| 1. |
- Bergh, Niklas, 1979, et al.
(författare)
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Invasive haemodynamics in de novo everolimus vs. calcineurin inhibitor heart transplant recipients
- 2020
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Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 7:2, s. 567-576
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Invasive haemodynamic profiles at rest and during exercise after heart transplantation (HTx) have never been described in a randomized trial where de novo everolimus (EVR)-based therapy with early calcineurin inhibitor (CNI) withdrawal has been compared with conventional CNI treatment. We report central invasive haemodynamic parameters at rest and exercise during a 3 year follow-up after HTx in a sub-study of the SCandiavian Heart transplant Everolimus De novo stUdy with earLy calcineurin inhibitor avoidancE trial. We hypothesized that the nephroprotective properties, the less development of cardiac allograft vasculopathy (CAV), and the antifibrotic properties of EVR, in comparison with CNI-based immunosuppression, would demonstrate favourable invasive haemodynamic profiles in patients at rest and during exercise. Methods and results: Ninety of 115 HTx recipients randomized to EVR or CNI treatment performed right heart catheterization at rest and 68 performed right heart catheterization at exercise up to 3 years after HTx. Haemodynamic profiles were compared between EVR and CNI treatment groups. Resting haemodynamics improved in both groups from pre-HTx to the first follow-up at 7–11 weeks post-HTx and thereafter remained unchanged up to 3 years of follow-up. During follow-up, cardiac reserve during exercise increased with higher levels of maximum heart rate (118 to 148 b.p.m., P < 0.001), mean arterial pressure (103 to 128 mmHg, P < 0.001), and cardiac output (10.3 to 12.2 l/min, P < 0.001). No significant differences in haemodynamic parameters were observed between the EVR and CNI groups at rest or exercise. Isolated post-capillary pulmonary hypertension (mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≥ 15 mmHg, and pulmonary vascular resistance <3) were measured in 11% of the patients at 7–11 weeks, 5% at 12 months, and 6% at 36 months after HTx. The EVR group had significantly better kidney function (76 mL/min/1 vs. 60 mL/min/1, P < 0.001) and reduced CAV (P < 0.01) but an increased rate of early biopsy-proven treated rejections (21.2% vs 5.7%, P < 0.01) compared with the CNI group at any time point. The differences in renal function, CAV, or early biopsy-proven treated acute rejections were not associated with altered haemodynamics. Conclusions: De novo EVR treatment with early CNI withdrawal compared with conventional CNI therapy did not result in differences in haemodynamics at rest or during exercise up to 3 years after HTx despite significant differences in renal function, reduced CAV, and number of early biopsy-proven treated rejections.
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| 2. |
- Broch, Kaspar, et al.
(författare)
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Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De-novo heart transplant recipients : Design of the randomized controlled EVOLVD trial
- 2020
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 34:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiac allograft vasculopathy (CAV) is characterized by diffuse thickening of the arterial intima. Statins reduce the incidence of CAV, but despite the use of statins, CAV remains one of the leading causes of long-term death after heart transplant. Inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK9) substantially reduce cholesterol levels but have not been tested in heart transplant recipients. Methods: The Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De-novo heart transplant recipients (EVOLVD) trial (ClinicalTrials.gov Identifier: NCT03734211) is a randomized, double-blind trial designed to test the effect of the PCSK9 inhibitor evolocumab on coronary intima thickness in heart transplant recipients. Adults who have received a cardiac transplant within the past 4-8 weeks are eligible. Exclusion criteria include an estimated glomerular filtration rate < 20 mL/min/1.73 m2, renal replacement therapy, or contraindications to coronary angiography with intravascular ultrasound. 130 patients will be randomized (1:1) to 12-month treatment with evolocumab or matching placebo. The primary endpoint is the coronary artery intima thickness as measured by intravascular ultrasound. Conclusion: The EVOLVD trial is a randomized clinical trial designed to show whether treatment with the PCSK9 inhibitor evolocumab can ameliorate CAV over the first year after heart transplant.
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| 3. |
- Gustafsson, Finn, et al.
(författare)
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Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients : Long-term Follow-up From the Randomized SCHEDULE Study
- 2020
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Ingår i: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1534-6080 .- 0041-1337. ; 104:1, s. 154-164
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A calcineurin inhibitor (CNI)-free immunosuppressive regimen has been demonstrated to improve renal function early after heart transplantation, but long-term outcome of such a strategy has not been well described. METHODS: In the randomized SCHEDULE trial, de novo heart transplant recipients received (1) everolimus with reduced-exposure CNI (cyclosporine) followed by CNI withdrawal at week 7-11 posttransplant or (2) standard-exposure cyclosporine, both with mycophenolate mofetil and corticosteroids; 95/115 randomized patients were followed up at 5-7 years posttransplant. RESULTS: Mean measured glomerular filtration rate was 74.7 mL/min and 62.4 mL/min with everolimus and CNI, respectively. The mean difference was in favor of everolimus by 11.8 mL/min in the intent-to-treat population (P = 0.004) and 17.2 mL/min in the per protocol population (n = 75; P < 0.001). From transplantation to last follow-up, the incidence of biopsy-proven acute rejection (BPAR) was 77% (37/48) and 66% (31/47) (P = 0.23) with treated BPAR in 50% and 23% (P < 0.01) in the everolimus and CNI groups, respectively; no episode led to hemodynamic compromise. Coronary allograft vasculopathy (CAV) assessed by coronary intravascular ultrasound was present in 53% (19/36) and 74% (26/35) of everolimus- and CNI-treated patients, respectively (P = 0.037). Graft dimensions and function were similar between the groups. Late adverse events were comparable. CONCLUSIONS: These results suggest that de novo heart transplant patients randomized to everolimus and low-dose CNI followed by CNI-free therapy maintain significantly better long-term renal function as well as significantly reduced CAV than patients randomized to standard CNI treatment. Increased BPAR in the everolimus group during year 1 did not impair long-term graft function.
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| 4. |
- Nelson, Lærke Marie, et al.
(författare)
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Mild acute cellular rejection and development of cardiac allograft vasculopathy assessed by intravascular ultrasound and coronary angiography in heart transplant recipients—a SCHEDULE trial substudy
- 2020
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 33:5, s. 517-528
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the association between mild acute cellular rejection (ACR) and the development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). Substudy of the SCHEDULE trial (n = 115), where de novo HTx recipients were randomized to (i) everolimus with early CNI elimination or (ii) CNI-based immunosuppression. Seventy-six patients (66%) were included based on matched intravascular ultrasound (IVUS) examinations at baseline and year 3 post-HTx. Biopsy-proven ACR within year 1 post-HTx was recorded and graded (1R, 2R, 3R). Development of CAV was assessed by IVUS and coronary angiography at year 3 post-HTx. Median age was 53 years (45–61), and 71% were male. ACR was recorded in 67%, and patients were grouped by rejection profile: no ACR (33%), only 1R (42%), and ≥2R (25%). Median ∆MIT (maximal intimal thickness)BL-3Y was not significantly different between groups (P = 0.84). The incidence of CAV was 49% by IVUS and 26% by coronary angiography with no significant differences between groups. No correlation was found between number of 1R and ∆MITBL-3Y (r = −0.025, P = 0.83). The number of 1R was not a significant predictor of ∆MITBL-3Y (P = 0.58), and no significant interaction with treatment was found (P = 0.98). The burden of mild ACR was not associated with CAV development.
