| 1. |
- Ahlberg, Erik, et al.
(författare)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
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Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 2. |
- Ammenberg, Jonas, et al.
(författare)
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Biogas Research Center, BRC : Slutrapport för etapp 1
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Biogas Research Center (BRC) är ett kompetenscentrum för biogasforskning som finansieras av Energimyndigheten, LiU och ett flertal externa organisationer med en tredjedel vardera. BRC har en mycket bred tvärvetenskaplig inriktning och sammanför biogasrelaterad kompetens från flera olika områden för att skapa interaktion på flera olika plan:mellan näringsliv, akademi och samhälle,mellan olika perspektiv, samtmellan olika discipliner och kompetensområden.BRC:s vision är:Resurseffektiva biogaslösningar finns genomförda i många nya tillämpningar och bidrar till en mer hållbar energiförsörjning, förbättrat miljötillstånd och goda affärer.BRC:s särskilda roll för att uppnå denna vision är att bidra med kunskapsförsörjning och process-/teknikutveckling för att facilitera utveckling, innovation och implementering av biogaslösningar. Resurseffektivitet är ett nyckelord, vilket handlar om att förbättra befintliga processer och system samt utveckla biogaslösningar i nya sektorer och möjliggöra användning av nya substrat.For BRC:s etapp 1, den första tvåårsperioden mellan 2012-2014, var forskningsprojekten organiserade enligt tabellen nedan. Den visar viktiga utmaningar för biogasproducenter och andra intressenter, samt hur dessa ”angreps” med åtta forskningsprojekt. Fem av projekten var av explorativ karaktär i bemärkelsen att de var bredare och mer framtidsorienterade - exempelvis utvärderade flera möjliga tekniska utvecklingsmöjligheter (EP1-5). Tre projekt hade ett tydligare fokus på teknik- och processutveckling (DP6-8).I den här slutrapporten ges en kortfattad bakgrundsbeskrivning och det finns en introduktion till vad den här typen av kompetenscentrum innebär generellt. Därefter finns mer detaljerad information om BRC, exempelvis gäller det centrumets etablering, relevans, vision, hörnstenar och utveckling. De deltagande organisationerna presenteras, både forskargrupperna vid Linköpings universitet och partners och medlemmar. Vidare finns en mer utförlig introduktion till och beskrivning av utmaningarna i tabellen och kortfattat information om forskningsprojekten, följt av ett kapitel som berör måluppfyllelse och den externa utvärdering som gjorts av BRC:s verksamhet. Detaljerad, listad information finns till stor del i bilagorna.Kortfattat kan det konstateras att måluppfyllelsen överlag är god. Det är speciellt positivt att så många vetenskapliga artiklar publicerats (eller är på gång att publiceras) kopplat till forskningsprojekten och även i det vidare centrumperspektivet. Helt klart förekommer en omfattande verksamhet inom och kopplat till BRC. I etapp 2 är det viktigt att öka andelen mycket nöjda partner och medlemmar, där nu hälften är nöjda och hälften mycket nöjda. Det handlar framför allt om stärkt kommunikation, interaktion och projektledning. Under 2015 förväntas åtminstone två doktorsexamina, där avhandlingarna har stor koppling till forskningen inom etapp 1.I början på år 2014 skedde en extern utvärdering av verksamheten vid BRC med huvudsyftet att bedöma hur väl centrumet lyckats med etableringen samt att granska om det fanns förutsättningar för framtida framgångsrik verksamhet. Generellt var utfallet mycket positivt och utvärderarna konstaterade att BRC på kort tid lyckats etablera en verksamhet som fungerar väl och engagerar det stora flertalet deltagande aktörer, inom relevanta områden och där de flesta involverade ser BRC som en befogad och väl fungerande satsning, som de har för avsikt att även fortsättningsvis stödja. Utvärderingen bidrog också med flera relevant tips och till att belysa utmaningar.Utöver denna slutrapport finns separata publikationer från forskningsprojekten.Arbetet som presenteras i rapporten har finansierats av Energimyndigheten och de medverkande organisationerna.
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| 3. |
- Berntsson, Jonna, et al.
