| 1. |
- Andersson, Claes, et al.
(author)
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Mebendazole is unique among tubulin-active drugs in activating the MEK-ERK pathway
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity in monocyte/macrophage models and induces ERK signalling. In the present study we investigated whether MBZ induced ERK activation is shared by other tubulin binding agents (TBAs) and if it is observable also in other human cell types. Curated gene signatures for a panel of TBAs in the LINCS Connectivity Map (CMap) database showed a unique strong negative correlation of MBZ with MEK/ERK inhibitors indicating ERK activation also in non-haematological cell lines. L1000 gene expression signatures for MBZ treated THP-1 monocytes also connected negatively to MEK inhibitors. MEK/ERK phosphoprotein activity testing of a number of TBAs showed that only MBZ increased the activity in both THP-1 monocytes and PMA differentiated macrophages. Distal effects on ERK phosphorylation of the substrate P90RSK and release of IL1B followed the same pattern. The effect of MBZ on MEK/ERK phosphorylation was inhibited by RAF/MEK/ERK inhibitors in THP-1 models, CD3/IL2 stimulated PBMCs and a MAPK reporter HEK-293 cell line. MBZ was also shown to increase ERK activity in CD4+ T-cells from lupus patients with known defective ERK signalling. Given these mechanistic features MBZ is suggested suitable for treatment of diseases characterized by defective ERK signalling, notably difficult to treat autoimmune diseases.
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| 2. |
- Bahl, Aileen, et al.
(author)
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Hormone Replacement Therapy Associated White Blood Cell DNA Methylation and Gene Expression are Associated With Within-Pair Differences of Body Adiposity and Bone Mass
- 2015
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In: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 18:6, s. 647-661
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Journal article (peer-reviewed)abstract
- The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body composition, including muscle and bone measures of monozygotic (MZ) female twin pairs discordant for HRT. We identified 7,855 nominally significant differentially methylated regions (DMRs) associated with 4,044 genes. Of the genes with DMRs, five (ACBA1, CCL5, FASLG, PPP2R2B, and UHRF1) were also differentially expressed. All have been previously associated with HRT or estrogenic regulation, but not with HRT-associated DNA methylation. All five genes were associated with bone mineral content (BMC), and ABCA1, FASLG, and UHRF1 were also associated with body adiposity. Our study is the first to show that HRT associates with genome-wide DNA methylation alterations in WBCs. Moreover, we show that five differentially expressed genes with DMRs associate with clinical measures, including body fat percentage, lean body mass, bone mass, and blood lipids. Our results indicate that at least part of the known beneficial HRT effects on body composition and bone mass may be regulated by DNA methylation associated alterations in gene expression in circulating WBCs.
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| 3. |
- Berglund, Eva C, et al.
(author)
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Accurate detection of subclonal single nucleotide variants in whole genome amplified and pooled cancer samples using HaloPlex target enrichment
- 2013
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In: BMC Genomics. - : BioMed Central. - 1471-2164. ; 14, s. 856-
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Journal article (peer-reviewed)abstract
- Background: Target enrichment and resequencing is a widely used approach for identification of cancer genes and genetic variants associated with diseases. Although cost effective compared to whole genome sequencing, analysis of many samples constitutes a significant cost, which could be reduced by pooling samples before capture. Another limitation to the number of cancer samples that can be analyzed is often the amount of available tumor DNA. We evaluated the performance of whole genome amplified DNA and the power to detect subclonal somatic single nucleotide variants in non-indexed pools of cancer samples using the HaloPlex technology for target enrichment and next generation sequencing. Results: We captured a set of 1528 putative somatic single nucleotide variants and germline SNPs, which were identified by whole genome sequencing, with the HaloPlex technology and sequenced to a depth of 792-1752. We found that the allele fractions of the analyzed variants are well preserved during whole genome amplification and that capture specificity or variant calling is not affected. We detected a large majority of the known single nucleotide variants present uniquely in one sample with allele fractions as low as 0.1 in non-indexed pools of up to ten samples. We also identified and experimentally validated six novel variants in the samples included in the pools. Conclusion: Our work demonstrates that whole genome amplified DNA can be used for target enrichment equally well as genomic DNA and that accurate variant detection is possible in non-indexed pools of cancer samples. These findings show that analysis of a large number of samples is feasible at low cost, even when only small amounts of DNA is available, and thereby significantly increases the chances of indentifying recurrent mutations in cancer samples.
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| 4. |
- Berglund, Eva, et al.
(author)
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Communicative development in Swedish children 16-28 months old : The Swedish early communicative development inventory - words and sentences
- 2000
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In: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 41:2, s. 133-144
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Journal article (peer-reviewed)abstract
- To describe the development of words and sentences in Swedish children 16-28 months old, 900 parental reports on 336 children were analyzed. Subjects were randomly selected from the national birth register, and there was a response rate of 88%. The assessments were made using the Swedish Early Communicative Development Inventory-words and sentences (SECDI-w&s). Age-based norms for productive vocabulary, pragmatic skills, grammar skills, and maximum length of utterance (MaxLU) were determined. We describe the development of feedback morphemes, semantic categories, and single words and tasks. Correlation across measures was significant, and especially strong between vocabulary size and grammar skills. Optimized positive predictive values were high for 25 to 28 month predictions (71%-88%), and vocabulary scores were found to be of particular predictive importance. No significant gender differences were detected. The clinical relevance of the instrument is discussed.
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| 5. |
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| 6. |
- Berglund, Ellinor, et al.
