| 1. |
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| 2. |
- Maxwell, Christopher A., et al.
(author)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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In: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Journal article (peer-reviewed)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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| 3. |
- Welen, Karin, et al.
(author)
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COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial.
- 2021
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
-
Journal article (peer-reviewed)abstract
- The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority.Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden.Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19.The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion).Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + "standard of care": "standard of care"). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) BLINDING (MASKING): This is an open-label trial.The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total.The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021.Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601 , registered June 8, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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| 4. |
- Zeng, Chenjie, et al.
(author)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Journal article (peer-reviewed)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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| 5. |
- Ekstrand, Eva-Maria, 1985-, et al.
(author)
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Identifying targets for increased biogasproduction through chemical and organicmatter characterization of digestate from full‑scale biogas plants : what remains and why?
- 2022
-
In: Biotechnology for Biofuels and Bioproducts. - London, United Kingdom : BioMed Central. - 2731-3654. ; 15:1
-
Journal article (peer-reviewed)abstract
- Background: This study examines the destiny of macromolecules in different full-scale biogas processes. From previousstudies it is clear that the residual organic matter in outgoing digestates can have significant biogas potential,but the factors dictating the size and composition of this residual fraction and how they correlate with the residualmethane potential (RMP) are not fully understood. The aim of this study was to generate additional knowledge of thecomposition of residual digestate fractions and to understand how they correlate with various operational and chemicalparameters. The organic composition of both the substrates and digestates from nine biogas plants operating onfood waste, sewage sludge, or agricultural waste was characterized and the residual organic fractions were linked tosubstrate type, trace metal content, ammonia concentration, operational parameters, RMP, and enzyme activity.Results: Carbohydrates represented the largest fraction of the total VS (32–68%) in most substrates. However, inthe digestates protein was instead the most abundant residual macromolecule in almost all plants (3–21 g/kg). Thedegradation efficiency of proteins generally lower (28–79%) compared to carbohydrates (67–94%) and fats (86–91%).High residual protein content was coupled to recalcitrant protein fractions and microbial biomass, either from thesubstrate or formed in the degradation process. Co-digesting sewage sludge with fat increased the protein degradationefficiency with 18%, possibly through a priming mechanism where addition of easily degradable substrates alsotriggers the degradation of more complex fractions. In this study, high residual methane production (> 140 L CH4/kgVS) was firstly coupled to operation at unstable process conditions caused mainly by ammonia inhibition (0.74 mgNH3-N/kg) and/or trace element deficiency and, secondly, to short hydraulic retention time (HRT) (55 days) relative tothe slow digestion of agricultural waste and manure.Conclusions: Operation at unstable conditions was one reason for the high residual macromolecule content andhigh RMP. The outgoing protein content was relatively high in all digesters and improving the degradation of proteinsrepresents one important way to increase the VS reduction and methane production in biogas plants. Post-treatment
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| 6. |
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| 7. |
- Ericsson, Olle, et al.
(author)
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Clinical validation of a novel automated cell-free DNA screening assay for trisomies 21, 13, and 18 in maternal plasma.
- 2019
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In: Prenatal diagnosis. - : Wiley. - 1097-0223 .- 0197-3851. ; 39:11, s. 1011-1015
-
Journal article (peer-reviewed)abstract
- To evaluate clinical performance of a new automated cell-free (cf)DNA assay in maternal plasma screening for trisomies 21, 18, and 13, and to determine fetal sex.Maternal plasma samples from 1200 singleton pregnancies were analyzed with a new non-sequencing cfDNA method, which is based on imaging and counting specific chromosome targets. Reference outcomes were determined by either cytogenetic testing, of amniotic fluid or chorionic villi, or clinical examination of neonates.The samples examined included 158 fetal aneuploidies. Sensitivity was 100% (112/112) for trisomy 21, 89% (32/36) for trisomy 18, and 100% (10/10) for trisomy 13. The respective specificities were 100%, 99.5%, and 99.9%. There were five first pass failures (0.4%), all in unaffected pregnancies. Sex classification was performed on 979 of the samples and 99.6% (975/979) provided a concordant result.The new automated cfDNA assay has high sensitivity and specificity for trisomies 21, 18, and 13 and accurate classification of fetal sex, while maintaining a low failure rate. The study demonstrated that cfDNA testing can be simplified and automated to reduce cost and thereby enabling wider population-based screening.
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| 8. |
- Fu, Huamei, 1979, et al.
(author)
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Changes in the ratio between FPR and FPRL1 triggered superoxide production in human neutrophils-a tool in analysing receptor specific events
- 2008
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In: Journal of Immunological Methods. - : Elsevier BV. - 0022-1759. ; 331:1-2, s. 50-8
-
Journal article (peer-reviewed)abstract
- Neutrophils express the G protein-coupled N-formyl peptide receptor (FPR) as well as its closely related homologue, formyl peptide like receptor 1 (FPRL1), and activation of these receptors induce a release of superoxide anions. The magnitude of the responses induced by the two peptide agonists fMLF and WKYMVM, specific for FPR and FPRL1, respectively, was found to be very variable in different neutrophil populations. The ratio between the FPR and FPRL1 triggered respiratory burst was, however, very constant and close to 1. The ratio was changed in neutrophils that were desensitized as well as when the signaling through either of the receptors was inhibited by receptor specific antagonists or by a PIP(2) binding peptide. The FPR/FPRL1 ratio was not changed in primed neutrophils or in differentiated HL-60 cells. We show that the change in the ratio, calculated from the amount of radical release in neutrophils triggered with FPR and FPRL1 specific agonists can be used as a valuable tool to find/identify receptor specific/selective changes mediated by peptides/proteins/drugs, as well as to identify cells from patients or groups of patients that diverge from normal cells in their FPR/FPRL1 triggered functions.