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| 5. |
- Ng, Nawi, 1974, et al.
(författare)
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Sustainable Behavior Change for Health Supported by Person-Tailored, Adaptive, Risk-Aware Digital Coaching in a Social Context: Study Protocol for the STAR-C Research Programme
- 2021
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Ingår i: Frontiers in Public Health. - : Frontiers Media SA. - 2296-2565. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Vasterbotten Intervention Programme (VIP) in the Region Vasterbotten Sweden is one of the very few cardiovascular disease (CVD) prevention programmes globally that is integrated into routine primary health care. The VIP has been shown as a cost-effective intervention to significantly reduce CVD mortality. However, little is known about the effectiveness of a digital solution to tailor risk communication strategies for supporting behavioral change. STAR-C aims to develop and evaluate a technical platform for personalized digital coaching that will support behavioral change aimed at preventing CVD. Methods: STAR-C employs a mixed-methods design in seven multidisciplinary projects, which runs in two phases during 2019-2024: (i) a formative intervention design and development phase, and (ii) an intervention implementation and evaluation phase. In the 1st phase, STAR-C will model the trajectories of health behaviors and their impact on CVDs (Project 1), evaluate the role of the social environment and social networks on behavioral change (Project 2) and assess whether and how social media facilitates the spread of health information beyond targeted individuals and stimulates public engagement in health promotion (Project 3). The findings will be utilized in carrying out the iterative, user-centered design, and development of a person-tailored digital coaching platform (Project 4). In the 2nd phase, STAR-C will evaluate the implementation of the coaching programme and its effectiveness for promoting behavioral change and the spreading of health information across social networks and via social media (Project 5). The cost-effectiveness (Project 6) and ethical issues (Project 7) related to the coaching programme intervention will be evaluated. Discussion: The STAR-C research programme will address the knowledge and practice research gaps in the use of information technologies in health promotion and non-communicable disease (NCD) prevention programmes in order to narrow the health inequality gaps. Ethics: STAR-C has received approval from the Swedish Ethical Review Authority (Dnr. 2019-02924;2020-02985). Dissemination: The collaboration between Umea University and Region Vasterbotten will ensure the feasibility of STAR-C in the service delivery context. Results will be communicated with decision-makers at different levels of society, stakeholders from other regions and healthcare professional organizations, and through NGOs, local and social media platforms.
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| 6. |
- Andersson Ersman, Peter, et al.
(författare)
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Monolithic integration of display driver circuits and displays manufactured by screen printing
- 2020
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Ingår i: Flexible and Printed Electronics. - : Institute of Physics Publishing. - 2058-8585. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Here, we report all-screen printed display driver circuits, based on organic electrochemical transistors (OECTs), and their monolithic integration with organic electrochromic displays (OECDs). Both OECTs and OECDs operate at low voltages and have similar device architectures, and, notably, they rely on the very same electroactive material as well as on the same electrochemical switching mechanism. This then allows us to manufacture OECT-OECD circuits in a concurrent manufacturing process entirely based on screen printing methods. By taking advantage of the high current throughput capability of OECTs, we further demonstrate their ability to control the light emission in traditional light-emitting diodes (LEDs), where the actual LED addressing is achieved by an OECT-based decoder circuit. The possibility to monolithically integrate all-screen printed OECTs and OECDs on flexible plastic foils paves the way for distributed smart sensor labels and similar Internet of Things applications.
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| 7. |
- Asayama, Shinichiro, et al.
(författare)
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Three institutional pathways to envision the future of the IPCC
- 2023
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Ingår i: Nature Climate Change. - : Nature Portfolio. - 1758-678X .- 1758-6798. ; 13:9, s. 877-880
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Tidskriftsartikel (refereegranskat)abstract
- The IPCC has been successful at building its scientific authority, but it will require institutional reform for staying relevant to new and changing political contexts. Exploring a range of alternative future pathways for the IPCC can help guide crucial decisions about redefining its purpose.
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| 8. |
- Badam, Tejaswi, et al.
(författare)
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CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases
- 2022
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Ingår i: Epigenetics. - : Taylor & Francis Group. - 1559-2294 .- 1559-2308. ; 17:9, s. 1040-1055
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases.
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| 9. |
- Blomqvist, Göran, 1963-, et al.
(författare)
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Microplastics in snow in urban traffic environments
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Microplastics from road traffic, mainly from tyre wear, are globally considered to be one of the largest sources of microplastic contamination in the environment. Plastics can either be deposited in the road vicinity, at the roadside and in ditches or spread via stormwater and air to the environment and receiving water bodies. In cold climates, microplastics, as well as other traffic-related pollutants, can be temporarily stored in snow and ice on and around roads and streets. The location and concentration of these pollutants is influenced by winter operations, where ploughing and skid control contribute to redistribution, and by melting and compaction of ice and snow. This creates reservoirs of microplastics and other pollutants, which are released into stormwater or surrounding soil during thaws, but also provides an opportunity to reduce the spread of microplastics by managing snow and ice appropriately. In the present report, a case study of microplastics in snow has been carried out in the municipality of Karlstad in Sweden, to get an idea of the potential variation, both in terms of concentration and total amounts in relation to traffic and the location of the sampling in the street environment. Microplastics have been analysed by pyrolysis GC/MS to identify tyre-specific polymers in combination with eight commonly occurring plastic types. In addition, six municipalities in different parts of the country responded to a questionnaire on microplastics in snow and urban snowmelt management. The results show that microplastics related to tyre wear (rubber polymers) tend to be present in higher concentrations on and near the carriageway. Other plastics show a less clear link to traffic. Along a salted bicycle lane, an elevated level of polypropylene, from which the brush of the sweep-salting machine is made, could be detected in the surface layer of the snow. In general, knowledge about microplastics in urban snow is low in the municipalities that responded to the survey.
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| 10. |
- Engquist, Isak, et al.
(författare)
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Highly conducting nanographite-filled paper fabricated via standard papermaking techniques
- 2020
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society. - 1944-8244 .- 1944-8252. ; 12:43, s. 48828-48835
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Tidskriftsartikel (refereegranskat)abstract
- Eco-friendly and cost-effective materials and processes to manufacture functional substrates are crucial to further advance the area of printed electronics. One potential key component in the printed electronics platform is an electrically functionalized paper, produced by simply mixing common cellulosic pulp fibers with high-performance electroactive materials. Herein, an electronic paper including nanographite has been prepared using a standardized and scalable papermaking technique. No retention aid was needed to achieve a conducting nanographite loading as high as 50 wt %. The spontaneous retention that provides the integrity and stability of the nanographite paper, likely originates partially from an observed water-stable adhesion of nanographite flakes onto the fiber surfaces. The resulting paper exhibits excellent electrical characteristics, such as an in-plane conductivity of 107 S/cm and an areal capacitance of 9.2 mF/cm2, and was explored as the back-electrode in printed electrochromic displays.
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| 11. |
- Garre, Elena, 1978, et al.