(författare)
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The clinical impact of tumour-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite : A cohort study
- 2017
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 141:8, s. 1654-1666
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence demonstrates an association between dense infiltration of lymphocytes and prognosis in colorectal cancer (CRC), but whether this prognostic impact differs by tumour location remains unknown. This study investigated the prognostic impact of cytotoxic and regulatory T cells in CRC, with particular referennfiltrating T cce to the anatomical subsite of the primary tumour. The density of CD3(+), CD8(+) and FoxP3(+) tumour-iells was calculated in tissue microarrays with tumours from 557 incident CRC cases from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of high and low lymphocyte density on 5-year overall survival, in subgroup analysis of right colon, left colon and rectum. High CD8(+) cell density was a favourable prognostic factor for patients with right-sided colon tumours (hazard ratio [HR]=0.53, 95% confidence interval [CI] 0.29-0.95), independent of age, sex, TNM stage, differentiation grade and vascular invasion, with a significant prognostic interaction between CD8(+) cells and right-sidedness (p=0.031). High FoxP3(+) cell density was an independent favourable prognostic factor only in patients with rectal tumours (HR=0.54, 95% CI 0.30-0.99), and CD3(+) cell density was an independent favourable prognostic factor for tumours in the right colon and rectum, but there was no significant prognostic interaction between CD3(+) or FoxP3(+) cells and sidedness. These results demonstrate that the prognostic impact of tumour-infiltrating lymphocytes in CRC differs by primary tumour site, further indicating that tumour location may be an important factor to take into consideration in therapeutic decisions, including eligibility for immunotherapy.
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| 4. |
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| 5. |
- Charalampopoulos, Dimitrios, et al.
(författare)
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Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes
- 2018
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Ingår i: Diabetes Care. - : AMER DIABETES ASSOC. - 0149-5992 .- 1935-5548. ; 41:6, s. 1180-1187
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA(1c) levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA(1c) across and within eight high-income countries to best inform international benchmarking and policy recommendations. RESEARCH DESIGN AND METHODS Data were collected between 2013 and 2014 from 64,666 children with T1D who were amp;lt; 18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed-and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA(1c) levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and childrens glycemic control. RESULTS Sweden had the lowest mean HbA(1c) (59mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC amp;lt;= 4%). Germany and Austria had the next lowest mean HbA(1c) (61-62 mmol/mol [7.7-7.8%]) but showed the largest center variations (ICC similar to 15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value amp;lt; 0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA(1c) levels (5.6mmol/mol [0.5%] per 5mmol/mol [0.5%] increase in center SD of HbA(1c) values of all children attending a specific center). CONCLUSIONS A tsimilar average levels of HbA(1c), countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.
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| 8. |
- Svensson, Maria C., et al.
(författare)
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Expression of PD-L1 and PD-1 in chemoradiotherapy-Naïve esophageal and gastric adenocarcinoma : Relationship with mismatch repair status and survival
- 2019
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 9:MAR
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Tidskriftsartikel (refereegranskat)abstract
- Background: The outlook for patients with esophageal and gastric (EG) cancer remains poor. Hence, there is a compelling need to identify novel treatment strategies and complementary biomarkers. Programmed death ligand 1 (PD-L1) and mismatch repair deficiency (dMMR) are putative biomarkers of response to immune-checkpoint blockade, but their prognostic value and interrelationship in EG cancer have been sparsely investigated. Methods: Immunohistochemical expression of PD-L1 on tumour cells (TC) and tumour-infiltrating immune cells (TIC), and of PD-1 (programmed death receptor 1) on TIC was assessed using tissue microarrays with primary tumours and a subset of paired lymph node metastases from a consecutive, retrospective cohort of 174 patients with chemoradiotherapy-naïve EG adenocarcinoma. MMR proteins MLH1, PMS2, MSH2, and MSH6 were assessed by immunohistochemistry. The total number (intratumoural, tumour-adjacent, and stromal) of CD8+ T cells in each core was calculated by automated analysis. Results: High PD-L1 expression on both TC and TIC, but not PD-1 expression, was significantly associated with dMMR. PD-L1 expression on TIC was significantly higher in lymph node metastases than in primary tumours. High expression of PD-L1 or PD-1 on TIC was significantly associated with a prolonged survival, the former independently of established prognostic factors. A significant stepwise positive association was found between CD8 + T cells and categories of PD-L1 expression on TIC. Conclusion: PD-L1 expression on TIC is higher in lymph node metastases compared to primary tumours, correlates with dMMR, and is an independent factor of prolonged survival in patients with chemoradiotherapy-naïve EG adenocarcinoma. These findings suggest that PD-L1 expression on TIC may be a useful biomarker for identifying patients who may not need additional chemo-or chemoradiotherapy, and who may benefit from PD-1/PD-L1 immune-checkpoint blockade.
