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Sökning: WFRF:(Larsson Markus)

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1.
  • Falk, Anna, et al. (författare)
  • Discrimination between glioma grades II and III in suspected low-grade gliomas using dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging : a histogram analysis approach
  • 2014
  • Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 0028-3940 .- 1432-1920. ; 56:12, s. 1031-1038
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionPerfusion magnetic resonance imaging (MRI) can be used in the pre-operative assessment of brain tumours. The aim of this prospective study was to identify the perfusion parameters from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) perfusion imaging that could best discriminate between grade II and III gliomas.MethodsMRI (3 T) including morphological ((T2 fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W)+Gd)) and perfusion (DCE and DSC) sequences was performed in 39 patients with newly diagnosed suspected low-grade glioma after written informed consent in this review board-approved study. Regions of interests (ROIs) in tumour area were delineated on FLAIR images co-registered to DCE and DSC, respectively, in 25 patients with histopathological grade II (n = 18) and III (n  = 7) gliomas. Statistical analysis of differences between grade II and grade III gliomas in histogram perfusion parameters was performed, and the areas under the curves (AUC) from the ROC analyses were evaluated.ResultsIn DCE, the skewness of transfer constant (k trans) was found superior for differentiating grade II from grade III in all gliomas (AUC 0.76). In DSC, the standard deviation of relative cerebral blood flow (rCBF) was found superior for differentiating grade II from grade III gliomas (AUC 0.80).ConclusionsHistogram parameters from k trans (DCE) and rCBF (DSC) could most efficiently discriminate between grade II and grade III gliomas.
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2.
  • Falk Delgado, Anna, et al. (författare)
  • Diffusion kurtosis imaging of gliomas grades II and III : a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation
  • 2017
  • Ingår i: Radiology and Oncology. - : Walter de Gruyter GmbH. - 1318-2099 .- 1581-3207. ; 51:2, s. 121-129
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Diffusion kurtosis imaging (DKI) allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM) differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas).Patients and methods. Forty-eight patients with suspected low-grade glioma were prospectively recruited to this institutional review board-approved study and investigated with preoperative DKI at 3T after written informed consent. Patients with histologically proven glioma grades II or III were further analyzed (n=35). Regions of interest (ROIs) were delineated on T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data were compared between perilesional and contralesional NAWM (student's t-test for dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared between glioma types and glioma grades (multiple comparisons of mean ranks for all groups). The discriminating potential for DKI in assessing glioma type and grade was assessed with receiver operating characteristics (ROC) curves.Results. There were significant differences in all mean DKI variables between perilesional and contralesional NAWM (p=< 0.000), except for axial kurtosis (p=0.099). Forty-four histogram variables differed significantly between glioma grades II (n=23) and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between ACs (n=18) and ODs (n=17) (p=0.011-0.050). ROC curves of the best discriminating variables had an area under the curve (AUC) of 0.657-0.815.Conclusions. Mean DKI variables in perilesional NAWM differ significantly from contralesional NAWM, suggesting altered microstructure by tumor infiltration not depicted on morphological MRI. Histogram analysis of DKI data identifies differences between glioma grades and subtypes.
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4.
  • Jonsdottir, Berglind, et al. (författare)
  • Childhood thyroid autoimmunity and relation to islet autoantibodies in children at risk for type 1 diabetes in the diabetes prediction in skåne (DiPiS) study
  • 2018
  • Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 51:5, s. 228-237
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim was to determine prevalence and age at seroconversion of thyroid autoimmunity in relation to islet autoantibodies, gender and HLA-DQ genotypes in children with increased risk for type 1 diabetes followed from birth. Methods: In 10-year-old children (n = 1874), blood samples were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase 65 (GADA), Zink transporter 8 (ZnT8R/W/QA), insulinoma-associated protein-2 (IA-2A), insulin (IAA) and HLA-DQ genotypes. Prospectively collected samples from 2 years of age were next analysed for TPOAb, and TGAb and, finally, in confirming samples at 11–16 years of age along with TSH and FT4. Frequencies were tested with Chi-square or Fischer’s exact tests, autoantibody levels with Wilcoxon and correlations between autoantibody levels with Spearman’s rank correlation test. Results: The prevalence of thyroid autoimmunity was 6.9%, overrepresented in girls (p <.001) also having higher TPOAb levels at 10 years (p =.049). TPOAb was associated with GADA (p =.002), ZnT8R/W/QA (p =.001) and IA-2A (p =.001) while TGAb were associated with ZnT8R/W/QA (p =.021). In boys only, TPOAb were associated with GADA (p =.002), IA-2A (p =.001), ZnT8R/W/QA (p =.001) and IAA (p =.009), and TGAb with GADA (p =.013), IA-2A (p =.005) and ZnT8R/W/QA (p =.003). Levels of IA-2A correlated to both TPOAb (p =.021) and to TGAb (p =.011). In boys only, levels of GADA and TGAb correlated (p =.009 as did levels of IA-2A and TPOAb (p =.013). The frequency and levels of thyroid autoantibodies increased with age. At follow-up, 22.3% had abnormal thyroid function or were treated with thyroxine. Conclusions: Thyroid autoimmunity and high TPOAb levels were more common in girls. In contrast, in boys only, there was a strong association with as well as correlation between levels of thyroid and islet autoantibodies. It is concluded that while girls may develop autoimmune thyroid disease (AITD) independent of islet autoantibodies, the risk for thyroid disease in boys may be linked to concomitant islet autoimmunity.
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5.
  • Kuhlmann, Markus, et al. (författare)
  • Silencing of retrotransposons in Dictyostelium by DNA methylation and RNAi
  • 2005
  • Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 33:19, s. 6405-6417
  • Tidskriftsartikel (refereegranskat)abstract
    • We have identified a DNA methyltransferase of the Dnmt2 family in Dictyostelium that was denominated DnmA. Expression of the dnmA gene is downregulated during the developmental cycle. Overall DNA methylation in Dictyostelium is approximately 0.2% of the cytosine residues, which indicates its restriction to a limited set of genomic loci. Bisulfite sequencing of specific sites revealed that DnmA is responsible for methylation of mostly asymmetric C-residues in the retrotransposons DIRS-1 and Skipper. Disruption of the gene resulted in a loss of methylation and in increased transcription and mobilization of Skipper. Skipper transcription was also upregulated in strains that had genes encoding components of the RNA interference pathway disrupted. In contrast, DIRS-1 expression was not affected by a loss of DnmA but was strongly increased in strains that had the RNA-directed RNA polymerase gene rrpC disrupted. A large number of siRNAs were found that corresponded to the DIRS-1 sequence, suggesting concerted regulation of DIRS-1 expression by RNAi and DNA modification. No siRNAs corresponding to the standard Skipper element were found. The data show that DNA methylation plays a crucial role in epigenetic gene silencing in Dictyostelium but that different, partially overlapping mechanisms control transposon silencing.
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7.
  • Lundgren, Markus, et al. (författare)
  • Cord blood insulinoma-associated protein 2 autoantibodies are associated with increased risk of type 1 diabetes in the population-based Diabetes Prediction in Skane study
  • 2015
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 58:1, s. 75-78
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis The aim of this study was to examine the effect of cord blood autoantibodies on the risk for type 1 diabetes in children followed prospectively from birth. Methods The Diabetes Prediction in Skane (DiPiS) study consists of 35,853 children from the general population born during 2000-2004. Samples were collected at birth and analysed for HLA genotypes and autoantibodies to glutamate decarboxylase 65 (GAD65), insulin and insulinoma-associated protein 2 (IA-2). After adjusting for HLA, sex, maternal age and parental type 1 diabetes, independent associations with risk of diabetes were assessed using multivariate Cox proportional hazards models. Results In total, 151 children (0.4%) had developed type 1 diabetes by the end of 2013 at a median age of 5.8 years (0.8-12.2 years). In the multivariate analysis, the presence of IA-2 autoantibodies (IA-2A) in cord blood (HR 6.88, 95% CI 1.46,32.4; p = 0.003), but not maternal diabetes (HR 1.38, 95% CI 0.24,7.84; p = 0.71), was associated with risk of developing type 1 diabetes. No increased risk could be seen for the presence of autoantibodies to GAD65 or insulin. Conclusions/interpretation Our study indicates that the presence of cord blood IA-2A superimposes maternal diabetes and other cord blood islet autoantibodies as a predictor of type 1 diabetes development in the child. These findings may be of significance for future screening and study protocols on type 1 diabetes prediction.
