1. |
- Benisty, S, et al.
(author)
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Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study.
- 2009
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In: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:5, s. 478-83
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Journal article (peer-reviewed)abstract
- OBJECTIVES: In cerebral small vessel disease, white-matter hyperintensities (WMH) and lacunes are both related to cognition. Still, their respective contribution in older people remains unclear. The purpose of this study is to assess the topographic distribution of lacunes and determine whether it has an impact on cognitive functions in a sample of non-disabled patients with age-related white-matter changes. METHODS: Data were drawn from the baseline evaluation of the LADIS (Leucoaraioisis and Disability study) cohort of non-disabled subjects beyond 65 years of age. The neuropsychological evaluation was based on the Mini Mental Status Examination (MMSE), a modified Alzheimer Diseases Assessment Scale for global cognitive functions, and compound Z scores for memory, executive functions, speed and motor control. WMH were rated according to the Fazekas scale; the number of lacunes was assessed in the following areas: lobar white matter, putamen/pallidum, thalamus, caudate nucleus, internal/external capsule, infratentorial areas. An analysis of covariance was performed after adjustment for possible confounders. RESULTS: Among 633 subjects, 47% had at least one lacune (31% at least one within basal ganglia). The presence of lacunes in the thalamus was associated with lower scores of MMSE (beta = -0.61; p = 0.043), and worse compound scores for speed and motor control (beta = -0.25; p = 0.006), executive functions (beta = -0.19; p = 0.022) independently of the cognitive impact of WMH. There was also a significant negative association between the presence of lacunes in putamen/pallidum and the memory compound Z score (beta = -0.13; p = 0.038). By contrast, no significant negative association was found between cognitive parameters and the presence of lacunes in internal capsule, lobar white matter and caudate nucleus. CONCLUSION: In non-disabled elderly subjects with leucoaraisosis, the location of lacunes within subcortical grey matter is a determinant of cognitive impairment, independently of the extent of WMH.
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- Wallin, Anders, 1950, et al.
(author)
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Donepezil in Alzheimer's disease : What to expect after 3 years of treatment in a routine clinical setting
- 2007
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In: Dementia and Geriatric Cognitive Disorders. - Basel : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:3, s. 150-160
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Journal article (peer-reviewed)abstract
- Background/Aims: Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer's disease. The outcome of continuous long-term treatment in the routine clinical settings remains to be investigated. Methods: The Swedish Alzheimer Treatment Study (SATS) is a descriptive, prospective, longitudinal, multicentre study. Four hundred and thirty-five outpatients with the clinical diagnosis of Alzheimer's disease, received treatment with donepezil. Patients were assessed with Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), global rating (CIBIC) and Instrumental Activities of Daily Living (IADL) at baseline and every 6 months for a total period of 3 years. Results: The mean MMSE change from baseline was positive for more than 6 months and in subgroups of patients for 12 months. After 3 years of treatment the mean change from baseline in MMSE-score was 3.8 points (95% CI, 3.0-4.7) and the ADAS-cog rise was 8.2 points (95% CI, 6.4-10.1). This is better than expected in untreated historical cohorts, and better than the ADAS-cog rise calculated by the Stern equation (15.6 points, 95% CI, 14.5-16.6). After 3 years with 38% of the patients remaining, 30% of the them were unchanged or improved in the global assessment. Conclusion: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting. Copyright © 2007 S. Karger AG.
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- Teodorczuk, A., et al.
(author)
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White matter changes and late-life depressive symptoms - Longitudinal study
- 2007
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In: BRITISH JOURNAL OF PSYCHIATRY. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 191, s. 212-217
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Journal article (peer-reviewed)abstract
- Evidence from cross-sectional studies suggests a link between cerebral age-related white matter changes and depressive symptoms in older people, although the temporal association remains unclear.AimsTo investigate age-related white matter changes on magnetic resonance imaging (MRI) as an independent predictor of depressive symptoms at 1 year after controlling for known confounders.MethodIn a pan-European multicentre study of 639 older adults without significant disability, MRI white matter changes and demographic and clinical variables, including cognitive scores, quality of life, disability and depressive symptoms, were assessed at baseline. Clinical assessments were repeated at 1 year.ResultsUsing logistic regression analysis, severity of white matter changes was shown to independently and significantly predict depressive symptoms at 1 year after controlling for baseline depressive symptoms, quality of life and worsening disability (P<0.01).ConclusionsWhite matter changes pre-date and are associated with the development of depressive symptoms. This has implications for treatment and prevention of depression in later life.