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| 9. |
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| 10. |
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| 11. |
-
KTH Utbildningar 2027/2028
- 2017
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Artistic workabstract
- I projektet Framtidens KTH-utbildningar har vi tagit fram förslag på hur vår verksamhet skulle kunna se ut för studenter, lärare, alumner och arbetsgivare – eller vad de kommer att vara. Visioner blir ofta luddiga så vi har istället skapat konkreta bilder som vi hoppas öppnar för samtal och ett vidare arbete med utbildningar för läsåret 2027/2028 då KTH firar tvåhundraårsjubileum.Denna katalog är endast till för idévärlden och innebär inget åtagande för KTH att erbjuda de utbildningar eller koncept som beskrivs. Men det är tillåtet att önska sig dem.
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| 12. |
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| 13. |
- Sotak, Matus, et al.
(author)
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Intestinal sodium/glucose cotransporter 3 expression is epithelial and downregulated in obesity.
- 2021
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In: Life sciences. - : Elsevier BV. - 1879-0631 .- 0024-3205. ; 267
-
Journal article (peer-reviewed)abstract
- We aimed to determine whether the sodium/glucose cotransporter family member SGLT3, a proposed glucose sensor, is expressed in the intestine and/or kidney, and if its expression is altered in mouse models of obesity and in humans before and after weight-loss surgery.We used in-situ hybridization and quantitative PCR to determine whether the Sglt3 isoforms 3a and 3b were expressed in the intestine and kidney of C57, leptin-deficient ob/ob, and diabetic BTBR ob/ob mice. Western blotting and immunohistochemistry were also used to assess SGLT3 protein levels in jejunal biopsies from obese patients before and after weight-loss Roux-en-Y gastric bypass surgery (RYGB), and in lean healthy controls.Sglt3a/3b mRNA was detected in the small intestine (duodenum, jejunum and ileum), but not in the large intestine or kidneys of mice. Both isoforms were detected in epithelial cells (confirmed using intestinal organoids). Expression of Sglt3a/3b mRNA in duodenum and jejunum was significantly lower in ob/ob and BTBR ob/ob mice than in normal-weight littermates. Jejunal SGLT3 protein levels in aged obese patients before Roux-en-Y gastric bypass (RYGB) were lower than in lean individuals, but substantially upregulated 6months post-RYGB.Our study shows that Sglt3a/3b is expressed primarily in epithelial cells of the small intestine in mice. Furthermore, we observed an association between intestinal mRNA Sglt3a/3b expression and obesity in mice, and between jejunal SGLT3 protein levels and obesity in humans. Further studies are required to determine the possible role of SGLT3 in obesity.
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| 14. |
- Sylvan, Sandra Eketorp, et al.
(author)
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First-line therapy in chronic lymphocytic leukemia : a Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 2013
- 2019
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In: Haematologica. - : FERRATA STORTI FOUNDATION. - 0390-6078 .- 1592-8721. ; 104:4, s. 797-805
-
Journal article (peer-reviewed)abstract
- The aim of this study was to investigate long-term outcome following first-line therapy in consecutive chronic lymphocytic leukemia (CLL) patients in a well-defined geographic area: Sweden. All patients diagnosed with CLL (2007-2013) (n=3672) were identified from national registries, screening of patient files identified all (100%) treated first line (n=1053) and for those, an in-depth analysis was performed. End points were overall response rate, progression-free survival (PFS), overall survival (OS), and safety. Median age was 71 years; 53% had Rai stage III-IV and 97% had performance status grade 0-2. Fluorescence in situ hybridization (FISH) was performed in 57% of patients: 15% had del(17p). Chlorambucil + prednisone was used in 39% (5% also received rituximab). Fludarabine+cyclophosphamide+rituximab or fludarabine+cyclophosphamide was used in 43% and bendamustine + rituximab in 6%. Overall response rate was 64%; chlorambucil 43%, fludarabine+cyclophosphamide+rituximab 84%, fludarabine+cyclophosphamide 75% and bendamustine + rituximab 75%. Median PFS and OS was 24 and 58 months, respectively, both were significantly associated (multivariate analysis) with type of treatment, del(17p), performance status, gender, age and geographical region (OS only). Chlorambucil-treated patients had a median PFS and OS of only 9 and 33 months, respectively. Chlorambucil usage declined gradually throughout the study period, but one-third of patients still received chlorambucil + rituximab in 2013. Infections >= grade III were significantly associated with treatment; chlorambucil 19% versus fludarabine+cyclophosphamide+rituximab 30%. Richter transformation occurred in 5.5% of the patients, equally distributed across therapies. This is the largest retrospective, real-world cohort of consecutive first-line treated CLL patients with a complete follow up. In elderly patients, an unmet need for more effective, well-tolerated therapies was identified.
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| 15. |
- Uhlén, Mathias, et al.
(author)
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The human secretome
- 2019
-
In: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 12:609
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Journal article (peer-reviewed)abstract
- The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.
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| 16. |
- Walsh, Sarah H, et al.
(author)
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Telomere length and correlation with histopathogenesis in B-cell leukemias/lymphomas
- 2007
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 78:4, s. 283-289
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Journal article (peer-reviewed)abstract
- Telomere length was recently reported to correlate with cellular origin of B-cell malignancies in relation to the germinal center (GC). In this report, we measured telomere length by quantitative-PCR in 223 B-cell lymphomas/leukemias and correlated results with immunoglobulin (Ig) mutation status and immunostainings for GC/non-GC subtypes of diffuse large B-cell lymphoma (DLBCL). Shortest telomeres were found in Ig-unmutated chronic lymphocytic leukemia (CLL) [median telomere to single copy gene value (T/S) 0.33], differing significantly to Ig-mutated CLL (0.63). Contrary to this, mantle cell lymphomas (MCLs) exhibited similar telomere lengths regardless of Ig mutation status (0.47). Telomere length differed significantly between GC-like (0.73) and non-GC-like DLBCLs (0.43), and follicular lymphomas (FLs) had shorter telomeres (0.53) than GC-DLBCL. Hairy cell leukemias, which display Ig gene intraclonal heterogeneity, had longer telomeres (0.62) than FLs and non-GC-DLBCL, but shorter than GC-DLBCL. We conclude that although DLBCL and CLL subsets can be clearly distinguished, telomere length reflects many parameters and may not simply correlate with GC-related origin.
