| 1. |
- Kalla, Rahul, et al.
(författare)
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EPIGENETIC ALTERATIONS IN IBD : DEFINING GEOGRAPHICAL, GENETIC, AND IMMUNEIN-FLAMMATORY INFLUENCES ON THE CIRCULATING METHYLOME
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:Suppl. 4, s. A5-A5
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: DNA methylation may provide critical insights into gene-environment interactions in inflammatory bowel disease (IBD).Methods: Using the multi-centre IBD Character inception cohort (295 controls, 154 CD, 161 UC, 28 IBD-U), epigenome-wide methylation was profiled using Illumina HumanMethylation450 platform. Differentially methylated position analysis was performed using age, sex and cell proportions as covariates. Integration of paired genomic and transcriptomic layers was done with Multi-Omics Factor Analysis v2 (MOFA). Unsupervised principal component analyses were performed to examine correlates of treatment escalation and clinical predictors of disease severity.Results: We report 137 differentially methylated positions (DMP) in whole blood in IBD, including VMP1/MIR21 (p=9.11×10-15) and RPS6KA2 (6.43×10-13); with consistency seen across Scandinavia and UK. Cell of origin analysis preferentially implicated the monocyte lineage. Dysregulated loci demonstrate strong genetic influence, notably VMP1 (p=1.53×10-15). Age acceleration is seen in IBD (coefficient 0.94, p<2.2x10-16). Several immuno-active genes demonstrated highly significant correlations between methylation and gene expression in IBD, in particular OSM: IBD r -0.32, p 3.64×10-7 vs. non-IBD r -0.14, p=0.77). Multi-omic integration of methylome, genome and transcriptome also identified specific pathways that associate with immune activation, response and regulation at disease inception. At follow up, a signature of 3 DMPs (TAP1, TESPA1, RPTOR) associated with treatment escalation to biological agents or surgery (hazard ratio of 5.19 (CI:2.14-12.56, logrank p=9.70×10-4).Conclusion: This study highlights the stability of the IBD-specific circulating methylome across regions with shared ancestry. Through integrative multi-omic analyses we identify key pro-inflammatory genes that are upregulated in IBD at inception. Furthermore, differential methylation within certain genes such as TAP1 associate with disease course over time.
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| 2. |
- Olbjern, Christine, et al.
(författare)
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Fecal microbiota profiles in treatment-naive pediatric inflammatory bowel disease : associations with disease phenotype, treatment, and outcome
- 2019
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Ingår i: Clinical and Experimental Gastroenterology. - Macclesfield, United Kingdom : DOVE MEDICAL PRESS LTD. - 1178-7023. ; 12, s. 37-49
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Imbalance in the microbiota, dysbiosis, has been identified in inflammatory bowel disease (IBD). We explored the fecal microbiota in pediatric patients with treatment-naive IBD, non-IBD patients with gastrointestinal symptoms and healthy children, its relation to IBD subgroups, and treatment outcomes. Patients and methods: Fecal samples were collected from 235 children below 18 years of age. Eighty children had Crohns disease (CD), 27 ulcerative colitis (UC), 3 IBD unclassified, 50 were non-IBD symptomatic patients, and 75 were healthy. The bacterial abundance of 54 predefined DNA markers was measured with a 16S rRNA DNA-based test using GA-Map (TM) technology at diagnosis and after therapy in IBD patients. Results: Bacterial abundance was similarly reduced in IBD and non-IBD patients in 51 of 54 markers compared to healthy patients (Pamp;lt;0.001). Only Prevotella was more abundant in patients (Pamp;lt;0.01). IBD patients with ileocolitis or total colitis had more Ruminococcus gnavus (P=0.02) than patients with colonic CD or left-sided UC. CD patients with upper gastrointestinal manifestations had higher Veillonella abundance (Pamp;lt;0.01). IBD patients (58%) who received biologic therapy had lower baseline Firmicutes and Mycoplasma hominis abundance (Pamp;lt;0.01) than conventionally treated. High Proteobacteria abundance was associated with stricturing/penetrating CD, surgery (Pamp;lt;0.01), and nonmucosal healing (Pamp;lt;0.03). Low Faecalibacterium prausnitzii abundance was associated with prior antibiotic therapy (P=0.001), surgery (P=0.02), and nonmucosal healing (Pamp;lt;0.03). After therapy, IBD patients had unchanged dysbiosis. Conclusion: Fecal microbiota profiles differentiated IBD and non-IBD symptomatic children from healthy children, but displayed similar dysbiosis in IBD and non-IBD symptomatic patients. Pretreatment fecal microbiota profiles may be of prognostic value and aid in treatment individualization in pediatric IBD as severe dysbiosis was associated with an extensive, complicated phenotype, biologic therapy, and nonmucosal healing. The dysbiosis persisted after therapy, regardless of treatments and mucosal healing.