(author)
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Effect of Smartphone Dispatch of Volunteer Responders on Automated External Defibrillators and Out-of-Hospital Cardiac Arrests : The SAMBA Randomized Clinical Trial
- 2023
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In: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 8:1, s. 81-88
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Journal article (peer-reviewed)abstract
- Importance Smartphone dispatch of volunteer responders to nearby out-of-hospital cardiac arrests (OHCAs) has emerged in several emergency medical services, but no randomized clinical trials have evaluated the effect on bystander use of automated external defibrillators (AEDs).Objective To evaluate if bystander AED use could be increased by smartphone-aided dispatch of lay volunteer responders with instructions to collect nearby AEDs compared with instructions to go directly to patients with OHCAs to start cardiopulmonary resuscitation (CPR).Design, Setting, and Participants This randomized clinical trial assessed a system for smartphone dispatch of volunteer responders to individuals experiencing OHCAs that was triggered at emergency dispatch centers in response to suspected OHCAs and randomized 1:1. The study was conducted in 2 main Swedish regions: Stockholm and Västra Götaland between December 2018 and January 2020. At study start, there were 3123 AEDs in Stockholm and 3195 in Västra Götaland and 24 493 volunteer responders in Stockholm and 19 117 in Västra Götaland. All OHCAs in which the volunteer responder system was activated by dispatchers were included. Excluded were patients with no OHCAs, those with OHCAs not treated by the emergency medical services, and those with OHCAs witnessed by the emergency medical services.Interventions Volunteer responders were alerted through the volunteer responder system smartphone application and received map-aided instructions to retrieve nearest available public AEDs on their way to the OHCAs. The control arm included volunteer responders who were instructed to go directly to the OHCAs to perform CPR.Main Outcomes and Measures Overall bystander AED attachment, including those attached by volunteer responders and lay volunteers who did not use the smartphone application.Results Volunteer responders were activated for 947 patients with OHCAs. Of those, 461 were randomized to the intervention group (median [IQR] age of patients, 73 [61-81] years; 295 male patients [65.3%]) and 486 were randomized to the control group (median [IQR] age of patients, 73 [63-82] years; 312 male patients [65.3%]). Primary outcome of AED attachment occurred in 61 patients (13.2%) in the intervention arm vs 46 patients (9.5%) in the control arm (difference, 3.8% [95% CI, −0.3% to 7.9%]; P = .08). The majority of AEDs were attached by lay volunteers who were not using the smartphone application (37 in intervention arm, 28 in control). There were no significant differences in secondary outcomes. Among the volunteer responders using the application, crossover was 11% and compliance to instructions was 31%. Volunteer responders attached 38% (41 of 107) of all AEDs and provided 45% (16 of 36) of all defibrillations and 43% (293 of 666) of all CPR.Conclusions and Relevance In this study, smartphone dispatch of volunteer responders to OHCAs to retrieve nearby AEDs vs instructions to directly perform CPR did not significantly increase volunteer AED use. High baseline AED attachement rate and crossover may explain why the difference was not significant.Trial Registration ClinicalTrials.gov Identifier: NCT02992873
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| 7. |
- Berglund, E, et al.
(author)
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Parental reports of spoken language skills in children with Down syndrome.
- 2001
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In: Journal of Speech, Language and Hearing Research. - 1092-4388 .- 1558-9102. ; 44:1, s. 179-191
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Journal article (peer-reviewed)abstract
- Spoken language in children with Down syndrome and in children in a normative group was compared. Growth trends, individual variation, sex differences, and performance on vocabulary, pragmatic, and grammar scales as well as MaxLU (maximum length of utterance) were explored. Subjects were 330 children with Down syndrome (age range: 1-5 years) and 336 children in a normative group (1;4-2; 4 years;months). The Swedish Early Communicative Development inventory-words and sentences (SECDI-w&s) was employed. Performance of children with Down syndrome at ages 3;0 and 4;0 was comparable with that of children in the normative group at ages 1,4 and 1;8 respectively. In comparison with children in the normative group of similar vocabulary size, children with Down syndrome lagged slightly on pragmatic and grammar scales. The early development proceeded in most cases with exponential or logistic growth. This stresses the great potential of early intervention.
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| 8. |
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| 9. |
- Berglund, Lukas, et al.
(author)
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Decreasing incidence of knee arthroscopy in Sweden between 2002 and 2016 : a nationwide register-based study
- 2023
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 94, s. 26-31
-
Journal article (peer-reviewed)abstract
- Background and purpose: Several randomized trials have demonstrated the lack of effect of arthroscopic lavage as treatment for knee osteoarthritis (OA). These results have in turn resulted in a change in Swedish guidelines and reimbursement. We aimed to investigate the use of knee arthroscopies in Sweden between 2002 and 2016. Patient demographics, regional differences, and the magnitude of patients with knee OA undergoing knee arthroscopy were also analyzed.Patients and methods: Trends in knee arthroscopy were investigated using the Swedish Hospital Discharge Register (SHDR) to conduct a nationwide register-based study including all adults (>18 years of age) undergoing any knee arthroscopy between 2002 and 2016.Results: The total number of knee arthroscopies performed during the studied period was 241,055. The annual surgery rate declined in all age groups, for males and females as well as patients with knee OA. The incidence dropped from 247 to 155 per 105 inhabitants. Over 50% of arthroscopies were performed in metropolitan regions.Conclusion: We showed a dramatic decline in knee arthroscopy. There is variability in the surgery rate between males and females and among the regions of Sweden.
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| 10. |
- Berglund, Linn, et al.
(author)
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Self-Assembly of Nanocellulose Hydrogels Mimicking Bacterial Cellulose for Wound Dressing Applications
- 2023
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In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 24:5, s. 2264-2277
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Journal article (peer-reviewed)abstract
- The self-assembly of nanocellulose in the form of cellulose nanofibers (CNFs) can be accomplished via hydrogen-bonding assistance into completely bio-based hydrogels. This study aimed to use the intrinsic properties of CNFs, such as their ability to form strong networks and high absorption capacity and exploit them in the sustainable development of effective wound dressing materials. First, TEMPO-oxidized CNFs were separated directly from wood (W-CNFs) and compared with CNFs separated from wood pulp (P-CNFs). Second, two approaches were evaluated for hydrogel self-assembly from W-CNFs, where water was removed from the suspensions via evaporation through suspension casting (SC) or vacuum-assisted filtration (VF). Third, the W-CNF-VF hydrogel was compared to commercial bacterial cellulose (BC). The study demonstrates that the self-assembly via VF of nanocellulose hydrogels from wood was the most promising material as wound dressing and displayed comparable properties to that of BC and strength to that of soft tissue.
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| 11. |
- Berglund, Pontus, et al.
(author)
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Cyclin E confers a prognostic value in premenopausal breast cancer patients with tumours exhibiting an infiltrative growth pattern
- 2008
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In: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 61:2, s. 184-191
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Journal article (peer-reviewed)abstract
- Aims: To investigate the prognostic value of cyclin E in relation to tumour growth pattern by analysing stage II primary breast cancers from premenopausal women not subjected to any further adjuvant treatment. To analyse the value of cyclin E as a predictor of tamoxifen response, by comparing untreated and treated patients with oestrogen receptor positive tumours. Methods: Breast cancer samples, assembled in tissue microarrays, were immunohistochemically stained for cyclin E and evaluated regarding the presence of nuclear staining. The overall growth characteristics of each tumour were assessed using whole tissue sections. Results: Tumours displaying a pushing margin phenotype were strongly associated with high cyclin E levels, lymph node negative disease, a high histological grade and oestrogen receptor negativity, and exhibited a better prognosis compared to tumours with an infiltrative growth pattern. In the total cohort of non-treated patients (n = 187), cyclin E was not associated with recurrence free survival (RFS). However, when analysing the subgroup of tumours lacking a pushing growth pattern (n = 141), cyclin E was significantly associated with RFS, independent of histological grade and node status. There was no significant difference in tamoxifen response with regard to different cyclin E levels. Conclusion: The prognostic value of cyclin E in premenopausal breast cancer is limited to patients with breast carcinomas exhibiting an exclusively infiltrative growth pattern. This limitation could be explained by the presence of a small but distinct subgroup of cyclin E-high breast cancers with a pushing margin phenotype and a more favourable outcome.