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| 17. |
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| 18. |
- Winqvist, Maria, et al.
(author)
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Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group
- 2016
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In: Haematologica. - : FERRATA STORTI FOUNDATION. - 0390-6078 .- 1592-8721. ; 101:12, s. 1573-1580
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Journal article (peer-reviewed)abstract
- Ibrutinib, a Brutons tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine healthcare are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy amp;gt;= 10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richters transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia.
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| 19. |
- Öfverholm, Anna, et al.
(author)
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Extended genetic analysis and tumor characteristics in over 4600 women with suspected hereditary breast and ovarian cancer
- 2023
-
In: BMC Cancer. - : BioMed Central (BMC). - 1471-2407. ; 23:1
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Journal article (peer-reviewed)abstract
- BackgroundGenetic screening for pathogenic variants (PVs) in cancer predisposition genes can affect treatment strategies, risk prediction and preventive measures for patients and families. For decades, hereditary breast and ovarian cancer (HBOC) has been attributed to PVs in the genes BRCA1 and BRCA2, and more recently other rare alleles have been firmly established as associated with a high or moderate increased risk of developing breast and/or ovarian cancer. Here, we assess the genetic variation and tumor characteristics in a large cohort of women with suspected HBOC in a clinical oncogenetic setting.MethodsWomen with suspected HBOC referred from all oncogenetic clinics in Sweden over a six-year inclusion period were screened for PVs in 13 clinically relevant genes. The genetic outcome was compared with tumor characteristics and other clinical data collected from national cancer registries and hospital records.ResultsIn 4622 women with breast and/or ovarian cancer the overall diagnostic yield (the proportion of women carrying at least one PV) was 16.6%. BRCA1/2 PVs were found in 8.9% of women (BRCA1 5.95% and BRCA2 2.94%) and PVs in the other breast and ovarian cancer predisposition genes in 8.2%: ATM (1.58%), BARD1 (0.45%), BRIP1 (0.43%), CDH1 (0.11%), CHEK2 (3.46%), PALB2 (0.84%), PTEN (0.02%), RAD51C (0.54%), RAD51D (0.15%), STK11 (0) and TP53 (0.56%). Thus, inclusion of the 11 genes in addition to BRCA1/2 increased diagnostic yield by 7.7%. The yield was, as expected, significantly higher in certain subgroups such as younger patients, medullary breast cancer, higher Nottingham Histologic Grade, ER-negative breast cancer, triple-negative breast cancer and high grade serous ovarian cancer. Age and tumor subtype distributions differed substantially depending on genetic finding.ConclusionsThis study contributes to understanding the clinical and genetic landscape of breast and ovarian cancer susceptibility. Extending clinical genetic screening from BRCA1 and BRCA2 to 13 established cancer predisposition genes almost doubles the diagnostic yield, which has implications for genetic counseling and clinical guidelines. The very low yield in the syndrome genes CDH1, PTEN and STK11 questions the usefulness of including these genes on routine gene panels.
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| 20. |
- Adman, Per, et al.
(author)
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171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
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In: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
-
Journal article (pop. science, debate, etc.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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| 21. |
- Ahlbeck Bergendahl, Ida, et al.
(author)
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Fisk- och skaldjursbestånd i hav och sötvatten 2016 : Resursöversikt
- 2016
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Reports (other academic/artistic)abstract
- I rapporten kan du ta del av bedömningen som görs av situationen för bestånd som regleras inom ramen för EU:s gemensamma fiskeripolitik (GFP). Bedömningarna baseras på det forskningssamarbete och den rådgivning som sker inom det Internationella Havsforskningsrådet (ICES).De bestånd som förvaltas nationellt baseras på de biologiska underlagen, och rådgivningen i huvudsak på den forskning och övervakning samt analys som bedrivs av Institutionen för akvatiska resurser vid Sveriges lantbruksuniversitet (SLU Aqua) samt yrkesfiskets rapportering.Rapporten omfattar 41 fiskarter uppdelade i olika bestånd, samt sju skal- och blötdjursarter.Nytt för årets upplaga är kapitlet om ekosystemtjänster. Avsnittet beskriver de fördelar människan får genom ekosystemen, till exempel hur fisk och skaldjur kommer till nytta för människan genom föda, rekreation och biologisk mångfald. Nytt för i år är också att rapportens diagram och figurer anpassats för läsare med defekt färgseende.Översikten är utarbetad av SLU Aqua på uppdrag av Havs- och vattenmyndigheten.
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| 22. |
- Ahlgren, Kerstin M., et al.
(author)
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Increased IL-17A secretion in response to Candida albicans in autoimmune polyendocrine syndrome type 1 and its animal model
- 2011
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 41:1, s. 235-245
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Journal article (peer-reviewed)abstract
- Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal failure are hallmarks of the disease. The critical mechanisms causing chronic mucocutaneous candidiasis in APS-1 patients have not been identified although autoantibodies to cytokines are implicated in the pathogenesis. To investigate whether the Th reactivity to Candida albicans (C. albicans) and other stimuli was altered, we isolated PBMC from APS-1 patients and matched healthy controls. The Th17 pathway was upregulated in response to C. albicans in APS-1 patients, whereas the IL-22 secretion was reduced. Autoantibodies against IL-22, IL-17A and IL-17F were detected in sera from APS-1 patients by immunoprecipitation. In addition, Aire-deficient (Aire(0/0) ) mice were much more susceptible than Aire(+/+) mice to mucosal candidiasis and C. albicans-induced Th17- and Th1-cell responses were increased in Aire(0/0) mice. Thus an excessive IL-17A reactivity towards C. albicans was observed in APS-1 patients and Aire(0/0) mice.
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| 23. |
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| 24. |
- Ahlgren, Serina, et al.
