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Sökning: WFRF:(Jakobsson Mattias) > Medicin och hälsovetenskap

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1.
  • Säll, T., et al. (författare)
  • Chloroplast DNA indicates a single origin of the allotetraploid Arabidopsis suecica
  • 2003
  • Ingår i: Journal of Evolutionary Biology. - : John Wiley & Sons Inc.. - 1010-061X .- 1420-9101. ; 16:5, s. 1019-1029
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA sequencing was performed on up to 12 chloroplast DNA regions [giving a total of 4288 base pairs (bp) in length] from the allopolyploid Arabidopsis suecica (48 accessions) and its two parental species, A. thaliana (25 accessions) and A. arenosa (seven accessions). Arabidopsis suecica was identical to A. thaliana at all 93 sites where A. thaliana and A. arenosa differed, thus showing that A. thaliana is the maternal parent of A. suecica. Under the assumption that A. thaliana and A. arenosa separated 5 million years ago, we estimated a substitution rate of 2.9 x 10(-9) per site per year in noncoding single copy sequence. Within A. thaliana we found 12 substitution (single bp) and eight insertion/deletion (indel) polymorphisms, separating the 25 accessions into 15 haplotypes. Eight of the A. thaliana accessions from central Sweden formed one cluster, which was separated from a cluster consisting of central European and extreme southern Swedish accessions. This latter cluster also included the A. suecica accessions, which were all identical except for one 5 bp indel. We interpret this low level of variation as a strong indication that A. suecica effectively has a single origin, which we dated at 20 000 years ago or more.
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2.
  • Jakobsson, Mattias, et al. (författare)
  • Evolution of chloroplast mononucleotide microsatellites in Arabidopsis thaliana
  • 2007
  • Ingår i: Theoretical and Applied Genetics. - : Springer. - 0040-5752 .- 1432-2242. - 0040-5752 ; 114:2, s. 223-235
  • Tidskriftsartikel (refereegranskat)abstract
    • The level of variation and the mutation rate were investigated in an empirical study of 244 chloroplast microsatellites in 15 accessions of Arabidopsis thaliana. In contrast to SNP variation, microsatellite variation in the chloroplast was found to be common, although less common than microsatellite variation in the nucleus. No microsatellite variation was found in coding regions of the chloroplast. To evaluate different models of microsatellite evolution as possible explanations for the observed pattern of variation, the length distribution of microsatellites in the published DNA sequence of the A. thaliana chloroplast was subsequently used. By combining information from these two analyses we found that the mode of evolution of the chloroplast mononucleotide microsatellites was best described by a linear relation between repeat length and mutation rate, when the repeat lengths exceeded about 7 bp. This model can readily predict the variation observed in non-coding chloroplast DNA. It was found that the number of uninterrupted repeat units had a large impact on the level of chloroplast microsatellite variation. No other factors investigated-such as the position of a locus within the chromosome, or imperfect repeats-appeared to affect the variability of chloroplast microsatellites. By fitting the slippage models to the Genbank sequence of chromosome 1, we show that the difference between microsatellite variation in the nucleus and the chloroplast is largely due to differences in slippage rate.
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3.
  • Bridel, Claire, et al. (författare)
  • Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
  • 2019
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
  • Forskningsöversikt (refereegranskat)abstract
    • Importance  Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives  To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources  PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection  Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis  Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure  The cNfL levels adjusted for age and sex across diagnoses.Results  Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance  These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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4.
  • Jonsson, Pernilla, 1978, et al. (författare)
  • Holding on to the indispensable medication –A grounded theory on medication use from the perspective of persons with medication overuse headache
  • 2013
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 14:43, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Medication overuse headache (MOH) is a chronic headache disorder, caused by overuse of acute medication. To date, it remains unclear why some people overuse these medications. The aim of this qualitative study was to explore how individuals with MOH use medications and other strategies to manage headaches in their daily lives, and their thoughts about their own use of acute medication. Our intention was to develop a theoretical model about the development of MOH, from the perspective of those with MOH. Methods: Data collection and analysis were conducted according to grounded theory methodology. The participants were recruited via newspaper advertisements. Fourteen persons with MOH were interviewed in individual qualitative interviews. Results: The basic process leading to medication overuse was holding on to the indispensable medication. The acute medication was indispensable to the participants because they perceived it as the only thing that could prevent headaches from ruining their lives. The participants perceived headaches as something that threatened to ruin their lives. As a result, they went to great lengths trying to find ways to manage it. They tried numerous strategies. However, the only strategy actually perceived as effective was the use of acute medication and they eventually became resigned to the idea that it was the only effective aid. The acute medication thus became indispensable. Their general intention was to use as little medication as possible but they found themselves compelled to medicate frequently to cope with their headaches. They did not like to think about their medication use and sometimes avoided keeping track of the amount used. Conclusions: This qualitative study adds understanding to the process via which MOH develops from the perspective of those having MOH. Such knowledge may help bridge the gap between the perspectives of patients and health-care professionals.