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6. |
- Österlund, m, et al.
(author)
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Tomography of canisters for spent nuclear fuel
- 2006
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In: International workshop on Fast Neutron Detectors and Applications,Cape Town, South Africa, April 3-6, 2006. ; , s. 030-
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Conference paper (peer-reviewed)
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7. |
- Curtin, W. A., et al.
(author)
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Multi-scale plasticity modeling : Coupled discrete dislocation and continuum crystal plasticity
- 2008
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In: Advances in Heterogeneous Material Mechanics 2008 - 2nd International Conference on Heterogeneous Material Mechanics, ICHMM 2008. - 9781932078800 ; , s. 320-320
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Conference paper (peer-reviewed)abstract
- A hierarchical multiscale model that couples a region of material described by discrete dislocation plasticity1 to a surrounding region described by conventional crystal plasticity is presented. The coupled model captures size-dependent plasticity phenomena, such as dislocation structuring and formation of geometrically necessary dislocations, that can occur at the micron scale while also capturing the plastic flow, and associated energy dissipation, at much larger scales where size-dependent effects are minimal. The key to the model is the treatment of the interface between the discrete and continuum regions, where continuity of tractions and displacements is maintained in an average sense and the flow of burgers vector via "passing" of discrete dislocations is managed. The model is validated through uniaxial plane-strain tension tests which show that the coupled model deforms similarly to both single-scale models. The multiscale model is then applied to study crack growth, where both near-tip dislocation structures and far-field plastic dissipation are crucial to the overall toughening. Results show that the toughening is nearly independent of the size of the discrete dislocation plasticity region around the crack tip down to 5um, simultaneously validating the model and identifying the lengths scales over which size dependence plays a role in this problem. The multiscale model reduces the computational burden of discrete dislocation plasticity modeling substantially with little or no loss of fidelity in the predictions of material behavior, thereby greatly extending the range of discrete dislocation modeling. Future work will combine this method with the Coupled Atomistic/Discrete-Dislocation2 model developed by one of the co-authors, leading to a true atom-to-continuum multiscale model for metallic materials.
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- Gray, Marcus A, et al.
(author)
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Following one's heart: cardiac rhythms gate central initiation of sympathetic reflexes.
- 2009
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In: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 29:6, s. 1817-25
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Journal article (peer-reviewed)abstract
- Central nervous processing of environmental stimuli requires integration of sensory information with ongoing autonomic control of cardiovascular function. Rhythmic feedback of cardiac and baroreceptor activity contributes dynamically to homeostatic autonomic control. We examined how the processing of brief somatosensory stimuli is altered across the cardiac cycle to evoke differential changes in bodily state. Using functional magnetic resonance imaging of brain and noninvasive beat-to-beat cardiovascular monitoring, we show that stimuli presented before and during early cardiac systole elicited differential changes in neural activity within amygdala, anterior insula and pons, and engendered different effects on blood pressure. Stimulation delivered during early systole inhibited blood pressure increases. Individual differences in heart rate variability predicted magnitude of differential cardiac timing responses within periaqueductal gray, amygdala and insula. Our findings highlight integration of somatosensory and phasic baroreceptor information at cortical, limbic and brainstem levels, with relevance to mechanisms underlying pain control, hypertension and anxiety.
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13. |
- Hyvonen, R., et al.
(author)
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The likely impact of elevated [CO2], nitrogen deposition, increased temperature and management on carbon sequestration in temperate and boreal forest ecosystems: a literature review
- 2007
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In: New Phytologist. - Cambridge : Wiley. - 0028-646X .- 1469-8137. ; 173:3, s. 463-480
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Research review (peer-reviewed)abstract
- Temperate and boreal forest ecosystems contain a large part of the carbon stored on land, in the form of both biomass and soil organic matter. Increasing atmospheric [CO2], increasing temperature, elevated nitrogen deposition and intensified management will change this C store. Well documented single-factor responses of net primary production are: higher photosynthetic rate (the main [CO2] response); increasing length of growing season (the main temperature response); and higher leaf-area index (the main N deposition and partly [CO2] response). Soil organic matter will increase with increasing litter input, although priming may decrease the soil C stock initially, but litter quality effects should be minimal (response to [CO2], N deposition, and temperature); will decrease because of increasing temperature; and will increase because of retardation of decomposition with N deposition, although the rate of decomposition of high-quality litter can be increased and that of low-quality litter decreased. Single-factor responses can be misleading because of interactions between factors, in particular those between N and other factors, and indirect effects such as increased N availability from temperature-induced decomposition. In the long term the strength of feedbacks, for example the increasing demand for N from increased growth, will dominate over short-term responses to single factors. However, management has considerable potential for controlling the C store.
