| 1. |
- Glibert, Maarten, et al.
(author)
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The Influence of Initial Hard and Soft Tissue Dimensions on Initial Crestal Bone Loss of Immediately Loaded Dental Implants
- 2018
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In: The international journal of periodontics & restorative dentistry. - : Quintessence Publishing Co. Inc.. - 0198-7569 .- 1945-3388. ; 38:6, s. 873-878
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Journal article (peer-reviewed)abstract
- The aim of this case-control study was to evaluate the influence of soft tissue thickness at implant placement (thin [< 3 mm] vs thick [>= 3 mm]) and bone volume (abundant vs limited) on initial crestal bone remodeling of immediate postextraction and delayed (healed site) implants in immediate loading situations. A total of 67 patients with 133 implants could be evaluated, of which 77 were placed immediately after extraction and 56 in healed ridges. If sufficient bone volume is present and primary stability is achieved, immediate loading of the implant yields good clinical and radiographic outcomes, yet implants placed in healed ridges with thin soft tissues are more prone to initial crestal bone loss.
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| 2. |
- Moro, Carlos Fernandez, et al.
(author)
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An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver
- 2023
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Journal article (peer-reviewed)abstract
- A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule's extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFR(high) stroma at the liver edge to FAP(high) stroma towards the tumor. Encapsulation correlates with decreased tumor viability and preoperative chemotherapy. In mice, chemotherapy and tumor cell ablation induce capsule formation. Our results suggest that encapsulation develops where tumor invasion into the liver plates stalls, representing a reparative process rather than tumor-induced desmoplasia. We propose a model of metastases growth, where the efficient tumor colonization of the liver parenchyma and a reparative liver injury reaction are opposing determinants of metastasis aggressiveness.
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| 3. |
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| 4. |
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| 5. |
- Beier, Sara, et al.
(author)
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Pronounced seasonal dynamics of freshwater chitinase genes and chitin processing
- 2012
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In: Environmental Microbiology. - : Wiley. - 1462-2912 .- 1462-2920. ; 14:9, s. 2467-2479
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Journal article (peer-reviewed)abstract
- Seasonal variation in activity of enzymes involved in polymer degradation, including chitinases, has been observed previously in freshwater environments. However, it is not known whether the seasonal dynamics are due to shifts in the activity of bacteria already present, or shifts in community structure towards emergence or disappearance of chitinolytic organisms. We traced seasonal shifts in the chitinase gene assemblage in a temperate lake and linked these communities to variation in chitinase activity. Chitinase genes from 20 samples collected over a full yearly cycle were characterized by pyrosequencing. Pronounced temporal shifts in composition of the chitinase gene pool (beta diversity) occurred along with distinct shifts in richness (alpha diversity) as well as chitin processing. Changes in the chitinase gene pool correlated mainly with temperature, abundance of crustacean zooplankton and phytoplankton blooms. Also changes in the physical structure of the lake, e.g. stratification and mixing were associated with changes in the chitinolytic community, while differences were minor between surface and suboxic hypolimnetic water. The lake characteristics influencing the chitinolytic community are all linked to changes in organic particles and we suggest that seasonal changes in particle quality and availability foster microbial communities adapted to efficiently degrade them.
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| 6. |
- Corvigno, Sara, et al.
(author)
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High density of stroma-localized CD11c-positive macrophages is associated with longer overall survival in high-grade serous ovarian cancer.
- 2020
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 159:3, s. 860-868
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Pre-clinical studies have identified marker- and tumor compartment-defined functionally distinct macrophage subsets. Our study analyzes marker-defined macrophage subsets in different tumor compartments of high-grade serous ovarian cancer (HGSC).METHODS: A discovery cohort (N = 113) was subjected to immunohistochemistry (IHC) analyses. CD68-positivity was confirmed for CD11c-, CD80- and CD163-positive cells. Subset-marker-positive cells were scored in the total tumor and in four tumor compartments. Correlation analyses investigated co-expression of subsets, relationship to CD8+ cells and survival associations. A validation cohort (N = 121) was used to confirm selected findings from the discovery cohort.RESULTS: CD163-positve cells was the most abundant subtype in all compartments. CD11c and CD163 subsets were strongly correlated with each other in stroma and epithelial areas, whereas CD80 and CD163 were correlated in epithelial areas. CD80 and CD11c in perivascular areas showed low correlations. Strong associations were detected between CD8 and CD80 in the tumor epithelium-dominated areas, and between CD8 and CD11c in stroma areas. High stromal CD11c density was associated with a longer median overall survival in the discovery cohort (HR 0.39; CI 95%, 0.23-0.68; p = 0.001) and in the validation cohort (HR 0.46; CI 95%, 0.22-0.93; p = 0.03).CONCLUSIONS: Our study supports the existence of clinically relevant marker- and localization defined macrophage subsets in HGSC, which are independently regulated. Moreover, it suggests stromal CD11c as a novel prognostic marker in HGSC.
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| 7. |
- Frödin, Magnus, et al.
