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Sökning: WFRF:(Hansson William)

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2.
  • Donis, Daphne, et al. (författare)
  • Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
  • 2021
  • Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:12, s. 4314-4333
  • Tidskriftsartikel (refereegranskat)abstract
    • To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.
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3.
  • Jansen, Willemijn J, et al. (författare)
  • Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
  • 2018
  • Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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4.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
  • 2022
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
  • Tidskriftsartikel (refereegranskat)abstract
    • One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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5.
  • Mattsson, Niklas, et al. (författare)
  • Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease
  • 2018
  • Ingår i: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.
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6.
  • Mattsson, Niklas, et al. (författare)
  • Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
  • 2018
  • Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
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7.
  • Svensson Frej, Marcus, et al. (författare)
  • Involvement of CCR9 at multiple stages of adult T lymphopoiesis.
  • 2008
  • Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 83:1, s. 156-164
  • Tidskriftsartikel (refereegranskat)abstract
    • The chemokine CCL25 is constitutively expressed in the thymus, and its receptor CCR9 is expressed on subsets of developing thymocytes. Nevertheless, the function of CCL25/CCR9 in adult thymopoiesis remains unclear. Here, we demonstrate that purified CCR9–/– hematopoietic stem cells are deficient in their ability to generate all major thymocyte subsets including double-negative 1 (DN1) cells in competitive transfers. CCR9–/– bone marrow contained normal numbers of lineage– Sca-1+c-kit+, common lymphoid progenitors, and lymphoid-primed multipotent progenitors (LMPP), and CCR9–/– LMPP showed similar T cell potential as their wild-type (WT) counterparts when cultured on OP9–{delta}-like 1 stromal cells. In contrast, early thymic progenitor and DN2 thymocyte numbers were reduced in the thymus of adult CCR9–/– mice. In fetal thymic organ cultures (FTOC), CCR9–/– DN1 cells were as efficient as WT DN1 cells in generating double-positive (DP) thymocytes; however, under competitive FTOC, CCR9–/– DP cell numbers were reduced significantly. Similarly, following intrathymic injection into sublethally irradiated recipients, CCR9–/– DN cells were out-competed by WT DN cells in generating DP thymocytes. Finally, in competitive reaggregation thymic organ cultures, CCR9–/– preselection DP thymocytes were disadvantaged significantly in their ability to generate CD4 single-positive (SP) thymocytes, a finding that correlated with a reduced ability to form TCR-MHC-dependent conjugates with thymic epithelial cells. Together, these results highlight a role for CCR9 at several stages of adult thymopoiesis: in hematopoietic progenitor seeding of the thymus, in the DN-DP thymocyte transition, and in the generation of CD4 SP thymocytes.
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8.
  • Aghaee, Naghmeh, et al. (författare)
  • Interaction Gaps in PhD Education and ICT as a Way Forward: Results from a Study in Sweden
  • 2016
  • Ingår i: International Review of Research in Open and Distance Learning. - : Athabasca University Press. - 1492-3831. ; 17:3, s. 360-383
  • Tidskriftsartikel (refereegranskat)abstract
    • Many research studies have highlighted the low completion rate and slow progress in PhD education. Universities strive to improve throughput and quality in their PhD education programs. In this study, the perceived problems of PhD education are investigated from PhD students' points of view, and how an Information and Communication Technology Support System (ICTSS) may alleviate these problems. Data were collected through an online open questionnaire sent to the PhD students at the Department of (the institution's name has been removed during the double-blind review) with a 59% response rate. The results revealed a number of problems in the PhD education and highlighted how online technology can support PhD education and facilitate interaction and communication, affect the PhD students' satisfaction, and have positive impacts on PhD students' stress. A system was prototyped, in order to facilitate different types of online interaction through accessing a set of online and structured resources and specific communication channels. Although the number of informants was not large, the result of the study provided some rudimentary ideas that refer to interaction problems and how an online ICTSS may facilitate PhD education by providing distance and collaborative learning, and PhD students' self-managed communication.
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9.
  • Artaxo, Paulo, et al. (författare)
  • Tropical and Boreal Forest – Atmosphere Interactions : A Review
  • 2022
  • Ingår i: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 74:1, s. 24-163
  • Forskningsöversikt (refereegranskat)abstract
    • This review presents how the boreal and the tropical forests affect the atmosphere, its chemical composition, its function, and further how that affects the climate and, in return, the ecosystems through feedback processes. Observations from key tower sites standing out due to their long-term comprehensive observations: The Amazon Tall Tower Observatory in Central Amazonia, the Zotino Tall Tower Observatory in Siberia, and the Station to Measure Ecosystem-Atmosphere Relations at Hyytiäla in Finland. The review is complemented by short-term observations from networks and large experiments.The review discusses atmospheric chemistry observations, aerosol formation and processing, physiochemical aerosol, and cloud condensation nuclei properties and finds surprising similarities and important differences in the two ecosystems. The aerosol concentrations and chemistry are similar, particularly concerning the main chemical components, both dominated by an organic fraction, while the boreal ecosystem has generally higher concentrations of inorganics, due to higher influence of long-range transported air pollution. The emissions of biogenic volatile organic compounds are dominated by isoprene and monoterpene in the tropical and boreal regions, respectively, being the main precursors of the organic aerosol fraction.Observations and modeling studies show that climate change and deforestation affect the ecosystems such that the carbon and hydrological cycles in Amazonia are changing to carbon neutrality and affect precipitation downwind. In Africa, the tropical forests are so far maintaining their carbon sink.It is urgent to better understand the interaction between these major ecosystems, the atmosphere, and climate, which calls for more observation sites, providing long-term data on water, carbon, and other biogeochemical cycles. This is essential in finding a sustainable balance between forest preservation and reforestation versus a potential increase in food production and biofuels, which are critical in maintaining ecosystem services and global climate stability. Reducing global warming and deforestation is vital for tropical forests.
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10.
  • Beverborg, Niels Grote, et al. (författare)
  • Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy
  • 2021
  • Ingår i: Nature Communications. - Stockholm : Karolinska Institutet, Dept of Cell and Molecular Biology. - 2041-1723.