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8.
  • Lundgren, Markus, et al. (författare)
  • Reduced morbidity at diagnosis and improved glycemic control in children previously enrolled in DiPiS follow-up
  • 2014
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X. ; 15:7, s. 494-501
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: Children participating in longitudinal type 1 diabetes prediction studies were reported to have less severe disease at diabetes diagnosis. Our aim was to investigate children who from birth participated in the Diabetes Prediction in Skane (DiPiS) study for metabolic status at diagnosis and then continued to be followed for 2 yr of regular clinical care. Methods: Children, followed in DiPiS before diagnosis, were compared to children in the same birth cohort, who did not participate in follow-up. Metabolic status, symptoms at diagnosis as well as hemoglobin A1c (HbA1c) and doses of insulin at 3, 6, 12, and 24 months after diagnosis were compared. Results: Children, followed in DiPiS and diagnosed at 2-12 yr of age, had 0.8% (9 mmol/mol) lower HbA1c at diagnosis than those who were not followed (p=0.006). At diagnosis, fewer DiPiS children had symptoms (p=0.014) and ketoacidosis at diagnosis were reduced (2% compared to 18%, p=0.005). During regular clinical care, HbA1c levels for the DiPiS children remained lower both at 12 (0.4% (4 mmol/mol); p=0.009) and 24 months (0.8% (9 mmol/mol) p < 0.001) after diagnosis, despite no difference in total daily insulin between the two groups. Conclusions: Participation in prospective follow-up before diagnosis of type 1 diabetes leads to earlier diagnosis with fewer symptoms, decreased incidence of ketoacidosis as well as better metabolic control up to 2 yr after diagnosis. Our data indicate that metabolic control at the time of diabetes diagnosis is important for early metabolic control possibly affecting the risk of long-term complications.
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10.
  • Manni, Giovanni Li, et al. (författare)
  • The OpenMolcas Web : A Community-Driven Approach to Advancing Computational Chemistry
  • 2023
  • Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 19:20, s. 6933-6991
  • Tidskriftsartikel (refereegranskat)abstract
    • The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations.
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11.
  • Agardh, Anette, et al. (författare)
  • Health Risks in Same-Sex Attracted Ugandan University Students : Evidence from Two Cross-Sectional Studies
  • 2016
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Widespread discrimination across much of sub-Saharan Africa against persons with same-sex sexuality, including recent attempts in Uganda to extend criminal sanctions against same-sex behavior, are likely to have profound effects on this group's health, health care access, and well-being. Yet knowledge of the prevalence of same-sex sexuality in this region is scarce. This study aimed to systematically examine prevalence of same-sex sexuality and related health risks in young Ugandan adults. We conducted two cross-sectional survey studies in south-western Uganda targeting student samples (n = 980, n = 1954) representing 80% and 72% of the entire undergraduate classes attending a university in 2005 and 2010, respectively. A questionnaire assessed items concerning same-sex sexuality (same-sex attraction/fantasies, same-sex sexual relations), mental health, substance use, experience of violence, risky sexual behavior, and sexual health counseling needs. Our findings showed that same-sex sexual attraction/fantasies and behavior were common among male and female students, with 10-25% reporting having sexual attraction/fantasies regarding persons of the same-sex, and 6-16% reporting same-sex sexual relations. Experiences of same-sex sexuality were associated with health risks, e.g. poor mental health (2010, AOR = 1.5; 95% CI: 1.0-2.3), sexual coercion (2010, AOR 2.9; CI: 1.9-4.6), and unmet sexual health counseling needs (2010, AOR 2.2; CI: 1.4-3.3). This first study of young adults in Uganda with same-sex sexuality found high levels of health needs but poor access to health care. Effective response is likely to require major shifts in current policy, efforts to reduce stigmatization, and reorientation of health services to better meet the needs of this vulnerable group of young people.
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12.
  • Agardh, Charlotte, et al. (författare)
  • Risk of poor mental health and experience of violence among a young adult population with same-sex sexuality : a cross-sectional study in southern Sweden
  • 2022
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTo assess prevalence and correlates of same-sex sexuality and its relationship to poor mental health and experiences of violence among youth and young adults in Sweden. A secondary aim was to estimate the same-sex sexuality attributable fractions.DesignA population-based cross-sectional survey.SettingSouthern Sweden.Participants2968 respondents out of 7000 youth and young adults between 18 and 29 years old, resident in southern Sweden, selected randomly by the Swedish Central Population Registry (final sample=2931 respondents, 318 with same-sex sexuality and 2613 without).Outcome measuresThe outcome measures were self-reported poor mental health (depression and anxiety) and experience of violence (physical violence, sexual violence and sexual coercion).ResultsIncreased odd of high scores of depression (adjusted OR 1.8, 95% CI 1.39 to 2.26) and anxiety (adjusted OR 1.6, 95% CI 1.28 to 2.07) were observed among youth and young adults with same-sex sexuality. Similarly, increased odds of experience of physical violence (OR 1.8, 95% CI 1.23 to 2.51), sexual violence (OR 2.8, 95% CI 1.96 to 3.89) and sexual coercion (OR 2.5, 95% CI 1.95 to 3.30) were observed with same-sex sexuality. Within the entire young population, same-sex sexuality accounted for 4.7% and 4.1% of the self-reported experience of depression and anxiety, respectively. The estimated same-sex sexuality attributable fractions of violence within the entire population of young people were 4.5% for physical violence, 7.3% for sexual violence and 6.4% for sexual coercion.ConclusionsThis study findings suggest that same-sex sexuality is associated with poor self-rated mental health and experience of violence among youth and young adults in Sweden. Some differences were observed between males and females, indicating that the vulnerabilities and experiences vary between young males and females. Further research is needed in order to gain a deeper knowledge of the factors underlying these associations and the gender differences observed.
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13.
  • Agardh, Charlotte, et al. (författare)
  • Using pharmacists and drugstore workers as sexual healthcare givers : A qualitative study of men who have sex with men in Dar es Salaam, Tanzania
  • 2017
  • Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Previous research has shown that men who have sex with men (MSM) avoid formal healthcare services because of the fear of discrimination as homosexuality is illegal and stigmatized in Tanzania. Instead, self-treatment by medications obtained directly from pharmacies or drugstores may be common when MSM experience symptoms of suspected sexually transmitted infections (STIs) related to sexual activity with men. Objective: To explore MSM’s perceptions and experiences of seeking treatment and advice from pharmacists and drugstore workers in Dar es Salaam, Tanzania, with regards to their sexual health and STI-related problems. Materials and Methods: 15 in-depth interviews were conducted with MSM with experience of seeking assistance relating to their sexual health at pharmacies and drugstores in Dar es Salaam in 2016. A qualitative manifest and latent content analysis was applied to the collected data. Results: Four themes related to different aspects of MSM’s perceptions and experiences of pharmacy care emerged from the analysis: (1) Balancing threats against need for treatment reflected informants’ struggles concerning risks and benefits of seeking assistance at pharmacies and drugstores; (2) Identifying strategies to access required services described ways of approaching a pharmacist when experiencing a sexual health problem; (3) Seeing pharmacists as a first choice of care focused on informants’ reasons for preferring contact with pharmacies/drugstores rather than formal healthcare services; and (4) Lacking reliable services at pharmacies indicated what challenges existed related to pharmacy care. Conclusions: MSM perceived the barriers for accessing assistance for STI and sexual health problems at pharmacies and drugstores as low, thereby facilitating their access to potential treatment. However, the results further revealed that MSM at times received inadequate drugs and consequently inadequate treatment. Multi-facetted approaches are needed, both among MSM and drugstore, pharmacy, and healthcare workers, to improve knowledge of MSM sexual health, STI treatment, and risks of antibiotic resistance.