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| 12. |
- Blom, Kristin, et al.
(author)
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Mebendazole-induced M1 polarisation of THP-1 macrophages may involve DYRK1B inhibition
- 2019
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In: BMC Research Notes. - : Springer Nature. - 1756-0500. ; 12:1
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Journal article (peer-reviewed)abstract
- Objective: We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity by inducing a M2 to M1 phenotype switch in monocyte/macrophage models. In the present study we investigated the potential role of protein kinases in mediating this effect.Results: MBZ potently binds and inhibits Dual specificity tyrosine-phosphorylation-regulated kinase 1B (DYRK1B) with a Kd and an IC50 of 7 and 360 nM, respectively. The specific DYRK1B inhibitor AZ191 did not mimic the cytokine release profile of MBZ in untreated THP-1 monocytes. However, in THP-1 cells differentiated into macrophages, AZ191 strongly induced a pro-inflammatory cytokine release pattern similar to MBZ and LPS/IFNγ. Furthermore, like MBZ, AZ191 increased the expression of the M1 marker CD80 and decreased the M2 marker CD163 in THP-1 macrophages. In this model, AZ191 also increased phospho-ERK activity although to a lesser extent compared to MBZ. Taken together, the results demonstrate that DYRK1B inhibition could, at least partly, recapitulate immune responses induced by MBZ. Hence, DYRK1B inhibition induced by MBZ may be part of the mechanism of action to switch M2 to M1 macrophages.
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| 13. |
- Blom, Kristin, et al.
(author)
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The anticancer effect of mebendazole may be due to M1 monocyte/macrophage activation via ERK1/2 and TLR8-dependent inflammasome activation
- 2017
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In: Immunopharmacology and immunotoxicology. - : Informa UK Limited. - 0892-3973 .- 1532-2513. ; 39:4, s. 199-210
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Journal article (peer-reviewed)abstract
- Mebendazole (MBZ), a drug commonly used for helminitic infections, has recently gained substantial attention as a repositioning candidate for cancer treatment. However, the mechanism of action behind its anticancer activity remains unclear. To address this problem, we took advantage of the curated MBZ-induced gene expression signatures in the LINCS Connectivity Map (CMap) database. The analysis revealed strong negative correlation with MEK/ERK1/2 inhibitors. Moreover, several of the most upregulated genes in response to MBZ exposure were related to monocyte/macrophage activation. The MBZ-induced gene expression signature in the promyeloblastic HL-60 cell line was strongly enriched in genes involved in monocyte/macrophage pro-inflammatory (M1) activation. This was subsequently validated using MBZ-treated THP-1 monocytoid cells that demonstrated gene expression, surface markers and cytokine release characteristic of the M1 phenotype. At high concentrations MBZ substantially induced the release of IL-1 beta and this was further potentiated by lipopolysaccharide (LPS). At low MBZ concentrations, cotreatment with LPS was required for MBZ-stimulated IL-1 beta secretion to occur. Furthermore, we show that the activation of protein kinase C, ERK1/2 and NF-kappaB were required for MBZ-induced IL-1 release. MBZ-induced IL-1 release was found to be dependent on NLRP3 inflammasome activation and to involve TLR8 stimulation. Finally, MBZ induced tumor-suppressive effects in a coculture model with differentiated THP-1 macrophages and HT29 colon cancer cells. In summary, we report that MBZ induced a pro-inflammatory (M1) phenotype of monocytoid cells, which may, at least partly, explain MBZ's anticancer activity observed in animal tumor models and in the clinic.
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| 14. |
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| 15. |
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| 16. |
- Eriksson, Mårten, et al.
(author)
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A screening version of the Swedish Communicative Development Inventories designed for use with 18-month-old children.
- 2002
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In: Journal of Speech, Language and Hearing Research. - : American Speech Language Hearing Association. - 1092-4388 .- 1558-9102. ; 46:5, s. 948-960
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Journal article (peer-reviewed)abstract
- An instrument designed to assess young children's communicative skills at 18 months is described. The instrument consists of a 103-item parental report checklist based on the Swedish version of the Communicative Development Inventories (SECDI). We present descriptive data from a study at the Swedish Community Health Care Centres, including parental reports of 1021 18-month-old children. The response rate was 88%. Performance at the 10th percentile consisted of 8 communicative gestures, 45 comprehended words, and 7 spoken words. The overall results indicate that the instrument is reliable and has validity approximating that of the SECDI. Furthermore, parents of the children with the poorest vocabulary indicated approval of the assessment procedure in interviews especially directed to this group.
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| 17. |
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| 18. |
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| 19. |
- Eriksson, Mårten, et al.
(author)
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Swedish early communicative development inventories : words and gestures
- 1999
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In: First language. - : SAGE Publications. - 0142-7237 .- 1740-2344. ; 19:55, s. 55-90
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Journal article (peer-reviewed)abstract
- This study describes the typical course and variability in major areas of communicative development for 228 Swedish-speaking children between 8 and 16 months of age. The assessments were made by parental reports with the Swedish Early Communicative Development Inventories (SECDI) using a semi-longitudinal design. Age-based norms for understanding of phrases, vocabulary comprehension, vocabulary production and use of gestures are described at the 10th, 25th, 50th, 75th and 90th percentile levels. More lexical verbs were found among the first words in comprehension than in production. An extensive variability within individuals in onset and development was found for the assessed skills. The individual differences proved to be stable over 4–6 months. No gender differences were found for comprehension of phrases, total gestures, vocabulary compre-hension, or for vocabulary production. Strong, unique associations were found between total gestures and vocabulary comprehension and between vocabulary comprehension and vocabulary production. In contrast, no unique association was found between gestures and vocabulary production. The results generally concur with those reported for English-speaking American children by Fenson et al. (1993, 1994).
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| 20. |
- Eskilson, Olof, 1992-, et al.
(author)
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Nanocellulose composite wound dressings for real-time pH wound monitoring
- 2023
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In: Materials Today Bio. - : Elsevier. - 2590-0064. ; 19
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Journal article (peer-reviewed)abstract
- The skin is the largest organ of the human body. Wounds disrupt the functions of the skin and can have catastrophic consequences for an individual resulting in significant morbidity and mortality. Wound infections are common and can substantially delay healing and can result in non-healing wounds and sepsis. Early diagnosis and treatment of infection reduce risk of complications and support wound healing. Methods for monitoring of wound pH can facilitate early detection of infection. Here we show a novel strategy for integrating pH sensing capabilities in state-of-the-art hydrogel-based wound dressings fabricated from bacterial nanocellulose (BC). A high surface area material was developed by self-assembly of mesoporous silica nanoparticles (MSNs) in BC. By encapsulating a pH-responsive dye in the MSNs, wound dressings for continuous pH sensing with spatiotemporal resolution were developed. The pH responsive BC-based nanocomposites demonstrated excellent wound dressing properties, with respect to conformability, mechanical properties, and water vapor transmission rate. In addition to facilitating rapid colorimetric assessment of wound pH, this strategy for generating functional BC-MSN nanocomposites can be further be adapted for encapsulation and release of bioactive compounds for treatment of hard-to-heal wounds, enabling development of novel wound care materials.
