| 1. |
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| 2. |
- Schmidt, R., et al.
(författare)
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White Matter Lesion Progression in LADIS Frequency, Clinical Effects, and Sample Size Calculations
- 2012
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 43:10, s. 2643-2647
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-White matter lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between lesion progression and cognition, and estimated sample sizes for clinical trials with pure WML progression vs combined WML progression-cognitive outcomes. Methods-Those 394 participants of the Leukoaraiosis and Disability Study (LADIS) study with magnetic resonance imaging scanning at baseline and 3-year follow-up were analyzed. WML progression rating relied on the modified Rotterdam Progression Scale. The Vascular Dementia Assessment Scale global score and a composite score of specific executive function tests assessed longitudinal change in cognition. Sample size calculations were based on the assumption that treatment reduces WML progression by 1 grade on the Rotterdam Progression Scale. Results-WML progression related to deterioration in cognitive functioning. This relationship was less pronounced in subjects with early confluent and confluent lesions. Consequently, studies in which the outcome is cognitive change resulting from treatment effects on lesion progression will need between 1809 subjects per treatment arm when using executive tests and up to 18 853 subjects when using the Vascular Dementia Assessment Scale score. Studies having WML progression as the sole outcome will need only 58 or 70 individuals per treatment arm. Conclusions-WML progression is an interesting outcome for proof-of-concept studies in cerebral small vessel disease. If cognitive outcome measures are added to protocols, then sample size estimates increase substantially. Our data support the use of an executive test battery rather than the Vascular Dementia Assessment Scale as the primary cognitive outcome measure. (Stroke. 2012; 43:2643-2647.)
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| 3. |
- Firbank, M. J., et al.
(författare)
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Relationship between progression of brain white matter changes and late-life depression: 3-year results from the LADIS study
- 2012
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 201:1, s. 40-45
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Tidskriftsartikel (refereegranskat)abstract
- Background Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear. Aims To investigate the relationship between baseline and incident depression and progression of white matter changes. Method In a longitudinal multicentre pan-European study (Leukoaraiosis and Disability in the elderly, LADIS), participants aged over 64 underwent baseline magnetic resonance imaging (MRI) and clinical assessments. Repeat scans were obtained at 3 years. Depressive outcomes were assessed in terms of depressive episodes and the Geriatric Depression Scale (GDS). Progression of WMC was measured using the modified Rotterdam Progression scale. Results Progression of WMC was significantly associated with incident depression during year 3 of the study (P = 0.002) and remained significant after controlling for transition to disability, baseline WMC and baseline history of depression. There was no significant association between progression of WMC and GDS score, and no significant relationship between progression of WMC and history of depression at baseline. Conclusions Our results support the vascular depression hypothesis and implicate WMC as causal in the pathogenesis of late-life depression.
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| 4. |
- Jokinen, H., et al.
(författare)
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Diffusion changes predict cognitive and functional outcome: The LADIS study
- 2013
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134. ; 73:5, s. 576-583
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Tidskriftsartikel (refereegranskat)abstract
- Objective A study was undertaken to determine whether diffusion-weighted imaging (DWI) abnormalities in normal-appearing brain tissue (NABT) and in white matter hyperintensities (WMH) predict longitudinal cognitive decline and disability in older individuals independently of the concomitant magnetic resonance imaging (MRI) findings. Methods A total of 340 LADIS (Leukoaraiosis and Disability Study) participants, aged 65 to 84 years, underwent brain MRI including DWI at baseline. Neuropsychological and functional assessments were carried out at study entry and repeated annually over a 3-year observational period. Linear mixed models and Cox regression survival analysis adjusted for demographics, WMH volume, lacunes, and brain atrophy were used to evaluate the independent effect of the DWI measures on change in cognitive performance and functional abilities. Results The mean global apparent diffusion coefficient (ADC) and the relative peak height and peak position of the ADC histogram in NABT predicted faster rate of decline in a composite score for speed and motor control. Higher mean ADC and lower peak height were also related to deterioration in executive functions and memory (specifically working memory), with peak height also being related to more rapid transition to disability and higher rate of mortality. Mean ADC in WMH had less pronounced effects on cognitive and functional outcomes. Interpretation DWI microstructural changes in NABT predict faster decline in psychomotor speed, executive functions, and working memory regardless of conventional MRI findings. Moreover, these changes are related to functional disability and higher mortality. Ann Neurol 2013;73:576–583
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| 7. |
- Glover, A. G., et al.
(författare)
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A live video observatory reveals temporal processes at a shelf-depth whale-fall
- 2010
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Ingår i: Cahiers De Biologie Marine. - 0007-9723. ; 51:4, s. 375-381
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Tidskriftsartikel (refereegranskat)abstract
- There have been very few studies of temporal processes at chemosynthetic ecosystems, even at relatively more accessible shallow water sites. Here we report the development and deployment of a simple cabled video observatory at 30 m water depth in Gullmarsfjorden, Sweden. The camera provides a live video feed to the internet of faunal activity in the experiments, which to date have included 5 separate whale-fall deployments. Our data suggest that the time to decomposition of small cetacean carcasses at shelf-depth settings is considerably slower than at deep-sea sites. We have also provided a new methodology for the deployment of low-cost live video observatories at up to 30 m water depth, which can be used both for research and outreach activities.
