| 1. |
- Christiansen, M, et al.
(author)
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Mutations in the HERG K+-Ion channel: A novel link between long QT syndrome and sudden infant death syndrome
- 2005
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In: American Journal of Cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 95:3, s. 433-434
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Journal article (peer-reviewed)abstract
- In a 7-week-old infant who experienced sudden infant death syndrome (SIDS), a novel missense mutation was identified in KCNH2, causing a lysine-to-glutamic acid amino acid substitution at position 101 (K101E). KCNH2 codes for the HERG ion channel and mutations in the gene are associated with congenital long-QT syndrome (LQTS), and in the family of this case of SIDS, the mutation was associated with Torsades de pointes tachycardia, making SIDS the most likely outcome of congenital LQTS.
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| 2. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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In: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Research review (peer-reviewed)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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| 3. |
- Simonsen, A. H., et al.
(author)
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A novel panel of cerebrospinal fluid biomarkers for the differential diagnosis of Alzheimer's disease versus normal aging and frontotemporal dementia
- 2007
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In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 24:6, s. 434-440
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Journal article (peer-reviewed)abstract
- BACKGROUND: An early and accurate diagnosis of Alzheimer's disease (AD) is important in order to initiate symptomatic treatment with currently approved drugs and will be of even greater importance with the advent of disease-modifying compounds. METHODS: Protein profiles of human cerebrospinal fluid samples from patients with AD (n = 85), frontotemporal dementia (n = 20), and healthy controls (n = 32) were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to verify previously discovered biomarkers. RESULTS: We verified 15 protein biomarkers that were able to differentiate between AD and controls, and 7 of these 15 markers also differentiated AD from FTD. CONCLUSION: A panel of cerebrospinal fluid protein markers was verified by a proteomics technology which may potentially improve the accuracy of the AD diagnosis.
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| 4. |
- Simonsen, A H, et al.
(author)
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Amyloid beta1-40 quantification in CSF: comparison between chromatographic and immunochemical methods.
- 2007
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:4, s. 246-50
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Journal article (peer-reviewed)abstract
- BACKGROUND/AIMS: Amyloid beta (Abeta) is the principal component of senile plaques, one of the hallmarks of Alzheimer's disease (AD). Evidence is accumulating that soluble aggregates (oligomers) of Abeta are important in the pathogenesis of AD. METHODS: We compared three different methods for quantification of the 40 amino acid form of Abeta (Abeta40) in CSF, two based on antibodies [ELISA and surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF) with antibody-coated arrays] and one based on direct binding of proteins to a protein array [SELDI-TOF and immobilized metal affinity [copper] (IMAC30)]. RESULTS: CSF Abeta40 concentration was only found to be significantly elevated in AD (127% of control levels; p=0.0095) using SELDI-TOF with IMAC30 arrays. CONCLUSIONS: These data suggest that the measured Abeta level in CSF may differ depending on whether antibody-based methods are used or not, possibly caused by epitope masking due to Abeta oligomerization or to binding of Abeta to carrier proteins.
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| 5. |
- Simonsen, A H, et al.
(author)
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Identification of a novel panel of cerebrospinal fluid biomarkers for Alzheimer's disease.
- 2008
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In: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 29:7, s. 961-8
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Journal article (peer-reviewed)abstract
- An early and accurate diagnosis of Alzheimer's disease (AD) is required to initiate symptomatic treatment with currently approved drugs and will be of even greater importance if disease modifying compounds in development display a clinical effect. Protein profiles of human cerebrospinal fluid samples from AD patients (n=95) and population-based healthy controls (n=72) were analyzed by SELDI-TOF-MS in order to discover and characterize novel candidate biomarker combinations that differentiate AD patients from normal aging in this explorative study. Thirty candidate biomarkers (ROC AUC>0.7) were discovered that could differentiate patients with AD from healthy controls. Protein sequence determination and positive identification of 15 biomarkers revealed potential associations between the identified markers and AD pathogenesis. A multi-marker combination of five peaks could distinguish AD from healthy control individuals with high sensitivity (97%) and specificity (98%). The panel of five markers was tested on a blinded independent data set of 30 AD samples and 28 controls giving 100% sensitivity and 97% specificity. This novel panel of biomarkers could potentially be used to improve the accuracy of diagnosis of AD.
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| 6. |
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| 7. |
- Laamanen, R, et al.