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart failure (HF) is a major cause of morbidity and mortality worldwide, highlighting an urgent need for novel treatment options, despite recent improvements. Aberrant Ca2+ handling is a key feature of HF pathophysiology. Restoring the Ca2+ regulating machinery is an attractive therapeutic strategy supported by genetic and pharmacological proof of concept studies. Here, we study antisense oligonucleotides (ASOs) as a therapeutic modality, interfering with the PLN/SERCA2a interaction by targeting Pln mRNA for downregulation in the heart of murine HF models. Mice harboring the PLN R14del pathogenic variant recapitulate the human dilated cardiomyopathy (DCM) phenotype; subcutaneous administration of PLN-ASO prevents PLN protein aggregation, cardiac dysfunction, and leads to a 3-fold increase in survival rate. In another genetic DCM mouse model, unrelated to PLN (Cspr3/Mlp−/−), PLN-ASO also reverses the HF phenotype. Finally, in rats with myocardial infarction, PLN-ASO treatment prevents progression of left ventricular dilatation and improves left ventricular contractility. Thus, our data establish that antisense inhibition of PLN is an effective strategy in preclinical models of genetic cardiomyopathy as well as ischemia driven HF.
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12.
  • Björnfot, Cecilia, et al. (författare)
  • Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults : a 4D flow MRI study
  • 2024
  • Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016.
  • Tidskriftsartikel (refereegranskat)abstract
    • White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.
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13.
  • Brinkmalm-Westman, Ann, 1966, et al. (författare)
  • SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer's disease
  • 2014
  • Ingår i: Molecular Neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Synaptic degeneration is an early pathogenic event in Alzheimer's disease, associated with cognitive impairment and disease progression. Cerebrospinal fluid biomarkers reflecting synaptic integrity would be highly valuable tools to monitor synaptic degeneration directly in patients. We previously showed that synaptic proteins such as synaptotagmin and synaptosomal-associated protein 25 (SNAP-25) could be detected in pooled samples of cerebrospinal fluid, however these assays were not sensitive enough for individual samples. Results: We report a new strategy to study synaptic pathology by using affinity purification and mass spectrometry to measure the levels of the presynaptic protein SNAP-25 in cerebrospinal fluid. By applying this novel affinity mass spectrometry strategy on three separate cohorts of patients, the value of SNAP-25 as a cerebrospinal fluid biomarker for synaptic integrity in Alzheimer's disease was assessed for the first time. We found significantly higher levels of cerebrospinal fluid SNAP-25 fragments in Alzheimer's disease, even in the very early stages, in three separate cohorts. Cerebrospinal fluid SNAP-25 differentiated Alzheimer's disease from controls with area under the curve of 0.901 (P < 0.0001). Conclusions: We developed a sensitive method to analyze SNAP-25 levels in individual CSF samples that to our knowledge was not possible previously. Our results support the notion that synaptic biomarkers may be important tools for early diagnosis, assessment of disease progression, and to monitor drug effects in treatment trials.
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14.
  • Cossarizza, A., et al. (författare)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Tidskriftsartikel (refereegranskat)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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15.
  • De Genst, Erwin, et al. (författare)
  • Blocking phospholamban with VHH intrabodies enhances contractility and relaxation in heart failure
  • 2022
  • Ingår i: Nature Communications. - Stockholm : Karolinska Institutet, Dept of Cell and Molecular Biology. - 2041-1723.
  • Tidskriftsartikel (refereegranskat)abstract
    • The dysregulated physical interaction between two intracellular membrane proteins, the sarco/endoplasmic reticulum Ca2+ ATPase and its reversible inhibitor phospholamban, induces heart failure by inhibiting calcium cycling. While phospholamban is a bona-fide therapeutic target, approaches to selectively inhibit this protein remain elusive. Here, we report the in vivo application of intracellular acting antibodies (intrabodies), derived from the variable domain of camelid heavy-chain antibodies, to modulate the function of phospholamban. Using a synthetic VHH phage-display library, we identify intrabodies with high affinity and specificity for different conformational states of phospholamban. Rapid phenotypic screening, via modified mRNA transfection of primary cells and tissue, efficiently identifies the intrabody with most desirable features. Adeno-associated virus mediated delivery of this intrabody results in improvement of cardiac performance in a murine heart failure model. Our strategy for generating intrabodies to investigate cardiac disease combined with modified mRNA and adeno-associated virus screening could reveal unique future therapeutic opportunities.
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16.
  • Goldstein, Alisa M, et al. (författare)
  • Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents
  • 2007
  • Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 44:2, s. 99-106
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The major factors individually reported to be associated with an increased frequency of CDKN2A mutations are increased number of patients with melanoma in a family, early age at melanoma diagnosis, and family members with multiple primary melanomas (MPM) or pancreatic cancer. METHODS: These four features were examined in 385 families with > or =3 patients with melanoma pooled by 17 GenoMEL groups, and these attributes were compared across continents. RESULTS: Overall, 39% of families had CDKN2A mutations ranging from 20% (32/162) in Australia to 45% (29/65) in North America to 57% (89/157) in Europe. All four features in each group, except pancreatic cancer in Australia (p = 0.38), individually showed significant associations with CDKN2A mutations, but the effects varied widely across continents. Multivariate examination also showed different predictors of mutation risk across continents. In Australian families, > or =2 patients with MPM, median age at melanoma diagnosis < or =40 years and > or =6 patients with melanoma in a family jointly predicted the mutation risk. In European families, all four factors concurrently predicted the risk, but with less stringent criteria than in Australia. In North American families, only > or =1 patient with MPM and age at diagnosis < or =40 years simultaneously predicted the mutation risk. CONCLUSIONS: The variation in CDKN2A mutations for the four features across continents is consistent with the lower melanoma incidence rates in Europe and higher rates of sporadic melanoma in Australia. The lack of a pancreatic cancer-CDKN2A mutation relationship in Australia probably reflects the divergent spectrum of mutations in families from Australia versus those from North America and Europe. GenoMEL is exploring candidate host, genetic and/or environmental risk factors to better understand the variation observed.
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17.