(author)
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Review of methodological choices in LCA of biorefinery systems - key issues and recommendations
- 2015
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In: Biofuels, Bioproducts and Biorefining. - : Wiley. - 1932-1031 .- 1932-104X. ; 9:5, s. 606-619
-
Research review (peer-reviewed)abstract
- The current trend in biomass conversion technologies is toward more efficient utilization of biomass feedstock in multiproduct biorefineries. Many life-cycle assessment (LCA) studies of biorefinery systems have been performed but differ in how they use the LCA methodology. Based on a review of existing LCA standards and guidelines, this paper provides recommendations on how to handle key methodological issues when performing LCA studies of biorefinery systems. Six key issues were identified: (i) goal definition, (ii) functional unit, (iii) allocation of biorefinery outputs, (iv) allocation of biomass feedstock, (v) land use, and (vi) biogenic carbon and timing of emissions. Many of the standards and guidelines reviewed here provide only general methodological recommendations. Some make more specific methodological recommendations, but these often differ between standards. In this paper we present some clarifications (e.g. examples of research questions and suitable functional units) and methodological recommendations (e.g. on allocation).
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| 25. |
- Alakangas, Lena, et al.
(author)
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Min-North : Development, Evaluation and Optimization of Measures to Reduce the Environmental Impact of Mining Activities in Northern Regions
- 2019
-
Reports (other academic/artistic)abstract
- The Min-North (Development, Evaluation and Optimization of Measures to Reduce the Environment Impact of Mining Activities in Northern Regions) project was a trans-national cooperative project, with participants from the Geological Survey of Finland (GTK), University of Oulu (UO), UiT The Arctic University of Norway (UiT), Luleå University of Technology (LTU) and SMEs from Sweden, Finland and Norway. The project was funded by Interreg Nord and Norrbottens länsstyrelse. The participants have expertise in mine waste management, mine water treatment and geophysics. The overall aim of the project was to enhance the development of environmental protection technologies. An associated goal was to deepen cross-border cooperation by creating a larger critical mass of researchers in mine waste management and local SMEs in the Northern regions with greater capacities to disseminate and implement new methods, products and services. The project ran for 36 months from the 1st of January 2016 to the end of December 2018.
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| 26. |
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| 27. |
- Andersson Lundell, Anna-Carin, 1976, et al.
(author)
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Cat allergen induces proinflammatory responses by human monocyte-derived macrophages but not by dendritic cells
- 2005
-
In: Allergy. ; 60:9, s. 1184-91
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The upper airway mucosa of healthy humans contains a dense network of cells with dendritic morphology of which the majority express a macrophage-like phenotype (CD14+CD64+CD68+), whereas the smaller population are immature dendritic cells (DC; CD11c+CD14-). Our aim was to study the proinflammatory response of human monocytes and in vitro-generated macrophages and DC after contact with cat allergens. METHODS: Monocyte-derived DC and monocyte-derived macrophages were exposed to cat allergen extract or Escherichia coli. Purified monocytes were stimulated with allergen extracts from cat or house dust mite (HDM) or the major allergenic protein Fel d 1 and induction of proinflammatory cytokines by monocytes was analyzed before and after blocking CD14. RESULTS: We show that cat allergen extract induced tumor necrosis factor (TNF) and interleukin (IL)-6 production by CD14-positive macrophages but not by CD14-negative DC. Moreover, monocytes produced significantly higher levels of TNF in response to cat allergens than in response to HDM allergens. We observed no differences in levels of TNF and IL-6 from either macrophages or monocytes after exposure to cat allergen when comparing healthy and cat-allergic individuals. Finally, the proinflammatory cytokine production from monocytes in response to cat allergen extract but not to HDM allergen was significantly reduced by blocking CD14. CONCLUSION: These results indicate that closely related innate immune cells from the myeloid lineage respond differentially to cat allergen extract and that the pattern-recognition receptor CD14 might be one of the mediators involved in the inflammatory responses to inhalant allergens.
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| 28. |
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| 29. |
- Andersson, Magnus, et al.
(author)
-
Fiskbestånd och miljö i hav och sötvatten : Resurs- och miljööversikt 2012
- 2012
-
Reports (other academic/artistic)abstract
- Detta är den nionde utgåvan av den samlade översikten över fisk- och kräftdjursbeståndens status i våra vatten. Kunskap om fiskbestånden och miljön är en förutsättning för att utnyttjandet av fiskresurserna skall bli bärkraftigt. För svenska vattenområden beskrivs miljöutvecklingen i ett ekosystemsperspektiv, dels för att tydliggöra fiskens ekologiska roll och beskriva yttre miljöfaktorer som påverkar fiskbestånden, dels för att belysa fiskets effekter på miljön.Fiskbestånd och miljö i hav och sötvatten är utarbetad av Sveriges lantbruksuniversitet (SLU), Institutionen för akvatiska resurser (SLU Aqua), på uppdrag av Havs- och vattenmyndigheten. Rapporten sammanfattar utveckling och beståndsstatus för de kommersiellt viktigaste fisk- och kräftdjursarterna i våra vatten. Bedömningar och förvaltningsråd är baserade på Internationella Havsforskningsrådets (ICES) rådgivning, SLU Aquas nationella och regionala provfiskedata, samt yrkesfiskets rapportering.
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| 30. |
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| 31. |
- Assenhöj, Maria, et al.
(author)
-
Protein interaction, monocyte toxicity and immunogenic properties of cerium oxide crystals with 5% or 14% gadolinium, cobalt oxide and iron oxide nanoparticles–an interdisciplinary approach
- 2021
-
In: Nanotoxicology. - : Taylor and Francis Ltd.. - 1743-5390 .- 1743-5404. ; 15:8, s. 1035-1038
-
Journal article (peer-reviewed)abstract
- Metal oxide nanoparticles are widely used in both consumer products and medical applications, but the knowledge regarding exposure-related health effects is limited. However, it is challenging to investigate nanoparticle interaction processes with biological systems. The overall aim of this project was to improve the possibility to predict exposure-related health effects of metal oxide nanoparticles through interdisciplinary collaboration by combining workflows from the pharmaceutical industry, nanomaterial sciences, and occupational medicine. Specific aims were to investigate nanoparticle-protein interactions and possible adverse immune reactions. Four different metal oxide nanoparticles; CeOx nanocrystals with 5% or 14% Gd, Co3O4, and Fe2O3, were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides in silico. Monocyte interaction with nanoparticle–protein complexes was assessed in vitro. Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially Co3O4-protein complexes can induce both ‘danger signals’, verified by the production of inflammatory cytokines and simultaneously bind autologous proteins, which can be presented as immunogenic epitopes by MHC class II. The clinical relevance of these findings should be further evaluated to investigate the role of metal oxide nanoparticles in the development of autoimmune disease. The general workflow identified experimental difficulties, such as nanoparticle aggregate formation and a lack of protein-free buffers suitable for particle characterization, protein analyses, as well as for cell studies. This confirms the importance of future interdisciplinary collaborations. © 2021 The Author(s).