(author)
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Client perceptions of the performance of public and independent not-for-profit primary healthcare
- 2006
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In: Scandinavian journal of public health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 34:6, s. 598-608
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Journal article (peer-reviewed)abstract
- Aims: To compare primary healthcare (PHC) provided by an independent not-for-profit organization (INPO) with that provided by two public municipal organizations (MO1 and MO2), in terms of clients' perceptions of performance, acceptance, and trust. Methods: A survey using a pre-tested questionnaire to all clients visiting a health centre (HC) doctor or nurse during one week in 2000 (n=511, 51% response rate) and 2002 (n=275, 47%). The data were analysed by descriptive statistics and cumulative logistic regression analysis. Results: The INPO differed from both publicly provided services in accessibility, consistency of service, and outcomes. Clients reported lower trust in HC provided by public organizations compared with the INPO. Trust was higher if clients also reported experiencing ``very good'' or ``moderate'' organizational access — or if general satisfaction was ``very high'' or ``moderate'' or if they experienced outcomes as ``very good'' or ``moderate'' compared with the ``very poor or low'' situation. Women reported lower trust in HC than men. When the family doctor was included in the same logistic regression model with the service provider, only the family doctor was a significant explanatory variable. Reported acceptance of private alternative service providers among clients was similar between the study organizations. Conclusions: Clients of the INPO generally rated the service more positively than clients of publicly provided services. The results indicate that trust in HC depends more on a family doctor system than a service provider.
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| 8. |
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| 9. |
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| 10. |
- Messias, M. J, et al.
(author)
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The Greenland Sea tracer experiment 1996–2002: Horizontal mixing and transport of Greenland Sea Intermediate Water
- 2008
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In: Progress In Oceanography. - : Elsevier BV. - 0079-6611. ; 78:1, s. 85-105
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Journal article (peer-reviewed)abstract
- In summer 1996, a tracer release experiment using sulphur hexafluoride (SF6) was launched in the intermediate-depth waters of the central Greenland Sea (GS), to study the mixing and ventilation processes in the region and its role in the northern limb of the Atlantic overturning circulation. Here we describe the hydrographic context of the experiment, the methods adopted and the results from the monitoring of the horizontal tracer spread for the 1996–2002 period documented by 10 shipboard surveys. The tracer marked “Greenland Sea Arctic Intermediate Water” (GSAIW). This was redistributed in the gyre by variable winter convection penetrating only to mid-depths, reaching at most 1800 m depth during the strongest event observed in 2002. For the first 18 months, the tracer remained mainly in the Greenland Sea. Vigorous horizontal mixing within the Greenland Sea gyre and a tight circulation of the gyre interacting slowly with the other basins under strong topographic influences were identified. We use the tracer distributions to derive the horizontal shear at the scale of the Greenland Sea gyre, and rates of horizontal mixing at 10 and 300 km scales. Mixing rates at small scale are high, several times those observed at comparable depths at lower latitudes. Horizontal stirring at the sub-gyre scale is mediated by numerous and vigorous eddies. Evidence obtained during the tracer release suggests that these play an important role in mixing water masses to form the intermediate waters of the central Greenland Sea. By year two, the tracer had entered the surrounding current systems at intermediate depths and small concentrations were in proximity to the overflows into the North Atlantic. After 3 years, the tracer had spread over the Nordic Seas basins. Finally by year six, an intensive large survey provided an overall synoptic documentation of the spreading of the tagged GSAIW in the Nordic Seas. A circulation scheme of the tagged water originating from the centre of the GS is deduced from the horizontal spread of the tracer. We present this circulation and evaluate the transport budgets of the tracer between the GS and the surroundings basins. The overall residence time for the tagged GSAIW in the Greenland Sea was about 2.5 years. We infer an export of intermediate water of GSAIW from the GS of 1 to 1.85 Sv (1 Sv = 106 m3 s−1) for the period from September 1998 to June 2002 based on the evolution of the amount of tracer leaving the GS gyre. There is strong exchange between the Greenland Sea and Arctic Ocean via Fram Strait, but the contribution of the Greenland Sea to the Denmark Strait and Iceland Scotland overflows is modest, probably not exceeding 6% during the period under study.
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| 11. |
- Rüetschi, Ulla, 1962, et al.
(author)
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Identification of CSF biomarkers for frontotemporal dementia using SELDI-TOF.