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| 3. |
- Ahlen, Gustaf, et al.
(författare)
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Limited effect on NS3-NS4A protein cleavage after alanine substitutions within the immunodominant HLA-A2-restricted epitope of the hepatitis C virus genotype 3a non-structural 3/4A protease.
- 2012
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 93:Pt 8, s. 1680-1686
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Tidskriftsartikel (refereegranskat)abstract
- It has been well established that immunological escape mutations within the hepatitis C virus genotype (gt) 1a non-structural (NS) 3/4A protease is partly prevented by a reduction of the viral protease fitness. Surprisingly little is known whether similar mutations affect proteases from other genotypes. In the present study, we assessed both the human leukocyte antigen (HLA)-A2-restricted cytotoxic T cell response and gt3a NS3/4A protease fitness. Similar to gt1, the 1073-1081 epitope was also immunodominant within the gt3a-specific HLA-A2-restricted cytotoxic T cell response, despite a homology of only 56% between gt1a and gt3a genes. However, unlike the gt1a NS3/4A protease, all residues within the gt3a 1073-1081 epitope could sequentially be replaced by alanine with a, at least in part, retained protease activity.
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| 4. |
- Aleman, Soo, et al.
(författare)
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Frequent loss to follow-up after diagnosis of hepatitis C virus infection : A barrier towards the elimination of hepatitis C virus
- 2020
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Ingår i: Liver international (Print). - : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 40:8, s. 1832-1840
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies on hepatitis C cascade of care have been mainly focused on diagnosis and treatment rate, while less attention has been given to patients lost to follow-up (LTFU) after diagnosis. Analyses of this latter issue on population level are missing.AIMS: In this nationwide study of people with HCV, we aimed to estimate the proportion LTFU after HCV diagnosis, characterize them, and analyze their other healthcare contacts.METHODS: Patients diagnosed with chronic HCV in the Swedish National Patient register during 2001-2011 and still alive December 31, 2013, were included. The number of cured patients without need of follow-up was estimated. Visits to HCV specialist care during 2012-2013 were analysed. For those LTFU, other specialist care contacts were studied.RESULTS: In total 29,217 patients were included, with 24,733 with need of HCV care. 61% (n=15,007) of them were LTFU from HCV care in 2012-2013 and 58% did not attend HCV care during the second year after HCV diagnosis. The departments of surgery/orthopedic or psychiatry/dependency were the most common other non-primary healthcare contacts. Predictors for LTFU were young age, male sex, low education, presence of psychiatric/dependency diagnosis, unmarried, and longer duration since diagnosis of HCV.CONCLUSIONS: This study showed that almost two-thirds of patients were LTFU after HCV diagnosis, with frequent occurrence early after diagnosis. Efforts to link patients back to HCV care, in combination with early and easy access to HCV treatment and harm reduction, are necessary to reach the HCV elimination goal.
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| 5. |
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| 6. |
- Alm, Klas Håkan, et al.
