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Sökning: WFRF:(Rummukainen J.)

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1.
  • Adam, A, et al. (författare)
  • Abstracts from Hydrocephalus 2016.
  • 2017
  • Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
  • Tidskriftsartikel (refereegranskat)
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  • Leinonen, V, et al. (författare)
  • Positron emission tomography with [18F]flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients.
  • 2013
  • Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 20:7, s. 1043-52
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [(18) F]flutemetamol and amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical biopsy.METHODS: Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [18F]flutemetamol PET. Seven of these patients also underwent [11C] Pittsburgh compound B (PiB) PET. [18F]Flutemetamol and [11C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain.RESULTS: [18F]Flutemetamol and [11C]PiB SUVRs correlated with biopsy specimen amyloid-β levels contralateral (r = 0.86, P < 0.0001; r = 0.96, P = 0.0008) and ipsilateral (r = 0.82, P = 0.0002; r = 0.87, P = 0.01) to the biopsy site. Association between cortical composite [(18) F]flutemetamol SUVRs and [11C]PiB SUVRs was highly significant (r = 0.97, P = 0.0003).CONCLUSIONS: [18F]Flutemetamol detects brain amyloid-β in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-β pathology, both in patients with possible NPH and among the wider population.
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4.
  • Herukka, S. K., et al. (författare)
  • Amyloid-beta and Tau Dynamics in Human Brain Interstitial Fluid in Patients with Suspected Normal Pressure Hydrocephalus
  • 2015
  • Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 46:1, s. 261-269
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Amyloid-beta (A beta(1-42)), total tau (T-tau), and phosphorylated tau (P-tau(181)) in the cerebrospinal fluid (CSF) are the most promising biomarkers of Alzheimer's disease (AD). Still, little is known about the dynamics of these molecules in the living brain. In a transgenic mouse brain, soluble A beta decreases with increasing age and advanced A beta pathology as seen similarly in CSF. Objective: To assess the relationship between AD-related pathological changes in human brain tissue, ventricular and lumbar CSF, and brain interstitial fluid (ISF). Methods: Altogether 11 patients with suspected idiopathic normal pressure hydrocephalus underwent frontal cortical brain biopsy, 24-h intraventricular pressure monitoring, and a microdialysis procedure. AD-related biomarkers were analyzed from brain tissue, CSF, and ISF. Results: ISF T-tau levels decreased strongly within the first 12 h, then plateauing until the end of the experiment. A beta(1-42) and P-tau(181) remained stable during the experiment (n = 3). T-tau and P-tau were higher in the ISF than in ventricular or lumbar CSF, while A beta(1-42) levels were within similar range in both CSF and ISF samples. ISF P-tau correlated with the ventricular CSF T-tau (r = 0.70, p = 0.017) and P-tau(181) (r = 0.64, p = 0.034). Five patients with amyloid pathology in the brain biopsy tended to reveal lower ISF A beta(1-42) levels than those six without amyloid pathology. Conclusions: This is the first study to report ISF A beta and tau levels in the human brain without significant brain injury. The set-up used enables sampling from the brain ISF for at least 24 h without causing adverse effects due to the microdialysis procedure to follow the dynamics of the key molecules in AD pathogenesis in the living brain at various stages of the disease.
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5.
  • Pyykkö, O. T., et al. (författare)
  • APOE4 predicts amyloid-β in cortical brain biopsy but not idiopathic normal pressure hydrocephalus
  • 2012
  • Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 83:11, s. 1119-1124
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the association of apolipoprotein E (APOE) genotype, especially the APOE4 allele, to (1) idiopathic normal pressure hydrocephalus (iNPH) and (2) amyloid-β (Aβ) plaques in cortical brain biopsies of presumed NPH patients with and without a final clinical diagnosis of Alzheimer's disease (AD). Methods: 202 patients with presumed NPH were evaluated by intraventricular pressure monitoring and frontal cortical biopsy immunostained against Aβ (134 semiquantified by Aβ plaques/mm 2). The 202 patients and 687 cognitively healthy individuals were genotyped for APOE. The final clinical diagnoses in a median follow-up of 3.9 years were: 113 iNPH (94 shunt responsive, 16 shunt non-responsive, three not shunted); 36 AD (12 mixed iNPH + AD); 53 others. Results: The APOE genotypes distributed similarly in the 94 shunt responsive and 16 non-responsive iNPH patients and healthy controls. In multivariate analysis, the APOE4 allele correlated independently with Aβ plaques in the cortical biopsies (OR 8.7, 95% CI 3.6 to 20, p<0.001). The APOE4 allele in presumed NPH predicted later AD as follows: sensitivity 61%; specificity 77%; positive predictive value 37%; negative predictive value 90%. Conclusion: In presumed NPH patients, APOE4 associates independently with the presence of Aβ plaques in the frontal cortical biopsy. APOE4 is not a risk factor for iNPH and does not predict the response to shunt. Our data further support the view that the iNPH syndrome is a distinct dementing disease.
