry analyses, dependent upon an accurate and comprehensive foundation of genome sequence data, allowing for differentiation of species, at amino acid-level resolution. In this study, the high resolution and accuracy of MS/MS-based proteotyping was demonstrated, through analyses of the three phylogenetically and taxonomically most closely-related species of the Mitis Group of the genus Streptococcus: i.e., the pathogenic species, Streptococcus pneumoniae (pneumococcus), and the commensal species, Streptococcus pseudopneumoniae and Streptococcus mitis. To achieve high accuracy, a genome sequence database used for matching peptides was created and carefully curated. Here, MS-based, bottom-up proteotyping was observed and confirmed to attain the level of resolution necessary for differentiating and identifying the most-closely related bacterial species, as demonstrated by analyses of species of the Streptococcus Mitis Group, even when S. pneumoniae were mixed with S. pseudopneumoniae and S. mitis, by matching and identifying more than 200 unique peptides for each species.
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| 6. |
- Mirkoska, Vesna, et al.
(author)
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Detection of subclinical motor speech deficits after presumed low-grade glioma surgery
- 2023
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In: Brain Sciences. - : MDPI. - 2076-3425. ; 13:12
-
Journal article (peer-reviewed)abstract
- Motor speech performance was compared before and after surgical resection of presumed low-grade gliomas. This pre- and post-surgery study was conducted on 15 patients (mean age = 41) with low-grade glioma classified based on anatomic features. Repetitions of /pa/, /ta/, /ka/, and /pataka/ recorded before and 3 months after surgery were analyzed regarding rate and regularity. A significant reduction (6 to 5.6 syllables/s) pre- vs. post-surgery was found in the rate for /ka/, which is comparable to the approximate average decline over 10–15 years of natural aging reported previously. For all other syllable types, rates were within normal age-adjusted ranges in both preoperative and postoperative sessions. The decline in /ka/ rate might reflect a subtle reduction in motor speech production, but the effects were not severe. All but one patient continued to perform within normal ranges post-surgery; one performed two standard deviations below age-appropriate norms pre- and post-surgery in all syllable tasks. The patient experienced motor speech difficulties, which may be related to the tumor’s location in an area important for speech. Low-grade glioma may reduce maximum speech-motor performance in individual patients, but larger samples are needed to elucidate how often the effect occurs.
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| 7. |
- Mobini, Reza, 1965, et al.
(author)
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Metabolic effects of Lactobacillus reuteri DSM 17938 in people with type 2 diabetes: A randomized controlled trial
- 2017
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In: Diabetes, Obesity and Metabolism. - : Wiley. - 1463-1326 .- 1462-8902. ; 19:4, s. 579-589
-
Journal article (peer-reviewed)abstract
- Aims: To investigate the metabolic effects of 12-week oral supplementation with Lactobacillus reuteri DSM 17938 in patients with type 2 diabetes on insulin therapy. Materials and methods: In a double-blind trial, we randomized 46 people with type 2 diabetes to placebo or a low (10(8) CFU/d) or high dose (10(10) CFU/d) of L. reuteri DSM 17938 for 12 weeks. The primary endpoint was the effect of supplementation on glycated haemoglobin (HbA1c). Secondary endpoints were insulin sensitivity (assessed by glucose clamp), liver fat content, body composition, body fat distribution, faecal microbiota composition and serum bile acids. Results: Supplementation with L. reuteri DSM 17938 for 12 weeks did not affect HbA1c, liver steatosis, adiposity or microbiota composition. Participants who received the highest dose of L. reuteri exhibited increases in insulin sensitivity index (ISI) and serum levels of the secondary bile acid deoxycholic acid (DCA) compared with baseline, but these differences were not significant in the between-group analyses. Post hoc analysis showed that participants who responded with increased ISI after L. reuteri supplementation had higher microbial diversity at baseline, and increased serum levels of DCA after supplementation. In addition, increases in DCA levels correlated with improvement in insulin sensitivity in the probiotic recipients. Conclusions: Intake of L. reuteri DSM 17938 for 12 weeks did not affect HbA1c in people with type 2 diabetes on insulin therapy; however, L. reuteri improved insulin sensitivity in a subset of participants and we propose that high diversity of the gut microbiota at baseline may be important.
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| 8. |
- Tremaroli, Valentina, 1978, et al.
(author)
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Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation
- 2015
-
In: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 22:2, s. 228-238
-
Journal article (peer-reviewed)abstract
- Bariatric surgery is currently the most effective procedure for the treatment of obesity. Given the role of the gut microbiota in regulating host metabolism and adiposity, we investigated the long-term effects of bariatric surgery on the microbiome of patients randomized to Roux-en-Y gastric bypass or vertical banded gastroplasty and matched for weight and fat mass loss. The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and resulted in altered levels of fecal and circulating metabolites compared with obese controls. By colonizing germ-free mice with stools from the patients, we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice. These mice also had a lower respiratory quotient, indicating decreased utilization of carbohydrates as fuel. Our results suggest that the gut microbiota may play a direct role in the reduction of adiposity observed after bariatric surgery.
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| 9. |
- Örtegren, Unn, 1975-, et al.
(author)
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Lipids and glycosphingolipids in caveolae and surrounding plasma membrane of primary rat adipocytes
- 2004
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In: Eur J Biochem. - : Wiley. - 0014-2956 .- 1432-1033. ; 271:10, s. 2028-36
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Journal article (peer-reviewed)abstract
- We have made a comprehensive and quantitative analysis of the lipid composition of caveolae from primary rat fat cells and compared the composition of plasma membrane inside and outside caveolae. We isolated caveolae from purified plasma membranes using ultrasonication in carbonate buffer to disrupt the membrane, or extraction with nonionic detergent, followed by density gradient ultracentrifugation. The carbonate-isolated caveolae fraction was further immunopurified using caveolin antibodies. Carbonate-isolated caveolae were enriched in cholesterol and sphingomyelin, and the concentration was three- and twofold higher, respectively, in caveolae compared to the surrounding plasma membrane. The concentration of glycerophospholipids was similar suggesting that glycerophospholipids constitute a constant core throughout the plasma membrane. The composition of detergent-insoluble fractions of the plasma membrane was very variable between preparations, but strongly enriched in sphingomyelin and depleted of glycerophospholipids compared to carbonate-isolated caveolae; indicating that detergent extraction is not a suitable technique for caveolae preparation. An average adipocyte caveola contained about 22 x 10(3) molecules of cholesterol, 7.5 x 10(3) of sphingomyelin and 23 x 10(3) of glycerophospholipid. The glycosphingolipid GD3 was highly enriched in caveolae, whereas GM3, GM1 and GD1a were present inside as well as outside the caveolae membrane. GD1b, GT1b, GM2, GQ1b, sulfatide and lactosylceramide sulfate were not detected in caveolae.
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| 10. |
- Boulund, Fredrik, 1985, et al.