(author)
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Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma
- 2017
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 116:2, s. 195-201
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Journal article (peer-reviewed)abstract
- Background:Renal cell carcinoma (RCC) is a highly vascularised tumour, where anti-Angiogenic treatment with multi-Tyrosine-kinase-inhibitor, is used for first-line treatment of metastatic disease. Variations in vascular characteristics are likely to contribute to variations in intrinsic aggressiveness of the disease. Emerging studies are identifying perivascular status, including perivascular PDGFR-β, as a determinant of prognosis in other tumour types.Methods:This work explored the impact on prognosis of vascular characteristics in RCC through analyses of a population-based collection of tumours from surgery-Alone-Treated patients. The quantitative data from a panel of vascular metrics were obtained through computerised image analysis of sections double-stained for expression of the endothelial cell marker CD34 together with perivascular markers α-SMA or PDGFR-β.Results:Perivascular expression of PDGFR-β and α-SMA were positively correlated to each other, and negatively correlated to vessel density. High expression of PDGFR-β and α-SMA as well as low vessel density was significantly associated with short survival in uni-and multivariate analyses. Subgroup analyses demonstrated that the prognostic impact of the perivascular markers was particularly prominent in the T4-subgroup. A novel metric, related to PDGFR-β perivascular heterogeneity, was also associated with prognosis in uni-And multi-variate analyses. This novel metric also acted as a prognosis marker in ovarian cancer.Conclusions:The study demonstrates previously unrecognised associations between RCC survival and the absolute levels, and variability, of perivascular PDGFR-β. This marker should be further explored in other RCC cohorts. Findings also suggest mechanistic analyses and studies on the relationship between perivascular status and efficacy of multi-Tyrosine-kinase-inhibitors.
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| 8. |
- Gunell, Herbert, et al.
(author)
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Magnetosheath jets at Mars
- 2023
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 9:22
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Journal article (peer-reviewed)abstract
- Plasma entities, known as magnetosheath jets, with higher dynamic pressure than the surrounding plasma, are often seen at Earth. They generate waves and contribute to energy transfer in the magnetosheath. Affecting the magnetopause, they cause surface waves and transfer energy into the magnetosphere, causing throat auroras and magnetic signatures detectable on the ground. We show that jets exist also beyond Earth's environment in the magnetosheath of Mars, using data obtained by the MAVEN spacecraft. Thus, jets can be created also at Mars, which differs from Earth by its smaller bow shock, and they are associated with an increased level of magnetic field fluctuations. Jets couple large and small scales in magnetosheaths in the solar system and can play a similar part in astrophysical plasmas.
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| 9. |
- Hamrin, Maria, 1972-, et al.
(author)
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Space weather disturbances in non-stormy times : occurrence of dB/dt spikes during three solar cycles
- 2023
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In: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 128:10
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Journal article (peer-reviewed)abstract
- Spatio-temporal variations of ionospheric currents cause rapid magnetic field variations at ground level and Geomagnetically Induced Currents (GICs) that can be harmful for human infrastructure. The risk for large excursions in the magnetic field time derivative, “dB/dt spikes”, is known to be high during geomagnetic storms and substorms. However, less is known about the occurrence of spikes during non-stormy times. We use data from ground-based globally covering magnetometers (SuperMAG database) from the years 1985–2021. We investigate the spike occurrence (|dB/dt| > 100 nT/min) as a function of magnetic local time (MLT), magnetic latitude (Mlat), and the solar cycle phases during non-stormy times (−15 nT ≤ SYM-H < 0). We sort our data into substorm (AL < 200 nT) intervals (“SUB”) and less active intervals between consecutive substorms (“nonSUB”). We find that spikes commonly occur in both SUBs and nonSUBs during non-stormy times (3–23 spikes/day), covering 18–12 MLT and 65°–80° Mlat. This also implies a risk for infrastructure damage during non-stormy times, especially when several spikes occur nearby in space and time, possibly causing infrastructure weathering. We find that spikes are more common in the declining phase of the solar cycle, and that the occurrence of SUB spikes propagates from one midnight to one morning hotspot with ∼10 min in MLT for each minute in universal time (UTC). Finally, we discuss causes for the spikes in terms of spatio-temporal variations of ionospheric currents.
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| 10. |
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| 11. |
- Häggarth, Lars, et al.
(author)
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Diagnostic biomarkers of prostate cancer
- 2011
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In: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 45:1, s. 60-67
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Journal article (peer-reviewed)abstract
- Objective. Diagnostic tissue biomarkers for prostate cancer (PC) include basal cell markers and alpha-methylacyl-coenzyme A-racemase (AMACR), often used in combination. Their sensitivity and specificity are not perfect and there is a need for additional diagnostic biomarkers for PC in cases that are difficult to diagnose on routine stained sections. Material and methods. This study investigated the diagnostic accuracy of three novel tissue biomarkers for PC found through a search in the Human Protein Atlas database (www.proteinatlas.com): somatic cytochrome c (CYCS), intestinal cell kinase (ICK) and inhibitor of nuclear factor-kappa B kinase subunit beta (IKBKB), and compared the results with AMACR. A tissue microarray was constructed from 40 consecutive radical prostatectomy (RP) specimens including benign prostatic tissue, atrophy, high-grade prostatic intraepithelial neoplasia (HGPIN) and PC. Immunoreactivity was scored based on staining intensity and extent. Real-time polymerase chain reaction (PCR) was performed on malignant and benign frozen tissue samples from 32 RP specimens. Results. All four biomarkers showed a stronger expression in PC and HGPIN than in benign tissue (p < 0.001). The highest diagnostic accuracy for PC was achieved with ICK and AMACR at 97%. The area under the curve for CYCS, ICK, IKBKB and AMACR was 0.859, 0.997, 0.865 and 0.983, respectively. The presence of mRNA transcripts of the genes was confirmed by real-time PCR in benign and malignant prostatic tissue. Conclusions. AMACR is an accurate diagnostic tissue marker for PC. However, in some PCs AMACR is false negative and a panel of CYCS, ICK and IKBKB may serve as ancillary diagnostic tool.