  • Goldstein, Alisa M., et al. (författare)
  • High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL
  • 2006
  • Ingår i: Cancer Research. - 1538-7445 .- 0008-5472. ; 66:20, s. 9818-9828
  • Tidskriftsartikel (refereegranskat)abstract
    • GenoMEL, comprising major familial melanoma research groups from North America, Europe, Asia, and Australia has created the largest familial melanoma sample yet available to characterize mutations in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal melanoma (UM). This study included 466 families (2,137 patients) with at least three melanoma patients from 17 GenoMEL centers. Overall, 41% (n = 190) of families had mutations; most involved p16 (n = 178). Mutations in CDK4 (n = 5) and ARF (n = 7) occurred at similar frequencies (2-3%). There were striking differences in mutations across geographic locales. The proportion of families with the most frequent founder mutation(s) of each locale differed significantly across the seven regions (P = 0.0009). Single founder CDKN2A mutations were predominant in Sweden (p.R112_L113insR, 92% of family's mutations) and the Netherlands (c.225_243del19, 90% of family's mutations). France, Spain, and Italy had the same most frequent mutation (p.G101W). Similarly, Australia and United Kingdom had the same most common mutations (p.M53I, cdVS2-105A > G, p.R24P, and p.L32P). As reported previously, there was a strong association between PC and CDKN2A mutations (P < 0.0001). This relationship differed by mutation. In contrast, there was little evidence for an association between CDKN2A mutations and NST (P = 0.52) or UM (P = 0.25). There was a marginally significant association between NST and ARF (P = 0.05). However, this particular evaluation had low power and requires confirmation. This GenoMEL study provides the most extensive characterization of mutations in high-risk melanoma susceptibility genes in families with three or more melanoma patients yet available.
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18.
  • Gusarova, Viktoria, et al. (författare)
  • Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes
  • 2018
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.
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19.
  • Haghighi, Mona, et al. (författare)
  • A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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20.
  • Hansson, Henrik, et al. (författare)
  • Advanced Oxidation Treatment of Recalcitrant Wastewater from a Wood-Based Industry : a Comparative Study of O3 and O3/UV
  • 2015
  • Ingår i: Water, Air and Soil Pollution. - : Springer Science and Business Media LLC. - 0049-6979 .- 1573-2932. ; 226:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Ozone and ozone-based advanced oxidation processes were applied for the treatment of a recalcitrant wastewater generated by wood-based industries that contains different inorganic and organic constituents and high chemical oxygen demand (COD) varying between 3,400 and 4,000 mg/L. The investigation used a tubular ozone reactor combined with an UV reactor designed for different hydraulic retention times. The dependent variables addressed to evaluate the treatment efficiency were the reduction of COD and total organic carbon (TOC) and the biodegradability of the treated effluent based on respirometric studies using activated sludge from a wastewater treatment. The results showed that even though ozonation alone at acid pH promoted COD and TOC reductions of 65 and 31 % respectively, a decrease in the biodegradability was observed. The most effective treatment (COD and TOC reductions of 93 and 43 %, respectively) was obtained when applying ozone combined with UV light at basic pH. The ozone-UV combination was capable of increasing the amount of readily available COD by 75 % with an additional reduction of TOC by 60 %. In conclusion, ozonation at low pH effectively reduces the COD content in wastewater generated by the wood-based industry; however, in order to combine advanced oxidation with biological process, ozone combined with UV is recommended.
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21.
  • Hansson, Henrik, et al. (författare)
  • Chat yourself into the society : The development of an audio-visual online environment for the newly arrived
  • 2019
  • Ingår i: INTED2019 Proceedings. - Valencia : The International Academy of Technology, Education and Development. - 9788409086191 ; , s. 553-557
  • Konferensbidrag (refereegranskat)abstract
    • Large groups of refugees have arrived in Sweden during the last years with a peak in 2015 when there were around 1.3 million asylum applications. Many of the newly arrived are still not yet integrated into the Swedish society and language skills is a key factor for a successful inclusion and integration process. There is a need for new digital language learning tools, not least for informal self-learning. The aim of the study is to describe and discuss the development and evaluation of an audio-visual online tool for informal language learning as a complement to formal language training.The overall research strategy has been action research with a qualitative investigation where data were gathered in a mix of usability tests, observations and interviews. Main informants were 12 students from three separate courses on Swedish for newly arrived. Since the group of informants constitute an exposed group, personal details have been kept as anonymous as possible.Findings indicate that several design concepts were useful and appreciated by the test group, but several users wanted an alternative to the Facebook based login. Gamification seemed to be a promising way to increase motivation, and many participants perceived that a feature with direct translation of messages would be a good way to improve the language learning. Furthermore, there were requests for tool mechanisms to filter conversation partners by gender and by interests.   
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22.
  • Hansson, Henrik, 1978-, et al. (författare)
  • Electrocoagulation coupled to activated carbon sorption/filtration for treatment of cleaning wastewaters from wood-based industry
  • 2014
  • Ingår i: Desalination and Water Treatment. - London : Taylor & Francis Group. - 1944-3994 .- 1944-3986. ; 52:28-30, s. 5243-5251
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this investigation was to study the use of a coupled treatment (electrocoagulation(EC) and sorption/filtration treatment) with different sequencing to reduce the organic pollutantsmeasured as chemical oxygen demand (COD) of five highly polluted wastewater streamsgenerated after washing surfaces and machinery in the wooden floor industry and to evaluate,how different sequencing of these treatment units affects the overall system efficiency. On thebasis of preliminary studies, an EC reactor (1.0 L) was constructed with monopolar electrodes inparallel connection in an array of four Al electrodes with surface area of 93.2 cm2and an appliedcurrent density of 161 A m–2. This reactor was coupled to a sorption/filtration unit with coalactivated carbon. The EC reactor was tested in two different sequences (before and after the sorption/filtration unit). The overall COD reduction varied from 2% ± 0.5% to 77% ± 2.9%, dependingon the sequence and the treated wastewater stream. The best result from efficiency andoperational viewpoints was obtained with the EC reactor placed after the sorption/filtrationcolumn. The increase in efficiency is likely to be due to the removal by sorption in the activatedcarbon of compounds that interfere with EC. Additionally, as desired, the use of EC before thesorption unit extended the activated carbon lifetime.
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23.
