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1.
  • Joshi, Peter K, et al. (författare)
  • Directional dominance on stature and cognition in diverse human populations
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
  • Tidskriftsartikel (refereegranskat)abstract
    • Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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2.
  • Knopman, David S., et al. (författare)
  • The National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease : Perspectives from the Research Roundtable
  • 2018
  • Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:4, s. 563-575
  • Forskningsöversikt (refereegranskat)abstract
    • The Alzheimer's Association's Research Roundtable met in November 2017 to explore the new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease. The meeting allowed experts in the field from academia, industry, and government to provide perspectives on the new National Institute on Aging and the Alzheimer's Association Research Framework. This review will summarize the “A, T, N System” (Amyloid, Tau, and Neurodegeneration) using biomarkers and how this may be applied to clinical research and drug development. In addition, challenges and barriers to the potential adoption of this new framework will be discussed. Finally, future directions for research will be proposed.
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3.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
  • 2015
  • Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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4.
  • 2017
  • swepub:Mat__t
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5.
  • Divakar, Pradeep K., et al. (författare)
  • Evolution of complex symbiotic relationships in a morphologically derived family of lichen-forming fungi
  • 2015
  • Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 208:4, s. 1217-1226
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the evolutionary history of the Parmeliaceae (Lecanoromycetes, Ascomycota), one of the largest families of lichen-forming fungi with complex and variable morphologies, also including several lichenicolous fungi. We assembled a six-locus data set including nuclear, mitochondrial and low-copy protein-coding genes from 293 operational taxonomic units (OTUs). The lichenicolous lifestyle originated independently three times in lichenized ancestors within Parmeliaceae, and a new generic name is introduced for one of these fungi. In all cases, the independent origins occurred c. 24 million yr ago. Further, we show that the Paleocene, Eocene and Oligocene were key periods when diversification of major lineages within Parmeliaceae occurred, with subsequent radiations occurring primarily during the Oligocene and Miocene. Our phylogenetic hypothesis supports the independent origin of lichenicolous fungi associated with climatic shifts at the Oligocene-Miocene boundary. Moreover, diversification bursts at different times may be crucial factors driving the diversification of Parmeliaceae. Additionally, our study provides novel insight into evolutionary relationships in this large and diverse family of lichen-forming ascomycetes.
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6.
  • Fernández-Nieves, A., et al. (författare)
  • Microgel Suspensions: Fundamentals and Applications
  • 2011
  • Samlingsverk (redaktörskap) (refereegranskat)abstract
    • Providing a vital link between chemistry and physics on the nanoscale, this book offers concise coverage of the entire topic in five major sections, beginning with synthesis of microgel particles and continuing with their physical properties. The phase behavior and dynamics of resulting microgel suspensions feature in the third section, followed by their mechanical properties. It concludes with detailed accounts of numerous industrial, commercial and medical applications.Edited by David Weitz, Professor at Harvard and one of the world's pre-eminent experts in the field.
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7.
  • 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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8.
  • 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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9.
  • Mattsson, Johan, 1969, et al. (författare)
  • Soft colloids make strong glasses
  • 2009
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 462:7269, s. 83-86
  • Tidskriftsartikel (refereegranskat)abstract
    • Glass formation in colloidal suspensions has many of the hallmarks of glass formation in molecular materials1, 2, 3, 4, 5. For hard-sphere colloids, which interact only as a result of excluded volume, phase behaviour is controlled by volume fraction, ; an increase in drives the system towards its glassy state, analogously to a decrease in temperature, T, in molecular systems. When increases above * 0.53, the viscosity starts to increase significantly, and the system eventually moves out of equilibrium at the glass transition, g 0.58, where particle crowding greatly restricts structural relaxation1, 2, 3, 4. The large particle size makes it possible to study both structure and dynamics with light scattering1 and imaging3, 4; colloidal suspensions have therefore provided considerable insight into the glass transition. However, hard-sphere colloidal suspensions do not exhibit the same diversity of behaviour as molecular glasses. This is highlighted by the wide variation in behaviour observed for the viscosity or structural relaxation time, , when the glassy state is approached in supercooled molecular liquids5. This variation is characterized by the unifying concept of fragility5, which has spurred the search for a 'universal' description of dynamic arrest in glass-forming liquids. For 'fragile' liquids, is highly sensitive to changes in T, whereas non-fragile, or 'strong', liquids show a much lower T sensitivity. In contrast, hard-sphere colloidal suspensions are restricted to fragile behaviour, as determined by their dependence1, 6, ultimately limiting their utility in the study of the glass transition. Here we show that deformable colloidal particles, when studied through their concentration dependence at fixed temperature, do exhibit the same variation in fragility as that observed in the T dependence of molecular liquids at fixed volume. Their fragility is dictated by elastic properties on the scale of individual colloidal particles. Furthermore, we find an equivalent effect in molecular systems, where elasticity directly reflects fragility. Colloidal suspensions may thus provide new insight into glass formation in molecular systems.
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10.
  • Mattsson, Niklas, et al. (författare)
  • Plasma tau in Alzheimer disease
  • 2016
  • Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 87:17, s. 1827-1835
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. Methods: This was a study of plasma tau in prospectively followed patients with AD (n 179), patients with mild cognitive impairment (n 195), and cognitive healthy controls (n 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n 61), mild cognitive impairment (n 212), and subjective cognitive decline (n 174) and controls (n 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, 18 fluorodeoxyglucose-PET, and cognition. Results: Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ 42, but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up. Conclusions: Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD.
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11.
  • 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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12.
  • 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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13.
  • Mattsson, Niklas, 1979, et al. (författare)
  • The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.
  • 2011
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.
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14.
  • Micke, Patrick, et al. (författare)
  • The prognostic impact of the tumour stroma fraction : A machine learning-based analysis in 16 human solid tumour types
  • 2021
  • Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 65
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed.Methods: Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns.Findings: The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR (95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59 (1.49-8.62)) associations of the tumour stroma fraction with survival.Interpretation: Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance.
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15.