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6.
  • Ruti, P. M., et al. (författare)
  • The West African climate system: a review of the AMMA model inter-comparison initiatives
  • 2011
  • Ingår i: Atmospheric Science Letters. - : Wiley. - 1530-261X. ; 12:1, s. 116-122
  • Tidskriftsartikel (refereegranskat)abstract
    • We review the African Monsoon Multidisciplinary Analysis (AMMA) model inter-comparison activities for West Africa. The Model Inter-comparison Project is an evaluation exercise of how global and regional atmospheric models represent seasonal and intra-seasonal variations of the climate and rainfall over the Sahel. The Land surface Model Inter-comparison Project in turn focuses on modelling critical land surface processes over West Africa and on their link with the atmosphere. The CHEmistry Model Inter-comparison Project (CHEMIP) is a comparison of the tropospheric composition as simulated by a number of Chemical Transport Models (CTM) and Chemistry-Climate Models. We highlight the main model limitations and provide recommendations for future development. Copyright. (C) 2011 Royal Meteorological Society
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  • Seppala, T. T., et al. (författare)
  • CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings
  • 2012
  • Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 78:20, s. 1568-1575
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD. Methods: In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), A beta plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF A beta 42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia. Results: The patients with A beta 42 plaques in the cortical biopsy had lower (p = 0.009) CSF A beta 42 levels than those with no A beta plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) A beta 42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest A beta 42 and highest tau and p-tau 181 levels in CSF. The A beta 42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical A beta was independently predicted by the APOE epsilon 4 carrier status and age but not by CSF A beta 42 or tau levels. Conclusions: Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF A beta 42 and high CSF tau and p-tau levels, respectively. Neurology (R) 2012;78:1568-1575
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  • Luikku, Antti J., et al. (författare)
  • Multimodal analysis to predict shunt surgery outcome of 284 patients with suspected idiopathic normal pressure hydrocephalus
  • 2016
  • Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 158:12, s. 2311-2319
  • Tidskriftsartikel (refereegranskat)abstract
    • Optimal selection of idiopathic normal pressure hydrocephalus (iNPH) patients for shunt surgery is challenging. Disease State Index (DSI) is a statistical method that merges multimodal data to assist clinical decision-making. It has previously been shown to be useful in predicting progression in mild cognitive impairment and differentiating Alzheimer's disease (AD) and frontotemporal dementia. In this study, we use the DSI method to predict shunt surgery response for patients with iNPH. In this retrospective cohort study, a total of 284 patients (230 shunt responders and 54 non-responders) from the Kuopio NPH registry were analyzed with the DSI. Analysis included data from patients' memory disorder assessments, age, clinical symptoms, comorbidities, medications, frontal cortical biopsy, CT/MRI imaging (visual scoring of disproportion between Sylvian and suprasylvian subarachnoid spaces, atrophy of medial temporal lobe, superior medial subarachnoid spaces), APOE genotyping, CSF AD biomarkers, and intracranial pressure. Our analysis showed that shunt responders cannot be differentiated from non-responders reliably even with the large dataset available (AUC = 0.58). Prediction of the treatment response in iNPH is challenging even with our extensive dataset and refined analysis. Further research of biomarkers and indicators predicting shunt responsiveness is still needed.
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14.
  • Luikku, Antti J., et al. (författare)
  • Predicting Development of Alzheimer's Disease in Patients with Shunted Idiopathic Normal Pressure Hydrocephalus
  • 2019
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 71:4, s. 1233-1243
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Idiopathic normal pressure hydrocephalus (iNPH) patients often develop Alzheimer's disease (AD) related brain pathology. Disease State Index (DSI) is a method to combine data from various sources for differential diagnosis and progression of neurodegenerative disorders.Objective: To apply DSI to predict clinical AD in shunted iNPH-patients in a defined population.Methods: 335 shunted iNPH-patients (median 74 years) were followed until death (n = 185) or 6/2015 (n = 150). DSI model (including symptom profile, onset age of NPH symptoms, atrophy of medial temporal lobe in CT/MRI, cortical brain biopsy finding, and APOE genotype) was applied. Performance of DSI model was evaluated with receiver operating characteristic (ROC) curve analysis.Results: A total of 70 (21%) patients developed clinical AD during median follow-up of 5.3 years. DSI-model predicted clinical AD with moderate effectiveness (AUC= 0.75). Significant factors were cortical biopsy (0.69), clinical symptoms (0.66), and medial temporal lobe atrophy (0.66).Conclusion: We found increased occurrence of clinical AD in previously shunted iNPH patients as compared with general population. DSI supported the prediction of AD. Cortical biopsy during shunt insertion seems indicated for earlier diagnosis of comorbid AD.