(author)
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Typing and Characterization of Bacteria Using Bottom-up Tandem Mass Spectrometry Proteomics
- 2017
-
In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 16:6, s. 1052-1063
-
Journal article (peer-reviewed)abstract
- Methods for rapid and reliable microbial identification are essential in modern healthcare. The ability to detect and correctly identify pathogenic species and their resistance phenotype is necessary for accurate diagnosis and efficient treatment of infectious diseases. Bottom-up tandem mass spectrometry (MS) proteomics enables rapid characterization of large parts of the expressed genes of microorganisms. However, the generated data are highly fragmented, making downstream analyses complex. Here we present TCUP, a new computational method for typing and characterizing bacteria using proteomics data from bottom-up tandem MS. TCUP compares the generated protein sequence data to reference databases and automatically finds peptides suitable for characterization of taxonomic composition and identification of expressed antimicrobial resistance genes. TCUP was evaluated using several clinically relevant bacterial species (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae), using both simulated data generated by in silico peptide digestion and experimental proteomics data generated by liquid chromatography-tandem mass spectrometry (MS/MS). The results showed that TCUP performs correct peptide classifications at rates between 90.3 and 98.5% at the species level. The method was also able to estimate the relative abundances of individual species in mixed cultures. Furthermore, TCUP could identify expressed beta-lactamases in an extended spectrum beta-lactamase-producing (ESBL) E.coli strain, even when the strain was cultivated in the absence of antibiotics. Finally, TCUP is computationally efficient, easy to integrate in existing bioinformatics workflows, and freely available under an open source license for both Windows and Linux environments.
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| 11. |
- Bäckström, Malin, 1967, et al.
(author)
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Recombinant MUC1 mucin with a breast cancer-like O-glycosylation produced in large amounts in Chinese-hamster ovary cells.
- 2003
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In: The Biochemical journal. - 1470-8728. ; 376:Pt 3, s. 677-86
-
Journal article (peer-reviewed)abstract
- We have developed an expression system for the production of large quantities of recombinant MUC1 mucin in CHO-K1 (Chinese-hamster ovary K1) cells. The extracellular part of human MUC1, including 16 MUC1 tandem repeats, was produced as a fusion protein with murine IgG Fc, with an intervening enterokinase cleavage site for the removal of the Fc tail. Stable MUC1-IgG-producing CHO-K1 clones were generated and were found to secrete MUC1-IgG into the culture medium. After adaptation to suspension culture in protein-free medium in a bioreactor, the fusion protein was secreted in large quantities (100 mg/l per day) into the culture supernatant. From there, MUC1 could be purified to homogeneity using a two-step procedure including enterokinase cleavage and ion-exchange chromatography. Capillary liquid chromatography MS of released oligosaccharides from CHO-K1-produced MUC1 identified the main O-glycans as Galbeta1-3GalNAc (core 1) and mono- and di-sialylated core 1. The glycans occupied on average 4.3 of the five potential O-glycosylation sites in the tandem repeats, as determined by nano-liquid chromatography MS of partially deglycosylated Clostripain-digested protein. A very similar O-glycan profile and site occupancy was found in MUC1-IgG produced in the breast carcinoma cell line T47D, which has O-glycosylation typical for breast cancer. In contrast, MUC1-IgG produced in another breast cancer cell line, MCF-7, showed a more complex pattern with both core 1- and core 2-based O-glycans. This is the first reported production of large quantities of recombinant MUC1 with a breast cancer-like O-glycosylation that could be used for the immunotherapy of breast cancer.
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| 12. |
- Davidsson, Lisa, et al.
(author)
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A simple skin blister technique for the study of in vivo transmigration of human leukocytes.
- 2013
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In: Journal of immunological methods. - : Elsevier BV. - 1872-7905 .- 0022-1759. ; 393:1-2, s. 8-17
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Journal article (peer-reviewed)abstract
- The study of human leukocytes is almost exclusively conducted using cells isolated from peripheral blood. This is especially true for neutrophils, despite the fact that these cells are of main (pathological) importance in extravascular tissues upon e.g., infection and/or tissue damage. The journey from circulation to tissue is typically associated with a number of cellular changes, making the cells primed, or hyper-responsive, and in many aspects distinct from the cells present in circulation. Models to obtain in vivo transmigrated leukocytes from human tissue are available, but not widely used. We describe here an easy-to-use model for the study of local inflammation, stemming from limited tissue damage, which can be used to isolate viable and functional leukocytes. The model is based on the generation of aseptic skin blisters, formed by the application of negative pressure, and allows for investigations of the cellular infiltrate as well as of soluble mediators present in the exudate. We believe that this method, combined with modern analysis equipment suitable for small volumes and cell numbers, could be of great use for increasing our understanding of the nature and function of leukocytes that have left circulation and transmigrated to inflamed tissues.
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| 13. |
- Doorn, Jan van, et al.
(author)
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Influence of speech task and utterance length on the measurement of pitch variability in the speech of Parkinson's disease patients after deep brain stimulation
- 2013
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Conference paper (other academic/artistic)abstract
- Parkinson’s disease (PD) affects patients voice characteristics, reducing pitch variability compared to normal controls (1,2). Previous reports have shown an increase in pitch variability due to deep brain stimulation (DBS) of the Subthalamic nucleus (STN) (3). For patients stimulated in caudal zona incerta (cZi), the results indicate no effect on pitch variability in a read speech task{Karlsson:2012jr}.The present study aimed at investigating the effects of speech task (spontaneous or read speech) and the lenght of the utterance on overall measures of pitch variability observed in DBS-treated patients. Ten patients treated with STN-DBS and ten patients treated with cZi-DBS were included in this prospective study.Utterances produced sponatenously and produced during readings of a standard passage were compared in terms of treatment effects in pitch variability due to STN-DBS and cZi-DBS (Stim OFF and Stim ON recordings made 1,5 hour apart, all in Med ON) 6 and 12 months after operation. The results indicate that pitch variability is affected differently by STN-DBS and cZi-DBS depending on speech task and utterance length. In short utterances (<10 words), an increase in pitch variability is observed for both treatment groups and both speech tasks. For longer utterances, however, a more diverse effect of treatment and speech task is observed. The results therefore suggest that spech task and characteristics of thate utterance should be carefully considered when drawing conclusions on the overall effect of DBS on pitch variability.1. Jiménez-Jiménez FJ, Gamboa J, Nieto A, Guerrero J, Ortí-Pareja M, Molina JA, et al. Acoustic voice analysis in untreated patients with Parkinson's disease. Parkinsonism Relat. Disord. 1997 Apr;3(2):111–6. 2. Holmes RJ, Oates JM, Phyland DJ, Hughes AJ. Voice characteristics in the progression of Parkinson’s disease. International Journal of Language & Communication Disorders. 2000;35(3):407–18. 3. Dromey C, Kumar R, Lang AE, Lozano AM. An investigation of the effects of subthalamic nucleus stimulation on acoustic measures of voice. Mov. Disord. 2000;15(6):1132–8.