(författare)
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International Higher Education : Local Initiatives Enabling Global Citizens
- 2016
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Konferensbidrag (refereegranskat)abstract
- Education at University of Borås is internationally connected to varying degree and form. This report looks at a selection of initiatives in order to explore the past, present and future role of UB internationalization. As a basis for the review, 7 students are interviewed on their international experience in their education – exchange studies and minor field studies (MFS) respectively. The participants stress the role of personal development and career enablement, and perceive their international experience as a distinct, unique element of their education. Possibilities and problems are then identified and related to the current literature on international education, learning and pedagogics. The study lands in a critical discussion on the future development of UB education. Key points of development: To meet the Bologna 20 percent commitment, more efforts need to be made on promoting and enabling internationalization to students, faculty and administrators. Curricular hurdles need to be removed as not to hamper students’ programme progression for going abroad. Teachers’ competency building efforts such as the Teaching and learning in higher education course could benefit from further elements of internationalization.
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| 7. |
- Askarieh, Galia, 1983, et al.
(författare)
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Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C.
- 2010
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 51:5, s. 1523-1530
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Tidskriftsartikel (refereegranskat)abstract
- High systemic levels of interferon-gamma-inducible protein 10 kDa (IP-10) at onset of combination therapy for chronic hepatitis C virus (HCV) infection predict poor outcome, but details regarding the impact of IP-10 on the reduction of HCV RNA during therapy remain unclear. In the present study, we correlated pretreatment levels of IP-10 in liver biopsies (n = 73) and plasma (n = 265) with HCV RNA throughout therapy within a phase III treatment trial (DITTO-HCV). Low levels of plasma or intrahepatic IP-10 were strongly associated with a pronounced reduction of HCV RNA during the first 24 hours of treatment in all patients (P < 0.0001 and P = 0.002, respectively) as well as when patients were grouped as genotype 1 or 4 (P = 0.0008 and P = 0.01) and 2 or 3 (P = 0.002, and P = 0.02). Low plasma levels of IP-10 also were predictive of the absolute reduction of HCV RNA (P < 0.0001) and the maximum reduction of HCV RNA in the first 4 days of treatment (P < 0.0001) as well as sustained virological response (genotype 1/4; P < 0.0001). To corroborate the relationship between early viral decline and IP-10, pretreatment plasma samples from an independent phase IV trial for HCV genotypes 2/3 (NORDynamIC trial; n = 382) were analyzed. The results confirmed an association between IP-10 and the immediate reduction of HCV RNA in response to therapy (P = 0.006). In contrast, pretreatment levels of IP-10 in liver or in plasma did not affect the decline of HCV RNA between days 8 and 29, i.e., the second-phase decline, or later time points in any of these cohorts. CONCLUSION: In patients with chronic hepatitis C, low levels of intrahepatic and systemic IP-10 predict a favorable first-phase decline of HCV RNA during therapy with pegylated interferon and ribavirin for genotypes of HCV.
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| 8. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
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Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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| 9. |
- Björk, Gunnar, et al.
(författare)
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Quantum degrees of polarization
- 2010
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Ingår i: Optics Communications. - : Elsevier BV. - 0030-4018 .- 1873-0310. ; 283:22, s. 4440-4447
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Tidskriftsartikel (refereegranskat)abstract
- We discuss different proposals for the degree of polarization of quantum fields. The simplest approach, namely making a direct analogy with the classical description via the Stokes operators, is known to produce unsatisfactory results. Still, we argue that these operators and their properties should be basic for any measure of polarization. We compare alternative quantum degrees and put forth that they order various states differently. This is to be expected, since, despite being rooted in the Stokes operators, each of these measures only captures certain characteristics. Therefore, it is likely that several quantum degrees of polarization will coexist, each one having its specific domain of usefulness.
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| 10. |
- Björk, Gunnar, et al.