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| 12. |
- Ingvarsdotter, Karin, et al.
(author)
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Lost in interpretation : The use of interpreters in research on mental ill health
- 2012
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In: International Journal of Social Psychiatry. - : Sage Publications. - 0020-7640 .- 1741-2854. ; 58:1, s. 34-40
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Journal article (peer-reviewed)abstract
- BACKGROUND: : The literature concerning interpretation in research primarily concentrates on rigorous techniques to eliminate bias. This article analyses other significant issues that arise when interpreters participate in research. MATERIAL: : Empirical examples are drawn from a research project concerning mental ill health in a multicultural neighbourhood. DISCUSSION: : Interpreters influence interview data in ways commonly unnoticed by researchers. One often-overlooked factor is that languages are dynamic and interpreters are not instruments. CONCLUSION: : Research conducted with an interpreter is a complex undertaking. Solely relying on checklists to improve methodological rigour can result in a false sense of the material's validity.
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| 13. |
- Ingvarsdotter, Karin, et al.
(author)
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Normal life crises and insanity : mental illness contextualised
- 2012
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In: European Journal of Social Work. - : Taylor & Francis. - 1369-1457 .- 1468-2664. ; 15:3, s. 345-360
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Journal article (peer-reviewed)abstract
- Enligt en kartläggning från 2005 utnyttjar befolkningen i Rosengård, en kulturellt heterogen stadsdel i Malmö, avsevärt mindre psykiatrisk vård i relation till uppskattade behov i jämförelse med övrig befolkning i Malmö. Med stöd av data från en intervjustudie bland folk som bor eller arbetar i stadsdelen klargjordes flera möjliga orsaker till den låga konsumtionen. Den främsta orsaken var synen på psykisk ohälsa; om ett mentalt tillstånd inte uppfattas som en sjukdom utan en normal livskris söker man inte medicinsk behandling för det. Syftet med artikeln är att illustrera hur underkonsumtion av psykiatrisk vård bland invandrare kan förklaras av ett annorlunda synsätt på psykisk ohälsa. Interventioner bör även inkludera människors socioekonomiska och psykosociala värld snarare än att enbart fokusera på deras mentala tillstånd.
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| 14. |
- Jaraj, Sara Jonmarker, et al.
(author)
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GAD1 is a biomarker for benign and malignant prostatic tissue
- 2011
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In: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 45:1, s. 39-45
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Journal article (peer-reviewed)abstract
- Objective. Tissue-specific markers are useful for identification of tumour type in advanced cancers of unknown origin. This study investigated the expression of glutamate decarboxylase 1 (GAD1) in prostate and control tissue compared with the established prostate-specific markers prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA). Material and methods. A tissue microarray was constructed of 36 prostate adenocarcinomas, eight benign prostate samples and benign and malignant control tissues from urinary bladder, lung and rectum. Immunohistochemistry for GAD 1, PSA and PSMA was performed. The products of staining intensity and extent were analysed. The GAD1 antibody was validated by Western blot. Real-time polymerase chain reaction (RT-PCR) was performed on malignant and benign samples from each tissue type. Results. GAD 1 and PSA immunostains were significantly stronger in malignant and benign prostatic tissue than in controls. PSMA was stronger in prostate cancer than in urothelial and rectal cancer but had a lower specificity than GAD1 and PSA. GAD I expression decreased with increasing Gleason score. RT-PCR confirmed the presence of mRNA for GAD I, PSA and PSMA in prostate samples. Conclusion. GAD1 is expressed in benign and malignant prostatic tissue and may serve as a highly prostate-specific tissue biomarker.
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| 15. |
- Johansson, Sara, 1977, et al.
(author)
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Long-chain polyunsaturated fatty acids are consumed during allergic inflammation and affect T helper type 1 (Th1)- and Th2-mediated hypersensitivity differently
- 2010
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In: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 160:3, s. 411-419
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Journal article (peer-reviewed)abstract
- P>Studies have shown that atopic individuals have decreased serum levels of n-3 fatty acids. Indicating these compounds may have a protective effect against allergic reaction and/or are consumed during inflammation. This study investigated whether fish (n-3) or sunflower (n-6) oil supplementation affected T helper type 1 (Th1)- and Th2-mediated hypersensitivity in the skin and airways, respectively, and whether the fatty acid serum profile changed during the inflammatory response. Mice were fed regular chow, chow + 10% fish oil or chow + 10% sunflower oil. Mice were immunized with ovalbumin (OVA) resolved in Th1 or Th2 adjuvant. For Th1 hypersensitivity, mice were challenged with OVA in the footpad. Footpad swelling, OVA-induced lymphocyte proliferation and cytokine production in the draining lymph node were evaluated. In the airway hypersensitivity model (Th2), mice were challenged intranasally with OVA and the resulting serum immunoglobulin (Ig)E and eosinophilic lung infiltration were measured. In the Th1 model, OVA-specific T cells proliferated less and produced less interferon (IFN)-gamma, tumour necrosis factor (TNF) and interleukin (IL)-6 in fish oil-fed mice versus controls. Footpad swelling was reduced marginally. In contrast, mice fed fish oil in the Th2 model produced more OVA-specific IgE and had slightly higher proportions of eosinophils in lung infiltrate. A significant fall in serum levels of long-chain n-3 fatty acids accompanied challenge and Th2-mediated inflammation in Th2 model. Fish oil supplementation affects Th1 and Th2 immune responses conversely; significant consumption of n-3 fatty acids occurs during Th2-driven inflammation. The latter observation may explain the association between Th2-mediated inflammation and low serum levels of n-3 fatty acids.