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| 14. |
- Eklund, Elisabeth, 1988-, et al.
(author)
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Perceived articulatory precision in patients with Parkinson’s disease after deep brain stimulation of subthalamic nucleus and caudal zona incerta
- 2015
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In: Clinical Linguistics & Phonetics. - : Informa UK Limited. - 0269-9206 .- 1464-5076. ; 29:2, s. 150-166
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Journal article (peer-reviewed)abstract
- The effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and caudal zona incerta (cZi) on speech articulation in patients with Parkinson’s disease (PD) was investigated. Read speech samples were collected from nine patients with STN-DBS and ten with cZi-DBS. The recordings were made preoperatively and 12 months postoperatively with stimulator on and off (on medication). Blinded, randomized, repeated perceptual assessments were performed on words and isolated fricatives extracted from the recordings to assess 1) overall articulatory quality ratings, 2) frequency of occurrence of misarticulation patterns, and 3) fricative production. Statistically significant worsening of articulatory measures on- compared with off-stimulation occurred in the cZi-DBS group, with deteriorated articulatory precision ratings, increased presence of misarticulations (predominately altered realizations of plosives and fricatives) and a reduced accuracy in fricative production. A similar, but not significant, trend was found for the STN-DBS group.
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| 15. |
- Fahlén, Per, 1947, et al.
(author)
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Impact of design and thermal inertia on the energy saving potential of capacity controlled heat pump heating systems
- 2008
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In: International Journal of Refrigeration. - : Elsevier BV. - 0140-7007. ; 31:6, s. 1094-1103
-
Journal article (peer-reviewed)abstract
- The objective of this study was to develop a dynamic model of hydronic heating systems in order to get a more fair comparison of energy efficiency between continuously capacity controlled heat pumps and intermittently controlled heat pumps than what is achieved with steady-state models. Factors such as thermal inertia, different connection principles, temperature levels and lag times are also considered to see how they affect the comparison and the efficiency. The results show that performance of an intermittently controlled heat pump is reduced when using this dynamic model compared to the static models, whereas the results for a variable-speed controlled heat pump stay the same. Introducing different controller dead bands, thermal inertias, etc. change the result only to a small extent.
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| 16. |
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| 17. |
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| 18. |
- Godl, Klaus, et al.
(author)
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The N terminus of the MUC2 mucin forms trimers that are held together within a trypsin-resistant core fragment.
- 2002
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In: The Journal of biological chemistry. - 0021-9258 .- 1083-351X. ; 277:49, s. 47248-56
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Journal article (peer-reviewed)abstract
- The N terminus of the human MUC2 mucin (amino acids 1-1397) has been expressed as a recombinant tagged protein in Chinese hamster ovary cells. The intracellular form was found to be an endoglycosidase H-sensitive monomer, whereas the secreted form was an oligomer that gave monomers upon disulfide bond reduction. The secreted MUC2 N terminus contained a trypsin-resistant core fragment. Edman sequencing and mass spectrometry of the peptides obtained localized this core fragment to the C-terminal end of the recombinant protein. This core retained its oligomeric nature with an apparent mass of approximately 240 kDa. Upon reduction, peptides of approximately 85 kDa were found, suggesting that the N terminus forms trimers. This interpretation was also supported by gel electrophoresis and gel filtration of the intact MUC2 N terminus. Electron microscopy revealed three globular domains each linked via an extended and flexible region to a central part in a trefoil-like manner. Immunostaining with gold-labeled antibodies localized the N-terminal end to the three globular structures, and the antibodies directed against the Myc and green fluorescent protein tags attached at the C terminus localized these to the stalk side of the central trefoil. The N terminus of the MUC2 mucin is thus assembled into trimers that contain proteolytically stable parts, suggesting that MUC2 can only be partly degraded by intestinal proteases and thus is able to maintain a mucin network protecting the intestine.
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| 19. |
- Gonzales-Siles, Lucia, et al.
(author)
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Mass Spectrometry Proteotyping for detection, identification characterization and diagnostics of infectious bacteria in clinical respiratory-tract samples
- 2016
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In: 11th International Meeting on Microbial Epidemiological Markers (IMMEM XI) 9 - 12 March 2016, Estoril, Portugal.
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Conference paper (other academic/artistic)abstract
- Background. Lower respiratory tract infection (LRTI) is the leading cause of childhood deaths in most developing countries and the world (?) and are the most common causes of hospital and out-patient visits within the EU, comprising 1 of 3 admissions annually. In general, the over-prescription and use of broad-spectrum antibiotics are common practices that lead to the evolution and development of resistance in infectious bacteria and will lead to loss of time and resources in patient handling and adverse patient outcomes. Conventional approaches have depended upon cultivation of bacteria with subsequent testing for antibiotic sensitivity. Therefore, reliable and time-effective microbiological diagnostics are essential for more effective treatment of respiratory infections. In this project, we apply state-of-the-art proteomics techniques for identifications of pathogens and antibiotic resistance from clinical samples, without prior cultivation. Material and methods. Nasopharyngeal swab samples were collected, in commercial Amies medium supplemented with 5x STGG, as a part of the EU-TAILORED-Treatment project (www.tailored-treatment.eu/). Samples were stored at -20°C until analyses. Different protocols for removal of human cells and mucus were tested, including non-ionic detergents, i.e., Igepal, Saponin, Urea-Chaps, as well as cytolysis. Samples were concentrated and analyzed by ‘proteotyping’ (1), using a Lipid-based Protein Immobilization (LPITM) technology (WO2006068619), in which intact bacterial cells or cell fractions are bound to a surface. Peptides were generated, using enzymatic digestion, and then separated and analyzed, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The mass spectra profiles were compared to a database of reference peptide sequences, consisting of all complete genomes of the NCBI Reference Sequence (RefSeq) Database. Results were confirmed by standard microbiology, including cultivation of bacteria in selective media, MALDI-TOF MS analyses and qPCR. Results. Proteotyping applied to clinical samples demonstrated that the number of viable bacteria and detected proteins determined were ten-times higher when nasal swabs were stored in Amies media supplemented with STGG 5X media compared to Amies media without STGG, after 1 and 2 months of storage at -70C. Among the different protocols tested to remove human biomaterial, all treatments proved effective to varying degrees, although the Igepal treatment was able to retain the highest number of discriminatory peptides. Using proteotyping, we were able to identify the pathogenic bacteria directly within clinical samples (nasopharyngeal and nasal swabs) that had been identified to be positive for respiratory infectious bacteria by standard methodologies at clinical bacteriology laboratories at Sahlgrenska University Hospital (Sweden) or Universitair Medisch Centrum Utrecht (Netherlands). Conclusions. Proteotyping of infectious bacteria, using tandem LC-MS/MS enabled the differentiation and identification of infectious bacteria in clinical samples from LRTIs. It has high levels of resolution and highly reproducible detection of protein biomarkers. Proteotyping identified biomarkers for species- and sub-species-level strain discrimination and antibiotic resistance, all from single MS analyses. 1) Karlsson et al., 2015. Syst. Appl. Microbiol. 38 :246-257.