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5.
  • Salzer, Jonatan, et al. (författare)
  • Rituximab in multiple sclerosis : a retrospective observational study on safety and efficacy
  • 2016
  • Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 87:20, s. 2074-2081
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the safety and efficacy of rituximab in multiple sclerosis (MS). Methods: In this retrospective uncontrolled observational multicenter study, off-label rituximab-treated patients with MS were identified through the Swedish MS register. Outcome data were collected from the MS register and medical charts. Adverse events (AEs) grades 2-5 according to the Common Terminology Criteria for Adverse Events were recorded. Results: A total of 822 rituximab-treated patients with MS were identified: 557 relapsing-remitting MS (RRMS), 198 secondary progressive MS (SPMS), and 67 primary progressive MS (PPMS). At baseline, 26.2% had contrast-enhancing lesions (CELs). Patients were treated with 500 or 1,000 mg rituximab IV every 6-12 months, during a mean 21.8 (SD 14.3) months. During treatment, the annualized relapse rates were 0.044 (RRMS), 0.038 (SPMS), and 0.015 (PPMS), and 4.6% of patients displayed CELs. Median Expanded Disability Status Scale remained unchanged in RRMS (p = 0.42) and increased by 0.5 and 1.0 in SPMS and PPMS, respectively (p = 0.10 and 0.25). Infusion-related AEs occurred during 7.8% of infusions and most were mild. A total of 89 AEs grades >= 2 (of which 76 infections) were recorded in 72 patients. No case of progressive multifocal leukoencephalopathy was detected. Conclusions: This is the largest cohort of patients with MS treated with rituximab reported so far. The safety, clinical, and MRI findings in this heterogeneous real-world cohort treated with different doses of rituximab were similar to those reported in previous randomized controlled trials on B-cell depletion therapy in MS. Classification of evidence: This study provides Class IV evidence that for patients with MS, rituximab is safe and effective.
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6.
  • Sjödahl, Gottfrid, et al. (författare)
  • Molecular changes during progression from nonmuscle invasive to advanced urothelial carcinoma
  • 2020
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:9, s. 2636-2647
  • Tidskriftsartikel (refereegranskat)abstract
    • Molecular changes occurring during invasion and clinical progression of cancer are difficult to study longitudinally in patient-derived material. A unique feature of urothelial bladder cancer (UBC) is that patients frequently develop multiple nonmuscle invasive tumors, some of which may eventually progress to invade the muscle of the bladder wall. Here, we use a cohort of 73 patients that experienced a total of 357 UBC diagnoses to study the stability or change in detected molecular alterations during cancer progression. The tumors were subtyped by gene expression profiling and analyzed for hotspot mutations in FGFR3, PIK3CA and TERT, the most frequent early driver mutations in this tumor type. TP53 alterations, frequent in advanced UBC, were inferred from p53 staining pattern, and potential genomic alterations were inferred by gene expression patterns at regions harboring frequent copy number alterations. We show that early driver mutations were largely preserved in UBC recurrences. Changes in FGFR3, PIK3CA or TERT mutation status were not linked to changes in molecular subtype and aggressive behavior. Instead, changes into a more aggressive molecular subtype seem to be associated with p53 alterations. We analyze changes in gene expression from primary tumors, to recurrences and progression tumors, and identify two modes of progression: Patients for whom progression is preceded by or coincides with a radical subtype shift, and patients who progress without any systematic molecular changes. For the latter group of patients, progression may be either stochastic or depending on factors already present at primary tumor initiation.
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7.
  • Cotgreave, Ian, et al. (författare)
  • Pyriproxifen and microcephaly: an investigation of potential ties to the ongoing "Zika epidemic"
  • 2016
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • As part of the Swetox mission to react to emerging concerns in chemical health and environmental safety, a preliminary litterature investigation was undertaken to gather all readily available scientific information on PPF with respect to safety assessment, in order to better understand potential links between chemical exposure and the devopment of microcephaly in affected areas. Therefore the contents of the report do not constitute an attempt at either questioning the use of existing regulatory data in the manner prescribed by international regulatory proceedures, or as a new risk assessment, based on the scientific information and concepts discussed. Here we report our findings, with particular emphasis on exisiting regulatory information, potential for lack of translation of results from regulatory animal testing to humans, lack of human exposure data and suggestions on plausible mode(s) of action of PPF in human neurodevelopmental adversities such as microcephaly.
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8.
  • Gutte, Henrik, et al. (författare)
  • Automated interpretation of PET/CT images in patients with lung cancer.