(författare)
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Breast Cancer Patient-Derived Scaffolds Can Expose Unique Individual Cancer Progressing Properties of the Cancer Microenvironment Associated with Clinical Characteristics
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Despite huge progress in cancer diagnostics and medicine we still lack optimal cancer treatments for patients with aggressive diseases. This problem can be influenced by the biological heterogeneity of cancer cells as well as poorly understood cancer promoting effects of the cancer microenvironment being an important part of the cancer niche. In this study we have specifically monitored the activity of the cancer microenvironment in breast cancer patients using cell-free scaffolds repopulated with reporter cancer cells sensing the activity of the patient environment. The data show that scaffold induced changes in epithelial-mesenchymal transition and pluripotency markers were linked to clinical and prognostic properties of the original cancer and the information was even more precise when matching estrogen receptor status in our system. The findings highlight that patient-derived scaffolds uncover important information about varying malignant promoting properties in the cancer niche and can be used as a complementary diagnostic tool. Breast cancer is a heterogeneous disease in terms of cellular and structural composition, and besides acquired aggressive properties in the cancer cell population, the surrounding tumor microenvironment can affect disease progression and clinical behaviours. To specifically decode the clinical relevance of the cancer promoting effects of individual tumor microenvironments, we performed a comprehensive test of 110 breast cancer samples using a recently established in vivo-like 3D cell culture platform based on patient-derived scaffolds (PDSs). Cell-free PDSs were recellularized with three breast cancer cell lines and adaptation to the different patient-based microenvironments was monitored by quantitative PCR. Substantial variability in gene expression between individual PDS cultures from different patients was observed, as well as between different cell lines. Interestingly, specific gene expression changes in the PDS cultures were significantly linked to prognostic features and clinical information from the original cancer. This link was even more pronounced when ER alpha-status of cell lines and PDSs matched. The results support that PDSs cultures, including a cancer cell line of relevant origin, can monitor the activity of the tumor microenvironment and reveal unique information about the malignancy-inducing properties of the individual cancer niche and serve as a future complementary diagnostic tool for breast cancer.
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| 12. |
- Gustafsson, Anna, et al.
(författare)
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Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional cell culture platforms based on decellularised patient-based microenvironments provide in vivo-like growth conditions allowing cancer cells to interact with intact structures and components of the surrounding tissue. A patient-derived scaffold (PDS) model was therefore evaluated as a testing platform for the endocrine therapies (Z)-4-Hydroxytamoxifen (4OHT) and fulvestrant as well as the CDK4/6-inhibitor palbociclib, monitoring the treatment responses in breast cancer cell lines MCF7 and T47D adapted to the patient-based microenvironments. MCF7 cells growing in PDSs showed increased resistance to 4OHT and fulvestrant treatment (100- and 20-fold) compared to 2D cultures. Quantitative PCR analyses of endocrine treated cancer cells in PDSs revealed upregulation of pluripotency markers further supported by increased self-renewal capacity in sphere formation assays. When comparing different 3D growth platforms including PDS, matrigel, gelatin sponges and 3D-printed hydrogels, 3D based cultures showed slightly varying responses to fulvestrant and palbociclib whereas PDS and matrigel cultures showed more similar gene expression profiles for 4OHT treatment compared to the other platforms. The results support that the PDS technique maximized to provide a multitude of smaller functional PDS replicates from each primary breast cancer, is an up-scalable patient-derived drug-testing platform available for gene expression profiling and downstream functional assays.
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| 13. |
- Gustafsson, Mats, 1966-, et al.
(författare)
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Effekt på dammförråd och PM10-halter av tunnelstädning
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Driftmetoder mot höga partikelhalter orsakade av vägdamm i gatu- och vägmiljöer har under lång tid utvärderats i vanlig gatumiljö. Resultaten är dock ofta förhållandevis svårtolkade på grund av inverkan av meteorologi och omfattande inblandning från andra partikelkällor än just den gata som studeras. För att komma vidare med mer detaljerade studier av metodik och strategi och för att få mer lättolkade resultat, kan studierna förflyttas in i vägtunnlar. Dessa har en mer kontrollerad miljö med små meteorologiska variationer och en tydlig och helt dominerande partikelkälla – trafiken. Projektet ”Utvärdering av tekniker och strategier för damningsminimerad väg- och gatudrift i tunnelmiljö” avsåg att utvärdera olika varianter av damningsminimerande åtgärder i Södra länken, med fokus på dammbindningsstrategier och städning. På grund av säkerhetsmotiv fick vi inte möjlighet att testa olika dammbindningsstrategier varför projektet har fokuserat enbart på städning och i föreliggande rapport presenteras resultatet från två utvärderingar; en genomförd i januari, då partikelkällorna är starka och dammförrådet stort och en i juni, då källorna är svaga och dammförrådet litet. I januari städade först den så kallade supersugen och sedan Disa-Clean och i juni städade maskinerna i omvänd ordning. För utvärdering av effekterna användes VTI:s vägdammsprovtagare WDS II och luftkvalitetsdata från den mätstation i tunneln som testerna genomfördes vid. Resultaten visar att dammförrådet minskas mer i kombinationen i januari, det vill säga av högtryckstvätt följt av vakuumsug, än tvärtom, som i juni. Även om PM10-data är mer svårtolkade finns indikationer på att halterna i januari minskar något, medan halterna i juni snarare ökar efter städinsatsen. Resultatet att högtryckstvätt följt av vakuumsug fungerar väl för att städa bort vägdamm styrks av snarlika studier genomförda i Norge med samma utvärderingsteknik (WDS).
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| 14. |
- Gustafsson, Mats, 1966-, et al.
(författare)
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Street sweeping : a source to, or measure against, microplastic emissions?
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Microplastics from road traffic are mainly caused by tyre wear, which is globally considered to be one of the largest sources of microplastics. Tyre wear particles have been shown to occur in all media (road surface, air, soil, stormwater, lakes and rivers and coastal sediments) and are dispersed both by runoff and by atmospheric transport. To reduce the dispersion and possible effects of road traffic microplastics emissions, measures can be taken to prevent the formation of particles and to prevent their dispersion through treatment measures. This study focuses on street cleaning as a method to reduce emissions, but as many street cleaning methods are based on the use of plastic brushes, cleaning as a source of microplastics has also been considered. The study was carried out in collaboration with the municipality of Karlstad and included a review of how street cleaning is carried out in Karlstad in relation to uptake and dispersion of microplastics. Furthermore, a comparison between two cleaning machines (elevator and vacuum) has been made and a monitoring of microplastic amounts on the road surface during different phases of spring sweeping has been carried out. In order to estimate the amount of plastic torn from the brushes, weighing of the brushes has been carried out. In order to gain knowledge about the work of more municipalities on street sweeping from a microplastic perspective, a questionnaire study was sent out to six municipalities in different parts of the country. The results show that both cleaning machines have the capacity to reduce the amount of microplastics on the road surface. However, during spring sweeping, the amount of polypropylene (the most common plastic in the brushes) on the road surface increases. The distribution of analysed plastics differs significantly between the road surface and the material collected by the machines. This is thought to be due to the fact that the machines mainly collect coarser fractions, while finer fractions remain on the road surface. Knowledge of, and thus consideration of, microplastics in relation to operational measures such as street cleaning is currently low among the municipalities surveyed, but awareness exists, as does the need for support in implementing possible measures. The present study shows a complex problem picture and represents a first step in understanding how street cleaning can be used as a measure, but also indicates that the wear of plastic brushes leads to a net emission of microplastics.