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| 16. |
- Johnsdotter, Sara, et al.
(author)
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Koran reading and negotiation with jinn : strategies to deal with mental ill health among Swedish Somalis
- 2011
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In: Mental Health, Religion & Culture. - : Routledge. - 1367-4676 .- 1469-9737. ; 14:8, s. 741-755
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Journal article (peer-reviewed)abstract
- I den här artikeln diskuterar vi traditionella somaliska begrepp kring psykisk ohälsa. Kvalitativa intervjuer gjordes med ett tjugotal svensksomaliska informanter. Intervjuerna fokuserade på vilka faktorer som kan leda till psykisk ohälsa, traditionell klassifikation av dessa tillstånd, samt attityder till psykiatrisk vård i Sverige. Social mobilisering och religiösa helanderitualer är grundläggande traditionella strategier för att hantera psykisk ohälsa. Traditionella somaliska synsätt står i skarp kontrast till den västerländska biomedicinska modellens klassifikation. Dessa synsätt förtjänar uppmärksamhet då de kan påverka hur somaliska immigranter i väst söker vård. Likväl finns det risker med alltför starkt fokus på kulturella skillnader, då det riskerar att överskugga det faktum att psykiskt lidande bland somaliska migranter måste ses i samband med sociala, ekonomiska och politiska förhållanden.
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| 17. |
- Königson, Sara, et al.
(author)
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Will harbor porpoises (Phocoena phocoena) be deterred by a pinger that cannot be used as a "dinner bell" by seals?
- 2022
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In: Marine mammal science. - : WILEY. - 0824-0469 .- 1748-7692. ; 38:2, s. 469-485
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Journal article (peer-reviewed)abstract
- A measure proven successful in mitigating harbor porpoise bycatch, is the use of acoustic deterrents, i.e., pingers. However, most pingers are audible to seals. This may lead to seals associating pinger sounds with easily accessible food, leading to increased depredation, damage, and bycatch. In this study we tested if an experimental pinger, emitting sounds over 30 hr ON/OFF cycles, with low frequency components potentially audible to seals only at close distances, would effectively deter harbor porpoises. The porpoise response was measured by logging echolocation clicks, using C-POD click detectors, moored at different distances from the pinger. In addition, we calculated the theoretical pinger detection range for seals. Results showed that the pinger had a significant negative effect on the porpoise click activity logged at 0 m and 100 m distance but not at 400 m from the pinger. During pinger ON periods, we found no significant increase in echolocation over consecutive days of the study, suggesting no habituation to pinger sounds. Our theoretical detection distances indicate that seals can only detect the pinger at close distances, preventing seals from using this pinger as a "dinner bell."
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| 18. |
- Larkin, Cormac J.K., et al.
(author)
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M5 — Mars Magnetospheric Multipoint Measurement Mission: A multi-spacecraft plasma physics mission to Mars
- 2024
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In: Advances in Space Research. - : Elsevier. - 0273-1177 .- 1879-1948. ; 73:6, s. 3235-3255
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Journal article (peer-reviewed)abstract
- Mars, lacking an intrinsic dynamo, is an ideal laboratory to comparatively study induced magnetospheres, which can be found in other terrestrial bodies as well as comets. Additionally, Mars is of particular interest to further exploration due to its loss of habitability by atmospheric escape and possible future human exploration. In this context, we propose the Mars Magnetospheric Multipoint Measurement Mission (M5), a multi-spacecraft mission to study the dynamics and energy transport of the Martian induced magnetosphere comprehensively. Particular focus is dedicated to the largely unexplored magnetotail region, where signatures of magnetic reconnection have been found. Furthermore, a reliable knowledge of the upstream solar wind conditions is needed to study the dynamics of the Martian magnetosphere, especially the different dayside boundary regions but also for energy transport phenomena like the current system and plasma waves. This will aid the study of atmospheric escape processes of planets with induced magnetospheres. In order to resolve the three-dimensional structures varying both in time and space, multi-point measurements are required. Thus, M5 is a five spacecraft mission, with one solar wind monitor orbiting Mars in a circular orbit at 5 Martian radii, and four smaller spacecraft in a tetrahedral configuration orbiting Mars in an elliptical orbit, spanning the far magnetotail up to 6 Mars radii with a periapsis just outside the Martian magnetosphere of 1.8 Mars radii. We not only present a detailed assessment of the scientific need for such a mission but also show the resulting mission and spacecraft design taking into account all aspects of the mission requirements and constraints such as mass, power, and link budgets. Additionally, different aspects of the mission programmatics like a possible mission timeline, cost estimates, or public outreach are shown. The common requirements for acceptance for an ESA mission are considered. The mission outlined in this paper was developed during the Alpbach Summer School 2022 on the topic of “Comparative Plasma Physics in the Universe”.
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| 19. |
- Leiss, Lina, et al.
(author)
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Platelet-derived growth factor receptor α/glial fibrillary acidic protein expressing peritumoral astrocytes associate with shorter median overall survival in glioblastoma patients.
