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1.	Gad, Helge, et al. (författare) MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool 2014 Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221 Tidskriftsartikel (refereegranskat)abstract Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
2.	Jonasson, Lars S., et al. (författare) Dopamine release in nucleus accumbens during rewarded task switching measured by [C-11]raclopride 2014 Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 99, s. 357-364 Tidskriftsartikel (refereegranskat)abstract Reward and motivation have positive influences on cognitive-control processes in numerous settings. Models of reward implicate corticostriatal loops and the dopamine (DA) system, with special emphasis on D-2 receptors in nucleus accumbens (NAcc). In this study, 11 right-handed males (35-40 years) were scanned with positron emission tomography (PET) in a single [C-11]raclopride dynamic scan during rewarded and non-rewarded task switching. Rewarded task switching (relative to baseline task switching) decreased [11C]raclopride binding in NAcc. Decreasing NAcc [C-11]raclopride binding was strongly associated with task reaction time measures that reflect individual differences in effort and control strategies. Voxelwise analyses additionally revealed reward-related DA release in anterodorsal caudate, a region previously associated with task-switching. These PET findings provide evidence for striatal DA release during motivated cognitive control, and further suggest that NAcc DA release predicts the task reaction time benefits of reward incentives.
3.	Köhncke, Ylva, et al. (författare) Self-rated intensity of habitual physical activities is positively associated with dopamine D-2/3 receptor availability and cognition 2018 Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 181, s. 605-616 Tidskriftsartikel (refereegranskat)abstract Between-person differences in cognitive performance in older age are associated with variations in physical activity. The neurotransmitter dopamine (DA) contributes to cognitive performance, and the DA system deteriorates with advancing age. Animal data and a patient study suggest that physical activity modulates DA receptor availability, but data from healthy humans are lacking. In a cross-sectional study with 178 adults aged 64-68 years, we investigated links among self-reported physical activity, D(2/3)DA receptor (D2/3DR) availability, and cognitive performance. D2/3DR availability was measured with [C-11]raclopride positron emission tomography at rest. We used structural equation modeling to obtain latent factors for processing speed, episodic memory, working memory, physical activity, and D2/3DR availability in caudate, putamen, and hippocampus. Physical activity intensity was positively associated with D2/3DR availability in caudate, but not putamen and hippocampus. Frequency of physical activity was not related to D2/3DR availability. Physical activity intensity was positively related to episodic memory and working memory. D2/3DR availability in caudate and hippocampus was positively related to episodic memory. Taken together, our results suggest that striatal DA availability might be a neurochemical correlate of episodic memory that is also associated with physical activity.
4.	Lövdén, Martin, et al. (författare) Latent-Profile Analysis Reveals Behavioral and Brain Correlates of Dopamine-Cognition Associations 2018 Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 28:11, s. 3894-3907 Tidskriftsartikel (refereegranskat)abstract Evidence suggests that associations between the neurotransmitter dopamine and cognition are nonmonotonic and open to modulation by various other factors. The functional implications of a given level of dopamine may therefore differ from person to person. By applying latent-profile analysis to a large (n = 181) sample of adults aged 64-68 years, we probabilistically identified 3 subgroups that explain the multivariate associations between dopamine D2/3R availability (probed with C-11-raclopride-PET, in cortical, striatal, and hippocampal regions) and cognitive performance (episodic memory, working memory, and perceptual speed). Generally, greater receptor availability was associated with better cognitive performance. However, we discovered a subgroup of individuals for which high availability, particularly in striatum, was associated with poor performance, especially for working memory. Relative to the rest of the sample, this subgroup also had lower education, higher body-mass index, and lower resting-state connectivity between caudate nucleus and dorsolateral prefrontal cortex. We conclude that a smaller subset of individuals induces a multivariate non-linear association between dopamine D2/3R availability and cognitive performance in this group of older adults, and discuss potential reasons for these differences that await further empirical scrutiny.
5.	Papenberg, Goran, et al. (författare) Mapping the landscape of human dopamine D2/3 receptors with [11C]raclopride 2019 Ingår i: Brain Structure and Function. - : Springer Science and Business Media LLC. - 1863-2653 .- 1863-2661. ; 224:8, s. 2871-2882 Tidskriftsartikel (refereegranskat)abstract The dopamine D2/3 system is fundamental for sensory, motor, emotional, and cognitive aspects of behavior. Small-scale human histopathological and animal studies show high density of D2/3 dopamine receptors (D2/3DR) in striatum, but also demonstrate the existence of such receptors across cortical and limbic regions. Assessment of D2/3DR BPND in the extrastriatal regions with [C-11]raclopride has long been considered unreliable due to the relatively low density of D2/3DR outside the striatum. We describe the distribution and interregional links of D2/3DR availability measured with PET and [C-11]raclopride across the human brain in a large sample (N = 176; age range 64-68 years). Structural equation modeling revealed that D2/3DR availability can be organized according to anatomical (nigrostriatal, mesolimbic, mesocortical) and functional (limbic, associative, sensorimotor) dopamine pathways. D2/3DR availability in corticolimbic functional subdivisions showed differential associations to corresponding striatal subdivisions, extending animal and pharmacological work. Our findings provide evidence on the dimensionality and organization of [C-11]raclopride D2/3DR availability in the living human brain that conforms to known dopaminergic pathways.
6.	Salami, Alireza, et al. (författare) Dopamine D-2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion 2019 Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 39:3, s. 537-547 Tidskriftsartikel (refereegranskat)abstract Dopamine (DA) modulates corticostriatal connections. Studies in which imaging of the DA system is integrated with functional imaging during cognitive performance have yielded mixed findings. Some work has shown a link between striatal DA(measured by PET) and fMRI activations, whereas others have failed to observe such a relationship. One possible reason for these discrepant findings is differences in task demands, such that a more demanding task with greater prefrontal activations may yield a stronger association with DA. Moreover, a potential DA-BOLD association may be modulated by task performance. We studied 155 (104 normal-performing and 51 low-performing) healthy older adults (43% females) who underwent fMRI scanning while performing a working memory (WM) n-back task along with DA D-2/3 PET assessment using [C-11] raclopride. Using multivariate partial-least-squares analysis, we observed a significant pattern revealing positive associations of striatal as well as extrastriatal DA D-2/3 receptors to BOLD response in the thalamo-striatalcortical circuit, which supports WM functioning. Critically, the DA-BOLD association in normal-performing, but not low-performing, individuals was expressed in a load-dependent fashion, with stronger associations during 3-back than 1-/2-back conditions. Moreover, normal-performing adults expressing upregulated BOLD in response to increasing task demands showed a stronger DA-BOLD association during 3-back, whereas low-performing individuals expressed a stronger association during 2-back conditions. This pattern suggests a nonlinear DA-BOLD performance association, with the strongest link at the maximum capacity level. Together, our results suggest that DA may have a stronger impact on functional brain responses during more demanding cognitive tasks.