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| 15. |
- Gustafsson, Malin, et al.
(författare)
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Unlocking the secret life of blue mussels: Exploring connectivity in the Skagerrak through biophysical modeling and population genomics
- 2024
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Ingår i: Evolutionary Applications. - 1752-4571. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of functional dispersal barriers in the marine environment can be used to inform a wide variety of management actions, such as marine spatial planning, restoration efforts, fisheries regulations, and invasive species management. Locations and causes of dispersal barriers can be studied through various methods, including movement tracking, biophysical modeling, demographic models, and genetics. Combining methods illustrating potential dispersal, such as biophysical modeling, with realized dispersal through, e.g., genetic connectivity estimates, provides particularly useful information for teasing apart potential causes of observed barriers. In this study, we focus on blue mussels (Mytilus edulis) in the Skagerrak—a marginal sea connected to the North Sea in Northern Europe—and combine biophysical models of larval dispersal with genomic data to infer locations and causes of dispersal barriers in the area. Results from both methods agree; patterns of ocean currents are a major structuring factor in the area. We find a complex pattern of source-sink dynamics with several dispersal barriers and show that some areas can be isolated despite an overall high dispersal capability. Finally, we translate our finding into management advice that can be used to sustainably manage this ecologically and economically important species in the future.
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| 16. |
- Hjortshøj, Cristel S., et al.
(författare)
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Outcome after heart-lung or lung transplantation in patients with Eisenmenger syndrome
- 2020
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 106:2, s. 127-132
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The optimal timing for transplantation is unclear in patients with Eisenmenger syndrome (ES). We investigated post-transplantation survival and transplantation-specific morbidity after heart-lung transplantation (HLTx) or lung transplantation (LTx) in a cohort of Nordic patients with ES to aid decision-making for scheduling transplantation. Methods: We performed a retrospective, descriptive, population-based study of patients with ES who underwent transplantation from 1985 to 2012. Results: Among 714 patients with ES in the Nordic region, 63 (9%) underwent transplantation. The median age at transplantation was 31.9 (IQR 21.1-42.3) years. Within 30 days after transplantation, seven patients (11%) died. The median survival was 12.0 (95% CI 7.6 to 16.4) years and the overall 1-year, 5-year, 10-year and 15-year survival rates were 84.1%, 69.7%, 55.8% and 40.6%, respectively. For patients alive 1 year post-transplantation, the median conditional survival was 14.8 years (95% CI 8.0 to 21.8), with 5-year, 10-year and 15-year survival rates of 83.3%, 67.2% and 50.0%, respectively. There was no difference in median survival after HLTx (n=57) and LTx (n=6) (14.9 vs 10.6 years, p=0.718). Median cardiac allograft vasculopathy, bronchiolitis obliterans syndrome and dialysis/kidney transplantation-free survival rates were 11.2 (95% CI 7.8 to 14.6), 6.9 (95% CI 2.6 to 11.1) and 11.2 (95% CI 8.8 to 13.7) years, respectively. The leading causes of death after the perioperative period were infection (36.7%), bronchiolitis obliterans syndrome (23.3%) and heart failure (13.3%). Conclusions: This study shows that satisfactory post-transplantation survival, comparable with contemporary HTx and LTx data, without severe comorbidities such as cardiac allograft vasculopathy, bronchiolitis obliterans syndrome and dialysis, is achievable in patients with ES, with a conditional survival of nearly 15 years.
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| 17. |
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| 18. |
- Jostrup, Erica, et al.
(författare)
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Effects of stochastic vestibular stimulation on cognitive performance in children with ADHD
- 2023
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Ingår i: Experimental Brain Research. - 0014-4819. ; 241, s. 2693-2703
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Tidskriftsartikel (refereegranskat)abstract
- Previous work has shown that exposure to auditory white noise (WN) can improve cognitive performance in children with ADHD, but it is unknown whether this improvement generalizes to other sensory modalities. To address this knowledge gap, we tested the effect of Stochastic Vestibular Stimulation (SVS) on cognitive performance and reaction time (RT) variability in two groups: children with ADHD and typically developing children (TDC). Children with ADHD (N=42) and TDC (N=28) performed three cognitive tasks (Spanboard, Word Recall and N-back tasks) at two different occasions, with and without exposure to SVS, in a double blinded design. The results showed no main effects of SVS on neither performance nor RT variability for children in any of the groups, and no interactions between SVS and group. Based on these results we conclude that, using our stimulation protocol, the positive effects of WN exposure on cognition in children with ADHD do not generalize to Stochastic Vestibular Stimulation.
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| 19. |
- Järlskog, Ida, 1991-, et al.
(författare)
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Microplastic emissions from wear of road markings : overview and assessment for Swedish conditions
- 2024
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Traffic-derived microplastics, i.e., tyre wear particles, wear from polymer-modified bitumen, and road marking wear are assumed to be one of the largest sources of microplastic contamination. Road markings as a source of microplastic emissions are still a rather unexplored research area, and there arestill large knowledge gaps regarding annual wear, concentrations in different environments, and eventual risks for flora and fauna. This report has aimed to estimate the annual wear of road markings in Sweden and to investigate the knowledge on a municipal level related to road markings and wear. In addition, road markings from different traffic environments have been documented throughout the project, and the wear on these has been investigated. The project has also aimed to clarify which processes that contribute to the wear of road markings, as well as to map out which types of road markings that are subjected to specific types of wear. A survey was sent out to all municipalities in Sweden with questions about the type of road marking material, annual purchases, budget, wear rate, wear-prone traffic environments, and main causes of wear on road markings. In total, we received answers from 223 out of 290 municipalities. The result from the survey indicates that transverse road markings (e.g., yield lines, and pedestrian crossings), driving lines, and lines within roundabouts wear fast and that winter maintenance, use of studded tyres, and traffic loads are the main causes to wear. In general, the knowledge was low regarding annual purchases/applied amounts and many of the municipals mentioned that they do not have the budget to maintain road markings to a desirable extent. For upcoming procurements, we recommend the municipalities to make higher demands on the quality of the material, as well as adhesion and maintenance which might result in lower costs, a need for less material, and thereby also a reduced wear.
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| 20. |
- Kilbo Edlund, Karl, et al.
(författare)
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High-resolution dispersion modelling of PM2.5, PM10, NOx and NO2 exposure in metropolitan areas in Sweden 2000‒2018 – large health gains due to decreased population exposure
- 2024
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Ingår i: Air Quality, Atmosphere and Health. - 1873-9318 .- 1873-9326.