  • Hansson, Henrik, et al. (författare)
  • Inclusion and Integration in Sweden: Using Video Chat for New Arrivals in Sweden : How to Learn Swedish Live with Swedes Online – Easy, Flexible, Informal, Fast, Fun
  • 2017
  • Ingår i: EDEN 2017 Annual Conference: Diversity Matters!. - : European Distance and E-Learning Network. - 9786155511165 ; , s. 2-2
  • Konferensbidrag (refereegranskat)abstract
    • In a time when immigration often is described as a burden, this study focuses on how the resources brought by the new arrivals could enrich the Swedish society. The basis is an innovative video chat for new arrivals in Sweden and it is potential for language learning and contact between new arrivals and established Swedes. Focus is on the role of innovative information and communication technology (ICT) services including distance education and informal cross-border communication. Demonstration of the newly developed IT-service will be conducted in relation to the following issues: How can the language diversity of the new arrivals be utilized as a resource? How can a purpose built video-Internet system facilitate the integration of new arrivals? What incentives need to be developed to include the Swedes and the local community? What kind of ethical guidelines need to be applied regarding integrity and how open the personal data should be in a specially designed ICT system for new arrivals? How can innovative ICT systems shorten the time for new arrivals to get internships and work in Sweden? The e-service, www.snackasvenska.nu (“chat in Swedish now”) are constructed with: (a) safe and secure log in, (b) filter-search mechanisms (such as females can search and be matched only with female speakers, etc.), (c) a lingo point system (more speaking time = more points; new Swedes can show how much time the spoken to Swedes and Swedes can show how much they contributed), (d) a topic box of random speaking themes, (e) a text chat with auto translation from speakers mother tongue to speaking partners mother tongue and more features. The system has been tested with new arrivals/new Swedes – Swedes in Gotland. A demo will be given and results presented at the conference.
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24.
  • Hansson, Henrik, 1978-, et al. (författare)
  • Photo-fenton and fenton oxidation of recalcitrant industrial wastewater
  • 2012
  • Ingår i: Proceedings / Linnaeus ECO-TECH 2012, international conference on natural sciences and environmental technologies for waste and wastewater treatment, remediation, emissions related to climate, environmental and economic effects ; the eighth International Conference on the Establishment of Cooperation between Companies and Institutions in the Nordic Countries, the Baltic Sea Region, and the World, November 26-28, 2012, Kalmar, Sweden. - : Linnaeus University. - 9789186983864 ; , s. 187-
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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25.
  • Hansson, Henrik, et al. (författare)
  • Photo-Fenton and Fenton Oxidation of Recalcitrant Industrial Wastewater Using Nanoscale Zero-Valent Iron
  • 2012
  • Ingår i: International Journal of Photoenergy (Online). - : Hindawi Limited. - 1110-662X .- 1687-529X. ; 2012
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a need for the development of on-site wastewater treatment technologies suitable for "dry-process industries," such as the wood-floor sector. Due to the nature of their activities, these industries generate lower volumes of highly polluted wastewaters after cleaning activities. Advanced oxidation processes such as Fenton and photo-Fenton, are potentially feasible options for treatment of these wastewaters. One of the disadvantages of the Fenton process is the formation of large amounts of ferrous iron sludge, a constraint that might be overcome with the use of nanoscale zero-valent iron (nZVI) powder. Wastewater from a wood-floor industry with initial COD of 4956 mg/L and TOC of 2730 mg/L was treated with dark-Fenton (nZVI/H2O2) and photo-Fenton (nZVI/H2O2/UV) applying a 2-level full-factorial experimental design. The highest removal of COD and TOC (80% and 60%, resp.) was achieved using photo-Fenton. The supply of the reactants in more than one dose during the reaction time had significant and positive effects on the treatment efficiency. According to the results, Fenton and mostly photo-Fenton are promising treatment options for these highly recalcitrant wastewaters. Future investigations should focus on optimizing treatment processes and assessing toxic effects that residual pollutants and the nZVI might have. The feasibility of combining advanced oxidation processes with biological treatment is also recommended.
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26.
  • Hansson, Henrik, et al. (författare)
  • Photo-Fenton and Fenton Oxidation of Recalcitrant Wastewater from the Wooden Floor Industry
  • 2015
  • Ingår i: Water environment research. - 1061-4303 .- 1554-7531. ; 87:6, s. 491-497
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a need for development of on-site wastewater treatment technologies suitable to "dry-process'' industries, such as the wooden floor sector. Due to the nature of their activities, these industries generate low volumes of highly polluted and recalcitrant wastewaters due to washing and cleaning surfaces and machinery. Advanced oxidation processes such as Fenton and photo-Fenton are potentially feasible options for the treatment of wastewaters with not easily biodegradable pollutants. The wastewater from a wooden floor industry with initial COD value of 4956 mg/L and TOC value of 2730 mg/L was treated with Fenton (Fe/H2O2) and photo-Fenton (Fe/H2O2/UV) applying a 2-level full-factorial experimental design. The highest removals of COD and TOC (79% and 62% respectively) were achieved when photo-Fenton was applied. In conclusion, Fenton and photo-Fenton are promising treatment options for these highly recalcitrant wastewaters, photo-Fenton being a more promising option according to the results.
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27.
  • Hansson, Henrik, 1978- (författare)
  • Treatment of Wastewater Generated by Wood-based Dry Industries : Advances Oxidation Processes & Electrocoagulation
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Wood is a material with an enormous number of applications. For decades, the development of wastewater treatment technologies tailored for the wood sector has focused on those industries that have water as an integral part of the industrial production, such as paper and pulp. However, there is a large and potentially growing sector that has been neglected, which is formed by industries in which water is not part of their production line, as for example, the wood floor and furniture industries (named wood-based dry industries). These industries still produces relatively low volumes of highly polluted wastewaters, with COD up to 30,000 mg/L, due to cleaning/washing procedure (named cleaning wastewaters). These cleaning wastewaters are often sent to the municipal wastewater treatment plant after dilution with potable water. Once there, recalcitrant pollutants are diluted and discharged into recipient water bodies or trapped in the municipal wastewater sludge. Another type of contaminated water these “dry industries” often generate in high volumes, and which is usually discharged with no previous treatment, is storm-water containing contaminants that have leached from large wood storage areas. The overall aim of this thesis was to increase the level of knowledge and competence and to present on-site wastewater treatment options for wood-based dry industries using the wood floor industry as a case-study, with a focus on combined treatment methods and solutions applicable to both the cleaning wastewater and storm-water. Among the treatment technologies investigated, electrocoagulation was studied both as a standalone treatment and combined with sorption using activated carbon. The combined treatment achieved a COD reduction of approximately 70%. Some advanced oxidation processes (AOP) were also studied: a COD reduction of approximately 70% was achieved by photo-Fenton, but the most successful AOP was ozone combined with UV light, were a COD reduction around 90% was achieved, with additional improvement in the biodegradability of the treated effluent. Ozone also proved to be effective in degrading organic compounds (approximately 70% COD reduction) and enhanced the biodegradability of the storm-water runoff from wood storage areas. The results have shown that the application of ozone can be considered an option for treatment of cleaning wastewaters and possibly for storm-water biodegradation enhancement.
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28.