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14.
  • Ahlström, Björn (författare)
  • The epidemiology of risk factors and short- and long-term outcome in the Swedish intensive care cohort
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The sepsis syndrome is present in ¼ to ⅓ of patients in intensive care units (ICUs) worldwide. The short-term prognosis is grim, with a 30-day mortality of 30–35%; however, the long- term outcomes are now being explored, as multi-professional follow-up after ICU care is increasingly being implemented. In 2020 the first and second waves of another severe infection, the Coronavirus disease 2019 (Covid-19) hit Sweden. The number of ICU beds were scaled up by several hundred percent while we simultaneously tried to understand the disease. Reports on risk factors for adverse outcomes in Covid-19 started to appear, but we needed to know more. Thus, we initiated this project aiming at assessing sepsis as an independent risk factor for later morbidity and mortality. Subsequently, with the onset of the pandemic, our focus shifted to identifying risk factors for adverse outcomes in Covid-19 and describing the functional recovery after severe Covid-19. We used the Swedish Intensive Care Registry and several governmental registries to this end.In Cox regression, we compared one-year ICU sepsis survivors without previous dementia with ICU patients without sepsis, finding no increased risk of dementia during follow- up. In a similar cohort, we assessed the impact of sepsis on long-term mortality and causes of death in a series of Cox and multinomial models. We found a surprisingly small overall association between sepsis and mortality and a persistently increased risk of infectious causes of death in sepsis patients. We compared the prevalence of several common comorbidities and medications as risk factors for ICU admission and mortality in ICU patients with Covid-19 with that of age- and sex-matched population controls and in patients discharged alive with those that were deceased at discharge. We found associations between several comorbidities and medications with these adverse outcomes. To better understand the meaning of these comorbidities as risk factors for short-term mortality, we compared them in logistic regression models on patients with Covid-19, sepsis and acute respiratory distress syndrome (ARDS). We found very similar impacts from the comorbidities; however, greater age was more associated with mortality in Covid-19 than in either sepsis or ARDS. Finally, we investigated the long-term functional recovery in ICU patients with Covid-19 compared to hospital-admitted patients with Covid-19 and population controls matched to the ICU group. The ICU patients had a markedly impeded recovery that was not explained by demographics or comorbidities in statistical models.
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15.
  • Akos, Dennis, et al. (författare)
  • Receiver measured time in the VDL mode 4 system
  • 2000
  • Ingår i: IEEE 2000 Position Location and Navigation Symposium. - Piscataway, NJ : IEEE Communications Society. - 0780358724 ; , s. 309-316
  • Konferensbidrag (refereegranskat)abstract
    • This paper details an investigation into the receiver measured time (RMT) concept of VDL Mode 4, basically the ability to derive estimates of time from the transmission of the VDL Mode 4 signals themselves. The RMT concept is based on determining the accurate time of transmission by measuring the time of arrival (TOA) of a received signal. The reverse aspect, or that of user position, can also be computed in the same manner and all computed simulations hold for errors in position. If synchronized time is available, or can be derived, then the user position can be computed based on signals from known transmitter locations. A complete, end-to-end RMT simulation model for the Gaussian filtered frequency shift keying (GFSK) and differential 8-phase shift keying (D8PSK) modulation techniques has been developed in which various transmitters, channels and receiver models as well as an RMT measurement system have been included. The timing results, which are included, are described in terms of two-sigma errors as a function of signal-to-noise ratios (SNRs). The performance varies for the different receiver structures over the typical operation region and for a 1-bit differential GFSK detector the two-sigma error is as low as 0.40 microseconds, corresponding to a ranging error of approximately 120 meters. When incorporating co-channel interference (CCI), multipath and Doppler frequency shifts the RMT performance has been shown to decrease in terms of higher two-sigma errors
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16.
  • Andersdotter, Amelia, et al. (författare)
  • Godtyckligt regelverk hotar friheten på nätet
  • 2013
  • Ingår i: Dagens Nyheter. - 1101-2447. ; :2013-09-03
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Reglerna som möjliggör stängning av hemsidor på internet präglas av godtycke och otydlighet. Men det behöver inte vara särskilt svårt att skapa ett nytt och rättssäkert regelverk. Här har Sveriges EU-kommissionär Cecilia Malmström en viktig roll. Frågan är om hon tar sitt ansvar, skriver politiker och nätdebattörer.
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17.
  • Andersdotter, Amelia, et al. (författare)
  • Utfästelser räcker inte
  • 2013
  • Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Det är nedslående att Cecilia Malmström givit upp kampen när det gäller fri- och rättigheter på nätet, skriver politiker och nätdebattörer. Den rättssäkerhet vi efterfrågar är en sådan som skyddar yttrandefriheten.
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18.
  • Andersson Svärd, Agnes, et al. (författare)
  • Decreased HLA-DQ expression on peripheral blood cells in children with varying number of beta cell autoantibodies
  • 2020
  • Ingår i: Journal of Translational Autoimmunity. - : Elsevier BV. - 2589-9090. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • The risk for type 1 diabetes is strongly associated with HLA-DQ and the appearance of beta cell autoantibodies against either insulin, glutamate decarboxylase (GAD65), insulinoma-associated protein-2 (IA-2), or zinc transporter 8 (ZnT8). Prolonged exposure to autoantibodies may be related to T cell exhaustion known to occur in chronic infections or autoimmune disorders. It was hypothesized that autoantibody exposure may affect HLA-DQ expression on peripheral blood cells and thereby contribute to T cell exhaustion thought to be associated with the pathogenesis of type 1 diabetes. The aim of this study was to determine whether autoantibody exposure as an expression of autoimmunity burden was related to peripheral blood cell HLA-DQ cell surface expression in either 1) a cross-sectional analysis or 2) cumulative as area under the trajectory of autoantibodies during long term follow-up in the Diabetes Prediction in Skåne (DiPiS) study. Children (n = 67), aged 10-15 years were analyzed for complete blood count, HLA-DQ cell surface median fluorescence intensity (MFI), autoantibody frequency, and HLA genotypes by Next Generation Sequencing. Decreased HLA-DQ cell surface MFI with an increasing number of autoantibodies was observed in CD16+, CD14+CD16-, CD4+ and CD8+ cells but not in CD19+ cells and neutrophils. HLA-DQ cell surface MFI was associated with HLA-DQ2/8 in CD4+ T cells, marginally in CD14+CD16- monocytes and CD8+ T cells. These associations appeared to be related to autoimmunity burden. The results suggest that HLA-DQ cell surface expression was related to HLA and autoimmunity burden.
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19.