(författare)
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Two-photon imaging and quantum holography
- 2004
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Ingår i: Journal of Optics B-Quantum and Semiclassical Optics. - : IOP Publishing. - 1464-4266 .- 1741-3575. ; 6:6, s. S478-S482
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Tidskriftsartikel (refereegranskat)abstract
- We discuss when the use of entangled photon pairs in an imaging system can be simulated with a classically correlated source. In particular, we consider two recently proposed schemes with 'bucket detection' of one of the photons. We argue that these schemes give identical results for entangled states as for appropriately prepared classically correlated states.
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| 11. |
- Brenndörfer, Erwin Daniel, et al.
(författare)
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Hepatitis C virus non-structural 3/4A protein interferes with intrahepatic interferon-γ production.
- 2012
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 61:4, s. 589-96
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Tidskriftsartikel (refereegranskat)abstract
- The non-structural (NS) 3/4A protease/helicase of the hepatitis C virus is known to modulate signalling pathways in the infected hepatocyte by cleaving CARD adaptor inducing IFNβ (Cardif), T-cell protein tyrosine phosphatase (TC-PTP) and TIR domain-containing adaptor inducing IFNβ (TRIF), but the effects of NS3/4A in vivo still remain unclear.
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| 12. |
- Bång, Magnus, et al.
(författare)
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Automatisk trafikövervakning genom AI i svenska farvatten : Slutrapport AutoMon Del I
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna slutrapport redogör för resultatet av projektet: AutoMon Del I—Automatisk trafikövervakning genom AI i svenska farvatten (TRV2019/95873). Projektägare är Linköpings universitet och genomförts tillsammans med Sjöfartsverket, SAAB, VTI, och Luftfartsverket. Vi kommer i denna rapport redogöra för resultaten samt diskutera framtida utmaningar med konceptet AutoMon. Syftet med AutoMon är att undersöka och belysa problemområdet automatiserad trafikövervakning genom att implementera en AI-demonstrator för svenska farvatten, initialt med fokus på att detektera anomalier i trafiken, och där hanteringen (dvs. granskning och lösning) av problemsituationer lämnas över till en mänsklig operatör. Förekomsten av fartygsolyckor och -incidenter, med potentiellt stora konsekvenser för individ och miljö - utanför etablerade VTS-områden - visar på behovet av utökad övervakning av sjötrafiken i svenska farvatten för att möjliggöra proaktiva åtgärder för att minimera olycksrisker till sjöss. Forskningsprojektet undersöker hur en hög nivå av automation kan användas för att upptäcka och hantera trafikavvikelser på svenskt vatten samt ge möjlighet till s.k. situational awareness (lägesbild) över hela dess yta, samtidigt som stöd för centralt eller distribuerat beslutsfattande ges. Runt om i världen förekommer även manipulation av AIS-systemet och dess positionsangivelser; ett problem som sannolikt kommer att öka även i Sverige. Båda problemställningarna är globala, vilket ger hög relevans. Lösningar har högt värde där digitalisering och artificiell intelligens kan användas som medel för ökad sjösäkerhet (safety och cyber security).
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| 13. |
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| 14. |
- Chen, Antony, et al.
(författare)
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Heterologous T cells can help restore function in dysfunctional hepatitis C virus nonstructural 3/4A-specific T cells during therapeutic vaccination.
- 2011
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Ingår i: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 186:9, s. 5107-18
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Tidskriftsartikel (refereegranskat)abstract
- The hepatitis C virus (HCV)-specific T cell response in patients with chronic HCV is dysfunctional. In this study, we aimed at restoring immunological function through therapeutic vaccination in a transgenic mouse model with impaired HCV-specific T cell responses due to a persistent presence of hepatic HCV nonstructural (NS)3/4A Ags. The HCV-specific T cells have an actively maintained dysfunction reflected in reduced frequency, impaired cytokine production, and impaired effector function in vivo, which can be partially restored by blocking regulatory T cells or programmed cell death ligand 1. We hypothesized that the impairment could be corrected by including sequences that created a normal priming environment by recruiting "healthy" heterologous T cells and by activating innate signaling. Endogenously expressed hepatitis B core Ag (HBcAg) can recruit heterologous T cells and activate TLR (TLR7) signaling. Hence, by combining HCV NS3/4A with different forms of HBcAg we found that heterologous sequences somewhat improved activation and expansion of NS3/4A-specific T cells in a wild-type host. Importantly, the signals provided by HBcAg effectively restored the activation of HCV-specific T cells in a tolerant NS3/4A-transgenic mouse model. The adjuvant effect could also be transferred to the priming of dysfunctional HLA-A2-restricted NS3-specific T cells in vivo. Thus, recruiting healthy heterologous T cells to the site of priming may also help restore HCV-specific responses present in a chronically infected host.