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Tidskriftsartikel (refereegranskat)abstract
- Ambient air pollution remains the major environmental cause of disease. Accurate assessment of population exposure and small-scale spatial exposure variations over long time periods is essential for epidemiological studies. We estimated annual exposure to fine and coarse particulate matter (PM2.5, PM10), and nitrogen oxides (NOx, NO2) with high spatial resolution to examine time trends 2000‒2018, compliance with the WHO Air Quality Guidelines, and assess the health impact. The modelling area covered six metropolitan areas in Sweden with a combined population of 5.5 million. Long-range transported air pollutants were modelled using a chemical transport model with bias correction, and locally emitted air pollutants using source-specific Gaussian-type dispersion models at resolutions up to 50 × 50m. The modelled concentrations were validated using quality-controlled monitoring data. Lastly, we estimated the reduction in mortality associated with the decrease in population exposure. The validity of modelled air pollutant concentrations was good (R2 for PM2.5 0.84, PM10 0.61, and NOx 0.87). Air pollution exposure decreased substantially, from a population weighted mean exposure to PM2.5 of 12.2µgm−3 in 2000 to 5.4µgm−3 in 2018. We estimated that the decreased exposure was associated with a reduction of 2719 (95% CI 2046–3055) premature deaths annually. However, in 2018, 65%, 8%, and 42% of residents in the modelled areas were still exposed to PM2.5, PM10, or NO2 levels, respectively, that exceeded the current WHO Air Quality Guidelines for annual average exposure. This emphasises the potential public health benefits of reductions in air pollution emissions.
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| 21. |
- Klauson, Artur, et al.
(författare)
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A case study of printed circuit boards recycling by disintegrator technology
- 2024
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Ingår i: AIP Conference Proceedings. - 1551-7616 .- 0094-243X. ; 2989:1
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Konferensbidrag (refereegranskat)abstract
- The constant accumulation of Waste Electric and Electronic Equipment (WEEE) at an accelerating pace pose a threat to the environment and people. On the other hand, the WEEE and specifically their component Waste Printed Circuit Boards (WPCBs) are rich in Precious Metals (PMs) and Base Metals (BMs), more than ten times their content in natural ores. Such an opportunity has already attracted the minerals processing industry (e.g., metallurgical companies) to the WEEE recycling problem solving. However, analogically to virgin mining, the presently more or less worthless parts of WPCBs also pose a health threat since they contain toxic pollutants. The key to efficient metal recovery from WPCBs is selective processes for fragmentation and separation which are accurate for both metals and non-metals. Fragmentation is a prerequisite for accurate separation. The closed-circuit grinding (size reduction) method is preferred in the case of WPCB processing, and a prospective technology for carrying it out is High Intensity Impact Milling (HIIM). In this paper, the HIIM (disintegrator) technology is compared with commonly known technologies for selective WPCB size reduction. The HIIM demonstrated possibility to adjust the size reduction process to different materials and replication of the initial results obtained under laboratory conditions.
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| 22. |
- Landberg, Göran, 1963, et al.
(författare)
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Characterization of cell-free breast cancer patient-derived scaffolds using liquid chromatography-mass spectrometry/mass spectrometry data and RNA sequencing data
- 2020
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Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Patient-derived scaffolds (PDSs) generated from primary breast cancer tumors can be used to model the tumor microenvironment in vitro . Patient-derived scaffolds are generated by repeated detergent washing, removing all cells. Here, we analyzed the protein composition of 15 decellularized PDSs using liquid chromatography-mass spectrometry/mass spectrometry. One hundred forty-three proteins were detected and their relative abundance was calculated using a reference sample generated from all PDSs. We performed heatmap analysis of all the detected proteins to display their expression patterns across different PDSs together with pathway enrichment analysis to reveal which processes that were connected to PDS protein composition. This protein dataset together with clinical information is useful to investigators studying the microenvironment of breast cancers. Further, after repopulating PDSs with either MCF7 or MDA-MB-231 cells, we quantified their gene expression profiles using RNA sequencing. These data were also compared to cells cultured in conventional 2D conditions, as well as to cells cultured as xenografts in immune-deficient mice. We investigated the overlap of genes regulated between these different culture conditions and performed pathway enrichment analysis of genes regulated by both PDS and xenograft cultures compared to 2D in both cell lines to describe common processes associated with both culture conditions. Apart from our described analyses of these systems, these data are useful when comparing different experimental model systems. Downstream data analyses and interpretations can be found in the research article "Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment" [1] . (C) 2020 The Authors. Published by Elsevier Inc.
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| 23. |
- Landberg, Göran, et al.
(författare)
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Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment
- 2020
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Ingår i: Biomaterials. - : Elsevier Ltd. - 0142-9612 .- 1878-5905. ; 235
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Tidskriftsartikel (refereegranskat)abstract
- Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment. © 2019 The Authors
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| 24. |
- Larsson, Stefan, et al.
(författare)
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Bedömning av status för nationellt förvaltade fisk- och skaldjursbestånd
- 2024
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Institutionen för akvatiska resurser vid Sveriges lantbruksuniversitet (SLU Aqua) presenterar årligen statusbedömningar för nationellt förvaltade fisk- och skaldjursbestånd i svenska vatten på webbportalen www.fiskbarometern.se. Fiskbarometerns statusbedömningar av fisk- och skaldjursbestånd, utgör ett viktigt underlag för hållbart nyttjande, bevarandeåtgärder och uppföljning inom fisk-, vatten- och miljöförvaltningen. I denna rapport redovisas metodiken för dessa statusbedömningar. Metodiken bidrar till en standardiserad och kvalitetssäkrad bedömningsprocess som är transparent och som vilar på vetenskaplig grund. För de flesta bestånd i Fiskbarometern baseras bedömningen på indikatorer indelade i dödlighet, biomassa/abundans och storleks-/åldersstruktur, vilka motsvarar Havsmiljödirektivets tre kriterier för bedömning av kommersiellt nyttjade bestånd (2008/56/EC). Baserat på sammanvägningen av de tre kriterierna ges respektive bestånd sedan en av fem möjliga statusbedömningar:• kan ej bedömas • mycket sannolikt inte inom biologiskt säkra gränser • sannolikt inte inom biologiskt säkra gränser • sannolikt inom biologiskt säkra gränser • mycket sannolikt inom biologiskt säkra gränserFör några nationellt förvaltade bestånd finns eller pågår arbete med att utveckla analytiska beståndsmodeller. I den här rapporten presenteras riktlinjer för kvalitetssäkring och tillämpning av dem översiktligt, men den vetenskapliga granskningen av sådana modeller hanteras separat inom en process som kallas riktmärkning, vilken inte beskrivs i denna rapport. Utfall från dessa modeller översätts till samma statuskategorier som för de indikatorbaserade bedömningarna.
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| 25. |
- Leiva, Maria Carmen, et al.
(författare)
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Breast cancer patient-derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments
- 2021
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Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541 .- 1097-4652. ; 236:6, s. 4709-4724
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a heterogeneous disease where the tumor microenvironment, including extracellular components, plays a crucial role in tumor progression, potentially modulating treatment response. Different approaches have been used to develop three-dimensional models able to recapitulate the complexity of the extracellular matrix. Here, we use cell-free patient-derived scaffolds (PDSs) generated from breast cancer samples that were recellularized with cancer cell lines as an in vivo-like culture system for drug testing. We show that PDS cultured MCF7 cancer cells increased their resistance against the front-line chemotherapy drugs 5-fluorouracil, doxorubicin and paclitaxel in comparison to traditional two-dimensional cell cultures. The gene expression of the environmentally adapted cancer cells was modulated in different ways depending on the drug and the concentration used. High doses of doxorubicin reduced cancer stem cell features, whereas 5-fluorouracil increased stemness and decreased the proliferative phenotype. By using PDSs repopulated with other breast cancer cell lines, T-47D and MDA-MB-231, we observed both general and cell line specific drug responses. In summary, PDSs can be used to examine the extracellular matrix influence on cancer drug responses and for testing novel compounds in in vivo-like microenvironments.