  • Wuestefeld, Anika, et al. (författare)
  • Age-related and amyloid-beta-independent tau deposition and its downstream effects
  • 2023
  • Ingår i: Brain : a journal of neurology. - 1460-2156. ; 146:8, s. 3192-3205
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyloid-β (Aβ) is hypothesized to facilitate the spread of tau pathology beyond the medial temporal lobe. However, there is evidence that, independently of Aβ, age-related tau pathology might be present outside of the medial temporal lobe. We therefore aimed to study age-related Aβ-independent tau deposition outside the medial temporal lobe in two large cohorts and to investigate potential downstream effects of this on cognition and structural measures. We included 545 cognitively unimpaired adults (40-92 years) from the BioFINDER-2 study (in vivo) and 639 (64-108 years) from the Rush Alzheimer's Disease Center cohorts (ex vivo). 18F-RO948- and 18F-flutemetamol-PET standardized uptake value ratios were calculated for regional tau and global/regional Aβ in vivo. Immunohistochemistry was used to estimate Aβ load and tangle density ex vivo. In vivo medial temporal lobe volumes (subiculum, cornu ammonis 1) and cortical thickness (entorhinal cortex, Brodmann area 35) were obtained using Automated Segmentation for Hippocampal Subfields packages. Thickness of early and late neocortical Alzheimer's disease regions was determined using FreeSurfer. Global cognition and episodic memory were estimated to quantify cognitive functioning. In vivo age-related tau deposition was observed in the medial temporal lobe and in frontal and parietal cortical regions, which was statistically significant when adjusting for Aβ. This was also observed in individuals with low Aβ load. Tau deposition was negatively associated with cortical volumes and thickness in temporal and parietal regions independently of Aβ. The associations between age and cortical volume or thickness were partially mediated via tau in regions with early Alzheimer's disease pathology, i.e. early tau and/or Aβ pathology (subiculum/Brodmann area 35/precuneus/posterior cingulate). Finally, the associations between age and cognition were partially mediated via tau in Brodmann area 35, even when including Aβ-PET as covariate. Results were validated in the ex vivo cohort showing age-related and Aβ-independent increases in tau aggregates in and outside the medial temporal lobe. Ex vivo age-cognition associations were mediated by medial and inferior temporal tau tangle density, while correcting for Aβ density. Taken together, our study provides support for primary age-related tauopathy even outside the medial temporal lobe in vivo and ex vivo, with downstream effects on structure and cognition. These results have implications for our understanding of the spreading of tau outside the medial temporal lobe, also in the context of Alzheimer's disease. Moreover, this study suggests the potential utility of tau-targeting treatments in primary age-related tauopathy, likely already in preclinical stages in individuals with low Aβ pathology.
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16.
  • Andersson, Evelyn, et al. (författare)
  • Genetics of response to cognitive behavior therapy in adults with major depression : a preliminary report
  • 2019
  • Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 24:4, s. 484-490
  • Tidskriftsartikel (refereegranskat)abstract
    • Major depressive disorder is heritable and a leading cause of disability. Cognitive behavior therapy is an effective treatment for major depression. By quantifying genetic risk scores based on common genetic variants, the aim of this report was to explore the utility of psychiatric and cognitive trait genetic risk scores, for predicting the response of 894 adults with major depressive disorder to cognitive behavior therapy. The participants were recruited in a psychiatric setting, and the primary outcome score was measured using the Montgomery Asberg Depression Rating Scale-Self Rated. Single-nucleotide polymorphism genotyping arrays were used to calculate the genomic risk scores based on large genetic studies of six phenotypes: major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, intelligence, and educational attainment. Linear mixed-effect models were used to test the relationships between the six genetic risk scores and cognitive behavior therapy outcome. Our analyses yielded one significant interaction effect (B = 0.09, p < 0.001): the autism spectrum disorder genetic risk score correlated with Montgomery Asberg Depression Rating Scale-Self Rated changes during treatment, and the higher the autism spectrum disorder genetic load, the less the depressive symptoms decreased over time. The genetic risk scores for the other psychiatric and cognitive traits were not related to depressive symptom severity or change over time. Our preliminary results indicated, as expected, that the genomics of the response of patients with major depression to cognitive behavior therapy were complex and that future efforts should aim to maximize sample size and limit subject heterogeneity in order to gain a better understanding of the use of genetic risk factors to predict treatment outcome.
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17.
  • Andersson, Martin, et al. (författare)
  • An internal radiation dosimetry computer program, IDAC 2.0, for estimation of patient doses from radiopharmaceuticals
  • 2014
  • Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 162:3, s. 299-305
  • Tidskriftsartikel (refereegranskat)abstract
    • The internal dosimetry computer program internal dose assessment by computer (IDAC) for calculations of absorbed doses to organs and tissues as well as effective doses to patients from examinations with radiopharmaceuticals has been developed. The new version, IDAC2.0, incorporates the International Commission on Radiation Protection (ICRP)/ICRU computational adult male and female voxel phantoms and decay data from the ICRP publication 107. Instead of only 25 source and target regions, calculation can now be made with 63 source regions to 73 target regions. The major advantage of having the new phantom is that the calculations of the effective doses can be made with the latest tissue weighting factors of ICRP publication 103. IDAC2.0 uses the ICRP human alimentary tract (HAT) model for orally administrated activity and for excretion through the gastrointestinal tract and effective doses have been recalculated for radiopharmaceuticals that are orally administered. The results of the program are consistent with published data using the same specific absorption fractions and also compared with published data from the same computational phantoms but with segmentation of organs leading to another set of specific absorption fractions. The effective dose is recalculated for all the 34 radiopharmaceuticals that are administered orally and has been published by the ICRP. Using the new HAT model, new tissue weighting factors and the new adult computational voxel phantoms lead to an average effective dose of half of its earlier estimated value. The reduction mainly depends on electron transport simulations to walled organs and the transition from the stylised phantom with unrealistic interorgan distances to more realistic voxel phantoms.
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18.