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| 8. |
- Jokinen, H., et al.
(författare)
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Brain atrophy accelerates cognitive decline in cerebral small vessel disease The LADIS study
- 2012
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Ingår i: Neurology. - 0028-3878. ; 78:22, s. 1785-1792
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the independent contributions and combined interactions of medial temporal lobe atrophy (MTA), cortical and subcortical atrophy, and white matter lesion (WML) volume in longitudinal cognitive performance. Methods: A total of 477 subjects with age-related WML were evaluated with brain MRI and annual neuropsychological examinations in 3-year follow-up. Baseline MRI determinants of cognitive decline were analyzed with linear mixed models controlling for multiple confounders. Results: MTA and subcortical atrophy predicted significantly steeper rate of decline in global cognitive measures as well as compound scores for psychomotor speed, executive functions, and memory after adjusting for age, gender, education, lacunes/infarcts, and WML volume. Cortical atrophy independently predicted decline in psychomotor speed. WML volume remained significantly associated with cognitive decline even after controlling for the atrophy scores. Moreover, significant synergistic interactions were found between WML and atrophy measures in overall cognitive performance across time and the rate of cognitive decline. Synergistic effects were also observed between baseline lacunar infarcts and all atrophy measures on change in psychomotor speed. The main results remained robust after exclusion of subjects with clinical stroke or incident dementia, and after additional adjustments for progression of WML and lacunes. Conclusions: Brain atrophy and WML are independently related to longitudinal cognitive decline in small vessel disease. MTA, subcortical, and cortical atrophy seem to potentiate the effect of WML and lacunes on cognitive decline. Neurology (R) 2012;78:1785-1792
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| 9. |
- Jokinen, H, et al.
(författare)
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Incident lacunes influence cognitive decline: the LADIS study.
- 2011
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 76:22, s. 1872-8
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Tidskriftsartikel (refereegranskat)abstract
- In cerebral small vessel disease, the core MRI findings include white matter lesions (WML) and lacunar infarcts. While the clinical significance of WML is better understood, the contribution of lacunes to the rate of cognitive decline has not been established. This study investigated whether incident lacunes on MRI determine longitudinal cognitive change in elderly subjects with WML.
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| 10. |
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| 11. |
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| 13. |
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| 14. |
- Curtin, W. A., et al.
(författare)
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Hybrid discrete dislocation models for fatigue crack growth
- 2010
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Ingår i: International Journal of Fatigue. - : Elsevier BV. - 1879-3452 .- 0142-1123. ; 32:9, s. 1511-1520
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Tidskriftsartikel (refereegranskat)abstract
- A framework for accurately modeling fatigue crack growth in ductile crystalline solids is necessarily multiscale The creation of new free surface occurs at the atomistic scale, where the material's cohesive strength is controlled by the local chemistry On the other hand, significant dissipation during fatigue crack growth takes place at a size scale that can be modeled appropriately by conventional continuum mechanics. The intermediate size scale where the discreteness of dislocations comes Into play is the main origin of the hysteresis needed for fatigue and of the high stresses required for atomistic separation to take place. We focus on recent developments which permit analyses of fatigue crack growth involving the direct coupling of disparate size scales. Although no analyses have been carried out directly coupling size scales from the atomic to the conventional continuum, the ingredients to do so are in place. We provide background that illustrates the key role played by the intermediate discrete dislocation size scale and review steps that have been taken to permit direct size scale coupling. The prospects and modeling needs for further developments are also discussed (C) 2009 Elsevier Ltd All rights reserved.
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| 15. |
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| 16. |
- Gifford, Wendy A, et al.
(författare)
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Managerial leadership for research use in nursing and allied health care professions : a narrative synthesis protocol
- 2014
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Ingår i: Systematic Reviews. - : BioMed Central. - 2046-4053. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Nurses and allied health care professionals (physiotherapists, occupational therapists, speech and language pathologists, dietitians) form more than half of the clinical health care workforce and play a central role in health service delivery. There is a potential to improve the quality of health care if these professionals routinely use research evidence to guide their clinical practice. However, the use of research evidence remains unpredictable and inconsistent. Leadership is consistently described in implementation research as critical to enhancing research use by health care professionals. However, this important literature has not yet been synthesized and there is a lack of clarity on what constitutes effective leadership for research use, or what kinds of intervention effectively develop leadership for the purpose of enabling and enhancing research use in clinical practice. We propose to synthesize the evidence on leadership behaviours amongst front line and senior managers that are associated with research evidence by nurses and allied health care professionals, and then determine the effectiveness of interventions that promote these behaviours.Methods/design: Using an integrated knowledge translation approach that supports a partnership between researchers and knowledge users throughout the research process, we will follow principles of knowledge synthesis using a systematic method to synthesize different types of evidence involving: searching the literature, study selection, data extraction and quality assessment, and analysis. A narrative synthesis will be conducted to explore relationships within and across studies and meta-analysis will be performed if sufficient homogeneity exists across studies employing experimental randomized control trial designs.DISCUSSION: With the engagement of knowledge users in leadership and practice, we will synthesize the research from a broad range of disciplines to understand the key elements of leadership that supports and enables research use by health care practitioners, and how to develop leadership for the purpose of enhancing research use in clinical practice.