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| 26. |
- Leiva, Maria Carmen, et al.
(författare)
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Patient-derived scaffolds representing breast cancer microenvironments influence chemotherapy responses in adapted cancer cells consistent with clinical features.
- 2023
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Ingår i: Journal of translational medicine. - 1479-5876. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- The tumor microenvironment clearly influences cancer progressing properties but less is known about how individual cancer microenvironments potentially moderate cancer treatment effects. By cultivating and treating cancer cell lines in patient-derived scaffolds (PDS), the impact of specific characteristics of individual cancer microenvironments can be incorporated in human-like growth modelling and cancer drug treatment testing.PDSs from 78 biobanked primary breast cancer samples with known patient outcomes, were prepared and repopulated with donor breast cancer cell lines, followed by treatment with 5-fluorouracil or doxorubicin after cellular adaption to the various microenvironments. Cancer cell responses to the treatments were monitored by RNA-analyses, highlighting changes in gene sets representative for crucial tumor biological processes such as proliferation, cancer stem cell features, differentiation and epithelial-to-mesenchymal transition.The chemotherapy treatments induced distinct gene expression patterns in adapted cancer cells with clusters of similar treatment responses depending on the patient-derived cancer microenvironment used as growth substrate. The doxorubicin treatment displayed a favorable gene signature among surviving cancer cells with low proliferation (MKI67) and pluripotency features (NANOG, POU5F1), in comparison to 5-fluorouracil showing low proliferation but increased pluripotency. Specific gene changes monitored post-treatment were also significantly correlated with clinical data, including histological grade (NANOG), lymph node metastasis (SLUG) and disease-free patient survival (CD44).This laboratory-based treatment study using patient-derived scaffolds repopulated with cancer cell lines, clearly illustrates that the human cancer microenvironment influences chemotherapy responses. The differences in treatment responses defined by scaffold-cultures have potential prognostic and treatment predictive values.
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| 27. |
- Lundberg, Joacim, 1991-, et al.
(författare)
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Temporal Variation of Road Dust Load and Its Size Distribution—a Comparative Study of a Porous and a Dense Pavement
- 2020
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Ingår i: Water, Air and Soil Pollution. - : Springer Science and Business Media Deutschland GmbH. - 0049-6979 .- 1573-2932. ; 231:12
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Tidskriftsartikel (refereegranskat)abstract
- Resuspension of road dust contributes to air quality issues with resulting health impacts. Limited studies imply that porous pavements can initially mitigate PM10 emissions by acting as a dust trap, but the abrasion wear generates road dust and thus accelerates the clogging processes. In addition, knowledge regarding the impact of pavement types on road dust load dynamics is limited. Road traffic noise can be mitigated using porous pavements, but the use of studded tyres increases the abrasion wear of the pavement as well as increasing the noise emission. Due to this durability problem, porous pavements are rarely used in the Nordic countries where, instead, dense pavements which are abrasion resistant are more common. Linköping municipality, in Sweden, constructed a porous pavement to mitigate road traffic noise. This led to the opportunity to investigate the temporal variation of the dust load dynamics and inherent size distributions over the winter and spring in comparison to those of an adjacent dense pavement. Results, when using the wet dust sampler (WDS) method, showed similar dust load dynamics for the dense and porous pavements. The results were also compared to previous studies using the same method on different dense pavements in Stockholm, Sweden. All locations showed a seasonal variation with higher dust loads during winter and early spring and declining loads towards summer. The size distributions were more complex for the wheel tracks at the porous pavement, having primarily properties of a mixture model compared to the simple size distributions for the dense pavement. On the other hand, the dust load and size distribution were more similar between the porous and dense pavements regarding loads and shapes, indicating a less pronounced but similar behaviour between the surfaces outside of the wheel tracks.
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| 28. |
- Martens, Jannik, et al.
(författare)
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CASCADE - The Circum-Arctic Sediment CArbon DatabasE
- 2021
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 13:6, s. 2561-2572
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Tidskriftsartikel (refereegranskat)abstract
- Biogeochemical cycling in the semi-enclosed Arctic Ocean is strongly influenced by land-ocean transport of carbon and other elements and is vulnerable to environmental and climate changes. Sediments of the Arctic Ocean are an important part of biogeochemical cycling in the Arctic and provide the opportunity to study present and historical input and the fate of organic matter (e.g., through permafrost thawing). Comprehensive sedimentary records are required to compare differences between the Arctic regions and to study Arctic biogeochemical budgets. To this end, the Circum-Arctic Sediment CArbon DatabasE (CASCADE) was established to curate data primarily on concentrations of organic carbon (OC) and OC isotopes (delta C-13, Delta C-14) yet also on total N (TN) as well as terrigenous biomarkers and other sediment geochemical and physical properties. This new database builds on the published literature and earlier unpublished records through an extensive international community collaboration. This paper describes the establishment, structure and current status of CASCADE. The first public version includes OC concentrations in surface sediments at 4244 oceanographic stations including 2317 with TN concentrations, 1555 with delta C-13-OC values and 268 with Delta C-14-OC values and 653 records with quantified terrigenous biomarkers (high-molecular-weight n-alkanes, n-alkanoic acids and lignin phenols). CASCADE also includes data from 326 sediment cores, retrieved by shallow box or multi-coring, deep gravity/piston coring, or sea-bottom drilling. The comprehensive dataset reveals large-scale features of both OC content and OC sources between the shelf sea recipients. This offers insight into release of pre-aged terrigenous OC to the East Siberian Arctic shelf and younger terrigenous OC to the Kara Sea. Circum-Arctic sediments thereby reveal patterns of terrestrial OC remobilization and provide clues about thawing of permafrost. CASCADE enables synoptic analysis of OC in Arctic Ocean sediments and facilitates a wide array of future empirical and modeling studies of the Arctic carbon cycle. The database is openly and freely available online (https://doi.org/10.17043/cascade; Martens et al., 2021), is provided in various machine-readable data formats (data tables, GIS shapefile, GIS raster), and also provides ways for contributing data for future CASCADE versions. We will continuously update CASCADE with newly published and contributed data over the foreseeable future as part of the database management of the Bolin Centre for Climate Research at Stockholm University.
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| 29. |
- Martínez-Carranza, Markel, 1992-, et al.
(författare)
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Synaptotagmin Binding to Botulinum Neurotoxins
- 2020
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 59:4, s. 491-498
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Tidskriftsartikel (refereegranskat)abstract
- Botulinum neurotoxins (BoNTs) are exceptionally toxic proteins that cause paralysis but are also extensively used as treatment for various medical conditions. Most BoNTs bind two receptors on neuronal cells, namely, a ganglioside and a protein receptor. Differences in the sequence between the protein receptors from different species can impact the binding affinity and toxicity of the BoNTs. Here we have investigated how BoNT/B, /DC, and /G, all three toxins that utilize synaptotagmin I and II (Syt-I and Syt-II, respectively) as their protein receptors, bind to Syt-I and -II of mouse/rat, bovine, and human origin by isothermal titration calorimetry analysis. BoNT/G had the highest affinity for human Syt-I, and BoNT/DC had the highest affinity for bovine Syt-II. As expected, BoNT/B, /DC, and /G showed very low levels of binding to human Syt-II. Furthermore, we carried out saturation transfer difference (STD) and STD-TOCSY NMR experiments that revealed the region of the Syt peptide in direct contact with BoNT/G, which demonstrate that BoNT/G recognizes the Syt peptide in a model similar to that in the established BoNT/B-Syt-II complex. Our analyses also revealed that regions outside the Syt peptide’s toxin-binding region are important for the helicity of the peptide and, therefore, the binding affinity.