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- Mattsson, Niklas, 1979, et al.
(author)
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Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis.
- 2009
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 15:4, s. 448-54
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Journal article (peer-reviewed)abstract
- BACKGROUND: Cell and animal experiments have shown that beta-site APP-cleaving enzyme 1 (BACE1) may be involved in myelination. OBJECTIVE: Here, we assess the association of cerebrospinal fluid (CSF) BACE1 activity with multiple sclerosis (MS). METHODS: BACE1 activity and levels of secreted amyloid precursor protein (APP) and amyloid-beta (Abeta) isoforms were analyzed in CSF from 100 patients with MS and 114 neurologically healthy controls. Patients with systemic lupus erythematosus (SLE), 26 with and 41 without cerebral engagement, were also included to enable comparisons with regards to another autoimmune disease. A subset of patients with MS and controls underwent a second lumbar puncture after 10 years. RESULTS: MS patients had lower CSF BACE1 activity than controls (P = 0.03) and patients with cerebral SLE (P < 0.001). Patients with cerebral SLE had higher BACE1 activity than any other group (P < 0.05 for all comparisons). BACE1 activity correlated with the different amyloid markers in all study groups. BACE1 activity decreased over 10 years in the MS group (P = 0.039) and correlated weakly with clinical disease severity scores in an inverse manner. CONCLUSIONS: These results suggest an involvement of BACE1 in the MS disease process.
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18. |
- Meijers, Judith M M, et al.
(author)
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Assessing the relationships between contextual factors and research utilization in nursing : systematic literature review
- 2006
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In: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 55:5, s. 622-35
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Journal article (peer-reviewed)abstract
- AIM: This paper reports a systematic literature review examining relationships between contextual factors and research utilization in nursing, examining the strength of these relationships, and mapping the contextual factors to the Promoting Action on Research Implementation in Health Services model of research implementation.BACKGROUND: Healthcare organizations have long struggled with how to improve clinical care outcomes. Understanding which contextual factors enhance nursing research utilization may support organizations in creating environments that facilitate the uptake of evidence in nursing practice to improve these outcomes.METHODS: A search of five electronic bibliographic databases and a manual search of specific journals were conducted for studies that were published in English and examined contextual factors as independent variables and research utilization as the dependent variable from the perspective of nurses working in clinical practice. The studies were assessed for quality of design, sample, measurement and statistical analysis.RESULTS: Ten papers met the search criteria. Six contextual factors were identified as having a statistically significant relationship with research utilization, namely the role of the nurse, multi-faceted access to resources, organizational climate, multi-faceted support, time for research activities and provision of education. The contextual factors could successfully be mapped to the dimensions of context in the Promoting Action on Research Implementation in Health Services framework (context, culture, leadership), with the exception of evaluation.CONCLUSION: The strength of the relationship between the six contextual factors and research utilization by nurses is still largely unknown as (a) few studies were found of sufficient quality because of methodological limitations and (b) the results in reviewed studies were mixed. More robust methods in future work would yield a better understanding of the full impact of contextual factors on nurses' use of research.
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21. |
- 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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27. |
- Teodorczuk, A., et al.
(author)
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Relationship between baseline white-matter changes and development of late-life depressive symptoms: 3-year results from the LADIS study.