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| 20. |
- Gonzales-Siles, Lucia, et al.
(author)
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Mass Spectrometry Proteotyping of Streptococcus pneumoniae and commensal Streptococcus: identification of biomarkers for infectious strain characterization
- 2016
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In: 26th ECCMID 2016 Amsterdam, The Netherlands. 9 - 12 April 2016.
-
Conference paper (other academic/artistic)abstract
- Background: Streptococcus pneumoniae (pneumococcus) is the leading cause of community-acquired pneumonia, with morbidity and mortality worldwide. S. pneumoniae belongs to the S. mitis-Group (viridans streptococci), phenotypically and genotypically similar to commensal species of the upper respiratory tract, S. mitis, S. oralis, and S. pseudopneumoniae, causing problems for identifications in clinical laboratories. In this project, we apply state-of-the-art proteomics for Streptococcus spp. 'proteotyping'; identifying and characterizing protein biomarkers for species-level identification, antibiotic resistance, virulence and strain typing for epidemiological analyses (1). Material/methods: Bacterial proteins, from intact bacteria or cell fractions, are bound to a membrane surface, using patented (WO2006068619) FlowCell (LPITM) technology. Peptides are generated from the bound proteins, by enzymatic digestion, separated and analyzed, using LC-MS/MS. The mass spectra profiles are compared to reference peptide sequences and whole genome sequence (wgs) data of the NCBI RefSeq Database. The S. mitis-Group specie, S. pneumoniae, S. mitis, S. oralis, S. psedopneumoniae, as well as the more distantly-related, Group A Streptococcus (GAS) species, S. pyogenes , were analyzed individually and in mixtures, to demonstrate the resolution of proteotyping for differentiating bacteria. Results: Using proteotyping protocols, S. pneumoniae were detected and differentiated from other streptococci, S. mitis, S. oralis, S. psedopneumoniae and the more distant relative, S. pyogenes, by identification of unique discriminatory peptides. Metabolic protein biomarkers were identified, including for antibiotic resistance and virulence. It was possible to find discriminatory biomarkers for a target species when analyzing 1:1 mixes of S. pneumoniae and other species from the S. mitis-Group. The different strains of S. pneumoniae, analyzed in different ratio combinations, were successfully differentiated and identified. For successful proteotyping, a comprehensive and accurate genomic database was observed to be key for obtaining reliable peptide matching and proteotyping data. Importantly, because of observed high rates of misclassified wgs data in the public databases, the taxonomic classifications of genomes in GenBank were analyzed against reference type strain genomes of target species by calculating wgs similarities, using Average Nucleotide Identity with BLAST (ANIb). While wgs data for S. pneumoniae were confirmed to be classified correctly, approximately one-third of wgs data for other species of the S. mitis-Group were determined to be misclassified. Streptococci strains that could not be identified, using standard genotypic and phenotypic approaches, were characterized by proteotyping and genome sequencing to establish their taxonomy and biomarker features to enhance species database matching. Conclusions: Proteotyping enables differentiation, identification and characterization of pneumococcus from the most closely related species attaining, as well, strain-level discrimination from single LC-MS/MS analyses. The protocol enhances identification and characterization of pathogenic bacterial isolates through identifications of expressed biomarkers, ultimately for cultivation-independent analyses of clinical samples. 1) Karlsson et al., 2015. Syst Appl Microbiol. 38:246-257.
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| 21. |
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| 22. |
- Holmberg, Jenny, et al.
(author)
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Exploring motives and perceived barriers for voice modification : the views of transgender and gender-diverse voice clients
- 2023
-
In: Journal of Speech, Language and Hearing Research. - : American Speech Language Hearing Association. - 1092-4388 .- 1558-9102. ; 66:7, s. 2246-2259
-
Journal article (peer-reviewed)abstract
- Purpose: To date, transgender and gender-diverse voice clients' perceptions and individual goals have been missing in discussions and research on gender-affirming voice therapy. Little is, therefore, known about the client's expectations of therapy outcomes and how these are met by treatments developed from views of vocal gender as perceived by cisgender persons. This study aimed to explore clients' individual motives and perceived barriers to undertaking gender-affirming voice therapy.Method: Individual, semistructured interviews with 15 transgender and gender-diverse voice clients considering voice therapy were conducted and explored using qualitative content analysis.Results: Three themes were identified during the analysis of the participants' narratives. In the first theme, “the incongruent voice setting the rules,” the contribution of the voice on the experienced gender dysphoria is put in focus. The second theme, “to reach a voice of my own choice,” centers around anticipated personal gains using a modified voice. The third theme, “a voice out of reach,” relates to worries and restricting factors for not being able to reach one's set goals for voice modification.Conclusions: The interviews clearly indicate a need for a person-centered voice therapy that starts from the individuals' expressed motives for modifying the voice yet also are affirmative of anticipated difficulties related to voice modification. We recommend that these themes should form the basis of the pretherapy joint discussion between the voice client and the speech-language pathologist to ensure therapy goals that are realistic and relevant to the client.
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| 23. |
- Holmén, Jessica, 1971, et al.
(author)
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Two glycosylation alterations of mouse intestinal mucins due to infection caused by the parasite Nippostrongylus brasiliensis.
- 2002
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In: Glycoconjugate journal. - 0282-0080. ; 19:1, s. 67-75
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Journal article (peer-reviewed)abstract
- The glycosylation alterations of mouse small intestinal mucins during a 12-day infectious cycle caused by the parasite Nippostrongylus brasiliensis have been studied. The guanidinium chloride insoluble mucins were isolated at day 0 to 12 from the small intestine of infected and non-infected C57BL/6 mice. The O-linked oligosaccharides were released by reductive beta-elimination from the mucins and separated into neutral, sialylated and sulfated fractions. All fractions were analyzed by monosaccharide composition analysis and the neutral oligosaccharides were structurally characterized by gas chromatography/mass spectrometry. Two oligosaccharides containing blood group H-type epitopes (Fucalpha1-2Gal-) were transiently expressed with a maximum at day 6. Additional oligosaccharides with the common structure HexNAc-Gal-3GalNAcol were transiently induced with a maximum at day 10. Northern blot analysis on total RNA showed a transient expression at day 4-6 of the Fut2 gene encoding a Fucalpha1-2 fucosyltransferase, probably responsible for the detected blood group H-type epitopes. Comparisons with the corresponding infection in rat studied previously, revealed structurally different alterations, although occurring as transient events in both species. Both showed an induced blood group-type transferase halfway through the infection (a blood group A transferase in rat) and an induced transferase adding a terminal GalNAc (to a sialic acid- containing epitope in rat) towards the end of the infection. These differences between closely related species suggest rapid evolutionary alterations in glycosyltransferase expression.
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| 24. |
- Hong, Mun-Gwan, et al.