- 2020
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In: Glia. - : Wiley. - 0894-1491 .- 1098-1136. ; 68:5, s. 979-988
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Journal article (peer-reviewed)abstract
- The microenvironment and architecture of peritumoral tissue have been suggested to affect permissiveness for infiltration of malignant cells. Astrocytes constitute a heterogeneous population of cells and have been linked to proliferation, migration, and drug sensitivity of glioblastoma (GBM) cells. Through double-immunohistochemical staining for platelet-derived growth factor receptor α (PDGFRα) and glial fibrillary acidic protein (GFAP), this study explored the intercase variability among 45 human GBM samples regarding density of GFAP+ peritumoral astrocytes and a subset of GFAP+ peritumoral astrocyte-like cells also expressing PDGFRα. Large intercase variability regarding the total peritumoral astrocyte density and the density of PDGFRα+/GFAP+ peritumoral astrocyte-like cells was detected. DNA fluorescence in situ hybridization analyses for commonly altered genetic tumor markers supported the interpretation that these cells represented a genetically unaffected host cell subset referred to as PDGFRα+/GFAP+ peritumoral astrocytes. The presence of PDGFRα+/GFAP+ peritumoral astrocytes was significantly positively correlated to older patient age and peritumoral astrocyte density, but not to other established prognostic factors. Notably, presence of PDGFRα+/GFAP+ peritumoral astrocytes, but not peritumoral astrocyte density, was associated with significantly shorter patient overall survival. The prognostic association of PDGFRα+/GFAP+ peritumoral astrocytes was confirmed in multivariable analyses. This exploratory study thus demonstrates previously unrecognized intercase variability and prognostic significance of peritumoral abundance of a novel PDGFRα+ subset of GFAP+ astrocytes. Findings suggest clinically relevant roles of the microenvironment of peritumoral GBM tissue and encourage further characterization of the novel astrocyte subset with regard to origin, function, and potential as biomarker and drug target.
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| 20. |
- Lundström, Sara, 1981, et al.
(author)
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Minimal selective concentrations of tetracycline in complex aquatic bacterial biofilms
- 2016
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In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 553, s. 587-95
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Journal article (peer-reviewed)abstract
- Selection pressure generated by antibiotics released into the environment could enrich for antibiotic resistance genes and antibiotic resistant bacteria, thereby increasing the risk for transmission to humans and animals. Tetracyclines comprise an antibiotic class of great importance to both human and animal health. Accordingly, residues of tetracycline are commonly detected in aquatic environments. To assess if tetracycline pollution in aquatic environments promotes development of resistance, we determined minimal selective concentrations (MSCs) in biofilms of complex aquatic bacterial communities using both phenotypic and genotypic assays. Tetracycline significantly increased the relative abundance of resistant bacteria at 10 μg/L, while specific tet genes (tetA and tetG) increased significantly at the lowest concentration tested (1 μg/L). Taxonomic composition of the biofilm communities was altered with increasing tetracycline concentrations. Metagenomic analysis revealed a concurrent increase of several tet genes and a range of other genes providing resistance to different classes of antibiotics (e.g. cmlA, floR, sul1, and mphA), indicating potential for co-selection. Consequently, MSCs for the tet genes of ≤ 1 μg/L suggests that current exposure levels in e.g. sewage treatment plants could be sufficient to promote resistance. The methodology used here to assess MSCs could be applied in risk assessment of other antibiotics as well.
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| 21. |
- Mezheyeuski, Artur, et al.
(author)
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Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:27, s. 41948-41958
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Journal article (peer-reviewed)abstract
- Perivascular cells (PC) were recently implied as regulators of metastasis and immune cell activity. Perivascular heterogeneity in clinical samples, and associations with other tumor features and outcome, remain largely unknown.Here we report a novel method for digital quantitative analyses of vessel characteristics and PC, which was applied to two collections of human metastatic colorectal cancer (mCRC).Initial analyses identified marker-defined subsets of PC, including cells expressing PDGFR-β or α-SMA or both markers. PC subsets were largely independently expressed in a manner unrelated to vessel density and size. Association studies implied specific oncogenic mutations in malignant cells as determinants of PC status. Semi-quantitative and digital-image-analyses-based scoring of the NORDIC-VII cohort identified significant associations between low expression of perivascular PDGFR-α and -β and shorter overall survival. Analyses of the SPCRC cohort confirmed these findings. Perivascular PDGFR-α and -β remained independent factors for survival in multivariate analyses.Overall, our study identified host vasculature and oncogenic status as determinants of tumor perivascular features. Perivascular PDGFR-α and -β were identified as novel independent markers predicting survival in mCRC. The novel methodology should be suitable for similar analyses in other tumor collections.
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| 22. |
- Micke, Patrick, et al.
(author)
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A fluid cover medium provides superior morphology and preserves RNA integrity in tissue sections for laser microdissection and pressure catapulting.