  • Andersson, Martin, et al. (författare)
  • An upgrade of the internal dosimetry computer program IDAC
  • 2012
  • Ingår i: Medical Physics in the Baltic States. - : Kaunas University of Technology. - 1822-5721. ; , s. 120-123
  • Konferensbidrag (refereegranskat)abstract
    • A full update of the internal dosimetry computer program IDAC has been conducted. The new update is based on new and more accurate computational phantoms to calculate effective dose and absorbed dose to organs and tissues. The new ICRP Adult Reference Computational Phantoms has been adopted as well as the latest of the ICRP standardized biokinetic models. The updated computer program includes a user-friendly graphical user interface.
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19.
  • Andersson, Martin, et al. (författare)
  • Effective dose to adult patients from 338 radiopharmaceuticals estimated using ICRP biokinetic data, ICRP/ICRU computational reference phantoms and ICRP 2007 tissue weighting factors
  • 2014
  • Ingår i: EJNMMI Physics. - : Springer. - 2197-7364. ; 1:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Effective dose represents the potential risk to a population of stochastic effects of ionizing radiation (mainly lethal cancer). In recent years, there have been a number of revisions and updates influencing the way to estimate the effective dose. The aim of this work was to recalculate the effective dose values for the 338 different radiopharmaceuticals previously published by the International Commission on Radiological Protection (ICRP).Method: The new estimations are based on information on the cumulated activities per unit administered activity in various organs and tissues and for the various radiopharmaceuticals obtained from the ICRP publications 53, 80 and 106. The effective dose for adults was calculated using the new ICRP/International Commission on Radiation Units (ICRU) reference voxel phantoms and decay data from the ICRP publication 107. The ICRP human alimentary tract model has also been applied at the recalculations. The effective dose was calculated using the new tissue weighting factors from ICRP publications 103 and the prior factors from ICRP publication 60. The results of the new calculations were compared with the effective dose values published by the ICRP, which were generated with the Medical Internal Radiation Dose (MIRD) adult phantom and the tissue weighting factors from ICRP publication 60.Results: For 79% of the radiopharmaceuticals, the new calculations gave a lower effective dose per unit administered activity than earlier estimated. As a mean for all radiopharmaceuticals, the effective dose was 25% lower. The use of the new adult computational voxel phantoms has a larger impact on the change of effective doses than the change to new tissue weighting factors.Conclusion: The use of the new computational voxel phantoms and the new weighting factors has generated new effective dose estimations. These are supposed to result in more realistic estimations of the radiation risk to a population undergoing nuclear medicine investigations than hitherto available values.
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20.
  • Andersson, Martin, et al. (författare)
  • Improved age and gender specific radiation risk models applied on cohorts of Swedish patients
  • 2021
  • Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 195:3-4, s. 334-338
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM:The aim of this study is to implement lifetime attributable risk (LAR) predictions for radiation induced cancers for Swedish cohorts of patients of various age and sex, undergoing diagnostic investigations by nuclear medicine methods. METHODS: Calculations are performed on Swedish groups of patients with Paget's disease and with bone metastases from prostatic cancer and diagnosed with bone scintigraphy with an administration of 500 MBq 99mTc-phosphonate. RESULTS: The inclusion of patient survival rates into the calculations lowers the induced radiation cancer risk, as it takes into account that cohorts of patients have shorter predicted survival times than the general population. CONCLUSION: LAR estimations could be valuable for referring physicians, nuclear medicine physicians, nurses, medical physicists, radiologists, and oncologists and as well as ethical committees for risk estimates for specific subgroups of patients. Caution is however advised with respect to application of LAR predictions to individuals (because of individual sensitivities, circumstances, etc.).
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21.
  • Andersson, Martin, et al. (författare)
  • Improved estimates of the radiation absorbed dose to the urinary bladder wall
  • 2014
  • Ingår i: Physics in Medicine and Biology. - : Institute of Physics Publishing (IOPP). - 0031-9155 .- 1361-6560. ; 59:9, s. 2173-2182
  • Tidskriftsartikel (refereegranskat)abstract
    • Specific absorbed fractions (SAFs) have been calculated as a function of the content in the urinary bladder in order to allow more realistic calculations of the absorbed dose to the bladder wall. The SAFs were calculated using the urinary bladder anatomy from the ICRP male and female adult reference computational phantoms. The urinary bladder and its content were approximated by a sphere with a wall of constant mass, where the thickness of the wall depended on the amount of urine in the bladder. SAFs were calculated for males and females with 17 different urinary bladder volumes from 10 to 800 mL, using the Monte Carlo computer program MCNP5, at 25 energies of mono-energetic photons and electrons ranging from 10 KeV to 10 MeV. The decay was assumed to be homogeneously distributed in the urinary bladder content and the urinary bladder wall, and the mean absorbed dose to the urinary bladder wall was calculated. The Monte Carlo simulations were validated against measurements made with thermoluminescent dosimeters. The SAFs obtained for a urine volume of 200 mL were compared to the values calculated for the urinary bladder wall using the adult reference computational phantoms. The mean absorbed dose to the urinary wall from F-18-FDG was found to be 77 mu Gy/MBq formales and 86 mu Gy/MBq for females, while for (99)mTc-DTPA the mean absorbed doses were 80 mu Gy/MBq for males and 86 mu Gy/MBq for females. Compared to calculations using a constant value of the SAF from the adult reference computational phantoms, the mean absorbed doses to the bladder wall were 60% higher for F-18-FDG and 30% higher for (99)mTc-DTPA using the new SAFs.
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22.