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| 17. |
- Jakobsson, Martin, 1966-, et al.
(författare)
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An Arctic Ocean ice shelf during MIS 6 constrained by new geophysical and geological data
- 2010
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 29:25-26, s. 3505-3517
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis of floating ice shelves covering the Arctic Ocean during glacial periods was developed in the 1970s. In its most extreme form, this theory involved a 1000 m thick continuous ice shelf covering the Arctic Ocean during Quaternary glacial maxima including the Last Glacial Maximum (LGM). While recent observations clearly demonstrate deep ice grounding events in the central Arctic Ocean, the ice shelf hypothesis has been difficult to evaluate due to a lack of information from key areas with severe sea ice conditions. Here we present new data from previously inaccessible, unmapped areas that constrain the spatial extent and timing of marine ice sheets during past glacials. These data include multibeam swath bathymetry and subbottom profiles portraying glaciogenic features on the Chukchi Borderland, southern Lomonosov Ridge north of Greenland, Morris Jesup Rise, and Yermak Plateau. Sediment cores from the mapped areas provide age constraints on the glaciogenic features. Combining these new geophysical and geological data with earlier results suggests that an especially extensive marine ice sheet complex, including an ice shelf, existed in the Amerasian Arctic Ocean during Marine Isotope Stage (MIS) 6. From a conceptual oceanographic model we speculate that the cold halocline of the Polar Surface Water may have extended to deeper water depths during MIS 6 inhibiting the warm Atlantic water from reaching the Amerasian Arctic Ocean and, thus, creating favorable conditions for ice shelf development. The hypothesis of a continuous 1000 m thick ice shelf is rejected because our mapping results show that several areas in the central Arctic Ocean substantially shallower than 1000 m water depth are free from glacial influence on the seafloor.
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| 18. |
- Jonsson, Michael, 1955, et al.
(författare)
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Low Cerebrospinal Fluid Sulfatide Predicts Progression of White Matter Lesions - The LADIS Study
- 2012
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 34:1, s. 61-67
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Demyelination and axonal degeneration are the hallmarks of established white matter lesions (WML). The neurochemistry of ongoing WML is only partially known. We explored cerebrospinal fluid (CSF) substances as markers of brain tissue damage in relation to progression of WML rated on magnetic resonance imaging. Methods: CSF from elderly individuals with WML was analyzed for amyloid markers, total tau, hyperphosphorylated t, neurofilament protein light subunit, sulfatide and CSF/serum-albumin ratio. After 3 years, a follow-up magnetic resonance imaging was performed. Progression of WML was rated using the Rotterdam Progression Scale (RPS). Results: 37 subjects (age 73.6 +/- 4.6 years) were included. Subjects with more pronounced progression (RPS > 2; n = 15) had lower mean sulfatide concentration at baseline as compared to subjects with no or minimal progression (RPS 0-2; n = 22) according to univariate analyses (p = 0.009). Sulfatide was the only biomarker that predicted the RPS score according to regression analysis, explaining 18.9% of the total variance (r = 0.38, p = 0.015). Conclusion: The correlation of CSF sulfatide levels and RPS scores may reflect a remyelination response to the demyelination process associated with WML. Furthermore, the results strengthen the notion that WML pathology is different from that of Alzheimer's disease.
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| 19. |
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| 23. |
- Poggesi, A., et al.
(författare)
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Cerebral white matter changes are associated with abnormalities on neurological examination in non-disabled elderly: the LADIS study
- 2013
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 260:4, s. 1014-1021
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral white matter changes (WMC) are associated with motor, cognitive, mood, urinary disturbances, and disability, but little is known about the prevalence of neurological signs in patients with these brain lesions. We assessed the presence and occurrence of neurological abnormalities over a 3-year period and their possible associations with WMC in a cohort of initially non-disabled elderly subjects. Data from the multicenter Leukoaraiosis And DISability study were used. A standard neurological examination was performed at baseline and at each of the annual follow-up visits. A standard MRI scan was performed at baseline and after 3-years. WMC severity was graded as mild, moderate, or severe on the Fazekas scale, while the Rotterdam scale was used to assess progression. Infarcts and their occurrence were also assessed. Six hundred and thirty-nine non-disabled subjects were enrolled (mean age 74.1 +/- A 5.0, M/F: 288/351). Severe WMC at baseline were associated with gait and stance abnormalities, upper motor signs, and fingertap slowing. This effect was independent of age, sex, lacunar and non-lacunar infarcts. The occurrence of stance abnormalities, upper motor signs, primitive reflexes and fingertap slowing during the 3-year follow-up period was associated with both baseline WMC load and their progression. The occurrence of the same abnormalities plus extrapyramidal and primitive reflexes was associated with incident lacunar infarcts. In our cohort of non-disabled elders, severe WMC were associated with the presence and the occurrence of neurological signs, independently of other vascular brain lesions, confirming that these lesions have clinical relevance.