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| 21. |
- Finnveden, Göran, et al.
(author)
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Consumption based national indicators for use of hazardous chemicals : mixed results for time series
- 2023
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In: Book of Abstracts. ; , s. 487-
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Conference paper (peer-reviewed)abstract
- Risks associated with the use of hazardous chemicals are becoming more apparent. It was forexample recently suggested that the safe operating space of the planetary boundary of novelentities (including hazardous chemicals) is exceeded since annual production and releases areincreasing at a pace that outstrips the global capacity for assessment and monitoring.Consumption based indicators for national emissions of greenhouse gases are now producedregularly, for example as part of the Swedish Official Statistics. Consumption-based nationalindicators the use of hazardous chemicals are however largely lacking. The aim of this studywas to develop times series for three consumption-based indicators for Sweden: use ofpesticides, use of veterinary antibiotics and use of hazardous chemical products. The methodhas previously been developed and described for a single year, but time series for these types ofindicators have to our knowledge never been presented. The indicators were calculated bycombining data from Sweden’s Environmental Accounts with a Multi-Regional Input-OutputDataset (EXIOBASE) which is the same approach as used for calculating Swedish officialstatistics for greenhouse gas emissions. Data for the use of hazardous chemicals were takenfrom regularly updated institutional national and international databases. The results show thatthe use of veterinary antibiotics decreased by about 50 percent whereas the use of pesticidesdecreased by about 10 percent. In contrast, the use of hazardous chemical products increased.Results show that construction (including buildings and infrastructure), is the single largestproduct group for the use of hazardous chemical products followed by retail, real estate andchemical and pharmaceutical. All have increased their use of hazardous chemical productsbetween 2013 and 2019. Results also show that although Sweden is the country that contributesmost to the use of hazardous chemical products for Swedish consumption, the majority comesfrom imported products of which most comes from countries within the European Union. Theresults for the use of hazardous chemical products for Swedish consumption is worrying andsuggests that this needs further follow-up and also policy initiatives. The decreasing trends forthe use of pesticides and veterinary antibiotics, which are areas where there are policies, aremore encouraging.
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| 22. |
- Lagergren, Mårten, et al.
(author)
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Horizontal and vertical target efficiency - a comparison between users and non-users of public long-term care in Sweden
- 2014
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In: Ageing & Society. - : Cambridge University Press. - 0144-686X .- 1469-1779. ; 34:4, s. 700-719
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Journal article (peer-reviewed)abstract
- The extent to which a system of services is in tune with the needs of the population can be expressed in terms of target efficiency, which includes horizontal target efficiency - the extent to which those deemed to need a service receive it - and vertical target efficiency - the corresponding extent to which those who receive a service actually need it. Vertical efficiency can be measured by looking only at those receiving services. To measure horizontal target efficiency in a population, one must have access to population surveys. Data were taken from the baseline survey of the Swedish National Study on Ageing and Care (SNAC study). The results show that more than 80 per cent of those dependent in personal activities of daily living in the studied geographic areas were users of public long-term care (LTC). Dependency in instrumental activities of daily living was identified as the most important predictor of using LTC. Vertical target efficiency was 83-95 per cent depending on age, gender and type of household, if need was defined as dependency in instrumental activities of daily living. It was considerably lower, 35-61 per cent when defined as dependency in personal daily activities. Overall, long-term target efficiency in Sweden must be regarded as high. Few persons who need public LTC services fail to receive them.
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| 23. |
- Lagergren, Mårten, et al.
(author)
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Horizontal and vertical targeting : a population-based comparison of public eldercare services in urban and rural areas of Sweden
- 2016
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In: Aging Clinical and Experimental Research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 28:1, s. 147-158
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Journal article (peer-reviewed)abstract
- The concepts of target efficiency can be used to assess the extent to which service provision is in line with the needs of the population. Horizontal target efficiency denotes the extent to which those deemed to need a service receive it and vertical target efficiency is the corresponding extent to which those who receive services actually need them. The aim of this study was to assess the target efficiency of the Swedish eldercare system and to establish whether target efficiencies differ in different geographical areas such as large urban, midsize urban and rural areas. Vertical efficiency was measured by studying those people who received eldercare services and was expressed as a percentage of those who received services who were functionally dependent. To measure horizontal target efficiency, data collected at baseline in the longitudinal population study SNAC (Swedish National study on Aging and Care) during the years 2001-2004 were used. The horizontal efficiency was calculated as the percentage of functionally dependent persons who received services. Functional dependency was measured as having difficulty with instrumental activities of daily living (IADL) and/or personal activities of daily living (PADL). Services included long-term municipal eldercare services (LTC). Horizontal target efficiency for the public LTC system was reasonably high in all three geographical areas, when using dependency in PADL as the measure of need (70-90 %), but efficiency was lower when the less restrictive measure of IADL dependency was used (40-50 %). In both cases, the target efficiency was markedly higher in the large urban and the rural areas than in the midsize urban areas. Vertical target efficiency showed the same pattern-it was almost 100 % in all areas for IADL dependency, but only 50-60 % for PADL dependency. Household composition differed in the areas studied as did the way public long-term care was provided to people living alone as compared to those co-habiting.
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| 24. |
- Lindqvist, C. Mårten, et al.
(author)
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Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:39, s. 64071-64088
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Journal article (peer-reviewed)abstract
- To characterize the mutational patterns of acute lymphoblastic leukemia (ALL) we performed deep next generation sequencing of 872 cancer genes in 172 diagnostic and 24 relapse samples from 172 pediatric ALL patients. We found an overall greater mutational burden and more driver mutations in T-cell ALL (T-ALL) patients compared to B-cell precursor ALL (BCP-ALL) patients. In addition, the majority of the mutations in T-ALL had occurred in the original leukemic clone, while most of the mutations in BCP-ALL were subclonal. BCP-ALL patients carrying any of the recurrent translocations ETV6-RUNX1, BCR-ABL or TCF3-PBX1 harbored few mutations in driver genes compared to other BCP-ALL patients. Specifically in BCP-ALL, we identified ATRX as a novel putative driver gene and uncovered an association between somatic mutations in the Notch signaling pathway at ALL diagnosis and increased risk of relapse. Furthermore, we identified EP300, ARID1A and SH2B3 as relapse-associated genes. The genes highlighted in our study were frequently involved in epigenetic regulation, associated with germline susceptibility to ALL, and present in minor subclones at diagnosis that became dominant at relapse. We observed a high degree of clonal heterogeneity and evolution between diagnosis and relapse in both BCP-ALL and T-ALL, which could have implications for the treatment efficiency.