(author)
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A genome-wide assessment of variability in human serum metabolism
- 2013
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In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 34:3, s. 515-524
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Journal article (peer-reviewed)abstract
- The study of the genetic regulation of metabolism in human serum samples can contribute to a better understanding of the intermediate biological steps that lead from polymorphism to disease. Here, we conducted a genome-wide association study (GWAS) to discover metabolic quantitative trait loci (mQTLs) utilizing samples from a study of prostate cancer in Swedish men, consisting of 402 individuals (214 cases and 188 controls) in a discovery set and 489 case-only samples in a replication set. A global nontargeted metabolite profiling approach was utilized resulting in the detection of 6,138 molecular features followed by targeted identification of associated metabolites. Seven replicating loci were identified (PYROXD2, FADS1, PON1, CYP4F2, UGT1A8, ACADL, and LIPC) with associated sequence variants contributing significantly to trait variance for one or more metabolites (P = 10(-13) -10(-91)). Regional mQTL enrichment analyses implicated two loci that included FADS1 and a novel locus near PDGFC. Biological pathway analysis implicated ACADM, ACADS, ACAD8, ACAD10, ACAD11, and ACOXL, reflecting significant enrichment of genes with acyl-CoA dehydrogenase activity. mQTL SNPs and mQTL-harboring genes were over-represented across GWASs conducted to date, suggesting that these data may have utility in tracing the molecular basis of some complex disease associations.
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| 25. |
- Hägglund, Patricia, et al.
(author)
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The Test of Masticating and Swallowing Solids (TOMASS) : Normative data for two crackers available in the Scandinavian and international markets
- 2021
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In: International Journal of Speech-Language Pathology. - : Taylor & Francis. - 1754-9507 .- 1754-9515. ; 23:3, s. 329-337
-
Journal article (peer-reviewed)abstract
- Purpose: To establish normative data of crackers common in the Scandinavian and international markets for use in the Test of Masticating and Swallowing Solids (TOMASS), and to investigate possible sex and age effects on masticatory performances.Method: 234 healthy participants (>20 years of age) were asked to either ingest the Göteborgskex Guld Marie™ cracker (n = 234) or to ingest both a Guld Marie cracker and a Tuc Original™ cracker (n = 115). Quantifiable measures of masticatory performance (number of bites, number of chewing cycles, number of swallows, and total time) were observed during TOMASS for each participant, directly on-site or by video recording.Result: There were no significant differences in masticatory performances between the crackers. Significant age effects were observed for all masticatory measurements, except for the number of swallows. The results showed insufficient support for an effect of sex, and that results obtained on-site and from video recordings were highly correlated.Conclusion: These findings suggest that similar masticatory performance is to be expected when performing TOMASS using the evaluated crackers. The age of the participant affects TOMASS performance, but the effect of sex is considerably smaller.
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| 26. |
- Hägglund, Patricia, et al.
(author)
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Voice Tremor in Patients With Essential Tremor : Effects of Deep Brain Stimulation of Caudal Zona Incerta
- 2016
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In: Journal of Voice. - : Elsevier BV. - 0892-1997 .- 1873-4588. ; 30:2, s. 228-233
-
Journal article (peer-reviewed)abstract
- Objectives. The present study aimed at evaluating the effect of deep brain stimulation (DBS) of the caudal zona incerta (cZi) on voice tremor in patients with essential tremor (ET). Study Design. This is a prospective nonrandomized design with consecutive patients.Methods. Twenty-six patients operated with cZi DBS were evaluated under two conditions: without stimulation (Stim OFF) and with stimulation (Stim ON). Voice tremor was assessed on the basis of recordings of sustained vowel productions using a four-point rating scale in a blinded and randomized procedure. Averaged values of multiple assessments for each stimulus were used in statistical testing. The group of patients with voice tremor in Stim OFF was analyzed separately from the group of patients without voice tremor.Results. Voice tremor was significantly reduced on stimulation compared with off for the subgroup with initial voice tremor. Voice tremor prevalence was found to be 50% (13 patients). Individual differences in voice tremor outcome were noticeable. Six of the patients with voice tremor at baseline improved substantially by cZi DBS treatment.Conclusions. On the group level, voice tremor in patients with ET was found to reduce when stimulating the cZi. Bilateral stimulation was indicated to be more effective in reducing voice tremor than unilateral stimulation. However, individual voice tremor outcomes suggest that not all patients benefit from cZi DBS. Severity of voice tremor at baseline may not be a good predictor of voice tremor outcome after cZi DBS. Patients should be informed before surgery regarding individual differences in response to DBS treatment.
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| 27. |
- Identeg, Fredrik, 1990, et al.
(author)
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Patterns of traumatic outdoor rock-climbing injuries in Sweden between 2008 and 2019
- 2021
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In: Journal of Experimental Orthopaedics. - : Springer Science and Business Media LLC. - 2197-1153. ; 8:1
-
Journal article (peer-reviewed)abstract
- Purpose Injury prevalence patterns for climbers have been presented in several papers but results are heterogenous largely due to a mix of included climbing disciplines and injury mechanisms. This study describes the distribution and pattern of acute traumatic climbing injuries sustained during outdoor climbing in Sweden. Methods Patients that experienced a climbing related traumatic injury during outdoor climbing between 2008 and 2019 and who submitted a self-reported questionnaire to the Swedish Climbing Association were included in the study. Medical records were retrieved, and the International Climbing and Mountaineering Federation injury classification system was used for injury presentation. Results Thirty-eight patients were included in the study. Seven (18%) injuries occurred during traditional climbing, 13 (34%) during sport climbing and 9 (24%) during bouldering. Varying with climbing discipline, 84-100% injuries were caused by falls. Injuries of the foot and ankle accounted for 72-100% of the injuries. Fractures were the most common injury (60%) followed by sprains (17%) and contusions (10%). Conclusions Traumatic injuries sustained during outdoor climbing in Sweden were predominantly caused by falls and affected the lower extremities in all major outdoor climbing disciplines. Rope management errors as a cause of injury were common in sport climbing and in activity surrounding the climbing, indicating there is room for injury-preventing measures.
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| 28. |
- Jakobsson, Hedvig E, et al.
(author)
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Draft Genome Sequence of Moraxella catarrhalis Type Strain CCUG 353T.
- 2016
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In: Genome Announcements. - 2169-8287. ; 4:3
-
Journal article (peer-reviewed)abstract
- Moraxella catarrhalis is a Gram-negative commensal and pathogenic bacterium found in the human respiratory tract. It is associated with otitis media and respiratory tract infections. Here, we report the draft genome sequence of M. catarrhalis type strain CCUG 353(T), composed of 18 contigs and a total size of 1.89 Mb.
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| 29. |
- Jakobsson, Hedvig E, et al.