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| 15. |
- Fejrskov, Anja, et al.
(författare)
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Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease : protocol for the Nordic inception cohort study (NORDTREAT)
- 2024
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death.METHODS AND ANALYSIS: We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits.ETHICS AND DISSEMINATION: This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.CLINICAL TRIAL REGISTRATION NUMBER: NCT05414578; Pre-results.
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| 16. |
- Gill, H S, et al.
(författare)
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Cutaneous vaccination using microneedles coated with hepatitis C DNA vaccine.
- 2010
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Ingår i: Gene therapy. - : Springer Science and Business Media LLC. - 1476-5462 .- 0969-7128. ; 17:6, s. 811-814
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Tidskriftsartikel (refereegranskat)abstract
- The skin is potentially an excellent organ for vaccine delivery because of accessibility and the presence of immune cells. However, no simple and inexpensive cutaneous vaccination method is available. Micron-scale needles coated with DNA were tested as a simple, inexpensive device for skin delivery. Vaccination with a plasmid encoding hepatitis C virus nonstructural 3/4A protein using microneedles effectively primed specific cytotoxic T lymphocytes (CTLs). Importantly, the minimally invasive microneedles were as efficient in priming CTLs as more complicated or invasive delivery techniques, such as gene gun and hypodermic needles. Thus, microneedles may offer a promising technology for DNA vaccination.
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| 17. |
- Grafström, Jonas, 1985-, et al.
(författare)
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Knowledge Accumulation from Public Renewable Energy R&D in the European Union: Converging or Diverging Trends?
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this paper is to investigate the presence of convergence (or divergence) in public renewable energy R&D spending accumulation in 12 Member States of the European Union (EU) and an extended set of 17 OECD countries. Specifically, we employ a data set covering the period 1980-2012. The motivation for investigating convergence in the selected countries are in part due to the political economy of imposing stricter targets for renewable energy. The method draws inspiration from the classic economic convergence literature. Various empirical specifications for conditional β-convergence is tested. The empirical results suggest divergence in public R&D-based knowledge accumulation, and this is consistent with free-riding behavior on the part of some Member States. Energy import dependence and electricity regulation also affect the divergence pattern, e.g., the speed of divergence.
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| 18. |
- Grafström, Jonas, et al.
(författare)
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Knowledge Accumulation fromPublic Renewable Energy R&D in the European Union : Converging or Diverging Trends?
- 2017
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Rapport (refereegranskat)abstract
- Bottom-up processes of policy convergence are increasingly discussed as a substitute for the absence of supranational energy policy coordination and harmonization in the EU. The overall objective of this paper is to analyse the development of government support to renewable energy R&D across EU countries over time: does the empirical evidence suggest bottom-up convergence? In order to answer this question, we first construct country-specific R&D-based knowledge stocks, and then investigate whether the developments of these stocks tend to converge or diverge across EU countries. A data set covering 12 EU Member States over the time period 1990-2012 is employed to test for the presence of conditional β-convergence using a bias-corrected dynamic panel data estimator. The empirical results are overall robust and suggest divergence in terms of public R&D-based knowledge build-up in renewable energy technology. This finding is consistent with free-riding behavior on the part of some Member States, and the presence of industrial policy motives in other States in combination with agglomeration effects in the renewable energy sector. Energy import dependence and electricity regulation are found to influence the growth of the R&D-based knowledge stock, and the deregulation of the EU electricity markets has tended to contribute to a lower speed of divergence.