- 2005
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In: Experimental neurology. - : Elsevier BV. - 0014-4886. ; 196:2, s. 273-81
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Journal article (peer-reviewed)abstract
- This investigation describes the discovery of novel possible cerebrospinal fluid (CSF) biomarkers for frontotemporal dementia (FTD) using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS). Sixteen clinically diagnosed FTD patients and 12 non-demented controls were included in the study. CSF was collected and analyzed for protein expression by SELDI-TOF MS. The samples were analyzed on four different array surfaces using two different energy-absorbing molecules as matrices. In total each sample was subjected to eight different surface/matrix conditions. About 2000 protein peaks (mass/charge ratios) were detected. Forty-two peaks were differentially expressed in FTD (P < 0.01). After exclusion of peaks with low signal-to-noise ratio and/or poor resolution and peaks representing differentially charged proteins, 10 peaks remained, five of which were increased and five decreased in FTD cases compared to controls. Using partial least square discriminant analysis (PLS-DA), the combination of these biomarkers discriminated FTD from non-demented controls with a sensitivity of 94%, a specificity of 83% and an accuracy of 89%. Five of the peaks were purified further and identified by tandem MS as a fragment of neurosecretory protein VGF, transthyretin, S-cysteinylated transthyretin, truncated cystatin C and a fragment of chromogranin B. With use of these potential biomarkers, FTD can be distinguished from control subjects with high accuracy in this pilot study.
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| 12. |
- Simonsen, Anja H, et al.
(author)
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Novel panel of cerebrospinal fluid biomarkers for the prediction of progression to Alzheimer dementia in patients with mild cognitive impairment.
- 2007
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In: Archives of neurology. - : American Medical Association (AMA). - 0003-9942. ; 64:3, s. 366-70
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To use proteomic analysis of cerebrospinal fluid to discover novel proteins and peptides able to differentiate between patients with stable mild cognitive impairment (MCI) and those who will progress to Alzheimer disease (AD). DESIGN: Baseline cerebrospinal fluid samples from patients with MCI and healthy controls were profiled using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. SETTING: Memory disorder clinic. PARTICIPANTS: Patients with MCI (n = 113), of whom 56 were cognitively stable and 57 progressed to AD with dementia during a 4- to 6-year follow-up, as well as 28 healthy controls who were followed up for 3 years. Main Outcome Measure During follow-up, 57 patients progressed to AD and 56 patients had stable MCI. Cerebrospinal fluid from these 2 groups of patients was compared using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. RESULTS: We identified a panel of 17 potential biomarkers that could distinguish between patients with stable MCI and patients with MCI who progressed to AD. We have positively identified and characterized 5 of the potential biomarkers. CONCLUSIONS: Proteomic profiling of cerebrospinal fluid provided a novel panel of 17 potential biomarkers for prediction of MCI progression to AD. The 5 identified biomarkers are relevant to the pathogenesis of AD and could help gain an understanding of the molecular pathways in which they may function.
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| 13. |
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| 14. |
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| 15. |
- Simonsen-Rehn, N, et al.
(author)
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Determinants of health promotion action in primary health care: comparative study of health and home care personnel in four municipalities in Finland
- 2009
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In: Scandinavian journal of public health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 37:1, s. 4-12
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Journal article (peer-reviewed)abstract
- Aims: The purpose of this paper is to contribute to understanding which factors influence health promotion action in primary health care (PHC) on the municipal, i.e. local, level. Methods: A cross-sectional mail survey of all PHC personnel in four municipalities in Finland in 2002. The data were analysed by descriptive statistics, and univariate and multivariate logistic regression analyses. Results: A total of 417 (response rate 57%) healthcare professionals participated in the study; 65% of the personnel working in ambulatory care, 52% working in home care and 44% working in inpatient care were engaged in health promotion action (=higher than median engagement). Factors independently associated with engagement in health promotion were organizational values, reflected in perceived skill discretion and social support from coworkers, and the personnel's competence, reflected in knowledge about the health and living conditions of the population served. Further, the opportunities, reflected in cooperation with partners outside the organization were strongly associated with engagement in health promotion action. Conclusions: The results suggest that working conditions such as possibilities for skill usage, reflection and development as well as collegial support enable higher engagement in health promotion action in PHC. However, access to data on the local population's health and living conditions, in addition to opportunities to cooperate with decision makers and partners in the community turned out to be as important. This should be taken into consideration when striving to reorient health services to health promotion.
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