- 2004
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In: The Journal of pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 202:(1), s. 130-8
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Journal article (peer-reviewed)abstract
- Laser microdissection and pressure catapulting has become a powerful tool to obtain homogeneous cell populations from tissue samples in nearly all fields of biomedical research. The isolated cells can be subsequently used for the analysis of proteins, DNA or RNA. However, the method requires physical access to the tissue surface and the sections therefore need to be air-dried and uncovered. The consequence is poor morphology, which severely reduces the potential of the technique, especially in non-homogeneous tissues or tissues with infiltrating immune cells. To overcome this limitation, a fluid cover medium was developed and the effects on frozen and paraffin wax-embedded tissue morphology were evaluated. The cover medium improved the morphology such that it was almost comparable to sections overlaid with glass coverslips. Moreover, the laser microdissection procedure was facilitated, since the medium allowed larger areas of tissues to be laser pressure-catapulted. Neither the isolation of proteins nor the extraction of genomic DNA was adversely affected by the use of the fluid cover medium. No significant differences in RNA quantity and integrity were detected by TaqMan real-time PCR for GAPDH, and microchip electrophoresis, between covered and uncovered tissue sections. In conclusion, this method provides considerably improved morphology for laser microdissection and pressure catapulting techniques without affecting RNA-dependent downstream applications. This not only facilitates established procedures, but will also extend the application to tissues that require superior morphological resolution.
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| 23. |
- Moreno-Ruiz, Pablo, et al.
(author)
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Stromal FAP is an independent poor prognosis marker in non-small cell lung adenocarcinoma and associated with p53 mutation
- 2021
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In: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 155, s. 10-19
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Journal article (peer-reviewed)abstract
- ObjectivesFibroblasts regulate tumor growth and immune surveillance. Here, we study FAP, PDGFβR and α-SMA fibroblast markers in a well-annotated clinical cohort of non–small-cell lung cancer (NSCLC) for analyses of associations with immune cell infiltration, mutation status and survival.Materials and MethodsA well-annotated NSCLC cohort was subjected to IHC analyses of stromal expression of FAP, PDGFβR and α-SMA and of stromal CD8 density. Fibroblast markers-related measurements were analyzed with regard to potential associations with CD8 density, cancer genetic driver mutations, survival and PD-L1 expression in the whole NSCLC cohort and in subsets of patients.ResultsHigh stromal FAP expression was identified as an independent poor prognostic marker in the whole study population (HR 1.481; 95 % CI, 1.012–2.167, p = 0.023) and in the histological subset of adenocarcinoma (HR 1.720; 95 % CI, 1.126–2.627, p = 0.012). Among patients with adenocarcinoma, a particularly strong association of FAP with poor survival was detected in patients with low stromal CD8 infiltration, and in other subpopulations identified by specific clinical characteristics; elderly patients, females, non-smokers and patients with normal ECOG performance status. α-SMA expression was negatively associated with CD8 infiltration in non-smokers, but none of the fibroblast markers expression was associated with CD8 density in the whole study population. Significant associations were detected between presence of p53 mutations and high α-SMA (p = 0.003) and FAP expression (p < 0.001).ConclusionThe study identifies FAP intensity as a candidate independent NSCLC prognostic biomarker. The study also suggests continued analyses of the relationships between genetic driver mutations and the composition of tumor stroma, as well as continued probing of marker-defined fibroblasts as NSCLC subset-specific modifiers of immune surveillance and outcome.
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| 24. |
- Ort, Christoph, et al.
(author)
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Spatial differences and temporal changes in illicit drug use in Europe quantified by wastewater analysis
- 2014
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In: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 109:8, s. 1338-1352
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Journal article (peer-reviewed)abstract
- Aims To perform wastewater analyses to assess spatial differences and temporal changes of illicit drug use in a large European population. Design Analyses of raw wastewater over a 1-week period in 2012 and 2013. Setting and Participants Catchment areas of wastewater treatment plants (WWTPs) across Europe, as follows: 2012: 25 WWTPs in 11 countries (23 cities, total population 11.50 million); 2013: 47 WWTPs in 21 countries (42 cities, total population 24.74 million). Measurements Excretion products of five illicit drugs (cocaine, amphetamine, ecstasy, methamphetamine, cannabis) were quantified in wastewater samples using methods based on liquid chromatography coupled to mass spectrometry. Findings Spatial differences were assessed and confirmed to vary greatly across European metropolitan areas. In general, results were in agreement with traditional surveillance data, where available. While temporal changes were substantial in individual cities and years (P ranging from insignificant to <10(-3)), overall means were relatively stable. The overall mean of methamphetamine was an exception (apparent decline in 2012), as it was influenced mainly by four cities. Conclusions Wastewater analysis performed across Europe provides complementary evidence on illicit drug consumption and generally concurs with traditional surveillance data. Wastewater analysis can measure total illicit drug use more quickly and regularly than is the current norm for national surveys, and creates estimates where such data does not exist.
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| 25. |
- Stymne, Sara, 1977-, et al.
(author)
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Parser Evaluation for Analyzing Swedish 19th–20th Century Literature
- 2023
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In: Proceedings of the 24th Nordic Conference on Computational Linguistics (NoDaLiDa). - Tartu : University of Tartu. - 9789916219997 ; , s. 335-346
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Conference paper (peer-reviewed)abstract
- In this study, we aim to find a parser for accurately identifying different types of subordinate clauses, and related phenomena, in 19th–20th-century Swedish literature. Since no test set is available for parsing from this time period, we propose a lightweight annotation scheme for annotating a single relation of interest per sentence. We train a variety of parsers for Swedish and compare evaluations on standard modern test sets and our targeted test set. We find clear trends in which parser types perform best on the standard test sets, but that performance is considerably more varied on the targeted test set. We believe that our proposed annotation scheme can be useful for complementing standard evaluations, with a low annotation effort.
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| 26. |
- Stymne, Sara, 1977-, et al.