7.	Axelsson, Inge, et al. (författare) Så kan Sverige verka för en värld utan kärnvapen 2013 Ingår i: Aftonbladet. - Stockholm : Aftonbladet debatt. - 1103-9000. Recension (populärvet., debatt m.m.)
8.	Borgehammar, Stephan, et al. (författare) Svensk medeltida predikan på S:t Olofsdagen 2014 Ingår i: Pilgrim S:t Olof 800 år. - 9789163756405 ; , s. 51-62 Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract 29 sermons for the celebration of the Norwegian St. Olof/Olaf (July 29) have been preserved in medieval manuscripts of Swedish provenance. 27 of these were composed by friars of Vadstena Abbey. The article discusses what they tell us about the Saint, what sources the preachers used, and which characteristics of the Saint they emphasize. Finally, the main contents of a sermon on St. Olaf by the Vadstena friar Johannes Borquardi are related by way of example.
9.	de Boer, Lieke, et al. (författare) Attenuation of dopamine-modulated prefrontal value signals underlies probabilistic reward learning deficits in old age 2017 Ingår i: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 6 Tidskriftsartikel (refereegranskat)abstract Probabilistic reward learning is characterised by individual differences that become acute in aging. This may be due to age-related dopamine (DA) decline affecting neural processing in striatum, prefrontal cortex, or both. We examined this by administering a probabilistic reward learning task to younger and older adults, and combining computational modelling of behaviour, fMRI and PET measurements of DA D1 availability. We found that anticipatory value signals in ventromedial prefrontal cortex (vmPFC) were attenuated in older adults. The strength of this signal predicted performance beyond age and was modulated by D1 availability in nucleus accumbens. These results uncover that a value-anticipation mechanism in vmPFC declines in aging, and that this mechanism is associated with DA D1 receptor availability.
10.	de Boer, Lieke, et al. (författare) Corticostriatal White Matter Integrity and Dopamine D1 Receptor Availability Predict Age Differences in Prefrontal Value Signaling during Reward Learning 2020 Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:10, s. 5270-5280 Tidskriftsartikel (refereegranskat)abstract Probabilistic reward learning reflects the ability to adapt choices based on probabilistic feedback. The dopaminergically innervated corticostriatal circuit in the brain plays an important role in supporting successful probabilistic reward learning. Several components of the corticostriatal circuit deteriorate with age, as it does probabilistic reward learning. We showed previously that D1 receptor availability in NAcc predicts the strength of anticipatory value signaling in vmPFC, a neural correlate of probabilistic learning that is attenuated in older participants and predicts probabilistic reward learning performance. We investigated how white matter integrity in the pathway between nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC) relates to the strength of anticipatory value signaling in vmPFC in younger and older participants. We found that in a sample of 22 old and 23 young participants, fractional anisotropy in the pathway between NAcc and vmPFC predicted the strength of value signaling in vmPFC independently from D1 receptor availability in NAcc. These findings provide tentative evidence that integrity in the dopaminergic and white matter pathways of corticostriatal circuitry supports the expression of value signaling in vmPFC which supports reward learning, however, the limited sample size calls for independent replication. These and future findings could add to the improved understanding of how corticostriatal integrity contributes to reward learning ability.
11.	de Boer, Lieke, et al. (författare) Dorsal striatal dopamine D1 receptor availability predicts an instrumental bias in action learning 2019 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:1, s. 261-270 Tidskriftsartikel (refereegranskat)abstract Learning to act to obtain reward and inhibit to avoid punishment is easier compared with learning the opposite contingencies. This coupling of action and valence is often thought of as a Pavlovian bias, although recent research has shown it may also emerge through instrumental mechanisms. We measured this learning bias with a rewarded go/no-go task in 60 adults of different ages. Using computational modeling, we characterized the bias as being instrumental. To assess the role of endogenous dopamine (DA) in the expression of this bias, we quantified DA D1 receptor availability using positron emission tomography (PET) with the radioligand [11C]SCH23390. Using principal-component analysis on the binding potentials in a number of cortical and striatal regions of interest, we demonstrated that cortical, dorsal striatal, and ventral striatal areas provide independent sources of variance in DA D1 receptor availability. Interindividual variation in the dorsal striatal component was related to the strength of the instrumental bias during learning. These data suggest at least three anatomical sources of variance in DA D1 receptor availability separable using PET in humans, and we provide evidence that human dorsal striatal DA D1 receptors are involved in the modulation of instrumental learning biases.
12.	Eriksson, Niclas, et al. (författare) Genetic determinants of warfarin maintenance dose and time in therapeutic treatment range : a RE-LY genomics substudy 2016 Ingår i: Pharmacogenomics (London). - : Future Medicine Ltd. - 1462-2416 .- 1744-8042. ; 17:13, s. 1425-1439 Tidskriftsartikel (refereegranskat)abstract Aims: We investigated associations between genetic variation in candidate genes and on a genome-wide scale with warfarin maintenance dose, time in therapeutic range (TTR), and risk of major bleeding. Materials & methods: In total, 982 warfarin-treated patients from the RE-LY trial were studied. Results: After adjusting for SNPs in VKORC1 and CYP2C9, SNPs in DDHD1 (rs17126068) and NEDD4 (rs2288344) were associated with dose. Adding these SNPs and CYP4F2 (rs2108622) to a base model increased R-2 by 2.9%. An SNP in ASPH (rs4379440) was associated with TTR (-6.8% per minor allele). VKORC1 was associated with time less than INR 2.0. VKORC1 and CYP2C9 were associated with time more than INR 3.0, but not with major bleeding. Conclusions: We identified two novel genes associated with warfarin maintenance dose and one gene associated with TTR. These genes need to be replicated in an independent cohort.