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| 30. |
- Nosratabadi, Ali Reza, et al.
(författare)
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Airway contraction and cytokine release in isolated rat lungs induced by wear particles from the road and tire interface and road vehicle brakes
- 2023
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Ingår i: Inhalation Toxicology. - : Taylor & Francis. - 0895-8378 .- 1091-7691. ; 35:13-14, s. 309-323
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Tidskriftsartikel (refereegranskat)abstract
- The dominant road traffic particle sources are wear particles from the road and tire interface, and from vehicle brake pads. The aim of this work was to investigate the effect of road and brake wear particles on pulmonary function and biomarkers in isolated perfused rat lungs. Particles were sampled from the studded tire wear of three road pavements containing different rock materials in a road simulator; and from the wear of two brake pad materials using a pin-on-disk machine. Isolated rat lungs inhaled the coarse and fine fractions of the sampled particles resulting in an estimated total particle lung dose of 50 μg. The tidal volume (TV) was measured during the particle exposure and the following 50 min. Perfusate and BALF were analyzed for the cytokines TNF, CXCL1 and CCL3. The TV of lungs exposed to rock materials was significantly reduced after 25 min of exposure compared to the controls, for quartzite already after 4 min. The particles of the heavy-duty brake pads had no effect on the TV. Brake particles resulted in a significant elevation of CXCL1 in the perfusate. Brake particles showed significant elevations of all three measured cytokines, and quartzite showed a significant elevation of TNF in BALF. The study shows that the toxic effect on lungs exposed to airborne particles can be investigated using measurements of tidal volume. Furthermore, the study shows that the choice of rock material in road pavements has the potential to affect the toxicity of road wear PM10.
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| 31. |
- Persson, Emma, 1989, et al.
(författare)
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Patient-derived scaffolds influence secretion profiles in cancer cells mirroring clinical features and breast cancer subtypes
- 2021
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Ingår i: Cell Communication and Signaling. - : Springer Science and Business Media LLC. - 1478-811X. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBreast cancer is a common malignancy with varying clinical behaviors and for the more aggressive subtypes, novel and more efficient therapeutic approaches are needed. Qualities of the tumor microenvironment as well as cancer cell secretion have independently been associated with malignant clinical behaviors and a better understanding of the interplay between these two features could potentially reveal novel targetable key events linked to cancer progression.MethodsA newly developed human derived in vivo-like growth system, consisting of decellularized patient-derived scaffolds (PDSs) recellularized with standardized breast cancer cell lines (MCF7 and MDA-MB-231), were used to analyze how 63 individual patient specific microenvironments influenced secretion determined by proximity extension assays including 184 proteins and how these relate to clinical outcome.ResultsThe secretome from cancer cells in PDS cultures varied distinctly from cells grown as standard monolayers and besides a general increase in secretion from PDS cultures, several secreted proteins were only detectable in PDSs. Monolayer cells treated with conditioned media from PDS cultures, further showed increased mammosphere formation demonstrating a cancer stem cell activating function of the PDS culture induced secretion. The detailed secretomic profiles from MCF7s growing on 57 individual PDSs differed markedly but unsupervised clustering generated three separate groups having similar secretion profiles that significantly correlated to different clinical behaviors. The secretomic profile that associated with cancer relapse and high grade breast cancer showed induced secretion of the proteins IL-6, CCL2 and PAI-1, all linked to cancer stem cell activation, metastasis and priming of the pre-metastatic niche. Cancer promoting pathways such as "Suppress tumor immunity" and "Vascular and tissue remodeling" was also linked to this more malignant secretion cluster.ConclusionPDSs repopulated with cancer cells can be used to assess how cancer secretion is effected by specific and varying microenvironments. More malignant secretion patterns induced by specific patient based cancer microenvironments could further be identified pinpointing novel therapeutic opportunities targeting micro environmentally induced cancer progression via secretion of potent cytokines.
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| 32. |
- Pyko, Andrei, et al.
(författare)
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Long-Term Exposure to Transportation Noise and Ischemic Heart Disease: A Pooled Analysis of Nine Scandinavian Cohorts.
- 2023
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Ingår i: Environmental health perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 131:1
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Tidskriftsartikel (refereegranskat)abstract
- Transportation noise may induce cardiovascular disease, but the public health implications are unclear.The study aimed to assess exposure-response relationships for different transportation noise sources and ischemic heart disease (IHD), including subtypes.Pooled analyses were performed of nine cohorts from Denmark and Sweden, together including 132,801 subjects. Time-weighted long-term exposure to road, railway, and aircraft noise, as well as air pollution, was estimated based on residential histories. Hazard ratios (HRs) were calculated using Cox proportional hazards models following adjustment for lifestyle and socioeconomic risk factors.A total of 22,459 incident cases of IHD were identified during follow-up from national patient and mortality registers, including 7,682 cases of myocardial infarction. The adjusted HR for IHD was 1.03 [95% confidence interval (CI) 1.00, 1.05] per 10 dB Lden for both road and railway noise exposure during 5 y prior to the event. Higher risks were indicated for IHD excluding angina pectoris cases, with HRs of 1.06 (95% CI: 1.03, 1.08) and 1.05 (95% CI: 1.01, 1.08) per 10 dB Lden for road and railway noise, respectively. Corresponding HRs for myocardial infarction were 1.02 (95% CI: 0.99, 1.05) and 1.04 (95% CI: 0.99, 1.08). Increased risks were observed for aircraft noise but without clear exposure-response relations. A threshold at around 55 dB Lden was suggested in the exposure-response relation for road traffic noise and IHD.Exposure to road, railway, and aircraft noise in the prior 5 y was associated with an increased risk of IHD, particularly after exclusion of angina pectoris cases, which are less well identified in the registries. https://doi.org/10.1289/EHP10745.
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| 33. |
- Ranji, Parmida, et al.
(författare)
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Deciphering the role of FUS::DDIT3 expression and tumor microenvironment in myxoid liposarcoma development
- 2024
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Ingår i: Journal of Translational Medicine. - : BioMed Central Ltd. - 1479-5876. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Myxoid liposarcoma (MLS) displays a distinctive tumor microenvironment and is characterized by the FUS::DDIT3 fusion oncogene, however, the precise functional contributions of these two elements remain enigmatic in tumor development. Methods: To study the cell-free microenvironment in MLS, we developed an experimental model system based on decellularized patient-derived xenograft tumors. We characterized the cell-free scaffold using mass spectrometry. Subsequently, scaffolds were repopulated using sarcoma cells with or without FUS::DDIT3 expression that were analyzed with histology and RNA sequencing. Results: Characterization of cell-free MLS scaffolds revealed intact structure and a large variation of protein types remaining after decellularization. We demonstrated an optimal culture time of 3 weeks and showed that FUS::DDIT3 expression decreased cell proliferation and scaffold invasiveness. The cell-free MLS microenvironment and FUS::DDIT3 expression both induced biological processes related to cell-to-cell and cell-to-extracellular matrix interactions, as well as chromatin remodeling, immune response, and metabolism. Data indicated that FUS::DDIT3 expression more than the microenvironment determined the pre-adipocytic phenotype that is typical for MLS. Conclusions: Our experimental approach opens new means to study the tumor microenvironment in detail and our findings suggest that FUS::DDIT3-expressing tumor cells can create their own extracellular niche.