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| 32. |
- Augustsson, Anna, et al.
(author)
-
Challenges in assessing the health risks of consuming vegetables in metal-contaminated environments
- 2018
-
In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 113, s. 269-280
-
Journal article (peer-reviewed)abstract
- A great deal of research has been devoted to the characterization of metal exposure due to the consumption of vegetables from urban or industrialized areas. It may seem comforting that concentrations in crops, as well as estimated exposure levels, are often found to be below permissible limits. However, we show that even a moderate increase in metal accumulation in crops may result in a significant increase in exposure. We also highlight the importance of assessing exposure levels in relation to a regional baseline. We have analyzed metal (Pb, Cd, As) concentrations in nearly 700 samples from 23 different vegetables, fruits, berries and mushrooms, collected near 21 highly contaminated industrial sites and from reference sites. Metal concentrations generally complied with permissible levels in commercial food and only Pb showed overall higher concentrations around the contaminated sites. Nevertheless, probabilistic exposure assessments revealed that the exposure to all three metals was significantly higher in the population residing around the contaminated sites, for both low-, medianand high consumers. The exposure was about twice as high for Pb and Cd, and four to six times as high for As. Since vegetable consumption alone did not result in exposure above tolerable intakes, it would have been easy to conclude that there is no risk associated with consuming vegetables grown near the contaminated sites. However, when the increase in exposure is quantified, its potential significance is harder to dismiss - especially when considering that exposure via other routes may be elevated in a similar way.
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| 33. |
- Augustsson, Anna, et al.
(author)
-
Persistent hazardous waste and the quest towards a circular economy : the example of arsenic in Chromated Copper Arsenate-treated wood
- 2017
-
In: Journal of Industrial Ecology. - : Wiley-Blackwell. - 1088-1980 .- 1530-9290. ; 21:3, s. 689-699
-
Journal article (peer-reviewed)abstract
- The importance of a circular economy is today widely accepted and advocated, but among the challenges in achieving this, we find difficulties in the implementation of legislation and policies designed to control various waste streams from society. The example used in this article is wood that has been treated with chromated copper arsenate (CCA), which, in Sweden, has been covered by the rules for hazardous waste since 2002. One year later, in 2003, a survey showed that only 42% to 50% of the expected amount of CCA waste could be traced to the public waste management system. An updated material flow analysis for 2010 revealed that the figure had increased to 73%, whereas the fraction of correctly treated CCA wood waste had increased from 11% to 35%. However, almost one third of the expected volume was still not tracable, and half of the amount that was correctly submitted was incinerated together with nontoxic waste fractions. This results in, for example, arsenic contamination of slag and fly ashes that prevents the further use of these residue products. So, despite legislative instruments, there is still an urgent need for an improved collection of hazardous wood waste, as well as better routines for identifying hazardous flows and separating them from nonhazardous ones. For a circular economy to be achievable, a key priority should be to reduce the gap between intended directions and legislation, on one hand, and activities in practice on the other.
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| 34. |
- Barlow, Lotti, et al.
(author)
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Nationellt fackspråk för vård och omsorg : Slutrapport
- 2011
-
Reports (pop. science, debate, etc.)abstract
- SammanfattningEtt tillgängligt och använt nationellt fackspråk ska bidra till en god och säker vård och omsorg. Det ska även medverka till att kvaliteten och resultaten på området ska kunna följas upp och jämföras på ett mer effektivt sätt. Slutrapporten presenterar resultatet av projektet Nationellt fackspråk för vård och omsorg samt förslag till förvaltning och utveckling.ResultatetResultatet innefattar bland annat att det internationella begreppssystemet Snomed CT är översatt till svenska och att det är förberett för förvaltning och distribution. Socialstyrelsen har även tagit fram och testat metoder för förvaltning och utveckling av det nationella fackspråket i sin helhet. Därtill har representanter för målgrupperna informerats och fått kunskap.Rapporten innehåller en utförlig beskrivning av det nationella fackspråkets sammantagna innehåll: Socialstyrelsens termbank, klassifikationer och kodverk, den svenska versionen av Snomed CT, metoder för utveckling och förvaltning samt regler för användning.Förvaltning, införande och resursbehovI rapporten finns förslag till hur hela det nationella fackspråket kan tas omhand av Socialstyrelsen och hur det kan införas i vården och omsorgen. Projektets övergång till en långsiktigt hållbar organisation kräver resurser. Därför redogör rapporten för det förväntade resursbehovet för förvaltning och utveckling. Bland annat föreslås en treårig utbildningsinsats samt stimulansbidrag för införande.Krav på styrning, samordning och förtydligat ansvarRapporten betonar behovet av en samlad och medveten styrning av utvecklingen inom området. Socialstyrelsen vill ha en samordnande roll i utvecklingen och förvaltningen av det nationella fackspråket. Myndigheten föreslås få det initiala ansvaret för att utbilda användare och att driva frågor om det nationella fackspråket.Vidare vill Socialstyrelsen få ett uttalat mandat att samordna de nationella aktiviteter som drivs med koppling till Snomed CT. Rapporten pekar ut några särskilt prioriterade områden som myndigheten borde få i uppdrag att arbeta vidare inom.Kunskapsstyrning och normgivningEn viktig slutsats i rapporten är att användningen av det nationella fackspråket behöver regleras för att målet om ökad säkerhet för klienter och patienter ska kunna uppnås. I dagsläget bedöms föreskrifter vara den metod som bäst kan garantera ett brett genomförande.Målgrupper för slutrapportenSlutrapporten riktar sig till beslutsfattare i kommuner och landsting, vård- och omsorgspersonal med särskilt intresse eller ansvar för dokumentationsfrågor och professionella organisationer. Den riktar sig också till terminologiansvariga i kommuner och landsting, IT-direktörer, IT-leverantörer samt aktörer inom den nationella strategin för eHälsa.