- 2009
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In: Psychological medicine. - 1469-8978. ; 40:4, s. 603-610
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Journal article (peer-reviewed)abstract
- BACKGROUND: Growing evidence suggests that cerebral white-matter changes and depressive symptoms are linked directly along the causal pathway. We investigated whether baseline severity of cerebral white-matter changes predict longer-term future depressive outcomes in a community sample of non-disabled older adults.MethodIn the Leukoaraiosis and Disability in the Elderly (LADIS) study, a longitudinal multi-centre pan-European study, 639 older subjects underwent baseline structural magnetic resonance imaging (MRI) and clinical assessments. Baseline severity of white-matter changes was quantified volumetrically. Depressive outcomes were assessed in terms of depressive episodes and depressive symptoms, as measured by the Geriatric Depression Scale (GDS). Subjects were clinically reassessed annually for up to 3 years. Regression models were constructed to determine whether baseline severity of white-matter changes predicted future depressive outcomes, after controlling for confounding factors. RESULTS: Baseline severity of white-matter changes independently predicted depressive symptoms at both 2 (p<0.001) and 3 years (p=0.015). Similarly, white-matter changes predicted incident depression (p=0.02). Over the study period the population became significantly more disabled (p<0.001). When regression models were adjusted to account for the influence of the prospective variable transition to disability, baseline severity of white-matter changes no longer predicted depressive symptoms at 3 years (p=0.09) or incident depression (p=0.08). CONCLUSIONS: Our results support the vascular depression hypothesis and strongly implicate white-matter changes in the pathogenesis of late-life depression. Furthermore, the findings indicate that, over time, part of the relationship between white-matter changes and depression may be mediated by loss of functional activity.
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32. |
- Baezner, H, et al.
(author)
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Association of gait and balance disorders with age-related white matter changes: the LADIS study.
- 2008
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 70:12, s. 935-42
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Journal article (peer-reviewed)abstract
- OBJECTIVE: In the Leukoaraiosis and Disability (LADIS) Study, 11 European centers are evaluating the role of age-related white matter changes (ARWMC) as an independent determinant of the transition to disability in the elderly (65 to 84 years). We aimed at determining the influence of ARWMC on different objective measures of gait and balance. METHODS: Six hundred thirty-nine nondisabled individuals were prospectively enrolled and are being followed-up for 3 years. Subjects are graded in three standardized categories of ARWMC (mild, moderate, and severe) according to central MRI reading. Quantitative tests of gait and balance include the Short Physical Performance Battery (SPPB; range: 0 [poor] to 12 [normal]), a timed 8-m walk, and a timed single leg stance test. RESULTS: In cross-sectional analysis, deficiencies in gait and balance performance were correlated with the severity of ARWMC (SPPB: 10.2 +/- 2.1 in the mild, 9.9 +/- 2.0 in the moderate, 8.9 +/- 2.6 in the severe group; p < 0.001). Walking speed correlated with the severity of ARWMC (1.24 +/- 0.28 m/second in the mild, 1.18 +/- 0.32 m/second in the moderate, and 1.09 +/- 0.31 m/second in the severe group; p < 0.001). Balance was best in individuals with mild ARWMC (single leg stance time: 18.9 +/- 10.8 seconds) compared with moderate and severe ARWMC (16.4 +/- 10.8 and 13.6 +/- 11.2 seconds) (p < 0.001). Physically inactive individuals had a higher risk of a pathologic SPPB score (moderate vs mild ARWMC: odds ratio 1.60, 95% CI 1.02 to 2.52; severe vs mild ARWMC: odds ratio 1.75, 95% CI 1.09 to 2.80). CONCLUSIONS: Our findings support a strong association between the severity of age-related white matter changes and the severity of gait and motor compromise. Physical activity might have the potential to reduce the risk of limitations in mobility.
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33. |
- Balocco, C, et al.
(author)
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Microwave detection at 110 GHz by nanowires with broken symmetry
- 2005
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In: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 5:7, s. 1423-1427
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Journal article (peer-reviewed)abstract
- By using arrays of nanowires with intentionally broken symmetry, we were able to detect microwaves up to 110 GHz at room temperature. This is, to the best of our knowledge, the highest speed that has been demonstrated in different types of novel electronic nanostructures to date. Our experiments showed a rather stable detection sensitivity over a broad frequency range from 100 MHz to 110 GHz. The novel working principle enabled the nanowires to detect microwaves efficiently without a dc bias. In principle, the need for only one high-resolution lithography step and the planar architecture allow an arbitrary number of nanowires to be made by folding a linear array as many times as required over a large area, for example, a whole wafer. Our experiment on 18 parallel nanowires showed a sensitivity of approximately 75 mV dc output/mW of nominal input power of the 110 GHz signal, even though only about 0.4% of the rf power was effectively applied to the structure because of an impedance mismatch. Because this array of nanowires operates simultaneously, low detection noise was achieved, allowing us to detect -25 dBm 110 GHz microwaves at zero bias with a standard setup.
