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- Adori, Csaba, et al.
(författare)
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Disorganization and degeneration of liver sympathetic innervations in nonalcoholic fatty liver disease revealed by 3D imaging
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:30
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Tidskriftsartikel (refereegranskat)abstract
- Hepatic nerves have a complex role in synchronizing liver metabolism. Here, we used three-dimensional (3D) immunoimaging to explore the integrity of the hepatic nervous system in experimental and human nonalcoholic fatty liver disease (NAFLD). We demonstrate parallel signs of mild degeneration and axonal sprouting of sympathetic innervations in early stages of experimental NAFLD and a collapse of sympathetic arborization in steatohepatitis. Human fatty livers display a similar pattern of sympathetic nerve degeneration, correlating with the severity of NAFLD pathology. We show that chronic sympathetic hyperexcitation is a key factor in the axonal degeneration, here genetically phenocopied in mice deficient of the Rac-1 activator Vav3. In experimental steatohepatitis, 3D imaging reveals a severe portal vein contraction, spatially correlated with the extension of the remaining nerves around the portal vein, enlightening a potential intrahepatic neuronal mechanism of portal hypertension. These fundamental alterations in liver innervation and vasculature uncover previously unidentified neuronal components in NAFLD pathomechanisms.
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| 2. |
- Alakangas, Lena, et al.
(författare)
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Norrbottens malm- och mineralresurs och dess potentiella betydelse för innovation, samhälle och miljö
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Gruvindustrins betydelse för samhällsutveckling och infrastruktur i Sverige och inte minst i Norrbottens län är mycket stor. De geologiska förutsättningarna att hitta nya brytvärda förekomster i Norrbotten är goda. Länet är tillsammans med Västerbotten en av Europas viktigaste regioner för utvinning av metaller. Det syns också i den nyligen framtagna regionala mineralstrategin för Norrbotten och Västerbotten. Visionen för den regionala mineralstrategin: ”Genom långsiktigt hållbart nyttjande av Norrbottens och Västerbottens läns mineralresurser har ytterligare tillväxt skapats i regionen och hela Sverige. Vi har utvecklat och stärkt vår ställning som ledande gruv- och mineralnation.”Eftersom framtidspotentialen för gruvnäringen är mycket god men okunnigheten hos både allmänhet och beslutsfattare om näringens betydelse för innovation och samhällsutveckling är stor, kopplat med en utbredd oro för miljöpåverkan, måste dessa viktiga framtidsfrågor belysas. Med finansiering från Länsstyrelsen i Norrbotten bedrevs därför under första hälften av 2014 en förstudie som syftade till att sammanfatta kunskapsläget om framtidens gruvindustri i Norrbotten. Resultaten av förstudien redovisas i den här rapporten. En viktig slutsats är att det under nästa strukturfondsperiod (med start 2015) behövs ett framtidsinriktat forskningsprogram för att belysa de möjligheter som finns. Denna förstudie utgör grund för en kommande ansökan till strukturfonderna. Kompetensen som finns vid Luleå tekniska universitet, Sveriges centrum för gruvrelaterad forskning och utbildning, bör användas för att studera troliga framtidsmöjligheter och hur de ska kunna användas för att få en så positiv utveckling som möjligt för länet. Projektet bör innehålla följande tre huvudinriktningar, som naturligtvis hör ihop:Vilka malm- och mineralresurser finns det potential för i Norrbotten, och vilka kommer sannolikt att exploateras i framtiden?Vad kommer den exploateringen att ha för betydelse för innovation och samhällsutveckling?Vad kommer den exploateringen att få för miljöeffekter och hur ska man göra för att minska miljöbelastningen?En annan slutsats är att nedlagda gruvområden inte måste ses som förstörd natur. Betydande mervärden som gruvturism skulle kunna skapas om vilja, kreativitet och beslutsamhet finns. Detta är ett givet utvecklingsområde där småföretag och entreprenörer kan göra stor insats om de politiska och myndighetsmässiga förutsättningarna finns. Dessa aspekter skulle också kunna belysas i det föreslagna forskningsprogrammet eller i ett eget projekt.
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| 5. |
- Bark, Glenn, et al.
(författare)
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Textural setting of gold and its implications on mineral processing: preliminary results from three gold deposits in northern Sweden
- 2013
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Ingår i: Mineral deposit research for a high-tech world. - Uppsala : Sveriges Geologiska Undersökning. - 9789174032079 ; , s. 302-305
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Konferensbidrag (refereegranskat)abstract
- Within the European Union (EU27) the two most important gold producers are Finland and Sweden, covering more than two thirds of the European market. Due to the high gold prize mining companies are looking to extract more of the metal by improving recovery. We have done textural analysis on three gold-bearing deposits to better understand how the gold-textures seen in drill cores might affect the processing of different gold-ore types. In the Nautanen IOCG deposit, gold deportment is different whether gold is associated with pyrite or magnetite, and this must be considered when optimising the future mine and process planning. In the VMS-type Kristineberg deposit, the gold is associated with pyrite, sphalerite, and galena. Low gold recoveries from flotation could be explained by the occurrence of gold-inclusions in the pyrite. In the epigenetic Svartliden lode gold deposit, the gold is rather coarse-grained and associated with arsenopyrite-löllingite, and silicates. The relatively large grain size of gold can result in incomplete breakdown of the largest gold grains in the cyanide leaching process. To properly understand gold deportment in ores and to be able to improve mine planning and predict metal recoveries a comprehensive textural analysis of gold in drill core-samples is essential.
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| 8. |
- Gromada, Jesper, et al.
(författare)
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Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic beta cells through activation of phosphatidylinositol 4-kinase beta
- 2005
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 102:29, s. 10303-8
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Tidskriftsartikel (refereegranskat)abstract
- Cytosolic free Ca2+ plays an important role in the molecular mechanisms leading to regulated insulin secretion by the pancreatic beta cell. A number of Ca2+-binding proteins have been implicated in this process. Here, we define the role of the Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1) in insulin secretion. In pancreatic beta cells, NCS-1 increases exocytosis by promoting the priming of secretory granules for release and increasing the number of granules residing in the readily releasable pool. The effect of NCS-1 on exocytosis is mediated through an increase in phosphatidylinositol (PI) 4-kinase beta activity and the generation of phosphoinositides, specifically PI 4-phosphate and PI 4,5-bisphosphate. In turn, PI 4,5-bisphosphate controls exocytosis through the Ca2+-dependent activator protein for secretion present in beta cells. Our results provide evidence for an essential role of phosphoinositide synthesis in the regulation of glucose-induced insulin secretion by the pancreatic beta cell. We also demonstrate that NCS-1 and its downstream target, PI 4-kinase beta, are critical players in this process by virtue of their capacity to regulate the release competence of the secretory granules.
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| 9. |
- Ibarz, Mercedes, et al.
(författare)
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Sepsis at ICU admission does not decrease 30-day survival in very old patients : a post-hoc analysis of the VIP1 multinational cohort study
- 2020
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Ingår i: Annals of Intensive Care. - : Springer. - 2110-5820. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival.RESULTS: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85].CONCLUSIONS: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival.
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| 10. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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