  • Andersson, Martin, et al. (författare)
  • Improved radiation risk models applied to different patient groups in Sweden
  • 2019
  • Ingår i: Radiatsionnaya Gygiena. - 1998-426X. ; 12:2, s. 44-54
  • Tidskriftsartikel (refereegranskat)abstract
    • In radiological diagnostics and therapy, it is important that practitioners, referrers, (i.e. radiologists, radiation oncologists and others in healthcare) are aware of how much radiation a patient may receive from the various procedures used and associated health risk. The profession has a duty to inform patients or their representatives of the advantages and disadvantages of specific investigations or treatment plans. The need to estimate and communicate risks in connection with medical use of ionizing radiation is highlighted e.g. in the Russian Federation State Law No 3, §17.2, 1996 and in the EU directive (2013/59/EURATOM 2014). The most commonly used way to express harm in relation to low doses of ionizing radiation is use of the quantity effective dose (E). Effective dose, a radiation protection quantity, however is not intended to provide risk estimates for medical exposures. Its purpose is to optimize conditions for radiation workers (1865 years) or the general public; all groups with age distributions that differ from patients. In this paper the lifetime attributable risk was used to estimate the excess risk of receiving and dying of radiogenic cancer. The lifetime attributable risk estimations are generated from three different variables, gender, attained age and age at exposure giving the possibility to create age and gender specific cancer risk estimations. Initially, the US Environmental Protection Agency lifetime attributable risk coefficients which are intended to predict the cancer risk from ionizing radiation to a normal US population were applied. In this work, the lifetime attributable risk predictions were modified to the normal Swedish population and to cohorts of Swedish patients undergoing radiological and nuclear medicine examinations or treatments with survival times that differ from the normal population. For Swedish males, all organs were given the same absorbed dose, exposed at 20, 40 and 70 years, the lifetime attributable risk coefficients (Gy1) were 0.11, 0.068, and 0.038, respectively, which is lower than the corresponding figures for US males, 0.13, 0.077, and 0.040. For Swedish females, all organs were given the same absorbed dose, exposed at 40 years of age with a diagnosis of breast, colon or liver cancer, the lifetime attributable risk coefficients are 0.064, 0.034, and 0.0038, respectively, which is much lower than if a 40 years female without known cancer is exposed, 0.073.
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23.
  • Andersson, Martin, et al. (författare)
  • ORGAN DOSES AND EFFECTIVE DOSE FOR FIVE PET RADIOPHARMACEUTICALS
  • 2016
  • Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 169:1-4, s. 8-253
  • Tidskriftsartikel (refereegranskat)abstract
    • Diagnostic investigations with positron-emitting radiopharmaceuticals are dominated by (18)F-fluorodeoxyglucose ((18)F-FDG), but other radiopharmaceuticals are also commercially available or under development. Five of them, which are all clinically important, are (18)F-fluoride, (18)F-fluoroethyltyrosine ((18)F-FET), (18)F-deoxyfluorothymidine ((18)F-FLT), (18)F-fluorocholine ((18)F-choline) and (11)C-raclopride. To estimate the potential risk of stochastic effects (mainly lethal cancer) to a population, organ doses and effective dose values were updated for all five radiopharmaceuticals. Dose calculations were performed using the computer program IDAC2.0, which bases its calculations on the ICRP/ICRU adult reference voxel phantoms and the tissue weighting factors from ICRP publication 103. The biokinetic models were taken from ICRP publication 128. For organ doses, there are substantial changes. The only significant change in effective dose compared with previous estimations was a 46 % reduction for (18)F-fluoride. The estimated effective dose in mSv MBq(-1) was 1.5E-02 for (18)F-FET, 1.5E-02 for (18)F-FLT, 2.0E-02 for (18)F-choline, 9.0E-03 for (18)F-fluoride and 4.4E-03 for (11)C-raclopride.
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24.
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25.
  • Baliakas, Panagiotis, 1977-, et al. (författare)
  • Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia
  • 2019
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 104:2, s. 360-369
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to-first-treatment and a treatment probability at five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest time-to-first-treatment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage CLL patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in CLL.
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26.
  • Baumeister, Hannah, et al. (författare)
  • A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings
  • Ingår i: Brain : a journal of neurology. - 1460-2156. ; 147:7, s. 2400-2413
  • Tidskriftsartikel (refereegranskat)abstract
    • Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± SD age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (CU; n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (SCD; n = 342), mild cognitive impairment (MCI; n = 118), or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid AD biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5), as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test if baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and MCI conversion rates of CU and SCD participants. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy first affected the medial temporal lobes, followed by further temporal and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological AD biomarker levels, APOE ε4 carriership, and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive AD biomarkers and was associated with more generalised cognitive impairment. Limbic-predominant atrophy, in all and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of MCI conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, both on the subject and group level, were excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for AD in applied settings. The implementation of atrophy subtype- and stage-specific end-points may increase the statistical power of pharmacological trials targeting early AD.
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27.
  • Bergeron, David, et al. (författare)
  • Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia
  • 2018
  • Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 84:5, s. 729-740
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. METHODS: We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-β pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) ε4 status was determined using generalized estimating equation models. RESULTS: Amyloid-β positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p
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28.
  • Berron, David, et al. (författare)
  • Early stages of tau pathology and its associations with functional connectivity, atrophy and memory
  • 2021
  • Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144:9, s. 2771-2783
  • Tidskriftsartikel (refereegranskat)abstract
    • In Alzheimer's disease, post-mortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with Brodmann area 35, and the entorhinal cortex. Here we used tau-PET imaging to investigate the sequence of tau pathology progression within the human medial temporal lobe and across regions in the posterior-medial system. Our objective was to study how medial temporal tau is related to functional connectivity, regional atrophy, and memory performance. We included 215 amyloid-β- cognitively unimpaired, 81 amyloid-β+ cognitively unimpaired and 87 amyloid-β+ individuals with mild cognitive impairment, who each underwent 18F-RO948 tau and 18F-flutemetamol amyloid PET imaging, structural T1-MRI and memory assessments as part of the Swedish BioFINDER-2 study. First, event-based modelling revealed that the entorhinal cortex and Brodmann area 35 show the earliest signs of tau accumulation followed by the anterior and posterior hippocampus, Brodmann area 36 and the parahippocampal cortex. In later stages, tau accumulation became abnormal in neocortical temporal and finally parietal brain regions. Second, in cognitively unimpaired individuals, increased tau load was related to local atrophy in the entorhinal cortex, Brodmann area 35 and the anterior hippocampus and tau load in several anterior medial temporal lobe subregions was associated with distant atrophy of the posterior hippocampus. Tau load, but not atrophy, in these regions was associated with lower memory performance. Further, tau-related reductions in functional connectivity in critical networks between the medial temporal lobe and regions in the posterior-medial system were associated with this early memory impairment. Finally, in patients with mild cognitive impairment, the association of tau load in the hippocampus with memory performance was partially mediated by posterior hippocampal atrophy. In summary, our findings highlight the progression of tau pathology across medial temporal lobe subregions and its disease stage-specific association with memory performance. While tau pathology might affect memory performance in cognitively unimpaired individuals via reduced functional connectivity in critical medial temporal lobe-cortical networks, memory impairment in mild cognitively impaired patients is associated with posterior hippocampal atrophy.