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| 24. |
- Poggesi, A., et al.
(författare)
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Neurological abnormalities predict disability: the LADIS (Leukoaraiosis And DISability) study
- 2014
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 261:6, s. 1160-1169
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination was performed. MRI assessment included age-related white matter changes (ARWMC) grading (mild, moderate, severe according to the Fazekas' scale), count of lacunar and non-lacunar infarcts, and global atrophy rating. Of the 633 (out of the 639 enrolled) patients with follow-up information (mean age 74.1 +/- A 5.0 years, 45 % males), 327 (51.7 %) presented at the initial visit with a parts per thousand yen1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological abnormality independently predicted transition to disability or death [HR (95 % CI) 1.53 (1.01-2.34)]. The hazard increased with increasing number of abnormalities. Among MRI lesions, only ARWMC of severe grade independently predicted disability or death [HR (95 % CI) 2.18 (1.37-3.48)]. In our cohort, presence and number of neurological examination abnormalities predicted global functional decline independent of MRI lesions typical of the aging brain and other determinants of disability in the elderly. Systematically checking for neurological examination abnormalities in older patients may be cost-effective in identifying those at risk of functional decline.
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| 25. |
- Saeed, A., et al.
(författare)
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7 alpha-hydroxy-3-oxo-4-cholestenoic acid in cerebrospinal fluid reflects the integrity of the blood-brain barrier
- 2014
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 55:2, s. 313-318
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Tidskriftsartikel (refereegranskat)abstract
- There is a continuous flux of the oxysterol 27-hydroxycholesterol (27-OHC) from the circulation across the blood-brain barrier (BBB) into the brain. The major metabolite of 27-OHC in the brain is 7 alpha-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA). We confirm a recent report describing the presence of this metabolite in cerebrospinal fluid (CSF) at a relatively high concentration. A simple and accurate method was developed for assay of 7-HOCA in CSF based on isotope dilution-mass spectrometry and use of H-2(4)-labeled internal standard. The concentration of this metabolite was found to be markedly increased in CSF from patients with a dysfunctional BBB. There was a high correlation between the levels of 7-HOCA in CSF and the CSF/serum albumin ratio. The concentration of 7-HOCA in CSF was not significantly affected by neurodegeneration. Our findings suggest that 7-HOCA could be used as a diagnostic marker for conditions with a dysfunctional BBB.
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| 26. |
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| 27. |
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| 28. |
- Språngberg, A, et al.
(författare)
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SBU. Godartad prostataförstoring med avflödeshinder. En systematisk litteraturöversikt : Godartad prostataförstoring med avflödeshinder
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Slutsatser Godartad prostataförstoring (benign prostatahyperplasi, BPH) är ett vanligt tillstånd som med stigande ålder drabbar i princip alla män. En del av dessa män får urineringsproblem och cirka 4 500 opereras varje år för en förstorad prostata. Många med lindrigare besvär behandlas med läkemedel eller behöver ingen behandling alls. Avflödeshinder kan obehandlat ge allvarlig urinretention som skadar njurarna, och en urinstämma kan vara livshotande. För att avgränsa den grupp av män där problemen med urineringen beror på en förstorad prostata används ett tiotal olika diagnostiska metoder. När det gäller behandling finns det flera olika kirurgiska metoder, varav några är väl etablerade och andra av mer experimentell karaktär. Under 1990-talet har också flera läkemedel introducerats. SBU har därför bedömt att det funnits ett behov av att göra en systematisk genomgång av den vetenskapliga grunden för dessa olika metoder. Nedan följer de viktigaste slutsatserna av arbetet.
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| 29. |
- Verdelho, A., et al.
(författare)
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Depressive symptoms predict cognitive decline and dementia in older people independently of cerebral white matter changes: the LADIS study
- 2013
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 84:11, s. 1250-1254
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Tidskriftsartikel (refereegranskat)abstract
- Objective Depressive symptoms (DS) have been associated with increased risk of cognitive decline. Our aim was to evaluate the longitudinal influence of DS on cognition in independent older people, accounting for the severity of white matter changes (WMC). Methods The LADIS (Leukoaraiosis And DISability in the elderly) prospective study evaluated the impact of WMC on the transition of independent older subjects into disability. Subjects were evaluated annually over a 3 year period with a comprehensive clinical and neuropsychological evaluation. Previous episodes of depression and current DS were assessed during each interview. Severity of DS was assessed using the self-rated 15 item Geriatric Depression Scale. A neuropsychological battery and clinical criteria for cognitive impairments were applied in all clinical visits, and cognitive compound measures were made based on neuropsychological results. MRI was performed at baseline and at year 3. Results 639 subjects were included (74.1 +/- 5 years old, 55% women, 9.6 +/- 3.8 years of schooling). Dementia was diagnosed in 90 patients and cognitive impairment not dementia in 147 patients at the last clinical evaluation. DS were an independent predictor of cognitive impairment (dementia and not dementia) during follow-up, independent of the effect of the severity of WMC, medial temporal lobe atrophy, age, education or global cognitive function at baseline. Conclusions DS are associated with an increase risk of cognitive decline, independent of the effect of WMC, probably due to an additive or synergistic effect. In this context, DS probably represent a subtle ongoing organic dysfunction
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| 30. |
- Verdelho, A., et al.