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Lindqvist, C Mårten, et al.
(author)
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The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
- 2015
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In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 36:1, s. 118-128
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Journal article (peer-reviewed)abstract
- Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.
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| 29. |
- Marincevic-Zuniga, Yanara, et al.
(author)
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Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles
- 2017
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In: Journal of Hematology & Oncology. - : Springer Science and Business Media LLC. - 1756-8722. ; 10
-
Journal article (peer-reviewed)abstract
- Background: Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. Methods: We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes. Results: We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations. Conclusion: Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.
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| 30. |
- Mawdsley, Ingrid, et al.
(author)
-
Förslag på indikatorer baserade på utsläppsdata från PRTR
- 2016
-
Reports (other academic/artistic)abstract
- Ända sedan PRTR-protokollet instiftades har syftet varit att ge allmänheten kännedom om utsläpp från industriella anläggningar, och att försöka popularisera och kommunicera de utsläppsdata som finns. Nyligen beskrev EU-kommissionen sitt arbete med att arbeta för en ökad användning av PRTR-data för policy och till allmänhet, och EEA har i sin fleråriga plan för 2014–2018 uttryckt ambitionen att ta fram indikatorer inom området industriella utsläpp. I Sverige jobbar Naturvårdsverket med PRTR-frågor, man har även här betonat vikten av allmänhetens tillgång till miljöinformation från PRTR, samt att indikatorer baserat på PRTR som kopplar till miljömålet Giftfri miljö borde tas fram.Detta projekt har tagit avstamp i dessa ambitioner, och presenterar här en lista på möjliga indikatorer främst med anknytning till PRTR-data. Syftet med projektet har inte varit att ta fram data för indikatorerna, utan endast ge förslag på vilka indikatorer som vore intressanta att utveckla.
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| 31. |
- Mawdsley, Ingrid, et al.
(author)
-
Suggestions for indicators based on emission data from the Swedish PRTR
- 2016
-
Reports (other academic/artistic)abstract
- Ever since the Protocol on PRTR was introduced, the purpose of the Protocol has been to make information on emissions from the industry available to the public, and to try to popularize and communicate existing emissions data. Recently, the EU Commission described its work towards an increased use of PRTR data for policy making and for the public, and the EEA has, in its plan for 2014-2018, expressed the ambition to develop indicators regarding industrial emissions. In Sweden, the Environmental Protection Agency is working with issues regarding the PRTR, and also here public availability of emission data from the PRTR is emphasized and also the need to develop indicators that are based on PRTR data and that relates to the Swedish environmental objective A Non-Toxic Environment.The present project is based on these ambitions and presents a list of potential indicators that are mostly based on PRTR data. The aim with the project has not been to retrieve data for the indicators, but to give suggestions on which indicators that would be interesting to develop.
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| 32. |
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| 33. |
- Palm, Viveka, et al.
(author)
-
Environmental pressures from Swedish consumption – A hybrid multi-regional input-output approach
- 2019
-
In: Journal of Cleaner Production. - : Elsevier. - 0959-6526 .- 1879-1786. ; 228, s. 634-644
-
Journal article (peer-reviewed)abstract
- Sweden has a policy goal of solving major environmental problems in Sweden within a generation, without increasing environmental or health problems in other countries. Following up this goal requires indicators for domestic and external footprints of Swedish consumption. This paper presents such macro-level indicators for the years 2008–2014.The new indicators are consistent with Swedish statistics from the System of Environmental-Economic Accounts. They combine a multi-regional input-output (MRIO) database, to capture the external components of Sweden's consumption, with national input-output, trade and environmental statistics. The hybrid MRIO-Sweden model provides a comprehensive environmental account for follow-up of the Generational Goal.This paper presents impacts from household consumption, government consumption and capital formation, covering emissions of greenhouse gases, sulphur dioxide, nitrogen oxides, and particulate matter smaller than 2.5 μm (PM2.5), land use, materials consumption, and blue water consumption.Except for land use, the majority (60% or more) of the environmental pressures due to consumption occurred outside Sweden in 2014; more than 90% of sulphur emissions and more than 80% of the water use fell abroad. The environmental pressures from consumption decreased over this period for all indicators (except materials consumption). This suggests an absolute decoupling between environmental pressure due to consumption and economic growth, which rose over the period. It is, however, too early to determine whether this is a genuine trend or a temporary stabilisation.
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| 34. |
- Persson, Linn, et al.
(author)
-
Indicators for national consumption-based accounting of chemicals
- 2019
-
In: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526 .- 1879-1786. ; 215, s. 1-12
-
Journal article (peer-reviewed)abstract
- Increased chemical use is causing a growing number of environmental problems and chemical products are pervasive in societies within animal and crop-based agriculture, in industrial processes and in households. National environmental targets, as well as the global chemical-related goals in the 2030 Agenda, call for the monitoring of chemical use and emissions. The growing international trade of goods, where use and regulation of chemical inputs vary highly between countries, complicates measurements. This paper addresses these issues by deriving a set of indicators on chemical use and emissions and connect the global impacts to a country's total consumption, here using the case of Sweden. The indicators are based on a hybrid model combining the multi-regional input-output analysis database EXIOBASE with data from the Swedish System of Economic and Environmental Accounts together with a novel set of environmental extensions. A review of databases is conducted and discussed in relation to the driver-pressure-state-impact-response (DPSIR) framework for indicators. Five indicators are calculated, showing the chemical use and emissions connected to consumption, both within a country and abroad. The indicators are: use of hazardous chemical products, use of pesticides, use of antimicrobial veterinary medicines, emissions of hazardous substances, and of the potential toxicity of these emissions. The results show that the impact of Swedish consumption in terms of use and emissions of hazardous substances is largely taking place outside the Swedish borders. Only 10e24% of the pressure from Swedish consumption is shown to occur within Sweden's borders, depending on the indicator. The use of hazardous chemical products and veterinary medicines related to Swedish consumption primarily takes place in other EU countries, whereas the use of pesticides as well as reported emissions of pollutants occur mainly in countries outside the EU. The results highlight the need for improved international accounting of chemical flows, as well as for strengthened policy frameworks to address cross-border impacts of consumption of hazardous chemical products.
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| 35. |
- Segerman, Anna, et al.
(author)
-
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition
- 2016
-
In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 17:11, s. 2994-3009
-
Journal article (peer-reviewed)abstract
- Intratumoral heterogeneity is a hallmark of glioblastoma multiforme and thought to negatively affect treatment efficacy. Here, we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability among clones, including a range of responses to radiation and drugs. This widespread variability was observed as a continuumof multitherapy resistance phenotypes linked to a proneural-mesenchymal shift in the transcriptome. Multitherapy resistance was associated with a semi-stable cell state that was characterized by an altered DNA methylation pattern at promoter regions of mesenchymal master regulators and enhancers. The gradient of cell states within the GIC compartment constitutes a distinct form of heterogeneity. Our findings may open an avenue toward the development of new therapeutic rationales designed to reverse resistant cell states.