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29.
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30.
  • Bridel, Claire, et al. (författare)
  • Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
  • 2019
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
  • Forskningsöversikt (refereegranskat)abstract
    • Importance  Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives  To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources  PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection  Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis  Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure  The cNfL levels adjusted for age and sex across diagnoses.Results  Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance  These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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31.
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32.
  • Colleoni, Marco, et al. (författare)
  • Site of primary tumor has a prognostic role in operable breast cancer: the international breast cancer study group experience.
  • 2005
  • Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 23:7, s. 1390-400
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Cancer presenting at the medial site of the breast may have a worse prognosis compared with tumors located in external quadrants. For medial tumors, axillary lymph node staging may not accurately reflect the metastatic potential of the disease. PATIENTS AND METHODS: Eight-thousand four-hundred twenty-two patients randomly assigned to International Breast Cancer Study Group clinical trials between 1978 and 1999 were classified as medial site (1,622; 19%) or lateral, central, and other sites (6,800; 81%). Median follow-up was 11 years. RESULTS: A statistically significant difference was observed for patients with medial tumors versus those with nonmedial tumors in disease-free survival (DFS; 10-year DFS, 46% v 48%; HR, 1.10; 95% CI, 1.02 to 1.18; P = .01) and overall survival (10-year OS 59% v 61%; HR, 1.09; 1.01 to 1.19; P = .04). This difference increased after adjustment for other prognostic factors (HR, 1.22; 95% CI, 1.13 to 1.32 for DFS; and HR, 1.24; 95% CI, 1.14 to 1.35 for OS; both P = .0001). The risk of relapse for patients with medial presentation was largest for the node-negative cohort and for patients with tumors larger than 2 cm. In the subgroup of 2,931 patients with negative axillary lymph nodes, 10-year DFS was 61% v 67%, and OS was 73% v 80% for medial versus nonmedial sites, respectively (HR 1.33; 95% CI, 1.15 to 1.54; P = .0001 for DFS; and HR 1.40; 95% CI, 1.17 to 1.67; P = .0003 for OS). CONCLUSION: Tumor site has a significant prognostic utility, especially for axillary lymph node-negative disease, that should be considered in therapeutic algorithms. New staging procedures such as biopsy of the sentinel internal mammary nodes or novel imaging methods should be further studied in patients with medial tumors.
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33.
  • Cooper, Ed, et al. (författare)
  • Pressure Pulse Technique – A New Method for Measuring the Leakage of the Building Envelope of Churches
  • 2011
  • Konferensbidrag (refereegranskat)abstract
    • The University of Gävle is currently involved in a project on saving energy in historic buildings (churches). An important factor in the determination of the natural ventilation rate is the adventitious leakage of the envelope. Measurement of leakage is therefore a key feature of the investigations. It was decided to adopt a new technique developed at the University of Nottingham (UNott). It is a pulse technique compared to the conventional steady technique.The conventional technique consists of generating a steady and high pressure difference (50 Pa) across the envelope by means of a fan. Such pressures are rarely encountered in ventilation and this leads to errors in the low-pressure leakage. Furthermore the use of the conventional blower door technique in churches is difficult due to their large volume and the need to replace the doors.The underlying principle of the UNott technique is described and examples of results are given. The most important advantage of the Unott technique is that the leakage is determined at the low pressure differences that are encountered with ventilation e.g. 4 Pa. This is made possible primarily by the fact that the effects of wind and buoyancy at the time of the test are eliminated by taking account of the pressure variation before and after the pulse.For measurements in large buildings, a number of identical piston/cylinder units have to be operated simultaneously. The University of Gavle has developed a system whereby up to seven units can be used. Such a number is required for a leaky church and this is the first time this has been done.
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34.
  • Cooper, Ed W, et al. (författare)
  • Measurement of the adventitious leakage of churches with a novel pulse technique
  • 2011
  • Ingår i: Proc. Roomvent 2011. - Trondheim, Norge : Tapir Akademisk Forlag. - 9788251928120
  • Konferensbidrag (refereegranskat)abstract
    • The University of Gavle is currently involved in a project on saving energy in historic buildings (churches). An important factor in the determination of the natural ventilation rate is the adventitious leakage of the envelope. Measurement of leakage is therefore a key feature of the investigations. It was decided to adopt a new technique developed at the University of Nottingham (UNott). It is a pulse technique compared to the conventional steady technique.The conventional technique consists of generating a steady and high pressure difference (50 Pa) across the envelope by means of a fan. Such pressures are rarely encountered in ventilation and this leads to errors in the low-pressure leakage. Furthermore the use of the conventional blower door technique in churches is difficult due to their large volume and the need to replace the doors.The underlying principle of the UNott technique is described and examples of results are given. The most important advantage of the Unott technique is that the leakage is determined at the low pressure differences that are encountered with ventilation e.g. 4 Pa. This is made possible primarily by the fact that the effects of wind and buoyancy at the time of the test are eliminated by taking account of the pressure variation before and after the pulse.For measurements in large buildings, a number of identical piston/cylinder units have to be operated simultaneously. The University of Gävle has developed a system whereby up to seven units can be used. Such a number is required for a leaky church and this is the first time this has been done.
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35.
  • Crespo, Ana, et al. (författare)
  • Phylogenetic generic classification of parmelioid lichens (Parmeliaceae,Ascomycota) based on molecular, morphological and chemical evidence.