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| 19. |
- Grafström, Jonas, 1985-
(författare)
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Technological Change in the Renewable Energy Sector : Essays on Knowledge Spillovers and Convergence
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall purpose of this thesis is to investigate the determinants of technological change in the renewable energy sector, with a special emphasis on the role of knowledge spillovers and convergence across countries. The thesis consists of a preface and five self-contained papers. In Paper I technological change is broken down into the three major development stages laid out by Joseph Schumpeter: invention, innovation and diffusion. Econometric models of each of these stages are specified in the empirical context of wind power. The models are estimated employing a panel dataset consisting of eight western European countries over the time period 1991-2008. The results display evidence of national and international knowledge spillovers in the invention (i.e., patenting) model. The results from the technology learning models indicate evidence of global learning-by-doing, and that the prices of input factors have been important determinants of wind power costs. In line with previous research, the diffusion model results show that investment costs have influenced the development of installed wind power capacity. Paper II investigates how wind power inventions in European countries have affected the technological development achievements in neighboring countries. Data on the number of patents granted at the European Patent Office (EPO) during the period 1978-2008 in the eight technologically leading wind power countries in Europe are employed in a patent production function framework. The presence of international knowledge spillovers is found to constitute a statistically significant determinant of a country’s patent production. Geographical distance is also taken into consideration, and the results suggest that knowledge spillovers are subject to spatial transaction costs: with longer distances the role of international spillovers becomes weaker. Paper III investigates the convergence of inventive capabilities in the EU. Data on total patents per capita in 13 EU countries over the period 1990-2011 are analyzed using both parametric and non-parametric techniques. Converging inventive abilities may be important for the future of the EU given that rapid technological change has resulted in major structural changes in the Member States’ economies during the last decades. The β-convergence and σ-convergence tests suggest convergence in inventive capabilities, and this finding gains some support when analyzing the intra-distributional dynamics of the invention capabilities. Paper IV specifically investigates whether the generation of renewable energy patents per capita has converged or diverged across 13 EU countries over the period 1990-2012. The results indicate the presence of conditional β- and σ-divergence in renewable energy invention abilities. This could be critical for assessing the future prospects of EU policy in the renewable energy field; divergence in terms of invention outcomes could imply a less rapid and yet more expensive goal fulfillment due to free-rider behavior and sub-optimal investment levels. Finally, Paper V tests for convergence/divergence based on countries’ public spending to renewable energy R&D. The empirical analysis focuses on the presence of conditional β-convergence across 13 EU countries over the period 1990-2012. The results suggest divergence in public R&D-based knowledge accumulation, and this is consistent with free-riding behavior on the part of some EU Member States. Energy import dependence and electricity deregulation also affect this divergence pattern. For instance, the higher the energy import dependence, the lower is the speed of divergence across the EU countries in terms of public R&D support. Overall, the diverging pathways in terms of both public R&D and private patenting efforts may raise concerns about an unfair burden-sharing in terms of renewable energy development efforts.
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| 20. |
- Groenheit, Ramona, et al.
(författare)
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High Prevalence of SARS-CoV-2 Omicron Infection Despite High Seroprevalence, Sweden, 2022
- 2023
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Ingår i: Emerging Infectious Diseases. - : CENTERS DISEASE CONTROL & PREVENTION. - 1080-6040 .- 1080-6059. ; 29:6
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Tidskriftsartikel (refereegranskat)abstract
- We performed 2 surveys during 2022 to estimate point prevalences of SARS-CoV-2 infection compared with overall viral seroprevalence in Sweden. Point prevalence was 1.4% in March and 1.5% in September. Estimated seroprevalence was >80%, including among unvaccinated children. Continued SARS-CoV-2 surveillance is necessary for detecting emerging, possibly more pathogenic variants.