(author)
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Draft Genome Sequences of Six Strains of Streptococcus pneumoniae from Serotypes 5, 6A, 6B, 18C, 19A, and 23F
- 2017
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In: Genome Announcements. - 2169-8287. ; 5:14
-
Journal article (peer-reviewed)abstract
- Streptococcus pneumoniae is a pathogenic bacterium found most commonly in the respiratory tract of humans and is a common cause of pneumonia and bacterial meningitis. Here, we report the draft genome sequences of six S. pneumoniae strains: CCUG 1350, CCUG 7206, CCUG 11780, CCUG 33774, CCUG 35180, and CCUG 35272.
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| 30. |
- Jakobsson, Hedvig E, et al.
(author)
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Proteotyping of Streptococcus pneumoniae, using tandem mass spectrometry for identification of biomarkers for species and strain differentiation
- 2016
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In: 11th International Meeting on Microbial Epidemiological Markers (IMMEM XI) 9 - 12 March 2016, Estoril, Portugal. - : European Society for Clinical Microbiology and Infectious Diseases.
-
Conference paper (other academic/artistic)abstract
- Background. Streptococcus pneumoniae (pneumococcus) is the leading cause of community-acquired pneumonia and a major cause of morbidity and mortality worldwide. S. pneumoniae is phenotypically and genotypically similar to commensal species of the upper respiratory tract of the Streptococcus mitis-Group (viridans streptococci), S. mitis, S. oralis, and S. pseudopneumoniae, causing problems of identification in clinical microbiology laboratories. We have applied state-of-the-art proteomics techniques for Streptococcus spp. proteotyping; to detecting and characterizing expressed protein biomarkers for species-level identification, determination of antibiotic resistance and virulence biomarkers and strain typing for epidemiological analyses. Material and methods. The proteins of intact bacteria or cell fractions are bound to a membrane surface, using patented (WO2006068619) Lipid-based Protein Immobilization (LPITM) technology. Peptides are generated from the bound proteins, using enzymatic digestion, separated and analyzed, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The mass spectra profiles are compared to a database of reference peptide sequences. Subsequently, the identified peptides are compared to a database of reference genome sequences, all complete genomes of the NCBI Reference Sequence (RefSeq) Database. In this study, the type strains of the close-related mitis complex species S. pneumoniae (CCUG 28588T), S. mitis (CCUG 31611T), S. oralis (CCUG 13229T), S. psedopneumoniae (CCUG 49455T) and the more distantly-related S. pyogenes (CCUG 4207T) were analysed individually and in mixtures, to demonstrate proteotyping capability and differentiate closely related species,. Additionally, mixes containing different S. pneumoniae strains were analyzed. Results. Using proteotyping protocols, it was possible to detect and correctly identify S. pneumoniae from the closely related bacterial species, S. mitis, S. oralis S. psedopneumoniae and S. pyogenes, as well as different strains of S. pneumoniae by identification of unique discriminatory peptides. For successful proteotyping,a comprehensive and accurate genomic database is the key to obtaining reliable proteotyping data. Importantly, because of questionable classifications of sequenced genomes in the public databases, before incorporation of reference genomic sequence data for proteotyping, the genome sequences should be verified and confirmed for accurate classifications. Furthermore, it is also essential to include all relevant species with as many as 25 genomes in order to obtain a comprehensive coverage of coding sequences for accurate peptide matching and to be able to discriminate between the most closely related species. In this study, all genomes of the S. mitis-Group in the database were analyzed, using Average Nucleotide Identity Blast (ANIb) and S. mitis-Group strains that cannot be identified to the species level, using standard genotypic and phenotypic approaches, where characterized by proteotyping and whole genome sequencing to describe their taxonomy and to improve the database matching. Conclusions: Proteotyping, using LC-MS/MS, enabled the differentiation and identification of pneumococcus from its closely related species and sub-species-level strain discrimination, all from single MS analyses. The whole method will enhance the identification and characterization of microorganisms, allowing high-resolution discrimination of closely related species through the confident identification of new biomarkers, ultimately for cultivation-independent application to the analyses of clinical samples.
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| 31. |
- Karlsson, Fredrik, Docent, 1975-, et al.
(author)
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A within-subject comparison of face-to-face and telemedicine screening using the timed water swallow test (TWST) and the test of mastication and swallowing of solids (TOMASS)
- 2023
-
In: Dysphagia (New York. Print). - : Springer. - 0179-051X .- 1432-0460. ; 38, s. 483-490
-
Journal article (peer-reviewed)abstract
- The Timed Water Swallow Test (TWST) and the Test of Mastication of Solids (TOMASS) are dysphagia screening procedures that have been shown to be reliably assessed from video. The reliability of the procedures performed over telemedicine has not previously been assessed. TWST and TOMASS outcomes in two situations (both face-to-face and over telemedicine) were compared for 48 participants (aged 60-90; 27 with clinical conditions and 21 older persons). Both testing situation and test performed order were randomized, and all assessment procedures were performed within 3 h of each other. The results indicated a high level of agreement between face-to-face and telemedicine screening outcomes for TWST and TOMASS, respectively. The assessments indicated an 83% and 76% agreement in classifications of individual participants as within or outside normal limits for the TWST and TOMASS for the two test situations. The TWST showed a balanced distribution in differing classification in telemedicine (0.16-0.19 error rates). The TOMASS procedure classified more participants as outside normal limits over telemedicine compared to face-to-face administration. Agreement in the observed number of swallows was substantially lower than other outcome measures, which is attributed to increased difficulty in observing this property over video. Most participants (60%) reported that they would prefer telemedicine over face-to-face assessments, and 90% viewed the procedure as more accessible than expected. All participants were satisfied with the telemedicine procedures. The results suggest that clinical assessment of dysphagia over telemedicine using the TWST and TOMASS are viable alternatives to face-to-face administration of the procedures.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Karlsson, Fredrik, 1975-, et al.