13.	Eriksson, Niclas, 1978-, et al. (författare) Genetic determinants of warfarin response, efficacy and safety : a RE-LY genomics substudy Annan publikation (övrigt vetenskapligt/konstnärligt)
14.	Garzón, Benjamín, et al. (författare) Role of dopamine and gray matter density in aging effects and individual differences of functional connectomes 2021 Ingår i: Brain Structure and Function. - : Springer Science and Business Media LLC. - 1863-2653 .- 1863-2661. ; 226, s. 743-758 Tidskriftsartikel (refereegranskat)abstract With increasing age, functional connectomes become dissimilar across normal individuals, reflecting heterogenous aging effects on functional connectivity (FC). We investigated the distribution of these effects across the connectome and their relationship with age-related differences in dopamine (DA) D1 receptor availability and gray matter density (GMD). With this aim, we determined aging effects on mean and interindividual variance of FC using fMRI in 30 younger and 30 older healthy subjects and mapped the contribution of each connection to the patterns of age-related similarity loss. Aging effects on mean FC accounted mainly for the dissimilarity between connectomes of younger and older adults, and were related, across brain regions, to aging effects on DA D1 receptor availability. Aging effects on the variance of FC indicated a global increase in variance with advancing age, explained connectome dissimilarity among older subjects and were related to aging effects on variance of GMD. The relationship between aging and the similarity of connectomes can thus be partly explained by age differences in DA modulation and gray matter structure.
15.	Grill, Filip, et al. (författare) Dopamine release in human associative striatum during reversal learning 2024 Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1 Tidskriftsartikel (refereegranskat)abstract The dopaminergic system is firmly implicated in reversal learning but human measurements of dopamine release as a correlate of reversal learning success are lacking. Dopamine release and hemodynamic brain activity in response to unexpected changes in action-outcome probabilities are here explored using simultaneous dynamic [11C]Raclopride PET-fMRI and computational modelling of behavior. When participants encounter reversed reward probabilities during a card guessing game, dopamine release is observed in associative striatum. Individual differences in absolute reward prediction error and sensitivity to errors are associated with peak dopamine receptor occupancy. The fMRI response to perseverance errors at the onset of a reversal spatially overlap with the site of dopamine release. Trial-by-trial fMRI correlates of absolute prediction errors show a response in striatum and association cortices, closely overlapping with the location of dopamine release, and separable from a valence signal in ventral striatum. The results converge to implicate striatal dopamine release in associative striatum as a central component of reversal learning, possibly signifying the need for increased cognitive control when new stimuli-responses should be learned.
16.	Grill, Filip, et al. (författare) Human in vivo evidence for striatal dopamine release in response to reward-prediction errors during reversal learning Annan publikation (övrigt vetenskapligt/konstnärligt)
17.	Guitart-Masip, Marc, et al. (författare) Microscopic Structure of Frontal White Matter Predict Delay Discounting 2020 Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 87:9, s. S197-S197 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
18.	Herlitz, Johan, et al. (författare) Suspicion and treatment of severe sepsis : An overview of the prehospital chain of care 2012 Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central. - 1757-7241. ; 20:42 Tidskriftsartikel (refereegranskat)abstract BackgroundSepsis is a life-threatening condition where the risk of death has been reported to be even higher than that associated with the major complications of atherosclerosis, i.e. myocardial infarction and stroke. In all three conditions, early treatment could limit organ dysfunction and thereby improve the prognosis.AimTo describe what has been published in the literature a/ with regard to the association between delay until start of treatment and outcome in sepsis with the emphasis on the pre-hospital phase and b/ to present published data and the opportunity to improve various links in the pre-hospital chain of care in sepsis.MethodsA literature search was performed on the PubMed, Embase (Ovid SP) and Cochrane Library databases.ResultsIn overall terms, we found a small number of articles (n=12 of 1,162 unique hits) which addressed the prehospital phase. For each hour of delay until the start of antibiotics, the prognosis appeared to become worse. However, there was no evidence that prehospital treatment improved the prognosis.Studies indicated that about half of the patients with severe sepsis used the emergency medical service (EMS) for transport to hospital. Patients who used the EMS experienced a shorter delay to treatment with antibiotics and the start of early goal-directed therapy (EGDT). Among EMS-transported patients, those in whom the EMS staff already suspected sepsis at the scene had a shorter delay to treatment with antibiotics and the start of EGDT.There are insufficient data on other links in the prehospital chain of care, i.e. patients, bystanders and dispatchers.ConclusionSevere sepsis is a life-threatening condition. Previous studies suggest that, with every hour of delay until the start of antibiotics, the prognosis deteriorates. About half of the patients use the EMS. We need to know more about the present situation with regard to the different links in the prehospital chain of care in sepsis.
19.	Hibar, Derrek P., et al. (författare) Novel genetic loci associated with hippocampal volume 2017 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8 Tidskriftsartikel (refereegranskat)abstract The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
20.	Holm, Anna-Karin, et al. (författare) Bettavvikelser och tandreglering i ett hälsoperspektiv : en systematisk litteraturöversikt 2005 Rapport (övrigt vetenskapligt/konstnärligt)
21.	Holm, Anna-Karin, et al. (författare) Bettavvikelser, tandreglering och hälsa. SBU :s systematiska litteraturöversikt och slutsatser 2005 Ingår i: Tandläkartidningen. - 0039-6982. ; 97:12, s. 94-101 Forskningsöversikt (övrigt vetenskapligt/konstnärligt)
22.	Jacobsson, Josefin A., et al. (författare) Detailed Analysis of Variants in FTO in Association with Body Composition in a Cohort of 70-Year-Olds Suggests a Weakened Effect among Elderly 2011 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:5, s. e20158- Tidskriftsartikel (refereegranskat)abstract Background: The rs9939609 single-nucleotide polymorphism (SNP) in the fat mass and obesity (FTO) gene has previously been associated with higher BMI levels in children and young adults. In contrast, this association was not found in elderly men. BMI is a measure of overweight in relation to the individuals' height, but offers no insight into the regional body fat composition or distribution. Objective: To examine whether the FTO gene is associated with overweight and body composition-related phenotypes rather than BMI, we measured waist circumference, total fat mass, trunk fat mass, leg fat mass, visceral and subcutaneous adipose tissue, and daily energy intake in 985 humans (493 women) at the age of 70 years. In total, 733 SNPs located in the FTO gene were genotyped in order to examine whether rs9939609 alone or the other SNPs, or their combinations, are linked to obesity-related measures in elderly humans. Design: Cross-sectional analysis of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Results: Neither a single SNP, such as rs9939609, nor a SNP combination was significantly linked to overweight, body composition-related measures, or daily energy intake in elderly humans. Of note, these observations hold both among men and women. Conclusions: Due to the diversity of measurements included in the study, our findings strengthen the view that the effect of FTO on body composition appears to be less profound in later life compared to younger ages and that this is seemingly independent of gender.