(författare)
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Physical Activity Prevents Progression for Cognitive Impairment and Vascular Dementia Results From the LADIS (Leukoaraiosis and Disability) Study
- 2012
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 43:12, s. 3331-3335
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-We aimed to study if physical activity could interfere with progression for cognitive impairment and dementia in older people with white matter changes living independently. Methods-The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes on the transition of independent elderly subjects into disability. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and cognitive assessment with classification of cognitive impairment and dementia according to usual clinical criteria. Physical activity was recorded during the clinical interview. MRI was performed at entry and at the end of the study. Results-Six hundred thirty-nine subjects were included (74.1 +/- 5 years old, 55% women, 9.6 +/- 3.8 years of schooling, 64% physically active). At the end of follow-up, 90 patients had dementia (vascular dementia, 54; Alzheimer disease with vascular component, 34; frontotemporal dementia, 2), and 147 had cognitive impairment not dementia. Using Cox regression analysis, physical activity reduced the risk of cognitive impairment (dementia and not dementia: beta=-0.45, P=0.002; hazard ratio, 0.64; 95% CI, 0.48-0.85), dementia (beta=-0.49, P=0.043; hazard ratio, 0.61; 95% CI, 0.38-0.98), and vascular dementia (beta=-0.86, P=0.008; hazard ratio, 0.42; 95% CI, 0.22-0.80), independent of age, education, white matter change severity, medial temporal atrophy, previous and incident stroke, and diabetes. Conclusions-Physical activity reduces the risk of cognitive impairment, mainly vascular dementia, in older people living independently. (Stroke. 2012; 43: 3331-3335.)
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| 31. |
- Wallin, A., et al.
(författare)
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Red and processed meat consumption and risk of ovarian cancer : a dose-response meta-analysis of prospective studies
- 2011
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Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 104:7, s. 1196-1201
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: During the last decade, the epidemiological evidence on consumption of meat and risk of ovarian cancer has accumulated. METHODS: We assessed the relationship between red and processed meat consumption and risk of ovarian cancer with a dose-response meta-analysis. Relevant prospective cohort studies were identified by searching the PubMed and EMBASE databases through 21 January 2011, and by reviewing the reference lists of retrieved articles. Study-specific relative risk (RR) estimates were combined using a random-effects model. RESULTS: Eight cohort studies were included in the meta-analysis. The summary RR for an intake increment of 100 g per week was 1.02 (95% confidence interval (CI), 0.99-1.04) for red meat and 1.05 (95% CI, 0.98-1.14) for processed meat. For an intake increment of four servings per week, the summary RR of ovarian cancer was 1.07 (95% CI, 0.97-1.19) for red meat (100 g per serving) and 1.07 (95% CI, 0.97-1.17) for processed meat (30 g per serving). CONCLUSION: Results from this dose-response meta-analysis suggest that red and processed meat consumption is not associated with risk of ovarian cancer. Although a lower consumption of red and processed meat may offer protection against other types of cancer, other interventions are needed to reduce the risk of ovarian cancer. British Journal of Cancer (2011) 104, 1196-1201. doi: 10.1038/bjc.2011.49 www.bjcancer.com Published online 22 February 2011 (c) 2011 Cancer Research UK
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| 32. |
- Weidner, Jessica M., et al.
(författare)
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Rapid cytoskeleton remodelling in dendritic cells following invasion by Toxoplasma gondii coincides with the onset of a hypermigratory phenotype
- 2013
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 15:10, s. 1735-1752
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Tidskriftsartikel (refereegranskat)abstract
- Host cell manipulation is an important feature of the obligate intracellular parasite Toxoplasma gondii. Recent reports have shown that the tachyzoite stages subvert dendritic cells (DC) as a conduit for dissemination (Trojan horse) during acute infection. To examine the cellular basis of these processes, we performed a detailed analysis of the early events following tachyzoite invasion of human monocyte-derived DC. We demonstrate that within minutes after tachyzoite penetration, profound morphological changes take place in DC that coincide with a migratory activation. Active parasite invasion of DC led to cytoskeletal actin redistribution with loss of adhesive podosome structures and redistribution of integrins (CD18 and CD11c), that concurred with the onset of DC hypermotility in vitro. Inhibition of parasite rhoptry secretion and invasion, but not inhibition of parasite or host cell protein synthesis, abrogated the onset of morphological changes and hypermotility in DC dose-dependently. Also, infected DC, but not by-stander DC, exhibited upregulation of C-C chemokine receptor 7 (CCR7). Yet, the onset of parasite-induced DC hypermotility preceded chemotactic migratory responsesin vitro. Collectively, present data reveal that invasion of DC by T. gondii initiates a series of regulated events, including rapid cytoskeleton rearrangements, hypermotility and chemotaxis, that promote the migratory activation of DC.