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| 36. |
- Selvin, Tove, et al.
(author)
-
Immuno-oncological effects of standard anticancer agents and commonly used concomitant drugs : an in vitro assessment
- 2024
-
In: BMC Pharmacology & Toxicology. - : BioMed Central (BMC). - 2050-6511. ; 25:1
-
Journal article (peer-reviewed)abstract
- BackgroundIt has become evident in the field of oncology that the outcome of medical treatment is influenced by the combined effect exerted on both cancer- and immune cells. Therefore, we evaluated potential immunological effects of 46 standard anticancer agents and 22 commonly administered concomitant non-cancer drugs.MethodsWe utilized a miniaturized in vitro model system comprised of fluorescently labeled human colon and lung cancer cell lines grown as monocultures and co-cultured with activated peripheral blood mononuclear cells (PBMCs). The Bliss Independence Model was then applied to detect antagonism and synergy between the drugs and activated immune cells.ResultsAmong the standard anticancer agents, tyrosine kinase inhibitors (TKIs) stood out as the top inducers of both antagonism and synergy. Ruxolitinib and dasatinib emerged as the most notably antagonistic substances, exhibiting the lowest Bliss scores, whereas sorafenib was shown to synergize with activated PBMCs. Most concomitant drugs did not induce neither antagonism nor synergy. However, the statins mevastatin and simvastatin were uniquely shown to synergize with activated PBMC at all tested drug concentrations in the colon cancer model.ConclusionWe utilized a miniaturized tumor-immune model to enable time and cost-effective evaluation of a broad panel of drugs in an immuno-oncology setting in vitro. Using this approach, immunomodulatory effects exerted by TKIs and statins were identified.
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| 37. |
- Selvin, Tove, et al.
(author)
-
Phenotypic screening platform identifies statins as enhancers of immune cell-induced cancer cell death.
- 2023
-
In: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 23:1
-
Journal article (peer-reviewed)abstract
- High-throughput screening (HTS) of small molecule drug libraries has greatly facilitated the discovery of new cancer drugs. However, most phenotypic screening platforms used in the field of oncology are based solely on cancer cell populations and do not allow for the identification of immunomodulatory agents.We developed a phenotypic screening platform based on a miniaturized co-culture system with human colorectal cancer- and immune cells, providing a model that recapitulates part of the tumor immune microenvironment (TIME) complexity while simultaneously being compatible with a simple image-based readout. Using this platform, we screened 1,280 small molecule drugs, all approved by the Food and Drug Administration (FDA), and identified statins as enhancers of immune cell-induced cancer cell death.The lipophilic statin pitavastatin had the most potent anti-cancer effect. Further analysis demonstrated that pitavastatin treatment induced a pro-inflammatory cytokine profile as well as an overall pro-inflammatory gene expression profile in our tumor-immune model.Our study provides an in vitro phenotypic screening approach for the identification of immunomodulatory agents and thus addresses a critical gap in the field of immuno-oncology. Our pilot screen identified statins, a drug family gaining increasing interest as repurposing candidates for cancer treatment, as enhancers of immune cell-induced cancer cell death. We speculate that the clinical benefits described for cancer patients receiving statins are not simply caused by a direct effect on the cancer cells but rather are dependent on the combined effect exerted on both cancer and immune cells.
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| 38. |
- Selvin, Tove, et al.
(author)
-
The Immuno-Oncology Hollow Fiber Assay
-
Other publication (other academic/artistic)abstract
- In order to facilitate the translation of novel immunotherapies from bench to bedside, continued development of predictive preclinical models is essential. Herein, we developed the immuno-oncology hollow fiber assay (HFA) to bridge the gap between cell based in vitro assays and more complex mouse models for evaluation of immuno-oncological agents. The colorectal cancer (CRC) cell line HCT116-GFP and human peripheral blood mononuclear cells (PBMCs) were co-cultured inside semipermeable hollow fibers. As a proof of concept, aCD3 and IL-2 was used to induce immune cell-mediated cancer cell death. During in vitro characterization of the model system, an enhanced effect of aCD3 and IL-2 was observed in the HFA compared to conventional monolayers. Further investigation demonstrated that increased cell proximity alone is sufficient to augment immune cell activation and effector function. To assess the functionality of the assay in vivo, a pilot study was performed using nude mice. Hollow fibers were surgically implanted intraperitoneally (i.p.) and the mice received local injections of aCD3 at the time of implantation and/ or systemic IL-2 via i.p. injection once daily for 3 consecutive days. Compared to untreated mice and mice receiving IL-2 alone, the combination of aCD3 and IL-2 resulted in a significant decrease in cancer cell viability. Traditional in vivo models often necessitate lengthy observation periods to monitor tumor growth and treatment response. We have developed a simplified model system that enables initial in vivo evaluation of immunological agents on cancer and immune cells of human origin within a matter of days.
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| 39. |
- Skånberg, Kristian, et al.
(author)
-
Integrated sustainability assessment of a circular economy
- 2020
-
In: Handbook of the Circular Economy. - Cheltenham : Edward Elgar Publishing. ; , s. 147-161
-
Book chapter (other academic/artistic)abstract
- Governments and businesses are acknowledging that the prevailing ’linear systems of resource use’ expose our societies to serious risks. Resource constraints and increasing volumes of waste and pollution pose a threat to people’s well-being and businesses’ competitiveness and sustainability efforts. The ’circular economy’, conversely, is described as an industrial system that is circular in the cradle-to-cradle-recyclability sense by intention and design. This chapter focuses on some assessed integrated impacts - possible societal benefits - that a transformation from a linear to a circular economy might result in. This has been done by applying “what-if-scenarios” into a for this purpose constructed interactive input–output model with a number of changes linked to a circular economy implemented in the model. The model has then been applied to eight European economies showing close to 70% reductions in CO2-emissions while offering new and additional employment and improving the trade balance of fossil-fuels-importing countries.
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| 40. |
- Steinbach, Nancy, et al.