23.	Jonasson, Lars, 1983-, et al. (författare) Aerobic fitness influences working memory updating via the striatal dopaminergic system in older adults Annan publikation (övrigt vetenskapligt/konstnärligt)abstract There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influences dopaminergic neurotransmission in the striatum as measured by positron emission tomography (PET) and the non-displacable binding potential (BPND ) of [11C]raclopride, and in turn performance on offline working-memory updating tasks. In a sample of 58 older sedentary adults undergoing a six-months exercise intervention, aerobic exercise compared to stretching, toning, and resistance training did not have a differential effect on BPND . At baseline, higher aerobic fitness levels (VO2peak ) were associated with higher BPND in the striatum. Following the intervention, for both forms of training, we found reduced BPND , indicating increased dopamine (DA), in a cluster in the anterior striatum in individuals with larger improvements in VO2peak . This reduction in BPND mediated a positive indirect effect of VO2peak on working-memory updating performance. Collectively these findings implicate DA as a neurocognitive mechanism explaining the positive effects of staying physically active at an old age for working memory.
24.	Jonasson, Lars S., 1983-, et al. (författare) Higher striatal D2-receptor availability in aerobically fit older adults but non-selective intervention effects after aerobic versus resistance training 2019 Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 202 Tidskriftsartikel (refereegranskat)abstract There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influence dopaminergic neurotransmission in the striatum, and in turn performance on offline working-memory updating tasks. Dopaminergic neurotransmission was measured by positron emission tomography (PET) and the non-displacable binding potential (BPND) of [11C]raclopride, i.e. dopamine (DA) D2-receptor (D2R) availability. Fifty-four sedentary older adults underwent a six-months exercise intervention, performing either aerobic exercise or stretching, toning, and resistance active control training. At baseline, higher aerobic fitness levels (VO2peak) were associated with higher BPND in the striatum, providing evidence of a link between an objective measure of aerobic fitness and D2R in older adults. BPND decreased substantially over the intervention in both groups but the intervention effects were non-selective with respect to exercise group. The decrease was several times larger than any previously estimated annual decline in D2R, potentially due to increased endogenous DA. Working-memory was unrelated to D2R both at baseline and following the intervention. To conclude, we provide partial evidence for a link between physical exercise and DA. Utilizing a PET protocol able to disentangle both D2R and DA levels could shed further light on whether, and how, aerobic exercise impacts the dopaminergic system in older adults.
25.	Karalija, Nina, 1984-, et al. (författare) C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition 2019 Ingår i: Journal of cognitive neuroscience. - : MIT Press. - 0898-929X .- 1530-8898. ; 31:2, s. 314-325 Tidskriftsartikel (refereegranskat)abstract The dopamine (DA) system plays an important role in cognition. Accordingly, normal variation in DA genes has been found to predict individual differences in cognitive performance. However, little is known of the impact of genetic differences on the link between empirical indicators of the DA system and cognition in humans. The present work used PET with C-11-raclopride to assess DA D2-receptor binding potential (BP) and links to episodic memory, working memory, and perceptual speed in 179 healthy adults aged 64-68 years. Previously, the T-allele of a DA D2-receptor single-nucleotide polymorphism, C957T, was associated with increased apparent affinity of C-11-raclopride, giving rise to higher BP values despite similar receptor density values between allelic groups. Consequently, we hypothesized that C-11-raclopride BP measures inflated by affinity rather than D2-receptor density in T-allele carriers would not be predictive of DA integrity and therefore prevent finding an association between C-11-raclopride BP and cognitive performance. In accordance with previous findings, we show that C-11-raclopride BP was increased in T-homozygotes. Importantly, C-11-raclopride BP was only associated with cognitive performance in groups with low or average ligand affinity (C-allele carriers of C957T, n = 124), but not in the high-affinity group (T-homozygotes, n = 55). The strongest C-11-raclopride BP-cognition associations and the highest level of performance were found in C-homozygotes. These findings show that genetic differences modulate the link between BP and cognition and thus have important implications for the interpretation of DA assessments with PET and C-11-raclopride in multiple disciplines ranging from cognitive neuroscience to psychiatry and neurology.
26.	Karalija, Nina, 1984-, et al. (författare) Cardiovascular factors are related to dopamine integrity and cognition in aging 2019 Ingår i: Annals of Clinical and Translational Neurology. - : Wiley-Blackwell. - 2328-9503. ; 6:11, s. 2291-2303 Tidskriftsartikel (refereegranskat)abstract Objective: The aging brain undergoes several changes, including reduced vascular, structural, and dopamine (DA) system integrity. Such brain changes have been associated with age‐related cognitive deficits. However, their relative importance, interrelations, and links to risk factors remain elusive.Methods: The present work used magnetic resonance imaging and positron emission tomography with 11C‐raclopride to jointly examine vascular parameters (white‐matter lesions and perfusion), DA D2‐receptor availability, brain structure, and cognitive performance in healthy older adults (n = 181, age: 64–68 years) from the Cognition, Brain, and Aging (COBRA) study.Results: Covariance was found among several brain indicators, where top predictors of cognitive performance included caudate and hippocampal integrity (D2DR availability and volumes), and cortical blood flow and regional volumes. White‐matter lesion burden was negatively correlated with caudate DA D2‐receptor availability and white‐matter microstructure. Compared to individuals with smaller lesions, individuals with confluent lesions (exceeding 20 mm in diameter) had reductions in cortical and hippocampal perfusion, striatal and hippocampal D2‐receptor availability, white‐matter microstructure, and reduced performance on tests of episodic memory, sequence learning, and processing speed. Higher cardiovascular risk as assessed by treatment for hypertension, systolic blood pressure, overweight, and smoking was associated with lower frontal cortical perfusion, lower putaminal D2DR availability, smaller grey‐matter volumes, a larger number of white‐matter lesions, and lower episodic memory performance.Interpretation: Taken together, these findings suggest that reduced cardiovascular health is associated with poorer status for brain variables that are central to age‐sensitive cognitive functions, with emphasis on DA integrity.
27.	Karalija, Nina, 1984-, et al. (författare) Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging 2022 Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 99 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND OBJECTIVES: Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates. METHODS: We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with 11C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity. RESULTS: Longitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion. DISCUSSION: These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline.