  • Andersson Svärd, Agnes, et al. (författare)
  • Possible Relationship between the HLA-DRA1 Intron Haplotype of Three Single-Nucleotide Polymorphisms in Intron 1 of the HLA-DRA1 Gene and Autoantibodies in Children at Increased Genetic Risk for Autoimmune Type 1 Diabetes
  • 2022
  • Ingår i: ImmunoHorizons. - : The American Association of Immunologists. - 2573-7732. ; 6:8, s. 614-629
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, a haplotype of three single-nucleotide polymorphisms (tri-SNP) in intron 1 of the HLA-DRA1 gene was found to be strongly associated with type 1 diabetes risk in HLA-DR3/3 individuals. The tri-SNP reportedly function as “expression quantitative trait loci,” modulating HLA-DR and -DQ expression. The aim was to investigate HLA-DRA1 tri-SNPs in relation to extended HLA class II haplotypes and human peripheral blood cell HLA-DQ cell-surface median fluorescence intensity (MFI), the first-appearing islet autoantibody, and autoimmunity burden. A total of 67 healthy subjects (10–15 y) at increased HLA risk for type 1 diabetes and with (n = 54) or without (n = 13) islet autoantibodies were followed longitudinally in the Diabetes Prediction in Skåne study. Among four tri-SNPs, AGG (n = 67), GCA (n = 47), ACG (n = 11), and ACA (n = 9), HLA-DQ cell-surface MFI on CD4+ T cells was lower in AGG than GCA (p = 0.030) subjects. Cumulative autoimmunity burden was associated with reduced HLA-DQ cell-surface MFI in AGG compared with GCA in CD16+ cells (p = 0.0013), CD4+ T cells (p = 0.0018), and CD8+ T cells (p = 0.016). The results suggest that HLA-DRA1 tri-SNPs may be related to HLA-DQ cell-surface expression and autoimmunity burden.
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21.
  • Apelqvist, Anna, et al. (författare)
  • Pneumatic wound compression after hip fracture surgery did not reduce postoperative blood transfusion
  • 2009
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 80:1, s. 26-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose Patients with fracture of the proximal femur often undergo blood transfusion. A pneumatic compression bandage has been shown to reduce transfusion after primary hip arthroplasty for osteoarthritis. In this randomized trial, we evaluated the efficacy of this bandage following surgery for hip fracture. Patients and methods 288 patients, 50 years or older with 292 fractured hips treated with hemiarthroplasty or internal fixation (except pinning), were randomized to an experimental group with pneumatic wound compression applied after surgery (n = 138) and a control group with the same dressing but no compression (n = 154). Transfusion threshold was blood hemoglobin below 100 g/L. The primary outcome measures were the number of blood units and the proportion of patients transfused after surgery. Results The primary outcome measures were similar in both groups. The mean number of postoperatively transfused blood units was 1.3 in the compression group and 1.1 in the non-compression group. Blood transfusion was given to 84 patients (62%) in the compression group and to 85 patients (55%) in the non-compression group. Interpretation Pneumatic wound compression does not reduce the need for transfusion after hip fracture surgery.
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22.
  • Appleby, D.M., et al. (författare)
  • Systems of Imprimitivity for the Clifford Group
  • 2014
  • Ingår i: Quantum information & computation. - : Rinton Press. - 1533-7146. ; 14:3-4, s. 339-360
  • Tidskriftsartikel (refereegranskat)abstract
    • It is known that if the dimension is a perfect square the Clifford group can be represented by monomial matrices. Another way of expressing this result is to say that when the dimension is a perfect square the standard representation of the Clifford group has a system of imprimitivity consisting of one dimensional subspaces. We generalize this result to the case of an arbitrary dimension. Let k be the square-free part of the dimension. Then we show that the standard representation of the Clifford group has a system of imprimitivity consisting of k-dimensional subspaces. To illustrate the use of this result we apply it to the calculation of SIC-POVMs (symmetric informationally complete positive operator valued measures), constructing exact solutions in dimensions 8 (hand-calculation) as well as 12 and 28 (machine-calculation).
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23.
  • Appleby, D. M., et al. (författare)
  • The monomial representations of the Clifford group
  • 2012
  • Ingår i: Quantum information & computation. - : Rinton Press, Inc.. - 1533-7146. ; 12:5-6, s. 404-431
  • Tidskriftsartikel (refereegranskat)abstract
    • We show that the Clifford group-the normaliser of the Weyl-Heisenberg group-can be represented by monomial phase-permutation matrices if and only if the dimension is a square number. This simplifies expressions for SIC vectors, and has other applications to SICs and to Mutually Unbiased Bases. Exact solutions for SICs in dimension 16 are presented for the first time.
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24.
  • Aquilante, Francesco, et al. (författare)
  • Modern quantum chemistry with [Open]Molcas
  • 2020
  • Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 152:21
  • Tidskriftsartikel (refereegranskat)abstract
    • MOLCAS/OpenMolcas is an ab initio electronic structure program providing a large set of computational methods from Hartree-Fock and density functional theory to various implementations of multiconfigurational theory. This article provides a comprehensive overview of the main features of the code, specifically reviewing the use of the code in previously reported chemical applications as well as more recent applications including the calculation of magnetic properties from optimized density matrix renormalization group wave functions.
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25.
  • Arunda, Malachi Ochieng, et al. (författare)
  • Survival patterns of neonates born to adolescent mothers and the effect of pregnancy intentions and marital status on newborn survival in Kenya, Uganda, and Tanzania, 2014-2016
  • 2022
  • Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9880 .- 1654-9716. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Adolescent pregnancy and associated neonatal mortality are major global health challenges. In low-income settings where 90% of the 21 million global adolescent pregnancies occur, half are unintended and a fifth experience unsafe abortion. In Kenya, Uganda, and Tanzania, the survival patterns of neonates born to adolescents are unclear.Objectives: To assess survival patterns among neonates born to adolescents and the effect of pregnancy intentions and marital status on survival in Kenya, Uganda, and Tanzania.Methods: Cross-sectional data from demographic and health surveys in Kenya, Uganda, and Tanzania 2014-2016 were used. Kaplan-Meier estimates investigated patterns of neonatal survival among adolescent mothers, aged 15-19 years, compared to mothers aged 20-29 years. Cox proportional hazards regression determined the hazard ratios (HR) for the predictors of neonatal survival.Results: About 50% of adolescent pregnancies were unintended and neonatal death rate was twice as high than older mothers (26.6 versus 12.0 deaths/1000 live births). The median survival time was two days for adolescent-born babies and four days among older mothers. The hazard of death for all adolescent-born neonates was about twofold that of 20-29 years-old-mothers, HR 1.80 (95% CI 1.22-2.63). Among married adolescents with unintended newborn pregnancies, the HR was 4-folds higher than corresponding older mothers, HR 4.08 (95% CI 1.62-10.31). Among married, primiparous adolescents with unintended pregnancies, the HR was six times higher than corresponding older mothers.Conclusion: Our findings reveal how unintended pregnancies and deaths of neonates born to adolescents contribute substantially to preventable neonatal deaths in East Africa. Full implementation of existing adolescent health policies and utilization of contraceptives should be ensured. Partnership with youths and novel efforts that address sociocultural norms to reduce adolescent pregnancies or marriage should be supported. Regulations requiring adolescents' obstetric care conducted by only skilled personnel should be introduced and implemented.Keywords: Adolescents; East Africa; marital status; neonatal mortality; survival analysis; unintended pregnancy.
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26.
  • Bartoschek, Michael, et al. (författare)
  • Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing
  • 2018
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment, although their origin and roles in shaping disease initiation, progression and treatment response remain unclear due to significant heterogeneity. Here, following a negative selection strategy combined with single-cell RNA sequencing of 768 transcriptomes of mesenchymal cells from a genetically engineered mouse model of breast cancer, we define three distinct subpopulations of CAFs. Validation at the transcriptional and protein level in several experimental models of cancer and human tumors reveal spatial separation of the CAF subclasses attributable to different origins, including the peri-vascular niche, the mammary fat pad and the transformed epithelium. Gene profiles for each CAF subtype correlate to distinctive functional programs and hold independent prognostic capability in clinical cohorts by association to metastatic disease. In conclusion, the improved resolution of the widely defined CAF population opens the possibility for biomarker-driven development of drugs for precision targeting of CAFs.