(author)
-
Miljöpåverkan från svensk konsumtion - nya indikatorer för uppföljning. Slutrapport för forskningsprojektet PRINCE
- 2018
-
Reports (other academic/artistic)abstract
- NATURVÅRDSVERKET RAPPORT 6842 Miljöpåverkan från svensk konsumtion - nya indikatorer för uppföljning Sammanfattning Projektet Policy Relevant Indicators for Consumption and Environment (PRINCE) har haft som syfte att analysera potentiell miljöpåverkan kopplad till svensk konsumtion, både i Sverige och utomlands, och att kvantifiera denna med indikatorer. För att kunna producera de föreslagna indikatorerna har projektet utvecklat en ny matematisk metod för att kombinera svenska miljöekonomiska data med en multiregional input-outputmodell, som är relativt lättarbetad och bevarar en flexibilitet som möjliggör ett byte till andra multiregionala modeller om så önskas. Baserat på detta har projektet konstruerat en ny indikatormodell, kallad PRINCE-modellen, och uppskattat en lång rad utsläpp och resursanvändning kopplat till svensk konsumtion med den. Detta inkluderar förutom växthusgasutsläpp och luftföroreningar, en rad naturresurser och utsläpp som tidigare inte har studerats lika mycket, såsom markanvändning, vattenanvändning, användning och utsläpp av kemikalier och växthusgasutsläpp från avskogning. För vissa variabler har projektet tagit fram indikatorer för ett visst år, och för vissa andra har vi producerat tidsserier för åren 2008-2014. För växthusgaser, utsläpp av kväveoxider, svaveldioxid och partiklar har utsläppen från svensk konsumtion minskat under denna tid. Även arealen mark som tagits i anspråk kopplat till den svenska konsumtionen har minskat något under denna tid, medan totala materialflöden ökat. Under denna tidsperiod har förädlingsvärdet, som är ett mått på ekonomisk aktivitet, ökat vilket visar på en absolut frikoppling mellan ekonomisk utveckling och utsläpp av växthusgaser (med reservation för att inga höghöjdseffekter av utsläpp från flyg har ingått i denna studie). Utsläppsminskningen är dock betydligt mindre än den som krävs för att vara i linje med globala överenskommelser om klimatet så frikopplingen har inte varit tillräckligt stor. Det svenska generationsmålet anger bland annat att de svenska miljöproblemen ska lösas utan att orsaka ökade miljö- och hälsoproblem utanför Sverige. För de indikatorer där en tidsserie producerats (växthusgaser, utsläpp av kväveoxider, svaveldioxid och partiklar) har andelen av utsläppen som sker i Sverige respektive utomlands kopplat till den svenska konsumtionen varit relativt oförändrad under den studerade tidsperioden. Då de totala utsläppen minskat så har även utsläppen som skett utomlands under perioden minskat något. Projektet har med indikatorernas hjälp studerat vilka geografiska områden där miljöpåverkan från svensk konsumtion är störst och vilka produktkategorier som ger stort utslag i uppföljningen. Resultaten är något olika för olika typer av miljöpåverkan men produkter från byggsektorn, livsmedel och jordbruksprodukter, samt hushållens direkta utsläpp bland annat från fossila bränslen är kategorier med stor miljöpåverkan. Miljöpåverkan kopplat till svensk konsumtion sker i många olika länder. Förutom i Sverige sker utsläppen bland annat i stora länder som Kina, Ryssland, Tyskland och USA men också i många andra länder som Sverige importerar ifrån. Projektet har också tagit fram en grupp med indikatorer som kan mäta kemikalieanvändningen och utsläpp på en övergripande nivå. De täcker både användning av farliga kemiska produkter och utsläpp av vissa farliga ämnen. Resultaten pekar bland annat på att både användning och utsläpp av farliga kemikalier i stor utsträckning sker utomlands. Till exempel sker endast 22% av användningen av farliga kemikalier och 20% av utsläppen av farliga ämnen, som ingår i indikatorn, för svensk konsumtions räkning inom Sveriges gränser. Kemikalieindikatorerna kräver ett visst fortsatt utvecklingsarbete, exempelvis med framtagande av tidsserier. Vidare har projektet tagit fram nya förslag på hur man kan följa upp miljöpåverkan av fiskkonsumtion beroende på typ av fisk som konsumeras och vilken fångstmetod som använts. Även fiskindikatorerna kräver fortsatt arbete innan de kan läggas till ordinarie uppföljningsprogram. Projektet har också undersökt metoder för att fördjupa analysen av miljöpåverkan av vattenanvändning i produktionen genom att urskilja vilka områden som har särskilda problem med vattenbrist. Detta är inte möjligt att göra med någon större precision i dagsläget. Två olika metoder provades inom projektet, en som använde vattenåtgång för jordbruksprodukter och en som använde data om vattenbrist per land. Slutligen har specialstudier även gjorts av viktiga produktgrupper som mat och dryck, IKT-sektorn (informations- och kommunikationsteknik), fossilbränsleanvändningen i sjöfarten med två olika metoder, samt socioekonomisk påverkan av svensk konsumtion i Kina. Baserat på resultaten har projektet genererat ett antal rekommendationer för hur arbetet med konsumtionsbaserade indikatorer kan drivas vidare: • SCB ändrar den tidigare beräkningsmetoden för att beräkna utsläpp från konsumtion och använder de multiregionala data som finns tillgängliga i EXIOBASE för att beräkna miljöpåverkan från import. • För utsläpp av växthusgaser samt för utsläpp till luft av kväveoxider, svaveldioxid och partiklar: generationsmålet följs upp med den utvecklade PRINCE-modellen som kombinerar svensk miljöekonomisk data med multiplikatorer som beräknas med en multiregional input-outputmodell. • Det internationella arbetet med förbättrad tillgång till harmoniserad miljöstatistik stöttas. • Arbetet med vidareutveckling av indikatorer för användning av naturresurser (som markanvändning och dess koppling till avskogning och biologisk mångfald, vattenanvändning, materialflöden och energi) fortsätter bland annat avseende kopplingen mellan dessa flöden och miljöpåverkan, de svenska miljömålen och de globala hållbarhetsmålen. • Forsknings- och utvecklingsarbetet med kemikalieindikatorerna fortsätter och tidsserier tas fram för att så småningom kunna ta in dem i analysen av generationsmålet. • Metoderna som föreslagits för att bedöma miljöpåverkan från fiskkonsumtion vidareutvecklas. • Metoderna som föreslagits för att beräkna utsläpp från internationella transporter vidareutvecklas.
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| 41. |
- Strandberg, Gabriel, et al.
(author)
-
Prompt Thrombo-Inflammatory Response to Ischemia-Reperfusion Injury and Kidney Transplant Outcomes
- 2023
-
In: KIDNEY INTERNATIONAL REPORTS. - : Elsevier. - 2468-0249. ; 8:12, s. 2592-2602
-
Journal article (peer-reviewed)abstract
- Introduction: In kidney transplantation (KT), the role of the intravascular innate immune system (IIIS) in response to ischemia-reperfusion injury (IRI) is not well-understood. Here, we studied parallel changes in the generation of key activation products of the proteolytic cascade systems of the IIIS following living donor (LD) and deceased donor (DD) transplantation and evaluated potential associations with clinical outcomes.Methods: In a cohort study, 63 patients undergoing LD (n = 26) and DD (n = 37) transplantation were prospectively included. Fifteen DD kidneys were preserved with hypothermic machine perfusion (HMP), and the remaining were cold stored. Activation products of the kallikrein-kinin, coagulation, and complement systems were measured in blood samples obtained systemically at baseline and locally from the transplant renal vein at 1, 10, and 30 minutes after reperfusion.Results: DD kidneys exhibited a prompt and interlinked activation of all 3 cascade systems of IIIS post-reperfusion, indicating a robust and local thrombo-inflammatory response to IRI. In this initial response, the complement activation product sC5b-9 exhibited a robust correlation with other IIIS activation markers and displayed a strong association with short-term and mid-term (24-month) graft dysfunction. In contrast, LD kidneys did not exhibit this thrombo-inflammatory response. The use of HMP was associated with reduced thromboinflammation and preserved mid-term kidney function.Conclusion: Kidneys from DD are vulnerable to a prompt thrombo-inflammatory response to IRI, which adversely affects both short-term and long-term allograft function. Strategies aimed at minimizing graft immunogenicity prior to reperfusion are crucial to mitigate the intricate inflammatory response to IRI.