28.	Karalija, Nina, 1984-, et al. (författare) Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline 2024 Ingår i: NEUROBIOLOGY OF AGING. - 0197-4580 .- 1558-1497. ; 136, s. 125-132 Tidskriftsartikel (refereegranskat)abstract Dopamine decline is suggested to underlie aging -related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5 -year longitudinal data for a sample of healthy, older adults (baseline: n = 181, age: 64-68 years; 5 -year follow-up: n = 129) who underwent positron emission tomography with 11C- raclopride to assess dopamine D2 -like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A datadriven approach (k -means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age -sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide -ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5 -year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging.
29.	Karalija, Nina, 1984-, et al. (författare) Sex differences in dopamine integrity and brain structure among healthy older adults : Relationships to episodic memory 2021 Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 105, s. 272-279 Tidskriftsartikel (refereegranskat)abstract Normal brain aging is a multidimensional process that includes deterioration in various brain structures and functions, with large heterogeneity in patterns and rates of decline. Sex differences have been reported for various cognitive and brain parameters, but little is known in relation to neuromodulatory aspects of brain aging. We examined sex differences in dopamine D2-receptor (D2DR) availability in relation to episodic memory, but also, grey-matter volumes, white-matter lesions, and cerebral perfusion in healthy older adults (n = 181, age: 64-68 years) from the Cognition, Brain, and Aging study. Women had higher D2DR availability in midbrain and left caudate and putamen, as well as superior episodic memory performance. Controlling for left caudate D2DR availability attenuated sex differences in memory performance. In men, lower left caudate D2DR levels were associated with lower cortical perfusion and higher burden of white-matter lesions, as well as with episodic memory performance. However, sex was not a significant moderator of the reported links to D2DR levels. Our findings suggest that sex differences in multiple associations among DA receptor availability, vascular factors, and structural connectivity contribute to sex differences in episodic memory. Future longitudinal studies need to corroborate these patterns by lead-lag associations. This manuscript is part of the Special Issue entitled 'Cognitive Neuroscience of Healthy and Pathological Aging' edited by Drs. M. N. Rajah, S. Belleville, and R. Cabeza.
30.	Meisgen, Sabrina, et al. (författare) The HLA locus contains novel foetal susceptibility alleles for congenital heart block with significant paternal influence 2014 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 275:6, s. 640-651 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The main aim of this study was to identify foetal susceptibility genes on chromosome six for Ro/SSA autoantibody-mediated congenital heart block.SUBJECTS AND DESIGN: Single nucleotide polymorphism (SNP) genotyping of individuals in the Swedish Congenital Heart Block (CHB) study population was performed. Low-resolution HLA-A, -Cw and -DRB1 allele typing was carried out in 86 families comprising 339 individuals (86 Ro/SSA autoantibody-positive mothers, 71 fathers, 87 CHB index cases, and 95 unaffected siblings).RESULTS: A case-control comparison between index cases and population-based out-of-study controls (n=1710) revealed association of CHB with 15 SNPs in the 6p21.3 MHC locus at a chromosome-wide significance of p<2.59×10(-6) (OR 2.21-3.12). In a family-based analysis of association of SNP markers as well as distinct MHC class I and II alleles with CHB, HLA-DRB104 and HLA-Cw05 variants were significantly more frequently transmitted to affected individuals (p<0.03 and p<0.05, respectively), while HLA-DRB113 and HLA-Cw06 variants were significantly less often transmitted to affected children (p<0.04 and p<0.03). We further observed marked association of increased paternal (but not maternal) HLA-DRB104 transmission to affected offspring (p<0.02).CONCLUSIONS: HLA-DRB104 and HLA-Cw05 were identified as novel foetal HLA allele variants that confer susceptibility to CHB in response to Ro/SSA autoantibody exposure, while DRB113 and Cw*06 emerged as protective alleles. Additionally, we demonstrated a paternal contribution to foetal susceptibility to CHB for the first time.
31.	Molin, Jonas, 1972- (författare) Business Streamlining : Toward a Substantive Theory of the Streamlining of Outsourced Business Processes 2014 Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract Research comparing public-private services outsourcing applying a longitudinal approach including the production/delivery processes (life after purchase) in services sourcing contexts is scarce. In addition, prior studies on service sourcing tend be under conceptualized.To address the above this licentiate thesis presents the results of a comparative and grounded theory inspired case study of two major Swedish FM services outsourcing projects, a public and a private case of operational partnering. Client-provider interaction processes on management level have been followed regularly over time utilizing participant observation as a core element combined with interviews and documentary studies. Observed variations in relational orientation over time, are problematized and discussed. A substantive theory – Business streamlining - of Facility Management outsourcing processes, including the seldom-researched life after purchase processes, is outlined and contextualized. It is argued that existing relational classifications, such as operational partnering, do not capture the life after purchase dynamics of the studied relationships. Business streamlining rests on four main categories, which have major influence on how Facility Management relationships evolve over time.
32.	Nyberg, Lars, et al. (författare) Dopamine D2 receptor availability is linked to hippocampal-caudate functional connectivity and episodic memory 2016 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:28, s. 7918-7923 Tidskriftsartikel (refereegranskat)abstract D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [C-11]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions.
33.	Olsson, Per-Ola, et al. (författare) Unbroken Digital Data Flow In The Built Environment Process : A Case Study In Sweden 2019 Ingår i: Int. Arch. Photogramm. Remote Sens. Spatial Inf. Sci., XLII-2/W13. ; XLII-2/W13, s. 1347-1352 Konferensbidrag (refereegranskat)abstract An unbroken digital data flow would save substantial resources in the built environment process. In this study, which is part of a larger Swedish project, data delivery specifications and methods to integrate BIM and geodata are developed and tested with the aim to facilitate such an unbroken data flow. The main focus areas of the study are: (1) specifications that enables building permission applications based on BIM data to automate the building permission process, (2) reuse of as-built BIM models to update geodata when a building is constructed and (3) a national Swedish CityGML ADE for buildings. The study shows that building permission applications can be partly automated even though the delivery specifications were in the early stages of development at the time of a performed test case. With fully implemented delivery specifications more regulations can be checked. Furthermore, the study demonstrates how a BIM model can be georeferenced with a standard deviation of the transformation of 3 cm compared to field measurements performed with a total station. The georeferenced BIM model can then be converted to a LOD2 geodata building model to update existing geodata. Finally, a proposal for a national Swedish CityGML ADE for buildings is presented.