  • 2007
  • Ingår i: Nuclear Medicine Communications. - 1473-5628. ; 28:2, s. 79-84
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To develop a completely automated method based on image processing techniques and artificial neural networks for the interpretation of combined [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) images for the diagnosis and staging of lung cancer. Methods: A total of 87 patients who underwent PET/CT examinations due to suspected lung cancer comprised the training group. The test group consisted of PET/CT images from 49 patients suspected with lung cancer. The consensus interpretations by two experienced physicians were used as the 'gold standard' image interpretation. The training group was used in the development of the automated method. The image processing techniques included algorithms for segmentation of the lungs based on the CT images and detection of lesions in the PET images. Lung boundaries from the CT images were used for localization of lesions in the PET images in the feature extraction process. Eight features from each examination were used as inputs to artificial neural networks trained to classify the images. Thereafter, the performance of the network was evaluated in the test set. Results: The performance of the automated method measured as the area under the receiver operating characteristic curve, was 0.97 in the test group, with an accuracy of 92%. The sensitivity was 86% at a specificity of 100%. Conclusions: A completely automated method using artificial neural networks can be used to detect lung cancer with such a high accuracy that the application as a clinical decision support tool appears to have significant potential.
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9.
  • Holm, Alexander, et al. (författare)
  • Patients' perspective on prostatic artery embolization : A qualitative study
  • 2021
  • Ingår i: SAGE Open Medicine. - : SAGE Open. - 2050-3121. ; 9, s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim was to describe the patients' experience of undergoing prostatic artery embolization.Methods: A retrospective qualitative interview study was undertaken with 15 patients of mean age 73 years who had undergone prostatic artery embolization with a median duration of 210 min at two medium sized hospitals in Sweden. The reasons for conducting prostatic artery embolization were clean intermittent catheterization (n = 4), lower urinary tract symptoms (n = 10) or haematuria (n = 1). Data were collected through individual, semi-structured telephone interviews 1-12 months after treatment and analysed using qualitative content analysis.Results: Four categories with sub-categories were formulated to describe the results: a diverse experience; ability to control the situation; resumption of everyday activities and range of opinions regarding efficacy of outcomes. Overall, the patients described the procedure as painless, easy and interesting and reported that while the procedure can be stressful, a calm atmosphere contributed to achieving a good experience. Limitations on access to reliable information before, during and after the procedure were highlighted as a major issue. Practical ideas for improving patient comfort during the procedure were suggested. Improved communications between treatment staff and patients were also highlighted. Most patients could resume everyday activities, some felt tired and bruising caused unnecessary worry for a few. Regarding functional outcome, some patients described substantial improvement in urine flow while others were satisfied with regaining undisturbed night sleep. Those with less effect were considering transurethral resection of the prostate as a future option. Self-enrolment to the treatment and long median operation time may have influenced the results.Conclusions: From the patients' perspective, prostatic artery embolization is a well-tolerated method for treating benign prostate hyperplacia.
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10.
  • Jakobsson, Johan, et al. (författare)
  • Acute physiological effects of supramaximal high-intensity interval training in people with or without COPD
  • 2023
  • Ingår i: Medicine & Science in Sports & Exercise. - : Wolters Kluwer. - 0195-9131 .- 1530-0315. ; 55, s. 549-549
  • Tidskriftsartikel (refereegranskat)abstract
    • High-intensity exercise is essential for optimal development of cardiorespiratory fitness and health. This is, however, challenging for most people with chronic obstructive pulmonary disease (COPD) due to ventilatory limitations, leading to exercise at lower intensities accompanied by suboptimal stress on the cardiovascular and muscular system.PURPOSE: To compare the acute effects of a novel concept of short-duration supramaximal high-intensity interval training (HIIT) vs. moderate-intensity continuous training (MICT) in people with COPD and matched healthy controls (HC).METHODS: Sixteen people with mild to severe COPD (75 ± 6 yr; 8 males; 73 ± 13 FEV1%pred; 119 ± 37 W max aerobic power [MAP]) and 14 HC (74 ± 5 yr; 8 males; 106 ± 14 FEV1%pred; 169 ± 38 W MAP) performed HIIT and MICT on a cycle ergometer in a randomized order. HIIT consisted of 10x6s sprints interspersed with 1-min recovery and was performed at two intensities: 60% of max mean power output for 6-sec (MPO6) and 80%MPO6, estimated from the Borg cycle strength test. MICT consisted of 20-min at 60% of MAP, derived from a cardiopulmonary exercise test. Cardiorespiratory parameters, blood lactate concentration, ratings of exertion/symptoms, and exercise modality preference were obtained.RESULTS: Exercise characteristics and physiological data collected at the end of exercise are shown in Table 1. All HIIT sessions were completed, while 1 in 3 people with COPD did not complete MICT. The HIIT modality was preferred by 13/16 (COPD) and 12/14 (HC).CONCLUSION: Short-duration supramaximal HIIT was feasible and enabled a 3.5-fold increase in exercise intensity vs. MICT in people with COPD and HC. Notably, despite the higher exercise intensities, the cardiorespiratory demand during HIIT was similar to MICT and clinically relevant reductions in symptoms were seen in favor of HIIT, in people with COPD. Also, >80% of participants preferred HIIT over MICT.
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