  • Hansson, Lars-Anders, et al. (författare)
  • Experimental evidence for a mismatch between insect emergence and waterfowl hatching under increased spring temperatures
  • 2014
  • Ingår i: Ecosphere. - : Ecological Society of America. - 2150-8925 .- 2150-8925. ; 5:9, s. 120-
  • Tidskriftsartikel (refereegranskat)abstract
    • By combining a large-scale experimental assessment on timing of insect emergence with longtermmonitoring of waterfowl hatching date, we here show that insect emergence is mainly driven bytemperature, whereas there is only a weak effect of increasing spring temperatures on inter-annualvariability in observations of waterfowl chicks. Hence, a change in timing of the mass-emergence of insectsfrom lakes and wetlands, which is the crucial food source for waterfowl chicks, will likely result in aconsumer/resource mismatch in a future climate change perspective. Specifically, we experimentally showthat a moderate increase in temperature of 38C above ambient, expected to occur within 25–75 years, leadsto a considerably (2 weeks) earlier, and more pronounced, peak in insect emergence (Chironomus sp).Moreover, by utilizing long-term Citizen Science databases, ranging over several decades, we also showthat common waterfowl species are unable to significantly adjust their reproduction to fit futuretemperature increase. Hence, based on our data we predict a future mismatch between insect emergenceand waterfowl species basing their reproduction on temperature. This will have a profound impact onreproductive success and population dynamics of many aquatic birds, as well as on freshwaterbiodiversity.
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29.
  • Hansson, Lars-Anders, et al. (författare)
  • Experimental evidence for a mismatch between insect emergence and waterfowl hatching under increased spring temperatures
  • 2014
  • Ingår i: Ecosphere. - : Wiley-Blackwell. - 2150-8925. ; 5:9, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • By combining a large-scale experimental assessment on timing of insect emergence with long-term monitoring of waterfowl hatching date, we here show that insect emergence is mainly driven by temperature, whereas there is only a weak effect of increasing spring temperatures on inter-annual variability in observations of waterfowl chicks. Hence, a change in timing of the mass-emergence of insects from lakes and wetlands, which is the crucial food source for waterfowl chicks, will likely result in a consumer/resource mismatch in a future climate change perspective. Specifically, we experimentally show that a moderate increase in temperature of 3 degrees C above ambient, expected to occur within 25-75 years, leads to a considerably (2 weeks) earlier, and more pronounced, peak in insect emergence (Chironomus sp). Moreover, by utilizing long-term Citizen Science databases, ranging over several decades, we also show that common waterfowl species are unable to significantly adjust their reproduction to fit future temperature increase. Hence, based on our data we predict a future mismatch between insect emergence and waterfowl species basing their reproduction on temperature. This will have a profound impact on reproductive success and population dynamics of many aquatic birds, as well as on freshwater biodiversity.
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30.
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31.
  • Hansson, Markus, et al. (författare)
  • Biosynthesis, processing, and sorting of human myeloperoxidase.
  • 2006
  • Ingår i: Archives of Biochemistry and Biophysics. - : Elsevier BV. - 0003-9861. ; 445:2, s. 214-224
  • Forskningsöversikt (refereegranskat)abstract
    • Exclusively synthesized by normal neutrophil and monocyte precursor cells, myeloperoxidase (MPO) functions not only in host defense by mediating efficient microbial killing but also can contribute to progressive tissue damage in chronic inflammatory states Such as atherosclerosis. The biosynthetic precursor, apoproMPO, is processed slowly in the ER, undergoing cotranslational N-glycosylation, transient interactions with the molecular chaperones calreticulin and calnexin, and heme incorporation to generate enzymatically active proMPO that is competent for export into the Golgi. After exiting the Golgi the propeptide is removed prior to final proteolytic processing in azurophil granules, resulting in formation of a symmetric MPO homodimer linked by a disulfide bond. Some proMPO escapes granule targeting and becomes constitutively secreted to the extracellular environment. Although the precise mechanism is Unknown, the pro-segirient is required for normal processing and targeting. as propeptide-deleted MPO precursor is either degraded or constitutively secreted. Characterizing the molecular consequences of naturally Occurring mutations that cause inherited MPO deficiency provides unique insight into the structural determinants of MPO involved in biosynthesis, processing and targeting. (C) 2005 Elsevier Inc. All rights reserved.
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32.
  • Hansson, Per-Olof, et al. (författare)
  • Daily Usage of Smartphones : New Activities for Kenyan Elite Runners
  • 2016
  • Ingår i: Journal of Mobile Technologies, Knowledge and Society. - : International Business Information Management Association (IBIMA). - 2155-4811. ; 2016
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper analyzes how a group of Kenyan elite runners used smartphones in their daily activities for one year. This study used a participatory action research approach to explore 30 young Kenyan runners’ appropriation and day-to-day use of smartphones. The runners lived in two different low-income areas in Nairobi and were not accustomed to smartphones. The research focused on how the participants utilized the smartphone, its applications, and the Web to improve their learning, training, living conditions, and social interactions. To investigate the participants’ progress, every smartphone was tracked and its usage was analyzed according to Koole’s (2009) FRAME model. Findings highlighted that new activities arose through frequent usage of the Web and smartphone applications. 180,000 different visits to websites were made and the most popular usage was searching with Google and Yahoo, entertainment, social media, news, and sports related websites. In total, 346,832 applications were used and the phone, launcher and contacts were the primary applications. However, the findings showed a significant use of communication, camera, native applications and applications for running. A concluding remark is that the smartphone acted as a powerful tool for real-life improvement such as improved learning, current events awareness and social interactions for poor people in a developing country.
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33.
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34.
  • Hansson, Per-Olof, 1968-, et al. (författare)
  • Frontrunners in ICT : Kenyan runners’ improvement in training, informal learning and economic opportunities using smartphones
  • 2014
  • Ingår i: ijEDict - International Journal of Education and Development using Information and Communication Technology. - 1814-0556. ; 10:4, s. 4-20
  • Tidskriftsartikel (refereegranskat)abstract
    • The primary aim of this research was to study how mobile technology shapes, changes, and develops informal learning outside the classroom and school environment. In this study we provided each of the 30 Kenyan elite runners with a simple Android smartphone and free Internet for one year. This research project was a developmental intervention with a participatory action research approach, and aimed to facilitate innovation and examine how the runners developed their training, informal learning, and economic opportunities using a smartphone. Logs and tracking of smartphone usage recorded quantitative data, and interviews and participatory observations gathered qualitative data. Key findings were that the smartphone improved the runners’ training and race performance and created business opportunities. Second, a smartphone with an Internet connection empowered marginalized groups and augmented informal learning opportunities. Third, that a smartphone was not a significant technological hurdle for impoverished or uneducated individuals. Fourth, the participants were able to learn with little or no guidance or scaffolding. Fifth, the tracking log data indicated both a breadth and depth to individual learning. This participatory action research made a significant impact on the participants’ lives and the most common statement from the interviews was the statement “it helps us a lot”.