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| 33. |
- Wettermark, B., et al.
(författare)
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The Nordic prescription databases as a resource for pharmacoepidemiological researcha literature review
- 2013
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 22:7, s. 691-699
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Forskningsöversikt (refereegranskat)abstract
- Purpose All five Nordic countries have nationwide prescription databases covering all dispensed drugs, with potential for linkage to outcomes. The aim of this review is to present an overview of therapeutic areas studied and methods applied in pharmacoepidemiologic studies using data from these databases. Methods The study consists of a Medline-based structured literature review of scientific papers published during 2005-2010 using data from the prescription databases in Denmark, Finland, Iceland, Norway, and Sweden, covering 25 million inhabitants. Relevant studies were analyzed in terms of pharmacological group, study population, outcomes examined, type of study (drug utilization vs. effect of drug therapy), country of origin, and extent of cross-national collaboration. Results A total of 515 studies were identified. Of these, 262 were conducted in Denmark, 97 in Finland, 4 in Iceland, 87 in Norway, and 61 in Sweden. Four studies used data from more than one Nordic country. The most commonly studied drugs were those acting on the nervous system, followed by cardiovascular drugs and gastrointestinal/endocrine drugs. A total of 228 studies examined drug utilization and 263 focused on the effects and safety of drug therapy. Pregnant women were the most commonly studied population in safety studies, whereas prescribers' adherence to guidelines was the most frequent topic of drug utilization studies. Conclusions The Nordic prescription databases, with their possibility of record-linkage, represent an outstanding resource for assessing the beneficial and adverse effects of drug use in large populations, under routine care conditions, and with the potential for long-term follow-up. Copyright (c) 2013 John Wiley & Sons, Ltd.
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| 34. |
- Alakangas, Linda J., et al.
(författare)
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Sampling and Characterizing Rare Earth Elements in Groundwater in Deep-Lying Fractures in Granitoids Under In Situ High-Pressure and Low-Redox Conditions
- 2014
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Ingår i: Aquatic geochemistry. - : Springer Science and Business Media LLC. - 1380-6165 .- 1573-1421. ; 20:4, s. 405-418
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Tidskriftsartikel (refereegranskat)abstract
- Several countries are preparing to dispose of radioactive nuclear waste deep underground in crystalline rock. This type of bedrock is commonly extensively fractured and consequently carries groundwater that serves as a medium for transporting metals and radionuclides. A group of metals of particular interest in this context is the rare earth elements (REEs), because they are analogues of actinides contained within radioactive waste and are tracers of hydrological pathways and geochemical processes. Concentrations of REEs are commonly low in these groundwaters, leading to values below detection limits of standard monitoring methods, particularly for the heavy REEs. We present a new technical set-up for monitoring REEs (and other trace metals) in groundwater in fractured crystalline rock. The technique consists of passing the fracture groundwater, commonly under high pressure and containing reduced chemical species, through a device that maintains the physicochemical character of the groundwater. Within the device, diffusive gradient in thin-film (DGT) discs are installed in triplicate. With this set-up, we studied REEs in groundwater in fractures at depths of approximately -144, -280, and -450 m in granitoids in the A"spo Hard Rock Laboratory in southern Sweden. The entire REE suite was detected (concentrations down to 0.1 ng L-1) and was differently fractionated among the groundwaters. The shallowest groundwater, composed of dilute modern Baltic Sea water, was enriched in the heavy REEs, whereas the deeper groundwaters, dominated by old saline water, were depleted in the heavy REEs. Deployment periods varying from 1 to 4 weeks delivered similar REE concentrations, indicating stability and reproducibility of the experimental set-up. The study finds that 1 week of deployment may be enough. However, if the overall setting and construction allow for longer deployment times, 2-3 weeks will be optimal in terms of reaching reliable REE concentrations well above the detection limit while maintaining the performance of the DGT samplers.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Blennow, Kaj, 1958, et al.
(författare)
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No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.
- 2011
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 123, s. 245-51
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Tidskriftsartikel (refereegranskat)abstract
- Blennow K, Jonsson M, Andreasen N, Rosengren L, Wallin A, Hellström PA, Zetterberg H. No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01408.x .(c) 2010 John Wiley & Sons A/S. Background - Psychiatric and neurological symptoms are common among soldiers exposed to blast without suffering a direct head injury. It is not known whether such symptoms are direct consequences of blast overpressure. Objective - To examine if repeated detonating explosions or firing if of heavy weapons is associated with neurochemical evidence of brain damage. Materials and methods - Three controlled experimental studies. In the first, army officers were exposed to repeated firing of a FH77B howitzer or a bazooka. Cerebrospinal fluid (CSF) was taken post-exposure to measure biomarkers for brain damage. In the second, officers were exposed for up to 150 blasts by firing a bazooka, and in the third to 100 charges of detonating explosives of 180 dB. Serial serum samples were taken after exposure. Results were compared with a control group consisting of 19 unexposed age-matched healthy volunteers. Results - The CSF biomarkers for neuronal/axonal damage (tau and neurofilament protein), glial cell injury (GFAP and S-100b), blood-brain barrier damage (CSF/serum albumin ratio) and hemorrhages (hemoglobin and bilirubin) and the serum GFAP and S-100b showed normal and stable levels in all exposed officers. Discussion - Repeated exposure to high-impact blast does not result in any neurochemical evidence of brain damage. These findings are of importance for soldiers regularly exposed to high-impact blast when firing artillery shells or other types of heavy weapons.