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| 34. |
- Ström, Mikael, 1959, et al.
(författare)
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A set-based-inspired design process supported by axiomatic design and interactive evolutionary algorithms
- 2023
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Ingår i: International Journal of Product Development. - : Inderscience Publishers. - 1477-9056 .- 1741-8178. ; 27:3, s. 186-212
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an approach towards a set-based design-inspired concept development process for products with a solution space consisting principally of different solution alternatives and parameterised variants of these. The hypothesis is that such a concept development process can be based on traditional synthesis methods, an SBD-inspired elimination strategy, axiomatic design and interactive Evolutionary Algorithms (IEAs) for the synthesis of solution candidates and the successive reduction of the solution space. Axiomatic design and its axioms are used to evaluate and eliminate unfeasible alternatives, whereas IEAs, combined with human judgement, are employed for the evaluation and elimination of variants. Stated criteria specifying a design problem can be of different kinds with different ontologies described by different authors. This study focuses on functional, constraining and qualitative criteria. Results from performed industrial case studies show that the proposed method can reduce the lead time in design work.
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| 35. |
- Ström, Mikael, et al.
(författare)
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New combination of methods for supporting a simplified set-based design approach
- 2024
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Ingår i: <em>Proceedings of the Design Society</em>. - : Cambridge University Press. ; , s. 135-144
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Konferensbidrag (refereegranskat)abstract
- This work presents a Set-Based Design inspired approach for generation, evaluation and reduction of a solution space of alternative product concepts. Also, the aspect of how to implement the process in an industrial environment was investigated. The hypothesis, confirmed by case studies, is that it can be done using existing methods like Enhanced functional modelling, brainwriting, the Gallery method, Axiomatic Design, causal diagrams and Pugh matrices. The method can be successfully introduced in a timeframe of a few working days and support development engineers in the concept design phase.
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| 36. |
- Svensson, Nina, 1988-, et al.
(författare)
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Korsningars inverkan på partikelhalterna
- 2024
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Vägkorsningar har ofta visat sig vara hotspots för höga luftföroreningshalter på grund av ökad acceleration och inbromsning i samband med korsningen samt på grund av den ökade trafiken där flera vägar möts. Det finns få luftkvalitetsmätningar utförda i korsningar eftersom dessa miljöer är svårtolkade och sällan representativa. Mer kunskap behövs om korsningars påverkan på luftföroreningar exempelvis för att kunna utforma korsningar för att minska exponeringen för gående och cyklister. En möjlighet vore att införa ett korsningstillägg i emissions- eller luftkvalitetsmodeller för att kunna ta hänsyn till detta.För att öka kunskapen kring partikelhalter i korsningar har två mätkampanjer utförts i anslutning till korsningen Hornsgatan–Ringvägen i Stockholm. Under den första mätkampanjen mättes partikelhalter på två punkter: i korsningen och cirka 90 meter in på länken. Resultaten visade att det i genomsnitt var högre halter på länken än i korsningen och att halternas inbördes variation till största delen var beroende av vinden. Under den andra mätkampanjen mättes partikelhalter med 12 mikrosensorer placerade längs med Hornsgatan för att undersöka hur halterna varierade på olika avstånd från korsningen. Inga tydliga skillnader mellan halterna på olika avstånd från korsningen kunde dock ses, vilket kan tyda på att mikrosensorerna inte kunde registrera de trafikinducerade partiklarna med önskvärd noggrannhet. Högre halter kunde dock ibland registreras på den södra sidan av vägen, där fordonen bromsar inför korsningen och det är svagt nedåtlut, vilket kan tyda på att halterna påverkas av en ökad mängd bromspartiklar eller på grund av något vindmönster.
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| 37. |
- Svensson, Nina, 1988-, et al.
(författare)
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Luftkvalitet vid Testsite E18 : analys av påverkansfaktorer
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Mätningar av luftkvalitet (PM10, PM2,5 och NOX (NO och NO2)) har genomförts under perioden 2014-01-01 till 2015-12-31 vid Testsite E18, belägen längs E18 mellan Västerås och Enköping. Vid Testsite E18 görs kontinuerliga mätningar av trafik (i östgående riktning), luftföroreningar och meteorologi och vägbanans fuktighet. Under en kortare mätkampanj utfördes också mätningar av vägdammsinnehåll. Huvudsyftet med mätningarna är att skapa ett dataunderlag för en motorvägsmiljö, som kan användas för modellering av luftkvalitet och beräkning av exponering och hälsoeffekter i ett senare skede. Resultaten visar att halterna inte överskrider gällande miljökvalitetsnormer eller miljökvalitetsmålet för frisk luft. Kväveoxidhalten är högst under höst och vinter, vilket främst antas bero på meteorologiska faktorer. Partikelhalten är högst på våren på grund av den stora tillgången på uppvirvlingsbara partiklar. Kväveoxidhalten är till större del beroende av meteorologiska faktorer som vindhastighet, vindriktning och vertikal temperaturskillnad än partikelhalten och följer också trafikmängdens variation i högre grad. Partikelhalterna är till stor del beroende på vägbanans fuktighet. Halterna per fordon för både partiklar och kvävedioxider är betydligt högre nattetid än dagtid, vilket beror på en kombination av en ökad andel tung trafik, lägre medelvindhastighet och mer stabil temperaturskiktning. Mätning av vägdammsinnehåll visar på större dammförråd i mars än i maj och indikerar att det är färre och grövre partiklar i körfälten medan partiklarna på vägkanten är fler och mindre. Testsite E18 genererar stora datamängder om trafik och meteorologi, som kan användas för att analysera samband mellan sådana faktorer och luftföroreningar på platsen, samt utgöra lämpliga data för såväl underlag som validering av emissionsmodeller under utveckling, t.ex. Nortrip.
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| 38. |
- Svensson, Nina, 1988-, et al.
(författare)
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Ride the future – strategisk satsning : fem studier med fokus på autonoma bussar i städer
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Fem noga utvalda förstudier har initierats av VTI som en del i den strategiska satsningen ”Ride the future” kopplad till framtidens mobilitetslösningar. Förstudiernas titel är följande: ▪ Databearbetning och visualisering av mobila luftkvalitetsmätningar. ▪ SUMO och Unreal Engine för co-simulering. ▪ Exploring spatio-temporal accessibility in Lambohov: a pre-study. ▪ Vägytans betydelse för vibrationer och komfort i långsamma fordon. ▪ Infrastrukturbehov vid busshållplatser. Föreliggande pm innehåller en kort beskrivning av studierna och den mer utförliga redovisningen återfinns i bilagan.
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