34.	Oltean, Mihai, 1976, et al. (författare) The microsurgical training programme in Gothenburg, Sweden: early experiences 2017 Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Medical Journals Sweden AB. - 2000-656X .- 2000-6764. ; 51:3, s. 193-198 Tidskriftsartikel (refereegranskat)abstract Objective: Microsurgical techniques are increasingly used in routine surgical practice as well as in biomedical research. The training opportunities at standardised training courses are limited, and no microsurgical training facility or programme existed in Scandinavia before 2013. Methods: A microsurgery laboratory was set up and two different courses were started, aiming separately at biomedical researchers and surgeons. The course for biomedical researchers teaches basic microsurgical skills such as vessel isolation, cannulation, and arterial microvascular suture under magnification. The more advanced course for surgeons focuses on various techniques of microvascular and nerve anastomosis. Both courses use a combination of theory and practice, with emphasis on the practical part, the course for surgeons also includes clinically relevant information. Results: Twelve 5-day courses using both non-living models and exercises on laboratory animals have been conducted and attended by 49 researchers and 44 surgeons. The organisation and the programme of the training courses as well as 'The 4E concept' behind the course (educational curriculum, equipment, ergonomy, and evaluation) are further detailed. Conclusions: We have successfully established the first training laboratory and series of microsurgical training courses in Scandinavia at two different levels. The experience from the first 12 courses shows the need for this type of structured training, and confirms that the microsurgical education curriculums needs to be adapted to participants' prerequisites and expectations, and various difficulty levels should be considered.
35.	Papenberg, Goran, et al. (författare) Balance between Transmitter Availability and Dopamine D2 Receptors in Prefrontal Cortex Influences Memory Functioning 2020 Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:3, s. 989-1000 Tidskriftsartikel (refereegranskat)abstract Insufficient or excessive dopaminergic tone impairs cognitive performance. We examine whether the balance between transmitter availability and dopamine (DA) D2 receptors (D2DRs) is important for successful memory performance in a large sample of adults (n= 175, 64-68 years). The Catechol-O-Methyltransferase polymorphism served as genetic proxy for endogenous prefrontal DA availability, and D2DRs in dorsolateral prefrontal cortex (dlPFC) were measured with [C-11]raclopride-PET. Individuals for whom D2DR status matched DA availability showed higher levels of episodic and working-memory performance than individuals with insufficient or excessive DA availability relative to the number of receptors. A similar pattern restricted to episodic memory was observed for D2DRs in caudate. Functional magnetic resonance imaging data acquired during working-memory performance confirmed the importance of a balanced DA system for load-dependent brain activity in dlPFC. Our data suggest that the inverted-U-shaped function relating DA signaling to cognition is modulated by a dynamic association between DA availability and receptor status.
36.	Papenberg, Goran, et al. (författare) The influence of hippocampal dopamine D2 receptor losses on episodic-memory decline across 5 years is moderated by BDNF and KIBRA polymorphisms 2024 Ingår i: Cortex. - : Elsevier. - 0010-9452 .- 1973-8102. ; 176, s. 53-61 Tidskriftsartikel (refereegranskat)abstract Losses in dopamine (DA) functioning may contribute to aging-related decline in cognition. Hippocampal DA is necessary for successful episodic memory formation. Previously, we reported that higher DA D2 receptor (D2DR) availability in hippocampus is beneficial for episodic memory only in older carriers of more advantageous genotypes of well-established plasticity-related genetic variations, the brain-derived neurotrophic factor (BDNF, rs6265) and the kidney and brain expressed protein (KIBRA, rs17070145) polymorphisms. Extending our observations to the longitudinal level, the current data show that individuals with one or no beneficial BDNF and KIBRA genotype (n = 80) decline more in episodic memory across five years, without any contribution of losses in hippocampal D2DR availability to memory decline. Although carriers of two beneficial genotypes (n = 39) did not decline overall in episodic memory, losses of hippocampal D2DR availability were predictive of episodic-memory decline among these individuals. Our findings have implications for interventions targeting DA modulation to enhance episodic memory in aging, which may not benefit all older individuals.
37.	Papenberg, Goran, et al. (författare) The Influence of Hippocampal Dopamine D2 Receptors on Episodic Memory Is Modulated by BDNF and KIBRA Polymorphisms 2019 Ingår i: Journal of cognitive neuroscience. - : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 31:9, s. 1422-1429 Tidskriftsartikel (refereegranskat)abstract Episodic memory is a polygenic trait influenced by different molecular mechanisms. We used PET and a candidate gene approach to investigate how individual differences at the molecular level translate into between-person differences in episodic memory performance of elderly persons. Specifically, we examined the interactive effects between hippocampal dopamine D2 receptor (D2DR) availability and candidate genes relevant for hippocampus-related memory functioning. We show that the positive effects of high D2DR availability in the hippocampus on episodic memory are confined to carriers of advantageous genotypes of the brain-derived neurotrophic factor (BDNF, rs6265) and the kidney and brain expressed protein (KIBRA, rs17070145) polymorphisms. By contrast, these polymorphisms did not modulate the positive relationship between caudate D2DR availability and episodic memory.
38.	Satizabal, Claudia L., et al. (författare) Genetic architecture of subcortical brain structures in 38,851 individuals 2019 Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624- Tidskriftsartikel (refereegranskat)abstract Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
39.	Wohlin, Martin, et al. (författare) Apolipoprotein E epsilon 4 genotype is independently associated with increased intima-media thickness in a recessive pattern 2007 Ingår i: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 42:5, s. 451-456 Tidskriftsartikel (refereegranskat)abstract Polymorphisms in the apolipoprotein E (Apo E) gene have been associated with lipid levels, carotid intima media thickness (CCA-IMT), inflammation and cardiovascular disease (CVD). Earlier findings suggested an association of the Apo E alleles with increased CCA-IMT following a recessive pattern. Whether associations might be independent of C-reactive protein (CRP), lipid levels and other CVD risk factors is not known. We investigated the relationships between Apo E (epsilon2, epsilon3 and epsilon4 alleles) and CCA-IMT, measured by B-mode ultrasound, in dominant and recessive models in a community-based sample of 437 men 75 years of age. In men homozygous for the epsilon4 allele CCA-IMT was significantly increased by 0.13 mm to 0.86 +/- 0.16 mm compared to 0.73 +/- 0.19 mm in non- epsilon4-carriers (P = 0.0012) and 0.73 +/- 0.21 mm in epsilon4 heterozygous (P = 0.0044) in unadjusted recessive models. The association between Apo E epsilon4 genotype and CCA-IMT was independent of Apo E epsilon2 and Apo E epsilon3 alleles, CRP, lipid variables (TG, LDL, HDL) and other CVD risk factors (smoking, hypertension, body mass index, diabetes) (P = 0.018). No relations between Apo E genotype and CCA-IMT were observed in dominant models. No significant associations between the Apo E epsilon2 and epsilon3 alleles and CCA-IMT were found. In this study, men homozygous with the ApoE epsilon4 allele had thicker CCA-IMT, independently of Apo E epsilon2 and epsilon3 alleles, CRP, lipid variables (TG, LDL, HDL) and other CVD risk factors (smoking, hypertension, body mass index, diabetes), suggesting CCA-IMT to be modified by the ApoE epsilon4 genotype in a recessive pattern.