(author)
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SLäNDa : An Annotated Corpus of Narrative and Dialogue in Swedish Literary Fiction
- 2020
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In: Proceedings of the 12th Language Resources and Evaluation Conference. - 9791095546344 ; , s. 826-834
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Conference paper (peer-reviewed)abstract
- We describe a new corpus, SLäNDa, the Swedish Literary corpus of Narrative and Dialogue. It contains Swedish literary fiction, which has been manually annotated for cited materials, with a focus on dialogue. The annotation covers excerpts from eight Swedish novels written between 1879-1940, a period of modernization of the Swedish language. SLäNDa contains annotations for all cited materials that are separate from the main narrative, like quotations and signs. The main focus is on dialogue, for which we annotate speech segments, speech tags, and speakers. In this paper we describe the annotation protocol and procedure and show that we can reach a high inter-annotator agreement. In total, SLäNDa contains annotations of 44 chapters with over 220K tokens. The annotation identified 4,733 instances of cited material and 1,143 named speaker-speech mappings. The corpus is useful for developing computational tools for different types of analysis of literary narrative and speech. We perform a small pilot study where we show how our annotation can help in analyzing language change in Swedish. We find that a number of common function words have their modern version appear earlier in speech than in narrative.
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| 27. |
- Stymne, Sara, 1977-, et al.
(author)
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SLäNDa Version 2.0 : Improved and Extended Annotation of Narrative and Dialogue in Swedish Literature
- 2022
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In: Proceedings of the 13th International Conference on Language Resources and Evaluation (LREC 2022). - : European Language Resources Association. - 9791095546726 ; , s. 5324-5333
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Conference paper (peer-reviewed)abstract
- In this paper, we describe version 2.0 of the SLaNDa corpus. SLäNDa, the Swedish Literary corpus of Narrative and Dialogue, now contains excerpts from 19 novels, written between 1809–1940. The main focus of the SLaNDa corpus is to distinguish between direct speech and the main narrative. In order to isolate the narrative, we also annotate everything else which does not belong to the narrative, such as thoughts, quotations, and letters. SLäNDa version 2.0 has a slightly updated annotation scheme from version 1.0. In addition, we added new texts from eleven authors and performed quality control on the previous version. We are specifically interested in different ways of marking speech segments, such as quotation marks, dashes, or no marking at all. To allow a detailed evaluation of this aspect, we added dedicated test sets to SLaNDa for these different types of speech marking. In a pilot experiment, we explore the impact of typographic speech marking by using these test sets, as well as artificially stripping the training data of speech markers.
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| 28. |
- Stymne, Sara, 1977-, et al.
(author)
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Språklig rytm i skönlitterär prosa. En fallstudie i Karin Boyes Kallocain
- 2018
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In: Samlaren. - Uppsala : Svenska Litteratursällskapet. - 0348-6133 .- 2002-3871. ; 139, s. 128-161
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Journal article (peer-reviewed)abstract
- Sara Stymne, Department of Linguistics and Philology, Uppsala UniversityJohan Svedjedal, Department of Literature, Uppsala UniversityCarin Östman, Department of Scandinavian Languages, Uppsala UniversityLinguistic Rhythm in Narrative Prose: the case of Karin Boye’s Kallocain (Språklig rytm i skönlitterär prosa. En fallstudie i Karin Boyes Kallocain)The concept of rhythm in prose is ambiguous, and there is no consensus on how to define it. In this work, we focus on linguistic rhythm, at word, sentence and paragraph levels. We adopt and slightly extend rhythm indicators used in previous research, and show that these can be calculated fully automatically, on a much larger scale than previously done.We adopt the Swedish poet and novelist Karin Boye’s (1900–41) novel Kallocain (1940), as a case study. It is an icily dystopian depiction of a totalitarian future, where the protagonist Leo Kall first embraces this system, but for various reasons later rebels against it. The peripety comes when he gives a public speech, questioning the State. It has been pointed out that the novel from precisely this point on is characterized by a much freer rhythm, and that Boye as an author had considerable interest in questions of linguistic rhythm. This paper sets out to test this hypothesis by applying sixteen indicators of linguistic rhythm in narrative prose (such as word length, sentence length, ratio of punctuation, etc.).We first note that we can expect differences between narrative and dialogue and limit most of our study to the first-person narrative. We find that there are significant differences mainly between phrase and word lengths in the parts before and after Leo Kall’s conversion. In a further investigation we note that there is also great variation among indicators within each part of the novel. We also show that machine learning can be used to differentiate small segments from each part of the novel, with higher accuracy than a random classifier. Finally, we undertake a small study of dialogue, which, however is mainly inconclusive. In summary we find some support for the claim that there is a rhythm break in Kallocain. We also believe that our study is important from a methodological point of view, since it provides a method for largescale studies of prose rhythm in the future.
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| 29. |
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| 30. |
- Söder, Josefin, et al.