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| 21. |
- Grännö, O., et al.
(författare)
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Preclinical protein signatures in blood predict Crohn's disease and Ulcerative colitis several years before the diagnosis
- 2024
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I660-I661
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: We aimed to identify protein signatures predictive of a future diagnosis of inflammatory bowel disease (IBD).Methods: We conducted a case-control study, nested within large population-based cohorts with biorepositories. Samples were obtained from individuals who later in life were diagnosed with IBD (preclinical cases) and compared with age and sex-matched individuals who remained free from IBD during follow-up (controls). Using proximity extension assays (Olink, Uppsala), we measured 176 proteins. We applied regularized logistic regression to identify protein signatures of preclinical disease in serum from the discovery cohort (n=312). Their performance was validated in an external preclinical cohort (n=222). The biological relevance of identified proteins was further assessed in an inception cohort (n=144). Finally, we used an IBD twin cohort (n=327) to examine the impact of genetic and shared environmental factors on identified proteins.Results: We identified 34 proteins associated with preclinical Crohn’s disease (CD) in the discovery cohort (Pfalse discovery rate <0.10), with 9 confirmed in the validation cohort (Pfalse discovery rate <0.05). For preclinical ulcerative colitis (UC), 45 proteins were identified and 12 validated (Fig. 1A-B). In the discovery cohort, a signature of 29 proteins differentiated preclinical CD cases from controls with an AUC of 0.85 (Fig. 1G). Its performance was confirmed when applied to the preclinical validation cohort (AUC=0.84, Fig. 1H). Moreover, the signature had excellent capacity to differentiate newly diagnosed CD from healthy controls in the inception cohort (AUC = 0.99, Fig. 1I). The preclinical UC signature had a significant, but albeit lower, predictive capacity in the discovery (AUC=0.77), validation (AUC=0.67) and inception cohort (AUC=0.90, Fig. 1G-I).15 of 17 proteins associated with preclinical IBD demonstrated significantly higher intra-pair correlation coefficients in healthy monozygotic- compared to dizygotic twin pairs, indicating an influence from genetic factors on the regulation of these protein markers. The preclinical signature for CD demonstrated an AUC of 0.87 when comparing twins with preclinical CD (n=10) to matched external healthy twins. However, its predictive capacity was lower when comparing preclinical CD twins with their healthy twin siblings (AUC=0.58), i.e., when accounting for genetic and shared environmental factors. The difference in AUC estimates in the twin cohort was not significant (P=0.07).
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| 22. |
- Hellstrand, Kristoffer, 1956, et al.
(författare)
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Age-Related Efficacy of Immunotherapy with Histamine Dihydrochloride and Interleukin-2 for Relapse Prevention in Acute Myeloid Leukemia
- 2011
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Ingår i: Annals of Hematology. - : Springer Science and Business Media LLC. - 0939-5555 .- 1432-0584. ; 90:Suppl. 1
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Tidskriftsartikel (refereegranskat)abstract
- Recurrence of leukemia after the completion of induction and consolidation chemotherapy is a significant clinical concern in acute myeloid leukemia (AML). Apart from allogeneic bone marrow transplantation there is no consensus about effective relapse-protective therapy beyond the consolidation phase, and the standard of care for the majority of patients in complete remission (CR) hence is no treatment. Here we present updated results from a phase 3 trial (n=320) evaluating the prevention of relapse in AML patients receiving immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2). This trial was previously reported to meet the primary endpoint of improved leukemia-free survival (LFS) in the primary population of all randomized patients. Our results imply that treatment with HDC/IL-2 prevents relapse in patients 40–70 years old in first CR (p=0.008, leukemia-free survival (LFS), n=190, log rank test) with a more than 80% relative increase in the likelihood of LFS at 3 years. HDC/IL-2 was not significantly efficacious in young patients (<40 years old). Further studies are underway to define the impact of HDC/IL-2 on immune function and the putative efficacy of therapy in genetic subgroups of AML.