40.	Adams, HHH, et al. (författare) Novel genetic loci underlying human intracranial volume identified through genome-wide association 2016 Ingår i: Nature neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 19:12, s. 1569-1582 Tidskriftsartikel (refereegranskat)
41.	Ahlgren, Bengt, et al. (författare) Experiments with Subversion Over OpenNetInf and CCNx 2011. - 7 Konferensbidrag (refereegranskat)abstract We describe experiences and insights from adapting the Subversion version control system to use the network service of two information-centric networking (ICN) prototypes: OpenNetInf and CCNx. The evaluation is done using a local collaboration scenario, common in our own project work where a group of people meet and share documents through a Subversion repository. The measurements show a performance benefit already with two clients in some of the studied scenarios, despite being done on un-optimised research prototypes. The conclusion is that ICN clearly is beneficial also for non mass-distribution applications.
42.	Ahlgren, Bengt, et al. (författare) Subversion over OpenNetInf and CCNx 2011 Ingår i: Proceedings - Conference on Local Computer Networks, LCN. - 9781612849287 ; , s. 1056-1063 Konferensbidrag (refereegranskat)abstract We describe experiences and insights from adapting the Subversion version control system to use the network service of two information-centric networking (ICN) prototypes: OpenNetInf and CCNx. The evaluation is done using a local collaboration scenario, common in our own project work where a group of people meet and share documents through a Subversion repository. The measurements show a performance benefit already with two clients in some of the studied scenarios, despite being done on un-optimised research prototypes. The conclusion is that ICN clearly is beneficial also for non mass-distribution applications. It was straightforward to adapt Subversion to fetch updated files from the repository using the ICN network service. The adaptation however neglected access control which will need a different approach in ICN than an authenticated SSL tunnel. Another insight from the experiments is that care needs to be taken when implementing the heavy ICN hash and signature calculations. In the prototypes, these are done serially, but we see an opportunity for parallelisation, making use of current multi-core processors.
43.	Ahlgren, Erik, 1962, et al. (författare) Biokombi Rya - slutrapporter från ingående delprojekt 2007 Rapport (övrigt vetenskapligt/konstnärligt)abstract Inom projektet Biokombi Rya har ett flertal olika forskargrupper samarbetat för att studera system¬effekterna av förgasning av biobränsle ur olika aspekter. Syftet med projektet är att öka kunskapen om biobränsleförgasning i Sverige samt att utreda förutsättningar för att sådana anläggningar ska vara ekonomiskt och miljömässigt intressanta. En referensgrupp har varit kopplad till projektet där förutsättningar, resultat och slutsatser har behandlats.I denna underlagsrapport har slutrapporterna från projektets delprojekt samlats. De beskriver förutsättningar, metodansatser, använda data och resultat utförligt och utgör på så sätt ett viktigt komplement till den mer övergripande beskrivningen i projektets syntesrapport. De delrapporter som ingår har valts för att täcka in samtliga delar av projektet som är av allmänt intresse. Projektresultat som publicerats på annat sätt berörs dock mer kortfattat.Projektet Biokombi Rya har pågått under två år (2005-2006) och drivits av Chalmers EnergiCentrum. Förutom de omfattande analysinsatser som författarna till denna rapport står för, har Avdelningen för kemisk teknologi vid KTH, Siemens Industrial Turbines AB och Göteborg Energi AB bidragit med expertstöd. CIT Industriell Energianalys, med undertecknad som projektledare, har stått för projektledning och koordination.Projektet har finansierats av Energimyndigheten, Göteborg Energis forsknings¬stiftelse samt Göteborg Energi AB.
44.	Allard, Christina, et al. (författare) Rasbiologiskt språkbruk i statens rättsprocess mot sameby 2015 Ingår i: Dagens Nyheter. - 1101-2447. Tidskriftsartikel (populärvet., debatt m.m.)abstract Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
45.	Allard, Christina, et al. (författare) Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11 2015 Annan publikation (populärvet., debatt m.m.)abstract Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
46.	Alsholm, Linda, et al. (författare) Interrupted transport by the emergency medical service in stroke/transitory ischemic attack : A consequence of changed treatment routines in prehospital emergency care. 2019 Ingår i: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279. Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The discovery that not all patients who call for the emergency medical service (EMS) require transport to hospital has changed the structure of prehospital emergency care. Today, the EMS clinician at the scene already distinguishes patients with a time-critical condition such as stroke/transitory ischemic attack (TIA) from patients without. This highlights the importance of the early identification of stroke/TIA.AIM: To describe patients with a final diagnosis of stroke/TIA whose transport to hospital was interrupted either due to a lack of suspicion of the disease by the EMS crew or due to refusal by the patient or a relative/friend.METHODS: Data were obtained from a register in Gothenburg, covering patients hospitalised due to a final diagnosis of stroke/TIA. The inclusion criterion was that patients were assessed by the EMS but were not directly transported to hospital by the EMS.RESULTS: Among all the patients who were assessed by the EMS nurse and subsequently diagnosed with stroke or TIA in 2015, the transport of 34 of 1,310 patients (2.6%) was interrupted. Twenty-five of these patients, of whom 20 had a stroke and five had a TIA, are described in terms of initial symptoms and outcome. The majority had residual symptoms at discharge from hospital. Initial symptoms were vertigo/disturbed balance in 11 of 25 cases. Another three had symptoms perceived as a change in personality and three had a headache.CONCLUSION: From this pilot study, we hypothesise that a fraction of patients with stroke/TIA who call for the EMS have their direct transport to hospital interrupted due to a lack of suspicion of the disease by the EMS nurse at the scene. These patients appear to have more vague symptoms including vertigo and disturbed balance. Instruments to identify these patients at the scene are warranted.