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34. |
- Bergenfelz, Anders, et al.
(author)
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Scandinavian quality register for thyroid and parathyroid surgery: audit of surgery for primary hyperparathyroidism
- 2007
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In: Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie. - : Springer Science and Business Media LLC. - 1435-2443 .- 1435-2451. ; 392:4, s. 445-51
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIM: Scandinavian Quality Register for Thyroid and Parathyroid Surgery is an on-line web-based database with the aim to improve the quality of thyroid and parathyroid surgery. Preliminary data from surgery for primary hyperparathyroidism are reported here. MATERIALS AND METHODS: Fifteen departments registered 806 operations, with 639 women (79.7%) and 167 men. The median age of the patients was 62 years. RESULTS: Approximately 95.4% of the patients had sporadic disease and first time operation was performed in 93.8% of the patients. Localization examinations were performed in 524 patients (65%); sestamibi scintigraphy in 413 patients, with a true positive adenoma localization in 64.4% and ultrasound in 293 patients with adenoma localization in 61.1%. Bilateral neck exploration was performed in 66.8%, unilateral exploration in 16.1%, and focused minimal invasive surgery in 17.1%. In 301 patients planned for limited parathyroid exploration, conversion to bilateral neck surgery occurred in 11%. The cure rate, based on short follow-up, was 91.9%. Postoperative hypocalcemia occurred in 11.4% of the patients, and was associated with reoperation, concomitant thyroid operation, and the weight of excised parathyroid tissue. CONCLUSION: Localization examinations are performed in 2/3 of the patients, but limited neck exploration was performed in only approximately 1/3 of the operations. The cure rate was lower and postoperative hypocalcemia was more frequent than expected.
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- Betson, N. R., et al.
(author)
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No diurnal variation in rate or carbon isotope composition of soil respiration in a boreal forest
- 2007
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In: Tree Physiology. - 0829-318X. ; 27:5, s. 749-756
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Journal article (peer-reviewed)abstract
- Characterization of soil respiration rates and delta(13C) values of soil-respired CO2 are often based on measurements at a particular time of day. A study by Gower et al. (2001) in a boreal forest demonstrated diurnal patterns of soil CO2 flux using transparent measurement chambers that included the understory vegetation. It is unclear whether these diurnal patterns were solely the result of photosynthetic CO2 uptake during the day by the understory or whether there were underlying trends in soil respiration, perhaps driven by plant root allocation, as recently demonstrated in Mediterranean oak savannah. We undertook intensive sampling campaigns in a boreal Picea abies L. Karst. forest to investigate whether diurnal variations in soil respiration rate and stable carbon isotope ratio (delta C-13) exist in this ecosystem when no understory vegetation is present in the measurement chamber. Soil respiration rates and delta C-13 were measured on plots in which trees were either girdled (to terminate the fraction of soil respiration directly dependent on recent photosynthate from the trees), or not girdled, every 4 h over two 48-hour cycles during the growth season of 2004. Shoot photosynthesis and environmental parameters were measured concurrently. No diurnal patterns in soil respiration rates and delta C-13 were observed in either treatment, despite substantial variations in climatic conditions and shoot photosynthetic rates in non-girdled trees. Consequently, assessment of daily soil respiration rates and delta C-13 in boreal forest systems by single, instantaneous daily measurements does not appear to be confounded by substantial diurnal variation.
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- Blahak, C, et al.
(author)
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Deep frontal and periventricular age related white matter changes but not basal ganglia and infratentorial hyperintensities are associated with falls: cross sectional results from the LADIS study.