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| 9. |
- Svensson, Maria C, et al.
(författare)
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The integrative clinical impact of tumor-infiltrating T lymphocytes and NK cells in relation to B lymphocyte and plasma cell density in esophageal and gastric adenocarcinoma
- 2017
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Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:42, s. 72108-72126
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have demonstrated a prognostic impact of tumor-infiltrating T lymphocytes and natural killer (NK) cells in esophageal and gastric adenocarcinoma, but whether these associations differ by the density of tumor-infiltrating immune cells of the B cell lineage remains largely unknown. Results: High infiltration of any T and NK lymphocytes investigated was in general associated with a favorable prognosis, but the strongest beneficial prognostic impact was seen in combination with high B lymphocyte infiltration. These findings were most evident in gastric cancer, where significant interactions in relation to OS were observed for CD3(+), CD8(+) and FoxP3(+) with CD20(+) cells (p(interaction) = 0.012, 0.009 and 0.007, respectively) and for FoxP3(+) with IGKC(+) cells (p(interaction) = 0.034). In esophageal tumors, there was only a significant interaction for CD3(+) and CD20 (+) cells (p(interaction) = 0.028). Methods: Immunohistochemistry and automated image analysis was applied to assess the density of T lymphocytes (CD3(+), CD8(+), FoxP3(+)) and NK cells (NKp46(+)) in chemoradiotherapy-naive tumors from a consecutive cohort of 174 patients with resected esophageal or gastric adenocarcinoma. The density of B lymphocytes (CD20(+)) and plasma cells (IGKC(+)) had been assessed previously. Kaplan-Meier analysis and Cox proportional hazard's modelling was applied to examine the impact of the investigated markers on time to recurrence (TTR) and overall survival (OS). Conclusions: These data support that the antitumoral effects of tumor-infiltrating T lymphocytes in esophageal and gastric adenocarcinoma may be largely dependent on a functional interplay between T and B lymphocytes or plasma cells.
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| 10. |
- Åsberg, Dennis, 1988-, et al.
(författare)
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A quality control method enhancement concept : Continual improvement of regulatory approved QC methods
- 2016
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Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier. - 0731-7085 .- 1873-264X. ; 129, s. 273-281
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Tidskriftsartikel (refereegranskat)abstract
- Quality Control methods (QC-methods) play an important role in the overall control strategy for drug manufacturing. However, efficient life-cycle management and continual improvement are hindered due to a variety of post-approval variation legislations across territories and a lack of harmonization of the requirements. As a result, many QC-methods fall behind the technical development. Developing the QC-method in accordance with the Quality by Design guidelines gives the possibility to do continual improvements inside the original Method Operable Design Region (MODR). However, often it is necessary to do changes outside the MODR, e.g. to incorporate new technology that was not available at the time the original method was development. Here, we present a method enhancement concept which allows minor adjustments, within the same measuring principle, outside the original MODR without interaction with regulatory agencies. The feasibility of the concept is illustrated by a case study of a QC-method based on HPLC, assumed to be developed before the introduction of UHPLC, where the switch from HPLC to UHPLC is necessary as a continual improvement strategy. The concept relies on the assumption that the System Suitability Test (SST) and failure modes are relevant for other conditions outside the MODR as well when the same measuring principle is used. It follows that it should be possible to move outside the MODR as long as the SST has passed. All minor modifications of the original, approved QC-method must be re-validated according to a template given in the original submission and a statistical equivalence should be shown between the original and modified QC-methods. To summarize, revalidation is handled within the pharmaceutical quality control system according to internal change control procedures, but without interaction with regulating agencies.
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