  • 2010
  • Ingår i: Taxon. - : John Wiley & Sons. - 0040-0262 .- 1996-8175. ; 59:6, s. 1735-1753
  • Tidskriftsartikel (refereegranskat)abstract
    • Parmelioid lichens are a diverse and ubiquitous group of foliose lichens. Generic delimitation in parmelioid lichens has been in a state of flux since the late 1960s with the segregation of the large, heterogeneous genus Parmelia into numerous smaller genera. Recent molecular phylogenetic studies have demonstrated that some of these new genera were monophyletic, some were not, and others, previously believed to be unrelated, fell within single monophyletic groups, indicating the need for a revision of the generic delimitations. This study aims to give an overview of current knowledge of the major clades of all parmelioid lichens. For this, we assembled a dataset of 762 specimens, including 31 of 33 currently accepted parmelioid genera (and 63 of 84 accepted genera of Parmeliaceae). We performed maximum likelihood and Bayesian analyses of combined datasets including two, three and four loci. Based on these phylogenies and the correlation of morphological and chemical characters that characterize monophyletic groups, we accept 27 genera within nine main clades. We re-circumscribe several genera and reduce Parmelaria to synonymy with Parmotrema. Emodomelanelia Divakar & A. Crespo is described as a new genus (type: E. masonii). Nipponoparmelia (Kurok.) K.H. Moon, Y. Ohmura & Kashiw. ex A. Crespo & al. is elevated to generic rank and 15 new combinations are proposed (in the genera Flavoparmelia, Parmotrema, Myelochroa, Melanelixia and Nipponoparmelia). A short discussion of the accepted genera is provided and remaining challenges and areas requiring additional taxon sampling are identified.
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36.
  • David, M., et al. (författare)
  • Ammonia sources and sinks in an intensively managed grassland canopy
  • 2009
  • Ingår i: Biogeosciences. - Goettingen, Germany : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 6:9, s. 1903-1915
  • Tidskriftsartikel (refereegranskat)abstract
    • Grasslands represent canopies with a complex structure where sources and sinks of ammonia (NH3) may coexist at the plant level. Moreover, management practices such as mowing, hay production and grazing may change the composition of the sward and hence the source-sink relationship at the canopy level as well as the interaction with the atmosphere. There is therefore a need to understand the exchange of ammonia between grasslands and the atmosphere better, especially regarding the location and magnitude of sources and sinks. Fluxes of atmospheric NH3 within a grassland canopy were assessed in the field and under controlled conditions using a dynamic chamber technique (cuvette). These cuvette measurements were combined with extraction techniques to estimate the ammonium (NH+4 ) concentration and the pH of a given part of the plant or soil, leading to an estimated ammo- nia compensation point (Cp ). The combination of the cuvette and the extraction techniques was used to identify the poten- tial sources and sinks of NH3 within the different compart- ments of the grassland: the soil, the litter or senescent “litter leaves”, and the functioning “green leaves”. A set of six field experiments and six laboratory experiments were performed in which the different compartments were either added or removed from the cuvettes.The results show that the cuvette measurements agree with the extraction technique in ranking the strength of compartment sources. It suggests that in the studied grassland the green leaves were mostly a sink for NH3 with a compensation point around 0.1–0.4 μg m−3 and   an NH3 flux of 6 to 7 ng m−2 s−1. Cutting of the grass did not increase the NH3 fluxes of the green leaves. The litter was found to be the largest source of NH3 in the canopy, with a Cp of up to 1000μgm−3 NH3 andanNH3 fluxupto90ngm−2 s−1. The litter was found to be a much smaller NH3 source when dried (Cp =160 μg m−3 and FNH3 =35 ng m−2 s−1 NH3 ). Moreover emissions from the litter were found to vary with the relative humidity of the air. The soil was a strong source of NH3 in the period immediately after cutting (Cp =320 μg m−3 and FNH3 =60 ng m−2 s−1 ), which was nevertheless always smaller than the litter source. The soil NH3 emissions lasted, however, for less than one day, and were not observed with sieved soil. They could not be solely explained by xylem sap flow extruding NH+4 . These results indicate that future research on grassland-ammonia relationships should focus on the post-mowing period and the role of litter in interaction with meteorological conditions.
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37.
  • De Jonghe, Joachim, et al. (författare)
  • A community effort to track commercial single-cell and spatial 'omic technologies and business trends
  • 2024
  • Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 42:7, s. 1017-1023
  • Tidskriftsartikel (refereegranskat)abstract
    • There is an ever-growing choice of single-cell and spatial 'omics platforms for industry and academia. The scTrends Consortium provides a brief historical overview of the established platforms and companies, revealing market trends and presenting possible angles for how technologies may differentiate themselves.
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38.
  • Ebner, Florian, et al. (författare)
  • Serum GFAP and UCH-L1 for the prediction of neurological outcome in comatose cardiac arrest patients
  • 2020
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 154, s. 61-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Neurological outcome prediction is crucial early after cardiac arrest. Serum biomarkers released from brain cells after hypoxic-ischaemic injury may aid in outcome prediction. The only serum biomarker presently recommended in the European Resuscitation Council prognostication guidelines is neuron-specific enolase (NSE), but NSE has limitations. In this study, we therefore analyzed the outcome predictive accuracy of the serum biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in patients after cardiac arrest. Methods: Serum GFAP and UCH-L1 were collected at 24, 48 and 72 h after cardiac arrest. The primary outcome was neurological function at 6-month follow-up assessed by the cerebral performance category scale (CPC), dichotomized into good (CPC1-2) and poor (CPC3-5). Prognostic accuracies were tested with receiver-operating characteristics by calculating the area under the receiver-operating curve (AUROC) and compared to the AUROC of NSE. Results: 717 patients were included in the study. GFAP and UCH-L1 discriminated between good and poor neurological outcome at all time-points when used alone (AUROC GFAP 0.88–0.89; UCH-L1 0.85–0.87) or in combination (AUROC 0.90–0.91). The combined model was superior to GFAP and UCH-L1 separately and NSE (AUROC 0.75–0.85) at all time-points. At specificities ≥95%, the combined model predicted poor outcome with a higher sensitivity than NSE at 24 h and with similar sensitivities at 48 and 72 h. Conclusion: GFAP and UCH-L1 predicted poor neurological outcome with high accuracy. Their combination may be of special interest for early prognostication after cardiac arrest where it performed significantly better than the currently recommended biomarker NSE.