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35.
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36.
  • Hansson, William, et al. (författare)
  • Cerebral Microbleeds-Long-Term Outcome After Cerebrospinal Fluid Shunting in Idiopathic Normal Pressure Hydrocephalus
  • 2023
  • Ingår i: Neurosurgery. - : Wolters Kluwer. - 0148-396X .- 1524-4040. ; 93:2, s. 300-308
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cerebral microbleeds (CMBs) are common in idiopathic normal pressure hydrocephalus (INPH) and have been suggested as radiological markers of a brain prone to bleeding. The presence of CMBs might be relevant when selecting patients for shunt surgery.OBJECTIVE: To evaluate whether CMBs increases long-term risk of hemorrhagic complications and mortality or affects outcomes after cerebrospinal fluid shunt surgery in a cohort of patients with INPH.METHODS: One hundred and forty nine shunted patients with INPH (mean age, 73 years) were investigated with MRI (T2* or susceptibility-weighted imaging sequences) preoperatively. CMBs were scored with the Microbleed Anatomic Rating Scale. Patients were observed for a mean of 6.5 years (range 2 weeks to 13 years) after surgery. Hemorrhagic events and death were noted. Improvement in gait was evaluated 3 to 6 months after surgery.RESULTS: At baseline, 74 patients (50%) had CMBs. During follow-up, 7 patients (5%) suffered a hemorrhagic stroke and 43 (29%) suffered a subdural hematoma/hygroma with a median time from surgery of 30.2 months (IQR 50). Overall, having CMBs was not associated with suffering a subdural hematoma/hygroma or hemorrhagic stroke during follow-up with 1 exception that an extensive degree of CMBs (≥50 CMB) was more common in patients suffering a hemorrhagic stroke ( P = .03). CMBs were associated with increased mortality ( P = .02, Kaplan-Meier, log-rank test). The presence of CMBs did not affect gait outcome ( P = .28).CONCLUSION: CMBs were associated with hemorrhagic stroke and mortality. CMBs do not seem to reduce the possibility of gait improvement after shunt surgery or contribute to the risk of hemorrhagic complications regarding subdural hematoma or hygroma.
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37.
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38.
  • Holmén, Jessica, 1971, et al. (författare)
  • Mucins and their O-Glycans from human bronchial epithelial cell cultures.
  • 2004
  • Ingår i: American journal of physiology. Lung cellular and molecular physiology. - : American Physiological Society. - 1040-0605 .- 1522-1504. ; 287:4
  • Tidskriftsartikel (refereegranskat)abstract
    • A longstanding question in obstructive airway disease is whether observed changes in mucin composition and/or posttranslational glycosylation are due to genetic or to environmental factors. We tested whether the mucins secreted by second-passage primary human bronchial epithelial cell cultures derived from noncystic fibrosis (CF) or CF patients have intrinsically different specific mucin compositions, and whether these mucins are glycosylated differently. Both CF and non-CF cultures produced MUC5B, predominantly, as judged by quantitative agarose gel Western blots with mucin-specific antibodies: MUC5B was present at approximately 10-fold higher levels than MUC5AC, consistent with our previous mRNA studies (Bernacki SH, Nelson AL, Abdullah L, Sheehan JK, Harris A, William DC, and Randell SH. Am J Respir Cell Mol Biol 20: 595-604, 1999). O-linked oligosaccharides released from purified non-CF and CF mucins and studied by HPLC mass spectrometry had highly variable glycan structures, and there were no observable differences between the two groups. Hence, there were no differences in either the specific mucins or their O-glycans that correlated with the CF phenotype under the noninfected/noninflammatory conditions of cell culture. We conclude that the differences observed in the mucins sampled directly from patients are most likely due to environmental factors relating to infection and/or inflammation.
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39.
  • Holmkvist, Petra, et al. (författare)
  • A major population of mucosal memory CD4(+) T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality.
  • 2015
  • Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 8:3, s. 545-558
  • Tidskriftsartikel (refereegranskat)abstract
    • Mucosal tissues contain large numbers of memory CD4(+) T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4(+) T cells at barrier surfaces that coexpress interleukin-18 receptor alpha (IL-18Rα) and death receptor-3 (DR3), and display innate lymphocyte functionality. The cytokines IL-15 or the DR3 ligand tumor necrosis factor (TNF)-like cytokine 1A (TL1a) induced memory IL-18Rα(+)DR3(+)CD4(+) T cells to produce interferon-γ, TNF-α, IL-6, IL-5, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα(+)DR3(+)CD4(+) T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively, these results suggest that human memory IL-18Rα(+)DR3(+) CD4(+) T cells may contribute to antigen-independent innate responses at barrier surfaces.Mucosal Immunology advance online publication, 1 October 2014; doi:10.1038/mi.2014.87.
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40.
  • Insel, Philip S., et al. (författare)
  • Time to amyloid positivity and preclinical changes in brain metabolism, atrophy, and cognition : Evidence for emerging amyloid pathology in alzheimer's disease
  • 2017
  • Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 11:MAY
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Aβ pathology is associated with longitudinal changes of brain metabolism, atrophy, and cognition, in cognitively healthy elders. However, Aβ information is usually measured cross-sectionally and dichotomized to classify subjects as Aβ-positive or Aβ-negative, making it difficult to evaluate when brain and cognitive changes occur with respect to emerging Aβ pathology. In this study, we use longitudinal Aβ information to combine the level and rate of change of Aβ to estimate the time to Aβ-positivity for each subject and test this temporal proximity to significant Aβ pathology for associations with brain structure, metabolism, and cognition. Methods: In 89 cognitively healthy elders with up to 10 years of follow-up, we estimated the points at which rates of fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to the time to Aβ-positivity. Points of initial acceleration in rates of decline were estimated using mixed-effects models with penalized regression splines. Results: Acceleration of rates of FDG PET were observed to occur 20+ years before the conventional threshold for Aβ-positivity. Subtle signs of cognitive dysfunction were observed 10+ years before Aβ-positivity. Conclusions: Aβ may have subtle associations with other hallmarks of Alzheimer's disease before Aβ biomarkers reach conventional thresholds for Aβ-positivity. Therefore, we propose that emerging Aβ pathology occurs many years before cognitively healthy elders reach the current threshold for Aβ positivity (preclinical AD). To allow prevention in the earliest disease stages, AD clinical trials may be designed to also include subjects with Aβ biomarkers in the sub-threshold range.