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27.
  • Benedict, Christian, et al. (författare)
  • Acute Sleep Deprivation Enhances the Brain's Response to Hedonic Food Stimuli : An fMRI Study
  • 2012
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 97:3, s. E443-447
  • Tidskriftsartikel (refereegranskat)abstract
    • Context:There is growing recognition that a large number of individuals living in Western society are chronically sleep deprived. Sleep deprivation is associated with an increase in food consumption and appetite. However, the brain regions that are most susceptible to sleep deprivation-induced changes when processing food stimuli are unknown.Objective:Our objective was to examine brain activation after sleep and sleep deprivation in response to images of food.Intervention:Twelve normal-weight male subjects were examined on two sessions in a counterbalanced fashion: after one night of total sleep deprivation and one night of sleep. On the morning after either total sleep deprivation or sleep, neural activation was measured by functional magnetic resonance imaging in a block design alternating between high- and low-calorie food items. Hunger ratings and morning fasting plasma glucose concentrations were assessed before the scan, as were appetite ratings in response to food images after the scan.Main Outcome Measures:Compared with sleep, total sleep deprivation was associated with an increased activation in the right anterior cingulate cortex in response to food images, independent of calorie content and prescan hunger ratings. Relative to the postsleep condition, in the total sleep deprivation condition, the activation in the anterior cingulate cortex evoked by foods correlated positively with postscan subjective appetite ratings. Self-reported hunger after the nocturnal vigil was enhanced, but importantly, no change in fasting plasma glucose concentration was found.Conclusions:These results provide evidence that acute sleep loss enhances hedonic stimulus processing in the brain underlying the drive to consume food, independent of plasma glucose levels. These findings highlight a potentially important mechanism contributing to the growing levels of obesity in Western society.
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28.
  • Borén, Eleonora, 1985- (författare)
  • Off-gassing from thermally treated lignocellulosic biomass
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Off-gassing of hazardous compounds is, together with self-heating and dust explosions, the main safety hazards within large-scale biomass storage and handling. Formation of CO, CO2, and VOCs with concurrent O2 depletion can occur to hazardous levels in enclosed stored forest products. Several incidents of CO poisoning and suffocation of oxygen depletion have resulted in fatalities and injuries during cargo vessel discharge of forest products and in conjunction with wood pellet storage rooms and silos. Technologies for torrefaction and steam explosion for thermal treatment of biomass are under development and approaching commercialization, but their off-gassing behavior is essentially unknown.The overall objective of this thesis was to provide answers to one main question: “What is the off-gassing behaviour of thermally treated lignocellulosic biomass during storage?”. This was achieved by experimental studies and detailed analysis of off-gassing compounds sampled under realistic conditions, with special emphasis on the VOCs.Presented results show that off-gassing behavior is influenced by numerous factors, in the following ways. CO, CO2 and CH4 off-gassing levels from torrefied and stream-exploded biomass and pellets, and accompanying O2 depletion, are comparable to or lower than corresponding from untreated biomass. The treatments also cause major compositional shifts in VOCs; emissions of terpenes and native aldehydes decline, but levels of volatile cell wall degradation products (notably furans and aromatics) increase. The severity of the thermal treatment is also important; increases in torrefaction severity increase CO off-gassing from torrefied pine to levels comparable to emissions from conventional pellets, and increase O2 depletion for both torrefied chips and pellets. Both treatment temperature and duration also influence degradation rates and VOC composition. The product cooling technique is influential too; water spraying in addition to heat exchange increased CO2 and VOCs off-gassing from torrefied pine chips, as well as O2 depletion. Moreover, the composition of emitted gases co-varied with pellets’ moisture content; pellets of more severely treated material retained less moisture, regardless of their pre-conditioning moisture content. However, no co-variance was found between off-gassing and pelletization settings, the resulting pellet quality, or storage time of torrefied chips before pelletization. Pelletization of steam-exploded bark increased subsequent VOC off-gassing, and induced compositional shifts relative to emissions from unpelletized steam-exploded material. In addition, CO, CO2 and CH4 off-gassing, and O2 depletion, were positively correlated with the storage temperature of torrefied softwood. Similarly, CO and CH4 emissions from steam-exploded softwood increased with increases in storage temperature, and VOC off-gassing from both torrefied and steam-exploded softwood was more affected by storage temperature than by treatment severity. Levels of CO, CO2 and CH4 increased, while levels of O2 and most VOCs decreased, during storage of both torrefied and steam-exploded softwood.CO, CO2 and O2 levels were more affected by storage time than by treatment severity. Levels of VOCs were not significantly decreased or altered by nitrogen purging of storage spaces of steam-exploded or torrefied softwood, or controlled headspace gas exchange (intermittent ventilation) during storage of steam-exploded bark.In conclusion, rates of off-gassing of CO and CO2 from thermally treated biomass, and associated O2 depletion, are comparable to or lower than corresponding rates for untreated biomass. Thermal treatment induces shifts in both concentrations and profiles of VOCs. It is believed that the knowledge and insights gained provide refined foundations for future research and safe implementation of thermally treated fuels as energy carriers in renewable energy process chains.
  •  
29.
  • Borén, Eleonora, et al. (författare)
  • Off-gassing of VOCs and permanent gases during storage of torrefied and steam exploded wood
  • 2017
  • Ingår i: Energy & Fuels. - Washington : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 31:10, s. 10954-10965
  • Tidskriftsartikel (refereegranskat)abstract
    • Thermal treatment for upgrading of low-value feedstocks to improve fuel properties has gained large industrial interest in recent years. From a storage and transport perspective, hazardous off-gassing could be expected to decrease through the degradation of reactive biomass components. However, thermal treatment could also shift chemical compositions of volatile organic components, VOCs. While technologies are approaching commercialization, off-gassing behavior of the products, especially in terms of VOCs, is still unknown. In the present study, we measured off-gassing of VOCs together with CO, CO2, CH4, and O2 depletion from torrefied and steam exploded softwood during closed storage. The storage temperature, head space gas (air and N2), and storage time were varied. VOCs were monitored with a newly developed protocol based on active sampling with Tenax TA absorbent analyzed by thermal desorption-GC/MS. High VOC levels were found for both untreated and steam exploded softwood, but with a complete shift in composition from terpenes dominating the storage gas for untreated wood samples to an abundance of furfural in the headspace of steam exploded wood. Torrefied material emitted low levels of VOCs. By using multivariate statistics, it was shown that for both treatment methods and within the ranges tested, VOC off-gassing was affected first by the storage temperature and second by increasing treatment severity. Both steam exploded and torrefied biomass formed lower levels of CO than the reference biomass, but steam explosion caused a more severe O2 depletion.
  •  
30.
  • Borén, Eleonora, et al. (författare)
  • Reducing VOC off-gassing during the production of pelletized steam-exploded bark : impact of storage time and controlled ventilation
  • 2018
  • Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 32:4, s. 5181-5186
  • Tidskriftsartikel (refereegranskat)abstract
    • Volatile organic compound (VOC) off-gassing behavior of thermally treated biomass intended for bioenergy production has recently been shown to be vastly different from that of untreated biomass. Simple measures to reduce emissions, such as controlled ventilation and prolonged storage time, have been suggested but not yet studied in detail. In the present study, we monitored how VOC off-gassing was reduced over time (24–144 h) in enclosed storage with and without ventilation. Steam-exploded bark was collected directly from a pilot-scale steam explosion plant as well as before and after subsequent pelletizing. Active Tenax-TA absorbent sampling of VOCs was performed from the headspaces of a bench-scale sample storage setup. The impact of storage time and ventilation on VOC levels was evaluated through multivariate statistical analysis. The results showed that relative VOC concentrations in the headspace were reduced by increased storage time, with heavier VOCs reduced at a higher rate. VOC composition was neither reduced nor shifted by controlled intermittent ventilation during storage; instead, VOC levels equilibrated at the same levels as those stored without ventilation, and this was independent of the process step, storage time, or number of ventilations.