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39.
  • Edgren, FRedrik, et al. (författare)
  • Formation of damage and its effects on non-crimp fabric reinforced composites loaded in tension
  • 2004
  • Ingår i: Composites Science And Technology. - 0266-3538 .- 1879-1050. ; 64:5, s. 675-692
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-crimp fabric (NCF) composites, manufactured by resin infusion techniques are one of the most promising next generation composite materials. They offer large potential for application in primary structures as they give excellent performance at low production costs. However, before NCF composites will be efficiently used in design, detailed understanding of governing micro mechanisms must be accumulated and described by predictive models. In the present study, NCF cross-ply laminates have been tested in tension. Intralaminar cracks caused in the 90° fibre bundle layers and their effect on laminate mechanical properties have been monitored. Occurrence of 'novel' type of cracks propagating in the load direction (longitudinal cracks) is explained by a thorough FE analysis using an Representative Volume Element (RVE) approach, revealing stress concentrations caused by 0° fibre bundle waviness. Effects of damage on mechanical properties are modelled using modified micro mechanical models developed for analysis of conventional laminated composites. The analysis reveals mechanical degradation to be ruled by the crack opening displacement (COD). However, unlike traditional composites, transverse cracks do not generally extend through the entire thickness of the 90° layer, but are rather contained in single fibre bundles, limiting the COD. © 2003 Elsevier Ltd. All rights reserved.
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40.
  • Eriksson, Gustav, et al. (författare)
  • Boundary and interface methods for energy stable finite difference discretizations of the dynamic beam equation
  • 2023
  • Ingår i: Journal of Computational Physics. - : Elsevier. - 0021-9991 .- 1090-2716. ; 476
  • Tidskriftsartikel (refereegranskat)abstract
    • We consider energy stable summation by parts finite difference methods (SBP-FD) for the homogeneous and piecewise homogeneous dynamic beam equation (DBE). Previously the constant coefficient problem has been solved with SBP-FD together with penalty terms (SBP-SAT) to impose boundary conditions. In this work, we revisit this problem and compare SBP-SAT to the projection method (SBP-P). We also consider the DBE with discontinuous coefficients and present novel SBP-SAT, SBP-P, and hybrid SBP-SAT-P discretizations for imposing interface conditions. To demonstrate the methodology for two-dimensional problems, we also present a discretization of the piecewise homogeneous dynamic Kirchoff-Love plate equation based on the hybrid SBP-SAT-P method. Numerical experiments show that all methods considered are similar in terms of accuracy, but that SBP-P can be more computationally efficient (less restrictive time step requirement for explicit time integration methods) for both the constant and piecewise constant coefficient problems.
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41.
  • Ford, David, et al. (författare)
  • Management in the interactive business world
  • 2017
  • Ingår i: No business is an island making sense of the interactive business world. - : Emerald Publishing Limited. - 9781787145498 - 9781787145504 ; , s. 27-45
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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42.
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43.
  • Gaynullin, Bakhram, 1967- (författare)
  • High accuracy low-cost NDIR sensing
  • 2019
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Sensing gas concentrations using optical absorption offers valuable advantages over other methods ina wide variety of real-world applications from industrial processes to environmental change. One of the most rapidly developing detection techniques on the global market is the non-dispersive infrared method (NDIR). Sensors developed based on this technique satisfy a growing demand for low-cost, reliable and long-term maintenance-free solutions. The technologies available to support this field for sensor key components such as light sources, photo detectors, optic cavities, and electronic components, have advanced rapidly in recent years. This development has led to an increasing number of application fields, due to significant improvements in accuracy, sensitivity and resolution.However, this technique has limitations related to basic physical principles and sensor design performance. Variation in sensing environments’ temperature and pressure, the impact of water vapour presence and sensor component ageing are the most important interfering factors for investigation. Errors in measured values could be caused by any of these factors because they influence various sensor parts and the environment’s physical properties. The correct interpretation of error sources is one the most difficult and important tasks involved in designing stable, high-precision sensors.To facilitate investigations into measurement performance limitations, test equipment was developed along with test approaches capable of creating experimental conditions that exceed the tested sensor’ stolerances. The studied resolution limit for long-path sensors is about 100 ppb. For measurements in fresh air concentrations (approximately 400 ppm of CO2), this is equivalent to a precision of less than0.1%. The methods used to reduce possible inaccuracies due to various error sources’ impacts should possess compensatory capabilities and precisions that exceed this value.To improve the pressure compensation procedure’s performance, a complete advanced system that includes everything from a lab test bench to the supporting software and comprehensive calculation algorithm was developed. The test bench creates pressure conditions that deviate from the reference value by less than 0.2 mbar (or 0.02% of the standard pressure, 1013 mbar).One of this study’s major findings is the concentration range-independent pressure compensation method. The advanced conditions achieved with the test station also facilitated the discovery and characterisation of the sources of long-term drift in methane concentration measurement.
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44.
  • Gonzales, Mitzi M., et al. (författare)
  • Chronic depressive symptomatology and CSF amyloid beta and tau levels in mild cognitive impairment
  • 2018
  • Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 0885-6230 .- 1099-1166. ; 33:10, s. 1305-1311
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To investigate the association between chronic subsyndromal symptoms of depression (SSD), cerebrospinal fluid (CSF) biomarkers, and neuropsychological performance in individuals with mild cognitive impairment (MCI). Methods: Participants included 238 older adults diagnosed with MCI from the Alzheimer's Disease Neuroimaging Initiative repository with cognitive and CSF amyloid beta (Aβ1–42), total tau (t-tau), and phosphorylated tau (p-tau) data. The Neuropsychiatric Inventory identified individuals with chronic endorsement (SSD group N = 80) or no endorsement (non-SSD group N = 158) of depressive symptoms across timepoints. CSF biomarker and cognitive performance were evaluated with linear regression models adjusting for age, education, gender, APOE genotype, global cognitive status, and SSD group. Results: As compared to the non-SSD group, the SSD group displayed lower CSF Aβ1–42 levels (β = −24.293, S.E. = 6.345, P < 0.001). No group differences were observed for CSF t-tau (P = 0.497) or p-tau levels (P = 0.392). Lower CSF Aβ1–42 levels were associated with poorer performance on learning (β = 0.041, S.E. = 0.018, P = 0.021) and memory (β = −0.012, S.E. = 0.005, P = 0.031) measures, whereas higher CSF t-tau levels were associated with poorer performance on measures of global cognition (β = 0.022, S.E = 0.008, P = 0.007) and language (β = −0.010, S.E = 0.004, P = 0.019). SSD was independently associated with diminished global cognition, learning and memory, language, and executive function performance over and above the effects of CSF biomarkers (all P < 0.05). Conclusions: MCI participants with SSD displayed diminished CSF Aβ1–42 levels but did not differ from non-SSD controls in CSF tau levels. Additionally, CSF biomarkers and SSD independently accounted for variance in cognitive performance, suggesting that these factors may uniquely confer cognitive risk in MCI.