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| 23. |
- Kalla, R., et al.
(författare)
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Analysis of systemic epigenetic alterations in inflammatory bowel disease : defining geographical, genetic, and immune-inflammatory influences on the circulating methylome
- 2023
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 17:2, s. 170-184
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epigenetic alterations may provide valuable insights into gene-environment interactions play in the pathogenesis of Inflammatory Bowel Disease (IBD).METHODS: Genome-wide methylation was measured from peripheral blood using the Illumina 450k platform in a case-control study in an inception cohort (295 controls, 154 CD, 161 UC, 28 IBD-U) with covariates of age, sex, and cell counts, deconvoluted by the Houseman method. Genotyping was performed using Illumina HumanOmniExpressExome-8 BeadChips and gene expression using Ion AmpliSeq Human Gene Expression Core Panel. Treatment escalation was characterised by the need for biological agents or surgery after initial disease remission.RESULTS: A total of 137 differentially methylated positions (DMP) were identified in IBD, including VMP1/MIR21 (p=9.11×10 -15) and RPS6KA2 (6.43×10 -13); with consistency seen across Scandinavia and UK. Dysregulated loci demonstrate strong genetic influence, notably VMP1 (p=1.53×10 -15). Age acceleration is seen in IBD (coefficient 0.94, p<2.2x10 -16). Several immuno-active genes demonstrated highly significant correlations between methylation and gene expression in IBD, in particular OSM: IBD r -0.32, p 3.64×10 -7 vs. non-IBD r -0.14, p=0.77). Multi-omic integration of methylome, genome and transcriptome also implicate specific pathways that associate with immune activation, response and regulation at disease inception. At follow up, a signature of 3 DMPs (TAP1, TESPA1, RPTOR) associated with treatment escalation to biological agents or surgery (hazard ratio of 5.19 (CI:2.14-12.56, logrank p=9.70×10 -4).CONCLUSION: These data demonstrate consistent epigenetic alterations at diagnosis in European patients with IBD, providing insights into the pathogenetic importance and translational potential of epigenetic mapping in complex disease.
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| 24. |
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| 25. |
- Kalla, R., et al.
(författare)
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Serum proteomic profiling at diagnosis predicts clinical course, and need for intensification of treatment in inflammatory bowel disease
- 2021
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Ingår i: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 15:5, s. 699-708
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Success in personalised medicine in complex disease is critically dependent on biomarker discovery. We profiled serum proteins using a novel proximity extension assay (PEA) to identify diagnostic and prognostic biomarkers in inflammatory bowel disease (IBD).METHODS: We conducted a prospective case-control study in an inception cohort of 552 patients (328 IBD, 224 non-IBD), profiling proteins recruited across 6 centres. Treatment escalation was characterised by the need for biological agents or surgery after initial disease remission. Nested leave-one-out cross validation was used to examine the performance of diagnostic and prognostic proteins.RESULTS: A total of 66 serum proteins differentiated IBD from symptomatic non-IBD controls including MMP-12 (Holm adjusted p=4.1×10 -23 ) and OSM (p=3.7×10 -16). Nine of these proteins associate with cis- germline variation (59 independent SNPs). Fifteen proteins, all members of TNF independent pathways including IL-1 and OSM predicted escalation, over a median follow-up of 518 (IQR 224-756) days. Nested cross-validation of the entire data set allows characterisation of 5-protein-models (96% comprising five core proteins ITGAV, EpCAM, IL18, SLAMF7, and IL8) which define a high-risk subgroup in IBD (HR 3.90, CI: 2.43-6.26), or allows distinct 2, and 3 protein models for UC and CD respectively.CONCLUSION: We have characterised a simple oligo-protein panel that has the potential to identify IBD from symptomatic controls and to predict future disease course. Further prospective work is required to validate our findings.
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