  •  
31.
  • Borén, Eleonora, et al. (författare)
  • Reducing VOCs off-gassing during production of pelletized steam exploded bark : impact of storage time and controlled ventilation
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • VOC off-gassing behavior of thermally treated biomass intended for bioenergy production has recently been shown to be vastly different to that of untreated biomass. Simple measures to reduce emissions, such as controlled ventilation and prolonged storage time, has been suggested but not previously studied in detail. In the present study, we monitored how VOC off-gassing was reduced over time (24–144h) in closed storage with and without ventilation. Steam exploded bark was collected directly from a pilot scale steam explosion plant, and before and after subsequent pelletizing. Storage and active sampling of VOCs in the headspace was done in a bench-scale set-up using Tenax-TA absorbent. The impact of storage time and ventilation to reduce VOCs was evaluated through multivariate statistical analysis. The results showed that VOC concentrations in the headspace were reduced by increased storage time, and that heavier VOCs reduced faster. No impact on either reducing or shifting VOC composition could be achieved by controlled ventilation during storage; instead, VOCs emitted to the same concentrations anew, independent of process step, storage time, or number of ventilations.
  •  
32.
  • Borén, Eleonora, et al. (författare)
  • VOC off-gassing from pelletized steam exploded softwood bark : emissions at different industrial process steps
  • 2018
  • Ingår i: Fuel processing technology. - : Elsevier. - 0378-3820 .- 1873-7188. ; 171, s. 70-77
  • Tidskriftsartikel (refereegranskat)abstract
    • Formation of hazardous gases during transport and storage of biomass for large-scale bioenergy production is an important safety concern. While off-gassing has been addressed in numerous studies for raw woody biomass, very few describe it in the context of biomass for bioenergy production pre-treated by thermal technologies such as steam explosion. Volatile Organic Components (VOCs) are expected to be altered by the treatment, but until now there is no research published on VOC profiles of steam exploded materials in industrial scale. In the present study, VOCs emitted from the products were evaluated by sampling from different production steps from steam explosion of softwood bark, and following the production chain including also pelletization. Off-gasses were actively sampled using Tenax TA absorbent and analyzed by GC-MS. The VOC formation dependency of operation and storage conditions at different process steps was evaluated by multivariate statistical analysis. We showed that the different process steps along the production line was the main influencing factor for VOC off-gassing amounts, with highest VOC levels directly after the steam explosion process. Treatment severity mainly altered the relative composition of VOC profiles with more terpenes emitted from milder treatment, whereas more severe treatment shifted VOCs composition to contain more furans, e.g. furfural. In summary, treatment by steam explosion leads to potentially problematic VOC off-gassing profiles from the material, and levels vary considerable along the production line. The findings are important from a fuel handling and working environment perspective.
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33.
  • Campbell, PJ, et al. (författare)
  • Pan-cancer analysis of whole genomes
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
  •  
34.
  • Carlevaro-Fita, J, et al. (författare)
  • Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
  • 2020
  • Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 56-
  • Tidskriftsartikel (refereegranskat)abstract
    • Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.
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35.
  • Carlsson, Axel C., et al. (författare)
  • Use of a proximity extension assay proteomics chip to discover new biomarkers associated with albuminuria
  • 2017
  • Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; :4, s. 340-348
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The underlying mechanisms for the development of albuminuria and the increased cardiovascular risk in patients with elevated albuminuria levels are incompletely understood. We therefore investigated the associations between 80 cardiovascular proteins and the urinary albumin to creatinine ratio (ACR).METHODS: We used a discovery/replication approach in two independent community-based cohorts of elderly patients: the Uppsala Longitudinal Study of Adult Men (n = 662; mean age 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (n = 757; mean age 75 years; 51% women). A proteomic chip with a panel of 80 plasma proteins associated with different aspects of cardiovascular disease was analysed. In the discovery cohort, we used a false discovery rate of 5% to take into account the multiple statistical testing. Nominal p values were used in the replication.RESULTS: Higher levels of T-cell immunoglobulin mucin-1, placenta growth factor, growth/differentiation factor-15, urokinase plasminogen activator surface receptor and kallikrein-11 were robustly associated with a higher ACR in both cohorts in multivariable linear regression models adjusted for sex, established cardiovascular risk factors, antihypertensive treatment, prevalent cardiovascular disease and glomerular filtration rate (p < 0.02 for all). All associations were also significant in separate analyses of patients without diabetes.CONCLUSIONS: We discovered and replicated associations between ACR and five cardiovascular proteins involved in tubular injury, atherosclerosis, endothelial function, heart failure, inflammation, glomerulosclerosis and podocyte injury. Our findings put forward multiplex proteomics as a promising approach to explore novel aspects of the complex detrimental interplay between kidney function and the cardiovascular system.
  •  
36.
  • Carlsson, Axel C, et al. (författare)
  • Use of proteomics to investigate kidney function decline over 5 years
  • 2017
  • Ingår i: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 12:8, s. 1226-1235
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR. There were 231 and 206 incident cases of CKD during follow-up in the PIVUS and ULSAM studies, respectively. Proteomic profiling of 80 proteins was assessed by a multiplex assay (proximity extension assay). The assay uses two antibodies for each protein and a PCR step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations.RESULTS: In the discovery cohort from the PIVUS Study, 28 plasma proteins were significantly associated with eGFR decline per year, taking into account the multiple testing. Twenty of these proteins were significantly associated with eGFR decline per year in the replication cohort from the ULSAM Study after adjustment for age, sex, cardiovascular risk factors, medications, and urinary albumin-to-creatinine ratio (in order of significance: TNF-related apoptosis-inducing ligand receptor 2*, CD40L receptor, TNF receptor 1*, placenta growth factor*, thrombomodulin*, urokinase plasminogen activator surface receptor*, growth/differentiation factor 15*, macrophage colony-stimulating factor 1, fatty acid-binding protein*, cathepsin D, resistin, kallikrein 11*, C-C motif chemokine 3, proteinase-activated receptor 1*, cathepsin L, chitinase 3-like protein 1, TNF receptor 2*, fibroblast growth factor 23*, monocyte chemotactic protein 1, and kallikrein 6). Moreover, 11 of the proteins predicted CKD incidence (marked with * above). No protein consistently predicted eGFR decline per year independently of baseline eGFR in both cohorts.CONCLUSIONS: Several circulating proteins involved in phosphate homeostasis, inflammation, apoptosis, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction were associated with worsening kidney function. Multiplex proteomics appears to be a promising way of discovering novel aspects of kidney disease pathology.
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37.
  • Carlsson, Markus, et al. (författare)
  • Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock : a model of endotoxin elimination
  • 2009
  • Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 37:3, s. 1031-e4
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective:To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.Design:Prospective parallel-grouped placebo-controlled randomized interventional experimental study.Setting:University research unit.Subjects: Healthy pigs.Interventions:The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 µg endotoxin × kg-1 × h-1 for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.Measurements and Main Results:During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-[alpha] (TNF-[alpha]) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-[alpha] concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.Conclusions:Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-[alpha] peak or later will have very little or no effect on TNF-[alpha]–mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.
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38.