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45.
  • Gottlieb-Vedi, Eivind, et al. (författare)
  • Extent of Lymphadenectomy and Long-Term Survival in Esophageal Cancer
  • 2023
  • Ingår i: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 277:3, s. 429-436
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To examine the hypothesis that survival in esophageal cancer increases with more removed lymph nodes during esophagectomy up to a plateau, after which it levels out or even decreases with further lymphadenectomy.Summary of Background Data: There is uncertainty regarding the ideal extent of lymphadenectomy during esophagectomy to optimize long-term survival in esophageal cancer.Methods: This population-based cohort study included almost every patient who underwent esophagectomy for esophageal cancer in Sweden or Finland in 2000-2016 with follow-up through 2019. Degree of lymphadenectomy, divided into deciles, was analyzed in relation to all-cause 5-year mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for all established prognostic factors.Results: Among 2,306 patients, the 2nd (4-8 nodes), 7th (21-24 nodes) and 8th decile (25-30 nodes) of lymphadenectomy showed the lowest all-cause 5-year mortality compared to the 1st decile (HR = 0.77, 95% CI 0.61-0.97, HR = 0.76, 95% CI 0.59-0.99, and HR = 0.73, 95% CI 0.57-0.93, respectively). In stratified analyses, the survival benefit was greatest in decile 7 for patients with pathological T-stage T3/T4 (HR = 0.56, 95% CI 0.40-0.78), although it was statistically improved in all deciles except decile 10. For patients without neoadjuvant chemotherapy, survival was greatest in decile 7 (HR = 0.60, 95% CI 0.41-0.86), although survival was also statistically significantly improved in deciles 2, 6, and 8.Conclusion: Survival in esophageal cancer was not improved by extensive lymphadenectomy, but resection of a moderate number (20-30) of nodes was prognostically beneficial for patients with advanced T-stages (T3/T4) and those not receiving neoadjuvant therapy.
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46.
  • Hassellöv, Martin, et al. (författare)
  • Progress towards monitoring of microlitter in Scandinavian marine environments
  • 2018
  • Ingår i: TemaNord, 2018, 551, 2018. - Copenhagen : Nordic Council of Ministers.
  • Tidskriftsartikel (refereegranskat)abstract
    • Four different case studies were carried out to determine dominating microlitter types from urban environments to the regional Scandinavian seas (eastern North Sea). The sampling was both from sediment near sources (urban runoff and road dust sediment), and further out from coastal sediments. The sea surface layer and subsurface samples was taken in two different gradients, in the Oslo and Roskilde fjords, where also blue mussels were sampled. Best available technologies for sampling each compartment was used and evaluated, and while the water samples was analysed as collected, the sediment and biota samples needed some pretreatment of chemical digestion and/or heavy density liquid floatation or elutriation.In order to develop visual identification as objective as possible, a visual and physical observation scheme was proposed. The visual identification scheme should be complemented with spectroscopic identification to different degrees depending on the size fractions.Spectroscopic identification is still often a quite time-consuming process, meaning that for monitoring purposes it is not currently advisable to aim to identify all particles during monitoring studies. Until fully or partly automated spectroscopic methods are available they are still important tools for verification of representative types of particles in samples above 100 μm.The amount of particles that should be identified to provide adequate compositional information would be dependent on the aim of the study as well as the type and composition of the samples. However, in order to do monitoring and include sample composition in the results a minimum of 100 of the fewest particles should be counted in a sample to achieve 10% standard deviation in terms of counting statistical uncertainty.The field is however rapidly evolving, and automated procedures are already being published. For research purposes and more detailed monitoring and screening studies spectroscopic methods can aside from providing particle identification also give clues on additives and level of degradation.The most common types of microlitter found varied between studies but common trends could be identified between the road tunnel sediment and the urban creek sediment that these contained black particles resembling tire rubber from both visual and tactile tests, and also asphalt, charcoal, oil/tar particles and road marker particles. In the coastal water samples the surface layer was dominated by polystyrene foam particles and polyethylene fragments and films.In the subsurface water samples fibres, films and fragments of plastic was most common. In both the Gothenburg urban creek sediment and Oslo fjord surface water samples particles that could be related to artificial sports turf (polyethylene green grass and clear cut, tire granulate) was observed. The microlitter in mussels was dominated by fibres. The approach of using gradient studies, and include both near source sampling as well as recipient gradient sampling, was concluded to be very suitable to determine sources and fate.
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47.
  • Hassellöv, Martin, 1970, et al. (författare)
  • Progress towards monitoring of microlitter in Scandinavian marine environments: State of knowledge and challenges
  • 2018
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Microlitter consists of minute particles of anthropogenic or processed natural material. The project brings together research groups to conduct specific case studies in gradients from near urban sources such as the traffic environment and cities to the coastal water and sediments in order to study the relative occurrence of specific sources and their environmental dispersion and distribution. The conclusion were first that in sediments from the road environment (tunnel runoff water), tire particles, asphalt and road markings could be identified, and in the urban creek sediments many black particles including elastomers, charcoal-like and oil and soot where in high abundance and decreased rapidly out in the recipient. The results emphasize the role of the cities as hotspot source functions for microlitter in the coastal environment and also where mitigating measures could be directed.
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