- 2009
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In: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:6, s. 608-13
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Journal article (peer-reviewed)abstract
- BACKGROUND: Global age related white matter changes (ARWMC) are associated with progressive gait disturbances and falls, hypothesised to result from interruptions of cortico-subcortical circuits controlling balance, posture and locomotion. METHODS: The location of ARWMC in a large cohort of elderly non-disabled individuals with reported falls was analysed, using the cross sectional data of the Leukoaraiosis and Disability (LADIS) study. Detailed anatomical distributions of ARWMC assessed by MRI studies were analysed with respect to falls and balance performance. RESULTS: The severity of global ARWMC was significantly associated with a history of falls in the year prior to study inclusion (22.2% in the mild, 31.6% in the moderate and 37.3% in the severe ARWMC group according to the Fazekas scale; p = 0.002). Analysing the anatomical distribution of ARWMC, using the semiquantitative Scheltens scale, in multivariate analysis, periventricular (p = 0.006) and frontal deep (p = 0.033) ARWMC were independently associated with falls. Furthermore, logistic regression identified frontal deep (p = 0.003) ARWMC, but not basal ganglia and infratentorial hyperintensities, as significantly associated with balance disturbances. CONCLUSION: The association of frontal and periventricular ARWMC with falls supports the hypothesis that interruption of frontal subcortical motor circuits lead to balance disturbances and hence to an increased risk for falls in ARWMC.
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40. |
- Blennow, K., et al.
(author)
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EVOLUTION OF A beta 42 AND A beta 40 LEVELS AND A beta 42/A beta 40 RATIO IN PLASMA DURING PROGRESSION OF ALZHEIMER'S DISEASE: A MULTICENTER ASSESSMENT
- 2009
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In: Journal Of Nutrition Health & Aging. - 1279-7707. ; 13:3, s. 205-208
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Conference paper (peer-reviewed)abstract
- Objective: To better understand the seemingly contradictory plasma beta-amyloid (A beta) results in Alzheimer's disease (AD) patients by using a newly developed plasma A beta assay, the INNO-BIA plasma A beta forms, in a multicenter study. Methods: A combined retrospective analysis of plasma A beta isoforms on mild cognitive impairment (MCI) from three large cross-sectional studies involving 643 samples from the participating German and Swedish centers. Results: Detection modules based on two different amino (N)-terminal specific A beta monoclonal antibodies demonstrated that A beta in plasma could be reliable quantified using a sandwich immunoassay technology with high precision, even for low A beta 42 plasma concentrations. A beta 40 and A beta 42 concentrations varied consistently with the ApoE genotype, while the A beta 42/A beta 40 ratio did not. Irrespective of the decrease of the A beta 42/A beta 40 ratio with age and MMSE, this parameter was strongly associated with AD, as defined in this study by elevated hyperphosphorylated (P-tau181P) levels in cerebrospinal fluid (CSF). Conclusion: A highly robust assay for repeatedly measuring A beta forms in plasma such as INNO-BIA plasma A beta forms might be a useful tool in a future risk assessment of AD.
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- Brys, Miroslaw, et al.
(author)
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Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment.
- 2009
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In: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:5, s. 682-90
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To longitudinally evaluate five cerebrospinal fluid (CSF) biomarkers in the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD). METHODS: A baseline and 2-year follow-up clinical and CSF study of 86 subjects, including 22 MCI patients that declined to AD (MCI-AD), 43 MCI that did not deteriorate (MCI-MCI) and 21 controls (NL-NL). All subjects were studied for total and phosphorylated tau (T-tau, P-tau(231)), amyloid beta (Abeta) Abeta(42)/Abeta(40) ratio, isoprostane (IP) as well as P-tau(231)/Abeta(42/40) and T-tau/Abeta(42/40) ratios. RESULTS: At baseline and at follow-up MCI-AD showed higher levels P-tau(231), T-tau, IP, P-tau(231)/Abeta(42/40) and T-tau/Abeta(42/40) ratios and lower Abeta(42)/Abeta(40) than MCI-MCI or NL-NL. Baseline P-tau(231) best predicted MCI-AD (80%, p<0.001) followed in accuracy by P-tau(231)/Abeta(42/40) and T-tau/Abeta(42/40) ratios (both 75%, p's<0.001), T-tau (74%, p<0.001), Abeta(42)/Abeta(40) (69%, p<0.01), and IP (68%, p<0.01). Only IP showed longitudinal effects (p<0.05). CONCLUSIONS: P-tau(231) is the strongest predictor of the decline from MCI to AD. IP levels uniquely show longitudinal progression effects. These results suggest the use of CSF biomarkers in secondary prevention trials.
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44. |
- Charkoudian, N., et al.