  • Castegren, Markus, et al. (författare)
  • Differences in Organ Dysfunction in Endotoxin Tolerant Pigs Under Intensive Care Exposed to a Second Hit of Endotoxin
  • 2012
  • Ingår i: Shock. - 1073-2322 .- 1540-0514. ; 37:5, s. 501-510
  • Tidskriftsartikel (refereegranskat)abstract
    • Endotoxin tolerance is a well-studied phenomenon associated with a reduced inflammatory response. In the switch from an inflammatory to an anti-inflammatory response in clinical sepsis the concept of endotoxin tolerance is of obvious interest. However, only limited data exist regarding the effect of endotoxin tolerance on organ dysfunction and, therefore, this was investigated in a porcine intensive care sepsis model. Twenty-seven healthy pigs, including nine control animals, were included in the study. Twelve pigs pre-exposed to 24 h of intravenous endotoxin infusion and intensive care and six unexposed pigs were given either a high- or low-dose endotoxin challenge for 6 h. Inflammatory, circulatory, hypoperfusion and organ dysfunction parameters were followed. The inflammatory responses as well as parameters representing circulation, hypoperfusion, cardiac and renal function were all markedly attenuated in animals pre-exposed to endotoxin and intensive care as compared with animals not pre-exposed. In animals pre-exposed to endotoxin and given the high-dose of endotoxin challenge, deterioration in pulmonary function was equal to or even worse than in animals not pre-exposed.In contrast to the overall protective effect of endotoxin tolerance observed in other organ systems, the lungs of endotoxin tolerant animals demonstrated an increased responsiveness to high-dose endotoxin challenge.
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39.
  • Castegren, Markus, 1976-, et al. (författare)
  • Endotoxin tolerance variation over 24 h during porcine endotoxemia : association to changes in circulation and organ dysfunction
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1, s. e53221-
  • Tidskriftsartikel (refereegranskat)abstract
    • Endotoxin tolerance (ET), defined as reduced inflammatory responsiveness to endotoxin challenge following a first encounter with endotoxin, is an extensively studied phenomenon. Although reduced mortality and morbidity in the presence of ET has been demonstrated in animal studies, little is known about the temporal development of ET. Further, in acute respiratory distress syndrome ET correlates to the severity of the disease, suggesting a complicated relation between ET and organ dysfunction. Eighteen pigs were subjected to intensive care and a continuous endotoxin infusion for 24 h with the aim to study the time course of early ET and to relate ET to outcome in organ dysfunction. Three animals served as non-endotoxemic controls. Blood samples for cytokine analyses were taken and physiological variables registered every third hour. Production of TNF-α, IL-6, and IL-10 before and after endotoxin stimulation ex vivo was measured. The difference between cytokine values after and before ex vivo LPS stimulation (Δ-values) was calculated for all time points. ΔTNF-α was employed as the principal marker of ET and lower ΔTNF-α values were interpreted as higher levels of ET. During endotoxin infusion, there was suppression of ex vivo productions of TNF-α and IL-6 but not of IL-10 in comparison with that at 0 h. The ex vivo TNF-α values followed another time concentration curve than those in vivo. ΔTNF-α was at the lowest already at 6 h, followed by an increase during the ensuing hours. ΔTNF-α at 6 h correlated positively to blood pressure and systemic vascular resistance and negatively to cardiac index at 24 h. In this study a temporal variation of ET was demonstrated that did not follow changes in plasma TNF-α concentrations. Maximal ET occurred early in the course and the higher the ET, the more hyperdynamic the circulation 18 h later.
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40.
  • Daniels, Markus, et al. (författare)
  • Studie visar fördelarna med borrad spont med avseende på markvibrationer
  • 2015
  • Ingår i: Bygg och Teknik. - Stockholm : Bygg & teknik. - 0281-658X .- 2002-8350. ; :1, s. 36-39
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Då det byggs allt tätare och i känsliga områden blir det allt vanligare att man måste ta hänsyn till markvibrationer. Anläggningsarbeten såsom packning, borrning och pål- och spontinstallationer genererar markvibrationer som kan skada intilliggande bebyggelse, påverka marken negativt samt skapa en otrivsam vistelsemiljö. I känsliga områden är det viktigt att kunna välja rätt metod som skapar acceptabla vibrationsnivåer.  Det är allmänt vedertaget att vibrationerna som skapas vid installation av borrade stålrör är mindre än vibrationer genererade vid installation av vibrerad spont och slagna pålar. Det har dock inte gått att finna några tillgängliga studier där markvibrationer genererad från borrning respektive vibrerad spont har uppmätts parallellt. Fördelen av att använda borrade stålrör har därför inte kunnat påvisas. Att förutspå vibrationerna analytiskt är mycket komplicerat då det finns ett stort antal parametrar som inverkar på resultatet, både vad det gäller installationsmetoden samt markens beskaffenhet. I Daniels & Lovéns (2014) examensarbete utfört för KTH och Skanska Grundläggning har för första gången en borrad RD-vägg och en vibrerad spont installerats inom samma område med lika markförhållanden samtidigt som vibrationerna uppmätts både i marken och på respektive sponttyp (Figur 1 och 2). Resultaten från undersökningen visar tydligt på skillnaderna i vibrationer och är tänkta att kunna användas vid projektering av spontarbeten där vibrationer blir en faktor att ta hänsyn till.
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41.
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42.
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43.
  • Dhara, Ashis Kumar, et al. (författare)
  • Segmentation of Post-operative Glioblastoma in MRI by U-Net with Patient-specific Interactive Refinement
  • 2019
  • Ingår i: Brainlesion. - Cham : Springer. - 9783030117221 - 9783030117238 ; , s. 115-122
  • Konferensbidrag (refereegranskat)abstract
    • Accurate volumetric change estimation of glioblastoma is very important for post-surgical treatment follow-up. In this paper, an interactive segmentation method was developed and evaluated with the aim to guide volumetric estimation of glioblastoma. U-Net based fully convolutional network is used for initial segmentation of glioblastoma from post contrast MR images. The max flow algorithm is applied on the probability map of U-Net to update the initial segmentation and the result is displayed to the user for interactive refinement. Network update is performed based on the corrected contour by considering patient specific learning to deal with large context variations among different images. The proposed method is evaluated on a clinical MR image database of 15 glioblastoma patients with longitudinal scan data. The experimental results depict an improvement of segmentation performance due to patient specific fine-tuning. The proposed method is computationally fast and efficient as compared to state-of-the-art interactive segmentation tools. This tool could be useful for post-surgical treatment follow-up with minimal user intervention.
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44.
  • Dublon, Ian, et al. (författare)
  • Scintillate : An open-source graphical viewer for time-series calcium imaging evaluation and pre-processing
  • 2016
  • Ingår i: Journal of Neuroscience Methods. - : Elsevier BV. - 0165-0270 .- 1872-678X. ; 273, s. 120-127
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Calcium imaging is based on the detection of minute signal changes in an image time-series encompassing pre- and post-stimuli. Depending on the function of the elicited response, change may be pronounced, as in the case of a genetically encoded calcium-reporter protein, or subtle, as is the case in a bath-applied dye system. Large datasets are thus often acquired and appraised only during post-processing where specific Regions of Interest (ROIs) are examined. New method The scintillate software provides a platform allowing for near instantaneous viewing of time-sequenced tiffs within a discrete GUI environment. Whole sequences may be evaluated. In its simplest form scintillate provides change in florescence (ΔF) across the entire tiff image matrix. Evaluating image intensity level differences across the whole image allows the user to rapidly establish the value of the preparation, without a priori ROI-selection. Additionally, an implementation of Independent Component Analysis (ICA) provides additional rapid insights into areas of signal change. Results We imaged transgenic flies expressing Calcium-sensitive reporter proteins within projection neurons and moth mushroom bodies stained with a Ca2+ sensitive bath-applied dye. Instantaneous pre-stimulation background subtraction allowed us to appraise strong genetically encoded neuronal Ca2+ responses in flies and weaker, less apparent, responses within moth mushroom bodies. Comparison with existing methods At the time of acquisition, whole matrix ΔF analysis alongside ICA is ordinarily not performed. We found it invaluable, minimising time spent with unresponsive samples, and assisting in optimisation of subsequent acquisitions. Conclusions We provide a multi-platform open-source system to evaluate time-series images.