(author)
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Applying the Vowel Formant Dispersion (VFD) method to the study of reduced or alterered vowel productions
- 2012
-
Conference paper (other academic/artistic)abstract
- Formant centre frequencies are regularly used as acoustic measure of vowel quality because of the well established correlation between them and properties of vowel production(Fant, 1960). While it is recognised that it is important transform formant frequencies, as measured from the spectrogram, into relevant psychoacoustic scales when addressing issues of vowel perception, production studies are still largely based on the the raw, Hz-scaled, formant measurements. As a consequence, systematic studies of vowel articulation proficiency due to clinical conditions or effects of treatment are not easily afforded. A number of derived measures have been proposed to capture whole-system effect of vowel production. Previous research has primarily used the calculated total area of formants measured from either [a], [u], [i] and [æ] or only [a], [u] and [i] productions, joined together to form a quadrilateral or a triangle (Vowel space area, VSA)(Kent & Kim, 2003). In the reduced articulatory range of hypokinetic dysarthria, VSA is expected to be reduced by the dysarthria, and increased due to successful treatment the patient’s articulatory range. However, VSA has been proposed to be not powerful enough to capture effects on vowel articulation found specifically in patients with Parkinson’s disease (PD), and therefore not able to establish treatment effects.Two alternative measures have been proposed previously that are more focused towards specifically towards finding expansion and reductions in vowel spaces, the Vowel articulation index (VAI)(Roy, Nissen, Dromey, & Sapir, 2009) or Formant Centralization Ratio (FCR)(Sapir, Ramig, Spielman, & Fox, 2010). Both VAI and FCR has been shown to be able to establish significant reductions vowel articulation due to PD. Similar to VSA, however, the VAI and FCR measures do not given any detailed insight into the nature of the change in articulation. Further, all three measures reduces all obtained vowel formant measurements into a single metric, resulting in a substantial loss of statistical power and a considerable reduction in quality of intra-speaker models of articulatory proficiency. In response to the problematic properties of previous metrics, a revised view of formant frequencies more suitable for studies of changes in vowel articulation has recently been outlined, along with a new metric (Vowel Formant Dispersion, VFD). The VFD view of vowel formants are more closely connected to properties of vowel articulation and therefore affords more more detailed interpretations to be drawn concerning speakers’ production proficiency and offers increased reliability of within speaker estimates of this proficiency. This paper presents a detailed view of how VFD may applied to clinical populations where vowel production is affected by the condition (e.g. hypokinetic dysarthria) or where production should be affected (e.g. transexual patients or in successful treatment of dysarthric patients). It will be shown that most aspects of the study of vowel articulation proficiency will be significantly enhanced by the VFD method.
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| 36. |
- Karlsson, Fredrik, 1975-, et al.
(author)
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Articulatory closure proficiency in Parkinson's disease patients following deep brain stimulation of the subthalamic nucleus and caudal zona incerta.
- 2014
-
In: Journal of Speech, Language and Hearing Research. - 1092-4388 .- 1558-9102. ; 57, s. 1178-1190
-
Journal article (peer-reviewed)abstract
- OBJECTIVEThe present study aimed at comparing the effects of deep brain stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) on Parkinson's disease patients' proficiency in achieving oral closure and release during plosive production. METHODS Nineteen patients were evaluated preoperatively and 12 months after DBS surgery. Nine patients were implanted in the STN, seven bilaterally and two unilaterally (left). Ten were bilaterally implanted in the cZi. Postoperative examinations were made off and on stimulation. All patients received simultaneous L-dopa treatment in all conditions. For a series of plosives extracted from a reading passage, absolute and relative measures of duration of frication and amplitude of plosive release were compared between conditions within each treatment group. RESULTS Relative duration of frication increased in voiceless plosives in the on stimulation condition in cZi patients. Similar trends were observed across the data set. Duration of pre-release frication and the release peak prominence increased in voiceless plosives on stimulation for both groups. CONCLUSIONS The increased release prominence suggests that patients achieved a stronger closure gesture due to DBS, but that the increased energy available resulted in increased frication.
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| 37. |
- Karlsson, Fredrik, Docent, 1975-, et al.
(author)
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Assessment of speech impairment in patients with Parkinson's disease from acoustic quantifications of oral diadochokinetic sequences
- 2020
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In: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966 .- 1520-8524. ; 147:2, s. 839-851
-
Journal article (peer-reviewed)abstract
- This investigation aimed at determining whether an acoustic quantification of the oral diadochokinetic (DDK) task may be used to predict the perceived level of speech impairment when speakers with Parkinson's disease (PD) are reading a standard passage. DDK sequences with repeated [pa], [ta], and [ka] syllables were collected from 108 recordings (68 unique speakers with PD), along with recordings of the speakers reading a standardized text. The passage readings were assessed in five dimensions individually by four speech-language pathologists in a blinded and randomized procedure. The 46 acoustic DDK measures were merged with the perceptual ratings of read speech in the same recording session. Ordinal regression models were trained repeatedly on 80% of ratings and acoustic DDK predictors per dimension in 10-folds, and evaluated in testing data. The models developed from [ka] sequences achieved the best performance overall in predicting the clinicians' ratings of passage readings. The developed [pa] and [ta] models showed a much lower performance across all dimensions. The addition of samples with severe impairments and further automation of the procedure is required for the models to be used for screening purposes by non-expert clinical staff.
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| 38. |
- Karlsson, Fredrik, 1975-, et al.
(author)
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Automatic acquisition of jitter and shimmer measurements across large sets of sustained vowel productions
- 2012
-
Conference paper (other academic/artistic)abstract
- Measurements of jitter and shimmer are frequently employed to quantify laryngeal control and stability during voice production in patients(1-3). Accurate estimates of jitter and shimmer may be obtained from acoustic recordings of sustained vowels produced by patients using computer software implementing algorithms for their extraction (e.g. Praat(4) or MDVP(5)). The jitter and shimmer algorithms do not, in themselves, exclude non-stable productions and are influenced by the inclusion of silence in the analysed intervals. As a consequence, reliable measurements of jitter and shimmer are made by manually opening each sound file and selecting an interval for the computations. The current paper proposes an alternative approach to afford a more efficient estimation of jitter and shimmer across a large set of sustained vowel recordings. Using information readily available in the acoustic signal and a combination of algorithms already available within the Praat program, a reliable method for automatic processing of only the sustained vowel in each recording of a large corpus is outlined. The method further affords the acquisition of multiple, repeatable, measurements of jitter and shimmer for sub-intervals of the vowel’s duration (applying more than one algorithm), which additionally provides information concerning the reliability of the jitter or shimmer estimates for a specific vowel production. Comparisons with manually obtained measurements are made for the purpose of validation of the segmentation method.
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| 39. |
- Karlsson, Fredrik, 1975
(author)
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Capacity Control of Residential Heat Pump Heating Systems
- 2007
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Doctoral thesis (other academic/artistic)abstract
- Heat pumps used for space and sanitary hot water heating of residential buildings are increasingly popular in northern Europe. As they compete with other heating equipment and in order to limit the environmental impact of their use, it is very important that heat pumps are energy efficient. The scope of this thesis is to investigate the potential for increased energy efficiency of heat pumps by applying variable-speed capacity control to compressor, pumps and fans, as well as an overall optimisation strategy for on-line optimisation of the operation. Focus has been on ground-source heat pumps connected to hydronic heating systems but the same principles apply also to other types of heat pumps. For air-source heat pumps the defrost function adds one extra parameter to consider and this is partly investigated by the evaluation of a proposal for optimised defrost initiation. Two prototype heat pumps with variable-speed compressors were designed and evaluated by laboratory measurements. The results from these measurements were used as input to models for calculating the energy efficiency of different heat pump systems. The models were used to compare the annual performance of the two prototype heat pumps to the performance of a state-of-the-art intermittently operated ground-source heat pump. One major result is that for the comparison between variable-speed and intermittent operation it is important to consider the transient behaviour of the heating system. In a separate study the possible benefits of using variable-speed controlled circulators were investigated. Results show that the use of efficient circulators is of primary importance, especially for heat pumps with a variable-speed capacity controlled compressor. Of secondary importance comes the variable-speed operation and optimisation of circulator and compressor capacities. Most important in this respect is to control the capacity of the circulator for the bore hole system. Capacity control of the circulators can be implemented by a simple strategy with results very close to an optimised control. Comparing the Seasonal Performance Factor (SPF) of an all variable-speed controlled heat pump (variable-speed pumps and compressor) with optimised pump and compressor capacities to the state-of-the-art intermittently controlled heat pump shows that the SPF could be increased by approximately 30 %. However, this requires improved compressor and system design compared to the two prototype heat pumps.