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| 35. |
- Belgrano, Andrea, et al.
(author)
-
Överfiske - en miljöfarlig aktivitet : orsaker till fiskbeståndens utarmning och dess konsekvenser i svenska hav
- 2011
-
Reports (other academic/artistic)abstract
- Bestånden av marina fiskarter har minskat dramatiskt i både Västerhavet och i Östersjön under de senaste 100 åren. Flera olika faktorer påverkar fiskbeståndens storlek, men ett ökande antal studier tyder på att överfiske är en huvudorsak i de flesta fall. Fisket med trål anses också skada många bottenlevande organismer, men det är idag oklart hur omfattande denna miljöpåverkan är. Vidare tyder nya studier på att förlusten av stora rovfiskar kan ge negativa effekter på hela ekosystem genom trofiska kedjereaktioner. Sammantaget anser många forskare idag att fisket utgör ett av de allvarligaste miljöhoten mot svenska hav. Denna rapport sammanställer det vetenskapliga kunskapsläget över orsakerna till nedgången av svenska marina fiskbestånd, samt fiskets roll för minskning av biodiversitet och förändringar i svenska kust- och utsjöekosystem.
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| 36. |
- Bellner, Lars, 1973, et al.
(author)
-
A Monocyte-Specific Peptide from Herpes Simplex Virus Type 2 Glycoprotein G Activates the NADPH-Oxidase but Not Chemotaxis through a G-Protein-Coupled Receptor Distinct from the Members of the Formyl Peptide Receptor Family.
- 2007
-
In: Journal of immunology (Baltimore, Md. : 1950). - 0022-1767. ; 179:9, s. 6080-7
-
Journal article (peer-reviewed)abstract
- We have recently identified a peptide derived from the secreted portion of the HSV-2 glycoprotein G, gG-2p20, to be proinflammatory. Based on its ability to activate neutrophils and monocytes via the formyl peptide receptor (FPR) to produce reactive oxygen species (ROS) that down-regulate NK cell function, we suggested it to be of importance in HSV-2 pathogenesis. We now describe the effects of an overlapping peptide, gG-2p19, derived from the same HSV-2 protein. Also, this peptide activated the ROS-generating NADPH-oxidase, however, only in monocytes and not in neutrophils. Surprisingly, gG-2p19 did not induce a chemotactic response in the affected monocytes despite using a pertussis toxin-sensitive, supposedly G-protein-coupled receptor. The specificity for monocytes suggested that FPR and its homologue FPR like-1 (FPRL1) did not function as receptors for gG-2p19, and this was also experimentally confirmed. Surprisingly, the monocyte-specific FPR homologue FPRL2 was not involved either, and the responsible receptor thus remains unknown so far. However, the receptor shares some basic signaling properties with FPRL1 in that the gG-2p19-induced response was inhibited by PBP10, a peptide that has earlier been shown to selectively inhibit FPRL1-triggered responses. We conclude that secretion and subsequent degradation of the HSV-2 glycoprotein G can generate several peptides that activate phagocytes through different receptors, and with different cellular specificities, to generate ROS with immunomodulatory properties.
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| 37. |
- Bengtsson-Palme, Johan, 1985, et al.
(author)
-
Strategies to improve usability and preserve accuracy in biological sequence databases
- 2016
-
In: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 16:18, s. 2454-2460
-
Journal article (peer-reviewed)abstract
- Biology is increasingly dependent on large-scale analysis, such as proteomics, creating a requirement for efficient bioinformatics. Bioinformatic predictions of biological functions rely upon correctly annotated database sequences, and the presence of inaccurately annotated or otherwise poorly described sequences introduces noise and bias to biological analyses. Accurate annotations are, for example, pivotal for correct identifications of polypeptide fragments. However, standards for how sequence databases are organized and presented are currently insufficient. Here, we propose five strategies to address fundamental issues in the annotation of sequence databases: (i) to clearly separate experimentally verified and unverified sequence entries; (ii) to enable a system for tracing the origins of annotations; (iii) to separate entries with high-quality, informative annotation from less useful ones; (iv) to integrate automated quality-control software whenever such tools exist; and (v) to facilitate post-submission editing of annotations and metadata associated with sequences. We believe that implementation of these strategies, for example as requirements for publication of database papers, would enable biology to better take advantage of large-scale data.
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| 38. |
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| 39. |
- Bjoreland, Anders, et al.
(author)
-
Liquid ionization chamber calibrated gel dosimetry in conformal stereotactic radiotherapy of brain lesions
- 2008
-
In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 47:6, s. 1099-1109
-
Journal article (peer-reviewed)abstract
- Hypofractionated conformal stereotactic radiotherapy (HCSRT) is an established method of treating brain lesions such as arteriovenous malformations (AVMs) and brain metastases. The aim of this study was to investigate the reliability of treatment plans in the terms of dose distribution and absorbed dose for HCSRT. Methods and materials. Treatment plans for three different clinical intracerebral targets, AVMs, were transferred to a CT study of a spherical water filled phantom simulating the human head and recalculated for the phantom geometry using a standard treatment planning system utilizing a pencil beam algorithm for dose calculation. The calculated absorbed dose, relative three dimensional (3D) dose distribution and dose conformity were investigated using gel dosimetry normalized to liquid ionization chamber (LIC) measurements. Results. The measured absorbed dose to the dose reference point was found to be within 2% of the calculated dose for all three targets. The measured dose distribution was found to be within 3% and 2 mm of the calculated dose for more than 93% of all points in the target volume for all three targets. Conclusions. The results show that the investigated standard treatment planning system can correctly predict the absorbed dose and dose distribution in different types of intracerebral targets and that the treatment can be delivered according to the plan.