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| 42. |
- Svennberg, Emma, et al.
(author)
-
NT-proBNP is a powerful predictor for incident atrial fibrillation : Validation of a multimarker approach
- 2016
-
In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 223, s. 74-81
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Biomarkers may be of value to identify individuals at risk of developing atrial fibrillation (AF). Using a multimarker approach, this study investigated if the biomarkers; NT-proBNP, high-sensitivity cardiac troponin (hs-cTn), growth differentiation factor-15 (GDF-15), cystatin C and high-sensitivity C-reactive protein (CRP) are independent predictors for incident AF.METHODS: Blood samples were collected from 883 individuals in the Uppsala Longitudinal Study of Adult Men (ULSAM) and 978 individuals in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Participants were followed for 10-13years with n=113 incident AF cases in ULSAM and n=148 in PIVUS. The associations between biomarkers and incident AF were analysed in Cox proportional hazards regression models.RESULTS: The hazard ratio (HR) for incident AF was significant for all five biomarkers in unadjusted analyses in both cohorts. Only NT-proBNP remained significant when adjusting for cardiovascular risk factors and the other biomarkers (HR (1SD) 2.05 (1.62-2.59) (ULSAM) and 1.56 (1.30-1.86) (PIVUS), both p<0.001). The C-index improved from 0.64 to 0.69 in ULSAM and from 0.62 to 0.68 in PIVUS, by adding NT-proBNP to cardiovascular risk factors (both p<0.001). The C-index of the CHARGE-AF risk score increased from 0.62 to 0.68 (ULSAM) and 0.60 to 0.66 (PIVUS) by addition of NT-proBNP (p<0.001).CONCLUSIONS: Using a multimarker approach NT-proBNP was the strongest predictor of incident AF in two cohorts, and improved risk prediction when added to traditional risk factors. NT-proBNP significantly improved the predictive ability of the novel CHARGE-AF risk score, although the predictive value remained modest.
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| 43. |
- Sörme, Louise, et al.
(author)
-
Indikatorer för att följa konsumenters omställning till en hållbar konsumtion
- 2015
-
Reports (other academic/artistic)abstract
- Generationsmålet är det övergripande målet för miljöpolitiken i Sverige och innebär att vi till nästa generation ska kunna lämna över ett samhälle där de stora miljöproblemen är lösta, utan att orsaka ökade miljö- och hälsoproblem utanför Sveriges gränser. Som del av detta mål ska miljöpolitiken bland annat fokusera på att konsumtionsmönstren av varor och tjänster orsakar så små miljö- och hälsoproblem som möjligt. Naturvårdsverket ska på uppdrag av Regeringen redovisa en fördjupad utvärdering av generationsmålet och miljökvalitetsmålen 2015. Uppdraget ska redovisas senast den 1 september 2015. Redovisningen ska bland annat innehålla en målövergripande analys av utvecklingen mot generationsmålet och miljökvalitetsmålen. En del av denna analys genomförs inom ramen för tre utvalda fokusområden, däribland hållbar konsumtion. Projektet syftade till att ta fram ett av flera faktaunderlag till Regeringens ovanstående uppdrag om fördjupad utvärdering av miljökvalitetsmålen. Det konkreta målet var att ta fram förslag på möjliga indikatorer samt att beskriva för- och nackdelar med olika förslag samt att dataförsörja fyra indikatorer som följer konsumenters/individers omställning till en mer hållbar konsumtion. De fyra indikatorerna valdes ut av Naturvårdsverket. För att få fram det preliminära indikatorurvalet hämtades bland annat inspiration från andra projekt och sammanställningar av indikatorer i Sverige och utomlands, samt från aktuell diskussion i media och liknande. Därefter gjordes en genomgång ifall det fanns data tillgängliga eller inte. Fanns det data tillgängligt och indikatorn i övrigt uppfyllde kriterier som Naturvårdsverket satt upp ingick den i det urval av 27 indikatorer som beskrevs mer utförligt. I beskrivningen ingick enhet, för- och nackdelar, tidsserie och datakälla. Indikatorerna delades upp i olika områden; mat, textil, elektronik, boende samt transporter. Rapporten nämner också indikatorer som skulle vara önskvärda men där det saknas data, totalt 42 stycken. Naturvårdsverket valde ut följande indikatorer som också har dataförsörjts inom projektet: M1 - Konsumtion av nötkött, kg/person och år M8 - Energiöverskott i matkonsumtionen, procent Tr1 - Persontransporter (totalt och uppdelat på gång/cykel, kollektivtrafik, bil, och övrigt), km/person och år B3 - Uppvärmd boendeyta i hushåll, m2/person
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| 44. |
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| 45. |
- Uhlén, Mathias, et al.
(author)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
-
In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
-
Journal article (peer-reviewed)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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| 46. |
- Westerlund, M., et al.
(author)
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A short-term follow-up of children with poor word production at the age of 18 months
- 2004
-
In: Acta Paediatrica. - 0803-5253 .- 1651-2227. ; 93:5, s. 702-706
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Journal article (peer-reviewed)abstract
- Aim: (a) To study the stability of poor language development assessed by a new screening instrument based on parents' recognition of words their 18-mo-old children use; (b) to evaluate the predictability of the less-than-eight-words cut-off used by Child Health Centres (CHCs) in Sweden at the present 18-mo check-up--an assessment based on parents' recall of their children's vocabulary. Methods: All failures of the less-than-eight-words criterion, corresponding to about 10% of 1000 children from a community-based study, were followed up within half a year after the first assessment. The follow-up instrument was an extensive, internationally well-known and structured parent questionnaire, standardized for Swedish children. Results: Almost half of the followed-ups performed below the 10th percentile and more than two-thirds were found below the 20th percentile. Thus, after a few months about one-third of the children had caught up to a fairly normal level of performance. Two of the children who had recovered performed above median. More relaxed cut-off criteria were applied ad hoc , reducing the proportion of children with a fast recovery.
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