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41.
  • Jaensson Gyllenbäck, Elin, et al. (författare)
  • Small intestinal CD103(+) dendritic cells display unique functional properties that are conserved between mice and humans
  • 2008
  • Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205:9, s. 2139-2149
  • Tidskriftsartikel (refereegranskat)abstract
    • A functionally distinct subset of CD103(+) dendritic cells (DCs) has recently been identified in murine mesenteric lymph nodes (MLN) that induces enhanced FoxP3(+) T cell differentiation, retinoic acid receptor signaling, and gut-homing receptor (CCR9 and alpha 4 beta 7) expression in responding T cells. We show that this function is specific to small intestinal lamina propria (SI-LP) and MLN CD103(+) DCs. CD103(+) SI-LP DCs appeared to derive from circulating DC precursors that continually seed the SI- LP. BrdU pulse-chase experiments suggested that most CD103(+) DCs do not derive from a CD103(-) SI- LP DC intermediate. The majority of CD103(+) MLN DCs appear to represent a tissue- derived migratory population that plays a central role in presenting orally derived soluble antigen to CD8(+) and CD4(+) T cells. In contrast, most CD103(+) MLN DCs appear to derive from blood precursors, and these cells could proliferate within the MLN and present systemic soluble antigen. Critically, CD103(+) DCs with similar phenotype and functional properties were present in human MLN, and their selective ability to induce CCR9 was maintained by CD103(+) MLN DCs isolated from SB Crohn ' s patients. Thus, small intestinal CD103(+) DCs represent a potential novel target for regulating human intestinal infl ammatory responses.
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42.
  • Janelidze, Shorena, et al. (författare)
  • Detection of Brain Tau Pathology in Down Syndrome Using Plasma Biomarkers
  • 2022
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 79:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Novel plasma biomarkers, especially phosphorylated tau (p-tau), can detect brain tau aggregates in Alzheimer disease. Objective: To determine which plasma biomarker combinations can accurately detect tau pathological brain changes in Down syndrome (DS). Design, Setting, and Participants: The cross-sectional, multicenter Alzheimer's Biomarker Consortium-Down Syndrome study included adults with DS and a control group of siblings without DS. All participants with plasma, positron emission tomography (PET), and cognitive measures available by the time of data freeze 1.0 were included. Participants were enrolled between 2016 and 2019, and data were analyzed from August 2021 to April 2022. Exposures: Plasma p-tau217, glial fibrillary acidic protein (GFAP), amyloid β42/40 (Aβ42/Aβ40), neurofilament light (NfL), and total tau (t-tau); tau positron emission tomography (tau-PET) and Aβ-PET. Main Outcomes and Measures: The primary outcome was tau-PET status. Secondary outcomes included Aβ-PET status and cognitive performance. Results: Among 300 participants with DS and a control group of 37 non-DS siblings, mean (SD) age was 45.0 (10.1) years, and 167 (49.6%) were men. Among participants with DS who all underwent plasma p-tau217 and GFAP analyses, 258 had other plasma biomarker data available and 119, 213, and 288 participants had tau-PET, Aβ-PET, and cognitive assessments, respectively. Plasma p-tau217 and t-tau were significantly increased in Aβ-PET-positive tau-PET-positive (A+T+) DS and A+T-DS compared with A-T-DS while GFAP was only increased in A+T+DS. Plasma p-tau217 levels were also significantly higher in A+T+DS than A+T-DS. In participants with DS, plasma p-tau217 and GFAP (but not other plasma biomarkers) were consistently associated with abnormal tau-PET and Aβ-PET status in models covaried for age (odds ratio range, 1.59 [95% CI, 1.05-2.40] to 2.32 [95% CI, 1.36-3.96]; P <.03). A combination of p-tau217 and age performed best when detecting tau-PET abnormality in temporal and neocortical regions (area under the curve [AUC] range, 0.96-0.99). The most parsimonious model for Aβ-PET status included p-tau217, t-tau, and age (AUC range, 0.93-0.95). In multivariable models, higher p-tau217 levels but not other biomarkers were associated with worse performance on DS Mental Status Examination (β, -0.24, 95% CI, -0.36 to -0.12; P <.001) and Cued Recall Test (β, -0.40; 95% CI, -0.53 to -0.26; P <.001). Conclusions and Relevance: Plasma p-tau217 is a very accurate blood-based biomarker of both tau and Aβ pathological brain changes in DS that could help guide screening and enrichment strategies for inclusion of individuals with DS in future AD clinical trials, especially when it is combined with age as a covariate.
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43.
  • Jobe, William Byron, et al. (författare)
  • Putting a MOOC for Human Rights in the Hands of Kenyans : THe Haki Zangu Case for Non-Formal Learning
  • 2014
  • Ingår i: The Electronic Journal of Information Systems in Developing Countries. - 1681-4835. ; 65:3, s. 1-17
  • Tidskriftsartikel (refereegranskat)abstract
    • The research goal of this project was to explore the use and effects of non-formal education and incentives in the context of a developing country. The practical aim of this project was to create, implement, and evaluate a platform about human rights that was available to any Kenyan for free in order to increase knowledge and engagement. Therefore, a non-formal massive open online course (MOOC) about human rights was designed and launched. The course was free and open to anyone in Kenya and offered both a digital badge and certificate from Stockholm University in Sweden upon completion. The course was called Haki Zangu (Kiswahili for “My Rights”), and it explored how using incentives such as a digital badge and certificate of completion affected learning outcomes. This course offered ubiquitous access based on principles of responsive web design and used audio recordings of the entire course content. The course is perpetual and still on-going, but after six months there were 160 participants who had enrolled, and ten participants had completed the course and received certificates and digital badges. The participants showed extensive enthusiasm and engagement for human rights issues, and they expressed desires to learn more and further spread knowledge about human rights. The current findings suggest that the availability of digital badges and certificates increased interest for participation and positively affected learning outcomes. Moreover, the use of a Massive Open Online Course (MOOC) format with incentives proved successful, combined with the contextualization and accessibility of the course content. Furthermore, the technical platform proved adequate for disseminating education for free in a developing country, and allowed for unencumbered access regardless of device. Lastly, a key challenge for future non-formal learning efforts in developing countries is the cost of Internet access.