47.	Amini, Hashem, et al. (författare) Comparison of ultrasound and autopsy findings in pregnancies terminated due to fetal anomalies 2006 Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 85:10, s. 1208-1216 Tidskriftsartikel (refereegranskat)abstract Objective. To compare antenatal diagnoses with autopsy findings in pregnancies terminated after ultrasound detection of fetal anomalies. A second aim was to study the quality of antenatal fetal diagnosis over time. Design. Retrospective, multicenter study over two consecutive six-year periods in Uppsala and Stockholm. Setting. Cases were identified through fetal autopsy reports. Subjects. Three hundred and twenty-eight fetuses from pregnancies terminated between 1992 and 2003 because of ultrasonographically diagnosed anomalies. Main outcome measures. The findings at the last ultrasound examination were compared with the autopsy reports. Results. In 299 cases (91.2%) ultrasound findings either exactly matched or were essentially similar to the autopsy findings. In 23 cases (7%) ultrasound findings were not confirmed at autopsy, but the postnatal findings were at least as severe as the antenatal ones. In six cases (1.8%) termination was performed for an anomaly which proved to be less severe than was predicted by ultrasound. The number of such cases was the same in both six-year periods, while the total number of cases increased from 113 in the first to 215 in the second period. Fetal examination provided further diagnostic information in 47% of the cases. In 10% a syndrome was disclosed. Conclusion. Termination of pregnancy was not always based on a correct antenatal diagnosis. All fetuses but one from terminated pregnancies had evident anomalies. In six cases (1.8%) the decision to terminate was based on suboptimal prognostic and diagnostic information. Fetal autopsy by an experienced perinatal pathologist is essential to provide a definitive diagnosis.
48.	Andersson, Ellen, et al. (författare) Treatment with anti-factor VIIa in acute pancreatitis in rats: Blocking both coagulation and inflammation? 2007 Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 42:6, s. 765-770 Tidskriftsartikel (refereegranskat)abstract Objective. Acute pancreatitis starts as an autodigestive process restricted to the pancreas and progresses to a systemic inflammation via cytokine release into the blood stream. Several inhibitors of the coagulation cascade, including active- siteinactivated factor VIIa, have shown anti- inflammatory properties in other inflammatory models than acute pancreatitis. Free radical scavengers have proven useful in reducing the oxidative damage during hyperinflammatory conditions. The aim of this study was to investigate whether pretreatment with FVIIai would have any effect on the multiple organ dysfunction syndrome ( MODS) in severe acute pancreatitis. Material and methods. Experimental acute pancreatitis was induced by intraductal infusion of taurodeoxycholate in the pancreatic duct. The animals were pretreated with N- acetyl- cysteine and active- site- inactivated factor VIIa. Neutrophil infiltration in the lungs, ileum and colon was quantified by myeloperoxidase activity. Inflammatory markers, IL- 6 and MIP- 2, were measured using ELISA. Results. Tissue infiltration of neutrophils in the lungs, ileum and colon significantly increased during acute pancreatitis as compared to sham operation. These levels were reduced by pretreatment with N- acetylcysteine and active- site- inactivated factor VIIa. Levels of interleukin- 6 and macrophage inflammatory protein- 2 increased significantly during acute pancreatitis. Pretreatment with NAC and FVIIai reduced these levels. Conclusions. Both N- acetylcysteine and active- site- inactivated factor VIIa showed powerful antiinflammatory properties in experimental acute pancreatitis. As they exert their effects through different physiological mechanisms, they represent potential candidates for future multimodal treatment of acute pancreatitis.
49.	Andreou, Dimitrios, et al. (författare) Associations between a locus downstream DRD1 gene and cerebrospinal fluid dopamine metabolite concentrations in psychosis 2016 Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 619, s. 126-130 Tidskriftsartikel (refereegranskat)abstract Dopamine activity, mediated by the catecholaminergic neurotransmitter dopamine, is prominent in the human brain and has been implicated in schizophrenia. Dopamine targets five different receptors and is then degraded to its major metabolite homovanillic acid (HVA). We hypothesized that genes encoding dopamine receptors may be associated with cerebrospinal fluid (CSF) HVA concentrations in patients with psychotic disorder. We searched for association between 67 single nucleotide polymorphisms (SNPs) in the five dopamine receptor genes i.e., DRD1, DRD2, DRD3, DRD4 and DRD5, and the CSF HVA concentrations in 74 patients with psychotic disorder. Nominally associated SNPs were also tested in 111 healthy controls. We identified a locus, located downstream DRD1 gene, where four SNPs, rs11747728, rs11742274, rs265974 and rs11747886, showed association with CSF HVA concentrations in psychotic patients. The associations between rs11747728, which is a regulatory region variant, and rs11742274 with HVA remained significant after correction for multiple testing. These associations were restricted to psychotic patients and were absent in healthy controls. The results suggest that the DRD1 gene is implicated in the pathophysiology of psychosis and support the dopamine hypothesis of schizophrenia.
50.	Andreou, Dimitrios, et al. (författare) Cerebrospinal fluid monoamine metabolite concentrations as intermediate phenotypes between glutamate-related genes and psychosis 2015 Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 229:1-2, s. 497-504 Tidskriftsartikel (refereegranskat)abstract Glutamate-related genes have been associated with schizophrenia, but the results have been ambiguous and difficult to replicate. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major degradation products of the monoamines dopamine, serotonin and noradrenaline, respectively, and their concentrations in the cerebrospinal fluid (CSF), mainly HVA, have been associated with schizophrenia. In the present study, we hypothesized that CSF HVA, 5-HIAA and MHPG concentrations represent intermediate phenotypes in the association between glutamate-related genes and psychosis. To test this hypothesis, we searched for association between 238 single nucleotide polymorphisms (SNPs) in ten genes shown to be directly or indirectly implicated in glutamate transmission and CSF HVA, 5-HIAA and MHPG concentrations in 74 patients with psychotic disease. Thirty-eight nominally significant associations were found. Further analyses in 111 healthy controls showed that 87% of the nominal associations were restricted to the patients with psychosis. Some of the psychosis-only-associated SNPs found in the D-amino acid oxidase activator (DADA) and the kynurenine 3-monooxygenase (KMO) genes have previously been reported to be associated with schizophrenia. The present results suggest that CSF monoamine metabolite concentrations may represent intermediate phenotypes in the association between glutamate-related genes and psychosis.

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