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45.
  • Dullin, Christian, et al. (författare)
  • Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples
  • 2015
  • Ingår i: Journal of Synchrotron Radiation. - : International Union of Crystallography. - 0909-0495 .- 1600-5775. ; 22, s. 143-155
  • Tidskriftsartikel (refereegranskat)abstract
    • Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were kept in situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites.
  •  
46.
  • Dullin, Christian, et al. (författare)
  • Phase-contrast computed tomography for quantification of structural changes in lungs of asthma mouse models of different severity
  • 2015
  • Ingår i: Journal of Synchrotron Radiation. - : International Union of Crystallography. - 0909-0495 .- 1600-5775. ; 22, s. 1106-1111
  • Tidskriftsartikel (refereegranskat)abstract
    • Lung imaging in mouse disease models is crucial for the assessment of the severity of airway disease but remains challenging due to the small size and the high porosity of the organ. Synchrotron inline free-propagation phase-contrast computed tomography (CT) with its intrinsic high soft-tissue contrast provides the necessary sensitivity and spatial resolution to analyse the mouse lung structure in great detail. Here, this technique has been applied in combination with single-distance phase retrieval to quantify alterations of the lung structure in experimental asthma mouse models of different severity. In order to mimic an in vivo situation as close as possible, the lungs were inflated with air at a constant physiological pressure. Entire mice were embedded in agarose gel and imaged using inline free-propagation phase-contrast CT at the SYRMEP beamline (Synchrotron Light Source, Elettra, Trieste, Italy). The quantification of the obtained phase-contrast CT data sets revealed an increasing lung soft-tissue content in mice correlating with the degree of the severity of experimental allergic airways disease. In this way, it was possible to successfully discriminate between healthy controls and mice with either mild or severe allergic airway disease. It is believed that this approach may have the potential to evaluate the efficacy of novel therapeutic strategies that target airway remodelling processes in asthma.
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47.
  • Dumitrescu, Mihail, et al. (författare)
  • 10 Gb/s uncooled dilute nitride optical transmitters operating at 1300 nm
  • 2009
  • Ingår i: 2009 Conference on Optical Fiber Communication, OFC 2009; San Diego, CA; United States; 22 March 2009 through 26 March 2009. - Washington, D.C. : OSA. - 9781557528650
  • Konferensbidrag (refereegranskat)abstract
    • Dilute-nitride lasers with record performances have been used to build uncooled transceivers and failure free 10 Gb/s optical transmission was achieved over 815 m of multimode Corning InfiniCor fiber under the LRM standard.
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48.
  •  
49.
  • Dwibedi, Chinmay Kumar, 1987- (författare)
  • Francisella tularensis: persistence, dissemination and source attribution : a theoretical and computational approach
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The bacterium Francisella tularensis causing tularemia in humans and other mammals displays little genetic diversity among genomes across temporal and spatial scales. F. tularensis infects humans with an extremely low infectious dose and causes natural seasonal tularemia outbreaks. During the Cold War, this bacterium was developed as a biological weapon.In paper I, we aimed at investigating the genetic diversity of F. tularensis over space and time and were especially interested in the influence of spatial dispersal on the genetic diversity. By analyses of single-nucleotide polymorphisms (SNPs) among 205 F. tularensis genomes, we found that tularemia had moved from East to West over the European continent by dispersal patterns characterized by multiple long-range dispersal events. Evolutionary rate estimates based on the year of bacterial isolation from 1947 to 2012 indicated non-measurable rates. In outbreak areas with multiple recent outbreaks, however, there was a measurable rate of 0.4 SNPs/genome/year indicating that in areas with more intense disease activity, there is a detectable evolutionary rate. The findings suggest that long-range geographical dispersal events and mostly very low evolutionary rates are important factors contributing to a very low genetic diversity of F. tularensis populations.In paper II, we focused on a geographically restricted area with a history of frequent tularemia outbreaks to study F. tularensis persistence. By analyzing F. tularensis genomes from 138 individuals infected from 1994 to 2010 in Örebro County in Sweden and performing a long-term laboratory storage experiment, we explored the microbial population concept of a pathogen seed-bank. We found that eight indistinguishable genomes – each of them defined by no SNPs across 1.65 million whole-genome nucleotides – locally persisted over 2-9 years. We found unmeasurable SNP accumulation rates and overlapping bacterial generations among the outbreak genomes and that F. tularensis survived in saline for four years without nutrients. By these findings, and analyses of nucleotide substitution patterns, we suggest that a pathogen seed-bank effect is an important feature of F. tularensis ecology influencing genetic diversity.In paper III, we developed a new concept for source attribution of a F. tularensis sample. We aimed to identify genetic variation that is characteristic to laboratory culturing and we used culture amplification to identify genetic variation present at exceedingly low frequencies in a sample. Based on a biological enrichment scheme followed by high-throughput sequencing, we could track genetic variation back to a source sample. These results suggest that the concept has potential for linking a F. tularensis sample to its laboratory source sample.Taken together, the results presented in this thesis provide new understanding of the dissemination patterns and local persistence of tularemia. This is important for the interpretation of molecular epidemiology investigations of the disease. In a wider context, the results demonstrate how spatial dispersal and a microbial seed-bank effect may contribute to the diversity of a disease-causing agent. Finally, we have described a promising concept for source attribution of F. tularensis samples
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50.
  • Eivazzadeh, Shahryar, 1975-, et al. (författare)
  • Design of a Semi-Automated and Continuous Evaluation System : Customized for Application in e-Health
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background and ObjectivesSurvey-based evaluation of a system, such as measuring user’s satisfaction or patient-reported outcomes, entails a set of burdens that limits the feasibility, frequency, extendability, and continuity of the evaluation. Automating the evaluation process, that is reducing the burden of evaluators in questionnaire curation or minimizing the need for explicit user attention when collecting their attitudes, can make the evaluation more feasible, repeatable, extendible, continuous, and even flexible for improvement. An automated evaluation process can be enhanced to include features, such as the ability to handle heterogeneity in evaluation cases. Here, we represent the design of a system that makes it possible to have a semi-automated evaluation system. The design is presented and partially implemented in the context of health information systems, but it can be applied to other contexts of information system usages as well.MethodThe system was divided into four components. We followed a design research methodology to design the system, where each component reached a certain level of maturity. Already implemented and validated methods from previous studies were embedded within components, while they were extended with improved automation proposals or new features.ResultsA system was designed, comprised of four major components: Evaluation Aspects Elicitation, User Survey, Benchmark Path Model, and Alternative Metrics Replacement. All components have the essential maturity of identification of the problem, identification of solution objectives, and the overall design. In the overall design, the primary flow, process-entities, data-entities, and events for each component are identified and illustrated. Parts of some components have been already verified and demonstrated in real-world cases.ConclusionA system can be developed to minimize human burden, both for the evaluators and respondants, in survey-based evaluation. This system automates finding items to evaluate, creating questionnaire based on those items, surveying the users' attitude about those items, modeling the relations between the evaluation items, and incrementally changing the model to rely on automatically collected metrics, usually implicit indicators, collected from the users, instead of requiring their explicit expression of their attitudes. The system provides the possibility of minimal human burden, frequent repetition, continuity and real-time reporting, incremental upgrades regarding environmental changes, proper handling of heterogeneity, and a higher degree of objectivity.
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