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| 40. |
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| 41. |
- Karlsson, Fredrik, 1975-, et al.
(author)
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Control of phonatory onset and offset in Parkinson patients following deep brain stimulation of the subthalamic nucleus and caudal Zona Incerta
- 2012
-
In: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 18:7, s. 824-827
-
Journal article (peer-reviewed)abstract
- Laryngeal hypokinesia is a common symptom in Parkinson’s disease (PD) that affects quality of life. Deep brain stimulation (DBS) is well recognized as a complementary method for treatment of motor symptoms in PD but the outcomes on patients’ control over phonatory alternation have yet not been clearly elucidated. The present study examined the effect of subthalamic nucleus STN-DBS (n=8, aged 51-72 yrs; median=63 yrs) and caudal Zona incerta cZi-DBS (n=8,aged 49-71 yrs; median=61 yrs) on control of onset and offset of phonation in connected speech. The patients were evaluated in a preoperatively (Med ON, 1.5 times the ordinary Levodopa dose) and 12 months postoperatively (Med ON, ordinary Levodopa dose). The results provided evidence of a progressive reduction in the ability to manifest alternations between voicing and voiceless states in a reading task. Mean proportion produced with inappropriate voicing increased from 47.6% to 55.3% and from 62.9% to 68.6% of the total duration for the two groups of patients between Pre-op and Post-op, Stim OFF evaluations. The medial and final parts of the fricative were more affected than the initial part, indicating an increased voicing lead into the following vowel. We propose that this reduction in phonatory control is be due to either progression of the disease, an effect of reduced Levodopa dosage or a microlesional effect. Patients’ proficiency in alternating between voiced and voiceless states in connected speech remained unaffected by both STN-DBS and cZi-DBS.
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| 42. |
- Karlsson, Fredrik, 1975-, et al.
(author)
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Deep brain stimulation of caudal zona incerta and subthalamic nucleus in patients with Parkinson’s disease : effects on diadochokinetic rate
- 2011
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In: Parkinson's Disease. - : Hindawi Publishing Corporation. - 2090-8083 .- 2042-0080. ; 2011, s. 605607-
-
Journal article (peer-reviewed)abstract
- The hypokinetic dysarthria observed in Parkinson's disease (PD) affects the range, speed, and accuracy of articulatory gestures in patients, reducing the perceived quality of speech acoustic output in continuous speech. Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) and of the caudal zona incerta (cZi-DBS) are current surgical treatment options for PD. This study aimed at investigating the outcome of STN-DBS (7 patients) and cZi-DBS (7 patients) in two articulatory diadochokinesis tasks (AMR and SMR) using measurements of articulation rate and quality of the plosive consonants (using the percent measurable VOT metric). The results indicate that patients receiving STN-DBS increased in articulation rate in the Stim-ON condition in the AMR task only, with no effect on production quality. Patients receiving cZi-DBS decreased in articulation rate in the Stim-ON condition and further showed a reduction in production quality. The data therefore suggest that cZi-DBS is more detrimental for extended articulatory movements than STN-DBS.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Karlsson, Fredrik, Docent, 1975-, et al.
(author)
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How Well Does Diadochokinetic Task Performance Predict Articulatory Imprecision? : Differentiating Individuals with Parkinson's Disease from Control Subjects
- 2019
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In: Folia Phoniatrica et Logopaedica. - : S. Karger. - 1021-7762 .- 1421-9972. ; 71:5-6, s. 251-260
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate whether syllables produced in an oral diadochokinetic (DDK) task may be quantified so that persons with Parkinson's disease (PD) perceived to have reduced articulatory precision when reading may be correctly identified using that quantification.PATIENTS AND METHODS: Syllable sequences from 38 speakers with PD and 38 gender- and age-matched control speakers (normal controls [NC]) were quantified acoustically and evaluated in terms of (1) the speakers' ability to accurately predict speaker group membership (PD or NC) and (2) their ability to predict reduced/non-reduced articulatory precision.RESULTS: A balanced accuracy of 80-93% in predicting speaker group membership was achieved. The best measures were related to the proportion of a syllable made up of a vowel, amplitude slope and syllable-to-syllable variation in duration and amplitude. The best material was that based on /ka/. Reduced articulatory precision was accurately predicted from DDK measures in 89% of the samples. Release-transient prominence and voicing during the onset of plosives were particularly strong predictors.CONCLUSIONS: DDK sequences can predict articulatory imprecision as observed in another speech task. The linking of performance across speech tasks probably requires measures of stability in syllable durations and amplitudes, as well as measures of subsyllabic acoustic features.
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| 49. |
- Karlsson, Fredrik, 1975
(author)
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Integrated Control of Heat Pumps
- 2003
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Licentiate thesis (other academic/artistic)abstract
- The purpose of the work presented in this thesis is to investigate the potential and prerequisites for improved energy efficiency of heat pump systems using efficient components and proper methods for optimisation of operation. The background is that several investigations have reported on possibilities for increased energy efficiency of heat pumps if variable-speed capacity control is used instead of conventional on/off control. Further improvements are possible if variable speed pumps or fans and electronically controlled expansion valves are used as well. To take full advantage of these new controls they should be properly co-ordinated and optimised. In this work, a measuring system consisting of three temperature sensors and two pressure sensors was used for on-line measurement of the coefficient of performance in an experimental investigation. Knowledge of the performance provides a basis for self-optimising closed-loop control. The measurement system can also be used for Fault Detection and Diagnosis (FDD) and Performance Indication and thus contribute to an integrated control system. The Nelder-Mead simplex method was applied for on-line optimisation. The method was evaluated by computer simulations and shows promising results. It was possible to find the optimal set point, maximising COP, and the method could also handle soft constraints, such as a desired set point for the heating capacity. The potential of variable-speed capacity control was investigated both by laboratory tests and annual energy savings calculations. The laboratory tests were made on a brine-to-water heat pump with a variable-speed piston compressor and an electronic expansion valve. The results from the tests showed a decrease in efficiency when applying variable-speed capacity control to the compressor when compared to conventional on/off control. Analyses indicate that this is due to losses in the frequency converter and increased losses within the compressor, most likely in the electric motor. The electronic valve gave only a marginal increase in efficiency compared to a conventional thermostatic expansion valve. Using these test results as a basis, the possible annual energy savings were calculated. This analysis indicates that there exists an energy saving potential also for variable-speed controlled brine-to-water heat pumps but it requires product development mainly of the compressors. A conservative estimate indicates savings of 10 % compared to on/off control.
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