(author)
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Relationship between muscle sympathetic nerve activity and systemic hemodynamics during nitric oxide synthase inhibition in humans
- 2006
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In: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 291:3
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Journal article (peer-reviewed)abstract
- Large interindividual differences exist in resting sympathetic nerve activity (SNA) among normotensive humans with similar arterial pressure (AP). We recently showed inverse relationships of resting SNA with cardiac output (CO) and vascular adrenergic responsiveness that appear to balance the influence of differences in SNA on blood pressure. In the present study, we tested whether nitric oxide (NO)-mediated vasodilation has a role in this balance by evaluating hemodynamic responses to systemic NO synthase (NOS) inhibition in individuals with low and high resting muscle SNA (MSNA). We measured MSNA via peroneal microneurography, CO via acetylene uptake and AP directly, at baseline and during increasing systemic doses of the NOS inhibitor NG-monomethyl-l-arginine (l-NMMA). Baseline MSNA ranged from 9 to 38 bursts/min (13 to 68 bursts/100 heartbeats). l-NMMA caused dose-dependent increases in AP and total peripheral resistance and reflex decreases in CO and MSNA. Increases in AP with l-NMMA were greater in individuals with high baseline MSNA ( PANOVA < 0.05). For example, after 8.5 mg/kg of l-NMMA, in the low MSNA subgroup ( n = 6, 28 ± 4 bursts/100 heartbeats), AP increased 9 ± 1 mmHg, whereas in the high-MSNA subgroup ( n = 6, 58 ± 3 bursts/100 heartbeats), AP increased 15 ± 2 mmHg ( P < 0.01). The high-MSNA subgroup had lower baseline CO and smaller decreases in CO with l-NMMA, but changes in total peripheral resistance were not different between groups. We conclude that differences in CO among individuals with varying sympathetic traffic have important hemodynamic implications during disruption of NO-mediated vasodilation.
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47. |
- Cummings, Greta G, et al.
(author)
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Influence of organizational characteristics and context on research utilization
- 2007
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In: Nursing Research. - 0029-6562 .- 1538-9847. ; 56:4 Suppl, s. 24-39
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Journal article (peer-reviewed)abstract
- BACKGROUND: Despite three decades of empirical investigation into research utilization and a renewed emphasis on evidence-based medicine and evidence-based practice in the past decade, understanding of factors influencing research uptake in nursing remains limited. There is, however, increased awareness that organizational influences are important.OBJECTIVES: To develop and test a theoretical model of organizational influences that predict research utilization by nurses and to assess the influence of varying degrees of context, based on the Promoting Action on Research Implementation in Health Services (PARIHS) framework, on research utilization and other variables.METHODS: The study sample was drawn from a census of registered nurses working in acute care hospitals in Alberta, Canada, accessed through their professional licensing body (n = 6,526 nurses; 52.8% response rate). Three variables that measured PARIHS dimensions of context (culture, leadership, and evaluation) were used to sort cases into one of four mutually exclusive data sets that reflected less positive to more positive context. Then, a theoretical model of hospital- and unit-level influences on research utilization was developed and tested, using structural equation modeling, and 300 cases were randomly selected from each of the four data sets.RESULTS: Model test results were as follows--low context: chi2= 124.5, df = 80, p <. 001; partially low: chi2= 144.2, p <. 001, df = 80; partially high: chi2= 157.3, df = 80, p <. 001; and partially low: chi2= 146.0, df = 80, p <. 001. Hospital characteristics that positively influenced research utilization by nurses were staff development, opportunity for nurse-to-nurse collaboration, and staffing and support services. Increased emotional exhaustion led to less reported research utilization and higher rates of patient and nurse adverse events. Nurses working in contexts with more positive culture, leadership, and evaluation also reported significantly more research utilization, staff development, and lower rates of patient and staff adverse events than did nurses working in less positive contexts (i.e., those that lacked positive culture, leadership, or evaluation).CONCLUSION: The findings highlight the combined importance of culture, leadership, and evaluation to increase research utilization and improve patient safety. The findings may serve to strengthen the PARIHS framework and to suggest that, although it is not fully developed, the framework is an appropriate guide to implement research into practice.
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- Estabrooks, Carole A, et al.