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| 40. |
- Björklund, Karin, 1979, et al.
(author)
-
Hydrodynamic modelling of the influence of stormwater and combined sewer overflows on receiving water quality: Benzo(a)pyrene and copper risks to recreational water
- 2018
-
In: Journal of Environmental Management. - : Elsevier BV. - 0301-4797 .- 1095-8630. ; 207, s. 32-42
-
Journal article (peer-reviewed)abstract
- The risk from chemical substances in surface waters is often increased during wet weather, due to surface runoff, combined sewer overflows (CSOs) and erosion of contaminated land. There are strong incentives to improve the quality of surface waters affected by human activities, not only from ecotoxicity and ecosystem health perspectives, but also for drinking water and recreational purposes. The aim of this study is to investigate the influence of urban stormwater discharges and CSOs on receiving water in the context of chemical health risks and recreational water quality. Transport of copper (Cu) and benzo[a]pyrene (BaP) in the Göta River (Sweden) was simulated using a hydrodynamic model. Within the 16 km modelled section, 35 CSO and 16 urban stormwater point discharges, as well as the effluent from a major wastewater treatment plant, were included. Pollutant concentrations in the river were simulated for two rain events and investigated at 13 suggested bathing sites. The simulations indicate that water quality guideline values for Cu are exceeded at several sites, and that stormwater discharges generally give rise to higher Cu and BaP concentrations than CSOs. Due to the location of point discharges and the river current inhibiting lateral mixing, the north shore of the river is better suited for bathing. Peak concentrations have a short duration; increased concentrations of the pollutants may however be present for several days after a rain event. Monitoring of river water quality indicates that simulated Cu and BaP concentrations are in the same order of magnitude as measured concentrations. It is concluded that hydrodynamic modelling is a useful tool for identifying suitable bathing sites in urban surface waters and areas of concern where mitigation measures should be implemented to improve water quality.
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| 41. |
- Björkman, Lena, 1965, et al.
(author)
-
Serum amyloid A mediates human neutrophil production of reactive oxygen species through a receptor independent of formyl peptide receptor like-1
- 2008
-
In: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 83:2, s. 245-53
-
Journal article (peer-reviewed)abstract
- Serum amyloid A (SAA) is one of the acute-phase reactants, a group of plasma proteins that increases immensely in concentration during microbial infections and inflammatory conditions, and a close relationship between SAA levels and disease activity in rheumatoid arthritis (RA) has been observed. RA is an inflammatory disease, where neutrophils play important roles, and SAA is thought to participate in the inflammatory reaction by being a neutrophil chemoattractant and inducer of proinflammatory cytokines. The biological effects of SAA are reportedly mediated mainly through formyl peptide receptor like-1 (FPRL1), a G protein-coupled receptor (GPCR) belonging to the formyl peptide receptor family. Here, we confirmed the affinity of SAA for FPRL1 by showing that stably transfected HL-60 cells expressing FPRL1 were activated by SAA and that the response was inhibited by the use of the FPRL1-specific antagonist WRWWWW (WRW4). We also show that SAA activates the neutrophil NADPH-oxidase and that a reserve pool of receptors is present in storage organelles mobilized by priming agents such as TNF-alpha and LPS from Gram-negative bacteria. The induced activity was inhibited by pertussis toxin, indicating the involvement of a GPCR. However, based on FPRL1-specific desensitization and use of FPRL1 antagonist WRW4, we found the SAA-mediated effects in neutrophils to be independent of FPRL1. Based on these findings, we conclude that SAA signaling in neutrophils is mediated through a GPCR, distinct from FPRL1. Future identification and characterization of the SAA receptor could lead to development of novel, therapeutic targets for treatment of RA.
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| 42. |
- Bondelind, Mia, 1980, et al.
(author)
-
Hydrodynamic modelling of traffic-related microplastics discharged with stormwater into the Göta River in Sweden
- 2020
-
In: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 27:19, s. 24218-24230
-
Journal article (peer-reviewed)abstract
- Microplastics (MP) are transported from land-based sources from rivers to marine waters. However, there is currently little knowledge about MP fate from land sources to marine waters. Traffic is estimated to be one of the largest sources of MP; hence, stormwater is expected to be an important transportation route of MP to marine waters. The aim of this study was to investigate the effect of the size and density of tyre wear particles in road run-off on their fate in the Gota River in Sweden using hydrodynamic modelling. The model of the stretch of Gota River, Sweden's largest river, passing through Gothenburg (Sweden's second largest city) and out to the sea, was set up using MIKE 3 FM software. Literature data were used to define the MP characteristics: concentrations in stormwater, prevalent particle sizes, density of MP commonly occurring in road run-off and settling velocities. Results show that higher concentrations of MP are found on the south side of the river, compared with the north side, due to higher annual average daily traffic loads along the south side of the river. The mixing processes in the river and the MP concentrations were generally influenced by the vertical water density gradient caused by saline water from the Kattegat strait. While most MP with higher density and larger size settle in the river, smaller MP with density close to 1.0 g/cm(3) do not settle in the river and therefore reach the Kattegat strait and the marine environments. Further research is needed to describe the fate and transport of microplastics in the stormwater system, including treatment facilities, i.e. biofouling, aggregation, degradation and/or further fragmentation and settling.
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| 43. |
- Bondelind, Mia, 1980, et al.
(author)
-
Influence of stormwater and CSOs on copper and benzo[a]pyrene in receiving waters – hydrodynamic modelling approach
- 2017
-
In: Conference Proceedings, 14th IWA/IAHR International Conference on Urban Drainage, September 10-15, 2017, Prague, Czech Republic. ; , s. 540-543
-
Conference paper (peer-reviewed)abstract
- In this study the influence of urban stormwater discharges and combined sewer overflows on receiving water was investigated in the context of chemical risks and recreational water quality. Transport of copper and benzo[a]pyrene in the Göta River, running through the city of Gothenburg (Sweden), was simulated using a hydrodynamic model. The modelling results showed that during rain events the water quality along the river deteriorates for different periods of time, at times exceeding the guideline values established by the city of Gothenburg. The model can be used as an effective tool to prognosticate the water quality in the river.