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44.
  • Jobe, William, 1970- (författare)
  • Do-It-Yourself Learning in Kenya : Exploring mobile technologies for merging non-formal and informal learning
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The educational landscape is changing and a variety of technologies and techniques are blurring the lines between traditional and non-traditional learning. This change is substantial in low-income countries: individuals in developing countries have a great desire to educate themselves and improve their quality of life. Kenyans are adequately literate and accustomed to mobile technology despite being a largely impoverished, poorly educated populace. Kenya represents an optimal setting in which to research the use and feasibility of modern mobile and educational technologies. The broad aim of this dissertation is to explore how mobile devices can catalyze and enhance both informal and non-formal learning. In particular, this dissertation explores how technologies and concepts such as mobile web apps, Massive Open Online Courses (MOOCs), and learning incentives via a smartphone specifically affect informal and non-formal learning in Kenya. The primary research question is how can learning efforts that utilize mobile learning, MOOCs, and learning incentives combine non-formal and informal learning to develop and contribute to a do-it-yourself (DIY) approach to learning in Kenya? The primary method is action research. The first contribution of this dissertation is the finding that mobile web apps are currently better suited for data exchange than producing new content. The second contribution is the finding that a smartphone can enhance informal learning in a developing country with little or no scaffolding. The third contribution is the finding that non-formal learning efforts as a MOOC are shown to be a viable means of delivering non-formal learning in a developing country via a smartphone. The fourth contribution is the finding that the use of incentives such as digital badges provide a means by which to validate non-formal learning and contribute to a DIY attitude towards learning creation, where individuals can freely complement or replace a traditional curriculum.
  •  
45.
  • Jobe, William, et al. (författare)
  • Mobile Learning for Human Rights in Kenya : The Haki Zangu Case For Non-Formal Learning
  • 2013
  • Ingår i: ICT for Anti-Corruption, Democracy And Education In East Africa. - Kista : SPIDER. - 9789163746031 ; , s. 67-82
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • This project, entitled “Mobile Online Learning for Human Rights”, was conducted in cooperation with the Kenya Human Rights Commission (KHRC) in their Spider project “Reforms through citizen participation and government accountability”. The primary goal was to create a platform to spread information about human rights to any Kenyan for free in order to increase knowledge and engagement. The research goals of this project were to explore the viability of using a Massive Open Online Course (MOOC) with incentives to reach, engage, and educate Kenyans. Therefore, a non-formal MOOC (Massive Open Online Course) about human rights using any Internet connected device was designed and created. The course was free and open to anyone in Kenya and offered both a digital badge and certificate from Stockholm University in Sweden upon completion. The course was called Haki Zangu (Kiswahili for “My Rights”), and explored how using incentives such as digital badges and certificates of completion affected learning outcomes and ubiquitous access based on principles of responsive web design and using audio recordings of the entire course content. The course is still ongoing, but after six months there were 160 participants who had enrolled, and ten participants had completed the course and received certificates and digital badges. The participants showed extensive enthusiasm and engagement for human rights issues and expressed desires to learn more and further spread knowledge about human rights. The current findings indicate that the availability of digital badges and certificates increased interest for participation and positively affected learning outcomes. Furthermore, the platform proved adequate for disseminating education in a developing country, and allowed for unencumbered, ubiquitous access regardless of device. Additionally, pedagogically the participants found ethical dilemmas and forum discussions regarding various Human Rights issues most rewarding. Lastly, key challenges for future MOOC efforts in developing countries are Internet access and its costs.
  •  
46.
  • Lacson, John Charles A., et al. (författare)
  • Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families
  • 2021
  • Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited. Methods: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates. Results: A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis. Conclusions: Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families.
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47.
  •  
48.
  •  
49.
  • Lebreton, Sebastien, et al. (författare)
  • A Drosophila female pheromone elicits species-specific long-range attraction via an olfactory channel with dual specificity for sex and food
  • 2017
  • Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mate finding and recognition in animals evolves during niche adaptation and involves social signals and habitat cues. Drosophila melanogaster and related species are known to be attracted to fermenting fruit for feeding and egg-laying, which poses the question of whether species-specific fly odours contribute to long-range premating communication. Results: We have discovered an olfactory channel in D. melanogaster with a dual affinity to sex and food odorants. Female flies release a pheromone, (Z)-4-undecenal (Z4-11Al), that elicits flight attraction in both sexes. Its biosynthetic precursor is the cuticular hydrocarbon (Z,Z)-7,11-heptacosadiene (7,11-HD), which is known to afford reproductive isolation between the sibling species D. melanogaster and D. simulans during courtship. Twin olfactory receptors, Or69aB and Or69aA, are tuned to Z4-11Al and food odorants, respectively. They are co-expressed in the same olfactory sensory neurons, and feed into a neural circuit mediating species-specific, long-range communication; however, the close relative D. simulans, which shares food resources with D. melanogaster, does not respond to Z4-11Al. Conclusion: The Or69aA and Or69aB isoforms have adopted dual olfactory traits. The underlying gene yields a collaboration between natural and sexual selection, which has the potential to drive speciation.
  •  
50.
  • Leden, Lotta, et al. (författare)
  • Introducing the human elements of science through a context-rich thematic project
  • 2020
  • Ingår i: Nature of science in science instruction. - Cham : Springer Publishing Company. ; , s. 697-709
  • Bokkapitel (populärvet., debatt m.m.)abstract
    • The chapter describes how nature of science (NOS), and especially the human elements of science (i.e., creativity, subjectivity, and influences from sociocultural factors), can be taught to 12-year-old students. An extensive example is provided of how human elements of science were introduced through a thematic project on the topic of “Sugar and Sweeteners.” Throughout the projects, teachers used various contexts and approaches such as a small scale home investigation, readings and discussions of news articles and web-based articles, a panel debate, and planning of a small investigation. A focus on human elements of science as well as highly contextualized teaching means a shift away from traditional school science teaching. Myths about science are challenged at the same time as structures for school science practice are challenged. The detailed example provided here can serve to show that such teaching is possible and thereby become a means in the hard work of breaking traditional patterns of school science teaching that more often strengthen myths of science than challenge them.
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