(author)
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Predicting research use in nursing organizations : a multilevel analysis
- 2007
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In: Nursing Research. - 0029-6562 .- 1538-9847. ; 56:4 Suppl, s. 7-23
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Journal article (peer-reviewed)abstract
- BACKGROUND: No empirical literature was found that explained how organizational context (operationalized as a composite of leadership, culture, and evaluation) influences research utilization. Similarly, no work was found on the interaction of individuals and contextual factors, or the relative importance or contribution of forces at different organizational levels to either such proposed interactions or, ultimately, to research utilization.OBJECTIVE: To determine independent factors that predict research utilization among nurses, taking into account influences at individual nurse, specialty, and hospital levels.DESIGN: Cross-sectional survey data for 4,421 registered nurses in Alberta, Canada were used in a series of multilevel (three levels) modeling analyses to predict research utilization.METHODS: A multilevel model was developed in MLwiN version 2.0 and used to: (a) estimate simultaneous effects of several predictors and (b) quantify the amount of explained variance in research utilization that could be apportioned to individual, specialty, and hospital levels.FINDINGS: There was significant variation in research utilization (p <.05). Factors (remaining in the final model at statistically significant levels) found to predict more research utilization at the three levels of analysis were as follows. At the individual nurse level (Level 1): time spent on the Internet and lower levels of emotional exhaustion. At the specialty level (Level 2): facilitation, nurse-to-nurse collaboration, a higher context (i.e., of nursing culture, leadership, and evaluation), and perceived ability to control policy. At the hospital level (Level 3): only hospital size was significant in the final model. The total variance in research utilization was 1.04, and the intraclass correlations (the percent contribution by contextual factors) were 4% (variance = 0.04, p <.01) at the hospital level and 8% (variance = 0.09, p <.05) at the specialty level. The contribution attributable to individual factors alone was 87% (variance = 0.91, p <.01).CONCLUSIONS: Variation in research utilization was explained mainly by differences in individual characteristics, with specialty- and organizational-level factors contributing relatively little by comparison. Among hospital-level factors, hospital size was the only significant determinant of research utilization. Although organizational determinants explained less variance in the model, they were still statistically significant when analyzed alone. These findings suggest that investigations into mechanisms that influence research utilization must address influences at multiple levels of the organization. Such investigations will require careful attention to both methodological and interpretative challenges present when dealing with multiple units of analysis.
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- Estabrooks, Carole A, et al.
(author)
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The intellectual structure and substance of the knowledge utilization field : a longitudinal author co-citation analysis, 1945 to 2004
- 2008
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In: Implementation Science. - : Springer Science and Business Media LLC. - 1748-5908. ; 3, s. 49-
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Journal article (peer-reviewed)abstract
- BACKGROUND: It has been argued that science and society are in the midst of a far-reaching renegotiation of the social contract between science and society, with society becoming a far more active partner in the creation of knowledge. On the one hand, new forms of knowledge production are emerging, and on the other, both science and society are experiencing a rapid acceleration in new forms of knowledge utilization. Concomitantly since the Second World War, the science underpinning the knowledge utilization field has had exponential growth. Few in-depth examinations of this field exist, and no comprehensive analyses have used bibliometric methods.METHODS: Using bibliometric analysis, specifically first author co-citation analysis, our group undertook a domain analysis of the knowledge utilization field, tracing its historical development between 1945 and 2004. Our purposes were to map the historical development of knowledge utilization as a field, and to identify the changing intellectual structure of its scientific domains. We analyzed more than 5,000 articles using citation data drawn from the Web of Science. Search terms were combinations of knowledge, research, evidence, guidelines, ideas, science, innovation, technology, information theory and use, utilization, and uptake.RESULTS: We provide an overview of the intellectual structure and how it changed over six decades. The field does not become large enough to represent with a co-citation map until the mid-1960s. Our findings demonstrate vigorous growth from the mid-1960s through 2004, as well as the emergence of specialized domains reflecting distinct collectives of intellectual activity and thought. Until the mid-1980s, the major domains were focused on innovation diffusion, technology transfer, and knowledge utilization. Beginning slowly in the mid-1980s and then growing rapidly, a fourth scientific domain, evidence-based medicine, emerged. The field is dominated in all decades by one individual, Everett Rogers, and by one paradigm, innovation diffusion.CONCLUSION: We conclude that the received view that social science disciplines are in a state where no accepted set of principles or theories guide research (i.e., that they are pre-paradigmatic) could not be supported for this field. Second, we document the emergence of a new domain within the knowledge utilization field, evidence-based medicine. Third, we conclude that Everett Rogers was the dominant figure in the field and, until the emergence of evidence-based medicine, his representation of the general diffusion model was the dominant paradigm in the field.
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