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| 44. |
- Bray, Lucy, et al.
(author)
-
Developing rights-based standards for children having tests, treatments, examinations and interventions : using a collaborative, multi-phased, multi-method and multi-stakeholder approach to build consensus
- 2023
-
In: European Journal of Pediatrics. - : Springer Nature. - 0340-6199 .- 1432-1076.
-
Journal article (peer-reviewed)abstract
- Children continue to experience harm when undergoing clinical procedures despite increased evidence of the need to improve the provision of child-centred care. The international ISupport collaboration aimed to develop standards to outline and explain good procedural practice and the rights of children within the context of a clinical procedure. The rights-based standards for children undergoing tests, treatments, investigations, examinations and interventions were developed using an iterative, multi-phased, multi-method and multi-stakeholder consensus building approach. This consensus approach used a range of online and face to face methods across three phases to ensure ongoing engagement with multiple stakeholders. The views and perspectives of 203 children and young people, 78 parents and 418 multi-disciplinary professionals gathered over a two year period (2020–2022) informed the development of international rights-based standards for the care of children having tests, treatments, examinations and interventions. The standards are the first to reach international multi-stakeholder consensus on definitions of supportive and restraining holds.Conclusion: This is the first study of its kind which outlines international rights-based procedural care standards from multi-stakeholder perspectives. The standards offer health professionals and educators clear evidence-based tools to support discussions and practice changes to challenge prevailing assumptions about holding or restraining children and instead encourage a focus on the interests and rights of the child.What is Known:• Children continue to experience short and long-term harm when undergoing clinical procedures despite increased evidence of the need to improve the provision of child-centred care.• Professionals report uncertainty and tensions in applying evidence-based practice to children’s procedural care. What is New:• This is the first study of its kind which has developed international rights-based procedural care standards from multi-stakeholder perspectives.• The standards are the first to reach international multi-stakeholder consensus on definitions of supportive and restraining holds.
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| 45. |
- Bäckman, Lars, et al.
(author)
-
Dopamine D(1) receptors and age differences in brain activation during working memory
- 2011
-
In: Neurobiology of Aging. - Fayetteville, N.Y : Elsevier. - 0197-4580 .- 1558-1497. ; 32:10, s. 1849-1856
-
Journal article (peer-reviewed)abstract
- In an fMRI study, 20 younger and 20 healthy older adults were scanned while performing a spatial working-memory task under two levels of load. On a separate occasion, the same subjects underwent PET measurements using the radioligand [(11)C] SCH23390 to determine dopamine D(1) receptor binding potential (BP) in caudate nucleus and dorsolateral prefrontal cortex (DLPFC). The fMRI study revealed a significant load modulation of brain activity (higher load>lower load) in frontal and parietal regions for younger, but not older, adults. The PET measurements showed marked age-related reductions of D(1) BP in caudate and DLPFC. Statistical control of caudate and DLPFC D(1) binding eliminated the age-related reduction in load-dependent BOLD signal in left frontal cortex, and attenuated greatly the reduction in right frontal and left parietal cortex. These findings suggest that age-related alterations in dopaminergic neurotransmission may contribute to underrecruitment of task-relevant brain regions during working-memory performance in old age.
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| 46. |
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| 47. |
- Carneiro, Ana, et al.
(author)
-
Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer
- 2008
-
In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 8:98
-
Journal article (peer-reviewed)abstract
- Background: Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. Methods: A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival. Results: Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis. Conclusion: aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC.
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| 48. |
- Coviello, Andrea D, et al.
(author)
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A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
- 2012
-
In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 8:7
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Journal article (peer-reviewed)abstract
- Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p=1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p=1.4×10(-11)), GCKR (rs780093, 2p23.3, p=2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p=3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p=6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p=1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p=8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p=3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p=4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p=1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p=2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p=5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p=2.5×10(-08), women p=0.66, heterogeneity p=0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
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- Dahlin, Anna M., 1979-, et al.
(author)
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Genetic Variants in the 9p21.3 Locus Associated with Glioma Risk in Children, Adolescents, and Young Adults : A Case-Control Study
- 2019
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 28:7, s. 1252-1258
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Journal article (peer-reviewed)abstract
- Background: Genome-wide association studies have identified germline genetic variants in 25 genetic loci that increase the risk of developing glioma in adulthood. It is not known if these variants increase the risk of developing glioma in children and adolescents and young adults (AYA). To date, no studies have performed genome-wide analyses to find novel genetic variants associated with glioma risk in children and AYA.Methods: We investigated the association between 8,831,628 genetic variants and risk of glioma in 854 patients diagnosed up to the age of 29 years and 3,689 controls from Sweden and Denmark. Recruitment of patients and controls was population based. Genotyping was performed using Illumina BeadChips, and untyped variants were imputed with IMPUTE2. We selected 41 established adult glioma risk variants for detailed investigation.Results: Three adult glioma risk variants, rs634537, rs2157719, and rs145929329, all mapping to the 9p21.3 (CDKN2B-AS1) locus, were associated with glioma risk in children and AYA. The strongest association was seen for rs634537 (odds ratioG = 1.21; 95% confidence interval = 1.09–1.35; P = 5.8 × 10−4). In genome-wide analysis, an association with risk was suggested for 129 genetic variants (P <1 × 10−5).Conclusions: Carriers of risk alleles in the 9p21.3 locus have an increased risk of glioma throughout life. The results from genome-wide association analyses require validation in independent cohorts.Impact: Our findings line up with existing evidence that some, although not all, established adult glioma risk variants are associated with risk of glioma in children and AYA. Validation of results from genome-wide analyses may reveal novel susceptibility loci for glioma in children and AYA.
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