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| 39. |
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| 40. |
- Dahlgren, Markus K, et al.
(författare)
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Synthesis of 2-(2-Aminopyrimidine)-2,2-difluoroethanols as Potential Bioisosters of Salicylidene Acylhydrazides
- 2010
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 15:6, s. 4207-12
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Tidskriftsartikel (refereegranskat)abstract
- Salicylidene acylhydrazides are inhibitors of type III secretion in several Gramnegative pathogens. To further develop the salicylidene acylhydrazides, scaffold hopping was applied to replace the core fragment of the compounds. The novel 2-(2-aminopyrimidine)-2,2-difluoroethanol scaffold was identified as a possible analog to thesalicylidene acylhydrazide core structure. The synthesis of a library of 2-(2-aminopyrimidine)-2,2-difluoro-ethanols is described in this paper.
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| 41. |
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| 42. |
- Duits, Flora H., et al.
(författare)
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The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean?
- 2014
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 10:6, s. 713-723
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-beta(1-42) (A beta(42)), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimers disease (AD). Methods: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). Results: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/A beta(42) ratio and 0.08 for the p-tau/A beta(42) ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/A beta(42) ratio. Conclusions: A tau/A beta(42) ratio of greater than0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.
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| 43. |
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| 44. |
- Eldh, Ann Catrine, 1965-, et al.
(författare)
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Translating and testing the Alberta Context Tool for use among nurses in Swedish elder care
- 2013
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background. There is emerging evidence that context is important for successful transfer of research knowledge into health care practice. The Alberta Context Tool (ACT) is a Canadian developed research-based instrument that assesses 10 modifiable concepts of organizational context considered important for health care professionals’ use of evidence. Swedish and Canadian health care have similarities in terms of organisational and professional aspects, suggesting that the ACT could be used for measuring context in Sweden. This paper reports on the translation of the ACT to Swedish and a testing of preliminary aspects of its validity, acceptability and reliability in Swedish elder care.Methods. The ACT was translated into Swedish and back-translated into English before being pilot tested in ten elder care facilities for response processes validity, acceptability and reliability (Cronbach’s alpha). Subsequently, further modification was performed.Results. In the pilot test, the nurses found the questions easy to respond to (52%) and relevant (65%), yet the questions’ clarity were mainly considered ‘neither clear nor unclear’ (52%). Missing data varied between 0 (0%) and 19 (12%) per item, the most common being 1 missing case per item (15 items). Internal consistency (Cronbach’s Alpha > .70) was reached for 5 out of 8 contextual concepts. Translation and back translation identified 21 linguistic- and semantic related issues and 3 context related deviations, resolved by developers and translators.Conclusion. Modifying an instrument is a detailed process, requiring time and consideration of the linguistic and semantic aspects of the instrument, and understanding of the context where the instrument was developed and where it is to be applied. A team, including the instrument’s developers, translators, and researchers is necessary to ensure a valid translation. This study suggests preliminary validity, reliability and acceptability evidence for the ACT when used with nurses in Swedish elder care.
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| 45. |
- Eltz, Thomas, et al.
(författare)
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(6R,10R)-6,10,14-Trimethylpentadecan-2-one, a Dominant and Behaviorally Active Component in Male Orchid Bee Fragrances
- 2010
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Ingår i: Journal of Chemical Ecology. - : Springer Science and Business Media LLC. - 0098-0331 .- 1573-1561. ; 36:12, s. 1322-1326
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Tidskriftsartikel (refereegranskat)abstract
- 6,10,14-Trimethylpentadecan-2-one (Hexahydrofarnesyl acetone; HHA) previously has been found to be a major component in tibial fragrances of male orchid bees, Euglossa spp. HHA is a chiral molecule with four possible stereoisomers, (6R,10R)-, (6R,10S)-, (6S,10R)-, and (6S,10S)-6,10,14-trimethylpentadecan-2-one. In the present study, we characterized HHA extracted from Euglossa as the pure enantiomer (6R,10R)-6,10,14-trimethylpentadecan-2-one. During bioassays in Mexico and Panama, the synthetic RR-isomer attracted males of six species of orchid bees, including three that were known to contain HHA in their tibial fragrances. Possible sources of HHA for wild bees are flowers of euglossophilous orchids and aroids. With a molecular weight of 268, HHA is the largest natural molecule known to attract male orchid bees in pure form. Its attractiveness to males suggests that low-volatility compounds have a function in male signals, e.g., serve as a "base note" in complex odor bouquets. © 2010 Springer Science+Business Media, LLC.