(author)
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Indication of metabolic inflexibility to food intake in spontaneously overweight Labrador Retriever dogs
- 2019
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In: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 15
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Journal article (peer-reviewed)abstract
- BackgroundObesity in dogs is an increasing problem associated with morbidity, shortened life span and poor life quality. Overweight dogs exhibit postprandial hyperlipidaemia, highlighting the need to identify potential dysregulations in lipid metabolism. This study investigated metabolites related to lipid metabolism (i.e. acylcarnitines and taurine) and phospholipids in a feed-challenge test and aimed to identify metabolic variations in spontaneously overweight dogs. Twenty-eight healthy male Labrador Retriever dogs were included, 12 of which were classified as lean (body condition score (BCS) 4-5 on a 9-point scale) and 16 as overweight (BCS 6-8). After overnight fasting (14-17h), fasting blood samples were collected and dogs were fed a high-fat meal followed by postprandial blood sample collection hourly for 4h. Liquid chromatography-time of flight mass spectrometry (LC-TOFMS) was used to identify plasma metabolites and phospholipids. Multivariate models, mixed model repeated measures and linear regression analyses were used for data interpretation.ResultsIn all dogs, propionylcarnitine, stearoylcarnitine and nine phospholipids increased in response to food intake, while vaccenylcarnitine decreased (P0.005 for all). Overall, carnitine and acetylcarnitine signal areas in the feed-challenge test were lower in overweight dogs (P0.004). Notably, fasting plasma acetylcarnitine was lower in overweight dogs than in lean dogs (P=0.001) and it did not change in response to feeding. The latter finding was in contrast to the decreased acetylcarnitine signal area found in lean dogs at one hour postprandially (P<0.0001). One fasting phosphatidylcholine (PCaa C38:4) was higher in prominently overweight dogs (BCS>6) than in lean dogs (P<0.05).ConclusionsPlasma carnitine status was overall lower in spontaneously overweight dogs than in lean dogs in this cohort of healthy Labrador Retriever dogs, indicating a potential carnitine insufficiency in the overweight group. The acetylcarnitine response in overweight dogs indicated decreased fatty acid oxidation at fasting and metabolic inflexibility to food intake. Further studies on metabolic inflexibility and its potential role in the metabolism of overweight dogs are warranted.
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| 31. |
- Westin, Jonas, et al.
(author)
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Regionala konsekvenser av Trafikverkets plan för förändrade hastighetsgränser
- 2019
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Reports (other academic/artistic)abstract
- Inom Trafikverket pågår en översyn av hastighetsgränserna i det svenska vägnätet. Ett syfte med översynen är att stärka ”nollvisionen” genom att justera skyltad hastighet så att den bättre stämmer överens med faktisk vägstandard. För att bättre och mer systematiskt beskriva konsekvenser för utveckling av, och fördelningseffekter mellan, regioner av förändrade hastighetsgränser i vägnätet krävs fördjupade analysmetoder. I denna rapport beskrivs en metodik för att ta fram ett kompletterande beslutsunderlag för analys av effekter på tillgänglighet och regionalekonomiska konsekvenser av förändrade hastighetsgränser inom ramen för Trafikverkets arbete med hastighetsöversynen.Genom att jämföra beräknade effekter av hastighetsjusteringar från olika modellsystem skapas en fördjupad bild av hur förändrade hastighetsgränser i vägnätet inverkar på tillgänglighet och regional utveckling. Ett syfte med analyserna är att identifiera områden (delar av landet i form av regioner, stråk och vägsträckor) där nedsatt hastighet kan få särskilt negativ regional inverkan på tillgängligheten och därmed i en förlängning påverka möjligheterna till utveckling av samhälle och näringsliv.Varje enskild omskyltning av ett vägobjekt i Trafikverkets hastighetsjustering är en del i ett större åtgärdspaket. Effekten av varje enskild åtgärd behöver därför analyseras mot bakgrund av det samlade paketet av åtgärder och hastighetsjusteringar i hastighetsjusteringen. Metoden bygger därför på en scenarioanalys där effekter på olika former av tillgänglighet analyseras för två olika scenarier. Det första scenariot är ett trafiksäkerhetsscenario (UA1) där principerna för Trafikverkets hastighetsöversyn tillämpats i hela landet. Det andra scenariot är ett tillgänglighetsscenario (UA2) där förändringarna i UA1 kompletterats med åtgärder för att höja hastigheten på vägar som ingår i Trafikverkets funktionellt prioriterade vägnät (FPV).Metoden för att analysera effekter av en föreslagen hastighetsförändring kan delas in i tre steg:Effektberäkning i EVA: I det första steget beräknas och värderas effekter på restid, trafiksäkerhet, emissioner, drift och underhåll av en hastighetsförändring med hjälp av Trafikverkets kalkylverktyg EVA.Scenarioanalys: I det andra steget analyseras och jämförs beräknade tillgänglighetseffekter i de två scenarierna UA1 och UA2. Genom att studera kartor över hur tillgängligheten i närområdet påverkas av de hastighetsförändringar som ingår i hastighetsöversynen, kan områden med särskilt negativ inverkan på olika former av tillgänglighet identifieras.Sammanställning: I de fall scenarioanalysen visat på närområden med där minskningarna i tillgänglighet är alltför stora kan olika typer av kompensatoriska åtgärder undersökas.En möjlig kompensatorisk åtgärd är att investera i vägförbättringar med syfte att kunna höja hastighetsgränserna utan att försämra trafiksäkerheten. En slutsats från analysen är att generella investeringar i FPV med syfte att höja hastigheten i framförallt det nationellt prioriterade vägnätet inte är en effektiv åtgärd för att kompensera för sänkta hastighetsgränser på framförallt mindre vägar. För att kompensera områden som påverkas negativt av hastighetsjusteringarna i UA1 bör därför alternativa steg 1 och steg 2 åtgärder istället undersökas. Exempelvis kan satsningar på kollektivtrafik eller satsningar på utbyggd lokal service öka tillgängligheten trots att hastigheten i vägnätet sänkts. Många av dessa åtgärder ligger dock utanför Trafikverkets ansvarsområde.
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| 32. |
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