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15.
  • Nilsson, Annika E., et al. (författare)
  • Hög tid för klimatanpassning
  • 2010
  • Ingår i: Miljöaktuellt. - 0345-763X. ; 37:10, s. 9-
  • Tidskriftsartikel (populärvet., debatt m.m.)
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16.
  • Paeth, Heiko, et al. (författare)
  • Progress in regional downscaling of west African precipitation
  • 2011
  • Ingår i: Atmospheric Science Letters. - : Wiley. - 1530-261X. ; 12:1, s. 75-82
  • Tidskriftsartikel (refereegranskat)abstract
    • We review the recent progress in dynamical and statistical downscaling approaches for west African precipitation and perform a regional climate model (RCM) intercomparison using the novel multi-model RCM data set from the Ensembles-based Predictions of Climate Changes and Their Impacts (ENSEMBLES) and African Monsoon Multidisciplinary Analyses (AMMA) projects. Present RCMs have distinct systematic errors in terms of west African precipitation varying in amplitude and pattern across models. This is also reflected in a relatively large spread in projected future precipitation trends. Altogether, the ENSEMBLES RCMs indicate a prevailing drying tendency in sub-Saharan Africa. Statistical post-processing of simulated precipitation is a promising tool to reduce systematic model errors before application in impact studies.
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  • Rummukainen, Markku, et al. (författare)
  • Klimatet
  • 2006
  • Ingår i: Klimatet och skogen - underlag för nationell forskning (Kungliga skogs- och lantbruksakademiens tidskrift). - 9185205427 ; 9, s. 35-41
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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19.
  • Rummukainen, Markku, et al. (författare)
  • Klimatomställning krävs – men vi klarar utmaningen
  • 2019
  • Ingår i: SVT Nyheter. Opinion.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • "Med tanke på att uppvärmningen redan nått cirka en grad, är de närmaste tio årens beslut, investeringar och andra åtgärder avgörande”, skriver fyra forskare.
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20.
  • Rummukainen, M, et al. (författare)
  • Vacancy-impurity pairs in n-type Si1-xGex studied by positron spectroscopy
  • 2006
  • Ingår i: Physica. B, Condensed matter. - : Elsevier BV. - 0921-4526 .- 1873-2135. ; 376, s. 208-211
  • Tidskriftsartikel (refereegranskat)abstract
    • Positron annihilation spectroscopy was applied to study relaxed P-doped n-type Si1-xGex layers with Ge concentrations up to 30%. As-grown SiGe layers were defect-free and annihilations are superpositions from bulk Si and Ge. Proton irradiation at 2 MeV energy with a 1.6 x 10(15) cm(-2) fluence was used to produce saturated positron trapping in monovacancy related defects. The defects were identified as V-P pairs, the E-center. The distribution of Si and Ge atoms surrounding the E-center is the same as in the host lattice. The vacancy migration process leading to the formation of V-P pairs therefore does not seem to have a preference for either Si or Ge atoms. (c) 2005 Elsevier B.V. All rights reserved.
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21.
  • Rummukainen, M, et al. (författare)
  • Vacancy-impurity pairs in relaxed Si1-xGex layers studied by positron annihilation spectroscopy
  • 2006
  • Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 73:16
  • Tidskriftsartikel (refereegranskat)abstract
    • Positron annihilation spectroscopy was applied to study relaxed P-doped n-type and undoped Si1-xGex layers with x up to 0.30. The as-grown SiGe layers were found to be defect free and annihilation parameters in a random SiGe alloy could be represented as superpositions of annihilations in bulk Si and Ge. A 2 MeV proton irradiation with a 1.6x10(15) cm(-2) fluence was used to produce saturated positron trapping in monovacancy related defects in the n-type layers. The defects were identified as V-P pairs, the E center. The distribution of Si and Ge atoms surrounding the E center was the same as in the host lattice. The process leading to the formation of V-P pairs therefore does not seem to have a significant preference for either Si or Ge atoms. In undoped Si1-xGex we find that a similar irradiation produces a low concentration of divacancies or larger vacancy defects and found no evidence of monovacancies surrounded by several Ge atoms.
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