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| 46. |
- Estabrooks, Carole A, et al.
(författare)
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Towards better measures of research utilization : a collaborative study in Canada and Sweden
- 2011
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Ingår i: Journal of Advanced Nursing. - : Wiley-Blackwell. - 0309-2402 .- 1365-2648. ; 67:8, s. 1705-18
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: This paper is a report of a study examining research utilization in nursing. The specific aims were to (1) clarify the construct of research utilization, and (2) identify observable indicators of research utilization.BACKGROUND: Robust measures of research utilization do not exist despite steadily increasing numbers of studies in the field. One reason for this is theoretical confusion surrounding the central concepts in the field.METHOD: A qualitative (focus group) design was used to explore the construct of research utilization in two countries: Canada and Sweden. A systematic and sequential (three phases) approach to expert sampling framed the study. Phase 1 consisted of initial construct clarification by the research team (2005). In Phase 2, a face-to-face meeting with a panel of international research utilization nursing experts was held (2005). Phase 3 consisted of a series of focus groups with nursing care (direct and non-direct) providers (2005-2007). Data were analysed using content analysis.FINDINGS: The nursing care providers did not commonly use the term 'research utilization'. Several examples of research utilization were provided; a majority of these examples related to instrumental research utilization and became increasingly concrete as one moved from non-direct to direct care participants. Participants identified several indicators of research utilization (instrumental and conceptual). From these indicators, a measurement schematic was derived.CONCLUSIONS: The construct of research utilization is multi-faceted. Several indicators of research utilization were identified, which can be used to augment existing or develop a new and improved measure that taps both instrumental and conceptual use.
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| 47. |
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| 48. |
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| 49. |
- Fuks, Jonas M, et al.
(författare)
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GABAergic Signaling Is Linked to a Hypermigratory Phenotype in Dendritic Cells Infected by Toxoplasma gondii
- 2012
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Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 8:12, s. e1003051-
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Tidskriftsartikel (refereegranskat)abstract
- During acute infection in human and animal hosts, the obligate intracellular protozoan Toxoplasma gondii infects a variety of cell types, including leukocytes. Poised to respond to invading pathogens, dendritic cells (DC) may also be exploited by T. gondii for spread in the infected host. Here, we report that human and mouse myeloid DC possess functional γ-aminobutyric acid (GABA) receptors and the machinery for GABA biosynthesis and secretion. Shortly after T. gondii infection (genotypes I, II and III), DC responded with enhanced GABA secretion in vitro. We demonstrate that GABA activates GABA(A) receptor-mediated currents in T. gondii-infected DC, which exhibit a hypermigratory phenotype. Inhibition of GABA synthesis, transportation or GABA(A) receptor blockade in T. gondii-infected DC resulted in impaired transmigration capacity, motility and chemotactic response to CCL19 in vitro. Moreover, exogenous GABA or supernatant from infected DC restored the migration of infected DC in vitro. In a mouse model of toxoplasmosis, adoptive transfer of infected DC pre-treated with GABAergic inhibitors reduced parasite dissemination and parasite loads in target organs, e.g. the central nervous system. Altogether, we provide evidence that GABAergic signaling modulates the migratory properties of DC and that T. gondii likely makes use of this pathway for dissemination. The findings unveil that GABA, the principal inhibitory neurotransmitter in the brain, has activation functions in the immune system that may be hijacked by intracellular pathogens.
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| 50. |
- Granlund, Margareta, et al.
(författare)
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Antimicrobial resistance in colonizing group B Streptococci before the implementation of a Swedish intrapartum antibiotic prophylaxis program.
- 2010
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Ingår i: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. - : Springer Science and Business Media LLC. - 1435-4373 .- 0934-9723. ; 29:10, s. 1195-201
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of antibiotic resistance and their genetic determinants in colonizing group B streptococci (GBS) sampled in a Swedish nationwide survey was examined. In five GBS isolates (1.3%), kanamycin/amikacin resistance and the presence of the aphA-3 gene was identified. Three of these isolates carried the aad-6 gene and were streptomycin-resistant. Screening with kanamycin and streptomycin 1,000-μg disks enabled a rapid and easy detection of these isolates. In all, 312/396 (79%) GBS were tetracycline-resistant and 95% of the examined isolates harbored the tetM gene. Among the 22 (5.5%) GBS resistant to erythromycin and/or clindamycin, the ermB gene was detected in nine isolates (41%) and erm(A/TR) in ten isolates (45%). A high level of erythromycin and clindamycin resistance with minimum inhibitory concentrations (MICs) >256mg/L was found in four serotype V isolates that harbored ermB. The erythromycin/clindamycin resistance was distributed among all of the common serotypes Ia, Ib, II, III, IV, and V, but was not present in any of the 44 serotype III isolates associated to clonal complex 17. Screening for penicillin resistance with 1-μg oxacillin disks showed a homogenous population with a mean inhibition zone of 20mm. A change in the present oxacillin breakpoints for GBS is suggested.
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